Miracle-dz/UniFAR-FTUs huggingface dataset:
Autologous Hematopoietic Cell Transplantation for Male Germ Cell Tumors: Improved Outcomes Over 3 Decades

The curative potential of autologous hematopoietic cell transplantation (autoHCT) for male germ cell tumors (GCTs) is well established. The optimal timing and number (single transplant [ST] versus tandem transplants [TT] versus triple transplants) of autoHCT are controversial, with wide practice variations. We examined survival trends among 2395 recipients of autoHCT for male GCTs between 1990 and 2015 reported to the Center for International Blood and Marrow Transplant Research. Trends and outcomes were analyzed by year of transplantation for intervals 1990 to 1994 (N = 288), 1995 to 1999 (N = 351), 2000 to 2004 (N = 376), 2005 to 2009 (N = 509), and 2010 to 2015 (N = 871). Multivariate analysis was restricted to the subset from 2000 to 2015 with research-level data (n = 267). The median duration of follow-up was 51 months. The median age at autoHCT was 31 years; 633 patients (26%) had primary extragonadal GCT, and 1167 (49%) underwent TT. The 3-year progression-free (PFS) and overall survival (OS) improved from 24% (95% confidence interval [CI], 18% to 31%) and 35% (95% CI, 29% to 40%), respectively, in 1990 to 1994 to 47% (95% CI, 43% to 50%) and 54% (95% CI, 50% to 57%), respectively, in 2010 to 2015 (P < .0001). TT recipients were more likely than ST recipients to undergo autoHCT as first salvage treatment. The proportion of TTs increased from 38% of all autoHCTs in 2000 to 2004 to 77% in 2010 to 2015. Nonseminoma histology, residual disease at autoHCT, >1 line of pretransplantation chemotherapy, and ST versus TT were associated with inferior PFS and OS. Post-transplantation survival has improved significantly over time for relapsed/refractory male GCT and is associated with the increased use of TTs (compared with STs) and performance of autoHCT earlier in the disease course. transplantation-related recorded and continuous variables a percentage of categorical Estimates of outcomes were reported as probabilities with 95% confidence intervals (CI). The probabilities of PFS and OS were estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. The probabilities of relapse/progression and NRM were estimated using the cumulative incidence function. Multivariate analysis was performed using Cox proportional hazards models to identify risk factors the outcomes of The variables tested in the multivariate analysis transplantation
Sedentary Time and White Matter Hyperintensity Volume in Older Adults.

PURPOSE Cerebrovascular disease in the form of white matter hyperintensities (WMH) increases with age and is associated separately with sedentary time and reduced kidney function. A better understanding of the relationships among these variables would help clarify whether sedentary time should be considered more closely in older adults at particular levels of kidney function to reduce the risk of WMH. METHODS We analyzed information from 94 healthy community-dwelling older adults to determine the association of sedentary time and WMH in non-demented, non-depressed older adults, and whether level of kidney function was an effect modifier of the relationship between sedentary time and WMH. Sedentary behavior was measured using the Sedentary Behavior Questionnaire. WMH was assessed using whole-brain 3T MRI T1- and T2-weighted images. Kidney function was calculated by the epi-CKD formula for estimated glomerular filtration rate (eGFR). Exposures or predictors were sedentary time, age, sex, education in years, Framingham stroke risk 10-year prediction score (FSRP-10), and eGFR. The analytical approach was multiple linear regression. RESULTS Adjusting for age, sex, education in years, FSRP-10, greater sedentary time was associated with greater WMH but this effect was dependent on level of eGFR (sedentary time*eGFR interaction b=-0.0005, p=.022). At eGFR values of 69, 81, and 93 ml/min/per 1.73m (the 25, 50, and 75 percentiles), sedentary time b coefficients were b=0.021 (95% CI 0.011-0.031), b=0.015 (95% CI 0.008-0.022), and b=0.009 (95% CI 0.003-0.016). The effect weakened linearly as eGFR increased, with no significant association at eGFR ≥97 ml/min/per 1.73m. CONCLUSIONS Findings suggest that sedentary time is associated with WMH in persons with an eGFR ≤96 ml/min/per 1.73m and that this association is stronger with lower levels of kidney function.
The Role of L- and T-Type Calcium Channels in Local and Remote Calcium Responses in Rat Mesenteric Terminal Arterioles

