Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of 1,3,4-oxadiazoles as tubulin-targeted anticancer agents: a combined field-based 3D-QSAR, pharmacophore model-based virtual screening, molecular docking, molecular dynamics simulation, and density functional theory calculation approach.

Cancer is one of the most prominent causes of death worldwide and tubulin is a crucial protein of cytoskeleton that maintains essential cellular functions including cell division as well as cell signalling, that makes an attractive drug target for cancer drug development. 1,3,4-oxadiazoles disrupt microtubule causing G2-M phase cell cycle arrest and provide anti-proliferative effect. In this study, field-based 3D-QSAR models were developed using 62 bioactive anti-tubulin 1,3,4-oxadiazoles. The best model characterized by PLS factor 7 was rigorously validated using various statistical parameters. Generated 3D-QSAR model having high degree of confidence showed favourable and unfavourable contours around 1,3,4-oxadiazole core that assisted in defining proper spatial positioning of desired functional groups for better bioactivity. A five featured pharmacophore model (AAHHR_1) was developed using same ligand library and validated through enrichment analysis (BEDROC160.9 value = 0.59, Average EF 1% = 27.05, and AUC = 0.74). Total 30,212 derivatives of 1,3,4-oxadiazole obtained from PubChem database was prefiltered through validated pharmacophore model and docked in XP mode on binding cavity of tubulin protein (PDB code: 1SA0) which led into the identification of 11 HITs having docking scores between -7.530 and -9.719 kcal/mol while the reference compound Colchicine exerted docking score of -7.046 kcal/mol. Following the analysis of MM-GBSA and ADME studies, HIT1 and HIT4 emerged as the two promising hits. To verify their thermodynamic stability at the target site, molecular dynamic simulations were carried out. Both HITs were further subjected to DFT analysis to determine their HOMO-LUMO energy gap for ensuring their biological feasibility. Finally, molecular docking based structural exploration for 1,3,4-oxadiazoles to set up a lead of Formula I for further advancements of tubulin polymerization inhibitors as anti-cancer agents.Communicated by Ramaswamy H. Sarma.
New progress in an old debate? Applying the DSM‐5 criteria to assess traumatic events and stressor‐related disorders in cancer survivors

The rather broad definition of medical trauma within DSM‐IV has contributed to long‐lasting debates on the applicability of Posttraumatic Stress Disorder (PTSD) in oncological patients and its differentiation from Adjustment Disorder (AjD) which results from non‐traumatic critical life events. The DSM‐5 criteria have introduced a narrower definition of medical traumatization. However, studies on updated prevalence rates in cancer patients are missing.
Ultrasonic Bone Scalpel versus Conventional Methods for Osteotomy in Posterior Surgery for Cervical Spondylotic Myelopathy: A Review and Meta-Analysis

Posterior methods for cervical myelopathy include laminoplasty and laminectomy with/without fusion. A more recent innovation in these treatments is the use of an ultrasonic bone shaver for osteotomy. In this study, we examined the perioperative results after laminectomy/laminoplasty between conventional methods (rongeur/high-speed drill) vs. piezosurgery-based instruments. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed and the search was performed on four databases (PubMed, Scopus, EMBASE, and Google Scholar). Seven comparative studies were chosen after thorough screening by the authors and a meta-analysis was performed between piezosurgery and conventional technique to ascertain intraoperative and postoperative results after laminectomy/laminoplasty. The analysis includes four retrospective cohort studies and three randomized controlled trials published between 2015 and 2022. The mean age ranged from 55.5 to 64.2 years. Blood loss was significantly reduced in the piezosurgery group, other findings were not significant. On subgroup analysis, laminoplasty dramatically reduced blood loss and the rate of iatrogenic dural rips in the piezosurgery group. The use of ultrasonic bone shaver for osteotomy in cervical spondylotic myelopathy is related to significantly decreased blood loss and no significant increase in postoperative drainage, operative time, complication rate, and functional outcomes as compared to traditional techniques. We noticed significantly reduced blood and rate of dural tears in the laminoplasty subgroup with the use of ultrasonic bone shaver, which was not mirrored in the laminectomy subgroup. Careful intraoperative handling of the instrument can help prevent iatrogenic dural tears and nerve damage.
EXPLORING THE ROLE OF CENTRAL VENOUS OXYGEN SATURATION IN THE EVALUATION AND MANAGEMENT OF SEVERE HYPOXEMIA IN MECHANICALLY VENTILATED PATIENTS

