bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of a massive open online course (MOOC) incorporating interactive simulation videos on residents’ knowledge retention regarding mechanical ventilation
Authors: Pham Tài , Beloncle François , Piquilloud Lise , Ehrmann Stephan , Roux Damien , Mekontso-Dessap Armand , Carteaux Guillaume 
Published: December 2021

Abstract
Background
Understanding respiratory physiology and mechanical ventilation is a challenge for healthcare workers, particularly, medical residents. A team of French-speaking experts developed an innovative MOOC incorporating interactive simulation-based videos and serious games aiming at improving knowledge and skills in mechanical ventilation. Our objective was to evaluate the long-term knowledge retention regarding key concepts presented in this MOOC.

Methods
French residents registered for the MOOC 2020’s winter session were invited to participate in a two-step study. The first step consisted in evaluating students’ pre-course knowledge of respiratory physiology and mechanical ventilation fusing a 20 five-item multiple choice questions test with a total score ranging from 0 to 100. For the second step, the same students answered the same test (after shuffling the questions) six months after the completion of the course. We assessed the impact of this MOOC on the students’ knowledge retention by comparing pre-course and post-course scores.

Result
Of the 102 residents who agreed to participate in the study, 80 completed the course and their mean ± SD pre-course score was 76.0 ± 8.0. Fifty-one respondents also completed the second and their post-course score was significantly higher than the baseline one (83.1 ± 7.3 vs. 77.5 ± 7.6, p < 0.001). Scores of the first and second rounds did not differ upon comparing respondents’ background specialty or number of years of residency. For the vast majority of individual questions (96%), the success rate was higher at the post-course than at the pre-course assessment.

Conclusion
An innovative MOOC incorporating simulation-based videos was effective in teaching medical residents basic mechanical ventilation knowledge and skills, especially in the field of respiratory physiology and ventilatory modes. We observed effective long-term knowledge retention with a higher score at the post-course assessment six months after the completion of the course compared with the pre-course score.
A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens
Authors: Liu Wei , Johansson Åsa , Rask-Andersen Helge , Rask-Andersen Mathias 
Published: December 2021

AbstractBackgroundSensorineural hearing loss is one of the most common sensory deficiencies. However, the molecular contribution to age-related hearing loss is not fully elucidated.MethodsWe performed genome-wide association studies (GWAS) for hearing loss-related traits in the UK Biobank (N= 362,396) and selected a high confidence set of ten hearing-associated gene products for staining in human cochlear samples: EYA4, LMX1A, PTK2/FAK, UBE3B, MMP2, SYNJ2, GRM5, TRIOBP, LMO-7, and NOX4.ResultsAll proteins were found to be expressed in human cochlear structures. Our findings illustrate cochlear structures that mediate mechano-electric transduction of auditory stimuli, neuronal conductance, and neuronal plasticity to be involved in age-related hearing loss.ConclusionsOur results suggest common genetic variation to influence structural resilience to damage as well as cochlear recovery after trauma, which protect against accumulated damage to cochlear structures and the development of hearing loss over time.
Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases
Authors: McGuire Sams Cierla , Shepp Kasey , Pugh Jada , Bishop Madison R. , Merner Nancy D. 
Published: December 2021

Abstract
Background
Three genes clustered together on chromosome 12 comprise a group of hydroxycarboxylic acid receptors (HCARs): HCAR1, HCAR2, and HCAR3. These paralogous genes encode different G-protein coupled receptors responsible for detecting glycolytic metabolites and controlling fatty acid oxidation. Though better known for regulating lipid metabolism in adipocytes, more recently, HCARs have been functionally associated with breast cancer proliferation/survival; HCAR2 has been described as a tumor suppressor and HCAR1 and HCAR3 as oncogenes. Thus, we sought to identify germline variants in HCAR1, HCAR2, and HCAR3 that could potentially be associated with breast cancer risk.

Methods
Two different cohorts of breast cancer cases were investigated, the Alabama Hereditary Cancer Cohort and The Cancer Genome Atlas, which were analyzed through nested PCRs/Sanger sequencing and whole-exome sequencing, respectively. All datasets were screened for rare, non-synonymous coding variants.

