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Létourneau-Montminy, Marie-Pierre, and Theophane de Rauglaudre. "PSIX-18 Prediction of urinary P excretion as a tool to assess mineral status of growing pigs." Journal of Animal Science 98, Supplement_3 (November 2, 2020): 182–83. http://dx.doi.org/10.1093/jas/skaa054.323.
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Abstract Urinary losses of phosphorus (P) and calcium (Ca) are indicators of absorbed compared to amount needed for tissue growth as well as their balance for bone deposition. They can thus be a good indicator of the mineral status. This hypothesis has been validated through meta-analysis using a database of P and Ca retention in growing pigs including 43 publications published between 1969 and 2018 for a total of 51 experiments and 251 dietary treatments. P urinary excretion has been simulated using a multiple regression analysis with the proc MIXED (Minitab® 19) with trial effect as random. Average body weight of the pigs was 32kg ±18kg. Urinary P losses (urineP) was influenced by apparent digestible P (digP, recalculated for each treatment; g/kg), total Ca (Ca, g/kg), and microbial phytase (PhytM, FTU/kg). The model created explains 90% of urineP (R2 = 91%). UrineP was increased with digP from about 2 g/kg of digP (digP, P = 0.02, digP x digP, P < 0.001), before this point it was very low. Increasing dietary Ca decreased urineP linearly when exceeding the 2 g/kg of digP (Ca x digP, P < 0.001); P can then be fixed into bone as hydroxyapatite. The contribution of P is thus to manage in conjunction with dietary Ca. PhytM effect depends of both Ca and P (PhytM x Ca x digP; P = 0.03) showing that phytM addition reduces urineP depending of digP and Ca. As an example, in 6 g Ca/kg diet, 500 FTU/kg addition reduce urineP by 28% in 2 g digP/kg and by only 4% in 4 g digP g/kg. This is due to a better retention of P into bone in low digP. Next step will be urinary Ca modeling and then looking at meaning of their ratio in relation to mineral status to develop a practical tool to assess Ca and P status of pig.
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Parker, Gordon, Stacey McCraw, and Adam Bayes. "Borderline personality disorder: does its clinical features show specificity to differing developmental risk factors?" Australasian Psychiatry 26, no. 4 (March 13, 2018): 410–13. http://dx.doi.org/10.1177/1039856218760732.
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Objectives: To determine if differing developmental factors show specificity to differing manifestations of borderline personality disorder (BPD). Methods: A clinical sample of 73 females diagnosed with BPD undertook a psychiatrist interview and completed self-report questionnaires, including the semi-structured Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV) assessing for BPD status. A set of negative and potentially traumatic developmental factors were included in the assessment. Results: Childhood sexual abuse, affirmed by 49% of the sample, showed specificity in being linked with DIPD-defined affective instability. DIPD-defined identity disturbance also showed specificity in being associated only with reporting significant non-sexual developmental trauma. DIPD-defined anger and paranoia/dissociation showed minimal specificity and were associated with most antecedent developmental factors in adulthood. Conclusions: Differing manifestations of BPD are likely to be shaped by specific and non-specific developmental events. Clarification of such links has the potential to shape more specific therapeutic interventions.
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Borissevitch, Iouri E., Christiane P. F. Borges, Galina P. Borissevitch, Victor E. Yushmanov, Sonia R. W. Louroh, and Marcel Tabak. "Binding and Location of Dipyridamole Derivatives in Micelles: the Role of Drug Molecular Structure and Charge." Zeitschrift für Naturforschung C 51, no. 7-8 (August 1, 1996): 578–90. http://dx.doi.org/10.1515/znc-1996-7-818.
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Abstract Binding and localization of the vasodilator and antitumor drug coactivator dipyridamole (DIP) and of its three derivatives, RA14. RA47 and RA25 (DIPD), to cationic (cetyltrimethylammonium chloride), anionic (sodium dodecylsulfate), zwitterionic (N-hexadecyl-N,N-di-methyl-3-ammonio-1-propanesulfonate), and neutral (t-octylphenoxypolyethoxyethanol) micelles was studied using fluorescence, optical absorption and 1H NMR spectroscopy. The analysis of NMR, optical absorption and fluorescence data indicates that the depth of localization of the drugs in the micelles from the surface decreased in the order DIP > RA14 > RA47 > RA25. The binding constants for the neutral drug forms change in the same order in the range of 1400-3100 м-1 for DIP to 80-300 м-1 for RA25. This order is identical with the reported biological activity of DIPD. For the protonated drugs in zwitterionic or neutral micelles the binding constants are reduced by a factor of 20-75.
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Bernardo, Ana Paula, M. Auxiliadora Bajo, Olivia Santos, Gloria Del Peso, Maria João Carvalho, António Cabrita, Rafael Selgas, and Anabela Rodrigues. "Two-in-One Protocol: Simultaneous Small-Pore and Ultrasmall-Pore Peritoneal Transport Quantification." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 32, no. 5 (September 2012): 537–44. http://dx.doi.org/10.3747/pdi.2011.00175.
