bluuebunny/crossref_metadata_2025_split huggingface dataset:
Schizophrenia-associated somatic copy number variants from 12,834 cases reveal contribution to risk and recurrent, isoform-specific NRXN1 disruptions
Authors: Maury Eduardo A. , Sherman Maxwell A. , Genovese Giulio , Gilgenast Thomas G. , Rajarajan Prashanth , Flaherty Erin , Akbarian Schahram , Chess Andrew , McCarroll Steven A. , Loh Po-Ru , Phillips-Cremins Jennifer E. , Brennand Kristen J. , Walters James T. R. , O’ Donovan Michael , Sullivan Patrick ,   Psychiatric Genomic Consortium Schizophrenia and CNV workgroup,   Brain Somatic Mosaicism Network, Sebat Jonathan , Lee Eunjung A. , Walsh Christopher A. 
Published: January 2022

AbstractWhile inherited and de novo copy number variants (CNV) have been implicated in the genetic architecture of schizophrenia (SCZ), the contribution of somatic CNVs (sCNVs), present in some but not all cells of the body, remains unknown. Here we explore the role of sCNVs in SCZ by analyzing blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls. sCNVs were more common in cases (0.91%) than in controls (0.51%, p = 2.68e-4). We observed recurrent somatic deletions of exons 1-5 of the NRXN1 gene in 5 SCZ cases. Allele-specific Hi-C maps revealed ectopic, allele-specific loops forming between a potential novel cryptic promoter and non-coding cis regulatory elements upon deletions in the 5’ region of NRXN1. We also observed recurrent intragenic deletions of ABCB11, a gene associated with anti-psychotic response, in 5 treatment-resistant SCZ cases. Taken together our results indicate an important role of sCNVs to SCZ risk and treatment-responsiveness.
Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants
Authors: Miyamoto Sho , Arashiro Takeshi , Adachi Yu , Moriyama Saya , Kinoshita Hitomi , Kanno Takayuki , Saito Shinji , Katano Harutaka , Iida Shun , Ainai Akira , Kotaki Ryutaro , Yamada Souichi , Kuroda Yudai , Yamamoto Tsukasa , Ishijima Keita , Park Eun-Sil , Inoue Yusuke , Kaku Yoshihiro , Tobiume Minoru , Iwata-Yoshikawa Naoko , Shiwa-Sudo Nozomi , Tokunaga Kenzo , Ozono Seiya , Hemmi Takuya , Ueno Akira , Kishida Noriko , Watanabe Shinji , Nojima Kiyoko , Seki Yohei , Mizukami Takuo , Hasegawa Hideki , Ebihara Hideki , Maeda Ken , Fukushi Shuetsu , Takahashi Yoshimasa , Suzuki Tadaki 
Published: January 2022

SUMMARYBackgroundThe immune profile against SARS-CoV-2 has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by the Omicron in individuals with various immune histories.MethodsThe neutralization susceptibility of the variants including the Omicron and their ancestor was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections by the Alpha/Delta with multiple time intervals following vaccination.FindingsThe Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against the Omicron were induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies.ConclusionsImmune histories with breakthrough infections can overcome the resistance to infection by the Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against the Omicron and future variants.FundingThis study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
Association between having a pregnancy complicated by vaginal bleeding and risk of cancer
Authors: Dudukina Elena , Horváth-Puhó Erzsébet , Sørensen Henrik Toft , Ehrenstein Vera 
Published: January 2022

