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1
Salah Fararjeh, AbdulFattah, Ali Al-Khader, Malak Al-Saleem e Rinad Abu Qauod. "The Prognostic Significance of Proteasome 26S Subunit, Non-ATPase (PSMD) Genes for Bladder Urothelial Carcinoma Patients". Cancer Informatics 20 (gennaio 2021): 117693512110676. http://dx.doi.org/10.1177/11769351211067692.
Testo completoAbstract (sommario):
Proteasome a highly sophisticated systems that alter protein structure and function. Proteasome 26S Subunit, Non-ATPase (PSMD) genes have been implicated in several types of malignancies. This is the first study to look at how proteasomal subunits are expressed in patients with bladder urothelial carcinoma (BLCA). BLCA was used to evaluate the predictive value of PSMD genes (PSMD1 to PSMD12) in relation to clinicopathological characteristics. PSMD genes’ expression patterns at the mRNA level were analyzed using a variety of bioinformatics methods, including gene expression profile integrative analysis (GEPIA), Oncomine, TCGA, and Gene expression Omnibus (GEO) databases. The GEPIA and TCGA dataset survival plot functions were used to assess the prognostic significance of PSMD genes. PSMD2, PSMD3, PSMD4, PSMD8, and PSMD11 genes were significantly overexpressed in BLCA compared with normal bladder tissues. PSMD2 and PSMD8 were significantly overexpressed in BLCA more than other types of cancer. High level of PSMD2 and PSMD8 predicted shorter overall (OS) and progression free survival (PFS) in BLCA patients. High level of PSMD2 was significantly associated with elder age ( P < .001), female gender ( P = .014), tumor grade ( P < .001), and metastasis ( P = .003). PSMD2 has been shown to be an independent predictor for OS in BLCA patients based on univariate and multivariate analysis ( P < .001). Overall, according to this study, PSMD2 and PSMD8 could be served as a prognostic biomarker for BLCA patients.
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Jacelon, Cynthia, Maral Torrisan e Sarah Fiske. "OLDER DYADS USING A WEARABLE PERSONAL SLEEP MONITORING DEVICE FOR SLEEP SELF-MANAGEMENT". Innovation in Aging 6, Supplement_1 (1 novembre 2022): 692–93. http://dx.doi.org/10.1093/geroni/igac059.2539.
Testo completoAbstract (sommario):
Abstract Normally occurring changes in sleep patterns can affect behavior, safety, and function in older individuals. In addition, altered sleep of one partner can affect the functioning of the other. We tested a novel intervention using an off the shelf, wrist-worn actigraph as a personal sleep monitoring device (PSMD) with dyads comprised of individuals who were 70 years old or older, and slept in the same house. Aims included: 1) Establish the feasibility of sleep self-monitoring using PSMDs, as a self-management strategy. 2) Establish the feasibility of PSMD data sharing among members of the dyad to improve sleep self-management and improve sleep quality; and 3) Evaluate the usability of PSMDs and data sharing for dyads of older individuals. Over the course of a five-week trial, we used a mixed methods approach. Data were comprised of daily sleep diaries, data from the PSMD, weekly questionnaires regarding sleep patterns and function, and qualitative interviews focused on sleep, self-management within the dyad, and the usability of the PSMD. Data were analyzed using qualitative or statistical methods. The use of the PSMD increased awareness of sleep patterns at the individual and dyadic levels, but the limitations of the PSMD were frustrating. Participants valued having a graphic image of how their daily activities affected their sleep patterns. The dyadic approach was effective in improving sleep patterns for older individuals, and using over the counter activity monitoring devices provide a relatively inexpensive way to assist older adults to improve their sleep self-management.
3
Septiansyah, Dhimas Anggi, Emi Wuri Wuryaningsih e Fitrio Deviantony. "Relationship between National Health Insurance Ownership and Compliance with Access to Health Services for Patients with Severe Mental Disorders (PSMD) “Pasung” in Blitar Regency, Indonesia". Journal of Community Empowerment for Health 6, n. 3 (8 dicembre 2023): 128. http://dx.doi.org/10.22146/jcoemph.66649.
Testo completoAbstract (sommario):
Patients with Severe Mental Disorders (PSMD) "Pasung" require long-term care, which causes a financial burden on the family. The Indonesian government has guaranteed funding for the treatment. However, there are still PSMDs who do not make regular visits to health services. This study aimed to describe the Relationship between National Health Insurance Ownership and Compliance with Access to Health Services for PSMDin Blitar Regency, Indonesia. This study used an analytic observational design with a retrospective cohort study approach. Total sampling techniques selected 50 PSMD "pasung" recorded health insurance and several visits to primary health services. The data was obtained from the primary health services reporting records from January to March 2020. This study used the biserial point correlation (CI: 99%) test for analyzing data. This study has ethical clearance approval. The results showed that there was a positive relationship between ownership of NHI and compliance with access to health services (t-obs (3,491) ≥ critical (2,678); p-value = 0,001; r-bis = 0,450; α = 0,01). Indonesia has guaranteed the cost of PSMD treatment with shackles, but patients and families who use these facilities are not optimal. In conclusion, national health insurance ownership is related to compliance with access to health services for PSMD "Pasung". Health agencies can pay attention to policy-making for enhancing access to health services of PSMD "Pasung".
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Lara, Joshua J., Alfonso E. Bencomo-Alvarez, Mayra A. Gonzalez, Idaly M. Olivas, James E. Young, Jose L. Lopez, Vanessa V. Velazquez et al. "19S Proteasome Subunits as Oncogenes and Prognostic Biomarkers in FLT3-Mutated Acute Myeloid Leukemia (AML)". International Journal of Molecular Sciences 23, n. 23 (23 novembre 2022): 14586. http://dx.doi.org/10.3390/ijms232314586.
Testo completoAbstract (sommario):
26S proteasome non-ATPase subunits 1 (PSMD1) and 3 (PSMD3) were recently identified as prognostic biomarkers and potential therapeutic targets in chronic myeloid leukemia (CML) and multiple solid tumors. In the present study, we analyzed the expression of 19S proteasome subunits in acute myeloid leukemia (AML) patients with mutations in the FMS-like tyrosine kinase 3 (FLT3) gene and assessed their impact on overall survival (OS). High levels of PSMD3 but not PSMD1 expression correlated with a worse OS in FLT3-mutated AML. Consistent with an oncogenic role for PSMD3 in AML, shRNA-mediated PSMD3 knockdown impaired colony formation of FLT3+ AML cell lines, which correlated with increased OS in xenograft models. While PSMD3 regulated nuclear factor-kappa B (NF-κB) transcriptional activity in CML, we did not observe similar effects in FLT3+ AML cells. Rather, proteomics analyses suggested a role for PSMD3 in neutrophil degranulation and energy metabolism. Finally, we identified additional PSMD subunits that are upregulated in AML patients with mutated versus wild-type FLT3, which correlated with worse outcomes. These findings suggest that different components of the 19S regulatory complex of the 26S proteasome can have indications for OS and may serve as prognostic biomarkers in AML and other types of cancers.
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Ramdas, Premdass, Ammu Kutty Radhakrishnan, Asmahani Azira Abdu Sani, Mangala Kumari, Jeya Seela Anandha Rao e Puteri Shafinaz Abdul-Rahman. "Advancing the Role of Gamma-Tocotrienol as Proteasomes Inhibitor: A Quantitative Proteomic Analysis of MDA-MB-231 Human Breast Cancer Cells". Biomolecules 10, n. 1 (21 dicembre 2019): 19. http://dx.doi.org/10.3390/biom10010019.
Testo completoAbstract (sommario):
Tocotrienol, an analogue of vitamin E has been known for its numerous health benefits and anti-cancer effects. Of the four isoforms of tocotrienols, gamma-tocotrienol (γT3) has been frequently reported for their superior anti-tumorigenic activity in both in vitro and in vivo studies, when compared to its counterparts. In this study, the effect of γT3 treatment in the cytoplasmic and nuclear fraction of MDA-MB-231 human breast cancer cells were assessed using the label-free quantitative proteomics analysis. The cytoplasmic proteome results revealed the ability of γT3 to inhibit a group of proteasome proteins such as PSMA, PSMB, PSMD, and PSME. The inhibition of proteasome proteins is known to induce apoptosis in cancer cells. As such, the findings from this study suggest γT3 as a potential proteasome inhibitor that can overcome deficiencies in growth-inhibitory or pro-apoptotic molecules in breast cancer cells. The nuclear proteome results revealed the involvement of important nuclear protein complexes which hardwire the anti-tumorigenesis mechanism in breast cancer following γT3 treatment. In conclusion, this study uncovered the advancing roles of γT3 as potential proteasomes inhibitor that can be used for the treatment of breast cancer.
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Jochems, Angela C. C., Susana Muñoz Maniega, Una Clancy, Daniela Jaime Garcia, Carmen Arteaga, Will Hewins, Rachel Penman et al. "Associations of Peak-Width Skeletonized Mean Diffusivity and Post-Stroke Cognition". Life 12, n. 9 (31 agosto 2022): 1362. http://dx.doi.org/10.3390/life12091362.
Testo completoAbstract (sommario):
Post-stroke cognitive impairment is common and can have major impact on life after stroke. Peak-width of Skeletonized Mean Diffusivity (PSMD) is a diffusion imaging marker of white matter microstructure and is also associated with cognition. Here, we examined associations between PSMD and post-stroke global cognition in an ongoing study of mild ischemic stroke patients. We studied cross-sectional associations between PSMD and cognition at both 3-months (N = 229) and 1-year (N = 173) post-stroke, adjusted for premorbid IQ, sex, age, stroke severity and disability, as well as the association between baseline PSMD and 1-year cognition. At baseline, (mean age = 65.9 years (SD = 11.1); 34% female), lower Montreal Cognitive Assessment (MoCA) scores were associated with older age, lower premorbid IQ and higher stroke severity, but not with PSMD (βstandardized = −0.116, 95% CI −0.241, 0.009; p = 0.069). At 1-year, premorbid IQ, older age, higher stroke severity and higher PSMD (βstandardized = −0.301, 95% CI −0.434, −0.168; p < 0.001) were associated with lower MoCA. Higher baseline PSMD was associated with lower 1-year MoCA (βstandardized = −0.182, 95% CI −0.308, −0.056; p = 0.005). PSMD becomes more associated with global cognition at 1-year post-stroke, possibly once acute effects have settled. Additionally, PSMD in the subacute phase after a mild stroke could help predict long-term cognitive impairment.
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Yadav, Anurag, Kusum Yadav e Anupam Vashistha. "Phosphate solubilizing activity of Pseudomonas fluorescens PSM1 isolated from wheat rhizosphere". Journal of Applied and Natural Science 8, n. 1 (1 marzo 2016): 93–96. http://dx.doi.org/10.31018/jans.v8i1.754.
Testo completoAbstract (sommario):
A study was designed to screen and analyze the efficient phosphate solubilizing bacteria (PSBs) from wheat rhizosphere. Five biovars of Pseudomonas fluorescens (PSM1, PSM2, PSM3, PSM4 and PSM5) were isolated from wheat rhizosphere and Bacillus megaterium MTCC 8755 procured from microbial type culture collection (MTCC) Chandigarh, India. The P. fluorescens biovar PSM1 was observed to be most efficient phosphate solubilizer. Inoculation of P. fluorescens PSM1 and B. megaterium MTCC 8755, alone and in combination, caused the highest phosphate solubilization at pH 5. At this pH, maximum phosphate solubilization was observed with B. megaterium MTCC 8755 inoculation (8.2 mg mL-1) on sixth day of incubation with P. fluorescens PSM1 (8 mg mL-1) on seventh day of incubation and with dual bacterial treatment (10.5 mg mL-1) on the fourth day of incubation. A correlation coefficient of linear regression equation of phosphate solubilization with pH indicated that pH value of the medium was directly correlated with tricalcium phosphate solubilization. The study will help in choosing soil pH specific PSB inoculant for optimizing plant growth.
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Zulfiqar, Usman, Muhammad Ahmad, Mohammad Valipour, Muhammad Ishfaq, Muhammad Faisal Maqsood, Rashid Iqbal, Muhammad Fraz Ali, Rana Roy e Ayman El Sabagh. "Evaluating Optimum Limited Irrigation and Integrated Nutrient Management Strategies for Wheat Growth, Yield and Quality". Hydrology 10, n. 3 (25 febbraio 2023): 56. http://dx.doi.org/10.3390/hydrology10030056.
