bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health Economic Burden of COVID-19 in Saudi Arabia
Authors: Alenzi Khalidah A. , Al-malky Hamdan S. , Altebainawi Ali F. , Abushomi Hamidah Q. , Alatawi Fahad O. , Atwadi Moosa H. , Khobrani Moosa A. , Almazrou Dlal A. , Alrubeh Nariman , Alsoliabi Zainab A. , Kardam Abdulaziz M. , Alghamdi Shakr A. , Alasiri Abdulrahman , Alshammari Thamir M. 
Published: April 2022

AbstractBackgroundThe coronavirus disease 2019 (COVID-19) pandemic has placed a massive economic burden on health care systems worldwide. Saudi Arabia is one of the numerous countries that have been economically affected by this pandemic. The objective of this study was to provide real-world data on the health economic burden of COVID-19 on the Saudi health sector and assess the direct medical costs associated with the management of COVID-19.MethodsA retrospective cohort study was conducted based on data collected from patients hospitalized with COVID-19 across ten institutions in eight different regions in Saudi Arabia. The study calculated the estimated costs of all cases during the study period by using direct medical costs. These costs included costs directly related to medical services, such as the health care treatment, hospital stays, laboratory investigations, treatment, outcome, and other related care.ResultsA total of 5,286 adult patients admitted with COVID-19 during the study period were included in the study. The average age of the patients was 54 years, and the majority were male. Among the COVID-19 patients hospitalized in a general ward, the median hospital length of stay was 5.5 days (mean: 9.18 days), while the ICU stay was 4.26 days (mean: 7.94 days). The total medical costs for general ward and ICU patients were 14,585,640 SAR and 90,776,250 SAR, respectively. The total laboratory investigations ranked as the highest-cost services (22,086,296 SAR), followed by treatment (14,574,233.1 SAR). Overall, the total cost of all medical services for patients hospitalized with COVID-19 was 193,394,103.1 SAR.ConclusionThis national study found that COVID-19 was not only a serious concern for patients but also a serious economic burden on the health care system in Saudi Arabia.Key pointsThe nursing costs and length of stay were lower in the ICU than in the general ward.The costs of hospitalization in general medical wards were less than those of admission to the ICU.These cost data will be valuable for future researchers evaluating the COVID-19 pandemic’s increasing health care economic burden in Saudi Arabia and the implementation of cost-effective models to assess the possible implications of COVID-19 prevention and treatment initiatives.
Racial differences in white matter hyperintensity burden in aging, MCI, and AD
Authors: Morrison Cassandra , Dadar Mahsa , Manera Ana L. , Collins D. Louis ,   Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

AbstractWhite matter hyperintensities may be one of the earliest pathological changes in aging and may potentially accelerate cognitive decline. Whether race influences WMH burden has been conflicting. The goal of this study was to examine if race differences exist in WMH burden and whether these differences are influenced by vascular factors [i.e., diabetes, hypertension, body mass index (BMI)]. Participants from the Alzheimer’s Disease Neuroimaging Initiative were included if they had a baseline MRI, diagnosis, and WMH measurements. Ninety-one Black and 1937 White individuals were included. Using bootstrap re-sampling, 91 Whites were randomly sampled and matched to Black participants based on age, sex, education, and diagnosis 1000 times. Linear regression models examined the influence of race on baseline WMHs with and without vascular factors: WMH ∼ Race + Age + Sex + Education + BMI + Hypertension + Diabetes and WMH ∼ Race + Age + Sex + Education. The 95% confidence limits of the t-statistics distributions for the 1000 samples were examined to determine statistical significance. All vascular risk factors had significantly higher prevalence in Black than White individuals. When not including vascular risk factors, Black individuals had greater WMH volume overall as well as in frontal and parietal regions, compared to White individuals. After controlling for vascular risk factors, no WMH group differences remained significant. These findings suggest that vascular risk factors are a major contributor to racial group differences observed in WMHs.
White matter hyperintensity load varies depending on subjective cognitive decline criteria
Authors: Morrison Cassandra , Dadar Mahsa , Villeneuve Sylvia , Ducharme Simon , Collins D. Louis ,   Alzheimer’s Disease Neuroimaging Initiative
Published: April 2022

