Miracle-dz/UniFAR-FTUs huggingface dataset:
Downregulation of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1) in a co-culture system with human stimulated X-linked CGD neutrophils

Phagocytes in patients with chronic granulomatous disease (CGD) do not generate reactive oxidative species (ROS), whereas nitric oxide (NO) production is increased in response to the calcium ionophore A23187 in CGD phagocytes compared with healthy phagocytes. Recently, patients with X-linked CGD (X-CGD) have been reported to show higher flow-mediated dilation, suggesting that endothelial cell function is affected by NO production from phagocytes. We studied NOS3 and EDN1 mRNA and protein expression in human umbilical vein endothelial cells (HUVECs) in a co-culture system with neutrophils from X-CGD patients. HUVECs were co-cultured for 30 minutes with human neutrophils from X-CGD or healthy participants in response to A23187 without cell-to-cell contact. The expression of NOS3 and EDN1 mRNA in HUVECs was quantified by real-time polymerase chain reaction. Moreover, we demonstrated the protein expression of eNOS, ET-1, and NFκB p65, including phosphorylation at Ser1177 of eNOS and Ser536 of NFκB p65. Neutrophils from X-CGD patients showed significantly higher NO and lower H2O2 production in response to A23187 than healthy neutrophils in vitro. Compared with healthy neutrophils, X-CGD neutrophils under A23187 stimulation exhibited significantly increased NO and decreased H2O2, and promoted downregulated NOS3 and EDN1 expression in HUVECs. The total expression and phosphorylation at Ser1177 of eNOS and ET-1 expression were significantly decreased in HUVECs co-cultures with stimulated X-CGD neutrophils. Also, phosphorylation at Ser536 of NFκB p65 were significantly decreased. In conclusions, eNOS and ET-1 significantly down-regulated in co-culture with stimulated X-CGD neutrophils through their excessive NO and the lack of ROS production. These findings suggest that ROS generated from neutrophils may mediate arterial tone affecting eNOS and ET-1 expression via their NO and ROS production.
A Patient With Tricyclic Antidepressant Overdose With Catecholamine-Resistant Hypotension Rescued With Angiotensin II

This case report explores the novel use of angiotensin II (Giapreza) for the treatment of vasodilation in the setting of a tricyclic overdose. The purpose of this case is to describe how the use of angiotensin II can improve hemodynamic parameters and result in a dose reduction of other catecholamine vasopressors in vasodilatory shock. The use of angiotensin II is new to clinical practice and has the potential to change outcomes for patients.
Drug-specific risk of severe QT prolongation following acute drug overdose

Abstract Background: Severe QT prolongation (SQTP) has been identified as a strong predictor of adverse cardiovascular events in acute drug overdose, but drug-specific causes of SQTP in the setting of acute drug overdose remain unclear. We aimed to perform the most definitive study to date describing drug-specific risk of SQTP following acute drug overdose. Methods: This was a prospective multicenter cohort study at >50 hospital sites across the US using the ToxIC Registry between 2015 and 2018. Inclusion criteria were adults (≥18 years) receiving medical toxicology consultation for acute drug overdose. The primary outcome was SQTP, which was defined using the computer automated Bazett QT correction (QTc) on the ECG with the previously validated cut point of 500 milliseconds. Mean difference in QTc was also calculated for specific drugs. Drugs associated with SQTP were analyzed using multivariable logistic regression to control for known confounders of QT risk (age, sex, race, cardiac disease). Results: From 25,303 patients screened, 6473 met inclusion criteria with SQTP occurring in 825 (13%). Drugs associated with increased adjusted odds of SQTP included Class III antidysrhythmics (sotalol), sodium channel blockers (amitriptyline, diphenhydramine, doxepin, imipramine, nortriptyline), antidepressants (bupropion, citalopram, escitalopram, trazodone), antipsychotics (haloperidol, quetiapine), and the antiemetic serotonin antagonist ondansetron. Conclusions: This large US cohort describes drug-specific risk of SQTP following acute drug overdose. Healthcare providers caring for acute drug overdoses from any of these implicated drugs should pay close attention to cardiac monitoring for occurrence of SQTP.
Establishment and Characterisation of Heterotopic Patient-Derived Xenografts for Glioblastoma

