bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing the low-risk threshold for patients with upper gastrointestinal bleeding during the COVID-19 pandemic: a prospective, multicentre feasibility study
Authors: Dunne Philip , Livie Victoria , McGowan Aaron , Siu Wilson , Chaudhary Sardar , Groome Maximillian , Phull Perminder , Fraser Andrew , Morris Allan John , Penman Ian D , Stanley Adrian J 
Published: August 2021

ObjectiveDuring the COVID-19 pandemic, we extended the low-risk threshold for patients not requiring inpatient endoscopy for upper gastrointestinal bleeding (UGIB) from Glasgow Blatchford Score (GBS) 0–1 to GBS 0–3. We studied the safety and efficacy of this change.MethodsBetween 1 April 2020 and 30 June 2020 we prospectively collected data on consecutive unselected patients with UGIB at five large Scottish hospitals. Primary outcomes were length of stay, 30-day mortality and rebleeding. We compared the results with prospective prepandemic descriptive data.Results397 patients were included, and 284 index endoscopies were performed. 26.4% of patients had endoscopic intervention at index endoscopy. 30-day all-cause mortality was 13.1% (53/397), and 33.3% (23/69) for pre-existing inpatients. Bleeding-related mortality was 5% (20/397). 30-day rebleeding rate was 6.3% (25/397). 84 patients had GBS 0–3, of whom 19 underwent inpatient endoscopy, 0 had rebleeding and 2 died. Compared with prepandemic data in three centres, there was a fall in mean number of UGIB presentations per week (19 vs 27.8; p=0.004), higher mean GBS (8.3 vs 6.5; p<0.001) with fewer GBS 0–3 presentations (21.5% vs 33.3%; p=0.003) and higher all-cause mortality (12.2% vs 6.8%; p=0.02). Predictors of mortality were cirrhosis, pre-existing inpatient status, age >70 and confirmed COVID-19. 14 patients were COVID-19 positive, 5 died but none from UGIB.ConclusionDuring the pandemic when services were under severe pressure, extending the low-risk threshold for UGIB inpatient endoscopy to GBS 0–3 appears safe. The higher mortality of patients with UGIB during the pandemic is likely due to presentation of a fewer low-risk patients.
Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition
Authors: Sundar Raghav , Huang Kie-Kyon , Kumar Vikrant , Ramnarayanan Kalpana , Demircioglu Deniz , Her Zhisheng , Ong Xuewen , Bin Adam Isa Zul Fazreen , Xing Manjie , Tan Angie Lay-Keng , Tai David Wai Meng , Choo Su Pin , Zhai Weiwei , Lim Jia Qi , Das Thakur Meghna , Molinero Luciana , Cha Edward , Fasso Marcella , Niger Monica , Pietrantonio Filippo , Lee Jeeyun , Jeyasekharan Anand D , Qamra Aditi , Patnala Radhika , Fabritius Arne , De Simone Mark , Yeong Joe , Ng Cedric Chuan Young , Rha Sun Young , Narita Yukiya , Muro Kei , Guo Yu Amanda , Skanderup Anders Jacobsen , So Jimmy Bok Yan , Yong Wei Peng , Chen Qingfeng , Göke Jonathan , Tan Patrick 
Published: August 2021

ObjectivesEpigenomic alterations in cancer interact with the immune microenvironment to dictate tumour evolution and therapeutic response. We aimed to study the regulation of the tumour immune microenvironment through epigenetic alternate promoter use in gastric cancer and to expand our findings to other gastrointestinal tumours.DesignAlternate promoter burden (APB) was quantified using a novel bioinformatic algorithm (proActiv) to infer promoter activity from short-read RNA sequencing and samples categorised into APBhigh, APBintand APBlow.Single-cell RNA sequencing was performed to analyse the intratumour immune microenvironment. A humanised mouse cancer in vivo model was used to explore dynamic temporal interactions between tumour kinetics, alternate promoter usage and the human immune system. Multiple cohorts of gastrointestinal tumours treated with immunotherapy were assessed for correlation between APB and treatment outcomes.ResultsAPBhighgastric cancer tumours expressed decreased levels of T-cell cytolytic activity and exhibited signatures of immune depletion. Single-cell RNAsequencing analysis confirmed distinct immunological populations and lower T-cell proportions in APBhightumours. Functional in vivo studies using ‘humanised mice’ harbouring an active human immune system revealed distinct temporal relationships between APB and tumour growth, with APBhightumours having almost no human T-cell infiltration. Analysis of immunotherapy-treated patients with GI cancer confirmed resistance of APBhightumours to immune checkpoint inhibition. APBhighgastric cancer exhibited significantly poorer progression-free survival compared with APBlow(median 55 days vs 121 days, HR 0.40, 95% CI 0.18 to 0.93, p=0.032).ConclusionThese findings demonstrate an association between alternate promoter use and the tumour microenvironment, leading to immune evasion and immunotherapy resistance.
Incident aortic stenosis in 49 449 men and 42 229 women investigated with routine echocardiography
Authors: Stewart Simon , Chan Yih-Kai , Playford David , Strange Geoffrey A 
Published: August 2021

