bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic polymorphisms of Leukocyte Immunoglobulin-Like Receptor B3 (LILRB3) gene in African American kidney transplant recipients are associated with post-transplant graft failure
Authors: Sun Zeguo , Yi Zhengzi , Wei Chengguo , Wang Wenlin , Cravedi Paolo , Tedla Fasika , Ward Stephen C. , Azeloglu Evren , Schrider Daniel R. , Li Yun , Ali Sumaria , Ren Tianyuan , Liu Shun , Liang Deguang , Fu Jia , Liu Tong , Li Hong , Xi Caixia , Vy Thi Ha , Mosoyan Gohar , Sun Quan , Kumar Ashwani , Zhang Zhongyang , Farouk Samira , Campell Kirk , Ochando Jordi , Lee Kyung , Coca Steve , Xiang Jenny , Connolly Patti , Gallon Lorenzo , Colvin Robert , Menon Madhav , Nadkarni Girish , He John C. , Kraft Monica , Jiang Xuejun , Zhang Xuewu , Zhang Weiguo , Chen Shu-hsia , Heeger Peter , Zhang Weijia 
Published: March 2024

AbstractBackgroundAfrican American (AA) kidney transplant recipients exhibit a higher rate of graft loss compared to other racial and ethnic populations, highlighting the need to identify causative factors underlying this disparity.MethodWe analyzed RNA sequences of pretransplant whole blood from subjects followed in three kidney transplant cohorts to identify single nucleotide polymorphisms (SNPs) associated with death censored graft loss (DCGL). We employed a meta-analysis to uncover key transcriptional signatures and pathways associated with the identified SNPs and used single cell RNA to define cellular specificity. We characterized SNP functions usingin vitroimmunological and survival assays and tested for associations between the identified SNPs and other immune-related diseases using a ∼30,100 subject, electronic health record (EHR)-linked database.ResultsWe uncovered a cluster of four consecutive missense SNPs in the Leukocyte Immunoglobulin-Like Receptor B3 (LILRB3, a negative immune response regulator) gene that strongly associated with DCGL. ThisLILRB3-4SNPs cluster encodes missense mutations at amino acids 617-618 proximal to a SHP-1/2 phosphatase-binding ITIM motif.LILRB3-4SNPs is specifically enriched within subjects of AA ancestry (8.6% prevalence vs 2.3% in Hispanic and 0.1% in European populations), is not linked toAPOL1G1/G2 alleles, and exhibited a strong association with DCGL. Analysis of PBMC and transplant biopsies from recipients withLILRB3-4SNPs showed evidence of enhanced adaptive immune responsiveness and ferroptosis-associated death in monocytes. Overexpression of the variant allele in THP-1 cells (macrophage line) induced augmented inflammation and ferroptosis, which were attenuated by a ferroptosis inhibitor, verifying a causal link. TheLILRB3-4SNPs also associated with multiple systemic and organ-specific immune-related diseases in AAs, consistent with conferring a broadly relevant immune function.ConclusiontheLILRB3-4SNPs represent a functionally important, distinct genetic risk factor for kidney transplant outcome and development/severity of other immune-related diseases in patients of AA ancestry. Pharmacological targeting of ferroptosis should be tested to prevent or treat these disease processes in AA recipients carryingLILRB3-4SNPs.
Charting is Never Exciting: Measuring Physician Time Use in Medical Dramas
Authors: Jackson Katelin C , Miller Kayla A , Hill Samantha M , Johnson Stephanie S. , Reimanis Laila A. , Lofgren Eric T 
Published: March 2024

AbstractObjectivesThis study aimed to explore the use of medical dramas to train observers when in-person observations or patient contact in clinical settings is impossible. The study also assessed the media’s portrayal of the medical profession and compared time use patterns in medical dramas to previous hospital observational studies.DesignActivity-pattern observational study using Work Observation by Activity Timing software.SettingThe hospital, ICU, and community settings of medical television shows.ParticipantsThe first and last season of the main cast of three medical dramas; Grey’s Anatomy, Scrubs, and ER.Main outcome measuresInter-rater reliability scores were used to assess how well medical dramas can be used as a training tool for observers. Proportions of time spent on daily medical tasks were compared to other in-person hospital studies.ResultsGrey’s Anatomy and Scrubs had excellent Intraclass Correlation Coefficients (ICC) scores for a general medical setting, with Grey’s Anatomy ICC scores for Season 1 0.99 (0.97 to 1.0), and Season 16 0.98 (0.90 to 1.0) and Scrubs ICC scores of 0.91 (0.65 to 0.98) for Season 1 and 0.91 (0.55, 0.99) for Season 8. In contrast, ER had an acceptable ICC score of 0.89 (0.59 to 0.98) for Season 1 and 0.81 (0.35 to 0.96) for Season 15 and might be more suitable for studies exploring activity patterns in the Emergency Department. All had p-values of <0.001.ConclusionsMedical dramas can serve as training tools when clinical observation is limited or impossible, and our methods reflect these shows’ ease of use and flexibility. Additionally, medical dramas can be selected for their similarity to in-person studies. Still, one should be mindful that inaccuracies in the representation of clinical activity patterns are present. However, using medical dramas to train research staff in direct observation is a feasible and reliable method.
Loss ofEsr1Does Not Affect Hearing and Balance
Authors: Simms Shion S , Milani Marcus N , Kim Mi-Jung , Husain Ryan , Infante Laura , Cooke Paul S , Someya Shinichi 
Published: March 2024

