bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-vitamin K antagonist oral anticoagulants, proton pump inhibitors and gastrointestinal bleeds
Authors: Komen Joris , Pottegård Anton , Hjemdahl Paul , Mantel-Teeuwisse Aukje K , Wettermark Björn , Hellfritzsch Maja , Hallas J , Herings Ron , Smits Lisa , Forslund Thomas , Klungel Olaf 
Published: August 2021

ObjectiveTo evaluate if proton pump inhibitor (PPI) treatment reduces the risk of upper gastrointestinal bleeding (UGIB) in patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs).DesignWe used a common protocol, common data model approach to conduct a cohort study including patients with AF initiated on a NOAC in Stockholm, Denmark and the Netherlands from April 2011 until July 2018. The outcome of interest was a UGIB diagnosed in a secondary care inpatient setting. We used an inverse probability weighted (IPW) Poisson regression to calculate incidence rate ratios (IRRs), contrasting PPI use to no PPI use periods.ResultsIn 164 290 NOAC users with AF, providing 272 570 years of follow-up and 39 938 years of PPI exposure, 806 patients suffered a UGIB. After IPW, PPI use was associated with lower UGIB rates (IRR: 0.75; 95% CI: 0.59 to 0.95). On an absolute scale, the protective effect was modest, and was found to be largest in high-risk patients, classified as age 75–84 years (number needed to treat for 1 year (NNTY): 787), age ≥85 years (NNTY: 667), HAS-BLED score ≥3 (NNTY: 378) or on concomitant antiplatelet therapy (NNTY: 373).ConclusionConcomitant treatment with a PPI in NOAC-treated patients with AF is associated with a reduced risk of severe UGIB. This indicates that PPI cotreatment can be considered, in particular among the elderly patients, patients with a HAS-BLED score ≥3, and/or in patients on concomitant antiplatelet therapy.
Association between community-level social capital and frailty onset among older adults: a multilevel longitudinal study from the Japan Gerontological Evaluation Study (JAGES)
Authors: Noguchi Taiji , Murata Chiyoe , Hayashi Takahiro , Watanabe Ryota , Saito Masashige , Kojima Masayo , Kondo Katsunori , Saito Tami 
Published: August 2021

BackgroundLittle is known about the prospective association between community-level social capital and individual-level frailty onset. Therefore, this study aimed to examine the impact of community-level social capital on frailty onset among older adults using 3-year longitudinal data.MethodsThis prospective cohort study recruited non-institutionalised older adults from the Japan Gerontological Evaluation Study, established in 2013 and robust older adults were followed up for 3 years. We assessed three aspects of community-level social capital (civic participation, social cohesion and reciprocity), and employed a multilevel logistic regression analysis; frailty was evaluated using the Kihon Checklist questionnaire, which has been widely used as a screening tool for frailty in Japan.ResultsIn total, 21 940 older adults (from 384 communities) who were robust at baseline (2013) completed the follow-up survey (2016). Participants’ mean age (SD) was 71.8 (4.9) years, and 51.2% were female. In the follow-up period, frailty onset occurred in 622 participants (2.8%). Regarding community-level social capital variables, civic participation was inversely associated with frailty onset (OR=0.94, 95% CI 0.90 to 0.97, p=0.001), after adjusting for individual-level and community-level covariates. The potential intermediate factors of individual social relationships and health behaviours did not largely change the results. This association was found regardless of individual socioeconomic status.ConclusionsLiving in a community with rich civic participation, such as engagement in social activities, was associated with lower frailty onset among older adults. Community development that fosters social participation is essential for frailty prevention.
Longitudinal changes of spinal cord grey and white matter following spinal cord injury
Authors: David Gergely , Pfyffer Dario , Vallotton Kevin , Pfender Nikolai , Thompson Alan , Weiskopf Nikolaus , Mohammadi Siawoosh , Curt Armin , Freund Patrick 
Published: August 2021

