bluuebunny/crossref_metadata_2025_split huggingface dataset:
General practitioner wellbeing during the COVID-19 pandemic: a qualitative interview study
Authors: Jefferson Laura , Heathcote Claire , Bloor Karen 
Published: January 2022

AbstractBackgroundWorkload pressures and poor job satisfaction have been reported by UK general practitioners (GPs) for some time. The COVID-19 pandemic presented new challenges, with growing international evidence of its negative impact on GPs’ mental health and wellbeing. While there has been wide commentary on this topic, UK research evidence is lacking. Developing greater understanding of these lived experiences and subgroup differences is important as doctor wellbeing may affect the sustainability of health care systems and quality of patient care.ObjectivesTo explore the lived experience of UK GPs during COVID-19, and the pandemic’s impact on their psychological wellbeing.Design and SettingIn-depth qualitative interviews, conducted remotely by telephone or video call, with NHS GPs.ParticipantsGPs were sampled purposively across three career stages (early career, established and late career or retired GPs) with variation in other key demographics. A comprehensive recruitment strategy used multiple channels. Data were analysed thematically using Framework Analysis.ResultsWe interviewed 40 GPs; most described generally negative sentiment and many displayed signs of psychological distress and burnout. Causes of stress and anxiety related to personal risk, workload, practice changes, public perceptions and leadership, teamworking and wider collaboration and personal challenges. GPs described facilitators of their wellbeing, including sources of support and plans to reduce clinical hours or change career path.ConclusionsA range of factors detrimentally affected the wellbeing of GPs during the pandemic and we highlight the potential impact of this on workforce retention and quality of care. As the pandemic progresses and general practice faces continued challenges, urgent policy measures are now needed.Strengths and limitations of this studyWhile there is growing international evidence base demonstrating the impact of the COVID-19 pandemic on GPs’ wellbeing and much UK media coverage, this qualitative interview study provides much-needed research evidence of UK GPs’ lived experiences and wellbeing during COVID-19.40 GPs were sampled purposively to include GPs with different demographic and practice characteristics.While there are no easy solutions to the problems highlighted, this research provides increased contextualised understanding of how these experiences may impact future workforce retention and the sustainability of health systems longer-term.Sub-group differences by gender and age are reported; highlighting a potential need for further research and support targeted at specific groups.Findings are necessarily limited to the time of data collection (Spring/Summer 2021); further tensions in general practice have since arisen, particularly regarding negative and misleading media portrayal.
SARS-CoV-2 third vaccine immune response in MS patients treated with ocrelizumab
Authors: Brill Livnat , Raposo Catarina , Rechtman Ariel , Zveik Omri , Levin Netta , Oiknine-Djian Esther , Wolf Dana G. , Vaknin-Dembinsky Adi 
Published: January 2022

AbstractThe introduction of a third dose vaccination along with new variants of concerns raises questions regarding serology and T-cell responses in patients with MS (pwMS) treated with B-cell depletion who develop attenuated humoral response to vaccines. The aim of this study is to longitudinally evaluate humoral and cellular response to SARS-CoV-2 mRNA vaccine in ocrelizumab-treated pwMS before and following third vaccine dose. Following the third vaccine dose, patients who are low or non-responders following initial vaccination did not increase antibody titers. In HCs and ocrelizumab-treated pwMS, cellular response decreased 6 months following initial vaccination and increased significantly after the third booster.
Mentalizing abilities mediate the impact of the low-level social cognitive processes on negative symptoms
Authors: Okruszek Ł. , Chrustowicz M. , Jarkiewicz M. , Krawczyk M. , Manera V. , Piejka A. , Schudy A. , Wiśniewska M. , Wysokiński A. 
Published: January 2022

AbstractSocial cognitive deficits are currently considered as one of the main predictors of clinical symptoms and functional outcome in patients with schizophrenia. Multiple studies have suggested that two-factor solution (low-level vs. high-level) best describes the structure of social cognitive processes in patients. While higher-order processes have been repeatedly linked to negative symptoms, no such association was found for lower-level processes. Thus, the aim of the current study is to examine whether the association between low-level socio-perceptual processes and symptoms in patients with schizophrenia is mediated by higher-order socio-inferential abilities. One hundred thirty-nine patients have completed basic communicative interactions processing (CID-12) and mind reading (Reading the Mind in the Eyes task) tasks. In line with our hypothesis, we have observed full mediation of the effects of basic social perception abilities on negative symptoms via mentalizing abilities in patients. This effect suggests that, similarly as in the case of positive symptoms, a hierarchical nature of social cognitive processes should be considered while investigating negative symptoms of schizophrenia.
Fifteen Days in December: Capture and Analysis of Omicron-Related Travel Restrictions
Authors: Schermerhorn Jordan , Case Alaina , Graeden Ellie , Kerr Justin , Moore Mackenzie , Robinson-Marshall Siobhan , Wallace Trae , Woodrow Emily , Katz Rebecca 
Published: January 2022

