bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Student Patient Alliance: Development and formative evaluation of an initiative to support collaborations between patient and public involvement contributors and doctoral students
Authors: Simons Gwenda , Birch Rebecca , Stocks Joanne , Insch Elspeth , Rijckborst Rob , Neag Georgiana , McColm Heidi , Romaniuk Leigh , Wright Claire , Phillips Bethan E , Jones Simon W , Pratt Arthur G , Siebert Stefan , Raza Karim , Falahee Marie 
Published: January 2023

ABSTRACTBackgroundWhile the integration of patient and public involvement (PPI) in clinical research is now widespread and recommended as standard practice, meaningful PPI in pre-clinical, discovery science research is more difficult to achieve. One potential way to address this is by integrating PPI into the doctoral training programmes of discovery science postgraduate students. This paper describes the development and formative evaluation of the Student Patient Alliance (SPA), a programme developed at the University of Birmingham that partners PPI contributors with doctoral students.MethodsFollowing a successful pilot of the SPA by the Rheumatology Research Group at the University of Birmingham, the scheme was implemented across collaborating Versus Arthritis / MRC centres of excellence at a number of different collaborating centres. Students were partnered with PPI contributors, provided with initial information and guidance, and then encouraged to work together on research and public engagement activities. After six months, students, their PPI partners and the PPI coordinators at each centre completed brief surveys about their participation in the SPA.ResultsBoth students and their PPI partners felt that taking part in SPA had a very positive impact. Students reported an increased understanding of PPI and patient priorities and reported improved public engagement and communication skills. Their PPI partners reported a positive impact of the collaboration with the students. They enjoyed learning about the student’s research and contributing to the students ‘personal development. PPI coordinators also highlighted the benefits of the SPA, but noted some challenges they had experienced, such as matching students with PPI partners.ConclusionsThe SPA was valued by students and PPI partners, and it is likely that initiatives of this kind would enhance students’ PPI and public engagement skills and awareness of patients’ experiences on a wider scale. However, appropriate resources are needed at an institutional level to support the implementation of effective programmes of this kind on a larger scale.
Pontine pathology mediates common symptoms of blast-induced chronic mild traumatic brain injury
Authors: Meabon James S. , Schindler Abigail G. , Murray Daniel R. , Colasurdo Elizabeth A. , Sikkema Carl L. , Rodriguez Joshua W. , Omer Mohamed , Cline Marcella M. , Logsdon Aric F. , Cross Donna J. , Richards Todd L. , Meeker Kole D. , Shutes-David Andrew , Yagi Mayumi , Perl Daniel P. , Marshall Desiree A. , Keene C. Dirk , Banks William A. , Thomas Ronald G. , McEvoy Cory , Crabtree Adam , Powell Jake R. , Mihalik Jason P. , Pagulayan Kathleen F. , Raskind Murray A. , Peskind Elaine R. , Cook David G. 
Published: January 2023

AbstractUnderstanding how diffuse mild traumatic brain injuries can provoke common and persistent post-concussive symptoms (PCS), such as impaired sleep, is crucial to prevent and treat chronic disability and neurodegeneration. We mapped the spatially-resolved single cell landscape of diffuse mTBI pathology in a mouse model of blast exposure; identifying brainstem injuries predictive of later PCS. Repeated mTBI was necessary to establish chronic microglial activation and phagocytosis of myelin in the pontine reticular formation; where IL33 release by oligodendrocytes predicted microgliopathy. In postmortem brainstem tissues from patients with traumatic brain injury, chronic microglial activation and myelin phagocytosis was evident up to 20 years after diffuse mTBI caused by blast. In living patients with chronic blast mTBI, myelin injury in pontine projections mediated sleep disturbance and other PCS, with a dose dependent effect of mTBI number on sleep disturbance severity. These results support a mechanism for diffuse mTBIs to cause delayed persistent PCS.
Effects of Mitigation and Control Policies in Realistic Epidemic Models Accounting for Household Transmission Dynamics
Authors: Alarid-Escudero Fernando , Andrews Jason , Goldhaber-Fiebert Jeremy D. 
Published: January 2023

