Miracle-dz/UniFAR-FTUs huggingface dataset:
Differences In Nutritional And Physical Health Indicators Among Older African Americans, European Americans, And Hispanic Americans

Abstract Inadequate protein intake contributes to poor nutritional status, reduced muscle mass, strength and function, and increased mortality. Evaluating differences in protein intake and related health indicators among racial/ethnic groups enables the development of targeted interventions. This study’s purpose was to determine differences in protein intake, nutritional status, and muscle strength/function among 273 older African, European, and Hispanic Americans. Protein intake, nutritional status, grip strength, timed-up-and-go (TUG), and chair stand assessments were conducted. Protein intake was significantly greater among Hispanic Americans (0.96 g/kg body weight) followed by European Americans (0.83 g/kg body weight), and African Americans (0.64 g/kg body weight). Intakes by all groups were below recommendations. Low nutritional status, grip strength, chair rise, and TUG scores were observed in African Americans and European American females and were consistent with lower protein intakes. Results show significant differences among the groups and the need for interventions to improve diet and physical health.
Running economy, mechanics, and marathon racing shoes

ABSTRACT The choice of marathon racing shoes can greatly affect performance. The purpose of this study is to metabolically and mechanically compare the consumer version of the Nike Vaporfly 4% shoe to two other popular marathon shoes, and determine differences in running economy. Nineteen subjects performed two 5-minute trials at 4.44m/s wearing the Adidas Adios Boost (AB), Nike Zoom Streak (ZS), and Nike Vaporfly 4% (VP) in random order. Oxygen uptake was recorded during minutes 3–5 and averaged across both shoe trials. On a second day, subjects wore reflective markers, and performed a 3-minute trial in each shoe. Motion and force data were collected over the final 30 seconds of each trial. VP oxygen uptake was 2.8% and 1.9% lower than the AB and ZS. Stride length, plantar flexion velocity, and center of mass vertical oscillation were significantly different in the VP. The percent benefit of the VP over AB shoe was predicted by subject ground time. These results indicate that use of the VP shoe results in improved running economy, partially due to differences in running mechanics. Subject variation in running economy improvement is only partially explained by variation in ground time.
Degradation Characteristics of Phosphorus in Phytoplankton-Derived Particulate Organic Matter and Its Effects on the Growth of Phosphorus-Deficient Microcystis aeruginosa in Lake Taihu

To illustrate the contribution of phytoplankton-derived particulate organic matter (PPOM) to endogenous phosphorus (P) cycling and its effects on cyanobacteria blooms, PPOM characteristics, the degradation mechanism, and the growth of P-deficient Microcystis aeruginosa were studied in Lake Taihu. Results showed that PPOM is the most important P pool in the water column during cyanobacteria bloom, accounting for more than 80% of the total P (TP) in the water. During PPOM degradation, the particulate orthophosphate (Ortho-P) is the main species of P release from PPOM in the early degradation stage. The variations of polyphosphate (Poly-P) and phosphodiesters (Diester-P) contents were most significant, which were degraded completely within four days and eight days. Cell density and growth rate of M. aeruginosa using PPOM as P source were similar to those growing on Na2HPO4. The above results show that P in PPOM can be converted into available P by degradation, thus promoting the growth of M. aeruginosa. Therefore, the contribution of P release from PPOM degradation needs to be paid attention to in lake eutrophication control in the future.
A cell topography-based mechanism for ligand discrimination by the T cell receptor

