bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participatory Development of a Speech-Language Telerehabilitation Intervention combined with Home-based Transcranial Direct Current Stimulation for Primary Progressive Aphasia: a Qualitative Study
Authors: Rysop Anna Uta , Schiwek Roxana , Grewe Tanja , Breitenstein Caterina , Binkofski Ferdinand , Roheger Mandy , Unger Nina , Flöel Agnes , Meinzer Marcus 
Published: December 2024

AbstractPurposeIntensive speech-language therapy (SLT) delivered as telerehabilitation in combination with transcranial direct current stimulation (tDCS) may be an effective treatment option for people with primary progressive aphasia (pwPPA). However, such combined treatment approaches are technically challenging and feasibility for pwPPA has not yet been established.We aimed to involve stakeholders in the development of a novel approach combining remotely-supervised but independently self-administered home-based tDCS with an intensive aphasia telerehabilitation (naming and communicative-pragmatic therapy).MethodEight pwPPA and 16 caregivers participated in two semi-structured interviews to identify the needs, preferences, and perceived barriers and challenges with regard to SLT, telerehabilitation and tDCS, and the combination of all components. Based on the results, a step-by-step manual was developed and tested by means of home-based usability tests and follow-up interviews involving four dyads. Interview data were transcribed and analysed qualitatively and quantitatively. Competency checklists used in the usability tests were analysed quantitatively.ResultsPwPPA and their caregivers provided valuable insights into all aspects of the planned treatment programme. Overall, the findings suggest a high level of acceptance and perceived need for an intensive telerehabilitation SLT approach combined with tDCS. Using the developed step-by-step manual and training, pwPPA were able to independently perform more than half of the actions required for telerehabilitation but needed assistance with technically more demanding aspects of tDCS. To ensure feasibility, caregiver-assistance is needed to support pwPPA during technically challenging interventions.ConclusionsThis mixed-methods study identified needs and preferences of pwPPA and their caregivers with regard to speech-language telerehabilitation, as well as barriers and challenges regarding telerehabilitation and home-based tDCS. We demonstrate high acceptability and initial feasibility of such combined programmes. Our findings highlight the importance of stakeholder involvement in intervention development, which will inform future development and optimisation of technologically demanding intervention programmes.
Cell-type-resolved chromatin accessibility in the human intestine identifies complex regulatory programs and clarifies genetic associations in Crohn’s disease
Authors: Zhao Yu , Zhou Ran , Mu Zepeng , Carbonetto Peter , Zhong Xiaoyuan , Xie Bingqing , Luo Kaixuan , Cham Candace M , Koval Jason , He Xin , Dahl Andrew W. , Liu Xuanyao , Chang Eugene B , Basu Anindita , Pott Sebastian 
Published: December 2024

AbstractCrohn’s disease (CD) is a complex inflammatory bowel disease resulting from an interplay of genetic, microbial, and environmental factors. Cell-type-specific contributions to CD etiology and genetic risk are incompletely understood. Here we built a comprehensive atlas of cell-type- resolved chromatin accessibility comprising 557,310 candidate cis-regulatory elements (cCREs) in terminal ileum and ascending colon from patients with active and inactive CD and healthy controls. Using this atlas, we identified cell-type-, anatomic location-, and context-specific cCREs and characterized the regulatory programs underlying inflammatory responses in the intestinal mucosa of CD patients. Genetic variants that disrupt binding motifs of cell-type-specific transcription factors significantly affected chromatin accessibility in specific mucosal cell types. We found that CD heritability is primarily enriched in immune cell types. However, using fine- mapped non-coding CD variants we identified 29 variants located within cCREs several of which were accessible in epithelial and stromal cells implicating cell types from additional lineages in mediating CD risk in some loci. Our atlas provides a comprehensive resource to study gene regulatory effects in CD and health, and highlights the cellular complexity underlying CD risk.
An Individually Tailored, Home-Based Supervised Exercise Programme for People with Early Dementia: An RCT-informed Health Economic Evaluation
Authors: Ezeofor Victory ‘Segun , Hartfiel Ned , Doungsong Kodchawan , Goldberg Sarah , van der Wardt Veronika , Howe Louise , Gladman John , Harwood Rowan H , Edwards Rhiannon T. 
Published: December 2024

