bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal transitions and phenotypic evolution in Barrett esophagus
Authors: Evans James A , Carlotti Emanuela , Lin Meng-Lay , Hackett Richard J , Passman Adam , Dunn Lorna , Elia George , Porter Ross J , McClean Mairi H , Hughes Frances , ChinAleong Joanne , Woodland Philip , Preston Sean L , Griffin S Michael , Lovat Laurence , Rodriguez-Justo Manuel , Wright Nicholas A , Jansen Marnix , McDonald Stuart AC 
Published: April 2021

AbstractBackground & AimsBarrett esophagus (BE) is a risk factor for the development of esophageal adenocarcinoma, however our understanding of how Barrett esophagus evolves is still poorly understood. We demonstrate that dynamic clonal phenotypic changes occur at the gland level, the mechanism by which these changes evolve, and how diversity may play a role in progression.MethodsWe analyzed the distribution and diversity of gland phenotype between and within BE biopsies and the background mucosa of those that had progressed to dysplasia or developed BE post-esophagectomy, using immunohistochemistry and H&E analysis. Clonal relationships between distinct gland types were determined by laser capture microdissection sequencing of the mitochondrial genome.ResultsFive different non-dysplastic gland phenotypes were identified in a cohort of 64 patients biopsies taken at the same physical location in the esophagus; most non-dysplastic patients showed a single gland phenotype per biopsy, but some showed two or three gland types. We reveal a shared common ancestor between parietal cell-containing oxynto-cardiac glands and goblet cell-containing specialized Barrett glands through a shared somatic mtDNA mutation. We also reveal a similar relationship between specialized and cardiac-type glands, and specialized and Paneth cell-containing glands. The diversity of gland types was significantly increased adjacent to dysplasia compared to non-dysplastic BE and patients with post-esophagectomy BE, suggesting that gland diversity evolves in BE patients over time.ConclusionsWe have shown that the range of BE phenotypes represent an evolutionary process and that changes in gland diversity may play a role in progression. Furthermore, we demonstrate common ancestry between gastric and intestinal glands in BE.Graphic abstractA) The cardiac gland as the basic unit of Barrett esophagus that can evolve into phenotypes that adapt to the esophageal microenvironment. B) Phenotypic diversity of non-dysplastic glands is associated with the presence of dysplasia or cancer in patients with BE.
Loss of C2orf69 defines a fatal auto-inflammatory mitochondriopathy in Humans and Zebrafish
Authors: Wong Hui Hui , Seet Sze Hwee , Maier Michael , Traspas Ricardo Moreno , Lee Cheryl , Shan Zhang , Loh Abigail Y. T. , Chia Crystal Y. , Teoh Tze Shin , Sng Danielle , Cepni Ece , Nathan Fatima M. , Sirota Fernanda L. , Chao Liang , Tadahiro Mitani , Mbarek Hamdi , Georgiadou Danai , Sotiropoulou Kortessa , Paul Franziska , Pehlivan Davut , Lainé Candice , Chai Guoliang , Ali Nur Ain , Choo Siew Chin , Boisson Bertrand , Xue Shifeng , Kayserili Hulya , Zaki Maha , Isfort Robert J. , Bauer Peter , Rezaei Nima , Seyedpour Simin , Khotaei Ghamar Taj , Bascom Charles C. , Chaabouni Myriam , AlSubhi Afaf , Eyaid Wafaa , Işıkay Sedat , Gleeson Joseph G. , Lupski James R. , Casanova Jean-Laurent , Maurer-Stroh Sebastian , Bertoli-Avella Aida , Mathuru Ajay S. , Ho Lena , Bard Frederic , Reversade Bruno 
Published: April 2021