Significance One approach to testing biological theories is to determine if they are predictive. We have developed a simple, theoretical treatment of T cell receptor (TCR) triggering that relies on just two physical principles: (i) the time TCRs spend in cell–cell contacts depleted of large tyrosine phosphatases and (ii) constraints on the size of these contacts imposed by cell topography. The theory not only distinguishes between agonistic and nonagonistic TCR ligands but predicts the relative signaling potencies of agonists with remarkable accuracy. These findings suggest that the theory captures the essential features of receptor triggering. The T cell receptor (TCR) initiates the elimination of pathogens and tumors by T cells. To avoid damage to the host, the receptor must be capable of discriminating between wild-type and mutated self and nonself peptide ligands presented by host cells. Exactly how the TCR does this is unknown. In resting T cells, the TCR is largely unphosphorylated due to the dominance of phosphatases over the kinases expressed at the cell surface. However, when agonist peptides are presented to the TCR by major histocompatibility complex proteins expressed by antigen-presenting cells (APCs), very fast receptor triggering, i.e., TCR phosphorylation, occurs. Recent work suggests that this depends on the local exclusion of the phosphatases from regions of contact of the T cells with the APCs. Here, we developed and tested a quantitative treatment of receptor triggering reliant only on TCR dwell time in phosphatase-depleted cell contacts constrained in area by cell topography. Using the model and experimentally derived parameters, we found that ligand discrimination likely depends crucially on individual contacts being ∼200 nm in radius, matching the dimensions of the surface protrusions used by T cells to interrogate their targets. The model not only correctly predicted the relative signaling potencies of known agonists and nonagonists but also achieved this in the absence of kinetic proofreading. Our work provides a simple, quantitative, and predictive molecular framework for understanding why TCR triggering is so selective and fast and reveals that, for some receptors, cell topography likely influences signaling outcomes.
An EGFR-Induced Drosophila Lung Tumor Model Identifies Alternative Combination Treatments

Lung cancer is the leading cause of cancer-associated mortality. Mutations in the EGFR gene are among the most important inducers of lung tumor development, but success of personalized therapies is still limited because of toxicity or developing resistances. We expressed constitutively active EGFR (EGFRCA) exclusively in the airway system of Drosophila melanogaster and performed comprehensive phenotyping. Ectopic expression of EGFRCA induced massive hyper- and metaplasia, leading to early death. We used the lethal phenotype as a readout and screened a library of FDA-approved compounds and found that among the 1,000 compounds, only the tyrosine kinase inhibitors (TKI) afatinib, gefitinib, and ibrutinib rescued lethality in a whole-animal screening approach. Furthermore, we screened the library in the presence of a subtherapeutic afatinib dose and identified bazedoxifene as a synergistically acting compound that rescues EGFR-induced lethality. Our findings highlight the potential of Drosophila-based whole-animal screening approaches not only to identify specific EGFR inhibitors but also to discover compounds that act synergistically with known TKIs. Moreover, we showed that targeting the EGFR together with STAT-signaling is a promising strategy for lung tumor treatment.
Identification of gene variants in 130 Han Chinese patients with hypospadias by targeted next‐generation sequencing

Hypospadias is a common congenital malformation of male external genitalia, which mainly manifests as an abnormal urethral opening on the ventral side of the penis. The etiology and clinical phenotype of hypospadias is highly heterogeneous, and its clinical diagnosis is challenging. Currently, over 70% of patients have an unknown etiology. Here, we performed a targeted analysis of gene mutations in 130 patients with hypospadias of unknown etiology to find the precise genetic cause.
Orthopaedic Faculty and Resident Sex Diversity Are Associated with the Orthopaedic Residency Application Rate of Female Medical Students.

BACKGROUND The representation of women in orthopaedics in the United States remains among the lowest in all fields of medicine, and prior research has suggested that this underrepresentation may stem from lower levels of interest among female medical students. Of the many proposed reasons for this lack of interest, the male-dominated nature of the field is one of the most commonly cited. The purpose of this study was to determine the degree to which the representation of women among orthopaedic faculty and residents influences female medical students at that institution to apply for a residency in orthopaedics. METHODS Using data provided by the Association of American Medical Colleges, we identified all U.S. medical schools that were affiliated with an orthopaedic surgery department and an orthopaedic surgery residency program (n = 107). For each institution, data on the representation of women among the orthopaedic faculty and residents from 2014 through 2016 were collected, as well as data on the proportion of female medical school graduates who applied to an orthopaedic residency program from 2015 through 2017. The association between institutional factors and the female medical student orthopaedic application rate was assessed. RESULTS Of 22,707 women who graduated from medical school during the 3-year study period, 449 (1.98%) applied to an orthopaedic surgery residency program. Women who attended medical school at institutions with high orthopaedic faculty sex diversity were more likely to apply for a residency in orthopaedics (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.04 to 1.64; p = 0.023), as were women who attended medical school at institutions with high orthopaedic resident sex diversity (OR, 1.30; 95% CI, 1.05 to 1.61; p = 0.019). CONCLUSIONS In this study, we found that increased sex diversity among orthopaedic faculty and residents was associated with a greater likelihood that female medical students at that institution would apply for an orthopaedic residency. These results suggest that at least some of the factors currently impeding female medical student interest in orthopaedics may be modifiable. These findings may have important implications for efforts to improve the sex diversity of the field of orthopaedics going forward.
Weightlifting load effect on intra-limb coordination of lower extremity during pull phase in snatch: Vector coding approach

