bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sit-up Test for Assessing Blood Pressure Dysregulation in Community-Dwelling Older Adults: A Cross-Sectional Study
Authors: Oyake Kazuaki , Yokokawa Yoshiharu 
Published: February 2025

AbstractBackgroundThe sit-up test enables the assessment of orthostatic hypotension without using a tilt table in individuals at high risk of falling when standing; however, no studies have compared blood pressure responses between those with and without orthostatic hypotension during this test. The primary objective of this study was to compare blood pressure responses during the sit-up test between community-dwelling older adults with and without orthostatic hypotension. The secondary objective was to determine the associations between orthostatic hypotension detected by the sit-up test and poor health conditions in these individuals.MethodsOne hundred-two community-dwelling older adults underwent the sit-up test. Orthostatic hypotension was defined as a decrease of ≥10 mmHg in systolic blood pressure and/or ≥5 mmHg in diastolic blood pressure during the test. Supine and seated hypertension were evaluated, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Blood pressure responses during the test were compared between participants with and without orthostatic hypotension. Moreover, associations of orthostatic hypotension with demographic, clinical, and geriatric outcomes were examined.ResultsThirty-four participants (33.3%) showed orthostatic hypotension during the test. Participants with orthostatic hypotension demonstrated a greater decrease in systolic blood pressure (F(3,297)= 47.0, p < 0.001), a smaller increase in diastolic blood pressure (F(3,297)= 26.5, p < 0.001), and higher supine systolic blood pressure (t = 3.363, p = 0.005) during the test than those without orthostatic hypotension. Consequently, 52.9% of participants with orthostatic hypotension had supine hypertension. Orthostatic hypotension was associated with a higher proportion of participants with at least one comorbidity (odds ratio = 4.50, p = 0.002) and those with non-robust status (odds ratio = 3.08, p = 0.022), even after adjusting for supine and seated hypertension.ConclusionCommunity-dwelling older adults with orthostatic hypotension were characterized by an impaired orthostatic increase in diastolic blood pressure and high supine systolic blood pressure during the sit-up test. Orthostatic hypotension was associated with poor health conditions, independently of supine and seated hypertension. These findings contribute valuable insights for the application of the sit-up test in preventive health screenings for older adults.
Matrix Metalloproteinase-9 Mediates Endothelial Glycocalyx Degradation and Correlates with Severity of Hemorrhagic Fever with Renal Syndrome
Authors: Jacquet Chloé , Gustafsson Rasmus , Patel Ankit Kumar , Hansson Magnus , Rankin Gregory , Bano Fouzia , Byström Julia Wigren , Blomberg Anders , Rasmuson Johan , Satchell Simon , Thunberg Therese , Ahlm Clas , Bally Marta , Connolly Anne-Marie Fors 
Published: February 2025

SummaryHemorrhagic fever with renal syndrome (HFRS) caused by Puumala virus (PUUV) leads to vascular dysfunction contributing to acute kidney injury and pulmonary complications. The endothelial glycocalyx (eGLX) is crucial for vascular integrity, and its degradation may exacerbate disease severity. In this study, we examined the association between eGLX degradation and renal and pulmonary dysfunction in 44 patients with laboratory-confirmed PUUV infection. We measured plasma levels of eGLX degradation markers—syndecan-1, heparan sulfate, soluble thrombomodulin, and albumin— and found that these correlated with severe acute kidney injury and the need for oxygen therapy. In vitro experiments showed that matrix metalloproteinase-9 (MMP-9) and heparanase can degrade eGLX components, but albumin at physiological concentrations can mitigate this degradation and protect endothelial barrier function. These findings indicate that eGLX degradation contributes to HFRS pathogenesis and suggest that targeting the eGLX could be a therapeutic strategy to improve patient outcomes.
Climate versus human impacts on the marine fauna of the Mediterranean Sea during the pre-industrial period
Authors: Leal Daniela , Agiadi Konstantina , Bas Maria 
Published: February 2025

