Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans

Significance Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes. Here we show that a bispecific anti-FGFR1/KLB agonist antibody, BFKB8488A, mimics the actions of FGF21 in monkeys and humans. BFKB8488A induced marked weight loss in obese monkeys while elevating expression of FGFR1 target genes in adipose tissue. A clinical study in overweight human participants demonstrated that a single dose of BFKB8488A caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that antibody-mediated activation of the FGFR1/KLB complex in humans recapitulates the effects of FGF21 and can be used as therapy for obesity-related metabolic defects. Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating/drinking behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. Chronic administration of recombinant FGF21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic. In a randomized, placebo-controlled, single ascending-dose study in overweight/obese human participants, subcutaneous BFKB8488A injection caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that specific activation of the FGFR1/KLB complex in humans can be used as therapy for obesity-related metabolic defects.
Simple Method to Isolation and Culture of Neuron Progenitor Cells (NPCs) from Whole Brain Post-Natal Rat

Background: Using of neuron cells for in vitro neurobiology study is needed. Neuron cell can be obtained from a primary neuron or neuronal cell lines, depend on the aim of the study because both are not equivalent. Various methods are performed to obtain primary neurons from the cortical, hippocampal and whole brain of pre or neonatal rat. The limitations of neuron cells to proliferate so that is necessary to develop a method to isolate neuron progenitor cells (NPCs). The aim of the present study was to isolate NPCs from whole brain post-natal rat. Methods: Whole brain were obtained from neonates Sprague Dawley rat. There are 2 step to get NSC; first isolation by taking the brain into the 15 ml of tube with 1 ml of 0,05% trypsin EDTA for 400g brain (incubated in the 370C, 5% CO2 for 10 minutes), tirturation with adding 1 ml culture medium and 5 ml HBSS-glucose then filtered by 70μm pore size membrane and centrifuged 2000 rpm for 10 minutes. Second: remove of supernatant with add 1 ml of HBSS-Glucose and taking it into a tube with 35% and 65% concentration of Ficoll then centrifuged at 1800 g for 10 minutes then supernatant were replated twice with poly D lysine (100µg/ml). Characterization of progenitor neuron immunotype was checked by immunohistochemistry with positive marker (NeuN and MAP2) and flow cytometry (PSANCAM+ and A2B5 -). Results: In this study, our result show that this method does not take longer than one hours and > 95% cells that obtained are expressing PSANCAM+. After 4 days culture, cells exhibit positive for neuron marker as MAP2 and NeuN. Conclusion: The method that our develope to isolate neuron progenitor cell from whole-brain are more effective and more simple with high viability and purity.
Hydrothermal Activation of Porous Nitrogen-Doped Carbon Materials for Electrochemical Capacitors and Sodium-Ion Batteries

Highly porous nitrogen-doped carbon nanomaterials have distinct advantages in energy storage and conversion technologies. In the present work, hydrothermal treatments in water or ammonia solution were used for modification of mesoporous nitrogen-doped graphitic carbon, synthesized by deposition of acetonitrile vapors on the pyrolysis products of calcium tartrate. Morphology, composition, and textural characteristics of the original and activated materials were studied by transmission electron microscopy, X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy, infrared spectroscopy, and nitrogen gas adsorption method. Both treatments resulted in a slight increase in specific surface area and volume of micropores and small mesopores due to the etching of carbon surface. Compared to the solely aqueous medium, activation with ammonia led to stronger destruction of the graphitic shells, the formation of larger micropores (1.4 nm vs. 0.6 nm), a higher concentration of carbonyl groups, and the addition of nitrogen-containing groups. The tests of nitrogen-doped carbon materials as electrodes in 1M H2SO4 electrolyte and sodium-ion batteries showed improvement of electrochemical performance after hydrothermal treatments especially when ammonia was used. The activation method developed in this work is hopeful to open up a new route of designing porous nitrogen-doped carbon materials for electrochemical applications.
Frailty Is a Better Predictor than Age of Mortality and Perioperative Complications after Surgery for Degenerative Cervical Myelopathy: An Analysis of 41,369 Patients from the NSQIP Database 2010–2018

