bluuebunny/crossref_metadata_2025_split huggingface dataset:
Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study
Authors:   for the COVADIS study group, Vandenbunder Benoit , Ehrmann Stephan , Piagnerelli Michael , Sauneuf Bertrand , Serck Nicolas , Soumagne Thibaud , Textoris Julien , Vinsonneau Christophe , Aissaoui Nadia , Blonz Gauthier , Carbutti Giuseppe , Courcelle Romain , D’hondt Alain , Gaudry Stephane , Higny Julien , Horlait Geoffroy , Hraiech Sami , Lefebvre Laurent , Lejeune Francois , Ly Andre , Lascarrou Jean-Baptiste , Grimaldi David 
Published: February 2021

AbstractBackgroundControversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14.MethodsIn this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation.ResultsThe mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98–1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13–3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88–0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O,p < 0.001). The decrease in Crs was not associated with day-28 outcome.ConclusionIn a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH2O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.
Characterization of esophageal motor activity, gastroesophageal reflux, and evaluation of prokinetic effectiveness in mechanically ventilated critically ill patients: a high-resolution impedance manometry study
Authors: Balihar Karel , Kotyza Jan , Zdrhova Lucie , Kozeluhova Jana , Krcma Michal , Matejovic Martin 
Published: February 2021

Abstract
Background
Motility disorders of upper gastrointestinal tract are common in critical illness and associated with significant clinical consequences. However, detailed quantitative and qualitative analyses of esophageal motor functions are lacking. Therefore, we aimed to characterize the key features of esophageal motility functions using high-resolution impedance manometry (HRIM) and to evaluate an objective link between esophageal motor patterns, gastric emptying, and gastroesophageal reflux. We also studied the prokinetic effects of metoclopramide.

Methods
We prospectively performed HRIM for 16 critically ill hemodynamically stable patients. Patients were included if they had low gastric volume (LGV; < 100 mL/24 h, n = 8) or high gastric volume (HGV; > 500 mL/24 h, n = 8). The HRIM data were collected for 5 h with intravenous metoclopramide administration (10 mg) after the first 2 h.

Results
The findings were grossly abnormal for all critically ill patients. The esophageal contraction vigor was markedly increased, indicating prevailing hypercontractile esophagus. Ineffective propulsive force was observed for 73% of esophageal activities. Panesophageal pressurization was the most common pressurization pattern (64%). Gastroesophageal reflux predominantly occurred with transient lower esophageal sphincter relaxation. The common features of the LGV group were a hyperreactive pattern, esophagogastric outflow obstruction, and frequent reflux. Ineffective motility with reduced lower esophageal sphincter tone, and paradoxically fewer reflux episodes, was common in the HGV group. Metoclopramide administration reduced the number of esophageal activities but did not affect the number of reflux episodes in either group.

Conclusion
All critically ill patients had major esophageal motility abnormalities, and motility patterns varied according to gastric emptying status. Well-preserved gastric emptying and maintained esophagogastric barrier functions did not eliminate reflux. Metoclopramide failed to reduce the number of reflux episodes regardless of gastric emptying status.
Trial registration ISRCTN, ISRCTN14399966. Registered 3.9.2020, retrospectively registered. https://www.isrctn.com/ISRCTN14399966.
Carboxypeptidase B blocks ex vivo activation of the anaphylatoxin-neutrophil extracellular trap axis in neutrophils from COVID-19 patients
Authors: Zhang Yue , Han Kai , Du Chunjing , Li Rui , Liu Jingyuan , Zeng Hui , Zhu Liuluan , Li Ang 
Published: February 2021

Abstract
Background
Thrombosis and coagulopathy are highly prevalent in critically ill patients with COVID-19 and increase the risk of death. Immunothrombosis has recently been demonstrated to contribute to the thrombotic events in COVID-19 patients with coagulopathy. As the primary components of immunothrombosis, neutrophil extracellular traps (NETs) could be induced by complement cascade components and other proinflammatory mediators. We aimed to explore the clinical roles of NETs and the regulation of complement on the NET formation in COVID-19.

Methods
We recruited 135 COVID-19 patients and measured plasma levels of C5, C3, cell-free DNA and myeloperoxidase (MPO)-DNA. Besides, the formation of NETs was detected by immunofluorescent staining and the cytotoxicity to vascular endothelial HUVEC cells was evaluated by CCK-8 assay.

