bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of RSV-A and RSV-B in Adults and Children with Medically-Attended Acute Respiratory Illness over Three Seasons
Authors: Begley Katherine M. , Leis Aleda M. , Petrie Joshua G. , Truscon Rachel , Johnson Emileigh , McSpadden Erin , Lamerato Lois E , Wei Melissa , Monto Arnold S. , Martin Emily T. 
Published: November 2022

AbstractBackgroundRSV is a frequent cause of respiratory illness less often diagnosed outside hospital settings; thus, overall prevalence of RSV-associated illness is under-recognized. Information about presence of RSV among those with chronic conditions is especially needed with recent advances in vaccine development.MethodsParticipants prospectively enrolled in an ambulatory surveillance study of respiratory illness (MFIVE) were tested by RT-PCR for RSV and influenza. Participant and illness characteristics were collected by in-person survey and EMR review. Chronic conditions were characterized by the Multimorbidity-weighted index (MWI). Viral factors, including subtype and viral load, were compared between RSV-A and RSV-B. Multivariate logistic regression models were used to compare participant and illness characteristics between those with RSV and those with influenza. Comparisons were also made across RSV subtypes.ResultsAmong 4,442 individuals enrolled in MFIVE from fall 2017 to spring 2020, 9.9% (n=441) had RSV detected. RSV+ participants with increased viral load had increased odds of illness lasting ≥ 7 days [ORadj=2.39 (95% CI: 1.03-5.51) p-value=0.04]. Adults with RSV had higher median MWI scores compared to influenza and RSV/influenza-negative (1.62, 0.40, 0.64, respectively).ConclusionsOur findings support the need for ongoing RSV surveillance, particularly in older adults and those with multimorbidity. Our findings support a recognition of multimorbidity as a significant contributor to RSV-associated MAARI among outpatient adults, with particularly notable impacts among adults under 65.
Factors Impacting Quality of Life in Multiple System Atrophy
Authors: Ali Nabila , Nesspor Vanessa , Bang Jee , Scholz Sonja W. , Pantelyat Alexander 
Published: November 2022

ABSTRACTBackgroundMultiple system atrophy (MSA) is an atypical parkinsonian disorder that involves parkinsonism, cerebellar ataxia, and autonomic dysfunction. Patient-reported quality of life is an important benchmark for clinicians and clinical trials. The Unified Multiple System Atrophy Rating Scale (UMSARS) allows healthcare providers to rate and assess MSA progression. The MSA-QoL questionnaire is a health-related quality of life scale intended to provide patient-reported outcome measures. In this article, we investigated inter-scale correlations between the MSA-QoL and UMSARS to determine factors impacting the quality of life of patients with MSA.MethodsTwenty patients at the Johns Hopkins Atypical Parkinsonism Center’s Multidisciplinary Clinic with a diagnosis of clinically probable MSA and who filled out the MSA-QoL and UMSARS questionnaires within two weeks of each other were included. Inter-scale correlations between MSA-QoL and UMSARS responses were examined. Linear regressions were also performed to examine relationships between both scales.ResultsSignificant inter-scale correlations were found between the MSA-QoL and UMSARS, both between MSA-QoL total score and UMSARS Part I subtotal scores and for individual scale items. There were no significant correlations between MSA-QoL life satisfaction rating and UMSARS subtotal scores or any specific UMSARS items. Linear regression analysis found significant associations between MSA-QoL total score and UMSARS Part I and total scores, and between MSA-QoL life satisfaction rating and UMSARS Part I, Part II, and total scores (after adjustment for age).ConclusionsOur study demonstrates significant inter-scale correlations between MSA-QoL and UMSARS, particularly relating to activities of daily living and hygiene. MSA-QoL total score and UMSARS Part I subtotal scores, which assess patients’ functional status, were strongly and significantly correlated. The lack of significant associations between MSA-QoL life satisfaction rating and any UMSARS item suggests there may be aspects to quality of life that are not fully captured by this assessment. Larger cross-sectional and longitudinal analyses utilizing UMSARS and MSA-QoL are warranted and modification of the UMSARS should be considered.
Prioritizing interventions for cholera control in Kenya, 2015-2020
Authors: Boru Waqo , Xiao Shaoming , Amoth Patrick , Kareko David , Langat Daniel , Were Ian , Ali Mohammad , Sack David A. , Lee Elizabeth C. , Debes Amanda K. 
Published: November 2022

