bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global patterns and drivers of influenza decline during the COVID-19 pandemic
Authors: Bonacina Francesco , Boëlle Pierre-Yves , Colizza Vittoria , Lopez Olivier , Thomas Maud , Poletto Chiara 
Published: July 2022

AbstractInfluenza circulation declined during the COVID-19 pandemic. The timing and extent of decline and its association with interventions against COVID-19 were described for some regions. Here, we provide a global analysis of the influenza decline between March 2020 and September 2021 and investigate its potential drivers. We computed influenza change by country and trimester relative to the 2014-2019 period using the number of samples in the FluNet database. We used random forests to determine important predictors in a list of 20 covariates including demography, weather, pandemic preparedness, COVID-19 incidence, and COVID-19 pandemic response. With a regression tree we then classified observations according to these predictors. We found that influenza circulation decreased globally, with COVID-19 incidence and pandemic preparedness being the two most important predictors of this decrease. The regression tree showed interpretable groups of observations by country and trimester: Europe and North America clustered together in spring 2020, with limited influenza decline despite strong COVID-19 restrictions; in the period afterwards countries of temperate regions, with high pandemic preparedness, high COVID-19 incidence and stringent social restrictions grouped together having strong influenza decline. Conversely, countries in the tropics, with altogether low pandemic preparedness, low reported COVID-19 incidence and low strength of COVID-19 response showed low influenza decline overall. A final group singled out four “zero-Covid” countries, with the lowest residual influenza levels. The spatiotemporal decline of influenza during the COVID-19 pandemic was global, yet heterogeneous. The sociodemographic context and stage of the COVID-19 pandemic showed non-linear associations with this decline. Zero-Covid countries maintained the lowest levels of reduction with strict border controls and despite close-to-normal social activity. These results suggest that the resurgence of influenza could take equally diverse paths. It also emphasises the importance of influenza reseeding in driving countries’ seasonal influenza epidemics.
Genome-wide analysis of genetic pleiotropy and causal genes across three age-related ocular disorders
Authors: Yao Xueming , Yang Hongxi , Han Han , Kou Xuejing , Jiang Yuhan , Luo Menghan , Zhou Yao , Wang Jianhua , Fan Xutong , Wang Xiaohong , Li Mulin Jun , Yan Hua 
Published: July 2022

AbstractPurposeAge-related macular degeneration (AMD), cataract, and glaucoma are leading causes of blindness worldwide. Previous genome-wide association studies (GWASs) have revealed a variety of susceptible loci associated with age-related ocular disorders, yet the genetic pleiotropy and causal genes across these diseases remain poorly understood. This study aims to identify genetic pleiotropic genes among AMD, cataract, and glaucoma.MethodsWe leveraged large-scale genetic and observational data from ocular disease GWASs and UK Biobank (UKBB) to investigate correlations among these ocular disorders. We undertook meta-analyses with the largest GWAS summary statistics of these ocular disorders to identify pleiotropic loci. We then comprehensively integrated eye-specific gene expression quantitative loci (eQTLs), epigenomic profiling, and 3D genome data to prioritize causal pleiotropic genes. Pathway enrichment analysis and drug repurposing analysis were also conducted.ResultsWe found significant pairwise genetic correlations and consistent epidemiological associations among AMD, cataract, and glaucoma. Cross-disease meta-analysis uncovered seven pleiotropic loci, three of which were replicated in an additional cohort. Integration of variants in pleiotropic loci and multiple single-cell omics data identified that Müller cells and astrocytes were likely causal cell types underlying ocular comorbidity. After the integration with multi-omics data, 15 causal genes were identified. We found that pleiotropic genes were essential in nerve development and eye pigmentation, and targetable by existing drugs for the treatment of single ocular disorder.ConclusionsThese findings will not only facilitate the mechanistic research of ocular comorbidities but also benefit the therapeutic optimization of age-related ocular diseases.
Susceptibility to monkeypox virus infection: seroprevalence of orthopoxvirus in 4 population samples; France, Bolivia, Laos and Mali
Authors: Luciani Léa , Lapidus Nathanaël , Amroun Abdennour , Falchi Alessandra , Souksakhone Chanthala , Mayxay Mayfong , Dubot-Pérès Audrey , Saba Villarroel Paola Mariela , Diarra Issa , Koita Ousmane , Gallian Pierre , de Lamballerie Xavier 
Published: July 2022