AbstractBackgroundThe effectiveness of exercise interventions to improve activities of daily living function in people with dementia is inconclusive. This study aimed to assess the long-term cost-effectiveness of the PrAISED intervention from a National Health Service (NHS) perspective.MethodThis novel robust economic analysis used a Markov model to evaluate the incremental cost-effectiveness ratio (ICER) over a lifetime horizon of 15 years for a cohort of patients. Sensitivity analyses were conducted to investigate the uncertainty and robustness of high-impacting parameters and results.ResultsThis study included 365 adults, aged 65 years and above with 183 and 182 randomised to the PrAISED and standard care groups respectively. The PrAISED intervention had mean per-patient cost of £60,465 for the PrAISED arm and £54,604 for standard care. The Praised intervention gained an incremental QALYs of 0.05 resulting in an ICER of £129,614 per QALY. The sensitivity analysis of the intervention cost varied the ICER value between £68,173 and £191,054/QALY. To achieve the recommended NICE willingness to pay threshold value of less than £30,000/QALYs would require the intervention cost to be reduced from £1,236 (current cost) to £263 to break even and be cost-effective. The sensitivity analyses revealed that there was a 40% probability of standard care dominating the PrAISED treatment.ConclusionsAlthough the PrAISED intervention was a low-cost intervention, it did not produce a cost-effective intervention in this analysis. The flexibility of the PrAISED program to adapt to government policy during the COVID-19 pandemic was positive.Trial registrationISRCTN15320670
Algorithm Refinement of the National Early Warning Score 2 (NEWS2): Study Protocol
Authors: Plummer Chris , Milne-Ives Madison , Cong Cen , Threlfall Lynsey , Meinert Edward 
Published: December 2024

AbstractIntroductionThe second iteration of the National Early Warning Score (NEWS2) has been widely adopted for predicting patient deterioration in healthcare settings using routinely collected physiological observations. The use of NEWS2 has been shown to reduce in-hospital mortality, but it has limited accuracy in the prediction of clinically important outcomes, especially over longer time periods. The increasing implementation of digital patient observations and health records presents an opportunity to investigate whether the addition of individual patient characteristics and information about their care-setting, would improve the predictive accuracy of the score.Methods and analysisThis protocol describes the work to determine whether the performance of the current NEWS2 system could be improved by the use of additional variables. The project has been designed after an extensive scoping review of existing literature on NEWS2 and an exploration of retrospective cohort data in The Newcastle upon Tyne Hospitals NHS Foundation Trust, with input from key clinical stakeholders.Ethics and disseminationThe project has received competitive funding following peer-review, from the NIHR Newcastle Biomedical Research Centre as an Interdisciplinary Research Award. Ethical approval has been requested. Findings are expected to be produced by June 2025, and will be disseminated at symposia, conferences and in journal publications.Strengths and limitations of this studyStrengths-This work highlights the importance of investigating the use of additional clinical variables to those used in NEWS2, in the development of a new early warning score-The study design was informed by an evidence synthesis of the literatureLimitations-Some retrospective data sets may be of low quality and/or incomplete-External validation will be needed to test algorithm generalisability
Heterogeneity in and correlation between host transmissibility and susceptibility can greatly impact epidemic dynamics
Authors: Tuschhoff Beth M. , Kennedy David A. 
Published: December 2024