AbstractKenya has experienced cholera outbreaks since 1971, with the most recent wave beginning in late 2014. Between 2015-2020, 32 of 47 counties reported 30,431 suspected cholera cases. The Global Task Force for Cholera Control (GTFCC) developed aGlobal Roadmap for Ending Cholera by 2030, which emphasizes the need to target multi-sectoral interventions to priority areas known as “cholera burden hotspots.” This study utilizes the GTFCC’s hotspot method to identify hotspots in Kenya at the county and sub-county administrative levels from 2015 through 2020. 32 of 47 (68.1%) counties reported cholera cases during this time while only 149 of 301 (49.5%) sub-counties reported cholera cases. The analysis identifies hotspots based on the mean annual incidence (MAI) over the past five-year period and cholera’s persistence in the area. Applying a MAI threshold of 90thpercentile and the median persistence at both the county and sub-county levels, we identified 13 high risk sub-counties from 8 counties, including the 3 high risk counties of Garissa, Tana River and Wajir. This demonstrates that several sub-counties are high level hotspots while their counties are not. In addition, when cases reported by county versus sub-county hotspot risk are compared, 1.4 million people overlapped in the areas identified as both high-risk county and high-risk sub-county. However, assuming that finer scale data is more accurate, 1.6 million high risk sub-county people would have been misclassified as medium risk with a county-level analysis. Furthermore, an additional 1.6 million people would have been classified as living in high-risk in a county-level analysis when at the sub-county level, they were medium, low or no-risk sub-counties. This results in 3.2 million people being misclassified when county level analysis is utilized rather than a more-focused sub-county level analysis. This analysis highlights the need for more localized risk analyses to target cholera intervention and prevention efforts towards the populations most vulnerable.
Use of home pulse oximetry to enhance remote COVID-19 monitoring: Evaluating a single centre experience
Authors: France Megan W , Porter Angus H , Bennett Cameron J , McCarthy Kate L 
Published: November 2022

ABSTRACTIntroductionTelehealth and remote monitoring of patients of patients with mild COVID-19 infection have developed rapidly in response to the pandemic. Many healthcare systems have embraced telehealth for remote clinical monitoring and pulse oximetry for enhanced monitoring.MethodsThe experience of a large healthcare centre’s COVID Virtual Ward was reviewed retrospectively with a particular focus on evaluating the effectiveness, safety and utility of finger pulse oximetry within the home. Data from a 2 month period in early 2022 during a BA1 Omicron wave was retrospectively reviewed.551 high risk patients were issued with pulse oximeters for monitoring oxygen saturations within their home. All patients received daily clinical review via telephone by a nurse or doctor. The group was highly vaccinated with only 6.4% of the cohort unvaccinated. Oximeters were promptly delivered via a courier service across a vast geographical area.ResultsPulse oximetry was well utilised by almost all patients. Only 2.7% of the cohort demonstrated resting oxygen saturations of <94% during their Virtual Ward admission. 91% of patients reporting dyspnoea were able to be safely managed without escalation to an emergency department due to reassuring clinical and oximetry assessment. Home oxygen saturations correlated well with saturations recorded within the ED, with no patients found to have lower saturations compared with home saturations.DiscussionWithin a high risk population experiencing COVID-19 infection, pulse oximetry was a useful tool in clinical assessment, correlated well with hospital-based pulse oximetry and allowed a substantial reduction in COVID-19 related ED presentations.
Corticostriatal connectivity mediates the reciprocal relationship between sleep and impulsivity in early adolescents
Authors: Yang Fan Nils , Liu Tina Tong , Wang Ze 
Published: November 2022

