Miracle-dz/UniFAR-FTUs huggingface dataset:
The Association of Intra-Tumoral and Stromal Vitamin D Receptor (VDR) Expressions with Molecular Subtypes and Clinicopathological Factors in Breast Carcinoma

Objective: This study aimed to investigate the association between intra-tumoral and stromal VDR expressions with molecular subtypes and clinicopathological factors. Methods: A total of 75 formalin-fixed paraffin embedded tissue samples were stained using immunohistochemical methods. The VDR expressions were measured by counting brown-stained nuclei in intra-tumoral and stromal areas. The association of VDR expression with molecular subtypes and clinopathological factors was examined. Statistical analysis was performed by chi square tests. Results: High intra-tumoral VDR expression was found in carcinomas with luminal molecular subtypes (p=0.039) and low histological degrees (p=0.035). High VDR expression in the stroma was found in breast carcinomas with large tumor sizes. Conclusions: High intra-tumoral VDR expression is found in breast carcinomas with luminal subtypes and low histological grade (I/II). Both factors are known to have a good prognosis. These findings further strengthen the function of VDR as anti-tumorigenesis.
Consequences of partially recessive deleterious genetic variation for the evolution of inversions suppressing recombination between sex chromosomes

The evolution of suppressed recombination between sex chromosomes is widely hypothesized to be driven by sexually antagonistic selection (SA), where tighter linkage between the sex‐determining gene(s) and nearby SA loci is favored when it couples male‐beneficial alleles to the proto‐Y chromosome, and female‐beneficial alleles to the proto‐X. Despite limited empirical evidence, the SA selection hypothesis overshadows several alternatives, including an incomplete but often‐repeated “sheltering hypothesis” that suggests that expansion of the sex‐linked region (SLR) reduces homozygous expression of partially recessive deleterious mutations at selected loci. Here, we use population genetic models to evaluate the consequences of deleterious mutational variation for the evolution of neutral chromosomal inversions expanding the SLR on proto‐Y chromosomes. We find that SLR‐expanding inversions face a race against time: lightly loaded inversions are initially beneficial, but eventually become deleterious as they accumulate new mutations, and must fix before this window of opportunity closes. The outcome of this race is strongly influenced by inversion size, the mutation rate, and the dominance coefficient of deleterious mutations. Yet, small inversions have elevated fixation probabilities relative to neutral expectations for biologically plausible parameter values. Our results demonstrate that deleterious genetic variation can plausibly drive recombination suppression in small steps and would be most consistent with empirical patterns of small evolutionary strata or gradual recombination arrest.
Comparative high‐throughput analysis of sperm membrane proteins from crossbred bulls with contrasting fertility

The aim of the present study was to identify fertility associated sperm membrane proteins in crossbred bulls. Sperm membrane proteins from high‐ and low‐fertile Holstein Friesian crossbred bulls (n = 3 each) were subjected to high‐throughput liquid chromatography–mass spectrometry (LC–MS/MS) for comparative proteomic analysis. Proteomic profiling identified a total of 456 proteins in crossbred bull spermatozoa; it was found that 108 proteins were up regulated while 26 proteins were down regulated (>1.5‐folds) in spermatozoa from low‐ compared to high‐fertile bulls. Gene ontology classification revealed that upregulated proteins in low‐fertile bulls were involved in biological process such as oxidation–reduction process (p = 3.14E−06), fusion of sperm to egg plasma membrane (p = 7.51E−04), sperm motility (p = 0.03), and capacitation (p = 0.09), while down regulated proteins were associated with transport (p = 6.94E−04), superoxide metabolic process (p = 0.02), and tricarboxylic acid cycle (p = 0.04). KEGG pathway analysis revealed that oxidative phosphorylation and tricarboxylic acid cycle pathways are the most significantly affected pathway in low‐fertile bulls. It was concluded that expression of proteins associated with oxidative phosphorylation and tricarboxylic acid cycle pathways were altered in low‐fertile crossbred bulls, and expression levels of SPATA19, ELSPBP1, ACRBP, CLU, SUCLA2, and SPATC1 could aid in assessing potential fertility of crossbred bulls.
Mammalian D‐cysteine: A novel regulator of neural progenitor cell proliferation

