bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive phenotypes 1 month after ICU discharge in mechanically ventilated patients: a prospective observational cohort study
Authors: Fernández-Gonzalo Sol , Navarra-Ventura Guillem , Bacardit Neus , Gomà Fernández Gemma , de Haro Candelaria , Subirà Carles , López-Aguilar Josefina , Magrans Rudys , Sarlabous Leonardo , Aquino Esperanza Jose , Jodar Mercè , Rué Montse , Ochagavía Ana , Palao Diego J. , Fernández Rafael , Blanch Lluís 
Published: October 2020

Abstract
Background
ICU patients undergoing invasive mechanical ventilation experience cognitive decline associated with their critical illness and its management. The early detection of different cognitive phenotypes might reveal the involvement of diverse pathophysiological mechanisms and help to clarify the role of the precipitating and predisposing factors. Our main objective is to identify cognitive phenotypes in critically ill survivors 1 month after ICU discharge using an unsupervised machine learning method, and to contrast them with the classical approach of cognitive impairment assessment. For descriptive purposes, precipitating and predisposing factors for cognitive impairment were explored.

Methods
A total of 156 mechanically ventilated critically ill patients from two medical/surgical ICUs were prospectively studied. Patients with previous cognitive impairment, neurological or psychiatric diagnosis were excluded. Clinical variables were registered during ICU stay, and 100 patients were cognitively assessed 1 month after ICU discharge. The unsupervised machine learning K-means clustering algorithm was applied to detect cognitive phenotypes. Exploratory analyses were used to study precipitating and predisposing factors for cognitive impairment.

Results
K-means testing identified three clusters (K) of patients with different cognitive phenotypes: K1 (n = 13), severe cognitive impairment in speed of processing (92%) and executive function (85%); K2 (n = 33), moderate-to-severe deficits in learning-memory (55%), memory retrieval (67%), speed of processing (36.4%) and executive function (33.3%); and K3 (n = 46), normal cognitive profile in 89% of patients. Using the classical approach, moderate-to-severe cognitive decline was recorded in 47% of patients, while the K-means method accurately classified 85.9%. The descriptive analysis showed significant differences in days (p = 0.016) and doses (p = 0.039) with opioid treatment in K1 vs. K2 and K3. In K2, there were more women, patients were older and had more comorbidities (p = 0.001) than in K1 or K3. Cognitive reserve was significantly (p = 0.001) higher in K3 than in K1 or K2.

Conclusion
One month after ICU discharge, three groups of patients with different cognitive phenotypes were identified through an unsupervised machine learning method. This novel approach improved the classical classification of cognitive impairment in ICU survivors. In the exploratory analysis, gender, age and the level of cognitive reserve emerged as relevant predisposing factors for cognitive impairment in ICU patients.

Trial registration
ClinicalTrials.gov Identifier:NCT02390024; March 17,2015.
CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway
Authors: Hou Sheng-Mou , Chen Po-Chun , Lin Chieh-Mo , Fang Mei-Ling , Chi Miao-Ching , Liu Ju-Fang 
Published: October 2020

AbstractBackgroundOsteoarthritis (OA) and rheumatoid arthritis (RA) are common joint disorders that are considered to be different diseases due to their unique molecular mechanisms and pathogenesis. Chemokines and their corresponding receptors have been well characterized in RA progression, but less so in OA pathogenesis.MethodsThe human primary synovial fibroblasts (SFs) were obtained from human OA and RA tissue samples. The Western blot and qPCR were performed to analyze the expression levels of CXCL1, as well as CXCL-promoted IL-6 expression in both OASFs and RASFs. The signal cascades that mediate the CXCL1-promoted IL-6 expression were identified by using chemical inhibitors, siRNAs, and shRNAs.ResultsHere, we found that both diseases feature elevated levels of CXCL1 and interleukin (IL)-6, an important proinflammatory cytokine that participates in OA and RA pathogenesis. In OASFs and RASFs, CXCL1 promoted IL-6 expression in a dose- and time-dependent manner. In OASFs and RASFs overexpressing CXCL1 or transduced with shRNA plasmid, IL-6 expression was markedly upregulated. CXCR2, c-Raf, and MAPKs were found to regulate CXCL1-induced IL-6 expression in OASFs and RASFs. Finally, CXCL1 triggered the transcriptional activities of c-Jun (which regulates the expression of proinflammatory proteins) in OASFs and RASFs.ConclusionsOur present work suggests that the CXCL1/CXCR2 axis helps to orchestrate inflammatory responses in OA and RA SFs.
ASP5094, a humanized monoclonal antibody against integrin alpha-9, did not show efficacy in patients with rheumatoid arthritis refractory to methotrexate: results from a phase 2a, randomized, double-blind, placebo-controlled trial
Authors: Takeuchi Tsutomu , Tanaka Yoshiya , Erdman Jay , Kaneko Yuichiro , Saito Masako , Higashitani Chieri , Smulders Ronald , Lademacher Christopher 
Published: October 2020