ABSTRACTClimate and human impacts have impacted the Mediterranean ecosystem for thousands of years. Still, their evidence has been incomplete, hindering a proper assessment of the marine ecosystem’s baseline state and resources. In an attempt to disentangle these impacts, we conducted a study focused on commercially important species of marine mammals, fishes, and molluscs over the last 130,000 (130 ka) years until the Industrial Revolution (the year 1850). To assess differences within the basin, we subdivided the Mediterranean Sea into three subregions – Western, Eastern and Adriatic. Our work revealed significant climatic and anthropogenic impacts on three species: the banded-dye murex, the Atlantic bluefin tuna and the gilthead sea bream. Climate change, particularly temperature changes, influenced the abundance and body size of Atlantic bluefin tuna, while subregional differences in the stable isotopic composition of archaeological skeletal material reflected shifts in the system’s primary productivity. Human activities, particularly overexploitation, impacted the abundance of both banded-dye murex and Atlantic bluefin tuna, as well as the body size of gilthead sea bream and Atlantic bluefin tuna. These results highlight the significance of studying the relationships between climate, human activities, and marine resources in this large marine ecosystem. As well as integrating past data with contemporary data to reconstruct ecological baselines and obtain longer and more comprehensive time series of ecosystem change. Understanding the history of marine ecosystems and species-specific responses to environmental and anthropogenic disturbances is essential to ensure the development of effective present and future environmental management strategies while supporting the implementation of targeted conservation measures.
Human gut microbiota subspecies carry implicit information for in-depth microbiome research
Authors: Trickovic Matija , Kieser Silas , Zdobnov Evgeny M. , Trajkovski Mirko 
Published: February 2025

SummaryMicrobial strains from same species can have distinct functional characteristics owing to their different gene content. As the highest resolution, strains are mainly host-specific, thus obscuring unbiased associations, and hindering deductive research. Here, we comprehensively define the human gut microbiota at consistently-annotated subspecies resolution in an unbiased, cohort-independent manner, and demonstrate that we can generalize across distinct populations worldwide while maintaining specificity and improving interstudy reproducibility. We developed panhashome, a sketching-based method for rapid subspecies quantification and identification of genes that drive the intraspecies variations, and showed that subspecies carry implicit information undetectable at species level. By meta-analysis of colorectal cancer (CRC) datasets, we identified disease-associated subspecies whose sibling subspecies or species are not. Subspecies-based machine-learning CRC diagnostic algorithm outperformed species-level methods by leveraging the unique subspecies-level information. This subspecies catalogue allows identification of genes that drive the functional differences between subspecies as fundamental step in mechanistically understanding microbiome-phenotype interactions.
Integrated deep learning and geo-referencing for drone-based animal tracking with flexible camera angles
Authors: Samad Imran , Sutaria Dipani , Farine Damien R. , Shanker Kartik , Cantor Mauricio 
Published: February 2025

AbstractThe ability of drones to provide detailed information on animals and their surroundings makes them ideal for studying animal behaviour at fine scales. While drones can provide high-resolution images of what animals are doing, they should also, in theory, be able to provide data on where they are. However, reconstructing geo-referenced tracks from drone videos that follow animals is challenging, particularly because current methods require specific drone flight patterns and large computational power.Here, we combine deep learning and object tracking methods with a novel geo-referencing algorithm which allows us to track individuals across video frames and reconstruct their geo-referenced trajectories. We used a Region-based Convoluted Neural Network to detect animals and a Hungarian tracking algorithm to link detections across video frames, and then geo-referenced each detection in every frame to reconstruct individual trajectories.We tested our geo-refencing algorithm through multiple drone flights with varying flight parameters over known Ground Control Points. The median (95% CI) geo-referencing error was 2.81 (0.74 – 23.23) meters, which reduced by 50% when the drone camera was positioned between -90° and -40°. Error increased with drone height and camera angle (-90° refers to the camera pointing towards the ground) but was not impacted by drone orientation.We then demonstrate the utility of our framework with empirical examples using consumer-level drones. First, we tracked a volunteer carrying a high-resolution GPS unit and overlayed their GPS tracks on our estimated tracks to quantify tracking error. Next, we used drone videos of two delphinid species (Tursiops truncates gephyreus, andSousa plumbea) representing varying environmental and flight conditions. We were able to successfully infer individual tracks across all conditions except when individuals formed tight clusters, in which case tracks were assigned a group identifier.Our framework demonstrates an easy and robust approach to translate drone videos of moving animals into geo-referenced animal tracks which is applicable in many research contexts. A major advance over previous methods is that our algorithm is robust to different camera angles, and provides tracks with accuracy on-par with, or even exceeding, the accuracy from GPS tracking.HeadlineAutomated drone-based animal tracking
Cryo-EM reveals a new allosteric binding site at the M5mAChR
Authors: Burger Wessel A. C. , Mobbs Jesse I. , Rana Bhavika , Wang Jinan , Joshi Keya , Gentry Patrick R. , Yeasmin Mahmuda , Venugopal Hariprasad , Bender Aaron M. , Lindsley Craig W. , Miao Yinglong , Christopoulos Arthur , Valant Celine , Thal David M. 
Published: February 2025

