bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Adipose-Derived Endothelial Progenitor Cells Accelerate Epithelialization of Radiation Ulcer in Nude Mice
Authors: Mori Masanori , Saito Natsumi , Shirado Takako , Wu Yunyan , Asahi Rintaro , Yoshizumi Kayo , Yamamoto Yoshihiro , Zhang Bihang , Yoshimura Kotaro 
Published: May 2023

Background:
Co-transplantation of adipose-derived stem cells (ASCs) and endothelial progenitor cells (EPCs) has shown superior angiogenic effects than ASCs alone in recent animal studies. However, EPCs could only be collected from blood vessels or bone marrow. Thus, we have established a method for purifying adipose-derived endothelial progenitor cells (AEPCs). We hypothesized that AEPCs would enhance the therapeutic effect of ASCs on radiation ulcer.

Methods:
Seven-week-old male nude mice (BALB/cAJcl-nu/nu) were irradiated on the dorsal skin (total 40 Gy) and twelve weeks later 6 mm diameter wounds were created. The mice were then treated with subcutaneous injection of human ASCs (1×10 5, n = 4), human AEPCs (2×10 5 or 5×10 5, n = 5), combinations of those (ASCs 1×10 5 + AEPCs 2×10 5 (n = 4) or 5×10 5 (n = 5)), or only vehicle (n = 7). Non-irradiated group was also prepared as a control (n = 6). The days required for macroscopic epithelialization was compared and immunostaining for human-derived cells and vascular endothelial cells was performed at Day 28.

Results:
AEPC-ASC combination-treated groups healed faster than ASC-treated group (14 ± 0 vs 17 ± 2 days, p < 0.01). Engraftment of the injected cells could not be confirmed. Only the non-irradiated mice had significantly higher vascular density (0.988 ± 0.183 vs 0.474 ± 0.092 ×10 -5µm -2, p = 0.02).

Conclusions:
The results suggested therapeutic potentials of AEPCs and an enhanced effect of combination with ASCs. This study is a xenogenic transplantation model and further validation in an autologous transplantation model is needed.

Clinical Relevance Statement:
Human AEPCs and its combination with ASCs accelerated epithelialization of radiation ulcer in nude mice. It was also suggested that administration of humoral factors secreted from AEPCs, e.g. treatment with culture conditioned media, could be used for the same purpose.
The ever-growing case for clozapine in the treatment of schizophrenia: an obligation for psychiatrists and psychiatry
Authors: Bittner Robert A. , Reif Andreas , Qubad Mishal 
Published: May 2023

Purpose of review
Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). Although the evidence base for its wide-ranging, unique efficacy continues to expand, clozapine remains alarmingly underutilized in industrialized countries. Analyzing the causes and consequences of this problem is crucial for substantially improving the quality of care for TRS patients.

Recent findings
Clozapine is the most effective antipsychotic for reducing all-cause mortality in TRS. In most cases, treatment resistance emerges during the first psychotic episode. Delaying clozapine treatment has a negative impact on long-term outcome. Patients’ experience with clozapine treatment is largely positive despite a comparatively high rate of side effects. Patients prefer clozapine, while psychiatrists regard it as a burden due to concerns regarding safety and side effect management. Shared decision-making (SDM), which increases the likelihood of a clozapine recommendation, is not routinely used, possibly due to stigmatization of TRS patients.

Summary
The mortality-reducing effects of clozapine alone warrant its regular use. Therefore, psychiatrists must not exclude patients from the decision regarding a clozapine trial by not even offering it. Rather, they have a clear obligation to align their actions more closely with the existing evidence and patients’ needs and to facilitate the timely initiation of clozapine.
Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact of self-reported fatigue and illness duration
Authors: Byrne Hollie , Josev Elisha K , Knight Sarah J , Scheinberg Adam , Rowe Katherine , Lubitz Lionel , Seal Marc L 
Published: May 2023

AbstractAdolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex illness of unknown aetiology. Emerging theories suggest ME/CFS may reflect a progressive, aberrant state of homeostasis caused by disturbances within the hypothalamus, yet few studies have investigated this using magnetic resonance imaging in adolescents with ME/CFS. We conducted a volumetric analysis to investigate whether whole and regional hypothalamus volumes in adolescents with ME/CFS differed compared to healthy controls, and whether these volumes were associated with fatigue severity and illness duration. 48 adolescents (25 ME/CFS, 23 controls) were recruited. Lateralised whole and regional hypothalamus volumes, including the anterior–superior, superior tubular, posterior, anterior-inferior and inferior tubular subregions, were calculated from T1-weighted images. When controlling for age, sex and intracranial volume, Bayesian linear regression revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a negative linear relationship between right anterior-superior volumes and fatigue severity was identified, which was absent in controls. In addition, Bayesian ordinal regression revealed a likely-positive association between illness duration and right superior tubular volumes in the ME/CFS group. While these findings suggest overall comparability in regional and whole hypothalamus volumes between adolescents with ME/CFS and controls, preliminary evidence was identified to suggest greater fatigue and longer illness duration were associated with greater right anterior-superior and superior-tubular volumes, respectively. These regions contain the anterior and superior divisions of the paraventricular nucleus, involved in the neuroendocrine response to stress, suggesting involvement in ME/CFS pathophysiology. However, replication in a larger, longitudinal cohort is required.
Disentangling visual exploration differences in cognitive impairment
Authors: Jiang Zifan , Seyedi Salman , Vickers Kayci L. , Manzanares Cecelia M. , Lah James J. , Levey Allan I. , Clifford Gari D. 
Published: May 2023

AbstractObjectiveCompared to individuals without cognitive impairment (CI), those with CI exhibit differences in both basic oculomotor functions and complex viewing behaviors. However, the characteristics of the differences and how those differences relate to various cognitive functions have not been widely explored. In this work we aimed to quantify those differences and assess general cognitive impairment and specific cognitive functions.MethodsA validated passive viewing memory test with eyetracking was administered to 348 healthy controls and CI individuals. Spatial, temporal, semantic, and other composite features were extracted from the estimated eye-gaze locations on the corresponding pictures displayed during the test. These features were then used to characterize viewing patterns, classify cognitive impairment, and estimate scores in various neuropsychological tests using machine learning.ResultsStatistically significant differences in spatial, spatiotemporal, and semantic features were found between healthy controls and individuals with CI. CI group spent more time gazing at the center of the image, looked at more regions of interest (ROI), transitioned less often between ROI yet in a more unpredictable manner, and had different semantic preferences. A combination of these features achieved an area under the receiver-operator curve of 0.78 in differentiating CI individuals from controls. Statistically significant correlations were identified between actual and estimated MoCA scores and other neuropsychological tests.ConclusionEvaluating visual exploration behaviors provided quantitative and systematic evidence of differences in CI individuals, leading to an improved approach for passive cognitive impairment screening.SignificanceThe proposed passive, accessible, and scalable approach could help with earlier detection and a better understanding of cognitive impairment.
BRAVEHEART: Open-source software for automated electrocardiographic and vectorcardiographic analysis
Authors: Stabenau Hans Friedrich , Waks Jonathan W. 
Published: May 2023

