bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential protective effects of increased serum uric acid concentration in sarcopenia: A meta-analysis and systematic review
Authors: He Jie , Hu Fenghui , Wang Yan , Mei Yang 
Published: March 2024

Background:
Previous studies on the association between serum uric acid (UA) levels and sarcopenia have yielded contradictory results. This meta-analysis and literature review assessed the association between serum UA levels and sarcopenia. Moreover, we conducted a comparative analysis of the differences in serum UA concentrations between individuals with and without sarcopenia.

Methods:
A systematic search was conducted across various medical databases, namely PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, and Wanfang (from the start to August 20, 2023). This search focused on published studies that investigated the relationship between serum UA levels and sarcopenia. The relationship between serum UA concentration and the occurrence of sarcopenia was analyzed, and the differences in serum UA concentrations between individuals with sarcopenia and control groups were reviewed. Statistical analysis was performed using STATA 11.0 and R 4.1.3.

Results:
Sixteen studies were considered for our analysis. The results indicated a significant association between low serum UA concentration and a higher sarcopenia risk, particularly among male patients (adjusted odds ratio = 0.65, 95% confidence interval [CI] = 0.49, 0.87, P = .004, I
2 = 0%). Individuals with sarcopenia exhibited decreased serum UA concentrations compared with those of the control group (mmol/L: weighted mean difference = −28.25, 95% CI = −40.45, −16.05, P < .001; mg/dL: weighted mean difference = −0.82, 95% CI = −1.05, −0.58, P < .001). Additionally, serum UA concentration was positively correlated with skeletal muscle mass index and handgrip strength (skeletal muscle index: correlation coefficient = 0.17, 95% CI = 0.11, 0.22, P < .001; handgrip strength: common odds ratios = 0.10, 95% CI = 0.06, 0.14, P < .001).

Conclusion:
Individuals with sarcopenia have relatively low serum UA concentrations. A notable correlation between serum UA concentration and sarcopenia was observed. Hence, monitoring UA levels could aid in the early detection and treatment of sarcopenia, enabling timely intervention to preserve muscle mass and strength.
A new potential therapeutic approach for ALS: A case report with NGS analysis
Authors: Hu Chaur-Jong , Chen Po-Chih , Padmanabhan Neeraj , Zahn Andre , Ho Chih-Ming , Wang Kuan , Yen Yun 
Published: March 2024

Rationale:
Amyotrophic lateral sclerosis (ALS) poses a significant clinical challenge due to its rapid progression and limited treatment options, often leading to deadly outcomes. Looking for effective therapeutic interventions is critical to improve patient outcomes in ALS.

Patient concerns:
The patient, a 75-year-old East Asian male, manifested an insidious onset of right-hand weakness advancing with dysarthria. Comprehensive Next-generation sequencing analysis identified variants in specific genes consistent with ALS diagnosis.

Diagnoses:
ALS diagnosis is based on El Escorial diagnostic criteria.

Interventions:
This study introduces a novel therapeutic approach using artificial intelligence phenotypic response surface (AI-PRS) technology to customize personalized drug-dose combinations for ALS. The patient underwent a series of phases of AI-PRS-assisted trials, initially incorporating a 4-drug combination of Ibudilast, Riluzole, Tamoxifen, and Ropinirole. Biomarkers and regular clinical assessments, including nerve conduction velocity, F-wave, H-reflex, electromyography, and motor unit action potential, were monitored to comprehensively evaluate treatment efficacy.

Outcomes:
Neurophysiological assessments supported the ALS diagnosis and revealed the co-presence of diabetic polyneuropathy. Hypotension during the trial necessitated an adaptation to a 2-drug combinational trial (ibudilast and riluzole). Disease progression assessment shifted exclusively to clinical tests of muscle strength, aligning with the patient’s well-being.

Lessons:
The study raises the significance of personalized therapeutic strategies in ALS by AI-PRS. It also emphasizes the adaptability of interventions based on patient-specific responses. The encountered hypotension incident highlights the importance of attentive monitoring and personalized adjustments in treatment plans. The described therapy using AI-PRS, offering personalized drug-dose combinations technology is a potential approach in treating ALS. The promising outcomes warrant further evaluation in clinical trials for searching a personalized, more effective combinational treatment for ALS patients.
Sexual Behavior and Perceived Risk for Oropharyngeal Cancer Among Men Who Have Sex With Men: A Psychometric Scale Validation
Authors: Bennis Sarah L. , Rohloff Corissa T. , Zhang Ziwei , Kohli Nidhi , Zoschke I. Niles , Rosser B.R. Simon , Nyitray Alan G. , Wilkerson J. Michael , Stull Cynthia L. , Khariwala Samir S. , Ross Michael W. 
Published: March 2024

Background
Men who have sex with men (MSM) are at increased risk for human papillomavirus–associated oropharyngeal cancer (HPV-OPC). The objective of this analysis was to create a psychometrically validated scale to measure perception of risk for HPV-OPC.

