bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental epidemiology in a crossfire
Authors: Etzel Ruth A. , Grandjean Philippe , Ozonoff David M. 
Published: August 2021

AbstractTwo tendencies have emerged in environmental epidemiology that hamper the translation of research findings into prevention of environmental hazards. One is the increased focus on highlighting weaknesses of epidemiology research that is clearly meant to explain away the research conclusions and weaken their possible implications for interventions to control environmental hazards. Another is the voluminous amount of information sharing that involves a substantial amount of misinformation, as part of the ongoing infodemic. In this light, the appearance of the catalogue of doubt-raising strategies, indeed the worst practices of scientific inference, is good news. Collected under the auspices of the International Network for Epidemiology in Policy, it serves to illustrate the range of possible (and impossible) forms of critique that may be raised on behalf of vested interests or other groups who for some reason disagree with the epidemiological conclusions. We believe that this systematic list will be useful in our field and help to identify critiques of policy options that are hidden and sometimes suppressed in weighing the epidemiological evidence.
A modified Delphi study to enhance and gain international consensus on the Physical Activity Messaging Framework (PAMF) and Checklist (PAMC)
Authors: Williamson Chloë , Kelly Paul , Tomasone Jennifer R. , Bauman Adrian , Mutrie Nanette , Niven Ailsa , Richards Justin , Baker Graham 
Published: August 2021

AbstractIntroductionPhysical activity messaging is an important step in the pathway towards improving population physical activity levels, but best practice is not yet understood. A gap in the literature exists for a physical activity messaging framework to help guide creation and evaluation of messages. This study aimed to further develop and improve, and gain international expert consensus on, a standardised Physical Activity Messaging Framework and Checklist.MethodsA modified Delphi study consisting of three online survey rounds was conducted. Each survey gathered feedback from an international expert panel using quantitative and qualitative methods. The framework and checklist were amended between each round based on survey results until consensus (defined a priori as 80% agreement) was reached.ResultsThe final expert panel (n = 40, 55% female) came from nine countries and comprised academics (55%), healthcare and other professionals (22.5%) and government officials or policymakers (22.5%). Consensus was reached in survey 3 with 85 and 87.5% agreement on the framework and checklist, respectively.ConclusionThis study presents an expert- and evidence-informed framework and checklist for physical activity messaging. If used consistently, the Physical Activity Messaging Framework and Checklist may improve practice by encouraging evidence-based and target audience-focused messages, as well as enhance the research base on physical activity messaging by harmonising key terminologies and improving quality of reporting. Key next steps include further refining the Physical Activity Messaging Framework and Checklist based on their use in real-world settings.
High-dose radiotherapy in newly diagnosed low-grade gliomas with nonmethylated O(6)-methylguanine-DNA methyltransferase
Authors: Liu Yanwei , Li Yanong , Wang Peng , Chen Li , Feng Jin , Qiu Xiaoguang 
Published: August 2021

Abstract
Background
Patients with low-grade gliomas (LGGs) harboring O6-methylguanine-DNA methyltransferase promoter nonmethylation (MGMT-non-pM) have a particularly short survival and are great resistance to chemotherapy. The objective of this study was to assess the efficacy of high-dose radiotherapy (RT) for LGGs with MGMT-non-pM.

Methods
268 patients with newly diagnosed adult supratentorial LGGs from the multicenter Chinese Glioma Cooperative Group (CGCG) received postoperative RT during 2005–2018. MGMT promoter methylation analysis was conducted by pyrosequencing in all patients. Univariate and multivariate analysis were performed using the Cox regression to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RT dose–response on MGMT status defined subtypes was analyzed.

Results
On univariate analysis, the following were statistically significant favorable factors for both PFS and OS: oligodendrogliomas(p = 0.002 and p = 0.005), high-dose RT (> 54 Gy) (p = 0.021 and p = 0.029) and 1p/19q codeletion (p < 0.001 and p = 0.001). On multivariate analysis, RT dose (> 54 Gy vs. ≤ 54 Gy) and IDH mutation were independently prognostic markers for OS (HR, 0.47; 95%CI, 0.22–0.98; p = 0.045; and HR, 0.44; 95%CI, 0.21–0.96; p = 0.038, respectively) and PFS (HR, 0.48; 95%CI, 0.26–0.90; p = 0.022; and HR, 0.51; 95%CI, 0.26–0.98; p = 0.044, respectively). High-dose RT was associated with longer OS (HR, 0.56; 95%CI, 0.32–0.96; p = 0.036) and PFS (HR, 0.58; 95%CI, 0.35–0.96; p = 0.033) than low-dose RT in MGMT-non-pM subtype. In contrast, no significant difference in either OS (p = 0.240) or PFS (p = 0.395) was observed with high-dose RT in the MGMT-pM subtype.