ObjectivesTraumatic and non-traumatic spinal cord injury produce neurodegeneration across the entire neuraxis. However, the spatiotemporal dynamics of spinal cord grey and white matter neurodegeneration above and below the injury is understudied.MethodsWe acquired longitudinal data from 13 traumatic and 3 non-traumatic spinal cord injury patients (8–8 cervical and thoracic cord injuries) within 1.5 years after injury and 10 healthy controls over the same period. The protocol encompassed structural and diffusion-weighted MRI rostral (C2/C3) and caudal (lumbar enlargement) to the injury level to track tissue-specific neurodegeneration. Regression models assessed group differences in the temporal evolution of tissue-specific changes and associations with clinical outcomes.ResultsAt 2 months post-injury, white matter area was decreased by 8.5% and grey matter by 15.9% in the lumbar enlargement, while at C2/C3 only white matter was decreased (−9.7%). Patients had decreased cervical fractional anisotropy (FA: −11.3%) and increased radial diffusivity (+20.5%) in the dorsal column, while FA was lower in the lateral (−10.3%) and ventral columns (−9.7%) of the lumbar enlargement. White matter decreased by 0.34% and 0.35% per month at C2/C3 and lumbar enlargement, respectively, and grey matter decreased at C2/C3 by 0.70% per month.ConclusionsThis study describes the spatiotemporal dynamics of tissue-specific spinal cord neurodegeneration above and below a spinal cord injury. While above the injury, grey matter atrophy lagged initially behind white matter neurodegeneration, in the lumbar enlargement these processes progressed in parallel. Tracking trajectories of tissue-specific neurodegeneration provides valuable assessment tools for monitoring recovery and treatment effects.
Anti-CD20 therapies decrease humoral immune response to SARS-CoV-2 in patients with multiple sclerosis or neuromyelitis optica spectrum disorders
Authors: Louapre Céline , Ibrahim Michella , Maillart Elisabeth , Abdi Basma , Papeix Caroline , Stankoff Bruno , Dubessy Anne-Laure , Bensa-Koscher Caroline , Créange Alain , Chamekh Zina , Lubetzki Catherine , Marcelin Anne-Geneviève , Corvol Jean-Christophe , Pourcher Valérie 
Published: August 2021

BackgroundSARS-CoV-2 seroconversion rate after COVID-19 may be influenced by disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMO-SD).ObjectiveTo investigate the seroprevalence and the quantity of SARS-CoV-2 antibodies in a cohort of patients with MS or NMO-SD.MethodsBlood samples were collected in patients diagnosed with COVID-19 between 19 February 2020 and 26 February 2021. SARS-CoV-2 antibody positivity rates and Ig levels (anti-S IgG titre, anti-S IgA index, anti-N IgG index) were compared between DMTs groups. Multivariate logistic and linear regression models were used to estimate the influence of DMTs and other confounding variables on SARS-CoV-2 serological outcomes.Results119 patients (115 MS, 4 NMO, mean age: 43.0 years) were analysed. Overall, seroconversion rate was 80.6% within 5.0 (SD 3.4) months after infection. 20/21 (95.2%) patients without DMT and 66/77 (85.7%) patients on DMTs other than anti-CD20 had at least one SARS-CoV-2 Ig positivity, while this rate decreased to only 10/21 (47.6%) for patients on anti-CD20 (p<0.001). Being on anti-CD20 was associated with a decreased odd of positive serology (OR, 0.07 (95% CI 0.01 to 0.69), p=0.02) independently from time to COVID-19, total IgG level, age, sex and COVID-19 severity. Time between last anti-CD20 infusion and COVID-19 was longer (mean (SD), 3.7 (2.0) months) in seropositive patients compared with seronegative patients (mean (SD), 1.9 (1.5) months, p=0.04).ConclusionsSARS-CoV-2 antibody response was decreased in patients with MS or NMO-SD treated with anti-CD20 therapies. Monitoring long-term risk of reinfection and specific vaccination strategies in this population may be warranted.Trial registration numberNCT04568707.
Experimental consolidation and absolute measurement of the $$^\text {nat}$$C(p,x)$$^{11}$$C nuclear activation cross section at 100 MeV for particle therapy physics
Authors: Bäcker Claus Maximilian , Horst Felix , Adi Wihan , Bäumer Christian , Gerhardt Marcel , Jentzen Walter , Kazek Sandra Laura , Kröninger Kevin , Schuy Christoph , Verbeek Nico , Weingarten Jens , Wulff Jörg , Timmermann Beate 
Published: August 2021