ABSTRACT This study examined the weightlifting load effects on the lower extremity coordination pattern during a snatch pull movement. Twenty male elite weightlifters performed snatch trials in each of the three load conditions [light (30%), medium (65%) and heavy (90%) of their maximum weightlifting capacities]. Kinematic data for the transition, second pull and take-off phases of a snatch were collected at 200 Hz using an eight-camera motion capture system. Angle-angle plots and coupling angles were calculated for further analyses. The results indicate that participants utilised knee flexion control-strategy in light and medium load conditions during the transition phase, but not for in-phase strategy in heavy load condition. In the second pull phase, participants utilised concurrent ankle dorsiflexion and knee extension, followed by hip extension strategy. The heavy load condition exhibited the distinct coordination strategies before knee extension. In the take-off phase, light and medium load conditions appeared to use thigh-phase strategy (right ankle-knee: p = 0.788, left: p = 0.035, right knee-hip: p = 0.012, left: p = 0.017, right ankle-hip: p = 0.029, left: p = 0.011). This suggests that the heavy load condition requires the use of two-joint coordination patterns (in-phase or anti-phase) as compared to the other lighter load conditions.
Filaggrin and atopic march

There is an increasing number of experimental, genetic and clinical evidence of atopic dermatitis expression as a pre-condition for later development of other atopic diseases such as asthma, food allergy and allergic rhinitis. Atopic dermatitis is a heterogeneous, recurrent childhood disease, also present in the adult age. It is increasingly attributed to systemic features and is characterized by immunological and skin barrier integrity and function dysregulation. To maintain the protective function of the skin barrier, in particular the maintenance of pH, hydration and antimicrobial functions, the filaggrin, among others, plays a significant role. Filaggrin is a multifunctional, histidine-rich, insoluble protein. The lack of filaggrin is associated with various cutaneous (e.g. ichthyosis vulgaris, allergic contact dermatitis) and non-cutaneous (e.g. diabetes, inflammatory conditions of the gastrointestinal tract) diseases and may be a result of genetic, immunological factors combined with environmental factors. In this review we summarised (emphasized) recent findings in understanding the role of filaggrin in atopic dermatitis and other diseases, participants in the atopic march.
Long‐Term Risk of Hepatocellular Carcinoma in HCV Patients Treated With Direct Acting Antiviral Agents