AbstractEurope is experiencing an epidemic of monkeypox virus against a background of limited knowledge of population immunity to orthopoxviruses. We tested antibodies neutralizing vaccinia virus in blood samples from Bolivia (n=601), Laos (n=657), Mali (n=255) and France (n=4876). We also tested neutralization of cowpox virus in 4448 French samples, which confirmed extensive cross-immunity between both viruses. Using a cut-off titer of 20, seroprevalence is <1% in Bolivia, <5% in Laos (mainly related to vaccination in the elderly), 17.25% in Mali (related to both smallpox vaccination and the likely natural circulation of orthopoxviruses). In France, neutralizing antibodies are found (but at low prevalence) in age groups supposed to be vaccinated, suggesting both decrease in antibody titer in vaccinated individuals and decline in smallpox vaccine compliance before the end of compulsory vaccination. We conclude that the populations tested in Europe, Africa, Asia and South-America are massively susceptible to orthopoxvirus (e.g. monkeypox) infections.Article summary lineSeroprevalence of orthopoxvirus tested on 4 continents is very low, even for people born before the eradication of smallpox, making populations vulnerable to the emergence of zoonotic orthopoxviruses such as monkeypox virus.
Differential symptoms among COVID-19 outpatients before and during periods of SARS-CoV-2 Omicron variant dominance in Blantyre, Malawi: a prospective observational study
Authors: Chibwana Marah G. , Thole Herbert W. , Anscombe Cat , Ashton Philip M. , Green Edward , Barnes Kayla G. , Cornick Jen , Turner Ann , Witte Desiree , Nthala Sharon , Thom Chikondi , Kanyandula Felistas , Ainani Anna , Mtike Natasha , Tambala Hope , N’goma Veronica , Mwafulirwa Dorah , Asima Erick , Morton Ben , Gmeiner Markus , Gundah Zaziwe , Kawalazira Gift , French Neil , Feasey Nicholas , Heyderman Robert S. , Swarthout Todd D , Jambo Kondwani C. 
Published: July 2022

ABSTRACTBackgroundIt is widely reported that the SARS-CoV-2 Omicron variant has resulted in high number of cases, but relatively low incidence of severe disease and deaths, compared to the pre-Omicron variants of concern. We aim to assess the differences in symptom prevalence between Omicron and pre-Omicron infections in a sub-Saharan African population.MethodsIn this cross-sectional observational study, we collected data from children and adult outpatients presenting at two primary healthcare facilities in Blantyre, Malawi. Eligible participants were aged >1month old, with signs suggestive of COVID-19, and those not suspected of COVID-19. Nasopharyngeal swabs were collected for SARS-CoV-2 PCR testing and positive samples whole genome sequenced to identify the infecting variant. The primary outcome was the likelihood of presenting with a given symptom in individuals testing positive during the period in which Omicron-dominated (December 2021 to March 2022) with those infected during the pre-Omicron period (August 2021 to November 2021).FindingsAmong 5176 study participants, the median age was 28 years (IQR 21-38), of which 6.4% were under 5, 9.2% were 6 to 17 years, 77% were 18 to 50 years, and 7.1% were above 50 years old. Prevalence of SARS-CoV-2 infection was 23% (1187/5188), varying over time, with peaks in January 2021, July 2021 and December 2021, driven by the Beta (B.1.351), Delta (B.1.617.2) and Omicron (BA.1/2) variants, respectively. Headache (OR 0.47[CI 0.29 – 0.79]), cough (OR 0.37[CI 0.22 – 0.61]), fatigue (OR 0.20[CI 0.08 – 0.48]) and abdominal pain (OR 0.38[CI 0.18 – 0.78]) were less common in participants infected during the Omicron-dominant period than during pre-Omicron period. Fever was more common in participants infected during the Omicron-dominated period than during pre-Omicron period (OR 2.46[CI 1.29 – 4.97]). COVID-19 vaccination, accounting for number of doses and days since last dose, was not associated with a reduced risk of PCR-confirmed SARS-CoV-2 infection (1 dose, OR 1.10[CI 0.39 – 2.66]; 2 doses, OR 1.11[CI 0.40 – 2.57]; all p=0.8).InterpretationIn this Malawian population, the prevalence of clinical symptoms associated with Omicron infection differ from those of pre-Omicron infections and may be harder to identify clinically with current symptom guidelines. To maintain robust surveillance for COVID-19 and emerging variants, case definitions and testing policies will need to be regularly reviewed to ensure case ascertainment.
From The Plague Horrors of Cholera, What Partnership Lessons Can Be Learnt in Addressing COVID-19 in Zambia
Authors: Chota Pevious , Matenga Tulani Francis L. , Zulu Joseph Mumba , Mweemba Oliver 
Published: July 2022