AbstractThe $$^\text {nat}$$

nat

C(p,x)$$^{11}$$

11

C reaction has been discussed in detail in the past [EXFOR database, Otuka et al. (Nuclear Data Sheets 120:272–276, 2014)]. However, measured activation cross sections by independent experiments are up to 15% apart. The aim of this study is to investigate underlying reasons for these observed discrepancies between different experiments and to determine a new consensus reference cross section at 100 MeV. Therefore, the experimental methods described in the two recent publications [Horst et al. (Phys Med Biol https://doi.org/10.1088/1361-6560/ab4511, 2019) and Bäcker et al. (Nuclear Instrum Methods Phys Res B 454:50–55, 2019)] are compared in detail and all experimental parameters are investigated for their impact on the results. For this purpose, a series of new experiments is performed. With the results of the experiments a new reference cross section of (68±3) mb is derived at (97±3) MeV proton energy. This value combined with the reliably measured excitation function could provide accurate cross section values for the energy region of proton therapy. Because of the well-known gamma-ray spectrometer used and the well-defined beam characteristics of the treatment machine at the proton therapy center, the experimental uncertainties on the absolute cross section could be reduced to 3%. Additionally, this setup is compared to the in-beam measurement setup from the second study presented in the literature (Horst et al. 2019). Another independent validation of the measurements is performed with a PET scanner.
Improving Tumor Penetration of Antibodies and Antibody–Drug Conjugates: Taking Away the Barriers for Trojan Horses
Authors: van Dongen Guus A.M.S. 
Published: August 2021

Abstract
The high affinity of an antibody can result in restricted tumor penetration and heterogenous tumor distribution, with preferential binding of the antibody to tumor cells localized around tumor vasculature. This so-called “binding site barrier” effect limits the efficacy of antibody-based therapies like antibody–drug conjugates (ADC). In this issue, Bordeau and colleagues introduce an original approach to overcome this barrier through transient competitive inhibition of antibody–antigen binding. By coadministration of an anti-idiotypic anti-trastuzumab domain antibody as a competitive inhibitor, increased tumor penetration of trastuzumab as well as enhanced efficacy of the ADC ado-trastuzumab emtansine were observed in tumor-bearing mice
See related article by Bordeau et al., p. 4145
PAX9 Determines Epigenetic State Transition and Cell Fate in Cancer
Authors: Zhao Zibo , Szczepanski Aileen P. , Tsuboyama Natsumi , Abdala-Valencia Hiam , Goo Young Ah , Singer Benjamin D. , Bartom Elizabeth T. , Yue Feng , Wang Lu 
Published: August 2021

AbstractAbnormalities in genetic and epigenetic modifications can lead to drastic changes in gene expression profiles that are associated with various cancer types. Small cell lung cancer (SCLC) is an aggressive and deadly form of lung cancer with limited effective therapies currently available. By utilizing a genome-wide CRISPR-Cas9 dropout screen in SCLC cells, we identified paired box protein 9 (PAX9) as an essential factor that is overexpressed in human malignant SCLC tumor samples and is transcriptionally driven by the BAP1/ASXL3/BRD4 epigenetic axis. Genome-wide studies revealed that PAX9 occupies distal enhancer elements and represses gene expression by restricting enhancer activity. In multiple SCLC cell lines, genetic depletion of PAX9 led to significant induction of a primed-active enhancer transition, resulting in increased expression of a large number of neural differentiation and tumor-suppressive genes. Mechanistically, PAX9 interacted and cofunctioned with the nucleosome remodeling and deacetylase (NuRD) complex at enhancers to repress nearby gene expression, which was reversed by pharmacologic HDAC inhibition. Overall, this study provides mechanistic insight into the oncogenic function of the PAX9/NuRD complex epigenetic axis in human SCLC and suggests that reactivation of primed enhancers may have potential therapeutic efficacy in treating SCLC expressing high levels of PAX9.Significance:A genome-wide screen in small cell lung cancer reveals PAX9/NuRD-mediated epigenetic enhancer silencing and tumor progression, supporting the development of novel personalized therapeutic approaches targeting the PAX9-regulated network.
Growing Disparity in the Incidence of Colorectal Cancer among Non-Hispanic American Indian and Alaska Native Populations—United States, 2013–2017
Authors: Haverkamp Donald , Melkonian Stephanie C. , Jim Melissa A. 
Published: August 2021

Abstract

Background:
American Indian and Alaska Native (AI/AN) populations have experienced regional variation and disparities in colorectal cancer incidence rates.

Methods:
We examined colorectal cancer incidence (2013–2017) and colorectal cancer incidence trends (1999–2017) among AI/AN persons. Incidence data were linked to Indian Health Service enrollment records, and analyses were restricted to Purchased/Referred Care Delivery Areas. Incidence rates of colorectal cancer among AI/AN and White persons were analyzed in six geographic regions; Hispanic persons were excluded. Incidence trends were analyzed using linear modeling.