D‐amino acids are being recognized as functionally important molecules in mammals. We recently identified endogenous D‐cysteine in mammalian brain. D‐cysteine is present in neonatal brain in substantial amounts (mM) and decreases with postnatal development. D‐cysteine binds to MARCKS and a host of proteins implicated in cell division and neurodevelopmental disorders. D‐cysteine decreases phosphorylation of MARCKS in neural progenitor cells (NPCs) affecting its translocation. D‐cysteine controls NPC proliferation by inhibiting AKT signaling. Exogenous D‐cysteine inhibits AKT phosphorylation at Thr 308 and Ser 473 in NPCs. D‐cysteine treatment of NPCs led to 50% reduction in phosphorylation of Foxo1 at Ser 256 and Foxo3a at Ser 253. We hypothesize that in the developing brain endogenous D‐cysteine is as a physiologic regulator of NPC proliferation by inhibiting AKT signaling mediated by Foxo1 and Foxo3a. Endogenous D‐cysteine may regulate mammalian neurodevelopment with roles in schizophrenia and Alzheimer's disease (AD).
FLT3 mutations in acute myeloid leukemia: a review focusing on clinically applicable drugs

FMS-like tyrosine kinase 3 (FLT3) mutations, the most frequently detected genetic aberrations in patients with acute myeloid leukemia (AML), are identified in approximately 30% of patients with newly diagnosed AML and are more common in patients with normal karyotypes. Since the discovery of FLT3 mutations in AML, clinical trials have been actively conducted in patients with FLT3 mutated AML, and FLT3 inhibitors have been introduced into clinical practice. The current standard treatment for patients with newly diagnosed FLT3-mutated AML is 7+3 induction chemotherapy combined with midostaurin. Additionally, gilteritinib is more effective than salvage chemotherapy for relapsed or refractory FLT3-mutated AML. Ongoing trials are expected to provide additional treatment options depending on the disease state and patient vulnerability. This review summarizes information on clinically available FLT3 inhibitors for the management of AML with FLT3 mutations.
Analysis of Precision Test for Digital Navy Gun Servo System

The test methods of angle deviation and full angle of tracking precision were analyzed for digital naval gun servo system.The angle deviation with typical SDC(1700/2 series) module was simulated by Matlab,and the results show that the inevitable measuring error exists when the traditional test method of angle deviation being used in naval gun servo system with SDC module.We proposed a new method which uses the test method of full angle and error elimination principle to transform and test the input signal of naval gun servo system.The simulation indicates that the new method can reduce the precision test error of servo system greatly.
Prognostic value of high FOXO3a expression in patients with solid tumors: A meta-analysis and systematic review

Background FOXO3a (previously termed FKHRL1), plays an evolutionarily conserved role in the control of biological process, including DNA damage, apoptosis, and cell cycle regulation. However, the role of FOXO3a in tumors remains controversial. This meta-analysis was conducted to evaluate the prognostic value of FOXO3a expression in patients with solid tumors. Methods A systematic literature search of the PubMed, Web of Science, Embase, and Cochrane Library databases was performed. Eligible publications on FOXO3a and cancer prognosis were collected and screened according to the eligibility criteria. The combined odds ratios (ORs) or hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were used to assess the prognostic value of FOXO3a. Stata 12.0 software was used for statistical analysis. Results A total of 4058 patients from 21 articles on a variety of solid tumors were included. Meta-analysis showed that the increased FOXO3a expression level was associated with longer overall survival (HR = 0.62; 95% CI: 0.46–0.85). The pooled ORs indicated high expression level of FOXO3a in tumors was significantly associated with lymph node metastasis (OR = 0.46; 95% CI: 0.30–0.71), TNM stage (OR = 0.37; 95% CI: 0.25–0.54), tumor differentiation (OR = 0.46; 95% CI: 0.26–0.80), distant metastasis (OR = 0.44; 95% CI: 0.32–0.61), and age (OR = 1.28; 95% CI: 1.08–1.51). However, we did not observe a significant correlation between the high expression of FOXO3a and sex or tumor size. Conclusions The high expression level of FOXO3a was associated with better clinical outcomes in solid tumors. FOXO3a may therefore serve as a potential prognostic biomarker and a promising molecular target.
Using machine learning for the personalised prediction of revision endoscopic sinus surgery

