Miracle-dz/UniFAR-FTUs huggingface dataset:
Myeloperoxidase‐induced fibrinogen unfolding and clotting

Due to its unique properties and high biomedical relevance fibrinogen is a promising protein for the development of various matrixes and scaffolds for biotechnological applications. Fibrinogen molecules may form extensive clots either upon specific cleavage by thrombin or in thrombin‐free environment, for example, in the presence of different salts. Here, we report the novel type of non‐conventional fibrinogen clot formation, which is mediated by myeloperoxidase and takes place even at low fibrinogen concentrations (<0.1 mg/ml). We have revealed fibrillar nature of myeloperoxidase‐mediated fibrinogen clots, which differ morphologically from fibrin clots. We have shown that fibrinogen clotting is mediated by direct interaction of myeloperoxidase molecules with the outer globular regions of fibrinogen molecules followed by fibrinogen unfolding from its natural trinodular to a fibrillar structure. We have demonstrated a major role of the Debye screening effect in regulating of myeloperoxidase‐induced fibrinogen clotting, which is facilitated by small ionic strength. While fibrinogen in an aqueous solution with myeloperoxidase undergoes changes, the enzymatic activity of myeloperoxidase is not inhibited in excess of fibrinogen. The obtained results open new insights into fibrinogen clotting, give new possibilities for the development of fibrinogen‐based functional biomaterials, and provide the novel concepts of protein unfolding.
In Vitro Assessment of Transporter Mediated Perpetrator DDIs for Several Hepatitis C Virus Direct-Acting Antiviral Drugs and Prediction of DDIs with Statins Using Static Models

Inhibitory effects of asunaprevir, daclatasvir, grazoprevir, paritaprevir, simeprevir, and voxilaprevir, direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C virus (HCV) infection, were evaluated in vitro against a range of clinically important drug transporters. In vitro inhibition studies were conducted using transporter transfected cells and membrane vesicles. The risk of clinical drug-drug interactions (DDIs) was assessed using simplified static models recommended by regulatory agencies. Furthermore, we refined and developed static models to predict complex DDIs with several statins (pitavastatin, rosuvastatin, atorvastatin, and pravastatin) by mechanistically assessing differential inhibitory effects of perpetrator drugs on multiple transporters, such as organic anion transporting polypeptides (OATP1B), breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), organic anion transporter 3 (OAT3), and cytochrome P450 CYP3A enzyme, as they are known to contribute to absorption, distribution, metabolism and excretion (ADME) of above statins. These models successfully predicted a total of 46 statin DDIs, including above DAA drugs and their fix-dose combination regimens. Predicted plasma area under curve ratio (AUCR) with and without perpetrator drugs was within ~ 2-fold of observed values. In contrast, simplified static R-value model resulted in increased false negative and false positive predictions when different prediction cut-off values were applied. Our studies suggest that mechanistic static model is a promising and useful tool to provide more accurate prediction of the risk and magnitude of DDIs with statins in early drug development and may help to improve the management of clinical DDIs for HCV drugs to ensure effective and safe HCV therapy. GRAPHICAL ABSTRACT GRAPHICAL ABSTRACT
Air-liquid interface culture promotes maturation and allows environmental exposure of pluripotent stem cell–derived alveolar epithelium

Type 2 alveolar epithelial cells (AT2s), facultative progenitor cells of the lung alveolus, play a vital role in the biology of the distal lung. In vitro model systems that incorporate human cells, recapitulate the biology of primary AT2s, and interface with the outside environment could serve as useful tools to elucidate functional characteristics of AT2s in homeostasis and disease. We and others recently adapted human induced pluripotent stem cell–derived AT2s (iAT2s) for air-liquid interface (ALI) culture. Here, we comprehensively characterize the effects of ALI culture on iAT2s and benchmark their transcriptional profile relative to both freshly sorted and cultured primary human fetal and adult AT2s. We find that iAT2s cultured at ALI maintain an AT2 phenotype while upregulating expression of transcripts associated with AT2 maturation. We then leverage this platform to assay the effects of exposure to clinically significant, inhaled toxicants including cigarette smoke and electronic cigarette vapor.
The effect of arch-support insole on knee kinematics and kinetics during a stop-jump maneuver

