Miracle-dz/UniFAR-FTUs huggingface dataset:
Accelerating cardiovascular research: recent advances in translational 2D and 3D heart models

In vitro modelling the complex (patho‐) physiological conditions of the heart is a major challenge in cardiovascular research. In recent years, methods based on three‐dimensional (3D) cultivation approaches have steadily evolved to overcome the major limitations of conventional adherent two‐dimensional (2D) monolayer cultivation. These 3D approaches aim to study, reproduce or modify fundamental native features of the heart such as tissue organization and cardiovascular microenvironment. Therefore, these systems have great potential for (patient‐specific) disease research, for the development of new drug screening platforms, and for the use in regenerative and replacement therapy applications. Consequently, continuous improvement and adaptation is required with respect to fundamental limitations such as cardiomyocyte maturation, scalability, heterogeneity, vascularization, and reproduction of native properties. In this review, 2D monolayer culturing and the 3D in vitro systems of cardiac spheroids, organoids, engineered cardiac microtissue and bioprinting as well as the ex vivo technique of myocardial slicing are introduced with their basic concepts, advantages, and limitations. Furthermore, recent advances of various new approaches aiming to extend as well as to optimize these in vitro and ex vivo systems are presented.
No Benefits of Adding Dexmedetomidine, Ketamine, Dexamethasone, and Nerve Blocks to an Established Multimodal Analgesic Regimen after Total Knee Arthroplasty

Background: An optimal opioid-sparing multimodal analgesic regimen to treat severe pain can enhance recovery after total knee arthroplasty. The hypothesis was that adding five recently described intravenous and regional interventions to multimodal analgesic regimen can further reduce opioid consumption. Methods: In a double-blinded fashion, 78 patients undergoing elective total knee arthroplasty were randomized to either (1) a control group (n = 39) that received spinal anesthesia with intrathecal morphine, periarticular local anesthesia infiltration, intravenous dexamethasone, and a single injection adductor canal block or (2) a study group (n = 39) that received the same set of analgesic treatments plus five additional interventions: local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intraoperative intravenous dexmedetomidine and ketamine, and postoperatively, one additional intravenous dexamethasone bolus and two additional adductor canal block injections. The primary outcome measure was 24-h cumulative opioid consumption after surgery and secondary outcomes were other analgesics, patient recovery, functional outcomes, and adverse events. Results: Opioid consumption was not different between groups at 24 h (oral morphine equivalents, mean ± SD; study: 23.7 ± 18.0 mg vs. control: 29.3 ± 18.7 mg; mean difference [95% CI], –5.6 mg [–2.7 to 13.9]; P = 0.189) and all other time points after surgery. There were no major differences in pain scores, quality of recovery, or time to reach rehabilitation milestones. Hypotensive episodes occurred more frequently in the study group (25 of 39 [64.1%] vs. 13 of 39 [33.3%]; P = 0.010). Conclusions: In the presence of periarticular local anesthesia infiltration, intrathecal morphine, single-shot adductor canal block and dexamethasone, the addition of five analgesic interventions—local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intravenous dexmedetomidine, intravenous ketamine, an additional intravenous dexamethasone dose, and repeated adductor canal block injections—failed to further reduce opioid consumption or pain scores or to improve functional outcomes after total knee arthroplasty. A randomized trial design compared analgesic requirements after total knee replacement surgery for patients receiving a standard multimodal regime versus one with additional analgesics. Compared to the combination of intrathecal morphine, periarticular anesthetic infiltration, dexamethasone, and adductor canal block, additional intravenous analgesics and nerve blocks provided no incremental benefit.
Choose Wisely: Surgical Selection of Candidates for Outpatient Anterior Cervical Surgery Based on Early Complications Among Inpatients