ObjectiveWe addressed the paucity of data describing the characteristics and consequences of incident aortic stenosis (AS).MethodsAdults undergoing echocardiography with a native aortic valve (AV) and no AS were studied. Subsequent age-specific and sex-specific incidence of AS were derived from echocardiograms conducted a median of 2.8 years apart. Progressive AV dysfunction and individually linked mortality were examined per AS category.Results49 449 men (53.9%, 60.9±15.8 years) and 42 229 women (61.6±16.9 years) with no initial evidence of AS were identified. Subsequently, 6293 (6.9%) developed AS—comprising 5170 (5.6%), 636 (0.7%), 339 (0.4%) and 148 (0.2%) cases of mild, moderate, severe low-gradient and severe high-gradient AS, respectively. Age-adjusted incidence rates of all grades of AS were 17.5 cases per 1000 men/annum and 18.7 cases per 1000 women/annum: rising from ~5 to ~40 cases per 1000/annum in those aged <30 years vs >80 years. Median peak AV velocity increased by +0.57 (+0.36 to +0.80) m/s in mild AS compared with +2.75 (+2.40 to +3.19) m/s in severe high-gradient AS cases between first and last echocardiograms. During subsequent median 7.7 years follow-up, 24 577 of 91 678 cases (26.8%) died. Compared with no AS, the adjusted risk of all-cause mortality was 1.42-fold higher in mild AS, 1.92-fold higher in moderate AS, 1.95-fold higher in severe low-gradient AS and 2.27-fold higher in severe, high-gradient AS cases (all p<0.001).ConclusionsNew onset AS is a common finding among older patients followed up with echocardiography. Any grade of AS is associated with higher mortality, reinforcing the need for proactive vigilance.
The impact of software-based metal artifact reduction on the liquid embolic agent Onyx in cone-beam CT: a systematic in vitro and in vivo study
Authors: Schmitt Niclas , Weyland Charlotte S , Wucherpfennig Lena , Sommer Christof M , Bendszus Martin , Möhlenbruch Markus A , Vollherbst Dominik F 
Published: August 2021

BackgroundOnyx is frequently used for endovascular embolization of intracranial arteriovenous malformations (AVMs) and dural arteriovenous fistulas (dAVFs). One drawback of using Onyx is the generation of artifacts in cone-beam CT (CBCT). These artifacts can represent an obstacle for the detection of periprocedural hemorrhage or planning of subsequent radiosurgery. This study investigates the effect of artifact reduction by the syngo DynaCT SMART Metal Artifact Reduction (MAR) software.MethodsA standardized in vitro tube model (n=10) was filled with Onyx 18 and CBCT image acquisition was conducted in a brain imaging phantom. Furthermore, post-interventional CBCT images of 20 patients with AVM (n=13) or dAVF (n=7), each treated with Onyx, were investigated. The MAR software was applied for artifact reduction. Artifacts of the original and the post-processed images were analyzed quantitatively (standard deviation in a region of interest on the layer providing the most artifacts) and qualitatively. For the patient images, the effect of the MAR software on brain parenchyma on artifact-free images was further investigated.ResultsQuantitative and qualitative analyses of both datasets demonstrated a lower degree of artifacts in the post-processed images (eg, patient images: 38.30±22.03 density units (no MAR; mean SD±SD) vs 19.83±12.31 density units (with MAR; p<0.001). The MAR software had no influence on the brain parenchyma in artifact-free images.ConclusionThe MAR software significantly reduced the artifacts evoked by Onyx in CBCT without affecting the visualization of brain parenchyma on artifact-free images. Applying this software could thus improve the quality of periprocedural CBCT images after embolization with Onyx.
Patterns of negative seroconversion in ongoing surveys of SARS-CoV-2 antibodies among workers in New York’s largest healthcare system
Authors: Sembajwe Grace , Rasul Rehana , Jacobs Yehuda , Edwards Keisha , Chambers Lewis Lorraine , Chang Tylis , Lowe William , Moline Jacqueline 
Published: August 2021

