bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal profiling of peripheral blood identifies proliferating circulating effector CD4+T cells as predictors for response to integrin α4β7-blocking therapy in patients with inflammatory bowel disease
Authors: Horn Veronika , Cancino Camila , Steinheuer Lisa , Obermayer Benedikt , Fritz Konstantin , Nguyen Anke L. , Plattner Christina , Bösel Diana , Burns Marie , Schulz Axel Ronald , Mantzivi Eleni , Lissner Donata , Conrad Thomas , Mashreghi Mir-Farzin , Sonnenberg Elena , Beule Dieter , Flatz Lukas ,   TRR241 IBDome Consortium, Trjanoski Zlatko , Weidinger Carl , Mei Henrik E. , Siegmund Britta , Thurley Kevin , Hegazy Ahmed N. 
Published: October 2023

ABSTRACTDespite the success of biological therapies in inflammatory bowel disease (IBD), patient management remains challenging due to a lack of therapy response predictors. Here we prospectively sampled two cohorts of IBD patient cohorts receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, serum proteomics, and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunological changes in the peripheral blood and their potential associations with treatment response. Vedolizumab induced changes in the abundance of both circulating innate and adaptive immune cell compartments and modified the T cell receptor diversity of circulating gut-homing CD4+memory T cells. Through integration of multimodal parameters and machine learning, we identify that pretreatment activated proliferating CD4+memory T cell abundance is associated with treatment failure, independent of clinical variables, thereby providing a reliable predictive classifier with significant implications for the personalized management of IBD patients.
A Normative Framework Dissociates Need and Motivation in Hypothalamic Neurons
Authors: Kim Kyu Sik , Lee Young Hee , Kim Yu-Been , Yun Jong Won , Song Ha Young , Park Joon Seok , Jung Sang-Ho , Sohn Jong-Woo , Kim Ki Woo , Kim HyungGoo R. , Choi Hyung Jin 
Published: October 2023

AbstractPhysiological needs evoke motivational drives to produce natural behaviours for survival. However, the temporally intertwined dynamics of need and motivation have made it challenging to differentiate these two components in previous experimental paradigms. Based on classic homeostatic theories, we established a normative framework to derive computational models of neural activity and behaviours for need-encoding and motivation-encoding neurons during events that induce predicted gain or loss. We further developed simple and intuitive experimental paradigms that enabled us to distinguish the distinct roles of subpopulations of neurons in the hypothalamus. Our results show that AgRP neurons and LHLepRneurons are consistent with need and motivation, respectively. Our study provides a parsimonious understanding of how distinct hypothalamic neurons separately encode need and motivation to produce adaptive behaviours for maintaining homeostasis.
Mendelian Randomization Reveals the Role of HMGCR in Pulmonary Arterial Hypertension Treatment, Independent of LDL Cholesterol Concentration
Authors: Wu Shixun , Pu Jie , Tang Zhiguo , Zhang Wei , Hou Fangxia , Wei Na , Cui Qianwei , Liu Fuqiang , Wang Junkui , Lu Ying , Wei Tao 
Published: October 2023

AbstractIntroductionSpecific lipid-reducing therapeutics, including statins, are known for mitigating cardiovascular diseases due to their comprehensive benefits including anti-inflammatory properties, antioxidative stress response, and enhancement of endothelial function. The objective of our study was to determine the causative impact of lipid-reducing agents (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitor) on the outcomes of pulmonary hypertension via a two-sample Mendelian randomization (MR) analysis.MethodsTwo types of genetic tools were employed to estimate the exposure to lipid-lowering drugs, comprising expression quantitative trait loci of the drug’s target genes and genetic variations close to or within the target genes related to low-density lipoprotein (LDL cholesterol derived from a genome-wide association study). We utilized summary-data-based MR (SMR) and inverse-variance-weighted MR (IVWMR) methodologies for estimating effect sizes.ResultsSMR analysis indicated that elevated HMGCR expression correlates with increased pulmonary hypertension risk (β=-0.964, se=0.276). Yet, no evident causative link between HMGCR-regulated LDL cholesterol and COVID-19 hospitalization was observed in the IVW-MR analysis (β = -0.21, se= 0.17).ConclusionsOur Mendelian randomization investigation unveiled a possible positive impact of lipid-lowering therapeutics on the prognosis of pulmonary hypertension. Importantly, no causal relation was established between LDL cholesterol and pulmonary hypertension.
Parallel detection of multi-contrast MRI and Deuterium Metabolic Imaging (DMI) for time-efficient characterization of neurological diseases
Authors: Liu Yanning , De Feyter Henk M. , Corbin Zachary A. , Fulbright Robert K. , McIntyre Scott , Nixon Terence W. , de Graaf Robin A. 
Published: October 2023