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BackgroundReduced free water transport (FWT) through ultrasmall pores contributes to net ultrafiltration failure (UFF) and should be seen as a sign of more severe functional deterioration of the peritoneal membrane. The modified peritoneal equilibration test (PET), measuring the dip in dialysate Na concentration, estimates only FWT. Our aim was to simultaneously quantify small-solute transport, FWT, and small-pore ultrafiltration (SPUF) during a single PET procedure.MethodsWe performed a 4-hour, 3.86% glucose PET, with additional measurement of ultrafiltration (UF) at 60 minutes, in 70 peritoneal dialysis patients (mean age: 50 ± 16 years; 61% women; PD vintage: 26 ± 23 months). We calculated the dialysate-to-plasma ratios (D/P) of creatinine and Na at 0 and 60 minutes, and the Na dip (DipD/PNa60,), the delta dialysate Na 0–60 (ΔDNa0–60), FWT, and SPUF.ResultsSodium sieving (as measured by ΔDNa0–60) correlated strongly with the corrected DipD/PNa60, ( r = 0.85, p < 0.0001) and the corrected FWT ( r = 0.41, p = 0.005). Total UF showed better correlation with FWT than with indirect measurements of Na sieving ( r = 0.46, p < 0.0001 for FWT; r = 0.360, p < 0.0001 for DipD/PNa60,). Corrected FWT fraction was 0.45 ± 0.16. A negative correlation was found between time on PD and both total UF and FWT ( r = -0.253, p = 0.035 and r = -0.272, p = 0.023 respectively). The 11 patients (15.7%) diagnosed with UFF had lower FWT (89 mL vs 164 mL, p < 0.05) and higher D/P creatinine (0.75 vs 0.70, p < 0.05) than did the group with normal UF. The SPUF correlated positively with FWT in the normal UF group, but negatively in UFF patients ( r = -0.709, p = 0.015). Among UFF patients on PD for a longer period, 44.4% had a FWT percentage below 45%.ConclusionsMeasurement of FWT and SPUF is feasible by simultaneous quantification during a modified 3.86% glucose PET, and FWT is a decisive parameter for detecting causes of UFF in addition to increased effective capillary surface.
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Kumar, Anupama Deepa, Michelle Padilla, Lin Liu, Minya Pu, Emily Pittman, Dimitrios Tzachanis, Sarah Marie Larson, et al. "Phase II study of the combination of daratumumab, ixazomib, pomalidomide, and dexamethasone as salvage therapy in relapsed/refractory multiple myeloma: Stage 2 interim results." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 8041. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.8041.
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8041 Background: The combination of daratumumab (Dara), pomalidomide (POM), and dexamethasone (dex) (DPd) has previously demonstrated deep and durable responses including high rates of minimal residual disease (MRD) negativity, in patients with relapsed/refractory (R/R) MM. Quadruplet regimens may further improve results. We report updated findings from a phase 2 multicenter trial of the addition of ixazomib to DPd (DIPd) in patients with early R/R MM. Methods: This is a prospective, multi-center, open-label, single arm phase II trial with a primary objective to evaluate the overall response rate (ORR), safety, and efficacy of DIPd. Secondary endpoints include progression-free survival (PFS), overall survival (OS), and MRD-negativity rate. A Simon’s optimal 2-stage design was used, with 14 subjects in stage 1 to assess response and 32 patients for stage 2. Eligible patients may not have had exposure Dara or ixazomib, may not have progressed on POM, and may have received ≥1 and ≤3 prior lines of therapy. The first six patients in the safety run-in received Dara 16mg/kg IV weekly x 8 doses, biweekly x 8 doses, then monthly, POM 4mg orally on days 1-21 of a 28-day cycle, ixazomib 4mg orally on days 1,8,15 every 28 days, and dex 20-40mg weekly. Grade 3-4 neutropenia was observed in 100% of patients, prompting dose reduction to ixazomib 3 mg and POM 3 mg by the DSMB. An amendment allowed subcutaneous Dara administration. MRD assessments are being performed by EuroFlow for patients in VGPR or suspected CR. Pharmacodynamic changes in patients’ tumor microenvironments were established by custom panel mass cytometry to include T-cell memory and activated subpopulations, B-cell content, NK-cell subpopulations as well as MDSCs, Tregs and T-exhaustive markers, monocytes and dendritic cells. Results: To date, 14 subjects have been treated in stage 1, and 18 patients in stage 2. Median age was 61.5 (range 41-87) years, 50% were female and 72% white. Median number of prior regimens was 1 (range 1-3), all patients were lenalidomide-exposed, and 47% (11/23) had high-risk cytogenetic features. The most common grade 3-4 treatment emergent adverse events included neutropenia (78%), infection (30%), leukopenia (11%), respiratory conditions (7%), psychiatric disturbance (4%), and thrombosis (4%). Median time on treatment was 4 months (1-29), with 11 patients remaining on DIPd and 5 deaths (4 due to progressive disease and 1 due to sepsis). ORR to date was 84% (16/19), and the best responses included: 5 (26%) sCR; 4 (21%) VGPR; 7 (37%) PR. After a median follow up of 12 months, the median OS was 39 months and PFS was 9.5 months. Conclusions: The quadruplet regimen DIPd is a well-tolerated combination that has shown early safety, efficacy, and ORR in early R/R myeloma, including patients with high-risk genetic abnormalities. Clinical trial information: NCT03590652.
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Kato, Kaori, Dai Yamanouchi, Karla Esbona, Kentaro Kamiya, Fan Zhang, K. Craig Kent, and Bo Liu. "Caspase-mediated protein kinase C-δ cleavage is necessary for apoptosis of vascular smooth muscle cells." American Journal of Physiology-Heart and Circulatory Physiology 297, no. 6 (December 2009): H2253—H2261. http://dx.doi.org/10.1152/ajpheart.00274.2009.
