Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Bispecific Antibody Targeting CD3 and Lewis Y with Potent Therapeutic Efficacy against Gastric Cancer

Lewis Y antigen, a glycan highly expressed on most epithelial cancers, was targeted for cancer treatment but lacked satisfactory results in some intractable and refractory cancers. Thus, it is highly desirable to develop an effective therapy against these cancers, hopefully based on this target. In this work, we constructed a novel T cell-engaging bispecific antibody targeting Lewis Y and CD3 (m3s193 BsAb) with the IgG-[L]-scfv format. In vitro activity of m3s193 BsAb was evaluated by affinity assay to target cells, cytotoxicity assay, cytokines releasing assay, and T cells proliferation and recruiting assays. Anti-tumor activity against gastric cancer was evaluated in vivo by subcutaneous huPBMCs/tumor cells co-grafting model and huPBMCs intravenous injecting model. In vitro, m3s193 BsAb appeared to have a high binding affinity to Lewis Y positive cells and Jurkat cells. The BsAb showed stronger activity than its parent mAb in T cell recruiting, activation, proliferation, cytokine release, and cytotoxicity. In vivo, m3s193 BsAb not only demonstrated higher therapeutic efficacy in the huPBMCs/tumor co-grafting gastric carcinoma model than the parent mAb but also eliminated tumors in the model of intravenous injection with huPBMCs. Strong anti-tumor activity of m3s193 BsAb revealed that Lewis Y could be targeted in T cell-engaging BsAb for gastric cancer therapy.
Optimisation of Lapping Process Parameters for Single-Crystal 4H–SiC Using Orthogonal Experiments and Grey Relational Analysis

Lapping is one of the standard essential methods to realise the global planarization of SiC and other semiconductor substrates. It is necessary to deeply study the mechanism to obtain SiC lapping process parameters with a strong comprehensive lapping performance (i.e., high material removal rate (MRRm), small surface roughness (Ra), and low total thickness variation (TTV)). The effects of the lapping process parameters and their interactions on lapping performance for SiC were investigated using orthogonal experiments; the effects on the MRRm, Ra, TTV, and optimal parameters under the conditions of a single evaluation index were investigated using intuitive analysis (range analysis, variance analysis, and effect curve analysis). The entropy value method and grey relational analysis were used to transform the multi-evaluation-index optimisation into a single-index optimisation about the grey relational grade (GRG) and to comprehensively evaluate the lapping performance of each process parameter. The results showed that the lapping plate types, abrasive size, and their interaction effect had the most significant effects on MRRm and Ra, with a contribution of over 85%. The interaction between the lapping plate types and abrasive size was also found to have the most significant effect on TTV, with a contribution of up to 51.07%. As the lapping plate’s hardness and abrasive size increased, the MRRm and Ra also gradually increased. As the lapping normal-pressure increased, MRRm increased, Ra gradually decreased, and TTV first decreased and then increased. MRRm, Ra, and TTV first increased and then decreased with increasing abrasive concentration. Compared to the optimisation results obtained by intuitive analysis, the process parameter optimised by the grey relational analysis resulted in a smooth surface with an MRRm of 90.2 μm/h, an Ra of 0.769 nm, and a TTV of 3 μm, with a significant improvement in the comprehensive lapping performance. This study reveals that a combination of orthogonal experiments and grey relational analysis can provide new ideas for optimising the process parameters of SiC.
Evaluation Approach of Fracture Behavior for Asphalt Concrete with Different Aggregate Gradations and Testing Temperatures Using Acoustic Emission Monitoring

