bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of high-intensity gait training with and without soft robotic exosuits in people post-stroke: a development-of-concept pilot crossover trial
Authors: Porciuncula Franchino , Arumukhom Revi Dheepak , Baker Teresa C. , Sloutsky Regina , Walsh Conor J. , Ellis Terry D. , Awad Louis N. 
Published: November 2023

Abstract
Introduction
High-intensity gait training is widely recognized as an effective rehabilitation approach after stroke. Soft robotic exosuits that enhance post-stroke gait mechanics have the potential to improve the rehabilitative outcomes achieved by high-intensity gait training. The objective of this development-of-concept pilot crossover study was to evaluate the outcomes achieved by high-intensity gait training with versus without soft robotic exosuits.

Methods
In this 2-arm pilot crossover study, four individuals post-stroke completed twelve visits of speed-based, high-intensity gait training: six consecutive visits of Robotic Exosuit Augmented Locomotion (REAL) gait training and six consecutive visits without the exosuit (CONTROL). The intervention arms were counterbalanced across study participants and separated by 6 + weeks of washout. Walking function was evaluated before and after each intervention using 6-minute walk test (6MWT) distance and 10-m walk test (10mWT) speed. Moreover, 10mWT speeds were evaluated before each training visit, with the time-course of change in walking speed computed for each intervention arm. For each participant, changes in each outcome were compared to minimal clinically-important difference (MCID) thresholds. Secondary analyses focused on changes in propulsion mechanics and associated biomechanical metrics.

Results
Large between-group effects were observed for 6MWT distance (d = 1.41) and 10mWT speed (d = 1.14). REAL gait training resulted in an average pre-post change of 68 ± 27 m (p = 0.015) in 6MWT distance, compared to a pre-post change of 30 ± 16 m (p = 0.035) after CONTROL gait training. Similarly, REAL training resulted in a pre-post change of 0.08 ± 0.03 m/s (p = 0.012) in 10mWT speed, compared to a pre-post change of 0.01 ± 06 m/s (p = 0.76) after CONTROL. For both outcomes, 3 of 4 (75%) study participants surpassed MCIDs after REAL training, whereas 1 of 4 (25%) surpassed MCIDs after CONTROL training. Across the training visits, REAL training resulted in a 1.67 faster rate of improvement in walking speed. Similar patterns of improvement were observed for the secondary gait biomechanical outcomes, with REAL training resulting in significantly improved paretic propulsion for 3 of 4 study participants (p < 0.05) compared to 1 of 4 after CONTROL.

Conclusion
Soft robotic exosuits have the potential to enhance the rehabilitative outcomes produced by high-intensity gait training after stroke. Findings of this development-of-concept pilot crossover trial motivate continued development and study of the REAL gait training program.
Top-level leaders and implementation strategies to support organizational diversity, equity, inclusion, and belonging (DEIB) interventions: a qualitative study of top-level DEIB leaders in healthcare organizations
Authors: Hogan Tory H. , O’Rourke Brian P. , Weeks Eddie , Silvera Geoffrey A. , Choi Seongwon 
Published: November 2023

Abstract
Background
The Black Lives Matter movement and COVID-19 pandemic motivated the wide-scale adoption of diversity, equity, inclusion, and belonging (DEIB) initiatives within healthcare organizations and the creation of DEIB top-level leader positions. The next step is to understand how these leaders contribute to the implementation of DEIB interventions, a task with notable salience due to not only the historical difficulties associated with DEIB strategy execution, but also the substantial evidence that leadership plays a significant role in implementation processes. Therefore, the objective of this qualitative study is to understand the role of top-level DEIB leaders in the implementation of healthcare organizational DEIB interventions.

Methods
A qualitative research approach which used an in-depth semi-structured interview approach was employed. We conducted thirty-one 60–90-min semi-structured interviews with DEIB top-level leaders between February 2022 and October 2022 over Zoom. An iterative coding process was used to identify the key implementation strategies and activities of DEIB top-level leaders.