Methods
We conducted an exploratory and a confirmatory factor analysis to determine and confirm the latent factor structure. We used a path diagram to evaluate the relationship between the validated scale and perceived risk for HPV-OPC. The model was determined to be a good fit if it met all criteria: root mean square error of approximation ≤0.06, standardized root mean residual ≤0.08, Comparative Fit Index ≥0.90, and Tucker-Lewis Index ≥0.90. We report standardized estimates and 95% confidence intervals.

Results
This cross-sectional study recruited 1315 MSM. A majority (73.33%) of MSM had performed fellatio on ≥20 partners, 36.98% had rimmed ≥20 partners, and 5.31% had performed cunnilingus on ≥10 partners in their lifetime.
Six sexual history survey items loaded onto 2 latent factors: sexual risk behaviors: class 1 and sexual risk behaviors: class 2. The final model statistics indicated good fit: root mean square error of approximation = 0.064, standardized root mean residual = 0.059, Comparative Fit Index = 0.996, and Tucker-Lewis Index = 0.993. Sexual risk behaviors: class 1 was associated with greater perceived risk for HPV-OPC (0.217; 95% confidence interval, 0.138–0.295). Age, HIV status, HPV vaccination status, and sexual risk behaviors: class 2 were not associated with perceived risk for HPV-OPC.

Conclusion
Men who have sex with men assessed risk for HPV-OPC based on their lifetime number of cisgender male sexual partners, rimming partners, and fellatio partners but not other sexual behaviors. Men who have sex with men may be responsive to future HPV-OPC educational interventions and opportunities for screening.
HKDC1 Promotes Liver Cancer Stemness Under Hypoxia via Stabilizing β-Catenin
Authors: Fan Li , Tian Cheng , Yang Wentao , Liu Xiaoli , Dhungana Yogesh , Tan Haiyan , Glazer Evan S , Yu Jiyang , Peng Junmin , Ma Lichun , Ni Min , Zhu Liqin 
Published: March 2024

ABSTRACTBackground and AimsHexokinases (HKs), a group of enzymes catalyzing the first step of glycolysis, have been shown to play important roles in liver metabolism and tumorigenesis. Our recent studies identified HKDC1 as a top candidate associated with liver cancer metastasis. We aimed to compare its cell-type specificity with other HKs upregulated in liver cancer and investigate the molecular mechanisms underlying its involvement in liver cancer metastasis.Approach and ResultsWe found that, compared to HK1 and HK2, the other two commonly upregulated HKs in liver cancer, HKDC1 was most strongly associated with the metastasis potential of tumors and organoids derived from two liver cancer mouse models we previously established. RNA in situ hybridization and single-cell RNA-seq analysis revealed that HKDC1 was specifically upregulated in malignant cells in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) patient tumors, whereas HK1 and HK2 were widespread across various tumor microenvironment lineages. An unbiased metabolomic profiling demonstrated that HKDC1 overexpression in HCC cells led to metabolic alterations distinct from those from HK1 and HK2 overexpression, with HKDC1 particularly impacting the tricarboxylic acid (TCA) cycle. HKDC1 was prometastatic in HCC orthotopic and tail vein injection mouse models and, molecularly, HKDC1 was induced by hypoxia and bound to glycogen synthase kinase 3β to stabilize β-catenin, leading to enhanced stemness of HCC cells.ConclusionsOverall, our findings underscore HKDC1 as a prometastatic HK specifically expressed in the malignant compartment of primary liver tumors, thereby providing a mechanistic basis for targeting this enzyme in advanced liver cancer.
Human Foot Force Informs Balance Control Strategies when Standing on a Narrow Beam
Authors: Shiozawa Kaymie , Russo Marta , Lee Jongwoo , Hogan Neville , Sternad Dagmar 
Published: March 2024