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Apoptotic death of vascular smooth muscle cells (SMCs) is a prominent feature of blood vessel remodeling and various vascular diseases. We have previously shown that protein kinase C-δ (PKC-δ) plays a critical role in SMC apoptosis. In this study, we tested the importance of PKC-δ proteolytic cleavage and tyrosine phosphorylation within the apoptosis pathway. Using hydrogen peroxide as a paradigm for oxidative stress, we showed that proteolytic cleavage of PKC-δ occurred in SMCs that underwent apoptosis, while tyrosine phosphorylation was detected only in necrotic cells. Furthermore, using a peptide (z-DIPD-fmk) that mimics the caspase-3 binding motif within the linker region of PKC-δ, we were able to prevent the cleavage of PKC-δ, as well as apoptosis. Inhibition of PKC-δ with rottlerin or small-interfering RNA diminished caspase-3 cleavage, caspase-3 activity, cleavage of poly (ADP-ribose) polymerase, cleavage of PKC-δ, and DNA fragmentation, confirming the previously reported role of PKC-δ in initiation of apoptosis. In contrast, z-DIPD-fmk markedly diminished caspase-3 activity, cleavage of PKC-δ, and DNA fragmentation without affecting cleavage of caspase-3 and poly (ADP-ribose) polymerase. Taken together, our data suggest that caspase-3-mediated PKC-δ cleavage underlies SMC apoptosis induced by oxidative stress, and that PKC-δ acts both upstream and downstream of caspase-3.
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Li, Xiao Gen, Zhi Quan Huang, Tong Jiang, and An Ming Wang. "Analysis of Constructing 3-Dimensional Virtual Scene Technique Based on DEM." Advanced Materials Research 271-273 (July 2011): 404–9. http://dx.doi.org/10.4028/www.scientific.net/amr.271-273.404.
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High resolution DEM(Digital Elevation Model, DEM) is created based on original CAD terrain map (one reservoir as example). Then the article offers precision analysis、topographic factors analysis、visibility analysis、reservoir volume and submerging acreage computing. Then adopting GeoVRML technique is to implement the functions of WebGIS 、visualization and query of computing result、graph data visualization and reservoir region virtual scene roaming etc. The system implements deep administrative levels information diged and long-distance visualization expression. The result shows on the basic high resolution DEM to realize 3-Dimensional Visualization Analyse and calculation functions and compress the spatial data to release these data in the WebGIS(Web Geographical Information System, WebGIS) as well as.
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Xiaofeng, Liu, Li Lianfang, Chen Fei, Li Yuming, Chen Hui, Li Qing, Cheng Lu, and Cui Shude. "An Intraoperative Localization Technique for a Postexcision Specimen of Nonpalpable Breast Calcifications: A Pilot Study." American Surgeon 77, no. 11 (November 2011): 1467–71. http://dx.doi.org/10.1177/000313481107701135.
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The specimens obtained through excisional biopsy (EB) are commonly large in size and it is difficult to remove the tissues containing nonpalpable calcifications accurately from them for pathologic examination. Therefore, the aim of the study is to develop a novel method of subarea localization technique (SLT) for sampling from the postexcisional specimens. A retrospective clinical study of 48 consecutive patients with breast microcalcifications were divided into a study group (n = 24 patients, 25 breasts) and a control group (n = 24 patients, 24 breasts) in time sequence. The specimens of study group were localized by SLT performed by cutting lines and/or metallic markers. The main study end points were the duration of intraoperative pathologic diagnosis (DIPD) and duration of conclusive pathology diagnosis (DCPD). The number of frozen blocks, number of paraffin blocks, number of sections, and other parameters correlated with pathologic diagnosis were compared between the two groups. SLT was succeeded in 48 of 48 (100%) patients, which shortened DIPD (29.3 vs 45.5 minutes, P < 0.01) significantly with less frozen blocks (6.2 vs 12.6, P < 0.01) and less frozen sections (8.5 vs 13.7, P = 0.01) than that of the control group. Moreover, SLT shortened DCPD (4.1 vs 5.1 days, P = 0.02) with less paraffin blocks (12.2 vs 21.7, P < 0.01) and less paraffin sections (20.0 vs 39.9, P < 0.01) than that of the control group. SLT decreased workload of the specimens sampling procedure and SLT may be recommended as a reliable specimens sampling method to guide pathology test for EB specimens containing calcifications.
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Grilo, C., M. Pagano, and R. Stout. "Do Stressful Life Events Predict Eating Disorder Relapse?: Six-year Outcomes from the Collaborative Personality Disorders Study." European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70615-7.
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Aims:To examine the natural course of eating disorders (ED) prospectively over 6 years and to examine link between stressful life events (SLEs) and ED relapse among women with personality-disorders (PDs).Method:Subjects were 132 female patients with bulimia nervosa (N=40) or EDNOS (N=92) in the Collaborative Longitudinal Personality Disorders Study. EDs were assessed with the Structured Clinical Interview for DSM-IV Axis-I, and monitored with the Longitudinal Interval Follow-up Evaluation during follow-up. PDs were assessed with the Diagnostic Interview for DSM-IV PD (DIPD-IV), and monitored with the Follow-Along version of the DIPD-IV during follow-up. SLEs were assessed with the Life Events Assessment (LEA). Follow-up assessments were conducted at 6- and 12-months and then yearly through 72 months. Proportional hazard regression analyses were performed to examine the link between time-varying levels of SLEs and ED relapse. Cox regressions controlled for the same covariates used in prior work: duration of ED, number of co-morbid psychiatric disorders, and time-varying status of PDs.Results:Of the 132 patients, 59% had remissions from ED, 68% of whom subsequently relapsed over the course of 6 years (BN and EDNOS did not differ in relapse). Total number of negative SLEs reported by ED patients significantly predicted subsequent ED relapse (HazardRatio=1.5, p< .05). The types of SLEs that predicted ED relapse were elevated work stressors (HazardRatio=3.0, p< .01) and elevated recreation stressors (HazardRatio=3.1, p< .05).Conclusion:Higher work stress and higher recreation stress represent significant warning signs for triggering relapse for women in remission from BN and EDNOS.
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Grilo, C., M. Pagano, and R. Stout. "Do Stressful Life Events Predict Eating Disorder Relapse?: Six-year Outcomes from the Collaborative Personality Disorders Study." European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70979-4.
