bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of body mass index, weight loss and progression of idiopathic pulmonary fibrosis
Authors: Jouneau Stéphane , Crestani Bruno , Thibault Ronan , Lederlin Mathieu , Vernhet Laurent , Valenzuela Claudia , Wijsenbeek Marlies , Kreuter Michael , Stansen Wibke , Quaresma Manuel , Cottin Vincent 
Published: November 2020

Abstract
Background
Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF.

Methods
Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m2) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression.

Results
In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (− 283.3 [SE 22.4], − 207.9 [20.9] and − 104.5 [21.4] in patients with BMI < 25 kg/m2, ≥25 to < 30 kg/m2 and ≥ 30 kg/m2, respectively). Nintedanib reduced the rate of FVC decline versus placebo in all subgroups by BMI, with a consistent treatment effect across subgroups (interaction p = 0.31). In the placebo group, the mean rate of FVC decline was numerically greater in patients with > 5% than ≤5% weight loss over 52 weeks (− 312.7 [SE 32.2] versus − 199.5 [SE 14.4] mL/year). Nintedanib reduced the rate of FVC decline versus placebo in both subgroups by weight loss, with a greater treatment effect in patients with > 5% weight loss (interaction p = 0.0008). The adverse event profile of nintedanib was similar across subgroups.

Conclusions
In patients with IPF, lower BMI and weight loss may be associated with faster decline in FVC. Nintedanib reduces the rate of FVC decline both in patients who lose weight on treatment and those who do not.

Trial registration
ClinicalTrials.gov; Nos. NCT01335464 and NCT01335477; URL: www.clinicaltrials.gov.
Outcome quality standards in advanced ovarian cancer surgery
Authors:   on behalf MUAPOS Working Group, Llueca Antoni , Serra Anna , Climent Maria Teresa , Segarra Blanca , Maazouzi Yasmine , Soriano Marta , Escrig Javier 
Published: November 2020

Abstract
Introduction
Advanced ovarian cancer surgery (AOCS) frequently results in serious postoperative complications. Because managing AOCS is difficult, some standards need to be established that allow surgeons to assess the quality of treatment provided and consider what aspects should improve. This study aimed to identify quality indicators (QIs) of clinical relevance and to establish their acceptable quality limits (i.e., standard) in AOCS.

Materials and methods
We performed a systematic search on clinical practice guidelines, consensus conferences, and reviews on the outcome and quality of AOCS to identify which QIs have clinical relevance in AOCS. We then searched the literature (from January 2006 to December 2018) for each QI in combination with the keywords of advanced ovarian cancer, surgery, outcome, and oncology. Standards for each QI were determined by statistical process control techniques. The acceptable quality limits for each QI were defined as being within the limits of the 99.8% interval, which indicated a favorable outcome.

Results
A total of 38 studies were included. The QIs selected for AOCS were complete removal of the tumor upon visual inspection (complete cytoreductive surgery), a residual tumor of < 1 cm (optimal cytoreductive surgery), a residual tumor of > 1 cm (suboptimal cytoreductive surgery), major morbidity, and 5-year survival. The rates of complete cytoreductive surgery, optimal cytoreductive surgery, suboptimal cytoreductive surgery, morbidity, and 5-year survival had quality limits of < 27%, < 23%, > 39%, > 33%, and < 27%, respectively.

Conclusion
Our results provide a general view of clinical indicators for AOCS. Acceptable quality limits that can be considered as standards were established.
The role of mitophagy in innate immune responses triggered by mitochondrial stress
Authors: Song Yinjuan , Zhou Yang , Zhou Xiangmei 
Published: November 2020

Abstract
Mitochondria are important cellular organelles involved in many different functions, from energy generation and fatty acid oxidation to cell death regulation and immune responses. Accumulating evidence indicates that mitochondrial stress acts as a key trigger of innate immune responses. Critically, the dysfunctional mitochondria can be selectively eliminated by mitophagy. The elimination of dysfunctional mitochondria may function as an effective way employed by mitophagy to keep the immune system in check. In addition, mitophagy can be utilized by pathogens for immune evasion. In this review, we summarize how mitochondrial stress triggers innate immune responses and the roles of mitophagy in innate immunity and in infection, as well as the molecular mechanisms of mitophagy.

