bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomechanical Comparison of Ulnar Collateral Ligament Reconstruction Between Palmaris Longus Autograft and Knee Medial Collateral Ligament Allograft
Authors: Stone Michael A. , Chao Linda , Huang Dave T. , Parikh Harin B. , Sun Michael , Kulber David A. , Metzger Melodie F. 
Published: March 2024

Background: Medial ulnar collateral ligament (mUCL) injury can cause significant pain and alter throwing mechanics. Common autograft options for mUCL reconstruction (UCLR) include the palmaris longus (PL) and hamstring tendons. Allograft use may reduce donor site morbidity and decrease function related to PL autografts. Purpose: To compare varus stability and load to failure between a novel allograft for UCLR—knee medial collateral ligament (kMCL)—and a PL autograft in human donor elbow specimens. Study Design: Controlled laboratory study. Methods: A total of 24 fresh-frozen human elbows were dissected to expose the mUCL. Medial elbow stability was tested with the mUCL intact (native), deficient, and reconstructed utilizing the humeral single-docking technique with either a (1) kMCL allograft (n = 12) or (2) a PL autograft (n = 12). A 3-N·m valgus torque was applied to the elbow, and valgus rotation of the ulna was recorded via motion tracking cameras. The elbow was cycled through a full range of motion 5 times. After kinematic testing, specimens were loaded to failure at 70° of elbow flexion, and failure modes were recorded. Results: The mUCL-deficient elbows demonstrated significantly greater valgus rotation compared with the intact and reconstructed elbows at every flexion angle tested (10°-120°) ( P <.001). Both kMCL- and PL-reconstructed elbows exhibited significantly higher mean valgus rotation compared with the intact state between 10° and 40° of flexion ( P < .01). There were no significant differences in valgus rotation at any flexion angle between the kMCL and PL graft groups. When loaded to failure, elbows reconstructed with both kMCL and PL grafts failed at similar torque values (18.6 ± 4 and 18.1 ± 3.4 N·m, respectively; P = .765). Conclusion: Fresh-frozen and aseptically processed kMCL allografts demonstrated similar kinematic and failure properties to PL tendon autografts in UCL-reconstructed elbows, although neither graft fully restored kinematics between 10° and 40°. Clinical Relevance: Prepared kMCL ligament allografts may provide a viable graft material when reconstructing elbow ligaments while avoiding the potential complications related to PL autografts— including donor site morbidity.
Health Provider Experiences in Supporting Social Connectedness Between Families and Older Adults Living in Long-Term Care Homes
Authors: Garnett Anna , Pollock Hannah , Prentice Kristin , Floriancic Natalie , Donelle Lorie , Hand Carri , Oudshoorn Abe , Babenko-Mould Yolanda , Forchuk Cheryl 
Published: March 2024

Introduction Many people, often older adults, living in long-term care homes (OA-LTCH) became socially isolated during the COVID-19 pandemic due to variable restrictions on in-person visits and challenges associated with using technology for social connectivity. Health providers were key to supporting these OA by providing additional care and facilitating their connections with family using technology such as smartphones and iPads. It is important to learn from these experiences to move forwards from the COVID-19 pandemic with evidence-informed strategies that will better position health providers to foster social engagement for OA-LTCH across a range of contextual situations. Objective This exploratory qualitative description study sought to explore health provider experiences in supporting social connectedness between family members and OA-LTCH within the COVID-19 context. Methods Qualitative, in-depth semistructured interviews were conducted with 11 health providers. Results Using inductive qualitative content analysis study findings were represented by the following themes: (a) changes in provider roles and responsibilities while challenging for health providers did not impact their commitment to supporting OA-LTCH social and emotional health, (b) a predominant focus on OA-LTCH physical well-being with resultant neglect for emotional well-being resulted in collective trauma, and (c) health providers faced multiple challenges in using technology to support social connectivity. Conclusion Study findings suggest the need for increased funding for LTC to support activities and initiatives that promote the well-being of health providers and OA living in LTC, the need to prioritize social well-being during outbreak contexts, and more formalized approaches to guide the appropriate use of technology within LTC.
Minimally Invasive Chevron Akin Osteotomy: Preoperative Planning Using the Radiographic First-Ray Squeeze Test
Authors: Nunes Gustavo Araujo , Ferreira Gabriel Ferraz , Pereira Filho Miguel Viana , Carvalho Kepler Alencar Mendes de , Lewis Thomas Lorchan , Castellini Jorge , Ray Robbie , Vernois Joel 
Published: March 2024

