Journal articles on the topic 'EA heterogeneity'
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1
Helou, C. M., and J. Marchetti. "Morphological heterogeneity of renal glomerular arterioles and distinct [Ca2+]i responses to ANG II." American Journal of Physiology-Renal Physiology 273, no. 1 (July 1, 1997): F84—F96. http://dx.doi.org/10.1152/ajprenal.1997.273.1.f84.
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The present study compares cytosolic calcium concentration ([Ca2+]i) responses to angiotensin II (ANG II) of afferent (AA) and efferent arterioles (EA) by taking account of the localization and morphological differences of EA. In outer cortex, 1 nM ANG II induced smaller [Ca2+]i increases in thin EA than in AA[48 +/- 10 (n = 12) vs. 94 +/- 7 nM (n = 11); P < 0.001]. In inner cortex, two types of EA were considered, i.e., thin and muscular ones. The response to 1 nM ANG II was 35% lower in thin than in muscular EA (P < 0.05) but did not differ from that obtained with corresponding AA. In EA of the outer cortex, 1 microM nifedipine, a dihydropyridine blocker of voltage-operated channels (VOCC), did not affect calcium influx, which was suppressed by 1 mM NiCl2, a nonselective calcium entry blocker. In other arterioles, nifedipine inhibited by approximately 40% calcium entry, and remaining influx was blocked by NiCl2. These results indicate a relationship between the magnitude of [Ca2+]i responses, activation of dihydropyridine-sensitive VOCC by ANG II, and the muscular morphology in renal glomerular arterioles. They suggest that ANG II regulates differently local renal microcirculation. They do not, however, support the hypothesis of a greater sensitivity to ANG II of EA compared with the AA of a given nephron.
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Lisha, Nadra Erin, Adam M. Leventhal, Luanne Rohrbach, Donna Spruijt-Metz, Ping Sun, and Steve Sussman. "The relationship of emerging adulthood trajectories to drug use, and other correlates." Health and Addictions/Salud y Drogas 15, no. 2 (July 30, 2015): 91–102. http://dx.doi.org/10.21134/haaj.v15i2.235.
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Interest in “Emerging Adulthood” (EA) as a unique developmental period has increased. This study examined the heterogeneity of EA among at-risk youth (N=1,677) by identifying trajectories of development across individuals. First, an 8-item version of the Inventory of Dimensions of EA (IDEA) measure was tested for factorial invariance across three time points; the 5-item EA measure was found to be factorially invariant. Next, latent class growth modeling identified three unique developmental trajectories. Lastly, classes were compared on demographics and health-risk behaviors. Class 1 represented a large, low-risk class (highest on EA). Classes 2 and 3 were comparably sized (~5% of the sample). Class 2 appears to be a high-risk class that decreases in EA, while Class 3 appears to be a medium-risk class that increases in EA. This study confirms that not everyone experiences EA similarly and that continuation high school students do not circumvent EA (move directly to adulthood).
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Chen, Min’an, Sisi Zhao, Yu Guo, Luxi Cao, Hai Zeng, Zhuowen Lin, Shiqi Wang, Yimin Zhang, and Mingmin Zhu. "The Influence of Acupuncture Parameters on Efficacy and the Possible Use of Acupuncture in Combination with or as a Substitute for Drug Therapy in Patients with Ulcerative Colitis." Evidence-Based Complementary and Alternative Medicine 2022 (March 22, 2022): 1–16. http://dx.doi.org/10.1155/2022/8362892.
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Background. Ulcerative colitis (UC) is an inflammatory disease of the colonic mucosa, which is accompanied by chronic, idiopathic characteristics. Acupuncture may be an effective therapy for UC. Here we focused on manual acupuncture and electroacupuncture (MA/EA), two widely used and studied acupuncture interventions, to probe the effects of acupuncture parameters on clinical efficacy in patients with UC and the use of MA/EA alone or with other drugs to support their wider adoption in clinical practice. Methods. The PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure Database, and Wanfang databases were searched from inception to April 27, 2021. Randomized clinical trials (RCTs) published in Chinese or English were included, and subgroup analyses were performed according to acupuncture parameter, acupuncture type, and control medicine type. The risk of bias was assessed using the Cochrane Risk of Bias tool and modified Jadad scale, and Review Manager 5.4 and Stata 14.0 were used to perform a meta-analysis. Sources of heterogeneity were explored; sensitivity analysis was performed; and the GRADE methodology was used to assess the evidence level. Results. Sixteen studies (1454 individuals) were included. Retention of the needle [10–30 minutes (RR 1.18, 95% CI [1.11, 1.26], P < 0.01 ; heterogeneity: χ2 = 6.25, df = 6 ( P = 0.40 ), I2 = 4%)], the frequency of MA [once every other day (RR 1.21, 95% CI [1.08, 1.35], P < 0.01 ; heterogeneity: χ2 = 0.80, df = 1 ( P = 0.37 ), I2 = 0%)], and the length of treatment [8 weeks (RR 1.35, 95% CI [1.01, 1.81], P = 0.04 )] improved clinical efficacy at the end of treatment compared with medications alone. MA (RR 1.18, 95% CI [1.11, 1.25], P < 0.01 ; heterogeneity: χ2 = 6.19, df = 7 ( P = 0.52 ), I2 = 0%) increased clinical efficacy compared with medications. Furthermore, MA plus medications (RR 1.26, 95% CI [1.13, 1.40], P < 0.01 ; heterogeneity: χ2 = 0.95, df = 2 ( P = 0.62 ), I2 = 0%) and EA plus medications (RR 1.36, 95% CI [1.13, 1.63], P < 0.01 ; heterogeneity: χ2 = 0.13, df = 1 ( P = 0.72 ), I2 = 0%) both dramatically improved clinical efficacy. The clinical efficacy of MA plus mesalazine or MA plus metronidazole and sulfasalazine was greater than with mesalazine or metronidazole and sulfasalazine alone. Similarly, EA plus sulfasalazine was more effective than sulfasalazine alone. MA/EA resulted in fewer adverse reactions than medical therapies. The use of MA plus medications significantly reduced Baron scores. GRADE evaluations indicated that the evidence strength was moderate to low but mostly low. Conclusions. Our study provides the latest evidence to allow us to speculate about the possible optimal MA parameters to treat patients with UC. The low number of adverse reactions and high efficacy make MA/EA a possible supplement to or replacement for traditional UC drugs. The variable parameter settings preferred by patients and acupuncturists may be an important factor limiting the wider clinical deployment of acupuncture as a potential UC therapy.
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Ayoub, Fares, Tony S. Brar, Debdeep Banerjee, Ali M. Abbas, Yu Wang, Dennis Yang, and Peter V. Draganov. "Laparoscopy-assisted versus enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) in Roux-en-Y gastric bypass: a meta-analysis." Endoscopy International Open 08, no. 03 (February 21, 2020): E423—E436. http://dx.doi.org/10.1055/a-1070-9132.
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Abstract Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients with Roux-en-Y gastric bypass (RYGB) anatomy, which is increasing in frequency given the rise of obesity. Laparoscopy-assisted ERCP (LA-ERCP) and enteroscopy-assisted ERCP (EA-ERCP) are distinct approaches with their respective strengths and weaknesses. We conducted a meta-analysis comparing the procedural time, rates of success and adverse events of each method. Patients and methods A search of PubMed, EMBASE and the Cochrane library was performed from inception to October 2018 for studies reporting outcomes of LA or EA-ERCP in patients with RYGB anatomy. Studies using single, double, ‘short’ double-balloon or spiral enteroscopy were included in the EA-ERCP arm. Outcomes of interest included procedural time, papilla identification, papilla cannulation, therapeutic success and adverse events. Therapeutic success was defined as successful completion of the originally intended diagnostic or therapeutic indication for ERCP. Results A total of 3859 studies were initially identified using our search strategy, of which 26 studies met the inclusion criteria. The pooled rate of therapeutic success was significantly higher in LA-ERCP (97.9 %; 95 % CI: 96.7–98.7 %) with little heterogeneity (I2 = 0.0 %) when compared to EA-ERCP (73.2 %; 95 % CI: 62.5–82.6 %) with significant heterogeneity (I2: 80.2 %). Conversely, the pooled rate of adverse events was significantly higher in LA-ERCP (19.0 %; 95 % CI: 12.6–26.4 %) when compared to EA-ERCP (6.5 %; 95% CI: 3.9–9.6 %). The pooled mean procedure time for LA-ERCP was 158.4 minutes (SD ± 20) which was also higher than the mean pooled procedure time for EA-ERCP at 100.5 minutes (SD ± 19.2). Conclusions LA-ERCP is significantly more effective than EA-ERCP in patients with RYGB but is associated with a higher rate of adverse events and longer procedural time.
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Triguero-Martínez, Ana, Emilia Roy-Vallejo, Nuria Montes, Hortensia de la Fuente, Ana María Ortiz, Santos Castañeda, Isidoro González-Álvaro, and Amalia Lamana. "Genetic LGALS1 Variants Are Associated with Heterogeneity in Galectin-1 Serum Levels in Patients with Early Arthritis." International Journal of Molecular Sciences 23, no. 13 (June 28, 2022): 7181. http://dx.doi.org/10.3390/ijms23137181.
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Galectin 1 (Gal1) exerts immunomodulatory effects leading to therapeutic effects in autoimmune animal models. Patients with rheumatoid arthritis have been reported to show higher Gal1 serum levels than the healthy population. Our study aimed to find genetic variants on the Gal1 gene (LGALS1) modulating its expression and/or clinical features in patients with early arthritis (EA). LGALS1 was sequenced in 53 EA patients to characterize all genetic variants. Then, we genotyped rs9622682, rs929039, and rs4820293, which covered the main genetic variation in LGALS1, in 532 EA patients. Gal1 and IL-6 serum levels were measured by ELISA and Gal1 also by western blot (WB) in lymphocytes from patients with specific genotypes. Once disease activity improved with treatment, patients with at least one copy of the minor allele in rs9622682 and rs929039 or those with GG genotype in rs4820293 showed significantly higher Gal1 serum levels (p < 0.05). These genotypic combinations were also associated with higher Gal1 expression in lymphocytes by WB and lower IL-6 serum levels in EA patients. In summary, our study suggests that genetic variants studied in LGALS1 can explain heterogeneity in Gal1 serum levels showing that patients with higher Gal1 levels have lower serum IL-6 levels.
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Heise, Christian, Einas Abou Ali, Dirk Hasenclever, Francesco Auriemma, Aiste Gulla, Sara Regner, Sébastien Gaujoux, and Marcus Hollenbach. "Systematic Review with Meta-Analysis: Endoscopic and Surgical Resection for Ampullary Lesions." Journal of Clinical Medicine 9, no. 11 (November 10, 2020): 3622. http://dx.doi.org/10.3390/jcm9113622.
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Ampullary lesions (ALs) can be treated by endoscopic (EA) or surgical ampullectomy (SA) or pancreaticoduodenectomy (PD). However, EA carries significant risk of incomplete resection while surgical interventions can lead to substantial morbidity. We performed a systematic review and meta-analysis for R0, adverse-events (AEs) and recurrence between EA, SA and PD. Electronic databases were searched from 1990 to 2018. Outcomes were calculated as pooled means using fixed and random-effects models and the Freeman-Tukey-Double-Arcsine-Proportion-model. We identified 59 independent studies. The pooled R0 rate was 76.6% (71.8–81.4%, I2 = 91.38%) for EA, 96.4% (93.6–99.2%, I2 = 37.8%) for SA and 98.9% (98.0–99.7%, I2 = 0%) for PD. AEs were 24.7% (19.8–29.6%, I2 = 86.4%), 28.3% (19.0–37.7%, I2 = 76.8%) and 44.7% (37.9–51.4%, I2 = 0%), respectively. Recurrences were registered in 13.0% (10.2–15.6%, I2 = 91.3%), 9.4% (4.8–14%, I2 = 57.3%) and 14.2% (9.5–18.9%, I2 = 0%). Differences between proportions were significant in R0 for EA compared to SA (p = 0.007) and PD (p = 0.022). AEs were statistically different only between EA and PD (p = 0.049) and recurrence showed no significance for EA/SA or EA/PD. Our data indicate an increased rate of complete resection in surgical interventions accompanied with a higher risk of complications. However, studies showed various sources of bias, limited quality of data and a significant heterogeneity, particularly in EA studies.
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RATNER, Svetlana V., and Andrei O. KOVALEV. "Assessing the regional environmental management system's efficiency based on data envelopment models." Economic Analysis: Theory and Practice 20, no. 6 (June 30, 2021): 1014–42. http://dx.doi.org/10.24891/ea.20.6.1014.
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Subject. The article addresses the eco-efficiency of regional economy. Objectives. The purpose is to design a methodology for assessing the comparative effectiveness of regional environmental management systems, taking into account the significant heterogeneity of regions in terms of eco-efficiency; develop approaches to assessing the eco-efficiency of regional economic systems; integrate these approaches into a single methodology. Methods. The study employs general scientific research methods. Results. The developed approach involves simultaneous solution of two tasks in the data envelopment analysis; one of them is formulated to assess the eco-efficiency of region's economy, and the other – to assess the value for money, aimed at protecting the environment in the region. The solution of these two problems enables to receive a large amount of data that can be used in designing strategies for regional development. Conclusions. The paper offers a new approach to solving the problems of comparative assessment of the effectiveness of regional environmental management systems, considering the structural heterogeneity of regional economies. The findings can be used to elaborate measures to encourage the activities of regional authorities in the field of environmental management and increase their responsibility for the effectiveness of environmental measures.
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Keller, Brett, Dale Rhoda, Caitlin Clary, Claire Rothschild, Mark Conlon, and Paul Bouanchaud. "Bias in product availability estimates from contraceptive outlet surveys: Evidence from the Consumer’s Market for Family Planning (CM4FP) study." PLOS ONE 17, no. 8 (August 30, 2022): e0271896. http://dx.doi.org/10.1371/journal.pone.0271896.
