bluuebunny/crossref_metadata_2025_split huggingface dataset:
Task interference as a neuronal basis for the cost of cognitive flexibility
Authors: Xue Cheng , Markman Sol K. , Chen Ruoyi , Kramer Lily E. , Cohen Marlene R. 
Published: March 2024

AbstractHumans and animals have an impressive ability to juggle multiple tasks in a constantly changing environment. This flexibility, however, leads to decreased performance under uncertain task conditions. Here, we combined monkey electrophysiology, human psychophysics, and artificial neural network modeling to investigate the neuronal mechanisms of this performance cost. We developed a behavioural paradigm to measure and influence participants’ decision-making and perception in two distinct perceptual tasks. Our data revealed that both humans and monkeys, unlike an artificial neural network trained for the same tasks, make less accurate perceptual decisions when the task is uncertain. We generated a mechanistic hypothesis by comparing this neural network trained to produce correct choices with another network trained to replicate the participants’ choices. We hypothesized, and confirmed with further behavioural, physiological, and causal experiments, that the cost of task flexibility comes from what we term task interference. Under uncertain conditions, interference between different tasks causes errors because it results in a stronger representation of irrelevant task features and entangled neuronal representations of different features. Our results suggest a tantalizing, general hypothesis: that cognitive capacity limitations, both in health and disease, stem from interference between neural representations of different stimuli, tasks, or memories.
Novel Approach to Advance Directive Training: Palliative Fellow Led Workshop Feasible and Effective in Increasing Confidence in End of Life Conversations
Authors: Chelsea Chang , Cano Jose , Lopez-Alvarenga Juan , Rodriguez-Paez Josenny , Montes Sonya , Rao Meghana 
Published: March 2024

AbstractDespite the benefits of Advance directives, approximately only 1 in 3 U.S adults have documented advance directives. In medical school and residency, learners are often not taught or given very brief information on conducting end-of-life planning conversations with patients. Due to this deficiency, some institutions have conducted advance directive workshops but not many have been both palliative fellow and resident led, though some have been led by a geriatric fellow. Therefore, we approached advance directives with a resident and palliative fellow-led workshop. We aimed to develop and conduct a workshop on advance directives to assess feasibility and effectiveness. We sent a survey to 52 residents prior to two one-hour didactic sessions. For the first session, a small group of residents discussed common terminology and the tools available to help patients complete advanced directives in the outpatient setting. A hospice and palliative care fellow led the second session and focused on patient communication and approach. Our results showed that the workshop was well-received and improved resident confidence in discussing advance directives with patients. In conclusion, a resident and palliative fellow-led advance directive workshop for internal medicine residents was feasible and effective in increasing resident confidence.
Accelerated brain age in young to early middle-aged adults after mild to moderate COVID-19 infection
Authors: Kesler Shelli R , Franco-Rocha Oscar Y. , De La Torre Schutz Alexa , Lewis Kimberly A. , Aziz Rija M , Brode W. Michael , Melamed Esther 
Published: March 2024

AbstractCognitive decline is a common adverse effect of the Coronavirus Disease of 2019 (COVID-19), particularly in the post-acute disease phase. The mechanisms of cognitive impairment after COVID-19 (COGVID) remain unclear, but neuroimaging studies provide evidence of brain changes, many that are associated with aging. Therefore, we calculated Brain Age Gap (BAG), which is the difference between brain age and chronological age, in a cohort of 25 mild to moderate COVID-19 survivors (did not experience breathlessness, pneumonia, or respiratory/organ failure) and 24 non-infected controls (mean age = 30 +/− 8) using magnetic resonance imaging (MRI). BAG was significantly higher in the COVID-19 group (F = 4.22, p = 0.046) by 2.65 years. Additionally, 80% of the COVID-19 group demonstrated an accelerated BAG compared to 13% in the control group (X2= 20.0, p < 0.001). Accelerated BAG was significantly correlated with lower cognitive function (p < 0.041). Females in the COVID-19 group demonstrated a 99% decreased risk of accelerated BAG compared to males (OR = 0.015, 95% CI: 0.001 to 0.300). There was also a small (1.4%) but significant decrease in risk for accelerated BAG associated with longer time since COVID-19 diagnosis (OR = 0.986, 95% CI: 0.977 to 0.995). Our findings provide a novel biomarker of COGVID and point to accelerated brain aging as a potential mechanism of this adverse effect. Our results also offer further insight regarding gender-related disparities in cognitive morbidity associated with COVID-19.
PRAGMATIC - PRostate cancer diAGnosis and MAnagement – Triage In the Clinical care pathway
Authors: Sharma Abishek , Campbell Teresa , Bates Anthony , John Rincy , Adams Charlotte , Brassill Aisling , Lennon Bryony , Camilleri Philip , Sabharwal Ami , Charlton Philip , Andrade Gerard , Tuthill Mark , Protheroe Andrew , Lamb Alastair D , Leslie Tom , Leiblich Aaron , Lopez Francisco , Verrill Clare , Gleeson Fergus , MacPherson Ruth , Hamdy Freddie C , Bell Richard , Bryant Richard J 
Published: March 2024

AbstractBackgroundIt is important to investigate, diagnose and commence treatment for locally advanced and metastatic prostate cancer quickly to optimise treatment outcomes. Since the introduction of national 2-week wait and 31/62-day targets in the United Kingdom for investigation of suspected prostate cancer over 2 decades ago, the clinical pathway has become increasingly complex. This may lead to some patients with the most clinically significant disease having the rapidity of their diagnosis and commencement of treatment compromised by resource use in diagnosing less significant, or clinically insignificant, disease.MethodsWe will conduct a retrospective review of timelines for diagnosis and commencement of treatment for all men referred to a tertiary unit for investigation of suspected prostate cancer on the 2-week wait pathway in a 3-month period in 2023. In parallel, we will introduce triaging of all new 2-week wait referrals in a prospective 3-month period, with a dedicated nurse navigator streamlining patients for the most rapid investigation and treatment, based on pre-specified risk criteria including PSA, pre-biopsy mpMRI findings including TNM staging, and histology results. We hypothesise that this bespoke triaging system, above and beyond the 2-week wait and 2022 Faster Diagnostic Pathway guidance issued by NHS England, will improve timings for investigation and commencement of treatment for the most clinically significant prostate cancer cases.ConclusionsThe use of in-house criteria for triaging and stratification of the most clinically urgent and significant prostate cancer cases, identified by a nurse specialist navigator, may improve clinical outcomes for patients with greatest need for rapid prostate cancer imaging, diagnosis and treatment.
Cell-type specific contributions to theta-gamma coupled rhythms in the hippocampus
Authors: Sengupta Spandan , Talidou Afroditi , Lefebvre Jeremie , Skinner Frances K 
Published: March 2024

AbstractDistinct inhibitory cell types participate in cognitively relevant nested brain rhythms, and particular changes in such rhythms are known to occur in disease states. Specifically, the co-expression of theta and gamma rhythms in the hippocampus is believed to represent a general coding scheme, but cellular-based generation mechanisms for these coupled rhythms are currently unclear. We develop a population rate model of the CA1 hippocampus that encompasses circuits of three inhibitory cell types (bistratified cells, parvalbumin (PV)-expressing and cholecystokinin (CCK)-expressing basket cells) and pyramidal cells to examine this. We constrain parameters and perform numerical and theoretical analyses. The theory, in combination with the numerical explorations, predicts circuit motifs and specific cell-type mechanisms that are essential for the co-existence of theta and gamma oscillations. We find that CCK-expressing basket cells initiate the coupled rhythms and regularize theta, and PV-expressing basket cells enhance both theta and gamma rhythms. Pyramidal and bistratified cells govern the generation of theta rhythms, and PV-expressing basket and pyramidal cells play dominant roles in controlling theta frequencies. Our circuit motifs for theta-gamma coupled rhythm generation could be applicable to other brain regions.AUTHOR SUMMARYThere are many different types of inhibitory cells in our brains that are differentially affected in disease. Concomitantly, coupled rhythms change in particular ways with disease. To help understand cell-type specific changes in coupled rhythms, we develop a mathematical network model that is both respective of the cell type and also amenable to analyses. We focus on theta-gamma coupled rhythms in the hippocampus and include three different inhibitory cell types in our model circuits. By combining theoretical analysis and numerical explorations, we find distinct contributions of these inhibitory cell types to coupled rhythms, and predict motifs that are essential for the expression of theta-gamma coupled rhythms. Moving forward, we can leverage our model insights to help unravel cell-type contributions in disease states.
Reflection confocal microscopy for quantitative assessment of airway surface liquid dysregulation and pharmacological rescue in cystic fibrosis under near-physiological conditions
Authors: Agircan Ayca Seyhan , Lampe Marko , Scheuermann Heike , Albrecht Tobias , Graeber Simon Y. , Balázs Anita , Baumann Ingo , Block Stephan , Pepperkok Rainer , Mall Marcus A. , Duerr Julia 
Published: March 2024

ABSTRACTProper regulation of airway surface liquid (ASL) is essential for effective mucociliary clearance (MCC) in healthy airways, and ASL depletion due to deficient cystic fibrosis transmembrane conductance regulator (CFTR)-mediated anion/fluid secretion plays an important role in the pathogenesis of mucociliary dysfunction and chronic muco-obstructive lung disease in patients with cystic fibrosis (CF). The current standard for quantitative measurements of ASL height is confocal fluorescence microscopy that has the disadvantage that it requires apical addition of volume for fluorescent staining, and hence perturbation of the ASL. Therefore, our aim was to develop a method that enables studies of ASL regulation under unperturbed conditions using reflected light by confocal microscopy of primary airway epithelial cultures grown at air-liquid interface (ALI). After apical volume addition to primary tracheal mouse cultures, confocal reflection microscopy yielded comparable ASL height as confocal fluorescence microscopy on cultures of wild-type mice, and was sensitive to detect ASL depletion on cultures of βENaC-Tg mice. Under unperturbed conditions, ASL determined by confocal reflection microscopy was significantly higher in wild-type and βENaC-Tg mice compared to values obtained by confocal fluorescence microscopy. Studies in normal and CF primary human airway epithelial cultures showed that confocal reflection microscopy was sensitive to detect effects of low temperature rescue and pharmacological modulation including improvement of CFTR function by VX-809 and VX-770 in cultures from CF patients with the F508del mutation. Our results support confocal reflection microscopy as a novel sensitive technique for quantitative studies of ASL regulation and response to therapeutic intervention under unperturbed near-physiological conditions in healthy and CF airways.NEW & NOTEWORTHYMeasurement of airway surface liquid (ASL) height by confocal fluorescence microscopy is an important tool to investigate ASL dysregulation and effects of therapeutic strategies aiming at restoring ASL volume to improve mucociliary clearance and lung function in patients with cystic fibrosis. However, confocal fluorescence microscopy has the disadvantage that it requires apical addition of volume for fluorescent staining of the ASL leading to perturbation of its height and composition. Here, we developed confocal reflection microscopy as a new method that enables quantitative assessment of ASL on highly-differentiated primary airway epithelial cultures under unperturbed near-physiological conditions by detection of refracted light.
Thymic epithelial organoids mediate T cell development
Authors: Hübscher Tania , Lorenzo-Martín L. Francisco , Barthlott Thomas , Tillard Lucie , Langer Jakob J. , Rouse Paul , Blackburn C. Clare , Holländer Georg , Lutolf Matthias P. 
Published: March 2024

AbstractAlthough the advent of organoids opened unprecedented perspectives for basic and translational research, immune system-related organoids remain largely underdeveloped. Here we established organoids from the thymus, the lymphoid organ responsible for T cell development. We identified conditions enabling thymic epithelial progenitor cell proliferation and development into organoids with in vivo-like transcriptional profiles and diverse cell populations. Contrary to two-dimensional cultures, thymic epithelial organoids maintained thymus functionality in vitro and mediated physiological T cell development upon reaggregation with T cell progenitors. The reaggregates showed in vivo-like epithelial diversity and ability to attract T cell progenitors. Thymic epithelial organoids provide new opportunities to study TEC biology and T cell development in vitro, pave the way for future thymic regeneration strategies and are the first organoids originating from the stromal compartment of a lymphoid organ.Summary statementEstablishment of organoids from the epithelial cells of the thymus which resemble their in vivo counterpart and have thymopoietic ability in reaggregate culture.
Derivation of elephant induced pluripotent stem cells
Authors: Appleton Evan , Hong Kyunghee , Rodríguez-Caycedo Cristina , Tanaka Yoshiaki , Ashkenazy-Titelman Asaf , Bhide Ketaki , Rasmussen-Ivey Cody , Ambriz-Peña Xochitl , Korover Nataly , Bai Hao , Quieroz Ana , Nelson Jorgen , Rathod Grishma , Knox Gregory , Morgan Miles , Malviya Nandini , Zhang Kairui , McNutt Brody , Kehler James , Kowalczyk Amanda , Bow Austin , McLendon Bryan , Cantarel Brandi , James Matt , Mason Christopher E. , Gray Charles , Koehler Karl R. , Pearson Virginia , Lamm Ben , Church George , Hysolli Eriona 
Published: March 2024

ABSTRACTThe crisis of biodiversity loss in the anthropogenic era requires new tools for studying non-model organisms. Elephants, for example, are both an endangered species and excellent models studying complex phenotypes like size, social behavior, and longevity, but they remain severely understudied. Here we report the first derivation of elephant (Elephas maximus) induced pluripotent stem cells (emiPSCs) achieved via a two-step process of chemical-media induction and colony selection, followed by overexpression of elephant transcription factorsOCT4, SOX2, KLF4, MYC±NANOGandLIN28A, and modulation of theTP53pathway. Since the seminal discovery of reprogramming by Shinya Yamanaka, iPSCs from many species including the functionally extinct northern white rhinocerous have been reported, but emiPSCs have remained elusive. While for multiple species the reprogramming protocol was adopted with little changes compared to model organisms like mouse and human, our emiPSC protocol requires a longer timeline and inhibition ofTP53expansion genes that are hypothesized to confer unique cancer resistance in elephants. iPSCs unlock tremendous potential to explore cell fate determination, cell and tissue development, cell therapies, drug screening, disease modeling, cancer development, gametogenesis and beyond to further our understanding of this iconic megafauna. This study opens new frontiers in advanced non-model organism cellular models for genetic rescue and conservation.
Effect of terminal phosphate groups on collisional dissociation of RNA oligonucleotide anions
Authors: Zuo Mei-Qing , Song Ge , Dong Meng-Qiu , Sun Rui-Xiang 
Published: March 2024

ABSTRACTAn increasing need of mass spectrometric analysis of RNA molecules calls for a better understanding of their gas-phase fragmentation behaviors. In this study, we investigated the effect of terminal phosphate groups on the fragmentation spectra of RNA oligonucleotides (oligos) using high-resolution mass spectrometry (MS). Negative-ion mode collision-induced dissociation (CID) and higher-energy collisional dissociation (HCD) were carried out on RNA oligos containing a terminal phosphate group on either or both ends, or neither. We find that terminal phosphate groups affect the fragmentation behavior of RNA oligos in a way that depends on the precursor charge state and the oligo length. Specifically, for precursor ions of RNA oligos of the same sequence, those with 5’- or 3’-phosphate, or both, have a higher charge state distribution and lose upon CID or HCD the phosphate group(s) in the form of a neutral (H3PO4or HPO3) or an anion ([H2PO4]-or [PO3]-). Such neutral or charged loss is most conspicuous for precursor ions of an intermediate charge state, e.g. 3-for 4-nt oligos or 4-and 5-for 8-nt oligos. This decreases the intensity of sequencing ions (a-, a-B, b-, c-, d-, w-, x-, y-, z-ions), hence unfavorable for sequencing by CID or HCD. Removal of terminal phosphate groups by calf intestinal alkaline phosphatase improved MS analysis of RNA oligos. Additionally, the intensity of a fragment ion atm/z158.925, which we have identified as a dehydrated pyrophosphate anion ([HP2O6]-), is markedly increased by the presence of a terminal phosphate group. These findings expand the knowledge base necessary for software development for MS analysis of RNA.
Rare VariableM. tuberculosisAntigens induce predominant Th17 responses in human infection
Authors: Ogongo Paul , Wassie Liya , Tran Anthony , Columbus Devin , Sharling Lisa , Ouma Gregory , Ouma Samuel Gurrion , Bobosha Kidist , Lindestam Arlehamn Cecilia S. , Gandhi Neel R. , Auld Sara C. , Rengarajan Jyothi , Day Cheryl L. , Altman John D. , Blumberg Henry M. , Ernst Joel D. ,   the TBRU ASTRa Study Group
Published: March 2024

AbstractCD4 T cells are essential for immunity toM. tuberculosis(Mtb), and emerging evidence indicates that IL-17-producing Th17 cells contribute to immunity toMtb. While identifying protective T cell effector functions is important for TB vaccine design, T cell antigen specificity is also likely to be important. To identify antigens that induce protective immunity, we reasoned that as in other pathogens, effective immune recognition drives sequence diversity in individualMtbantigens. We previously identifiedMtbgenes under evolutionary diversifying selection pressure whose products we term Rare Variable Mtb Antigens (RVMA). Here, in two distinct human cohorts with recent exposure to TB, we found that RVMA preferentially induce CD4 T cells that express RoRγt and produce IL-17, in contrast to ‘classical’Mtbantigens that induce T cells that produce IFNγ. Our results suggest that RVMA can be valuable antigens in vaccines for those already infected withMtbto amplify existing antigen-specific Th17 responses to prevent TB disease.
The relationship between ethnicity and socioeconomic deprivation as determinants of health: a systematic review
Authors: Coates Melanie , Shah Aroon Bhardwaj , Igwe Richard , Wan Yize I 
Published: March 2024

AbstractBackgroundEthnicity and socioeconomic status (SES) are well known social determinants of health. However, the impact of the intersection between ethnicity and SES on health remains poorly understood, with many studies examining these factors separately.MethodsWe conducted a systematic review using MEDLINE (PubMed), EMBASE, and The Cochrane Library databases. Studies were eligible if they compared outcomes defined by mortality, attendance, readmission, or hospital length of stay, for any acute or chronic illness, according to one or more measures of both ethnicity and SES in adult patients (≥18 years of age) attending primary care or admitted to hospital.ResultsNine studies met eligibility criteria. There was significant heterogeneity in cohort demographics, key variables, and outcome measures. Therefore, qualitative analysis was used. Definitions and categories of ethnicity were inconsistent, using race, country of origin, and sociocultural characteristics. Definitions of SES varied, with studies using between one and seven metrics. Different sub-categories were often used, even when the same metric was utilised. Primary outcomes were mortality (n=7) or admissions-related (n=2). Approaches varied between studies, regarding cause, time periods, and end points. Of those looking at mortality, four reported seeing an interaction between ethnicity and SES groups on outcomes.ConclusionsHeterogeneity in the categorisation of ethnicity and SES is a barrier to research and understanding of health inequalities. This could be tackled by standardising data collection in healthcare routine data nationally and internationally, to enable translation of information between settings. For SES, using multifaceted methods could better capture the complexity of this factor.
Influenza mortality as an indicator of the effectiveness of public health interventions and their impact on United States COVID mortality
Authors: Morris Robert 
Published: March 2024

AbstractThe synergistic nature of non-pharmaceutical interventions (NPIs) for control of COVID makes it difficult to assess the efficacy of any individual strategy. This study uses influenza mortality reduction (IMR) during the pandemic as an indicator of the aggregate efficacy of NPIs to assess their impact on COVID mortality.Age-adjusted COVID mortality for US states were modeled as a function of four variables: mortality prior to the introduction of NPIs, vaccination rates, IMR relative to historical averages, and population density.A simple linear model with only these variables explained 69% of the state-to-state variability in age adjusted COVID mortality. The resulting model suggests that NPIs alone prevented 840,000 COVID related deaths in the United States over the course of the pandemic. These results demonstration the utility of IMRs as an indicator of the aggregate impact of NPIs for controlling transmission of respiratory infections, including COVID.
WITHDRAWN: Onchocerciasis Elimination Mapping in Tanzania Mainland: A case of Kilindi DC, Handeni DC and Kilolo DC, Iringa DC
Authors: Chihoma Evangelina , Mbwambo Stephen G. , Moirana Ezekiel , Masayi Casmil , Masanika Julius , Lalji Shabbir , Crowley Kathlyn , Post Rory , Evans Darin , Katabarwa Moses , Mwingira Upendo , Kabona George 
Published: March 2024

Withdrawal Statement“This manuscript has been withdrawn by the authors as they did not obtain the necessary ethical clearance for the study. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.”