AbstractHuman C2orf69 is an evolutionary-conserved gene whose function is unknown. Here, we report 9 children from 5 unrelated families with a fatal syndrome consisting of severe auto-inflammation, progredient leukoencephalopathy with recurrent seizures that segregate homozygous loss-of-function C2orf69 variants. C2ORF69 orthologues, which can be found in most eukaryotic genomes including that of unicellular phytoplanktons, bear homology to esterase enzymes. We find that human C2ORF69 is loosely bound to the mitochondrion and its depletion affects mitochondrial membrane potential in human fibroblasts and neurons. Moreover, we show that CRISPR/Cas9-inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures which is accompanied by persistent brain inflammation. Collectively, our results delineate a novel auto-inflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems as demonstrated in patients and in a zebrafish model of the disease.One Sentence SummaryC2orf69 is a putative enzyme whose inactivation in humans and zebrafish causes a hitherto unknown auto-inflammatory syndrome.
Pharmacotherapy, drug-drug interactions and potentially inappropriate medication in depressive disorders
Authors: Wolff Jan , Reißner Pamela , Hefner Gudrun , Normann Claus , Kaier Klaus , Binder Harald , Hiemke Christoph , Toto Sermin , Domschke Katharina , Marschollek Michael , Klimke Ansgar 
Published: April 2021

AbstractIntroductionThe aim of this study was to describe the number and type of drugs used to treat depressive disorders in inpatient psychiatry and to analyse the determinants of potential drug-drug interactions (pDDI) and potentially inappropriate medication (PIM).MethodsOur study was part of a larger pharmacovigilance project funded by the German Innovation Funds. It included all inpatients with a main diagnosis in the group of depressive episodes (F32, ICD-10) or recurrent depressive disorders (F33) discharged from eight psychiatric hospitals in Germany between 1 October 2017 and 30 September 2018 or between 1 January and 31 December 2019.ResultsThe study included 14,418 inpatient cases. The mean number of drugs per day was 3.7 (psychotropic drugs = 1.7; others = 2.0). Thirty-one percent of cases received at least five drugs simultaneously (polypharmacy). Almost one half of all cases received a combination of multiple antidepressant drugs (24.8%, 95% CI 24.1% - 25.5%) or a treatment with antidepressant drugs augmented by antipsychotic drugs (21.9%, 95% CI 21.3% - 22.6%). The most frequently used antidepressants were selective serotonin reuptake inhibitors, followed by serotonin and norepinephrine reuptake inhibitors and tetracyclic antidepressants. In multivariate analyses, cases with recurrent depressive disorders and cases with severe depression were more likely to receive a combination of multiple antidepressant drugs (Odds ratio recurrent depressive disorder: 1.56, 95% CI 1.41 - 1.70, severe depression 1.33, 95% CI 1.18 - 1.48). The risk of any pDDI and PIM in elderly patients increased substantially with each additional drug (Odds Ratio: pDDI 1.32, 95% CI: 1.27 - 1.38, PIM 1.18, 95% CI: 1.14 - 1.22) and severity of disease (Odds Ratio per point on CGI-Scale: pDDI 1.29, 95% CI: 1.11 - 1.46, PIM 1.27, 95% CI: 1.11 - 1.44), respectively.ConclusionThis study identified potential sources and determinants of safety risks in pharmacotherapy of depressive disorders and provided additional data which were previously unavailable. Most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and pDDI and PIM are relatively frequent. Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles.
Predicting Infection-related Consultations on Intensive Care Units - Development of a Machine Learning Prediction Model
Authors: Luz Christian F. , Soudis Dimitrios , Renes Maurits H. , Zwerwer Leslie R. , Giudice Nicoletta , Glasner Corinna , Nijsten Maarten W. N. , Sinha Bhanu 
Published: April 2021