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Aims:To examine the natural course of eating disorders (ED) prospectively over 6 years and to examine link between stressful life events (SLEs) and ED relapse among women with personality-disorders (PDs).Method:Subjects were 132 female patients with bulimia nervosa (N=40) or EDNOS (N=92) in the Collaborative Longitudinal Personality Disorders Study. EDs were assessed with the Structured Clinical Interview for DSM-IV Axis-I, and monitored with the Longitudinal Interval Follow-up Evaluation during follow-up. PDs were assessed with the Diagnostic Interview for DSM-IV PD (DIPD-IV), and monitored with the Follow-Along version of the DIPD-IV during follow-up. SLEs were assessed with the Life Events Assessment (LEA). Follow-up assessments were conducted at 6- and 12-months and then yearly through 72 months. Proportional hazard regression analyses were performed to examine the link between time-varying levels of SLEs and ED relapse. Cox regressions controlled for the same covariates used in prior work: duration of ED, number of co-morbid psychiatric disorders, and time-varying status of PDs.Results:Of the 132 patients, 59% had remissions from ED, 68% of whom subsequently relapsed over the course of 6 years (BN and EDNOS did not differ in relapse). Total number of negative SLEs reported by ED patients significantly predicted subsequent ED relapse (HazardRatio=1.5, p< .05). The types of SLEs that predicted ED relapse were elevated work stressors (HazardRatio=3.0, p< .01) and elevated recreation stressors (HazardRatio=3.1, p< .05).Conclusion:Higher work stress and higher recreation stress represent significant warning signs for triggering relapse for women in remission from BN and EDNOS.
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Costello, Caitlin L., Benjamin Brookhart, Matthew J. Wieduwilt, Nina Shah, Carolyn Mulroney, and Edward D. Ball. "Phase 2 Study of the Combination of Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone As Salvage Therapy in Relapsed/Refractory Multiple Myeloma: Stage I Results." Blood 136, Supplement 1 (November 5, 2020): 5–6. http://dx.doi.org/10.1182/blood-2020-143147.
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Background: Triplet combination regimens have been widely accepted as the standard of care for the management of multiple myeloma (MM) due to improved outcomes as compared to doublet regimens. The combination of daratumumab, pomalidomide, and dexamethasone (DPd) has previously demonstrated deep and durable responses including high rates of minimal residual disease (MRD) negativity in patients with relapsed/refractory (R/R) MM. Quadruplet regimens may further improve these outcomes. We report preliminary findings from an ongoing phase 2 multi-center trial of the addition of ixazomib to DPd (DIPd) in patients with R/R MM. Methods: We are conducting a prospective, multi-center, open-label, single-arm phase 2 study to determine the efficacy and safety of DIPd as salvage therapy in R/R MM. A Simon's optimal 2-stage design includes a safety run-in period at the beginning of Stage 1 where the first 6 patients are enrolled for toxicity assessment. If ≤1 patient experiences any DLT, the study continues to accrue more Stage 1 patients. Key secondary endpoints include progression-free survival (PFS), overall survival (OS) and MRD-negativity rates. Eligible patients may have received ≥1 and ≤3 prior lines of therapy, have had no prior exposure to daratumumab or ixazomib, are lenalidomide refractory, and may have not progressed on prior pomalidomide. The first six patients were treated in a safety run-in with daratumumab 16mg/kg IV weekly x 8 doses, biweekly x 8 doses, then monthly, pomalidomide 4mg orally daily on days 1-21 of a 28-day cycle, ixazomib 4mg orally daily on days 1,8,15 every 28 days, and dexamethasone 20-40mg weekly. Patients continued therapy until disease progression, intolerability or preference. Dose-limiting toxicities (DLT) were defined as grade 3-4 hematologic adverse events (AE) or any AE that required a dose modification of pomalidomide or ixazomib at the lowest dose levels on a dose de-escalation plan. An interim safety review is being performed after the enrollment and completion of the DLT observation period for the 14 planned patients in stage I. An interim efficacy analysis was also planned after all patients had completed 3 months of therapy. Minimal residual disease assessments are being performed by EuroFlow for patients in VGPR or suspected CR. Pharmacodynamic changes in patients' tumor microenvironments were established by custom panel mass cytometry to include T-cell memory and activated subpopulations, B-cell content, NK-cell subpopulations as well as MDSCs, Tregs and T-exhaustive markers, monocytes and dendritic cells. Results: At the time of this analysis, all 14 patients have enrolled and started treatment as part of stage I of the trial. Patients had a median age of 61 (range 52-65) and median number of 1 prior line of therapy (range 1-3). All patients were refractory to lenalidomide and all were pomalidomide naïve. In the safety run-in, all 6 patients experienced ≥ grade 3 neutropenia, and per DSMB recommendation, the starting doses of pomalidomide and ixazomib were both reduced to 3mg for the subsequent 8 patients in stage 1. Common AEs included neutropenia, thrombocytopenia, and upper respiratory infection. Grade 3-4 AEs were predominantly hematologic, including neutropenia and thrombocytopenia. One patient had a grade 3 infusion-related reaction (IRR) with daratumumab administration. No DLTs have occurred. After median follow up of 4.1 months (range 1-22), all 14 patients were evaluable for efficacy. At the time of data analysis, the overall response rate to date is 85%, and the best responses include: 5 (36%) stringent complete response; 1 (7%) very good partial response; 5 (36%) partial responses; and 3 (21%) patients with stable disease. Six (42%) patients are off study treatment: 3 due to disease progression, 1 to undergo salvage autologous SCT, and 2 due to toxicity related to treatment (IRR and upper respiratory infection). MRD and pharmacodynamic data will be presented at ASH. Conclusion: The quadruplet regimen DIPd in patients with R/R MM is a well-tolerated combination and has shown early safety and promising efficacy in the first 14 patients enrolled to stage 1 of the trial. A pre-planned interim efficacy analysis is ongoing prior to future enrollment in stage 2 at multiple sites within the University of California Hematologic Malignancies Consortium. Disclosures Costello: Celgene: Honoraria, Research Funding; Janssen: Research Funding; Poseida Therapeutics: Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Wieduwilt:Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Shire: Research Funding; Macrogeneics: Research Funding; Amgen: Research Funding; Leadiant: Research Funding; Merck: Research Funding; Reata Pharmaceuticals: Current equity holder in publicly-traded company. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding.