AbstractWhile it is well established that host heterogeneity in transmission and host heterogeneity in susceptibility each individually impact disease dynamics in characteristic ways, it is generally unknown how disease dynamics are impacted when both types of heterogeneity are simultaneously present. Here we explore this question. We first conducted a systematic review of published studies from which we determined that the effects of correlations have been drastically understudied. We then filled in the knowledge gaps by developing and analyzing a stochastic, individual-based SIR model that includes both heterogeneity in transmission and susceptibility and flexibly allows for positive or negative correlations between transmissibility and susceptibility. We found that in comparison to the uncorrelated case, positive correlations result in major epidemics that are larger, faster, and more likely, whereas negative correlations result in major epidemics that are smaller and less likely. We additionally found that, counter to the conventional wisdom that heterogeneity in susceptibility always reduces outbreak size, heterogeneity in susceptibility can lead to major epidemics that are larger and more likely than the homogeneous case when correlations between transmissibility and susceptibility are positive, but this effect only arises at small to moderateR0. Moreover, positive correlations can frequently lead to major epidemics with subcriticalR0. Ultimately, we show that correlations between transmissibility and susceptibility profoundly impact disease dynamics.HighlightsSystematic review finds that effects of correlations on epidemics are understudiedPositive correlations lead to larger, faster, more likely epidemicsNegative correlations lead to smaller, less likely epidemicsPositive correlations consistently lead to major epidemics with subcriticalR0
Distinct genetic architecture for trait mean and plasticity in chickpea
Authors: Alagarasan Ganesh , Varshney Rajeev K. , Ramireddy Eswarayya 
Published: December 2024

AbstractCrop plants often face rapid environmental changes, and their ability to adapt to novel conditions depends on whether specific traits can adjust to match these changes. This capacity for adjustment, known as phenotypic plasticity, is frequently regarded as a mere “response” rather than a distinct trait with its own genetic basis, particularly in agricultural science. As a result, plasticity is often oversimplified and viewed as an undesirable phenomenon when the goal is to achieve trait stability. In this study, we present a quantitative metric to measure phenotypic plasticity and provide evidence, through genome-wide association studies (GWAS) in chickpea, that plasticity is indeed a genetically based trait, comparable to any other agronomic trait. This foundational study paves the way for future GWAS efforts to harness phenotypic plasticity, offering new insights for crop improvement strategies.
Gut Microbiome Signatures During Acute Infection Predict Long COVID
Authors: Comba Isin Y. , Mars Ruben A. T. , Yang Lu , Dumais Mitchell , Chen Jun , Van Gorp Trena M. , Harrington Jonathan J. , Sinnwell Jason P. , Johnson Stephen , Holland LaRinda A. , Khan Adam K. , Lim Efrem S. , Aakre Christopher , Athreya Arjun P. , Gerber Georg K. , O’Horo Jack C. , Lazaridis Konstantinos N. , Kashyap Purna C. 
Published: December 2024

AbstractLong COVID (LC), manifests in 10-30% of non-hospitalized individuals post-SARS-CoV-2 infection leading to significant morbidity. The predictive role of gut microbiome composition during acute infection in the development of LC is not well understood, partly due to the heterogeneous nature of disease. We conducted a longitudinal study of 799 outpatients tested for SARS-CoV-2 (380 positive, 419 negative) and found that individuals who later developed LC harbored distinct gut microbiome compositions during acute infection, compared with both SARS-CoV-2–positive individuals who did not develop LC and negative controls with similar symptomatology. However, the temporal changes in gut microbiome composition between the infectious (0–1 month) and post-infectious (1–2 months) phases was not different between study groups. Using machine learning, we showed that microbiome composition alone more accurately predicted LC than clinical variables. Including clinical data only marginally enhanced this prediction, suggesting that microbiome profiles during acute infection may reflect underlying health status and immune responses thus, help predicting individuals at risk for LC. Finally, we identified four LC symptom clusters, with gastrointestinal and fatigue-only groups most strongly linked to gut microbiome alterations.
Muscle length modulates recurrent inhibition and post-activation depression differently according to contraction type
Authors: Colard Julian , Duclay Julien , Betus Yohan , Cattagni Thomas , Jubeau Marc 
Published: December 2024

