Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential Biomarkers for Early Diagnosis, Evaluation, and Prognosis of Sepsis-Induced Coagulopathy

Sepsis-induced coagulopathy (SIC) is a life-threatening complication characterized by the systemic activation of coagulation in sepsis. The diagnostic criteria of SIC consist of three items, including Sequential Organ Failure Assessment (SOFA) score, platelet count, and prothrombin time (PT)-international normalized ratio (INR). SIC has a high prevalence and it can lead to a higher mortality rate and longer length of hospital and ICU stay. Thus, the early detection of SIC is extremely important. It is unfortunate that there is still no precise biomarker for early diagnosis and assessment of the prognosis of SIC. We reviewed the current literature and discovered that some potential biomarkers, such as soluble thrombomodulin (sTM), thrombin–antithrombin complex (TAT), tissue plasminogen activator-inhibitor complex (t-PAIC), α2-plasmin inhibitor-plasmin complex (PIC), C-type lectin-like receptor 2 (CLEC-2), neutrophil extracellular traps (NETs), prothrombin fragment 1.2 (F1.2), Angiopoietin-2 (Ang-2), plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be useful for early diagnosis, evaluation, and prognosis of SIC. Early initiation of treatment without missing any therapeutic opportunities may improve SIC patients’ prognosis. Further large-scale clinical studies are still needed to confirm the role of these biomarkers in the diagnosis and prognosis assessment of SIC.
Sequencing‐based analysis of clonal evolution of 25 mantle cell lymphoma patients at diagnosis and after failure of standard immunochemotherapy

Our knowledge of genetic aberrations, that is, variants and copy number variations (CNVs), associated with mantle cell lymphoma (MCL) relapse remains limited. A cohort of 25 patients with MCL at diagnosis and the first relapse after the failure of standard immunochemotherapy was analyzed using whole‐exome sequencing. The most frequent variants at diagnosis and at relapse comprised six genes: TP53, ATM, KMT2D, CCND1, SP140, and LRP1B. The most frequent CNVs at diagnosis and at relapse included TP53 and CDKN2A/B deletions, and PIK3CA amplifications. The mean count of mutations per patient significantly increased at relapse (n = 34) compared to diagnosis (n = 27). The most frequent newly detected variants at relapse, LRP1B gene mutations, correlated with a higher mutational burden. Variant allele frequencies of TP53 variants increased from 0.35 to 0.76 at relapse. The frequency and length of predicted CNVs significantly increased at relapse with CDKN2A/B deletions being the most frequent. Our data suggest, that the resistant MCL clones detected at relapse were already present at diagnosis and were selected by therapy. We observed enrichment of genetic aberrations of DNA damage response pathway (TP53 and CDKN2A/B), and a significant increase in MCL heterogeneity. We identified LRP1B inactivation as a new potential driver of MCL relapse.
Monte Carlo Techniques in Planning

The Monte Carlo Tree Search (MCTS) algorithm has recently proved to be able to solve difficult problems in the field of optimization as well as game-playing. It has been able to address several problems that no conventional techniques have been able to solve efficiently. In this thesis we investigate possible ways to use MCTS in the field of planning and scheduling. We analyze the problem theoretically trying to identify possible difficulties when using MCTS in this field. We propose the solutions to these problems based on a modification of the algorithm and preprocessing the planning domain. We present the techniques we have developed for these tasks and we combine them into an applicable algorithm. We specialize the method for a specific kind of planning problems the transportation problems. We compare our planner with other planning system.
Hypoxia induces a glycolytic complex in intestinal epithelial cells independent of HIF-1-driven glycolytic gene expression

Significance In hypoxia, cells undergo a metabolic switch toward an enhanced rate of glycolysis. This has important implications for cell behavior, phenotype, and fate in both cancerous and healthy cells. Here, we describe a mechanism by which hypoxia, in addition to increasing glycolytic enzyme expression via HIF-1α (hypoxia-inducible factor-1α), promotes glycolysis via the nontranscriptional formation of a metabolic complex in human intestinal epithelial cells.
Risk of Reintervention or Postoperative Bleeding after Laparoscopy for Benign Gynecological Disease: A Clinical Prediction Model