Sustained virologic response (SVR) after direct acting antiviral agents (DAAs) holds promise for reducing hepatocellular cancer (HCC). DAAs have recently been available long enough to estimate the long‐term risk. We conducted a retrospective cohort study of hepatitis C virus (HCV) patients who achieved SVR with DAAs from 129 Veterans Health Administration hospitals between January 1, 2015, and December 31, 2015, with follow‐up through September 30, 2018. We calculated the overall and quarterly HCC incidence rates. We examined the effect of demographic, clinical, and behavioral factors and the decline or increase of FIB‐4 and aspartate aminotransferase to platelet ratio index (APRI) on HCC risk. Among the 18,076 patients with SVR, 544 incident cases of HCC were diagnosed during the mean 2.9 years of follow‐up. The cumulative 1, 2, and 3‐year risks of HCC were 1.1%, 1.9% and 2.8%, respectively. Cirrhosis was strongly associated with HCC risk (adjusted hazard ratio = 4.13, 95% confidence interval = 3.34‐5.11). The quarterly incidence rate of HCC remained stable between 1.00 and 1.23/100 person‐years (PY) and 1.5 to 2.3/100 PY in patients with cirrhosis. The risk of HCC was the highest in patients who had persistently high FIB‐4/APRI and both with and without cirrhosis. HCC risk fell in patients with cirrhosis who experienced a decrease of FIB‐4/APRI scores yet remained higher than the accepted threshold for HCC surveillance. HCC risk was also higher in patients with alcohol use, older age, and infection with HCV genotype 3. Most patients treated at an early stage of liver fibrosis had a stable low risk. Conclusion: Patients successfully treated with DAAs and at risk of HCC did not regress after 3.6 years of follow‐up. HCC risk remained above the accepted thresholds for surveillance in patients with cirrhosis. These data have important implications for HCC surveillance in cured HCV patients.
Yellow Wine Polyphenolic Compounds prevents Doxorubicin‐induced cardiotoxicity through activation of the Nrf2 signalling pathway

Doxorubicin (DOX) is considered as the major culprit in chemotherapy‐induced cardiotoxicity. Yellow wine polyphenolic compounds (YWPC), which are full of polyphenols, have beneficial effects on cardiovascular disease. However, their role in DOX‐induced cardiotoxicity is poorly understood. Due to their antioxidant property, we have been suggested that YWPC could prevent DOX‐induced cardiotoxicity. In this study, we found that YWPC treatment (30 mg/kg/day) significantly improved DOX‐induced cardiac hypertrophy and cardiac dysfunction. YWPC alleviated DOX‐induced increase in oxidative stress levels, reduction in endogenous antioxidant enzyme activities and inflammatory response. Besides, administration of YWPC could prevent DOX‐induced mitochondria‐mediated cardiac apoptosis. Mechanistically, we found that YWPC attenuated DOX‐induced reactive oxygen species (ROS) and down‐regulation of transforming growth factor beta 1 (TGF‐β1)/smad3 pathway by promoting nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) nucleus translocation in cultured H9C2 cardiomyocytes. Additionally, YWPC against DOX‐induced TGF‐β1 up‐regulation were abolished by Nrf2 knockdown. Further studies revealed that YWPC could inhibit DOX‐induced cardiac fibrosis through inhibiting TGF‐β/smad3‐mediated ECM synthesis. Collectively, our results revealed that YWPC might be effective in mitigating DOX‐induced cardiotoxicity by Nrf2‐dependent down‐regulation of the TGF‐β/smad3 pathway.
Effects of overfeeding on the fatty acid profile and stearoyl-CoA desaturase-1 indices in the liver and subcutaneous adipose tissue in cats

To evaluate the effect of overfeeding on fatty acid distribution and metabolism, especially stearoyl-CoA desaturase-1 (SCD-1) indices, 8 cats in the experimental and control groups (4 per group) were evaluated in this study. The experiments involved feeding the experimental group cats twice their daily energy requirement with a commercial diet for 4 weeks. The control group was fed the estimated daily energy requirement with the same diet. Body weight, feline body mass index, body condition score, several zoometry measurements, and plasma metabolites/hepatic injury markers were measured in all the cats before and after the experiment. In addition, the fatty acid profiles in the liver and subcutaneous adipose tissue were measured after the experiment. After 4 weeks of overfeeding, the experimental group demonstrated significant increases in hepatic C18:1, plasma triglyceride, and nonesterified fatty acid (NEFA) concentrations and in alanine aminotransferase activity. Furthermore, hepatic SCD-1 indices were positively correlated with body weight, feline body mass index, body condition score, and plasma NEFA concentration, although subcutaneous adipose tissue did not demonstrate any increase in SCD-1 indices in this study. The increase in hepatic SCD-1 indices might be enhanced by the inflow of plasma NEFA into the liver, and NEFA toxicity might stimulate C18:1 synthesis by SCD-1.
Effects of Perinatal Fluoride Exposure on Short- and Long-Term Memory, Brain Antioxidant Status, and Glutamate Metabolism of Young Rat Pups

