Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcomes of patients with spinal metastases from renal cell carcinoma treated with conventionally-fractionated external beam radiation therapy

Abstract Renal cell carcinoma (RCC) has been traditionally thought to be radioresistant. This retrospective cohort study aims to assess the outcomes of patients with spinal metastases from RCC treated with conventionally-fractionated external beam radiation therapy (cEBRT) in our institution. Patients diagnosed with histologically or radiologically-proven RCC who received palliative cEBRT to spinal metastases, using 3-dimensional conformal technique between 2009 and 2018 were reviewed. Local progression-free survival (PFS), overall survival (OS) and common terminology criteria for adverse events version 4.0-graded toxicity were assessed. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate for predictors associated with survivals. Thirty-five eligible patients with forty spinal segments were identified, with a median follow-up of 7 months (range, 0–47). The median equivalent dose in 2 Gy fractions (EQD2) was 32.5 Gy 10 (range, 12–39). Thirty-seven percent of patients underwent surgical intervention. At the time of last follow-up, all but 1 patient had died. Seven patients developed local progression, with the median time to local progression of 10.2 months. The median local PFS and OS were 3.3 and 4.8 months. There was no grade 3 or higher toxicity. A higher radiation dose (equivalent dose to 2 Gy fraction <32.5 Gy 10 vs ≥32.5Gy 10) (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.17–3.18; P-value (P) = . 68) and spinal surgery (HR, 2.35; 95% CI, 0.53–10.29; P = .26) were not significantly associated with local PFS on univariable analysis. Multivariable analysis showed that higher Tokuhashi score (HR, 0.41; 95% CI, 0.19–0.88; P = .02), lower number of spinal segments irradiated (HR, 1.18; 95% CI, 1.01–1.37; P = .04) and use of targeted therapy (HR, 0.41; 95% CI, 0.18–0.96; P = .04) were independent predictors for improved OS. For an unselected group of patients with RCC, there is no significant association between higher radiation dose and improved local control following cEBRT. This may be due to their short survivals. With the use of more effective systemic therapy, including targeted therapy and immunotherapy, survival will likely be prolonged. A tailored-approach is needed to identify patients with good prognosis who may still benefit from aggressive local treatments.
Patients with paroxysmal nocturnal hemoglobinuria demonstrate a prothrombotic clotting phenotype which is improved by complement inhibition with eculizumab

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement‐mediated intravascular hemolysis and thrombosis. The increased incidence of PNH‐driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement‐mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients. Based on previously described links between changes in fibrin clot structure and thrombosis in other disorders, our aim was to investigate clot structure as a possible mechanism of thrombosis in patients with PNH and the anti‐thrombotic effects of eculizumab treatment on clot structure. Clot structure, fibrinogen levels and thrombin generation were examined in plasma samples from 82 patients from the National PNH Service in Leeds, UK. Untreated PNH patients were found to have increased levels of fibrinogen and thrombin generation, with subsequent prothrombotic changes in clot structure. No link was found between increasing disease severity and fibrinogen levels, thrombin generation, clot formation or structure. However, eculizumab treated patients showed decreased fibrinogen levels, thrombin generation and clot density, with increasing time spent on treatment augmenting these antithrombotic effects. These data suggest that PNH patients have a prothrombotic clot phenotype due to increased fibrinogen levels and thrombin generation, and that the antithrombotic effects of eculizumab are, in‐part, due to reductions in fibrinogen and thrombin generation with downstream effects on clot structure.
Neurological manifestations of the coronavirus (SARS-CoV-2) pandemic 2019–2020

Since December 2019, a cluster of cases with contact history of live animals in Huanan seafood wholesale market of Wuhan city developed an unexplained course of pneumonia. A novel virus was identified and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Later on, WHO declared that the outbreak constitutes a Public Health Emergency of International Concern and named the disease COVID-19. As of 6 April 2020, more than 1 270 000 human infections with the novel coronavirus have been confirmed in more than 200 countries or regions with nearly 70 000 reported deaths. Studies revealed that angiotensin-converting enzyme 2 (ACE2) is the main host cell receptor of SARS-CoV-2.1 Since ACE2 is expressed in the neurons and glial cells, COVID-19 may also cause neurological symptoms. Considering the neurological manifestations of COVID-19 have been rarely mentioned in past literature,2 familiarising neurologists with the clinical course of the disease is critical in treating and controlling the disease. The coronavirus known as SARS-CoV-2 is a novel beta coronavirus in the form of RNA and has nearly 29 000 nucleotide base pairs that hold the genetic code for viral production. SARS-CoV-2 is transmitted mainly through respiratory tract secretions or by direct contact. Asymptomatic persons are also potential …
Mesenchymal Stromal Cell–Derived Small Extracellular Vesicles Induce Ischemic Neuroprotection by Modulating Leukocytes and Specifically Neutrophils