ABSTRACT Background: Although central venous oxygen saturation (ScvO2) has been used as an endpoint for the treatment of circulatory shock, its role in guiding the evaluation and treatment of patients with severe hypoxemia remains to be assessed. The aim of this study was to assess the incidence of low ScvO2 in a cohort of hypoxemic patients and the association of this finding with differences in clinical management and patient outcomes. Methods: Retrospective review of data from adult intensive care unit patients with hypoxemia who required invasive mechanical ventilation for over 24 h and had at least one ScvO2 measured within 6 h of a PaO2/FiO2 ratio <200. Results: Of 442 mechanically ventilated patients with severe hypoxemia, 249 (56%) had an ScvO2 <70%. When compared with patients with ScvO2 ≥70%, those with low ScvO2 had worse systemic oxygenation and hemodynamic parameters and were more likely to receive red blood cell transfusions (31.7% vs. 18.1%, P = 0.001), epinephrine (27.3% vs. 16.6%, P = 0.007), and inodilators. Outcomes such as median intensive care unit length of stay (7.5 vs. 8.3 days, P = 0.337) and hospital mortality (39.8% vs. 35.7%, P = 0.389) were not different between groups. When stratified by the central venous-to-arterial CO2 difference (∆PCO2), patients with a low ScvO2 and normal ∆PCO2 had lower median PaO2 and hemoglobin levels and received more red blood cell transfusions, whereas those with an increased ∆PCO2 had a lower pulse pressure and cardiac index and were more likely to receive epinephrine and milrinone. Conclusion: Low ScvO2 is frequently observed in mechanically ventilated patients with severe hypoxemia, and these patients receive different interventions. Clinicians often use therapies targeting systemic oxygen delivery to correct low ScvO2. Prospective research is needed to identify patients with severe hypoxemia that might benefit from interventions targeting systemic oxygen delivery.
Metacognitive bias resulting from trade-off between local and global motion signals

Visual confidence generally depends on performance in targeted perceptual tasks. However, it remains unclear how factors unrelated to performance affect confidence. Given the hierarchical nature of visual processing, both local and global stimulus features can influence confidence, but their strengths of influence remain unknown. To address this question, we independently manipulated the local contrast signals and the global coherence signals in a multiple-aperture motion pattern. The drifting-Gabor elements were individually manipulated to give rise to a coherent global motion percept. In both dichotomous direction-discrimination task (Experiment 1) and analog direction-judgment task (Experiment 2), we found stimulus-dependent biases in metacognition despite matched perceptual performance. Specifically, participants systematically gave higher confidence ratings to an incoherent pattern with clear elements (i.e., strong local but weak global signals) than a coherent pattern with noisy elements (i.e., weak local but strong global signals). We did not find any systematic effects of local/global stimulus features on metacognitive sensitivity. Model comparisons show that variation in local/global signals in the stimulus should be considered a factor influencing confidence, even after controlling for the effects of performance. Our results suggest that the metacognitive system, when generating confidence for a perceptual task, puts more weights on local than global signals.
Characterization and designing of an SAM riboswitch to establish a high‐throughput screening platform for SAM overproduction in Saccharomyces cerevisiae