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Area-based sampling approaches designed to capture pharmacies, drug shops, and other non-facility service delivery outlets are critical for accurately measuring the contraceptive service environment in contexts of increasing de-medicalization of contraceptive commodities and services. Evidence from other disciplines has demonstrated area-based estimates may be biased if there is spatial heterogeneity in product distribution, but this bias has not yet been assessed in the context of contraceptive supply estimates. The Consumer’s Marker for Family Planning (CM4FP) study conducted censuses and product audits of contraceptive outlets across 12 study sites and 2–3 rounds of quarterly data collection in Kenya, Nigeria, and Uganda. We assessed bias in estimates of contraceptive product availability by comparing estimates from simulations of area-based sampling approaches with census counts among all audited facilities for each study site and round of data collection. We found evidence of bias in estimates of contraceptive availability generated from simulated area-based sampling. Within specific study sites and rounds, we observed biased sampling estimates for several but not all contraceptive method types, with bias more likely to occur in sites with heterogeneity in both spatial distribution of outlets and product availability within outlets. In simulations varying size of enumeration areas (EA) and number of outlets sampled per EA, we demonstrated that the likelihood of substantial bias decreases as EA size decreases and as the number of outlets sampled per EA increases. Straightforward approaches such as increasing sample size per EA or applying statistical weights may be used to reduce area-based sampling bias, indicating a pragmatic way forward to improve estimates where design-based sampling is infeasible. Such approaches should be considered in development of improved methods for area-based estimates of contraceptive supply-side environments.
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Wang, Xinwei, Antonio Sánchez Egea, Jie Xu, Xianyu Meng, Zhenlong Wang, Debin Shan, Bin Guo, and Jian Cao. "Current-Induced Ductility Enhancement of a Magnesium Alloy AZ31 in Uniaxial Micro-Tension Below 373 K." Materials 12, no. 1 (December 31, 2018): 111. http://dx.doi.org/10.3390/ma12010111.
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The size effects in metal forming have been found to be crucial in micro-scale plastic deformation or micro-forming processes, which lead to attenuation of the material’s formability due to the increasing heterogeneity of the plastic flow. The use of an electric field during micro-scale plastic deformation has shown to relieve size effects, enhance the material’s formability, modify the microstructure, etc. Consequently, these electric-assisted (EA) micro-forming processes seem to bring many potential benefits that need to be investigated. Accordingly, here we investigated the influence of an electric field on the size effects to describe the fracture behavior in uniaxial micro-tension tests of an AZ31 alloy with various grain sizes. In order to decouple the thermal-mechanical and microstructure changes, room temperature (RT), oven-heated (OH), air-cooled (AC), and EA uniaxial micro-tension tests were conducted. The size effects contribution on the fracture stress and strain showed a similar trend in all the testing configurations. However, the smallest fracture stresses and the largest fracture strains were denoted in the EA configuration. EBSD examination shows that current-induced dynamic recrystallization (DRX) and texture evolution could be negligible under the studied conditions. The kernel average misorientation (KAM) maps give the larger plastic deformation in the EA specimens due to the reduction of plastic micro-heterogeneity. Finally, the fracture morphology indicates that the current-induced ductility enhancement may be attributed to the arrest of micro-crack propagation and the inhibition of void initiation, growth, and coalescence caused by lattice melting and expansion.
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Adam, Klaus, and Junyi Zhu. "Price-Level Changes and the Redistribution of Nominal Wealth across the Euro Area." Journal of the European Economic Association 14, no. 4 (November 26, 2015): 871–906. http://dx.doi.org/10.1111/jeea.12155.
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Abstract We show that unexpected price-level movements generate sizable wealth redistribution in the Euro Area (EA), using sectoral accounts and newly available data from the Household Finance and Consumption Survey. The EA as a whole is a net loser of unexpected price-level decreases, with Italy, Greece, Portugal, and Spain losing most in per capita terms, and Belgium and Malta being net winners. Governments are net losers of deflation, while the household (HH) sector is a net winner in the EA as a whole. HHs in Belgium, Ireland, Malta, and Germany experience the biggest per capita gains, while HHs in Finland and Spain turn out to be net losers. Considerable heterogeneity exists also within the HH sector: relatively young middle class HHs are net losers of deflation, while older and richer HHs are winners. As a result, wealth inequality in the EA increases with unexpected deflation, although in some countries (Austria, Germany, and Malta) inequality decreases due to the presence of relatively few young borrowing HHs. We document that HHs’ inflation exposure varies systematically across countries, with HHs in high-inflation EA countries holding systematically lower nominal exposures.
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Zhong, Zhiyan, Haoxu Dong, Hui Wang, Yao Huang, Dongmei Huang, and Guangying Huang. "Electroacupuncture for the treatment of perimenopausal syndrome: a systematic review and meta-analysis of randomized controlled trials." Acupuncture in Medicine 40, no. 2 (November 9, 2021): 111–22. http://dx.doi.org/10.1177/09645284211055742.
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Objective: To assess the efficacy, comparative effectiveness and safety of electroacupuncture (EA) in the treatment of perimenopausal syndrome (PMS). Methods: Nine databases were searched until June 2019. Only relevant randomized controlled trials (RCTs) of EA for PMS were included. Results: Twelve trials involving 746 women were included. EA and hormone therapy (HT) did not significantly differ in terms of effective rate (risk ratio (RR) = 0.98, 95% confidence interval (CI) = 0.93 to 1.04), Kupperman index (KI) (mean difference (MD) = −0.25, 95% CI = −0.76 to 0.26) and serum levels of follicle-stimulating hormone (FSH) (MD = −3.80, 95% CI = −11.59 to 3.98) or luteinizing hormone (LH) (MD = −2.51, 95% CI = −10.72 to 5.70). Serum estradiol (E2) levels were significantly lower in EA versus HT groups (MD = −60.58, 95% CI = −71.93 to −49.23). Compared with sham EA, EA had a significantly greater effect on reductions in KI (MD = −4.71, 95% CI = −6.57 to −2.86) and hot flushes score/24 h (MD = −2.43, 95% CI = −2.93 to −1.93). There were no significant differences between EA and manual acupuncture (MA) in terms of effective rate (RR = 1.14, 95% CI = 0.98 to 1.33) or serum FSH (MD = −2.87, 95% CI = −29.65 to 23.91), LH (MD = 2.73, 95% CI = −9.65 to 15.11) or E2 (MD = 26.80, 95% CI = −12.06 to 65.65). However, it seemed that EA had a better effect than MA on KI (MD = −2.44, 95% CI = −4.80 to −0.08). Subgroup analyses indicated that EA may have more of a benefit in the pre-menopausal state (hot flushes score/24 h: MD = −1.66, 95% CI = −3.49 to 0.17) compared to post-menopause (p > 0.05). Conclusion: The effect of EA appeared broadly similar to HT and MA in the treatment of PMS, although EA-associated reductions in KI were superior to MA and sham EA, suggesting effects beyond placebo. The evidence base is limited by a small number of eligible studies, risk of bias and clinical/statistical heterogeneity, limiting our ability to draw firm conclusions. As such, additional larger scale, high-quality RCTs are needed.
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Nadeu, F., R. Royo, F. Maura, K. J. Dawson, A. Dueso, D. Torrents, M. Aymerich, et al. "PS1147 SPATIAL HETEROGENEITY IN CHRONIC LYMPHOCYTIC LEUKAEMIA ANALYSED BY WHOLE-GENOME/EXOME SEQUENCING AT DIAGNOSIS." HemaSphere 3, S1 (June 2019): 519–20. http://dx.doi.org/10.1097/01.hs9.0000562872.19873.ea.
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Wongprachum, Kasama, Kanokwan Sanchaisuriya, Maneelay Dethvongphanh, Boualay Norcharoen, Bousanit Htalongsengchan, Virack Vidamaly, Pattara Sanchaisuriya, Supan Fucharoen, Goonnapa Fucharoen, and Frank P. Schelp. "Molecular Heterogeneity of Thalassemia among Pregnant Laotian Women." Acta Haematologica 135, no. 2 (October 8, 2015): 65–69. http://dx.doi.org/10.1159/000438739.
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Background and Aims: A pilot screening program for thalassemia was initiated in the Lao People's Democratic Republic. This study aimed to describe the genotype diversity and hematologic features of thalassemia among the participating pregnant women. Methods: Blood samples of 411 pregnant Laotian women were collected. Hemoglobin (Hb) profiles were determined using a capillary zone electrophoresis system. Mutations of α- and β-globin genes were investigated using a polymerase chain reaction and related techniques. Results: As many as 26 different thalassemia genotypes including non-transfusion-dependent thalassemia, i.e. Hb E-β-thalassemia, Hb H, and EA Bart's diseases, were identified. A variety of phenotypic expressions of hematologic features and Hb profiles were observed, including an unusual phenotype of Hb E-β⁰ thalassemia with 89.1% Hb E, 1.6% Hb F, and 9.3% Hb A2. Conclusions: The remarkable genotype-phenotype diversity indicates a need for careful laboratory interpretation in order to provide appropriate genetic counseling and care to the Laotian population.
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Smith, Ryan, Anne E. Chuning, Colin A. Tidwell, John J. B. Allen, and Richard D. Lane. "Psychopathic tendencies are selectively associated with reduced emotional awareness in the context of early adversity." PLOS ONE 17, no. 12 (December 22, 2022): e0277475. http://dx.doi.org/10.1371/journal.pone.0277475.
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It is unclear at present whether psychopathic tendencies are associated with lower or higher levels of emotional awareness (EA). Given that psychopathy includes a proficiency for manipulating others, one might expect an elevated ability to identify and use information about others’ emotions. On the other hand, empathic deficits in psychopathy could arise from reduced emotional awareness. Further, heterogeneity in psychopathy may also play a role, wherein ‘secondary’ psychopathy is associated with early adversity and high negative affect, while ‘primary’ psychopathy is not. In this paper, we tested the relationship between EA and psychopathic tendencies in 177 undergraduate students (40 males) who completed the levels of emotional awareness scale (LEAS), the triarchic psychopathy measure (TPM), the affective (empathy-related) subscales of the interpersonal reactivity index (IRI), and two measures of early adversity: the childhood experiences of care and abuse questionnaire (CECA) and the childhood trauma questionnaire (CTQ). We found that lower LEAS scores were associated with higher TPM and lower IRI empathy scores, but these relationships were primarily present in those with early adversity and high negative affect. This suggests that lower EA may be selectively associated with higher levels of secondary psychopathy, while those with higher levels of primary psychopathy remain capable of higher EA.
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Turgaeva, A. A. "Cluster analysis in the control over the activity of insurance companies." Economic Analysis: Theory and Practice 19, no. 3 (March 30, 2020): 541–63. http://dx.doi.org/10.24891/ea.19.3.541.
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Subject. The article considers clustering of insurance companies as a type of informatization of economy for practical application by the internal control system. Objectives. The purpose is to present clusters and give their interpretation for insurance companies in relation to internal control; identify the possibility of clustering, using the Deductor Studio platform developed by Base Group for internal control systems. Methods. The study employs techniques of statistical research and data processing, mathematical methods, methods of grouping, and cluster analysis. Results. Clusters are presented by several indicators of insurance companies. The study reveals heterogeneity in the results of distribution according to the rating of companies in terms of various indicators. It confirms the need to use the cluster analysis in the internal control system. Conclusions. Cluster analysis enables the internal control system to take into account all data regardless of their amount, and avoid data sampling. It reduces the level of errors in the results of analysis and control.
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Flieder, Sofie, Michaela Dellenmark-Blom, Stefanie Witt, Carmen Dingemann, Julia Quitmann, Linus Jönsson, Vladimir Gatzinsky, et al. "Generic Health-Related Quality of Life after Repair of Esophageal Atresia and Its Determinants within a German–Swedish Cohort." European Journal of Pediatric Surgery 29, no. 01 (September 27, 2018): 075–84. http://dx.doi.org/10.1055/s-0038-1672144.
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Aim Despite advances of outcomes of esophageal atresia (EA), knowledge on patients' health-related quality of life (HRQoL) is sparse. Due to the heterogeneity of EA, larger cohorts need to be investigated to ensure reliability of data. Aim was to determine generic HRQoL after EA repair in a Swedish–German cohort. Patients and Methods Ethical approval was obtained. A total of 192 patients (2–18 years; 134 Swedish; 58 German) were included. Clinical data were reviewed. EA was classified in “severe” and “mild/moderate.” Pediatric Quality of Life Inventory 4.0 Generic Core Scale (PedsQL 4.0) was used in appropriate versions (2–7 years; 8–18 years; self- [SR] and proxy report [PR]) to determine generic HRQoL. Results Swedish and German samples were clinically and demographically comparable. HRQoL was lower in “severe EA” versus “mild/moderate” (2–18 years; total score; PR 85.6 vs. 73.6; p < 0.001) and Gross A versus Gross C type EA (2–7 years; total score; PR 61.0 vs. 79.3; p = 0.035). Total HRQoL was higher in the Swedish versus German sample (2–18 years; total score; PR 82.3 vs. 72.7; p = 0.002). HRQoL was impaired in the German sample versus healthy population (2–18 years; total score; PR 72.7 vs. 82.7; p = 0.001). In German patients (8–18 years), HRQoL was higher in SR versus PR (80.7 vs. 74.7; p = 0.044). Patients' age and presence of VACTERL association or isolated anorectal malformations did not affect HRQoL. Various differences were detected regarding different dimensions of PedsQL 4.0. Conclusion In this first international study, we found several differences in perception of generic HRQoL. HRQoL appears to be determined by the type of EA and severity rather than patients' age or the presence of typical associated malformations. Country-specific differences may be culturally dependent, but further investigations are suggested. A condition-specific instrument validated for EA may provide additional insights.
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Zhu, Jiajie, Yu Guo, Shan Liu, Xiaolan Su, Yijie Li, Yang Yang, Liwei Hou, et al. "Acupuncture for the Treatment of Gastro-Oesophageal Reflux Disease: A Systematic Review and Meta-Analysis." Acupuncture in Medicine 35, no. 5 (October 2017): 316–23. http://dx.doi.org/10.1136/acupmed-2016-011205.