ABSTRACTIt is well documented that, in soleus, motoneuron output and the effectiveness of activated Ia afferents to discharge α-motoneurons both decrease during eccentric contractions. Evidence suggests that these regulations can be explained by (1) recurrent inhibition and (2) greater post-activation depression by primary afferent depolarization. However, the influence of muscle length on the regulation of the effectiveness of Ia afferents to discharge α-motoneurons observed during eccentric contractions remains unclear. We conducted a study on 16 healthy young individuals. We used simple and conditioned Hoffmann reflex with different conditioning techniques such as paired H reflex, D1 method and heteronymous Ia facilitation coupled with electromyography during eccentric, isometric and concentric contractions at long, intermediate and short soleus muscle lengths. Our results confirm that during eccentric contraction the effectiveness of Ia afferents to dischargeU-motoneurons decreases only at intermediate and short muscle lengths but is similar between all contraction types at long muscle length. Findings are similar for recurrent inhibition. Post-activation depression is significantly more pronounced during eccentric contractions compared with isometric and concentric contractions at long muscle length. Our analysis also shows that recurrent inhibition and post-activation depression are greater at long muscle length compared with short muscle length, whatever the contraction type. These new findings demonstrate an important influence of muscle length on the activity of spinal regulatory mechanisms and the effectiveness of activated Ia afferents to discharge α-motoneurons during eccentric contractions.
Toxicity and Biodegradation of Two Different Hydrothermal Liquefaction Process Waters to Anaerobic Digestion and the Effect of Microaeration
Authors: Zhou Mei , Usack Joseph G. , Smith Aidan Mark , Angenent Largus T. 
Published: December 2024

AbstractHydrothermal liquefaction (HTL) can convert a considerable portion of the carbon in complex feedstocks into renewable bio-oil, but it also generates a liquid byproduct (i.e., HTL process water) that retains 15 – 55% of the carbon from the HTL feedstock. Feeding HTL process water to anaerobic digestion (AD) is a promising approach for maximizing resource recovery, enabling the conversion of the retained carbon into biogas. However, various toxic and poorly biodegradable compounds in HTL process water make its treatment with AD challenging. Presently, the underlying mechanisms remain often unclear. We investigated the impact of HTL process water from two different feedstocks – a food-waste proxy (i.e., dog food, rich in proteins) and wheat straw (rich in lignocellulose) – on the different trophic groups in the food web of AD. We found that methanogens rather than acidogens were inhibited by HTL process water. Comparative toxicity and biodegradability analyses showed that wheat-straw process water had a higher biodegradability regardless of its higher toxicity to acetoclastic methanogens than food-waste process water, due to its higher content in toxic but easily degradable aromatic compounds. Microaeration enhanced the biodegradation and methane yields of food-waste process water, particularly under anoxic conditions. However, microaeration was ineffective for wheat-straw process water. These findings highlight the importance of feedstock-specific strategies to optimize AD for biogas production from HTL process water.
Near-infrared real time non-destructive monitoring of sugar accumulation reveals that single berries ripen two times faster than previously documented on standard asynchronous samples
Authors: Tavernier Flora , Motelica-Heino Elias , Thomas Miguel , Herbold Theresa , Shi Mengyao , Cunff Loïc Le , Romieu Charles , Segura Vincent 
Published: December 2024

AbstractUnderstanding how climate change impacts berry ripening physiology is essential for selecting genotypes that balance sugars and acids under warming conditions. In this context, we used a portable near-infrared spectrometer in the vineyard, to monitor sugar and acid evolution in individual berries from 10 grapevine varieties over two years. Spectra were periodically acquired on the same berries all along ripening, and a subset of these berries was also collected for sugars and organic acids quantification by HPLC, to train partial least square regression models. Prediction models for glucose, fructose, and malic acid concentrations were fairly accurate with validation R² of 0.71, 0.64, and 0.55, respectively. We further used these models to study sugar accumulation in individual berries and observed that the single berries ripen two times faster than average samples. Our results pave avenues toward precise quantitative approaches on sugar and acid fluxes in berry ripening studies.
Human plasma metabolic environment favours HIV replication in primary CD4 T lymphocytes
Authors: Chauveau Lise , Fortuin Annemarie , Lecante Arnaud , Lager-Lachaud Nina , Boulay Aude , Blanchet Fabien P , Bellvert Floriant , Briant Laurence , Battini Jean-Luc 
Published: December 2024