ObjectivesGiven the importance of continued COVID-19 surveillance, our objective was to present findings from a short follow-up survey of workforce SARS-CoV-2 antibody testing in previously seropositive participants and describe associations between work locations and negative seroconversion.MethodsWe conducted a follow-up cross-sectional survey on previously seropositive healthcare workers, using questionnaires and serology testing. Eligible employees previously consented to be contacted were invited by email to participate in a survey and laboratory blood draws. SAS V.9.4 was used to describe employee characteristics and seroconversion status. Binomial regression models were used to calculate unadjusted and adjusted prevalence ratios (PRs) of seronegativity. The multivariable analyses included age, gender, race/ethnicity, region of residence, work location, prior diagnosis/PCR results and days between antibody tests. Unadjusted and adjusted PRs 95% CIs and p values were reported.ResultsOf the 3990 employees emailed in the follow-up, 1631 completed an exposure survey and generated a blood-draw requisition form. Average time between serology testing was 4 months. Of the 955 employees with complete serology results, 79.1% were female, 53.4% were white and 46.4% resided in Long Island; 176 participants seroconverted to negative. In multivariable regression analyses adjusted for gender, race/ethnicity and region of residence, younger employees (<20–30 years), intensive care unit workers and those with no/negative prior PCR results were more likely to have negative seroconversion.Conclusions and relevancePatterns of negative seroconversion showed significant differences by sociodemographic and workplace characteristics. These results contribute information to workplace serosurveillance.
Child involvement in meal preparation and grocery shopping is associated with lower levels of food fussiness among young children
Authors: Broad Julia , Forbes Laura , Darlington Gerarda , Ma David W.L. , Haines Jess 
Published: August 2021

This study examined associations between child food involvement and food fussiness. Analyses used survey data from 62 children ages 1.5 to 5.9 years who participated in the Guelph Family Health Study Pilot. Overall involvement (β = –0.51, p = 0.02), involvement in meal preparation (β = –0.42, p = 0.009), and involvement in grocery shopping (β = –0.29, p = 0.04) were inversely associated with food fussiness. Experimental research including larger, more diverse samples is needed to test whether food involvement reduces food fussiness among young children. Novelty: Our study identified significant, inverse associations between child food involvement and food fussiness
Fine-scale altitudinal gradients influence the relationships between structural attributes and aboveground biomass in Central Africa
Authors: Menanzala Miambam Eymard , Loubota Panzou Grace Jopaul , Bocko Yannick Enock , Loumeto Jean Joël 
Published: August 2021

There is increasing interest in altitude effects on structural attributes and aboveground biomass (AGB) in tropical forests. However, we continue to lack a clear understanding of relationships between structural attributes and AGB along altitudinal gradients in Central Africa. Using a new network of 76 permanent plots of 0.5 ha, the relationships between structural attributes and AGB were explored along fine-scale altitudinal gradients in the Republic of Congo. We chose four fine-scale altitudinal gradients (71–350 m, 350–550 m, 550–650 m, and 650–853 m) and measured the diameter and heights of 4192 trees with a ≥10 cm diameter and calculated the structural attributes and the AGB for each 0.5 ha plot. For a given diameter, trees were shorter and had narrower crowns in the altitudinal gradient of 71–350 m than in the other altitudinal gradients. The relationships between structural attributes and AGB differ along fine-scale altitudinal gradients, with higher stem density, wood density, crown depth, and AGB for the altitudinal gradient of 71–350 m. These results provide important advances in our understanding of the relationships between structural attributes and AGB along fine-scale altitudinal gradients in Central Africa. They should improve AGB estimates for the low altitudinal gradient when combined with other field and remotely sensed data sets in Central Africa.
The Relationship between Body Mass Index and Incident Diabetes Mellitus in Chinese Aged Population: A Cohort Study
Authors: Tang M. L. , Zhou Y. Q. , Song A. Q. , Wang J. L. , Wan Y. P. , Xu R. Y. 
Published: August 2021