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Background Gastro-oesophageal reflux disease (GORD) is one of the most common diseases presenting to gastroenterology clinics. Acupuncture is widely used as a complementary and alternative treatment for patients with GORD. Objective To explore the effectiveness of acupuncture for the treatment of GORD. Methods Four English and four Chinese databases were searched through June 2016. Randomised controlled trials investigating the effectiveness of manual acupuncture or electroacupuncture (MA/EA) for GORD versus or as an adjunct to Western medicine (WM) were selected. Data extraction and quality evaluation were performed by two authors independently and RevMan 5.2.0 was used to analyse data. Results A total of 12 trials involving 1235 patients were included. Meta-analyses demonstrated that patients receiving MA/EA combined with WM had a superior global symptom improvement compared with those receiving WM alone (relative risk (RR) 1.17, 95% CI 1.09 to 1.26; p=0.03; six studies) with no significant heterogeneity (I2=0%, p=0.41). Recurrence rates of those receiving MA/EA alone were lower than those receiving WM (RR 0.42,95% CI 0.29 to 0.61; p<0.001; three studies) with low heterogeneity (I2=7%, p=0.34), while global symptom improvement (six studies) and symptom scores (three studies) were similar (both p>0.05). Descriptive analyses suggested that acupuncture also improves quality of life in patients with GORD. Conclusion This meta-analysis suggests that acupuncture is an effective and safe treatment for GORD. However, due to the small sample size and poor methodological quality of the included trials, further studies are required to validate our conclusions. Trial registration number PROSPERO Systematic review registration no. CRD42016041916.
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Liu, Hui, Baowei Zhao, Xin Zhang, and Yin Zhang. "Influence of Intrinsic Physicochemical Properties of Agroforestry Waste on Its Pyrolysis Characteristics and Behavior." Materials 16, no. 1 (December 26, 2022): 222. http://dx.doi.org/10.3390/ma16010222.
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To obtain a comprehensive understanding of the qualitative and quantitative effects of the intrinsic properties of biomass on its pyrolysis characteristics and assess the behavior of agroforestry waste, thermogravimetric analyses of three representative agroforestry wastes, namely rape (Brassica campestris L.) straw (RS), apple (Malus domestica) tree branches (ATB), and pine (Pinus sp.) sawdust (PS), were carried out by pyrolysis under dynamic conditions (30 to 900 °C) at different heating rates of 5, 10, and 15 °C·min−1. Correlation analysis showed that intrinsic physicochemical properties play distinct roles in different stages of pyrolysis. The ash content was negatively correlated with the temperature range (R2) of the second stage (190–380 °C) of pyrolysis. The lignin content and the amount of pyrolysis residues (RSS) were positively correlated. Kinetic triplets, including the activation energy (Ea), pre-exponential factor (A), and reaction model [f(α)], were obtained using different methods, including the Flynn–Wall–Ozawa (FWO), Freidman, Kissinger–Akahira–Sunose (KAS), and Starink methods. The mean activation energy (Ea[mean]) for RS, ATB, and PS calculated by the different methods ranged from 167.15 to 195.58 kJ·mol−1, 195.37 to 234.95 kJ·mol−1, and 191.27–236.45 kJ·mol−1, respectively. Correlation analysis of the intrinsic physicochemical characteristics and kinetic factors of agroforestry waste showed that the minimum Ea (Ea[min]) was significantly positively correlated with heat capacity (C0) and negatively correlated with thermal diffusivity (D). The Ea[mean] and the maximum value of Ea (Ea[max]) significantly positively correlated with the sum content of cellulose and lignin, indicating that the contents of cellulose and lignin determines the energy required for the pyrolysis process of agroforestry waste. The mechanism of degradation involves the diffusion model (D1, D2, and D3), the growth model (A4), and the geometrical contraction model (R3). These results indicate that the pyrolysis of agroforestry waste is a complex process due to the heterogeneity of its intrinsic physicochemical properties.
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He, Kelin, Fengjia Ni, Yi Huang, Mengyi Zheng, Han Yu, Dexiong Han, and Ruijie Ma. "Efficacy and Safety of Electroacupuncture for Pain Control in Herpes Zoster: A Systematic Review and Meta-Analysis." Evidence-Based Complementary and Alternative Medicine 2022 (July 4, 2022): 1–11. http://dx.doi.org/10.1155/2022/4478444.
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Introduction. Herpes zoster is caused by the reactivation of the latent varicella-zoster virus, which leads to acute pain that may disturb routine activities and affect patients’ quality of life. Electroacupuncture (EA) has been commonly used for treating herpetic pain in clinical treatment. However, no relevant studies have been performed to evaluate the efficacy and safety of EA for acute control in herpetic neuralgia patients. The purpose of the current study was to conduct a systematic review and meta-analysis to address the deficiencies of the current research. Methods. Three English (PubMed, Cochrane Library, and Web of Science) and four Chinese (China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature database (CBM), Wan-fang database, and the Chinese Scientific Journals Full-text Database (VIP)) were comprehensively searched from inception to 31 December 2021. Two independent reviewers evaluated the retrieved data based on the eligibility criteria in advance. In addition, the Cochrane Risk of Bias Tool was used to assess the methodological quality of the included studies. Outcome indexes in this study included the visual analog scale, the time to cessation of pustules, the time to scabs, the time to rash healing, adverse reactions, and the incidence of postherpetic neuralgia. Sensitivity and subgroup analyses were also performed to evaluate the intervention effect specifically. In addition, publication bias was analyzed. Results. Six randomized controlled trials (167 participants in the experimental groups and 174 participants in the control groups) were identified as reporting the application of EA for acute herpes zoster pain and were included in this study. The results from our meta-analysis revealed that EA was superior to control treatment according to visual analog scale, the time of rash healing, and the incidence of postherpetic neuralgia. However, in terms of the time to cessation of pustules, scabs, and adverse reactions, the results showed that EA compared with the control group showed no significant difference. In addition, subgroup analyses indicated that 2/100 Hz-EA has more significant effects on herpetic pain. Sensitivity analyses revealed that the results of EA for acute pain control and the rash healing time in herpetic neuralgia patients were stable. However, a publication bias was observed. Conclusion. Our meta-analysis results showed that EA could offer certain advantages in treating acute pain in herpetic neuralgia patients. However, small sample sizes, heterogeneity in study design, and variable methodological quality weaken these inferences. In addition, weak evidence was found for the safety of EA.
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Zimmer, Julia, Simon Eaton, Louise Murchison, Paolo De Coppi, Benno Ure, and Carmen Dingemann. "State of Play: Eight Decades of Surgery for Esophageal Atresia." European Journal of Pediatric Surgery 29, no. 01 (August 15, 2018): 039–48. http://dx.doi.org/10.1055/s-0038-1668150.
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Aim Surgical expertise and advances in technical equipment and perioperative management have led to enormous progress in survival and morbidity of patients with esophageal atresia (EA) in the last decades. We aimed to analyze the available literature on surgical outcome of EA for the past 80 years. Materials and Methods A PubMed literature search was conducted for the years 1944 to 2017 using the keywords “esophageal/oesophageal atresia,” “outcome,” “experience,” “management,” and “follow-up/follow up.” Reports on long-gap EA only, non-English articles, case reports, and reviews without original patient data were excluded. We focused on mortality and rates of recurrent fistula, leakage, and stricture. Results Literature search identified 747 articles, 118 manuscripts met the inclusion criteria. The first open end-to-end anastomosis and fistula ligation was reported in 1941. Thoracoscopic fistula ligation and primary anastomosis was performed first in 2000. Reported mortality rate decreased from 100% before 1941 to 54% in 1950 to 1959, 28% in 1970 to 1979, 16% in 1990 to 1999, and 9% nowadays. Rates of recurrent fistula varied over time between 4 and 9%. Leakage rate remained stable between 11 and 16%. However, stricture rate increased from 25 to 38%. Conclusion Including a full range of articles reflecting the heterogeneity of EA, mortality rate significantly decreased during the course of 80 years. Along with the decrease in mortality, there is a shift to the importance of major postoperative complications and long-term morbidity regardless of surgical technique.
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Vergara, Pasquale, Maria Cristina Digilio, Andrea De Zorzi, Duccio Di Carlo, Rossella Capolino, Alessandro Rimini, Monica Pelegrini, Raffaele Calabro`, and Bruno Marino. "Genetic heterogeneity and phenotypic anomalies in children with atrioventricular canal defect and tetralogy of Fallot." Clinical Dysmorphology 15, no. 2 (April 2006): 65–70. http://dx.doi.org/10.1097/01.mcd.0000198925.94082.ea.
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Gkolfakis, Paraskevas, Apostolis Papaefthymiou, Antonio Facciorusso, Georgios Tziatzios, Daryl Ramai, Spyridon Dritsas, Theodosia Florou, et al. "Comparison between Enteroscopy-, Laparoscopy- and Endoscopic Ultrasound-Assisted Endoscopic Retrograde Cholangio-Pancreatography in Patients with Surgically Altered Anatomy: A Systematic Review and Meta-Analysis." Life 12, no. 10 (October 20, 2022): 1646. http://dx.doi.org/10.3390/life12101646.
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Background and Aims: Endoscopic retrograde cholangiopancreatography (ERCP), in surgically altered anatomy (SAA), can be challenging and the optimal technique selection remains debatable. Most common foregut interventions resulting to this burden consist of Billroth II gastrectomy, Whipple surgery and Roux-en-Y anastomoses, including gastric by-pass. This systematic review, with meta-analysis, aimed to compare the rates of successful enteroscope-assisted (EA)-, endosonography-directed transgastric- (EDGE), and laparoscopy-assisted (LA)-ERCP. Methods: A systematic research (Medline) was performed for relative studies, through January 2022. The primary outcome was technical success, defined as approaching the ampulla site. Secondary outcomes included the desired duct cannulation, successful therapeutic manipulations, and complication rates. We performed meta-analyses of pooled data, and subgroup analysis considering the EA-ERCP subtypes (spiral-, double and single balloon-enteroscope). Pooled rates are reported as percentages with 95% Confidence Intervals (95%CIs). Results: Seventy-six studies were included (3569 procedures). Regarding primary outcome, EA-ERCP was the least effective [87.3% (95%CI: 85.3–89.4); I2: 91.0%], whereas EDGE and LA-ERCP succeeded in 97.9% (95%CI: 96.4–99.4; I2: 0%) and 99.1% (95%CI: 98.6–99.7; I2: 0%), respectively. Similarly, duct cannulation and therapeutic success rates were 74.7% (95%CI: 71.3–78.0; I2: 86.9%) and 69.1% (95%CI: 65.3–72.9; I2: 91.8%) after EA-ERCP, 98% (95%CI: 96.5–99.6; I2: 0%) and 97.9% (95%CI: 96.3–99.4) after EDGE, and 98.6% (95%CI: 97.9–99.2; I2: 0%) and 98.5% (95%CI: 97.8–99.2; I2: 0%) after LA-ERCP, respectively. The noticed high heterogeneity in EA-ERCP results probably reflects the larger number of included studies, the different enteroscopy modalities and the variety of surgical interventions. Comparisons revealed the superiority of LA-ERCP and EDGE over EA-ERCP (p ≤ 0.001) for all success-related outcomes, though LA-ERCP and EDGE were comparable (p ≥ 0.43). ERCP with spiral-enteroscope was inferior to balloon-enteroscope, while the type of the balloon-enteroscope did not affect the results. Most adverse events were recorded after LA-ERCP [15.1% (95%CI: 9.40–20.8); I2: 87.1%], and EDGE [13.1% (95%CI: 7.50–18.8); I2: 48.2%], significantly differing from EA-ERCP [5.7% (95%CI: 4.50–6.80); p ≤ 0.04; I2: 64.2%]. Conclusions: LA-ERCP and EDGE were associated with higher technical, cannulation, and therapeutic success compared to EA-ERCP, though accompanied with more adverse events.
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Edmonds, Andrew, Ellen Brazier, Beverly S. Musick, Marcel Yotebieng, John Humphrey, Lisa L. Abuogi, Adebola Adedimeji, et al. "Clinical and programmatic outcomes of HIV-exposed infants enrolled in care at geographically diverse clinics, 1997–2021: A cohort study." PLOS Medicine 19, no. 9 (September 15, 2022): e1004089. http://dx.doi.org/10.1371/journal.pmed.1004089.
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Background Although 1·3 million women with HIV give birth annually, care and outcomes for HIV-exposed infants remain incompletely understood. We analyzed programmatic and health indicators in a large, multidecade global dataset of linked mother–infant records from clinics and programs associated with the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. Methods and findings HIV-exposed infants were eligible for this retrospective cohort analysis if enrolled at <18 months at 198 clinics in 10 countries across 5 IeDEA regions: East Africa (EA), Central Africa (CA), West Africa (WA), Southern Africa (SA), and the Caribbean, Central, and South America network (CCASAnet). We estimated cumulative incidences of DNA PCR testing, loss to follow-up (LTFU), HIV diagnosis, and death through 24 months of age using proportional subdistribution hazard models accounting for competing risks. Competing risks were transfer, care withdrawal, and confirmation of negative HIV status, along with LTFU and death, when not the outcome of interest. In CA and EA, we quantified associations between maternal/infant characteristics and each outcome. A total of 82,067 infants (47,300 EA, 10,699 CA, 6,503 WA, 15,770 SA, 1,795 CCASAnet) born from 1997 to 2021 were included. Maternal antiretroviral therapy (ART) use during pregnancy ranged from 65·6% (CCASAnet) to 89·5% (EA), with improvements in all regions over time. Twenty-four-month cumulative incidences varied widely across regions, ranging from 12·3% (95% confidence limit [CL], 11·2%,13·5%) in WA to 94·8% (95% CL, 94·6%,95·1%) in EA for DNA PCR testing; 56·2% (95% CL, 55·2%,57·1%) in EA to 98·5% (95% CL, 98·3%,98·7%) in WA for LTFU; 1·9% (95% CL, 1·6%,2·3%) in WA to 10·3% (95% CL, 9·7%,10·9%) in EA for HIV diagnosis; and 0·5% (95% CL, 0·2%,1·0%) in CCASAnet to 4·7% (95% CL, 4·4%,5·0%) in EA for death. Although infant retention did not improve, HIV diagnosis and death decreased over time, and in EA, the cumulative incidence of HIV diagnosis decreased substantially, declining to 2·9% (95% CL, 1·5%,5·4%) in 2020. Maternal ART was associated with decreased infant mortality (subdistribution hazard ratio [sdHR], 0·65; 95% CL, 0·47,0·91 in EA, and sdHR, 0·51; 95% CL, 0·36,0·74 in CA) and HIV diagnosis (sdHR, 0·40; 95% CL, 0·31,0·50 in EA, and sdHR, 0·41; 95% CL, 0·31,0·54 in CA). Study limitations include potential misclassification of outcomes in real-world service delivery data and possible nonrepresentativeness of IeDEA sites and the population of HIV-exposed infants they serve. Conclusions While there was marked regional and temporal heterogeneity in clinical and programmatic outcomes, infant LTFU was high across all regions and time periods. Further efforts are needed to keep HIV-exposed infants in care to receive essential services to reduce HIV infection and mortality.