AbstractThe M5muscarinic acetylcholine receptor (M5mAChR) represents a promising therapeutic target for neurological disorders. However, the high conservation of its orthosteric binding site has posed significant challenges for drug development. While selective positive allosteric modulators (PAMs) offer a potential solution, a structural understanding of the M5mAChR and its allosteric binding sites has remained limited. Here, we present a 2.8 Å cryo-electron microscopy structure of the M5mAChR complexed with heterotrimeric Gqprotein and the agonist iperoxo, completing the active-state structural characterization of the mAChR family. To identify the binding site of M5-selective PAMs, we implemented an integrated approach combining mutagenesis, pharmacological assays, structural biology, and molecular dynamics simulations. Our mutagenesis studies revealed that selective M5PAMs bind outside previously characterized M5mAChR allosteric sites. Subsequently, we obtained a 2.1 Å structure of M5mAChR co-bound with acetylcholine and the selective PAM VU6007678, revealing a novel allosteric pocket at the extrahelical interface between transmembrane domains 3 and 4 that was confirmed through mutagenesis and simulations. These findings demonstrate the diverse mechanisms of allosteric regulation in mAChRs and highlight the value of integrating pharmacological and structural approaches to identify novel allosteric binding sites.
CobVar — a comprehensive resource of Vitamin B12-associated genomic variants
Authors: HS Neha , Kilpady Chaitra A , Kamath Akshata A , Ahmed Ashikh , Thomas Tinku , Kurpad Anura V , Sivadas Ambily 
Published: February 2025

AbstractThe importance of vitamin B12(cobalamin) in numerous biological processes, including DNA synthesis and cellular energy production, underscores the need for therapeutic and public health strategies to address B12insufficiency/deficiency in the population. Genetic variations in pathways influencing cobalamin absorption, transport, and metabolism can affect various direct and indirect measures of vitamin B12status. To facilitate a structured approach to studying these genetic factors, we aimed to systematically curate and create a user-friendly web database that offers comprehensive data on genetic variants influencing B12biomarkers. A Pubmed search was performed for 5 B12traits (total serum/plasma B12, holotranscobalamin (active B12), total transcobalamin, holo haptocorrin, and methylmalonic acid) resulting in 493 research publications, of which 47 relevant publications were reviewed further. The database backend was built using MongoDB and the web interface was coded in PHP, JavaScript, HTML and CSS on an Apache HTTP server. We have manually curated and compiled the Cobalamin Associated Genetic Variant (CobVar) database, comprising a total of 324 genetic variant associations for 5 different vitamin B12traits involving 222 unique genetic variants and 84 genes identified across several genome-wide association studies (GWAS) and candidate gene studies. About one-third of the total genetic variant associations have been reported in >1 independent studies and 15 variants in >1 ethnic group. FUT2 gene showed the maximum number of associations for total serum/plasma B12(N=39), followed by MTHFR (N=24) and TCN2 (N=23). The database is accessible online athttps://datatools.sjri.res.in/VBG/. CobVar is a vital resource for researchers and nutritionists, offering quick access to the latest developments in B12-related genetic variant research and serves as a valuable tool for advancing personalized treatment.Database URLhttps://datatools.sjri.res.in/VBG/.
NKG7 is a stable marker of cytotoxicity across immune contexts and within the tumor microenvironment
Authors: Turiello Roberta , Ng Susanna S. , Tan Elisabeth , Voort Gemma van der , Salim Nazhifah , Yong Michelle , Khassenova Malika , Oldenburg Johannes , Rühl Heiko , Hasenaur Jan , Surace Laura , Toma Marieta , Bald Tobias , Hölzel Michael , Corvino Dillon 
Published: February 2025