Exposure to fluoride (F) during the development affects central nervous system of the offspring rats which results in the impairment of cognitive functions. However, the exact mechanisms of F neurotoxicity are not clearly defined. To investigate the effects of perinatal F exposure on memory ability of young rat offspring, dams were exposed to 5 and 10 mg/L F during gestation and lactation. Additionally, we evaluated the possible underlying neurotoxic mechanisms implicated. The results showed that the memory ability declined in 45-day-old offspring, together with a decrease of catalase and glutamate transaminases activity in specific brain areas. The present study reveals that exposure to F in early stages of rat development leads to impairment of memory in young offspring, highlighting the alterations of oxidative stress markers as well as the activity of enzymes involved in the glutamatergic system as a possible mechanisms of neurotoxicity.
Hepatitis C virus leaves an epigenetic signature post cure of infection by direct-acting antivirals

The increasing worldwide prevalence of Hepatocellular carcinoma (HCC), characterized by resistance to conventional chemotherapy, poor prognosis and eventually mortality, place it as a prime target for new modes of prevention and treatment. Hepatitis C Virus (HCV) is the predominant risk factor for HCC in the US and Europe. Multiple epidemiological studies showed that sustained virological responses (SVR) following treatment with the powerful direct acting antivirals (DAAs), which have replaced interferon-based regimes, do not eliminate tumor development. We aimed to identify an HCV-specific pathogenic mechanism that persists post SVR following DAAs treatment. We demonstrate that HCV infection induces genome-wide epigenetic changes by performing chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) for histone post-translational modifications that are epigenetic markers for active and repressed chromatin. The changes in histone modifications correlate with reprogramed host gene expression and alter signaling pathways known to be associated with HCV life cycle and HCC. These epigenetic alterations require the presence of HCV RNA or/and expression of the viral proteins in the cells. Importantly, the epigenetic changes induced following infection persist as an "epigenetic signature" after virus eradication by DAAs treatment, as detected using in vitro HCV infection models. These observations led to the identification of an 8 gene signature that is associated with HCC development and demonstrate persistent epigenetic alterations in HCV infected and post SVR liver biopsy samples. The epigenetic signature was reverted in vitro by drugs that inhibit epigenetic modifying enzyme and by the EGFR inhibitor, Erlotinib. This epigenetic “scarring” of the genome, persisting following HCV eradication, suggest a novel mechanism for the persistent pathogenesis of HCV after its eradication by DAAs. Our study offers new avenues for prevention of the persistent oncogenic effects of chronic hepatitis infections using specific drugs to revert the epigenetic changes to the genome.
Raman Spectroscopic and Chemometric Investigation of Lipid–Protein Ratio Contents of Soybean Mutants

Seeds belonging to fourth generation mutants (M4) of Ataem-7 cultivar (A7) variety and S04-05 (S) breeding line salt-tolerant soybeans were investigated by Raman spectroscopy, complemented by chemometrics methods, in order to evaluate changes induced by mutations in the relative lipid–protein contents, and to find fast, efficient strategies for discrimination of the mutants and the control groups based on their Raman spectra. It was concluded that gamma irradiation caused an increase in the lipid to protein ratio of the studied Ataem-7 variety mutants, while it led to a decrease of this ratio in the investigated S04-05 breeding line mutants. These results were found to be in agreement with data obtained by reflectance spectrum analysis of the seeds in the full ultraviolet to near-infrared spectral region and suggest the possibility of developing strategies where gamma irradiation can be used as a tool to improve mutant soybean plants targeted to different applications, either enriched in proteins or in lipids. Ward's clustering and principal component analysis showed a clear discrimination between mutants and controls and, in the case of the studied S-type species, discrimination between the different mutants. The grouping scheme is also found to be in agreement with the compositional information extracted from the analysis of the lipid–protein contents of the different samples.