Testo completoAbstract (sommario):
Agricultural productivity is significantly influenced by the restricted availability of irrigation water and poor soil health. To assess the influence of different potential soil moisture deficit (PSMD) regimes and integrated nutrient levels on the growth, yield, and quality of wheat, an experiment was carried out at the research area of the University of Agriculture, Faisalabad. The experiment includes three levels of PSMD (I1: 25 mm PSMD, I2: 50 mm PSMD, and I3: 75 mm PSMD) and four integrated nutrition levels (N1: 50% organic manure + 50% Inorganic NPK, N2: 75% organic manure + 25% inorganic NPK, N3: 100% application of organic manure, and N4: 100% application of inorganic NPK). Results of the experiment revealed that maximum grain yield (4.78 t ha−1) was obtained as a result of irrigation at 50 mm PSMD with the combined use of organic and inorganic sources in equal proportions. In contrast, the minimum yield was observed at I3: 75 mm PSMD with 100% application of organic manure. The highest plant height (99.11 cm), fertile tillers (284.4), 1000-grain weight (44.48 g), biological yield (14.82 t ha−1), radiation use efficiency for grain yield (RUEGY) (5.71 g MJ−1), and radiation use efficiency for total dry matter (RUETDM) (2.15 g MJ−1) were observed under N1: 50% organic manure with 50% inorganic NPK treatment. The highest value of these parameters was also observed in I2 (50 mm PSMD). The results of this study can be extended to arid and semi-arid regions, where deficit irrigation is a key strategy to address water crises and to meet sustainable development goals.
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Algristian, Hafid, Fifi Khoirul Fitriyah, Abdul Hakim Zakkiy Fasya, Difran Nobel Bistara, Rahmadaniar Aditya Putri e Khadijah Khairul Bariyah. "PATIENT-SELECTION PROGRAM TRAINING FOR MENTAL HEALTH CADRES IN DEVELOPING INDEPENDENT BUSINESS FOR THE FAMILY". Community Service Journal of Indonesia 6, n. 1 (4 giugno 2024): 26–34. http://dx.doi.org/10.36720/csji.v6i1.630.
Testo completoAbstract (sommario):
People with severe mental disorder (PSMD; Orang Dengan Gangguan Jiwa, ODGJ) are a vulnerable group of people who experience loss of their rights to life because of their mental limitations, namely the right to work and earn an income independently. In previous activities, there was an opportunity for PSMD to recover through a series of training. To achieve recovery, it is necessary to hold a patient selection program so that patients who take part in the training series are not in the acute phase. Mental health cadres who are close to the community have a big role in determining which PSMD will then take part in entrepreneurship training activities. Therefore, mental health cadres need to deepen their insight into mental disorders and increase their empowerment in patient selection programs for PSMD. This activity aims to increase the understanding of mental health cadres regarding mental disorders and increase their empowerment in implementing patient selection programs for PSMD. The method used was by conducting outreach to mental health cadres regarding the topic of mental disorders as well as providing patient selection program training to mental health cadres. Before counseling and training, a 10-minute pre-test was conducted for the participants, then continued with an outreach and training session as well as questions and answers and discussions for approximately 60 minutes, and at the end a 10-minute post-test was carried out. The results showed an increase in pre-test and post-test data on the topic of mental disorders as well as an increase in empowerment by mental health cadre participants in carrying out patient selection programs. Community service activities regarding patient selection program training for mental health cadres in developing independent businesses for PSMD families in the Gresik district have provided improvements to mental health cadres, namely in the form of increased insight regarding mental disorders and increased empowerment in carrying out patient selection programs for PSMD.
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LeBlanc, Raeann G., Maral Torossian, Paige Czarnecki, Rebecca Spencer, Cynthia Jacelon e Jenna Marquard. "PERSONAL SELF-MONITORING DEVICES TO IMPROVE SLEEP AMONG OLDER PEOPLE: A FEASIBILITY STUDY". Innovation in Aging 3, Supplement_1 (novembre 2019): S919. http://dx.doi.org/10.1093/geroni/igz038.3348.
Testo completoAbstract (sommario):
Abstract Chronic sleep disturbances reduce physical and mental health and affect over 8 million people age 65 years and older in the United States. There is evidence that use of a wearable Personal Self-Monitoring Device (PSMD) may improve sleep self-management in young adult populations. Feasibility of PSMD use for older individuals has not been explored and was the goal of this study. Persons age 65 years and over with self-reported sleep disturbances were recruited in a local community and were asked to wear a commercial PSMD for a 4-week period. To assess whether such an intervention may be feasible, outcomes included consent rate, study completion rate, data download interpretation, identification of a sleep self-management goal, improved knowledge about sleep, and improved sleep. Twenty-six persons (12 males and 14 females) were recruited over 3 months, out of a total of 33 expressing interest. Mean age=72, SD=4.99. Ninety-two percent of participants completed the study and reported improved awareness of sleep patterns and identified a sleep goal. Total sleep time was M=7 hours 14 minutes, SD=40 minutes; total restful sleep time was M=4 hours 33 minutes, SD=1 hour 22 minutes. In conclusion, sleep self-management with the use of a PSMD is feasible and of interest among persons in the young-old age category (65-74 years). There is potential for the use of PSMD among older people with the goal of improved sleep self-management. Future studies for sleep health self-management and interventions using personal sleep monitoring are recommended.
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Villa, María, María Martínez-Vega, Aarón del Pozo, Itziar Muneta-Arrate, Ana Gómez-Soria, Carolina Muguruza, María de Hoz-Rivera et al. "The Role of the Dopamine System in Post-Stroke Mood Disorders in Newborn Rats". International Journal of Molecular Sciences 24, n. 4 (6 febbraio 2023): 3229. http://dx.doi.org/10.3390/ijms24043229.
Testo completoAbstract (sommario):
Post-stroke mood disorders (PSMD) affect disease prognosis in adults. Adult rodent models underlie the importance of the dopamine (DA) system in PSMD pathophysiology. There are no studies on PSMD after neonatal stroke. We induced neonatal stroke in 7-day-old (P7) rats by temporal left middle cerebral artery occlusion (MCAO). Performance in the tail suspension test (TST) at P14 and the forced swimming test (FST) and open field test (OFT) at P37 were studied to assess PSMD. DA neuron density in the ventral tegmental area, brain DA concentration and DA transporter (DAT) expression as well as D2 receptor (D2R) expression and G-protein functional coupling were also studied. MCAO animals revealed depressive-like symptoms at P14 associated with decreased DA concentration and reduced DA neuron population and DAT expression. At P37, MCAO rats showed hyperactive behavior associated with increased DA concentration, normalization of DA neuron density and decreased DAT expression. MCAO did not modify D2R expression but reduced D2R functionality at P37. MCAO-induced depressive-like symptoms were reversed by the DA reuptake inhibitor GBR-12909. In conclusion, MCAO in newborn rats induced depressive-like symptoms and hyperactive behavior in the medium and long term, respectively, that were associated with alterations in the DA system.
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Rodríguez Díaz, J. A., J. W. Knox e E. K. Weatherhead. "Uso del indicador agroclimático PSMD para la representación y evaluación del impacto del cambio climático en las necesidades de agua de riego en España". Ingeniería del agua 13, n. 4 (31 dicembre 2006): 311. http://dx.doi.org/10.4995/ia.2006.10496.
Testo completoAbstract (sommario):
<p>Con 3.3 Mha, España es el país europeo con mayor superficie de regadío, el cual es con diferencia el mayor consumidor de agua en el país. En los últimos años la superficie del mismo ha experimentado un considerable aumento, lo que ha ocasionado que la competencia por el agua sea la mayor que nunca ha existido. <br />No obstante, a medio plazo, el regadío en España se enfrenta al reto del cambio climático, el cual previsiblemente incrementará, aún más si cabe, las necesidades de agua de riego de los cultivos. E.n este trabajo se presenta una metodología de evaluación de los impactos del mismo en términos agroclimáticos mediante el uso del Indicador "Potentlal Soil Moisture Deficit'' (PSMD). El Indicador PSMD es un balance acumulado de agua en el suelo que relaciona las dos variables que determinan las necesidades de agua de riego: precipitación y evapotransplración. <br />En este trabajo el indicador PSMD se ha calculado para toda la superficie de España, Importando los resultados dentro de un SIG. De esta forma se han obtenido mapas de Impacto del cambio climático en términos agrocllmátlcos para todo el país. <br />El análisis de los mismos muestra incrementos de PSMD de más del 20 % para el horizonte temporal 2050 y aproximadamente del 50 o/o para 2080.</p>
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Kumar, P. Lava, A. T. Jones, P. Sreenivasulu, B. Fenton e D. V. R. Reddy. "Characterization of a Virus from Pigeonpea with Affinities to Species in the Genus Aureusvirus, Family Tombusviridae". Plant Disease 85, n. 2 (febbraio 2001): 208–15. http://dx.doi.org/10.1094/pdis.2001.85.2.208.
Testo completoAbstract (sommario):
In attempts to identify the causal agent of pigeonpea sterility mosaic disease (PSMD), which is transmitted by eriophyid mites, a virus was isolated with great difficulty from some PSMD-affected pigeonpea (Cajanus cajan) plants from different locations in India. Once isolated from pigeonpea, the virus was transmitted readily by mechanical inoculation to several herbaceous species, reaching very high concentrations in some species. The virus was transmitted experimentally through soil to herbaceous test plants but not to pigeonpea. When virus particles were purified and inoculated mechanically to healthy pigeonpea, the virus induced necrosis in inoculated leaves only and did not spread systemically. Therefore, the virus is not the causal agent of PSMD. The virus has isometric particles approximately 30 nm in diameter that sediment as a single component and had a buoyant density in CsCl and Cs2SO4 of 1.34 and 1.27 g·cc-1, respectively. Purified virus particle preparations contained a single major protein of approximately 44 kDa and three RNA species of approximately 4,300, 2,700, and 1,500 nucleotides. Only the largest RNA species was infective to plants; the two smaller species were encapsidated subgenomic species of the 3′ end of the larger genomic RNA. The viral genome was sequenced and showed 93% homology to that of Pothos latent virus (PoLV), a recently described virus in the genus Aureusvirus, family Tombusviridae, and was indistinguishable from PoLV in gel double-diffusion serological tests. This virus, therefore, is regarded as a pigeonpea isolate of PoLV (PoLV-PP). In field studies in different locations in India, enzyme-linked immunosorbent assay and reverse-transcriptase polymerase chain reaction detected PoLV-PP in 10.7% of PSMD-affected and 8.1% of asymptomatic pigeonpea plants. The significance of these findings is discussed.
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Mayer, Carola, Felix L. Nägele, Marvin Petersen, Maximilian Schell, Ghazal Aarabi, Thomas Beikler, Katrin Borof et al. "Association between Coffee Consumption and Brain MRI Parameters in the Hamburg City Health Study". Nutrients 15, n. 3 (28 gennaio 2023): 674. http://dx.doi.org/10.3390/nu15030674.
Testo completoAbstract (sommario):
Despite associations of regular coffee consumption with fewer neurodegenerative disorders, its association with microstructural brain alterations is unclear. To address this, we examined the association of coffee consumption with brain MRI parameters representing vascular brain damage, neurodegeneration, and microstructural integrity in 2316 participants in the population-based Hamburg City Health Study. Cortical thickness and white matter hyperintensity (WMH) load were measured on FLAIR and T1-weighted images. Microstructural white matter integrity was quantified as peak width of skeletonized mean diffusivity (PSMD) on diffusion-weighted MRI. Daily coffee consumption was assessed in five groups (<1 cup, 1–2 cups, 3–4 cups, 5–6 cups, >6 cups). In multiple linear regressions, we examined the association between brain MRI parameters and coffee consumption (reference group <1 cup). After adjustment for covariates, 3–4 cups of daily coffee were associated with lower PSMD (p = 0.028) and higher cortical thickness (p = 0.015) compared to <1 cup. Moreover, 1–2 cups per day was also associated with lower PSMD (p = 0.022). Associations with WMH load or other groups of coffee consumption were not significant (p > 0.05). The findings indicate that regular coffee consumption is positively associated with microstructural white matter integrity and cortical thickness. Further research is necessary to determine longitudinal effects of coffee on brain microstructure.
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Kesić, Lazar, Vanja Vuksanović, Velisav Karaklić e Erna Vaštag. "Variation of leaf water potential and leaf gas exchange parameters of seven Silver linden (Tilia tomentosa Moench) genotypes in urban environment". Topola, n. 206 (2020): 15–24. http://dx.doi.org/10.5937/topola2005015k.