Conclusions
High-dose RT (> 54 Gy) is an independently protective factor for LGGs and is associated with improved survival in patients with MGMT-non-pM.
Dosimetric comparison and biological evaluation of fixed-jaw intensity-modulated radiation therapy for T-shaped esophageal cancer
Authors: Chen Hua , Huang Ying , Wang Hao , Shao Yan , Yue Ning J. , Gu Hengle , Duan Yanhua , Feng Aihui , Xu Zhiyong 
Published: August 2021

Abstract
Background
To evaluate the dosimetric and biological benefits of the fixed-jaw (FJ) intensity-modulated radiation therapy (IMRT) technique for patients with T-shaped esophageal cancer.

Methods
FJ IMRT plans were generated for thirty-five patients and compared with jaw tracking (JT) IMRT, static jaw (SJ) IMRT and JT volumetric modulated arc therapy (VMAT). Dosimetric parameters, tumor control probability (TCP) and normal tissue complication probability (NTCP), monitor units (MUs), delivery time and gamma passing rate, as a measure of dosimetric verification, were compared. The correlation between the length of PTV-C below the upper boundary of lung tissue (PTV-Cinferior) and dosimetric parameters and NTCP of the lung tissue were analyzed.

Results
The homogeneity and conformity of the target in the four plans were basically equivalent. When compared to the JT IMRT and SJ IMRT plans, FJ IMRT plan led to a statistically significant improvement in the NTCP and low-middle dosimetric parameters of the lung, and the improvement had a moderately positive correlation with the length of PTV-Cinferior, with a correlation coefficient ranging from 0.523 to 0.797; the FJ IMRT plan exhibited better lung sparing in low-dose volumes than the JT VMAT plan. The FJ IMRT plan had similar MUs (888 ± 99) and delivery times (516.1 ± 54.7 s) as the JT IMRT plan (937 ± 194, 522 ± 5.6 s) but higher than SJ IMRT (713 ± 137, 488.8 ± 45.2 s) and JT VMAT plan (517 ± 59, 263.7 ± 43.3 s).

Conclusions
The FJ IMRT technique is superior in reducing the low-dose volumes of lung tissues for patients with T-shaped esophageal cancer.
Clinical features of gastric duplications: evidence from primary case reports and published data
Authors: Li Yang , Li Chen , Wu Hao , Wang Quan , Gao Zhi-Dong , Yang Xiao-Dong , Jiang Ke-Wei , Ye Ying-Jiang 
Published: August 2021

AbstractBackgroundAlimentary tract duplications are rare congenital lesions, and only 2–8% of them are located in the stomach. Gastric duplications (GD) can lead to severe adverse events. Thus, surgical resection is required once the disease is diagnosed. The main purpose of this study is to describe the clinical features of gastric duplications and to provide evidence for the diagnosis and treatment.MethodsA retrospective review of eight gastric duplications at two medical centers Peking University People’s Hospital (PKUPH) and Shandong Provincial Hospital from 2010 to 2020 was conducted. Furthermore, the literature search was also conducted by retrieving data from PubMed, EMBASE and Cochrane Library databases from the date of the database inception to January 15, 2021.ResultsEight patients who were diagnosed as gastric duplications and 311 published records were included in this study. In all, 319 patients were identified: Vomiting and abdominal pain were the most frequent clinical presentations among juveniles and adults respectively. There was no difference in gender distribution (F: 53.16% vs M: 46.84%), and the cystic gastric duplications were the most common type of the gastric duplications (87.04%). More than half (53.30%) of included cases were located in the greater curvature of stomach.ConclusionsGastric duplications could present with a wide spectrum of symptomatology, which might be misdiagnosed easily as other diseases. For cystic gastric duplications, the optimal treatment was a complete surgical removal. But conservative treatment might be an alternative strategy for tubular gastric duplications.
Outbreak of Pseudomonas aeruginosa producing VIM carbapenemase in an intensive care unit and its termination by implementation of waterless patient care
Authors: Catho Gaud , Martischang R. , Boroli F. , Chraïti M. N. , Martin Y. , Koyluk Tomsuk Z. , Renzi G. , Schrenzel J. , Pugin J. , Nordmann P. , Blanc D. S. , Harbarth S. 
Published: August 2021