Background: Anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) are attractive targets for transition to the outpatient setting. We assessed the prevalence of rapid responses and major complications in the inpatient setting following 1 or 2-level ACDFs and CDAs. We evaluated factors that may place patients at greater risk for a rapid response or a postoperative complication. Methods: This was an institutional review board-approved, retrospective cohort study of adults undergoing 1 or 2-level ACDF or CDA at 1 hospital over a 2-year period (2018 and 2019). Data on patient demographic characteristics, surgical procedures, and comorbidities were collected. Rapid response events were identified by hospital floor staff and involved acute changes in a patient’s clinical condition. Complications were events that were life-threatening, required an intervention, or led to delayed hospital discharge. Results: In this study, 1,040 patients were included: 888 underwent ACDF and 152 underwent CDA. Thirty-six patients (3.5%) experienced a rapid response event; 22% occurred >24 hours after extubation. Patients having a rapid response event had a significantly higher risk of developing a complication (risk ratio, 10; p < 0.01) and had a significantly longer hospital stay. Twenty-four patients (2.3%) experienced acute complications; 71% occurred >6 hours after extubation. Patients with a complication were older and more likely to be current or former smokers, have chronic obstructive pulmonary disease, have asthma, and have an American Society of Anesthesiologists (ASA) score of >2. The length of the surgical procedure was significantly longer in patients who developed a complication. All patients who developed dysphagia had a surgical procedure involving C4-C5 or more cephalad. Patients with a rapid response event or complication were more commonly undergoing revision surgical procedures. Conclusions: Rapid response and complications are uncommon following 1 or 2-level ACDFs or CDAs but portend a longer hospital stay and increased morbidity. Revision surgical procedures place patients at higher risk for rapid responses and complications. Additionally, older patients, patients with chronic obstructive pulmonary disease or asthma, patients who are current or former smokers, and patients who have an ASA score of ≥3 are at increased risk for postoperative complications. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Restoration of atypical protein kinase C ζ function in autosomal dominant polycystic kidney disease ameliorates disease progression

Significance Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder commonly caused by mutations in polycystin-1. The disease is associated with severe morbidity and has limited therapeutic options, with most patients requiring dialysis or transplantation by the sixth decade. Our work adds to understanding polycystic kidney disease (PKD) pathogenesis by clarifying the role of PKCζ in ADPKD and by presenting PKCζ as a potential therapeutic target. We show that PKCζ phosphorylates polycystin-1 at two specific serine residues. We demonstrate that PKCζ is aberrantly down-regulated in human ADPKD and mouse models of PKD and that its activity can be restored via treatment with the US Food and Drug Administration–approved drug FTY720. Last, we demonstrate that FTY720 treatment ameliorates disease progression in PKD mouse models and that these improvements are dependent on PKCζ expression.
Genetic modification of flavone biosynthesis in rice enhances biofilm formation of soil diazotrophic bacteria and biological nitrogen fixation

Summary Improving biological nitrogen fixation (BNF) in cereal crops is a long‐sought objective; however, no successful modification of cereal crops showing increased BNF has been reported. Here, we described a novel approach in which rice plants were modified to increase the production of compounds that stimulated biofilm formation in soil diazotrophic bacteria, promoted bacterial colonization of plant tissues and improved BNF with increased grain yield at limiting soil nitrogen contents. We first used a chemical screening to identify plant‐produced compounds that induced biofilm formation in nitrogen‐fixing bacteria and demonstrated that apigenin and other flavones induced BNF. We then used CRISPR‐based gene editing targeting apigenin breakdown in rice, increasing plant apigenin contents and apigenin root exudation. When grown at limiting soil nitrogen conditions, modified rice plants displayed increased grain yield. Biofilm production also modified the root microbiome structure, favouring the enrichment of diazotrophic bacteria recruitment. Our results support the manipulation of the flavone biosynthetic pathway as a feasible strategy for the induction of biological nitrogen fixation in cereals and a reduction in the use of inorganic nitrogen fertilizers.
Is Coronavirus Infection Associated With Musculoskeletal Health Complaints? Results From a Comprehensive Case-Control Study