Graphical abstract
The good, the bad, and the opportunities of the complement system in neurodegenerative disease
Authors: Schartz Nicole D. , Tenner Andrea J. 
Published: November 2020

AbstractThe complement cascade is a critical effector mechanism of the innate immune system that contributes to the rapid clearance of pathogens and dead or dying cells, as well as contributing to the extent and limit of the inflammatory immune response. In addition, some of the early components of this cascade have been clearly shown to play a beneficial role in synapse elimination during the development of the nervous system, although excessive complement-mediated synaptic pruning in the adult or injured brain may be detrimental in multiple neurogenerative disorders. While many of these later studies have been in mouse models, observations consistent with this notion have been reported in human postmortem examination of brain tissue. Increasing awareness of distinct roles of C1q, the initial recognition component of the classical complement pathway, that are independent of the rest of the complement cascade, as well as the relationship with other signaling pathways of inflammation (in the periphery as well as the central nervous system), highlights the need for a thorough understanding of these molecular entities and pathways to facilitate successful therapeutic design, including target identification, disease stage for treatment, and delivery in specific neurologic disorders. Here, we review the evidence for both beneficial and detrimental effects of complement components and activation products in multiple neurodegenerative disorders. Evidence for requisite co-factors for the diverse consequences are reviewed, as well as the recent studies that support the possibility of successful pharmacological approaches to suppress excessive and detrimental complement-mediated chronic inflammation, while preserving beneficial effects of complement components, to slow the progression of neurodegenerative disease.
Neurotransmitter and neuropeptide regulation of mast cell function: a systematic review
Authors: Xu Huaping , Shi Xiaoyun , Li Xin , Zou Jiexin , Zhou Chunyan , Liu Wenfeng , Shao Huming , Chen Hongbing , Shi Linbo 
Published: November 2020

AbstractThe existence of the neural control of mast cell functions has long been proposed. Mast cells (MCs) are localized in association with the peripheral nervous system (PNS) and the brain, where they are closely aligned, anatomically and functionally, with neurons and neuronal processes throughout the body. They express receptors for and are regulated by various neurotransmitters, neuropeptides, and other neuromodulators. Consequently, modulation provided by these neurotransmitters and neuromodulators allows neural control of MC functions and involvement in the pathogenesis of mast cell–related disease states. Recently, the roles of individual neurotransmitters and neuropeptides in regulating mast cell actions have been investigated extensively. This review offers a systematic review of recent advances in our understanding of the contributions of neurotransmitters and neuropeptides to mast cell activation and the pathological implications of this regulation on mast cell–related disease states, though the full extent to which such control influences health and disease is still unclear, and a complete understanding of the mechanisms underlying the control is lacking. Future validation of animal and in vitro models also is needed, which incorporates the integration of microenvironment-specific influences and the complex, multifaceted cross-talk between mast cells and various neural signals. Moreover, new biological agents directed against neurotransmitter receptors on mast cells that can be used for therapeutic intervention need to be more specific, which will reduce their ability to support inflammatory responses and enhance their potential roles in protecting against mast cell–related pathogenesis.
Feasibility and initial efficacy of a high-intensity interval training program using adaptive equipment in persons with multiple sclerosis who have walking disability: study protocol for a single-group, feasibility trial
Authors: Hubbard Elizabeth A. , Motl Robert W. , Elmer David J. 
Published: November 2020

Abstract
Background
There is considerable evidence for the efficacy of moderate-intensity continuous exercise benefitting clinically relevant outcomes in persons with multiple sclerosis (MS). However, persons with MS who have walking disability (pwMS-wd) are severely deconditioned and may achieve superior benefits by engaging in high-intensity interval training (HIIT), especially while utilizing adaptive equipment, such as recumbent arm/leg stepping (RSTEP). The proposed study will assess the feasibility of a 12-week, RSTEP HIIT program in pwMS-wd. The secondary aim will examine changes in aerobic fitness, physical activity, ambulation, upper arm function, cognition, fatigue, and depression as clinically relevant efficacy outcomes following the 12-week, RSTEP HIIT intervention.

Methods
The study will recruit 15 pwMS-wd. Feasibility will be measured via process, resource, management, and scientific outcomes throughout the entirety of the research study. The secondary, clinically relevant outcomes will consist of a neurological exam, aerobic capacity, physical activity, ambulation, cognition, upper arm function, fatigue, and depression. Outcomes will be assessed at baseline (T1), midpoint (T2, following 6 weeks), and post-intervention (T3, following 12 weeks). The intervention will involve 12 weeks of supervised, individualized HIIT sessions two to three times per week. The individual HIIT sessions will each involve 10 cycles of 60-s intervals at the wattage associated with 90% VO2peak followed by 60 s of active recovery intervals at 15 W, totaling 20 min in length plus 5-min warm-up and cool-down periods.

Discussion
The feasibility design of the proposed study will provide experience and preliminary data for advancing towards a proof-of-concept study comparing HIIT to moderate-intensity continuous RSTEP for improving clinically relevant outcomes in a randomized control trial design. The results will be disseminated via manuscripts for publication and a report for distribution among the National Multiple Sclerosis Society.