Background: Anterior cruciate ligament injuries commonly occur during sports that involve sudden stops or direction changes. Although athletes often use arch-support insoles in competition and training, little is known about the effect of foot insoles on knee biomechanics and jump take-off performances. Objective: This study aimed to investigate the effects of arch-support insoles on knee kinematics and kinetics during the stop-braking phase and the subsequent jump take-off performances. Study design: That is a quasi-experimental study, repeated-measures design. Methods: Twenty male healthy recreational university basketball athletes performed stop-jump with maximum effort in both arch-support and flat insole conditions. Paired t-tests were performed on knee kinetics and kinematics and jump performance variables to determine whether there were significant differences between insole conditions. Results: Wearing arch-support insoles experienced larger ground reaction forces (GRFs), loading rates of peak vertical and posterior GRFs, peak knee adduction and rotation moments, and knee flexion angular velocity than the flat insoles (P < 0.05). Conclusions: The increased GRFs and knee loading in arch-support insoles are indicative of a higher risk of anterior cruciate ligament injuries. The findings could be insightful to the knee mechanics that are related to performance and injury potential during stop-jump maneuvers.
Simplified Edinburgh CT Criteria for Identification of Lobar Intracerebral Hemorrhage Associated With Cerebral Amyloid Angiopathy

Background and Objectives In patients with lobar intracerebral hemorrhage (ICH), etiologic characterization represents a tradeoff between feasibility, resource allocation, and diagnostic certainty. This study investigated the accuracy and clinical utility of the simplified Edinburgh CT criteria to identify underlying cerebral amyloid angiopathy (CAA). Methods This external validation analyzed 210 consecutive patients with lobar ICH and available CT and MRI studies from a prospective single-center observational cohort study (2006–2015, Longitudinal Cohort Study on ICH Care [UKER-ICH,] NCT03183167). We investigated the interrater variability and diagnostic accuracy of the simplified Edinburgh CT-based criteria for identification of ICH associated with probable CAA according to MRI-based modified Boston criteria as a reference standard. We evaluated the utility of the simplified Edinburgh criteria by decision curve analysis, comparing the theoretical clinical net benefit (weighted benefit-harm at varying threshold probabilities) of the high-risk category (finger-like projections and subarachnoid hemorrhage) for ruling in and the low-risk category (neither finger-like projections nor subarachnoid hemorrhage) for ruling out with the assumptions of no or all patients having CAA (default strategies). Results Of 210 patients, 70 (33.3%) had high risk, 67 (31.9%) had medium risk, and 73 (34.8%) had low risk for CAA-associated ICH according to simplified Edinburgh CT criteria, showing moderate interrater variability. Discrimination was good (area under the receiver operating characteristics curve 0.74, 95% CI 0.67–0.81) without evidence of poor calibration (Hosmer-Lemeshow, p = 0.54) for validation of MRI-based diagnosis of probable CAA (n = 94 of 210, 44.8%). The rule-in criteria (high risk), had 87.1% (79.3%–92.3%) specificity, and the rule-out criteria (low risk), had 80.9% (71.1%–88.0%) sensitivity. Decision curve analysis suggested a theoretical clinical net benefit for ruling in but not for ruling out probable CAA compared to default strategies. Discussion Applying the simplified Edinburgh CT criteria during diagnostic workup seems clinically useful and may accurately identify CAA in patients with lobar ICH. Trial Registration Information ClinicalTrials.gov Identifier: NCT03183167. Classification of Evidence This study provides Class II evidence that in patients with lobar hemorrhages, the simplified Edinburgh criteria accurately identify those at high risk of CAA.
Quantile-specific heritability of serum growth factor concentrations

