bluuebunny/crossref_metadata_2025_split huggingface dataset:
White matter hyperintensities modify relationships between corticospinal tract damage and motor outcomes after stroke
Authors: Ferris Jennifer K. , Lo Bethany P. , Barisano Giuseppe , Brodtmann Amy , Buetefisch Cathrin M. , Conforto Adriana B. , Donnelly Miranda H. , Egorova-Brumley Natalia , Hayward Kathryn S. , Khlif Mohamed Salah , Revill Kate P. , Zavaliangos-Petropulu Artemis , Boyd Lara A. , Liew Sook-Lei 
Published: October 2023

AbstractMotor outcomes after stroke relate to corticospinal tract (CST) damage. Concurrent damage from white matter hyperintensities (WMHs) might impact neurological capacity for recovery after CST injury. Here, we evaluated if WMHs modulate the relationship between CST damage and post-stroke motor impairment outcome.We included 223 individuals from the ENIGMA Stroke Recovery Working Group. CST damage was indexed with weighted CST lesion load (CST-LL). Mixed effects beta-regression models were fit to test the impact of CST-LL, WMH volume, and their interaction on motor impairment.WMH volume related to motor impairment above and beyond CST-LL (β = 0.178, p = 0.022). We tested if relationships varied by WMH severity (mild vs. moderate-severe). In individuals with mild WMHs, motor impairment related to CST-LL (β = 0.888, p < 0.001) with a CST-LL x WMH interaction (β = -0.211, 0.026). In individuals with moderate-severe WMHs, motor impairment related to WMH volume (β = 0.299, p = 0.044), but did not significantly relate to CST-LL or a CST-LL x WMH interaction.WMH-related damage may be under-recognised in stroke research as a factor contributing to variability in motor outcomes. Our findings emphasize the importance of brain structural reserve in motor outcomes after brain injury.
Comparative Analysis of Machine Learning Models for Efficient Low Back Pain Prediction Using Demographic and Lifestyle Factors
Authors: Kim Jun-hee 
Published: October 2023

ABSTRACTBackgroundLow back pain (LBP) is one of the most frequently occurring musculoskeletal disorders, and factors such as lifestyle as well as individual characteristics are associated with LBP. The purpose of this study was to develop and compare efficient low back pain prediction models using easily obtainable demographic and lifestyle factors.MethodsData from adult men and women aged 50 years or older collected from the Korean National Health and Nutrition Examination Survey (KNHANES) were used. The dataset included 22 predictor variables, including demographic, physical activity, occupational, and lifestyle factors. Four machine learning algorithms, including XGBoost, LGBM, CatBoost, and RandomForest, were used to develop predictive models.ResultsAll models achieved an accuracy greater than 0.8, with the LGBM model outperforming the others with an accuracy of 0.830. The CatBoost model had the highest sensitivity (0.804), while the LGBM model showed the highest specificity (0.884) and F1-Score (0.821). Feature importance analysis revealed that EQ-5D was the most critical variable across all models.ConclusionIn this study, an efficient LBP prediction model was developed using easily accessible variables. Using this model, it may be helpful to identify the risk of LBP in advance or establish prevention strategies in subjects who have difficulty accessing medical facilities.
Protein language models-assisted engineering of Uracil-N glycosylase enables programmable T-to-G and T-to-C base editing
Authors: He Yan , Zhou Xibin , Chang Chong , Chen Ge , Liu Weikuan , Li Geng , Fan Xiaoqi , Ma Yunqing , Yuan Fajie , Chang Xing 
Published: October 2023