Trial registration
ClinicalTrials.gov NCT04416243. Retrospectively registered on June 4, 2020
The A2B trial, antibiotic prophylaxis for excision-graft surgery in burn patients: a multicenter randomized double-blind study
Authors:   for the A2B trial investigators, Dépret François , Farny Boris , Jeanne Mathieu , Klouche Kada , Leclerc Thomas , Nouette-Gaulain Karine , Pantet Olivier , Rémerand Francis , Roquilly Antoine , Rousseau Anne-Françoise , Sztajnic Simon , Wiramus Sandrine , Vicaut Eric , Legrand Matthieu 
Published: November 2020

Abstract
Background
The indication for antibiotic prophylaxis in burn patients remains highly controversial, with no consensus having been reached. The objective of antibiotic prophylaxis is to reduce the risk of postoperative local and systemic infections. Burn surgery is associated with a high incidence of bacteremia, postoperative infections, and sepsis. However, antibiotic prophylaxis exposes patients to the risk of selecting drug-resistant pathogens as well as to the adverse effects of antibiotics (i.e., Clostridium difficile colitis). The lack of data precludes any strong international recommendations regarding perioperative prophylaxis using systemic antibiotics in this setting.
The goal of this project is therefore to determine whether perioperative systemic antibiotic prophylaxis can reduce the incidence of postoperative infections in burn patients.

Methods
The A2B trial is a multicenter (10 centers), prospective, randomized, double-blinded, placebo-controlled study. The trial will involve the recruitment of 506 adult burn patients with a total body surface area (TBSA) burn of between 5 and 40% and requiring at least one excision-graft surgery for deep burn injury. Participants will be randomized to receive antibiotic prophylaxis (antibiotic prophylaxis group) or a placebo (control group) 30 min before the incision of the first two surgeries. The primary outcome will be the occurrence of postoperative infections defined as postoperative sepsis and/or surgical site infection and/or graft lysis requiring a new graft within 7 days after surgery. Secondary outcomes will include mortality at day 90 postrandomization, skin graft lysis requiring a new graft procedure, postoperative bacteremia (within 48 h of surgery), postoperative sepsis, postoperative surgical site infection, number of hospitalizations until complete healing (> 95% TBSA), number of hospitalization days living without antibiotic therapy at day 28 and day 90, and multiresistant bacterial colonization or infection at day 28 and day 90.

Discussion
The trial aims to provide evidence on the efficacy and safety of antibiotic prophylaxis for excision-graft surgery in burn patients.

Trial registration
ClinicalTrials.gov NCT04292054. Registered on 2 March 2020
Relationship between the severity of endometriosis symptoms (dyspareunia, dysmenorrhea and chronic pelvic pain) and the spread of the disease on ultrasound
Authors: Kor Elham , Mostafavi Seyed Reza Saadat , Mazhin Zahra Ahmadian , Dadkhah Adeleh , Kor Anis , Arvanagh Shirin Habibi , Noroozi Shima Ghafourian , Sadri Ghazal 
Published: November 2020

Abstract
Objectives
About 10–15% of women of childbearing age have endometriosis. The present study aimed to investigate the relationship between the severity of symptoms of endometriosis and the spread as well as the stage of the disease on ultrasonography. The present cross-sectional study evaluates the relationship between the severity of endometriosis symptoms and the spread of disease on ultrasonography in patients with endometriosis.

Results
Considering different analyses, the cumulative size of posterior deep infiltrative endometriosis (DIE) (less than 1 cm) is significantly correlated with minimal severity of dyspareunia and chronic pelvic pain. The incidence of dyspareunia was more prevalent in patients with complete stenosis of Douglas pouch than those with incomplete stenosis. Furthermore, the incidence of severe and very severe pain in patients with Douglas pouch stenosis is relatively higher than that in patients without stenosis. Only dyspareunia is related to the stage of endometriosis, and patients with dyspareunia are five times more at risk of a higher stage of the disease. The severity of dyspareunia is related to the stage of endometriosis and the severity of Douglas pouch stenosis. The results showed a correlation between chronic pelvic pain and r-ASRM score (revised American Society for Reproductive Medicine score).
Emerging roles of N6-methyladenosine (m6A) modification in breast cancer
Authors: Wang Yanyan , Zhang Yujie , Du Yushen , Zhou Meiqi , Hu Yue , Zhang Suzhan 
Published: November 2020

