Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase separation at the nanoscale quantified by dcFCCS

Significance Liquid–liquid phase separation causes formation of membraneless condensates containing concentrated biomolecules, which play essential roles in diverse cellular processes. Currently, micrometer-scale phase-separated condensates are examined routinely to elucidate their functions and mechanisms in details. However, limited by current commonly used methods, the transition process from miscible individual molecules to micrometer-scale condensates is mostly unknown. Herein, we captured formation of nanoscale condensates, whose size, growth rate, molecular stoichiometry, and binding affinity to recruit client molecules were all quantified. To achieve this, we developed a dual-color fluorescence cross-correlation spectroscopy (dcFCCS) method, and we expect that dcFCCS can be widely applied to investigate phase separation of other biomolecules at the nanoscale. Liquid–liquid phase separation, driven by multivalent macromolecular interactions, causes formation of membraneless compartments, which are biomolecular condensates containing concentrated macromolecules. These condensates are essential in diverse cellular processes. Formation and dynamics of micrometer-scale phase-separated condensates are examined routinely. However, limited by commonly used methods which cannot capture small-sized free-diffusing condensates, the transition process from miscible individual molecules to micrometer-scale condensates is mostly unknown. Herein, with a dual-color fluorescence cross-correlation spectroscopy (dcFCCS) method, we captured formation of nanoscale condensates beyond the detection limit of conventional fluorescence microscopy. In addition, dcFCCS is able to quantify size and growth rate of condensates as well as molecular stoichiometry and binding affinity of client molecules within condensates. The critical concentration to form nanoscale condensates, identified by our experimental measurements and Monte Carlo simulations, is at least several fold lower than the detection limit of conventional fluorescence microscopy. Our results emphasize that, in addition to micrometer-scale condensates, nanoscale condensates are likely to play important roles in various cellular processes and dcFCCS is a simple and powerful quantitative tool to examine them in detail.
Molecular epidemiology of Hepatitis B virus, Hepatitis C virus, and Hepatitis D virus in general population of Afghanistan.

BACKGROUND/AIMS This study gives a clue about genotypes, subgenotypes and subtypes of HBV, HCV and HDV viruses in general population of Afghanistan. MATERIALS AND METHODS A total of 234 HBsAg, 44 anti-HCV and 5 Anti-Delta positive patients belong to 25-70 age group were obtained through a rapid screening test among 5898 residents of Afghanistan. After quantifying viral load, genotyping of 61 HBV, 29 HCV and 1 HDV samples were accomplished by sequencing of a segment of the HBV Pre S, HCV NS5B, and HDV Delta antigen regions respectively. Clinically important variants of the HBV polymerase gene, the "a" determinant of HBsAg, HCV NS5B and NS3 regions were assessed. RESULTS All HBV isolates were dispersed throughout the genotype D branch and ayw2 was the only subtypes found. The anti-HDV prevalence among HBsAg positive individuals was 2.2% and the single HDV sample, belonged to HDV genotype I. Analysis of HCV isolates revealed subtype HCV-1b in 75.86%, HCV-3a in 20.69% and HCV-3b in 3.44% patients. The observed mutant variants in the MHR of HBsAg were Y100 15%, Q101 5%, G102 15%, T115 45%, P120 5%, T131 5%. Likewise, S213T 10%, Q215P 5% and N248H 100% mutations were detected in the HBV polymerase region. C316N mutation was prevalent in 72.7% of HCV 1b participants. CONCLUSION Genotypic variation in Afghan patients is in line with the ones existing in neighboring countries and regions. HBV genotypes D1, subtype ayw2, HDV RNA type I, and HCV RNA genotype 1b are likely to be dominant in Afghan patients.
Interplay between Regulatory RNAs and Signal Transduction Systems during Bacterial Infection