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ANTOHI, Elena-Laura, Oliviana GEAVLETE, Razvan RADU, Ovidiu CHIONCEL, and Serban MIHAILEANU. "Echocardiographic Hemodynamic Heterogeneity of Advanced Heart Failure Patients as Compared to Patients with „Pre-Heart Failure”." Romanian Journal of Cardiology 31, no. 2 (July 2, 2021): 351–59. http://dx.doi.org/10.47803/rjc.2021.31.2.351.
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Background: Advanced heart failure (HF) represents a clinical entity encompassing severely symptomatic HF with severely dysfunctional left ventricles (LV). The single most important parameter for defining severe LV dysfunction and indicating the prescription of evidence-based therapies is LV ejection fraction (EF). We sought to investigate the hemodynamics by echocardiography in a cohort of advanced HF patients during a hospitalization for HF decompensation and assess the relevant differences when compared to a control cohort of asymptomatic patients with minor structural/functional cardiac abnormalities. Methods and results: In this prospective study we selected 18 advanced HF patients and 12 asymptomatic preHF patients with only minor structural/functional abnormalities. The 2 groups were clearly delineated by size parameters (end -systolic and -diastolic diameters and volumes respectively, with very low p values p<0.0001). Hemodynamic parameters were signifi cantly different as well in the advanced HF group vs the ‘pre-HF’ group, including: ventricular-arterial coupling 1.745 vs. 0.895, p=0.0007; cardiac power output 0.762 vs. 0.932, p=0.044, systolic times ratio 0.406 vs. 0.200, p=0.0001. There were no significant differences for neither effective arterial elastance (Ea) and nor for cardiac index. Inside the advanced HF group, no correlation between LVEF and other parameters were found and none of these parameters could predict outcome. We observed a highly skewed variation of Ea in advanced HF patients. Conclusion: Among the most severe HF patients, the hemodynamic interaction between the dysfunctional LV and the compensatory response of the peripheral system is heterogenous and cannot predict outcome by single parameters. In these patients, assessment of cardiac performance should no longer rely on LEVF alone.
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Kozlik-Siwiec, Pawel, Sylwia Buregwa-Czuma, Izabela Zawlik, Sylwia Dziedzina, Aleksander Myszka, Joanna Zuk-Kuwik, Andzelika Siwiec-Kozlik, et al. "Co-Expression Analysis of Airway Epithelial Transcriptome in Asthma Patients with Eosinophilic vs. Non-Eosinophilic Airway Infiltration." International Journal of Molecular Sciences 24, no. 4 (February 14, 2023): 3789. http://dx.doi.org/10.3390/ijms24043789.
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Asthma heterogeneity complicates the search for targeted treatment against airway inflammation and remodeling. We sought to investigate relations between eosinophilic inflammation, a phenotypic feature frequent in severe asthma, bronchial epithelial transcriptome, and functional and structural measures of airway remodeling. We compared epithelial gene expression, spirometry, airway cross-sectional geometry (computed tomography), reticular basement membrane thickness (histology), and blood and bronchoalveolar lavage (BAL) cytokines of n = 40 moderate to severe eosinophilic (EA) and non-eosinophilic asthma (NEA) patients distinguished by BAL eosinophilia. EA patients showed a similar extent of airway remodeling as NEA but had an increased expression of genes involved in the immune response and inflammation (e.g., KIR3DS1), reactive oxygen species generation (GYS2, ATPIF1), cell activation and proliferation (ANK3), cargo transporting (RAB4B, CPLX2), and tissue remodeling (FBLN1, SOX14, GSN), and a lower expression of genes involved in epithelial integrity (e.g., GJB1) and histone acetylation (SIN3A). Genes co-expressed in EA were involved in antiviral responses (e.g., ATP1B1), cell migration (EPS8L1, STOML3), cell adhesion (RAPH1), epithelial–mesenchymal transition (ASB3), and airway hyperreactivity and remodeling (FBN3, RECK), and several were linked to asthma in genome- (e.g., MRPL14, ASB3) or epigenome-wide association studies (CLC, GPI, SSCRB4, STRN4). Signaling pathways inferred from the co-expression pattern were associated with airway remodeling (e.g., TGF-β/Smad2/3, E2F/Rb, and Wnt/β-catenin).
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Wang, Peng, Shiyi Zou, Jiajun Liu, and Wenjun Ke. "Matching biomedical ontologies with GCN-based feature propagation." Mathematical Biosciences and Engineering 19, no. 8 (2022): 8479–504. http://dx.doi.org/10.3934/mbe.2022394.
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<abstract> <p>With an increasing number of biomedical ontologies being evolved independently, matching these ontologies to solve the interoperability problem has become a critical issue in biomedical applications. Traditional biomedical ontology matching methods are mostly based on rules or similarities for concepts and properties. These approaches require manually designed rules that not only fail to address the heterogeneity of domain ontology terminology and the ambiguity of multiple meanings of words, but also make it difficult to capture structural information in ontologies that contain a large amount of semantics during matching. Recently, various knowledge graph (KG) embedding techniques utilizing deep learning methods to deal with the heterogeneity in knowledge graphs (KGs), have quickly gained massive attention. However, KG embedding focuses mainly on entity alignment (EA). EA tasks and ontology matching (OM) tasks differ dramatically in terms of matching elements, semantic information and application scenarios, etc., hence these methods cannot be applied directly to biomedical ontologies that contain abstract concepts but almost no entities. To tackle these issues, this paper proposes a novel approach called BioOntGCN that directly learns embeddings of ontology-pairs for biomedical ontology matching. Specifically, we first generate a pair-wise connectivity graph (PCG) of two ontologies, whose nodes are concept-pairs and edges correspond to property-pairs. Subsequently, we learn node embeddings of the PCG to predicate the matching results through following phases: 1) A convolutional neural network (CNN) to extract the similarity feature vectors of nodes; 2) A graph convolutional network (GCN) to propagate the similarity features and obtain the final embeddings of concept-pairs. Consequently, the biomedical ontology matching problem is transformed into a binary classification problem. We conduct systematic experiments on real-world biomedical ontologies in Ontology Alignment Evaluation Initiative (OAEI), and the results show that our approach significantly outperforms other entity alignment methods and achieves state-of-the-art performance. This indicates that BioOntGCN is more applicable to ontology matching than the EA method. At the same time, BioOntGCN substantially achieves superior performance compared with previous ontology matching (OM) systems, which suggests that BioOntGCN based on the representation learning is more effective than the traditional approaches.</p> </abstract>
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Tinajero, Maria, Sarah Jarvis, Jiayue Yu, Tauseef Khan, Vasanti Malik, John L. Sievenpiper, and Anthony Hanley. "Ethnic Differences in the Association Between Body Mass Index and Type 2 Diabetes Risk: A Meta-Analysis of Prospective Cohort Studies." Current Developments in Nutrition 5, Supplement_2 (June 2021): 1253. http://dx.doi.org/10.1093/cdn/nzab055_063.
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Abstract Objectives The association between body mass index (BMI) and total body adiposity differs across ethnic groups. For instance, South Asians (SA) and East Asians (EA) have lower body fat for a given BMI level than Europeans, while the opposite is true for African-Caribbeans (AC). This suggests that the relationship between BMI and type 2 diabetes (T2D) risk may also vary depending on ethnicity. We conducted a meta-analysis to investigate whether the association between BMI and the risk of T2D differs across ethnic groups. Methods MEDLINE, EMBASE and Web of Science were searched up to July 2020. We included prospective cohort studies of >2 years, which investigated the association between BMI and T2D incidence among adults of a specified ethnicity. Linear and non-linear dose-response meta-analyses were performed using random effects models, with subgroup analyses by ethnicity. The heterogeneity among studies was estimated using the Cochran Q test and I2 statistic. Study quality was assessed with the Newcastle-Ottawa Scale. Results 54 studies were included. Cohorts were stratified into the following ethnic subgroups: AC (N = 67,453), EA (N = 1,012,135), European (N = 206,424), Indigenous (N = 10,533), Latin American (LA) (N = 4,669), SA (N = 9,395), and Southeast Asian (SEA) (N = 51,129). Linear dose-response associations between 1 kg/m2 increase in BMI and T2D were observed for the SEA (RR = 1.26; 95% CI, 1.10, 1.30) and SA (RR = 1.11; 95% CI: 1.04, 1.19) subgroups with no evidence of departure from linearity. Associations departed from linearity for all other subgroups. At a BMI level of 30 kg/m2, the non-linear dose-response curves for each of the other subgroups displayed the following risk ratios; AC: RR = 3.13 (95% CI, 1.95, 5.02), EA: RR = 2.39 (95% CI, 1.96, 2.92), European: RR = 7.41 (95% CI, 3.88, 14.18), Indigenous: RR = 8.15 (95% CI, 6.07; 10.95), and LA: RR = 12.82 (95% CI, 5.50, 29.92). For all subgroups, there was a high degree of interstudy heterogeneity (I2 > 75%). Conclusions Our findings indicated that the association between BMI and the risk of T2D differs across ethnic groups, suggesting that ethnic-specific BMI cut-offs could be helpful in identifying cardiometabolic risk profiles across different populations. Funding Sources Canadian Institutes for Health Research.
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Miyashita, Minoru, Joshua S. Bell, Ezgi Karaesmen, Brooke Rhead, Stephane Wenric, Kristiyana Kaneva, Francisco M. De La Vega, et al. "Abstract 766: Genomic and transcriptomic comparison between breast cancers from patients of African and European genetically determined ancestries demonstrates potential for ancestry specific biomarker-informed therapies." Cancer Research 82, no. 12_Supplement (June 15, 2022): 766. http://dx.doi.org/10.1158/1538-7445.am2022-766.
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Abstract Background: Therapeutic approaches for breast cancer (BC) are informed by tumor subtypes and molecular heterogeneity, both of which may be associated with particular patient ancestries. While patients of African ancestry (AA) exhibit a relatively high mortality rate compared with patients of European ancestry (EA), the biological underpinnings of this disparity are not entirely understood. Here, we present a genomic and transcriptomic comparison between BC tumors from AA and EA patients stratified by clinical features in a real-world cohort. Methods: De-identified records from AA (n=629) and EA (n=2832) patients with BC were selected from the Tempus Oncology Database. All tumors underwent sequencing with the Tempus|xT assay, including targeted-panel DNA and full-transcriptome RNA-seq. Race metadata was obtained from abstracted records. Genetic ancestry was estimated using a set of ancestry-informative markers and a supervised version of the ADMIXTURE algorithm. Mutational prevalence, gene expression, and transcriptional signatures were compared between EA and AA groups, and stratified by stage and subtype. Statistical significance was assessed with Bonferroni correction applied to adjust for multiple testing. Results: Genetic ancestry estimates and race metadata had strong concordance, with 97% and 91% of race data matching genetic ancestry categories in AA and EA, respectively. Compared to EA patients, AA patients were slightly younger (median age 53.8 years vs. 56.1 years) and more likely to have stage IV disease (59.0% vs. 56.5%). The percentage of triple-negative BC (TNBC) patients was much higher among AA (23.5%) compared to EA (14.3%), while the proportion of HR+/HER2− patients was higher in EA (46.4%) compared to AA (36.5%). In HR+/HER2- patients, AA patients had a higher prevalence of KMT2C (24% vs. 14%), GATA3 (21% vs. 14%), and FGFR1 (18% vs. 12%) mutations, and a lower prevalence of PIK3CA (33% vs. 42%) and PTEN (6% vs. 13%) mutations. PRSS23 expression and estrogen response late signaling were significantly downregulated in late-stage HR+/HER2- AA patients, while PTEN signaling was downregulated in stages I-III. Among TNBC, AA patients had a higher prevalence of KMT2C (23% vs. 12%) mutations. LILRA6 and PTEN were significantly downregulated in early-stage TNBC patients of AA. Conclusions: After controlling for stage at diagnosis and subtype, we observed significant differences in BC mutational spectrums, gene expression, and relevant pathway activities between patients with genetically determined AA and EA, particularly within the TNBC and HR+/HER2- subtypes. These findings may guide future development of treatment strategies by providing data for biomarker-informed research and precision cancer care. Citation Format: Minoru Miyashita, Joshua S. Bell, Ezgi Karaesmen, Brooke Rhead, Stephane Wenric, Kristiyana Kaneva, Francisco M. De La Vega, Yonglan Zheng, Toshio Yoshimatsu, Galina Khramtsova, Elisabeth Sveen, Fang Liu, Fangyuan Zhao, Frederick Howard, Nora T. Jaskowiak, Rita Nanda, Dezheng Huo, Olufunmilayo I. Olopade. Genomic and transcriptomic comparison between breast cancers from patients of African and European genetically determined ancestries demonstrates potential for ancestry specific biomarker-informed therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 766.
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van Amstel, Paul, Tania C. Sluckin, Tim van Amstel, Johanna H. van der Lee, Ralph de Vries, Joep P. M. Derikx, Roel Bakx, L. W. Ernest van Heurn, and Ramon R. Gorter. "Management of appendiceal mass and abscess in children; early appendectomy or initial non-operative treatment? A systematic review and meta-analysis." Surgical Endoscopy 34, no. 12 (July 24, 2020): 5234–49. http://dx.doi.org/10.1007/s00464-020-07822-y.