AbstractFollowing the identification of the Omicron variant of the SARS-CoV-2 virus in late November 2021, governments worldwide took actions intended to minimize the impact of the new variant within their borders. Despite guidance from the World Health Organization advising a risk-based approach, many rapidly implemented stringent policies focused on travel restrictions. In this paper, we capture 221 national-level travel policies issued during the three weeks following publicization of the Omicron variant. We characterize policies based upon whether they target travelers from specific countries or focus more broadly on enhanced screening, and explore differences in approaches at the regional level. We find that initial reactions almost universally focused on entry bans and flight suspensions from Southern Africa, and that policies continued to target travel from these countries even after community transmission of the Omicron variant was detected elsewhere in the world. While layered testing and quarantine requirements were implemented by some countries later in this three-week period, these enhanced screening policies were rarely the first response. The timing and conditionality of quarantine and testing requirements were not coordinated between countries or regions, creating logistical complications and burdening travelers with costs. Overall, response measures were rarely tied to specific criteria or adapted to match the unique epidemiology of the new variant.Summary boxDuring the initial three-week period following the discovery of the SARS-CoV-2 Omicron variant, nations rushed to implement travel restrictions - often at odds with guidance from the World Health Organization.By sourcing and cataloging initial national-level travel restrictions worldwide, we demonstrate how the distribution of entry bans, flight suspensions, quarantine measures, vaccination requirements, and testing protocols evolved in response to emerging information during a period of uncertainty.Countries that issued entry bans almost universally targeted the same Southern African countries and continued to do so even after widespread community transmission of the Omicron variant was reported elsewhere in the world.Layers of testing and quarantine requirements were added later during the observation period but were rarely the initial response, with the exception of restrictions issued by countries in Africa, where leading with enhanced screening measures was more common.Analysis of the disconnect between travel restrictions and transmission patterns that followed emergence of the Omicron variant provides a basis to inform evidence-based control measures for future virus mitigation efforts.
Static magnetic stimulation induces structural plasticity at the axon initial segment of inhibitory cortical neurons
Authors: Beros J.L. , King E.S. , Clarke D. , Rodger J. , Tang A.D 
Published: January 2022

AbstractStatic magnetic stimulation (SMS) is a form of non-invasive brain stimulation that can alter neural activity and induce neural plasticity that outlasts the period of stimulation. While SMS is typically delivered for short periods (e.g., 10 minutes) to alter corticospinal excitability or motor behaviours, the plasticity mechanisms that can be induced with longer periods of stimulation have not been explored. In mammalian neurons, the axon initial segment (AIS) is the site of action potential initiation and undergoes structural plasticity as a homeostatic mechanism to counteract chronic changes in neuronal activity. Therefore, we investigated whether the chronic application of SMS would induce structural AIS plasticity in cortical neurons. SMS (0.5 Tesla in intensity) was delivered to postnatally derived mouse primary cortical neurons consisting of mainly inhibitory neurons, for 6 or 48 hours beginning from 7 days in vitro (DIV7). AIS structural plasticity (length and starting distance from the soma) was quantified immediately after and 24 hours post-stimulation. Following 6 hours of stimulation, we observed an immediate decrease in median AIS length compared to control, that persisted to 24 hours post stimulation. In addition, there was a distal shift in the AIS start position relative to the soma that was only observed 24 hours after the 6-hour stimulation. Following 48 hours of stimulation, we observed an immediate shortening of AIS length and a distal shift in AIS start position relative to the soma, however only the distal shift in AIS start position persisted to 24 hours post-stimulation. Our findings provide the foundation to expand the use of SMS to more chronic applications as a method to study or promote AIS plasticity non-invasively.
African-Ancestry Associated Gene Expression Signatures and Pathways in Triple Negative Breast Cancer, a Comparison across Women of African Descent
Authors: Martini Rachel , Delpe Princesca , Chu Timothy R. , Arora Kanika , Lord Brittany , Verma Akanksha , Chen Yalei , Gebregzabher Endale , Oppong Joseph K. , Adjei Ernest K. , Jibril Aisha , Awuah Baffour , Bekele Mahteme , Abebe Engida , Kyei Ishmael , Aitpillah Frances S. , Adinku Michael O. , Ankomah Kwasi , Osei-Bonsu Ernest B. , Chitale Dhananjay , Bensenhaver Jessica M. , Nathanson Saul David , Jackson LaToya , Jiagge Evelyn , Petersen Lindsay F. , Proctor Erica , Gyan Kofi K. , Gibbs Lee , Monojlovic Zarko , Kittles Rick , White Jason , Yates Clayton , Manne Upender , Gardner Kevin , Mongan Nigel , Cheng Esther , Ginter Paula , Hoda Syed , Elemento Olivier , Robine Nicolas , Sboner Andrea , Carpten John , Newman Lisa , Davis Melissa B. 
Published: January 2022