Objective: This case-control study investigated the association between SARS-CoV-2 infection and musculoskeletal health complaints (MHC). The specific aims of the study were (1) to compare the 1-month prevalence of MHC among post-acute COVID-19 patients and participants who never tested positive for COVID-19 matched by the former group’s age and gender; (2) to identify the predictors of MHC among all participants, and (3) define the factors independently associated with MHC in post-acute COVID-19 patients. Methods and Analysis: The study was conducted in Bangladesh from February 24 to April 7, 2022. The face-to-face interview was taken using a paper-based semi-structured questionnaire. MHC was measured using the musculoskeletal subscale of subjective health complaints produced by Eriksen et al. Descriptive analysis was conducted to compute MHC prevalence and compare them across groups. Multiple logistic analyses were employed to identify MHC predictors for the participants. Results: The prevalence of MHC was 38.7%. Adjusted analysis suggested that the SARS-CoV-2 infection was independently associated with MHC (AOR = 3.248,95% CI = 2.307-4.571). Furthermore, unemployment (AOR = 4.156, 95% CI = 1.308-13.208), moderate illness (AOR = 2.947,95% CI = 1.216-7.144), treatment in hospitals’ general word (AOR = 4.388,95% CI = 1.878-10.254) and health complaints after COVID-19 (AOR = 4.796,95% CI = 2.196-10.472) were found to be the predictors of MHC among post-acute COVID-19 patients. Conclusion: Our study found a robust association between SARS-CoV-2 infection and MHC and recommends that healthcare authorities be prepared to deal with the high burden of MHC among post-acute COVID-19 patients.
'Big data analytics' for construction firms insolvency prediction models

In a pioneering effort, this study is the first to develop a construction firms insolvency prediction model (CF-IPM) with Big Data Analytics (BDA); combine qualitative and quantitative variables; advanced artificial intelligence tools such as Random Forest and Bart Machine; and data of all sizes of construction firms (CF), ensuring wide applicability The pragmatism paradigm was employed to allow the use of mixed methods. This was necessary to allow the views of the top management team (TMT) of failed and existing construction firms to be captured using a qualitative approach. TMT members of 13 existing and 14 failed CFs were interviewed. Interview result was used to create a questionnaire with over hundred qualitative variables. A total of 272 and 259 (531) usable questionnaires were returned for existing and failed CFs respectively. The data of the 531 questionnaires were oversample to get a total questionnaire sample of 1052 CFs. The original and matched sample financial data of the firms were downloaded. Using Cronbach’s alpha and factor analysis, qualitative variables were reduced to 13 (Q1 to Q13) while11 financial ratios (i.e. quantitative variables) (R1 and R11) reported by large and MSM CFs were identified for the sample CFs. The BDA system was set up with the Amazon Web Services Elastic Compute Cloud using five ‘Instances’ as Hadoop DataNodes and one as NameNode. The NameNode was configured as Spark Master. Eleven variable selection methods and three voting systems were used to select the final seven qualitative and seven quantitative variables, which were used to develop 13 BDA-CF-IPMs. The Decision Tree BDA-CF-IPM was the model of choice in this study because it had high accuracy, low Type I error and transparency. The most important variables (factors) affecting insolvency of construction firms according to the best model are returned on total assets; liquidity; solvency ratio; top management characteristics; strategic issues and external relations; finance and conflict related issues; industry contract/project knowledge.
The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function

ABSTRACT Background In chronic kidney disease (CKD) patients, increased levels of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality. The relationship between FGF23 and heart hypertrophy has been documented, however, it is not known whether FGF23 has an effect on vasculature. Vascular smooth muscle cells VSMCs may exhibit different phenotypes; our hypothesis is that FGF23 favours a switch from a contractile to synthetic phenotype that may cause vascular dysfunction. Our objective was to determine whether FGF23 may directly control a change in VSMC phenotype. Methods This study includes in vitro, in vivo and ex vivo experiments and evaluation of patients with CKD stages 2–3 studying a relationship between FGF23 and vascular dysfunction. Results In vitro studies show that high levels of FGF23, by acting on its specific receptor FGFR1 and Erk1/2, causes a change in the phenotype of VSMCs from contractile to synthetic. This change is mediated by a downregulation of miR-221/222, which augments the expression of MAP3K2 and PAK1. miR-221/222 transfections recovered the contractile phenotype of VSMCs. Infusion of recombinant FGF23 to rats increased vascular wall thickness, with VSMCs showing a synthetic phenotype with a reduction of miR-221 expression. Ex-vivo studies on aortic rings demonstrate also that high FGF23 increases arterial stiffening. In CKD 2–3 patients, elevation of FGF23 was associated with increased pulse wave velocity and reduced plasma levels of miR-221/222. Conclusion In VSMCs, high levels of FGF23, through the downregulation of miR-221/222, causes a change to a synthetic phenotype. This change in VSMCs increases arterial stiffening and impairs vascular function, which might ultimately worsen cardiovascular disease.
Correlates of excessive daytime sleepiness in obstructive sleep apnea: Results from the nationwide SESAR cohort including 34,684 patients

