Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes.

BACKGROUND The cardiovascular effects of ertugliflozin, an inhibitor of sodium-glucose cotransporter 2, have not been established. METHODS In a multicenter, double-blind trial, we randomly assigned patients with type 2 diabetes and atherosclerotic cardiovascular disease to receive 5 mg or 15 mg of ertugliflozin or placebo once daily. With the data from the two ertugliflozin dose groups pooled for analysis, the primary objective was to show the noninferiority of ertugliflozin to placebo with respect to the primary outcome, major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The noninferiority margin was 1.3 (upper boundary of a 95.6% confidence interval for the hazard ratio [ertugliflozin vs. placebo] for major adverse cardiovascular events). The first key secondary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure. RESULTS A total of 8246 patients underwent randomization and were followed for a mean of 3.5 years. Among 8238 patients who received at least one dose of ertugliflozin or placebo, a major adverse cardiovascular event occurred in 653 of 5493 patients (11.9%) in the ertugliflozin group and in 327 of 2745 patients (11.9%) in the placebo group (hazard ratio, 0.97; 95.6% confidence interval [CI], 0.85 to 1.11; P<0.001 for noninferiority). Death from cardiovascular causes or hospitalization for heart failure occurred in 444 of 5499 patients (8.1%) in the ertugliflozin group and in 250 of 2747 patients (9.1%) in the placebo group (hazard ratio, 0.88; 95.8% CI, 0.75 to 1.03; P = 0.11 for superiority). The hazard ratio for death from cardiovascular causes was 0.92 (95.8% CI, 0.77 to 1.11), and the hazard ratio for death from renal causes, renal replacement therapy, or doubling of the serum creatinine level was 0.81 (95.8% CI, 0.63 to 1.04). Amputations were performed in 54 patients (2.0%) who received the 5-mg dose of ertugliflozin and in 57 patients (2.1%) who received the 15-mg dose, as compared with 45 patients (1.6%) who received placebo. CONCLUSIONS Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, ertugliflozin was noninferior to placebo with respect to major adverse cardiovascular events. (Funded by Merck Sharp & Dohme and Pfizer; VERTIS CV ClinicalTrials.gov number, NCT01986881.).
The Involvement of Hypothalamus–Pituitary–Adrenal (HPA) Axis in Suicide Risk

Stress and Hypothalamic–Pituitary–Adrenal (HPA) axis dysregulation play a major role in various pathophysiological processes associated with both mood disorders and suicidal behavior. We conducted a systematic review with the primary aim of clarifying the nature and extent of HPA axis activity and suicidal behavior. The second aim of this review was to investigate whether potential biomarkers related to HPA axis abnormalities act as individual susceptibility factors for suicide. The PRISMA statement for reporting systematic reviews was used. Only articles published in English peer-reviewed journals were considered for possible inclusion; we excluded case reports, meta-analyses, and systematic reviews, and studies that did not clearly report statistical analysis, diagnostic criteria, or the number of patients included. Overall, 36 articles on HPA axis and suicide risk met inclusion criteria and were reviewed. Studies that investigated tests detecting biomarkers and the role of early life stressors in suicide risk were also included. We found that HPA axis activity is involved in suicide risk, regardless of the presence or absence of psychiatric conditions. The HPA axis abnormalities, mainly characterized by hyperactivity of the HPA axis, may exert an important modulatory influence on suicide risk. Impaired stress response mechanisms contribute to suicide risk. Targeting HPA axis dysregulation might represent a fruitful strategy for identifying new treatment targets and improving suicide risk prediction.
Opioid Reduction and Long-Term Outcomes in Abdominal Myofascial Pain Syndrome (AMPS): A 6-Year Longitudinal Prospective Audit of 207 Patients.

BACKGROUND Abdominal myofascial pain syndrome is an important cause of refractory chronic abdominal pain. It causes severe functional impairment resulting in significant patient distress and substantial health care costs, and it can be a challenge to treat. Opioid consumption is a recognized challenge in this cohort. STUDY DESIGN We conducted a prospective longitudinal audit over a 6-year period. SETTING The study was conducted at a tertiary pain medicine clinic in a university teaching hospital. METHODS Over a 6-year period, 234 patients diagnosed with chronic abdominal pain secondary to abdominal myofascial pain syndrome were included in a structured management pathway. Long-term outcomes were prospectively audited at a tertiary-care university hospital. Patients who completed a minimum of 12 months in the pathway were included. The main outcome was reduction in opioid consumption. Treatment outcomes included treatment failure, number of patients with clinically significant pain relief, durable pain relief, and long-term pain relief. Other outcomes included patient satisfaction and success in maintaining gainful employment. RESULTS Two hundred seven patients completed a minimum of 12 months of follow-up. Seventy-eight percent (162 of 207) were on opioids at presentation. There was significant reduction in opioid consumption at >= 12 months' follow-up. Among patients who underwent interventional management, clinically significant relief was reported in 31 patients (31 of 180, 17%), durable relief in 71 patients (71 of 180, 40%) and long-term relief lasting 12 months in 23 patients (23 of 180, 13%). Twenty-six patients (26 of 180, 15%) reported cure from symptoms. The treatment failure rate was 15%. LIMITATIONS This was an open-label study that took place at a single center. CONCLUSION The authors present the first prospective practice-based evidence report on the long-term outcomes in patients diagnosed with abdominal myofascial pain syndrome. There was significant reduction in opioid consumption at 12 months and over two-thirds of patients reported significant durable relief on long-term follow-up. The authors present their recommendation for managing this complex group of patients.
Pathological features of COVID-19-associated myocardial injury: a multicentre cardiovascular pathology study