AbstractBackgroundCompartmental infectious disease (ID) models are often used to evaluate non-pharmaceutical interventions (NPIs) and vaccines. Such models rarely separate within-household and community transmission, potentially introducing biases in situations where multiple transmission routes exist. We formulated an approach that incorporates household structure into ID models, extending the work of House and Keeling.DesignWe developed a multi-compartment susceptible-exposed-infectious-recovered-susceptible-vaccinated (MC-SEIRSV) modeling framework, allowing non-exponentially distributed duration in Exposed and Infectious compartments, that tracks within-household and community transmission. We simulated epidemics that varied by community and household transmission rates, waning immunity rate, household size (3 or 5 members), and numbers of Exposed and Infectious compartments (1-3 each). We calibrated otherwise identical models without household structure to the early phase of each parameter combination’s epidemic curve. We compared each model pair in terms of epidemic forecasts and predicted NPI and vaccine impacts on: the timing and magnitude of the epidemic peak and on its total size. Meta-analytic regressions characterized the relationship between household structure inclusion and the size and direction of biases.ResultsOtherwise similar models with and without household structure produced equivalent early epidemic curves. However, forecasts from models without household structure were biased. Without intervention, they were upward-biased on peak size and total epidemic size, with biases also depending on the number of Exposed and Infectious compartments. Model-estimated NPI effects of a 60% reduction in community contacts on peak time and size were systematically overestimated without household structure. Biases were smaller with a 20% reduction NPI. Because vaccination impacted both community and household transmission, their biases were smaller.ConclusionsID models without household structure can produce biased outcomes in settings where within-household and community transmission differ.
The genetic architecture of recombination rates is polygenic and differs between the sexes in wild house sparrows (Passer domesticus)
Authors: McAuley John B. , Servin Bertrand , Burnett Hamish A. , Brekke Cathrine , Peters Lucy , Hagen Ingerid J. , Niskanen Alina K. , Ringsby Thor Harald , Husby Arild , Jensen Henrik , Johnston Susan E. 
Published: January 2023

AbstractMeiotic recombination through chromosomal crossing-over is a fundamental feature of sex and an important driver of genomic diversity. It ensures proper disjunction, allows increased selection responses, and prevents mutation accumulation; however, it is also mutagenic and can break up favourable haplotypes. This cost/benefit dynamic is likely to vary depending on mechanistic and evolutionary contexts, and indeed, recombination rates show huge variation in nature. Identifying the genetic architecture of this variation is key to understanding its causes and consequences. Here, we investigate individual recombination rate variation in wild house sparrows (Passer domesticus). We integrate genomic and pedigree data to identify autosomal crossover counts (ACC) and intra-chromosomal allelic shuffling (r̅intra) in 13,056 gametes. Females had 1.37 times higher ACC, and 1.55 times higherr̅intrathan males. ACC andr̅intrawere heritable in females and males (ACC h2= 0.23 and 0.11;r̅intrah2= 0.12 and 0.14), but cross-sex additive genetic correlations were low (rA= 0.29 and 0.32 for ACC andr̅intra). Conditional bivariate analyses showed that all measures remained heritable after accounting for genetic values in the opposite sex, indicating that sex-specific ACC andr̅intracan evolve somewhat independently. Genome-wide models showed that ACC andr̅intraare polygenic and driven by many small-effect loci, many of which are likely to act intransas global recombination modifiers. Our findings show that recombination rates of females and males can have different evolutionary potential in wild birds, providing a compelling mechanism for the evolution of sexual dimorphism in recombination.
Biohybrid restoration of the hippocampal loop re-establishes the non-seizing state in an in vitro model of limbic seizures
Authors: Caron Davide , Buccelli Stefano , Canal-Alonso Angel , Farsani Javad , Pruzzo Giacomo , Barranco Bernabé Linares , Corchado Juan Manuel , Chiappalone Michela , Panuccio Gabriella 
Published: January 2023