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Abstract Background Appendiceal mass and abscess and its treatment are associated with significant morbidity and high costs. Still, the optimal treatment strategy is the point of debate. Therefore, this systematic review and meta-analysis aimed to compare overall complications between initial non-operative treatment (NOT) and early appendectomy (EA) in children with appendiceal mass and/or abscess. Methods Pubmed and Embase were searched. Only randomized controlled trials and prospective or historical cohort studies that compared NOT with EA in children with appendiceal mass or abscess in terms of complications were eligible for inclusion. Risk of bias was assessed. Primary outcome was the overall complication rate. Secondary, length of stay and readmission rate were investigated. A meta-analysis of overall complications associated with both treatment strategies was performed. Results 14 of 7083 screened studies were selected, including 1022 children in the NOT group and 333 in the EA group. Duration of follow-up ranged between four weeks and 12 years. Risk of bias was moderate in four and serious in 10 studies. NOT was associated with a lower overall complication rate (risk ratio (RR) 0.37 [95% confidence interval (CI) 0.21–0.65]). However, NOT led to increased length of stay (mean difference varied between 0.2 and 8.4 days) and higher readmission rate (RR 1.75 [95%CI 0.79–3.89]), although not significantly. Interval appendectomy after NOT was performed as a routine procedure in all but one study. This study found a recurrence rate of 34% in a group of 38 patients during a follow-up period of 3.4 ± 1.7 years. Conclusion NOT may reduce the overall complication rate compared to EA, but the evidence is very uncertain. As evidence is scarce, and of low level, and heterogeneity between studies is substantial, the results should be interpreted with caution. Large prospective studies are needed to determine the optimal treatment strategy for children with appendiceal mass and/or abscess.
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Bedi, Deepa, Balasubramanyam Karanam, Isra Elhussin, Chitra R. Nayak, and Clayton Yates. "Abstract C111: Spatial transcriptome profiling of tumor and tumor microenvironment of triple negative breast cancer in patients of African American and European American descent." Cancer Epidemiology, Biomarkers & Prevention 32, no. 1_Supplement (January 1, 2023): C111. http://dx.doi.org/10.1158/1538-7755.disp22-c111.
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Abstract Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately affects women of African origin. AA women with TNBC have worse clinical outcomes than women of European descent as it presents with a more aggressive and progressive disease. Understanding the underlying biology of the tumor and its microenvironment is critical to address the disparity associated with racial differences in breast cancer. Bulk RNA-sequencing is the most common and useful method to analyze whole transcriptome. However, this method cannot deconvolute the individual components of the tumor and its associated stroma. The NanoString GeoMx digital spatial profiling is a multiplexed platform that spatially resolves and quantifies the abundance of genes present in tumor and stroma. In this study, we have utilized spatial RNA-seq technology to determine the differential gene expression in tumor epithelial cells and its associated stroma in AA and EA TNBC patients. Gene expression from spatially defined regions in tumor and stroma in each patient and in between races identified distinct molecular pathways. The tumor epithelial region of AA has high expression of fatty acid biosynthesis, nucleotide excision repair, RNA helicase like proteins and exhaustion signaling while EA tumor epithelial region had high expression of neuropilin 2, interferon signaling and TGF beta signaling. The pathways overexpressed in the AA stromal region included tryptophan metabolism, chemokine signaling pathway, interferon signaling and exhaustion signature while in the EA stromal region, the pathways pertinent to mTOR signaling, AURORA kinase, cysteine endopeptidases were more prominently expressed. AA tumors were significantly more inflamed than EA and exhibited high infiltration of immune cells. The stromal region of AA tumors has high population of macrophages, CD8 T memory, Treg’s and neutrophils more than EA tumors. The tumor epithelial region of AA has high infiltration of plasmacytoid dendritic cells (pDC), B memory, monocytes, natural killer cells (NK), CD4 memory, CD4 naïve, Treg’s and plasma cells. However, the exhaustion signature proteins, PDCD1 and LAG3 were also higher in tumor-infiltrated and stromal immune cells in AA tumor. The EA tumors were scarce in immune cells in the stroma as well as inside the tumor epithelial, though interferon signaling was substantially higher in EA tumor epithelial cells as compared to AA. Thus, using NanoString GeoMx digital spatial profiling platform, we have spatial profiled AA and EA TNBC and assessed the inter and intra-tumor heterogeneity within and in between races. This is one of the first study that describes not only expression variation of genes between races but also between stroma and tumor epithelial cells within the tissue of same patient and between different patients. These findings address the biological determinant of racial disparity by patient-centered investigation of factors associated with tumor and tumor microenvironment. Citation Format: Deepa Bedi, Balasubramanyam Karanam, Isra Elhussin, Chitra R. Nayak, Clayton Yates. Spatial transcriptome profiling of tumor and tumor microenvironment of triple negative breast cancer in patients of African American and European American descent [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C111.
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Zhu, Hai, Jie Zhang, and Xingsi Xue. "Semisupervised Learning-Based Sensor Ontology Matching." Security and Communication Networks 2021 (July 17, 2021): 1–5. http://dx.doi.org/10.1155/2021/2002307.
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Sensor ontology models the sensor information and knowledge in a machine-understandable way, which aims at addressing the data heterogeneity problem on the Internet of Things (IoT). However, the existing sensor ontologies are maintained independently for different requirements, which might define the same concept with different terms or context, yielding the heterogeneity issue. Since the complex semantic relationship between the sensor concepts and the large-scale entities is to be dealt with, finding the identical entity correspondences is an error-prone task. To effectively determine the sensor entity correspondences, this work proposes a semisupervised learning-based sensor ontology matching technique. First, we borrow the idea of “centrality” from the social network to construct the training examples; then, we present an evolutionary algorithm- (EA-) based metamatching technique to train the model of aggregating different similarity measures; finally, we use the trained model to match the rest entities. The experiment uses the benchmark as well as three real sensor ontologies to test our proposal’s performance. The experimental results show that our approach is able to determine high-quality sensor entity correspondences in all matching tasks.
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Pang, Zhiqiang, Guoqiang Wang, Cuizhu Wang, Weijie Zhang, Jinping Liu, and Fang Wang. "Serum Metabolomics Analysis of Asthma in Different Inflammatory Phenotypes: A Cross-Sectional Study in Northeast China." BioMed Research International 2018 (September 23, 2018): 1–14. http://dx.doi.org/10.1155/2018/2860521.
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Background and Objective. Asthma as a chronic heterogeneous disease seriously affects the quality of life. Incorrect identification for its clinical phenotypes lead to a huge waste of medical resources. Metabolomic technique as a novel approach to explore the pathogenesis of diseases have not been used to study asthma based on their clear defined inflammatory phenotypes. This study is aimed to distinguish the divergent metabolic profile in different asthma phenotypes and clarify the pathogenesis of them.Methods. Participants including eosinophilic asthmatics (EA, n=13), noneosinophilic asthmatics (NEA, n=16), and healthy controls (HC, n=15) were enrolled. A global profile of untargeted serum metabolomics was identified with Ultra Performance Liquid Chromatography–Mass Spectrometry technique.Results. Multivariate analysis was performed and showed a clear distinction between EA, NEA, and HC. A total of 18 different metabolites were recognized between the three groups based on OPLS-DA model and involved in 10 perturbed metabolic pathways. Glycerophospholipid metabolism, retinol metabolism, and sphingolipid metabolism were identified as the most significant changed three pathways (impact > 0.1 and -log(P) > 4) between the phenotypes.Conclusions. We showed that the different inflammatory phenotypes of asthma involve the immune regulation, energy, and nutrients metabolism. The clarified metabolic profile contributes to understanding the pathophysiology of asthma phenotypes and optimizing the therapeutic strategy against asthma heterogeneity.
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Lai, Zengjiao, Huihui Liu, and Guobin Liu. "Meta-Analysis on the Effects of Electric Acupuncture on Neural Functional Recovery and Related Pathways of Rats after Spinal Cord Injury." BioMed Research International 2022 (July 29, 2022): 1–12. http://dx.doi.org/10.1155/2022/8613384.
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Background. Spinal cord injury (SCI) is a type of damage to the central nervous system (CNS) caused by various factors. The secondary injury of SCI is more complicated. Studies have found that electroacupuncture can help the recovery of nerve function during spinal cord injury. Therefore, this study explored the efficacy of electroacupuncture on complications after spinal cord injury through meta-analysis. Methods. Relevant literatures published from January 2010 to March 2022 were searched with “Electric acupuncture, Spinal cord injury, Neural functional recovery, Spinal cord injury in rats, Neuronal Signaling” as search words. The risk of bias of included references was analyzed and assessed using RevMan 5.3 software and Stata software. Heterogeneity between studies was assessed using the Q -test and heterogeneity ( I 2 ). Results. There was no heterogeneity among the study groups. The comparison on the therapeutic effects of electroacupuncture and conventional therapy suggested that electroacupuncture was more effective for nerve recovery after spinal cord injury than conventional therapy. It can better improve the recovery of motor function after spinal cord injury in rats. On the other hand, SCI+EA had a good inhibitory effect on the expression of RhoA protein signal in rats and had a positive effect on the signal pathway. Discussion. The results of meta-analysis confirmed that electroacupuncture was more effective than conventional therapy in inhibiting pathways.
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Petty, D., H. Blankenship, W. Beuerlein, T. Naal, and W. Li. "Endometrial Adenocarcinoma Biopsies: Can Targeted Education Increase Reproducibility and Is It a Good Idea?" American Journal of Clinical Pathology 156, Supplement_1 (October 1, 2021): S76. http://dx.doi.org/10.1093/ajcp/aqab191.159.
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Abstract Introduction/Objective Assessing p53 mutation on biopsies could provide prognostic and therapeutic planning information, as it predicts worse outcomes for patients with endometrioid adenocarcinoma (EA). Immunohistochemistry (IHC) mutation pattern staining varies, easily causing misinterpretation. This study was designed to see if education clarifying staining issues would increase reproducibility, and if mutations detected in this setting were of prognostic import. Methods/Case Report p53 IHC on 46 FIGO grade 1 EA biopsies was scored by blinded participants. Education was provided regarding internal controls (IC), and common misinterpretations. The participants rescored to assess reproducibility. Outcome parameters (clinical stage [CS], progression free survival, higher FIGO grade on resection, and presence of mismatch repair mutations) were also assessed. Results (if a Case Study enter NA) 25% of scores changed post-education. Intraclass correlation among raters was 0.29 pre and 0.43 post (from fair to moderate). Mutation status changed in 5 cases. 2/5 caught IC failure for 1 case. Post-participation surveys found 0 participants were previously familiar with “high wild type,” and 60% were unfamiliar with cytoplasmic staining pattern, the possibility for heterogeneity, and necessary ICs. Every participant agreed grading was easier following education. Out of 6 patients with high CS disease (IIIC-IV), none had p53 mutation. 2/11 cases with higher FIGO grade (2-3) on resection had mutation. One patient had recurrence with no detectable mutation. 15/46 patients had MMR results available. No p53 mutation was detected in those with a loss of MLH1 and PMS2 (n=8). Conclusion Education on IHC issues can increase reproducibility in scoring, though overall reproducibility on biopsies was still subpar. Mutation detected in this setting did not correlate with current outcome parameters. Given the possibility of heterogenous expression and difficulties interpreting edge effect and assessing ICs in scant specimens, p53 IHC on EA biopsies is not recommended.
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Liu, Dengfeng, Li Pan, Yin Gao, Jiefan Liu, Feng Li, Xiangwei Li, Jiale Quan, Congcong Huang, and Chunwei Lian. "Efficaciousness of dexmedetomidine in children undergoing cleft lip and palate repair: a systematic review and meta-analysis." BMJ Open 11, no. 8 (August 2021): e046798. http://dx.doi.org/10.1136/bmjopen-2020-046798.
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ObjectiveTo systematically assess the efficacy and safety of dexmedetomidine as an anaesthesia adjuvant for cleft lip and palate (CLP) repair in children.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP) and Wanfang (up to October 2020). Studies in languages other than English and Chinese were excluded.Eligibility criteria for selecting studiesRandomised controlled trials (RCTs) evaluating the impact of dexmedetomidine on emergence agitation (EA), the need for postoperative rescue analgesics, postoperative nausea and vomiting (PONV), and other adverse events in paediatric patients during CLP repair.Data extraction and synthesisThe quality of evidence was assessed by using the Cochrane Review Methods and the Grading of Recommendations Assessment, Development and Evaluation approach. Data were screened, extracted and assessed by two independent authors. Outcomes were reported as a risk ratio (RR) with a 95% CI. A random-effect model was used when heterogeneity was detected.ResultsThirteen studies including 1040 children met the inclusion criteria. The incidence of EA was significantly decreased in the dexmedetomidine group (RR, 0.19; 95% CI 0.10 to 0.36; p<0.00001; I2=56%) as compared with the control group. Paediatric patients receiving dexmedetomidine had lower postoperative analgesic requirements (RR, 0.27; 95% CI 0.10 to 0.73; p=0.01; I2=84%) and a lower incidence of respiratory adverse events (RR, 0.49; 95% CI 0.31 to 0.78; p=0.003; I2=0%). There were no significant differences in the risk of PONV and cardiovascular adverse events.ConclusionsThere was a lack of high-quality studies in this field. Perioperative administration of dexmedetomidine reduced the need for postoperative rescue analgesics and the incidence of EA in children without side effects undergoing CLP repair. However, further verification with larger samples and higher-quality RCTs is needed.
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Cunningham, James R., Jon Rittenbach, Mitch Clemens, Cheryl Dodd, Ashley Wilson, and Kaikuihala Roberson. "Measuring parameters of the cancer ecosystem for cancer ecological staging." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e14684-e14684. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e14684.