AbstractDeuterium Metabolic Imaging (DMI) is a novel method that can complement traditional anatomical magnetic resonance imaging (MRI) of the brain. DMI relies on the MR detection of metabolites that become labeled with deuterium (2H) after administration of a deuterated substrate and can provide images with highly specific metabolic information. However, clinical adoption of DMI is complicated by its relatively long scan time. Here, we demonstrate a strategy to interleave DMI data acquisition with MRI that results in a comprehensive neuro-imaging protocol without adding scan time. The interleaved MRI-DMI routine includes four essential clinical MRI scan types, namely T1-weighted MP-RAGE, FLAIR, T2-weighted Imaging (T2W) and susceptibility weighted imaging (SWI), interwoven with DMI data acquisition. Phantom and in vivo human brain data show that MR image quality, DMI sensitivity, as well as information content are preserved in the MRI-DMI acquisition method. The interleaved MRI-DMI technology provides full flexibility to upgrade traditional MRI protocols with DMI, adding unique metabolic information to existing types of anatomical image contrast, without extra scan time.
The effect of primary health care on AIDS incidence and mortality: a cohort study of 3.4 million Brazilians
Authors: Pinto Priscila FPS , Macinko James , Silva Andréa F , Lua Iracema , Jesus Gabriela , Magno Laio , Santos Carlos AS Teles , Ichihara Maria Yury , Barreto Mauricio L , Moucheraud Corrina , Souza Luis E , Dourado Inês , Rasella Davide 
Published: October 2023

AbstractBackgroundPrimary Health Care (PHC) is essential for the health and wellbeing of people living with HIV/AIDS. This study evaluated the effects of one of the largest community-based PHC programs in the world, the Brazilian Family Health Strategy (FHS), on AIDS incidence and mortality.MethodsA retrospective cohort study carried out in Brazil, from January 1 2007 to December 31 2015. We conducted a quasi-experimental effect evaluation using a cohort of 3,435,068 ≥13 years low-income individuals who were members of the 100 Million Brazilians Cohort, linked to AIDS diagnoses and deaths registries. We evaluated the effect of FHS on AIDS incidence and mortality and comparing outcomes between residents of municipalities with no FHS coverage with those in municipalities with full FHS coverage. We used multivariable Poisson regressions adjusted for all relevant municipal and individual-level demographic, socioeconomic, and contextual variables, and weighted with inverse probability of treatment weighting (IPTW). We also estimated FHS effect by sex and age, and performed a wide range of sensitivity and triangulation analyses.FindingsFHS coverage was associated with lower AIDS incidence (rate ratio [RR]:0.76, 95%CI:0.68–0.84) and mortality (RR:0.68,95%CI:0.56–0.82). FHS effect was similar between men and women, but was larger in people aged ≥35 years old both for incidence (RR 0.62, 95%CI:0.53–0.72) and mortality (RR 0.56, 95%CI:0.43– 0.72).ConclusionsAIDS should be an avoidable outcome for most people living with HIV today, and our study shows that FHS coverage could significantly reduce AIDS incidence and mortality among low-income populations in Brazil. Universal access to comprehensive healthcare through community-based PHC programs should be promoted to achieve the Sustainable Development Goals of ending AIDS by 2030.FundingFunded by the National Institute of Allergy and Infectious Diseases - NIAID/NIH, Grant Number: 1R01AI152938.
Predicting Individualized Outcomes for Deceased Kidney Donor Waitlisted Candidates and Recipients
Authors: Litvinovich Igor , Ng Yue-Harn , Chong Kelly , Argyropoulos Christos , Zhu Yiliang 
Published: October 2023