Testo completoAbstract (sommario):
Differences between genotypes are considered to be the most important requisite for a resilient urban forest. Analyses of physiological traits, such as leaf water potential and leaf gas exchange could provide useful insight into the capacity of different species and genotypes to grow in harsh urban environments. In the present study, a variation of midday (Psmd) and predawn (Pspd) leaf water potential, net photosynthesis (A), rate of transpiration (E), stomatal conductance (gs), and intercellular CO2 concentration (Ci) of seven Silver linden genotypes (Tilia tomentosa Moench), planted in the urban environment in Novi Sad, were examined. Analysis of variance and LSD tests were used to show differences between studied silver linden genotypes. The results showed significant differences for all observed leaf gas exchange parameters (A, E, gs, Ci, Pspd and Psmd) between genotypes. The results indicate better physiological performances of genotypes T3, in comparison to other observed genotypes under the prevailing environmental condition of the studied site in the urban environment.
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Song, Chengqun, Bo Zeng, Jun Cheng, Fuxiang Wu e Fusheng Hao. "PSMD-SLAM: Panoptic Segmentation-Aided Multi-Sensor Fusion Simultaneous Localization and Mapping in Dynamic Scenes". Applied Sciences 14, n. 9 (30 aprile 2024): 3843. http://dx.doi.org/10.3390/app14093843.
Testo completoAbstract (sommario):
Multi-sensor fusion is pivotal in augmenting the robustness and precision of simultaneous localization and mapping (SLAM) systems. The LiDAR–visual–inertial approach has been empirically shown to adeptly amalgamate the benefits of these sensors for SLAM across various scenarios. Furthermore, methods of panoptic segmentation have been introduced to deliver pixel-level semantic and instance segmentation data in a single instance. This paper delves deeper into these methodologies, introducing PSMD-SLAM, a novel panoptic segmentation assisted multi-sensor fusion SLAM approach tailored for dynamic environments. Our approach employs both probability propagation-based and PCA-based clustering techniques, supplemented by panoptic segmentation. This is utilized for dynamic object detection and the removal of visual and LiDAR data, respectively. Furthermore, we introduce a module designed for the robust real-time estimation of the 6D pose of dynamic objects. We test our approach on a publicly available dataset and show that PSMD-SLAM outperforms other SLAM algorithms in terms of accuracy and robustness, especially in dynamic environments.
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Salinger, J. "Climate reality - actual and expected". NZGA: Research and Practice Series 11 (1 gennaio 2003): 13–18. http://dx.doi.org/10.33584/rps.11.2003.2999.
Testo completoAbstract (sommario):
New Zealand average surface temperatures have increased by 0.7 °C since 1871. In the last quarter of the 20th century, more prevalent west to southwest flows occurred, accompanying a higher incidence of El Niño events. This resulted in annual rainfall decreasing in eastern areas of the North Island. As well as the global warming signal, interannual to decadal climate variability is a strong feature of east coast dryland climates. The El Niño-Southern Oscillation, (ENSO), through El Niño/ and La Niña episodes, drives climate variability seasonally. The recently described Interdecadal Pacific Oscillation (IPO) shifts climate every one to three decades and changes precipitation averages in these areas. These features of the climate system leave east coast dryland farming open to considerable climate variability. Records of potential soil moisture deficit (PSMD) around Napier and Ashburton show that significant PSMD developed in these regions by 1 December, in 50 to 85% of years with severe deficits in 20 to 55% of years. These deficits build as summer progresses. El Niño events intensify, whilst La Niña episodes normally ameliorate these conditions on seasonal time scales. The IPO climate shifts significantly change the dryness of the soil of these areas, with the transition from negative to positive phases increasing PSMD by 35 to 50 mm. Climate change over the next few decades will be driven by the underlying trend of global warming. For New Zealand, this will be a warming of about 0.2 °C per decade. The latest scenarios and climate model results indicate that westerly circulation is likely to strengthen over New Zealand, with a drying of east coast climate in the order of 10% by 2080. These will cause an increase in PSMD in the order of 20 to 30%. ENSO and IPO variability will be a continuing feature of New Zealand climate in coming decades. East coast dryland farms experience substantial climate variability. As climate warming continues in the decades of the 21st century, these areas will become increasingly stressed as potential evapotranspiration (PET) rates increase, particularly when the IPO next changes phase and during El Niño events. Climate forecasting is an exciting new technology that will give farmers early warning and increase preparedness for dry seasons ahead, allowing them to make key strategic decisions. A mixture of new and traditional technologies will also assist, such as intercropping and use of seasonal climate forecasting. Despite this, dryland farming systems are likely to become increasingly limited owing to low rainfall and high potential evapotranspiration rates.
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Yeung, Shirley Mo Ching. "Using ISO (PDCA) and SCOR (PSMD) concepts for strategic partnership". International Journal of Six Sigma and Competitive Advantage 9, n. 1 (2015): 3. http://dx.doi.org/10.1504/ijssca.2015.070052.
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Adeshakin, Funmilayo, Guizhong Zhang, Adeleye Adeshakin e Xiaochun Wan. "Abstract 265: Inhibiting proteasome in extracellular matrix (ECM) detached cells promotes anoikis". Cancer Research 82, n. 12_Supplement (15 giugno 2022): 265. http://dx.doi.org/10.1158/1538-7445.am2022-265.
Testo completoAbstract (sommario):
Abstract The underlying mediators for altered cell-extracellular matrix (ECM) communication in tumors remain to be understood and are likely to be multifactorial. Detached cells from the ECM are often cleared by a death process called ‘anoikis’. Anoikis is critical for health and homeostasis maintenance. However, aggressive cancer cells acquire anoikis resistance to promote invasion and metastasis in new sites. We previously identified metabolic reprogramming and upregulation of Vacuolar-ATPase members responsible for anoikis resistance while the manipulation of these pathways induced anoikis. However, the mechanisms underlying anoikis resistance and subsequent metastasis are yet to be fully elucidated, thus limiting anoikis-targeting drug exploration for metastasis control. Herein, our RNA-seq data revealed upregulated genes associated with proteasome activity (such as PSMA, PSMB, PSMD, and POMP) in ECM detached cancer cells compared to adherent cancer cells. Targeting this, using proteasome inhibitors (MG132 or bortezomib) in breast cancer, cervical, and melanoma cell lines sensitized cancer cells to anoikis through increased cellular, mitochondrial stress, and misfolded protein accumulation. Moreover, Bortezomib treatment in vivo in melanoma tumor model repressed metastasis. These data demonstrate proteasome activity is hijacked by ECM detached cancer cells to maintain proteostasis thus promoting anoikis resistance and metastasis. Regardless of the impressive outcome in treating hematological malignancies, proteasome inhibitors show little effect against solid tumors in several clinical trials that utilized selective and more potent inhibitors either as a single or in combinatory therapy. In this sense, our finding suggests proteasome inhibitors may be more attractive for metastasis control rather than local tumor treatment. Altogether, our findings demonstrate enhanced proteasome activity within the tumor cells is critical for anoikis resistance, and targeting this can markedly overcome resistance and control tumor metastasis. Citation Format: Funmilayo Adeshakin, Guizhong Zhang, Adeleye Adeshakin, Xiaochun Wan. Inhibiting proteasome in extracellular matrix (ECM) detached cells promotes anoikis [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 265.
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Dewi, Erti Ikhtiarini, Emi Wuri Wuryaningsih e Tantut Susanto. "Stigma Against People with Severe Mental Disorder (PSMD) with Confinement “Pemasungan”". NurseLine Journal 4, n. 2 (7 febbraio 2020): 131. http://dx.doi.org/10.19184/nlj.v4i2.13821.
Testo completoAbstract (sommario):
ABSTRAK
Pasung adalah tindakan pengekangan atau pembatasan aktivitas secara fisik untuk mengendalikan Orang dengan Gangguan Jiwa (ODGJ) yang tidak terkontrol oleh masyarakat biasa atau non profesional. Masalah yang dijumpai pada ODGJ yang dipasung adalah stigma dari masyarakat. Stigma merupakan salah satu faktor penghambat dalam penyembuhan ODGJ. Tujuan dari penelitian ini untuk mengetahui gambaran stigma masyarakat terhadap ODGJ yang dipasung. Desain penelitian menggunakan deskriptif kuantitatif. Sampel 150 responden dengan menggunakan teknik purposive sampling. Instrumen penelitian menggunakan kuesioner Community Attitudes toward the Mentally Ill. Analisis data yang digunakan adalah distribusi frekuensi. Hasil penelitian menunjukan 50.7 % masyarakat pro stigma sedangkan 49.3 % kontra stigma. Hasil penelitian menunjukkan masih terdapat stigma tentang ODGJ yang dipasung. Stigma terhadap ODGJ yang dipasung memiliki dampak negatif pada seluruh aspek kehidupan. ODGJ sering menjadi korban pada tindakan – tindakan kriminal, didiskriminasikan, dan dikucilkan. Pemasungan pada ODGJ dapat dicegah dan diatasi dengan melibatkan peran aktif semua pihak secara komprehensif.
Kata kunci : Gangguan Jiwa, Pasung, Stigma.
ABSTRACT
Pasung is an act of restraint or physical limitation of activities to control people with mental health disorders (ODGJ) that are not controlled by ordinary people or non-professionals. The problem encountered in the installed ODGJ is the stigma from the community. Stigma is one of the inhibiting factors in healing ODGJ. The purpose of this study is to find out the description of the community's stigma of ODGJ being put in a parachute. The study design uses quantitative descriptive. Sample of 150 respondents using purposive sampling technique. The research instrument used the Community Attitudes questionnaire toward the Mentally Ill. Analysis of the data used is the frequency distribution. The results showed that 50.7% of the people were pro-stigmatized while 49.3% were counter-stigmatized. The results showed that there was still a stigma about the ODGJ being installed. The stigma of the ODGJ installed has a negative impact on all aspects of life. ODGJ are often victims of criminal acts, discriminated against and excluded. Inclusion in ODGJ can be prevented and overcome by involving the active role of all parties comprehensively.
Keywords: Mental Health Disorders, Pasung, Stigma.
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Park, Hyeyoung, Sunghoon Lee, Amelia Bailey, Yunda Liu e Cynthia Jacelon. "UNVEILING THE COMPLEX REALITIES: UNDERSTANDING SLEEP AND FATIGUE CHARACTERISTICS OF END-OF-LIFE CAREGIVERS". Innovation in Aging 7, Supplement_1 (1 dicembre 2023): 1148. http://dx.doi.org/10.1093/geroni/igad104.3684.
Testo completoAbstract (sommario):
Abstract This mixed methods multi-case study explores sleep and fatigue characteristics among end-of-life caregivers. The research sample encompasses cases aiding individuals with advanced (n=4) and chronic illnesses (n=1), including various caregiver demographics such as gender, age groups (19-64 and 65+), and health conditions. Data collection involves comprehensive surveys capturing demographics, care recipient symptom intensity, caregiver depressive symptoms, caregiving stress, caregiver sleep quality, and caregiver fatigue level. The study integrates data from a 30-day Personal Sleep Monitoring Device (PSMD) and a 14-day sleep journal, enriched by insights from semi-structured interviews and field notes. The outcomes indicate a PSQI (Pittsburgh Sleep Quality Index) score of 6.1, accompanied by 7.44 hours of sleep recorded by the PSMD. There were approximately 20.5 nocturnal awakenings within 30 days, with average fatigue at 55.28 and daily fatigue at 49.66. Objective sleep outcomes were consistent among caregivers, while their own sleep ratings ranged from “Fairly Bad” to “Very Good.” Themes for each case were formulated to delve into the context of these sleep and fatigue characteristics. These themes encompass adaptive leadership, linchpin roles, emotional labor management, self-reliance, and vigilance. A prevailing overarching theme is the perception of “Not having control.” A significant finding underscores the dynamic influence of care recipients’ daily statuses on caregivers’ sleep quality and fatigue levels, leading to unpredictable outcomes. This study offers profound insights into end-of-life caregivers’ intricate journeys, highlighting individual differences and the dynamic nature of caregiving roles, while recognizing the importance of tailored interventions for enhancing caregiver’s well-being and caregiving effectiveness.
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Du, Lianming, Qin Liu, Kelei Zhao, Jie Tang, Xiuyue Zhang, Bisong Yue e Zhenxin Fan. "PSMD: An extensive database for pan‐species microsatellite investigation and marker development". Molecular Ecology Resources 20, n. 1 (28 ottobre 2019): 283–91. http://dx.doi.org/10.1111/1755-0998.13098.