AbstractCurrent base editors use DNA deamination enzymes, such as cytidine deaminase (CBE) or adenine deaminase (ABE), to facilitate transition nucleotide substitutions. Combining CBE or ABE with glycosylase enzymes, including CGBE and AYBE, can induce limited transversion mutations. Nonetheless, a critical demand remains for base editors capable of generating alternative mutation types, such as T>G corrections, which could address over 17% of monogenic SNVs responsible for human genetic diseases. In this study, we leveraged protein language models to engineer a uracil-N-glycosylase (UNG) variant with altered substrate specificities to thymines (eTDG). Notably, after only two rounds of testing fewer than 50 predicted variants, more than 50% exhibited a 1.5-11-fold enhancement in enzymatic activities, a success rate much greater than random mutagenesis. When eTDG was fused with Cas9 nickase without deaminases, it effectively induced programmable T to G or T to C substitutions and precisely corrected db/db diabetic mutation in mice (up to 55%). Our findings not only establish orthogonal strategies for developing novel base editors, but also demonstrate the capacities of protein language models for optimizing enzymes without extensive task-specific training data or laborious experimental procedures.
Impairment of hippocampal astrocyte-mediated striatal dopamine release and locomotion in Alzheimer’s disease
Authors: Tournier Benjamin B. , Ceyzériat Kelly , Badina Aurélien M. , Gloria Yessica , Fall Aïda , Amossé Quentin , Tsartsalis Stergios , Millet Philippe 
Published: October 2023

AbstractClinical and translational research has identified deficits in the dopaminergic neurotransmission in the striatum in Alzheimer’s disease (AD) and this could be related to the pathophysiology of psychiatric symptoms appearing even at early stages of the pathology. We hypothesized that AD pathology in the hippocampus may influence dopaminergic neurotransmission even in the absence of AD-related lesion in the mesostriatal circuit. We thus chemogenetically manipulated the activity of hippocampal neurons and astrocytes in wild-type and hemizygous TgF344-AD (Tg) rats, an animal model of AD pathology. We assessed the brain-wide functional output of this manipulation usingin vivoSingle Photon Emission Computed Tomography to measure cerebral blood flow and D2/3receptor binding. We also assessed the effects of the chemogenetic manipulations on astrocytic and microglial capacity to surround and phagocytize Aβ both locally and in the striatum. Our results show that acute and chronic neuronal and astrocytic stimulation induces widespread effects on the brain regional activation pattern, notably with an inhibition of striatal activation. In the TgF344-AD rats, both these effects were blunted. Chemogenetic stimulation in the hippocampus increased microglial density and its capacity to limit AD pathology, whereas these effects were absent in the striatum perhaps as a consequence of the altered connectivity between the hippocampus and the striatum. Our work suggests that hippocampal AD pathology may alter mesostriatal signalling and induce widespread alterations of brain activity. Neuronal and astrocytic activation may induce a protective, Aβ-limiting phenotype of microglia, which surrounds Aβ plaques and limits Αβ concentration more efficiently.
Transcriptional phenocopies of deleteriousKEAP1mutations dictate survival outcomes in lung cancer treated with immunotherapy
Authors: Scalera Stefano , Ricciuti Biagio , Marinelli Daniele , Mazzotta Marco , Cipriani Laura , Bon Giulia , Schiavoni Giulia , Terrenato Irene , Federico Alessandro Di , Alessi Joao V. , Fanciulli Maurizio , Ciuffreda Ludovica , Nicola Francesca De , Goeman Frauke , Caravagna Giulio , Santini Daniele , Maria Ruggero De , Cappuzzo Federico , Ciliberto Gennaro , Jamal-Hanjani Mariam , Awad Mark M. , McGranahan Nicholas , Maugeri-Saccà Marcello 
Published: October 2023

AbstractMutational models denoting KEAP1-NRF2 pathway activation have emerged as determinants of survival outcomes in non-small cell lung cancer (NSCLC). Hypothesizing that genetically distinct tumors recapitulate the transcriptional footprint ofKEAP1mutations (KEAPness), we identified a KEAP1-NRF2-related gene set shared by tumors with and without pathway mutations. KEAPness-dominant tumors were associated with poor survival outcomes and immune exclusion in two independent cohorts of immunotherapy-treated NSCLC (SU2C and OAK/POPLAR). Moreover, patients with KEAPness tumors had survival outcomes comparable to theirKEAP1-mutant counterparts. In the TRACERx421, KEAPness exhibited limited transcriptional intratumoral heterogeneity and an immune-excluded microenvironment, as highlighted by orthogonal methods for T cell estimation. This phenotypic state widely occurred across genetically divergent tumors, exhibiting shared and private cancer genes under positive selection when compared toKEAP1-mutant tumors. Collectively, we discovered the pervasive nature of the KEAPness phenotypic driver across evolutionary divergent tumors. This model outperforms mutation-based classifiers in predicting survival outcomes.
Oxytocin-augmented modular-based group intervention for loneliness: A proof-of-concept randomized-controlled trial
Authors: Berger Ruben , Hurlemann Rene , Shamay-Tsoory Simone G. , Kantermann Alisa , Brauser Maura , Gorni Jessica , Luhmann Maike , Schramm Elisabeth , Schultz Johannes , Philipsen Alexandra , Lieberz Jana , Scheele Dirk 
Published: October 2023