AbstractObjectiveThe compromise of the hippocampal loop is a hallmark of mesial temporal lobe epilepsy (MTLE), the most frequent epileptic syndrome in the adult population and the most often refractory to medical therapy. Hippocampal sclerosis is found in >50% of drug-refractory MTLE patients and primarily involves the CA1, consequently disrupting the hippocampal output to the entorhinal cortex (EC). Closed-loop deep brain stimulation (DBS) is the latest frontier to improve drug-refractory MTLE; however, current approaches do not restore the functional connectivity of the hippocampal loop, they are designed by trial-and-error and heavily rely on seizure detection or prediction algorithms. The objective of this study is to evaluate the anti-ictogenic efficacy and robustness of an artificial bridge restoring the dialog between hippocampus and EC.ApproachIn mouse hippocampus-EC slices treated with 4-aminopyridine and in which the Schaffer Collaterals are severed, we established an artificial bridge between hippocampus and EC wherein interictal discharges originating in the CA3 triggered stimulation of the subiculum so to entrain EC networks. Combining quantification of ictal activity with tools from information theory, we addressed the efficacy of the bridge in controlling ictogenesis and in restoring the functional connectivity of the hippocampal loop.Main resultsThe bridge significantly decreased or even prevented ictal activity and proved robust to failure; when operating at 100% of its efficiency (i.e., delivering a pulse upon each interictal event), it recovered the functional connectivity of the hippocampal loop to a degree similar to what measured in the intact circuitry. The efficacy and robustness of the bridge stem in mirroring the adaptive properties of the CA3, which acts as biological neuromodulator. Significance. This work is the first stepping stone toward a paradigm shift in the conceptual design of stimulation devices for epilepsy treatment, from function control to functional restoration of the salient brain circuits.
The role of B cells in immune cell activation in polycystic ovary syndrome
Authors: Ascani Angelo , Torstensson Sara , Risal Sanjiv , Lu Haojiang , Eriksson Gustaw , Li Congru , Teshl Sabrina , Menezes Joana , Sandor Katalin , Ohlsson Claes , Svensson Camilla I , Karlsson Mikael C.I. , Stradner Martin Helmut , Obermayer-Pietsch Barbara , Stener-Victorin Elisabet 
Published: January 2023

AbstractVariations in B cell numbers are associated with polycystic ovary syndrome (PCOS) through unknown mechanisms. Here we demonstrate that B cells are not central mediators of PCOS pathology and that their frequencies are altered as a direct effect of androgen receptor activation. Hyperandrogenic women with PCOS have increased frequencies of age-associated double-negative B memory cells and increased levels of circulating immunoglobulin M (IgM). However, the transfer of serum IgG from women into wild-type female mice induces only an increase in body weight. Furthermore, RAG1 knock-out mice, which lack mature T- and B cells, fail to develop any PCOS-like phenotype. In wild-type mice, co-treatment with flutamide, an androgen receptor antagonist, prevents not only the development of a PCOS-like phenotype but also alterations of B cell frequencies induced by dihydrotestosterone (DHT). Finally, B cell-deficient mice, when exposed to DHT, are not protected from developing a PCOS-like phenotype. These results urge further studies on B cell functions and their effects on autoimmune comorbidities highly prevalent among women with PCOS.SummaryAndrogen receptor activation alters B cell frequencies and functionality as the transfer of human PCOS IgG increase weight in female mice. Lack of B cells does not protect from the development of a PCOS phenotype, suggesting an unrecognized role for B cells in PCOS autoimmune comorbidities.Graphical Abstract
Heterogeneous responsiveness to environmental stimuli*
Authors: Cavailles Jerome , Kuzmics Christoph , Grube Martin 
Published: January 2023

AbstractIndividuals of a species cope with environmental variability through behavioral adjustments driven by individuals’ responsiveness to environmental stimuli. Three key empirical observations have been made for many animal species: Thecoexistenceof different degrees of responsiveness within one species; theconsistencyof an individual’s degree of responsiveness across time; and thecorrelationof an individual’s degree of responsiveness across contexts. Taking up key elements of existing approaches, we provide one unifying explanation for all three observations, by identifying a unique evolutionarily stable strategy of an appropriately defined game within a stochastic environment that has all three features. Coexistence is explained by a form of negative frequency dependence. Consistency and correlation is explained through potentially small, individual, differences of states animals have and the resulting differential advantages they can get from it. Our results allow us to identify a variety of testable implications.
The Spread of Interferon-γ in Melanomas is Highly Spatially Confined, Driving Non-Genetic Variability in Tumor Cells
Authors: Centofanti Edoardo , Wang Chad , Iyer Sandhya , Krichevsky Oleg , Oyler-Yaniv Alon , Oyler-Yaniv Jennifer 
Published: January 2023

