Miracle-dz/UniFAR-FTUs huggingface dataset:
Mass spectrometry-based steroid profiling in primary bilateral macronodular adrenocortical hyperplasia.

Biochemical characterization of primary bilateral macronodular adrenocortical hyperplasia (PBMAH) by distinct plasma steroid profiles has not been previously studied. Our objective was to assess plasma steroid profiles in the diagnosis of PBMAH. Thirty six subjects (22 females, 14 males) with PBMAH matched in age and gender to 336 control subjects. Comparisons included an additional 39 subjects (26 females, 13 males) with other adrenal tumors. LC-MS/MS-based steroid profiling of 15 plasma steroids was used with classification by discriminant analysis. Germline ARMC5 sequencing was performed in all PBMAH cases. Compared to controls, PBMAH showed increased plasma 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycortisol and aldosterone, but lower progesterone, DHEA and DHEA-S with distinct differences in subjects with and without disease-causing variants in ARMC5 . Larger differences in PBMAH vs. CPA were most obvious for corticosterone, but there were also similar trends for 18-hydroxycortisol and aldosterone. Similar patterns for aldosterone and 18-hydroxycortisol were present in PBMAH and PA but not SCS disease groups, whereas 18-oxocortisol was clearly highest in PA. Discriminant analyses, restricted to panels of 9 selected steroids, indicated correct classification of PBMAH compared to control and CPA groups in 96% of cases and similarly correct classification of PBMAH and other bilateral disease groups; correct classification of subjects with and without disease-causing germline variants in ARMC5 was achieved in 92% of subjects with PBMAH. Subjects with PBMAH show distinctive plasma steroid profiles that may even point to their genetics and offer a supplementary single-test alternative for screening purposes.
Evaluation of MDA-MB-468 Cell Culture Media Analysis in Predicting Triple-Negative Breast Cancer Patient Sera Metabolic Profiles

Triple-negative breast cancer (TNBC) is characterized by limited survival, poor prognosis, and high recurrence. Understanding the metabolic adaptations of TNBC could help reveal improved treatment regiments. Here we performed a comprehensive 1H NMR metabolic characterization of the MDA-MB-468 cell line, a commonly used model of TNBC, followed by an analysis of serum samples obtained from TNBC patients and healthy controls. MDA-MB-468 cells were cultured, and changes in the metabolic composition of the medium were monitored for 72 h. Based on time courses, metabolites were categorized as being consumed, being produced, or showing a mixed behavior. When comparing TNBC and control samples (HC), and by using multivariate and univariate analyses, we identified nine metabolites with differing profiles). The serum of TNBC patients was characterized by higher levels of glucose, glutamine, citrate, and acetoacetate and by lower levels of lactate, alanine, tyrosine, glutamate, and acetone. A comparative analysis between MDA-MB-468 cell culture media and TNBC patients’ serum identified a potential systemic response to the carcinogenesis-associated processes, highlighting that MDA-MB-468 cells footprint does not reflect metabolic changes observed in studied TNBC serum fingerprint.
Dietary diversity and food intake of urban preschool children in North‐Western Sri Lanka

Abstract Childhood malnutrition, associated with poor diet, is a clear public health threat in Sri Lanka, with high rates of under‐nutrition and micronutrient deficiencies coupled with the growing risk of overweight/obesity in urban locations. This study explored the dietary diversity and food intake of urban living Sri Lankan preschool children. A cross‐sectional analysis of the baseline data from a cohort study was conducted with parents/caregivers of children aged 2–6 years, from 21 preschool centres in Kurunegala District, Sri Lanka. Demographic and socio‐economic factors, dietary diversity score (DDS) (n = 597) and food intake (n = 458) (using a food frequency questionnaire) were assessed. Children had a mean DDS of 4.56 ± 0·85 out of 9, with most (91.1%) in the medium DDS category (DDS of 3.1–6.0), consuming rice as most common food. Lentils were consumed more than any meat or alternative food groups at all DDS levels. Child DDS differs with parent/caregiver age and ethnicity. Mean daily intakes of fruit (1.02) and vegetables (0.84) servings align with approximately half of national recommendations, with less than 20% of children meeting daily recommendations. More than one‐third consumed sugary snacks and confectionaries daily and 1 in 10 had them twice a day. Around 40% reported watching television while eating the evening meal. Despite the majority having reasonable DDSs (medium category), findings highlighted inadequate intakes of fruits and vegetables, excessive intakes of sugary snacks and unhealthy dietary and social behaviours, suggests the need for population‐based interventions to promote healthier dietary habits.
An update on the epidemiology of ANCA-associated vasculitis.