Supplemental Digital Content is available in the text. Background and Purpose— Small extracellular vesicles (sEVs) obtained from mesenchymal stromal cells (MSCs) were shown to induce neurological recovery after focal cerebral ischemia in rodents and to reverse postischemic lymphopenia in peripheral blood. Since peripheral blood cells, especially polymorphonuclear neutrophils (PMNs), contribute to ischemic brain injury, we analyzed brain leukocyte responses to sEVs and investigated the role of PMNs in sEV-induced neuroprotection. Methods— Male C57Bl6/j mice were exposed to transient intraluminal middle cerebral artery occlusion. After reperfusion, vehicle or sEVs prepared from conditioned media of MSCs raised from bone marrow samples of 3 randomly selected healthy human donors were intravenously administered. sEVs obtained from normoxic and hypoxic MSCs were applied. PMNs were depleted in vehicle and MSC-sEV–treated mice. Neurological deficits, ischemic injury, blood-brain barrier integrity, peripheral blood leukocyte responses, and brain leukocyte infiltration were evaluated over 72 hours. Results— sEV preparations of all 3 donors collected from normoxic MSCs significantly reduced neurological deficits. Preparations of 2 of these donors significantly decreased infarct volume and neuronal injury. sEV-induced neuroprotection was consistently associated with a decreased brain infiltration of leukocytes, namely of PMNs, monocytes/macrophages, and lymphocytes. sEVs obtained from hypoxic MSCs (1% O2) had similar effects on neurological deficits and ischemic injury as MSC-sEVs obtained under regular conditions (21% O2) but also reduced serum IgG extravasation—a marker of blood-brain barrier permeability. PMN depletion mimicked the effects of MSC-sEVs on neurological recovery, ischemic injury, and brain PMN, monocyte, and lymphocyte counts. Combined MSC-sEV administration and PMN depletion did not have any effects superior to PMN depletion in any of the readouts examined. Conclusions— Leukocytes and specifically PMNs contribute to MSC-sEV–induced ischemic neuroprotection. Individual MSC-sEV preparations may differ in their neuroprotective activities. Potency assays are urgently needed to identify their therapeutic efficacy before clinical application.
Long‐term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT‐2 study): 52‐week results from a randomized controlled trial

Abstract Aim To investigate the long‐term efficacy and safety of dapagliflozin as an adjunct to adjustable insulin in adults with type 1 diabetes (T1D) and inadequate glycaemic control. Materials and Methods Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT‐2) was a placebo‐controlled, double‐blind, multicentre, phase III study of adults with T1D (HbA1c 7.5%‐10.5%) randomized (1:1:1) to receive dapagliflozin 5, 10 mg, or placebo. The efficacy and safety of dapagliflozin over 52 weeks were exploratory endpoints in this extension to DEPICT‐2. Results Of 813 participants randomized, 88.2% completed the study. From baseline to 52 weeks, dapagliflozin 5 and 10 mg were associated with reduction in HbA1c (difference [95% CI] vs. placebo: −0.20% [−0.34, −0.06] and −0.25% [−0.38, −0.11], respectively) and adjusted mean percentage change in body weight (difference [95% CI] vs. placebo: −4.42% [−5.19, −3.64] and −4.86% [−5.63, −4.08], respectively). Serious adverse events were reported in the dapagliflozin 5, 10 mg, and placebo groups (32 [11.8%], 19 [7.0%] and 16 [5.9%], respectively). The proportion of hypoglycaemic events was similar across groups; severe hypoglycaemia was uncommon. More participants with events adjudicated as definite diabetic ketoacidosis (DKA) were in the dapagliflozin 5 and 10 mg groups versus placebo (11 [4.1%], 10 [3.7%] and 1 [0.4%], respectively); the majority of events were mild or moderate in severity and all were resolved with treatment. Conclusions Dapagliflozin led to long‐term reductions in HbA1c and body weight in adults with T1D, but increased DKA risk compared with placebo.
Sex Disparities in Cardiovascular Outcome Trials of Populations With Diabetes: A Systematic Review and Meta-analysis