AbstractSince the outbreak of COVID-19 on 31 December 2019, different public health systems have been grappling with how to address the spread of the virus. During the cholera outbreak and the Covid-19 pandemic in Zambia, values such as equity, partnership and collaboration have been recognized as central to resilience and an effective response to the pandemic. In this study we identify lessons that can be used for addressing the COVID-19 pandemic from partnership approach used in confronting the cholera outbreak of 2017-2018 in Zambia, Chipata Compound.MethodData was collected using a qualitative approach; 26 interviews were conducted with Public Health Professionals and community Leaders. Document reviews from government institutions and non-government institutions were also conducted. The Bergen model of Collaborative Functioning was used to guide the analysis of data.ResultsA top-down approach was observed to be important in addressing cholera but there was a need to improve a bottom-up approach. Synergistic results, avoidance of duplication, Oral cholera vaccination intervention and collaborative capacity building. Challenges in the partnership collaboration included inadequate resources, poor communication, poor coordination, lack of clear shared vision, reactive response, poor involvement of the community, hegemonic powers and mistrust and resentmentConclusionFrom the experience of cholera outbreaks, partnerships are vital in addressing pandemics. Based on the lessons from the cholera outbreaks, we note that there is a need to improve collaboration in partnership if COVID-19 and cholera are to be effectively addressed.
Clinical outcomes of antimicrobial resistance in cancer patients: A systematic review of multivariable models
Authors: Danielsen Anders Skyrud , Franconeri Léa , Page Samantha , Myhre Anders Eivind , Tornes Ragnhild Agathe , Kacelnik Oliver , Bjørnholt Jørgen Vildershøj 
Published: July 2022

AbstractBackgroundInfections are major causes of disease in cancer patients and pose a major obstacle to the success of cancer care. The global rise of antimicrobial resistance threatens to make these obstacles even greater and hinder continuing progress in cancer care. To prevent and handle such infections, better multivariable models building on current knowledge are needed. This internally funded systematic review (PROSPERO registration: CRD42021282769) aimed to review multivariable models of resistant infections/colonisations and corresponding mortality, what risk factors have been investigated, and with what methodological approaches.MethodsWe employed two broad searches of antimicrobial resistance in cancer patients, using terms associated with antimicrobial resistance, in MEDLINE and Embase through Ovid, in addition to Cinahl through EBSCOhost and Web of Science Core Collection. Primary, observational studies in English from January 2015 to November 2021 on human cancer patients that explicitly modelled infection/colonisation or mortality associated with antimicrobial resistance in a multivariable model were included. We extracted data on the study populations and their malignancies, risk factors, microbial aetiology, and methods for variable selection, and assessed the risk of bias using the NHLBI Study Quality Assessment Tools.ResultsTwo searches yielded a total of 27151 unique records, of which 144 studies were included after screening and reading. Of the outcomes studied, mortality was the most common (68/144, 47%). Forty-five per cent (65/144) of the studies focused on haemato-oncological patients, and 27% (39/144) studied several bacteria or fungi. Studies included a median of 200 patients and 46 events. One-hundred-and-three (72%) studies used a p-value-based variable selection. Studies included a median of seven variables in the final (and largest) model, which yielded a median of 7 events per variable. An in-depth example of vancomycin-resistant enterococci was reported.ConclusionsWe found the current research on this topic to be heterogeneous, in both the methodological and epidemiological approaches. Methodological choices resulting in very diverse models made it difficult or even impossible to draw statistical inferences and summarise what risk factors were of clinical relevance. The development and adherence to more standardised protocols that build on existing literature are urgent.
Clinical Utility of SPECT Neuroimaging in the Diagnosis and Treatment of Traumatic Brain Injury: A Systematic Review
Authors: Hanna Michael , Herman Jaclyn , Zawada Bartosz , Andraos Christine , Karbi Oscar , D’Souza Carina , Kessie Atiemo , Mazengia Getachew , D’Souza Sameer 
Published: July 2022