Results
Variants were identified in both breast cancer cohorts, some of which appeared to be associated with breast cancer BC risk, including HCAR1 c.58C > G (p.P20A), HCAR2 c.424C > T (p.R142W), HCAR2 c.517_518delinsAC (p.G173T), HCAR2 c.1036A > G (p.M346V), HCAR2 c.1086_1090del (p.P363Nfs*26), HCAR3 c.560G > A (p.R187Q), and HCAR3 c.1117delC (p.Q373Kfs*82). Additionally, HCAR2 c.515C > T (p.S172L), a previously identified loss-of-function variant, was identified.

Conclusions
Due to the important role of HCARs in breast cancer, it is vital to understand how these genetic variants play a role in breast cancer risk and proliferation and their consequences on treatment strategies. Additional studies will be needed to validate these findings. Nevertheless, the identification of these potentially pathogenic variants supports the need to investigate their functional consequences.
Circulating noncoding RNAs as early predictive biomarkers in preeclampsia: a diagnostic meta-analysis
Authors: Su Sha , Yang Fang , Zhong Linlin , Pang Lihong 
Published: December 2021

Abstract
Background
We designed a meta-analysis to evaluate the clinical significance and efficacy of circulating noncoding RNAs (ncRNAs) in the early prediction of preeclampsia.

Methods
PubMed, Embase and the Cochrane Library were used to search for literature. The combined prediction performance was evaluated by calculating the area under the summary receiver operator characteristic (SROC) curve. The potential sources of heterogeneity were analysed by meta-regression analysis and subgroup analysis. All statistical analyses and mapping were performed by RevMan 5.3 and Stata 12.0.

Results
A total of 41 studies from 14 articles, including 557 preeclampsia patients and 842 controls, were included in our meta-analysis. All studies collected blood before onset. NcRNAs in blood performed relatively well in predicting preeclampsia. The combined sensitivity was 0.71, the specificity was 0.84, and the area under the SROC curve (AUC) was 0.86. Peripheral blood mononuclear cell (PBMC) samples showed the best diagnostic accuracy. The combined AUC was 0.93. Combined detection was better than single detection, and miRNA was better than circRNA. The heterogeneity of the study was determined by sample size, lncRNA characteristics, lncRNA source and race.

Conclusion
Circulating ncRNAs can be valuable biomarkers used as candidates for noninvasive early predictive biomarkers of preeclampsia and have great clinical application prospects. The clinical value of ncRNAs needs to be tested by further multicentre, comprehensive and prospective studies, and the test criteria should be established.
Feature selection revisited in the single-cell era
Authors: Yang Pengyi , Huang Hao , Liu Chunlei 
Published: December 2021

AbstractRecent advances in single-cell biotechnologies have resulted in high-dimensional datasets with increased complexity, making feature selection an essential technique for single-cell data analysis. Here, we revisit feature selection techniques and summarise recent developments. We review their application to a range of single-cell data types generated from traditional cytometry and imaging technologies and the latest array of single-cell omics technologies. We highlight some of the challenges and future directions and finally consider their scalability and make general recommendations on each type of feature selection method. We hope this review stimulates future research and application of feature selection in the single-cell era.
Efficacy of combined orthokeratology and 0.01% atropine for myopia control: the study protocol for a randomized, controlled, double-blind, and multicenter trial
Authors: Yuan Ying , Zhu Chengcheng , Liu Mingming , Zhou Yali , Yang Xiao , Zheng Bingru , Li Zhouyue , Mao Xinjie , Ke Bilian 
Published: December 2021

Abstract
Background
The prevalence of myopia is increasing worldwide and is presently recognized as a major public health issue. Researchers and clinicians have been devoted in exploring appropriate clinical interventions to slow its progression in children. Mounting publications have proven that both orthokeratology (OK lens) and 0.01% atropine eyedrop can retard eye growth and myopia progression. However, it remains unclear whether the combination of OK lens and 0.01% atropine has the potential to magnify the effectiveness of myopia control. The present study aims to compare the myopia control efficiency of the combination of OK lens and 0.01% atropine with the monotherapy of OK lens in children.