AbstractAlthough estrogen affects the structure and function of the nervous system and brain and has a number of effects on cognition, its roles in the auditory and vestibular systems remain unclear. The actions of estrogen are mediated predominately through two classical nuclear estrogen receptors, estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). In the current study, we investigated the roles of ESR1 in normal auditory function and balance performance using 3-month-old wild-type (WT) andEsr1knockout (KO) mice on a CBA/CaJ background, a normal-hearing strain. As expected, body weight ofEsr1KO females was lower than that ofEsr1KO males. Body weight ofEsr1KO females was higher than that of WT females, while there was no difference in body weight between WT andEsr1KO males. Similarly, head diameter was higher inEsr1KO vs. WT females. Contrary to our expectations, there were no differences in auditory brainstem response (ABR) thresholds, ABR waves I-V amplitudes and ABR waves I-V latencies at 8, 16, 32, and 48 kHz, distortion product otoacoustic emission (DPOAE) thresholds and amplitudes at 8, 16, and 32 kHz, and rotarod balance performance (latency to fall) between WT andEsr1KO mice. Furthermore, there were no sex differences in ABRs, DPOAEs, and rotarod balance performance inEsr1KO mice. Taken together, our findings show thatEsr1deficiency does not affect auditory function or balance performance in normal hearing mice, and suggest that loss ofEsr1is likely compensated by ESR2 or other estrogen receptors to maintain the structure and function of the auditory and vestibular systems under normal physiological conditions.HighlightsHead diameter of femaleEsr1KO mice was higher than that of female WT mice.ABRs and DPOAEs were not different in WT andEsr1KO mice.There were no sex differences in ABRs and DPOAEs inEsr1KO mice.Rotarod balance performance was not different in WT andEsr1KO mice.There were no sex differences in rotarod balance performance inEsr1KO mice.Loss ofEsr1does not affect auditory function or balance performance under normal physiological conditions.
Self-Other Voice Discrimination Task: A - Neuropsychological Tool For Clinical Assessment of Self-Related Deficits
Authors: Voruz Philippe , Orepic Pavo , Coll Selim Yahia , Haemmerli Julien , Blanke Olaf , Péron Julie Anne , Schaller Karl , Iannotti Giannina Rita 
Published: March 2024

AbstractBackgroundDeficits in self are commonly described through different neuro-pathologies, based on clinical evaluations and experimental paradigms. However, currently available approaches lack appropriate clinical validation, making objective evaluation and discrimination of self-related deficits challenging.MethodsWe applied a statistical standardized method to assess the clinical discriminatory role of a Self-Other Voice Discrimination (SOVD) task. This task, validated experimentally as a marker for self-related deficits, was administered to 17 patients eligible for neurosurgery due to focal hemispheric brain tumors or epileptic lesions.ResultsThe clinical discriminatory capacity of the SOVD task was evident in three patients who exhibited impairments for self-voice perception that could not be predicted by other neuropsychological performances. Impairments in other-voice perception were linked to inhibitory neuropsychological alterations, suggesting a potential association with executive deficits in voice recognition.ConclusionsThis exploratory study highlights the clinical discriminatory potential of the SOVD task and suggests that it could complement the standard neuropsychological assessment, paving the way for enhanced diagnoses and tailored treatments for self-related deficits.
Spinal Cord Motor Neuron Phenotypes and Polygenic Risk Scores in Sporadic Amyotrophic Lateral Sclerosis: Deciphering the Disease Pathology and Therapeutic Potential of Ropinirole Hydrochloride
Authors: Kato Chris , Morimoto Satoru , Takahashi Shinichi , Namba Shinichi , Wang Qingbo S. , Okada Yukinori , Okano Hideyuki 
Published: March 2024