ABSTRACTBackgroundA full-term pregnancy is associated with a lower cancer risk. The risk of cancer in women with vaginal bleeding in pregnancy is unknown.MethodsWe conducted a registry-based cohort study (1995-2017) in Denmark. We included pregnancies (n=37 082) affected by vaginal bleeding (VB) within 20 gestational weeks among 35 514 women, VB-unaffected pregnancies (n=1 363 614) among 783 314 women, pregnancies ending in a termination (n=324 328) among 239 638 women or miscarriage (n=137 104) among 121 353 women. We computed absolute risk of cancer and hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, morbidity, and socioeconomic factors using Cox proportional hazards regression.ResultsAt the end of the 24-year follow-up, there were 1 320 events among VB-affected cohort, 40 420 events among VB-unaffected cohort, 10 300 events among termination cohort, and 4 790 events among miscarriage cohort. The HR for any cancer was 1.03 (95% CI: 0.97-1.08) when comparing VB-affected vs VB-unaffected pregnancies, 1.03 (95% CI: 0.97-1.09) vs terminations, and 0.90 (95% CI: 0.84-0.95) vs miscarriages. Similar results were obtained for site-specific cancers.ConclusionsWe found no strong evidence for an association between vaginal bleeding in pregnancy and an increased risk of cancer.
Head-to-head comparison of nasal and nasopharyngeal sampling using SARS-CoV-2 rapid antigen testing in Lesotho
Authors: Labhardt Niklaus D , Fernández Lucia González , Katende Bulemba , Muhairwe Josephine , Bresser Moniek , Amstutz Alain , Glass Tracy R , Ruhwald Morten , Sacks Jilian A , Escadafal Camille , Mareka Mathabo , Mookho Mooko Sekhele , de Vos Margaretha , Reither Klaus 
Published: January 2022

AbstractObjectivesTo assess the real-world diagnostic performance of nasal and nasopharyngeal swabs for SD Biosensor STANDARD Q COVID-19 Antigen Rapid Diagnostic Test (Ag-RDT).MethodsIndividuals ≥5 years with COVID-19 compatible symptoms or history of exposure to SARS-CoV-2 presenting at hospitals in Lesotho received two nasopharyngeal and one nasal swab. Ag-RDT from nasal and nasopharyngeal swabs were performed as point-of-care on site, the second nasopharyngeal swab used for polymerase chain reaction (PCR) as the reference standard.ResultsOut of 2198 participants enrolled, 2131 had a valid PCR result (61% female, median age 41 years, 8% children), 84.5% were symptomatic. Overall PCR positivity rate was 5.8%. The sensitivity for nasopharyngeal, nasal, and combined nasal and nasopharyngeal Ag-RDT result was 70.2% (95%CI: 61.3-78.0), 67.3% (57.3-76.3) and 74.4% (65.5-82.0), respectively. The respective specificity was 97.9% (97.1-98.4), 97.9% (97.2-98.5) and 97.5% (96.7-98.2). For both sampling modalities, sensitivity was higher in participants with symptom duration ≤ 3days versus ≤ 7days. Agreement between nasal and nasopharyngeal Ag-RDT was 99.4%.ConclusionsThe STANDARD Q Ag-RDT showed high specificity. Sensitivity was, however, below the WHO recommended minimum requirement of ≥ 80%. The high agreement between nasal and nasopharyngeal sampling suggests that for Ag-RDT nasal sampling is a good alternative to nasopharyngeal sampling.Highlights-Prospective study on real-world diagnostic performance of nasal and nasopharyngeal SD Biosensor STANDARD Q COVID-19 Ag Test in 2131 participants in a rural African setting-The sensitivity of the STANDARD Q COVID-19 Ag Test was below the World Health Organization requirement of ≥ 80% but met the specificity requirement of ≥97%.-Sensitivity was higher in the following subpopulations: persons with symptoms ≤3 days, and Ct value < 25.-In head-to-head comparison nasal and nasopharyngeal sampling had comparable sensitivity and specificity and an overall test agreement of 99.4%, indicating that the more convenient nasal sampling could be used for SARS-CoV-2 rapid antigen tests.-24 of the 2131 participants with COVID-19 symptoms had pulmonary tuberculosis with a positive Xpert Ultra test on sputum.
Vaccine Effectiveness against COVID-19 among Symptomatic Persons Aged ≥12 Years with Reported Contact with COVID-19 Cases, February – September 2021
Authors: Chung Jessie R , Kim Sara S , Belongia Edward A , McLean Huong Q , King Jennifer P , Nowalk Mary Patricia , Zimmerman Richard K , Geffel Krissy Moehling , Martin Emily T , Monto Arnold S , Lamerato Lois E , Gaglani Manjusha , Hoffman Eric , Volz Marcus , Jackson Michael L , Jackson Lisa A , Patel Manish M , Flannery Brendan 
Published: January 2022