Abstract Background “Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g. growth factor concentration) is high or low relative to its distribution. Methods Quantile-regression analysis was applied to family sets from the Framingham Heart Study to determine whether the heritability (h2 ) of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), angiopoietin-2, and angiopoietin-2 (sTie-2) and VEGFR1 (sFlt-1) receptor concentrations were quantile-specific. Results Quantile-specific h2 (±SE) increased with increasing percentiles of the age- and sex-adjusted VEGF (P trend<10−16), HGF (P trend=0.0004), angiopoietin-2 (P trend=0.0002), sTie-2 (P trend=1.2 × 10−5), and sFlt-1 distributions (P trend=0.04). Conclusion Heritabilities of VEGF, HGF, angiopoitein-2, sTie-2 and sFlt-1 concentrations are quantile dependent. This may explain reported interactions of genetic loci (rs10738760, rs9472159, rs833061, rs3025039, rs2280789, rs1570360, rs2010963) with metabolic syndrome, diet, recurrent miscarriage, hepatocellular carcinoma, erysipelas, diabetic retinopathy, and bevacizumab treatment in their effect on VEGF concentrations. Graphical Abstract
New insights into an old question: can the MD-PhD physician-scientist pipeline be improved?

The US needs more physician-scientists. This was a major conclusion of the NIH-sponsored 2014 Physician-Scientist Workforce Report (1). As noted in that report, physician-scientists constitute only 1.5% of the total physician workforce. This percentage has been decreasing, and the average age of physician-scientists has been increasing, which leads to the conclusion that the current physician-scientist pipeline is inadequate to meet our country’s future needs. MD-PhDs are a critical component of this pipeline. They constitute about 50% of the physician-scientist workforce and are uniquely trained to integrate the complexities of basic biomedical science with those of clinical medicine. In 1964, the National Institute of General Medical Sciences (NIGMS) established Medical Scientist Training Program (MSTP) institutional T32 grants to foster and support combined MD-PhD degree education. Currently, there are approximately 50 NIGMS-funded MSTPs and nearly as many non-NIH-funded MD-PhD programs, which together awarded 620 combined MD-PhD degrees in 2020 (20,387 MD degrees were awarded by US medical schools in 2020) (2). It is not difficult to think of reasons why the MD-PhD pipeline is so small. Commonly cited reasons include, among others, the length of training and its associated opportunity costs, and the difficulty of sustaining research funding over the course of a career. Data from the American Association of Medical Colleges (AAMC) National MD-PhD program outcomes study (3, 4) showed that […] The US needs more physician-scientists. This was a major conclusion of the NIH-sponsored 2014 Physician-Scientist Workforce Report (1). As noted in that report, physician-scientists constitute only 1.5% of the total physician workforce. This percentage has been decreasing, and the average age of physician-scientists has been increasing, which leads to the conclusion that the current physician-sci-entist pipeline is inadequate to meet our country’s future needs. MD-PhDs are a critical component of this pipeline. They constitute about 50% of the physician-scientist workforce and are uniquely trained to integrate the complexities of basic biomedical science with those of clinical medicine. In 1964, the National Institute of General Medical Sciences established Medical Scientist Training Program (MSTP) institutional T32 grants to foster and support combined MD-PhD degree educa-tion. Currently, there are approximately 50 NIGMS-funded MSTPs and nearly as many non-NIH-funded MD-PhD programs, which together awarded 620 combined MD-PhD degrees in 2020 (20,387 MD degrees were awarded by US medical schools in 2020) It is not difficult to think of reasons why the MD-PhD pipeline is so small. Commonly cited reasons include, among others, the length of training and its associated opportunity costs, and the difficulty of sustaining research funding over the course of a career. Data from the American Association of Medical Colleges (AAMC) National MD-PhD program outcomes study (3, 4) showed that the average time
A Digital Storytelling Intervention for Vietnamese American Mothers to Promote Their Children's HPV Vaccination.