ABSTRACTThis study investigated the genetic factors associated with the onset of amyotrophic lateral sclerosis (ALS) and the mechanism of action of Ropinirole hydrochloride (ROPI) in ALS treatment. Firstly, ALS is a neurodegenerative disease characterized by the degeneration of both upper and lower motor neurons (MNs), and identifying the genetic factors of sporadic ALS (SALS) has been challenging. However, ALS-like phenotypes have been observed in induced pluripotent stem cell-derived lower MNs (iPSC-LMNs) of SALS patients, suggesting a polygenic contribution to SALS pathogenesis, and ROPI has emerged as a novel therapeutic candidate for ALS treatment. Moreover, recent genome-wide association studies (GWAS) have suggested an association between high levels of blood total cholesterol (bTC) and ALS. The study aimed to combine iPSC-LMN phenotypes and polygenic risk scores (PRS) to quantify the genetic background of patients and analyze the mechanism of action of ROPI in ALS treatment. Twenty SALS patients were included in the study, and iPSC-LMN phenotypes, PRS for 58 quantitative traits, and ALS were calculated. The results indicated that patients with a higher PRS for bTC showed changes in iPSC-LMN phenotypes, particularly a higher response to ROPI. Additionally, a correlation was observed between bTC levels and the expression of cholesterol biosynthesis (CB) enzymes in MNs, suggesting their involvement in the pathogenesis of SALS. Furthermore, the study compared the liver and spinal cord expression of CB enzymes and found a correlation between bTC levels and CB enzyme expression, particularly in MNs, which may partly explain the MN-specific pathogenesis of SALS. In conclusion, the study suggests that high bTC levels and increased CB activity may contribute to the pathogenesis of SALS, and CB suppression may be a potential therapeutic strategy for ALS, supported by the mechanism of action of ROPI in ALS treatment.
Genetic patterns, sublineages and dynamics of tuberculosis transmission in Cuba, a low burden country
Authors: Martinez-Rodriguez Ileana Margarita , Herrera-Avila Yoslany Mercedes , Goza-Valdes Roxana , Rodriguez-Bertheau Andrea Maria , Diaz-Rodriguez Raul 
Published: March 2024

AbstractContextIn Cuba, a country with a low incidence of tuberculosis (TB), there is no information on the dynamics of transmission of the disease for two decades.AimsDetermine the genetic patterns and sublineages ofMycobacterium tuberculosiscomplex (MTBC) isolates circulating in 2009 and their relationship with the epidemiological data of the patients.Settings and DesignA retrospective descriptive study was carried out in Cuba with 178 MTBC isolates.Materials and methodsSpoligotyping and mycobacterial interspersed repetitive-unit– variable-number tandem-repeat (MIRU-VNTR) typing with 24 loci were performed. For statistical analysis, non-parametric methods, analysis of variance and homogeneity test, were used.ResultsSpoligotyping produced 39 spoligotypes. The S, Beijing, LAM and Haarlem sublineages prevailed. The clustering rate was 75.84% and the Hunter-Gaston discriminatory index (HGDI): 0.8734. MIRU-VNTR typing with 24-loci defined 154 genetic patterns: six grouped 30 isolates and 148 showed unique patterns. The clustering rate was 14.60% and the HGDI: 0.9926. There was a predominance of sublineages by region: S, Beijing and LAM in the West, Center and East, respectively.ConclusionsThe dynamics of TB transmission in Cuba in 2009 is reported, inferring that this occurs in a limited manner and belonging to risk groups does not favor transmission. It serves to evaluate a megaproject of the Global Fund to reduce the transmission of TB in this country. The population genetic structure of MTBC resembles that of an Ibero-American country, with the exception of the high frequency of the Beijing and S sublineages.
Shared Medical Appointments in Heart Failure For Post-hospitalization Follow-up: A Randomized Controlled Trial
Authors: Taveira Tracey H. , Cohen Lisa B. , Laforest Sherry K. , Oliver Karen , Parent Melanie , Hearns Rene , Ball Sherry L. , Dev Sandesh , Wu Wen-Chih 
Published: March 2024