Background: Recognizing preoperative first-ray hypermobility is important to planning hallux valgus (HV) surgery. A recent study showed the minimally invasive chevron Akin (MICA) osteotomy increased varus displacement of the proximal fragment of the first metatarsal osteotomy. The present study aims to evaluate the ability of the radiographic first-ray squeeze test to predict the varus displacement of the proximal fragment of the first metatarsal osteotomy when performing the MICA procedure. Methods: A prospective case series of patients with moderate to severe HV who underwent MICA was performed. The HV deformity correction was analyzed by comparing the preoperative and 12-week postoperative hallux valgus angle (HVA) and the intermetatarsal angle between the first and second rays (1-2 IMA). The ability of the radiographic first-ray squeeze test to predict the varus displacement of the first metatarsal was done by comparing the preoperative 1-2 IMA measured in the AP radiographic first-ray squeeze test (IMA-ST) with the intermetatarsal angle between the second metatarsal and the axis of the first metatarsal osteotomy proximal fragment (IAPF) taken 12 weeks postoperatively. Results: Between July 2022 and May 2023, a total of 39 feet in 28 patients underwent MICA. The mean IMA improved from 13.8 (SD = 2.2) to 3.8 degrees (SD = 1.5) ( P < .001), and the mean HVA improved from 27.8 (SD = 6.1) to 4.9 degrees (SD = 2.5) ( P < .001). A linear regression analysis revealed that IMA-ST is highly associated with the 12 week assessed IAPF ( P < .001). Conclusion: The preoperative radiographic first-ray squeeze test appears to predict with high fidelity the varus displacement of the proximal fragment of the first metatarsal that can occur after the MICA procedure. Level of Evidence: Level III, prospective cohort study.
Genetic regulation of carnitine metabolism controls lipid damage repair and aging RBC hemolysis in vivo and in vitro
Authors: Nemkov Travis , Key Alicia , Stephenson Daniel , Earley Eric J. , Keele Gregory R. , Hay Ariel , Amireault Pascal , Casimir Madeleine , Dussiot Michaël , Dzieciatkowska Monika , Reisz Julie A. , Deng Xutao , Stone Mars , Kleinman Steve , Spitalnik Steven L. , Hansen Kirk C. , Norris Philip J. , Churchill Gary A. , Busch Michael P. , Roubinian Nareg , Page Grier P. , Zimring James C. , Arduini Arduino , D’Alessandro Angelo 
Published: March 2024

Abstract
Recent large-scale multiomics studies suggest that genetic factors influence the chemical individuality of donated blood. To examine this concept, we performed metabolomics analyses of 643 blood units from volunteers who donated units of packed red blood cells (RBCs) on 2 separate occasions. These analyses identified carnitine metabolism as the most reproducible pathway across multiple donations from the same donor. We also measured l-carnitine and acyl-carnitines in 13 091 packed RBC units from donors in the Recipient Epidemiology and Donor Evaluation study. Genome-wide association studies against 879 000 polymorphisms identified critical genetic factors contributing to interdonor heterogeneity in end-of-storage carnitine levels, including common nonsynonymous polymorphisms in genes encoding carnitine transporters (SLC22A16, SLC22A5, and SLC16A9); carnitine synthesis (FLVCR1 and MTDH) and metabolism (CPT1A, CPT2, CRAT, and ACSS2), and carnitine-dependent repair of lipids oxidized by ALOX5. Significant associations between genetic polymorphisms on SLC22 transporters and carnitine pools in stored RBCs were validated in 525 Diversity Outbred mice. Donors carrying 2 alleles of the rs12210538 SLC22A16 single-nucleotide polymorphism exhibited the lowest l-carnitine levels, significant elevations of in vitro hemolysis, and the highest degree of vesiculation, accompanied by increases in lipid peroxidation markers. Separation of RBCs by age, via in vivo biotinylation in mice, and Percoll density gradients of human RBCs, showed age-dependent depletions of l-carnitine and acyl-carnitine pools, accompanied by progressive failure of the reacylation process after chemically induced membrane lipid damage. Supplementation of stored murine RBCs with l-carnitine boosted posttransfusion recovery, suggesting this could represent a viable strategy to improve RBC storage quality.
RUNX1 C-terminal mutations impair blood cell differentiation by perturbing specific enhancer-promoter networks
Authors: Jayne Nathan D. , Liang Zhengyu , Lim Do-Hwan , Chen Poshen B. , Diaz Cristina , Arimoto Kei-Ichiro , Xia Lingbo , Liu Mengdan , Ren Bing , Fu Xiang-Dong , Zhang Dong-Er 
Published: March 2024

