Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical applications of extracellular vesicles in the diagnosis and treatment of traumatic brain injury.

Extracellular vesicles (EVs) have emerged as key mediators of cell-cell communication during homeostasis and in pathology. Central Nervous System (CNS)-derived EVs contain cell type-specific surface markers and intralumenal protein, RNA, DNA, and metabolite cargo that can be used to assess the biochemical and molecular state of neurons and glia during neurological injury and disease. The development of EV isolation strategies coupled with analysis of multiplexed biomarker and clinical data has the potential to improve our ability to classify and treat TBI and resulting sequelae. Additionally, their ability to cross the BBB has implications for both EV-based diagnostic strategies and for potential EV-based therapeutics. In the present review, we discuss encouraging data for EV-based diagnostic, prognostic, and therapeutic strategies in the context of TBI monitoring and management.
Iminodiacetic Acid as a Novel Metal‐Binding Pharmacophore for New Delhi Metallo‐β‐lactamase Inhibitor Development

The fungal natural product aspergillomarasmine A (AMA) has been identified as a noncompetitive inhibitor of New Delhi metallo‐β‐lactamase‐1 (NDM‐1) that inhibits by removing ZnII from the active‐site. The nonselective metal‐chelating properties and difficult synthesis and derivatization of AMA have hindered the development of this scaffold into a potent and selective inhibitor of NDM‐1. Iminodiacetic acid (IDA) has been identified as the metal‐binding pharmacophore (MBP) core of AMA that can be leveraged for inhibitor development. Herein, we report the use of IDA for fragment‐based drug discovery (FBDD) of NDM‐1 inhibitors. IDA (IC50=120 μM) was developed into inhibitor 23 f (IC50=8.6 μM, Ki=2.6 μM), which formed a ternary complex with NDM‐1, as evidenced by protein thermal‐shift and native‐state electrospray ionization mass spectrometry (ESI‐MS) experiments. Combining mechanistic analysis with inhibitor derivatization, the use of IDA as an alternative AMA scaffold for NDM‐1 inhibitor development is detailed.
Effect of carotenoid encapsulation on antioxidant activities

Abstract Background: Carotenoids play essential roles in human health, such as antioxidant activity, and therefore can decrease free radicals oxidation action, preventing numerous diseases. However, these compounds have an unstable nature, turning them susceptible to adverse conditions in food processing and storage. Thereby the search for alternatives that maintain and enhance carotenoid antioxidant function, such as encapsulation, has grown. The objective of this study was to establish a systematic review protocol to evaluate the effect of different encapsulation techniques on the antioxidant action of carotenoids, evaluating which one is the best and safest, and their role in enhancing the antioxidant activity. Methods: This protocol was guided by the preferred reporting items for protocols for systematic reviews and meta-analyzes. The databases to be searched are PubMed, EMBASE, Scopus, ScienceDirect, and Web of Science. Experimental studies conducted in rats and mice (in vivo) of both sexes and ages, evaluating the use of encapsulated and crude carotenoids will be included in the systematic review. The characteristics of the studies, the experimental model, and the main results will be described, and the risk of bias assessment will be evaluated. Three independent reviewers will proceed with the selection of studies, data extraction, and methodological quality assessment. A narrative synthesis will be made for the included studies. Besides, if sufficient qualitative data is available, a meta-analysis will be conducted. I2 statistics will be used to assess heterogeneity. Results: This protocol will guide the production of a systematic review that can determine the effect of different encapsulation techniques and encapsulating agents on the antioxidant action of carotenoids. Thus, it will enable the determination of the best encapsulation techniques to promote the preservation and increase of the antioxidant activity, contributing to future research that may reproduce the best carotenoid encapsulation technique in an animal model. Conclusion: The systematic review to be produced from this protocol will provide support for the construction of research that evaluates the effect of encapsulation on the antioxidant function of carotenoids and its possible application as a nutraceutical, considering that this functionality is directly associated with health promotion. Record of systematic review: This review was recorded in the International Register of Prospective Systematic Reviews on January 22, 2020 (registration: CRD42020142065). Available at: https://www.crd. york.ac. uk/prospero/display_record. php? ID=CRD42020142065
Effectiveness of behavioral therapy in obese children in outpatient clinic