Results
Interviewees were mostly Black, majority female, and mostly heterosexual and had a variety of educational backgrounds. We identified the DEIB top-level leader as the DEIB strategy implementation champion. These leaders drive five DEIB implementation strategies: (1) People, (2) Health Equity, (3) Monitoring and Feedback, (4) Operational Planning and Communication, and (5) External Partners. Within these, we identified 19 significant activities that describe the unique implementation strategies supported by the DEIB top-level leaders.

Conclusions
To move toward sustained commitment to DEIB, the organization must focus on not only establishing DEIB interventions, but on their successful implementation. Our findings help explicate the implementation activities that drive the DEIB initiatives of healthcare organizations and the role of DEIB leaders. Our work can help healthcare organizations systematically identify how to support the success of DEIB organizational interventions.
The association of osteoprotegerin and RANKL with osteoporosis: a systematic review with meta-analysis
Authors: Chi Guanghao , Qiu Longshun , Ma Jian , Wu Wei , Zhang Yuxin 
Published: November 2023

Abstract
Objectives
The OPG/RANKL signal pathway was important regulation mechanism of bone remodeling cycle, but the effect of osteoprotegerin (OPG) and RANKL in osteoporosis was uncertain. We did a systematic review with meta-analysis to assess the association between serum OPG/RANKL and osteoporosis.

Methods
The systematic search, data extraction, critical appraisal, and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Randomized controlled studies were searched in PubMed, OvidMedline, Embase (1946 to present). Standard mean difference (SMD), and associated credible interval (CI) were calculated using RevMan statistical software to assess the continuous data. Heterogeneity in studies was measured by I2 values. Subgroup analysis was performed based on different bone turnover.

Results
A total of 5 randomized controlled studies met the inclusion criteria. Both OPG and RANKL had no significant differences between the osteoporosis and control group, and the statistical heterogeneity was high in meta-analysis. However, RANKL had significant differences between the osteoporosis group with low bone turnover and control group (SMD =  − 1.17; 95% CI − 1.77 to 0.57; P value < 0.01) in subanalysis. Furthermore, the OPG/RANKL ratio was significant lower in the osteoporosis group than in the control group (SMD =  − 0.29; 95% CI − 0.57 to − 0.02; P value < 0.05), and the statistical heterogeneity was very low (Chi2 = 0.20, P = 0.66, I2 = 0%).

Conclusions
Our meta-analysis study supported OPG and RANKL were important modulatory factors of bone formation and resorption in bone turnover, respectively. Although the serum level of both OPG and RANKL were not associated with osteoporosis, but the OPG/RANKL ratio was associated with osteoporosis. In future, standardizing the test method and unit was good to clinical application.
Investigation of androgen receptor CAG repeats length in polycystic ovary syndrome diagnosed using the new international evidence-based guideline
Authors: Yan Xueqi , Gao Xueying , Shang Qian , Yang Ziyi , Wang Yuteng , Liu Li , Liu Wei , Liu Dan , Cheng Fang , Zhao Shigang , Zhao Han , Zhao Junli , Chen Zi-Jiang 
Published: November 2023

Abstract
Background
To study whether CAG repeat polymorphism of androgen receptor (AR) contributes to the risk of polycystic ovarian morphology (PCOM) with antral follicle count (AFC) ≥ 20 in the context of new international guideline of polycystic ovary syndrome (PCOS).

Methods
Blood of 109 PCOS cases and 61 controls were collected for the measurement of AR CAG repeats length by sequencing. The mean number and frequency distribution of CAG repeats length were observed. Detailed analysis was conducted by dividing PCOS cases into low AFC group (L-AFC, AFC < 20) and high AFC group (H-AFC, AFC ≥ 20) according to the new international evidence-based guideline.

Results
The portion of individuals with lower CAG repeats length in H-AFC group was significantly larger than those with higher CAG repeats length. Logistic model revealed individuals with lower CAG length tended to develop H-AFC.