AbstractKidney transplantation remains the optimal treatment for end-stage kidney disease (ESKD). However, the persistent disparity between the demand and supply of deceased donor (DD) kidneys underscores the need for better tools to assess transplant outcomes and donor kidney quality. The current Kidney Allocation System (KAS) relies on the Kidney Donor Risk Index (KDRI) to quantify DD kidney quality, yet it combines allograft failure and patient death into a single outcome, limiting its accuracy.In this paper we present refined statistical models to predict post-transplantation risk, differentiating between allograft failure and patient death as competing risks. Using comprehensive data from the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipient (OPTN/SRTR) for 2000-2017, our models incorporate biological and clinical factors instead of donor race, account for within-center clustering and between-center variation, and capture non-linear relationships between risk factors.Our results reveal distinct risk factors for allograft failure and patient death. These models provide more personalized risk estimates tailored to donor kidney quality and recipient characteristics, aiding shared decision-making on kidney acceptance. Comparisons with the original KDRI demonstrate the superiority of our separate models, with improved predictability and reduced bias. Our approach eliminates the need to conflate allograft failure and patient death, leading to more accurate risk assessment and better-informed decisions regarding kidney offers.In conclusion, our study underscores the importance of distinguishing between allograft failure and patient death in kidney transplant risk assessment. By offering more precise risk estimates, our models enhance the transparency and efficiency of kidney acceptance decisions, ultimately benefiting both transplant providers and candidates. We also provide a web-based tool to facilitate this process, promoting better outcomes in kidney transplantation.Key PointsImproved statistical models for kidney transplant risk assessment, separating the risks of allograft failure and patient death.Models provide more personalized risk estimates, outperforming the existing Kidney Donor Risk Index (KDRI).Models enhance transparency and accuracy in evaluating donor kidney quality, aiding both providers and candidates in decision-making.Research improves the efficiency of kidney acceptance processes, leading to more successful transplants.
Keywords to success: a practical guide to maximise the visibility and impact of academic papers
Authors: Pottier Patrice , Lagisz Malgorzata , Burke Samantha , Drobniak Szymon M. , Downing Philip A. , Macartney Erin L. , Martinig April Robin , Mizuno Ayumi , Morrison Kyle , Pollo Pietro , Ricolfi Lorenzo , Tam Jesse , Williams Coralie , Yang Yefeng , Nakagawa Shinichi 
Published: October 2023

AbstractIn a growing digital landscape, enhancing the discoverability and resonance of scientific articles is essential. Here, we offer ten recommendations to amplify the discoverability of studies in scientific databases. Particularly, we argue that the strategic use and placement of key terms in the title, abstract, and keyword sections can boost indexing and appeal. By surveying 237 journals in ecology and evolutionary biology, we found that current author guidelines may unintentionally limit article discoverability. Our survey of 5842 studies revealed that authors frequently exhaust abstract word limits — particularly those capped under 250 words. This suggests that current guidelines may be overly restrictive and not optimised to increase the dissemination and discoverability of digital publications. Additionally, 91.9% of studies used redundant keywords in the title or abstract, undermining optimal indexing in databases. We encourage adopting structured abstracts to maximise the incorporation of key terms in titles, abstracts, and keywords. In addition, we encourage the relaxation of abstract and keyword limitations in journals with strict guidelines, and the inclusion of multilingual abstracts to broaden global accessibility. These evidence-based recommendations to editors are designed to improve article engagement and facilitate evidence synthesis, thereby aligning scientific publishing with the modern needs of academic research.
The amino acid sequence determines protein abundance through its conformational stability and reduced synthesis cost
Authors: Buric Filip , Viknander Sandra , Fu Xiaozhi , Lemke Oliver , Zrimec Jan , Szyrwiel Lukasz , Mueleder Michael , Ralser Markus , Zelezniak Aleksej 
Published: October 2023