Abstract
Background
Long-term outbreaks of multidrug-resistant Gram-negative bacilli related to hospital-building water systems have been described. However, successful mitigation strategies have rarely been reported. In particular, environmental disinfection or replacement of contaminated equipment usually failed to eradicate environmental sources of Pseudomonas aeruginosa.

Methods
We report the investigation and termination of an outbreak of P. aeruginosa producing VIM carbapenemase (PA-VIM) in the adult intensive care unit (ICU) of a Swiss tertiary care hospital with active case finding, environmental sampling and whole genome sequencing (WGS) of patient and environmental strains. We also describe the implemented control strategies and their effectiveness on eradication of the environmental reservoir.

Results
Between April 2018 and September 2020, 21 patients became either infected or colonized with a PA-VIM strain. For 16 of them, an acquisition in the ICU was suspected. Among 131 environmental samples collected in the ICU, 13 grew PA-VIM in sink traps and drains. WGS confirmed the epidemiological link between clinical and environmental strains and the monoclonal pattern of the outbreak. After removing sinks from patient rooms and implementation of waterless patient care, no new acquisition was detected in the ICU within 8 months after the intervention.

Discussion
Implementation of waterless patient care with removal of the sinks in patient rooms was successful for termination of a PA-VIM ICU outbreak linked to multiple environmental water sources. WGS provides highly discriminatory accuracy to investigate environment-related outbreaks.
Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network
Authors: Du Zhonghua , Wen Xue , Wang Yichen , Jia Lin , Zhang Shilin , Liu Yudi , Zhou Lei , Li Hui , Yang Wang , Wang Cong , Chen Jingcheng , Hao Yajing , Salgado Figueroa Daniela , Chen Huiling , Li Dan , Chen Naifei , Celik Ilkay , Zhu Yanbo , Yan Zi , Fu Changhao , Liu Shanshan , Jiao Benzheng , Wang Zhuo , Zhang Hui , Gülsoy Günhan , Luo Jianjun , Qin Baoming , Gao Sujun , Kapranov Philipp , Esteban Miguel A. , Zhang Songling , Li Wei , Ay Ferhat , Chen Runsheng , Hoffman Andrew R. , Cui Jiuwei , Hu Ji-Fan 
Published: August 2021

AbstractBackgroundA specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate this architectural remodeling, we used a novel chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to profile long noncoding RNAs (lncRNAs) in theOct4promoter.ResultsWe identifyPlatr10as anOct4-Sox2binding lncRNA that is activated in somatic cell reprogramming.Platr10is essential for the maintenance of pluripotency, and lack of this lncRNA causes stem cells to exit from pluripotency. In fibroblasts, ectopically expressedPlatr10functions in trans to activate core stem cell factor genes and enhance pluripotent reprogramming. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we show thatPlatr10interacts with multiple pluripotency-associated genes, includingOct4,Sox2,Klf4, andc-Myc, which have been extensively used to reprogram somatic cells. Mechanistically, we demonstrate thatPlatr10helps orchestrate intrachromosomal promoter-enhancer looping and recruits TET1, the enzyme that actively induces DNA demethylation for the initiation of pluripotency. We further show thatPlatr10contains anOct4binding element that interacts with theOct4promoter and a TET1-binding element that recruits TET1. Mutation of either of these two elements abolishesPlatr10activity.ConclusionThese data suggest thatPlatr10functions as a novel chromatin RNA molecule to control pluripotencyin transby modulating chromatin architecture and regulating DNA methylation in the core stem cell factor network.
Effects of autonomic nervous system activation on endothelial function in response to acute exercise in hypertensive individuals: study protocol for a randomized double-blind study
Authors: Waclawovsky Gustavo , Boll Liliana Fortini Cavalheiro , Neto Salvador Gomes , Irigoyen Maria Claudia Costa , Lehnen Alexandre M. 
Published: August 2021

Abstract
Background
Arterial hypertension has a direct association with endothelial dysfunction and major cardiovascular events. There is evidence showing the benefits of aerobic exercise on flow-mediated dilation (FMD) in hypertensive individuals but little is known about the effect of autonomic nervous system (ANS) activation on FMD of the brachial artery in response to different types of exercise in this specific population. This study aims to examine the effects of ANS activation on FMD of the brachial artery in response to exercise in hypertensive individuals following a session of different types of exercise including aerobic exercise (AE), resistance exercise (RE), or combined exercise (CE).

