bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study of caudal ropivacaine with or without dexmedetomidine for postoperative analgesia in pediatric genitourinary infraumbilical surgery: A double-blinded randomized controlled trial
Authors: Tamang Kaushal , Baral Bidur Kumar , Shah Malla Sadichhya , KC Brihaspati , Kuikel Sandip , Shrestha Diwan , Pathak Nibesh 
Published: March 2024

Various studies have described the use of Dexmedetomidine with local anesthetic drugs in caudal blocks for the management of postoperative pain in children. This study was designed to determine the analgesic effect of caudal Dexmedetomidine with Ropivacaine in pediatric genitourinary infraumbilical surgeries. Postoperative analgesic effects of caudal Ropivacaine with or without Dexmedetomidine in pediatric genitourinary infraumbilical were evaluated. This study was a prospective, interventional, comparative study conducted after ethical approval from the institute. Informed expressed consent was taken from each patient’s guardians. The sample size was calculated to be 31 in each group. The two groups were randomly assigned and the intervention involved caudal epidural injection with either Ropivacaine combined with Dexmedetomidine or Ropivacaine with Normal Saline. Children receiving Ropivacaine with Dexmedetomidine had a significantly prolonged duration of analgesia compared to those receiving Ropivacaine alone (840.35 ± 149.97 minutes vs. 412.90 ± 93.46 minutes, P < 0.001). Postoperative rFLACC scores were consistently lower in the Dexmedetomidine group, indicating better pain control (P < 0.05 at 6, 12, and 24 hours). Total analgesic consumption was lower in the Dexmedetomidine group (500.67 ± 212.92 mg vs. 741.75 ± 268.06 mg, P < 0.01). No significant differences in adverse effects were observed between the groups. The addition of Dexmedetomidine to Ropivacaine in caudal epidural significantly prolongs analgesia, improves pain control, and reduces analgesic consumption in pediatric genitourinary infraumbilical surgeries.
Coverage of Congenital Anomalies: Ensuring Lasting Smiles Act in Legislation
Authors: Lentskevich Marina A. , Yau Alice , Chwa Emily , Reddy Narainsai K. , Gosain Arun K. 
Published: March 2024

Summary:
The Ensuring Lasting Smiles Act (ELSA) is a federal bill that would require all health federally regulated insurance products to cover the full treatment of a congenital anomaly or congenital disability until complete restoration of normal function or appearance. ELSA has been a key federal priority for the Legislative Advocacy Committee of the American Society of Plastic Surgeons since the 115th Congress in 2018. Although it has gained momentum, particularly in the 117th Congress, the bill remains stalled. Congressional Budget Office review, conducted in March of 2022, appears to have overestimated this bill’s cost for the private sector, secondary to an alleged lack of data on the prevalence of the conditions, extent of treatments and their costs, and the current extent of private sector coverage. The present review highlights the progress of the ELSA bill and serves to illustrate the hurdles involved in passing significant health care bills. This review emphasizes the need for health care professionals to provide their congressional representatives with accurate information on realistic cost of currently covered treatments of congenital defects, the necessary treatments not currently covered by insurance, and additional out-of-pocket costs covered by patients. A concerted effort by plastic surgeons should provide tools for ELSA legislative champions to reintroduce and pass the bill during the 118th Congress. This process highlights the essential role of organized medicine in advocating for the successful passage of health care legislation.
Bidirectional Associations Between Loneliness, Emotional Support, and Sleep in Daily Life
Authors: Dickman Kristina D. , Thomas Mark C. , Chin Brian N. , Kamarck Thomas W. 
Published: March 2024