Abstract
Background
Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune condition characterized by joint synovial inflammation. Current treatments include methotrexate (MTX), biologic agents, and Janus kinase (JAK) inhibitors. However, these agents are not efficacious in all patients and there are concerns regarding side effects and risk of infection as these treatments target immune-related pathways. Overexpression and activation of integrin alpha-9 (α9) on fibroblast-like synoviocytes are associated with RA disease onset and exacerbation. The humanized immunoglobulin G1 monoclonal antibody ASP5094 was designed to inhibit human α9 and is currently under investigation for the treatment of RA.

Methods
This phase 2a, multicenter, randomized, placebo-controlled, double-blind, parallel-group study (NCT03257852) evaluated the efficacy, safety, and biological activity of intravenous ASP5094 10 mg/kg in patients with moderate to severe RA that was refractory to MTX. Patients received ASP5094 or placebo every 4 weeks for a total of three administrations. Both treatment groups used concomitant MTX. The primary efficacy endpoint was the proportion of patients who responded per American College of Rheumatology 50% improvement using C-reactive protein (ACR50-CRP) after 12 weeks of treatment. Biological activity of ASP5094 was assessed via pharmacokinetics and pharmacodynamics of known downstream effectors of α9. Safety was also assessed.

Results
Sixty-six patients were enrolled and randomized to placebo (n = 33) or ASP5094 (n = 33). In the primary efficacy analysis, ACR50-CRP response rates were 6.3% and 18.2% at week 12 in the ASP5094 and placebo groups, respectively; a difference of − 11.9, which was not significant (2-sided P value = 0.258). No trends in ACR50 response rates were observed in subgroups based on demographics or baseline disease characteristics, and no significant differences between placebo and ASP5094 were identified in secondary efficacy or pharmacodynamic endpoints, despite achievement of target serum concentrations of ASP5094. Most treatment-emergent adverse events were mild to moderate in severity, and ASP5094 was considered safe and well tolerated overall.

Conclusion
Although no notable safety signals were observed in this study, ASP5094 was not efficacious in patients with moderate to severe RA with an inadequate response to MTX.

Trial registration
ClinicalTrials.gov, NCT03257852. Registered on 22 Aug. 2017
In vitro biological assessment of the stability of cigarette smoke aqueous aerosol extracts
Authors: Taylor Mark , Santopietro Simone , Baxter Andrew , East Nicole , Breheny Damien , Thorne David , Gaça Marianna 
Published: October 2020

Abstract
Objectives
Cigarette smoke aqueous aerosol extracts (AqE) have been used for assessing tobacco products, particularly with in vitro models such as oxidative stress and inflammation. These test articles can be generated easily, but there are no standardised methods for the generation and characterisation or stability. We investigated the effects of pro-oxidant smoke-derived chemicals by using 3R4F AqE generated under standardised conditioning and smoking regimes and assessed the stability over 31-week timeframe. Twenty batches generated from ten puffs per cigarette bubbled through 20 ml cell culture media were used fresh and thawed from frozen aliquots stored at – 80 ºC.