AbstractIndividuals in contact with persons with COVID-19 are at high risk of developing COVID-19, but protection offered by COVID-19 vaccines in the context of known exposure is unknown. Symptomatic outpatients reporting acute onset of COVID-19-like illness and tested for SARS-CoV-2 infection were enrolled. Among 2,229 participants, 283/451 (63%) of those reporting contact and 331/1778 (19%) without known contact tested SARS-CoV-2 positive. Using the test-negative design, adjusted vaccine effectiveness was 71% (95% confidence interval, 49%-83%) among fully vaccinated participants reporting contact versus 80% (95% CI, 72%-86%) among those without. This study supports COVID-19 vaccination and highlights the importance of efforts to increase vaccination coverage.
Urinary Biomarkers and Attainment of Cefepime Therapeutic Targets in Critically Ill Children
Authors: Downes Kevin J. , Sharova Anna , Gianchetti Lauren , Himebauch Adam S. , Fitzgerald Julie C. , Zuppa Athena F. 
Published: January 2022

ABSTRACTINTRODUCTIONThe recommended therapeutic target for cefepime (FEP) is the time above MIC (fT>MIC). The frequency of target attainment and risk factors for sub-therapeutic concentrations in children have not been extensively studied.METHODSWe performed a prospective observational pilot study in children in our PICU receiving standard dosing of FEP for suspected sepsis (≥2 SIRS criteria). Three FEP concentrations were measured per subject and a urine sample was collected prior to PK sampling for measurement of urinary biomarkers. We used log linear regression to calculate the fT>MIC for each subject across a range of MIC values (1-16 µg/mL). We compared clinical factors/biomarkers between patients who did and did not achieve 100% fT>MIC for 8 µg/mL (cut-point for Pseudomonas) and tested the correlation between covariates and FEP troughs.RESULTS21 subjects were enrolled (median SIRS criteria: 3). PK sampling occurred after a median of 5 doses (range: 3-9). 43% of subjects achieved 100% fT>MIC for an MIC of 8 µg/mL. Younger age (p=.005), higher estimated GFR (p=.03), and lower urinary NGAL (p=.006) and KIM-1 (.03) were associated with failure to attain 100% fT>8 µg/mL. Age (r = 0.53), eGFR (r = - 0.58), urinary NGAL (r = 0.42) and KIM-1 (r = 0.50) were significantly correlated with FEP troughs.CONCLUSIONSA significant proportion of critically ill children failed to attain target concentrations for treatment of Pseudomonas aeruginosa with FEP. Younger patients and those with good kidney function (high GFR, low urinary biomarkers) may be at highest risk for subtherapeutic FEP concentrations.
Waning of SARS-CoV-2 Antibody levels response to inactivated cellular vaccine over 6 months among healthcare workers
Authors: Taminato Monica , Chaves Ana Paula Cunha , Morais Richarlisson Borges de , Moreira Luiz Vinicius Leão , Conte Danielle Dias , Faico Filho Klinger Soares , Gabrielloni Maria Cristina , de Medeiros Eduardo Alexandrino , Bellei Nancy 
Published: January 2022

ABSTRACTBackgroundHealth Care workers (HCW) are an important group affected by this pandemic and COVID-19 has presented substantial challenges for health professionals and health systems in many countries. The Brazilian vaccination plan implemented in October, so that third dose for HCW. However, the persistence of CoronaVac vaccine-induced immunity is unknown, and immunogenicity according to age cohorts may differ among individuals.ObjectiveEvaluate the post vaccination immune humoral response and the relationship between post-vaccination seropositivity rates and demographic data among Healthcare Workers over 6 months after CoronaVac immunization.MethodsA cross section study including Healthcare professionals vaccinated with CoronaVac for 6 months or more. The study was carried with the analysis of post-vaccination serological test to assess the levels of humoral response after vaccination.Results329 participants were included. Among them, 76% were female. Overall, 18.5% were positive quantitative titles (IQR 42.87-125.5) and the negative group was 80%, quantitative titles (IQR 5.50-13.92).ConclusionIt was possible to identify a group with positive quantitative titles in serological test for IgG antibody against the SARS-CoV-2. Further investigation is required to determine the durability of post-vaccination antibodies and how serological tests can be determine the ideal timing of vaccine booster doses.
Preferential expansion upon boosting of cross-reactive “pre-existing” switched memory B cells that recognize the SARS-CoV-2 Omicron variant Spike protein
Authors: Perugino Cory A. , Liu Hang , Feldman Jared , Hauser Blake M. , Jacob-Dolan Catherine , Nathan Anusha , Zhou Zezhou , Kaseke Clarety , Tano-Menka Rhoda , Getz Matthew A. , Senjobe Fernando , Berrios Cristhian , Ofoman Onosereme , Lemieux Jacob E. , Goldberg Marcia B. , Nundel Kerstin , Moormann Ann , Marshak-Rothstein Ann , Iafrate John A. , Gaiha Gaurav , Charles Richelle , Balazs Alejandro B. , Naranbhai Vivek , Schmidt Aaron G. , Pillai Shiv 
Published: January 2022