Conclusion
Lower CAG repeats length in the AR gene of PCOS cases increases risk of PCOM.
Upregulation of RSPO3 via targeted promoter DNA demethylation inhibits the progression of cholangiocarcinoma
Authors: Wu Guanhua , Wang Da , Xiong Fei , Liu Wenzheng , Wang Qi , Chen Junsheng , Wang Bing , Chen Yongjun 
Published: November 2023

Abstract
Background
Cholangiocarcinoma (CCA) refers to a collection of malignant tumors that develop from the biliary epithelium. Extensive clinical evidence and epidemiological observations indicate a concerning increase in both the incidence and mortality rates of CCA. Surgical resection is currently the sole available cure for CCA. However, it is unfortunate that only a fraction of patients has access to surgery at the time of diagnosis. Moreover, there is a high incidence of cancer recurrence after resection, and systemic treatments have limited efficacy. Therefore, the identification of novel biomarkers for CCA-targeted molecular therapy remains a crucial task in oncology research.

Results
Our study demonstrated that low expression of RSPO3 was associated with poorer survival rates in patients with CCA. We found that the RSPO3 promoter DNA was hypermethylated in CCA, which was correlated with the low expression of RSPO3. The expression of RSPO3 was influenced by the balance between the DNA methyltransferase DNMT3a and the DNA demethylase TET1 in CCA. In vitro and in vivo experiments showed that targeting RSPO3 promoter DNA methylation using dCas9DNMT3a promoted tumorigenicity of CCA, while targeted RSPO3 promoter DNA demethylation using dCas9TET1CD inhibited CCA tumorigenicity. Additionally, in our primary CCA model, knockdown of Rspo3 promoted CCA progression, whereas overexpression of Rspo3 inhibited CCA progression.

Conclusions
Our findings suggest that increased methylation and decreased expression of RSPO3 may indicate a poor prognosis in CCA. Restoring RSPO3 expression by targeting promoter DNA demethylation could offer insights for precise treatment of CCA.
Subject classification and cross-time prediction based on functional connectivity and white matter microstructure features in a rat model of Alzheimer’s using machine learning
Authors: Diao Yujian , Lanz Bernard , Jelescu Ileana Ozana 
Published: November 2023

Abstract
Background
The pathological process of Alzheimer’s disease (AD) typically takes decades from onset to clinical symptoms. Early brain changes in AD include MRI-measurable features such as altered functional connectivity (FC) and white matter degeneration. The ability of these features to discriminate between subjects without a diagnosis, or their prognostic value, is however not established.

Methods
The main trigger mechanism of AD is still debated, although impaired brain glucose metabolism is taking an increasingly central role. Here, we used a rat model of sporadic AD, based on impaired brain glucose metabolism induced by an intracerebroventricular injection of streptozotocin (STZ). We characterized alterations in FC and white matter microstructure longitudinally using functional and diffusion MRI. Those MRI-derived measures were used to classify STZ from control rats using machine learning, and the importance of each individual measure was quantified using explainable artificial intelligence methods.

Results
Overall, combining all the FC and white matter metrics in an ensemble way was the best strategy to discriminate STZ rats, with a consistent accuracy over 0.85. However, the best accuracy early on was achieved using white matter microstructure features, and later on using FC. This suggests that consistent damage in white matter in the STZ group might precede FC. For cross-timepoint prediction, microstructure features also had the highest performance while, in contrast, that of FC was reduced by its dynamic pattern which shifted from early hyperconnectivity to late hypoconnectivity.

Conclusions
Our study highlights the MRI-derived measures that best discriminate STZ vs control rats early in the course of the disease, with potential translation to humans.
Management of traumatic cervical epidural hematoma in patients on Xa-inhibitors: a case report and review of the literature
Authors: Dang Robert , Issagholian Leo , Schmidt Tegan , Raoufi Pasha , Neeki Cameron C. , Neeki Michael M. 
Published: November 2023

Abstract
Background
Cervical epidural hematoma (CEH) is defined as a collection of blood in the suprameningeal space. Mechanisms of this rare pathology include spontaneous, postsurgical, and traumatic as the main subtypes. This unique case of traumatic CEH represents an even smaller subset of these cases. Management varies by symptom presentation, mechanism of injury, and other contraindications.