Results
Nicotine levels quantified by gas chromatography/mass spectrometry and optical density at 260 nm showed chemical and physical stability from week 0 (fresh sample) to weeks 1, 4, 8 and 31 (frozen samples). No significant change in H292 human bronchial epithelial cell viability or oxidative stress were observed between fresh AqE at week 0 and frozen AqE at 31 weeks. AqEs generated by our protocol were stable for up to 31 weeks for all tested end points, suggesting that it may not be necessary to use freshly generated AqE for each study, thus reducing batch-to-batch variability.
Sleep disturbances among physicians during COVID-19 pandemic
Authors: Alnofaiey Yasser H. , Alshehri Haneen A. , Alosaimi Maram M. , Alswat Shrooq H. , Alswat Raghad H. , Alhulayfi Rahaf M. , Alghamdi Meteb A. , Alsubaie Reem M. 
Published: October 2020

AbstractObjectivesTo assess prevalence and related factors of sleep disturbances among Saudi physicians during COVID-19 pandemic. Data were collected through a questionnaire including items about demographic characters, knowledge about covid-19 and items to assess sleep quality that were extracted from Pittsburgh Sleep Quality Index (PSQI) scale.ResultsPrevalence of sleep disorders was 43.9%, doctors in the age group of 31–40 years, associate consultants had a significant higher prevalence of sleep disorders. Medical interns and laboratory/pathology/microbiology doctors had a significant more difficulty in fall asleep during COVID-19, and internists and surgeons had a significant higher percent of those who used sleeping pills. Resident doctors had a significant higher percent of having trouble in staying awake, and residents and consultants had a significant higher percent of those who suffered decreased sleep duration. Sleep quality during COVID-19 was very good, fair good and very bad in 23.4%, 60% and 3.5% of HCW respectively. The study observed a negative impact of COVID-19 pandemic on HCW sleep quality. Hospitals administrations should provide optimal working hours with enough break and employ more doctors during the pandemic. Doctors experiencing sleep problems should have mandatory leaves.
Comparison of hospital worker anxiety in COVID-19 treating and non-treating hospitals in the same city during the COVID-19 pandemic
Authors: Milgrom Yael , Tal Yuval , Finestone Aharon S. 
Published: October 2020

Abstract
Background
The Hadassah Medical Organization operates two hospitals in Jerusalem. During the COVID-19 pandemic it made an administrative decision to operate one hospital as a COVID-19 treatment hospital (CTH) and to have the second function as a non-COVID-19 treating hospital (NCTH) offering general medical services. The purpose of this study was to assess how this decision affected hospital worker anxiety.

Methods
From April 27 to May 1, during the COVID-19 pandemic in Israel, while the country was under lock-down, an electronic questionnaire survey was carried out among hospital workers of the CTH and NCTH. The questionnaire includes personal demographics and attitudes about COVID-19 and assesses present anxiety state using the State-Trait Anxiety Inventory for Adults (STAI-S) validated questionnaire. A STAI-S score of ≥45 was considered to represent clinical anxiety.

Results
Completed questionnaires were received from 1570 hospital employees (24%). 33.5% of responders had STAI-S scores ≥45. Multivariable regression analysis showed that being a resident doctor (odds ration [OR] 2.13; 95% CL, 1.41–3.23; P = 0.0003), age ≤ 50 (OR, 2.08; 95% Cl, 1.62–2.67; P < .0001), being a nurse (OR, 1.29; 95% CL, 1.01–1.64; P = 0.039), female gender (OR, 1.63; 95% CL, 1.25–2.13; P = 0.0003) and having risk factors for COVID-19 (OR, 1.51; 95% CL, 1.19–1.91; P = 0.0007), but not hospital workplace (p = 0.08), were associated with the presence of clinical anxiety. 69% of the responders had been tested for COVID-19, but only nine were positive. CTH workers estimated that the likelihood of their already being infected with COVID-19 to be 21.5 ± 24.7% as compared to the 15.3 ± 19.5% estimate of NCTH workers (p = 0.0001). 50% (545/1099) of the CTH workers and 51% (168/330) of the NCTH workers responded that the most important cause of their stress was a fear of infecting their families (p = 0.7).