The ability of pathogenic bacteria to stably infect the host depends on their capacity to respond and adapt to the host environment and on the efficiency of their defensive mechanisms. Bacterial envelope provides a physical barrier protecting against environmental threats. It also constitutes an important sensory interface where numerous sensing systems are located. Signal transduction systems include Two-Component Systems (TCSs) and alternative sigma factors. These systems are able to sense and respond to the ever-changing environment inside the host, altering the bacterial transcriptome to mitigate the impact of the stress. The regulatory networks associated with signal transduction systems comprise small regulatory RNAs (sRNAs) that can be directly involved in the expression of virulence factors. The aim of this review is to describe the importance of TCS- and alternative sigma factor-associated sRNAs in human pathogens during infection. The currently available genome-wide approaches for studies of TCS-regulated sRNAs will be discussed. The differences in the signal transduction mediated by TCSs between bacteria and higher eukaryotes and the specificity of regulatory RNAs for their targets make them appealing targets for discovery of new strategies to fight against multi-resistant bacteria.
Improving the Quality of Care in Care Homes Using the Quality Improvement Collaborative Approach: Lessons Learnt from Six Projects Conducted in the UK and The Netherlands

The Breakthrough Series Quality Improvement Collaborative (QIC) initiative is a well-developed and widely used approach, but most of what we know about it has come from healthcare settings. In this article, those leading QICs to improve care in care homes provide detailed accounts of six QICs and share their learning of applying the QIC approach in the care home sector. Overall, five care home-specific lessons were learnt: (i) plan for the resources needed to support collaborative teams with collecting, processing, and interpreting data; (ii) create encouraging and safe working environments to help collaborative team members feel valued; (iii) recruit collaborative teams, QIC leads, and facilitators who have established relationships with care homes; (iv) regularly check project ideas are aligned with team members’ job roles, responsibilities, and priorities; and (v) work flexibly and accept that planned activities may need adapting as the project progresses. These insights are targeted at teams delivering QICs in care homes. These insights demonstrate the need to consider the care home context when applying improvement tools and techniques in this setting.
Uric acid as a predictor of endothelial dysfunction in patients with metabolic syndrome

ABSTRACT Objective: We conducted a study to examine the association of endothelial dysfunction and oxidative stress with uric acid levels in patients of metabolic syndrome. Subjects and methods: One hundred and two patients of Metabolic Syndrome (International Diabetes Federation definition) were included in the study. Anthropometric measurements, serum uric acid levels, fasting blood sugar levels and lipid levels, as well as malondialdehyde and reactive nitrogen intermediates were measured after an 8-hour fasting period. Flow mediated vasodilation (FMD) of the brachial artery was measured and endothelial dysfunction was defined as an increase in diameter < 10% post compression. Results: A total of 102 patients were included in the study. Mean uric acid level was 5.49 ± 1.61 mg%. A total of 59 patients in the study had endothelial dysfunction, defined by an abnormal FMD. Patients with an abnormal FMD had higher levels of serum uric acid which was statistically significant (p value = 0.010). Serum RNI and MDA levels were negatively correlated with uric acid, but did not reach statistical significance. Patients with an abnormal FMD had a lower RNI level, but this did not reach statistical significance. Serum MDA levels were significantly higher in patients with an abnormal FMD (p value = 0.038). Conclusions: Uric acid was significantly associated with endothelial dysfunction in patients with metabolic syndrome in our study. It was inversely correlated with serum RNI and MDA levels, but this did not reach statistical significance.
OV16 Seroprevalence among Persons with Epilepsy in Onchocerciasis Endemic Regions: A Multi-Country Study

There is growing epidemiological evidence that onchocerciasis may induce epilepsy. High prevalence of onchocerciasis has been reported in onchocerciasis-meso and hyper-endemic regions. We aimed to determine the OV16 antibody prevalence in persons with epilepsy (PWE) in four onchocerciasis-endemic regions. PWE were identified during studies in Mahenge area (Tanzania), Kitgum and Pader districts (Uganda), the Mbam and Sanaga river valleys (Cameroon), and the Logo health zone (Democratic Republic of Congo). Exposure to Onchocerca volvulus was assessed by testing PWE for OV16 IgG4 antibodies using a rapid diagnostic test. The OV16 seroprevalence among PWE in the four onchocerciasis-endemic study sites ranged from 35.2% to 59.7%. OV16 seroprevalence increased with age until the age of 39 years, after which it decreased drastically. Our study suggests that, in onchocerciasis-endemic regions, epilepsy in young people is often associated with onchocerciasis, while epilepsy in older persons seems unrelated to O. volvulus exposure.
Calcium Ionophore-Induced Extracellular Vesicles Mediate Cytoprotection against Simulated Ischemia/Reperfusion Injury in Cardiomyocyte-Derived Cell Lines by Inducing Heme Oxygenase 1