Objectives. Previous studies reported that overweight older adults had a lower mortality after cardiovascular diseases attack, indicating being thinner might not always be better. However, there is an ongoing debate about what is the optimal range of body mass index (BMI) for the aged population. We aimed to evaluate the value of BMI for the prediction of incident diabetes mellitus (DM) in the Chinese elderly population. Methods. A total number of 6,911 Chinese elderly people (4,110 men and 2,801 women, aged

71
±
6.0

years) were included in this cohort study. BMI was measured at baseline (Jan 1, 2014, to Dec 31, 2014). All the participants were further classified into six groups: <18.5 kg/m2, 18.5 to <22.5 kg/m2, 22.5 to <25.0 kg/m2, 25.0 to <27.5 kg/m2, 27.5 to <30.0 kg/m2, and ≥30.0 kg/m2. Fasting blood glucose (FBG) and glycated hemoglobin A1c (HbA1c) were annually measured during follow-up (Jan 1, 2015-May 31, 2019). DM was confirmed if either

FBG
≥
7.0

mmol
/
L

or

HbA
1
c
≥
6.5
%

. We used the Cox proportional hazard regression model to evaluate the association between BMI and the prediction of incident DM. Results. Comparing individuals with a BMI range of 18.5 to <22.5 kg/m2 (reference), the hazard ratio for incident DM was 2.13 (95% CI: 1.54~2.95), 2.14 (95% CI: 1.53~3.00), 3.17 (95% CI: 2.19~4.59), 3.15 (95% CI: 1.94~5.09), and 3.14 (95% CI: 1.94~5.09) for the group with a BMI range of 22.5 to <25.0 kg/m2, 25.0 to <27.5 kg/m2, 27.5 to <30.0 kg/m2, and ≥30.0 kg/m2 after adjusting for baseline age, sex, blood pressure, lipid profiles, and eGFR (

P

trend < 0.001), after adjusting for the abovementioned confounders. The association tended to be closer in men and young participants, compared with their counterparts. Conclusions. High BMI was associated with a high risk of developing DM in the Chinese aged population. Thus, it is optimal for the aged population to maintain their body weight within a reasonable range to prevent chronic diseases.
Fam20C Regulates Bone Resorption and Breast Cancer Bone Metastasis through Osteopontin and BMP4
Authors: Zuo Hao , Yang Dengbao , Wan Yihong 
Published: August 2021

Abstract

Fam20C is a kinase that generates the majority of secreted phosphoproteins and regulates biomineralization. However, its potential roles in bone resorption and breast cancer bone metastasis are unknown. Here we show that Fam20C in the myeloid lineage suppresses osteoclastogenesis and bone resorption, during which, osteopontin (OPN) is the most abundant phosphoprotein secreted in a Fam20C-dependent manner. OPN phosphorylation by Fam20C decreased OPN secretion, and OPN neutralization reduced Fam20C deficiency–induced osteoclast differentiation and bone metastasis. In contrast, Fam20C in breast cancer cells promoted bone metastasis by facilitating the phosphorylation and secretion of BMP4, which in turn enhanced osteoclastogenesis. Mutation of the BMP4 phosphorylation site elevated BMP4 lysosomal degradation and reduced BMP4 secretion. In breast cancer cells, BMP4 depletion or treatment with a BMP4 signaling inhibitor diminished osteoclast differentiation and bone metastasis and abolished Fam20C-mediated regulation of these processes. Collectively, this study discovers distinct roles for Fam20C in myeloid cells and breast cancer cells and highlights OPN and BMP4 as potential therapeutic targets for breast cancer bone metastasis.

Significance:
Osteoclastogenesis and bone metastasis are suppressed by myeloid-derived Fam20C, but enhanced by breast cancer–associated Fam20C, uncovering novel Fam20C functions and new therapeutic strategies via targeting Fam20C substrates OPN and BMP4.
Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health
Authors: Joyce Brian T. , Gao Tao , Zheng Yinan , Ma Jiantao , Hwang Shih-Jen , Liu Lei , Nannini Drew , Horvath Steve , Lu Ake T. , Bai Allen Norrina , Jacobs David R. , Gross Myron , Krefman Amy , Ning Hongyan , Liu Kiang , Lewis Cora E. , Schreiner Pamela J. , Sidney Stephen , Shikany James M. , Levy Daniel , Greenland Philip , Hou Lifang , Lloyd-Jones Donald 
Published: August 2021

Rationale:
Epigenetic aging is a novel measure of biological age, reflecting exposures and disease risks independent of chronological age. It may serve as a useful biomarker of cardiovascular health (CVH) or cardiovascular disease risk for early detection or prevention.