Background: The ability of frailty compared to age alone to predict adverse events in the surgical management of Degenerative Cervical Myelopathy (DCM) has not been defined in the literature. Methods: 41,369 patients with a diagnosis of DCM undergoing surgery were collected from the National Surgical Quality Improvement Program (NSQIP) Database 2010–2018. Univariate analysis for each measure of frailty (modified frailty index 11- and 5-point; MFI-11, MFI-5), modified Charlson Co-morbidity index and ASA grade) were calculated for the following outcomes: mortality, major complication, unplanned reoperation, unplanned readmission, length of hospital stay, and discharge to a non-home destination. Multivariable modeling of age and frailty with a base model was performed to define the discriminative ability of each measure. Results: Age and frailty have a significant effect on all outcomes, but the MFI-5 has the largest effect size. Increasing frailty correlated significantly with the risk of perioperative adverse events, longer hospital stay, and risk of a non-home discharge destination. Multivariable modeling incorporating MFI-5 with age and the base model had a robust predictive value (0.85). MFI-5 had a high categorical assessment correlation with a MFI-11 of 0.988 (p < 0.001). Conclusions and Relevance: Measures of frailty have a greater effect size and a higher discriminative value to predict adverse events than age alone. MFI-5 categorical assessment is essentially equivalent to the MFI-11 score for DCM patients. A multivariable model using MFI-5 provides an accurate predictive tool that has important clinical applications.
Quantification of Process Lethality (5-Log Reduction) of Salmonella and Salt Concentration during Sodium Replacement in Biltong Marinade

Salt (sodium chloride, NaCl) is commonly used in ready-to-eat (RTE) meat products such as biltong, a South African style dried beef product for flavor, enhanced moisture loss, and reduction of microbial growth. However, increased consumption of high sodium content foods is commonly associated with high blood pressure and heart disease. This study evaluated the use of alternative salts, potassium chloride (KCl) and calcium chloride (CaCl2) in the biltong marinade to achieve a ≥ 5-log reduction of Salmonella, a pathogen of concern in beef products. Beef pieces (1.9 cm × 5.1 cm × 7.6 cm) were inoculated with a five-serovar mixture of Salmonella (Salmonella Thompson 120, Salmonella Enteritidis H3527, Salmonella Typhimurium H3380, Salmonella Heidelberg F5038BG1, and Salmonella Hadar MF60404), vacuum-tumbled in a traditional biltong marinade of salt, spices, and vinegar containing either NaCl, KCl or CaCl2 (2.2% concentration) followed by an 8–10 day drying period at 23.9 °C (75 °F) and 55% relative humidity. Microbial enumeration of Salmonella was conducted following inoculation, after marination, and after 2, 4, 6, 8, and 10 days of drying in a humidity/temperature chamber. Biltong produced with CaCl2, NaCl, or KCl achieved a > 5-log reduction of Salmonella after 6, 7, and 8 days, respectively. The Salmonella reduction trends with biltong made with NaCl or CaCl2 were not significantly different (p < 0.05) while both were significantly different from that made with KCl (p > 0.05). Sodium, calcium, and potassium ion concentrations were measured using ion-specific electrode meters following biltong processing and drying. As expected, the biltong made with the corresponding salt had the most abundant ion in the sample. Regardless of the salt used in the marinade, the potassium ion levels were moderately elevated in all samples. This was determined to be from potassium levels naturally present in beef rather than from other ingredients. Sampling of several commercial brands of biltong for sodium content showed that some were significantly above the allowable level of claims made on package ingredient statements. The substitution of NaCl with KCl or CaCl2 during biltong processing can also provide a 5-log reduction of Salmonella to produce a safe product that can be marketed as a more healthy low-sodium food alternative that may appeal to consumers who need to reduce their blood pressure and are conscientious of sodium levels in their diet.
Myostatin-1 Inhibits Cell Proliferation by Inhibiting the mTOR Signal Pathway and MRFs, and Activating the Ubiquitin-Proteasomal System in Skeletal Muscle Cells of Japanese Flounder Paralichthys olivaceus

Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. The mechanisms of fish MSTN involved in muscle growth are not fully understood. In the present study, knockdown and overexpression of mstn-1 was performed in cultured Japanese flounder muscle cells to investigate the molecular function and the underlying mechanism of fish MSTN-1. Results showed that mstn-1 knockdown significantly induced cell proliferation and the mRNA expression of myogenic regulatory factors (MRFs), while overexpression of mstn-1 led to a significant decrease of cell proliferation and a suppression of the MRFs mRNA expression. The overexpression of mstn-1 also significantly increased the mRNA expression of ubiquitin–proteasomal pathway of proteolysis genes including muscle RING-finger protein 1 (murf-1) by 204.1% (p = 0.024) and muscle atrophy F-box protein (mafbx) by 165.7% (p = 0.011). However, mystn-1 overexpression inhibited the activation of mTOR signal pathway and the AKT/FoxO1 pathway through decreasing phosphorylation of AKT at Ser 473 by 56.0% (p = 0.001). Meanwhile, mystn-1 overexpression increased the dephosphorylation and nuclear localization of FoxO1 by 394.9% (p = 0.005). These results demonstrate that mstn-1 in Japanese flounder has the effects of inhibiting cell proliferation and growth, and the mTOR and AKT/FoxO1 pathways participated in these biological effects.
Ovarian Cancer: Tumor-Specific Urinary Micro-Peptides Profiling as Potential Biomarkers for Early Diagnosis

Ovarian cancer is the second major lethal gynecologic malignancy in developing countries. This study aimed to characterize urinary micro-peptides as potential diagnostic biomarkers for ovarian cancer. In a prospective, longitudinal and case-controlled study and following informed consent, urine and plasma samples were collected from 112 women with histologically-proven ovarian cancer and 200 apparently healthy age-matched volunteers. Urinary micro-peptides were detected and sequenced using SDS-PAGE and Edman degradation technique. Serum CA125 was detected in less than a quarter (23.2%, 26/112) of patients. One or more urinary micro-peptides were detected in about two thirds of the patients (62.5%, 70/112). A total of 40 patients had three bands (57.1%, 40/70), while two bands (15 and 35 kDa) were detected in 28.6% (20/70) of the patients. Isolated 45 kDa band was seen in 14.3% (10/70). No urinary micro-peptide was detected in the volunteers. The 15 and 35 kDa bands disappeared after 6 months of regular chemotherapy, while the 45 kDa band persisted in 2.9% (2/70) of the patients after treatment. The micro-peptides were identified as: Catalase (45 kDa), α-1 Acid Glycoprotein (35 kDa) and Peroxiredoxin-2 (15 kDa). Urinary catalase, α-1 Acid Glycoprotein and Peroxiredoxin-2 can be useful biomarkers for early detection and treatment response of ovarian cancer.
A dsRNA‐degrading nuclease (dsRNase2) limits RNAi efficiency in the Asian corn borer (Ostrinia furnacalis)

The efficiency of RNA interference (RNAi) varies substantially among different insect species. Rapid degradation of double‐stranded RNA (dsRNA) by dsRNA‐degrading nucleases (dsRNases) has been implicated to cause low RNAi efficiency in several insect species. In this study, we identified four dsRNase genes (OfdsRNase1, OfdsRNase2, OfdsRNase3 and OfdsRNase4) from the Asian corn borer (Ostrinia furnacalis) transcriptome database. Bioinformatic analyses showed that each deduced protein sequence contained endonuclease NS domains and signal peptides. Gene expression analysis revealed that OfdsRNase2 was exclusively expressed in the midgut of larvae. RNAi efficiency was investigated in 2‐d‐old fifth‐instar larvae (high expression of dsRNase2) and 2‐d‐old pupae (low expression of dsRNase2) by feeding or injecting dsRNA targeting a marker gene that encodes the lethal giant larvae protein (OfLgl). Our results showed that OfLgl only partially silenced the expression of OfLgl in pupae, but not in larvae, suggesting that OfdsRNase2 could contribute to lower RNAi efficiency in larval stages. This hypothesis was supported by our RNAi‐of‐RNAi experiment using a tissue culture technique where the silencing efficiency against the reporter gene, OfHex1, was significantly improved after knockdown of OfdsRNase2. When double luciferase assays were performed to evaluate the role of the four dsRNases in vitro, only OfdsRNase2 expressed in S2 cells significantly affected RNAi efficiency by degrading dsRNA. Taken together, our results suggested that the degradation of dsRNA by OfdsRNase2 in the midgut contributed to low RNAi efficiency in O. furnacalis larvae.
Familial Hypercholesterolemia in Premature Acute Coronary Syndrome. Insights from CholeSTEMI Registry