Conclusions
By multivariable analysis the creation of a NCTH during the COVID-19 pandemic was not found to be associated with a decrease in the number of hospital workers with clinical anxiety. Hospital worker support resources can be focused on the at-risk groups identified in this study.
Pseudo almost periodic synchronization of Clifford-valued fuzzy cellular neural networks with time-varying delays on time scales
Authors: Li Yongkun , Shen Shiping 
Published: October 2020

AbstractAt present, the research on discrete-time Clifford-valued neural networks is rarely reported. However, the discrete-time neural networks are an important part of the neural network theory. Because the time scale theory can unify the study of discrete- and continuous-time problems, it is not necessary to separately study continuous- and discrete-time systems. Therefore, to simultaneously study the pseudo almost periodic oscillation and synchronization of continuous- and discrete-time Clifford-valued neural networks, in this paper, we consider a class of Clifford-valued fuzzy cellular neural networks on time scales. Based on the theory of calculus on time scales and the contraction fixed point theorem, we first establish the existence of pseudo almost periodic solutions of neural networks. Then, under the condition that the considered network has pseudo almost periodic solutions, by designing a novel state-feedback controller and using reduction to absurdity, we obtain that the drive-response structure of Clifford-valued fuzzy cellular neural networks on time scales with pseudo almost periodic coefficients can realize the global exponential synchronization. Finally, we give a numerical example to illustrate the feasibility of our results.
Groundwater storage effects from restoring, constructing or draining wetlands in temperate and boreal climates: a systematic review protocol
Authors: Bring Arvid , Rosén Lars , Thorslund Josefin , Tonderski Karin , Åberg Charlotte , Envall Ida , Laudon Hjalmar 
Published: October 2020

Abstract
Background
Wetlands in many parts of the world have been degraded, as use of the land for food production and forestry for human needs have taken precedence. Drainage of wetlands has led to deteriorated wetland conditions and lowered water tables. Across the world, there are several programs for wetland restoration and construction, primarily to reintroduce lost habitats for wildlife, and to obtain nutrient retention functions. In Sweden, recent dry and hot summers have reinforced interest in the hydrological functions that wetlands may have, in particular as potential support for water storage in the landscape and added groundwater storage during dry periods. However, the agreement on substantial effects on groundwater is limited, and there are several critical knowledge gaps, including the extent to which such effects extend outside the wetland itself, and how they vary with local conditions, such as topography, soil, and climate. Therefore, this review will address the groundwater storage effect of restoring, constructing or draining wetlands in the boreo-temperate region.

Methods
We will conduct a systematic review of the evidence, drawing on both peer-reviewed and grey literature. Articles in English, Swedish, Norwegian, Danish, French, German and Polish will be retrieved from academic databases, Google Scholar, and websites of specialist organizations. We will screen literature in two stages, first at the title and abstract level and then in full text, the latter with blinded decisions by two independent reviewers for all articles. Articles will be included based on relevance criteria for a Swedish context: wetlands on previously glaciated soils in boreal and temperate climates. Data will be extracted from all included articles, including wetland type, intervention type, and hydrogeological setting. Studies will be subject to critical appraisal to evaluate their susceptibility to bias. Provided enough evidence of sufficient reliability, we will carry out meta-analyses of effect sizes in relation to various factors. The review will include a narrative synthesis in which we summarize the results of the review.
Colonization of a hand washing sink in a veterinary hospital by an Enterobacter hormaechei strain carrying multiple resistances to high importance antimicrobials
Authors: Kamathewatta Kanishka , Bushell Rhys , Rafa Fannana , Browning Glenn , Billman-Jacobe Helen , Marenda Marc 
Published: October 2020

Abstract
Background
Hospital intensive care units (ICUs) are known reservoirs of multidrug resistant nosocomial bacteria. Targeted environmental monitoring of these organisms in health care facilities can strengthen infection control procedures. A routine surveillance of extended spectrum beta-lactamase (ESBL) producers in a large Australian veterinary teaching hospital detected the opportunistic pathogen Enterobacter hormaechei in a hand washing sink of the ICU. The organism persisted for several weeks, despite two disinfection attempts. Four isolates were characterized in this study.