AbstractInterferon-γ (IFNγ) is a critical anti-tumor cytokine that has varied effects on different cell types. The global effect of IFNγ in the tumor depends on which cells it acts upon and the spatial extent of its spread. Reported measurements of IFNγ spread vary dramatically in different contexts, ranging from nearest-neighbor signaling to perfusion throughout the entire tumor. Here, we apply theoretical considerations to experiments bothin vitroandin vivoto study the spread of IFNγ in melanomas. We observe spatially confined niches of IFNγ signaling in 3-D mouse melanoma cultures and human tumors that generate cellular heterogeneity in gene expression and alter the susceptibility of affected cells to T cell killing. Widespread IFNγ signaling only occurs when niches overlap due to high local densities of IFNγ-producing T cells. We measured length scales of ∼30-40μm for IFNγ spread in B16 mouse melanoma cultures and human primary cutaneous melanoma. Our results are consistent with IFNγ spread being governed by a simple diffusion-consumption model, and offer insight into how the spatial organization of T cells contributes to intra-tumor heterogeneity in inflammatory signaling, gene expression, and immune-mediated clearance. Solid tumors are often viewed as collections of diverse cellular “neighborhoods”: our work provides a general explanation for such non-genetic cellular variability due to confinement in the spread of immune mediators.
Addressing the Southeast Asian snaring crisis: impact of 11 years of snare removal in a biodiversity hotspot
Authors: Tilker Andrew , Niedballa Jürgen , Viet Hung Luong , Abrams Jesse F. , Marescot Lucile , Wilkinson Nicholas , Rawson Benjamin M. , Sollmann Rahel , Wilting Andreas 
Published: January 2023

AbstractUnsustainable snaring is causing biodiversity declines across tropical protected areas, resulting in species extinctions and jeopardizing the health of forest ecosystems. Here, we used 11 years of ranger collected data to assess the impact of intensive snare removal on snaring levels in two protected areas in Viet Nam. Snare removal resulted in significant declines in snare occupancy (36.9, 95% BCI [4.6, 59.0] reduction in percent area occupied), but snaring levels nonetheless remained high (31.4, [23.6, 40.8] percent area occupied), and came with a substantial financial cost. Our results indicate that snare removal remains an important component of efforts to protect tropical protected areas, but by itself, is likely insufficient to address this threat. To stop snaring in protected areas, a multifaceted approach will be necessary that combines short-term reactive snare removal with long-term proactive programs that address the underlying drivers behind snaring.
Biventricular interaction during acute left ventricular ischemia in mice: a combined in-vivo and in-silico approach
Authors: Colebank M. J. , Taylor R. , Hacker T. A. , Chesler N.C. 
Published: January 2023

AbstractComputational models provide an efficient paradigm for integrating and linking multiple spatial and temporal scales. However, these models are difficult to parameterize and match to experimental data. Recent advances in both data collection and model analyses have helped overcome this limitation. Here, we combine a multiscale, biventricular interaction model with mouse data before and after left ventricular (LV) ischemia. Sensitivity analyses are used to identify the most influential parameters on pressure and volume predictions. The subset of influential model parameters are calibrated to biventricular pressure-volume loop data (n=3) at baseline. Each mouse underwent left anterior descending coronary artery ligation, during which changes in fractional shortening and RV pressure-volume dynamics were recorded. Using the calibrated model, we simulate acute LV ischemia and contrast outputs at baseline and in simulated ischemia. Our baseline simulations align with the LV and RV data, and our predictions during ischemia complement recorded RV data and prior studies on LV function during myocardial infarction. We show that a model with both biventricular mechanical interaction and systems level cardiovascular dynamics can quantitatively reproducein-vivodata and qualitatively match prior findings from animal studies on LV ischemia.
A flexible loop in the paxillin LIM3 domain mediates direct binding to integrin β3
Authors: Baade Timo , Michaelis Marcus , Prestel Andreas , Paone Christoph , Klishin Nikolai , Scheinost Laura , Nedielkov Ruslan , Hauck Christof R. , Möller Heiko M. 
Published: January 2023