Background/Aims: The roles of intercellular communication and T-type versus L-type voltage-dependent Ca2+ channels (VDCCs) in conducted vasoconstriction to local KCl-induced depolarization were investigated in mesenteric arterioles. Methods: Ratiometric Ca2+ imaging (R) using Fura-PE3 with micro-ejection of depolarizing KCl solution and VDCC blockers, and immunohistochemical and RT-PCR techniques were applied to isolated rat mesenteric terminal arterioles (n = 71 from 47 rats; intraluminal diameter: 24 ± 1 μm; length: 550–700 μm). Results: Local application of KCl (at 0 μm) led to local (ΔR = 0.54) and remote (ΔR = 0.17 at 500 μm) increases in intracellular Ca2+. Remote Ca2+ responses were inhibited by the gap junction uncouplers carbenoxolone and palmitoleic acid. CaV1.2, CaV3.1 and CaV3.2 channels were immunolocalized in vascular smooth muscle cells and CaV3.2 in adjacent endothelial cells. Local and remote Ca2+ responses were inhibited by bath application of L- and T-type blockers [nifedipine, NNC 55-0396 and R(–)-efonidipine]. Remote Ca2+ responses (500 μm) were not affected by abolishing Ca2+ entry at an intermediate position on the arterioles (at 200–300 μm) using micro-application of VDCC blockers. Conclusion: Both L- and T-type channels mediate Ca2+ entry during conducted vasoconstriction to local KCl in mesenteric arterioles. However, these channels do not participate in the conduction process per se.
Maturation of heart valve cell populations during postnatal remodeling

ABSTRACT Heart valve cells mediate extracellular matrix (ECM) remodeling during postnatal valve leaflet stratification, but phenotypic and transcriptional diversity of valve cells in development is largely unknown. Single cell analysis of mouse heart valve cells was used to evaluate cell heterogeneity during postnatal ECM remodeling and leaflet morphogenesis. The transcriptomic analysis of single cells from postnatal day (P)7 and P30 murine aortic (AoV) and mitral (MV) heart valves uncovered distinct subsets of melanocytes, immune and endothelial cells present at P7 and P30. By contrast, interstitial cell populations are different from P7 to P30. P7 valve leaflets exhibit two distinct collagen- and glycosaminoglycan-expressing interstitial cell clusters, and prevalent ECM gene expression. At P30, four interstitial cell clusters are apparent with leaflet specificity and differential expression of complement factors, ECM proteins and osteogenic genes. This initial transcriptomic analysis of postnatal heart valves at single cell resolution demonstrates that subpopulations of endothelial and immune cells are relatively constant throughout postnatal development, but interstitial cell subpopulations undergo changes in gene expression and cellular functions in primordial and mature valves. Summary: Transcriptomic single cell analysis of postnatal developing heart valves identifies novel cell populations and uncovers interstitial cell heterogeneity.
P‐selectin plays a role in haem‐induced acute lung injury in sickle mice

Dinisha Govender Amy A. Kirkwood Ajay Vora Sujith Samarasinghe Asim Khwaja Victoria Grandage Anupama Rao Philip Ancliff Vesna Pavasovic Danny Cheng Ben Carpenter Stephen Daw Rachael Hough David O’Connor Department of Adolescent Haematology, University College London Hospital (UCLH), Department of Paediatric Haematology, Great Ormond Street Hospital, Cancer Research UK & UCL Cancer Trials Centre, UCL Cancer Institute, Department of Young Adult Haematology, University College London Hospital (UCLH), and Department of Haematology, University College London Cancer Institute, London, UK. E-mail: maeve.o’reilly@ucl.ac. uk
Strongly Typed Genetic Programming

Genetic programming is a powerful method for automatically generating computer programs via the process of natural selection (Koza, 1992). However, in its standard form, there is no way to restrict the programs it generates to those where the functions operate on appropriate data types. In the case when the programs manipulate multiple data types and contain functions designed to operate on particular data types, this can lead to unnecessarily large search times and/or unnecessarily poor generalization performance. Strongly typed genetic programming (STGP) is an enhanced version of genetic programming that enforces data-type constraints and whose use of generic functions and generic data types makes it more powerful than other approaches to type-constraint enforcement. After describing its operation, we illustrate its use on problems in two domains, matrix/vector manipulation and list manipulation, which require its generality. The examples are (1) the multidimensional least-squares regression problem, (2) the multidimensional Kalman filter, (3) the list manipulation function NTH, and (4) the list manipulation function MAPCAR.
Diagnostic reference levels for 18F‐FDG whole body PET/CT procedures: Results from a survey of 12 centres in Australia and New Zealand

