Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations of Maternal Stress, Prenatal Exposure to Per- and Polyfluoroalkyl Substances (PFAS), and Demographic Risk Factors with Birth Outcomes and Offspring Neurodevelopment: An Overview of the ECHO.CA.IL Prospective Birth Cohorts

Background. Infants whose mothers experience greater psychosocial stress and environmental chemical exposures during pregnancy may face greater rates of preterm birth, lower birth weight, and impaired neurodevelopment. Methods. ECHO.CA. IL is composed of two cohorts, Chemicals in Our Bodies (CIOB; n = 822 pregnant women and n = 286 infants) and Illinois Kids Development Study (IKIDS; n = 565 mother-infant pairs), which recruit pregnant women from San Francisco, CA and Urbana-Champaign, IL, respectively. We examined associations between demographic characteristics and gestational age, birth weight z-scores, and cognition at 7.5 months across these two cohorts using linear models. We also examined differences in biomarkers of exposure to per- and polyfluoroalkyl substances (PFAS), measured in second-trimester serum, and psychosocial stressors by cohort and participant demographics. Results. To date, these cohorts have recruited over 1300 pregnant women combined. IKIDS has mothers who are majority white (80%), whereas CIOB mothers are racially and ethnically diverse (38% white, 34% Hispanic, 17% Asian/Pacific Islander). Compared to CIOB, median levels of PFOS, a specific PFAS congener, are higher in IKIDS (2.45 ng/mL versus 1.94 ng/mL), while psychosocial stressors are higher among CIOB. Across both cohorts, women who were non-white and single had lower birth weight z-scores relative to white women and married women, respectively. Demographic characteristics are not associated with cognitive outcomes at 7.5 months. Conclusions. This profile of the ECHO.CA. IL cohort found that mothers and their infants who vary in terms of socioeconomic status, race/ethnicity, and geographic location are similar in many of our measures of exposures and cognitive outcomes. Similar to past work, we found that non-white and single women had lower birth weight infants than white and married women. We also found differences in levels of PFOS and psychosocial stressors based on geographic location.
Response of the ENPP1‐Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto‐nucleotide pyrophosphatase/phosphodiesterase‐1 (ENPP1) may result in early‐onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1‐deficient Enpp1asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1‐Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1asj/asj mice on normal chow and to patients with mono‐ and biallelic ENPP1 mutations, 5‐week‐old Enpp1asj/asj mice on the high‐phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1asj/asj mice with recombinant Enpp1‐Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).
Pleiotropic activity of nerve growth factor in regulating cardiac functions and counteracting pathogenesis

Cardiac innervation density generally reflects the levels of nerve growth factor (NGF) produced by the heart—changes in NGF expression within the heart and vasculature contribute to neuronal remodelling (e.g. sympathetic hyperinnervation or denervation). Its synthesis and release are altered under different pathological conditions. Although NGF is well known for its survival effects on neurons, it is clear that these effects are more wide ranging. Recent studies reported both in vitro and in vivo evidence for beneficial actions of NGF on cardiomyocytes in normal and pathological hearts, including prosurvival and antiapoptotic effects. NGF also plays an important role in the crosstalk between the nervous and cardiovascular systems. It was the first neurotrophin to be implicated in postnatal angiogenesis and vasculogenesis by autocrine and paracrine mechanisms. In connection with these unique cardiovascular properties of NGF, we have provided comprehensive insight into its function and potential effect of NGF underlying heart sustainable/failure conditions. This review aims to summarize the recent data on the effects of NGF on various cardiovascular neuronal and non‐neuronal functions. Understanding these mechanisms with respect to the diversity of NGF functions may be crucial for developing novel therapeutic strategies, including NGF action mechanism‐guided therapies.
Pneumococcal Serotype-specific Opsonophagocytic Activity in Interleukin-1 Receptor-associated Kinase 4-deficient Patients.

BACKGROUND The antibody response after pneumococcal vaccines and their effectiveness against invasive pneumococcal disease (IPD) in patients with interleukin-1 receptor-associated kinase 4 (IRAK4) deficiency have not been fully evaluated. Here, we evaluated pneumococcal serotype-specific opsonophagocytic activity (OPA) in IRAK4-deficient patients along with their clinical course. METHODS We investigated 6 IRAK4-deficient patients in Japan, whose attending physicians could be contacted. We performed OPA measurements using stored and more recent serum samples obtained from these patients. RESULTS All patients had received pneumococcal vaccination. Among the 3 patients who had IPD, 2 had an episode of pneumococcal meningitis and the other developed pneumococcal bacteremia 3 years after the occurrence of pneumococcal meningitis. Only one episode of invasive bacterial infection was caused by a Streptococcus pneumoniae vaccine-type strain. An increased opsonization index was found in the sera after vaccination for all IRAK-deficient patients, including when the 23-valent pneumococcal polysaccharide vaccine was used. CONCLUSIONS A significant increase in levels of OPA against most of the pneumococcal vaccine antigens was observed for all IRAK4-deficient patients. However, IPD could not be prevented by pneumococcal vaccination alone. Therefore, adequate prophylaxis should be provided with antibiotics at least until 8 years of age, along with regular immunoglobulin therapy, particularly during the infantile period.
Bmi-1 regulates mucin levels and mucin O-glycosylation in the submandibular gland of mice