AbstractIntroductionLoneliness poses a significant health problem and existing psychological interventions have shown only limited positive effects on loneliness. Based on preliminary evidence for impaired oxytocin signaling in trait-like loneliness, the current proof-of-concept study used a randomized, double-blind, placebo- controlled design to probe intranasal oxytocin (OT) as an adjunct to a short-term modular-based group intervention for individuals suffering from high trait-like loneliness (HL, UCLA loneliness scale ≥ 55).MethodsSeventy-eight healthy HL adults (56 women) received five weekly group psychotherapy sessions targeting cognitive biases in loneliness. HL participants received OT or placebo before the intervention sessions. Primary outcomes were trait- like loneliness measured at baseline, after the intervention, and again at two follow-up time points (three weeks and three months), and, assessed at each session, state loneliness (visual analog scale), perceived stress (Perceived Stress Scale, PSS-10), quality of life (World Health Organization Five Well-Being Index, WHO-5), and the therapeutic relationship (Group Questionnaire, GQ-D).ResultsThe psychological intervention was associated with significantly reduced perceived stress and improved trait-like loneliness across treatment groups, which was still evident at the 3-month follow-up. OT had no significant effect on trait-like loneliness, quality of life, or perceived stress. However, compared to placebo, OT significantly facilitated the decrease in state loneliness within sessions and significantly improved positive bonding between the group members.ConclusionDespite significantly improved trait-like loneliness after the intervention, OT did not significantly augment this effect. Further studies are needed to determine optimal intervention designs to translate the observed acute effects of OT into long- term benefits.
Predictive factors of non-pharmacological measures to prevent SARS-CoV-2 contagion: Results of a large adult Spanish sample from the PSY-COVID study
Authors: Mateo-Canedo Corel , Sanabria-Mazo Juan P. , Navarro Jose-Blas , Cigarroa Igor , Álvarez María , Armayones Manuel , Martínez-Blanquet Luis J. , Lamana Rafael Zapata , Crespo Neus , Korniyenko Marta , Sanz Antoni 
Published: October 2023

ABSTRACTAim:the objective of the study was to identify the factors that predicted the intention to carry out coronavirus infection prevention behaviors in the Spanish population during the first wave of the pandemic, a time when the vaccines were in the development phase and the containment of the pandemic depended on non-pharmacological measures. Method: a cross-sectional study (PSY-COVID) was carried out based on an online form that contained instruments for possible predictor variables of seven prevention behaviors, based on a non-probabilistic sampling of 17725 Spanish adults. Results: self-efficacy and outcome expectations related to Coronavirus disease (COVID-19) preventive behaviors, as well as the interaction of perceived severity with both personal vulnerability and actual adherence, appeared as the main predictive variables of the intention to carry out preventive behaviors against the SARS-CoV-2 virus. Slight, but significant differences were observed in behavioral intentions among Spanish autonomous communities, probably linked to differences in the impact of the pandemic in each territory. Conclusion: It is necessary to implement consistent communications that allow for the development of appropriate expectations and encourage adherence to preventive behaviors, as well as recognizing regional disparities in preventive behaviors and their causes to promote compliance.
Real-World Data Collection from Expanded Access Case Studies for the Treatment of Nontuberculous Mycobacterial Infection with Clofazimine
Authors: Gravelin Misty , Nguyen Theophilus , Davies Madeleine , Richards Blair , Sexton Jonathan Z. , Gregg Kevin , Weatherwax Kevin J. 
Published: October 2023