ABSTRACTDespite the abundance of studies on the control of standing balance, insights about the roles of biomechanics and neural control have been limited. Previous work introduced an analysis combining the direction and orientation of ground reaction forces. The “intersection point” of the lines of actions of these forces exhibited a consistent pattern across healthy, young subjects when computed for different frequency components of the center of pressure signal. To investigate the control strategy of quiet stance, we applied this intersection point analysis to experimental data of 15 healthy, young subjects balancing in tandem stance on a narrow beam and on the ground. Data from the sagittal and frontal planes were analyzed separately. The task was modeled as a double-inverted pendulum controlled by an optimal controller with torque-actuated ankle and hip joints and additive white noise. To test our prediction that the controller that minimized overall joint effort would yield the best fit across the tested conditions and planes of analyses, experimental results were compared to simulation outcomes. The controller that minimized overall effort produced the best fit in both balance conditions and planes of analyses. For some conditions, the relative penalty on the hip and ankle joints varied in a way relevant to the balance condition or to the plane of analysis. These results suggest that unimpaired quiet balance in a challenging environment can be best described by a controller that maintains minimal effort through the adjustment of relative ankle and hip joint torques.NEW & NOTEWORTHYThis study explored balance control in humans during a challenging task using the novel intersection point analysis, based on ground reaction force direction and point of application. Experimental data of subjects standing on a narrow beam in tandem stance were compared with modeling results of a double-inverted pendulum. The analysis showed that individuals minimized effort by adjusting ankle and hip torques, shedding light on the interplay of biomechanics and neural control in maintaining balance.
High-throughput algorithm predicts F-Type ATP synthase rotor ring stoichiometries of 8 to 27 protomers
Authors: Osipov Stepan D. , Zinovev Egor V. , Anuchina Arina A. , Kuzmin Alexander S. , Minaeva Andronika V. , Ryzhykau Yury L. , Vlasov Alexey V. , Gushchin Ivan Yu. 
Published: March 2024

AbstractATP synthases are large enzymes present in every living cell. They consist of a transmembrane and a soluble domain, each comprising multiple subunits. The transmembrane part contains an oligomeric rotor ring (c-ring), whose stoichiometry defines the ratio between the number of synthesized ATP molecules and the number of ions transported through the membrane. Currently, c-rings of F-Type ATP synthases consisting of 8 to 17 (except 16) subunits have been experimentally demonstrated. Here, we present an easy-to-use high-throughput computational approach based on AlphaFold that allows us to estimate the stoichiometry of all homooligomeric c-rings, whose sequences are present in genomic databases. We validate the approach on the available experimental data, obtaining the correlation as high as 0.94 for the reference data set, and use it to predict the existence of c-rings with stoichiometry varying from 8 to 27. We then conduct molecular dynamics simulations of two c-rings with stoichiometry above 17 to corroborate the machine learning-based predictions. Our work strongly suggests existence of rotor rings with previously undescribed high stoichiometry in natural organisms and highlights the utility of AlphaFold-based approaches for studying homooligomeric proteins.
Using machine learning to count Antarctic shag (Leucocarbo bransfieldensis) nests on images captured by Remotely Piloted Aircraft Systems
Authors: Cusick Andrew , Fudala Katarzyna , Storożenko Piotr Pasza , Świeżewski Jędrzej , Kaleta Joanna , Oosthuizen W. Chris , Pfeifer Christian , Bialik Robert Józef 
Published: March 2024

ABSTRACTUsing 51 orthomosaics of 11 breeding locations of the Antarctic shag, we propose a method for automating counting of shag nests. This is achieved by training an object detection model based on the YOLO architecture and identifying nests on sections of the orthomosaic, which are later combined with predictions for the entire orthomosaic. Our results show that the current use of Remotely Piloted Aircraft Systems (RPAS) to collect images of areas with shag colonies, combined with machine learning algorithms, can provide reliable and fast estimates of shag nest counts (F1 score > 0.95). By using data from only two shag colonies for training, we show that models can be obtained that generalise well to images of both spatially and temporally distinct colonies. The proposed practical application opens the possibility of using aerial imagery to perform large-scale surveys of Antarctic islands in search of undiscovered shag colonies. We discuss the conditions for optimal performance of the model as well as its limitations. The code, data and trained model allowing for full reproducibility of the results are available athttps://github.com/Appsilon/Antarctic-nests.
Rare SNP in theHELBgene interferes with RPA interaction and cellular function of HELB
Authors: Osei Bertha , May Benjamin H. , Stiefel Clara M. , West Kirk L. , Zafar Maroof Khan , Thompson Matthew D. , Bergstrom Erik , Leung Justin W. , Enemark Eric J. , Byrd Alicia K. 
Published: March 2024