AbstractBackgroundAdolescence, a developmental period characterized by major changes in sleep and circadian rhythms, is associated with normative increases in impulsivity. While insufficient sleep has been linked to elevated impulsivity, the neural mechanism underlying the relationship remains poorly understood.MethodsWe analyzed a dataset of 7,884 drug-naive 9-10 year-olds from the Adolescent Brain Cognitive Development (ABCD) study. Among them, 5,166 have 2-year follow-up neuroimaging data. Linear mixed-effects models, mediation analysis, and longitudinal mediation analysis were used to investigate the relationship between sleep, impulsivity, and brain functional and structural connectivity between the cortex and the striatum.ResultsWe found that less sleep is significantly associated with higher impulsivity and disrupted functional connectivity between the cingulo-opercular network and the left caudate, and between the cingulo-parietal network and the right pallidum. These two connectivity measurements mediate the effect of sleep duration on impulsivity at both baseline and two-year follow-up. Longitudinal mediation analyses further revealed that sleep duration and impulsivity can reinforce each other through cortical-striatum connectivities in a reciprocal manner.ConclusionsThese results reveal neural mechanisms underlying the robust reciprocal relationship between insufficient sleep and impulsivity. Our findings highlight the role of early sleep intervention in helping early adolescents control their impulses, which might in turn prevent the development of substance use.
Disability and Post-traumatic Stress Symptoms in the Ukrainian General Population During the 2022 Russian Invasion
Authors: Kang Tarandeep S. , Goodwin Robin , Hamama-Raz Yaira , Leshem Elazar , Ben-Ezra Menachem 
Published: November 2022

AbstractBackgroundPrevious research has shown that people with disabilities are disproportionately vulnerable to symptoms of psychological distress after exposure to armed conflict. Past work has also shown that individuals displaced by conflict are at heightened risk of post-traumatic stress. However, we know of no research that has attempted to examine the association between disability severity and post-traumatic stress symptoms in a general population affected by armed conflict.MethodWe examined the association between levels of functional disability in the Ukrainian population and symptoms of post-traumatic stress during the 2022 Russian invasion of Ukraine. We analysed data from a national sample of 2000 participants from across this country, assessing disability using the WHODAS-12 (six domains of disability) and the ITQ assessment of ICD-11 PTSD symptomatology. Moderated regression examined the impact of displacement status on the disability-post-traumatic stress relationship.ResultsDifferent domains of disability predicted post-traumatic stress symptoms to varying extents, with overall disability score significantly associated with post-traumatic stress symptoms. This relationship was not moderated by displacement status. Consistent with previous research, females reported higher levels post-traumatic stress.ConclusionsIn a study of a general population during a time of armed conflict individuals with more severe disabilities were at greater risk of post-traumatic stress symptoms.Psychiatrists and related professionals should consider pre-existing disability as a risk factor for conflict -related post-traumatic stress.HighlightsWhat is already known on this topicPeople with disabilities are vulnerable to a variety of forms of psychological distress after experiencing disasters of various kinds, including armed conflict. However, associations between levels of disability in the general population and post-traumatic stress during a period of conflict have not previously been examined.What this study addsIncreasing severity of functional disability in the general population is associated with increasing post-traumatic stress symptoms in a conflict exposed population.How this study might affect research, practice or policyMental health professionals dealing with conflict affected populations should take account of the additional vulnerabilities caused by disability status, and work to mitigate this by providing access to functional and social support.
Heat Exposure Among Adult Women in Rural Tamil Nadu, India
Authors: Deshpande Aniruddha , Scovronick Noah , Clasen Thomas F. , Waller Lance , Aravindalochanan Vigneswari , Balakrishnan Kalpana , Puttaswamy Naveen , Peel Jennifer , Pillarisetti Ajay 
Published: November 2022