AbstractIn previously unvaccinated and uninfected individuals, non-RBD SARS-CoV-2 spike-specific B cells were prominent in two distinct, durable, resting, cross-reactive, “pre-existing” switched memory B cell compartments. While pre-existing RBD-specific B cells were extremely rare in uninfected and unvaccinated individuals, these two pre-existing switched memory B cell compartments were molded by vaccination and infection to become the primary source of RBD-specific B cells that are triggered by vaccine boosting. The frequency of wild-type RBD-binding memory B cells that cross-react with the Omicron variant RBD did not alter with boosting. In contrast, after a boost, B cells recognizing the full-length Omicron variant spike protein expanded, with pre-existing resting memory B cells differentiating almost quantitatively into effector B cell populations. B cells derived from “ancient” pre-existing memory cells and that recognize the full-length wild-type spike with the highest avidity after boosting are the B cells that also bind the Omicron variant spike protein.Abstract Figure
Effectiveness of COVID-19 vaccines against Omicron or Delta symptomatic infection and severe outcomes
Authors: Buchan Sarah A. , Chung Hannah , Brown Kevin A. , Austin Peter C. , Fell Deshayne B. , Gubbay Jonathan B. , Nasreen Sharifa , Schwartz Kevin L. , Sundaram Maria E. , Tadrous Mina , Wilson Kumanan , Wilson Sarah E. , Kwong Jeffrey C. 
Published: January 2022

ABSTRACTBackgroundThe incidence of SARS-CoV-2 infection, including among those who have received 2 doses of COVID-19 vaccines, increased substantially following the emergence of Omicron in Ontario, Canada.MethodsApplying the test-negative study design to linked provincial databases, we estimated vaccine effectiveness (VE) against symptomatic infection and severe outcomes (hospitalization or death) caused by Omicron or Delta between December 6 and 26, 2021. We used multivariable logistic regression to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose, compared to unvaccinated individuals.ResultsWe included 16,087 Omicron-positive cases, 4,261 Delta-positive cases, and 114,087 test-negative controls. VE against symptomatic Delta infection declined from 89% (95%CI, 86-92%) 7-59 days after a second dose to 80% (95%CI, 74-84%) after ≥240 days, but increased to 97% (95%CI, 96-98%) ≥7 days after a third dose. VE against symptomatic Omicron infection was only 36% (95%CI, 24-45%) 7-59 days after a second dose and provided no protection after ≥180 days, but increased to 61% (95%CI, 56-65%) ≥7 days after a third dose. VE against severe outcomes was very high following a third dose for both Delta and Omicron (99% [95%CI, 98-99%] and 95% [95%CI, 87-98%], respectively).ConclusionsIn contrast to high levels of protection against both symptomatic infection and severe outcomes caused by Delta, our results suggest that 2 doses of COVID-19 vaccines only offer modest and short-term protection against symptomatic Omicron infection. A third dose improves protection against symptomatic infection and provides excellent protection against severe outcomes for both variants.
The individual and combined associations of depression and socioeconomic status with risk of major cardiovascular events: a prospective cohort study
Authors: Prigge Regina , Wild Sarah H. , Jackson Caroline A. 
Published: January 2022