BackgroundIncreased age and cognitive impairment is associated with an increase in cerebrovascular pathology often measured as white matter hyperintensities (WMHs) on MRI. Whether WMH burden differs between cognitively unimpaired older adults with subjective cognitive decline (SCD+) and without subjective cognitive decline (SCD–) remains conflicting, and could be related to the methods used to identify SCD. Our goal was to examine if four common SCD classification methods are associated with different WMH accumulation patterns between SCD+ and SCD-.MethodsA total of 535 cognitively unimpaired older adults with 1353 time points from the Alzheimer’s Disease Neuroimaging Initiative were included in this study. SCD was operationalized using four different methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog+Worry, and Worry. Linear mixed-effects models were used to investigate the associations between SCD and overall and regional WMH burden.ResultsOverall temporal WMH burden differences were only observed with the Worry questionnaire. Higher WMH burden change over time was observed in SCD+ compared to SCD– in the temporal and parietal regions using the CCI (temporal, p=.01; parietal p=.03) and ECog (temporal, p=.03; parietal p=.01). For both the ECog+Worry and Worry questionnaire, change in WMH burden over time was increased in SCD+ compared to SCD- for overall, frontal, temporal, and parietal WMH burden (p<.05).ConclusionThese results show that WMH burden differs between SCD+ and SCD– depending on the questionnaire and the approach (regional/global) used to measure WMHs. The various methods used to define SCD may reflect different types of underlying pathologies.
Estimating the epidemiology of chronic Hepatitis B Virus (HBV) infection in the UK: what do we know and what are we missing?
Authors: Campbell Cori , Wang Tingyan , Burrow Rebekah , Mandal Sema , Hippisley-Cox Julia , Barnes Eleanor , Matthews Philippa C 
Published: April 2022

AbstractBackgroundHBV is the leading global cause of cirrhosis and primary liver cancer. The virus’s attributable disease burden in the UK is concentrated in vulnerable populatons including ethinic minorities, people experiencing homelessness and people born in high-prevalence countries. Despite this the UK HBV population has not been well characterised, and estimates of UK HBV prevalence and/or positivity rate vary widely across sources. We summarised datasets that are available to represent UK CHB epidemiology, consider differences between sources, and discuss deficiencies in current estimates.MethodsWe searched for estimates of CHB case numbers in the UK (incorporating incidence and/or prevalence-like data) across a range of available sources, including UK-wide reports from government bodies, publications from independent bodies (including medical charities and non-governmental organisations) and articles in peer-reviewed scientific journals. We present positivity rates from each respective data source but caution that estimates may not be representative of the true UK-wide population prevalence.Results and DiscussionSix CHB case number estimates were identified, with three estimates reporting information concerning population subgroups, including number of infected individuals across age, sex and ethnicity categories., Estimates among sources reporting prevalence varied from 0.27% to 0.73%. An alterantive proxy for population prevalence (obtained via the UK antenatal screening programme which achieves over 95% coverage of every pregnant woman) estimated a CHB prevalence of <0.5%. Estimates varied by sources of error, bias and missingness, data linkage, and substantial “blind spots” in consistent testing and registration of HBV diagnoses. Multi-parameter evidence synthesis and back-calculation model methods similar to those used to generate estimates of HCV ad HIV population-wide prevalence may be applicable to HBV.
Protection conferred by vaccine plus previous infection (hybrid immunity) with vaccines of three different platforms during the Omicron variant period in Brazil
Authors: Cerqueira-Silva Thiago , de Araujo Oliveira Vinicius , Paixão Enny S. , Veras Florentino Pilar Tavares , Penna Gerson O. , Pearce Neil , Werneck Guilherme L. , Barreto Maurício L. , Boaventura Viviane S. , Barral-Netto Manoel 
Published: April 2022