Abstract Aims Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction. The cardiac pathological changes in these patients with COVID-19 have yet to be well described. Methods and results In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists. The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry. Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement. Lymphocytic myocarditis was present in 3 (14%) of the cases. In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant. Increased interstitial macrophage infiltration was present in 18 (86%) of the cases. A mild pericarditis was present in four cases. Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases. There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified. Conclusions In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases. Other forms of myocardial injury are also present in these patients. The macrophage infiltration may reflect underlying diseases rather than COVID-19.
Towards a conceptual framework of the working alliance in a blended low-intensity cognitive behavioural therapy intervention for depression in primary mental health care: a qualitative study

Objectives To examine and adapt a conceptual framework of the working alliance (WA) in the context of a low-intensity blended (psychological well-being practitioner (PWP) plus computerised program) cognitive behavioural therapy intervention (b-CBT) for depression. Design Patient involvement was enlisted to collaboratively shape the design of the project from the onset, before data collection. In-depth semi-structured interviews were carried out with participants who experienced b-CBT as part of the E-compared trial. A thematic analysis was conducted using a constant comparative method informed by grounded theory. Setting Recruitment was carried out in four psychological primary care services across the UK. Participants Nineteen trial participants with major depressive disorder who completed at least one computerised program and face-to-face session with a PWP in the b-CBT arm were recruited to the study. Results Qualitative interviews that were guided by WA theory and patient involvement, revealed four themes: (1) a healthcare provider (PWP and computerised program) with good interpersonal competencies for building a working relationship with the client (‘bond’); (2) collaborative efforts between the client and the provider to appropriately identify what the client hopes to achieve through therapy (‘goals’); (3) the selection of acceptable therapeutic activities that address client goals and the availability of responsive support (‘task’) and (4) the promotion of active engagement and autonomous problem solving (‘usability heuristics’). Participants described how the PWP and computerised program uniquely and collectively contributed to different WA needs. Conclusions This study is the first to offer a preliminary conceptual framework of WA in b-CBT for depression, and how such demands can be addressed through blended PWP-computerised program delivery. These findings can be used to promote WA in technological design and clinical practice, thereby promoting engagement to b-CBT interventions and effective deployment of practitioner and program resources. Trial registration number ISRCTN12388725.
Extracting the elasticity of the human skin in microscale and in-vivo from atomic force microscopy experiments using viscoelastic models

Abstract Detecting mechanical properties of the intact skin in-vivo leads to a novel quantitative method to diagnose skin diseases and to monitor skin conditions in clinical settings. Current research and clinical methods that detect skin mechanics have major limitations. The in-vitro experiments are done in non-physiological conditions and in-vivo clinical methods measurer unwanted mechanics of underneath fat and muscle tissues but report the measurement as skin mechanics. An ideal skin mechanics should be captured at skin scale (i.e., micron-scale) and in-vivo. However, extreme challenges of capturing the in-vivo skin mechanics in micron-scale including skin motion due to heart beep, breathing and movement of the subject, has hindered measurement of skin mechanics in-vivo. This study for the first time captures micro-scale mechanics (elasticity and viscoelasticity) of top layers of skin (i.e., the stratum corneum (SC) and stratum granulosum (SG)) in-vivo. In this study, the relevant literature is reviewed and Atomic Force Microscopy (AFM) was used to capture force-indentation curves on the fingertip skin of four human subjects at a high indentation speed of 40 The skin of the same subject were tested in-vitro at 10 different indentation speeds ranging from 0.125 to 40 by AFM. This study extracts the in-vivo elasticity of SC and SG by detecting time-dependency of tested tissue using a fractional viscoelastic standard linear model developed for indentation. The in-vivo elasticity of SC and SG were smaller in females and in-vitro elasticity were higher than that of in-vivo results. The results were consistent with previous observations.
Aliarcobacter butzleri from Water Poultry: Insights into Antimicrobial Resistance, Virulence and Heavy Metal Resistance