ANCA-associated vasculitis (AAV) includes granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. Epidemiological studies in AAV are important in understanding possible aetiologic mechanisms and facilitating healthcare planning. However, epidemiological studies present a number of challenges including clear definition of cases differentiated from other clinical disorders, and identification of cases due to the rarity of AAV. The aim of this review is to summarize different aspects on the epidemiology of ANCA-associated vasculitis from different geographical areas throughout the world. During the past three decades, development of classification criteria worldwide, including the ACR classification of 1990, the Chapel Hill consensus definitions updated in 2012 and the EMA algorithm has facilitated epidemiology studies in AAV. The available epidemiological studies reported in AAV suggest that incidence and prevalence may have increased over the past 30 years. Possible explanations for this increase may be a genuine increase in incidence, the evolution of classification criteria and the definition, and availability and wider use of ANCA serology to aid diagnosis, and greater physician awareness through education. The age-specific incidence for the whole group of AAV showed a clear increase with age. However, there has been a clear shift in the peak age at onset towards a higher age during the last 20-30 years. In addition, variation in incidence of AAV between men and women has been clearly evident in a number of epidemiological studies.
Effect of incorporating probiotics into the diet of matrinxã ( brycon amazonicus ) breeders

Summary The aim of the present study was to evaluate the influence of probiotics prepared from Bacillus subtilis (strain C-3102-Calsporin®; Calpis, Tokyo, Japan) as a dietary supplement on several reproductive aspects of female ‘matrinxa’(Brycon amazonicus), including hematological parameters, immunological characteristics and total lipid concentrations in muscle and liver tissue. The broodstock were kept in two ponds of 600 m2, at a density of 50 fish per pond, from March to November 2008. The fish were divided into two treatment groups: untreated control fish (T1), and fish fed with 10 g of probiotics per kg of ration (T2). Fish were fed a diet containing 32% crude protein (CP), 7% crude fat (CF), and 6.5% ether extract (EE) twice daily at a rate of 1% of the total biomass per day during the coldest months (May through August) and 3% during the warm season (March, April and September through November). During the reproductive period, 20 individuals from each treatment group were selected for the experiments; two doses of crude carp pituitary extract were given to females in 10-h intervals, and one dose was given to the males at the same time the females were given the second dose. A total of 20 fish were used for the hematological analyses. After anesthetization, blood samples were withdrawn by caudal puncture to determine the total number of cells, differential and total leukocyte counts, thrombocyte count, hematocrit, hemoglobin rate and plasma cortisol and glucose levels. The hematimetric index mean corpuscular volume (VCM) and mean corpuscular hemoglobin concentration (MHCM) were calculated. Ten other ‘matrinxas’ from the same groups were used to assess macrophage phagocytic activity and lipid levels. The results showed that females fed a probiotics-supplemented diet exhibited an increase in numbers of oocytes and, consequently, had higher rates of fertilization and hatching of larvae. Probiotic-treated fish also exhibited a significant increase in the phagocytic activity of macrophages, indicating an improvement in the immune system of breeders. Hematologic parameters were different in comparison to the time-zero group, and plasma cortisol and glucose levels were higher in the females. The total lipids levels in muscle and liver tissue were lower in B. amazonicus that received feed supplemented with probiotics.
Distribution and Genetic Variability of Sapoviruses in Africa