Glioblastoma is an aggressive brain tumour with a patient median survival of approximately 14 months. The development of innovative treatment strategies to increase the life span and quality of life of patients is hence essential. This requires the use of appropriate glioblastoma models for preclinical testing, which faithfully reflect human cancers. The aim of this study was to establish glioblastoma patient-derived xenografts (PDXs) by heterotopic transplantation of tumour pieces in the axillae of NMRI nude mice. Ten out of 22 patients’ samples gave rise to tumours in mice. Their human origin was confirmed by microsatellite analyses, though minor changes were observed. The glioblastoma nature of the PDXs was corroborated by pathological evaluation. Latency times spanned from 48.5 to 370.5 days in the first generation. Growth curve analyses revealed an increase in the growth rate with increasing passages. The methylation status of the MGMT promoter in the primary material was maintained in the PDXs. However, a trend towards a more methylated pattern could be found. A correlation was observed between the take in mice and the proportion of Sox2+ cells (r = 0.49, p = 0.016) and nestin+ cells (r = 0.55, p = 0.007). Our results show that many PDXs maintain key features of the patients’ samples they derive from. They could thus be used as preclinical models to test new therapies and biomarkers.
Performance of eight‐color dry antibody reagent in the detection of minimal residual disease in chronic lymphocytic leukemia samples

Minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) has prognostic and predictive significance. One of the approaches to detect MRD by flow cytometry (FC) is the use of dry antibody reagents such as DuraClone® RE CLB (Beckman Coulter—BC). The aim of this study was to evaluate the performance of the DuraClone® RE CLB in detecting MRD in CLL compared to liquid reagents.
Colchicine for Secondary Cardiovascular Prevention: A Systematic Review

Despite advancements in medical and interventional therapy, patients with cardiovascular disease (CVD) continue to have residual risk for recurrent cardiovascular events. Colchicine has a unique antiinflammatory mechanism that has generated interest in its potential use as a secondary cardiovascular preventive therapy. The objective of this systematic review was to evaluate the evidence for long‐term (6 months or more) colchicine therapy in patients with established CVD. A search of Medline and Embase from inception to February 2020 was performed. Included were randomized controlled trials (RCTs) or propensity score‐matched observational studies that compared colchicine (at any dose) with placebo or no treatment. Outcomes of interest included any major adverse cardiovascular event, cardiovascular hospitalization, coronary artery restenosis, cardiovascular death, or all‐cause death. Five RCTs were included. The dose of colchicine ranged from 0.5 mg/day to 0.6 mg twice/day, and follow‐up ranged from ~6–36 months. Two trials (one double blind and one single blind) showed a reduction in composite outcomes of major adverse cardiovascular events. One study failed to demonstrate a benefit with colchicine in restenosis or recurrent ischemia after angioplasty; however, it was conducted before the routine use of modern percutaneous coronary intervention and medical therapies. In contrast, a more recent trial found that colchicine reduced the rate of in‐stent restenosis in patients who received a bare metal stent. Finally, one trial in patients with heart failure with reduced ejection fraction did not observe a benefit in death or heart failure hospitalization with colchicine despite a reduction in inflammatory markers. No trial demonstrated a reduction in cardiovascular or all‐cause death, and most trials showed an increase in the rate of diarrhea with colchicine. Overall, colchicine has demonstrated promising results for the secondary prevention of CVD; however, further studies are required to confirm these findings before colchicine can be routinely recommended in practice.
SBOR: a minimalistic soft self-burrowing-out robot inspired by razor clams