Mucins, the major components of salivary mucus, are large glycoproteins abundantly modified with O-glycans. Mucins present on the surface of oral tissues contribute greatly to the maintenance of oral hygiene by selectively adhering to the surfaces of microbes via mucin O-glycans. However, due to the complex physicochemical properties of mucins, there have been relatively few detailed analyses of the mechanisms controlling the expression of mucin genes and the glycosyltransferase genes involved in glycosylation. Analysis performed using supported molecular matrix electrophoresis, a methodology developed for mucin analysis, and knockout mice without the polycomb group protein Bmi-1 revealed that Bmi-1 regulates mucin levels in the submandibular gland by suppressing the expression of the mucin Smgc gene, and that Bmi-1 also regulates mucin O-glycosylation via suppression of the glycosyltransferase Gcnt3 gene in the submandibular gland.
A study of community knowledge, attitudes, practices, and health in Pakistan during the COVID‐19 pandemic

Abstract The ongoing outbreak of novel Coronavirus originated from Wuhan, China, and vigorously spread throughout the globe causing serious concerns. This study aimed to appraise the community demographics, knowledge, attitudes, practices mental health, symptoms, and precautionary measures during the COVID‐19 pandemic in Pakistan. This study was a cross‐sectional and observational study. An online semi‐structured questionnaire was designed by freely available Google Forms. A Referral Sampling technique was used, a total of 439 responses were recorded and analyzed by using Statistical Package for the Social Sciences. Regression analysis and multinomial logistic regression analysis were done to test the hypothesis. This study shows more than 63% of participants maintain social distancing at their workplaces, offices, markets, and so forth and 59% of participants stayed at their homes during the lockdown. Almost 75% of participants did not attend any gathering during COVID‐19. Most participants (75.4%) wear masks and gloves, and 85.6% of participants wash their hands with soap and using hand sanitizer regularly. This study shows that 40.8% and 36.2% of participants felt anxiety and fear due to Coronavirus. This study shows that knowledge among the population in Pakistan about COVID‐19 was low. Continued efforts are needed to address knowledge, attitudes, and practices to interrupt novel Coronavirus transmission.
Malignant Uterine Neoplasms Attended at a Brazilian Regional Hospital: 16-years Profile and Time Elapsed for Diagnosis and Treatment

Abstract Objective The present study aims to evaluate the profile of endometrial carcinomas and uterine sarcomas attended in a Brazilian cancer center in the period from 2001 to 2016 and to analyze the impact of time elapsed from symptoms to diagnoses or treatment in cancer stage and survival. Methods This observational study with 1,190 cases evaluated the year of diagnosis, age-group, cancer stage and histological type. A subgroup of 185 women with endometrioid histology attended in the period from 2012 to 2017 was selected to assess information about initial symptoms, diagnostic methods, overall survival, and to evaluate the influence of the time elapsed from symptoms to diagnosis and treatment on staging and survival. The statistics used were descriptive, trend test, and the Kaplan-Meier method, with p-values < 0.05 for significance. Results A total of 1,068 (89.7%) carcinomas (77.2% endometrioid and 22.8% non-endometrioid) and 122 (10.3%) sarcomas were analyzed, with an increasing trend in the period (p < 0.05). Histologies of non-endometrioid carcinomas, G3 endometrioid, and carcinosarcomas constituted 30% of the cases. Non-endometrioid carcinomas and sarcomas were more frequently diagnosed in patients over 70 years of age and those on stage IV (p < 0.05). The endometrioid subgroup with 185 women reported 92% of abnormal uterine bleeding and 43% diagnosis after curettage. The average time elapsed between symptoms to diagnosis was 244 days, and between symptoms to treatment was 376 days, all without association with staging (p = 0.976) and survival (p = 0.160). Only 12% of the patients started treatment up to 60 days after diagnosis. Conclusion The number of uterine carcinoma and sarcoma cases increased over the period of 2001 to 2016. Aggressive histology comprised 30% of the patients and, for endometrioid carcinomas, the time elapsed between symptoms and diagnosis or treatment was long, although without association with staging or survival.
Effects of Red Rice or Buckwheat Addition on Nutritional, Technological, and Sensory Quality of Potato-Based Pasta