Results
We found that the plasma levels of complements C3 and MPO-DNA were positively related to coagulation indicator fibrin(-ogen) degradation products (C3: r = 0.300, p = 0.005; MPO-DNA: r = 0.316, p = 0.002) in COVID-19 patients. Besides, C3 was positively related to direct bilirubin (r = 0.303, p = 0.004) and total bilirubin (r = 0.304, p = 0.005), MPO-DNA was positively related to lactate dehydrogenase (r = 0.306, p = 0.003) and creatine kinase (r = 0.308, p = 0.004). By using anti-C3a and anti-C5a antibodies, we revealed that the complement component anaphylatoxins in the plasma of COVID-19 patients strongly induced NET formation. The pathological effect of the anaphylatoxin-NET axis on the damage of vascular endothelial cells could be relieved by recombinant carboxypeptidase B (CPB), a stable homolog of enzyme CPB2 which can degrade anaphylatoxins to inactive products.

Conclusions
Over-activation in anaphylatoxin-NET axis plays a pathological role in COVID-19. Early intervention in anaphylatoxins might help prevent thrombosis and disease progression in COVID-19 patients.
Using ActionADE to create information continuity to reduce re-exposures to harmful medications: study protocol for a randomized controlled trial
Authors: Hau Jeffrey P. , Brasher Penelope M. A. , Cragg Amber , Small Serena , Wickham Maeve , Hohl Corinne M. 
Published: February 2021

Abstract
Background
Repeat exposures to culprit medications are a common cause of preventable adverse drug events. Health information technologies have the potential to reduce repeat adverse drug events by improving information continuity. However, they rarely interoperate to ensure providers can view adverse drug events documented in other systems. We designed ActionADE to enable rapid documentation of adverse drug events and communication of standardized information across health sectors by integrating with legacy systems.
We will leverage ActionADE’s implementation to conduct two parallel, randomized trials: patients with adverse drug reactions in the main trial and those diagnosed with non-adherence in a secondary trial. Primary objective of the main trial is to evaluate the effects of providing information continuity about adverse drug reactions on culprit medication re-dispensations over 12 months. Primary objective of the secondary trial is to evaluate the effect of providing information continuity on adherence over 12 months.

Methods
We will conduct two parallel group, triple-blind randomized controlled trials in participating hospitals in British Columbia, Canada. We will enroll adults presenting to hospital with an adverse drug event to prescribed outpatient medication. Clinicians will document the adverse drug event in ActionADE. The software will use an algorithm to determine patient eligibility and allocate eligible patients to experimental or control. In the experimental arm, ActionADE will transmit information to PharmaNet, where adverse drug event information will be displayed in community pharmacies when re-dispensations are attempted. In the control arm, ActionADE will retain information in the local record. We will enroll 3600 adults with an adverse drug reaction into the main trial. The main trial’s primary outcome is re-dispensation of a culprit or same-class medication within 12 months; the secondary trial’s primary outcome will be adherence to culprit medication. Secondary outcomes include health services utilization and mortality.

Discussion
These studies have the potential to guide policy decisions and investments needed to drive health information technology integrations to prevent repeat adverse drug events. We present an example of how a health information technology implementation can be leveraged to conduct pragmatic randomized controlled trials.

Trial registration
ClinicalTrials.gov NCT04568668, NCT04574648. Registered on 1 October 2020.
Efficacy and safety of Shi-style cervical manipulation therapy for treating acute and subacute neck pain: study protocol for a randomized controlled trial
Authors: Zhang Mingcai , Du Guoqing , Liu Congying , Li Wei , Yang Jiayu , Chen Bo , Yu Xiaoyue , Xiong Yizhe , Jiang Enyu , Gao Ningyang , Jiang Sumin , Xu Zhenqiu , Wang Xiang , Zhan Hongsheng 
Published: February 2021