Methods
Thirty-nine hypertensive volunteers aged 35 to 55 years will be randomly assigned to two exercise sessions: AE (40 min on a cycle ergometer at 60% of HR reserve), RE (4 lower limb sets with 12 repetitions at 60% 1-RM for 40 min), or CE (RE for 20 min + AE for 20 min). Each exercise group will be randomized to receive either an α1-adrenergic blocker (doxazosin 0.05 mg/kg−1) or placebo. Ultrasound measurement of FMD is performed 10 min before and 10, 40, and 70 min after exercise. ANS activation is monitored using a Finometer and measurements are taken during 10 min before each FMD assessment. Arterial stiffness is assessed by pulse wave velocity (PWV) analysis using a Complior device.

Discussion
We expect to demonstrate the effect of ANS activation on FMD of the brachial artery in hypertensive individuals in response to different types of exercise. This study may give some insight on how to improve exercise prescription for hypertension management.

Trial registration
https://clinicaltrials.gov and ID "NCT04371757". Registered on May 1, 2020.
Real-time interactive digital healthcare system for post-operative breast cancer patients: study protocol for a randomized controlled trial
Authors: Park Hae-Yeon , Nam Kyung Eun , Lim Jae-Young , Yeo Seung Mi , In Lee Jong , Hwang Ji Hye 
Published: August 2021

Abstract
Background
After receiving breast cancer surgery or reconstruction, shoulder dysfunctions including weakness, post-operative pain, shoulder joint instability, and limited range of motion (ROM) often occur. Due to limited ROM, patients may suffer difficulty in activities of daily living, and quality of life may be reduced. The objective of this study is to compare the effects on shoulder ROM of a real-time interactive digital healthcare system and brochure-based home rehabilitation program in post-operative breast cancer patients.

Methods
This study is a prospective, multi-center, assessor-blinded randomized controlled trial. The study aims to recruit 100 breast cancer patients exhibiting limited shoulder ROM after undergoing axillary lymph node dissection or breast reconstruction following mastectomy. Patients will be randomly assigned to two groups for 8 weeks of rehabilitation: a digital healthcare system rehabilitation (intervention) group and a brochure-based rehabilitation (control) group. The primary outcome is the change in ROM of the affected shoulder between baseline and 12 weeks after enrollment. Secondary outcomes include pain in the affected shoulder, as measured using a numerical rating scale, functional outcomes (QuickDASH scores), and quality of life (FACT-B and EQ-5D-5L scores), all of which will be measured on enrollment and 4, 8, and 12 weeks thereafter.

Discussion
This study will compare the effectiveness of a newly developed, augmented reality-based real-time interactive digital healthcare system with that of brochure-based home rehabilitation for improving the shoulder ROM, pain, functional outcomes, and quality of life of post-operative breast cancer patients.

Trial registration
ClinicalTrials.govNCT04316156. Registered on 20 March 2020.
Multi-omics of the esophageal microenvironment identifies signatures associated with progression of Barrett’s esophagus
Authors: Deshpande Nandan P. , Riordan Stephen M. , Gorman Claire J. , Nielsen Shaun , Russell Tonia L. , Correa-Ospina Carolina , Fernando Bentotage S. M. , Waters Shafagh A. , Castaño-Rodríguez Natalia , Man Si Ming , Tedla Nicodemus , Wilkins Marc R. , Kaakoush Nadeem O. 
Published: August 2021