BACKGROUND Sex differences have been described in diabetes cardiovascular outcome trials (CVOTs). PURPOSE We systematically reviewed for baseline sex differences in cardiovascular (CV) risk factors and CV protection therapy in diabetes CVOTs. DATA SOURCES Randomized placebo-controlled trials examining the effect of diabetes medications on major adverse cardiovascular events in people ≥18 years of age with type 2 diabetes. STUDY SELECTION Included trials reported baseline sex-specific CV risks and use of CV protection therapy. DATA EXTRACTION Two reviewers independently abstracted study data. DATA SYNTHESIS We included five CVOTs with 46,606 participants. We summarized sex-specific data using mean differences (MDs) and relative risks (RRs) and pooled estimates using random effects meta-analysis. There were fewer women than men in included trials (28.5–35.8% women). Women more often had stroke (RR 1.28; 95% CI 1.09, 1.50), heart failure (RR 1.30; 95% CI 1.21,1.40), and chronic kidney disease (RR 1.33; 95% CI 1.17; 1.51). They less often used statins (RR 0.90; 95% CI 0.86, 0.93), aspirin (RR 0.82; 95% CI 0.71, 0.95), and β-blockers (RR 0.93; 95% CI 0.88, 0.97) and had a higher systolic blood pressure (MD 1.66 mmHg; 95% CI 0.90, 2.41), LDL cholesterol (MD 0.34 mmol/L; 95% CI 0.29, 0.39), and hemoglobin A1c (MD 0.11%; 95% CI 0.09, 0.14 [1.2 mmol/mol; 1.0, 1.5]) than men. LIMITATIONS We could not carry out subgroup analyses due to the small number of studies. Our study is not generalizable to low CV risk groups nor to patients in routine care. CONCLUSIONS There were baseline sex disparities in diabetes CVOTs. We suggest efforts to recruit women into trials and promote CV management across the sexes.
Targeting the Adipose Tissue in COVID‐19

The WHO considers non-communicable diseases (NCDs), such as obesity, a major risk factor for becoming seriously ill with 2019 novel coronavirus (COVID-19) (1). A study by the UK Intensive Care National Audit and Research Centre indicates that two thirds of people who developed serious or fatal COVID-19-related complications were overweight or obese (2). The report includes data from all COVID-19 admissions in intensive care units in the UK until midnight, March 19, 2020. The study shows that almost 72 % of those in critical care units are either overweight or with obesity suggesting the impact of obesity in seriously ill COVID-19 patients.
Status of Pharmacy Ethics Education in Australia and New Zealand

Objective. To explore models of teaching in, resources available to, and delivery of a standardized course in pharmacy ethics. Methods. An email invitation was sent to the educator responsible for teaching pharmacy ethics at each of 19 institutions in Australia and New Zealand. Over a six- to eight-week period, semi-structured interviews were conducted in person, by email, or by phone, and were audio-recorded where possible, transcribed verbatim, and entered into data analysis software. Using an inductive analysis approach, themes related to the topics and issues discussed in the interview process were identified. Results. Of the educators invited to participate, 17 completed an interview and were included in this study. Participants reported a paucity of resources available for teaching pharmacy ethics at schools in Australia and New Zealand. Compounding this issue was the lack of expertise and ad-hoc process educators used to create their courses. Assessment methods varied between institutions. Participants felt schools needed to move toward a more standardized pharmacy ethics course with clear and defined guidelines. Conclusion. This study identified many areas in pharmacy ethics that need improvement and revealed the need to develop resources and course structure that adhere to the highest level of Miller’s pyramid, while using known frameworks to evaluate ethical competency.
Cognitive Reserve Proxies Do Not Differentially Account for Cognitive Performance in Patients with Focal Frontal and Non-Frontal Lesions