AbstractN6-Methyladenosine (m6A) is the most abundant, dynamic, and reversible epigenetic RNA modification that is found in coding and non-coding RNAs. Emerging studies have shown that m6A and its regulators affect multiple steps in RNA metabolism and play broad roles in various cancers. Worldwide, breast cancer is the most prevalent cancer in female. It is a very heterogeneous disease characterized by genetic and epigenetic variations in tumor cells. Increasing evidence has shown that the dysregulation of m6A-related effectors, as methyltransferases, demethylases, and m6A binding proteins, is pivotal in breast cancer pathogenesis. In this review, we have summarized the most up-to-date research on the biological functions of m6A modification in breast cancer and have discussed the potential clinical applications and future directions of m6A modification as a biomarker as well as a therapeutic target of breast cancer.
Fear of panoptic surveillance: using digital technology to control the COVID-19 epidemic
Authors: Keshet Yael 
Published: November 2020

AbstractBackgroundIn a bid to reduce infection rates by COVID-19 the authorities in some countries, in collaboration with medical regulators and experts, have employed digital technologies to control and regulate citizens’ behavior. Public opinion and the public’s compliance with these technologies come into play here. The objective of the present study was to examine attitudes expressed in the public discourse toward the use of digital technologies to control people’s behavior during the COVID-19 pandemic, as reflected in the media.MethodsQualitative analysis was performed on posts and comments submitted in response to 12 articles that appeared on the four leading Israeli news sites, on three significant occasions: first, upon the announcement of the use of surveillance technologies by the Israeli security agency (ISA); second, upon the announcement of the launch of the Health Ministry’s app that tracks contacts with COVID-19 patients; and third, following reports of petitions lodged with Israel’s supreme court challenging the use of surveillance technologies. The analysis was performed using ATLAS-Ti software for systematic analysis.ResultsA total of 2551 posts and comments referring to these 12 articles were found, 714 of which were relevant to the purpose of the study. The analysis revealed disagreement between those who supported the measures taken and opponents. Supporters regarded contact tracing by means of digital technologies as essential to the effort to protect people during the pandemic, and believed that employing the ISA’s capabilities was the correct way to combat the epidemic. Opponents of the measures rejected the use of tracking technologies, regarding this step as a move toward dictatorship and a violation of fundamental civil rights. Some proposed alternative measures that would obviate the use of such tracking.ConclusionsThe primary task of medical practice is to heal illness and alleviate suffering. The debate surrounding the employment of digital technologies during the COVID-19 pandemic highlights the complexity of the close connection between social control and care in times of pandemic. The context of this pandemic has highlighted the interrelatedness of advanced digital surveillance technologies, medical care, and social control exercised by authorities and medical regulators and experts, which raises issues of transparency, trust and mistrust among the public. These issues become all the more relevant when the number of patients grows rapidly, the authorities need to deal with the extended ongoing COVID-19 pandemic, the country has entered a second lockdown, and the public must be persuaded to comply with highly restrictive regulations. Recommendations to policy makers, practical implications, and suggestions for future research are discussed.
Stability of deficiency indices for discrete Hamiltonian systems under bounded perturbations
Authors: Liu Yan , Xu Meiru 
Published: November 2020

AbstractThis paper is concerned with stability of deficiency indices for discrete Hamiltonian systems under perturbations. By applying the perturbation theory of Hermitian linear relations we establish the invariance of deficiency indices for discrete Hamiltonian systems under bounded perturbations. As a consequence, we obtain the invariance of limit types for the systems under bounded perturbations. In particular, we build several criteria of the invariance of the limit circle and limit point cases for the systems. Some of these results improve and extend some previous results.
A spatio-temporal specification language and its completeness & decidability
Authors: Li Tengfei , Liu Jing , Sun Haiying , Chen Xiang , Zhang Lipeng , Sun Junfeng 
Published: November 2020

AbstractIn the past few years, significant progress has been made on spatio-temporal cyber-physical systems in achieving spatio-temporal properties on several long-standing tasks. With the broader specification of spatio-temporal properties on various applications, the concerns over their spatio-temporal logics have been raised in public, especially after the widely reported safety-critical systems involving self-driving cars, intelligent transportation system, image processing. In this paper, we present a spatio-temporal specification language, STSLPC, by combining Signal Temporal Logic (STL) with a spatial logic S4u, to characterize spatio-temporal dynamic behaviors of cyber-physical systems. This language is highly expressive: it allows the description of quantitative signals, by expressing spatio-temporal traces over real valued signals in dense time, and Boolean signals, by constraining values of spatial objects across threshold predicates. STSLPCcombines the power of temporal modalities and spatial operators, and enjoys important properties such as finite model property. We provide a Hilbert-style axiomatization for the proposed STSLPCand prove the soundness and completeness by the spatio-temporal extension of maximal consistent set and canonical model. Further, we demonstrate the decidability of STSLPCand analyze the complexity of STSLPC. Besides, we generalize STSL to the evolution of spatial objects over time, called STSLOC, and provide the proof of its axiomatization system and decidability.