AbstractIntegrins are fundamental for cell adhesion and the formation of focal adhesions (FA). Accordingly, these receptors guide embryonic development, tissue maintenance and haemostasis, but are also involved in cancer invasion and metastasis. A detailed understanding of the molecular interactions that drive integrin activation, focal adhesion assembly, and downstream signalling cascades is critical. Here, we reveal a direct association of paxillin, a marker protein of focal adhesion sites, with the cytoplasmic tails of the integrin β1 and β3 subunits. The binding interface resides in paxillin’s LIM3 domain, where based on the NMR structure and functional analyses a flexible, seven amino acid loop engages the unstructured part of the integrin cytoplasmic tail. Genetic manipulation of the involved residues in either paxillin or integrin β3 compromises cell adhesion and motility. This direct interaction between paxillin and the integrin cytoplasmic domain identifies an alternative, kindlin-independent mode of integrin outside-in signalling particularly important for integrin β3 function.
Scientific civility and academic performance
Authors: Camacho Emma , Dragotakes Quigly , Hartshorn Isabella , Casadevall Arturo , Buccino Daniel L 
Published: January 2023

AbstractIn modern science, interdisciplinary and collaborative research is encouraged among scientists to solve complex problems. However, when the time comes to measure an individual’s academic productivity, collaborative efforts are hard to conceptualize and quantify. In this study, we hypothesized that a social behavior coined “scientific civility”, which encompasses civility, collaboration, cooperation, or a combination of these, enhances an individual’s productivity influencing their academic performance. To facilitate recognition of this unique attribute within the scientific environment, we developed a new indicator: theCscore. We examined publicly available data from 1000 academic scientists at the individual-level, focusing on their scholarly output and collaborative networks as a function of geographic distribution and time. Our findings strongly suggest that theCscore gauges academic performance from an integral perspective based on a synergistic interaction between productivity and collaborative networks, prevailing over institutionally limited economic resources and minimizing inequalities related to the length of individual’s academic career, field of investigation, and gender.Author SummaryThe increased connectivity between fields and specialties of science is undeniable. We propose a new indicator, theCscore, to assess the value of collaborative efforts and research output to a scientist’s academic performance. This indicator reflects collaborative and interdisciplinary efforts and provides a measure of “scientific civility” and teamwork. TheCscore may be used as a decision-making tool to track career advancement within the academic environment. Along with other indicators such as thehindex, theCscore supports a more integrative and holistic assessment of an individual’s academic performance.
The mineralocorticoid receptor forms higher order oligomers upon DNA binding
Authors: Fettweis Gregory , Johnson Thomas A. , Almeida-Prieto Brian , Presman Diego M. , Hager Gordon L. , de la Rosa Diego Alvarez 
Published: January 2023

ABSTRACTThe prevailing model of steroid hormone nuclear receptor function assumes ligand-induced homodimer formation followed by binding to DNA hormone response elements (HREs). This model has been challenged by evidence showing that the glucocorticoid receptor (GR) forms tetramers upon ligand and DNA binding, which then drive receptor-mediated gene transactivation and transrepression. GR and the closely-related mineralocorticoid receptors (MR) interact to transduce corticosteroid hormone signaling, but whether they share the same quaternary arrangement is unknown. Here, we used a fluorescence imaging technique, Number & Brightness, to study oligomerization in a cell system allowing real-time analysis of receptor-DNA interactions. Agonist-bound MR forms tetramers in the nucleoplasm and higher order oligomers upon binding to HREs. Antagonists form intermediate quaternary arrangements, suggesting that large oligomers are essential for function. Divergence between MR and GR quaternary structure is driven by different functionality of known and new multimerization interfaces, which does not preclude formation of heteromers. Thus, influencing oligomerization may be important to selectively modulate corticosteroid signaling.