AbstractBackground and ObjectivesElectrocardiographic (ECG) and vectorcardiographic (VCG) analyses are used to diagnose current cardiovascular disease and for risk stratification for future adverse cardiovascular events. With increasing use of digital ECGs, research into novel ECG/VCG parameters has increased, but widespread computer-based ECG/VCG analysis is limited because there are no currently available, open-source, and easily customizable software packages designed for automated and reproducible analysis.Methods and ResultsWe present BRAVEHEART, an open-source, modular, customizable, and easy to use software package implemented in the MATLAB programming language, for scientific analysis of standard 12-lead ECGs acquired in a digital format. BRAVEHEART accepts a wide variety of digital ECG formats and provides complete and automatic ECG/VCG processing with signal filtering to remove high- and low-frequency artifact, non-dominant beat identification and removal, accurate fiducial point annotation, VCG construction, median beat construction, customizable measurements on median beats, and output of measurements and results in numeric and graphical formats.ConclusionsThe BRAVEHEART software package provides easily customizable scientific analysis of ECGs and VCGs. We hope that making BRAVEHART available will allow other researchers to further the field of EVG/VCG analysis without having to spend significant time and resources developing their own ECG/VCG analysis software and will improve the reproducibility of future studies. Source code, compiled executables, and a detailed user guide can be found athttp://github.com/BIVectors/BRAVEHEART. The source code is distributed under the GNU General Public License version 3.
Factors associated with unfavorable outcome after anterior circulation stroke despite successful reperfusion and early neurological improvement
Authors: Jesser Jessica , Nagel Simon , Bendszus Martin , Schönenberger Silvia , Ringleb Peter A. , Herweh Christian , Möhlenbruch Markus A. , Vey Johannes A. , Nguyen Thanh N. , Weyland Charlotte S. 
Published: May 2023

AbstractBackground and PurposeSuccessful reperfusion during endovascular therapy (EVT) usually leads to early neurological improvement (ENI), yet some patients do not achieve good long-term outcome. The aim of this study was to investigate factors associated with unfavorable clinical outcome (UCO) despite ENI.MethodsThis was a retrospective single-center analysis of consecutive patients treated for anterior circulation large vessel occlusion who achieved successful reperfusion and ENI (at least 20% lower follow-up NIHSS compared to NIHSS on admission) between 01/2014 and 04/2019. The primary endpoint was unfavorable outcome (90-day mRS > 2 or mRS > pre-stroke mRS). Patients with favorable clinical outcome (FCO) and UCO despite ENI were compared in univariable regression analysis.ResultsSuccessful EVT (mTICI 2c-3) and ENI occurred in 396/549 (72.1 %) patients and unfavorable outcome despite ENI in 168/396 (42.2 %) patients. Factors associated with UCO were pre-stroke mRS (Odds ratio (OR) 3.13 95% confidence interval (CI) 2.53–3.96, p < 0.001), age (OR 1.09 CI 1.07-1.12, p < 0.001), baseline NIHSs (OR 1.09 CI 1.06-1.13, p < 0.001), female sex (OR 1.92 CI 1.28-2.89, p = 0.002), hypertension (OR 2.32 CI 1.37-4.03, p = 0.002), smoking (OR 0.48 CI 0.25-0.87, p = 0.019), history of previous stroke (OR 2.7 CI 1.61-4.59, p < 0.001), atrial fibrillation (OR 1.73 CI 1.16-2.6, p = 0.007), neutrophil-lymphocyte ratio (OR 1.05 CI 1.01 – 1.09, p = 0.014), as well as ASPECTS after EVT (OR 0.77 CI 0.68-0.86, p < 0.001), TAN score (OR 0.60 CI 0.46-0.78, p < 0.001) and Swieten score (OR 2.55 CI 1.87-3.54, p < 0.001). Several ASPECTS regions were associated with UCO despite ENI (insula, M1-M3 and M5).ConclusionsRelevant factors associated with UCO despite successful EVT and ENI were patient age, sex, pre-stroke mRS, hypertension, history of smoking, previous stroke, atrial fibrillation, neutrophil-lymphocyte ratio, TAN and Swieten Score as well as ASPECTS after EVT. The involvement of certain brain regions by ASPECTS segments were associated with UCO despite ENI after EVT.
Psychiatric hospital admissions and linkages to ambulatory services in the Western Cape Province of South Africa (2015-2022): trends, risk factors and possible opportunities for intervention
Authors: Hussey Hannah , Mountford Timothy , Heekes Alexa , Dean Carol , Roelofse Marinda , Hendricks Lynne , Cossie Qhama , Koen Liezel , Cesar Warren , Lomas Vanessa , Pienaar David , Perez Giovanni , Boulle Andrew , Sorsdahl Katherine , Mahomed Hassan 
Published: May 2023