Familial hypercholesterolemia (FH) is an underdiagnosed genetic inherited condition that may lead to premature coronary artery disease (CAD). FH has an estimated prevalence in the general population of about 1:313. However, its prevalence in patients with premature STEMI (ST-elevation myocardial infarction) has not been widely studied. This study aimed to evaluate the prevalence of FH in patients with premature STEMI. Cardiovascular risk factors, LDLc (low-density lipoprotein cholesterol) evolution, and differences between genders were also evaluated. Consecutive patients were referred for cardiac catheterization to our center due to STEMI suspicion in 2018. From the 80 patients with confirmed premature CAD (men < 55 and women < 60 years old with confirmed CAD), 56 (48 men and eight women) accepted to be NGS sequenced for the main FH genes. Clinical information and DLCN (Dutch Lipid Clinic Network) score were analyzed. Only one male patient had probable FH (6–7 points) and no one reached a clinically definite diagnosis. Genetic testing confirmed that the only patient with a DLCN score ≥6 has HF (1.8%). Smoking and high BMI the most frequent cardiovascular risk factors (>80%). Despite high doses of statins being expected to reduce LDLc levels at STEMI to current dyslipidemia guidelines LDL targets (<55 mg/dL), LDLc control levels were out of range. Although still 5.4 times higher than in general population, the prevalence of FH in premature CAD is still low (1.8%). To improve the genetic yield, genetic screening may be considered among patients with probable or definite FH according to clinical criteria. The classical cardiovascular risk factors prevalence far exceeds FH prevalence in patients with premature STEMI. LDLc control levels after STEMI were out range, despite intensive hypolipemiant treatment. These findings reinforce the need for more aggressive preventive strategies in the young and for intensive lipid-lowering therapy in secondary prevention.
An eye for talent: The recruiters’ role in the Australian Football talent pathway

Talent identification and recruitment (TIR) in elite sport is a complex process with performance and career longevity implications for athletes, sports organisations, and scouts (hereafter referred to as recruiters). Although there is an established body of published research on TIR the critical roles that recruiters perform has only recently gained attention from researchers. In this study, we report on the practices that 12 full time Australian Football recruiters use to inform their TIR decisions. Inductive qualitative semi-structured interviews were conducted using open-ended questions. Thematic analysis resulted in the identification of four primary themes (the recruiter, processes and practices, assessment and selection). The results and discussion provide insights and an occupational ‘road map’ into the important role recruiters perform in sporting organisations.
Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD

Hyperphosphatemia has been proposed as a cardiovascular risk factor, contributing to long-term vascular calcification in hyperphosphatemic Chronic Kidney Disease (CKD) patients. However, more recent studies have also demonstrated acute effects of inorganic phosphate (Pi) on endothelial cells in vitro, especially generation of pro-coagulant endothelial microvesicles (MV). Hitherto, such direct effects of hyperphosphatemia have not been reported in vivo. Thirty-six male Sprague-Dawley rats were randomly allocated to three experimental groups: (1) CKD induced by partial nephrectomy receiving high (1.2%) dietary phosphorus; (2) CKD receiving low (0.2%) dietary phosphorus; and (3) sham-operated controls receiving 1.2% phosphorus. After 14 days the animals were sacrificed and plasma MVs counted by nanoparticle tracking analysis. MVs isolated by centrifugation were assayed for pro-coagulant activity by calibrated automated thrombography, and relative content of endothelium-derived MVs was assessed by anti-CD144 immunoblotting. When compared with sham controls, high phosphorus CKD rats were shown to be hyperphosphatemic (4.11 ± 0.23 versus 2.41 ± 0.22 mM Pi, p < 0.0001) with elevated total plasma MVs (2.24 ± 0.37 versus 1.31 ± 0.24 × 108 per ml, p < 0.01), showing increased CD144 expression (145 ± 25% of control value, p < 0.0001), and enhanced procoagulant activity (18.06 ± 1.75 versus 4.99 ± 1.77 nM peak thrombin, p < 0.0001). These effects were abolished in the low phosphorus CKD group. In this rat model, hyperphosphatemia (or a Pi-dependent hormonal response derived from it) is sufficient to induce a marked increase in circulating pro-coagulant MVs, demonstrating an important link between hyperphosphatemia and thrombotic risk in CKD.
Cholesterol-Rich Microdomains Contribute to PAR1 Signaling in Platelets Despite a Weak Localization of the Receptor in These Microdomains