AbstractObjectiveWe aimed to investigate the individual and combined associations of depression and low socioeconomic status (SES) with risk of major cardiovascular events (MCVE), defined as first-ever fatal or non-fatal stroke or myocardial infarction, in a large prospective cohort study.MethodsWe used data from 466,238 UK Biobank participants, aged 40 – 69 years without cardiovascular disease, bipolar disorder or schizophrenia at baseline. We performed Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) of the individual and combined associations of depression and each of educational attainment, area-based deprivation and income with risk of MCVE. We assessed effect modification and explored interaction on the additive and multiplicative scale.ResultsDepression, low education, high area-based deprivation and low income were individually associated with increased risks of MCVE (adjusted HR, 95% CI: 1.28, 1.19 – 1.38; 1.20, 1.14 – 1.27; 1.17, 1.11 – 1.23; and 1.22, 1.16 – 1.29, respectively). Depression was associated with increased risks of MCVE among individuals with high and low SES. Individuals with depression and each of low education, high area-based deprivation and low income were at particularly high risk of MCVE (HR, 95% CI: 1.50, 1.38 – 1.63; 1.63, 1.46 – 1.82; 1.31, 1.23 – 1.40, respectively). There was interaction between depression and area-based deprivation on multiplicative and additive scales but no interaction with education or income.ConclusionDepression was associated with increased risks of MCVE among individuals with high and low SES, with particularly high risks among those living in areas of high deprivation.
Global Perspective of COVID-19 Vaccine Nationalism
Authors: Basak Palash , Abir Tanvir , Mamun Abdullah Al , Zainol Noor Raihani , Khanam Mansura , Haque Md. Rashidul , Milton Abul Hasnat , Agho Kingsley Emwinyore 
Published: January 2022

AbstractThis study aimed to explore the global perspective of the association between GDP of various countries and progress of COVID-19 vaccinations; to explore how the global pattern holds in the continents, and investigate the spatial distribution pattern of COVID-19 vaccination progress for all countries. We have used consolidated data on COVID-19 vaccination and GDP from Our World in Data, an open-access data source. Data analysis and visualization were performed in R-Studio. There was a strong linear association between per capita income and the proportion of people vaccinated in countries with one million or more populations. GDP per capita accounts for a 50% variation in the vaccination rate across the nations. Our assessments revealed that the global pattern holds in every continent. Rich European and North-American countries are most protected against COVID-19. Less developed African countries barely initiated the vaccination program. There is a significant disparity among Asian countries. The security of wealthier nations (vaccinated their citizens) cannot be guaranteed unless adequate vaccination covers the less-endowed countries. Therefore, the global community should take initiatives to speed up the COVID-19 vaccination program in all countries of the world, irrespective of their wealth.
Improving air quality and health in Northern Italy: limits and perspectives
Authors: Robotto Angelo , Barbero Secondo , Cremonini Roberto , Brizio Enrico 
Published: January 2022

ABSTRACTA better air quality has led to a significant reduction of premature deaths over the past decade in Europe, as emissions of many pollutants declined considerably in the EU-27 Member States: SOx emissions by 76%, NOx by 42%, NMVOCs by 29% and PM2.5 by 29%. The present paper reports an in-depth analysis of the reasons why the regions of the Po valley, Northern Italy, still have difficulties to comply with EU air quality standards, in particular for PM10 and NO2, in spite of strong emission reductions carried out through careful Air Quality Plans put in practice during the last 2 decades. The analysis includes a consistent comparison of emission inventories for different European regions in Italy, Germany and Poland, the measured air quality trends and PM source apportionment in these areas, and, most of all, a thorough investigation of meteorological parameters influencing atmospheric pollutant dispersion and transport. The study reports that in the colder seasons, wind speed, PBL height and atmospheric pressure occurring in the Po basin are three to five times less efficient in diluting and dispersing pollutant if compared to regions north of the Alps. Due to the extremely disadvantageous orographic and climatic configuration of the Po Valley, only radical emission reductions could bring air quality into EU limit values with a questionable cost-benefit ratio of due policies. Provided that air quality standards (particularly for PM10 and PM2.5) aim at protecting people from adverse health effects arising from air pollution, it is however necessary to also consider the toxicity of atmospheric particulate in addition to PM10/PM2.5 mass concentration as a limit value. Based on existing toxicological studies and reports, a discussion is reported about PM toxicity factor depending on toxicity scores for source-specific aerosols and PM composition determined by Source Apportionment. Provided that PM components’ profiles are strongly different across Europe, the obtained PM toxicity factors range from 0.3 (for areas where the main PM contribution is referable to sea salts or inorganic matter) to 3.5 (where Elemental and Organic Carbon prevail), suggesting that, even at the same mass concentration, the effects of PM10/2.5 on human health are significantly variable and limit values should take into account differential toxicity.Modern PM Source Apportionment techniques, along with reliable toxicity and epidemiological analyses, represent the right tools to overcome the shortcomings of the current regulation standard and build a new consistent health metric for ambient PM in the future, helping policy makers impose effective air quality measures to protect people health.