AbstractExposure to heat is associated with a substantial burden of disease and is an emerging issue in the context of climate change. Heat exposure is of particular concern in India – one of the world’s hotter countries and soon to be its most populous – where a large fraction of the population works outdoors, lives in dwellings that are thermally inefficient, and is unable to access cooling technologies. Despite these concerns, relatively little is known about personal heat exposure in India, particularly in rural areas. Here we leverage temperature data collected as part of a randomized controlled trial of cookstove replacement to describe personal temperature exposures of older adult women in rural Tamil Nadu. We also compare personal exposure measurements to the nearest ambient monitoring stations, as well as to commonly used modelled temperature data products. We find that temperatures differ across individuals in the same location on the same day – sometimes by more than 5 °C within the same hour – and that some individuals experience sharp increases in heat exposure in the early morning or evening, potentially a result of cooking with solid fuels. In comparisons with the personal exposure measurements, we find stronger correlations with the modelled products (R2of ∼0.74) than with ambient monitors (R2of ∼0.6). We did not find evidence of systematic biases, which indicates that adjusting for discrepancies between personal and ambient exposure estimates is not straightforward. This study indicates a need for improved heat exposure assessment in epidemiological and burden of disease studies in India.
A gene essentiality signature enables predicting the mechanism of action of drugs
Authors: Wang Wenyu , Bao Jie , Zheng Shuyu , Huang Shan , Aldahdooh Jehad , Wang Yinyin , Eriksson Johanna , Tanoli Ziaurrehman , Zhang Xuepei , Gaetani Massimiliano , Tang Jing 
Published: November 2022

ABSTRACTCancer drugs often kill cells independent of their putative targets, suggesting the limitation of existing knowledge on the mechanisms of action. In this study, we explored whether the integration of loss-of-function genetic and drug sensitivity screening data can define a gene essentiality signature to better understand the drug target interactions. We showed that our gene essentiality signature can predict drug targets more accurately than chemical fingerprints and drug-perturbated gene expression signatures. We further showed how gene essentiality signature can help identify mechanisms of action of drugsde novo, including the EGFR inhibitor lapatinib, and drugs associated with DNA mismatch repair. Finally, we established gene essentiality signatures for noncancer drugs and used them to predict their anticancer targets. We have successfully validated the target predictions for multiple noncancer drugs, using cell-based drug target deconvolution by the proteome integral solubility alteration assay. Our study provides a novel signature of drugs that may facilitate the rational design of drug repurposing.
Limited emergence of resistance to Integrase strand transfer inhibitors (INSTIs) in HIV-experienced patients failing dolutegravir-based antiretroviral therapy: Cross-sectional analysis from a Northeast Nigerian cohort
Authors: Abdullahi Adam , Kida Ibrahim Musa , Maina Umar Abdullahi , Ibrahim Amina Husaini , Mshelia James , Wisso Haruna , Adamu Abdullahi , Onyemata James Ezenwa , Yusuph Haruna , Aliyu Sani H. , Charurat Man , Abimiku Alash’le , Abeler-Dorner Lucie , Fraser Christophe , Bonsall David , Kemp Steven A. , Gupta Ravindra K. 
Published: November 2022

AbstractBackgroundOwing to high levels of resistance to previous first-line non-nucleoside reverse transcriptase inhibitors (NNRTI)-based antiretroviral therapy (ART), consolidated recommendations since 2019, from the WHO and others, have indicated that dolutegravir (DTG) is the preferred drug of choice for HIV treatment, globally. There is a paucity of resistance outcome data from non-B HIV subtypes circulating across West Africa.AimWe aimed to characterise the mutational profiles of HIV-positive patients from a small North-East Nigeria cohort, failing a DTG-based ART regimen.MethodsPlasma samples were collected and stored from 61 HIV-1 infected participants. Following failure of DTG-based ART, all samples were sequenced by Illumina whole-genome, ultra-deep sequencing. Sequencing was successful in (n=33) participants with median age of 40 years and median time on ART of 9 years. HIV-1 subtyping was performed using SNAPPy. Haplotype reconstruction and transmission were inferred using standard phylogenetic methods.ResultMost patients had mutational profiles that were reflective of prior exposure to first- and second-line ART including exposure to thymidine analogues, efavirenz and nevirapine. One patient had evidence of major INSTI DRMs (T66A, G118R, E138K and R263K), reducing efficacy of DTG. The participant was aged 18, infected with a subtype G virus and likely vertically infected.ConclusionThis study found low level resistance to DTG in the cohort, with one patient having high-level resistance to DTG and other INSTIs. Critical population level and long-term data on DTG outcomes are required to guide implementation and policy action across the region.
Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease
Authors: Green Courtney R. , Bonelli Roberto , Ansell Brendan R.E. , Tzaridis Simone , Handzlik Michal , McGregor Grace H. , Hart Barbara , Trombley Jennifer , Reilly Mary M. , Bernstein Paul S. , Egan Catherine , Fruttiger Marcus , Wallace Martina , Bahlo Melanie , Friedlander Martin , Metallo Christian M. , Gantner Marin L. 
Published: November 2022