We observe that the Atlantic razor clam (Ensis directus) burrows out of sand rapidly by simply extending and contracting its muscular foot. This is notably different from its well-known downward burrowing strategy or the dual-anchor mechanism, where closing/opening of the shell and dilation of the foot are also involved. Inspired by this burrowing-out strategy, we design a simple self-burrowing-out robot (SBOR) consisting of a single segment of fiber-reinforced silicone tube actuator and an external control board. The reinforcing fibers limit the motion of the actuator to axial extension/contraction under inflation/deflation. For an actuator that is vertically buried in the sand, cyclic inflation and deflation naturally drives it out of the sand, mimicking the motion of a razor clam. We characterize the burrowing-out behavior of the actuator by varying the actuation period and the relative density (packing) of the sand. Each burrowing cycle features an initial upward advancement during inflation, followed by a downward slip during deflation, resulting in a net upward stride. During the burrowing-out process, the stride length first increases due to a drop in the overburden pressure, the end pull-out resistance, and the side frictional resistance; the stride length then decreases after the top of the actuator moves out of the sand layer, due to a reduction in the effective length of the actuator. The results also indicate that the average burrowing-out speed decreases with the relative density of the sand and changes with the actuation pressure. We developed a simplified model based on soil mechanics to predict the burrowing-out processes in relatively loose dry sands, and the modeling results match well with the experiment results. From this model, the burrowing-out behavior is readily explained by the asymmetric nature of the resistant forces on the two ends of the actuator and the flowing nature of sand upon yielding. Our findings imply that razor clams leverage the natural stress gradient of sand deposits to burrow upward. Another insight is that in order to burrow downward into the sand, additional symmetry-breaking features such as asymmetric geometry, friction, stress state or external load are needed to increase the resistant force (anchorage) in the upward direction and to reduce the resistant force (drag) in the downward direction.
Healthy Operator 4.0: A Human Cyber–Physical System Architecture for Smart Workplaces

Recent advances in technology have empowered the widespread application of cyber–physical systems in manufacturing and fostered the Industry 4.0 paradigm. In the factories of the future, it is possible that all items, including operators, will be equipped with integrated communication and data processing capabilities. Operators can become part of the smart manufacturing systems, and this fosters a paradigm shift from independent automated and human activities to human–cyber–physical systems (HCPSs). In this context, a Healthy Operator 4.0 (HO4.0) concept was proposed, based on a systemic view of the Industrial Internet of Things (IIoT) and wearable technology. For the implementation of this relatively new concept, we constructed a unified architecture to support the integration of different enabling technologies. We designed an implementation model to facilitate the practical application of this concept in industry. The main enabling technologies of the model are introduced afterward. In addition, a prototype system was developed, and relevant experiments were conducted to demonstrate the feasibility of the proposed system architecture and the implementation framework, as well as some of the derived benefits.
Templated folding of intrinsically disordered proteins

Much of our current knowledge of biological chemistry is founded in the structure-function relationship, whereby sequence determines structure that determines function. Thus, the discovery that a large fraction of the proteome is intrinsically disordered, while being functional, has revolutionized our understanding of proteins and raised new and interesting questions. Many intrinsically disordered proteins (IDPs) have been determined to undergo a disorder-to-order transition when recognizing their physiological partners, suggesting that their mechanisms of folding are intrinsically different from those observed in globular proteins. However, IDPs also follow some of the classic paradigms established for globular proteins, pointing to important similarities in their behavior. In this review, we compare and contrast the folding mechanisms of globular proteins with the emerging features of binding-induced folding of intrinsically disordered proteins. Specifically, whereas disorder-to-order transitions of intrinsically disordered proteins appear to follow rules of globular protein folding, such as the cooperative nature of the reaction, their folding pathways are remarkably more malleable, due to the heterogeneous nature of their folding nuclei, as probed by analysis of linear free-energy relationship plots. These insights have led to a new model for the disorder-to-order transition in IDPs termed “templated folding,” whereby the binding partner dictates distinct structural transitions en route to product, while ensuring a cooperative folding.
Prevalence and determinants of unintended pregnancy in Ethiopia: A systematic review and meta-analysis of observational studies