Methods
The present study is a randomized, controlled, double-blind and multicenter clinical trial. A total of 96 children within 8–12 years old were recruited. These participants are treated with the combination of OK lens and 0.01% atropine eyedrop or the combination of OK lens and placebo eyedrop. Each group includes 48 participants. The inclusion criteria are as follows: myopia between − 1.00 and − 4.00 D in either eye and astigmatism of no more than 1.50 D. The follow-up time points will be 1, 6, 12, 18, and 24 months from randomization. The primary outcome is determined by the difference in axial length of the two groups, between the baseline and 24 months from randomization.

Discussion
The present randomized, controlled clinical trial would indicate the additive effects of the combination of OK lens and 0.01% atropine, and the extent of these effects, in retarding myopia progression and axial elongation in children.

Trial registration
Chinese Clinical Trial Registry (ChiCTR), ChiCTR1800018419. Registered on 17 September 2018. http://www.chictr.org.cn/showproj.aspx?proj=29216
Characterization of the reproductive tract bacterial microbiota of virgin, mated, and blood-fed Aedes aegypti and Aedes albopictus females
Authors: Díaz Sebastián , Camargo Carolina , Avila Frank W. 
Published: December 2021

Abstract
Background
Aedes aegypti and Ae. albopictus are vectors of numerous arboviruses that adversely affect human health. In mosquito vectors of disease, the bacterial microbiota influence several physiological processes, including fertility and vector competence, making manipulation of the bacterial community a promising method to control mosquito vectors. In this study, we describe the reproductive tract tissue microbiota of lab-reared virgin Ae. aegypti and Ae. albopictus males, and virgin, mated, and mated + blood-fed females of each species, comparing the bacterial composition found there to the well-described gut microbiota.

Methods
We performed metabarcoding of the 16S rRNA isolated from the gut, upper reproductive tract (URT; testes or ovaries), and lower reproductive tract (LRT; males: seminal vesicles and accessory glands; females: oviduct, spermathecae, and bursa) for each species, and evaluated the influence of host species, tissue, nutritional status, and reproductive status on microbiota composition. Finally, based on the identified taxonomic profiles of the tissues assessed, bacterial metabolic pathway abundance was predicted.

Results
The community structure of the reproductive tract is unique compared to the gut. Asaia is the most prevalent OTU in the LRTs of both Ae. aegypti and Ae. albopictus. In the URT, we observed differences between species, with Wolbachia OTUs being dominant in the Ae. albopictus URT, while Enterobacter and Serratia were dominant in Ae. aegypti URT. Host species and tissue were the best predictors of the community composition compared to reproductive status (i.e., virgin or mated) and nutritional status (i.e., sugar or blood-fed). The predicted functional profile shows changes in the abundance of specific microbial pathways that are associated with mating and blood-feeding, like energy production in mated tissues and siderophore synthesis in blood-fed female tissues.

Conclusions
Aedes aegypti and Ae. albopictus have distinct differences in the composition of microbiota found in the reproductive tract. The distribution of the bacterial taxonomic groups indicates that some bacteria have tissue-specific tropism for reproductive tract tissue, such as Asaia and Wolbachia. No significant differences in the taxonomic composition were observed in the reproductive tract between virgin, mated, and mated + blood-fed females, but changes in the abundance of specific metabolic pathways were found in the predicted microbial functional profiles in mated and blood-fed females.

Graphical Abstract
“I wish it had a place to go”: a nominal group study of barriers to the effectiveness of non-surgical treatments for knee osteoarthritis inclusive of minority populations
Authors: Singh Jasvinder A. 
Published: December 2021

Abstract
Objective
To examine patient experience, views, and opinions regarding the ineffectiveness of the current knee osteoarthritis (OA) treatments.

Methods
Nominal groups were conducted with consecutive clinic patients with knee OA, oversampling African Americans. Patients discussed and rank-ordered their concerns.