Different aggregate gradations of asphalt concrete possess dissimilar skeleton structures, leading to diverse macroscopic and mechanical characteristics. Acoustic emission (AE) technology can realize real-time monitoring of the whole damage evolution process of materials. The objective of the present investigation was to demonstrate the fracture characteristics of asphalt concrete with three types of aggregate gradations, including dense-graded asphalt concrete (AC), stone mastic asphalt (SMA), and open-graded friction course (OGFC) under indirect tensile load on account of the acoustic emission (AE) technique. The Marshall compaction method was used to prepare specimens, and the indirect tensile test (IDT) and AE monitoring were conducted simultaneously at different temperatures. The corresponding AE parameters containing energy, cumulative energy, count, and cumulative count were adopted to characterize the fracture process of asphalt concrete with different aggregate gradations. The impact of temperature on the damage characteristics of asphalt concrete was also assessed. Test results indicated that the AE parameters could effectively classify the damage stages of asphalt concrete, and specimens with different aggregate gradations exhibited different AE characteristics during failure processes. The combination of AE parameters and cumulative AE parameters can accurately characterize the damage characteristics of asphalt concrete. SMA specimens possessed the best overall performance among these three types of asphalt concrete in terms of the variations in energy and cumulative energy at different temperatures. The findings obtained in this study can provide a practical AE-based evaluation approach for demonstrating the fracture mechanism of asphalt concrete with different aggregate gradations.
Novel STAG1 Frameshift Mutation in a Patient Affected by a Syndromic Form of Neurodevelopmental Disorder

The cohesin complex is a large evolutionary conserved functional unit which plays an essential role in DNA repair and replication, chromosome segregation and gene expression. It consists of four core proteins, SMC1A, SMC3, RAD21, and STAG1/2, and by proteins regulating the interaction between the complex and the chromosomes. Mutations in the genes coding for these proteins have been demonstrated to cause multisystem developmental disorders known as “cohesinopathies”. The most frequent and well recognized among these distinctive clinical conditions are the Cornelia de Lange syndrome (CdLS, OMIM 122470) and Roberts syndrome (OMIM 268300). STAG1 belongs to the STAG subunit of the core cohesin complex, along with five other subunits. Pathogenic variants in STAG1 gene have recently been reported to cause an emerging syndromic form of neurodevelopmental disorder that is to date poorly characterized. Here, we describe a 5 year old female patient with neurodevelopmental delay, mild intellectual disability, dysmorphic features and congenital anomalies, in which next generation sequencing analysis allowed us to identify a novel pathogenic variation c. 2769_2770del p.(Ile924Serfs*8) in STAG1 gene, which result to be de novo. The variant has never been reported before in medical literature and is absent in public databases. Thus, it is useful to expand the molecular spectrum of clinically relevant alterations of STAG1 and their phenotypic consequences.
Menaquinone 4 Reduces Bone Loss in Ovariectomized Mice through Dual Regulation of Bone Remodeling

Epidemiologic studies showed that higher vitamin K (VK) consumption correlates with a reduced risk of osteoporosis, yet the dispute remains about whether VK is effective in improving bone mineral density (BMD). We sought to discover the anti-osteoporotic effect of menaquinone-4 (MK-4) and evaluate the expression of critical genes related to bone formation and bone resorption pathways in the body. Fifty female C57BL/6 mice (aged 13 weeks) were randomly arranged to a sham-operated group (SHAM, treated with corn oil) and four ovariectomized groups that were administered corn oil (OVX group), estradiol valerate (EV, 2 mg/kg body weight as the positive control), low or high doses of VK (LVK and HVK; 20 and 40 mg MK-4/kg body weight, respectively) by gavage every other day for 12 weeks. Body and uterine weight, serum biochemical indicators, bone microarchitecture, hematoxylin-eosin (HE) staining, and the mRNA expression of critical genes related to bone formation and bone resorption pathways were assessed. Either dose of MK-4 supplementation increased the alkaline phosphatase (ALP), decreased the undercarboxylated osteocalcin (ucOC) and tartrate-resistant acid phosphatase (TRACP, p < 0.05) levels, and presented higher BMD, percent bone volume (BV/TV), trabecular thickness (Tb.Th), and lower trabecular separation (Tb.Sp) and structure model index (SMI, p < 0.05) compared with the OVX group. Additionally, both doses of MK4 increased the mRNA expression of Runx2 and Bmp2 (p < 0.05), whereas the doses down-regulated Pu.1 and Nfatc1 (p < 0.05) mRNA expression, the high dose decreased Osx and Tgfb (p < 0.05) mRNA expression, and the low dose decreased Mitd and Akt1 (p < 0.05) mRNA expression. These data show the dual regulatory effects of MK-4 on bone remodeling in ovariectomized mice: the promotion of bone anabolic activity and inhibition of osteoclast differentiation, which provides a novel idea for treating osteoporosis.
Genome-Wide Association Study Identifies 12 Loci Associated with Body Weight at Age 8 Weeks in Korean Native Chickens