Abstract Objective: Cognitive reserve (CR) suggests that premorbid efficacy, aptitude, and flexibility of cognitive processing can aid the brain’s ability to cope with change or damage. Our previous work has shown that age and literacy attainment predict the cognitive performance of frontal patients on frontal-executive tests. However, it remains unknown whether CR also predicts the cognitive performance of non-frontal patients. Method: We investigated the independent effect of a CR proxy, National Adult Reading Test (NART) IQ, as well as age and lesion group (frontal vs. non-frontal) on measures of executive function, intelligence, processing speed, and naming in 166 patients with focal, unilateral frontal lesions; 91 patients with focal, unilateral non-frontal lesions; and 136 healthy controls. Results: Fitting multiple linear regression models for each cognitive measure revealed that NART IQ predicted executive, intelligence, and naming performance. Age also signiﬁcantly predicted performance on the executive and processing speed tests. Finally, belonging to the frontal group predicted executive and naming performance, while membership of the non-frontal group predicted intelligence. Conclusions: These ﬁndings suggest that age, lesion group, and literacy attainment play independent roles in predicting cognitive performance following stroke or brain tumour. However, the relationship between CR and focal brain damage does not differ in the context of frontal and non-frontal lesions.
Fat and Protein Variability in Donor Human Milk and Associations with Milk Banking Processes.

Background: The impact of milk banking processes on macronutrient variability in donor human milk (DHM) is largely unknown. Objective: To gain a better understanding of fat and protein composition in DHM and assess potential relationships with modifiable milk bank processes. Methods: Samples of raw, pooled DHM were collected from 20 milk banks (n = 300) along with the following processing attributes: if macronutrient analysis was used to select donors for pooling (target pooling; yes/no), number of donors per pool, pooling container material (glass/plastic/other), and method for mixing during bottling (manual/mechanical). Fat and protein were assessed. Homoscedasticity was assessed and magnitude of the spread was quantified. Results: Fat ranged from 1.9 to 6.1 g/dL (n = 298) and protein ranged from 0.7 to 1.4 g/dL (n = 300). Variability in fat was significantly lower in samples that had been target pooled (p = 0.04), contained more donors per pool (p < 0.001), and had been mixed mechanically (p < 0.001). Variability in protein was significantly lower in samples that contained more donors per pool (p = 0.001). In a stratified analysis, increasing the number of donors per pool only reduced nutrient variability in samples that were not target pooled. Conclusion: For milk banks that do not target pool, using a greater number of donors in a pool may reduce fat and protein variability.
Pre-Transplant Angiotensin II Type 1 Receptor Antibodies and Anti-Endothelial Cell Antibodies Predict Graft Function and Allograft Rejection in a Low-Risk Kidney Transplantation Setting

Background Non-HLA antibodies, anti-angiotensin II type 1 receptor antibodies (anti-AT1R) and anti-endothelial cell antibodies (AECA), are known to play a role in allograft rejection. We evaluated the role of both antibodies in predicting post-transplant outcomes in low-risk living donor kidney transplantation (LDKT) recipients. Methods In 94 consecutive LDKT recipients who were ABO compatible and negative for pre-transplant HLA donor-specific antibodies, we determined the levels of anti-AT1Rs using an enzyme-linked immunosorbent assay and the presence of AECAs using a flow cytometric endothelial cell crossmatch (ECXM) assay with pre-transplant sera. Hazard ratio (HR) was calculated to predict post-transplant outcomes. Results Pre-transplant anti-AT1Rs (≥11.5 U/mL) and AECAs were observed in 36 (38.3%) and 22 recipients (23.4%), respectively; 11 recipients had both. Pre-transplant anti-AT1Rs were a significant risk factor for the development of acute rejection (AR) (HR 2.09; P=0.018), while a positive AECA status was associated with AR or microvascular inflammation only (HR 2.47; P=0.004) throughout the follow-up period. In particular, AECA (+) recipients with ≥11.5 U/mL anti-AT1Rs exhibited a significant effect on creatinine and estimated glomerular filtration rate (P<0.001; P=0.028), although the risk of AR was not significant. Conclusions Pre-transplant anti-AT1Rs and AECAs have independent negative effects on post-transplant outcomes in low-risk LDKT recipients. Assessment of both antibodies would be helpful in stratifying the pre-transplant immunological risk, even in low-risk LDKT recipients.
The impact of green spaces on mental health in urban settings: a scoping review