S‐adenosyl‐ l‐methionine (SAM) is a high‐value compound widely used in the treatment of various diseases. SAM can be produced through fermentation, but further enhancing the microbial production of SAM requires novel high‐throughput screening methods for rapid detection and screening of mutant libraries. In this work, an SAM‐OFF riboswitch capable of responding to the SAM concentration was obtained and a high‐throughput platform for screening SAM overproducers was established. SAM synthase was engineered by semirational design and directed evolution, which resulted in the SAM2S203F,W164R,T251S,Y285F,S365R mutant with almost twice higher catalytic activity than the parental enzyme. The best mutant was then introduced into Saccharomyces cerevisiae BY4741, and the resulting strain BSM8 produced a sevenfold higher SAM titer in shake‐flask fermentation, reaching 1.25 g L−1. This work provides a reference for designing biosensors to dynamically detect metabolite concentrations for high‐throughput screening and the construction of effective microbial cell factories.
Moho depth variation in the Baltic Shield from analysis of converted waves

Abstract Teleseismic data recorded at 52 permanent broad-band seismic stations in the Swedish National Seismic Network have been used to map Moho depth variation in the Baltic Shield. We use the receiver function technique to isolate signals associated with P to S conversion at the base of the crust. The delay times of this phase, and of crustal reverberations, are used to constrain Moho depth and crustal average V P /V S . For a majority of the stations in the study, well constrained results could be obtained and these are discussed in comparison to previous estimates of Moho depth in the area. Our results are found to be in very good agreement with previous estimates where these exist. For large parts of the area, estimates of Moho depth have not been available until now and the results of the present study serve as a valuable complement to constrain crustal thickness variation in the Baltic shield.
Combining pharmacometric models with predictive and prognostic biomarkers for precision therapy in Crohn's disease: A case study of brazikumab

Pharmacometric models were used to investigate the utility of biomarkers in predicting the efficacy (Crohn's Disease Activity Index [CDAI]) of brazikumab and provide a data‐driven framework for precision therapy for Crohn's disease (CD). In a phase IIa trial in patients with moderate to severe CD, treatment with brazikumab, an anti‐interleukin 23 monoclonal antibody, was associated with clinical improvement. Brazikumab treatment effect was determined to be dependent on the baseline IL‐22 (BIL22) or baseline C‐reactive protein (BCRP; predictive biomarkers), and placebo effect was found to be correlated with the baseline CDAI (a prognostic biomarker). A maximal total inhibition on CDAI input function of 50.6% and 42.4% was predicted for patients with extremely high BIL22 or BCRP, compared to a maximal total inhibition of 20.9% and 17.8% for patients with extremely low BIL22 or BCRP, respectively, which were mainly due to the placebo effect. We demonstrated that model‐derived baseline biomarker levels that achieve 50% of maximum unbound systemic concentration of 22.8 pg/mL and 8.03 mg/L for BIL22 and BCRP as the cutoffs to select subpopulations can effectively identify high‐response subgroup patients with improved separation of responders when compared to using the median values as the cutoff. This work exemplifies the utility of pharmacometrics to quantify biomarker‐driven responses in biologic therapies and distinguish between predictive and prognostic biomarkers, complementing clinical efforts of identifying subpopulations with higher likelihood of response to brazikumab.
Abnormal individualized peak functional connectivity toward potential repetitive transcranial magnetic stimulation treatment of autism spectrum disorder

Functional connectivity (FC) derived from resting‐state functional magnetic resonance imaging has been widely applied to guide precise repetitive transcranial magnetic stimulation (rTMS). The left, right, and bilateral dorsolateral prefrontal cortices (DLPFC) have been used as rTMS treatment target regions for autism spectrum disorder (ASD), albeit with moderate efficacy. Thus, we aimed to develop an individualized localization method for rTMS treatment of ASD. We included 266 male ASDs and 297 male typically‐developed controls (TDCs) from the Autism Brain Imaging Data Exchange Dataset. The nucleus accumbens (NAc) was regarded as a promising effective region, which was used as a seed and individualized peak FC strength in the DLPFC was compared between ASD and TDC. Correlation analysis was conducted between individualized peak FC strength and symptoms in ASD. We also investigated the spatial distribution of individualized peak FC locations in the DLPFC and conducted voxel‐wise analysis to compare NAc‐based FC between the two groups. ASD showed stronger peak FC in the right DLPFC related to TDC (Cohen's d = −.19, 95% CI: −0.36 to −0.03, t = −2.30, p = .02). Moreover, negative correlation was found between the peak FC strength in the right DLPFC and Autism Diagnostic Observation Schedule (ADOS) scores, which assessed both the social communication and interaction (r = −.147, p = .04, uncorrected significant), and stereotyped behaviors and restricted interests (r = −.198, p = .02, corrected significant). Peak FC locations varied substantially across participants. No significant differences in NAc‐based FC in the DLPFC were found in the voxel‐wise comparison. Our study supports the use of individualized peak FC‐guided precise rTMS treatment of male ASD. Moreover, stimulating the right DLPFC might alleviate core symptoms of ASD.
The Value of Predicting Human Epidermal Growth Factor Receptor 2 Status in Adenocarcinoma of the Esophagogastric Junction on CT-Based Radiomics Nomogram