Results:
During 2013–2017, colorectal cancer incidence was 41% higher among AI/AN than among White persons. AI/AN incidence rates per 100,000 varied regionally from 34.4 in the East to 96.1 in Alaska. Compared with White persons, AI/AN persons had higher colorectal cancer incidence rates among all age strata and were more likely to have late-stage diagnoses. Incidence rate trends indicated significant increases among both AI/AN and White persons ages &lt;50 years and among AI/AN persons ages 50–64 years. The colorectal cancer incidence rate trend increased among AI/AN persons in the Southwest.

Conclusions:
The disparity of colorectal cancer incidence rates between AI/AN and White persons has widened since 2005–2009. AI/AN populations have higher colorectal cancer incidence compared with White populations, especially in the Alaska region.

Impact:
Our finding of increased colorectal cancer incidence disparities suggests that enhanced screening efforts and culturally appropriate clinical and public health interventions are needed among AI/AN persons overall, and especially in regions and age groups in which colorectal cancer rates are increasing.
Looking for Proof in the Wrong Generation?
Authors: Fenton Suzanne E. , Boyles Abee L. 
Published: August 2021

Abstract
The article in this issue “Grandmaternal Perinatal Serum DDT in Relation to Granddaughter Early Menarche and Adult Obesity: Three Generations in the Child Health and Development Studies Cohort,” by Cirillo and colleagues, is the first to report multigenerational health effects in granddaughters stemming from early life exposures to the pesticide o,p'-DDT in grandmothers. Health effects associated with F0 environmental chemical exposures in multiple generations have been reported in rodent studies, but not in humans. The striking finding in this body of work by Cohn and her colleagues is that the granddaughters were never directly exposed to o,p'-DDT—only their grandmothers were, potentially when they were adolescents. The increased rise of obesity and early menarche due to o,p'-DDT exposures generations earlier may help explain why it has been so difficult to describe environmental contributors of disease. Have we been looking for exposures in the wrong generation?
See related article by Cirillo et al., p. 1480
Ipilimumab Combination Dosing: Less is More
Authors: Jameson-Lee Max , Luke Jason J. 
Published: August 2021

Abstract
Ipilimumab with and without anti–Programmed Death 1 (PD-1) improved overall survival (OS) in melanoma. Despite this, the optimal dose and therapeutic mechanism of ipilimumab in patients remains unclear. KEYNOTE-029 and other studies suggest that low-dose ipilimumab with anti-PD1 maintains efficacy while decreasing toxicity, emphasizing T-cell trafficking and reinvigoration as likely mechanisms.
See related article by Long et al., p. 5280
Evaluation of NOAA National Water Model Parameter Calibration in Semi-Arid Environments Prone to Channel Infiltration
Authors: Lahmers Timothy M. , Hazenberg Pieter , Gupta Hoshin , Castro Christopher , Gochis David , Dugger Aubrey , Yates David , Read Laura , Karsten Logan , Wang Yuan-Heng 
Published: August 2021

AbstractThe NOAA National Water Model (NWM), maintained and executed by the NOAA National Weather Service (NWS) Office of Water Prediction, provides operational hydrological guidance throughout the Contiguous United States. Based on the WRF-Hydro model architecture developed by the National Center for Atmospheric Research (NCAR), the NWM was recently modified for semi-arid domains, by permitting it to explicitly resolve infiltration from ephemeral channels into the underlying channel bed as an added model sink term. To analyze the added value of channel infiltration in semi-arid environments, we calibrated NWM v2.1 (with the channel infiltration function) to 56 independent basins in the western CONUS, following identical calibration methods as the pre-operational NWM v2.1 (not including channel infiltration). Calibration of the model consists of two parts, including 1) calibration of channel infiltration only with other parameters set to the calibrated parameters used for pre-operational NWM v2.1 and 2) calibration of all parameters including channel infiltration with settings otherwise equivalent to the calibration of NWM v2.1. The calibrated channel-infiltration enhanced NWM improves predictive skill compared to the control NWM in 85% of evaluated basins, for the calibration period. The current NWM settings for physical processes and the biases of the calibration scheme limit model performance in semi-arid environments. To explore whether channel infiltration paired with an alternative calibration scheme could address these limitations, NWM v2.1 was calibrated with a new objective function in selected basins. We found that this updated objective function could ameliorate model biases in some semi-arid environments.
Well-being: Diversified perspectives in search of operational definitions
Authors: Halbreich Uriel 
Published: August 2021