This work investigates the effects of red rice (R) or buckwheat (B) flour addition on nutritional, technological, and sensory quality of potato-based pasta (gnocchi). Three gluten-free (GF) and three conventional (C) samples were produced in an industrial line without any addition or with 20% R or B. R and B addition significantly (p < 0.05) reduced starch content and increased fat amount and ready digestible starch fraction (potential higher glycemic impact). R addition significantly (p < 0.05) worsened GF pasta structure, increasing solid loss in cooking water (5.4 ± 1.2 vs. 4.1 ± 0.5 g/100 g pasta) and reducing product firmness (408 ± 13 vs. 108 ± 2 N). B addition resulted in intermediate consistency (243 ± 8 N), despite the highest total fiber content and weight increase during cooking. Similar trends were found in C samples, indicating a better texturizing capacity of B in comparison to R. Samples without any addition were the most liked (C = 67.4 and GF = 60.6). Texture was the major contributor to liking: uniform structure and firm texture were positive predictors of liking, whereas a granular and coarse matrix contributed negatively. The outcomes of this research can be useful in developing GF potato-based pasta for consumers focused on healthier foods and for industries willing to better valorize their products.
Mesenchymal Stem/Stromal-Like Cells from Diploid and Triploid Human Embryonic Stem Cells Display Different Gene Expression Profiles.

Background Human embryonic stem cell-mesenchymal stem/stromal cell (hESCs-MSCs) open a new insight into future cell therapy applications, due to their unique characteristics, including immunomodulatory features, proliferation, and differentiation. Methods Herein, hESCs-MSCs were characterized by immunofluorescence technique with CD105 and FIBRONECTIN as markers and FIBRONECTIN, VIMENTIN, CD10, CD105, and CD14 genes using reverse transcription-polymerase chain reaction technique. Fluorescence-activated cell sorting was performed for CD44, CD73, CD90, and CD105 markers. Moreover, these fibroblast-like cells, due to multipotent characteristics, differentiated to the osteoblast. Results MSCs were derived from diploid and triploid hESC lines using sequential three dimensional and two dimensional cultures and characterized with the specific markers. Immunofluorescence showed the expression of FIBRONECTIN and CD105 in hESCs-MSCs. Flow cytometry data indicated no significant difference in the expression of MSC markers after 6 and 13 passages. Interestingly, gene expression profiles revealed slight differences between MSCs from diploid and triploid hESCs. hESCs-MSCs displayed osteogenic differentiation capacity, which was confirmed by Alizarin red staining. Cobnclusion Our findings reveal that both diploid and triploid hESC lines are capable of forming MSCs; however, there are some differences in their gene expression profiles. Generation of MSCs from hESCs, as a non-invasive procedure in large scale, will lend itself for the future cell-based therapeutic applications.
Effects of School-Based Exercise and Nutrition Intervention on Body Composition and Physical Fitness in Overweight Adolescent Girls

Regular exercise during school hours is encouraged since childhood obesity has reached epidemic proportions. Moreover, a great majority of adolescents do not meet the recommendations for moderate-to-vigorous physical activity. The present study aimed to determine the effects of school-based high-intensity interval training (HIIT) and nutrition intervention on body composition and physical fitness in overweight adolescent girls. Forty-eight girls were included in the study, of whom 24 (age = 15.5 ± 0.7 years) were randomized to a experimental group (EXP) (HIIT and nutrition intervention school-based program) and 24 (age = 15.7 ± 0.6 years) to a control group (CON) that maintained their usual physical education activities. HIIT consisted of 10 stations of own bodyweight exercise and was done three times per week for eight weeks. Moreover, the EXP participated in the nutrition program led by a nutritionist two times a week. Apart from body composition assessment, participants performed countermovement jump (CMJ), medicine ball throw, hand-grip test, and Yo-Yo Intermittent Recovery Level 1 Test (YYIRT1). A significant effect of group (EXP vs. CON) x time (pre vs. post) interaction was observed for weight [F(1,44) = 7.733; p = 0.008], body mass index [F(1,44) = 5.764; p = 0.020], body fat (in kg) [F(1,44) = 17.850; p < 0.001], and body fat (in %) [F(1,44) = 18.821; p < 0.001]. Moreover, a significant interaction was observed for the medicine ball throw [F(1,44) = 27.016; p < 0.001] and YYIRT1 [F(1,44) = 5.439; p = 0.024]. A significant main effect for time was found for hand grip [F(1,44) = 9.300; p = 0.004] and CMJ [F(1,44) = 12.866; p = 0.001]. The present study has demonstrated that just eight weeks school-based HIIT and nutrition intervention, including three sessions a week, can improve body composition and muscular and physical aerobic performance in overweighted adolescent girls.
Altered Gut Microbial Metabolites in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Signals in Host–Microbe Interplay