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Azouzi, Slim, Mahmoud Mikdar, Sara El Hoss, Alexandra Willemetz, Emilie-fleur Gautier, Patrick Mayeux, Wassim El Nemer, Yves Colin, Caroline Le Van Kim e Thierry Peyrard. "Comparative Proteomics and Functional Analysis of Red Blood Cell Membrane Proteins in the Rare in(Lu) Blood Type". Blood 130, Suppl_1 (7 dicembre 2017): 934. http://dx.doi.org/10.1182/blood.v130.suppl_1.934.934.
Testo completoAbstract (sommario):
Abstract KLF1 is an essential erythroid transcription factor (EKLF) involved both in the ß-globin switch from fetal to adult and in definitive erythropoiesis. KLF1 also activates genes encoding heme biosynthetic enzymes, as well as genes involved in the cell cycle and the synthesis of membrane proteins. Heterozygosity for one or several nucleotide changes in KLF1 may be responsible for the so-called dominant Lu(a-b-) phenotype, also known as In(Lu) for "Inhibitor Lutheran" and characterized by a dramatic reduction in the expression levels of the Lutheran blood group antigens and a slight elevation in hemoglobin F (HbF). Several other blood group antigens are also under the direct control of KLF1, but their number and expression level in In(Lu) red blood cells (RBCs) remain a matter of debate. In addition, mutations in KLF1 in humans lead to anemia, acantocytosis and some of these variants, such as CDA type IV, are characterized by ineffective terminal differentiation and defects in enucleation. Given the major role of KLF1 in erythropoiesis, it would not be surprising that In(Lu) RBCs show abnormal properties. In this work, we performed proteomic studies to quantify membrane proteins in In(Lu) vs control RBCs. Results: using label-free mass spectrometry, we analyzed the expression levels of membrane proteins in 5 In(Lu) and 4 control RBCs. Hierarchical clustering allowed to identify two modulation profiles of protein expression (Figure 1). The first profile (red color) is composed of 49 proteins over-expressed in In(Lu) RBCs, with the majority of them corresponding to the "26S proteasome complex" (PSMA, PSMB, PSMD, and PSME). In addition, we confirmed the overexpression of the 26S proteasome complex in In(Lu) RBCs by western blot analyses. The second profile (green color) includes 23 membrane proteins with a lower expression level in In(Lu) RBCs; these proteins correspond to blood group antigens (e.g. Lu/BCAM, CD44), and to cytoskeletal proteins (e.g. dematin, flotillin). Five proteins carrying blood group systems show a decrease of expression in In(Lu) RBCs over 40%: Chido/Rodgers, Xg, Indian, Duffy and Lutheran: antigens. While our results indicating of decreased expression of Indian and Chido/Rodgers systems are consistent with previous reports, the Duffy expression was unexpectedly found to be decreased by 86%. Since we evidenced an important increase in the proteasome complex, and taking into account that KLF1 is involved in the regulation or erythropoiesis, we, investigated the expression profile of the 26 S proteasome expression during erythropoiesis. We observed an important decrease of all proteins of the proteasome complex during erythropoiesis. Conclusion: from our preliminary results reported in this study, we hypothesized that the increase of the 26S proteasome in the In(Lu) individuals may result from defects in organelle loss and could explain the profound dyserytropoiesis observed in the "nan" mice null for KLF1. Figure 1: Comparative proteomics of red blood cell membrane proteins in In(Lu) blood group type. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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Koh, Seok-Keun, Cheol Su Lee, Jung Hwan Lee e Katherine Koh. "Initial Ag Thin-Film Growths on a Polycarbonate Substrate at Periodic Step Mode Deposition (PSMD)". Journal of Nanoscience and Nanotechnology 16, n. 11 (1 novembre 2016): 11542–47. http://dx.doi.org/10.1166/jnn.2016.13548.
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Haertle, Larissa, Santiago Barrio, Michal Simicek, Umair Munawar, Ricardo Sanchez, Max Bittrich, Matteo DaVia et al. "Mechanisms of Proteasome Inhibitor Resistance Selected By Clonal Evolution in Multiple Myeloma". Blood 134, Supplement_1 (13 novembre 2019): 4349. http://dx.doi.org/10.1182/blood-2019-130847.
Testo completoAbstract (sommario):
Background: Various treatment regimen in multiple myeloma (MM) are based on proteasome inhibition (PI). Although effective at therapy start, most patients relapse and develop drug resistance over time. To better understand the molecular underpinnings associated with PI resistance, we studied genetic and epigenetic alterations of the 26S proteasome genes in PI exposed patients. Methods: We performed a meta-analysis comprised of M3P targeted sequencing datasets and other publicly available WGS/WES sets. A selection of most frequently found mutations was tested in vitro regarding their impact on PI response. DNA promoter methylation of a subset of proteasome genes was determined by targeted Deep Bisulfite Sequencing (DBS), followed up on expression (Taqman qPCR) and validated at functional level (dual-luciferase reporter assay system). Results: The meta-analysis was conducted for a total of 1,752 MM cases, with 1,241 newly diagnosed (NDMM) and 511 progressed MM (PMM) samples. We identified mutations in 32 proteasome genes, with increased incidence from NDMM (6.1% of the patients had mutations in one or more genes) to 10.2% at PMM. Besides PSMB5 encoding for the inhibitor binding site, mainly 19S subunit genes were mutated in areas that impact the recognition of ubiquitinated proteins (PSMD1 and PSMD2), are involved in protein unfolding or gate opening (PSMC1-6). We stably expressed proteasome subunit components bearing frequently observed patient-derived mutations in RPMI-8226 MM cells. All mutants (PSMC6 R242Q, PSMD1 E824K, PSMD1 A887T, PSMD2 M646I, PSMC2 Y429S) displayed an impaired PI response towards Bortezomib (Figure A), Carfilzomib and Ixazomib. Of note, in a fluorescent based, in house clonal competition assay, Bortezomib resistant PSMB5 A20T mutants were outcompeted by WT cells when the drug was removed from co-culture, demonstrating a survival disadvantage through the mutation itself, when no selective pressure of proteasome inhibition was applied. In general, somatic mutations on single gene level were relatively rare, PSMD1, our best candidate gene, was mutated in only 2% of the analyzed MM patients, the remaining genes even to an lower extent, but the proteasome as a whole structure, was frequently affected by mutations. Therefore, we hypothesized that clonal evolution might also act by selecting epigenetic alterations. To address this, we analyzed promoter methylation of PSMC2, PSMC5, PSMC6, PSMD1 and PSMD5 in 42 MM patients by DBS. For PSMD5, NDMM patients and PBMCs were nearly unmethylated (mean methylation: 2.0%±0.020 and 2.0%±0.026), but PMM displayed noticeably increased hypermethylation (6%±0.099). We demonstrated epigenetic silencing by promoter hypermethylation (methylation degree ≥15%) in 20% of PI resistant patients. Moreover, at RNA level we confirmed that patients with high methylation had low expression of PSMD5 and vice versa. To explore the regulatory impact of PSMD5 promoter methylation on gene regulation, we now cloned our amplicon into the backbone of a CpG-free vector (pCpGL). The reporter vector with either the methylated or the unmethylated insert was co-transfected with a Renilla control vector into L363 cells. Luciferase activity of the unmethylated PSMD5 construct was 8 times increased compared to the methylated vector and the controls (vector without insert and non-transfected cells) (Figure B), confirming gene regulation through methylation of this gene. PSMD5, encodes a chaperon recently characterized as the main regulator of 19S proteasome assembly. Gene silencing may represent an adaptive way of cancer cells to bypass proteasome inhibition and escape PI induced proteolytic toxicity by increasing their protein turnover capacity. Conclusion: Altogether our data give evidence that after PI exposition, MM patients harbor acquired regulatory DNA mutations as well as epimutations that affect different proteasomal subunits and, by different modes of action, compromise proteasome activity to escape PI therapy. Figure Disclosures Bittrich: German Research Foundation (DFG): Other: N/A; University of Würzburg: Other: N/A; Bristol Myers Squibb: Research Funding; Otsuka Pharmaceuticals Europe: Other: N/A; Pfizer: Other: Travel Funding; Wilhelm Sander Foundation: Research Funding; Else Kröner Fresenius Foundation: Research Funding; Celgene: Other: Travel Funding, Research Funding; JAZZ Pharmaceuticals: Other: Travel Funding; AMGEN: Other: Travel Funding; University Hospital Wuerzburg: Employment; SANOFI Aventis: Membership on an entity's Board of Directors or advisory committees, N/A, Research Funding.
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Reed, Sarah A., Jeremy Balsbaugh, Xiaomeng Li, Timothy Moore, Amanda Jones, Sambhu Pillai, Maria L. Hoffman, Kristen E. Govoni e Steven A. Zinn. "526 Late-Breaking: Poor Maternal Diet Alters the Muscle Proteome at Mid-gestation in Sheep". Journal of Animal Science 99, Supplement_3 (8 ottobre 2021): 149–50. http://dx.doi.org/10.1093/jas/skab235.274.
Testo completoAbstract (sommario):
Abstract Maternal diet during gestation can negatively impact fetal development and postnatal growth and body composition. We hypothesized that poor maternal nutrition during gestation would alter protein expression in muscle at day 90 of gestation in sheep. Pregnant ewes (n = 24) were fed a control, restricted, or over-fed diet (100, 60, or 140% of NRC requirements for total digestible nutrients, respectively; n = 8 per treatment) starting at day 30 of gestation. At day 90 of gestation, fetal longissimus dorsi samples were collected (CON, RES, and OVER, respectively). Sarcoplasmic proteins were trypsin digested and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating Tandem Mass Tags. Differential expression of proteins was identified via two statistical techniques: ANOVA followed by Tukey’s HSD post-hoc tests, and regularized regression via elastic net. Significance was set at P < 0.05. Over-represented pathways containing differentially expressed proteins were identified by Reactome and included metabolism of proteins, immune system, cellular response to stress/external stimuli, developmental biology, and infectious disease. Within these pathways, 26S proteasome non-ATPase regulatory subunit (PSMD) 1, PSMD6, and PSMD14, components of the 26 S proteasome, were reduced 6 to 10% in OVER relative to CON offspring. Proteins involved in elongation and initiation, including eukaryotic initiation factor (EIF) 2 subunit 3, EIF 4 gamma 2, and EIF 3 subunit B were reduced 8 to 15% in OVER relative to CON offspring. Mitogen-activated protein kinase (MAPK) 1 and dual-specificity MAPK kinase (MEKK) 1 were increased by 12% in RES relative to OVER and CON offspring. Together, these data indicate that protein degradation and synthesis are altered in mid-gestation muscle development in OVER offspring, and that cell signaling related to cell proliferation is affected in RES offspring. These changes may contribute to the phenotypic and metabolic changes observed during fetal development and postnatal growth.
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Bencomo-Alvarez, Alfonso E., Andres J. Rubio, Idaly M. Olivas, Mayra A. Gonzalez, Rebecca Ellwood, Carme Ripoll Fiol, Christopher A. Eide et al. "Proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), play an oncogenic role in chronic myeloid leukemia by stabilizing nuclear factor-kappa B". Oncogene 40, n. 15 (12 marzo 2021): 2697–710. http://dx.doi.org/10.1038/s41388-021-01732-6.
Testo completoAbstract (sommario):
AbstractTyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 have revolutionized therapy for chronic myeloid leukemia (CML), paving the way for clinical development in other diseases. Despite success, targeting leukemic stem cells and overcoming drug resistance remain challenges for curative cancer therapy. To identify drivers of kinase-independent TKI resistance in CML, we performed genome-wide expression analyses on TKI-resistant versus sensitive CML cell lines, revealing a nuclear factor-kappa B (NF-κB) expression signature. Nucleocytoplasmic fractionation and luciferase reporter assays confirmed increased NF-κB activity in the nucleus of TKI-resistant versus sensitive CML cell lines and CD34+ patient samples. Two genes that were upregulated in TKI-resistant CML cells were proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), both members of the 19S regulatory complex in the 26S proteasome. PSMD1 and PSMD3 were also identified as survival-critical genes in a published small hairpin RNA library screen of TKI resistance. We observed markedly higher levels of PSMD1 and PSMD3 mRNA in CML patients who had progressed to the blast phase compared with the chronic phase of the disease. Knockdown of PSMD1 or PSMD3 protein correlated with reduced survival and increased apoptosis in CML cells, but not in normal cord blood CD34+ progenitors. Luciferase reporter assays and immunoblot analyses demonstrated that PSMD1 and PSMD3 promote NF-κB protein expression in CML, and that signal transducer and activator of transcription 3 (STAT3) further activates NF-κB in scenarios of TKI resistance. Our data identify NF-κB as a transcriptional driver in TKI resistance, and implicate PSMD1 and PSMD3 as plausible therapeutic targets worthy of future investigation in CML and possibly other malignancies.