AbstractCytotoxicity is a cornerstone of immune defense, critical for combating tumors and infections. This process relies on the coordinated action of granzymes and pore-forming proteins, with Granzyme B (GZMB) and Perforin (PRF1) being key markers and the most widely studied molecules pertaining to cytotoxicity. However, other human granzymes and cytotoxic components remain underexplored, despite growing evidence of their distinct, context-dependent roles. Natural Killer Cell Granule Protein 7 (NKG7) has recently emerged as a crucial cytotoxicity regulator, yet its expression patterns and function are poorly understood. Using large publicly available single-cell RNA sequencing atlases, we performed a comprehensive profiling of cytotoxicity across immune subsets and tissues. Our analysis highlights NKG7 expression as a strong marker of cytotoxicity, exhibiting a strong correlation with overall cytotoxic activity (r = 0.97) and surpassing traditional markers such as Granzyme B and Perforin in reliability. Furthermore, NKG7 expression is notably consistent across diverse immune subsets and tissues, reinforcing its versatility and robustness as a cytotoxicity marker. These findings position NKG7 as an invaluable tool for evaluating immune responses and a reliable indicator of cytotoxic functionality across biological and clinical contexts.
A method for efficient, rapid, and minimally invasive implantation of individual non-functional motes with penetrating subcellular-diameter carbon fiber electrodes into rat cortex
Authors: Letner Joseph G. , Lam Jordan L. W. , Copenhaver Miranda G. , Barrow Michael , Patel Paras R. , Richie Julianna M. , Lee Jungho , Kim Hun-Seok , Cai Dawen , Weiland James D. , Phillips Jamie , Blaauw David , Chestek Cynthia A. 
Published: February 2025

AbstractObjectiveDistributed arrays of wireless neural interfacing chips with 1-2 channels each, known as “neural dust”, could enhance brain machine interfaces (BMIs) by removing the wired connection through the scalp and increasing biocompatibility with their submillimeter size. Although several approaches for neural dust have emerged, a procedure for implanting them in batches that builds upon the safety and performance of currently used electrodes remains to be demonstrated.ApproachHere, we demonstrate the feasibility of implanting batches of wireless motes that rest on the cortical surface with carbon fiber electrodes of subcellular diameter (6.8-8.4 µm) that penetrate to a target brain depth of 1 mm without insertion aids. To simulate their implantation, we assembled more than 230 mechanically equivalent motes and affixed them to insertion tools with polyethylene glycol (PEG), a quickly dissolvable and biocompatible material. Then, we implanted mote grids of multiple configurations into rat cortexin vivoand evaluated insertion success and their arrangement on the brain surface using photos and videos captured during their implantation.Main ResultsWhen placing motes onto the insertion device, we found that they aggregated in molten PEG such that the array pitch was only 5% wider than the dimensions of the mote bases themselves (240 x 240 µm). Overall, we found that motes with this arrangement could be inserted into rat cortex with a high success rate, as 171/186 (92%) motes in 4x4 (N=4) and 5x5 (N=5) square grid configurations were successfully inserted using the insertion device alone. After implantation, measurements of how much motes tilted (22±9°, X̄±S) and had been displaced relative to their original positions were smaller than those measured for devices implanted inside the brain in the literature.SignificanceCollectively, these data establish the viability of safely implementing motes with ultrasmall electrodes and epicortically-situated chips for use in future BMIs.
Monoclonal antibody to Filarial serpin Wb123 impedes the urokinase plasminogen activator receptor mediated Alternative activation of macrophages
Authors: Upadhyay Prince , Munjal Akshay , Mondal Abir , Singh Gagandeep , Mukherjee Soumyadeep , Kaushik Mahesh C , Gupta Puneet K. , Pati Soumya , Singh Shailja 
Published: February 2025