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Valenzuela Guzmán, Maribel Alejandrina, Greta Lucía Teresa Oreno Pineda, Carmen María Santiso Rodríguez, José Edy Valiente Reyes, and María Iliana Cardona Monroy. "Perspectiva institucional y las competencias investigativas en Posgrados de USAC." Revista Ciencia Multidisciplinaria CUNORI 7, no. 1 (July 12, 2023): 59–70. http://dx.doi.org/10.36314/cunori.v7i1.208.
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OBJETIVO: determinar la perspectiva institucional en torno a las competencias investigativas en los postgrados de la USAC. MÉTODO: enfoque mixto, un estudio no experimental, de alcance descriptivo, con un diseño recurrente. RESULTADOS: se logró establecer a través de las entrevistas que existen siete aspectos que son esenciales para crear esa perspectiva institucional con respecto a las competencias investigativas, estas son: visión institucional, políticas que sustentan la investigación en Posgrados, promoción de la cultura investigativa, retos y desafíos de la investigación en posgrados, seguimiento de la tarea investigativa, impulso de las competencias investigativas y acciones a seguir CONCLUSIÓN: se logró establecer a nivel institucional la perspectiva que tienen las autoridades con relación al desarrollo de las competencias investigativas, la cual tiene varias aristas, entre ellas, el cambio de políticas para contratar a los docentes de postgrado por más tiempo para realizar investigación en el marco institucional. Es importante reconocer que en los postgrados se propicia el desarrollo de las competencias investigativas, a través de los planes de estudio, así como también a partir de acciones académicas que cada unidad y centro realiza, aunque estas son aisladas, no son de uso compartido, lo que se torna en una limitante, no todos los postgrados tienen la misma dinámica. Deben gestarse las condiciones para investigar para ir fortaleciendo la cultura, se debe trabajar de la mano con la DIGI-DIGED- SEP, quienes deben a partir de su liderazgo generar condiciones para los docentes y estudiantes para el fortalecimiento de la cultura investigativa.
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Çukurova, M., and A. Özdemir. "The Investigation of Cognitive Functions and Clinical High Risk Status for Psychosis in First-Degree Relatives of Patients with Substance Induced Psychotic Disorder." European Psychiatry 65, S1 (June 2022): S203. http://dx.doi.org/10.1192/j.eurpsy.2022.533.
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Introduction The etiology of substance-induced psychotic disorder (SIPD) is an important research area to study. Objectives It is aimed to investigate clinical risk status for psychosis, schizotypal features and neurocognitive functions in siblings of the patients who have been diagnosed as SIPD and who have no family history of psychotic spectrum disorder. Methods This study included 41 healthy siblings of patients who have been diagnosed as SIPD according to DSM-V and 41 healthy controls without family history of psychiatric disorders (matched on age, gender, and years of education). The data collected with sociodemographic and clinical data form, Digid Span Test, Trail Making Test A, Trail Making Test B, Verbal Fluency Test and Stroop Test, Comprehensive Assesment of At-Risk Mental States (CAARMS) and Structured Interview for Schizotypy-Revised. Results It is determined that %41.5 of siblings and %7.3 of healthy controls are in one of the clinical high risk groups for psychosis according to CAARMS. There is significant difference in Trail Making Test A error and Trail Making Test B error and correction, verbal fluency test- lexical fluency-perseveration mean scores between siblings of patients and healthy controls. Conclusions Siblings of patients with SIPD have more schizotypal features than healthy control group and they take part more frequent in one of high risk group for psychosis. Schizotypal features are known as trait factor and show genetic predisposition. Siblings who are in high risk groups have more schizotypal features and it may point that predisposition to psychosis is more related to underlying genetic predisposition than environmental factors and social stressors. Disclosure No significant relationships.
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Costello, Caitlin L., Michelle Padilla, Edward D. Ball, and Carolyn Mulroney. "Phase II Study of the Combination of Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone As Salvage Therapy in Relapsed/Refractory Multiple Myeloma: Results of a Safety Run-in Analysis." Blood 134, Supplement_1 (November 13, 2019): 3117. http://dx.doi.org/10.1182/blood-2019-123506.