Meat from Korean native chickens (KNCs) has high consumer demand; however, slow growth performance and high variation in body weight (BW) of KNCs remain an issue. Genome-wide association study (GWAS) is a powerful method to identify quantitative trait-associated genomic loci. A GWAS, based on a large-scale KNC population, is needed to identify underlying genetic mechanisms related to its growth traits. To identify BW-associated genomic regions, we performed a GWAS using the chicken 60K single nucleotide polymorphism (SNP) panel for 1328 KNCs. BW was measured at 8 weeks of age, from 2018 to 2020. Twelve SNPs were associated with BW at the suggestive significance level (p < 2.95 × 10−5) and located near or within 11 candidate genes, including WDR37, KCNIP4, SLIT2, PPARGC1A, MYOCD and ADGRA3. Gene set enrichment analysis based on the GWAS results at p < 0.05 (1680 SNPs) showed that 32 Gene Ontology terms and two Kyoto Encyclopedia of Genes and Genomes pathways, including regulation of transcription, motor activity, the mitogen-activated protein kinase signaling pathway, and tight junction, were significantly enriched (p < 0.05) for BW-associated genes. These pathways are involved in cell growth and development, related to BW gain. The identified SNPs are potential biomarkers in KNC breeding.
Transfer Learning for Automatic Cornea Segmentation based on Ocular Staining Images

In this work, we proposed and validated a novel transfer learning based method for automatic cornea segmentation from ocular staining images. An encoder-decoder structure was used, containing an Xception feature extractor, Atrous Spatial Pyramid Pooling and a simple but effective decoder. The proposed method successfully solved the problem of training a large network with limited data and capturing contextual information with a relatively simple network by fine-tuning a large network that had been pretrained on large-scale common object datasets. A total of 712 ocular staining images were used in our experiments. Evaluations were conducted both quantitatively and qualitatively through 5-fold cross-validation. Compared with several other deep learning based segmentation techniques, including U-Net, Fully Convolutional Network (FCN), and DeepLab, the proposed method was found to exhibit superior performance, with a Dice score of 95.82%, sensitivity of 95.37%, and accuracy of 97.63%. We also evaluated the method with different transfer learning strategies and found that fine-tuning the whole network worked the best in terms of segmentation accuracy.
Gender differences in self-reported sleep problems among older adults in six middle-income countries: a cross-sectional study

ABSTRACT This study examines gender differences in sleep problems among older adults in India, China, Ghana, Mexico, Russia, and South Africa. We used data on 33,929 individuals (50+ years) from the WHO-SAGE. Results showed significant gender differences in the prevalence of sleep problems with the largest difference in Russia followed by India. Regression results showed higher odds of sleep problems among women in India, China, Russia, and South Africa. Age, low back pain, depression, and poor self-rated health were significantly associated with sleep problems. This research confirms significant gender differences in sleep problems among the older population in middle-income countries.
Dummy Fragment Template Molecularly Imprinted Polymers for the Selective Solid-phase Extraction of Gonyautoxins from Seawater