Methods
Brilliance-ESBL selective plates were inoculated from environmental swabs collected throughout the hospital. Presumptive identification was done by conventional biochemistry. Genomes of multidrug resistant Enterobacter were entirely sequenced with Illumina and Nanopore platforms. Phylogenetic markers, mobile genetic elements and antimicrobial resistance genes were identified in silico. Antibiograms of isolates and transconjugants were established with Sensititre microdilution plates.

Results
The isolates possessed a chromosomal Tn7-associated silver/copper resistance locus and a large IncH12 conjugative plasmid encoding resistance against tellurium, arsenic, mercury and nine classes of antimicrobials. Clusters of antimicrobial resistance genes were associated with class 1 integrons and IS26, IS903 and ISCR transposable elements. The blaSHV-12, qnrB2 and mcr-9.1 genes, respectively conferring resistance to cephalosporins, quinolones and colistin, were present in a locus flanked by two IS903 copies. ESBL production and enrofloxacin resistance were confirmed phenotypically. The isolates appeared susceptible to colistin, possibly reflecting the inducible nature of mcr-9.1.

Conclusions
The persistence of this strain in the veterinary hospital represented a risk of further accumulation and dissemination of antimicrobial resistance, prompting a thorough disinfection of the ICU. The organism was not recovered from subsequent environmental swabs, and nosocomial Enterobacter infections were not observed in the hospital during that period. This study shows that targeted routine environmental surveillance programs to track organisms with major resistance phenotypes, coupled with disinfection procedures and follow-up microbiological cultures are useful to control these risks in sensitive areas of large veterinary hospitals.
Development of a circular economy and evolution of working conditions and occupational risks—a strategic foresight study
Authors: Héry Michel , Malenfer Marc 
Published: October 2020

AbstractThe circular economy can be defined as an economic system of exchange and production intended to increase the efficiency of the use of resources at all stages of products’ life cycle (including goods and services). Since most natural resources are not inexhaustible, and fossil fuel consumption is considered one of the major factors of global warming, its development seems inevitable, even if it can only be progressive (spanning several decades) and may not apply to all sectors. The circular economy is likely to challenge work methods and working conditions. Consequently, a strategic foresight study has been conducted in order to assess the main consequences on occupational safety and health. In the practice of INRS which carried out this work, foresight is above all a tool to improve and facilitate thinking and decision-making.
Assessment of intestinal parasites in the coexisting Bombus terrestris (Apidae) and Xylocopa augusti (Apidae) in central Chile
Authors: Fernández Kiara , Alcaíno Jennifer , Sepúlveda Dionisia , Medel Rodrigo 
Published: October 2020

AbstractBombus terrestris is a European bumblebee extensively commercialized worldwide for crop pollination. In Chile, this species was introduced in 1997 and after confinement escape, it has spread and established in several localities of central-southern Chile and in the Argentine Patagonia. The South American carpenter bee Xylocopa augusti, in turn, has been recently reported in central Chile, and as B. terrestris, this species has become increasingly common, often found in sympatry with B. terrestris in some localities. While intestinal parasites such as the flagellate trypanosome Crithidia bombi, the microsporidium Nosema bombi, and the neogregarine protozoan Apicystis bombi, show high levels of specialization on the Bombus genus, parasites often increase their host range, especially after invading novel habitats, hence creating new infection disease scenarios. In this work, we used molecular techniques to detect the presence of the intestinal pathogens of B. terrestris in coexisting X. augusti from different localities in the Metropolitan Region of Chile. Our results revealed the presence of the three pathogens in B. terrestris only, with population prevalence broadly similar to that reported in other studies. The carpenter bee X. augusti did not show evidence of any of the three parasites examined, indicating that this invader species is not recipient of any of the parasite species present in B. terrestris.