ABSTRACTThe non-essential amino acids serine, glycine, and alanine, as well as diverse sphingolipid species, are implicated in inherited neuro-retinal disorders and are metabolically linked by serine palmitoyltransferase (SPT), a key enzyme in membrane lipid biogenesis. To gain insights into the pathophysiological mechanisms linking these pathways to neuro-retinal diseases we performed a targeted metabolomic analysis of these pathways in sera from patients diagnosed with two metabolically intertwined diseases: macular telangiectasia type II (MacTel), hereditary sensory autonomic neuropathy type 1 (HSAN1), or both. In a cohort of >350 participants, MacTel patients exhibited broad alterations of amino acids, including changes in serine, glycine, alanine, glutamate, and branched-chain amino acids reminiscent of diabetes. MacTel patients had elevated 1-deoxysphingolipids but reduced levels of complex sphingolipids in circulation. A mouse model indicates this depletion in complex sphingolipids can be driven by low dietary serine and glycine. HSAN1 patients exhibited elevated serine, lower alanine, and a reduction in canonical ceramides and sphingomyelins compared to controls. Those patients diagnosed with both HSAN1 and MacTel showed the most significant decrease in circulating sphingomyelins. These results highlight metabolic distinctions between these two diseases, emphasize the importance of membrane lipids in the progression of MacTel, and suggest distinct therapeutic approaches.
Convergent Evolution and B-Cell Recirculation in Germinal Centers in a Human Lymph Node
Authors: Pelissier Aurelien , Stratigopoulou Maria , Donner Naomi , Dimitriadis Evangelos , Bende Richard J , Guikema Jeroen E , Martinez Maria Rodriguez , van Noesel Carel J M 
Published: November 2022

AbstractGerminal centers (GCs) are specialized compartments within the secondary lymphoid organs where B cells proliferate, differentiate, and mutate their antibody genes in response to the presence of foreign antigens. They play a central role in generating an effective immune response against infectious pathogens, and failures in their regulating mechanisms can lead to the development of autoimmune diseases and cancer. While previous works study experimental systems of the immune response with mouse models that are immunized with specific antigens, our study focuses on a real life situation, with an ongoing GC response in a human lymph node (LN) involving multiple asynchronized GCs reacting simultaneously to unknown antigens. We combined laser capture microdissection (LCM) of individual GCs from human LN with next-generation repertoire sequencing (Rep-seq) to characterize individual GCs as distinct evolutionary spaces. In line with well-characterized GC responses in mice, elicited by immunization with model antigens such as NP-CGG, we observe a relatively low sequence similarity, as well as heterogeneous clonal diversity across individual GCs from the same human LN. Still, we identify shared clones in several individual GCs, and phylogenetic tree analysis combined with paratope modeling suggest the re-engagement and rediversification of B-cell clones across GCs as well as expanded clones exhibiting shared antigen responses across distinct GCs, indicating convergent evolution of the GCs. Finally, our study allows for the characterization of non-functional clones, where frequencies of V(D)J or SHM induced stop codons are quantified.