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e14684 Background: Cancer progression through clonal evolution and emergent phenotypic heterogeneity is thought to reflect stochastic events such as genetic drift. This divergence over time in the character of a neoplasm might also reflect genetic selection, analogous to other populations in nature, to maximize niche resource utilization. We hypothesized that selection pressures operate in patients with cancer to drive cancer evolution, are clinically identifiable, their influence measurable. Methods: To develop a system for cancer ecology staging, a feasibility study recruited 15 patients with active cancer from any site, with expected survival of more than 6 months and providing informed consent. A set of clinical parameters obtained from a patient questionnaire, physical exam and laboratory testing was used to generate eight separate ecological profiles of tumor microenvironment, chronic inflammation, energy balance, psychosocial stress, GI microbiome, endocrine environment, skeletal remodeling and environmental mutagenesis. A scoring system, based on evidence of positive selection was designed to quantitate the individual profiles. Profile scores were then aggregated using a 2-D radar plot to generate a polygon, an ‘ecogram’, whose area, it is hypothesized, corresponds to the net level of selection pressure influencing tumor evolution. Results: Ecological profiles were obtained from each of 15 patients allowing determination of the ecogram area (EA) bounded by the polygon. EA determinations ranged widely among the 15 patient, from 0-12.7 arbitrary units (au, mean 5.01± 0.80). Ecograms from individual patients demonstrated unique shapes suggesting specificity for individual patient ecology. EA measurements were then used to inform an ecological staging system based on a simplified dichotomization, low/high, of ecosystem resources and threats. Of 15 patients, 6 were considered to have high resources (EA > 5au) available to support tumor evolution. High anti-tumor threat, measured by CD3 lymphocyte immunohistochemical scoring, was detected in 11 patients. Conclusions: An ecological assessment of patients with active cancer appears feasible. Inter-patient variation in ecogram area and morphology suggests there are potential important differences in genetic selection found between patients and should be correlated with survival outcomes in future studies, validation offering a target for ecosystem ‘restoration’.
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DUAN, JUBAO, MARIA MARTINEZ, ALAN R. SANDERS, CUIPING HOU, AARON J. KRASNER, DANIEL B. SCHWARTZ, and PABLO V. GEJMAN. "Neuregulin 1 (NRG1) and schizophrenia: analysis of a US family sample and the evidence in the balance." Psychological Medicine 35, no. 11 (July 4, 2005): 1599–610. http://dx.doi.org/10.1017/s0033291705005428.
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Background. Individual genome-wide linkage scans and meta-analyses support that one or more susceptibility genes for schizophrenia are located in chromosome 8p. A gene from this region, neuregulin 1 (NRG1), known to be involved with glutamatergic function, has been found to be associated in some studied samples.Method. We have examined a new combined schizophrenia sample with 136 schizophrenia families largely of European ancestry (EA) and 646 subjects with DNA. We genotyped 14 single nucleotide polymorphisms (SNPs) in NRG1 including those reported to comprise schizophrenia-associated haplotypes in Icelandic, Scottish, Irish, and Chinese Han populations.Results. We found no evidence of association at a single-marker or a haplotypic level. We review methodological aspects of previous studies to enable us to put our findings into context.Conclusions. Our failure to find an association between NRG1 and schizophrenia might reflect different linkage disequilibrium (LD) patterns found in different populations, disease allelic heterogeneity, clinical heterogeneity of schizophrenia, or inadequate statistical power deriving from moderate sample size. NRG1, if a true gene for schizophrenia, accounts for a small fraction of the disease in most populations. The confirmation of NRG1 as a schizophrenia susceptibility gene will require studies with a comprehensive set of markers and in larger samples. The possibility remains that reports of NRG1 association might reflect false positives.
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Glaspy, John A., Dusan Kotasek, Jean-Luc Canon, Dianne Tomita, Helen Collins, and Lee Steven Schwartzberg. "Meta-analysis of the effects on safety of front-loading (FL), every-2-week (Q2W), and Q3W dosing of darbepoetin alfa (DA) in patients (pts) with chemotherapy-induced anemia (CIA)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e19511-e19511. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e19511.
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e19511 Background: Several studies evaluated if alternate dosing could decrease the time to hemoglobin (Hb) response. With recent safety concerns, this is now of limited interest; however, these studies may contribute to the understanding of safety risks. This study-level meta-analysis examined effects of FL, Q2W, and Q3W dosing of DA vs epoetin alfa (EA) and weekly DA dosing on safety in pts with CIA. Methods: Data from 11 studies (4 FL, 5 Q2W, 1 Q3W, 1 Q2W/Q3W) conducted between 1999 and 2006 in which the comparison group received 3-times-per-week (TIW) or once-weekly (QW) EA or QW DA were included in the meta-analysis. FL dosing differed between the studies and was defined as DA 4.5 mcg/kg or 300 mg QW for 4 or 5 weeks or until Hb > 12 g/dL followed by either DA 4.5 mcg/kg Q3W or a lower QW dose. Endpoints included deaths on study; disease progression (PD); embolic, thrombotic, and thromboembolic events; and rapid Hb rise (1 g/dL within 14 days). Random effects odds ratios (ORs) are provided comparing FL, Q2W, or Q3W arms to either TIW or QW active control arms. Heterogeneity was assessed using I2 statistic. Results: No differences in ORs for death, PD, embolic, thrombotic, and thromboembolic events or evidence of a more rapid rate of Hb rise were observed in FL, Q2W, and Q3W arms compared with controls (table). Conclusions: Results of this meta-analysis suggested that these adverse events were not related to FL, Q2W, or Q3W dosing of DA. [Table: see text]
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Pang, Zhiqiang, Nan Ran, Yuze Yuan, Cuizhu Wang, Guoqiang Wang, Hongqiang Lin, Alan Chen-Yu Hsu, Jinping Liu, and Fang Wang. "Phenotype-Specific Therapeutic Effect of Rhodiola wallichiana var. cholaensis Combined with Dexamethasone on Experimental Murine Asthma and Its Comprehensive Pharmacological Mechanism." International Journal of Molecular Sciences 20, no. 17 (August 28, 2019): 4216. http://dx.doi.org/10.3390/ijms20174216.
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The heterogeneity of asthma involves complex pathogenesis leading to confusion regarding the choice of therapeutic strategy. In the clinic, asthma is commonly classified as having either eosinophilic asthma (EA) or non-eosinophilic asthma (NEA) phenotypes. Microbiota colonizing in airways has been demonstrated to induce distinct phenotypes of asthma and the resistance to steroids. Rhodiola wallichiana var. cholaensis (RWC) has the potential to alleviate asthmatic inflammation according to recent studies, but its pharmacological mechanisms remain unclarified. In our study, murine asthmatic phenotypes were established and treated with RWC and/or dexamethasone (DEX). Combined treatment with RWC and DEX could improve spirometry and airway hyperresponsiveness (AHR) in asthmatic phenotypes, alleviate steroid resistance in NEA, and reduce the inflammatory infiltration of the both phenotypes. The combined treatment increased Th1, regulated the imbalance of Th2/Th1, and decreased the related cytokines in EA. As for NEA, the combined treatment reduced Th17 and promoted the accumulation of regulatory T cells (Tregs) in lung. A microbiome study based on 16S rDNA sequencing technique revealed the significantly changed structure of the lower airway microbiota after combined treatment in NEA, with 4 distinct genera and 2 species identified. OPLS-DA models of metabolomics analysis based on UPLC-Q/TOF-MS technique identified 34 differentiated metabolites and 8 perturbed metabolic pathways. A joint multiomics study predicted that the colonized microbiota in airways might be associated with susceptibility of asthma and steroid resistance, which involved systematic and pulmonary metabolic perturbation. In summary, the pharmacological network of RWC included the complicated interaction mechanisms of immune regulation, microbiota change, and metabolic perturbation.
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Jiao, Juan, Zhaoping Wang, Yanfei Guo, Jie Liu, Xiuqing Huang, Xiaolin Ni, Danni Gao, et al. "Association between IL-1B (-511)/IL-1RN (VNTR) polymorphisms and type 2 diabetes: a systematic review and meta-analysis." PeerJ 9 (October 25, 2021): e12384. http://dx.doi.org/10.7717/peerj.12384.
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Interleukin-1 (IL-1) plays an essential role in the immune pro-inflammatory process, which is regarded as one of many factors in the development of type 2 diabetes mellitus (T2DM). Several case-control studies have illustrated the association of the IL-1B (-511) (rs16944, Chr 2:112,837,290, C/T Intragenic, Transition Substitution) and IL-1RN (VNTR) (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2) polymorphisms with T2DM risk. However, the results were inconsistent and inconclusive. We performed a meta-analysis (registry number: CRD42021268494) to assess the association of the IL-1B (-511) and IL-1RN (VNTR) polymorphisms with T2DM risk. Random-effects models were applied to calculate the pooled ORs (odds ratios) and 95% CIs (confidence intervals) to test the strength of the association in the overall group and subgroups stratified by ethnicity, respectively. Between-study heterogeneity and publication bias were evaluated by the Q-test, I2 statistic, Harbord test, and Peters test accordingly. Sensitivity analyses were also performed. A total of 12 publications evaluating the association of IL-1B (-511) and IL-1RN (VNTR) polymorphisms with the risk of T2DM development were included. The meta-analysis showed that IL-1RN (VNTR) was related to the increasing development of T2DM risk in the recessive model (OR = 1.62, 95% CI [1.09–2.42], Phet = 0.377, Pz = 0.018) and in the homozygous model (OR = 2.02, 95% CI [1.07–3.83], Phet = 0.085, Pz = 0.031), and the IL-1RN 2* allele was found a significant association with evaluated T2DM risk in all ethnicities (OR = 2.08, 95% CI [1.43–3.02], Phet < 0.001, Pz < 0.001) and in EA (OR = 2.01, 95% CI [1.53–2.66], Phet = 0.541, Pz < 0.001). Moreover, stratification by ethnicity revealed that IL-1B (-511) was associated with a decreased risk of T2DM in the dominant model (OR=0.76, 95% CI [0.59–0.97], Phet = 0.218, Pz = 0.027) and codominant model (OR = 0.73, 95% CI [0.54–0.99], Phet = 0.141, Pz = 0.040) in the East Asian (EA) subgroup. Our results suggest that the IL-1RN 2* allele and 2*2* homozygous polymorphism are strongly associated with increasing T2DM risk and that the IL-1B (-511) T allele polymorphism is associated with decreasing T2DM risk in the EA subgroup.
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Xue, Xingsi, and Wenbin Tan. "Matching Cybersecurity Ontologies on Internet of Everything through Coevolutionary Multiobjective Evolutionary Algorithm." Security and Communication Networks 2022 (August 10, 2022): 1–13. http://dx.doi.org/10.1155/2022/3572404.
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Since Internet of Everything (IoE) makes all the connections that come online more relevant and valuable, they are subject to numerous security and privacy concerns. Cybersecurity ontology is a shared knowledge model for tackling the security information heterogeneity issue on IoE, which has been widely used in the IoE domain. However, the existing CSOs are developed and maintained independently, yielding the CSO heterogeneity problem. To address this issue, we need to use the similarity measure (SM) to calculate two entities’ similarity value in two CSOs and, on this basis, determine the entity correspondences, i.e., CSO alignment. Usually, it is necessary to integrate various SMs to enhance the result’s correctness, but how to combine and tune these SMs to improve the alignment’s quality is still a challenge. To face this challenge, this work first models CSO matching problem as a Constrained Multiobjective Optimization Problem (CMOOP) and then proposes a Coevolutionary Multiobjective Evolutionary Algorithm (CE-MOEA) to effectively address it. In particular, CE-MOEA uses the multiobjective evolutionary paradigm to avoid the solutions’ bias improvement and introduces the coevolutionary mechanism to trade off Pareto Front’s (PF’s) diversity and convergence. The experiment uses Ontology Alignment Evaluation Initiative’s (OAEI’s) bibliographic track and conference track and five real CSO matching tasks to test CE-MOEA’s performance. Comparisons between OAEI’s participants and EA- and MOEA-based matching techniques show that CE-MOEA is able to effectively address various heterogeneous ontology matching problems and determine high-quality CSO alignments.
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Ahuno, Samuel Terkper, Yajas Shah, Rachel Martini, Andrea Sboner, Nicolas Robine, Olivier Elemento, Marcin Imielinski, Lisa Newman, and Melissa Davis. "Abstract 2935: Whole genome sequence of triple negative breast cancer (TNBC) tumors of African descent." Cancer Research 82, no. 12_Supplement (June 15, 2022): 2935. http://dx.doi.org/10.1158/1538-7445.am2022-2935.
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Abstract In the US, BC incidence has recently converged among self-reported European Americans (EA) and African Americans (AA), however BC mortality remains approximately 40% higher among AA compared to EA and other SRR groups. The initial divergence in mortality curves between these groups occurred at the advent of hormone receptor (HR) targeted treatment options, unmasking the heterogeneity of BC diagnoses. Here, we present Whole Genomes Sequencing of 30 Triple Negative Breast Cancers of African women presenting to the clinics in New York. These were collected as part of the ICSBCS cohort to identify ancestry related mutational signatures including complex structural variants which could help better explain etiology of cancer in these population and that we may leveraged for treatment or prognostic purposes. Somatic mutational landscape included higher frequency of TP53 (73%), BRCA1 (40%), ATK1 (37%), CDH1(37%), and CTCF (33%). We confirmed African ancestry of patients through ADMIXTURE and observed (>70%) African ancestry. Comparison between our cohort and TCGA BRCA showed higher tumor mutational burden in our cohort which could be accounted for by greater sensitivity in our updated sequencing technology and analysis pipelines. Mutational signature analysis showed cosmic Signature 3 suggesting evidence of defective homologous recombination and signature 16 with unknown etiology. In addition, we also observed evidence deletions and structural variants such as rigma, pyrgo and typhonas. Ongoing efforts are investigating complex structural variants in our cohort compared to similar populations from other studies while waiting on additional samples. Citation Format: Samuel Terkper Ahuno, Yajas Shah, Rachel Martini, Andrea Sboner, Nicolas Robine, Olivier Elemento, Marcin Imielinski, Lisa Newman, Melissa Davis. Whole genome sequence of triple negative breast cancer (TNBC) tumors of African descent [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2935.
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Kleinstern, Geffen, J. Brice Weinberg, Sameer A. Parikh, Esteban Braggio, Dennis P. Robinson, Aaron D. Norman, Kari G. Rabe, et al. "Polygenic Risk Score and Risk of Chronic Lymphocytic Leukemia, Monoclonal B-Cell Lymphocytosis (MBL), and MBL Subtypes." Blood 136, Supplement 1 (November 5, 2020): 35–36. http://dx.doi.org/10.1182/blood-2020-136548.