AbstractMacrophages play a multifaceted role in mounting an immune response against pathogens through phagocytosis, antigen presentation and cytokine production. Activated macrophages are critical for the initiation, maintenance, and resolution of inflammation. They can either be classically activated (Th1 response), which promotes inflammation or alternatively activated (Th2 response), which resolves inflammation. The alternate activation of macrophages, along with diminished T cell response, is thought to be an important immune evasion strategy employed by the filarial parasites. However, the mechanism behind filaria-induced alternate activation remains unclear. In this study, by using in-silico approach we identified filarial serpins which are highly expressed in the infective L3 larval stages. We characterized the filarial serine protease inhibitor, Wb123 and established its role in alternate activation. We observed that Wb123 impairs nitric oxide (NO) and reactive oxygen species (ROS) expression, which plays a crucial role in mounting a strong immune response. Surprisingly, we also observed elevated IL6 expression and phosphorylation of STAT3, indicating IL-6-dependent alternate activation. Our findings indicate that the urokinase plasminogen activator receptor (uPAR) is essential for Wb123-induced alternate activation. Furthermore, we demonstrated that the monoclonal antibody MAbG8 impedes the Wb123-induced alternate activation, as shown by reduced CD163 expression along with increased ROS and uPA expression in response to lipopolysaccharide (LPS) and interferon-gamma (IFN-γ). Overall, our study identifies the filarial serpin Wb123 and highlights its potent role in alternative activation. This interaction reveals, for the first time a mechanism exploited by filarial parasites to evade a strong pro-inflammatory immune response.
Biophysical Basis of thein vivoElectroretinogram of the Mouse: Current Source Density Analysis of Genetically and Pharmacologically Isolated Rod photoreceptor-driven Currents
Authors: Allina Gabriel Peinado , Alexander Prescott , Ronning Kaitryn , Burns Marie E. , Pugh Edward N. 
Published: February 2025

ABSTRACTTo better understand the molecular basis of the mouse electroretinogram (ERG) we have developed a biophysical model of the rod photoreceptor layer’s ionic mechanisms and applied current source-density (CSD) analysis to predict the genetically and pharmacologically isolated rod ERGa-wave. The saturatinga-wave is characterized by a rapid relaxation (τ ~ 6 ms) from its maximum that has been hypothesized to be caused by HCN1 channel opening consequent to light-triggered sustained hyperpolarization, or by extracellular flow of capacitive current during hyperpolarization. To test these hypotheses, the CSD model included an ensemble of 11 rods with cell body locations spanning the outer nuclear layer, and with ionic mechanisms -- including CNG channels, NCKX in the outer segment, NKX, Kv2.1 channels in the inner segment, and HCN1 throughout the “non-outer segment” -- fully specified as to axial distributions, voltage dependencies, and the extracellular conductivity of the photoreceptor layer extracellular space. Predicting with CSD the steady-state axial distributions of rod dark current and transretinal potential, and the spatio-temporal response of the activation phase of the rod’s light response to intense stimuli, the analysis confirmed the Robson-Frishman hypothesis that extracellular capacitive current flowing towards the inner segment upon the rapid closure of CNG current plays a major role in shaping the earlya-wave. The CSD analysis also reveals that extracellular current from HCN1 channels opened by the hyperpolarization contributes a net extracellular current flowing toward the ONL that contributes materially to the saturateda-wave relaxation and to setting its plateau level.