AbstractObjectivesInfection-related consultations on intensive care units (ICU) build an important cornerstone in the care for critically ill patients with (suspected) infections. The positive impact of consultations on quality of care and clinical outcome has previously been demonstrated. However, timing is essential and to date consultations are typically event-triggered and reactive. Here, we investigate a proactive approach by predicting infection-related consultations using machine learning models and routine electronic health records (EHR).MethodsWe used data from a mixed ICU at a large academic tertiary care hospital including 9684 admissions. EHR data comprised demographics, laboratory results, point-of-care tests, vital signs, line placements, and prescriptions. Consultations were performed by clinical microbiologists. The predicted target outcome (occurrence of a consultation) was modelled using random forest (RF), gradient boosting machines (RF), and long short-term memory neural networks (LSTM).ResultsOverall, 7.8 % of all admission received a consultation. Time-sensitive modelling approaches and increasing numbers of patient features (parameters) performed better than static approaches in predicting infection-related consultations at the ICU. Splitting a patient admission into eight-hour intervals and using LSTM resulted in the accurate prediction of consultations up to eight hours in advance with an area under the receiver operator curve of 0.921 and an area under precision recall curve of 0.673.ConclusionWe could successfully predict of infection-related consultations on an ICU up to eight hours in advance, even without using classical triggers, such as (interim) microbiology reports. Predicting this key event can potentially streamline ICU and consultant workflows and improve care and outcome for critically ill patients with (suspected) infections.
Efficient Maternal to Neonatal transfer of SARS-CoV-2 and BNT162b2 antibodies
Authors: Beharier Ofer , Mayo Romina Plitman , Raz Tal , Sacks Kira Nahum , Schreiber Letizia , Suissa-Cohen Yael , Chen Rony , Gomez-Tolub Rachel , Hadar Eran , Gabbay-Benziv Rinat , Moshkovich Yuval Jaffe , Biron-Shental Tal , Shechter-Maor Gil , Farladansky-Gershnabel Sivan , Sela Hen Yitzhak , Raischer Hedi Benyamini , Sela Nitzan Dana , Goldman-Wohl Debra , Shulman Ziv , Many Ariel , Barr Haim , Yagel Simcha , Neeman Michal , Kovo Michal 
Published: April 2021

ABSTRACTBackgroundThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.MethodsA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to three study groups: vaccinated (n=86); PCR confirmed SARS-CoV-2 infected during pregnancy (n=65), and unvaccinated non-infected controls (n=62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD and N).ResultsBNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (Anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer rate was significantly lower for third-trimester as compared to second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.ConclusionsAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.
Fundamental limitations of case isolation
Authors: Hansson Jonas , Govaert Alain , Pates Richard , Tegling Emma , Soltesz Kristian 
Published: April 2021

AbstractCase isolation is a strategy with the potential to curb infectious disease epidemics. Expressions for the stability boundary of a case isolation scheme defined through the proportion of the infectious population that it isolates with a given delay have recently been established. Here we quantify how this stability boundary moves when heterogeneity of the inter-individual contact network increases, and explain the underlying mechanism through insightful examples.
Immunogenicity of COVID-19 Tozinameran Vaccination in Patients on Chronic Dialysis
Authors: Schrezenmeier Eva , Bergfeld Leon , Hillus David , Lippert Joerg-Detlev , Weber Ulrike , Tober-Lau Pinkus , Landgraf Irmgard , Schwarz Tatjana , Kappert Kai , Stefanski Ana-Luisa , Sattler Arne , Kotsch Katja , Doerner Thomas , Sander Leif Erik , Budde Klemens , Halleck Fabian , Kurth Florian , Corman Victor Max , Choi Mira 
Published: April 2021