AbstractUnderstanding what drives protein abundance is essential to biology, medicine, and biotechnology. Driven by evolutionary selection, the amino acid sequence is tailored to meet the required abundance of proteomes, underscoring the intricate relationship between sequence and functional demand. Yet, the specific role of amino acid sequences in determining proteome abundance remains elusive. Here, we demonstrate that the amino acid sequence predicts abundance by shaping a protein’s conformational stability. We show that increasing the abundance provides metabolic cost benefits, underscoring the evolutionary advantage of maintaining a highly abundant and stable proteome. Specifically, using a deep learning model (BERT), we predict 56% of protein abundance variation inSaccharomyces cerevisiaesolely based on amino acid sequence. The model reveals latent factors linking sequence features to protein stability. To probe these relationships, we introduce MGEM (Mutation Guided by an Embedded Manifold), a methodology for guiding protein abundance through sequence modifications. We find that mutations increasing abundance significantly alter protein polarity and hydrophobicity, underscoring a connection between protein stability and abundance. Through molecular dynamics simulations andin vivoexperiments in yeast, we confirm that abundance-enhancing mutations result in longer-lasting and more stable protein expression. Importantly, these sequence changes also reduce metabolic costs of protein synthesis, elucidating the evolutionary advantage of cost-effective, high-abundance, stable proteomes. Our findings support the role of amino acid sequence as a pivotal determinant of protein abundance and stability, revealing an evolutionary optimization for metabolic efficiency.
A compact, ultrahigh-density headstage with high-fidelity hybrid integration for large-scale deep-brain opto-electrophysiology
Authors: Oh Sungjin , Kim Kanghwan , Lopez Ruiz Jose Roberto , Slager Nathan , Ko Eunah , Vöröslakos Mihály , Lanzio Vittorino , Song Hyunsoo , Park Sung-Yun , Yoon Euisik 
Published: October 2023

AbstractRecent neuroscientific research seeks to comprehend the sophisticated deep-brain networks of neural circuits consisting of large scale neuronal ensembles across multiple brain regions. An ideal way to unveil the complex connectome might be stimulating individual neurons with high spatial resolution in a broad range of brain, while seamlessly monitoring the correspondent neuronal activities. Optogenetics is known as a key technology to enable such a goal thanks to its high spatial and temporal selectivity in neuromodulation. Existing silicon probe technologies have been able to partially achieve such a goal by recording broad region of brain activities through multiple electrodes per shank, but those cannot complete perfect coverage due to the limited channel counts for the optogenetic stimulation. Here, we present an high-channel-count optogenetic system with simultaneous 256 recoding and 128 optogenetic stimulation sites, exhibiting the highest channel density ever reported, enabled by a flexible polyimide cable-based hybrid-integration of a low-stimulation-artifact micro-LED (µLED) opto-electrode with a low-power and -noise, area-efficient CMOS interfacing integrated-circuit (IC). The presented optogenetic system provides 256-neuron-size electrodes (11 × 15 µm2) with a 40 µm inter-electrode pitch for high spatial oversampling in recording and 128-soma-size µLEDs (8 × 11 µm2) with a 20 µm inter-LED pitch for single-cell resolution in stimulation, resulting in a vertical span of 640 µm and a horizontal span of 2,100 µm with a total 8 shanks. For versatility in optogenetics-based experiments from small rodents to primates with user-preferable settings, the system base that provides programmability of recording and stimulation parameters and rest of signal processing, such as filtering, digitization, and data transmission including serial peripheral interface (SPI) has also been designed within small area of 23.8 × 28.8 mm2with only 3.5-gram weight, resulting in the highest channel density both in size (0.56 channels/mm2) and weight (109.71 channels/gram) among the state-of-the-art optogenetics-based neuromodulation systems. To verify the system operationin vivo, a compact optogenetics headstage has been also fabricated. Using the prepared optogenetic headstage, 169 isolated neurons have been observed with various stimulation intensities. The results offered in this article indicate that the presented hybrid integrated ultrahigh-density, high-channel-count headstage can be used to realize the massive-scale in-depth brain studies with optogenetics.
Effects of ocean acidification on red king crab larval survival and development
Authors: Long W. Christopher , Conrad Allie , Gardner Jennifer , Foy Robert J. 
Published: October 2023