Cardioprotection against ischemia/reperfusion injury is still an unmet clinical need. The transient activation of Toll-like receptors (TLRs) has been implicated in cardioprotection, which may be achieved by treatment with blood-derived extracellular vesicles (EVs). However, since the isolation of EVs from blood takes considerable effort, the aim of our study was to establish a cellular model from which cardioprotective EVs can be isolated in a well-reproducible manner. EV release was induced in HEK293 cells with calcium ionophore A23187. EVs were characterized and cytoprotection was assessed in H9c2 and AC16 cell lines. Cardioprotection afforded by EVs and its mechanism were investigated after 16 h simulated ischemia and 2 h reperfusion. The induction of HEK293 cells by calcium ionophore resulted in the release of heterogenous populations of EVs. In H9c2 and AC16 cells, stressEVs induced the downstream signaling of TLR4 and heme oxygenase 1 (HO-1) expression in H9c2 cells. StressEVs decreased necrosis due to simulated ischemia/reperfusion injury in H9c2 and AC16 cells, which was independent of TLR4 induction, but not that of HO-1. Calcium ionophore-induced EVs exert cytoprotection by inducing HO-1 in a TLR4-independent manner.
Burden of mental health problems: quality of life and cost-of-illness in youth consulting Dutch walk-in youth health centres

Abstract Background Little is known about the burden of (sub-threshold) mental health problems in youth. Aim To examine the burden of mental health problems in terms of health-related quality of life (HRQoL) and cost-of-illness, for first visitors of the Dutch youth walk-in centres (@ease). Method A bottom-up, prevalence-based burden of disease study from a societal perspective. HRQoL was assessed through the EuroQoL (EQ-5D-5L), and cost-of-illness via items about truancy and health care utilization. Results Participants (N = 80) showed a decreased HRQoL compared to the general population of Dutch youth. In the three months prior to their 1st attendance, participants skipped on average 4.11 days of school and had 1.03 health care visits, leading to total costs of €512.64 per person. Females had significantly higher health care costs and lower HRQoL. Health care use was lower in those not speaking the Dutch language. Living alone was a significant predictor of truancy (costs), and therefore total costs. Conclusions Mental health problems in youth consulting @ease have a considerable impact on the individual’s HRQoL, and an economic impact on society, yet almost 75% is not receiving care. A lack of interventions in this critical period in life may have major lifelong consequences.
Sweet corn crop response to different dripline spacings in the dry Mediterranean area

Increasing the spacing between driplines is the most significant factor in reducing the high initial costs of drip irrigation system. A two-year field study (2017 and 2018) was conducted on a clay loam soil to evaluate the effects of different dripline spacings (75, 150, 225, and 300 cm) on sweet corn yields, soil water status, and irrigation water use efficiency (IWUE) in the dry Mediterranean area. Results showed that the average husked cob yield (HCY) and IWUE were significantly decreased as the dripline spacing increased. HCY was 13.93, 12.30, 9.18, and 6.86 t ha -1 , for dripline spacing of 75, 150, 225, and 300 cm, respectively, for an average irrigation water depth of 725 mm. Both soil water storages and yields decreased with distance from the dripline. The 150-, 225- and 300 cm dripline spacings yielded 11.7, 34.0 and 50.8 % less than the 75 cm dripline spacing, but these wider dripline spacings provided 50, 67 and 75 % less unit-area cost, respectively. However, these reductions in crop yield did not justify the extra cost of the closer dripline spacing, at low crop prices and high dripline costs. Finally, further studies are needed to benefit from the higher initial unit-area cost savings obtained under the wider dripline spacings.
In Vitro Apoptotic Bioactivity of Flavonoids from Astragalus Verrucosus Moris