Background Unintended pregnancy has significant consequences for the health and welfare of women and children. Despite this, a number of studies with inconsistent findings were conducted to reduce unintended pregnancy in Ethiopia; unavailability of a nationwide study that determines the prevalence of unintended pregnancy and its determinants is an important research gap. Thus, this study was conducted to determine the overall prevalence of unintended pregnancy and its determinants in Ethiopia. Methods We searched from Google Scholar, PubMed, Science Direct, Web of Science, CINAHL, and Cochrane Library databases for studies. Each of the original studies was assessed using a tool for the risk of bias of observational studies. The heterogeneity of studies was also assessed using I2 test statistics. Data were pooled and a random effect meta-analysis model was fitted to provide the overall prevalence of unintended pregnancy and its determinants in Ethiopia. In addition, the subgroup analyses were performed to investigate how the prevalence of unintended pregnancy varies across different groups of studies. Results Twenty-eight studies that satisfy the eligibility criteria were included. We found that the overall prevalence of unintended pregnancy in Ethiopia was 28% (95% CI: 26–31). The subgroup analyses showed that the highest prevalence of unintended pregnancy was observed from the Oromiya region (33.8%) followed by Southern Nations Nationalities and Peoples’ region (30.6%) and the lowest was in Harar. In addition, the pooled prevalence of unintended pregnancy was 26.4% (20.8–32.4) and 30.0% (26.6–33.6) for community-based cross-sectional and institution-based cross-sectional studies respectively. The pooled analysis showed that not communicating with one’s husband about family planning was more likely to lead to unintended pregnancy (OR: 3.56, 95%CI: 1.68–7.53). The pooled odds ratio also showed that unintended pregnancy is more likely among women who never use family planning methods (OR: 2.08, 95%CI: 1.18–3.69). Furthermore, the narrative review of this study showed that maternal education, age, and household wealth index are strongly associated with an unintended pregnancy. Conclusions In this study, the prevalence of unintended pregnancy was high. Lack of spousal communication, never using family planning, maternal education, and household wealth level were significantly associated with an unintended pregnancy. This study implies the need to develop plans and policies to improve the awareness of contraceptive utilization and strengthen spousal communication related to pregnancy.
A Replication Study Identified Seven SNPs Associated with Quantitative Traits of Type 2 Diabetes among Chinese Population in A Cross-Sectional Study

Genome-wide association studies (GWAS) have identified common variants for quantitative traits (insulin resistance and impaired insulin release) of type 2 diabetes (T2D) across different ethnics including China, but results were inconsistent. The study included 1654 subjects who were selected from the 2010–2012 China National Nutrition and Health Surveillance (CNNHS). Insulin resistance and impaired insulin release were assessed by homeostasis model assessment (HOMA). The study included 64 diabetes-related single nucleotide polymorphisms (SNPs), which were done using Mass ARRAY. A logistic regression model was employed to explore the associations of SNPs with insulin resistance and impaired insulin release by correcting for the confounders. The 5q11.2-rs4432842, RASGRP1-rs7403531, and SEC16B-rs574367 increased the risk of insulin resistance with OR = 1.23 (95% CI: 1.04–1.45, OR = 1.35 (95% CI: 1.13–1.62), OR = 1.34 (95% CI: 1.07–1.67), respectively, while MAEA-rs6815464 decreased the risk of insulin resistance (OR = 0.84, 95% CI: 0.71–1.00). CENTD2-rs1552224, TSPAN8-rs7961581 and ANK1-rs516946 was associated with increased risk of impaired insulin release with OR = 1.47 (95% CI: 1.09–1.99), OR = 1.25 (95% CI: 1.03–1.51), OR = 1.39 (95% CI: 1.07–1.81), respectively. Our findings would provide insight into the pathogenesis of individual SNPs and T2D.
Effect of the Pulsed Electromagnetic Field (PEMF) on Dental Implants Stability: A Randomized Controlled Clinical Trial