AbstractCellular metabolism provides all molecules essential for the cell’s functions including nucleic acids, amino acids and fatty acids, but also energy via glycolysis and mitochondrial respiration (also known as OXPHOS). Viruses hijack these pathways to support the different steps of their replication, making the metabolic state of the infected cell a key factor influencing viral replication. In particular, Human Immunodeficiency virus (HIV) remains latent in resting, metabolically inactive CD4 T lymphocytes but actively replicates in activated CD4 T cells. In these cells, enhanced glycolysis and OXPHOS, and access to the major carbon sources such as glucose and glutamine are required for infection. Here, we took advantage of the recently developed Human Plasma-Like Medium (HPLM), that mimics physiological plasma concentration of metabolites, including carbon sources, to investigate how this physiologic environment would modulate HIV-1 infection of primary CD4 T cells. Using CD4 T cells activated in the conventional culture medium (RPMI) or HPLM, we show that HPLM enhanced HIV-1 infection despite similar levels of cell activation, proliferation and expression of viral receptor. Specifically, HPLM increases the reverse transcription step of the HIV-1 replication cycle. In contrast with previous studies performed in RPMI only, this increased infection in HPLM correlated with decreased glycolysis and mitochondrial metabolism, reflecting the low concentration of glucose and glutamine in this medium. Adjusting glucose and glutamine concentrations in RPMI or decreasing energy metabolism using chemical inhibitors did not increase infection to levels similar to HPLM suggesting that other metabolic pathways are involved. Taken together, this study shows that the metabolic state of activated CD4 T cells in a physiologically relevant environment is more permissive to HIV-1 infection than previously suggested by studies using conventional cell culture media. Our study demonstrates the importance of physiologic culture conditions to study viral infections while also highlighting the importance of non-energetic cell metabolism in HIV-1 infection.
CRISPR-based environmental biosurveillance assisted via artificial intelligence design of guide-RNAs
Authors: DuránVinet Benjamín , Stanton Jo-Ann L. , Jeunen Gert-Jan , von Ammon Ulla , Treece Jackson , Pochon Xavier , Zaiko Anastasija , Gemmell Neil J. 
Published: December 2024

AbstractEnvironmental biosecurity challenges are worsening for aquatic ecosystems as climate change and increased anthropogenic pressures facilitate the spread of invasive species, thereby broadly impacting ecosystem composition, functioning, and services. Environmental DNA (eDNA) has transformed traditional biomonitoring through detection of trace DNA fragments left by organisms in their surroundings, primarily by application of the quantitative polymerase chain reaction (qPCR). However, qPCR presents challenges, including limited portability, reliance on precise thermal cycling, and susceptibility to inhibitors. To address these challenges and enable field-deployable monitoring, isothermal amplification techniques such as Recombinase Polymerase Amplification (RPA) paired with Clustered Regularly Interspaced Short Palindromic Repeats and associated proteins (CRISPR-Cas) have been proposed as alternatives. We report here the development of CORSAIR (CRISPR-based envirOnmental biosuRveillance aSsisted viaArtificialIntelligence guide-RNAs), that harnesses the programmability of the CRISPR-Cas technology, RPA and the artificial intelligence (AI)-based tool Activity-informed Design with All-inclusive Patrolling of Targets (ADAPT) to deploy a swift RPA-CRISPR-Cas13a-based method that detects eDNA from two invasive species as proof of concept:Sabella spallanzaniiandUndaria pinnatifida. CORSAIR showcased a robust, streamlined method augmented by ADAPT, reaching a high specificity when tested against co-occurring species and a 100% agreement with 12 PCR-benchmarked eDNA samples, reaching a sensitivity of 0.34 copies uL-1in 1 hour with a cost of 3.5 USD per sample; thus highlighting CORSAIR as a powerful environmental biosurveillance platform for environmental nucleic acid detection.Graphical abstract