AbstractBackgroundShared medical appointments (SMAs) in heart failure (HF) are medical visits where several patients with HF meet with multidisciplinary providers at the same time for efficient and comprehensive care. It is unknown whether HF-SMAs can improve overall and cardiac health status for high-risk patients discharged with HF.MethodsA 3-site, open-label, randomized-controlled-trial was conducted. Participants within 12 weeks of HF hospitalization were randomized to receive either HF-SMA or usual HF clinical care (usual-care) on a 1:1 ratio. The HF-SMA team, which consisted of a nurse, nutritionist, psychologist, nurse practitioner and/or a clinical pharmacist, provided four 2-hour session HF-SMAs that met every other week for 8 weeks. Primary outcomes were the overall health status measured by EQ5D-VAS and cardiac health status by KCCQ, 180 days post-randomization.ResultsOf the 242 patients enrolled (HF-SMA n=117, usual-care n=125, mean age 69.3±9.4 years, 71.5% white, 94.6% male), 84% of participants completed the study (n=8 HF-SMA and n=9 usual-care patients died). After 180 days, both HF-SMA and usual-care participants had similar and significant improvements from baseline in KCCQ, but only HF-SMA participants had significant improvements in EQ5D-VAS (mean change = 7.2 ± 15.8 in HF-SMA versus -0.4 ± 19.0 points in usual-care, p<0.001).ConclusionBoth HF-SMA and usual care in HF participants achieved significant improvements in cardiac health status, but only a team approach through HF-SMA achieved significant improvements in overall health status. A larger population and a longer follow-up time are needed in future studies to evaluate re-hospitalization and death outcomes.Clinical PerspectiveThis randomized controlled trial represents the first multi-site study to rigorously assess the outcomes of a multidisciplinary team intervention in a group medical clinic setting to improve patient-centered self-reported outcomes of high-risk patients with a recent heart failure hospitalization.Shared medical appointments can improve cardiac specific and overall health status in high-risk patients with heart failure.
STRIPAK controls cell-cell communication by promoting cytoneme biogenesis through the membrane-sculpting function of Slik
Authors: Rambaud Basile , Joseph Mathieu , Tsai Feng-Ching , De Jamblinne Camille , Del Guidice Emmanuelle , Sabelli Renata , Bassereau Patricia , Hipfner David R , Carréno Sébastien 
Published: March 2024

ABSTRACTCytonemes are signaling filopodia that facilitate long-range cell-cell communication by forming synapses between cells. Initially discovered in Drosophila for transporting morphogens during embryogenesis, they have since been identified in mammalian cells and recently implicated in carcinogenesis. Yet, despite their importance, the mechanisms controlling cytoneme biogenesis remain elusive. Here, we demonstrate that the Ser/Thr kinase Slik drives remote cell proliferation by promoting cytoneme formation. We discovered that this function depends on the coiled-coil domain of Slik (SlikCCD), which directly sculpts membranes into tubules. Importantly, Slik plays paradoxical roles in cytoneme biogenesis. While its membrane-sculpting activity promotes cytoneme formation, it is counteracted by its kinase activity, which enhances actin association with the plasma membrane via Moesin phosphorylation.In vivo, SlikCCDenhances formation of cytonemes in one epithelial layer of the wing disc to promote cell proliferation in an adjacent layer. Finally, we found that this function relies on the STRIPAK complex, which controls cytoneme formation and governs proliferation at a distance by regulating Slik association with the plasma membrane. Our study unveils the first family of kinases that directly sculpts membranes, a function crucial for cytoneme-mediated control of cell proliferation.
The sodium-proton exchangers sNHE and NHE1 control plasma membrane hyperpolarization in mouse sperm
Authors: Novero Analia G , Rodríguez Paulina Torres , De la Vega Beltrán José L , Schiavi-Ehrenhaus Liz J , Luque Guillermina M , Carruba Micaela , Stival Cintia , Gentile Iñaki , Ritagliati Carla , Santi Celia M , Nishigaki Takuya , Krapf Diego , Buffone Mariano G , Darszon Alberto , Treviño Claudia L , Krapf Dario 
Published: March 2024

ABSTRACTSperm capacitation, crucial for fertilization, occurs in the female reproductive tract and can be replicatedin vitrousing a medium rich in bicarbonate, calcium, and albumin. These components trigger the cAMP-PKA signaling cascade, proposed to promote hyperpolarization of the mouse sperm plasma membrane through activation of SLO3 K+channel. Hyperpolarization is a hallmark of capacitation: proper membrane hyperpolarization renders higherin vitrofertilizing ability, whileSlo3KO mice are infertile. However, the precise regulation of SLO3 opening remains elusive. Our study challenges the involvement of PKA in this event and reveals the role of Na+/H+exchangers. During capacitation, calcium increase through CatSper channels activates NHE1, while cAMP directly stimulates the sperm-specific NHE, collectively promoting the alkalinization threshold needed for SLO3 opening. Hyperpolarization then feeds back Na+/H+activity. Our work is supported by pharmacology, and a plethora of KO mouse models, and proposes a novel pathway leading to hyperpolarization.TeaserAlkalinization of sperm cytoplasm activates potassium channels to hyperpolarize the plasma membrane in a PKA independent cascade.
External task switches activate default mode regions without enhanced processing of the surrounding scene
Authors: Zhou Ashley X , Duncan John , Mitchell Daniel J 
Published: March 2024