AbstractBackgroundDue to its indolent nature, nontuberculous mycobacteria (NTM) are increasing in global prevalence as a cause of pulmonary infections and are difficult to treat with traditional antibiotics. Here, we study the repurposing of clofazimine (CFZ) to treat NTM through expanded access in a single health system. Our main objectives are to describe the feasibility of accessing and analyzing expanded access data and to generate hypotheses regarding CFZ use in NTM treatment.MethodsA retrospective chart review was performed on patients within a single health system who had been approved for expanded access of clofazimine or who received it through an outside hospital for NTM treatment. Data were collected on patients’ baseline demographics, details of their NTM infection, concomitant therapies, and results as of 30 June 2021.ResultsA total of 55 patients were identified upon initial review as potentially receiving CFZ for NTM infection. After excluding 19 patients who did not initiate CFZ, data from the remaining 36 patients were collected and summarized. The median age at which patients were diagnosed with NTM was 51.3 years old, with a median BMI of 21.2 kg/m2. Patients were more likely to be female (64%), have a baseline lung disease (72%), and 52% were current or former smokers at the time of their diagnosis. The most common species isolated wasM. aviumcomplex (47%) followed byM. abscessus(36%), with the most common site of infection being the lung (78%). The majority of patients presented with productive cough with excess sputum production followed by pulmonary nodules and bronchiectasis present on radiograph.ConclusionsThis study demonstrated the difficulty of collecting retrospective real-world data via electronic healthcare records on symptoms, side effects, and radiography from patients who obtained a drug through expanded access. Based on the findings of this study, we recommend further research into the potential use of CFZ in patients withM. abscessuspulmonary infections.
Consistency of the continuous flow pressure gradient despite aortic arch anomalies co-existing with coarctation
Authors: Ghorbannia Arash , Spearman Andrew D. , Sawalhi Shahd , Woods Ronald K. , Maadooliat Mehdi , LaDisa John F. 
Published: October 2023

AbstractAimsSeverity assessment for coarctation of the aorta (CoA) is challenging due to concomitant morphological anomalies (complex CoA) and inaccurate Doppler-based indices. Promising diagnostic performance has been reported for the continuous flow pressure gradient (CFPG), but it has not been studied in complex CoA. Our objective was to characterize the effect of complex CoA and associated hemodynamics on CFPG in a clinical cohort.Methods and ResultsRetrospective analysis identified discrete juxtaductal (n=25) and complex CoA (n=43; transverse arch and/or isthmus hypoplasia) patients with arm-leg systolic blood pressure gradients (BPG) within 24 hours of echocardiography for comparison to BPG by conventional Doppler indices (simplified Bernoulli equation and modified forms correcting for proximal kinetic energy and/or recovered pressure). Results were interpreted using the current CoA guideline (BPG ≥20 mmHg) to compare diagnostic performance indicators including receiver operating characteristic curves, sensitivity, specificity, and diagnostic accuracy, among others. Echocardiography Z-scored aortic diameters were applied with computational stimulations from a preclinical CoA model to understand aspects of the CFPG driving performance differences.Diagnostic performance was substantially reduced from discrete to complex CoA for conventional Doppler indices calculated from patient data, and by hypoplasia and/or long segment stenosis in simulations. In contrast, diagnostic indicators for the CFPG only modestly dropped for complex vs discrete CoA. Simulations revealed differences in performance due to inclusion of the Doppler velocity index and diastolic pressure half-time in the CFPG calculation.ConclusionCFPG is less affected by aortic arch anomalies co-existing with CoA when compared to conventional Doppler indices.
Clinical value of the fibrosis-4 index in predicting mortality in patients with right ventricular pacing
Authors: Inoue Naoya , Morikawa Shuji , Ogane Takashi , Hiramatsu Takehiro , Murohara Toyoaki 
Published: October 2023