Despite higher rates of human papillomavirus (HPV)-associated cancer in Vietnamese Americans (VAs), their vaccination rate remains low. Culturally grounded narratives incorporating culture-specific beliefs and practices may be a promising approach to promote HPV vaccination and potentially mitigate HPV-associated cancer disparities experienced by VAs. We co-developed personal, audiovisual digital stories about HPV vaccination with VA mothers of vaccinated children, and examined the effects of the digital storytelling (DST) intervention on vaccination intention among VA mothers of unvaccinated children aged 11-14. The stories (3 minutes each) were produced in both English and Vietnamese through a two-day workshop in collaboration with two VA first-generation immigrant mothers. A community sample of 114 VA mothers of unvaccinated children viewed the stories and filled out an anonymous survey before and after the intervention. Of these mothers (mean age = 41.5 years; SD = 5.4), 35.2% were immigrants, and about half (51%) reported having a child who received free or reduced-price lunch at school. After the intervention, changes in two items indicating mothers' positive attitudes toward HPV vaccination were significant. Mothers' intention to vaccinate their children increased from 53% to 74%; the difference was large (OR = 9.12; Cohen' g = .40) and statistically significant, X2(1, N = 114) = 17.63, p < . 001. Mothers' scores on the Narrative Quality Assessment scale were high, suggesting high levels of identification and engagement with the stories. This brief intervention using digital stories was feasible and showed preliminary effects on promoting VA mothers' intention to vaccinate their children against HPV.
Violations of International Code of Breast‐milk Substitutes (BMS) in commercial settings and media in Bangladesh

Abstract The International Code of Marketing of Breast‐milk Substitutes (BMS) instituted to protect breastfeeding against unethical marketing, has been adopted by many countries, including Bangladesh. Despite national adoption, evidence suggests violations occur and inadequate BMS Code implementation is an issue. The study aimed to assess violations of the International BMS Code and the national ‘Breast‐milk Substitutes, Infant Foods, Commercially Manufactured Complementary Foods and the Accessories Thereof (Regulation of Marketing) Act, 2013’ of Bangladesh in commercial settings (retail outlets and media) in Bangladesh, for different types of milk, bottles, and teats using a standardized Network for Global Monitoring and Support for Implementation of the Code and Subsequent relevant World Health Assembly Resolutions (NetCode) protocol. This cross‐sectional quantitative study was conducted in Bangladesh from January to September 2018 in Dhaka, Chattogram, and Sylhet cities. Descriptive statistics were reported and χ 2 tests were conducted to assess differences between categorical variables of interest. Data were analysed using SPSS version 20. In retail outlets, there were higher proportion of violations observed in Dhaka than in Sylhet and Chattogram (p < 0.001). Significantly greater proportion of violations in product labels occurred among products sold without local distributors compared to others (p < 0.05); violations were higher among “other milk” for children aged 0 to <36 months compared to formulas and growing‐up milk (p < 0.05). Among media channels, internet clips had significantly higher proportions of violations compared to television, radio and newspaper (p < 0.001). BMS Code violations were prevalent in product labels and promotion of products through retail outlets. The study findings highlight the need for specific multisectoral strategies for better enforcement of BMS Code and points to the need for periodic assessment of Code violations.
Ankle-foot orthosis adherence in children and adolescents with cerebral palsy: A scoping review

Background: Ankle-foot orthoses (AFOs) are commonly supplied to children with cerebral palsy (CP) to support their gait. However, usage is reported to decrease through adolescence. Because AFOs can allow users to engage in daily activities and develop their independence, a wider understanding of nonadherence is essential to determining the most appropriate ways to support orthotic prescription for children with CP in the future. This scoping review will present the literature that investigates AFO adherence of children or adolescents with CP and identify potential avenues for future research and practice. A literature search was carried out using the EBSCO and Web of Science databases to identify literature that investigates AFO adherence by children with CP through measurement of AFO usage and exploration of factors that may influence that usage. Papers that investigated AFO adherence in children/adolescents with CP, either through usage or factors that could affect usage, were included in this review. Data were synthesized using a charting form developed for this review. In total, three papers were included in this review. Two included assessments of AFO usage and all three included at least anecdotal references to factors that could influence that usage. Variation in usage time was seen across participants in all studies, although the method used to record usage may influence reported usage values. Key factors that could affect usage were observed in four key categories: physical/AFO-related factors, personal factors, social factors, and situational appropriateness. Adherence is a complex subject, and both measurement of usage and factors that influence usage are key components needed to understand how children engage with their AFO. By better understanding the motivators and barriers to adherence, it is possible to better support the provision of AFOs in the future.
Letter to the editor about “Determination of glycemic index of enteral formulas used in clinical practice” by Tosatti JAG, Bocardi VB, Jansen AK, Bernandes H, Silva FM published on March 2020