The aim of this work is to report diagnostic reference levels (DRLs) for hybrid positron emission tomography and x‐ray computed tomography (PET/CT) exams in Australia (AU) for Queensland (QLD) and Western Australia (WA) (AU QLD/WA) and New Zealand (NZ).
Moderate-to-severe obstructive sleep apnea is associated with telomere lengthening.

Obstructive sleep apnea (OSA) is associated with cardiometabolic diseases. Telomere shortening is linked to hypertension, diabetes mellitus, and cardiovascular diseases. Because these conditions are highly prevalent in OSA, we hypothesized that telomere length (TL) would be reduced in OSA patients. We identified 106 OSA and 104 non-OSA subjects who underwent polysomnography evaluation. Quantitative PCR was used to measure telomere length in genomic DNA isolated from peripheral blood samples. The association between OSA and TL was determined using unadjusted and adjusted linear models. There was no difference in TL between the OSA and non-OSA (control) group. However, we observed a J-shaped relationship between TL and OSA severity: the longest TL in moderate-to-severe OSA [4,918 ± 230 (SD) bp] and the shortest TL in mild OSA (4,735 ± 145 bp). Mean TL in moderate-to-severe OSA was significantly longer than in the control group after adjustment for age, sex, body mass index, hypertension, dyslipidemia, and depression (β = 96.0, 95% confidence interval: 15.4-176.6, P = 0.020). In conclusion, moderate-to-severe OSA is associated with telomere lengthening. Our findings support the idea that changes in TL are not unidirectional processes, such that telomere shortening occurs with age and disease but may be prolonged in moderate-to-severe OSA.NEW & NOTEWORTHY Here, we show that moderate-to-severe obstructive sleep apnea is associated with longer telomeres, independent of age and cardiovascular risk factors, challenging the hypothesis that telomere shortening is a unidirectional process related to age/disease. A better understanding of the mechanisms underlying telomere dynamics may identify targets for therapeutic intervention in cardiovascular aging/other chronic diseases.
Effectiveness of Providing Education About Alcohol Use Disorders and Compassion Fatigue for Emergency Department Nurses

Background: Emergency departments (EDs) treat over 20,000 patients daily with alcohol use disorders (AUDs). However, nurses receive limited education about AUDs. Studies have shown that ED nurses have negative attitudes about patients with AUDs. Negativity can contribute to the symptoms of compassion fatigue (CF) and to dissatisfaction with work. Purpose: The aim of this study was to design, implement, and evaluate education about AUDs and CF for ED nurses. Design: This study used a quasi-experimental pretest–posttest within-subjects design. Sample: A convenience sample of 44 nurses was recruited at a large urban ED. Methods: Nurses completed demographics, Professional Quality of Life: Compassion Satisfaction and Fatigue (ProQOL), and Short Alcohol and Alcohol Problems Perceptions Questionnaire. Then, the nurses participated in 5 hours of an online educational program and a 1-hour live class about AUDs and CF. The surveys were readministered. Results: The difference in pretest and posttest Short Alcohol and Alcohol Problems Perceptions Questionnaire subscales of role security (expected value = 8.5, p < .006) and therapeutic commitment (expected value = 7.50, p = .018) was statistically significant. For ProQOL constructs, no statistical significance was found. The ProQOL subscales were compared with norms and were statistically significantly different. Conclusion: Nurses’ attitudes about patients with AUDs improved after completing the curriculum. Studied nurses had higher levels of professional satisfaction at baseline.
Dorsal Onlay versus Ventral Onlay Urethroplasty for Anterior Urethral Stricture: A Meta-Analysis