In this review, we describe the distribution and genetic diversity of sapoviruses detected among humans, animals and the environment in African countries. Databases were searched for studies conducted in African countries and published between Jan 2005 and Mar 2019. Only studies where RT- PCR was used for initial detection were included in the systematic review. We identified 27 studies from 14 African countries with 18 focused on human sapoviruses, two on animal sapoviruses and seven on sapoviruses observed in the environment. Samples. The overall estimated pooled prevalence of human sapovirus infections among symptomatic and asymptomatic individuals was similar at 5.0% (95% Confidence Interval (CI): 3.0–7.0) and 2.0% (95% CI: 1.0–3.0), respectively. In environmental samples sapovirus detection rates ranged from 0% to 90% while in animal studies it was 1.7% to 34.8%. Multiple causes of gastroenteritis, sensitivity of detection method used, diversity of sapovirus strains and rotavirus vaccine coverage rate are some of the factors that could have contributed to the wide range of sapovirus detection rates that were reported. The studies reported human genogroups GI, GII, and GIV, with genogroup GI being the most prevalent. Some potential novel strains were detected from animal samples. Most studies genotyped a small portion of either the capsid and/or polymerase region. However, this is a limitation as it does not allow for detection of recombinants that occur frequently in sapoviruses. More studies with harmonized genotyping protocols that cover longer ranges of the sapovirus genome are needed to provide more information on the genomic characterization of sapoviruses circulating in African countries. Further investigations on animal to human transmission for sapoviruses are needed as inter-species transmissions have been documented for other viruses.
From slacktivism to activism: Improving the commitment power of e-pledges for prosocial causes

Prosocial organizations increasingly rely on e-pledges to promote their causes and secure commitment. Yet their effectiveness is controversial. Epitomized by UNICEF’s “Likes Don’t Save Lives” campaign, the threat of slacktivism has led some organizations to forsake social media as a potential platform for garnering commitment. We proposed and investigated a novel e-pledging method that may enable organizations to capitalize on the benefits of e-pledging without compromising on its mass outreach potential. In two pilot studies, we first explored whether and why conventional e-pledges may not be as effective as intended. Building on those insights, we conducted one field and two lab experiments to test our proposed e-pledge intervention. Importantly, the field study demonstrated the effectiveness of the intervention for commitment behavior across a 3-month period. The laboratory experiments provided a deeper and more refined mechanism understanding of the effect and ruled out effort, novelty, and social interaction mindset as alternative explanations for why the intervention may be effective. As technological innovations continue to redefine how people interact with the world, this research sheds light on a promising method for transforming a simple virtual acknowledgment into deeper commitment—and, ideally, to action.
Ability of a Risk Prediction Tool to Stratify Quality and Cost for Older Patients with Tibial Shaft and Plateau Fractures.

OBJECTIVES To determine whether a validated trauma triage tool can identify which middle-aged and geriatric trauma patients with tibial shaft and plateau fractures are at risk for costly admissions and poorer hospital quality measures. DESIGN Prospective cohort study. SETTING Level 1 trauma center. PATIENTS/PARTICIPANTS 64 patients over the age of 55 hospitalized with isolated tibial shaft or plateau fractures. INTERVENTION Patients with either isolated tibial plateau fractures or tibial shaft fractures over a three year period were prospectively enrolled in an orthopedic trauma registry. Demographic information, injury severity, and comorbidities were assessed and incorporated into the STTGMA score, a validated trauma triage score that calculates inpatient mortality risk upon admission. Patients were then grouped into tertiles based on their STTGMA score. MAIN OUTCOME MEASUREMENTS Length of stay, complications, discharge location, and direct variable costs. RESULTS 64 patients met inclusion criteria. 33 (51.6%) patients presented with tibial plateau fractures and 31 (48.4%) with tibial shaft fractures. The mean age was 66.7 ± 10.2 years. Mean length of stay was significantly different between risk groups with a mean of 6.8 ± 4 days (p<0.001). While 19 (90.5%) of minimal risk patients were discharged home, only 7 (33.3%) and 5 (22.7%) of moderate and high-risk patients were discharged home, respectively (p<0.001). Higher risk patients experienced a significantly greater number of complications during hospitalization but had no differences in the need for ICU level care (p=0.027 and p=0.344, respectively). The total cost difference between the lowest and highest risk group was nearly 50% ($14070 ± 8056 vs $25147 ± 14471, mean difference $11077; p=0.022). CONCLUSION Application of the STTGMA triage tool allows for prediction of key hospital quality measures and cost of hospitalization that can improve clinical decision-making. LEVEL OF EVIDENCE Prognostic Level III.
Fading puppy syndrome associated with Toxocara canis infection.