Excessive daytime sleepiness (EDS) is a hallmark symptom in obstructive sleep apnea (OSA). It is commonly eliminated by obstructive sleep apnea therapy and constitutes a major treatment indication. This study aimed to identify determinants of excessive daytime sleepiness by the Epworth Sleepiness Scale (ESS) scores in the large, representative national obstructive sleep apnea patient cohort of the Swedish Sleep Apnea Registry (SESAR, www.sesar.se). Data from 34,684 patients with obstructive sleep apnea recruited at 23 sites (33% females, mean age 55.7 ± 13.7 years, BMI 30.2 ± 6.3 kg/m2, AHI 29.1 ± 22.3, and ODI 24.9 ± 21.4 events/h) had a mean ESS score in the mild to moderate excessive daytime sleepiness range (9.7 ± 4.9). The proportion of patients with excessive daytime sleepiness was 41.4% in men and 44.6% in women. Independent predictors of excessive daytime sleepiness included gender, age, and hypoxic markers (high ODI and low mean saturation). Univariate and multivariate analyses were used to identify significant predictors for the ESS score and for excessive daytime sleepiness (ESS ≥10) amongst anthropometric factors, sleep apnea frequency (apnea‐hypopnea index (AHI)), markers of intermittent hypoxia (oxygen desaturation index (ODI), mean saturation (mSaO2)), as well as prevalent comorbidities. Depression was associated with higher ESS scores and hypertension/atrial fibrillation with lower scores. The oxygen desaturation index provided a stronger predictor of excessive daytime sleepiness than the apnea‐hypopnea index. The severity of obstructive sleep apnea, captured as the apnea‐hypopnea index, was only weakly associated with daytime sleepiness in this representative obstructive sleep apnea patient cohort. Age had different effects in men and women.The impact of obstructive sleep apnea in a wider patient related perspective needs to be determined after the inclusion of factors other than the apnea‐hypopnea index.
Epidemiological Evidence of Nosocomial and Zoonotic Transmission of Human T-Cell Leukemia Virus-1 in a Large Survey in a Rural Population of Central Africa

Abstract Background Central Africa is one of the largest areas of high endemicity for human T-cell leukemia virus-1 (HTLV-1). However, no preventive measures are yet implemented to reduce its transmission, which can be sexual, from mother-to-child, or through contaminated blood products. Rare zoonotic transmissions from nonhuman primates (NHPs) have also been reported in this region. Here we investigated the HTLV-1 prevalence and associated risk factors in a rural population in Cameroon. Methods From 2019 to 2021, we performed a cross-sectional survey in the eastern region of Cameroon. HTLV-1 infection was first screened by ELISA, then tested by western blot and envelope gene targeted polymerase chain reaction. Risk factors associated with HTLV-1 infection were identified by logistic regression in univariable and multivariable analyses. Results Among 3400 participants, HTLV-1 prevalence was 1.1% (95% confidence interval [CI], .7–1.5). Factors independently associated with HTLV-1 infection were Pygmy ethnicity (adjusted odd ratio [aOR], 2.9; 95% CI, 1.3–6.2), history of surgery (aOR, 6.3; 95% CI, 2.2–17.8), and NHP bite (aOR, 6.6; 95% CI, 2.2–19.8). Conclusions These results suggest both iatrogenic and zoonotic transmission of HTLV-1 in Cameroon. Further studies are needed to assess the risk of nosocomial transmission of HTLV-1, to guide public health authorities in implementing preventive measures to control HTLV-1 transmission.
The insomnia, fatigue, and psychological well‐being of hospital nurses 18 months after the COVID‐19 pandemic began: A cross‐sectional study