Results
Fourteen nominal groups with 48 knee OA patients were conducted with a mean age of 60.6 years (standard deviation, 9.8) and a knee OA duration of 7.8 years (sd, 5.4); 25% were men, and 54% were African American. The most frequently cited highly ranked concerns for the ineffectiveness of current knee OA treatments were as follows: (1) medication-related—(A) side effects (3 groups; 4% vote), (B) limited efficacy (5 groups; 11% vote), (C) medication not targeting underlying disease (7 groups; 16% vote), (D) lack of personalized medication use (3 groups; 4% vote), (E) temporary benefit (3 groups; 6% vote), and (F) fear of addiction/natural treatment preference (2 groups; 3% vote); (2) exercise/physical therapy-related—(G) exacerbation of joint pain (1 group; 3% vote), (H) difficulty in doing exercises (2 groups; 2% vote), (I) lack of motivation (8 groups; 12% vote), (J) technical challenges/lack of personalized exercise regimens (1 group; 1% vote), and (K) cost (2 groups; 3% vote); and (3) weight loss-related—(L) difficulty in achieving weight loss (4 groups; 6% vote) and (M) motivation (1 group; 1% vote).

Conclusions
A representative sample of participants with knee OA identified several barriers to the effectiveness of current knee OA treatments. This new knowledge provides insights for making the current treatment options potentially more usable and/or more effective.
High humidity aggravates the severity of arthritis in collagen-induced arthritis mice by upregulating xylitol and L-pyroglutamic acid
Authors: Wang Mingzhu , Chen Jiao , Lin Xiaoying , Huang Lin , Li Haichang , Wen Chengping , He Zhixing 
Published: December 2021

AbstractBackgroundHumidity was an unfavorable factor for patients with rheumatoid arthritis (RA). RA disease activity was severe in high humidity conditions. However, there is no evidence to demonstrate the effects of humidity on arthritis in the animal experiments and explore its relevant mechanism.MethodsUsing the DBA/1 mice, this study addressed the effects of a high humidity (80 ± 5%) on arthritis in collagen-induced arthritis (CIA) mice. Then, this study used the gas chromatography-mass spectrometer (GC-MS) to explore alterations in serum metabolome caused by the high humidity. Furthermore, xylitol and L-pyroglutamic acid, which were both significantly upregulated by the high humidity, were selected to further study their effects on arthritis in the CIA mice.ResultsThe high humidity (80 ± 5%) could aggravate arthritis variables including increasing arthritis score and swelling, serum autoantibodies (anti-COII and anti-CCP), and proinflammatory cytokines (IL-6, IL-17A, and G-CSF). In addition, the high humidity could cause significant alterations in serum metabolome in the CIA mice. Xylitol and L-pyroglutamic acid were the representative serum metabolites that were significantly upregulated by the high humidity. Further experiments demonstrated that the supplementation of 0.4 mg/mL xylitol in drinking water after inducing the CIA model and 2.0 mg/mL in drinking water before inducing the CIA model could both aggravate arthritis in the CIA mice.ConclusionsThese data demonstrated that high humidity was not beneficial for arthritis development and its mechanism might be associated with xylitol and L-pyroglutamic acid.
Ionizing radiations induce shared epigenomic signatures unraveling adaptive mechanisms of cancerous cell lines with or without methionine dependency
Authors: Siblini Youssef , Chéry Céline , Rouyer Pierre , Raso Jérémie , Julien Amélia , Hergalant Sébastien , François Aurélie , Bezdetnaya Lina , Vogin Guillaume , Guéant Jean-Louis , Oussalah Abderrahim 
Published: December 2021

Abstract
Background
Although radiation therapy represents a core cancer treatment modality, its efficacy is hampered by radioresistance. The effect of ionizing radiations (IRs) is well known regarding their ability to induce genetic alterations; however, their impact on the epigenome landscape in cancer, notably at the CpG dinucleotide resolution, remains to be further deciphered. In addition, no evidence is available regarding the effect of IRs on the DNA methylome profile according to the methionine dependency phenotype, which represents a hallmark of metabolic adaptation in cancer.

Methods
We used a case–control study design with a fractionated irradiation regimen on four cancerous cell lines representative of HCC (HepG2), melanoma (MeWo and MeWo-LC1, which exhibit opposed methionine dependency phenotypes), and glioblastoma (U251). We performed high-resolution genome-wide DNA methylome profiling using the MethylationEPIC BeadChip on baseline conditions, irradiated cell lines (cumulative dose of 10 Gy), and non-irradiated counterparts. We performed epigenome-wide association studies to assess the effect of IRs and methionine-dependency-oriented analysis by carrying out epigenome-wide conditional logistic regression. We looked for epigenome signatures at the locus and single-probe (CpG dinucleotide) levels and through enrichment analyses of gene ontologies (GO). The EpiMet project was registered under the ID#AAP-BMS_003_211.