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Sayiprathap, B. R., A. K. Patibanda, V. Prasanna Kumari, K. Jayalalitha, V. Srinivasa Rao e Hari Kishan Sudini. "Multi-location Evaluation of Phytohormones and Chemicals for the Management of Pigeonpea Sterility Mosaic Disease (PSMD)". International Journal of Current Microbiology and Applied Sciences 9, n. 7 (10 luglio 2020): 3278–84. http://dx.doi.org/10.20546/ijcmas.2020.907.381.
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Olivas, Idaly Maria, Joshua Lara, Rebecca Ellwood, Carme Ripoll Fiol, Andres J. Rubio, Alfonso Enrique Bencomo, Mayra Alejandra Gonzalez et al. "NF-κB-Dependent Activation of the Proteasome Components, PSMD1 and PSMD3, As a Mechanism of Resistance to Imatinib". Blood 134, Supplement_1 (13 novembre 2019): 2923. http://dx.doi.org/10.1182/blood-2019-126963.
Testo completoAbstract (sommario):
Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 are remarkably effective therapies in chronic myeloid leukemia (CML). Despite clinical success, TKIs do not target the CML leukemic stem cell (LSC), and the majority of patients must be treated for life to maintain remission. Our previous work has shown that BCR-ABL1-independent resistance is driven by STAT3 in CML stem/progenitor cells (Eiring et al. Leukemia 2015). Unexpectedly, RNA-sequencing on TKI-resistant K562 cells (K562-R) versus parental controls (K562-S) revealed that resistance is not associated with STAT3-mediated transcription, but is rather reminiscent of TNFa signaling via NF-κB (p=0.024). Nucleocytoplasmic fractionation confirmed these findings, demonstrating higher levels of phospho-NF-κB in the nucleus of CD34+ cells from TKI-resistant patients (n=3) compared to newly diagnosed CML patients (n=2) or normal individuals (n=2). Surprisingly, ELISA results revealed that K562-R cells do not produce autonomous TNFa, but they do produce IL-6 (p<0.01). These data suggest that NF-κB may be driving the gene expression signature of BCR-ABL1-independent resistance, and implicate non-canonical functions for STAT3. To better understand the mechanism by which NF-κB drives resistance, we correlated our RNA sequencing data with gene expression profiles of CML patients not responding to imatinib (McWeeney et al. Blood 2010), identifying 36 genes commonly dysregulated in both TKI-resistant cell lines and patient samples. Of the 30 upregulated genes, 21 had p65-NF-κB bound to their promoter regions via ChIP in hematopoietic cells (UCSC Genome Brower). Two of these genes are members of the ubiquitin proteasome system, including PSMD1 and PSMD3, both of which were implicated as hits in a previously published shRNA library screen for BCR-ABL1-independent resistance (Khorashad et al. Blood 2015). PSMD1 and PSMD3 are non-ATPase subunits of the 19S regulatory complex in the 26S proteasome, likely involved in proteasome substrate recognition and binding. In breast cancer, PSMD1 was shown to regulate cell growth by inducing p53 degradation (Okumura et al. 2018), whereas PSMD3 was shown to protect HER2 from degradation (Fararjeh et al. 2019). qRT-PCR confirmed upregulation of PSMD1 and PSMD3 by 3-fold and 6-fold, respectively, in K562-R cells versus parental controls in the presence of imatinib. Interestingly, according to data from The Cancer Genome Atlas (TGCA), higher levels of PSMD1 and PSMD3 mRNA correlates with a worse prognosis in acute myeloid leukemia (PSMD1, p=0.0138; PSMD3, p=0.0229). We hypothesized that PSMD1 and PSMD3 upregulation contributes to NF-κB activation and TKI resistance. We used doxycycline-inducible shRNAs to assess the function of PSMD1 and PSMD3 in CML cell survival and TKI response. Induction of knockdown (100 ng/mL doxycycline, 72h) resulted in a reduction of PSMD1 and PSMD3 mRNA and protein by ~73% and ~77%, respectively, in K562-R cells. Importantly, immunoblot analysis revealed that knockdown of either PSMD1 or PSMD3 in TKI-resistant K562-R cells resulted in a significant reduction of phospho-NF-κB (p65), suggesting that upregulation of these proteins promotes NF-κB activation. Reduced phospho-NF-κB (p65) correlated with phenotypic effects, including reduced colony formation, increased response to TKIs as assessed in MTS assays, and increased apoptosis in both the presence and absence of imatinib. Our results suggest that NF-κB activation in TKI resistance depends on the proteasome components, PSMD1 and PSMD3, forming a positive feedback loop potentiating NF-κB signaling. Our data also suggest that specific targeting of the ubiquitin proteasome system through either PSMD1 or PSMD3 may be a novel strategy to restore TKI sensitivity in patients with BCR-ABL1-independent TKI resistance. Future studies will address the non-canonical functions of STAT3 in TKI resistance. Disclosures Milojkovic: Novartis: Honoraria, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau. Apperley:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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Li, Xiao, Xinru Li, Yuexin Hu, Ouxuan Liu, Yuxuan Wang, Siting Li, Qing Yang e Bei Lin. "PSMD8 can serve as potential biomarker and therapeutic target of the PSMD family in ovarian cancer: based on bioinformatics analysis and in vitro validation". BMC Cancer 23, n. 1 (22 giugno 2023). http://dx.doi.org/10.1186/s12885-023-11017-8.
Testo completoAbstract (sommario):
Abstract Background The ubiquity-proteasome system is an indispensable mechanism for regulating intracellular protein degradation, thereby affecting human antigen processing, signal transduction, and cell cycle regulation. We used bioinformatics database to predict the expression and related roles of all members of the PSMD family in ovarian cancer. Our findings may provide a theoretical basis for early diagnosis, prognostic assessment, and targeted therapy of ovarian cancer. Methods GEPIA, cBioPortal, and Kaplan–Meier Plotter databases were used to analyze the mRNA expression levels, gene variation, and prognostic value of PSMD family members in ovarian cancer. PSMD8 was identified as the member with the best prognostic value. The TISIDB database was used to analyze the correlation between PSMD8 and immunity, and the role of PSMD8 in ovarian cancer tissue was verified by immunohistochemical experiments. The relationship of PSMD8 expression with clinicopathological parameters and survival outcomes of ovarian cancer patients was analyzed. The effects of PSMD8 on malignant biological behaviors of invasion, migration, and proliferation of ovarian cancer cells were studied by in vitro experiments. Results The expression levels of PSMD8/14 mRNA in ovarian cancer tissues were significantly higher than those in normal ovarian tissues, and the expression levels of PSMD2/3/4/5/8/11/12/14 mRNA were associated with prognosis. Up-regulation of PSMD4/8/14 mRNA expression was associated with poor OS, and the up-regulation of PSMD2/3/5/8 mRNA expression was associated with poor PFS in patients with ovarian serous carcinomas. Gene function and enrichment analysis showed that PSMD8 is mainly involved in biological processes such as energy metabolism, DNA replication, and protein synthesis. Immunohistochemical experiments showed that PSMD8 was mainly expressed in the cytoplasm and the expression level was correlated with FIGO stage. Patients with high PSMD8 expression had poor prognosis. Overexpression of PSMD8 significantly enhanced the proliferation, migration, and invasion abilities in ovarian cancer cells. Conclusion We observed different degrees of abnormal expression of members of PSMD family in ovarian cancer. Among these, PSMD8 was significantly overexpressed in ovarian malignant tissue, and was associated with poor prognosis. PSMDs, especially PSMD8, can serve as potential diagnostic and prognostic biomarkers and therapeutic targets in ovarian cancer.
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Huang, Guanrong, Jiannong Lu, Xuegui Yin, Liuqin Zhang, Haihong Lin, Xiaoxiao Zhang, Chaoyu Liu e Jinying Zuo. "Integrating QTL mapping with transcriptome analysis mined candidate genes of growth stages in castor (Ricinus communis L.)". BMC Genomics 26, n. 1 (22 febbraio 2025). https://doi.org/10.1186/s12864-025-11348-9.
Testo completoAbstract (sommario):
Abstract Background The growth stages largely determine the crop yield, while little is known about their genetic mechanisms in castor. In this study, the QTL mapping and candidate gene mining of growth stages were conducted using populations F2 and BC1, combining with differential expression analysis and weighted gene co-expression network analysis (WGCNA). The traits studied included the emergence date (ED), the budding date of primary spike (PSBD), the flowering date of primary spike (PSFD), the maturation date of primary spike (PSMD), and the maturation date of primary branch spike (PBSMD). Results A total of 20 QTLs conferring four traits (ED, PSBD, PSFD and PBSMD) were identified in the F2 population, with a phenotypic variation explained (PVE) of single QTL ranged from 0.24 to 25.46%. Five QTLs underlying PSMD and PBSMD were identified in the BC1 population, with a PVE of single QTL ranged from 4.74 to 10.82%. To our surprise, almost all the identified QTLs were clustered within two marker intervals, the RCM1769-RCM1838 on linkage group 6 and RCM950-RCM917 on linkage group 3. Subsequently, 473 open reading frames (ORFs) were searched out within these two clusters and 110 differentially expressed genes (DEGs) were screened out from these ORFs by the comparative transcriptome clean data (a total of 140.86 G) at the budding date, the initial flowering date and the full flowering date between parental racemes. With these DEGs, five distinct gene co-expression modules were generated using WGCNA. Showing significant differential expression between parents, four candidate genes (LOC8261128, LOC8278994, LOC8281165 and LOC8259049) in module MEturquoise, were recognized and were annotated as RcSYN3, RcNTT, RcGG3 and RcSAUR76 respectively. This finding implies their potential role in regulating the growth stages of castor. Conclusion In this study, numerous QTLs conferring growth stages were detected and four candidate genes were mined, which need to be functionally validated. The results provided a new insight into the genetic structure of ED, PSBD, PSFD, PSMD and PBSMD, offered the candidate genes and molecular markers for their improvement as well in castor.
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Khan, Shahbaz, Atif Rasool, Sohail Irshad, Muhammad Bilal Hafeez, Madad Ali, Maham Saddique, Muhammad Asif et al. "Potential soil moisture deficit: A useful approach to save water with enhanced growth and productivity of wheat crop". Journal of Water and Climate Change, 15 aprile 2021. http://dx.doi.org/10.2166/wcc.2021.356.
Testo completoAbstract (sommario):
Abstract Wheat is the main crop in the world ranks after rice and the largest grain source of Pakistan. Among several reasons for diminishing wheat yield in Pakistan, water stress throughout the growing season decreases crop production because of the short life span. Two years (2015–16 and 2016–17) of field experiments were conducted to assess the impact of various water regimes (full irrigation, irrigation at 45, 60, and 75 mm potential soil moisture deficit (PSMD)) on the growth and yield of wheat. Maximum crop growth rate was recorded by application of irrigation at 45 mm PSMD. Application of irrigation at 45 mm PSMD ensured maximum radiation use efficiency regarding total dry matter production and grain yield. The maximum number of productive tillers, spike length, and grain yield were recorded under 45 mm PSDM treatment. The present results show that the effect of water is more pronounced regarding the growth and productivity of wheat. Application of irrigation at 45 mm PSMD ensures higher economical yield.
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Xu, Man, Kangkang Xue, Xueqin Song, Yong Zhang, Jingliang Cheng e Junying Cheng. "Peak width of skeletonized mean diffusivity as a neuroimaging biomarker in first-episode schizophrenia". Frontiers in Neuroscience 18 (23 settembre 2024). http://dx.doi.org/10.3389/fnins.2024.1427947.