A pulsed electromagnetic field (PEMF) has been shown to contribute to heightening bone regeneration in a range of clinical areas, including dentistry. Due to the scarcity of studies using PEMF in oral implantology, the present experiment scrutinized the effect of PEMF can lead to improving the stability of the implant. A total of 19 subjects (40 implants in total) were selected to participate in the current study and were randomly allocated to either the PEMF group or control group. Subjects in the PEMF group received an activated miniaturized electromagnetic device (MED) while the control group received a sham healing cup. Implants stability was assessed by resonance frequency analyses (RFA) via implant stability quotient (ISQ) calculations. RFA were recorded as following: immediately after procedure, and then 2, 4, 6, 8 and 12 weeks later. Radiographic analysis was performed at baseline, 6 and 12 weeks after implant placement. Proinflammatory cytokines were evaluated in peri-implant crevicular fluid (PICF). The PEMF group presented higher ISQ mean values when compared to the control group. The primary stability time frame (the first 2 weeks) MED group depicted an increase in stability of 6.8%, compared to a decrease of 7.6% in the control group related to the baseline. An overall stability increase of 13% was found in MED treated group (p = 0.02), in contrast, the overall stability in the control group decreased by 2% (p = 0.008). TNF-α concentration during first 4 weeks was lower in the MED treated group. The data strongly suggests that MED generated continuing a PEMF may be considered as a new way to stimulate the stability of the implants at the early healing period.
A Qualitative Systematic Review of Caregivers’ Experiences of Caring for Family Diagnosed with Schizophrenia

Abstract Objective: To synthesise qualitative research that explored caregivers’ experiences of caring for family diagnosed with schizophrenia. Methods: Electronic databases including PsycINFO, PubMed, CINAHL and Scopus were searched to identify relevant journal articles published from 2000 to March 2019. Quality was assessed and thematic synthesis of the qualitative research evidence undertaken. Papers were screened and independently appraised by two reviewers using The Critical Appraisal Skills Programme (CASP) for Qualitative Studies Checklist. The review was guided by Thomas and Harden's framework for thematic synthesis of qualitative research evidence. Results: The breadth of information across the 43 papers was noteworthy. Review of the findings noted that almost all of what was discussed fell into three broad themes: the ‘feelings’ of the caregiver towards their role, the patient and others, including the health system; the ‘impacts’ of the diagnosis and their caregiving role on the caregiver; and the ‘needs’ of the caregiver to improve the patient’s quality of life and thereby the caregiver’s quality of life. Within needs also came recommendations for future changes. Conclusion: Studies have shown that the caregiving process is a complex one, with both negative and positive emotional reactions, societal barriers, such as stigma and isolation, and unmet needs, such as timely, relevant and helpful information. Meeting the needs identified by caregivers has the capacity to address the impacts of the illness and caregiving and thereby reduce the negative feelings associated with the caregiver role.
A biomechanical approach to evaluate overload and specificity characteristics within physical preparation exercises

ABSTRACT An essential component of any physical preparation programme is the selection of training exercises to facilitate desired performance outcomes, with practitioners balancing the principles of sports training to inform exercise selection. This study aimed to advance biomechanical understanding of the principles of overload and specificity within exercise selection, utilising novel joint kinetic and intra-limb joint coordination analyses. Three-dimensional kinematic and kinetic data were obtained from six male sprinters (100 m PB, 10.64–11.00) performing block starts (competitive motor task) and seven training exercises that encompassed traditionally viewed general and more specific exercises. Results highlighted the challenging nature of exercise selection, with all exercises demonstrating capacity to overload relevant joint kinetic features of the block start. In addition, all exercises were able to promote the emergence of proximal and in-phase extension joint coordination patterns linked with block start execution, although traditionally viewed non-specific exercises elicited greater overall coordination similarity. The current research helps advance biomechanical understanding of overload and specificity within exercise selection, by demonstrating how exercise selection should not solely be based on perceived replication of a competitive motor task. Instead, practitioners must consider how the musculoskeletal determinants of performance are overloaded, in addition to promoting task specific coordination patterns.