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Background: Triplet combination strategies have widely been accepted as the standard of care for the management of multiple myeloma due to improved outcomes as compared to doublets. The combination of daratumumab, pomalidomide and dexamethasone (DPd) has previously demonstrated deep and durable responses, including high rates of MRD negativity, in a heavily pretreated patient population. Quadruplet regimens offer an opportunity to further improve upon these results. We report preliminary findings from an ongoing phase 2 multicenter trial of the addition of ixazomib to the combination of DPd in patients with relapsed/refractory multiple myeloma. The primary objective is to determine overall response rate and the safety and tolerability of this novel regimen. Key secondary endpoints include PFS, OS and MRD negativity rates. Methods: Eligible patients may have received ≥1 and ≤3 prior lines of therapy, have had no prior exposure to daratumumab or ixazomib, and may have not progressed on prior pomalidomide. Patients receive daratumumab 16mg/kg IV weekly x 8 doses, biweekly x 8 doses, then monthly, pomalidomide 4mg PO days 1-21/28, ixazomib 4mg PO days 1,8,15 every 28 days, and dexamethasone 40mg PO weekly. Patients continue on therapy until disease progression, intolerability or preference. Dose-limiting toxicities (DLT) were defined as grade 3-4 hematologic adverse events (AE) or any AE that required a dose modification of pomalidomide or ixazomib at the lowest dose levels on a dose de-escalation plan. An interim safety review was performed after the first 6 patients were enrolled and completed the DLT observation period, which is the first cycle (28 days) since the start of a new dose level of pomalidomide and/or ixazomib. Results: At the time of this analysis, six patients have been enrolled and treated, and completed the DLT observation period. Patients had a median age of 62 (range 52-65) and median number of 2 prior lines of therapy (range 1-2). All patients were refractory to lenalidomide and pomalidomide-naïve. Common adverse events (AEs) included neutropenia, thrombocytopenia, GI upset, and upper respiratory infection. Grade 3-4 AEs were predominantly hematologic including neutropenia and thrombocytopenia, but also included grade 3 hypertension in 1 patient, and grade 3 hypophosphatemia, grade 4 hypokalemia, and grade 3 small bowel infection in 1 patient. No IRR > grade 2 occurred with daratumumab administration. No DLTs occurred in the first six patients in the safety run-in. The overall response rate of the cohort is 100% with 3 patients achieving a stringent complete response (CR), and 3 patients achieving a very good partial response (VGPR) after a median of 7 cycles of treatment. One patient discontinued therapy due to influenza A, the other five remain on therapy. Minimal residual disease assessments are being performed by EuroFlow for patients in VGPR or better due to concern for daratumumab interference. Pharmacodynamic changes in patients' tumor microenvironments were established by custom panel mass cytometry to include T-cell memory and activated subpopulations, B-cell content, NK-cell subpopulations as well as MDSCs, Tregs and T-exhaustive markers, monocytes and dendritic cells. Conclusion: The quadruplet regimen DIPd in patients with relapsed/refractory myeloma is a well-tolerated combination and has shown early safety in an initial safety run-in analysis. Enrollment continues in an expansion cohort to assess efficacy at multiple sites with the University of California Hematologic Malignancies Consortium. Figure Disclosures Costello: Takeda: Honoraria, Research Funding; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding.
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Hiraishi, Yoshihisa, Takehiro Izumo, Yuji Matsumoto, Christine Chavez, Shinji Sasada, and Takaaki Tsuchida. "Evaluation of bronchoalveolar lavage for differentiating between Pneumocystis jiroveci pneumonia and drug-induced pulmonary parenchymal disease after chemotherapy for solid tumors." Internal Medicine Review 2, no. 11 (December 12, 2016). http://dx.doi.org/10.18103/imr.v2i11.239.
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<p align="left">Background: Differentiating between <em>Pneumocystis jiroveci </em>pneumonia (PCP) and drug-induced pulmonary parenchymal disease (DIPPD) is difficult after chemotherapy for solid tumors. The aim of this study was to evaluate the utility of bronchoalveolar lavage fluid (BALF) analysis for the diagnosis of PCP and DIPPD.</p><p align="left">Methods: We evaluated patients who underwent bronchoscopy at our institution from April 2012 to December 2014. Patients’ characteristics, comorbidity, previous treatment of solid tumor, and BALF findings were examined from the medical records.</p><p align="left">Results: From a total of 2625 consecutive patients who underwent bronchoscopy, 89 underwent BALF examination; among these, 33 cases had prior chemotherapy for malignancy. PCP was diagnosed in 6 patients and DIPPD was diagnosed in 21 patients. Six patients were diagnosed to have other pathologies or were undiagnosed. The white blood cell count in BALF (PCP (median (%) (range), DIPPD (median (%) (range)) consisted of macrophages (24.7 (6.9-46.1), 26.5 (2.1-86.0)), lymphocytes (71.3 (49.6-84.8), 57.0 (4.3-96.4)), neutrophils (4.6 (1.0-14.0), 5.0 (0.5-69.8)), and eosinophils (0.3 (0-1.3), 2.5 (0-37.0)). Only the proportion of eosinophils in the BALF of DIPPD patients was significantly higher (p = 0.016) than that of PCP patients. BAL was performed without serious complications.</p>Conclusions: BALF differential count, especially eosinophils, may be useful in distinguishing between PCP and DIPPD to avoid unnecessary treatment. Further prospective studies would be needed to confirm this benefit of BAL.
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Koseoglu, Suzan, and Aras BOZKURT. "#DigPed Narratives in Education: Critical Perspectives on Power and Pedagogy." Online Learning 22, no. 3 (September 1, 2018). http://dx.doi.org/10.24059/olj.v22i3.1370.
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This mixed methods study addresses a knowledge gap in the nature and effects of networked scholarship. We analyze #DigPed, a Twitter hashtag on critical pedagogy, through the lens of Tufekci’s Capacities and Signals framework in order to understand (1) how educational narratives develop and spread on #DigPed, and (2) the nature of their capacities. Using Social Network Analysis and thematic analysis of content, we identify three prominent narratives in the network and discuss the network structures from a critical perspective. Based on the findings, we propose pedagogic capacity—the power to initiate a productive and potentially transformative educational discourse, within one’s self and within communities—as an additional lens to explore the spread and impact of critical narratives in education. Findings confirm the view that networked spaces are organized by hidden hierarchies marked by influence.