Objective:
To examine associations between GrimAge acceleration (GrimAA), a measure of epigenetic aging calculated from the residuals of GrimAge regressed on chronological age, and 2 repeated CVH measures: a full score for the AHA Life’s Simple 7 (diet, smoking, physical activity, body mass index, blood pressure, total cholesterol, and glucose) and a clinical CVH score (body mass index, blood pressure, cholesterol, and glucose).

Methods and Results:

We used Illumina array DNA methylation data from 2 prospective cohort studies, the CARDIA study (Coronary Artery Risk Development in Young Adults) and FHS (Framingham Heart Study), to calculate GrimAA and model associations with CVH. CARDIA randomly selected 1118 participants for assays at Y15 (2000–2001; mean age, 40 years) and Y20 (2005–2006); in FHS, 2106 Offspring participants had DNA methylation measured at exam 8 (2005–2008; mean age, 66 years). We examined multiple cross-sectional and longitudinal models of GrimAA and each CVH score measured at CARDIA Y0 to Y20 and FHS exams 7 to 8. In CARDIA, clinical CVH score from Y0 to Y20 was associated with Y15 and Y20 GrimAA (β range, −0.41 to −0.21 years per 1-point increase in CVH;
P
range, <0.01–0.01), as was full score (β range, −0.65 to −0.67 years;
P
<0.01 for all). These findings were validated in FHS (clinical score β range, −0.51 to −0.54 years; full score β range, −0.76 to −0.83 years;
P
<0.01 for all).

Conclusions:
Our data demonstrate that faster GrimAA is associated with the loss of CVH from young age. Epigenetic age may be a useful biomarker of cardiovascular disease risk and provides biological insight into the role of epigenetic mechanisms linking age-related CVH loss and cardiovascular disease.
Hemoglobin and Clinical Outcomes in the Vericiguat Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA)
Authors: Ezekowitz Justin A. , Zheng Yinggan , Cohen-Solal Alain , Melenovský Vojtěch , Escobedo Jorge , Butler Javed , Hernandez Adrian F. , Lam Carolyn S.P. , O’Connor Christopher M. , Pieske Burkert , Ponikowski Piotr , Voors Adriaan A. , deFilippi Christopher , Westerhout Cynthia M. , McMullan Ciaran , Roessig Lothar , Armstrong Paul W. ,   for the VICTORIA Study Group
Published: August 2021

Background:
In the VICTORIA trial (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction), anemia occurred more often in patients treated with vericiguat (7.6%) than with placebo (5.7%). We explored the association between vericiguat, randomization hemoglobin, development of anemia, and whether the benefit of vericiguat related to baseline hemoglobin.

Methods:
Anemia was defined as hemoglobin <13.0 g/dL in men and <12.0 g/dL in women (World Health Organization Anemia). Adverse events reported as anemia were also evaluated. We assessed the risk-adjusted relationship between hemoglobin and hematocrit with the primary outcome (composite of cardiovascular death or heart failure hospitalization) and the time-updated hemoglobin relationship to outcomes.

Results:

At baseline, 1719 (35.7%) patients had World Health Organization anemia; median hemoglobin was 13.4 g/L (25th, 75th percentile: 12.1, 14.7 g/dL). At 16 weeks from randomization, 1643 patients had World Health Organization anemia (284 new for vericiguat and 219 for placebo), which occurred more often with vericiguat than placebo (
P
<0.001). After 16 weeks, no further decline in hemoglobin occurred over 96 weeks of follow-up and the ratio of hemoglobin/hematocrit remained constant. Overall, adverse event anemia occurred in 342 patients (7.1%). A lower hemoglobin was unrelated to the treatment benefit of vericiguat (versus placebo) on the primary outcome. In addition, analysis of time-updated hemoglobin revealed no association with the treatment effect of vericiguat (versus placebo) on the primary outcome.

Conclusions:
Anemia was common at randomization and lower hemoglobin was associated with a greater frequency of clinical events. Although vericiguat modestly lowered hemoglobin by 16 weeks, this effect did not further progress nor was it related to the treatment benefit of vericiguat.

Registration:

URL:
https://www.clinicaltrials.gov
: Unique identifier: NCT02861534.