Case presentation
This case presents a 32 year old African American female on an oral anticoagulant sustaining traumatic cervical hematoma after a motor vehicle collision. Patient complained of neck, abdominal, and back pain. Imaging revealed a cervical spinal hematoma at the level of C3–C6. This case discusses the management of CEH for the general population and in the setting of anticoagulation.

Conclusion
Management of each case of CEH must be carefully considered and tailored based on their symptom presentation and progression of disease. As the use of anticoagulation including factor Xa inhibitors becomes more prevalent, there is greater need to understand the detailed pathophysiological aspect of the injuries. Targeted reversal agents such as Prothrombin Concentrate can be used for conservative treatment. Adjunct testing such as thromboelastogram can be used to help guide management.
Induced pluripotent stem cells derived from patients carrying mitochondrial mutations exhibit altered bioenergetics and aberrant differentiation potential
Authors: Meshrkey Fibi , Scheulin Kelly M. , Littlejohn Christopher M. , Stabach Joshua , Saikia Bibhuti , Thorat Vedant , Huang Yimin , LaFramboise Thomas , Lesnefsky Edward J. , Rao Raj R. , West Franklin D. , Iyer Shilpa 
Published: November 2023

Abstract
Background
Human mitochondrial DNA mutations are associated with common to rare mitochondrial disorders, which are multisystemic with complex clinical pathologies. The pathologies of these diseases are poorly understood and have no FDA-approved treatments leading to symptom management. Leigh syndrome (LS) is a pediatric mitochondrial disorder that affects the central nervous system during early development and causes death in infancy. Since there are no adequate models for understanding the rapid fatality associated with LS, human-induced pluripotent stem cell (hiPSC) technology has been recognized as a useful approach to generate patient-specific stem cells for disease modeling and understanding the origins of the phenotype.

Methods
hiPSCs were generated from control BJ and four disease fibroblast lines using a cocktail of non-modified reprogramming and immune evasion mRNAs and microRNAs. Expression of hiPSC-associated intracellular and cell surface markers was identified by immunofluorescence and flow cytometry. Karyotyping of hiPSCs was performed with cytogenetic analysis. Sanger and next-generation sequencing were used to detect and quantify the mutation in all hiPSCs. The mitochondrial respiration ability and glycolytic function were measured by the Seahorse Bioscience XFe96 extracellular flux analyzer.

Results
Reprogrammed hiPSCs expressed pluripotent stem cell markers including transcription factors POU5F1, NANOG and SOX2 and cell surface markers SSEA4, TRA-1-60 and TRA-1-81 at the protein level. Sanger sequencing analysis confirmed the presence of mutations in all reprogrammed hiPSCs. Next-generation sequencing demonstrated the variable presence of mutant mtDNA in reprogrammed hiPSCs. Cytogenetic analyses confirmed the presence of normal karyotype in all reprogrammed hiPSCs. Patient-derived hiPSCs demonstrated decreased maximal mitochondrial respiration, while mitochondrial ATP production was not significantly different between the control and disease hiPSCs. In line with low maximal respiration, the spare respiratory capacity was lower in all the disease hiPSCs. The hiPSCs also demonstrated neural and cardiac differentiation potential.

Conclusion
Overall, the hiPSCs exhibited variable mitochondrial dysfunction that may alter their differentiation potential and provide key insights into clinically relevant developmental perturbations.
Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes
Authors: Liu Mengyao , Ng Martin , Phu Tuan , Bouchareychas Laura , Feeley Brian T. , Kim Hubert T. , Raffai Robert L. , Liu Xuhui 
Published: November 2023

Abstract
Background
Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic progenitors (FAPs) cause fibrosis and fatty infiltration and that brown/beige adipogenesis of FAPs promotes rotator cuff muscle regeneration. However, how polarized macrophages and their exosomes regulate FAP differentiation remains unknown.

Methods
We cultured FAPs with M0, M1, and M2 macrophages or 2 × 109 exosomes derived from M0, M1 and M2 with and without GW4869, an exosome inhibitor. In vivo, M0, M1, and M2 macrophages were transplanted or purified macrophage exosomes (M0, M1, M2) were injected into supraspinatus muscle (SS) after massive tendon tears in mice (n = 6). SS were harvested at six weeks after surgery to evaluate the level of muscle atrophy and fatty infiltration.