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Naidoo, Karishma, Phikelelani S. Ngubane, and Andile Khathi. "Investigating the Effects of Diet-Induced Pre-Diabetes on the Functioning of Calcium-Regulating Organs in Male Sprague Dawley Rats: Effects on Selected Markers." Frontiers in Endocrinology 13 (July 11, 2022). http://dx.doi.org/10.3389/fendo.2022.914189.
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Derangements to the functioning of calcium-regulating organs have been associated with type 2 diabetes mellitus (T2DM), a condition preceded by pre-diabetes. Type 2 diabetes has shown to promote renal calcium wastage, intestinal calcium malabsorption and increased bone resorption. However, the changes to the functioning of calcium-regulating organs in pre-diabetes are not known. Subsequently, the effects of diet-induced pre-diabetes on the functioning of calcium-regulating organs in a rat model for pre-diabetes was investigated in this study. Male Sprague Dawley rats were separated into two groups (n=6, each group): non-pre-diabetic (NPD) group and a diet-induced pre-diabetic (DIPD) group for 20 weeks. After the experimental period, postprandial glucose and HOMA-IR were analysed in addition to plasma and urinary calcium concentrations. Gene expressions of intestinal vitamin D (VDR), intestinal calbindin-D9k, renal 1-alpha hydroxylase and renal transient receptor potential vanilloid 5 (TRPV5) expressions in addition to plasma osteocalcin and urinary deoxypyridinoline concentrations were analysed at week 20. The results demonstrated significantly increased concentrations of postprandial glucose, HOMA-IR and urinary calcium in addition to unchanged plasma calcium levels in the DIPD group by comparison to NPD. Renal TRPV5, renal 1-alpha hydroxylase, intestinal VDR and intestinal calbindin-D9k expressions were increased in the DIPD group by comparison to NPD. Furthermore, plasma osteocalcin levels were increased and urine deoxypyridinoline levels were decreased in the DIPD group by comparison to NPD. These observations may suggest that calcium-regulating organs compensate for the changes to calcium homeostasis by inducing increased renal calcium reabsorption, increased intestinal calcium absorption and decreased bone resorption followed by increased bone formation.
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Pan, Yue, Justin T. Landis, Razia Moorad, Di Wu, J. S. Marron, and Dirk P. Dittmer. "The Poisson distribution model fits UMI-based single-cell RNA-sequencing data." BMC Bioinformatics 24, no. 1 (June 17, 2023). http://dx.doi.org/10.1186/s12859-023-05349-2.
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Abstract Background Modeling of single cell RNA-sequencing (scRNA-seq) data remains challenging due to a high percentage of zeros and data heterogeneity, so improved modeling has strong potential to benefit many downstream data analyses. The existing zero-inflated or over-dispersed models are based on aggregations at either the gene or the cell level. However, they typically lose accuracy due to a too crude aggregation at those two levels. Results We avoid the crude approximations entailed by such aggregation through proposing an independent Poisson distribution (IPD) particularly at each individual entry in the scRNA-seq data matrix. This approach naturally and intuitively models the large number of zeros as matrix entries with a very small Poisson parameter. The critical challenge of cell clustering is approached via a novel data representation as Departures from a simple homogeneous IPD (DIPD) to capture the per-gene-per-cell intrinsic heterogeneity generated by cell clusters. Our experiments using real data and crafted experiments show that using DIPD as a data representation for scRNA-seq data can uncover novel cell subtypes that are missed or can only be found by careful parameter tuning using conventional methods. Conclusions This new method has multiple advantages, including (1) no need for prior feature selection or manual optimization of hyperparameters; (2) flexibility to combine with and improve upon other methods, such as Seurat. Another novel contribution is the use of crafted experiments as part of the validation of our newly developed DIPD-based clustering pipeline. This new clustering pipeline is implemented in the R (CRAN) package scpoisson.
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"P-C4-09 Incorporation of dipyridamole derivatives (DIPD) into organized lipid systems." Progress in Biophysics and Molecular Biology 65 (January 1996): 119. http://dx.doi.org/10.1016/s0079-6107(97)80413-0.
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Satake, Riko, Kiyoka Matsumoto, Mizuki Tanaka, Ririka Mukai, Kazuyo Shimada, Yu Yoshida, Misaki Inoue, et al. "Analysis of Drug-Induced Gastrointestinal Obstruction and Perforation Using the Japanese Adverse Drug Event Report Database." Frontiers in Pharmacology 12 (July 26, 2021). http://dx.doi.org/10.3389/fphar.2021.692292.
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Drug-induced gastrointestinal obstruction (DIGO) and gastrointestinal perforation (DIGP) may be the result of gastrointestinal hypomotility and severe constipation, which may lead to potentially fatal complications of bowel ischemia, sepsis and perforation. We evaluated the onset profile of DIGs (DIGO and DIGP) associated with prescription drugs by analyzing data in the Japanese Adverse Drug Event Report (JADER) database. We selected 161 DIG-related drugs and categorized them into 19 classes based on the Anatomical Therapeutic Chemical (ATC) Classification System. Finally, we focused on 58 drugs and conducted subsequent analyses for the time-to-onset and outcomes. We extracted 79 preferred terms (PTs) with the strings “ileus,” “stenosis,” “obstruction,” “obstructive,” “impaction,” “perforation,” “perforated,” “hypomotility,” and “intussusception” from the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) of SMQ20000104: gastrointestinal perforation, ulcer, hemorrhage, obstruction non-specific findings/procedures; SMQ20000105: gastrointestinal obstruction; and SMQ20000107: gastrointestinal perforation. Among the 667, 729 reports in the JADER database submitted between April 2004 and November 2020, we identified 11,351 occurrences of DIGs. The reporting odds ratios (RORs) (95% confidence interval) of “barium sulfate containing X-ray media,” “drugs for treatment of hyperkalemia and hyperphosphatemia,” and “oral bowel cleanser” were 142.0 (127.1–158.6), 25.8 (23.1–28.8), and 29.7 (24.8–35.6), respectively. The median number of days (interquartile range) until the onset of an adverse event caused by each drug category was as follows: barium sulfate containing X-ray contrast media [2.0 (1.0–3.0)], diazepines, oxazepines, thiazepines, and oxepines [8.0 (8.0–18.5)], drugs for treatment of hyperkalemia and hyperphosphatemia [29.0 (8.0–55.0)], non-selective monoamine reuptake inhibitors [19.0 (7.0–47.5)], and oral bowel cleanser [0.0 (0.0–0.0)]. Depending on the drug, the time to onset of side effects ranged from days to several months. Our results highlighted the need to perform detailed monitoring of each drug for possible association with DIGs, which might otherwise have fatal consequences.