AbstractObjectivePatients with kidney failure have notoriously weak responses to common vaccines. Thus, immunogenicity of novel SARS-CoV-2 vaccines might be impaired in this group. To determine immunogenicity of SARS-CoV-2 vaccination in patients with chronic dialysis, we analyzed the humoral and T-cell response after two doses of mRNA vaccine Tozinameran (BNT162b2 BioNTech/Pfizer).Design, Settings, and ParticipantsThis observational study included 43 patients on dialysis before vaccination with two doses of Tozinameran 21 days apart. Overall, 36 patients completed the observation period. Serum samples were analyzed by SARS-CoV-2 specific antibodies ∼1 and ∼3-4 weeks after the second vaccination. In addition, SARS-CoV-2-specific T-cell responses were assessed at the later time point by an interferon-gamma release assay (IGRA). Outcomes at later timepoints were compared to a group of 44 elderly patients with no dialysis after immunization with Tozinameran.ExposuresBlood drawings during regular laboratory routine assessment right before start of dialysis therapy or at the time of vaccination and at follow-up study visits.Main Outcomes and MeasuresAssessment of immunogenicity after vaccination against SARS-CoV-2 in patients on and without dialysis.ResultsMedian age of patients on chronic dialysis was 74.0 years (IQR 66.0, 82.0). The proportion of males was higher (69.4%) than females. Only 20/36 patients (55.6%, 95%CI: 38.29-71.67) developed SARS-CoV-2-IgG antibodies at first sampling, whereas 32/36 patients (88.9%, 95%CI:73.00-96.38) demonstrated seropositivity at the second sampling. Seroconversion rates and antibody titers were significantly lower compared to a cohort of vaccinees with similar age but no chronic dialysis (>90% seropositivity). SARS-CoV-2-specific T-cell responses 3 weeks after second vaccination were detected in 21/31 vaccinated dialysis patients (67.7%, 95%CI: 48.53-82.68) compared to 42/44 (93.3%, 95%CI: 76.49-98.84) in controls of similar age.Conclusion and RelevancePatients on dialysis demonstrate a delayed, but robust immune response three weeks after the second dose, which indicates effective vaccination of this vulnerable group. However, the lower immunogenicity of Tozinameran in these patients needs further attention to develop potential countermeasures such as an additional booster vaccination.
Impacts of worldwide individual non-pharmaceutical interventions on COVID-19 transmission across waves and space
Authors: Ge Yong , Zhang Wen-Bin , Liu Haiyan , Ruktanonchai Corrine W , Hu Maogui , Wu Xilin , Song Yongze , Ruktanonchai Nick W , Yan Wei , Cleary Eimear , Feng Luzhao , Li Zhongjie , Yang Weizhong , Liu Mengxiao , Tatem Andrew J , Wang Jin-Feng , Lai Shengjie 
Published: April 2021

AbstractGovernments worldwide have rapidly deployed non-pharmaceutical interventions (NPIs) to mitigate the COVID-19 pandemic. However, the effect of these individual NPI measures across space and time has yet to be sufficiently assessed, especially with the increase of policy fatigue and the urge for NPI relaxation in the vaccination era. Using the decay ratio in the suppression of COVID-19 infections, we investigated the changing performance of different NPIs across waves from global and regional levels (in 133 countries) to national and subnational (in the United States of America [USA]) scales before the implementation of mass vaccination. The synergistic effectiveness of all NPIs for reducing COVID-19 infections declined along waves, from 95.4% in the first wave to 56.0% in the third wave recently at the global level and similarly from 83.3% to 58.7% at the USA national level, while it had fluctuating performance across waves on regional and subnational scales. Regardless of geographical scale, gathering restrictions and facial coverings played significant roles in epidemic mitigation before the vaccine rollout. Our findings have important implications for continued tailoring and implementation of NPI strategies, together with vaccination, to mitigate future COVID-19 waves, caused by new variants, and other emerging respiratory infectious diseases.
Quantifying Face Mask Comfort
Authors: Koh Esther , Ambatipudi Mythri , Boone DaLoria L. , Luehr Julia B. W. , Blaise Alena , Gonzalez Jose , Sule Nishant , Mooney David J. , He Emily M. 
Published: April 2021

AbstractFace mask usage is one of the most effective ways to limit SARS-CoV-2 transmission, but a mask is only useful if user compliance is high. Through anonymous surveys, we show that mask discomfort is the primary source of noncompliance in mask wearing. Further, through these surveys, we identify three critical parameters that dictate mask comfort: air resistance, water vapor permeability, and face temperature change. To validate these parameters in a physiological context, we performed experiments to measure the respiratory rate and change in face temperature while wearing different types of commonly used masks. Finally, using values of these parameters from experiments and the literature, and surveys asking users to rate the comfort of various masks, three machine learning algorithms were trained and tested to generate overall comfort scores for those masks. Although all three models tested performed with an accuracy of approximately 70%, the multiple linear regression model also provides a simple analytical expression to predict the comfort scores for any face mask provided the input parameters. As face mask usage is crucial during the COVID-19 pandemic, the ability of this quantitative framework to predict mask comfort is likely to improve user experience and prevent discomfort-induced noncompliance.
Experiences of coping with the first wave of COVID-19 epidemic in Philadelphia, PA: Mixed methods analysis of a cross-sectional survey of worries and symptoms of mood disorders
Authors: Burstyn Igor , Huynh Tran 
Published: April 2021