Purpose We developed and validated a CT-based radiomics nomogram to predict HER2 status in patients with adenocarcinoma of esophagogastric junction (AEG). Method A total of 101 patients with HER2-positive (n=46) and HER2-negative (n=55) esophagogastric junction adenocarcinoma (AEG) were retrospectively analyzed. They were then randomly divided into a training cohort (n=70) and a verification cohort (n=31). The radiomics features were obtained from the portal phase of the CT enhanced scan. We used the least absolute shrinkage and selection operator (LASSO) logistic regression method to select the best radiomics features in the training cohort, combined them linearly, and used the radiomics signature formula to calculate the radiomics score (Rad-score) of each AEG patient. A multivariable logistic regression method was applied to develop a prediction model that incorporated the radiomics signature and independent risk predictors. The prediction performance of the nomogram was evaluated using the training and validation cohorts. Result In the training (P<0.001) and verification groups (P<0.001), the radiomics signature combined with seven radiomics features was significantly correlated with HER2 status. The nomogram composed of CT-reported T stage and radiomics signature showed very good predictive performance for HER2 status. The area under the curve (AUC) of the training cohort was 0.946 (95% CI: 0.919–0.973), and that of the validation group was 0.903 (95% CI: 0.847–0.959). The calibration curve of the radiomics nomogram showed a good degree of calibration. Decision-curve analysis revealed that the radiomics nomogram was useful. Conclusion The nomogram CT-based radiomics signature combined with CT-reported T stage can better predict the HER2 status of AEG before surgery. It can be used as a non-invasive prediction tool for HER2 status and is expected to guide clinical treatment decisions in clinical practice, and it can assist in the formulation of individualized treatment plans.
Breaking Down Machismo: Shifting Definitions and Embodiments of Latino Manhood in Middle-Aged Latino Men

There is a notable gap in empirical research regarding how Latino men define and demonstrate machismo, masculinity, and manhood as well as the behavioral consequences associated with these concepts. In our study, we employed a phenomenological thematic approach to analyze 20 semi-structured individual interviews conducted with Latino men residing in South Florida. Our primary objectives were twofold: to examine (1) how do Latino men ages 35 to 60 years describe what it means to be a man and (2) what are the attributes that these men seek to show others that demonstrate their character, cultural values, and gender identity. Findings suggest that Latino men understood expectations associated with machismo and explained that fulfillment of their role as provider, protector, and head of the family was important to their perception of self. While some participants reported a desire to embody characteristics associated with traditional machismo, others strived to demonstrate character, familism, and respect and to provide financial and other instrumental support to their families. Participants reported that their transition into middle age was accompanied by a shift in their perspectives on gender roles, moving away from rigid patriarchal views. Exposure to a more fluid and flexible approach to manhood offered relief from the pressures associated with inflexible manifestations of machismo, which can have negative social, behavioral, and physical health implications. The implications of our research extend to the conceptualization of gender ideals, highlighting the need to incorporate intersectionality, role strain, precarious manhood, and culturally specific notions of manhood as foundational elements in this discourse.
Cytidine deaminase status as a marker of response to azacytidine treatment in MDS and AML patients