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"Assessing Variation in Physicochemical Characteristics of Groundwater of Digod Tehsil of Kota District of Rajasthan, India, Using Statistical Correlation Study." Chemical Science Transactions, October 1, 2014. http://dx.doi.org/10.7598/cst2014.931.
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Matsumoto, Shuji. "Abstract WP458: Effect of Olmesartan / Azelnidipine Combination Tablets on Ambulatory Blood Pressure and Cognitive Function in the Post-Stroke Patients." Stroke 51, Suppl_1 (February 2020). http://dx.doi.org/10.1161/str.51.suppl_1.wp458.
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Background and aims: In patients with severe hypertension, or history of stroke, the lower limit of cerebral blood flow (CBF) autoregulation is shifted to a higher blood pressure (BP) than in healthy subjects. The aim of this study was to compare the effects of olmesartan/azelnidipine combination (OLM/AZ) vs high-dose of olmesartan on ambulatory blood pressure (ABPM), cognitive function, and rehabilitation outcome in the post-stroke patients with hypertension. Methods: A total of 36 patients, 20 men and 16 women, aged 58-72 years, with sitting diastolic BP >90mmHg and systolic BP >140mmHg were eligible for participation in the present study. We randomly assigned 36 patients to either the OLM/AZ group or high-dose olmesartan group for 12 weeks. At the end of a 2-week wash-out period and after 12 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed, and cognitive function was evaluated through neuropsychological testing. In addition, rehabilitation outcome measurements were also collected during study period. Results: Both treatments significantly reduced ambulatory BP. However, the OLM/AZ produced a greater reduction in 24-h, day-time and night time ABPM values. High-dose olmesartan did not induce significant changes in any of the cognitive function test scores, whereas at 12 weeks OLM/AZ significantly improved the neuropsychological test score (Digid span test, Token test, Digital symbol test, Trail making test part A and B) (p< 0.01). Patients treated with OLM/AZ showed effective rates of improvement in hand (38.9%), upper extremities (55.6%) and lower extremities (72.2%), measured by Brunnstrom stage; these improvements were significantly different from those in high-dose olmesartan group for the total (P< 0.05) scores. Conclusions: These results suggest that in hypertensive post-stroke patients treatment with OLM/AZ produces a slightly greater reduction in ambulatory BP than high-dose olmesartan, and unlike this latter, improves some of the components of cognitive function, particularly psychomotor speed, attention and mentation. Our results suggest that OLM/AZ may improve cognitive function and rehabilitation outcome in hypertensive stroke patients in whom CBF autoregulation is impaired.
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Wang, Huishan, Lisheng Liao, Shaohua Chen, and Lian-Hui Zhang. "A Quorum Quenching Bacterial Isolate Contains Multiple Substrate-Inducible Genes Conferring Degradation of Diffusible Signal Factor." Applied and Environmental Microbiology 86, no. 7 (January 24, 2020). http://dx.doi.org/10.1128/aem.02930-19.
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ABSTRACT Quorum quenching, which disrupts quorum sensing (QS) by either degradation of QS signals or interference of signal generation or perception, is a promising strategy for the prevention and control of QS-mediated bacterial infections. Diffusible signal factor (DSF) is widely conserved in many Gram-negative bacterial pathogens. In this study, we developed an efficient method for screening of highly active DSF degradation microorganisms. Among them, Pseudomonas sp. strain HS-18 showed a superior DSF degradation activity. Bioinformatics and genetic analyses showed that at least 4 genes, designated digA to digD, encoding fatty acyl coenzyme A ligase homologues, are responsible for DSF signal degradation. Interestingly, all 4 dig genes were induced by exogenous DSF, with digA being the most significantly induced. Expression of the dig genes in Xanthomonas campestris pv. campestris markedly reduced the accumulation of endogenous DSF, decreased production of virulence factors, and attenuated bacterial virulence on host plants. Similarly, application of strain HS-18 as a biocontrol agent could substantially reduce the disease severity caused by X. campestris pv. campestris. These results unveil the molecular basis of a highly efficient DSF degradation bacterial isolate and present useful genes and biocontrol agents for control of the infectious diseases caused by DSF-dependent bacterial pathogens. IMPORTANCE Diffusible signal factor (DSF) represents a family of widely conserved quorum sensing signals involved in the regulation of virulence factor production in many Gram-negative bacterial pathogens. In this study, we developed a novel and efficient method for screening highly active DSF degradation microorganisms. With this method, we identified a bacterial isolate, Pseudomonas sp. strain HS-18, with a superb DSF degradation activity. We further found that strain HS-18 contains 4 genes responsible for DSF signal degradation, and significantly, these were induced by exogenous DSF molecules. These findings unveil the molecular basis of a highly efficient DSF degradation bacterial isolate and present useful methods, genes, and agents for control of the infectious diseases caused by DSF-dependent bacterial pathogens.