Testo completoAbstract (sommario):
Background and objectivePeak width of skeletonized mean diffusivity (PSMD), a fully automated diffusion tensor imaging (DTI) biomarker of white matter (WM) microstructure damage, has been shown to be associated with cognition in various WM pathologies. However, its application in schizophrenic disease remains unexplored. This study aims to investigate PSMD along with other DTI markers in first-episode schizophrenia patients compared to healthy controls (HCs), and explore the correlations between these metrics and clinical characteristics.MethodsA total of 56 first-episode drug-naive schizophrenia patients and 64 HCs were recruited for this study. Participants underwent structural imaging and DTI, followed by comprehensive clinical assessments, including the Positive and Negative Syndrome Scale (PANSS) for patients and cognitive function tests for all participants. We calculated PSMD, peak width of skeletonized fractional anisotropy (PSFA), axial diffusivity (PSAD), radial diffusivity (PSRD) values, skeletonized average mean diffusivity (MD), average fractional anisotropy (FA), average axial diffusivity (AD), and average radial diffusivity (RD) values as well as structural network global topological parameters, and examined between-group differences in these WM metrics. Furthermore, we investigated associations between abnormal metrics and clinical characteristics.ResultsCompared to HCs, patients exhibited significantly increased PSMD values (t = 2.467, p = 0.015), decreased global efficiency (Z = −2.188, p = 0.029), and increased normalized characteristic path length (lambda) (t = 2.270, p = 0.025). No significant differences were observed between the groups in the remaining metrics, including PSFA, PSAD, PSRD, average MD, FA, AD, RD, local efficiency, normalized cluster coefficient, small-worldness, assortativity, modularity, or hierarchy (p > 0.05). After adjusting for relevant variables, both PSMD and lambda values exhibited a significant negative correlation with reasoning and problem-solving scores (PSMD: r = −0.409, p = 0.038; lambda: r = −0.520, p = 0.006). No statistically significant correlations were observed between each PANSS score and the aforementioned metrics in the patient group (p > 0.05). Multivariate linear regression analysis revealed that increased PSMD (β = −0.426, t = −2.260, p = 0.034) and increased lambda (β = −0.490, t = −2.994, p = 0.007) were independently associated with decreased reasoning and problem-solving scores respectively (Radj2 = 0.295, F = 2.951, p = 0.029). But these significant correlations did not withstand FDR correction (p_FDR > 0.05).ConclusionPSMD can be considered as a valuable neuroimaging biomarker that complements conventional diffusion measurements for investigating abnormalities in WM microstructural integrity and cognitive functions in schizophrenia.
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Jarholm, Jonas Alexander, Sandra Tecelao, Lene Pålhaugen, Bjørn‐Eivind Kirsebom, Atle Bjornerud, Tormod Fladby e Per Selnes. "The role of Peak width Skeletonized Mean Diffusivity in AD disease progression". Alzheimer's & Dementia 20, S8 (dicembre 2024). https://doi.org/10.1002/alz.095692.
Testo completoAbstract (sommario):
AbstractBackgroundCerebral small vessel disease (CSVD) is common in Alzheimer’s disease (AD), but it is unclear how CSVD affects cognition and disease progression. Peak width of Skeletonized Mean Diffusivity (PSMD) is a Magnetic Resonance Imaging (MRI) marker of global white matter integrity, believed to reflect both total vascular burden and the cognitive impact of CSVD. We examined the relationship between PSMD and memory, processing speed and executive function, and to assess the predictive value of PSMD on clinical progression.Method265 cases and controls between 40‐80 years old were recruited from the Norwegian multi‐center study DDI (Dementia Disease Initiation), with 2‐5 follow ups (0.7‐8 years). Subjects were according to the Clinical Dementia Rating (CDR), with 0 as cognitively unimpaired (CU) if, 0,5 as mild cognitive impairment (MCI) if CDR, and ≥ 1 as dementia. Amyloid status was determined from Amyloid‐PET or from amyloid‐β42/40. PSMD was obtained from 6 MRI scanners and harmonized for scanner effects in R using ComBat, with age, sex, staging and amyloid status at baseline as covariates.The relationship between PSMD and cognitive scores was assessed using a general linear model, with age, sex, education and an PSMD‐amyloid interaction variable as covariates. Subjects were classified into the following groups: A‐ low PSMD, A+ low PSMD, A‐ low PSMD, A+ high PSMD high, where PSMD high or low signifies above or below the group median. Survival analysis was performed in 195 subjects, using the “survival” package from R, with progression from CU to MCI/dementia or from MCI to dementia as the events of interest. Hazard ratios were assessed with the Cox proportional‐hazards model with age and A status/PSMD at baseline and sex as covariates.ResultThere was a significant relationship (p<0.01) between PSMD and TMT A and B, but not with CERAD recall. PSMD low A+ subjects had 5.5 times higher risk of cognitive decline (p<0.01) than PSMD low A‐, while PSMD high A+ had 14.3 times higher risk.ConclusionWe found that high PSMD load increases the risk of AD disease progression, but is not significantly associated with delayed recall, the core cognitive biomarker of AD.
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Wang, Dan, Zheng Sun e Yuehua Li. "Horizontal analysis and longitudinal cohort study of chronic renal failure correlates and cerebral small vessel disease relationship using peak width of skeletonized mean diffusivity". Frontiers in Neurology 15 (6 settembre 2024). http://dx.doi.org/10.3389/fneur.2024.1461258.
Testo completoAbstract (sommario):
Background and purposePeak width of skeletonized mean diffusivity (PSMD) is an MRI-based biomarker that may reflect white matter lesions (WML). PSMD is based on skeletonization of MR DTI data and histogram analysis. Both chronic renal failure (CRF) and WML may be affected by multisystemic small-vessel disorder. We aimed to explore the relationship between PSMD and estimated glomerular filtration rate (eGFR).MethodsFifty followed-up CRF patients matched for age, sex, hypertension and smoking status were enrolled and classified into a progressive group (n = 16) and stable group (n = 34) based on eGFR levels. Longitudinal and horizontal differences of PSMD were compared between the progressive and stable groups at the initial and follow-up time points. Pearson’s correlation was used for correlation of eGFR with PSMD and WML (per Fazekas scale score). ROC was used to measure the sensitivity of PSMD and WML score to changes of eGFR.ResultsAt the follow-up time point, PSMD of the progressive group was significantly higher than at the initial time point (p < 0.001), and PSMD of the progressive group was significantly higher than stable group (p < 0.001). PSMD and eGFR were significantly correlated. AUC curves explored that ΔPSMD (PSMD changes at the follow-up and initial time points) and follow-up PSMD was better for the classification of progressive and stable groups.ConclusionPSMD has significant correlation with eGFR, PSMD can reveal a close relationship between WML and CRF.
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Luckey, Alison M., Saptaparni Ghosh, Chen‐Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji et al. "Biological validation of peak‐width of skeletonized mean diffusivity as a VCID biomarker: The MarkVCID Consortium". Alzheimer's & Dementia, 21 novembre 2024. http://dx.doi.org/10.1002/alz.14345.
Testo completoAbstract (sommario):
AbstractBACKGROUNDPeak‐width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.METHODSWe included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID‐1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure of general cognitive function using linear regression models adjusting for confounders.RESULTSHigher PSMD was associated with lower general cognition in MarkVCID‐1 independent of age, sex, education, and intracranial volume (Beta [95% confidence interval], −0.8 [−1.2, −0.4], P < 0.001). These findings were replicated in independent samples. Furthermore, PSMD explained cognitive status above and beyond white matter hyperintensities.DISCUSSIONOur biological validation work supports the pursuit of larger clinical validation studies evaluating PSMD as a susceptibility/risk biomarker of small vessel disease contributing to cognitive impairment and dementia.Highlights Peak‐width of skeletonized mean diffusivity (PSMD) is a novel small vessel disease neuroimaging biomarker. A prior instrumental validation study demonstrated that PSMD is a robust biomarker. This biological validation study shows that high PSMD relates to worse cognition. PSMD explains cognitive function above and beyond white matter hyperintensities. Future clinical validation will assess PSMD as a vascular contribution to cognitive impairment and dementia biomarker in clinical trials.
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Kim, Jinseung, Dong Ah Lee, Ho-Joon Lee e Kang Min Park. "Small-vessel-disease-induced white matter damage in occipital lobe epilepsy". Frontiers in Neurology 16 (11 febbraio 2025). https://doi.org/10.3389/fneur.2025.1538598.
Testo completoAbstract (sommario):
BackgroundPeak width of skeletonized mean diffusivity (PSMD) is a novel marker of small vessel disease. This study aimed to investigate the presence of small vessel disease in patients with occipital lobe epilepsy (OLE) using PSMD.MethodsWe enrolled 27 patients newly diagnosed with OLE and included 29 healthy controls. The age and sex of the patients and controls were comparable. Diffusion tensor imaging (DTI) was performed using a 3 T MRI scanner. We measured the PSMD based on DTI in several steps, including preprocessing, skeletonization, application of a custom mask, and histogram analysis, using the FSL program. We compared PSMD between patients with OLE and healthy controls. Additionally, we performed a correlation analysis between PSMD and clinical factors in patients with OLE.ResultsOur findings revealed that the patients with OLE exhibited higher PSMD compared to healthy controls (2.459 vs. 2.079 × 10−4 mm2/s, p < 0.001). In addition, PSMD positively correlated with age (r = 0.412, p = 0.032). However, the PSMD of the patients with OLE was not associated with other clinical factors such as age at seizure onset and duration of epilepsy.ConclusionWe demonstrated that patients with OLE had a higher PSMD than healthy controls, indicating evidence of small vessel disease in patients with OLE. This finding also highlights the potential of PSMD as a marker for detecting small vessel diseases in epileptic disorders.
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Lee, Dong Ah, Ho‐Joon Lee e Kang Min Park. "Brain MRI Detection of an Abnormal Peak Width of Skeletonized Mean Diffusivity in REM Sleep Behavior Disorder". Journal of Neuroimaging 35, n. 1 (gennaio 2025). https://doi.org/10.1111/jon.70009.
Testo completoAbstract (sommario):
ABSTRACTBackground and PurposePeak width of skeletonized mean diffusivity (PSMD) is a novel marker of white matter damage, which may be related to small vessel disease. This study aimed to investigate the presence of white matter damage in patients with isolated rapid eye movement sleep behavior disorder (RBD) using PSMD.MethodsWe enrolled patients with newly diagnosed isolated RBD confirmed by polysomnography and age‐ and sex‐matched healthy controls. Diffusion tensor imaging (DTI) was conducted using a 3‐Tesla MRI scanner. We measured the PSMD based on DTI in several steps, including preprocessing, skeletonization, application of a custom mask, and histogram analysis, using the Functional Magnetic Resonance Imaging of the Brain Software Library program. We compared the incidence of PSMD between patients with RBD and healthy controls and performed a correlation analysis between PSMD and clinical factors in patients with RBD.ResultsThirty patients with isolated RBD and 41 healthy controls were enrolled. The PSMD was significantly higher in patients with RBD than that in the healthy controls (3.078 vs. 2.746 × 10−4 mm2/s, p = 0.001). In addition, PSMD positively correlated with age in patients with RBD (r = 0.477, p = 0.007). However, PSMD was not associated with other clinical or polysomnographic factors.ConclusionPatients with isolated RBD had a higher PSMD than healthy controls, indicating the evidence of white matter damage in patients with RBD. This finding highlights the potential of PSMD as a marker for detecting white matter damage, which may be related to small vessel diseases, in patients with sleep disorders.
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Nova, Renny, Heni Dwi Windarwati e Erik Meidianto. "Correlation between family support with work productivity of people with severe mental disorders (PSMD) in Bantur Community Health Center, Malang, Indonesia". Healthcare in Low-resource Settings 11, s1 (9 febbraio 2023). http://dx.doi.org/10.4081/hls.2023.11207.
Testo completoAbstract (sommario):
Introduction: One impact on People With Mental Disorders (PSMD) is decreased productivity. As the closest people, families are expected to support PSMD to be productive in the community. Therefore, this study aimed to identify the correlation between family support and the work productivity of people with mental disorders.
Design and Methods: This observational analytical study with a Cross-Sectional approach was conducted in the working area of the Bantur Community Health Center. Purposive sampling was used to obtain 107 samples. Data on family support were collected using a questionnaire and tested for validity, while the Endicott Work Productivity Scale (EWPS) questionnaire was used to measure PSMD work productivity.
Results: The results showed a significant correlation between family support and PSMD work productivity, p = 0.028. The correlation was negative, meaning lower PSMD work productivity implied higher family support. Furthermore,emotional support was the most form of support provided by family members to PSMD. Work productivity is generally low, with PSMD work attitudes in the high category only in sub-variables.