Aim of this work was studying the role of Toxocara canis infection in fading puppy syndrome and evaluating its treatment. Twelve German shepherd puppies suffered from fading puppy syndrome and their dam were presented. The dead puppies (N.=8) were necropsied. On the other hand, living puppies (N.=4) and their dam were examined both clinically and parasitologically. The collected worms from necropsied puppies were parasitologically identified as Toxocara canis and their counts ranged from 48 to 75 per puppy. The live cases were treated by Flubendazole. The parasitological examinations of stool of live puppies and dam revealed eggs identified as Toxocara canis eggs and their counts ranged from 50 to 350 eggs per gram stool. Post-treatment counts of Toxocara canis worms in stool of live puppies and their dam were ranged from 13 to 79 worms per animal. The results of treatment proved the efficacy of Flubendazole for eradication of Toxocara canis. Toxocara canis considers one of the causes of fading puppy syndrome and could be cured by Flubendazole .
Potato Protein Isolate Stimulates Muscle Protein Synthesis at Rest and with Resistance Exercise in Young Women

Skeletal muscle myofibrillar protein synthesis (MPS) increases in response to protein feeding and to resistance exercise (RE), where each stimuli acts synergistically when combined. The efficacy of plant proteins such as potato protein (PP) isolate to stimulate MPS is unknown. We aimed to determine the effects of PP ingestion on daily MPS with and without RE in healthy women. In a single blind, parallel-group design, 24 young women (21 ± 3 years, n = 12/group) consumed a weight-maintaining baseline diet containing 0.8 g/kg/d of protein before being randomized to consume either 25 g of PP twice daily (1.6 g/kg/d total protein) or a control diet (CON) (0.8 g/kg/d total protein) for 2 wks. Unilateral RE (~30% of maximal strength to failure) was performed thrice weekly with the opposite limb serving as a non-exercised control (Rest). MPS was measured by deuterated water ingestion at baseline, following supplementation (Rest), and following supplementation + RE (Exercise). Ingestion of PP stimulated MPS by 0.14 ± 0.09 %/d at Rest, and by 0.32 ± 0.14 %/d in the Exercise limb. MPS was significantly elevated by 0.20 ± 0.11 %/d in the Exercise limb in CON (p = 0.008). Consuming PP to increase protein intake to levels twice the recommended dietary allowance for protein augmented rates of MPS. Performance of RE stimulated MPS regardless of protein intake. PP is a high-quality, plant-based protein supplement that augments MPS at rest and following RE in healthy young women.
Hinge location and apical drill holes in opening wedge high tibial osteotomy: A finite element analysis

At the time of medial opening wedge high tibial osteotomy (HTO) to realign the lower limb and offload medial compartment knee osteoarthritis, unwanted fractures can propagate from the osteotomy apex. The aim of this study was to use finite element (FE) analysis to determine the effect of hinge location and apical drill holes on cortical stresses and strains in HTO. A monoplanar medial opening wedge HTO was created above the tibial tuberosity in a composite tibia. Using the FE method, intact lateral hinges of different widths were considered (5, 7.5, and 10 mm). Additional apical drill holes (2, 4, and 6 mm diameters) were then incorporated into the 10 mm hinge model. The primary outcome measure was the maximum principal strain in the cortical bone surrounding the hinge axis. Secondary outcomes included the force required for osteotomy opening, minimum principal strain, and mean cortical bone stresses (maximum principal/minimum principal/von Mises). Larger intact hinges (10 mm) were associated with higher cortical bone maximum principal strain and stress, lower minimum principal strain/stress, and required greater force to open. Lateral cortex strain concentrations were present in all scenarios, but extended to the joint surface with the 10 mm hinge. Apical drill holes reduced the mean cortical bone maximum principal strain adjacent to the hinge axis: 2 mm hole 6% reduction; 4 mm 35% reduction; and 6 mm 55% reduction. Incorporating a 4‐mm apical drill hole centered 10 mm from the intact lateral cortex maintains a cortical bone hinge, minimizes cortical bone strains and reduces the force required to open the HTO; thus improving control.
The Lysosomotropic Activity of Hydrophobic Weak Base Drugs is Mediated via Their Intercalation into the Lysosomal Membrane