ABSTRACTHybrid immunity (infection plus vaccination) provided high protection against infection and severe disease in the periods of delta and gamma variants of concern. However, the protection of hybrid immunity in the Omicron era remains unknown. We performed a test-negative study using Brazilian national databases between January 01 and March 22, 2022, a period of predominant circulation of the Omicron variant in Brazil. Hybrid immunity offered low protection against infection, with rapid waning, compared to unvaccinated with or without previous infection. For severe illness (hospitalisation or death), the protection, although already high for unvaccinated pre-infected increased regardless of the type of vaccine (Ad26.COV2.S, BNT162b2, ChAdOx-1 or CoronaVac).In conclusion, during the Omicron-dominant period in Brazil, hybrid immunity offered high protection against severe illness and low protection against infection.
Radioactive Contamination in Feral Dogs in the Chernobyl Exclusion Zone: Population Body-Burden Survey and Implications for Human Radiation Exposure
Authors: Hecla Jake , Kambarian Erik , Tubbs Robert , McKinley Carla , Berliner Aaron J. , Russell Kayla , Spatola Gabrielle , Chertok Jordan , Braun Weston , Hank Natalia , Marquette Courtney , Betz Jennifer , Paik Terry , Chenery Marie , Cagan Alex , Willis Carl , Mousseau Tim 
Published: April 2022

ABSTRACTThis report describes a two-year effort to survey the internal 137Cs and external β-emitter contamination present in the feral dog population near the Chernobyl nuclear power plant (ChNPP) site, and to quantify the potential for human radiation exposure from this contamination. This work was performed as an integral part of the radiation safety and control procedures of an animal welfare oriented trap-neuter-release (TNR) program. The measurement program employed handheld β-sensitive probes, and a simple whole-body counter to measure internal 137Cs burden during post-surgical observation and recovery. External β contamination surveys performed during intake showed that 21/288 animals had significant, removable external contamination. Measurements with the whole-body counter indicated internal 137Cs body burdens ranging from undetectable (minimum detection level ∼100 Bq/kg in 2017, ∼ 30 Bq/kg in 2018) to approximately 30,000 Bq/kg. A total of 33 animals had 137Cs body-burdens above 1 kBq/kg. We observe that internal contamination levels are positively correlated with capture locations within ChNPP boundaries. The large variation in the 137Cs concentration in these animals is not well-understood, could be due to prey selection, access to human food scraps, or extended residence in highly contaminated areas. These internally-contaminated animals are unlikely to pose an exposure hazard despite their large body-burdens due to their limited exposure to humans. However, the small minority of animals with external contamination may pose a contamination hazard to workers, tourists, and others interacting with the dogs, as evidenced by total quantity of removable activity and incidents of transfer to materials used in animal capture.
Conserved cell-type specific signature of resilience to Alzheimer’s disease nominates role for excitatory intratelencephalic cortical neurons
Authors: Telpoukhovskaia Maria A. , Hadad Niran , Gurdon Brianna , Dai Yanchao , Ouellette Andrew R. , Neuner Sarah M. , Dunn Amy R. , Willcox Jon A. L. , Wu Yiyang , Dumitrescu Logan , Bellur Orhan , Zhang Ji-Gang , O’Connell Kristen M.S. , Dammer Eric B. , Seyfried Nicholas T. , Muzumdar Sukalp , Gillis Jesse , Robson Paul , Arnold Matthias , Hohman Timothy J. , Philip Vivek M. , Menon Vilas , Kaczorowski Catherine C. 
Published: April 2022

SummaryAlzheimer’s disease (AD), the leading cause of dementia, affects millions of people worldwide. With no disease-modifying medication currently available, the human toll and economic costs are rising rapidly. Under current standards, a patient is diagnosed with AD when both cognitive decline and pathology (amyloid plaques and neurofibrillary tangles) are present. Remarkably, some individuals who have AD pathology remain cognitively normal. Uncovering factors that lead to “cognitive resilience” to AD is a promising path to create new targets for therapies. However, technical challenges discovering novel human resilience factors limit testing, validation, and nomination of novel drugs for AD. In this study, we use single-nucleus transcriptional profiles of postmortem cortex from human individuals with high AD pathology who were either cognitively normal (resilient) or cognitively impaired (susceptible) at time of death, as well as mouse strains that parallel these differences in cognition with high amyloid load. Our cross-species discovery approach highlights a novel role for excitatory layer 4/5 cortical neurons in promoting cognitive resilience to AD, and nominates several resilience genes that includeATP1A1,GRIA3,KCNMA1, andSTXBP1. This putative cell type has been implicated in resilience in previous studies on bulk RNA-seq tissue, but our single-nucleus and cross-species approach identifies particular resilience-associated gene signatures in these cells. These novel resilience candidate genes were tested for replication in orthogonal data sets and confirmed to be correlated with cognitive resilience. Based on these gene signatures, we identified several potential mechanisms of resilience, including regulation of synaptic plasticity, axonal and dendritic development, and neurite vesicle transport along microtubules that are potentially targetable by available therapeutics. Because our discovery of resilience-associated genes in layer 4/5 cortical neurons originates from an integrated human and mouse transcriptomic space from susceptible and resilient individuals, we are positioned to test causality and perform mechanistic, validation, and pre-clinical studies in our human-relevant AD-BXD mouse panel.
Microglia undergo rapid phenotypic transformation in acute brain slices but remain essential for neuronal synchrony
Authors: Berki Péter , Cserép Csaba , Pósfai Balázs , Szabadits Eszter , Környei Zsuzsanna , Kellermayer Anna , Nyerges Miklós , Wei Xiaofei , Mody Istvan , Araki Kunihiko , Beck Heinz , He Kaikai , Wang Ya , Wu Zhaofa , Jing Miao , Li Yulong , Gulyás Attila I. , Dénes Ádám 
Published: April 2022