AbstractBackgroundThe most common assessment modalities to determine the level of injury following a traumatic brain injury (TBI) includes computerized tomography (CT) scans and/or magnetic resonance imaging (MRI). Evidence is mixed as to whether single photon emission computed tomography (SPECT) is specific and accurate in identifying TBI.ObjectivesThis study systematically assessed recent evidence of the clinical utility of SPECT in the diagnosis of TBI and examined the diagnostic accuracy of SPECT in TBI and its performance in comparison to other imaging modalities (e.g., CT and MRI).MethodsPubMed, MEDLINE, and Embase databases were systematically searched for published articles from December 2012 to July 2022. Randomized controlled trials (RCTs) and observational studies published in English that used SPECT to evaluate patients with all severity of TBIs were eligible for inclusion. Titles and abstracts were screened, and 111 selected full-text articles were independently screened based on predefined inclusion/exclusion criteria (guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PRISMA) and assessed for quality using the Newcastle-Ottawa Scale.ResultsFourteen eligible studies, all observational, reporting location of lesions on brain SPECT were included, reporting data from 21632 participants of which 20,746 participants were from one study; the remaining 886 participants were from the remaining13 studies. The heterogeneity of the data precludes a meta-analysis. There was no consensus among experts from the thirteen smaller studies; however, the largest study indicated that the specificity of visual readings was 54%. In particular, abnormalities and brain perfusions may lead to false positives. Quantitative analysis theoretically increases the reliability of findings for brain SPECT, but error rates are unknown and not published.ConclusionThere is a lack of evidence to support the clinical utility of brain SPECT for the diagnosis and treatment of TBI.
Implementation of the Liberia National Community Health Assistant (NCHA) Program and Under-five Mortality: A study protocol
Authors: Jockers Dominik , Ngafuan Richard , Baernighausen Till , Kessley Albert , White Emily E. , Kenny Avi , Kraemer John , Geedeh John , Rozelle Jeffrey , Holmes Leah , Obaje Hawa , Wheh Sylvester , Pederson Jon , Siedner Mark J. , Mendin Savior , Subah Marion , Hirschhorn Lisa R 
Published: July 2022

AbstractIntroductionBetween 2018 and 2022 the Liberian Government implemented the National Community Health Assistant (NCHA) program to improve provision of maternal and child health care to underserved rural areas of the country. Whereas the contributions of this and similar community health worker (CHW) based healthcare programs have been associated with improved process measures, the impact of a governmental CHW program at scale on child mortality has not been fully established.Methods/DesignWe will conduct a cluster sampled, community-based survey with landmark event calendars to retrospectively assess child births and deaths among all children born to women in the Grand Bassa District of Liberia. We will use a mixed effects discrete survival model, taking advantage of the staggered program implementation in Grand Bassa districts over a period of 4 years to compare rates of under-5 child mortality between the pre- and post-NCHA program implementation periods.DiscussionThis study will be the first to estimate the impact of the Liberian NCHA program on under-5 mortality.Trial registrationclinicaltrials.govNCT:NCT05123378
A Phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (Phase 3 part)
Authors: Yotsuyanagi Hiroshi , Ohmagari Norio , Doi Yohei , Imamura Takumi , Sonoyama Takuhiro , Ichihashi Genki , Sanaki Takao , Tsuge Yuko , Uehara Takeki , Mukae Hiroshi 
Published: July 2022