AbstractBackgroundThe fibrosis-4 (FIB-4) index has attracted attention as a predictive factor for cardiovascular events and mortality in patients with heart disease. However, its clinical value in patients with implanted pacemakers remains unclear.MethodsThis study included patients who underwent pacemaker implantation. The FIB-4 index was calculated based on blood tests performed during the procedure. The primary outcome was all-cause mortality, and secondary outcomes included cardiovascular and non-cardiovascular death. The FIB-4 index was stratified into tertiles. Between-group comparisons were performed using log-rank tests and multivariate analysis using Cox proportional hazards. The predictive accuracy and cut-off value of the FIB-4 index were calculated from the receiver operating characteristic curve for all-cause mortality.ResultsThis study included 201 participants, of whom 38 (incidence rate: 5.8/100 person-years) experienced death events during the observation period (median: 1097 days). All-cause and non-cardiovascular death differed significantly between groups stratified by the FIB-4 index tertiles (log-rank test:P<0.001 andP<0.001, respectively). Using Cox proportional hazards analysis, the unadjusted hazard ratio was 4.75 (95% confidence interval [CI]: 2.05–11.0,P<0.001) for Tertile 3 compared to Tertile 1. After adjustment for confounding factors, including age, sex, the presence or absence of left bundle branch block at baseline, QRS duration during pacing, and pacing rate at the last check, the hazard ratio was 3.61 (95% CI: 1.37–9.48,P=0.009). The cut-off of the FIB-4 index was 3.75 (area under the curve: 0.72, 95% CI: 0.62–0.82).ConclusionsThe FIB-4 index was a potential predictive factor for all-cause mortality in patients with implanted pacemakers.
Setbacks, strain and stress: lived experiences of U.S. working mothers during COVID-19
Authors: Rosen Lisa , Scott Shannon , Urban Bek , Poe Darian , Shukla Roshni , Ahmed Shazia 
Published: October 2023

Purpose
The purpose of this study was to examine the lived experiences of working mothers during the first year of the COVID-19 pandemic and assess their perceptions of the types of training opportunities that would help advance their careers as they navigated pandemic-related challenges.

Design/methodology/approach
In study 1, 53 participants responded to an online survey that included open-ended questions regarding the impact COVID-19 has had on their careers and desires they have for training to ameliorate these concerns. For study 2, 10 participants completed an interview that included open-ended questions regarding workplace changes and professional development/training opportunities since the pandemic.

Findings
Thematic analysis showed mothers facing several setbacks in their careers, including delays, loss of hours and wages, childcare stressors and strained or lost relationships with colleagues and supervisors. A small number of participants also reported some surprisingly positive experiences, such as a push toward career innovation. Participants reported little to no exposure to career development opportunities and expressed a desire for training for leadership and interpersonal connection in the workplace.

Originality/value
Although quantitative data have been helpful in identifying and quantifying growing gender gaps in work during the pandemic, the qualitative analyses the authors used highlight how recent difficulties encountered by working mothers risk a growing gender gap in work and career mobility as women in the leadership pipeline struggle with challenges. Further, the findings suggest ways that women in management can support the working mothers on their staff, including by suggesting ways additional training may address some concerns.
A holistic model of resources to enhance the doctoral student's well-being
Authors: Acharya Vrinda , Rajendran Ambigai 
Published: October 2023

PurposeThis study aims to perform a scoping review of the recent studies on critical resources required for the doctoral program by mapping the resources at various levels of Bronfenbrenner's ecological systems and their underlying theories. The study proposes a holistic model of supportive resources in the doctoral education.Design/methodology/approachThe current scoping review is supported by Arksey and O'Malley's five-stage methodological guidance The authors reported sixty-eight articles that were published between 2010 and 2023 and complied with the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) checklist.FindingsThe study identified two categories of resources that promote doctoral student well-being: personal resources such as research self-efficacy and intrinsic motivation of the doctoral student. Second, the contextual resources provided by supervisors, department, family, peers, institution and Government policy impact the well-being of doctoral students. The study relied on the self-determination and conservation of resources theory to determine doctoral students' stress-free, high-quality research journey.Practical implicationsThe study findings can help higher education institutions, supervisors, peers and academicians plan and implement the finest resources to improve the well-being of doctoral students. The institutions can develop a wide range of strategies, tailored supportive programs, and interventions that can help in improving students' mental and emotional health, based on the developed multifaceted resource framework. Doctoral students can also use the review's findings to help them deal with program obstacles by encouraging themselves internally and participating in mentoring programs.Originality/valueThis review article proposes a comprehensive conceptual framework by considering Bronfenbrenner's ecological systems on multilevel resources that help to understand the inter-relationship between resources required in the doctoral student's program.