Abstract
The transcription factor RUNX1 is a master regulator of hematopoiesis and is frequently mutated in myeloid malignancies. Mutations in its runt homology domain (RHD) frequently disrupt DNA binding and result in loss of RUNX1 function. However, it is not clearly understood how other RUNX1 mutations contribute to disease development. Here, we characterized RUNX1 mutations outside of the RHD. Our analysis of the patient data sets revealed that mutations within the C-terminus frequently occur in hematopoietic disorders. Remarkably, most of these mutations were nonsense or frameshift mutations and were predicted to be exempt from nonsense-mediated messenger RNA decay. Therefore, this class of mutation is projected to produce DNA-binding proteins that contribute to the pathogenesis in a distinct manner. To model this, we introduced the RUNX1R320∗ mutation into the endogenous gene locus and demonstrated the production of RUNX1R320∗ protein. Expression of RUNX1R320∗ resulted in the disruption of RUNX1 regulated processes such as megakaryocytic differentiation, through a transcriptional signature different from RUNX1 depletion. To understand the underlying mechanisms, we used Global RNA Interactions with DNA by deep sequencing (GRID-seq) to examine enhancer-promoter connections. We identified widespread alterations in the enhancer-promoter networks within RUNX1 mutant cells. Additionally, we uncovered enrichment of RUNX1R320∗ and FOXK2 binding at the MYC super enhancer locus, significantly upregulating MYC transcription and signaling pathways. Together, our study demonstrated that most RUNX1 mutations outside the DNA-binding domain are not subject to nonsense-mediated decay, producing protein products that act in concert with additional cofactors to dysregulate hematopoiesis through mechanisms distinct from those induced by RUNX1 depletion.
PD1 inhibits PKCθ-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation
Authors: Chmiest Daniela , Podavini Silvia , Ioannidou Kalliopi , Vallois David , Décaillet Chantal , Gonzalez Montserrat , Quadroni Manfredo , Blackney Kevin , Schairer Rebekka , de Leval Laurence , Thome Margot 
Published: March 2024

Abstract
The inhibitory surface receptor programmed cell death protein 1 (PD1) is a major target for antibody–based cancer immunotherapies. Nevertheless, a substantial number of patients fail to respond to the treatment or experience adverse effects. An improved understanding of intracellular pathways targeted by PD1 is thus needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering inhibited the phosphorylation and physical association with protein kinase Cθ (PKCθ) of a variety of cytoskeleton-related proteins. PD1 blocked activation and recruitment of PKCθ to the forming immune synapse (IS) in a Src homology-2 domain–containing phosphatase-1/2 (SHP1/SHP2)-dependent manner. Consequently, PD1 engagement led to impaired synaptic phosphorylation of cytoskeleton-related proteins and formation of smaller IS. T-cell receptor induced phosphorylation of the PKCθ substrate and binding partner vimentin was long-lasting and it could be durably inhibited by PD1 triggering. Vimentin phosphorylation in intratumoral T cells also inversely correlated with the levels of the PD1 ligand, PDL1, in human lung carcinoma. Thus, PKCθ and its substrate vimentin represent important targets of PD1-mediated T-cell inhibition, and low levels of vimentin phosphorylation may serve as a biomarker for the activation of the PD1 pathway.
Mechanisms of resistance to bispecific T-cell engagers in multiple myeloma and their clinical implications
Authors: Letouzé Eric , Moreau Philippe , Munshi Nikhil , Samur Mehmet , Minvielle Stéphane , Touzeau Cyrille 
Published: March 2024