ObjectiveEvidence suggests a link between positive social relationship perceptions and improved sleep (e.g., quality, efficiency) across the life span. Less work has probed the directionality of these relationships. Here, we report findings from the first study to examine bidirectional between- and within-person associations between loneliness and emotional support with daily life measures of sleep.MethodsParticipants were 389 healthy adults aged 40 to 64 years (61% female) who completed hourly surveys assessing loneliness and perceptions of emotional support over the course of 4 days. Measures of actigraphy-assessed sleep and nightly sleep quality were also assessed for 7 to 10 days.ResultsIndividuals with lower average daily loneliness showed higher sleep quality and efficiency than individuals with higher loneliness (r= −0.19,p< .001;r= −0.14,p= .008, respectively), and greater average emotional support was likewise linked with better sleep quality (r= 0.18,p< .001). Controlling for neuroticism attenuated the effects of average loneliness on sleep. Within-person analyses showed unexpected bidirectional effects. Specifically, days in which people felt relatively lonelier were followed by nights with greater sleep efficiency (γ= 1.08,p= .015), and nights when people reported relatively poorer sleep quality were followed by days with greater emotional support (γ= −0.04,p= .013). These unexpected findings are probed in exploratory analyses.ConclusionsIndividuals with higher loneliness and lower emotional support report poorer sleep quality and efficiency, on average. Day-to-day fluctuations in perceptions of social relationships may affect the following night’s sleep, and vice versa.
Long-Term Home EEG Recording: Wearable and Implantable Devices
Authors: Rehman Mahnoor , Higdon Lindsay M. , Sperling Michael R. 
Published: March 2024

Summary:
Electroencephalography (EEG) monitoring has served as a cornerstone in the diagnostic and therapeutic evaluation of epilepsy since its development. This has been accomplished with short-term inpatient video-EEG hospitalization enabling observation of both the semiological and the electrographic features of seizures or with short-term home ambulatory EEG or video-EEG. The advantages of inpatient video-EEG monitoring are limited by high cost, inconvenience, and inability to monitor patients for long periods (weeks or months) as might be done in the outpatient setting. This limitation has impelled the development of wearable EEG devices, which aim to capture high-quality long-term EEG data in a user-friendly and unobtrusive manner. This review article aims to summarize three broad categories of wearable EEG devices, including scalp, subcutaneous, and intracranial EEG. In this review, we will discuss the features of each type of device and the implications for the management of epilepsy. This review does not aim to describe every wearable EEG device on the market but instead seeks to provide a broad overview of the various categories of device that are available, giving examples of each and those in development (with no intention to recommend or advocate for any particular product).
Self-Supervised Learning Reveals Clinically Relevant Histomorphological Patterns for Therapeutic Strategies in Colon Cancer
Authors: Liu Bojing , Polack Meaghan , Coudray Nicolas , Quiros Adalberto Claudio , Sakellaropoulos Theodore , Crobach Augustinus S.L.P. , van Krieken J. Han J.M. , Yuan Ke , Tollenaar Rob A.E.M. , Mesker Wilma E. , Tsirigos Aristotelis 
Published: March 2024

AbstractSelf-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-and-eosin-stained whole-slide images (WSIs). We trained an SSL Barlow Twins-encoder on 435 TCGA colon adenocarcinoma WSIs to extract features from small image patches. Leiden community detection then grouped tiles into histomorphological phenotype clusters (HPCs). HPC reproducibility and predictive ability for overall survival was confirmed in an independent clinical trial cohort (N=1213 WSIs). This unbiased atlas resulted in 47 HPCs displaying unique and sharing clinically significant histomorphological traits, highlighting tissue type, quantity, and architecture, especially in the context of tumor stroma. Through in-depth analysis of these HPCs, including immune landscape and gene set enrichment analysis, and association to clinical outcomes, we shed light on the factors influencing survival and responses to treatments like standard adjuvant chemotherapy and experimental therapies. Further exploration of HPCs may unveil new insights and aid decision-making and personalized treatments for colon cancer patients.
Comparison of Alternative pre-mRNA Splicing and Gene Expression Patterns in Midbrain Lineage Cells Carrying Familial Parkinson’s Disease Mutations
Authors: Lee Yeon J. , Syed Khaja , Busquets Oriol , Li Hanqin , Dunnack Jesse , Sahagun Atehsa , Bateup Helen S. , Soldner Frank , Hockemeyer Dirk , Rio Donald C. 
Published: March 2024