AbstractAcute brain slices represent a “workhorse” model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue injury, it is unclear how microglia, the main immune cells and damage sensors of the CNS shape tissue integrityex vivo. To this end, we have studied the mechanisms of microglial phenotype changes and contribution to neuronal network organisation and functioning in acute brain slices. Using a novel ATP- reporter mouse line and microglia reporter mice, we show that acute slice preparation induces rapid, P2Y12 receptor (P2Y12R) dependent dislocation and migration of microglia, paralleled with marked morphological transformations driven by early ATP surges and subsequent ATP flashes. Gradual depolarization of microglia is associated with the downregulation of purinergic P2Y12R and time-dependent changes of microglia-neuron interactions, paralleled by altered numbers of excitatory and inhibitory synapses. Importantly, functional microglia not only modulate synapse sprouting, but the absence of microglia or microglial P2Y12R markedly diminishes the incidence, amplitude, and frequency of sharp wave-ripple activity in hippocampal slices. Collectively, our data suggest that microglia are inherent modulators of complex neuronal networks, and their specific actions are indispensable to maintain neuronal network integrity and activityex vivo.These findings could facilitate new lines of research resulting in improvedex vivomethodologies and a better understanding of microglia-neuron interactions both in physiological and pathological conditions.
Validation of genetic variants from NGS data using Deep Convolutional Neural Networks
Authors: Vaisband Marc , Schubert Maria , Gassner Franz Josef , Geisberger Roland , Greil Richard , Zaborsky Nadja , Hasenauer Jan 
Published: April 2022

AbstractAccurate somatic variant calling from next-generation sequencing data is one most important tasks in personalised cancer therapy. The sophistication of the available technologies is ever-increasing, yet, manual candidate refinement is still a necessary step in state-of-the-art processing pipelines. This limits reproducibility and introduces a bottleneck with respect to scalability. We demonstrate that the validation of genetic variants can be improved using a machine learning approach resting on a Convolutional Neural Network, trained using existing human annotation. In contrast to existing approaches, we introduce a way in which contextual data from sequencing tracks can be included into the automated assessment. A rigorous evaluation shows that the resulting model is robust and performs on par with trained researchers following published standard operating procedure.
Systematic conformation-to-phenotype mapping via limited deep-sequencing of proteins
Authors: Serebryany Eugene , Zhao Victor Y. , Park Kibum , Bitran Amir , Trauger Sunia A. , Budnik Bogdan , Shakhnovich Eugene I. 
Published: April 2022