ABSTRACTWomen of sub-Saharan African ancestry have disproportionately higher incidence of aggressive, early-onset Triple Negative Breast Cancer (TNBC), and TNBC mortality across all race groups. Population-based comparative studies show racial differences in TNBC tumor biology, with higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, most investigations relied on self-reported race (SRR) of primarily United States (US) populations. However, given that genetic admixture in AAs is extremely heterogenous, and race-correlated social determinants can translate into biological differences, the true association of African ancestry with TNBC biology and gene expression is currently unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using genetic ancestry estimation in this African-enriched cohort, we identified 613 genes associated with African ancestry and more than 2200 genes associated with regional-level African ancestry. Functional enrichment and deconvolution revealed tumor-associated immune cell infiltration and activity.STATEMENT OF SIGNIFICANCEUsing a rigorous ancestry quantification process, we show that TNBC has ancestry-associated gene expression profiles, linked to immunological landscapes, which may contribute to racial differences in clinical outcomes. This is the first study to show the definitive link to tumor immunological landscape, associated with African ancestry, using a multiethnic African-enriched cohort.
Long-term and low-level envelope C2V3 stimulation from highly diverse virus isolates leads to frequent development of broad and elite antibody neutralization in HIV-1 infected individuals
Authors: Martin Francisco , Marcelino José Maria , Palladino Claudia , Bártolo Inês , Tracana Susana , Moranguinho Inês , Gonçalves Paloma , Mateus Rita , Calado Rita , Borrego Pedro , Leitner Thomas , Clemente Sofia , Taveira Nuno 
Published: January 2022

AbstractElicitation of potent neutralizing antibodies against genetically diverse HIV-1 isolates is important for an effective HIV-1 vaccine. Some HIV-1 infected patients produce such broadly neutralizing antibodies (bNAbs). Identification of host and viral correlates of bNAb production may help develop the next generation of HIV-1 vaccines. We carried out the first detailed characterization of the neutralizing antibody response and identify viral and host factors associated with the development of bNAbs in HIV-1 infected patients from Angola, one of the oldest, more dynamic, and diverse HIV-1 epidemics in the world. Plasma samples from 322 HIV-1 infected patients were collected in 2001, 2009 and 2014. Phylogenetic analysis of C2V3C3 envelope sequences identified a diverse array of subtypes including A1, A2, B, C, D, F1, G, H, J, untypable strains, and recombinant forms which prevailed over pure subtypes. Notably, 56% of the patients developed cross, broad, or elite neutralizing responses against a reference panel of tier 2 Env-pseudoviruses far exceeding results obtained elsewhere in the world. The frequency of elite neutralizers was higher in 2014, when patients were on ART and had low viremia, than in 2009 when patients were drug naive. In drug naïve patients, broad neutralization was associated with subtype C infection, lower CD4+ T cell counts, higher age, or higher titer of C2V3C3-specific antibodies relative to patients that did not develop bNAbs. Neutralizing antibodies targeted the V3-glycan supersite in most patients but antibodies specific for the V2 apex, the CD4 binding site, the gp41 membrane-proximal external region (MPER) and unknown epitopes were also found in some patients. V3 and C3 regions were significantly less variable and less subject to positive selection in elite neutralizers compared to weak or no neutralizers suggesting an active role of bNabs directed against these regions in controlling HIV-1 replication and diversification. Hence, development of broad and elite antibody neutralization against HIV-1 requires long-term and low-level envelope V3C3 stimulation from highly diverse subtype C isolates. These results have direct implications for the design of a new generation of HIV-1 vaccines.
Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1, updates to tumour pathology and cancer incidences
Authors: Lee Andrew , Mavaddat Nasim , Cunningham Alex P. , Carver Tim , Archer Stephanie , Walter Fiona M. , Tischkowitz Marc , Roberts Jonathan , Usher-Smith Juliet , Simard Jacques , Schmidt Marjanka K. , Devilee Peter , Zadnik Vesna , Jürgens Hannes , Mouret-Fourme Emmanuelle , De Pauw Antoine , Rookus Matti , Mooij Thea M. , Pharoah Paul P.D. , Easton Douglas F. , Antoniou Antonis C. 
Published: January 2022

AbstractBackgroundBOADICEA for breast cancer and the epithelial ovarian cancer (EOC) models included in the CanRisk tool (www.canrisk.org) provide future cancer risks based on rare pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast-density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors.MethodsBOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1, RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult-height as continuous.ResultsBARD1, RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34-44% of these carriers would be reclassified to the near-population and 15-22% to the high-risk categories based on the UK NICE guidelines. Including height as continuous, increased the BC relative-risk variance from 0.002 to 0.010.ConclusionsThese extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options.
Explainable deep transfer learning model for disease risk prediction using high-dimensional genomic data
Authors: Liu Long , Meng Qingyu , Weng Cherry , Lu Qing , Wang Tong , Wene Yalu 
Published: January 2022