Abstract
Bispecific T-cell engagers (TCEs) are revolutionizing patient care in multiple myeloma (MM). These monoclonal antibodies, that redirect T cells against cancer cells, are now approved for the treatment of triple-class exposed relapsed/refractory MM (RRMM). They are currently tested in earlier lines of the disease, including in first line. Yet, primary resistance occurs in about one-third of patients with RRMM, and most responders eventually develop acquired resistance. Understanding the mechanisms of resistance to bispecific TCE is thus essential to improve immunotherapies in MM. Here, we review recent studies investigating the clinical and molecular determinants of resistance to bispecific TCE. Resistance can arise from tumor-intrinsic or tumor-extrinsic mechanisms. Tumor-intrinsic resistance involves various alterations leading to the loss of the target antigen, such as chromosome deletions, point mutations, or epigenetic silencing. Loss of major histocompatibility complex (MHC) class I, preventing MHC class I: T-cell receptor (TCR) costimulatory signaling, was also reported. Tumor-extrinsic resistance involves abundant exhausted T-cell clones and several factors generating an immunosuppressive microenvironment. Importantly, some resistance mechanisms impair response to 1 TCE while preserving the efficacy of others. We next discuss the clinical implications of these findings. Monitoring the status of target antigens in tumor cells and their immune environment will be key to select the most appropriate TCE for each patient and to design combination and sequencing strategies for immunotherapy in MM.
Gasdermin B, an asthma-susceptibility gene, promotes MAVS-TBK1 signalling and airway inflammation
Authors: Liu Tao , Liu Siqi , Rui Xianliang , Cao Ye , Hecker Julian , Guo Feng , Zhang Yihan , Gong Lu , Zhou Yihan , Yu Yuzhen , Krishnamoorthyni Nandini , Bates Samuel , Chun Sung , Boyer Nathan , Xu Shuang , Park Jin-Ah , Perrella Mark A. , Levy Bruce D. , Weiss Scott T. , Mou Hongmei , Raby Benjamin A. , Zhou Xiaobo 
Published: March 2024

RationaleRespiratory virus-induced inflammation is the leading cause of asthma exacerbation, frequently accompanied by induction of interferon-stimulated genes (ISGs). How asthma-susceptibility genes modulate cellular response upon viral infection by fine-tuningISGinduction and subsequent airway inflammation in genetically susceptible asthma patients remains largely unknown.ObjectivesTo decipher the functions of gasdermin B (encoded byGSDMB) in respiratory virus-induced lung inflammation.MethodsIn two independent cohorts, we analysed expression correlation betweenGSDMBandISGs. In human bronchial epithelial cell line or primary bronchial epithelial cells, we generatedGSDMB-overexpressing andGSDMB-deficient cells. A series of quantitative PCR, ELISA and co-immunoprecipitation assays were performed to determine the function and mechanism ofGSDMBforISGinduction. We also generated a novel transgenic mouse line with inducible expression of human uniqueGSDMBgene in airway epithelial cells and infected the mice with respiratory syncytial virus to determine the role ofGSDMBin respiratory syncytial virus-induced lung inflammationin vivo.ResultsGSDMBis one of the most significant asthma-susceptibility genes at 17q21 and acts as a novel RNA sensor, promoting mitochondrial antiviral-signalling protein (MAVS)-TANK binding kinase 1 (TBK1) signalling and subsequent inflammation. In airway epithelium,GSDMBis induced by respiratory viral infections. Expression ofGSDMBandISGssignificantly correlated in respiratory epithelium from two independent asthma cohorts. Notably, inducible expression of humanGSDMBin mouse airway epithelium led to enhancedISGsinduction and increased airway inflammation with mucus hypersecretion upon respiratory syncytial virus infection.ConclusionsGSDMBpromotesISGsexpression and airway inflammation upon respiratory virus infection, thereby conferring asthma risk in risk allele carriers.
Ensemble learning for integrative prediction of genetic values with genomic variants
Authors: Gu Lin-Lin , Yang Run-Qing , Wang Zhi-Yong , Jiang Dan , Fang Ming 
Published: March 2024