Background: Ventral and dorsal sides of urethra were chosen to place grafts in free graft onlay urethroplasty. As the advantages and disadvantages of these two sites are still unclear, we systemically analyzed clinical articles reported in the literature. Materials and Methods: The literature till October 2007 regarding the use of ventral/dorsal graft urethroplasty in anterior urethral strictures was searched using the MEDLINE, Cochrane Library, and EMBASE databases. ‘Urethral stricture’ or ‘urethral stenosis’ and ‘urethroplasty’ or ‘urethral reconstruction’ were used as search terms. Data were analyzed independently by two reviewers. Results: 49 studies (1,263 cases) were included. The success rates of ventral onlay urethroplasty (750 cases) and dorsal onlay (513 cases) were 82.5 and 86.9% (p = 0.034). Buccal mucosa graft had the highest success rate (88.1%) and had a similar rate between the dorsal and ventral onlay techniques (89.2 vs. 87.6%, p = 0.472). For free skin graft, the dorsal onlay success rate was higher than ventral (84.7 vs. 74.7, p = 0.016). Bulbar urethral stricture achieved the higher success rate than pendulous urethral stricture (87.4 vs. 77.6%, p = 0.019). Conclusions: Dorsal onlay is better than ventral onlay in free skin graft urethroplasty. Bulbar urethra is the most suitable site for graft onlay urethroplasty, and buccal mucosa graft is helpful for achieving good results.
Structure Learning in Conditional Probability Models via an Entropic Prior and Parameter Extinction

We introduce an entropic prior for multinomial parameter estimation problems and solve for its maximum a posteriori (MAP) estimator. The prior is a bias for maximally structured and minimally ambiguous models. In conditional probability models with hidden state, iterative MAP estimation drives weakly supported parameters toward extinction, effectively turning them off. Thus, structure discovery is folded into parameter estimation. We then establish criteria for simplifying a probabilistic model's graphical structure by trimming parameters and states, with a guarantee that any such deletion will increase the posterior probability of the model. Trimming accelerates learning by sparsifying the model. All operations monotonically and maximally increase the posterior probability, yielding structure-learning algorithms only slightly slower than parameter estimation via expectation-maximization and orders of magnitude faster than search-based structure induction. When applied to hidden Markov model training, the resulting models show superior generalization to held-out test data. In many cases the resulting models are so sparse and concise that they are interpretable, with hidden states that strongly correlate with meaningful categories.
C‐reactive protein exacerbates epithelial‐mesenchymal transition through Wnt/β‐catenin and ERK signaling in streptozocin‐induced diabetic nephropathy

Previous studies have reported the pathogenic role of C‐reactive protein (CRP) during diabetic kidney disease (DKD) in human CRP transgenic and Crp−/− mice. However, because humans and mice have inverse acute phase expression patterns of CRP and serum amyloid P component, this could lead to the inaccurate evaluation of CRP function with the above‐mentioned CRP transgenic mouse. But different from mice, rats have the same acute phase protein expression pattern as human, which might avoid this problem and be a better choice for CRP function studies. To dispel this doubt and accurately define the role of CRP during diabetic nephropathy, we created the first Crp−/− rat model, which we treated with streptozocin to induce DKD for in vivo studies. Moreover, an established cell line (human kidney 2) was used to further investigate the pathologic mechanisms of CRP. We found that CRP promotes epimelial‐mesenchymal transition (EMT) through Wnt/β‐catenin and ERK1/2 signaling, which are dependent on CRP binding to FcγRII on apoptotic cells. By promoting EMT, CRP was demonstrated to accelerate the development of DKD. We thus present convincing evidence demonstrating CRP as a therapeutic target for DKD treatment—Zhang, L. , Shen, Z. ‐Y. , Wang, K. , Li, W. , Shi, J.‐M. , Osoro, E. K. , Ullah, N. , Zhou, Y. , Ji, S. ‐R. C‐reactive protein exacerbates epimelial‐mesenchymal transition through Wnt/β‐catenin and ERK signaling in streptozocin‐induced diabetic nephropathy. FASEB J. 33, 6551–6563 (2019). www.fasebj. org
Phase 3 study of subcutaneous bortezomib, thalidomide, and prednisolone consolidation after subcutaneous bortezomib-based induction and autologous stem cell transplantation in patients with previously untreated multiple myeloma: the VCAT study