SummaryParkinson’s disease (PD) is a devastating neurodegenerative disorder, with both genetic and environmental causes. Human genetic studies have identified ∼20 inherited familial genes that cause monogenic forms of PD. We have investigated the effects of individual familial PD mutations by developing a medium-throughput platform using genome-editing to install individual PD mutations in human pluripotent stem cells (hPSCs) that we subsequently differentiated into midbrain lineage cells including dopaminergic (DA) neurons in cell culture. Both global gene expression and pre-mRNA splicing patterns in midbrain cultures carrying inherited, pathogenic PD mutations in the PRKN and SNCA genes were analyzed. This analysis revealed that PD mutations lead to many more pre-mRNA splicing changes than changes in overall gene RNA expression levels. Importantly, we have also shown that these splicing changes overlap with changes found in PD patient postmortem brain sample RNA-seq datasets. These pre-mRNA splicing changes are in genes related to cytoskeletal and neuronal process formation, as well as splicing factors and spliceosome components. We predict that these mutation-specific pre-mRNA isoforms can be used as biomarkers for PD that are linked to the familial PD mutant genotypes.
Strategies for Inducing and Validating Zinc Deficiency and Zinc Repletion
Authors: Wenegieme Tara-Yesomi , Elased Dalia , McMichael Kelia E. , Rockwood Jananie , Hasrat Khanzada , Ume Adaku C. , Marshall Andrea G. , Neikirk Kit , Kirabo Annet , Elased Khalid M. , Hinton Antentor , Williams Clintoria R. 
Published: March 2024

SummaryGiven the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible and cost-effective methodology outlined will increase scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of diseases.New and NoteworthyThis methods paper details 1) dietary approaches to alter zinc homeostasis in rodents, and 2) qualitative and quantitative methods to ensure the zinc status of experimental animals. The outlined accessible and cost-effective protocol will elevate scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of a multitude of health conditions and diseases.Graphical Abstract
LRRK2G2019S mutation suppresses differentiation of Th9 and Treg cells via JAK/STAT3
Authors: Zheng Ningbo , Jaffery Roshni , Guerrero Ashley , Hou Jiakai , Pan Yuchen , Zhou Fang , Chen Si , Xu Chunyu , Egan Nicholas A. , Bohat Ritu , Chen Ken , Schwarzschild Michael A. , Chen Xiqun , Peng Weiyi 
Published: March 2024

AbstractThe Leucine-rich repeat kinase-2 (LRRK2) G2019S mutation, resulting in aberrantly enhanced kinase activity, is one of the well-recognized genetic risk factors in Parkinson’s Disease (PD). Increased LRRK2 activity was also observed in immune cells from PD patients. Emerging results have also unveiled an upsurge in α-synuclein (α-syn)-specific CD4+T cell responses in PD patients. Given thatLRRK2mutations in PD are germline mutations, there are unmet meets to explore whetherLRRK2G2019S mutation contributes to the pathogenesis of PD via altering CD4+T-cell functions. To fill this knowledge gap, we generated a new T cell receptor (TCR) transgenic mouse strain bearingLRRK2G2019S knock-in mutation, OT-II/LRRK2 (Refer to Mut). As CD4+T cells from OT-II mice specifically recognize ovalbumin, this new strain enables us to explore the impact ofLRRK2G2019S mutation on T-cell functions in an antigen-specific manner. We found that the abundance and proliferation of major immune subsets in spleen tissue from Mut mice are comparable to wild-type (OT-II, Refer to WT) control. However, when we characterized T cell differentiation in these two strains, T cells derived from Mut mice displayed increased Th2 differentiation (IL-4) and decreased Th9 (IL-9) and Treg (Foxp3+%) differentiation.LRRK2G2019S mutation significantly altered the expression levels of master transcription factors (TFs) for T cell differentiation. Specifically, Mut T cells displayed an increase in mRNA expression ofGata3(TF for Th2), a decrease in expression ofIrf4andFoxp3(TFs for Th9 and Treg, respectively). Mechanistically,LRRK2mutation decreased IL-9 production and Treg cell population through the JAK/STAT3 signaling. In conclusion, LRRK2 plays a critical role in regulating T cell differentiation, warranting further studies to evaluate the impacts of altered T cell differentiation led byLRRK2mutation in dopaminergic neuron damages.
Corneal keratocytes, fibroblasts, and myofibroblasts exhibit distinct transcriptional profilesin vitro
Authors: Poole Kara , Iyer Krithika S. , Schmidtke David W. , Petroll W. Matthew , Varner Victor D. 
Published: March 2024