Objective: The objective of the study was to develop a clinically applicable prediction tool to early seek for postoperative major complications after laparoscopic surgery for benign pathologies. Design: Retrospective analysis of prospectively collected data was performed. Setting: The study was conducted at Tertiary Care University Hospital. Participants: The participants of this study were reproductive-aged women undergoing laparoscopy for benign conditions. Methods: Anamnestic, intraoperative, and postoperative characteristics from January 2019 to December 2021 were retrospectively reviewed. Patients with postoperative complications (reintervention or postoperative bleeding) were matched in a 1:2 ratio with women with same surgical indications without complications. Cases and controls were matched for preoperative hemoglobin, hematocrit, weight, height, body mass index, age, and blood volume. A prediction model was created by inserting multiple independent modifying factors through logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive accuracy of the model, and the Hosmer-Lemeshow (H-L) test was carried out to evaluate the goodness-of-fit, and a calibration curve was drawn to confirm the predictive performance. A nomogram was depicted to visualize the prediction model. Results: Thirty-nine complicated procedures were matched with 78 uncomplicated controls. According to the multivariate logistic regression analysis findings, the prediction model was developed using C-reactive protein (CRP), intraoperative blood loss, and 24 h postoperative urinary volume, therefore a nomogram was generated. The area under the ROC curve of the prediction model was 0.879, depicting good accuracy, the sensitivity was 60.00%, while specificity reached 93.59%. The H-L test (χ2 = 4.45, p = 0.931) and the calibration curve indicated a good goodness-of-fit and prediction stability. Limitations: The retrospective design, moderate sensitivity, and study population limit the generalization of the findings, requiring additional research. Conclusions: This prediction model based on CRP, intraoperative blood loss, and 24 h postoperative urinary volume might be a potentially useful tool for predicting reintervention and postoperative bleeding in patients undergoing planned gynecological laparoscopy.
Sex Differences in Hospital Mortality in€Adults€With Congenital Heart Disease

Methods T he Quebec CHD database and the Dutch CONCOR (CONgenital CORvitia) registry were used to identify patients with CHD aged 18 to 65 years who were hospitalized between 1996 and 2005. Regression analyses were used to compare 30-day in-hospital mortality in men versus women and in women aged 18 to 45 years with versus without a pregnancy history, after adjustment for age, CHD severity, comorbidities, and admission diagnosis.
Prediction using serum glycosylated fibronectin of imminent pre‐eclampsia in women with new‐onset hypertension

To compare the predictive performance for delivery with pre‐eclampsia (PE) within 2 weeks after assessment in women with new‐onset hypertension at 24–41 weeks' gestation between serum glycosylated fibronectin (GlyFn) concentration, serum placental growth factor (PlGF) concentration and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to PlGF concentration ratio.
Optimized osteogenesis of porcine bone-derived xenograft through surface coating of magnesium-doped nanohydroxyapatite

As one of the key factors influencing the outcome of guided bone regeneration, the currently used xenografts possess insufficient capability in osteogenesis. With the aim of improving the osteogenic performance of xenografts, porcine bone-derived hydroxyapatite (PHA) was prepared and subsequently coated by magnesium-doped nano hydroxyapatite (nMgHA, 10%, 20%, and 30% of Mg/Ca + Mg) through a straightforward and cost-efficient approach. The physiochemical and biological properties of nMgHA/PHAs were examined in vitro and in vivo. The inherent three-dimensional (3D) porous framework with the average pore size of 300 μm was well preserved in nMgHA/PHAs. Meanwhile, excess magnesium released from the so-called ‘surface pool’ of PHA was verified. In contrast, slower release of magnesium at lower concentrations was detected for nMgHA/PHAs. Significantly more newly-formed bone and microvessels were observed in 20%nMgHA/PHA than the other specimens. With the limitations of the present study, it could be concluded that PHA coated by 20%nMgHA may have the optimized osteogenic performance due to the elimination of the excess magnesium from the ‘surface pool’, the preservation of the inherent 3D porous framework with the favorable pore size, and the release of magnesium at an appropriate concentration that possessed osteoimmunomodulatory effects on macrophages.
Cost–consequence analysis of ofatumumab for the treatment of relapsing-remitting multiple sclerosis in Canada