The referred study analysed the glycaemic index (GI) of enteral formulas commercially available in Brazil. One of the products analysed is Diamax, a specialised formula for glycaemic control produced by Prodiet Medical Nutrition, a Brazilian enteral nutrition company. We identified that the study presented a GI value of 79 for this formula, classifying it as high GI. However, Diamax had its GI evaluated by a clinical research following the methodology recommended by the Food and Agriculture Organisation (FAO) for GI and glycaemic load (GL) determination, which was con-ducted at the Food Research Centre (FoRC), an initiative of University of S ~ ao Paulo scientists to create the first research centre focussed on food and nutrition in Brazil. The results of this research showed GI ¼ 37.8 and GL ¼ 6.6, compatible with a low glycaemic response (Giuntini et al. 2019). The responses and GI values obtained. the analysis reference food each
The surprising underperformance of East Asians in US law and business schools: The liability of low assertiveness and the ameliorative potential of online classrooms

Significance To date, researchers and practitioners have focused on the academic challenges of underrepresented ethnic groups in the United States. In comparison, Asians have received limited attention, as they are commonly assumed to excel across all educational stages. Six large studies challenge this assumption by revealing that East Asians (but not South Asians) underperform in US law schools and business schools. This is not because East Asians are less academically motivated or less proficient in English but because their low verbal assertiveness is culturally incongruent with the assertiveness prized by US law and business schools. Online classes (via Zoom) mitigated East Asians’ underperformance in courses emphasizing assertiveness and class participation. Educators should reexamine pedagogical practices to create a culturally inclusive classroom.
Constipation: Prevalence in the Portuguese community using Rome IV—Associated factors, toilet behaviours and healthcare seeking

Abstract Background Chronic constipation (CC) is a major public health condition and CC management remains challenging. Objective We aimed to evaluate the CC (and subtypes) prevalence in a Southern Europe Mediterranean country using Rome IV criteria, and to assess related factors, toilet and healthcare seeking behaviours. Methods Cross‐sectional epidemiological survey, conducted in general community and representing the Portuguese population according to sex and age. The questionnaire covered bowel habits, factors potentially associated with CC (demographic, health/lifestyle, toilet behaviours) and data regarding healthcare seeking. Results From the study data of 1950 individuals were analyzed. The answer rate was 68% and 1335 questionnaires were available for calculation. The CC prevalence was 17.8%, with respectively 9.3% of Functional Constipation (FC) and 8.5% of Irritable Bowel Syndrome – subtype constipation (IBS‐C). The likelihood of constipation was significantly higher in younger (OR 1.01; 95% confidence interval [CI], 1.007–1.031), solo (OR 2.48; 95% CI, 1.7–3.47) and low‐income (OR 2.40; 95% CI, 1.77–3.47) individuals. Constipated individuals spent more time at defecation, longer than 5 min (p = 0.001), and had particular toilet behaviours (absence of a morning pattern [p = 0.008], the use of triggers [p = 0.001] and reading/technological material [p = 0.006]) to facilitate the evacuation. Only 39% of affected individuals sought medical advice, mainly IBS‐C patients (p = 0.018). Conclusion Chronic constipation seems to impact 1 in each 5 Portuguese. Constipated patients are younger, solo, less active and with low income. They develop a clear toilet behaviour profile. FC and IBS‐C patients assume particular behaviours.