ABSTRACT A multitemplate molecularly imprinted polymer was synthesized using fragments similar to gonyautoxins 1 and 4 including 2,4,6-triaminopyrimidine, 4-hydroxy-2-butanone, and imidazole as dummy templates by bulk polymerization. Scanning electron microscopy and infrared spectroscopy showed a porous structure and the formation of organic groups in the imprinting process of the polymer. One millilitre of 0.1 mol L−1 acetic acid and 1 mL of 95% methanol were the optimized washing and eluting solutions during the molecularly imprinted solid-phase extraction. The adsorption capacity of the multitemplate molecularly imprinted polymer was lower than for the monotemplate molecularly imprinted polymer prepared in a previous study in seawater in which Alexandrium tamarense and Alexandrium minutum were cultivated. This result may due to the inappropriate combination of the dummy template fragments in the synthesis resulting in the unfitness of the imprinting sites for gonyautoxins 1 and 4. In general, it is inappropriate to use fragments with the similar parts to the analyte as the dummy templates. However, this work indicated the optimal molecularly imprinted polymer for the selective extraction of gonyautoxins 1 and 4.
Understanding the Impact of Perfluorinated Compounds on Cardiovascular Diseases and Their Risk Factors: A Meta-Analysis Study

Perfluorinated compounds (PFCs) are non-biodegradable synthetic chemical compounds that are widely used in manufacturing many household products. Many studies have reported the association between PFCs exposure with the risk of developing cardiovascular diseases (CVDs). However, those reports are still debatable, due to their findings. Thus, this review paper aimed to analyse the association of PFCs compound with CVDs and their risk factors in humans by systematic review and meta-analysis. Google Scholar, PubMed and ScienceDirect were searched for PFCs studies on CVDs and their risk from 2009 until present. The association of PFCs exposure with the prevalence of CVDs and their risk factors were assessed by calculating the quality criteria, odds ratios (ORs), and 95% confidence intervals (CIs). CVDs risk factors were divided into serum lipid profile (main risk factor) and other known risk factors. The meta-analysis was then used to derive a combined OR test for heterogeneity in findings between studies. Twenty-nine articles were included. Our meta-analysis indicated that PFCs exposure could be associated with CVDs (Test for overall effect: z = 2.2, p = 0.02; Test for heterogeneity: I2 = 91.6%, CI = 0.92–1.58, p < 0.0001) and their risk factors (Test for overall effect: z = 4.03, p < 0.0001; Test for heterogeneity: I2 = 85.8%, CI = 1.00–1.14, p < 0.0001). In serum lipids, total cholesterol levels are frequently reported associated with the exposure of PFCs. Among PFCs, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) exposure increased the risk of CVDs than other types of PFCs. Although the risk of PFOA and PFOS were positively associated with CVDs and their risk factors, more observational studies shall be carried out to identify the long-term effects of these contaminants in premature CVDs development in patients.
Bone Cuts Accuracy of a System for Total Knee Arthroplasty including an Active Robotic Arm

Introduction: This study aimed to assess the bone cuts accuracy of a system for total knee arthroplasty including an active robotic arm. A second objective was to compare the accuracy among orthopaedic surgeons of different levels of experience. Methods: Three orthopaedic surgeons cut 10 sawbone knees each. Planned and actual bone cuts were compared using computed tomography. Difference with respect to the planning was expressed as three position and three orientation errors following the anatomical planes. Statistical tests were performed to detect bias and compare surgeons. Results: None of the 30 knees presented an outlier error, meaning an error ≥3 mm or ≥3°. The root-mean-square values of the 12 error types were below 0.8 mm or 0.8°, except for the femoral proximal–distal errors (1.7 mm) and the tibial anterior-posterior errors (1.4 mm). Biases were observed, particularly in femoral proximal–distal and tibial anterior–posterior positions. Median differences between surgeons were all lower than 0.8 mm and 0.5°, with statistically significant differences among surgeons in the femoral proximal–distal errors and the tibial anterior–posterior errors. Conclusions: The system tested in this study achieved accurate bone cuts independently of the surgeon’s level of experience. Biases were observed, suggesting that there might be options to improve the accuracy, particularly in proximal–distal position for the femur and in anterior–posterior position for the tibia.
Oat Intake and Risk of Type 2 Diabetes, Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis

Cardiovascular disease (CVD) and type 2 diabetes (T2D) remain the top disease and mortality burdens worldwide. Oats have been shown to benefit cardiovascular health and improve insulin resistance. However, the evidence linking oat consumption with CVD, T2D and all-cause mortality remains inconclusive. We conducted a comprehensive systematic review and meta-analysis of prospective cohort studies to evaluate the associations between oat consumption and risks of T2D, CVD and all-cause mortality in the general population. Five electronic databases were searched until September, 2020. Study specific relative risks (RR) were meta-analyzed using random effect models. Of 4686 relevant references, we included 9 articles, based on 8 unique studies and 471,157 participants. Comparing oat consumers versus non-consumers, RRs were 0.86 (95% CI 0.72–1.03) for T2D incidence and 0.73 (95% CI 0.5–1.07) for combined CVD incidence. Comparing participants with highest versus lowest oat intake, RRs were 0.78 (95% CI 0.74–0.82) for T2D incidence, 0.81 (95% CI 0.61–1.08) for CHD incidence and 0.79 (95% CI 0.59–1.07) for stroke. For all-cause mortality one study based on three cohorts found RR for men and women were 0.76 (95% CI 0.69–0.85) and 0.78 (95% CI 0.70–0.87), respectively. Most studies (n = 6) were of fair to good quality. This meta-analysis suggests that consumption of oat could reduce the risk for T2D and all-cause mortality, while no significant association was found for CVD. Future studies should address a lack of standardized methods in assessing overall oat intake and type of oat products, and investigate a dose-dependent response of oat products on cardiometabolic outcomes in order to introduce oat as preventive and treatment options for the public.
Incidence of Concussion and Time to Return-to-Play in the National Rugby League

Objectives: To examine the rates of concussion and recovery time over the course of 2 seasons of the National Rugby League (NRL). Design: Descriptive cohort study. Setting: The NRL match play concussion injury surveillance system. Participants: All NRL players who participated in the 2017 and 2018 season. Main Outcome Measures: The (1) frequency of sideline injury surveillance identified head impact events in real-time during the games, (2) frequency of head injury assessments conducted by the medical staff, (3) frequency of medically diagnosed concussions, (4) number of days to medical clearance to return-to-play, and (5) number of games missed after concussion. Main Results: There were 472 head injury assessments conducted during the games and 149 medically diagnosed concussions over the course of 2 NRL seasons (1 concussion every 2.70 games). The median number of days until medical clearance was 6 (M = 6.85, SD = 8.03, interquartile range = 4-7; range = 0-79 days). There was a statistically significant difference in the number of days to be medically cleared to return to full contact or match play between seasons (U = 3517.00, P = 0.001), and the percentage of players medically cleared to return-to-play at 5 days after injury was 60.6% in 2017 and 27.6% in 2018. Most players (87.9%) did not miss a game after injury. Conclusions: There is approximately one concussion sustained for every 3 games in the NRL. Most players are medically cleared to return-to-play in 4 to 7 days.
A Novel Missense Mutation in TNNI3K Causes Recessively Inherited Cardiac Conduction Disease in a Consanguineous Pakistani Family

Cardiac conduction disease (CCD), which causes altered electrical impulse propagation in the heart, is a life-threatening condition with high morbidity and mortality. It exhibits genetic and clinical heterogeneity with diverse pathomechanisms, but in most cases, it disrupts the synchronous activity of impulse-generating nodes and impulse-conduction underlying the normal heartbeat. In this study, we investigated a consanguineous Pakistani family comprised of four patients with CCD. We applied whole exome sequencing (WES) and co-segregation analysis, which identified a novel homozygous missense mutation (c.1531T>C;(p.Ser511Pro)) in the highly conserved kinase domain of the cardiac troponin I-interacting kinase (TNNI3K) encoding gene. The behaviors of mutant and native TNNI3K were compared by performing all-atom long-term molecular dynamics simulations, which revealed changes at the protein surface and in the hydrogen bond network. Furthermore, intra and intermolecular interaction analyses revealed that p.Ser511Pro causes structural variation in the ATP-binding pocket and the homodimer interface. These findings suggest p.Ser511Pro to be a pathogenic variant. Our study provides insights into how the variant perturbs the TNNI3K structure-function relationship, leading to a disease state. This is the first report of a recessive mutation in TNNI3K and the first mutation in this gene identified in the Pakistani population.