AbstractBackgroundNeck pain is a common clinical disease, which seriously affects people’s mental health and quality of life and results in loss of social productivity. Improving neck pain’s curative effect and reducing its recurrence rate are major medical problems. Shi’s manipulation therapy has unique advantages and technical features that aid in the diagnosis and treatment of neck pain. Compared with first-line non-steroidal anti-inflammatory drug (NSAID) treatment of neck pain, Shi’s cervical manipulation lacks the relevant research basis of therapeutic advantage, safety, and satisfaction for treating acute and subacute neck pain. Herein, we aim to confirm our hypothesis in a clinical trial that the safety and efficacy of Shi’s cervical manipulation will be more effective, safer, and more satisfactory than NSAIDs to treat acute and subacute neck pain.MethodsIn this multicenter, positive-controlled, randomized clinical trial, traditional analgesic drug (NSAID) is used to evaluate and show that Shi’s manipulation is more effective, safe, and satisfactory for treating acute and subacute neck pain. Overall, 240 subjects are randomly divided into the trial and control groups, with both groups treated by the corresponding main intervention method for up to 12 weeks. Clinical data will be collected before the intervention and immediately after the first treatment; at 3 days and 1, 2, 4, 8, and 12 weeks after the intervention; and at 26 and 52 weeks after treatment follow-up of clinical observation index data collection. The clinical observation indices are as follows: (1) cervical pain is the primary observation index, measured by Numerical Rating Scale. The secondary indices include the following: (2) cervical dysfunction index, measured by patient self-evaluation using cervical Neck Disability Index; (3) cervical activity measurement, measured by the cervical vertebra mobility measurement program of Android mobile phone system; (4) overall improvement, measured by patient self-evaluation with SF-36; and (5) satisfactory treatment, determined by patient self-evaluation.DiscussionWe will discuss whether Shi’s cervical manipulation has greater advantages in efficacy, safety, and satisfaction of acute and subacute neck pain than traditional NSAIDs, to provide a scientific basis for the dissemination and application of Shi’s cervical manipulation.Trial registrationChina Registered Clinical Trial Registration CenterChiCTR1900021371. Registered on 17 February 2019
Transitional care from skilled nursing facilities to home: study protocol for a stepped wedge cluster randomized trial
Authors: Toles M. , Colón-Emeric C. , Hanson L. C. , Naylor M. , Weinberger M. , Covington J. , Preisser J. S. 
Published: February 2021

Abstract
Background
Skilled nursing facility (SNF) patients are medically complex with multiple, advanced chronic conditions. They are dependent on caregivers and have experienced recent acute illnesses. Among SNF patients, the rate of mortality or acute care use is over 50% within 90 days of discharge, yet these patients and their caregivers often do not receive the quality of transitional care that prepares them to manage serious illnesses at home.

Methods
The study will test the efficacy of Connect-Home, a successfully piloted transitional care intervention targeting seriously ill SNF patients discharged to home and their caregivers. The study setting will be SNFs in North Carolina, USA, and, following discharge, in patients’ home. Using a stepped wedge cluster randomized trial design, six SNFs will transition at randomly assigned intervals from standard discharge planning to the Connect-Home intervention. The SNFs will contribute data for patients (N = 360) and their caregivers (N = 360), during both the standard discharge planning and Connect-Home time periods. Connect-Home is a two-step intervention: (a) SNF staff create an individualized Transition Plan of Care to manage the patient’s illness at home; and (b) a Connect-Home Activation RN visits the patient’s home to implement the written Transition Plan of Care. A key feature of the trial includes training of the SNF and Home Care Agency staff to complete the transition plan rather than using study interventionists. The primary outcomes will be patient preparedness for discharge and caregiver preparedness for caregiving role. With the proposed sample and using a two-sided test at the 5% significance level, we have 80% power to detect a 18% increase in the patient’s preparedness for discharge score. We will employ linear mixed models to compare observations between intervention and usual care periods to assess primary outcomes. Secondary outcomes include (a) patients’ quality of life, functional status, and days of acute care use and (b) caregivers’ burden and distress.

Discussion
Study results will determine the efficacy of an intervention using existing clinical staff to (a) improve transitional care for seriously ill SNF patients and their caregivers, (b) prevent avoidable days of acute care use in a population with persistent risks from chronic conditions, and (c) advance the science of transitional care within end-of-life and palliative care trajectories of SNF patients and their caregivers. While this study protocol was being implemented, the COVID-19 pandemic occurred and this protocol was revised to mitigate COVID-related risks of patients, their caregivers, SNF staff, and the study team. Thus, this paper includes additional material describing these modifications.

Trial registration
ClinicalTrials.gov NCT03810534. Registered on January 18, 2019.
Robotic natural orifice specimen extraction surgery versus traditional robotic-assisted surgery (NOTR) for patients with colorectal cancer: a study protocol for a randomized controlled trial
Authors: Luo Rui , Zheng Fangfang , Zhang Haobo , Zhu Weiquan , He Penghui , Liu Dongning 
Published: February 2021

Abstract
Background
Natural orifice specimen extraction surgery for colorectal cancer has been introduced in order to reduce the abdominal incision, demonstrating major development potential in minimally invasive surgery. We are conducting this randomized controlled trial to assess whether robotic NOSES is non-inferior to traditional robotic-assisted surgery for patients with colorectal cancer in terms of primary and secondary outcomes.