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Background MBL is a precursor to chronic lymphocytic leukemia (CLL) and is subclassified into low-count (LC) MBL (absolute B-cell count<0.5x109/L) and high-count (HC) MBL (absolute B-cell count between 0.5 and 5x109/L). We previously reported that a polygenic risk score (PRS) based on a weighted average of 41 CLL-susceptibility variants was associated with risk of both MBL and CLL among a cohort of individuals from CLL families. Here we evaluate this PRS in an independent cohort of MBL and CLL individuals of European ancestry (EA), all of whom were ascertained agnostic to CLL family-history status. We also evaluate the PRS by MBL subtype (LC/HC), and in African American (AA) CLL cases and controls. Methods We genotyped 535 EA MBLs (139 HC-MBL, 396 LC-MBLs), 735 CLLs (640 EA, 95 AA), and 2,866 controls (2,631 EA, 235 AA) from the Mayo Clinic CLL Resource, Duke University, and Weill Cornell Medical College. We computed the CLL-PRS for each individual and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals, adjusting for age and sex. To assess discriminatory accuracy, we computed the c-statistic. Among EA individuals, we calculated a trend test among LC-MBL, HC-MBL, and CLL risk using the P-value for heterogeneity from a polytomous logistic regression analysis. Moreover, we plotted a boxplot for the PRS among controls, LC-MBL, HC-MBL, and EA CLL, as well as for AA CLL cases and controls, and tested the statistical difference using the Kruskal Wallis test and Mann-Whitney test, respectively. Results We found a significant association of PRS with overall MBL risk (OR=1.87, P=1.1x10-28) with good discrimination (c-statistic=0.72). Significant associations were also found for LC-MBL (OR=1.75, P=7.5x10-19, c-statistic=0.72), HC-MBL (OR=2.22, P=1.4x10-17, c-statistic=0.74), and CLL of EA (OR=2.60, P=1.2x10-62, c-statistic=0.78), with a significant difference among these cohorts (Figure 1.A) and a significant positive trend across these cohorts (Pheterogeneity=8.4x10-6). Although we observed a 33% increased risk of CLL in AA (c-statistic=0.57), the PRS was borderline significant (P=0.07, Figure 1.B). Conclusion The CLL-PRS is a strong prediction-tool for risk of CLL and MBL among individuals of EA. Future studies are needed to improve the PRS for AAs including performing GWAS of AA in order to identify CLL-susceptibility SNPs that are more representative within known CLL loci and to discover novel CLL loci that are unique for AAs. Disclosures Parikh: GlaxoSmithKline: Honoraria; Janssen: Honoraria, Research Funding; Ascentage Pharma: Research Funding; AbbVie: Honoraria, Research Funding; Merck: Research Funding; TG Therapeutics: Research Funding; Genentech: Honoraria; Pharmacyclics: Honoraria, Research Funding; MorphoSys: Research Funding; AstraZeneca: Honoraria, Research Funding; Verastem Oncology: Honoraria. Braggio:DASA: Consultancy; Bayer: Other: Stock Owner; Acerta Pharma: Research Funding. Brander:Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding; MEI Pharma: Other, Research Funding; Ascentage: Other, Research Funding; ArQule: Consultancy, Other, Research Funding; NCCN: Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Pfizer: Consultancy, Other; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Novartis: Consultancy, Other; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Tolero: Research Funding; Teva: Consultancy, Honoraria; DTRM: Other, Research Funding; BeiGene: Other, Research Funding; Novartis: Consultancy, Other; NCCN: Other; Verastem: Consultancy, Honoraria, Other, Research Funding. Cerhan:NanoString: Research Funding; BMS/Celgene: Research Funding. Kay:Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Agios Pharma: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; Juno Theraputics: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Cytomx: Membership on an entity's Board of Directors or advisory committees; Tolero Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Research Funding; Abbvie: Research Funding; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Membership on an entity's Board of Directors or advisory committees. Furman:Acerta: Consultancy; AstraZeneca: Consultancy, Research Funding; Beigene: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Sunesis: Consultancy; TG Therapeutics: Consultancy, Research Funding; Verastem: Consultancy; Incyte: Consultancy; Genentech: Consultancy; Janssen: Consultancy, Speakers Bureau; Loxo Oncology: Consultancy; Oncotarget: Consultancy. Shanafelt:Mayo Clinic: Patents & Royalties: and other intellectual property; Genentech, Pharmacyclics LLC, an AbbVie Company, AbbVie, GlaxoSmithKline, and Merck: Research Funding.
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Ramadani, Gani, and Predrag Pandiloski. "Disinflationary Spillovers from The Euro Area into the Countries of Southeastern Europe." Journal of Central Banking Theory and Practice 8, no. 3 (September 1, 2019): 65–93. http://dx.doi.org/10.2478/jcbtp-2019-0025.
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Abstract We analyse the determinants of the inflation trends in ten Southeast European (SEE) countries. Global cost-related factors and euro area inflation developments play an important role in explaining inflation dynamics in SEE countries. Changes in world food and energy prices, together with related changes in administered prices, similarly contribute to these trends. In general, we show that disinflationary spillovers from the euro area have been an important factor for fixed exchange rate regime countries, especially those with more trade exchange with countries in the euro area. Furthermore, our heterogeneity analysis shows that countries with less rigid exchange rate regimes but with relatively high exposure of trade exchange to the euro area (EA) market appear to be susceptible to inflation spillovers from the euro area. Moreover, nominal effective exchange rate plays an important role in inflation process in SEE countries, particularly in floating regime countries. In line with several recent findings about flattening of the Phillips curve in many economies across the world, cyclical unemployment does not appear to be significant in our sample. We conclude with some policy implications of our results.
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Baek, Jung Hwan. "Characteristics of the Middle Cervical Sympathetic Ganglion: A Systematic Review and Meta-Analysis." January 2018 1, no. 21;1 (January 5, 2018): 9–18. http://dx.doi.org/10.36076/2018.1.9.
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Background: Understanding the characteristics of the middle cervical sympathetic ganglion (MCSG) may minimize procedure-related complications and maximize efficacy during surgery or ultrasound (US)-guided procedures. The location and detection rate of the MCSG were variable in small population studies. Therefore, a large population study or meta-analysis could give more information about the MCSG. Objectives: We aim to review the published literature and evaluate the anatomical features of the MCSG, including the detection rate, location, size, and a normal variation, and to review the clinical relevance of MCSG for procedures including, US-guided ganglion block, ethanol ablation (EA), or radiofrequency ablation (RFA). Study Design: A systematic review and meta-analysis. The Ovid-MEDLINE and EMBASE databases were searched to find the detection rate, location, and other characteristics of the MCSG. Setting: The pooled proportions for the detection rate of the MCSG were assessed using the DerSimonian-Laird random-effects model. Methods: Heterogeneity among the studies was determined using a chi-square analysis for the pooled estimates and inconsistency index (I2 ). In order to reduce the heterogeneity, sensitivity analyses were performed. Results: A review of 542 studies identified 8 eligible studies, with 273 MCSGs included in the meta-analysis. The pooled proportion for the detection rate of the MCSG was 50.4% (95% confidence interval [CI], 34.5–66.4%). Considerable heterogeneity among the studies was observed (I2 = 94.9%). In the sensitivity analysis, when excluding one study, heterogeneity was reduced with a recalculated pooled proportion of 44.2% (95% CI, 32.1–56.2%; I2 = 86.0%). The location of the MCSG is usually posterior to the carotid sheath and anterior to the longus colli muscle at the level of the C3–C7 vertebrae. There was a variant where the cervical sympathetic trunk was located at the posterior wall of the carotid sheath and was adherent to the sheath. The size of the MCSG is as follows: the width, length, and height ranges were 3.8–6.3 mm, 6.3–10.5 mm, and 1.7–2.1 mm, respectively. A specific type of MCSG, referred to as the “double middle cervical ganglion”, consisting of 2 ganglia, was demonstrated in 3 studies with a detection rate of 2.9–10%. Limitations: This meta-analysis included a relatively small number of studies. Significant heterogeneity was also present in the detection rate of MCSG in these studies. There was a lack of concentrated information about the MCSG, because the majority of the included studies focused on the entire cervical sympathetic chain, not only MCSG primarily. Improving complication rates might be limited due to the approximate 50% detection rate. Conclusion: Understanding the characteristics and variations of the MCSG could minimize complications and maximize efficacy during surgery and US-guided procedures. Key words: Middle cervical sympathetic ganglion, cervical sympathetic trunk, cervical sympathetic chain, ultrasound, nerve block, ethanol ablation, radiofrequency ablation, thyroid, Horner syndrome, meta-analysis
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Williams, Stephen B., Sungyong You, Minhyung Kim, Steven G. Widen, Alexander Yu, Eduardo J. Eyzaguirre, Lars Dyrskjøt, et al. "Characterizing molecular subtypes of high-risk nonmuscle-invasive bladder cancer in African American patients." Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022): 527. http://dx.doi.org/10.1200/jco.2022.40.6_suppl.527.
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527 Background: Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) have heterogeneous outcomes with African Americans (AAs) having worse survival than European Americans (EAs). It is unknown whether race-based biological differences contribute to this disparity. Methods: We performed a retrospective cohort study including patients from the University of Texas Medical Branch (UTMB) and the Durham VA Health Care System (DVAHCS) from 2010-2020 among treatment naïve, high-risk NMIBC. Profiled gene expressions of high-risk NMIBC by race were performed using the UROMOL classification system. Results: A total of 26 patients (14 AAs and 12 EAs) matched on age and sex were included with no significant difference in clinical stage group (CIS +/- T1 or TaHG vs. TaHG or T1, no CIS), smoking status, or progression. We found a similar racial UROMOL subtype distribution with class 2a being most common. A total of 10 genes were discovered to be commonly upregulated differentially expressed genes (up-DEGs) in AAs vs EAs. EFEMP1, which has been associated with progression to muscle-invasive bladder cancer (MIBC) in vitro, and S100A16 gene expression, which has been implicated with mitomycin C resistance in bladder cancer in vitro, was significantly more common among AAs. We used single nuclei analysis to map the malignant cell heterogeneity in urothelial cancer which five distinct malignant epithelial subtypes whose presence has been associated with different therapeutic response prediction ability. We mapped the expression of the 10 genes commonly up-DEGs by race as a function of the five malignant subtypes. This showed borderline (p = 0.056) differences among the subtypes suggesting AA and EA patients may be expected to have different therapeutic responses to treatments for BC. AAs were enriched with immune-related, inflammatory, and cellular regulation pathways compared to EAs, yet appeared to have reduced levels of the aggressive C3 bladder tumor cell population. Conclusions: In this small sample, we found similar subtype distribution among high-risk NMIBC patients according to race. However, gene expression differs by race, supporting potential novel race-based etiologies for differences in muscle-invasion, response to treatments, and transcriptome pathway regulations. Further biological studies in NMIBC molecular sub-stratification, associated treatment(s), and prognoses in a larger cohort are needed to support these hypotheses.
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Park, Sophie, Pierre Fenaux, Peter Greenberg, Bhakti Mehta, Fiona Callaghan, Christopher Kim, Dianne Tomita, and Hairong Xu. "Efficacy and Safety of Darbepoetin Alfa (DA) in Patients with Myelodysplastic Syndromes (MDS): A Systematic Review and Meta-Analysis." Blood 126, no. 23 (December 3, 2015): 5236. http://dx.doi.org/10.1182/blood.v126.23.5236.5236.
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Abstract Introduction: Erythropoiesis-stimulating agents (ESAs) have been used in treating anemic MDS patients to improve erythropoiesis and reduce the risk of red blood cell (RBC) transfusion. Two previous systematic reviews found that ESA use was efficacious, but these reviews focused on short-acting epoetin alfa (EA). Since then, the results of a number of prospective interventional trials of DA have been reported. We present an updated systematic review and meta-analysis to estimate the efficacy of DA in the treatment of MDS-related anemia. Methods: We conducted a systematic review of the medical literature to identify prospective interventional trials of DA in patients with MDS. The main inclusion-exclusion (IE) criteria were: that studies had to be prospective and interventional in nature; have at least 10 adult subjects with MDS reporting either World Health Organization (WHO), French-American-British (FAB) criteria, or International Prognostic Scoring System (IPSS) status; and report results for the pre-specified primary outcome (proportion of patients with erythroid response) or one of the secondary outcomes (which included major hemoglobin response, changes from baseline in hemoglobin levels, transfusion status, and quality of life (QoL) measures). We recorded and collated all reported adverse events. Two independent reviewers identified the studies and abstracted the information and a third reviewer adjudicated. Clinical and methodological heterogeneity across studies were evaluated with respect to the study population and participant selection method (e.g. MDS diagnosis, history of ESA use, baseline erythropoietin (EPO), hemoglobin, and creatinine levels, transfusion status, and other factors), the intervention (e.g. initial and maintenance ESA dose), and the endpoints of interest including the response criteria. Forest plots with formal testing using Cochran's Q-statistic was also used to assess the heterogeneity across the studies. We used random effects methodology to generate combined estimates when warranted by the data. Subgroup analyses and/or meta-regressions were conducted by dose level, ESA-naïve status, baseline EPO level, hemoglobin level, transfusion status, and other factors. Results: Ten studies (9 single-arm, 1 randomized controlled trial [RCT]) with a total of 647 patients were included in the systematic review, with response rates ranging from 38% to 72%, and the median duration of response varying from 5 to 12 months. The overall response rate for the nine studies that used IWG 2000 response criteria could not be evaluated because of heterogeneity. However, among studies that stratified response rates by baseline endogenous EPO levels, patients with EPO <100 IU/L had an overall response of 81% (95% confidence interval [CI]: 73-90%), and on average a 39% [95% CI: 22-56%] better response than patients with EPO >100 IU/L. Across the studies that reported response stratified by prior ESA use, ESA-naïve patients had a median response rate of 75% compared to 53% for patients previously treated with an ESA. Baseline mean hemoglobin was significantly associated with response (p=0.0204), with higher baseline levels associated with improved response. We also found that response tended to improve with dose (p=0.2; Figure 2): the estimated response for a mean initial dose of 150 μg once weekly (QW) was 57% (95% CI: 49-66%) compared to 64% (95% CI: 55-74%) for 300 μg QW. Baseline transfusion independence (6 studies), and low-risk IPSS status (2 studies) were reported to be significantly associated with better response in several studies. Treatment with DA tended to show an improvement in the quality of life (QoL) measures, transfusion rates, and hemoglobin levels, but the number of studies that reported these outcomes was small. Hypertension, thromboembolism, and progression to acute myeloid leukemia were respectively reported in 2%, 1%, and 1% of the patients. Conclusions: Published studies suggest that treatment with DA yielded high hemoglobin response (38-72%) in MDS patients with anemia. The response was strongest in patients with lower baseline serum EPO level, and ESA naïve patients. Disclosures Park: Hospira: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Fenaux:Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Mehta:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership. Callaghan:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership. Kim:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership. Tomita:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership. Xu:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership.