Platelet protease-activated receptor 1 (PAR1) is a cell surface G-protein-coupled receptor (GPCR) that acts as a thrombin receptor promoting platelet aggregation. Targeting the PAR1 pathway by vorapaxar, a PAR1 antagonist, leads to a reduction in ischemic events in cardiovascular patients with a history of myocardial infarction or with peripheral arterial disease. In platelets, specialized microdomains highly enriched in cholesterol act as modulators of the activity of several GPCRs and play a pivotal role in the signaling pathway. However, their involvement in platelet PAR1 function remains incompletely characterized. In this context, we aimed to investigate whether activation of PAR1 in human platelets requires its localization in the membrane cholesterol-rich microdomains. Using confocal microscopy, biochemical isolation, and proteomics approaches, we found that PAR1 was not localized in cholesterol-rich microdomains in resting platelets, and only a small fraction of the receptor relocated to the microdomains following its activation. Vorapaxar treatment increased the level of PAR1 at the platelet surface, possibly by reducing its endocytosis, while its colocalization with cholesterol-rich microdomains remained weak. Consistent with a cholesterol-dependent activation of Akt and p38 MAP kinase in thrombin receptor-activating peptide (TRAP)-activated platelets, the proteomic data of cholesterol-rich microdomains isolated from TRAP-activated platelets showed the recruitment of proteins contributing to these signaling pathways. In conclusion, contrary to endothelial cells, we found that PAR1 was only weakly present in cholesterol-rich microdomains in human platelets but used these microdomains for efficient activation of downstream signaling pathways following TRAP activation.
Alignment of Medical and Psychosocial Sectors for Promotion of Tobacco Cessation among Residents of Public Housing: A Feasibility Study

The inequity in cessation resources is at the forefront of the recently enacted US smoking ban in public housing facilities. This pre-post, non-randomized pilot study assessed the feasibility of a smoking cessation program targeting smokers in Baltimore City public housing. The study implemented a four-phased, 10-week, community-based cessation program using a joint academic–housing partnership that provided on-site cessation pharmacotherapy, behavioral counseling, and psychosocial/legal services. The community-led strategy involved: (1) two-week smoking cessation training for lay health workers; (2) screening and recruitment of smokers by housing authority residential leadership; (3) four-week resident-led cessation using evidenced-based strategies along with wraparound support services; (4) formative evaluation of the intervention’s acceptability and implementation. Thirty participants were recruited of which greater than one-half attended the majority of weekly cessation events. Thirty percent were able to achieve biomarker-proven cessation, as measured by a reduction in exhaled CO levels—a percentage comparable to the reported state quitline 30-day cessation rate. Despite weekly joint community–academic led-education of nicotine replacement therapy (NRT) therapies, only two participants regularly and properly used NRT transdermal patches; <20% of participants used NRT gum correctly at their first follow-up visit. Less than one-half utilized psychosocial and legal services by our community-based organization partners. Post-intervention interviews with participants noted broad approval of the ease in accessibility of the cessation intervention, but more diversification in the timing and personalization of offerings of services would have assisted in greater adoptability and participant retention. Though a reduction in smoking behaviors was not broadly observed, we elucidated modifiable social, educational, and physical features that could enhance the likelihood of smoking cessation among public housing residents.