Background Revision endoscopic sinus surgery (ESS) is often considered for chronic rhinosinusitis (CRS) if maximal conservative treatment and baseline ESS prove insufficient. Emerging research outlines the risk factors of revision ESS. However, accurately predicting revision ESS at the individual level remains uncertain. This study aims to examine the prediction accuracy of revision ESS and to identify the effects of risk factors at the individual level. Methods We collected demographic and clinical variables from the electronic health records of 767 surgical CRS patients ≥16 years of age. Revision ESS was performed on 111 (14.5%) patients. The prediction accuracy of revision ESS was examined by training and validating different machine learning models, while the effects of variables were analysed using the Shapley values and partial dependence plots. Results The logistic regression, gradient boosting and random forest classifiers performed similarly in predicting revision ESS. Area under the receiving operating characteristic curve (AUROC) values were 0.744, 0.741 and 0.730, respectively, using data collected from the baseline visit until six months after baseline ESS. The length of time during which data were collected improved the prediction performance. For data collection times of 0, 3, 6 and 12 months after baseline ESS, AUROC values for the logistic regression were 0.682, 0.715, 0.744 and 0.784, respectively. The number of visits before or after baseline ESS, the number of days from the baseline visit to the baseline ESS, patient age, CRS with nasal polyps (CRSwNP), asthma, non-steroidal anti-inflammatory drug exacerbated respiratory disease and immunodeficiency or suspicion of it all associated with revision ESS. Patient age and number of visits before baseline ESS carried non-linear effects for predictions. Conclusions Intelligent data analysis identified important predictors of revision ESS at the individual level, such as the frequency of clinical visits, patient age, Type 2 high diseases and immunodeficiency or a suspicion of it.
Platelet-targeted thrombolysis for treatment of acute ischemic stroke

Key Points • Platelet-targeted thrombolysis with SCE5-scuPA achieved favorable outcomes vs tenecteplase-tPA in 2 mouse models of ischemic stroke. • Thrombolytic strategies that harness activated platelets for drug targeting better suit the platelet-rich nature of stroke-causing thrombi.
Bone regeneration in rat using polycaprolactone/gelatin/epinephrine scaffold

Abstract Solid supports like the extracellular matrix network are necessary for bone cell attachment and start healing in the damaged bone. Scaffolds which are made of different materials are widely used as a supportive structure in bone tissue engineering. In the current study, a 3D polycaprolactone/gelatin bone scaffold was developed by blending electrospinning and freeze-drying techniques for bone tissue engineering. To improve the efficiency of the scaffold, different concentrations of epinephrine (EP) due to its effect on bone healing were loaded. Fabricated scaffolds were characterized by different tests such as surface morphology, FTIR, porosity, compressive strength, water contact angle, and degradation rate. The interaction between prepared scaffolds and blood and cells was evaluated by hemolysis, and MTT test, respectively, and bone healing was evaluated by a rat calvaria defect model. Based on the results, the porosity of scaffolds was about 75% and by adding EP, mechanical strength decreased while due to the hydrophilic properties of it, degradation rate increased. In vivo and in vitro studies showed the best cell proliferation and bone healing were in PCL/gelatin/EP1% treated group. These results showed the positive effect of fabricated scaffold on osteogenesis and bone healing and the possibility of using it in clinical trials.
Suppression of radio-frequency interference in HFGW radar based on eigen decomposition

The performance of HF ground wave radar may be affected by all kinds of radio-frequency interferences (RFI) . Take a chirp radar as example, the narrowband RFI with impulsive characteristic in range-Doppler map is analyzed, and eigen decomposition method is employed to extinct the interferences from the Doppler map. Computer simulations and experiments show that the method is feasiable.
Experimental evolution reveals differential evolutionary trajectories in male and female activity levels in response to sexual selection and metapopulation structure