well-being is a multi-faceted concept that should be an operational domain. The territory is claimed by many disciplines and professionals who usually emphasize their own unique perspective. Economists and politicians focus on finance, prosperity, per-capita product and jobs. Socially-minded activists focus on poverty, education, personal safety, quality of life, equality and disparities. Law-enforcement focuses on crime. Many health and Medical professionals see their patients mostly through the stethoscope, lab tests and imaging. Psychologists stress stressors, crises and their consequences. Psychiatrists see mental, emotional and cognitive disorders. clergy and philosophers emphasize spirituality, beliefs and cultural values. All are correct! Their outlooks are intertwined with each other and should be integrated into a single well-rounded comprehensive operational entity.
Treatment of ureteropelvic junction obstruction and urolithiasis in children with minimally invasive surgery
Authors: Masieri Lorenzo , Sforza Simone , Manera Alekseja , Lambertini Luca , Crisci Alfonso , Cini Chiara , Mantovani Alberto , Cocci Andrea , Minervini Andrea , Carini Marco 
Published: August 2021

Background: Ureteropelvic Junction Obstruction (UPJO) is the most common congenital ureteral anomaly. Nowadays, according to the increasing incidence of urolithiasis, 20% of children with UPJO presents urolithiasis. Open pyeloplasty was the standard treatment before the introduction of minimally invasive surgery (MIS). Nevertheless, only scattered experiences on MIS were previously described and universal agreement on the treatment of UPJO plus urolithiasis is still missing. Objective: The study aim was to describe our experience with a series of pediatric patients affected by UPJO and urolithiasis treated with robot-assisted pyeloplasty (RAP) and endoscopic removal of stones using a flexible cystoscope and a stones basket in a singular tertiary referral center. Material and methods: We retrospectively reviewed our data from pediatric patients affected by UPJO and urolithiasis undergoing RAP between April 2013 and December 2019. The analysis was conducted on seven patients. All procedures were performed by one expert robotic surgeon and one endoscopic surgeon skilled in the management of urolithiasis. Results: The mean age was 7 years (IQR 4–16). The median stone area was 77.7 mm two (IQR 50.2–148.4). Most of them (71.4%) presented preoperative symptoms. The median operative time was 110 min (IQR 104–125) with a console time of 90 (IQR 90–105). The median length of stay was 5 days (IQR 4–5). Median follow-up was 16 months (IQR 10–25). Conclusion: RAP with concomitant flexible ureteroscope is a safe and effective option for the simultaneous management of UPJO with urolithiasis with excellent outcomes in children.
The complex relationship between infertility and female genital tract cancer: A review
Authors: Alessandra Familiari , Vitalba Gallitelli , Antonella Biscione , Giulia Di Marco , Carmine Conte , Marco D’Indinosante , Rachel Schwab , Giacomo Corrado , Anna Fagotti , Valerio Gallotta , Giovanni Scambia 
Published: August 2021

Introduction: The link between female infertility and gynecological cancer has always been a debated and challenging topic. Although cervical cancer has the worst impact on female fertility, as it is usually diagnosed in patients of reproductive age, endometrial and ovarian cancer are also diagnosed and treated often in relatively younger patients in which fertility preservation is a relevant issue. The aim of this review is to highlight the correlation between therapy for female infertility and the developing cancer’s risk and to describe the fertility sparing treatments in gynecological oncology. Material and methods: A systematic review of the literature through the main scientific search engines (PubMed and Google Scholar) was performed. We selected the most relevant articles based on the largest case series and the latest updates. All selected documents have been listed in the references. Results: Fifty-six relevant articles published between 1996 and 2019 were identified. Results from the available evidence report no significant increased risk of endometrial, cervical, and ovarian cancer in patients having infertility treatments. In young patients diagnosed with gynecological cancer, preservation of fertility is a personalized choice depending on several factors (type, stage, age and desire to conceive, safety of the treatment, and feasibility of fertility sparing surgery). For ovarian cancer FIGO stage IA G1, IA G2 (grade), and IC G1; for endometrial adenocarcinoma grade 1 with no lymphovascular space invasion (LVSI) or myometrial invasion and for early-stage cervical cancer (FIGO stage 2018: IA1-IB1), fertility sparing treatment is possible. The role of fertility sparing treatment with the increase of personalization of therapies therapy is always a theme of discussion and research. Conclusion: At present data regarding the risk of gynecological cancers after infertility treatments are reassuring. Careful evaluation of female fertility-sparing options in young women interested by ovarian, endometrial, or cervical tumors should be carried out involving a multidisciplinary team and ensuring safety and efficacy.