ABSTRACTHELB is a human helicase involved in initiation of DNA replication, the replication stress response, and regulation of double-strand DNA break repair. rs75770066 is a rare SNP in the HELB gene that affects age at natural menopause. rs75770066 results in a D506G substitution in an acidic patch within the 1A domain of the helicase that is known to interact with RPA. We found that this amino acid change dramatically impairs the cellular function of HELB. D506G-HELB exhibits impaired interaction with RPA, which likely results in the effects of rs75770066 as this reduces recruitment of HELB to sites of DNA damage. Reduced recruitment of D506G-HELB to double-strand DNA breaks and the concomitant increase in homologous recombination likely alters the levels of meiotic recombination, which affects the viability of gametes. Because menopause occurs when oocyte levels drop below a minimum threshold, altered repair of meiotic double-stranded DNA breaks has the potential to directly affect the age at natural menopause.
Single-nucleus Multiomic Analyses Identifies Gene Regulatory Dynamics of Phenotypic Modulation in Human Aneurysmal Aortic Root
Authors: Liu Xuanyu , Zeng Qingyi , Yang Hang , Li Wenke , Chen Qianlong , Yin Kunlun , Pan Zihang , Wang Kai , Luo Mingyao , Shu Chang , Zhou Zhou 
Published: March 2024

AbstractAortic root aneurysm is a potentially life-threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, our understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single-nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions. Cell-type-specific transcriptomic and cis-regulatory profiles in the human aortic root are identified. Regulatory and spatial dynamics during phenotypic modulation of vascular smooth muscle cells (VSMCs), the cardinal cell type, are delineated. Moreover, candidate key regulators driving the phenotypic modulation of VSMC, such asFOXN3,TEAD1,BACH2, andBACH1, are identified.In vitroexperiments demonstrate that FOXN3 functions as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs through targeting ACTA2. These findings provide novel insights into the regulatory and spatial dynamics during phenotypic modulation in the aneurysmal aortic root of humans.
The Predictive Value of Diaphragm Muscle Ultrasound for Ventilator Weaning Outcomes after Cervical Spinal Cord Injury: A Retrospective Case Series
Authors: Bhatia Natasha S. , Kunzweiler Stephany , Conley Christopher , Kim Ki H. , Adewuyi Adenike A. , Mondriguez-Gonzalez Antonio , Wolfe Lisa F. , Kwasny Mary , Franz Colin K. 
Published: March 2024

AbstractObjectivesNeuromuscular respiratory failure after cervical spinal cord injury (cSCI) can lead to dependence on an invasive mechanical ventilator. Ventilator-free breathing after cSCI is associated with improved morbidity, mortality, and quality of life. We investigated the use of diaphragm muscle ultrasound to predict ventilator weaning outcomes after cSCI.MethodsThis is a retrospective case series conducted at a university-affiliated freestanding inpatient rehabilitation facility. We identified patients with cSCI who had a tracheostomy and were dependent on an invasive mechanical ventilator at the time of admission to inpatient rehabilitation. A diaphragm muscle ultrasound was performed, which included measurements of the thickness of the diaphragm and a calculation of the thickening ratio (TR), which reflects diaphragm muscle contraction. The primary outcome measure was the need for mechanical ventilation at time of discharge from the inpatient rehabilitation facility. Successful ventilator weaning was defined as either daytime or full 24-hour ventilator-free breathing.ResultsOf the 21 patients enrolled, 11 (52%) were able to wean successfully (partially or fully) from the ventilator. Of the ultrasound measurements that were taken, the TR was the optimal predictor for ventilator weaning outcomes. A threshold of TR≥1.2 as the maximum hemidiaphragm measurement had a sensitivity of 1.0 and specificity of 0.90 for predicting ventilator weaning.ConclusionNormal diaphragm contractility (TR ≥ 1.2) as determined by diaphragm muscle ultrasound is a strong positive predictor for successful ventilator weaning in patients with cSCI.Utilizing diaphragm ultrasound, rehabilitation physicians can set precision rehabilitation goals regarding ventilator weaning for inpatients with respiratory failure after cSCI, potentially improving both outcomes and quality of life.
Sex-Specific Effect of MTSS1 Downregulation on Dilated Cardiomyopathy
Authors: Choe Dongwook , Burke Megan , Brandimarto Jeffrey A , Marti-Pamies Ingrid , Yob Jaime , Yang Yifan , Morley Michael P , Drivas Theodore G. , Day Sharlene , Damrauer Scott , Wang Xiao , Cappola Thomas P 
Published: March 2024