Results
Our results showed that M2 rather than M0 or M1 macrophages stimulates brown/beige fat differentiation of FAPs. However, the effect of GW4869, the exosome inhibitor, diminished this effect. M2 exosomes also promoted FAP Beige differentiation in vitro. The transplantation of M2 macrophages reduced supraspinatus muscle atrophy and fatty infiltration. In vivo injections of M2 exosomes significantly reduced muscle atrophy and fatty infiltration in supraspinatus muscle.

Conclusion
Results from our study demonstrated that polarized macrophages directly regulated FAP differentiation through their exosomes and M2 macrophage-derived exosomes may serve as a novel treatment option for RC muscle atrophy and fatty infiltration.
Tropomyosin 3 (TPM3) function in skeletal muscle and in myopathy
Authors: Lambert Matthias R. , Gussoni Emanuela 
Published: November 2023

AbstractThe tropomyosin genes (TPM1-4) contribute to the functional diversity of skeletal muscle fibers. Since its discovery in 1988, the TPM3 gene has been recognized as an indispensable regulator of muscle contraction in slow muscle fibers. Recent advances suggest that TPM3 isoforms hold more extensive functions during skeletal muscle development and in postnatal muscle. Additionally, mutations in the TPM3 gene have been associated with the features of congenital myopathies. The use of different in vitro and in vivo model systems has leveraged the discovery of several disease mechanisms associated with TPM3-related myopathy. Yet, the precise mechanisms by which TPM3 mutations lead to muscle dysfunction remain unclear. This review consolidates over three decades of research about the role of TPM3 in skeletal muscle. Overall, the progress made has led to a better understanding of the phenotypic spectrum in patients affected by mutations in this gene. The comprehensive body of work generated over these decades has also laid robust groundwork for capturing the multiple functions this protein plays in muscle fibers.
Prediction of pulmonary aspergillosis in patients with ventilator-associated pneumonia
Authors: Massart Nicolas , Plainfosse Emma , Benameur Yanis , Dupin Clarisse , Legall Florence , Cady Anne , Gourmelin Frederic , Legay François , Barbarot Nicolas , Magalhaes Eric , Fillatre Pierre , Frerou Aurélien , Reizine Florian 
Published: November 2023

Abstract
Background
Predictors of ICU-acquired pulmonary aspergillosis (IPA) are not well-established in critically ill patients with ventilator-associated pneumonia (VAP), making IPA commonly misdiagnosed and anti-fungal therapy delayed. We aimed to develop a clinical score for prediction of IPA among patients with VAP.

Methods
Mechanically ventilated patients who developed VAP in 4 ICUs in Bretagne, Western France, were included. The score was constructed in a learning cohort, based on predictors of IPA in logistic regression model, and validated in a validation cohort.

Results
Among 1636 mechanically ventilated patients, 215 developed VAP but only 39 developed IPA (4 possible and 35 probable/putative) (18%). Most cases (31/39) were documented through a positive broncho-alveolar sample culture. Independent predictors of IPA were immunodepression (including onco-hematological disorder, immunomodulatory treatment, solid organ transplant, neutropenia < 0.5G/L and high-dose steroids ≥ 1 mg/kg/day of prednisolone equivalent) (p = 0.001; score = 1 point) and lymphocyte count at admission < 0.8 G/L (p = 0.019; score = 1 point). Operational values of the predictive score in the learning/validation cohort were 50%/52% sensitivity and 90%/87% specificity, respectively, for high PiPa score (score = 2) and 94%/91% sensitivity and 44%/46% specificity, respectively, for moderate PiPa score (score = 1). Finally, the AUC for the prediction of IPA was 0.783 in the learning cohort and 0.770 in the validation cohort.

Conclusions
We evaluated a clinical score with good predictive value which may help to predict IPA in patient with VAP. External validation will be needed to confirm our preliminary findings.