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Jabado, Omar, Li Fan, Patricia Coutinho de Souza, Angelo Harris, Arturo Chaparro, Mohammed Qutaish, Han Si, et al. "928 A translational approach to catalog pancreatic cancer heterogeneity using spatial genomics in large patient cohorts for target validation and rational combination selection." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A973—A974. http://dx.doi.org/10.1136/jitc-2021-sitc2021.928.
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BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with short overall survival; the standard of care (SoC) is chemotherapy. Immunotherapies in development aim to remodel the stroma by depleting immunosuppressive cell types or using T-cell redirection to kill tumor cells. To date, none of these methods have improved overall survival beyond SoC. Next generation immunotherapies that employ histopathology and molecular subtyping1 for target and patient selection may succeed. Here we leverage a spatial transcriptomics platform (Nanostring Digital Spatial Profiling, DSP) to reveal molecular signaling in tumoral and stromal cells in 57 PDAC patients using tumor microarrays (TMAs). This approach is rapid and clinically relevant as molecular and histology data can be easily bridged.MethodsTMAs generated from surgical resection tissue were commercially sourced. DSP was performed using the CTA RNA panel (1,800 target genes) using PanCK fluorescence for tumor/stroma segmentation. In parallel, slides were chromogenically stained for T-cells (CD3) and macrophages (CD68/CD163). Differential gene expression, gene signature and gene co-expression network analysis was performed using linear models in R.2 3ResultsDifferential gene expression analysis and correlation to IHC confirmed the DSP platform successfully profiled tumor and stromal compartments (figure 1). Immune cell signatures4 and pathway analysis revealed a heterogenous stromal environment. Using a fibroblast gene signature derived from single-cell RNAseq5 we found fibroblast density was positively correlated to PDGFR signaling and MHC-II expression but negatively correlated to B, CD4+ T and neutrophil cell levels (figure 2a). This finding supports the idea that atypical antigen presentation in cancer associated fibroblasts (CAFs) may be exploitable for immunotherapies.6 We constructed a co-expression network from in-situ stromal gene expression and used it to identify receptors coordinately expressed with the immunosuppressive macrophage marker CSF1R as a bispecific antibody partner (figure 2b).7 Classical macrophage markers were identified but also receptors with lesser-known functions in macrophages (TIM3/HAVCR2, FPR3, MS4A6A, LILRB4). Surveying target pairs in this method allows rapid, patient-specific confirmation in serial TMA sections with singleplex IHC or RNAscope.Abstact 928 Figure 1Segmentation strategy and validation of DSP (A) PanCK, CD68 and CD3 staining from two representative tumor cores; (B, C) correlation of gene transcripts in stroma to cell counts from chromogenic staining; (D) heatmap of selected genes differentially expressed in tumor and stroma (n=57 patients).Abstract 928 Figure 2Exploration of the stromal compartment in PDAC TMAs. (A) Heatmap of selected cell type and gene signatures from gene expression in the stroma, color represents single sample enrichment score using GSVA method; (B) a gene co-expression subnetwork in the stroma centered on CSF1R, edge thickness represents strength of correlation, green nodes have evidence for cell surface expression based on proteomic profiling.7ConclusionsIn this study we were able to recapitulate known PDAC biology using very small samples of primary tumors. The combination of TMAs and DSP enables a rapid validation of targets and hypothesis generation for bispecific parings. Further analysis of untreated (n=14) and post-adjuvant chemotherapy (n=26) patients using RNA DSP, IHC and bulk RNAseq is under way. Results from this cohort will enable an integrated histopathology and molecular approach to developing next-generation immunotherapies.ReferencesCollisson EA, Bailey P, Chang DK, Biankin AV. Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol 2019 April;16(4):207–220.Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015). “limma powers differential expression analyses for RNA-sequencing and microarray studies.” Nucleic Acids Research 43(7):e47.Hänzelmann S, Castelo R, Guinney J (2013). “GSVA: gene set variation analysis for microarray and RNA-Seq data.” BMC Bioinformatics 14,7.Charoentong P, Finotello F, Angelova M, Mayer C, Efremova M, Rieder D, Hackl H, Trajanoski Z. Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep 2017 January 3;18(1):248–262.Tirosh I, Izar B, Prakadan SM, Wadsworth MH 2nd, Treacy D, Trombetta JJ, Rotem A, Rodman C, Lian C, Murphy G, Fallahi-Sichani M, Dutton-Regester K, Lin JR, Cohen O, Shah P, Lu D, Genshaft AS, Hughes TK, Ziegler CG, Kazer SW, Gaillard A, Kolb KE, Villani AC, Johannessen CM, Andreev AY, Van Allen EM, Bertagnolli M, Sorger PK, Sullivan RJ, Flaherty KT, Frederick DT, Jané-Valbuena J, Yoon CH, Rozenblatt-Rosen O, Shalek AK, Regev A, Garraway LA. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 2016 April 8;352(6282):189–96.Elyada E, Bolisetty M, Laise P, Flynn WF, Courtois ET, Burkhart RA, Teinor JA, Belleau P, Biffi G, Lucito MS, Sivajothi S, Armstrong TD, Engle DD, Yu KH, Hao Y, Wolfgang CL, Park Y, Preall J, Jaffee EM, Califano A, Robson P, Tuveson DA. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov 2019 August;9(8):1102–1123. Bausch-Fluck D, Hofmann A, Bock T, Frei AP, Cerciello F, Jacobs A, Moest H, Omasits U, Gundry RL, Yoon C, Schiess R, Schmidt A, Mirkowska P, Härtlová A, Van Eyk JE, Bourquin JP, Aebersold R, Boheler KR, Zandstra P, Wollscheid B. A mass spectrometric-derived cell surface protein atlas. PLoS One 2015 April 20;10(3):e0121314.Ethics ApprovalSpecimens were harvested from unused tissue after a surgical tumor resection procedure. A discrete legal consent form from both hospital and individuals was obtained by the commercial tissue vendor BioMax US for all samples analyzed in this abstract. All human tissues are collected under HIPPA approved protocols.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
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Helmer, Simon, Robert Morasch, Hubert Andreas Gasteiger, and Bharatkumar Suthar. "LiC6 Phase Mobility in Highly Oriented Pyrolytic Graphite (HOPG)." ECS Meeting Abstracts MA2022-02, no. 3 (October 9, 2022): 266. http://dx.doi.org/10.1149/ma2022-023266mtgabs.
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Graphite, serving as the lithium host structure, is still the main component of the anode active material in today's commercial lithium-ion batteries [1]. Yet, the determination of solid diffusion coefficient of lithium in graphite has so far proved difficult, which is reflected by the observation that the values published in the literature vary over several orders of magnitude, which is likely due to the structural and phase-related complexity of the lithium intercalation kinetics in graphite, as well as the heterogeneity of the samples studied [2, 3]. To address the latter point, our study aims to examine the lithiation of a highly oriented pyrolytic carbon (HOPG) disk, in which the basal planes are oriented normal to the disk height. In a first approach, we followed the lithiation of an HOPG disk by in-situ optical monitoring of the radial movement of the golden LiC6 phase in top-view images of the HOPG crystal (see left panel of Figure 1a), as was done previously by Guo et al. [3]. This was compared to a subsequent post-mortem analysis by splitting the HOPG disk along its height (see right panel of Figure 1a), clearly illustrating that the apparent LiC6 phase movement suggested by top-view images is mostly an artefact caused by HOPG crystal imperfections and that the LiC6 phase front position can only be quantified from the post-mortem analysis of split crystals. Based on the latter analysis approach, we show that the LiC6 phase ring thickness for different intercalation times and temperatures can be well described using a model based on Fickian diffusion in cylindrical geometry by defining a concentration ratio c/c0 for the appearance of the golden phase between 0.7-0.8, as shown in Fig. 1b [4]. Within this model framework, an apparent diffusion coefficient of the LiC6 phase of D0=0.7-1.4×10-13 [m2/s] at 25°C can be determined, with an activation energy of Ea=36.5-37.1 [kJ/mol]. References: [1] J. Asenbauer, T. Eisenmann, M. Kuenzel, A. Kazzazi, Z. Chen, D. Bresser, Sustainable Energy & Fuels 2020 4(11), 5387-5416. [2] K. Persson, V. A. Sethuraman, L. J. Hardwick, Y. Hinuma, Y. S. Meng, A. Van Der Ven, V. Srinivasan, R. Kostecki, G. Ceder, J. Phys. Chem. Lett. 2010, 1(8), 1176-1180. [3] Y. Guo, R. B. Smith, Z. Yu, D. K. Efetov, J. Wang, P. Kim, M. Z. Bazant, L. E. Brus, J. Phys. Chem. Lett. 2016, 7(11), 2151-2156. [4] J. Crank, The Mathematics of Diffusion, Oxford university press, 1979. Figure 1 a) Lithiation of an HOPG disk, in which the basal planes are oriented normal to the disk height. Comparison of top view (left, obtained during in-situ lithiation experiment), vs bulk view (right, obtained after splitting it open during post-mortem) of the same HOPG disk, demonstrate the need to do post-mortem analysis of split crystal to have artefact-free penetration depth of the LiC6 phase front into the HOPG b) graph comparing the growth of golden ring (LiC6 phase) using Fickian diffusion in cylinder (lines) to experimental data (denoted by ×) at different intercalation times and temperatures. Figure 1
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Kaufman, Jacob, Doug Cress, Theresa Boyle, David Carbone, Neal Ready, and Kris Wood. "909 Differentiation subgroups within LKB1-deficient lung cancer influence both the immune exclusion phenotype and cellular composition of the immune microenvironment." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A954—A955. http://dx.doi.org/10.1136/jitc-2021-sitc2021.909.
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BackgroundLKB1 (STK11) is a commonly disrupted tumor suppressor in NSCLC. Its loss promotes an immune exclusion phenotype with evidence of low expression of interferon stimulated genes (ISG) and decreased microenvironment immune infiltration.1 2 Clinically, LKB1 loss induces primary immunotherapy resistance.3 LKB1 is a master regulator of a complex downstream kinase network and has pleiotropic effects on cell biology. Understanding the heterogeneous phenotypes associated with LKB1 loss and their influence on tumor-immune biology will help define and overcome mechanisms of immunotherapy resistance within this subset of lung cancer.MethodsWe applied multi-omic analyses across multiple lung adenocarcinoma datasets2 4–6 (>1000 tumors) to define transcriptional and genetic features enriched in LKB1-deficient lung cancer. Top scoring phenotypes exhibited heterogeneity across LKB1-loss tumors, and were further interrogated to determine association with increased or decreased markers of immune activity. Further, immune cell-types were estimated by Cibersort to identify effects of LKB1 loss on the immune microenvironment. Key conclusions were confirmed by blinded pathology review.ResultsWe show that LKB1 loss significantly affects differentiation patterns, with enrichment of ASCL1-expressing tumors with putative neuroendocrine differentiation. LKB1-deficient neuroendocrine tumors had lower expression of Interferon Stimulated Genes (ISG), MHC1 and MHC2 components, and immune infiltration compared to LKB1-WT and non-neuroendocrine LKB1-deficient tumors (figure 1).The abundances of 22 immune cell types assessed by Cibersort were compared between LKB1-deficient and LKB1-WT tumors. We observe skewing of immune microenvironmental composition by LKB1 loss, with lower abundance of dendritic cells, monocytes, and macrophages, and increased levels of neutrophils and plasma cells (table 1). These trends were most pronounced among tumors with neuroendocrine differentiation, and were concordant across three independent datasets. In a confirmatory subset of 20 tumors, plasma cell abundance was assessed by a blinded pathologist. Pathologist assessment was 100% concordant with Cibersort prediction, and association with LKB1 loss was confirmed (P=0.001).Abstract 909 Figure 1Immune-associated Gene Expression Profiles Affected by Neuroendocrine Differentiation within LKB1-Deficient Lung Adenocarcinomas. Gene expression profiles corresponding to five immune-associated phenotypes are shown with bars indicating average GEP scores for tumors grouped according to LKB1 and neuroendocrine status as indicated. P-values represent results from Student’s T-test between groups as indicated.Abstract 909 Table 1LKB1 Loss Affects Composition of Immune Microenvironment. Values indicate log10 P-values comparing LKB1-loss to LKB1-WT tumors. Positive (red) indicates increased abundance in LKB1 loss. Negative (blue) indicates decreased abundance.ConclusionsWe conclude that tumor differentiation patterns strongly influence the immune microenvironment and immune exclusion characteristics of LKB1-deficient tumors. Neuroendocrine differentiation is associated with the strongest immune exclusion characteristics and should be evaluated clinically for evidence of immunotherapy resistance. A novel observation of increased plasma cell abundance is observed across multiple datasets and confirmed by pathology. Causal mechanisms linking differentiation status to immune activity is not well understood, and the functional role of plasma cells in the immune biology of LKB1-deficient tumors is undefined. These questions warrant further study to inform precision immuno-oncology treatments for these patients.AcknowledgementsThis work was funded by SITC AZ Immunotherapy in Lung Cancer grant (SPS256666) and DOD Lung Cancer Research Program Concept Award (LC180633).ReferencesSkoulidis F, Byers LA, Diao L, et al. Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities. Cancer Discov 2015;5:860–77.Schabath MB, Welsh EA, Fulp WJ, et al. Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma. Oncogene 2016;35:3209–16.Skoulidis F, Goldberg ME, Greenawalt DM, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discovery 2018;8:822-835.Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014;511:543–50.Chitale D, Gong Y, Taylor BS, et al. An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors. Oncogene 2009;28:2773–83.Shedden K, Taylor JM, Enkemann SA, et al. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat Med 2008;14:822–7.