Aim: The costs and consequences of initial and delayed ofatumumab treatment were evaluated in relapsing-remitting multiple sclerosis with active disease in Canada. Materials & methods: A Markov cohort model was used (10-year horizon, annual cycle length, 1.5% discounting). Scenario analyses examined ofatumumab as first-line treatment versus 3 and 5 years following switch from commonly used first-line therapies. Results: Ofatumumab resulted in improvements in clinical outcomes (relapses and disease progression) and productivity (employment and full-time work), and reduction of economic burden (administration, monitoring and non-drug costs) that were comparable to other high-efficacy therapies (ocrelizumab, cladribine and natalizumab). Switching to ofatumumab earlier in the disease course may improve these outcomes. Conclusion: Results highlight the value of a high-efficacy therapy such as ofatumumab as initial treatment (i.e., first-line) in newly diagnosed relapsing-remitting multiple sclerosis patients with active disease.
Organic Zinc Glycine Chelate is Better than Inorganic Zinc in Improving Growth Performance of Cherry Valley ducks by Regulating Intestinal Morphology, Barrier Function, and the Gut Microbiome.

Zinc (Zn) is an essential trace element that has physiological and nutritional functions. However, excessive use of Zn can lead to waste of resources. In this study, we compared the effects of inorganic (ZnSO4) and organic Zn glycine chelate (Zn-Gly) on the growth performance, intestinal morphology, immune function, barrier integrity, and gut microbiome of Cherry Valley ducks. We randomly divided 180 1-day-old male meat ducks into three groups, each with six replicates of 10 birds: basal diet group (CON), basal diet with 70 mg Zn/kg from ZnSO4 (ZnSO4 group), and basal diet with 70 mg Zn/kg from Zn-Gly (Zn-Gly group). After 14 and 35 days of feeding, birds in the Zn groups had significantly increased body weight and average daily gain, decreased intestinal permeability indicator D-Lactate, improved intestinal morphology and barrier function-related tight junction protein levels, and upregulated mucin 2 and secretory immunoglobulin A levels compared to the control (P < 0.05). Additionally, compared to the ZnSO4 group, we found that supplementation with Zn-Gly at 70 mg/kg Zn resulted in the significant increase of body weight at 35 days, 1-35 day average daily gain and average daily feed intake, villus height at 14 and 35 days, secretory immunoglobulin A and immunoglobulin G at 14 days, and mucin 2 mRNA level at 14 days (P < 0.05). Compared with the control group, dietary Zn had a significant effect on the gene expression of metallothionein at 14 and 35 days (P < 0.05). 16S rRNA sequencing showed that Zn significantly increased alpha diversity (P < 0.05), whereas no differences in beta diversity were observed among groups (P > 0.05). Dietary Zn significantly altered the cecal microbiota composition by increasing the abundances of Firmicutes, Blautia, Lactobacillus, Prevotellaceae NK3B31, and [Ruminococcus] torques group and reducing that of Bacteroides (P < 0.05). Spearman correlation analysis revealed that the changes in microbiota were highly correlated (P < 0.05) with growth performance, intestinal morphology, and immune function-related parameters. Taken together, our data show that, under the condition of adding 70 mg/kg Zn, supplementation with Zn-Gly promoted growth performance by regulating intestinal morphology, immune function, barrier integrity and gut microbiota of Cherry Valley ducks compared with the use of ZnSO4 in feed.
Comparative Analysis of Alternative Calcium Chelators for the Treatment of Calcific Band Keratopathy