AbstractOur objective was to describe how residents of Philadelphia, PA, coped psychologically with the first wave of COVID-19 pandemic. In a cross-sectional design, we aimed to estimate the rates and correlates of anxiety and depression, examine how specific worries correlated with general anxiety and depression, and synthesized themes of “the most difficult experiences” shared by the respondents. We collected data through an on-line survey in a convenience sample of 1,293 adult residents of Philadelphia, PA between April 17 and July 3, 2020, inquiring about symptoms of anxiety and depression (via Hospital Anxiety and Depression Scale), specific worries, open-ended narratives of “the most difficult experiences” (code into themes), demographics, perceived sources of support, and general health. Anxiety was evident among 30 to 40% of participants and depression – about 10%. Factor analysis revealed two distinct, yet inter-related clusters of specific worries related to mood disorders: concern about “hardships” and “fear of infection”. Regression analyses revealed that anxiety, depression, and fear of infection, but not concern about hardships, worsened over the course of the epidemic. “The most difficult experiences” characterized by loss of income, poor health of self or others, uncertainty, death of a relative or a friend, and struggle accessing food were each associated with some of the measures of worries and mood disorders. Respondents who believed they could reply on support of close personal network fared better psychologically than those who reported replying primarily on government and social services organizations. Thematic analysis revealed complex perceptions of the pandemic by the participants, giving clues to both positive and negative experiences that may have affected how they coped with the pandemic. Despite concerns about external validity, our observations are concordant with emerging evidence of psychological toll of the COVID-19 pandemic and measures employed to mitigate risk of infection.
FINDING STUNTING HOTSPOT AREAS IN SEVEN MAJOR ISLANDS USING SPATIAL ANALYSIS: FOR THE ACCELERATION OF STUNTING PREVENTION IN INDONESIA
Authors: Sipahutar Tiopan , Eryando Tris , Budhiharsana Meiwita Paulina , Siregar Kemal N. , Aidi Muhammad Nur , Minarto  , Utari Diah Mulyawati , Rahmaniati Martya , Hendarwan Harimat 
Published: April 2021

AbstractObjectivesTo find stunting hotspots district/ cities in Indonesia in seven major islands in Indonesia.MethodThis is an ecological study that using aggregate data. We used data from The Basic Health Research Report of Indonesia 2018 and The Poverty Data and Information Report from the Central Bureau of Statistics (BPS) 2018. We analyzed 514 districts/ cities in Indonesia that spread out in 7 major Islands with 34 provinces. We used The Euclidean distance method to determine the neighborhood. Moran’s test was occupied to identify autocorrelation while Moran’s Scatter Plot particularly in the high-high quadrant was used to identify stunting hotspot areas.ResultIt was found that there is autocorrelation among districts/ cities in four major islands namely Sumatera, Java, Sulawesi, and Bali Nusa Tenggara Timur (NTT) Nusa Tenggara Barat (NTB). We identified 135 districts/ cities as stunting hotspot areas that spread in 14 provinces in four islands.ConclusionThere is autocorrelation among districts/ cities in Sumatera, Java, Sulawesi, and Bali NTT NTB which resulted in 135 districts/ cities identified as stunting hotspots in four major islands in IndonesiaPolicy implicationProvide information to the government in prioritizing stunting prevention areas in Indonesia in term of the acceleration of stunting prevention.SummaryStrengths and limitations of this study:The hypothesis which states that the prevalence of stunting in one area is associated with the prevalence of stunting in the neighboring area is a new method that should be considered to set the policy.The study results can be used by the government to set priority areas for stunting interventions in Indonesia because so far, the government has made priorities based on stunting prevalence and weighted by poverty. Thus, by setting the priority areas, the funds required will be less compare if it executed in districts of Indonesia simultaneously.The weakness in this study is the geographical differences of Indonesia regions given the vastness of the Indonesian territory. Some of the districts are separated by oceans and the size of the area is sometimes extremely different. It becomes difficult in determining the neighborhood definition method. Some regions will have no neighbors under certain conditions. Therefore, further research can be carried out with different methods of neighborhood definition.