AbstractBackgroundLimited treatment options exist for patients with mild-to-moderate coronavirus disease 2019 (COVID-19), irrespective of vaccination history or risk status. Ensitrelvir is a novel oral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor. While phase 2 studies of ensitrelvir have demonstrated promising results in treating mild-to-moderate COVID-19, evaluation of its clinical efficacy due to shifting vaccination status and emergence of the Omicron variant represents significant challenges. Here, we describe the protocol for a phase 3 study designed to evaluate the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19, regardless of risk status or vaccination history.MethodsThis is a multicenter, randomized, double-blind, placebo-controlled, phase 3 study. Patients with mild-to-moderate COVID-19 within 120 hours from onset will be randomized in a 1:1:1 ratio into 3 treatment arms–ensitrelvir 125 mg (375 mg loading dose on Day 1), ensitrelvir 250 mg (750 mg loading dose on Day 1), and placebo. The study interventions will be administered orally, once daily, for 5 days. The primary endpoint will be the time to resolution of 5 symptoms of COVID-19 (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness), and the key secondary endpoints will include the change from baseline on Day 4 in the amount of SARS-CoV-2 viral RNA and the time to first negative SARS-CoV-2 viral titer. The primary population for the primary and key secondary endpoints will be patients with <72 hours from COVID-19 onset to randomization and, subsequently, patients in entire patient population (<120 hours) in the ensitrelvir 125 mg group. Closed testing procedure will be used for the primary and key secondary endpoints in both the primary and entire patient populations. All safety assessments and adverse events will be reported.DiscussionIn a post hoc analysis of the phase 2b study, compared with placebo, ensitrelvir demonstrated a reduced time to resolution of 5 symptoms in patients with mild-to-moderate COVID-19. Through this study, we intend to validate and establish the efficacy and safety of ensitrelvir in patients with mild-to-moderate COVID-19.Trial registrationJapan Registry of Clinical Trials (https://jrct.niph.go.jp): jRCT2031210350.
The metabolomic signature of weight loss in the Diabetes Remission Clinical Trial (DiRECT)
Authors: Corbin Laura J. , Hughes David A. , Bull Caroline J. , Vincent Emma E. , Smith Madeleine L. , McConnachie Alex , Messow Claudia-Martina , Welsh Paul , Taylor Roy , Lean Michael E. J. , Sattar Naveed , Timpson Nicholas J. 
Published: July 2022

AbstractUse of high-throughput metabolomics technologies in a variety of study designs has demonstrated a strong and consistent metabolomic signature of overweight and type 2 diabetes. However, the extent to which these metabolomic patterns can be recovered with weight loss and diabetes remission has not been investigated. We aimed to characterise the metabolomic consequences of a weight loss intervention in diabetes, within an existing randomised controlled trial – the Diabetes Remission Clinical Trial (DiRECT) – to provide insight into how weight loss-induced metabolic changes could lead to improved health. Decreases in branched chain amino acids, sugars and LDL triglycerides, and increases in sphingolipids, plasmalogens and metabolites related to fatty acid metabolism were associated with the intervention. The change in metabolomic pattern with mean 8.8kg weight loss thus reverses many features associated with the development of type 2 diabetes. Furthermore, metabolomic profiling also appears to capture variation in response to treatment seen across patients.
COVID-19 Prevention at Institutions of Higher Education, United States, 2020 – 2021: Implementation of Nonpharmaceutical Interventions
Authors: Moreland Sarah , Zviedrite Nicole , Ahmed Faruque , Uzicanin Amra 
Published: July 2022

AbstractBackgroundIn early 2020, following the start of the coronavirus disease 2019 (COVID-19) pandemic, institutions of higher education (IHEs) across the United States rapidly pivoted to distance learning to reduce risk of on-campus virus transmission.ObjectiveTo explore IHE use of nonpharmaceutical interventions (NPIs) during the subsequent pandemic-affected academic year 2020–2021.DesignCross-sectional study of data collected January – June 2021. Setting: US four-year, undergraduate IHEs.Patients (or Participants)All public (n=547) and a stratified random sample of private (n=300) IHEs.MeasurementsFrom IHE websites, we documented NPIs, including changes to the calendar, learning environment, housing, common areas, and dining; COVID-19 testing; and facemask protocols, and performed weighted analysis to assess congruence with the US Centers for Disease Control and Prevention (CDC) guidance for IHEs. We used weighted multivariable linear regression to explore the association between IHE characteristics and the summated number of implemented NPIs.ResultsOverall, 20% of IHEs implemented all surveyed CDC-recommended NPIs. The most frequently utilized were learning environment changes (91%), practiced as one or more of the following: distance or hybrid learning opportunities (98%), 6-feet spacing (60%), and reduced class sizes (51%). Additionally, 88% of IHEs specified facemask protocols, 78% physically modified common areas, and 67% offered COVID-19 testing. Among the 33% of IHEs offering ≥50% of courses in person, having <1,000 students was associated with having implemented fewer NPIs than IHEs with ≥1,000 students.LimitationsData collected from publicly available sources may introduce observation biases but allow for large sample size.ConclusionOnly 1 in 5 IHEs implemented all surveyed CDC recommendations, while a majority implemented a subset. IHE size and location were associated with degree of NPI implementation. Additional research is needed to assess adherence to NPI implementation in IHE settings.Funding SourceUnited States Centers for Disease Control and Prevention