Purpose: In this study, we compared clinically relevant biochemical properties of each chelator for pH, osmolarity, and calcium chelation potential. Methods: In total, 0.2 M K2EDTA and K3EDTA (BD vacutainer tubes by Becton, Dickinson and Company) and Na2EDTA (Sigma Aldrich) solutions were made. The pH of each solution was measured (Mettler Toledo pH meter), and the theoretical osmolarity was calculated. Next, we determined the calcium chelation potential of each EDTA salt by titrating it with 10 μmol of calcium hydroxyapatite or CaCl2 containing Patton–Reeder colorimetric indicator. Statistical significance was analyzed using analysis of variance. Results: The 0.2 M solutions of Na2EDTA, K2EDTA, and K3EDTA have pH values of 4.43, 5.71, and 9.191 and theoretical osmolarities of 600, 600, and 800 mOsm/L, respectively. Calcium chelation ability was similar among all 3 solutions: 0.94 to 0.98 mol of EDTA was needed to fully chelate 1 mol calcium ions of CaCl2 (P = 0.296), 0.100 to 0.108 mol of EDTA for 1 mol calcium ions of the hydroxyapatite aqueous suspension (P = 0.296), and 0.992 to 0.996 mol for 1 mol calcium ions of hydroxyapatite in acidic solution (P = 0.178). Compared with the clinical standard of 3% (30 mg/mL) Na2EDTA, approximately 3.3% (33 mg/mL) K2EDTA and 3.6% (36 mg/mL) K3EDTA are needed to chelate an equivalent amount of calcium. Conclusions: In this article, we provide clinically relevant biochemical properties of 2 alternatives to Na2EDTA and demonstrate comparable calcium chelation ability among all 3 solutions. In situations where sterile sources of Na2EDTA are unavailable, potassium EDTA may provide a convenient and equally effective method of treatment for band keratopathy.
The facilitators and barriers to improving functional activity and wellbeing in people with dementia: a qualitative study from the process evaluation of Promoting Activity, Independence and Stability in Early Dementia (PrAISED)

Background. The PRomoting Activity, Independence and Stability in Early Dementia (PrAISED) study delivered an exercise and functional activity programme to participants living with dementia. A Randomised Controlled Trial (RCT) showed no measurable benefits in activities of daily living, physical activity or quality of life. Objective. To explore participant responses to PrAISED and explain the mechanisms behind a complex intervention that did not lead to expected health gains. Methods. A process evaluation using qualitative methods, comprising interviews and researcher notes Setting. Data were collected in the homes of participants or remotely by telephone or videoconferencing. Sample. Eighty-eight interviews were conducted with 44 participants living with dementia (n = 32 intervention group; n = 12 control group) and 39 caregivers. Sixty-nine interviews were conducted with 26 therapists. Results. Participants valued the intervention as proactively addressing health issues that were of concern to them, and as sources of social contact, interaction, information, and advice. Facilitators to achieving positive outcomes included perceiving progress toward desired goals, positive expectations, therapist skills and rapport with participants, and caregiver support. Barriers included: cognitive impairment, which prevented independent engagement and carryover between sessions; chronic physical health problems and intercurrent acute illness and injury; tapering (progressively infrequent supervision intended to help develop habits and independent activity); and the COVID-19 pandemic. Conclusions. Interventions aiming to maintain activity, independence and stability may not be appropriate in the context of dementia even in the mild stages of the condition. Various factors affected outcomes including caregiver support, rapport with therapists, availability of supervision, motivational factors, and the limitations of remote delivery. The effects of cognitive impairment, multimorbidity and frailty overwhelmed any positive impact of the intervention. Maintenance of functional ability is valued, but in the face of inevitable progression of disease, other less tangible outcomes become important, challenging how we frame health gain and trial outcomes.
Winter Activity of Bats in Southeastern Nebraska: An Acoustic Study

Many North American bats are active outside hibernacula in winter, but no information on winter activity has been reported for Nebraska. We recorded activity of bats during two winters (December-February 2012-2013 and 2013-2014) at one location in southeastern Nebraska with an acoustic detector. Bats were active throughout both winters and temperature at sunset was a good predictor of bat activity. Red bats (Lasiurus borealis) were active at our site in early December but were not recorded later in winter. We suspect these individuals were late migrants to more southern wintering sites. Big brown bats (Eptesicus fuscus) were recorded in each month during both winters, but reasons for winter activity at this site were not clear. This study provides baseline data for winter activity of bats in southeastern Nebraska; however, more research is encouraged to gain a better understanding of winter bat activity in Nebraska and other regions of the Great Plains.
HLA DQ protein changes the cell surface distribution pattern of HLA proteins as monitored by Förster resonance energy transfer and high‐resolution electron microscopy