AbstractBackgroundPsychiatric hospital admissions in the Western Cape are increasing, driven by poverty and substance use.AimTo assess the trend of psychiatric admissions from 2015-2022 and factors associated with repeat psychiatric admissions and linkage to ambulatory services post-discharge.SettingPublic hospitals in the Western Cape, South AfricaMethodsUsing electronic data from the Provincial Health Data Centre, a consolidated routine service database, all psychiatric hospital admissions in the Western Cape were analyzed, stratified by hospital level. Mixed effects logistic regression was used to determine factors associated with successful linkage to ambulatory services within 30 days following hospital discharge, and repeat psychiatric admission within 30 and 90 days.ResultsPsychiatric hospital admissions, particularly at the district/acute level, were increasing prior to 2020 and an increasing proportion were substance related. 40% of admissions at the district level had not been seen at a primary health care facility in the year prior to admission. Males and those with substance use disorders were less likely to be successfully linked to outpatient services post-discharge. Successful linkage was most protective against readmission within 90 days with an adjusted odds ratio of 0.76 (95%CI 0.73-0.79) and 0.45 (95%CI 0.42-0.49) at district/acute and specialized hospitals respectively.ConclusionImproving linkage to ambulatory services for mental health patients post-discharge is likely to avert hospital readmissions.ContributionThis research highlights how often mental health patients requiring admissions are not seen at the primary health care level and quantifies the risk for readmission of not following up psychiatric admissions post-discharge.
Large tandem duplications in cancer result from transcription and DNA replication collisions
Authors: Yang Yang , Badura Michelle L. , O’Leary Patrick C. , Delavan Henry M. , Robinson Troy M. , Egusa Emily A. , Zhong Xiaoming , Swinderman Jason T. , Li Haolong , Zhang Meng , Kim Minkyu , Ashworth Alan , Feng Felix Y. , Chou Jonathan , Yang Lixing 
Published: May 2023

AbstractDespite the abundance of somatic structural variations (SVs) in cancer, the underlying molecular mechanisms of their formation remain unclear. Here, we use 6,193 whole-genome sequenced tumors to study the contributions of transcription and DNA replication collisions to genome instability. After deconvoluting robust SV signatures in three independent pan-cancer cohorts, we detect transcription-dependent replicated-strand bias, the expected footprint of transcription-replication collision (TRC), in large tandem duplications (TDs). Large TDs are abundant in female-enriched, upper gastrointestinal tract and prostate cancers. They are associated with poor patient survival and mutations inTP53,CDK12, andSPOP. Upon inactivating CDK12, cells display significantly more TRCs, R-loops, and large TDs. Inhibition of G2/M checkpoint proteins, such as WEE1, CHK1, and ATR, selectively inhibits the growth of cells deficient in CDK12. Our data suggest that large TDs in cancer form due to TRCs, and their presence can be used as a biomarker for prognosis and treatment.
Functional connectivity of cognition-related brain networks in adults with fetal alcohol syndrome
Authors: Sundermann Benedikt , Feldmann Reinhold , Mathys Christian , Rau Johanna M. H. , Garde Stefan , Braje Anna , Weglage Josef , Pfleiderer Bettina 
Published: May 2023