Abstract Background Research has shown sleep problems, elevated fatigue, and high cases of burnout, as well as signs of post‐traumatic stress and psychological distress among nurses during the COVID‐19 pandemic. Many US hospitals attempted to minimise its impact on staff by providing basic resources, mental health services, and wellness programs. Therefore, it is critical to re‐evaluate these well‐being indices and guide future administrative efforts. Purpose To determine the long‐term impact of the COVID‐19 pandemic after 18 months on hospital nurses' insomnia, fatigue, burnout, post‐traumatic stress, and psychological distress. Design Cross‐sectional. Methods Data were collected online mainly through state board and nursing association listservs between July–September 2021 (N = 2488). The survey had psychometrically tested instruments (Insomnia Severity Index, Occupational Fatigue Exhaustion Recovery Scale, Maslach Burnout Inventory, Short Post‐Traumatic Stress Disorder, and Patient Health Questionnaire‐4) and sections on demographics, health, and work. The STrengthening the Reporting of Observational studies in Epidemiology checklist was followed for reporting. Results Nurses had subthreshold insomnia, moderate‐to‐high chronic fatigue, high acute fatigue, and low‐to‐moderate intershift recovery. Regarding burnout, they experienced increased emotional exhaustion and personal accomplishment, and some depersonalisation. Nurses had mild psychological distress but scored high on post‐traumatic stress. Nurses who frequently cared for patients with COVID‐19 in the past months scored significantly worse in all measures than their co‐workers. Factors such as nursing experience, shift length, and frequency of rest breaks were significantly related to all well‐being indices. Conclusion Nurses' experiences were similar to findings from the early pandemic but with minor improvements in psychological distress. Nurses who frequently provided COVID‐19 patient care, worked ≥12 h per shift, and skipped rest breaks scored worse on almost all well‐being indices. Relevance to clinical practice Administration can help nurses' recovery by providing psychological support, mental health services, and treatment options for insomnia, as well as re‐structure current work schedules and ensure that rest breaks are taken.
Return to flying duties of German military pilots after recovery from COVID-19

Background Pilots are working in a unique and exacting environment with hypobaric hypoxia and acceleration forces. In military flying, missions are often challenging with possible combat scenarios and in remote areas with impaired infrastructure. Methods We analysed all German military pilots and pilot candidates with confirmed SARS-CoV-2 infection, who have all been evaluated prior to their return to flying duties between April 2020 and January 2022 by the German Air Force Centre of Aerospace Medicine. Symptoms, comorbidities, scope of investigations, examination results, vaccination status and aeromedical disposition are described. Results 90 pilots (82 active pilots and 8 pilot candidates) with a median age of 35 years (IQR 15 years) were included. 78 pilots (87%) reported symptoms, with median duration of 6 days. Symptoms included influenza-like symptoms (70.0%), headache (45.6%), impaired physical fitness (37.8%), anosmia/ageusia (36.7%), fever (27.8%), exertional dyspnoea (8.9%), memory and concentration disorders (4.4%), diarrhoea (3.3%) and dyspnoea at rest (2.2%). Only one pilot (1.1%) was hospitalised, two (2.2%) required outpatient treatment. All pilots were allowed to return to unrestricted flying duties after the assessment, with eight (8.9%) reporting ongoing mild symptoms. Conclusion Due to their demanding working environment, pilots, and other high-hazard employees, should undergo medical evaluation prior to return to their duties to exclude ongoing symptoms and the development of post-acute COVID-19 or post-COVID-19 syndrome. The scope of examinations may depend on the severity of the disease, comorbidities, the vaccination status, the predominant SARS-CoV-2 variant and the type of aircraft flown.