Peptide presentation by MHC class I and MHC class II molecules plays important roles in the regulation of the immune response. One factor in these displays is the density of antigen, which must exceed a critical threshold for the effective activation of T cells. Nonrandom distribution of MHC class I and class II has already been detected at the nanometer level and at higher hierarchical levels. It is not clear how the absence and reappearance of some protein molecules can influence the nonrandom distribution. Therefore, we performed experiments on HLA II‐deficient bare lymphocyte syndrome (BLS1) cells: we created a stable transfected cell line, tDQ6‐BLS‐1, and were able to detect the effect of the appearance of HLA‐DQ6 molecules on the homo and heteroassociation of different cell surface molecules by comparing Förster resonance energy transfer (FRET) efficiency on transfected cells to that on nontransfected BLS‐1 and JY human B‐cell lines. Our FRET results show a decrease in homoassociation FRET between HLA I chains in HLA‐DQ6‐transfected tDQ6‐BLS‐1 cells compared with the parent BLS‐1 cell line and an increase in heteroassociation FRET between HLA I and HLA II (compared with JY cells), suggesting a similar pattern of antigen presentation by the HLA‐DQ6 allele. Transmission electron microscopy (TEM) revealed that both HLA class I and class II molecules formed clusters at higher hierarchical levels on the tDQ6‐BLS‐1 cells, and the de novo synthesized HLA DQ molecules did not intersperse with HLA class I islands. These observations could be important in understanding the fine tuning of the immune response.
The Implementation of Nongynecologic Reporting Systems in Cytopathology Laboratories Is Highly Variable: Analysis of Data From a 2020 Supplemental Survey of Participants in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

CONTEXT— In recent years, several reporting systems have been developed by national and international cytopathology organizations to standardize the evaluation of specific cytopathology specimen types. OBJECTIVE— To assess the current implementation rates, implementation methods, and barriers to implementation of commonly used nongynecologic reporting systems in cytopathology laboratories. DESIGN— Data were analyzed from a survey developed by the committee and distributed to participants in the College of American Pathologists Nongynecologic Cytopathology Education Program mailing. RESULTS— Nongynecologic reporting systems with the highest rate of adoption were the Bethesda System for Reporting Thyroid Cytopathology, 2nd edition (74.1%; 552 of 745); the Paris System for Reporting Urinary Cytology (53.9%; 397 of 736); and the Milan System for Reporting Salivary Gland Cytopathology (29.1%; 200 of 688). The most common reason given for not adopting a reporting system was satisfaction with a laboratory's current system. Implementation varied among laboratories with regard to which stakeholders were involved in deciding to implement a system and the amount of education provided during the implementation process. CONCLUSIONS— The implementation of nongynecologic reporting systems in cytopathology laboratories was highly variable.
Clinicopathological impact of VEGFR2 and VEGF‐C in patients with EGFR ‐major mutant NSCLC receiving osimertinib

Vascular endothelial growth factor (VEGF) has been identified as one of the resistant mechanisms to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs). However, the relationship between the efficacy of osimertinib and protein expression of VEGF family members in patients with advanced non‐small cell lung cancer (NSCLC) harboring EGFR mutations remains unclear.
The circRNA circVAMP3 restricts influenza A virus replication by interfering with NP and NS1 proteins

Circular RNAs (circRNAs) are involved in various biological roles, including viral infection and antiviral immune responses. To identify influenza A virus (IAV) infection-related circRNAs, we compared the circRNA profiles of A549 cells upon IAV infection. We found that circVAMP3 is substantially upregulated after IAV infection or interferon (IFN) stimulation. Furthermore, IAV and IFN-β induced the expression of QKI-5, which promoted the biogenesis of circVAMP3. Overexpression of circVAMP3 inhibited IAV replication, while circVAMP3 knockdown promoted viral replication, suggesting that circVAMP3 restricts IAV replication. We verified the effect of circVAMP3 on viral infection in mice and found that circVAMP3 restricted IAV replication and pathogenesis in vivo. We also found that circVAMP3 functions as a decoy to the viral proteins nucleoprotein (NP) and nonstructural protein 1 (NS1). Mechanistically, circVAMP3 interfered with viral ribonucleoprotein complex activity by reducing the interaction of NP with polymerase basic 1, polymerase basic 2, or vRNA and restored the activation of IFN-β by alleviating the inhibitory effect of NS1 to RIG-I or TRIM25. Our study provides new insights into the roles of circRNAs, both in directly inhibiting virus replication and in restoring innate immunity against IAV infection.