Six aglycone flavonoids and their corresponding glycosides: genistein and genistin, quercetin and rutin, apigenin and apigenin 7-O-β-D-(6-p-coumaroyl) glucoside, as well as the aglycone daidzein isolated from Astragalus verrucosus Moris, were tested for their apoptosis-inducing potential. In vitro techniques that monitor bioactivity through morphological and biochemical changes were carried out on HCT116 (human colon carcinoma) and MCF7 (human Caucasian breast adenocarcinoma) cancer cell lines. Dose-dependent cytotoxic effects were monitored through changes in mitochondrial dehydrogenase activity using the standard MTT assay. The median inhibitory concentration (GI50) determined from the dose-response curves showed that the aglycones apigenin and quercetin were the most bioactive (low GI50), whilst daidzein and genistein, which had not been previously tested on these cell lines, showed a smaller cytotoxic effect (high GI50). The remaining flavonoids, mostly glycosides, showed negligible cytotoxicity. Morphological changes were monitored by microscopic observation with a photographic record. Results showed important hallmarks of apoptosis, including cell rounding with reduction of cell volume, small condensed nuclei, membrane blebbing and formation of apoptotic bodies.
Collagen Organization in Relation to Ductal Carcinoma In Situ Pathology and Outcomes

Background: There is widespread interest in discriminating indolent from aggressive ductal carcinoma in situ (DCIS). We sought to evaluate collagen organization in the DCIS tumor microenvironment in relation to pathologic characteristics and patient outcomes. Methods: We retrieved fixed tissue specimens for 90 DCIS cases within the population-based Vermont DCIS Cohort. We imaged collagen fibers within 75 μm of the tumor/stromal boundary on hematoxylin and eosin–stained slides using multiphoton microscopy with second-harmonic generation. Automated software quantified collagen fiber length, width, straightness, density, alignment, and angle to the tumor/stroma boundary. Factor analysis identified linear combinations of collagen fiber features representing composite attributes of collagen organization. Results: Multiple collagen features were associated with DCIS grade, necrosis pattern, or periductal fibrosis (P < 0.05). After adjusting for treatments and nuclear grade, risk of recurrence (defined as any second breast cancer diagnosis) was lower among cases with greater collagen fiber width [hazard ratio (HR), 0.57 per one standard deviation increase; 95% confidence interval (CI), 0.39–0.84] and fiber density (HR, 0.60; 95% CI, 0.42–0.85), whereas risk was elevated among DCIS cases with higher fiber straightness (HR, 1.47; 95% CI, 1.05–2.06) and distance to the nearest two fibers (HR, 1.47; 95% CI, 1.06–2.02). Fiber length, alignment, and fiber angle were not associated with recurrence (P > 0.05). Five composite factors were identified, accounting for 72.4% of the total variability among fibers; three were inversely associated with recurrence (HRs ranging from 0.60 to 0.67; P ≤ 0.01). Conclusions: Multiple aspects of collagen organization around DCIS lesions are associated with recurrence risk. Impact: Collagen organization should be considered in the development of prognostic DCIS biomarker signatures.
Epidemiology, management, and economic impact of acute myeloid leukemia and myelodysplastic syndrome in Spain at the hospital level: a claims database analysis