Intimate metabolic host–microbiome crosstalk regulates immune, metabolic, and neuronal response in health and disease, yet remains untapped for biomarkers or intervention for disease. Our recent study identified an altered microbiome in patients with pre-onset amnestic mild cognitive impairment (aMCI) and dementia Alzheimer’s disease (AD). Thus, we aimed to characterize the gut microbial metabolites among AD, aMCI, and healthy controls (HC). Here, a cohort of 77 individuals (22 aMCI, 27 AD, and 28 HC) was recruited. With the use of liquid-chromatography/gas chromatography mass spectrometry metabolomics profiling, we identified significant differences between AD and HC for tryptophan metabolites, short-chain fatty acids (SCFAs), and lithocholic acid, the majority of which correlated with altered microbiota and cognitive impairment. Notably, tryptophan disorders presented in aMCI and SCFAs decreased progressively from aMCI to AD. Importantly, indole-3-pyruvic acid, a metabolite from tryptophan, was identified as a signature for discrimination and prediction of AD, and five SCFAs for pre-onset and progression of AD. This study showed fecal-based gut microbial signatures were associated with the presence and progression of AD, providing a potential target for microbiota or dietary intervention in AD prevention and support for the host–microbe crosstalk signals in AD pathophysiology.
Results with Posterior Scleral Reinforcement for Progressive Highly Myopic Children in Hungary

Abstract Purpose We have been performing posterior scleral reinforcement in our ophthalmological department since 1992 on progressive highly myopic eyes. Here, we report on our results with this technique in the foregoing 7 years in a retrospective comparative design. Methods Thirty-eight eyes of 32 patients, operated according to Snyder-Thompsonʼs method, were enrolled in this study, and a control group of 9 age- and myopia-matched childrenʼs 14 eyes was built for comparison. Pre- and postoperative best-corrected visual acuity, subjective refractive error (spherical equivalent of spectacle dioptres), and axial length were recorded. Changes within groups were calculated, as well as baseline parameters and their changes during follow-up, and compared between the groups. Correlation analysis was performed to identify factors that could influence myopia progression. Results Myopic progression was significantly lower in the operated than in the nonoperated group, both in terms of mean annual axial length as well as refractive error changes (0.21 ± 0.08 mm versus 0.49 ± 0.19 mm and 0.18 ± 0.29 D versus 0.6 ± 0.33 D, respectively). Mean overall visual improvement was more explicit in operated eyes as compared to those left untreated (0.15 ± 0.09 versus 0.01 ± 0.1). No association of any factor with myopia progression could be identified. We encountered no serious or lasting complications. Conclusion In our clinical practice, posterior scleral reinforcement according to Snyder-Thompson proved to be a safely applicable and effective surgical method to stop or significantly retard pathological increases in axial length and dioptres, and thus can help prevent the onset of myopic degenerative lesions, and irreversible visual impairment in the long run.
Delivering online alternatives to the anatomy laboratory: Early experience during the COVID‐19 pandemic

Social distancing measures due to the COVID‐19 pandemic will make anatomy dissecting room practicals difficult, if not impossible to run at some institutions in the upcoming academic year. The learning community that exists within physical anatomy practicals needs to be moved online. Virtual replacement of visuo‐spatial and social elements of learning anatomy pose particular challenges to educators. Our department has trialed Blackboard Collaborate, an online communication platform in conjunction with Visible Body, a 3D anatomical modeling program. We have delivered 266 hr of synchronous small group teaching to medical and physician associate students. We describe this approach and discuss the relevance of distance learning pedagogy to the design of new online anatomy teaching and development of online learning communities.
Current advances in plasma and cerebrospinal fluid biomarkers in Alzheimer's disease.

PURPOSE OF REVIEW This review provides a concise overview of recent advances in cerebrospinal fluid (CSF) and blood-based biomarkers of Alzheimer's disease lesions. RECENT FINDINGS Important recent advances for CSF Alzheimer's disease biomarkers include the introduction of fully automated assays, the development and implementation of certified reference materials for CSF Aβ42 and a unified protocol for handling of samples, which all support reliability and availability of CSF Alzheimer's disease biomarkers. Aβ deposition can be detected using Aβ42/Aβ40 ratio in both CSF and plasma, though a much more modest change is seen in plasma. Tau aggregation can be detected using phosphorylated tau (P-tau) at threonine 181 and 217 in CSF, with similar accuracy in plasma. Neurofilament light (NfL) be measured in CSF and shows similar diagnostic accuracy in plasma. Though total tau (T-tau) can also be measured in plasma, this measure is of limited clinical relevance for Alzheimer's disease in its current immunoassay format. SUMMARY Alzheimer's disease biomarkers, including Aβ, P-tau and NfL can now be reliably measured in both CSF and blood. Plasma-based measures of P-tau show particular promise, with potential applications in both clinical practice and in clinical trials.