ABSTRACTPurposeAfter stromal injury to the cornea, the release of growth factors and pro-inflammatory cytokines promotes the activation of quiescent keratocytes into a migratory fibroblast and/or fibrotic myofibroblast phenotype. Persistence of the myofibroblast phenotype can lead to corneal fibrosis and scarring, which are leading causes of blindness worldwide. This study aims to establish comprehensive transcriptional profiles for cultured corneal keratocytes, fibroblasts, and myofibroblasts to gain insights into the mechanisms through which these phenotypic changes occur.MethodsPrimary rabbit corneal keratocytes were cultured in either defined serum-free media (SF), fetal bovine serum (FBS) containing media, or in the presence of TGF-β1 to induce keratocyte, fibroblast, or myofibroblast phenotypes, respectively. Bulk RNA sequencing followed by bioinformatic analyses was performed to identify significant differentially expressed genes (DEGs) and enriched biological pathways for each phenotype.ResultsGenes commonly associated with keratocytes, fibroblasts, or myofibroblasts showed high relative expression in SF, FBS, or TGF-β1 culture conditions, respectively. Differential expression and functional analyses revealed novel DEGs for each cell type, as well as enriched pathways indicative of differences in proliferation, apoptosis, extracellular matrix (ECM) synthesis, cell-ECM interactions, cytokine signaling, and cell mechanics.ConclusionsOverall, these data demonstrate distinct transcriptional differences among cultured corneal keratocytes, fibroblasts, and myofibroblasts. We have identified genes and signaling pathways that may play important roles in keratocyte differentiation, including many related to mechanotransduction and ECM biology. Our findings have revealed novel molecular markers for each cell type, as well as possible targets for modulating cell behavior and promoting physiological corneal wound healing.
Widespread evolution of poricidal flowers: A striking example of morphological convergence across flowering plants
Authors: Russell Avery Leigh , Zenil-Ferguson Rosana , Buchmann Stephen L. , Jolles Diana D. , Kriebel Ricardo , Vallejo-Marín Mario 
Published: March 2024

SummaryThe evolution of tube-like floral morphologies that control pollen release via small openings (functionally poricidal flowers) represents a taxonomically and geographically widespread instance of repeated and independent evolution of a functionally similar morphology. Poricidal flowers are often closely associated with buzz pollination by bees, but we lack an updated angiosperm-wide survey of their phylogenetic distribution.We identify all presently known angiosperm genera containing poricidal flowers via a literature survey. We determined the phylogenetic distribution of poricidal flowers and minimum number of independent gains and losses via a genus-level and species level angiosperm-wide phylogeny. We estimated if evolution of poricidal flowers is associated with changes in speciation/extinction via diversification rate analyses.Poricidal flowers occur across at least 87 angiosperm families and 635 genera containing > 28,000 species. At the genus level, more than 200 independent gains and 145 independent losses of poricidal flowers occurred. Across angiosperms, genus-level analyses suggest poricidal flower evolution is associated with lower net diversification rates (origination-extinction). Species-level analyses argue no diversification linked to poricidal morphology but within the two focal families we found family-specific diversification effects.We present different hypotheses for the functional significance of poricidal flowers, including its association with buzz pollination, and suggest future directions for studies elucidating the extent to which morphological and functional convergence of poricidal flowers are correlated.
Evaluation Of Suitability Analysis of Gangetic Water from Upper, Middle, And Lower Ganga Rivers
Authors: Balkrishna Acharya , Ghosh Sourav , Nagose Ashwani , Joshi Divya , Singh Shelly , Kumud  , Saxena Aditi , Taneja Sanyam , Arya Vedpriya 
Published: March 2024