Conclusions: Family support is needed for people with mental disorders to be productive. Future studies should examine other factors that affect PSMD work productivity. Additionally, health services should innovate to create work programs that stimulate PSMD's potential and ability.
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Lee, Dong Ah, Ho‐Joon Lee, Sung Eun Kim e Kang Min Park. "Peak width of skeletonized mean diffusivity as a marker of small vessel disease in patients with temporal lobe epilepsy with hippocampal sclerosis". Epilepsia, 5 dicembre 2024. https://doi.org/10.1111/epi.18205.
Testo completoAbstract (sommario):
AbstractObjectiveWhite matter abnormalities in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) are well known. Peak width of skeletonized mean diffusivity (PSMD) is a novel marker for quantifying white matter integrity that may reflect small vessel disease. In this study, we aimed to quantify the extent of white matter damage in patients with TLE and HS by using PSMD.MethodsWe enrolled 52 patients with TLE with HS and 54 age‐ and sex‐matched healthy controls. Diffusion tensor imaging (DTI) was performed using a 3‐T magnetic resonance imaging scanner. We measured PSMD using DTI findings and compared PSMD between patients with TLE with HS and healthy controls. We also evaluated the correlation between PSMD and clinical factors in patients with TLE and HS.ResultsPSMD differed significantly between healthy controls and patients with TLE and HS, and it was higher in the patients (2.375 × 10−4 mm2/s vs. 2.108 × 10−4 mm2/s, p < .001). Furthermore, PSMD in the ipsilateral hemisphere of the HS was higher than in the contralateral hemisphere of the HS (2.472 × 10−4 mm2/s vs. 2.258 × 10−4 mm2/s, p = .040). PSMD was positively correlated with age (r = .512, p < .001) and age at seizure onset (r = .423, p = .002) in patients with TLE and HS.SignificancePatients with TLE and HS had higher PSMD values than healthy controls, and PSMD was positively correlated with age. These findings provide evidence of white matter damage probably due to small vessel disease in patients with TLE and HS and support the feasibility of PSMD as a promising imaging marker for epileptic disorders.
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Satizabal, Claudia L., Alexa S. Beiser, Alison M. Luckey, Rebecca Bernal, Saptaparni Ghosh, Chen‐Pin Wang, Zhiguang Li et al. "Instrumental and biological validation of PSMD as a VCID biomarker". Alzheimer's & Dementia 20, S2 (dicembre 2024). https://doi.org/10.1002/alz.086590.
Testo completoAbstract (sommario):
AbstractBackgroundPeak‐width of skeletonized mean diffusivity (PSMD) is an emerging biomarker of cerebral small vessel disease (cSVD)‐related vascular contributions to cognitive impairment and dementia (VCID). Higher PSMD values reflect greater white matter microstructural damage, and prior research has related PSMD to sporadic and monogenic forms of cSVD and worse cognitive function. Therefore, we proposed PSMD as a risk stratification biomarker for VCID. This study aimed to perform a rigorous instrumental and biological validation for PSMD in the MarkVCID‐1 consortium.MethodMethods to derive PSMD were packaged in a kit containing a protocol, scripts, and instructions. The instrumental validation included a pre‐specified plan to assess inter‐rater reliability, test‐retest repeatability, and inter‐scanner reproducibility among MarkVCID‐1 participants aged 53‐78 years across the spectrum of cSVD. We used intra‐class correlations for absolute agreement (ICCAA) and consistency (ICCC) to evaluate results, with ICC>0.07 as the pre‐specified goal.The biological validation was performed on 7,289 participants of diverse ages and racial/ethnic backgrounds from MarkVCID‐1 and population‐based cohorts from CHARGE, RUSH, and UCD‐ADRC. All sites derived a composite measure of general cognitive function using neuropsychological tests assessing distinct cognitive domains. Finally, we used linear regression models to assess the association between log‐PSMD and general cognition adjusting for age, age2, sex, and education.ResultOur instrumental validation results (Figure 1) showed excellent reliability between raters from seven sites (overall ICCAA=0.945, P<0.001), agreement between test and retest measurements obtained within two weeks (ICCAA=0.986, P<0.001), and reproducibility across Philips Achieva, Siemens Prisma, and Siemens Trio scanners (ICCC= 0.954, P<0.001).In the biological validation, higher PSMD values were associated with lower general cognitive function in MarkVCID‐1 (Beta=‐0.82, P<0.001), and these findings were replicated across the CHARGE, RUSH, and UCD‐ADRC cohorts (Table 1).ConclusionOur rigorous instrumental validation study showed excellent inter‐rater reliability, test‐retest repeatability, and inter‐scanner reproducibility for the PSMD kit. We further observed strong associations between higher PSMD values and poorer cognitive function across diverse samples in the biological validation. Taken together, our findings support using PSMD as a robust risk stratification biomarker in multi‐site clinical trials of VCID. Additional longitudinal validation studies for PSMD are underway in MarkVCID‐2.
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Etherton, Mark R., Markus D. Schirmer, Maria Clara Zanon Zotin, Pamela M. Rist, Gregoire Boulouis, Arne Lauer, Ona Wu e Natalia S. Rost. "Global white matter structural integrity mediates the effect of age on ischemic stroke outcomes". International Journal of Stroke, 3 novembre 2021, 174749302110559. http://dx.doi.org/10.1177/17474930211055906.
Testo completoAbstract (sommario):
Background The relationship of global white matter microstructural integrity and ischemic stroke outcomes is not well understood. Aims To investigate the relationship of global white matter microstructural integrity with clinical variables and functional outcomes after acute ischemic stroke. Methods A retrospective analysis of neuroimaging data from 300 acute ischemic stroke patients with magnetic resonance imaging brain obtained within 48 hours of stroke onset and long-term functional outcomes (modified Rankin, mRS) was performed. Peak width of skeletonized mean diffusivity (PSMD), as a measure of global white matter microstructural injury, was calculated in the hemisphere contralateral to the acute infarct. Multivariable linear and logistic regression analyses were performed to identify variables associated with PSMD and excellent functional outcome (mRS < 2) at 90 days, respectively. Mediation analysis was then pursued to characterize how PSMD mediates the effect of age on acute ischemic stroke functional outcomes. Results White matter hyperintensity volume, age, pre-stroke disability, and normal-appearing white matter mean diffusivity were independently associated with increased PSMD. In logistic regression analysis, increased infarct volume and PSMD were independent predictors of excellent functional outcome. Additionally, the effect of age on functional outcomes was indirectly mediated by PSMD ( P < 0.001). Conclusions As a marker of global white matter microstructural injury, increased PSMD mediates the effect of increased age to contribute to poor acute ischemic stroke functional outcomes. PSMD could serve as a putative radiographic marker of brain age for stroke outcomes prognostication.
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Luckey, Alison M., Saptaparni Ghosh, Rebecca Bernal, Haykel Snoussi, Angel G. Velarde, Hector Trevino, Monica Goss et al. "PSMD, a novel biomarker of small vessel disease, and its association with cognitive function — A comprehensive clinical validation study". Alzheimer's & Dementia 19, S16 (dicembre 2023). http://dx.doi.org/10.1002/alz.077894.
Testo completoAbstract (sommario):
AbstractBackgroundA recent instrumental validation analysis positioned peak‐width of skeletonized mean diffusivity (PSMD) as a biomarker for vascular contributions to cognitive impairment and dementia (VCID) with excellent reliability, repeatability, and reproducibility. As the next step of biomarker development, the current study aimed to (1) perform a clinical validation of PSMD and cognitive function in MarkVCID and three independent replication samples, and (2) assess whether PSMD explains cognitive function above and beyond white matter hyperintensities (WMH).MethodThe clinical validation of PSMD included n = 395 participants from the multi‐site MarkVCID consortium, n = 6172 from population‐based CHARGE cohorts, n = 287 from RUSH, and n = 435 from the UC Davis ADRC cohort spanning diverse ages and racial/ethnic backgrounds. PSMD was derived from DTI using an automated algorithm and further log‐transformed to normalize its distribution. A composite measure of general cognitive function was calculated from neuropsychological tests assessing at least three different cognitive domains. Linear regression models were run to determine the association between PSMD and cognitive function, adjusting for age, sex, and education. A secondary model was adjusted for vascular risk factors: hypertension, diabetes, and smoking. Lastly, both models included WMH volume to evaluate PSMD beyond WMH.ResultHigher PSMD values were associated with lower general cognitive function in the MarkVCID (Beta (95% CI), ‐0.82 (‐1.03, ‐0.61), p<0.001) in primary models, and remained unchanged after additional adjustment for vascular risk factors in secondary model (‐0.87 (‐1.09, ‐0.65), p<0.001). These findings were replicated across the CHARGE, RUSH, and UC Davis ADRC cohorts (Table 1). We further observed that PSMD explained an additional 0.2% of the variance in cognitive function beyond WMH in the youngest cohort (48.1 ±8.9 years), whereas the variance explained rose to 2.51% for the oldest cohort (76.4 ±5.2 years).ConclusionThis comprehensive clinical validation study suggests that PSMD is related to general cognition across diverse samples, potentially explaining more variation in cognitive function than a classic cerebrovascular marker such as WMH. Together, our instrumental and clinical validation studies support using PSMD as a robust biomarker with potential for risk stratification and disease monitoring in multi‐site clinical trials of VCID. Additional longitudinal validation studies are underway.
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Rasing, Ingeborg, Naomi Vlegels, Manon R. Schipper, Sabine Voigt, Emma A. Koemans, Kanishk Kaushik, Rosemarie van Dort et al. "Microstructural white matter damage on MRI is associated with disease severity in Dutch-type cerebral amyloid angiopathy". Journal of Cerebral Blood Flow & Metabolism, 17 giugno 2024. http://dx.doi.org/10.1177/0271678x241261771.
Testo completoAbstract (sommario):
Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77–9.50]mm2/s × 10−4) compared with presymptomatic mutation-carriers (2.62 [1.96–3.43]mm2/s × 10−4) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16–0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08–0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22–0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13–0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = −0.42 [−0.69–0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA.
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Wang, Yanmei, Qianxian Wu, Qian Zhou, Yuyu Chen, Xingxing Lei, Yiding Chen e Qiu Chen. "Circulating acyl and des-acyl ghrelin levels in obese adults: a systematic review and meta-analysis". Scientific Reports 12, n. 1 (17 febbraio 2022). http://dx.doi.org/10.1038/s41598-022-06636-3.
Testo completoAbstract (sommario):
AbstractGhrelin is the only known orexigenic gut hormone, and its synthesis, secretion and degradation are affected by different metabolic statuses. This meta-analysis aimed to investigate the potential differences in plasma acyl ghrelin (AG) and des-acyl ghrelin (DAG) concentrations between normal weight and obese adults. Systematic literature searches of PubMed, Embase and Web of Science through October 2021 were conducted for articles reporting AG or DAG levels in obesity and normal weight, and 34 studies with 1863 participants who met the eligibility criteria were identified. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to evaluate group differences in circulating AG and DAG levels. Pooled effect size showed significantly lower levels of baseline AG (SMD: − 0.85; 95% CI: − 1.13 to − 0.57; PSMD < 0.001) and DAG (SMD: − 1.06; 95% CI: − 1.43 to − 0.69; PSMD < 0.001) in obese groups compared with healthy controls, and similar results were observed when subgroup analyses were stratified by the assay technique or storage procedure. Postprandial AG levels in obese subjects were significantly lower than those in controls when stratified by different time points (SMD 30 min: − 0.85, 95% CI: − 1.18 to − 0.53, PSMD < 0.001; SMD 60 min: − 1.00, 95% CI: − 1.37 to − 0.63, PSMD < 0.001; SMD 120 min: − 1.21, 95% CI: − 1.59 to − 0.83, PSMD < 0.001). In healthy subjects, a postprandial decline in AG was observed at 120 min (SMD: − 0.42; 95% CI: − 0.77 to − 0.06; PSMD = 0.021) but not in obese subjects (SMD: − 0.28; 95% CI: − 0.60 to 0.03; PSMD = 0.074). The mean change in AG concentration was similar in both the obese and lean health groups at each time point (ΔSMD30min: 0.31, 95% CI: − 0.35 to 0.97, PSMD = 0.359; ΔSMD60min: 0.17, 95% CI: − 0.12 to 0.46, PSMD = 0.246; ΔSMD120min: 0.21, 95% CI: − 0.13 to 0.54, PSMD = 0.224). This meta-analysis strengthens the clinical evidence supporting the following: lower baseline levels of circulating AG and DAG in obese individuals; declines in postprandial circulating AG levels, both for the healthy and obese individuals; a shorter duration of AG suppression in obese subjects after meal intake. These conclusions have significance for follow-up studies to elucidate the role of various ghrelin forms in energy homeostasis.