Behavior is central to interactions with the environment and thus has significant consequences for individual fitness. Sexual selection and demographic processes have been shown to independently shape behavioral evolution. Although some studies have tested the simultaneous effects of these forces, no studies have investigated their interplay in behavioral evolution. We applied experimental evolution in the seed beetle Callosobruchus maculatus to investigate, for the first time, the interactive effects of sexual selection intensity (high [polygamy] vs. minimal [enforced monogamy]) and metapopulation structure (yes/no) on the evolution of movement activity, a crucial behavior involved in multiples functions (e.g., dispersal, predator avoidance, or resource acquisition) and thus, closely related to fitness. We found that the interactive effects of the selection regimes did not affect individual activity, which was assayed under two different environments (absence vs. presence of conspecific cues from both sexes). However, contrasting selection regimes led to sex‐ and context‐dependent divergence in activity. The relaxation of sexual selection favored an increase in female, but not male, movement activity that was consistent between environmental contexts. In contrast, selection associated with the presence/absence of metapopulation structure led to context‐dependent responses only in male activity. In environments containing cues from conspecifics, males from selection lines under population subdivision showed increased levels of activity compared to those assayed in an environment devoid of conspecifics cues, whereas the opposite was true for males from panmictic lines. These results underscore that both the effects of sexual selection and population spatial structure may be crucial in shaping sex‐specific behavioral evolution.
Age and sex associations of SARS-CoV-2 antibody responses post BNT162b2 vaccination in healthcare workers: A mixed effects model across two vaccination periods

This study aimed to examine the associations with epidemiological, behavioral and clinical parameters of IgG antibody responses against the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after immunization with two doses of the BNT162b2 vaccine in a cohort of healthcare workers (HCWs, n = 439) in Greece. We used a mixed effects model to investigate the potential associations of antibody levels one and three months after vaccination and examined by bootstrapping t-tests the putative effects of gender and age for each period. We also employed exact tests of independence in R × C contingency tables to explore associations between behavioral and gender variables with vaccinations side effects. We found significant differences between males and females as well as between subjects in the youngest (21–30 years) and the older age groups in both study periods. We also detected a decrease in titers with age and time. Males had steeper elimination rates across the age span in both periods, in contrast to females who exhibited a softer elimination titer rate with age in the first period and almost constant titers in the second. Concerning side effects, we found a significant association between pain at the injection site and female sex. Hence, our real-world data analyses revealed potentially important clues into the associations of antibody responses to SARS-CoV-2 spike. We discuss the importance of these findings in view of current mass vaccination perspectives and provide useful clues for the design and optimal timing of booster doses for COVID-19.
Cell wall-localized BETA-XYLOSIDASE4 contributes to immunity of Arabidopsis against Botrytis cinerea

Abstract Plant cell walls constitute physical barriers that restrict access of microbial pathogens to the contents of plant cells. The primary cell wall of multicellular plants predominantly consists of cellulose, hemicellulose, and pectin, and its composition can change upon stress. BETA-XYLOSIDASE4 (BXL4) belongs to a seven-member gene family in Arabidopsis (Arabidopsis thaliana), one of which encodes a protein (BXL1) involved in cell wall remodeling. We assayed the influence of BXL4 on plant immunity and investigated the subcellular localization and enzymatic activity of BXL4, making use of mutant and overexpression lines. BXL4 localized to the apoplast and was induced upon infection with the necrotrophic fungal pathogen Botrytis cinerea in a jasmonoyl isoleucine-dependent manner. The bxl4 mutants showed a reduced resistance to B. cinerea, while resistance was increased in conditional overexpression lines. Ectopic expression of BXL4 in Arabidopsis seed coat epidermal cells rescued a bxl1 mutant phenotype, suggesting that, like BXL1, BXL4 has both xylosidase and arabinosidase activity. We conclude that BXL4 is a xylosidase/arabinosidase that is secreted to the apoplast and its expression is upregulated under pathogen attack, contributing to immunity against B. cinerea, possibly by removal of arabinose and xylose side-chains of polysaccharides in the primary cell wall.
Dysbiosis of the Female Murine Gut Microbiome Exacerbates Neutrophil-mediated Vascular Allograft Injury by Affecting Immunoregulation by Acetate