AbstractMTSS1 (metastasis suppressor 1) is an I-BAR protein that regulates cytoskeleton dynamics through interactions with actin, Rac, and actin-associated proteins. In a prior study, we identified genetic variants in a cardiac-specific enhancer upstream ofMTSS1that reduce human left ventricular (LV) MTSS1 expression and associate with protection against dilated cardiomyopathy (DCM). We sought to probe these effects further using population genomics andin vivomurine models. We crossedMtss1-/-mice with a transgenic (Tg) murine model of human DCM caused by the D230N pathogenic mutation inTpm1(tropomyosin 1). In females,Tg/Mtss1+/-mice had significantly increased LV ejection fraction and reduced LV volumes relative to theirTg/Mtss1+/+counterparts, signifying partial rescue of DCM due toMtss1haploinsufficiency. No differences were observed in males. To study effects in humans, we fine-mapped theMTSS1locus with 82 cardiac magnetic resonance (CMR) traits in 22,381 UK Biobank participants.MTSS1enhancer variants showed interaction with biological sex in their associations with several CMR traits. After stratification by biological sex, associations with CMR traits and colocalization withMTSS1expression in the Genotype-Tissue Expression (GTEx) Project were observed principally in women and were substantially weaker in men. These findings suggest sex dimorphism in the effects of MTSS1-lowering alleles, and parallel the increased LV ejection fraction and reduced LV volumes observed femaleTg/Mtss1+/-mice. Together, our findings at theMTSS1locus suggest a genetic basis for sex dimorphism in cardiac remodeling and motivate sex-specific study of common variants associated with cardiac traits and disease.
Metabolic phenotyping of healthy and diseased human RPE cells
Authors: Rizwan Saira , Toothman Beverly , Li Bo , Engel Abbi J. , Lim Rayne R. , Niernberger Sheldon , Lu Jinyu , Ratliff Cloe , Xiang Yinxiao , Eminhizer Mark , Chao Jennifer R. , Du Jianhai 
Published: March 2024

AbstractPurposeMetabolic defects in the retinal pigment epithelium (RPE) underlie many retinal degenerative diseases. This study aims to identify the nutrient requirements of healthy and diseased human RPE cells.MethodsWe profiled nutrient utilization of various human RPE cells, including differentiated and dedifferentiated fetal RPE (fRPE), induced pluripotent stem cell derived-RPE (iPSC RPE), Sorsby fundus dystrophy (SFD) patient-derived iPSC RPE, CRISPR-corrected isogenic SFD (cSFD) iPSC RPE, and ARPE-19 cell lines using Biolog Phenotype MicroArray Assays.ResultsDifferentiated fRPE cells and healthy iPSC RPE cells can utilize 51 and 48 nutrients respectively, including sugars, intermediates from glycolysis and tricarboxylic acid (TCA) cycle, fatty acids, ketone bodies, amino acids, and dipeptides. However, when fRPE cells lose their epithelial phenotype through dedifferentiation, nutrient utilization becomes restricted to 17 nutrients, primarily sugar and glutamine-related amino acids. SFD RPE cells can utilize 37 nutrients; however, compared to cSFD RPE and healthy iPSC RPE, they are unable to utilize lactate, some TCA cycle intermediates, and short-chain fatty acids. Nonetheless, they show increased utilization of branch-chain amino acids (BCAAs) and BCAA-containing dipeptides. Dedifferentiated ARPE-19 cells grown in traditional culture media cannot utilize lactate and ketone bodies. In contrast, nicotinamide supplementation promotes differentiation towards an epithelial phenotype, restoring the ability to use these nutrients.ConclusionsEpithelial phenotype confers metabolic flexibility to healthy RPE for utilizing various nutrients. SFD RPE cells have reduced metabolic flexibility, relying on the oxidation of BCAAs. Our findings highlight the potentially important roles of nutrient availability and utilization in RPE differentiation and diseases.