Abstract Background Our planet is currently experiencing the largest wave of urban growth in history, with 55% of the world’s population (4.2 billion people) currently living in urban areas, a figure set to rise to 70% by 2050. Primary care is the first point of treatment for most mental health disorders. Since the urban environment and health are intrinsically linked, it is useful to examine the effectiveness of Nature-Based Solutions in addressing mental health. Aims The aim of this scoping review was to examine “How urban green spaces can improve mental health and wellbeing among patients attending general practice and primary care? ” Methods The scoping review framework comprised a five-stage process developed by Arksey and O’Malley. Results Twenty-five studies were included in the review, mostly cross-sectional studies. A wide range of mental health outcomes were identified. Out of the 25 included studies, 23 showed positive associations between mental health and green space characteristics. Conclusion Our findings suggest that while green spaces are associated with positive mental health outcomes, most studies were cross-sectional in nature and provided limited evidence for association. Furthermore, the population samples used in most of the studies were taken from national survey data and were not specifically primary care patients. Further studies that assess primary care patients specifically are warranted.
A meta-analysis of randomized controlled trials

Background: We conducted this meta-analysis to analyze the effectiveness of balance training in improving postoperative rehabilitation outcomes in hip fracture surgery patients. Methods: The Cochrane Library, Web of Science, Embase, and PubMed electronic databases were searched from their inception to December 2018. We selected prospective clinical control analyses and high-quality randomized controlled trials (RCTs) following the inclusion standards. We used Stata 12.0 to perform the meta-analysis. Where possible, the standard mean difference (SMD) with the 95% confidence interval (CI) was determined using a random effects model. Results: Ten RCTs involving 955 hips (balance training=487, control=468) published between 2002 and 2019 were assessed for eligibility of inclusion in the meta-analysis. Balance training was shown to remarkably improve the aspects of quality of life associated with physical health (standard mean difference [SMD], 2.20; 95% CI, 1.63–2.78, P= .000), a fast gait speed (SMD, 1.01; 95% CI, 0.25–1.77, P= .009), and balance (SMD=0.26, 95% CI: [0.12, 0.41], P= .000). Moreover, the balance training group showed increases in independence in activities of daily living (ADLs), performance task scores, and health-related quality of life (HRQoL) scores compared with the control group (P< .05). Conclusion: According to the present meta-analysis, balance training improves one’s independence in activities of daily living, performance tasks, lower limb strength, gait, and total physical function compared with no balance training. More high-quality RCTs with large sample sizes are required for the identification of the best balance training program after hip fracture. Abbreviations: ADLs = activities of daily living, CI = confidence interval, HRQoL = health-related quality of life, PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses, RCTs = randomized controlled trials, SMD = standard mean difference.
MASTITIS PATHOGENS AND THEIR RESISTANCE AGAINST ANTIMICROBIAL AGENTS IN DAIRY COWS IN NITRA, SLOVAKIA

The objective of this study was to evaluate the effectiveness of different antibiotics against mastitis causing microorganisms in lactating dairy cows in and around Nitra region, Slovakia. Milk samples from quarters were cultured and bacteriologically evaluated. All the bacteria isolated through microbiological procedures were subjected to antimicrobial susceptibility test by disc diffusion method to a large number of antibiotics. The results revealed higher sensitivity against tetradelta (100 % of Streptococcus agalactiae and uberis, Escherichia coli (E. coli), Coagulase Negative Staphylococci (CNS)), (97.37 % of Staphylococcus aureus) with highest number of bacterial isolates, followed by enrofloxacin (100 % of Strep. agalactiae and uberis), (97.37 % Staph. aureus), (97.14 % of (CNS), cefalexin + kanamycin (100 % of Strep. agalactiae and uberis), (97.14 % of CNS), (96.0 % of E. coli) and amoxicillin + clavulanat (100 % of Strep. agalactiae and uberis), (98.57 % of CNS), (94.74 % of Staph. aureus), (94.0 % of E. coli). Maximum resistance was observed against penicillin (96.0 % of E. coli) and streptomycin (66.67 % of Strep. uberis). In conclusion, in vitro antibiogram studies of bacterial isolates revealed higher sensitivity for tetradelta, enrofloxacin, a combination of cefalexin plus kanamycin and amoxicillin plus clavulanat acid.