SummaryNon-native conformations drive protein misfolding diseases, complicate bioengineering efforts, and fuel molecular evolution. No current experimental technique is well-suited for elucidating them and their phenotypic effects. Especially intractable are the transient conformations populated by intrinsically disordered proteins. We describe an approach to systematically discover, stabilize, and purify native and non-native conformations, generatedin vitroorin vivo, and directly link conformations to molecular, organismal, or evolutionary phenotypes. This approach involves high-throughput disulfide scanning (HTDS) of the entire protein. To reveal which disulfides trap which chromatographically resolvable conformers, we devised a deep-sequencing method for double-Cys variant libraries of proteins that precisely and simultaneously locates both Cys residues within each polypeptide. HTDS of the abundantE. coliperiplasmic chaperone HdeA revealed distinct classes of disordered hydrophobic conformers with variable cytotoxicity depending on where the backbone was cross-linked. HTDS can bridge conformational and phenotypic landscapes for many proteins that function in disulfide-permissive environments.
Estimation of Left Ventricular Mechanical Activation Times from Motion-Corrected Cardiac 4DCT Images
Authors: Manohar Ashish , Yang James , Pack Jed D. , McVeigh Elliot R. 
Published: April 2022

AbstractBackgroundMechanical activation times of the left ventricle (LV) are strongly correlated with patient response to cardiac resynchronization therapy (CRT); however, there remains an unmet clinical need for a simple, robust imaging modality that yields accurate and reproducible estimates of LV mechanical activation times. Modern four-dimensional computed tomography (4DCT) imaging systems with effective motion correction could fulfill this need.PurposeTo demonstrate the clinical utility of a newly developed cardiac motion correction algorithm called ResyncCT and to investigate its effect on estimating mechanical activation times of the LV.MethodsTwenty-four subjects with full cardiac volume, full cardiac cycle 4DCT images were retrospectively analyzed in this study. The reconstructed 4DCT images exhibited typical motion artifact characteristics that were dependent on the direction of LV wall motion with respect to the gantry position at each cardiac phase; these artifacts rotated synchronously with the gantry. The motion corrupted images, referred to as the uncorrected images, were processed with a novel cardiac motion correction algorithm called ResyncCT to yield motion corrected images (referred to as the ResyncCT images). Regional shortening (RSCT) of the LV was calculated over a 72-segment model for both the uncorrected and the ResyncCT images; each segment contained RSCT vs time data. From these RSCT vs time curves, LV mechanical activation was estimated as the time point at which the RSCT vs time curve shortened by 10% of its full dynamic range during systolic contraction; we refer to this time point as the time to onset of shortening (TOS). A shift in TOS > |35| ms has a significant effect on reclassifying patients based on their probabilities of responding to CRT; we investigated the effect of ResyncCT on the measured values of TOS over the LV.ResultsResyncCT had a pronounced effect on the TOS estimates; ResyncCT could potentially reclassify 23/24 (96%) subjects as either responders or non-responders to CRT. In 16/24 (67%) subjects, the differences in TOS that were sufficient to bring about a reclassification of CRT response were at least as large in surface area of the LV as one entire American Heart Association segment.ConclusionsWe demonstrated the clinical utility of ResyncCT in estimating LV mechanical activation times as ‘times to onset of shortening’ in 24 human subjects. ResyncCT has a pronounced effect on the estimation of LV mechanical activation times; the differences in activation times between the ResyncCT and uncorrected images are heterogenous and subject specific. The effect of ResyncCT could potentially reclassify 96% of the subjects used in this study based on their probabilities of responding to CRT. The results reported in this study highlight the potential utility of ResyncCT in estimating timing of mechanical events of interest of the LV for CRT planning.
Nav1.2 and BK channels interaction shapes the action potential in the axon initial segment
Authors: Filipis Luiza , Blömer Laila Ananda , Montnach Jérôme , De Waard Michel , Canepari Marco 
Published: April 2022

ABSTRACTIn neocortical layer-5 pyramidal neurons, the action potential (AP) is generated in the axon initial segment (AIS) when the membrane potential (Vm) reaches the threshold for activation of two diverse voltage-gated Na+ channels, that differ in spatial distribution and biophysical properties. Yet, the understanding of specific functional differences between these two channels remains elusive. Here, using ultrafast Na+, Vm and Ca2+ imaging in combination with partial block of Nav1.2 by a recent peptide, we demonstrate an exclusive role of Nav1.2 in shaping the generating AP. Precisely, Ca2+ influx via Nav1.2 activates BK Ca2+-activated K+ channels determining the amplitude and the early phase of repolarisation of the AP in the AIS. We mimicked this result with a NEURON model where the role of the different ion channels tested reproduced the experimental evidence. The exclusive role of Nav1.2 reported here is important for understanding the physiology and pathology of neuronal excitability.