AbstractBackgroundWhole genome variants offer sufficient information for genetic prediction of human disease risk, and prediction of animal and plant breeding values. Many sophisticated statistical methods have been developed for enhancing the predictive ability. However, each method has its own advantages and disadvantages, so far, no one method can beat others.ResultsWe herein propose an Ensemble Learning method for Prediction of Genetic Values (ELPGV), which assembles predictions from several basic methods such as GBLUP, BayesA, BayesB and BayesCπ, to produce more accurate predictions. We validated ELPGV with a variety of well-known datasets and a serious of simulated datasets. All revealed that ELPGV was able to significantly enhance the predictive ability than any basic methods, for instance, the comparisonp-value of ELPGV over basic methods were varied from 4.853E−118 to 9.640E−20 for WTCCC dataset.ConclusionsELPGV is able to integrate the merit of each method together to produce significantly higher predictive ability than any basic methods and it is simple to implement, fast to run, without using genotype data. is promising for wide application in genetic predictions.
Evaluating emergency response at a hospital near the Gaza border within 24 h of increased conflict
Authors: Levi Hezi , Givaty Gili , Ovadia Yaniv S. , Alon Yaniv , Saban Mor 
Published: March 2024

Abstract
Background
Frontline hospitals near active hostilities face unique challenges in delivering emergency care amid threats to infrastructure and personnel safety. Existing literature focuses on individual aspects like mass casualty protocols or medical neutrality, with limited analysis of operating acute services directly under fire.

Objectives
To describe the experience of a hospital situated meters from hostilities and analyze strategies implemented for triage, expanding surge capacity, and maintaining continuity of care during attacks with limited medical staff availability due to hazardous conditions. A focus will be placed on assessing how the hospital functioned and adapted care delivery models in the event of staffing limitations preventing all teams from arriving on site.

Methods
A retrospective case study was conducted of patient records from Barzilai University Medical Center at Ashkelon (BUMCA) Medical Center in Israel within the first 24 h after escalated conflict began on October 7, 2023. Data on 232 admissions were analyzed regarding demographics, treatment protocols, time to disposition, and mortality. Missile alert data correlated patient surges to attacks. Statistical and geospatial analyses were performed.

Results
Patients predominantly male soldiers exhibited blast/multisystem trauma. Patient surges at the hospital were found to be correlated with the detection of incoming missile attacks from Gaza within 60 min of launch. While 131 (56%) patients were discharged and 55 (24%) transferred within 24 h, probabilities of survival declined over time reflecting injury severity limitations. 31 deaths occurred from severe presentation.

Conclusion
Insights gleaned provide a compelling case study on managing mass casualties at the true frontlines. By disseminating BUMCA's trauma response experience, strategies can strengthen frontline hospital protocols optimizing emergency care delivery during hazardous armed conflicts through dynamic surge capacity expansion, early intervention prioritization, and infrastructure/personnel protection measures informed by risks.
Development and validation of cognitive ageing risk score (CARS) for early detection of subtle cognitive deficits in older people
Authors: Fung Ada Wai Tung , Lee Allen Ting Chun , Ma Suk Ling , Lam Linda Chiu Wa 
Published: March 2024

Abstract
Background
Early cognitive deficits commonly seen in older people have not been well defined and managed in primary care. The objectives are (1) to develop and validate a new risk score to estimate the risk of dementia in Chinese older population; and (2) to evaluate the use of risk score in conjunction with cognitive screening in detecting early cognitive deficits in community older people.

Methods
A development cohort of 306 cognitive healthy older adults aged 60 or above were followed for 6 years. A CARS was constructed using the estimated coefficients of risk factors associated with dementia at follow up. Validation was carried out in another five-year cohort of 383 older adults. The usefulness of CARS in detecting early cognitive deficits was evaluated.

Results
Risk factors include older age, male gender, low level of education, poorly controlled diabetes, prolonged sleep latency, fewer mind body or light exercise, loneliness, and being apolipoprotein e4 carriers. A cutoff of CARS at -1.3 had a sensitivity of 83.9% and a specificity of 75.4% to predict dementia. The area under curve was 82.5% in the development cohort. Early cognitive deficits were characterized by impaired retention (p <.001, 95% CI 0.2–0.9) and attention (p =.012, 95% CI 0.1–0.8).

Conclusion
The CARS can be used as a standard risk assessment of dementia or in conjunction with a computerized cognitive screening to evaluate a full cognitive profile for detecting early cognitive deficits. The result put forward the integration of risk algorithm into smart healthcare system to provide personalized lifestyle interventions.