ABSTRACTThis study assesses the suitability of water from distinct segments of the Ganga River in India for drinking, irrigation, and industrial purposes, utilizing various indices. Conducted in MAR-MAY 2023, water samples were collected from multiple sites along the river, and categorized into upper, middle, and lower stretches. The findings revealed differing levels of suitability for various purposes among the sampled sites within each stretch. Parameters for drinking water quality generally adhered to specified limits across all stretches, except for E. coli, emphasizing the importance of disinfection measures. Moreover, the study evaluated irrigation suitability, with most sites falling within the good to excellent range, albeit some exhibiting elevated sodium levels, particularly in the lower stretch. Analysis of major ion abundance revealed an alkaline nature dominated by sodium and potassium ions over calcium and magnesium ions across all stretches. Heavy metal concentrations were either within specified limits or absent, indicating minimal industrial pollution. However, caution is warranted regarding industrial applications due to water aggressiveness, as suggested by indices such as the Langelier saturation index and Ryznar stability index, which hint at potential corrosion issues. Water quality in the Ganga River in India exhibited variability across the upper, middle, and lower stretches, with each segment presenting unique characteristics and suitability levels. Continuous monitoring and control measures, especially concerning the most probable number (MPN) of contaminants, are imperative to ensure the sustainability of water quality and meet the diverse usage needs along the river. The evaluation of Gangetic water from the Upper, Middle, and Lower Ganga Rivers is crucial for understanding water quality in one of India’s vital river basins. This study assesses physical, chemical, and biological parameters to determine suitability for drinking, irrigation, and aquatic life. Factors like pH, dissolved oxygen, turbidity, nutrients, heavy metals, and microbial load are analyzed to reveal water quality and potential risks. Temporal and spatial variations, influenced by natural processes and human activities, are explored. The findings aid in sustainable water management and conservation in the Gangetic basin, addressing the urgent need to safeguard this critical resource.
Suppressing APOE4-induced mortality and cellular damage by targeting VHL
Authors: Jiang Wei I. , Cao Yiming , Xue Yue , Ji Yichun , Winer Benjamin Y. , Zhang Mengqi , Singhal Neel S. , Pierce Jonathan T. , Chen Song , Ma Dengke K. 
Published: March 2024

AbstractMortality rate increases with age and can accelerate upon extrinsic or intrinsic damage to individuals. Identifying factors and mechanisms that curb population mortality rate has wide-ranging implications. Here, we show that targeting the VHL-1 (Von Hippel– Lindau) protein suppressesC. elegansmortality caused by distinct factors, including elevated reactive oxygen species, temperature, andAPOE4, the genetic variant that confers high risks of neurodegeneration in Alzheimer’s diseases and all-cause mortality in humans. These mortality factors are of different physical-chemical nature, yet result in similar cellular dysfunction and damage that are suppressed by deleting VHL-1. Stabilized HIF-1 (hypoxia inducible factor), a transcription factor normally targeted for degradation by VHL-1, recapitulates the protective effects of deleting VHL-1. HIF-1 orchestrates a genetic program that defends against mitochondrial abnormalities, excess oxidative stress, cellular proteostasis dysregulation, and endo-lysosomal rupture, key events that lead to mortality. GeneticVhlinhibition also alleviates cerebral vascular injury and synaptic lesions inAPOE4mice, supporting an evolutionarily conserved mechanism. Collectively, we identify the VHL-HIF axis as a potent modifier of APOE4 and mortality and propose that targeting VHL-HIF in non-proliferative animal tissues may suppress tissue injuries and mortality by broadly curbing cellular damage.
Zero Shot Health Trajectory Prediction Using Transformer
Authors: Renc Pawel , Jia Yugang , Samir Anthony E. , Was Jaroslaw , Li Quanzheng , Bates David W. , Sitek Arkadiusz 
Published: March 2024

AbstractIntegrating modern machine learning and clinical decision-making has great promise for mitigating healthcare’s increasing cost and complexity. We introduce the Enhanced Transformer for Health Outcome Simulation (ETHOS), a novel application of the transformer deep-learning architecture for analyzing high-dimensional, heterogeneous, and episodic health data. ETHOS is trained using Patient Health Timelines (PHTs)—detailed, tokenized records of health events—to predict future health trajectories, leveraging a zero-shot learning approach. ETHOS represents a significant advancement in foundation model development for healthcare analytics, eliminating the need for labeled data and model fine-tuning. Its ability to simulate various treatment pathways and consider patient-specific factors positions ETHOS as a tool for care optimization and addressing biases in healthcare delivery. Future developments will expand ETHOS’ capabilities to incorporate a wider range of data types and data sources. Our work demonstrates a pathway toward accelerated AI development and deployment in healthcare.