Results
EWASs revealed shared GO annotation pathways associated with increased methylation signatures for several biological processes in response to IRs, including blood circulation, plasma membrane-bounded cell projection organization, cell projection organization, multicellular organismal process, developmental process, and animal organ morphogenesis. Epigenome-wide conditional logistic regression analysis on the methionine dependency phenotype highlighted several epigenome signatures related to cell cycle and division and responses to IR and ultraviolet light.

Conclusions
IRs generated a variation in the methylation level of a high number of CpG probes with shared biological pathways, including those associated with cell cycle and division, responses to IRs, sustained angiogenesis, tissue invasion, and metastasis. These results provide insight on shared adaptive mechanisms of the epigenome in cancerous cell lines in response to IR. Future experiments should focus on the tryptic association between IRs, the initiation of a radioresistance phenotype, and their interaction with methionine dependency as a hallmark of metabolic adaptation in cancer.

Graphical abstract
Hyperspectral imaging for perioperative monitoring of microcirculatory tissue oxygenation and tissue water content in pancreatic surgery — an observational clinical pilot study
Authors: Dietrich Maximilian , Marx Sebastian , von der Forst Maik , Bruckner Thomas , Schmitt Felix C. F. , Fiedler Mascha O. , Nickel Felix , Studier-Fischer Alexander , Müller-Stich Beat P. , Hackert Thilo , Brenner Thorsten , Weigand Markus A. , Uhle Florian , Schmidt Karsten 
Published: December 2021

Abstract
Background
Hyperspectral imaging (HSI) could provide extended haemodynamic monitoring of perioperative tissue oxygenation and tissue water content to visualize effects of haemodynamic therapy and surgical trauma. The objective of this study was to assess the capacity of HSI to monitor skin microcirculation and possible relations to perioperative organ dysfunction in patients undergoing pancreatic surgery.

Methods
The hyperspectral imaging TIVITA® Tissue System was used to evaluate superficial tissue oxygenation (StO2), deeper layer tissue oxygenation (near-infrared perfusion index (NPI)), haemoglobin distribution (tissue haemoglobin index (THI)) and tissue water content (tissue water index (TWI)) in 25 patients undergoing pancreatic surgery. HSI parameters were measured before induction of anaesthesia (t1), after induction of anaesthesia (t2), postoperatively before anaesthesia emergence (t3), 6 h after emergence of anaesthesia (t4) and three times daily (08:00, 14:00, 20:00 ± 1 h) at the palm and the fingertips until the second postoperative day (t5–t10). Primary outcome was the correlation of HSI with perioperative organ dysfunction assessed with the perioperative change of SOFA score.

Results
Two hundred and fifty HSI measurements were performed in 25 patients. Anaesthetic induction led to a significant increase of tissue oxygenation parameters StO2 and NPI (t1–t2). StO2 and NPI decreased significantly from t2 until the end of surgery (t3). THI of the palm showed a strong correlation with haemoglobin levels preoperatively (t2:r = 0.83, p < 0.001) and 6 h postoperatively (t4: r = 0.71, p = 0.001) but not before anaesthesia emergence (t3: r = 0.35, p = 0.10). TWI of the palm and the fingertip rose significantly between pre- and postoperative measurements (t2–t3). Higher blood loss, syndecan level and duration of surgery were associated with a higher increase of TWI. The perioperative change of HSI parameters (∆t1–t3) did not correlate with the perioperative change of the SOFA score.

Conclusion
This is the first study using HSI skin measurements to visualize tissue oxygenation and tissue water content in patients undergoing pancreatic surgery. HSI was able to measure short-term changes of tissue oxygenation during anaesthetic induction and pre- to postoperatively. TWI indicated a perioperative increase of tissue water content. Perioperative use of HSI could be a useful extension of haemodynamic monitoring to assess the microcirculatory response during haemodynamic therapy and major surgery.

Trial registration
German Clinical Trial Register, DRKS00017313 on 5 June 2019