Lipophilic weak base therapeutic agents, termed lysosomotropic drugs (LDs), undergo marked sequestration and concentration within lysosomes, hence altering lysosomal functions. This lysosomal drug entrapment has been described as luminal drug compartmentalization. Consistent with our recent finding that LDs inflict a pH-dependent membrane fluidization, we herein demonstrate that LDs undergo intercalation and concentration within lysosomal membranes. The latter was revealed experimentally and computationally by (a) confocal microscopy of fluorescent compounds and drugs within lysosomal membranes, and (b) molecular dynamics modeling of the pH-dependent membrane insertion and accumulation of an assortment of LDs, including anticancer drugs. Based on the multiple functions of the lysosome as a central nutrient sensory hub and a degradation center, we discuss the molecular mechanisms underlying the alteration of morphology and impairment of lysosomal functions as consequences of LDs’ intercalation into lysosomes. Our findings bear important implications for drug design, drug induced lysosomal damage, diseases and pertaining therapeutics.
Ribosomal Protein S27/Metallopanstimulin-1 (RPS27) in Glioma—A New Disease Biomarker?

Despite its significant overexpression in several malignant neoplasms, the expression of RPS27 in the central nervous system (CNS) is widely unknown. We identified the cell types expressing RPS27 in the CNS under normal and disease conditions. We acquired specimens of healthy brain (NB), adult pilocytic astrocytoma (PA) World Health Organization (WHO) grade I, anaplastic PA WHO grade III, gliomas WHO grade II/III with or without isocitrate dehydrogenase (IDH) mutation, and glioblastoma multiforme (GBM). RPS27 protein expression was examined by immunohistochemistry and double-fluorescence staining and its mRNA expression quantified by RT-PCR. Patients’ clinical and tumor characteristics were collected retrospectively. RPS27 protein was specifically expressed in tumor cells and neurons, but not in healthy astrocytes. In tumor tissue, most macrophages were positive, while this was rarely the case in inflamed tissue. Compared to NB, RPS27 mRNA was in mean 6.2- and 8.8-fold enhanced in gliomas WHO grade II/III with (p < 0.01) and without IDH mutation (p = 0.01), respectively. GBM displayed a 4.6-fold increased mean expression (p = 0.02). Although RPS27 expression levels did not affect the patients’ survival, their association with tumor cells and tumor-associated macrophages provides a rationale for a future investigation of a potential function during gliomagenesis and tumor immune response.
Visualizing the evolution of evidence: Cumulative network meta‐analyses of new generation antidepressants in the last 40 years

It is often challenging to present the available evidence in a timely and comprehensible manner. We aimed to visualize the evolution of evidence about antidepressants for depression by conducting cumulative network meta‐analyses (NMAs) and to examine whether it could have helped the selection of optimal drugs. We built a Shiny web application that performs and presents cumulative NMAs based on R netmeta. We used a comprehensive dataset of double‐blind randomized controlled trials of 21 antidepressants in the acute treatment of major depression. The primary outcomes were efficacy (treatment response) and acceptability (all‐cause discontinuation), and treatment effects were summarized via odds ratios. We evaluated the confidence in evidence using the CINeMA (Confidence in Network Meta‐Analysis) framework for a series of consecutive NMAs. Users can change several conditions for the analysis, such as the period of synthesis, among the others. We present the league tables and two‐dimensional plots that combine efficacy, acceptability and level of confidence in the evidence together, for NMAs conducted in 1990, 1995, 2000, 2005, 2010, and 2016. They reveal that through the past four decades, newly approved drugs often showed initially exaggerated results, which tended to diminish and stabilize after approximately a decade. Over the years, the drugs with relative superiority changed dramatically; but as the evidence network grew larger and better connected, the overall confidence improved. The Shiny app visualizes how evidence evolved over years, emphasizing the need for a careful interpretation of relative effects between drugs, especially for the potentially amplified performance of newly approved drugs.