Abstract Efficacy and safety of bortezomib-based consolidation following ASCT were investigated in newly diagnosed multiple myeloma patients from Australia, Korea, and China. Patients received three cycles of bortezomib-cyclophosphamide-dexamethasone induction followed by high-dose therapy/ASCT, then were randomized (1:1) to consolidation with TP (thalidomide 100 mg/d for ≤12 months/until disease progression; prednisolone 50 mg on alternate days indefinitely/until disease progression; n = 100) or VTP (subcutaneous bortezomib 1.3 mg/m2 every 2 weeks for 32 weeks, plus TP; n = 103). The hypothesized difference in CR + VGPR rate (after ≤12 months consolidation therapy) was not met. The rate of CR + VGPR was numerically higher with VTP versus TP; however, this was not statistically significant (85.7% versus 77.1%; rate difference 8.6%; 95% confidence interval −2.3%–19.5%; p = .122). Secondary efficacy outcomes were similar between treatment arms. Addition of bortezomib to TP consolidation was associated with limited additional toxicity but did not significantly improve efficacy versus TP. Trial registration: ClinicalTrials.gov identifier: NCT01539083.
Effects of social support and self‐efficacy on the psychosocial adjustment of Korean ostomy patients

This study aims to test which factors influence and aid the psychosocial adjustment of patients with an ostomy and to provide data for the development of programmes for the self‐management of and psychosocial adjustment to intestinal stomas. A total of 150 ostomy patients were recruited between December 1, 2017 and March 26, 2018 in Korea and completed self‐report questionnaires. Data of 25 participants were excluded, resulting in a sample size of 125 participants. Factors, including social support subtypes and self‐efficacy, that influence the psychosocial adjustment were analysed using Cox's regression. Of the factors that influenced the adjustment groups after adjusting for time, the following subtypes of social support were found to influence the patients' adjustment: the patients' psychosocial adjustment increased by 0.4 when the level of medical staff support increased by 1 (Exp[B] = 1.04, P = 0.007), and adjustment decreased by 0.3 when the level of family support increased by 1 (Exp[B] = 0.97, P < 0.001). As medical staff support who have expertise exert more of an influence on the psychosocial adjustment of ostomy patients than self‐efficacy and family support, psychosocial adjustment programmes that reflect this and nurses specialised in care for ostomy patients are required.
Effect of isoflurane on myocardial ischemia-reperfusion injury through the p38 MAPK signaling pathway.

OBJECTIVE To investigate the effect of isoflurane on myocardial ischemia-reperfusion injury through the p38 mitogen-activated protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS A total of 36 specific-pathogen-free (SPF) Sprague-Dawley rats were randomly divided into sham group (n=12), model group (n=12) and isoflurane group (n=12). In model group and isoflurane group, the myocardial ischemia-reperfusion injury model was established via the ligation of left anterior descending coronary artery (ischemia for 30 min and reperfusion for 3 h). In sham group, the left anterior descending coronary artery was not ligated, but the chest was opened and threaded using the same method. After ischemia, the rats in isoflurane group were inhaled with isoflurane. The cardiac function of rats in each group was detected before ischemia (T0) and once every 2 h after reperfusion (T1-T4) for a total of 5 times, and the cardiac function indexes included ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVEDP). After the rats were executed, the myocardial infarction tissues were taken for hematoxylin-eosin (HE) staining and 2,3,5-triphenyltetrazolium chloride (TTC) staining to observe the morphological changes in tissues and the degrees of myocardial ischemia and infarction. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in myocardial cells in the infarction site in each group were detected using the MDA and SOD kits. Moreover, the expression levels of related proteins in the p38 MAPK signaling pathway in myocardial cells in the infarction site were detected via Western blotting. RESULTS In model group, the cardiac function was significantly damaged (p<0.01), there was significant pathological damage in the myocardium, the area of myocardial infarction was significantly increased (p<0.01), the MDA content was significantly increased (p<0.01), the SOD activity declined obviously (p<0.01), and the expression levels of p-p38 and p-tau protein were significantly increased (p<0.01) compared with those in control group. After intervention with isoflurane, the cardiac function of rats was significantly improved (p<0.01), the pathological damage in myocardial tissues was alleviated, the area of myocardial infarction was reduced (p<0.01), the MDA content declined (p<0.01), the SOD activity was increased (p<0.01), and the expression levels of p-p38 and p-tau protein were decreased (p<0.01). CONCLUSIONS Isoflurane can, through inhibiting the p38 MAPK signaling pathway, effectively protect the cardiac function of rats from myocardial ischemia-reperfusion injury, reduce the area of myocardial infarction, alleviate the pathological damage in myocardial cells and reduce the oxidative stress response.