Method/design
Accordingly, a prospective, open-label, randomized controlled, parallel-group, multicenter, and non-inferiority trial will be conducted to discuss the safety and efficacy of robotic natural orifice extraction surgery compared to traditional robotic-assisted surgery. Here, 550 estimated participants will be enrolled to have 80% power to detect differences with a one-sided significance level of 0.025 in consideration of the non-inferiority margin of 10%. The primary outcome is the incidence of surgical complications, which will be classified using the Clavien-Dindo system.

Discussion
This trial is expected to reveal whether robotic NOSES is non-inferior to traditional robotic-assisted surgery, which is of great significance in regard to the development of robotic NOSES for patients with colorectal cancer in the minimally invasive era. Furthermore, robotic NOSES is expected to exhibit superiority to traditional robotic-assisted surgery in terms of both primary and secondary outcomes.

Trial registration
ClinicalTrials.govNCT04230772. Registered on January 15, 2020.
Cardinium symbiosis as a potential confounder of mtDNA based phylogeographic inference in Culicoides imicola (Diptera: Ceratopogonidae), a vector of veterinary viruses
Authors: Pilgrim Jack , Siozios Stefanos , Baylis Matthew , Venter Gert , Garros Claire , Hurst Gregory D. D. 
Published: February 2021

Abstract
Background
Culicoides imicola (Diptera: Ceratopogonidae) is an important Afrotropical and Palearctic vector of disease, transmitting viruses of animal health and economic significance including African horse sickness and bluetongue viruses. Maternally inherited symbiotic bacteria (endosymbionts) of arthropods can alter the frequency of COI (cytochrome c oxidase subunit I) mitochondrial haplotypes (mitotypes) in a population, masking the true patterns of host movement and gene flow. Thus, this study aimed to assess the mtDNA structure of C. imicola in relation to infection with Candidatus Cardinum hertigii (Bacteroides), a common endosymbiont of Culicoides spp.

Methods
Using haplotype network analysis, COI Sanger sequences from Cardinium-infected and -uninfected C. imicola individuals were first compared in a population from South Africa. The network was then extended to include mitotypes from a geographic range where Cardinium infection has previously been investigated.

Results
The mitotype network of the South African population demonstrated the presence of two broad mitotype groups. All Cardinium-infected specimens fell into one group (Fisher’s exact test, P = 0.00071) demonstrating a linkage disequilibrium between endosymbiont and mitochondria. Furthermore, by extending this haplotype network to include other C. imicola populations from the Mediterranean basin, we revealed mitotype variation between the Eastern and Western Mediterranean basins (EMB and WMB) mirrored Cardinium-infection heterogeneity.

Conclusions
These observations suggest that the linkage disequilibrium of Cardinium and mitochondria reflects endosymbiont gene flow within the Mediterranean basin but may not assist in elucidating host gene flow. Subsequently, we urge caution on the single usage of the COI marker to determine population structure and movement in C. imicola and instead suggest the complementary utilisation of additional molecular markers.

Graphical Abstract
Molecular characterization and serodiagnostic potential of Echinococcus granulosus hexokinase
Authors: Xin Qi , Yuan Miaomiao , Lv Wei , Li Huanping , Song Xiaoxia , Lu Jun , Jing Tao 
Published: February 2021

Abstract
Background
Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus (sensu stricto), is a life-threatening but neglected zoonosis. Glycolytic enzymes are crucial molecules for the survival and development of E. granulosus. The aim of this study was to investigate the molecular characterization, immunogenicity, tissue distribution and serodiagnostic potential of E. granulosus hexokinase (EgHK), the first key enzyme in the glycolytic pathway.

Methods
EgHK was cloned and expressed in Escherichia coli. Specific serum antibodies were evaluated in mice immunized with recombinant EgHK (rEgHK). The location of EgHK in the larval stage of E. granulosus was determined using fluorescence immunohistochemistry, and the potential of rEgHK as a diagnostic antigen was investigated in patients with CE using indirect enzyme-linked immunosorbent assay (ELISA).

Results
Recombinant EgHK could be identified in the sera of patients with CE and in mouse anti-rEgHK sera. High titers of specific immunoglobulin G were induced in mice after immunization with rEgHK. EgHK was mainly located in the tegument, suckers and hooklets of protoscoleces and in the germinal layer and laminated layer of the cyst wall. The sensitivity and specificity of the rEgHK-ELISA reached 91.3% (42/46) and 87.8% (43/49), respectively.

Conclusions
We have characterized the sequence, structure and location of EgHK and investigated the immunoreactivity, immunogenicity and serodiagnostic potential of rEgHK. Our results suggest that EgHK may be a promising candidate for the development of vaccines against E. granulosus and an effective antigen for the diagnosis of human CE.

Graphical Abstract