AbstractDefault mode network (DMN) activity, measured with fMRI, typically increases during internally directed thought, and decreases during tasks that demand externally focused attention. However, Crittenden et al. (2015) and Smith et al. (2018) reported increased DMN activity during demanding external task switches between different cognitive domains, compared to within-domain switches and task repeats. This finding is hard to reconcile with many dominant views of DMN function. Here, we aimed to replicate this DMN task-switch effect in a similar paradigm and test whether it reflects increased representation of broader context, specifically of a scene presented behind the focal task. In Core DMN, we found significant activity for all task switches, compared to task repeats, and stronger activity for switches between rest and task. Although the content of the background scene was attended, recalled, and neurally decodable, there was no evidence that this differed by switch type. Therefore, external task switches activated DMN without enhanced processing of the surrounding scene. Surprisingly, DMN activity at within-domain switches was no less than at between-domain switches. We suggest that modulation of DMN activity by task switches reflects a shift in the current cognitive model and depends on the overall complexity of that model.
Venomics and Peptidomics of Palearctic vipers: Clade-wide analysis of seven taxa of the generaVipera,Montivipera,MacroviperaandDaboiaacross Türkiye
Authors: Damm Maik , Karış Mert , Petras Daniel , Nalbantsoy Ayse , Göçmen Bayram , Süssmuth Roderich D. 
Published: March 2024

ABSTRACTSnake venom variations are a crucial factor to understand the consequences of snakebite envenoming worldwide and therefore it’s important to know about toxin composition alterations between taxa. Palearctic vipers of the generaVipera,Montivipera,MacroviperaandDaboiahave high medical impacts across the Old World. One hotspot for their occurrence and diversity is Türkiye on the border between the continents, but many of their venoms remain still understudied. Here, we present the venom compositions of seven Turkish viper taxa. By complementary mass spectrometry-based bottom-up and top-down workflows, the venom profiles were investigated on proteomics and peptidomics level. This study includes the first venom descriptions ofVipera berus barani,Vipera darevskii,Montivipera bulgardaghica albizonaandMontivipera xanthina, as well as first snake venomics profiles of TurkishMacrovipera lebetinus obtusaandDaboia palaestinae, including an in-depth reanalysis ofMontivipera bulgardaghica bulgardaghicavenom. Additionally, we identified the modular consensus sequence pEXW(PZ1–2P(EI)/(KV)PPLE for bradykinin-potentiating peptides (BPP) in viper venoms. For better insights into variations and potential impacts of medical significance the venoms were compared against other Palearctic viper proteomes, including the first genus-wideMontiviperavenom comparison. This will help the risk assessment of snakebite envenoming by these vipers and aid in predicting the venoms pathophysiology and clinical treatments.
GENOTYPIC SPECTRUM OF ALBINISM IN MALI
Authors: Diallo Modibo , Sylla Ousmane , Sidibé Mohamed Kole , Plaisant Claudio , Mercier Elina , Sequeira Angèle , Javerzat Sophie , Hadid Aziz , Lasseaux Eulalie , Michaud Vincent , Arveiler Benoit 
Published: March 2024

ABSTRACTAlbinism is a phenotypically and genetically heterogeneous condition characterized by a variable degree of hypopigmentation and by ocular features leading to reduced visual acuity. Whereas numerous genotypic studies have been conducted throughout the world, very little is known about the genotypic spectrum of albinism in Africa and especially in Sub-Saharan Western Africa. Here we report the analysis of all 20 known albinism genes in a series a 23 patients originating from Mali. Four were diagnosed with OCA 1 (oculocutaneous albinism type 1), 17 with OCA 2, and 2 with OCA 4.OCA2variant NM_000275.3:c.819_822delinsGGTC was most frequently encountered. Four novel variants were identified (2 inTYR, 2 inOCA2). A deep intronic variant was found to alter splicing of theOCA2RNA by inclusion of a pseudo exon. Of note, theOCA2exon 7 deletion commonly found in eastern, central and southern Africa was absent from this series. African patients with OCA 1 and OCA 4 had only been reported twice and once respectively in previous publications. This study constitutes the first report of the genotypic spectrum of albinism in a western Sub-Saharan country.