AbstractBackgroundFetal Alcohol Syndrome (FAS) can result in substantial cognitive dysfunction. Many of the cognitive functions affected are subserved by few functional brain networks. Functional connectivity (FC) in these networks can be assessed with resting state functional MRI (rs-fMRI). Alterations of FC have been reported in children and adolescents prenatally exposed to alcohol. However, previous reports varied substantially regarding which exact cognitive networks were affected, their interactions, and the directionalities of FC alterations. Despite persisting deficits, no previous studies have examined FC in older individuals. Purpose of this rs-fMRI study was to assess FC within and between cognition-related networks in young adults with FAS.MethodsCross-sectional study in patients with FAS (n = 39, age: 20.9 ± 3.4 years) and controls without prenatal alcohol exposure (n = 44, age: 22.2 ± 3.4 years). FC was calculated as correlation between cortical regions in ten cognition-related sub-networks. Subsequent modelling of overall FC was based on two-tailed t-tests comparing FC between FAS and controls. Results were subjected to a hierarchical statistical testing approach, first determining whether there is any alteration of FC in FAS (compared with controls) in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks, and finally to individual connections. The overall and network-level tests are based on the Higher Criticism (HC) approach for the detection of rare and week effects in high dimensional data. In an additional exploratory time- resolved FC analysis, potential group differences of dynamic FC states were assessed.ResultsComparing FAS subjects with controls, we observed altered FC of cognition-related brain regions globally, within 7 out of 10 networks, and between networks employing the HC statistic. This was most obvious in the dorsal attention A sub-network, followed by the salience / ventral attention A subnetwork. Findings also spanned subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the final high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences in the temporal behavior of FC states.ConclusionsFC in cognition-related brain networks was altered in adults with FAS. Effects were widely distributed across these networks, potentially reflecting the diversity of cognitive deficits in these individuals. Findings were pronounced in attention-related networks in line with attentional deficits previously reported. An additional exploratory time-resolved FC analysis did not reveal altered dynamic FC patterns.
Development of molecular subtype specific prognostic marker signature in immune response associated colon cancer through fuzzy based transcriptomic approach
Authors: Koçhan Necla , Dayanç Barış Emre 
Published: May 2023

AbstractObjectiveThe molecular heterogeneity of colon cancer makes the prediction of disease prognosis challenging. In order to resolve this heterogeneity, molecular tumor subtyping present solutions. These approaches are expected to contribute to clinical decision-making. In this study, we aimed to identify Consensus Molecular Subtype (CMS) specific prognostic genes of colon cancer, focusing on anti-tumor immune-response associated CMS1, through a fuzzy-based machine learning approach.Materials and MethodsWe applied Fuzzy C-Means (FCM) clustering to stratify patients into two groups and identified genes that predict significant disease-specific survival difference between groups. We then performed Cox regression analyses to identify the most significant genes associated with disease-specific survival. A subtype-specific risk score and a final risk score formulae were constructed and used to calculate risk scores to stratify patients into low and high-risk groups within each CMS (1 to 4) or independent of CMS respectively.ResultsWe identified CMS-specific genes and an overall 11-gene signature for prognostic risk prediction based on the disease-specific survival of colon cancer patients. The patients in both discovery and test cohorts were stratified into high and low-risk groups using subtype risk scores. The disease-specific survival of these risk groups within each CMS, except CMS3, was significantly different for both discovery and test cohorts.Discussion and ConclusionsWe have identified novel prognostic genes with potential immune regulatory roles within the immune-response associated CMS1. The low number of patients in the CMS3 cohort prevented subtype-specific prognostic gene validation. Tumor stage grouping of the validation cohort suggested the best prediction of prognosis in tumor stage III patients. In conclusion, newly identified eleven genes can efficiently predict the prognostic risk of colon cancer patients and classify patients into corresponding risk groups.Graphical Abstract
Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry
Authors: Mavura Yusuph , Sahin-Hodoglugil Nuriye , Hodoglugil Ugur , Kvale Mark , Martin Pierre-Marie , Van Ziffle Jessica , Devine W. Patrick , Ackerman Sara L. , Koenig Barbara A , Kwok Pui-Yan , Norton Mary E. , Slavotinek Anne , Risch Neil 
Published: May 2023

PurposeIt has been hypothesized that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort.MethodsCases (N=845) with suspected genetic disorders underwent ES for diagnosis. Continental genetic ancestry proportions were estimated from the ES data. We compared the distribution of genetic ancestries in positive, negative, and inconclusive cases by Kolmogorov Smirnov tests and linear associations of ancestry with DY by Cochran-Armitage trend tests.ResultsWe observed no reduction in overall DY associated with any continental genetic ancestry (Africa, America, East Asia, Europe, Middle East, South Asia). However, we observed a relative increase in proportion of autosomal recessive homozygous inheritance versus other inheritance patterns associated with Middle Eastern and South Asian ancestry, due to consanguinity.ConclusionsIn this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the ethical and equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations.