bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experiences of family caregivers in caring for patients with heart failure at Jakaya Kikwete Cardiac Institute, Dar es Salaam, Tanzania: a qualitative study
Authors: Mcharo Tunzo L. , Iseselo Masunga K. , Kahema Samwel E. , Tarimo Edith AM. 
Published: January 2023

AbstractBackgroundHeart failure (HF) continues to be a global health problem with its ramifications more pronounced in underdeveloped countries. Family members play a pivotal part in patient management which may influence the patient’s overall quality of life. Prolonged delay in attendance to health care facilities among patients indicates ineffective support from family caregivers. In the Tanzanian context, there is limited information about the experiences of family caregivers in caring for patients with HF. This study explored family caregivers’ experiences in caring for HF patients.MethodsA qualitative descriptive study design was conducted at Jakaya Kikwete Cardiac Institute in Dar es Salaam, Tanzania. A purposive sampling technique was used to select the potential participants. A sample size of 10 family caregivers of patients with HF was included in the study. Thematic analysis was used to derive the main theme and sub-themes.ResultsThree major themes were identified: demands for supportive care, new caring role and lifestyle, and professional support in caring for patients with HF. Caregivers needed social and financial support to facilitate the caring process. Learning to provide the required care at the right time was the new role acquired by caregivers while failing to participate in social events and caregiving in an unfavourable environment were reported as challenges in caregiving. However, compliance with instruction and effective interaction among the nurses and caregivers were considered to be positive professional support.ConclusionCaregivers need social and financial support to provide effective care to their patients. Caregiving is a learning process that needs continuous educational support to adapt to the new caring roles and challenges. Nurses should conduct regular assessments to explore caregivers’ needs, challenges, and concerns and provide timely counselling that can facilitate coping.
Influence of AI-based decision support on shared decision making in hemodialysis: a Wizard of Oz experiment
Authors: Osmanodja Bilgin , Samhammer David , Roller Roland , Beck Susanne , Burchardt Aljoscha , Duettmann Wiebke , Dabrock Peter , Gerndt Simon , Moeller Sebastian , Ronicke Simon , Budde Klemens 
Published: January 2023

AbstractArtificial Intelligence-based decision support systems (AI-DSS) to improve hemodialysis therapy are currently under development. However, the influence of AI-DSS on shared decision making (SDM) in hemodialysis patients has not been studied so far. We performed a Wizard of Oz experiment, using a sham AI-DSS suggesting ultrafiltration volume at the beginning of each dialysis session. We performed 10 patient interviews in 5 patients, and investigated views towards AI, different aspects of the SDM, and the influence of an AI-DSS on SDM in a real-life scenario.Five main topics were identified: (1) the patient as self-determined, (2) role of the medical staff, (3) other forms of automation, (4) attitude towards AI, (5) needs and preferences for future use of AI. The patients describe novel AI-DSS in dialysis as an opportunity to promote self-determination and to ensure more efficient therapy. At the same time, they describe the special relationship with the nursing staff and physicians, who, from the patients’ point of view, must be given control over an AI-DSS.This study provides first evidence regarding the influence of AI-DSS on SDM in the context of hemodialysis. Further studies should focus on other aspects that require SDM such as initiation of dialysis, and selection of dialysis modality.
Primate-conserved Carbonic Anhydrase IV and murine-restricted Ly6c1 are new targets for crossing the blood-brain barrier
Authors: Shay Timothy F. , Sullivan Erin E. , Ding Xiaozhe , Chen Xinhong , Kumar Sripriya Ravindra , Goertsen David , Brown David , Vielmetter Jost , Borsos Máté , Lam Annie W. , Gradinaru Viviana 
Published: January 2023

AbstractThe blood-brain barrier (BBB) presents a major challenge to delivering large molecules to study and treat the central nervous system (CNS). This is due in part to the scarcity of effective targets for BBB crossing, the identification of which is the crucial first step of drug development. Here, we leveraged a panel of adeno-associated viruses (AAVs) previously identified through directed evolution for improved BBB transport to reverse engineer protein targets for enhanced BBB crossing. We identify both murine-restricted Ly6c1 and primate-conserved carbonic anhydrase IV (Car4; CA4) as novel receptors for crossing the BBB. We demonstrate how these receptors can unlock new experimental and computational target-focused engineering strategies by creating the enhanced Ly6c1-binding vector AAV-PHP.eC and by applying AlphaFold2-enabled in silico methods to rank capsids against identified receptors and generate capsid-receptor binding models. Here, with Car4, we add a completely new receptor to the very short list currently available for crossing the BBB in humans and, with Ly6c1, we validate a pipeline for receptor-targeted engineering. The identification of Car4/CA4 and structural insights from computational modeling provide new paths toward human brain-penetrant chemicals (drugs) and biologicals (including gene delivery).
Temporal pattern recognition in retinal ganglion cells is mediated by dynamical inhibitory synapses
Authors: Ebert Simone , Buffet Thomas , Sermet B.Semihcan , Marre Olivier , Cessac Bruno 
Published: January 2023

AbstractA fundamental task for the brain is to generate predictions of future sensory inputs, and signal errors in these predictions. Many neurons have been shown to signal omitted stimuli during periodic stimulation, even in the retina. However, the mechanisms of this error signaling are unclear. Here we show that depressing inhibitory synapses enable the retina to signal an omitted stimulus in a flash sequence. While ganglion cells, the retinal output, responded to an omitted flash with a constant latency over many frequencies of the flash sequence, we found that this was not the case once inhibition was blocked. We built a simple circuit model and showed that depressing inhibitory synapses were a necessary component to reproduce our experimental findings. We also generated new predictions with this model, that we confirmed experimentally. Depressing inhibitory synapses could thus be a key component to generate the predictive responses observed in many brain areas.
Persistent Extrasynaptic Hyperdopaminergia in the mouse Hippocampus Induces Plasticity and Recognition Memory Deficits Reversed by Antipsychotics
Authors: Rocchetti Jill , Fasano Caroline , Dal-Bo Gregory , Guma Elisa , El Mestikawy Salah , Wong Tak Pan , Fakhfouri Gohar , Giros Bruno 
Published: January 2023

AbstractEvidence suggests that subcortical hyperdopaminergia alters cognitive function in schizophrenia and antipsychotic drugs (APD) fail at rescuing cognitive deficits in patients. In a previous study, we showed that blocking D2 dopamine receptors (D2R), a core action of APD, led to profound reshaping of mesohippocampal fibers, deficits in synaptic transmission and impairments in learning and memory in the mouse hippocampus (HP). However, it is currently unknown how excessive dopamine affects HP-related cognitive functions, and how APD would impact HP functions in such a state. After verifying the presence of DAT-positive neuronal projections in the ventral (temporal), but not in the dorsal (septal), part of the HP, GBR12935, a blocker of dopamine transporter (DAT), was infused in the CA1 of adult C57Bl/6 mice to produce local hyperdopaminergia. Chronic GBR12935 infusion in temporal CA1 induced a mild learning impairment in the Morris Water Maze and abolished long-term recognition memory in novel-object (NORT) and object-place recognition tasks (OPRT). Deficits were accompanied by a significant decrease in DAT+mesohippocampal fibers. Intrahippocampal or systemic treatment with sulpiride during GBR infusions improved the NORT deficit but not that of OPRT.In vitroapplication of GBR on hippocampal slices abolished long-term depression (LTD) of fEPSP in temporal CA1. LTD was rescued by co-application with sulpiride. In conclusion, chronic DAT blockade in temporal CA1 profoundly altered mesohippocampal modulation of hippocampal functions. Contrary to previous observations in normodopaminergic mice, antagonising D2Rs was beneficial for cognitive functions in the context of hippocampal hyperdopaminergia.
Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates
Authors: Chen Xinhong , Wolfe Damien A. , Sivadasan Bindu Dhanesh , Zhang Mengying , Taskin Naz , Goertsen David , Shay Timothy F. , Sullivan Erin , Huang Sheng-Fu , Ravindra Kumar Sripriya , Arokiaraj Cynthia M. , Plattner Viktor , Campos Lillian J. , Mich John , Monet Deja , Ngo Victoria , Ding Xiaozhe , Omstead Victoria , Weed Natalie , Bishaw Yeme , Gore Bryan , Lein Ed S , Akrami Athena , Miller Cory , Levi Boaz P. , Keller Annika , Ting Jonathan T. , Fox Andrew S. , Eroglu Cagla , Gradinaru Viviana 
Published: January 2023

ABSTRACTDelivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds and rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), andex vivohuman brain slices although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. Vasculature-secreted Hevin (a synaptogenic protein) rescued synaptic deficits in a mouse model.
Occupational determinants of COVID-19 cases and vaccination: an ecological analysis of counties in the United States as of December 2021
Authors: Ji John S. , Wang Yucheng , Duncan Dustin T. 
Published: January 2023

AbstractObjectiveWe aim to study the relationship between occupation distribution within each county and COVID-19 cumulative incidence and vaccination rate in the United States.MethodsWe collected county-level data from January 22, 2020 up to December 25, 2021. We fit multivariate linear models to find the relationship of the percentage of people employed by 23 main occupations.ResultsCounties with more health-related jobs, office support roles, community service, sales, production and material moving occupations had higher COVID-19 cumulative incidence. During the uptick of the “Delta” COVID variant (stratified period July 1-Dec 25), counties with more transportation occupations had significantly more COVID-19 cumulative incidence than before.SignificanceUnderstanding the association between occupations and COVID-19 cumulative incidence on an ecological level can provide information for precision public health strategies for prevention and protecting vulnerable workers.Impact StatementWe used data from US Census and COVID-19 data to explore the association between occupations and COVID-19 cumulative incidence and vaccination rate on an ecological level, which can provide information for precision public health strategies for prevention of spread of disease and protecting vulnerable workers.
SARS-CoV-2 VARIANT PREVALENCE ESTIMATION USING WASTEWATER SAMPLES
Authors: López-de-Ullibarri I. , Tomás L. , Trigo-Tasende N. , Freire B. , Vaamonde M. , Gallego-García P. , Barbeito I. , Vallejo J.A. , Tarrío-Saavedra J. , Alvariño P. , Beade E. , Estévez N. , Rumbo-Feal S. , Conde-Pérez K. , de Chiara L. , Iglesias-Corrás I. , Poza M. , Ladra S. , Posada D. , Cao R. 
Published: January 2023

AbstractThe present work describes a statistical model to account for sequencing information of SARS-CoV-2 variants in wastewater samples. The model expresses the joint probability distribution of the number of genomic reads corresponding to mutations and non-mutations in every locus in terms of the variant proportions and the joint mutation distribution within every variant. Since the variant joint mutation distribution can be estimated using GISAID data, the only unknown parameters in the model are the variant proportions. These are estimated using maximum likelihood. The method is applied to monitor the evolution of variant proportions using genomic data coming from wastewater samples collected in A Coruña (NW Spain) in the period May 2021 – March 2022. Although the procedure is applied assuming independence among the number of reads along the genome, it is also extended to account for Markovian dependence of counts along loci in the aggregated information coming from wastewater samples.
Consistency of left ventricular ejection fraction measurements in the early time course of STEMI
Authors: Georgieva Lilyana , Nienhaus Fabian T. , Haberkorn Sebastian , Erkens Ralf , Polzin Amin , Wischmann Patricia , Ipek Rojda , Marjani Kian , Christidi Aikaterini , Roden Michael , Jung Christian , Bönner Florian , Kelm Malte , Perings Stefan , Gastl Mareike 
Published: January 2023

Structured AbstractBackgroundAssessment of left ventricular (LV) function and volume after ST-segment elevation myocardial infarction (STEMI) is recommended to guide clinical decision within and after hospitalization. Early after STEMI, initial LV reshaping and hypokinesia may affect analysis of LV function. A comparative evaluation of left ventricular ejection fraction (LVEF) and stroke volume (SV) by different imaging modalities to assess LV function early after STEMI has not been performed so far.MethodsLV function was assessed by LVEF and SV using serial imaging within 24h and 5 days after STEMI with cineventriculography (CVG), 2-dimensional echocardiography (2DE), 2D and 3D cardiovascular magnetic resonance (2D/3D) in 82 patients. Respective parameters were compared between modalities and to 3D gold standard CMR.Results2D analyses of LVEF using CVG and 2DE as well as 2D CMR yielded uniform results within 24h and 5 days of STEMI. SV assessment between CVG and 2DE at day 1 after STEMI was comparable, whereas values for SV were higher using 2D CMR on all occasions (p<0.01 all). This was due to higher LVEDV measurements. LVEF by 2D versus 3D CMR was comparable, 3D CMR yielded consistently higher volumetric values. This was not influenced by infarct location or infarct size.ConclusionsEarly after STEMI, 2D analysis of LVEF yielded robust results across all imaging techniques implying that CVG, 2DE, and 2D CMR can be used interchangeably in this setting. SV measurements to assess cardiac function differed substantially between imaging techniques due to higher intermodality-differences of absolute volumetric measurements.
Uncertainty aversion predicts the neural expansion of semantic representations
Authors: Vives Marc-Lluís , de Bruin Daantje , van Baar Jeroen M. , FeldmanHall Oriel , Bhandari Apoorva 
Published: January 2023

AbstractCorrectly identifying the meaning of a stimulus requires activating the appropriate semantic representation among many alternatives. One way to reduce this uncertainty is to differentiate semantic representations from each other, thereby expanding the semantic space. In four experiments, we test this semantic-expansion hypothesis, finding that uncertainty averse individuals exhibit increasingly differentiated and separated semantic representations. This effect is mirrored at the neural level, where uncertainty aversion predicts greater distances between activity patterns in the left inferior frontal gyrus when reading words, and enhanced sensitivity to the semantic ambiguity of these words in the ventromedial prefrontal cortex. Two direct tests of the behavioral consequences of semantic-expansion further reveal that uncertainty averse individuals exhibit reduced semantic interference and poorer generalization. Together, these findings demonstrate that the internal structure of our semantic representations is shaped in a principled manner: aversion to uncertainty acts as an organizing principle to make the world more identifiable.
Enhancing glymphatic function with very low-intensity ultrasound via the transient receptor potential vanilloid-4-aquaporin-4 pathway
Authors: Liao Wei-Hao , Wu Chueh-Hung , Chu Ya-Cherng , Hsiao Ming-Yen , Kung Yi , Wang Jaw-Lin , Chen Wen-Shiang 
Published: January 2023

AbstractRecently, the glymphatic system has been proposed as a mechanism for waste clearance from the brain parenchyma. Glymphatic dysfunction has been associated with several neurological diseases such as Alzheimer’s disease, traumatic brain injury, and stroke. Therefore, it may be an important target for therapeutic interventions. In this study, we demonstrated that very low intensity ultrasound (VLIUS) (center frequency = 1 MHz; pulse repetition frequency = 1 kHz; duty factor = 1%, and spatial peak temporal average intensity [Ispta] = 3.68 mW/cm2; duration = 5 min) could significantly enhance the influx of cerebrospinal fluid tracers into the perivascular spaces of the brain and also facilitate interstitial substance clearance from the brain parenchyma. Notably, no evidence of brain damage was observed after VLIUS stimulation. We also demonstrated that VLIUS enhanced the glymphatic influx via the transient receptor potential vanilloid-4-aquaporin-4 pathway in the astrocytes. This mechanism may provide insights into VLIUS-regulated glymphatic function that modifies the natural course of central nervous system disorders related to waste clearance dysfunction.One Sentence SummaryVery low-intensity ultrasound enhances glymphatic influx via the TRPV4-AQP4 pathway in the astrocytes, without observable brain damage.
2P-FLIM unveils time-dependent metabolic shifts during osteogenic differentiation with a key role of lactate to fuel osteogenesis via glutaminolysis identified
Authors: Neto Nuno GB , Suku Meenakshi , Hoey David A. , Monaghan Michael G. 
Published: January 2023

AbstractHuman mesenchymal stem cells (hMSCs) fuel discrete biosynthetic pathways to multiply and differentiate into specific cell lineages; with undifferentiated hMSCs showing reliance on glycolysis. hMSCs differentiating towards an osteogenic phenotype rely on oxidative phosphorylation as an energy source. Here, the metabolic profile of hMSCs was profiled during osteogenic differentiation over 14 days using a non-invasive live-cell imaging platform- two-photon fluorescence lifetime imaging microscopy (2P-FLIM) which images and measures NADH fluorescence. During osteogenesis, we observe a higher dependence on oxidative phosphorylation for cellular energy; concomitant with an increased reliance on anabolic pathways. We validated this metabolic profile using qPCR and extracellular metabolite analysis and observed a higher reliance on glutaminolysis in the earlier time-points of osteogenic differentiation. Based on the results obtained, we sought to promote glutaminolysis further during osteogenic differentiation. An indirect method of promoting glutaminolysis was explored so as to not impact cellular differentiation. As Lactate has been shown to promote glutamine uptake via c-Myc activation triggering expression of glutamine transmembrane transporters and glutaminase 1; we chose to increase extracellular lactate concentrations to drive increased glutaminolysis rates leading to higher levels of mineral deposition and osteogenic gene expression. Lactate supplementation of osteogenic medium also promoted upregulation of lactate metabolism and increased the expression of transmembrane cellular lactate transporters. Higher rates of lactate dehydrogenase gene expression coupled with higher NADH fluorescence intensity demonstrate a conversion of lactate to pyruvate. During this conversion, NADH is formed by the reverse enzymatic reaction of lactate dehydrogenase resulting in increased NADH fluorescence intensity. In order to evaluate the importance of glutaminolysis and lactate metabolism in osteogenic differentiation, these metabolic pathways were shut down using BPTES and α-CHC respectively which led to reduced hMSC mineralisation. In summary, we demonstrate that hMSCs osteogenic differentiation has a temporal metabolic profile and shift that is observed as early as day 3 of cell culture. Osteogenic differentiation was demonstrated to be directly dependent on OxPhos and on glutaminolysis and validated using biochemical assays. Furthermore, extracellular lactate is an essential metabolite to ensure osteogenic differentiation as a metabolic fuel and signalling molecule to promote glutaminolysis. These findings have significant impact in generating potent approaches towards bone tissue engineeringin vitroandin vivoby engaging directly with metabolite driven osteogenesis.
Genome-wide CRISPR screen reveals genetic modifiers of Ca2+-mediated cell death
Authors: Reyes Gaido Oscar E. , Schole Kate L. , Anderson Mark E. , Luczak Elizabeth D. 
Published: January 2023

ABSTRACTCa2+is a fundamental determinant of survival in living cells. Excessive intracellular Ca2+causes cellular toxicity and death but the genetic pathways contributing to Ca2+induced cell death are incompletely understood. Here, we performed genome-wide CRISPR knock-out screening in human cells challenged with the Ca2+ionophore ionomycin and identified genes and pathways essential for cell death after Ca2+overload. We discovered 115 protective gene knockouts, 82 of which are non-essential genes and 21 of which belong to the druggable genome. Notably, members of store operated Ca2+entry (SOCE), very long-chain fatty acid synthesis, and SWItch/Sucrose Non-Fermentable (SWI/SNF) pathways provided marked protection against Ca2+toxicity. These results reveal pathways previously unknown to mediate Ca2+-induced cell death and provide a resource for the development of pharmacotherapies against the sequelae of Ca2+overload in disease.