AbstractOcean acidification, a decrease in oceanic pH resulting from the uptake of anthropogenic CO2, can be a significant stressor for marine organisms. In this study, we reared red king crab larvae from hatching to the first crab stage in four different pH treatments: current surface ambient, diel fluctuation to mimic larval migration between the surface and mixed layer under current ambient conditions, pH 7.8, and pH 7.5. Larvae were monitored throughout development and the average length of each stage was determined. At each of the zoeal stages, the glaucothoe stage, and the first crab stage, we measured survival, morphometry, dry mass, and carbon, nitrogen, calcium, and magnesium content. Red king crab larvae were highly resilient to ocean acidification. There were no differences among treatments in survival or in average stage length. Although there were clear ontogenetic trends in size, weight, and elemental composition, most of these did not vary with pH treatment. Zoeal morphology did not vary among treatments, although glaucothoe and C1 crabs were slightly smaller in pH 7.8 than in the ambient treatment. Ambient larvae also had a slightly higher mass than pH 7.8 larvae but not pH 7.5. Ambient larvae had higher magnesium contents than pH 7.8 and pH 7.5, but calcium levels were the same. Ambient larvae also had slightly lower carbon and nitrogen content than pH 7.8 and pH 7.5 larvae but only in the 4th zoeal stage. Overall this study suggests that red king crab larvae are well adapted to a wide range of pH conditions and are unlikely to be significantly affected by ocean acidification levels projected for the next two centuries.
NanoNERF: A nanoscale NERF blaster replica made of DNA
Authors: Takiguchi Lauren P. , Rober Mark B. , Olvera Jocelyn G. , Wacker Amanda L. , Fantasia Ryan J. , Liu Boyu , Shipley Wade , Tao Andrea , Kosuri Pallav 
Published: October 2023

ABSTRACTWe used DNA origami to create NanoNERF, the world’s smallest NERF blaster replica (Figure 1). We based our design on the NERF modelMaverick Rev-6, and scaled the dimensions down three million times. NanoNERF is planar and measures ∼100 nm in length, with a length-to-width ratio closely resembling the original toy. Here, we describe the design, prototyping, and validation pipeline used to create the NanoNERF. We also discuss potential applications to motivate the creation of future nanoscale blasters with a firing functionality.
WASP facilitates tumor mechanosensitivity in T lymphocytes
Authors: Mandal Srishti , Melo Mariane , Gordiichuk Pavlo , Acharya Sayanti , Poh Yeh-Chuin , Li Na , Aung Aereas , Dane Eric L. , Irvine Darrell J. , Kumari Sudha 
Published: October 2023

AbstractCytotoxic T lymphocytes (CTLs) carry out immunosurveillance by scanning target cells of diverse physical properties for the presence of antigens. While the recognition of cognate antigen by the T cell receptor is the primary signal for CTL activation, it has become increasingly clear that the mechanical stiffness of target cells plays an important role in antigen-triggered T cell responses. However, the molecular machinery within CTLs that transduces the mechanical information of tumor cells remains unclear. We find that CTL’s mechanosensitive ability requires the activity of the actin-organizing protein Wiskott-Aldrich Syndrome Protein (WASP). WASP activation is modulated by the mechanical properties of antigen-presenting contexts across a wide range of target cell stiffnesses and activated WASP then mediates mechanosensitive activation of early TCR signaling markers in the CTL. Our results provide a molecular link between antigen mechanosensing and CTL immune response and suggest that CTL-intrinsic cytoskeletal organizing principles enable the processing of mechanical information from diverse target cells.
Dynamic metabolic and molecular changes during seasonal shrinking inSorex araneus
Authors: Thomas William R. , Baldoni Cecilia , Zeng Yuanyuan , Carlson David , Holm-Jacobsen Julie , Muturi Marion , von Elverfeldt Dominik , Nieland John , Dechmann Dina K. N. , Corthals Angelique , Dávalos Liliana M. 
Published: October 2023

AbstractTo meet the challenge of wintering in place many high-latitude small mammals reduce energy demands through hibernation. In contrast, short-lived Eurasian common shrews,Sorex araneus, remain active and shrink, including energy-intensive organs in winter, regrowing in spring in an evolved strategy called Dehnel’s phenomenon. How this size change is linked to metabolic and regulatory changes to sustain their high metabolism is unknown. We analyzed metabolic, proteomic, and gene expression profiles spanning the entirety of Dehnel’s seasonal cycle in wild shrews. We show regulatory changes to oxidative phosphorylation and increased fatty acid metabolism during autumn-to-winter shrinkage, as previously found in hibernating species. But in shrews we also found upregulated winter expression of genes involved in gluconeogenesis: the biosynthesis of glucose from non-carbohydrate substrates. Co-expression models revealed changes in size and metabolic gene expression interconnect via FOXO signaling, whose overexpression reduces size and extends lifespan in many model organisms. We propose that while shifts in gluconeogenesis meet the challenge posed by high metabolic rate and active winter lifestyle, FOXO signaling is central to Dehnel’s phenomenon, with spring downregulation limiting lifespan in these shrews.