Abstract Objectives This study reviewed patient characteristics, management, and medical costs of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs) in Spanish hospitals. Methods Data were extracted from the Spanish Ministry of Health records via a claims database containing patient records from 192 private and 313 public hospitals between 1997 and 2015 for AML, and 2008 and 2015 for MDS. Direct medical costs at the hospital level were calculated based on mean medical procedure costs determined per the Spanish Ministry of Health. Results Records for 39,568 patients with AML and 33,091 with MDS were analyzed. The median age of AML patients was 65 years (interquartile range (IQR) = 27) and of MDS patients was 81 years (IQR = 12). In terms of disease management, 58% and 83% of admissions were due to emergencies for patients with AML and MDS, respectively; median length of hospital stay was 14 days (IQR = 25) for AML and seven days (IQR = 9) for MDS. There was an increase in allogeneic hematopoietic stem cell transplantations over time for patients with AML or MDS. Mean annual direct medical costs of AML and MDS, respectively, were €66,422,245 and €42,635,313 for total costs, and €30,775 and €10,312 per patient. Of the total costs, transplantations contributed total annual costs of €15,843,982 and €2,705,791 for patients with AML and MDS, respectively. Conclusions This study provides novel data to assist decision makers in allocating resources. AML and MDS represent a significant burden for the National Spanish Healthcare System, with substantial costs incurred in secondary care, principally associated with the increasing number of transplantations.
Fetal Undernutrition Induces Resistance Artery Remodeling and Stiffness in Male and Female Rats Independent of Hypertension

Fetal undernutrition programs hypertension and cardiovascular diseases, and resistance artery remodeling may be a contributing factor. We aimed to assess if fetal undernutrition induces resistance artery remodeling and the relationship with hypertension. Sprague–Dawley dams were fed ad libitum (Control) or with 50% of control intake between days 11 and 21 of gestation (maternal undernutrition, MUN). In six-month-old male and female offspring we assessed blood pressure (anesthetized and tail-cuff); mesenteric resistance artery (MRA) structure and mechanics (pressure myography), cellular and internal elastic lamina (IEL) organization (confocal microscopy) and plasma MMP-2 and MMP-9 activity (zymography). Systolic blood pressure (SBP, tail-cuff) and plasma MMP activity were assessed in 18-month-old rats. At the age of six months MUN males exhibited significantly higher blood pressure (anesthetized or tail-cuff) and plasma MMP-9 activity, while MUN females did not exhibit significant differences, compared to sex-matched controls. MRA from 6-month-old MUN males and females showed a smaller diameter, reduced adventitial, smooth muscle cell density and IEL fenestra area, and a leftward shift of stress-strain curves. At the age of eighteen months SBP and MMP-9 activity were higher in both MUN males and females, compared to sex-matched controls. These data suggest that fetal undernutrition induces MRA inward eutrophic remodeling and stiffness in both sexes, independent of blood pressure level. Resistance artery structural and mechanical alterations can participate in the development of hypertension in aged females and may contribute to adverse cardiovascular events associated with low birth weight in both sexes.
Are Arthroplasty Procedures Really Better in the Treatment of Complex Proximal Humerus Fractures? A Comprehensive Meta-Analysis and Systematic Review.

OBJECTIVE A meta-analysis and systematic review was performed to compare outcomes of open reduction and internal fixation (ORIF), hemiarthroplasty (HA), and reverse total shoulder arthroplasty (rTSA) for complex proximal humerus fractures. DATA SOURCES MEDLINE, Embase, and Cochrane Library databases were screened. Search terms included reverse total shoulder arthroplasty, open reduction internal fixation, hemiarthroplasty, and proximal humerus fracture. STUDY SELECTION English-language studies published within the last 15 years evaluating outcomes of ORIF, rTSA, or HA for complex proximal humerus fractures with minimum of one year follow-up were included, resulting in fifty-one studies with 3,064 total patients. Review articles, basic science studies, biomechanical studies, and cadaveric studies were excluded. DATA EXTRACTION The methodological quality of evidence (MQOE) was assessed using Jadad scale and methodological index for nonrandomized studies (MINORS). DATA SYNTHESIS Demographic data were compared using chi-squared test. Mean data were weighted by study size and used to calculate composite means and confidence intervals. Continuous data were compared using the Metan module with fixed effects. Count data were compared using the Kruskal-Wallis test. Alpha was set at 0.05 for all tests. CONCLUSIONS Patients undergoing rTSA had lower risks of complication (RR 0.41) and reoperation (RR 0.28) than HA patients. rTSA resulted in higher Constant scores (SMD 0.63) and improved active forward flexion when compared to HA (SMD 0.76). Pooled mean data demonstrated better outcome scores and active forward flexion of ORIF versus HA and rTSA, though the patients were younger and had more simple fracture patterns. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.