AbstractBuilding an accurate disease risk prediction model is an essential step in the modern quest for precision medicine. While high-dimensional genomic data provides valuable data resources for the investigations of disease risk, their huge amount of noise and complex relationships between predictors and outcomes have brought tremendous analytical challenges. Deep learning model is the state-of-the-art methods for many prediction tasks, and it is a promising framework for the analysis of genomic data. However, deep learning models generally suffer from the curse of dimensionality and the lack of biological interpretability, both of which have greatly limited their applications. In this work, we have developed a deep neural network (DNN) based prediction modeling framework. We first proposed a group-wise feature importance score for feature selection, where genes harboring genetic variants with both linear and non-linear effects are efficiently detected. We then designed an explainable transfer-learning based DNN method, which can directly incorporate information from feature selection and accurately capture complex predictive effects. The proposed DNN-framework is biologically interpretable, as it is built based on the selected predictive genes. It is also computationally efficient and can be applied to genome-wide data. Through extensive simulations and real data analyses, we have demonstrated that our proposed method can not only efficiently detect predictive features, but also accurately predict disease risk, as compared to many existing methods.Author summaryAccurate disease risk prediction is an essential step towards precision medicine. Deep learning models have achieved the state-of-the-art performance for many prediction tasks. However, they generally suffer from the curse of dimensionality and lack of biological interpretability, both of which have greatly limited their applications to the prediction analysis of whole-genome sequencing data. We present here an explainable deep transfer learning model for the analysis of high-dimensional genomic data. Our proposed method can detect predictive genes that harbor genetic variants with both linear and non-linear effects via the proposed group-wise feature importance score. It can also efficiently and accurately model disease risk based on the detected predictive genes using the proposed transfer-learning based network architecture. Our proposed method is built at the gene level, and thus is much more biologically interpretable. It is also computationally efficiently and can be applied to whole-genome sequencing data that have millions of potential predictors. Through both simulation studies and the analysis of whole-genome sequencing data obtained from the Alzheimer’s Disease Neuroimaging Initiative, we have demonstrated that our method can efficiently detect predictive genes and it has better prediction performance than many existing methods.
Regional connectivity drove bidirectional transmission of SARS-CoV-2 in the Middle East during travel restrictions
Authors: Parker Edyth , Anderson Catelyn , Zeller Mark , Tibi Ahmad , Havens Jennifer L. , Laroche Geneviève , Benlarbi Mehdi , Ariana Ardeshir , Robles-Sikisaka Refugio , Latif Alaa Abdel , Watts Alexander , Awidi Abdalla , Jaradat Saied A. , Gangavarapu Karthik , Ramesh Karthik , Kurzban Ezra , Matteson Nathaniel L. , Han Alvin X. , Hughes Laura D. , McGraw Michelle , Spencer Emily , Nicholson Laura , Khan Kamran , Suchard Marc A. , Wertheim Joel O. , Wohl Shirlee , Côté Marceline , Abdelnour Amid , Andersen Kristian G. , Abu-Dayyeh Issa 
Published: January 2022

SummaryRegional connectivity and land-based travel have been identified as important drivers of SARS-CoV-2 transmission. However, the generalizability of this finding is understudied outside of well-sampled, highly connected regions such as Europe. In this study, we investigated the relative contributions of regional and intercontinental connectivity to the source-sink dynamics of SARS-CoV-2 for Jordan and the wider Middle East. By integrating genomic, epidemiological and travel data we show that the source of introductions into Jordan was dynamic across 2020, shifting from intercontinental seeding from Europe in the early pandemic to more regional seeding for the period travel restrictions were in place. We show that land-based travel, particularly freight transport, drove introduction risk during the period of travel restrictions. Consistently, high regional connectivity and land-based travel also disproportionately drove Jordan’s export risk to other Middle Eastern countries. Our findings emphasize regional connectedness and land-based travel as drivers of viral transmission in the Middle East. This demonstrates that strategies aiming to stop or slow the spread of viral introductions (including new variants) with travel restrictions need to prioritize risk from land-based travel alongside intercontinental air travel to be effective.HighlightsRegional connectivity drove SARS-CoV-2 introduction risk in Jordan during the period travel restrictions were in place in genomic and travel data.Land-based travel rather than air travel disproportionately drove introduction risk during travel restrictions.High regional connectivity disproportionately drove Jordan’s export risk, with significant contribution from land-based travel.Regional transmission dynamics were underestimated in genomic data due to unrepresentative sampling.