Azacitidine (Aza) is a mainstay of treatment for patients with acute myeloid leukaemia (AML) ineligible for induction chemotherapy and other high‐risk myelodysplastic syndromes (MDS). Only half of patients respond, and almost all will eventually relapse. There are no predictive markers of response to Aza. Aza is detoxified in the liver by cytidine deaminase (CDA). Here, we investigated the association between CDA phenotype, toxicity and efficacy of Aza in real‐world adult patients. Median overall survival (OS) was 15 months and 13 months in AML and high‐risk MDS patients respectively. In addition, our data suggest that delaying Aza treatment was not associated with lack of efficacy and should not be considered a signal to switch to an alternative treatment. Half of the patients had deficient CDA activity (i.e. <2 UA/mg), with a lower proportion of deficient patients in MDS patients (34%) compared to AML patients (67%). In MDS patients, CDA deficiency correlated with longer landmark OS (14 vs. 8 months; p = 0.03), but not in AML patients. Taken together, our data suggest that CDA is an independent covariate and may therefore be a marker for predicting clinical outcome in MDS patients treated with Aza.
Evidence of introgression, ecological divergence and adaptation in Asterias sea stars

Hybrid zones are important windows into the evolutionary dynamics of populations, revealing how processes like introgression and adaptation structure population genomic variation. Importantly, they are useful for understanding speciation and how species respond to their environments. Here, we investigate two closely related sea star species, Asterias rubens and A. forbesi, distributed along rocky European and North American coastlines of the North Atlantic, and use genome‐wide molecular markers to infer the distribution of genomic variation within and between species in this group. Using genomic data and environmental niche modelling, we document hybridization occurring between northern New England and the southern Canadian Maritimes. We investigate the factors that maintain this hybrid zone, as well as the environmental variables that putatively drive selection within and between species. We find that the two species differ in their environmental niche breadth; Asterias forbesi displays a relatively narrow environmental niche while conversely, A. rubens has a wider niche breadth. Species distribution models accurately predict hybrids to occur within environmental niche overlap, thereby suggesting environmental selection plays an important role in the maintenance of the hybrid zone. Our results imply that the distribution of genomic variation in North Atlantic sea stars is influenced by the environment, which will be crucial to consider as the climate changes.
Streamlined Data Fusion: Unleashing the Power of Linear Combination with Minimal Relevance Judgments

Linear combination is a potent data fusion method in information retrieval tasks, thanks to its ability to adjust weights for diverse scenarios. However, achieving optimal weight training has traditionally required manual relevance judgments on a large percentage of documents, a labor-intensive and expensive process. In this study, we investigate the feasibility of obtaining near-optimal weights using a mere 20\%-50\% of relevant documents. Through experiments on four TREC datasets, we find that weights trained with multiple linear regression using this reduced set closely rival those obtained with TREC's official"qrels. "Our findings unlock the potential for more efficient and affordable data fusion, empowering researchers and practitioners to reap its full benefits with significantly less effort.
Beyond the mixture of generalized Pauli dephasing channels

In recent times, there has been a growing scholarly focus on investigating the intricacies of quantum channel mixing. It has been commonly believed, based on intuition in the literature, that every generalized Pauli channel with dimensionality $d$ could be represented as a convex combination of $(d+1)$ generalized Pauli dephasing channels (see [Phys. Rev. A 103, 022605 (2021)] as a reference). To our surprise, our findings indicate the inaccuracy of this intuitive perspective. This has stimulated our interest in exploring the properties of convex combinations of generalized Pauli channels, beyond the restriction to just $(d+1)$ generalized Pauli dephasing channels. We demonstrate that many previously established properties still hold within this broader context. For instance, any mixture of invertible generalized Pauli channels retains its invertibility. It's worth noting that this property doesn't hold when considering the Weyl channels setting. Additionally, we demonstrate that every Pauli channel (for the case of $d=2$) can be represented as a mixture of $(d+1)$ Pauli dephasing channels, but this generalization doesn't apply to higher dimensions. This highlights a fundamental distinction between qubit and general qudit cases. In contrast to prior understanding, we show that non-invertibility of mixed channels is not a prerequisite for the resulting mapping to constitute a Markovian semigroup.