AbstractBackgroundThe enrichment of Gram-negative bacteria of oral origin in the esophageal microbiome has been associated with the development of metaplasia. However, to date, no study has comprehensively assessed the relationships between the esophageal microbiome and the host.MethodsHere, we examine the esophageal microenvironment in gastro-esophageal reflux disease and metaplasia using multi-omics strategies targeting the microbiome and host transcriptome, followed by targeted culture, comparative genomics, and host-microbial interaction studies of bacterial signatures of interest.ResultsProfiling of the host transcriptome from esophageal mucosal biopsies revealed profound changes during metaplasia. Importantly, five biomarkers showed consistent longitudinal changes with disease progression from reflux disease to metaplasia. We showed for the first time that the esophageal microbiome is distinct from the salivary microbiome and the enrichment ofCampylobacterspecies as a consistent signature in disease across two independent cohorts. Shape fitting and matrix correlation identified associations between the microbiome and host transcriptome profiles, with a novel co-exclusion relationship found betweenCampylobacterand napsin B aspartic peptidase. Targeted culture ofCampylobacterspecies from the same cohort revealed a subset of isolates to have a higher capacity to survive within primary human macrophages. Comparative genomic analyses showed these isolates could be differentiated by specific genomic features, one of which was validated to be associated with intracellular fitness. Screening for theseCampylobacterstrain-specific signatures in shotgun metagenomics data from another cohort showed an increase in prevalence with disease progression. Comparative transcriptomic analyses of primary esophageal epithelial cells exposed to theCampylobacterisolates revealed expression changes within those infected with strains with high intracellular fitness that could explain the increased likelihood of disease progression.ConclusionsWe provide a comprehensive assessment of the esophageal microenvironment, identifying bacterial strain-specific signatures with high relevance to progression of metaplasia.
S100A8/A9 is not essential for the development of inflammation and joint pathology in interleukin-1 receptor antagonist knockout mice
Authors: Di Ceglie Irene , van Lent Peter L. E. M. , Geven Edwin J. W. , Koenders Marije I. , Blom Arjen B. , Vogl Thomas , Roth Johannes , van den Bosch Martijn H. J. 
Published: August 2021

Abstract
Background
Excessive osteoclast activity, which is strongly stimulated by pro-inflammatory mediators, results in bone and cartilage degeneration as central features of many arthritides. Levels of the alarmin S100A8/A9 and interleukin (IL)-1β are both increased in arthritis patients and correlate with disease activity and progression of tissue erosion. We previously presented S100A8/A9 as a good biomarker for joint inflammation and arthritis pathology under circumstances of high IL-1 signaling in mice that lack the gene encoding IL-1 receptor antagonist (Il1rn−/− mice). Here, we investigated whether S100A8/A9 is also actively involved in the development of joint inflammation and both cartilage and bone pathology under these conditions by comparing Il1rn−/− mice with mice that have an additional deficiency for S100a9 (Il1rn−/−XS100a9−/−).

Methods
Il1rn−/−XS100a9−/− on a BALB/c background were obtained by crossing S100a9−/− mice and Il1rn−/− mice. Arthritis incidence and severity were macroscopically scored. Myeloid cell populations in the bone marrow and spleen were determined using flow cytometry. In vitro osteoclastogenesis of bone marrow cells was evaluated with TRAP staining. Microscopic joint inflammation, cartilage degeneration, and bone destruction were evaluated using histology of ankle joints of 12- and 20-week-old mice.

Results
Macroscopically scored arthritis severity was comparable between Il1rn−/− and Il1rn−/−XS100a9−/− mice. Inflammation, cartilage erosion, and bone erosion were clearly present in 12-week-old mice of both strains lacking Il1rn−/−, but not significantly different between Il1rn−/−XS100a9−/− and Il1rn−/−. Moreover, we observed that the numbers of neutrophils and monocytes were increased by the absence of Il1rn, which was affected by the absence of S100a9 only in the spleen but not in the bone marrow. In line with our other findings, the absence of S100a9 did not affect the osteoclastogenic potential of osteoclast precursors in the absence of Il1rn. Finally, in agreement with the findings in early arthritis development in 12-week-old mice, cartilage and bone erosion in 20-week-old mice was significantly higher in both Il1rn−/− strains, but the additional absence of S100a9 did not further affect tissue pathology.

Conclusion
S100A8/A9 deficiency does not significantly affect inflammation and joint destruction in mice with high IL1β signaling suggesting that S100A8/A9 is not essential for the development of arthritis under these conditions.