Aliarcobacter butzleri is the most prevalent Aliarcobacter species and has been isolated from a wide variety of sources. This species is an emerging foodborne and zoonotic pathogen because the bacteria can be transmitted by contaminated food or water and can cause acute enteritis in humans. Currently, there is no database to identify antimicrobial/heavy metal resistance and virulence-associated genes specific for A. butzleri. The aim of this study was to investigate the antimicrobial susceptibility and resistance profile of two A. butzleri isolates from Muscovy ducks (Cairina moschata) reared on a water poultry farm in Thuringia, Germany, and to create a database to fill this capability gap. The taxonomic classification revealed that the isolates belong to the Aliarcobacter gen. nov. as A. butzleri comb. nov. The antibiotic susceptibility was determined using the gradient strip method. While one of the isolates was resistant to five antibiotics, the other isolate was resistant to only two antibiotics. The presence of antimicrobial/heavy metal resistance genes and virulence determinants was determined using two custom-made databases. The custom-made databases identified a large repertoire of potential resistance and virulence-associated genes. This study provides the first resistance and virulence determinants database for A. butzleri.
Ultrastrong low-carbon nanosteel produced by heterostructure and interstitial mediated warm rolling

We break the limit of grain refinement and strength of low-carbon steel by tuning deformation compatibility of heterostructure. Ultrastrong materials can notably help with improving the energy efficiency of transportation vehicles by reducing their weight. Grain refinement by severe plastic deformation is, so far, the most effective approach to produce bulk strong nanostructured metals, but its scaling up for industrial production has been a challenge. Here, we report an ultrastrong (2.15 GPa) low-carbon nanosteel processed by heterostructure and interstitial mediated warm rolling. The nanosteel consists of thin (~17.8 nm) lamellae, which was enabled by two unreported mechanisms: (i) improving deformation compatibility of dual-phase heterostructure by adjusting warm rolling temperature and (ii) segregating carbon atoms to lamellar boundaries to stabilize the nanolamellae. Defying our intuition, warm rolling produced finer lamellae than cold rolling, which demonstrates the potential and importance of tuning deformation compatibility of interstitial containing heterostructure for nanocrystallization. This previously unreported approach is applicable to most low-carbon, low-alloy steels for producing ultrahigh strength materials in industrial scale.
Gone, but haven't forgotten: insights on plasmapheresis donation from lapsed donors

Blood Collection Agencies in several countries have implemented strategies to increase the number of plasmapheresis collections. Despite this, a sizable minority of plasma donors lapse from donation each year, with little research conducted on this topic. An understanding of the plasma donation experience from the perspective of lapsed donors, insights into why they stopped donating and their views on returning to donate may provide opportunities to intervene to increase the retention and reactivation of plasma donors.
e-health usage and health workers’ motivation and job satisfaction in Ghana

Background The application of digital technology to improve health service delivery is increasing rapidly in Low- and Middle- Income Countries (LMICs). Digital tools such as electronic health (e-health) have been shown to improve healthcare quality, efficiency and patient satisfaction. However, evidence on health workers’ experiences using e-health services is limited in LMICs. This study examined the relationship between e-health usage and health workers’ motivation and job satisfaction. Methods This was a cross-sectional survey design involving health workers across public and private hospitals in the Accra Metropolitan Assembly (AMA). A structured questionnaire was designed and self-administered to 305 respondents. Partial Least Square-Structural Equation Modelling (PLS-SEM) was employed to analyse the data. Results Findings showed a significant positive association of job satisfaction with e-health (p < 0.01) and type of hospital (p < 0.01) but not motivation (p = 0.42). Although type of hospital significantly influenced job satisfaction (p < 0.01), it had no significant mediating effect on the relationship between e-health and job satisfaction. Finally, type of hospital interacted with e-health to moderate the association between e-health usage and job satisfaction. Conclusion The findings suggest that e-health systems can catalyse health workers job satisfaction. Thus, measures to strengthen e-health structures to improve on their efficiency and effectiveness is crucial.
DLK2 regulates arbuscule hyphal branching during arbuscular mycorrhizal symbiosis.