Background. The gut microbiota affects immune responses that cause organ transplant rejection, but the mechanisms by which this occurs remain poorly understood. Methods. We have examined, in a murine model, how disruption of the gut microbiota with antibiotics early in life alters this microbial community later in life to affect immune responses that injure vascular allografts. Results. Analysis of 16S rRNA and whole genome sequencing of the gut microbiota demonstrated that early life disruption of this microbial community with antibiotics caused a reduction in taxa and enzymatic genes involved in the synthesis of acetate, an immunoregulatory metabolite in mice and humans. When allograft vascular injury was examined, early life disruption of the gut microbiota increased neutrophil accumulation and related medial injury of transplanted arteries. Normalizing the gut microbiota by co-housing and oral administration of acetate prevented neutrophil-mediated vascular allograft injury. Conclusions. Dysbiosis of the gut microbiome that reduces its production of the immunoregulatory metabolite acetate exacerbates neutrophil-mediated allograft vascular injury.
Validation pipeline for machine learning algorithm assessment for multiple vendors

A standardized objective evaluation method is needed to compare machine learning (ML) algorithms as these tools become available for clinical use. Therefore, we designed, built, and tested an evaluation pipeline with the goal of normalizing performance measurement of independently developed algorithms, using a common test dataset of our clinical imaging. Three vendor applications for detecting solid, part-solid, and groundglass lung nodules in chest CT examinations were assessed in this retrospective study using our data-preprocessing and algorithm assessment chain. The pipeline included tools for image cohort creation and de-identification; report and image annotation for ground-truth labeling; server partitioning to receive vendor “black box” algorithms and to enable model testing on our internal clinical data (100 chest CTs with 243 nodules) from within our security firewall; model validation and result visualization; and performance assessment calculating algorithm recall, precision, and receiver operating characteristic curves (ROC). Algorithm true positives, false positives, false negatives, recall, and precision for detecting lung nodules were as follows: Vendor-1 (194, 23, 49, 0.80, 0.89); Vendor-2 (182, 270, 61, 0.75, 0.40); Vendor-3 (75, 120, 168, 0.32, 0.39). The AUCs for detection of solid (0.61–0.74), groundglass (0.66–0.86) and part-solid (0.52–0.86) nodules varied between the three vendors. Our ML model validation pipeline enabled testing of multi-vendor algorithms within the institutional firewall. Wide variations in algorithm performance for detection as well as classification of lung nodules justifies the premise for a standardized objective ML algorithm evaluation process.
Advances in laboratory assessment of thrombosis and hemostasis

Technologies in laboratory diagnostics are changing fast with progress in understanding and therapy of diseases. Unfortunately, new analyzers are often needed to be installed in a clinical laboratory to implement such techniques. The demand for new hardware is a bottleneck in improving the diagnostic services for many facilities with limited resources. In this regard, hemostasis laboratories take a slightly different position. Because many in vitro diagnostic tests target the functional aspects of hemostasis, further meaningful information can be obtained from the same analyzers as in current use. Automated coagulometers are good candidates for such further utilization. Clot waveform analysis is a leading example. Behind the simple values reported as clotting time, clotting curves exist that represent the process of fibrin clot formation. Clot waveform analysis examines the clotting curves and derives new parameters other than clotting times. The clot waveform parameters are now in active use in assessing the hemostatic potential of hemorrhagic patients. Clinical application of coagulometers can also be widened by modifying the reagent formulation. For example, the chromogenic factor VIII assay with bovine source reagent compositions has recently been introduced for hemophilia A patients on emicizumab prophylaxis. Also, new immunoturbidimetric functional assays for von Willebrand factor have been developed recently. Thus, new clinically relevant information can be mined from the automated coagulometers that are based on old technology.