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Luckey, Alison M., Alexa S. Beiser, Jayandra J. Himali, Carlos A. Gaona, Joy Zeynoun, Luis A. Mendez Rodriguez, Mohamad Habes et al. "Joint Contribution of NfL and PSMD for Improved Risk Stratification of VCID". Alzheimer's & Dementia 20, S2 (dicembre 2024). https://doi.org/10.1002/alz.090747.
Testo completoAbstract (sommario):
AbstractBackgroundAdvancing therapeutic and prevention strategies for vascular contributions to cognitive impairment and dementia (VCID) warrants identifying novel biomarkers. However, due to the high heterogeneity underlying dementia pathology, a single marker may not fully risk‐stratify for VCID. A blood‐based biomarker of neuroaxonal injury, neurofilament light chain (NfL), and a neuroimaging‐based biomarker of white matter microstructural damage on diffusion weighted imaging, peak width of skeletonized mean diffusivity (PSMD), have been related to worse general cognition and proposed as robust biomarkers for cerebral small vessel disease (cSVD). We investigated the joint contribution of NfL and PSMD for improved specificity/sensitivity to identify persons at risk for VCID.MethodDementia‐free participants from the Framingham Offspring Study with cognitive, neuroimaging, and NfL data were included (N=969). NfL was measured in plasma, and PSMD was derived from MRI diffusion weighted imaging. Executive function and general cognitive function were assessed from a neuropsychological battery. NfL and PSMD were dichotomized by the top quartile and combined to indicate a high cSVD burden. The high NfL‐PSMD risk category was related to cognitive function using linear regression adjusting for age, age‐squared, sex, education, renal function (eGFR), and total intracranial volume. Additional analyses incorporating amyloid PET uptake in 64 participants were performed to discern Alzheimer’s disease pathology from VCID.ResultHigher NfL‐PSMD was significantly associated with worse executive (Beta±SE, ‐0.06±0.02, p=0.002) and general cognitive function (‐0.15±0.07, p=0.02). Additionally, amyloid PET over‐predicted NfL levels in those with PSMD below the median (observed<predicted, Mean(SD), ‐0.06(0.31)) and under‐predicted NfL in those with PSMD above the median (observed>predicted, 0.06 (0.33)). Although results were not significant (p=0.15) due to the limited sample, they suggest that amyloid pathology does not explain cSVD burden measured with NfL and PSMD.ConclusionOur findings suggest combining NfL and PSMD can better risk‐stratify those with VCID and poorer cognitive function. This NfL‐PSMD multi‐biomarker has potential to discriminate vascular dysfunction from Alzheimer’s pathology, improving identification of persons better suited for VCID clinical trials. Utilizing a multi‐biomarker approach may improve accuracy for risk stratification of persons bearing covert cerebral vascular injury. Further studies are underway to confirm these findings in larger, diverse samples.
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Horn, Mitchell J., Elif Gokcal, J. A. Becker, Alvin S. Das, Kristin Schwab, Alessandro Biffi, Joshua Goldstein et al. "Abstract 9: Peak Width of Skeletonized Mean Diffusivity and Cognition in Cerebral Amyloid Angiopathy". Stroke 52, Suppl_1 (marzo 2021). http://dx.doi.org/10.1161/str.52.suppl_1.9.
Testo completoAbstract (sommario):
Background: We hypothesized that Peak Width of Skeletonized Mean Diffusivity (PSMD), an automated marker of cerebral microangiopathy representing microstructural disruption of white matter (WM), would be increased in patients with cerebral amyloid angiopathy (CAA) compared to healthy controls (HCs) and increased PSMD would be associated with lower processing speed scores (PSSs) in patients with CAA. Methods: Seventy-two nondemented probable CAA patients and 23 HCs prospectively underwent high-resolution brain MRIs and cognitive tests. PSMD scores were quantified from a probabilistic skeleton of the WM tracts as previously validated (http://www.psmd-marker.com). In subjects with intracerebral hemorrhage (ICH, n=27), ICH regions were masked and removed from the PSMD pipeline. The analyses were repeated in the non-ICH hemisphere. Raw scores of Trail Making Test-B and Symbol Substitution Test were transformed into standardized z -scores and averaged to obtain PSSs. Results: The mean age (p=0.366) and sex (p=0.811) were similar between CAA patients and HCs. PSMD was higher in the CAA group [(3.95±0.9) х 10 –4 mm 2 /s] compared to HCs [(3.32±0.6) х 10 –4 mm 2 /s] (p=0.003). This association remained significant in a linear regression model corrected for age and sex (β=0.700, 95%CI 0.3-1, p=0.001). Within the CAA cohort, higher PSMD was associated with higher WM hyperintensity volume in a multiple regression model adjusted for all relevant variables (β=0.890, 95%CI 0.7-1, p<0.001). In a regression model corrected for age, sex, years of education and presence of ICH, a lower PSS was independently associated with increased PSMD (β=-0.405, 95%CI {-0.6}-{-0.2}, p<0.001). These results did not change when the non-ICH hemisphere was used for PSMD processing. Conclusion: PSMD is increased in CAA and is associated with worse PSSs supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA.
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Horn, Mitchell J., Elif Gokcal, J. Alex Becker, Alvin S. Das, Kristin Schwab, Maria Clara Zanon Zotin, Joshua N. Goldstein et al. "Peak width of skeletonized mean diffusivity and cognitive performance in cerebral amyloid angiopathy". Frontiers in Neuroscience 17 (3 aprile 2023). http://dx.doi.org/10.3389/fnins.2023.1141007.
Testo completoAbstract (sommario):
BackgroundCerebral Amyloid Angiopathy (CAA) is a cerebral small vessel disease that can lead to microstructural disruption of white matter (WM), which can be measured by the Peak Width of Skeletonized Mean Diffusivity (PSMD). We hypothesized that PSMD measures would be increased in patients with CAA compared to healthy controls (HC), and increased PSMD is associated with lower cognitive scores in patients with CAA.MethodsEighty-one probable CAA patients without cognitive impairment who were diagnosed with Boston criteria and 23 HCs were included. All subjects underwent an advanced brain MRI with high-resolution diffusion-weighted imaging (DWI). PSMD scores were quantified from a probabilistic skeleton of the WM tracts in the mean diffusivity (MD) image using a combination of fractional anisotropy (FA) and the FSL Tract-Based Spatial Statistics (TBSS) algorithm (www.psmd-marker.com). Within CAA cohort, standardized z-scores of processing speed, executive functioning and memory were obtained.ResultsThe mean of age and sex were similar between CAA patients (69.6 ± 7.3, 59.3% male) and HCs (70.6 ± 8.5, 56.5% male) (p = 0.581 and p = 0.814). PSMD was higher in the CAA group [(4.13 ± 0.94) × 10–4 mm2/s] compared to HCs [(3.28 ± 0.51) × 10–4 mm2/s] (p < 0.001). In a linear regression model corrected for relevant variables, diagnosis of CAA was independently associated with increased PSMD compared to HCs (ß = 0.45, 95% CI 0.13–0.76, p = 0.006). Within CAA cohort, higher PSMD was associated with lower scores in processing speed (p < 0.001), executive functioning (p = 0.004), and memory (0.047). Finally, PSMD outperformed all other MRI markers of CAA by explaining most of the variance in models predicting lower scores in each cognitive domain.DiscussionPeak Width of Skeletonized Mean Diffusivity is increased in CAA, and it is associated with worse cognitive scores supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA. As a robust marker, PSMD can be used in clinical trials or practice.
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Li, Yongjin, Chao Kong, Baobao Wang, Wenzhi Sun, Xiaolong Chen, Weiguo Zhu, Junzhe Ding e Shibao Lu. "Identification of differentially expressed genes in mouse paraspinal muscle in response to microgravity". Frontiers in Endocrinology 13 (13 ottobre 2022). http://dx.doi.org/10.3389/fendo.2022.1020743.
Testo completoAbstract (sommario):
Lower back pain (LBP) is the primary reason leading to dyskinesia in patients, which can be experienced by people of all ages. Increasing evidence have revealed that paraspinal muscle (PSM) degeneration (PSMD) is a causative contributor to LBP. Current research revealed that fatty infiltration, tissue fibrosis, and muscle atrophy are the characteristic pathological alterations of PSMD, and muscle atrophy is associated with abnormally elevated oxidative stress, reactive oxygen species (ROS) and inflammation. Interestingly, microgravity can induce PSMD and LBP. However, studies on the molecular mechanism of microgravity in the induction of PSMD are strongly limited. This study identified 23 differentially expressed genes (DEGs) in the PSM (longissimus dorsi) of mice which were flown aboard the Bion M1 biosatellite in microgravity by bioinformatics analysis. Then, we performed protein–protein interaction, Gene Ontology function, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for the DEGs. We found that Il6ra, Tnfaip2, Myo5a, Sesn1, Lcn2, Lrg1, and Pik3r1 were inflammatory genes; Fbox32, Cdkn1a, Sesn1, and Mafb were associated with muscle atrophy; Cdkn1a, Sesn1, Lcn2, and Net1 were associated with ROS; and Sesn1 and Net1 were linked to oxidative stress. Furthermore, Lcn2, Fbxo32, Cdkn1a, Pik3r1, Sesn1, Net1, Il6ra, Myo5a, Lrg1, and Pfkfb3 were remarkably upregulated, whereas Tnfaip2 and Mafb were remarkably downregulated in PSMD, suggesting that they might play a significant role in regulating the occurrence and development of PSMD. These findings provide theoretical basis and therapeutic targets for the treatment of PSMD.
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Li, Yuanhao, Hongquan Zhu, Yufei Liu, Yujie Ding, Shihui Li, Li Li, Jiaxuan Zhang, Jingjing Jiang, Nanxi Shen e Wenzhen Zhu. "Assessment the Impact of IDH Mutation Status on MRI Assessments of White Matter Integrity in Glioma Patients: Insights From Peak Width of Skeletonized Mean Diffusivity and Free Water Metrics". Journal of Magnetic Resonance Imaging, 20 agosto 2024. http://dx.doi.org/10.1002/jmri.29561.
Testo completoAbstract (sommario):
BackgroundGliomas are highly invasive brain tumors that evade accurate geographic assessment by conventional MRI due to microscopic invasion along white matter (WM) tracts. Advanced diffusion MRI techniques are needed to assess occult WM involvement.PurposeTo evaluate peak width of skeletonized mean diffusivity (PSMD) and peak width of skeletonized free water (PSFW), and axonal water fraction (AWF) for assessing glioma‐induced alterations in normal‐appearing WM and their relationship with isocitrate dehydrogenase 1 (IDH1) mutation.Study TypeRetrospective.PopulationOne hundred five glioma patients (46 ± 13 years), 53 healthy controls (HCs) (46 ± 9 years).Field Strength/Sequence3.0 T, T1WI, T1‐CE, T2WI, T2FLAIR, and DKI.AssessmentPSMD and PSFW were compared between lesion and contralateral sides in glioma patients and between patients and HCs. The associations between these metrics and clinical variables, including IDH1 mutation, was assessed. Corpus callosum (CC) injury, quantified by the AWF, was evaluated for its mediated effect of IDH1 mutation on contralesional PSMD and PSFW.Statistical TestsPaired‐t tests, ANCOVA, univariate and multivariate linear regression, and mediation analysis with significance set at P < 0.05.ResultsContralateral PSMD and PSFW were significantly higher in left‐sided gliomas (PSMD: 0.206 ± 0.027 vs. 0.193 ± 0.023; PSFW: 0.119 ± 0.019 vs. 0.106 ± 0.020) than in HCs, with similar increases in right‐sided gliomas (PSMD: 0.219 ± 0.036 vs. 0.195 ± 0.023; PSFW: 0.129 ± 0.031 vs. 0.109 ± 0.020). IDH1 wild‐type gliomas were associated with higher contralateral PSMD and PSFW (β = −0.302 and −0.412). AWF of CC mediated the impact of IDH1 mutations on contralesional PSMD and PSFW (mediated proportion: 42.7% and 53.7%).Data ConclusionPSMD and PSFW are effective biomarkers for assessing WM integrity in gliomas, significantly associated with IDH1 mutation status. AWF of CC mediates the relationship between IDH1 mutation and contralesional PSMD and PSFW.Evidence Level4Technical EfficacyStage 2