D14 and KAI2 receptors enable plants to distinguish between strigolactones (SLs) and karrikins (KARs), respectively, in order to trigger appropriate environmental and developmental responses. Both receptors are related to the regulation of Arbuscular Mycorrhizal (AM) formation and are members of the RsbQ-like family of α,β-hydrolases. DLK2 proteins, whose function remains unknown, constitute a third clade from the RsbQ-like protein family. We investigated whether the tomato SlDLK2 is a new regulatory component in the AM symbiosis. Genetic approaches were conducted to analyse SlDLK2 expression and to understand SlDLK2 function in AM symbiosis. We show that SlDLK2 expression in roots is AM-dependent and is associated with cells containing arbuscules. SlDLK2 ectopic expression arrests arbuscule branching and downregulates AM-responsive genes, even in the absence of symbiosis; while the opposite effect was observed upon SlDLK2 silencing. Moreover, SlDLK2 overexpression in Medicago truncatula roots showed the same altered phenotype observed in tomato roots. Interestingly, SlDLK2 interacts with DELLA, a protein that regulates arbuscule formation/degradation in AM roots. We propose that SlDLK2 is a new component of the complex plant-mediated mechanism regulating the life cycle of arbuscules in AM symbiosis.
Implications of Oxidative Stress and Potential Role of Mitochondrial Dysfunction in COVID-19: Therapeutic Effects of Vitamin D

Due to its high degree of contagiousness and like almost no other virus, SARS-CoV-2 has put the health of the world population on alert. COVID-19 can provoke an acute inflammatory process and uncontrolled oxidative stress, which predisposes one to respiratory syndrome, and in the worst case, death. Recent evidence suggests the mechanistic role of mitochondria and vitamin D in the development of COVID-19. Indeed, mitochondrial dynamics contribute to the maintenance of cellular homeostasis, and its uncoupling involves pathological situations. SARS-CoV-2 infection is associated with altered mitochondrial dynamics with consequent oxidative stress, pro-inflammatory state, cytokine production, and cell death. Furthermore, vitamin D deficiency seems to be associated with increased COVID-19 risk. In contrast, vitamin D can normalize mitochondrial dynamics, which would improve oxidative stress, pro-inflammatory state, and cytokine production. Furthermore, vitamin D reduces renin–angiotensin–aldosterone system activation and, consequently, decreases ROS generation and improves the prognosis of SARS-CoV-2 infection. Thus, the purpose of this review is to deepen the knowledge about the role of mitochondria and vitamin D directly involved in the regulation of oxidative stress and the inflammatory state in SARS-CoV-2 infection. As future prospects, evidence suggests enhancing the vitamin D levels of the world population, especially of those individuals with additional risk factors that predispose to the lethal consequences of SARS-CoV-2 infection.
Pregnancy and COVID-19

There are many unknowns for pregnant women during the COVID-19 pandemic. Clinical experience of pregnancies complicated with infection by other coronaviruses e.g. SARS and MERS, has led to pregnant woman being considered potentially vulnerable to severe SARS-CoV-2 infection. Physiological changes during pregnancy have a significant impact on the immune system, respiratory system, cardiovascular function and coagulation. These may have positive or negative effects on COVID-19 disease progression. The impact of SARS-CoV-2 in pregnancy remains to be determined and a concerted, global effort is required to determine effects on implantation, fetal growth and development, labour and neonatal health. Asymptomatic infection presents a further challenge regarding service provision, prevention and management. As well as direct impacts of the disease, a plethora of indirect consequences of the pandemic will adversely affect maternal health including reduced access to reproductive health services, increased mental health strain and increased socioeconomic deprivation. In this review we explore the current knowledge of COVID-19 in pregnancy and signpost areas for further research to minimise its impact for women and their children.
Angiotensin II enhances the proliferation of Natural Killer/T-cell lymphoma cells via activating PI3K/Akt signaling pathway

Abstract The present study was to determine the roles of Angiotensin (Ang) II in the growth of lymphoma in nude mice and the proliferation and viability of the human Natural Killer/T (NK/T)-cell lymphoma cell line SNK-6, and the activation of downstream signaling pathway. Lymphoma samples and corresponding normal tissues were obtained from lymphoma patients. Proliferation of SNK-6 cells was detected by CCK8 or MTT assay. The levels of Ang II and its receptor Ang II type 1 receptor (AT1R) were higher in lymphoma tissues than those in control tissues. Ang II increased the lymphoma volume and size in nude mice, the proliferation and viability and the proliferating cell nuclear antigen (PCNA) and Ki67 levels of SNK-6 cells. Losartan, an antagonist of AT1R, reduced lymphoma volume and size in nude mice, and the proliferation and viability and the PCNA and Ki67 levels of SNK-6 cells. The levels of phosphorylated phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-Akt) were increased by Ang II and then reduced by losartan in SNK-6 cells. The proliferation and viability of SNK-6 cells were increased by Ang II, but these increases were inhibited by PI3K inhibitor wortmannin and Akt inhibitor MK2206. The increases of PCNA and Ki67 induced by Ang II were inhibited by wortmannin or MK2206 in SNK-6 cells. These results indicate that Ang II/AT1R is activated in lymphoma, and Ang II promotes the progression of lymphoma in nude mice and the proliferation and viability of SNK-6 cells via activating PI3K/Akt signaling pathway.