Objective: The aim of the study was to evaluate the effectiveness of behavioral therapy in childhood obesity in metabolic outpatient clinic. Material and methods: Records of the 587 (289 boys) obese children in the age of 10.73 ± 3.57 were retrospectively analyzed (2005-2016). The therapy included lifestyle modification (increased physical activity, and support from the dietician and psychologist). Anthropometrical assessment was based on BMI z-score index. Results: Initial BMI z-score was higher in boys (3.29 SD vs. 2.66 SD, p < 0.00001). At follow-up visit for an average of 3 months, with a 66.8% of the children reported, an improvement was observed in 70% of them, and greater weight loss was found in boys (∆BMI Z-score: 0.28 SD vs. –0.15 SD). Improvement of the nutritional status (∆BMI Z-score) correlated with the age of children and the initial weight (vs. age: r = 0.233, p < 0.01; vs. BMI Z-score: r = –0.610, p < 0.00001). Further follow-up showed a reduction in the number of children continuing the treatment (at the 3rd visit: 28.3%; at the 4th visit: 19.1%; at the 5th visit or more: 12.7%). In children, who remained under control of the outpatient clinic, a reduction in BMI z-score (p < 0.00001) was observed from the 3rd visit. Conclusions: Behavioral therapy on the outpatient clinic level is effective, but its effectiveness is pointedly reduced by the high number of children and their parents who avoid the treatment or refuse to continue this model of therapy. The essential challenge is to keep the motivation of both parents and children.
What Patients Want During Follow-Up After Cosmetic Plastic Surgeries.

BACKGROUND High follow-up rates are essential to minimize bias in clinical researches. And, now, social media is widely used in various fields of plastic surgeries. However, there are no reports about its usage in the follow-up after cosmetic plastic surgeries. PURPOSE The authors conducted a survey based on interview and questionnaires to get an insight into social media's usage in improving the retention among patients seeking cosmetic plastic surgery and what the patients want during the follow-up in China. METHODS The authors reviewed the works of literature and interviewed the surgeons who have rich experiences with the follow-up procedure with patients seeking cosmetic plastic surgery. And come up with the potential elements that may influence the retention, then they recruited the participants through both the new social media and the traditional way, then gathered the participants' preferences and opinions about the elements through questionnaires. Then the data were analyzed with SPSS. RESULTS The choices which make the follow-up more convenient to attend are usually more welcomed among the participants than those making the follow-up more costly and time-consuming. However, those choices that make the patients feel less concerned are less appreciated even they are easy to practice and time-saving. CONCLUSION Patients have preferences during the follow-up after cosmetic plastic surgeries. Clinicians should always consider such preferences and try to use appropriate follow-up approaches that are more acceptable to the patients. Other studies list out "tips to improve the retention. " However, the authors believe that patients' need is the core to improve retention.
Serial Assays of QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold-Plus in Subjects Exposed to Patients with Active Tuberculosis

Hee-Won Moon , M.D., Ph.D., Ahram Yi , M.D., Sumi Yoon , M.D., Hanah Kim , M.D., Ph.D., Hee-Jung Chung , M.D., Mina Hur , M.D., Ph.D., Yeo-Min Yun , M.D., Ph.D., and Kwang Ha Yoo , M.D., Ph.D. Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea; Department of Laboratory Medicine, Green Cross Laboratories, Yongin, Korea; Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
Further development of a reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of foot-and-mouth disease virus and validation in the field with use of an internal positive control.

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hooved animals. Global outbreaks have highlighted the significant economic, trade, psychosocial and animal welfare impacts that can arise from the detection of disease in previously 'FMD-free' countries. Rapid and early diagnosis provides significant advantages in disease control and minimisation of deleterious consequences. We describe the process of further development and validation of a reverse-transcription loop-mediated isothermal amplification foot-and-mouth disease virus (RT-LAMP-FMDV) test, using a published LAMP primer set, for use in the field. An internal positive control (IPC) was designed and introduced for use with the assay to mitigate any intrinsic interference from the unextracted field samples and avoid false negatives. Further modifications were included to improve the speed and operability of the test, for use by non-laboratory trained staff operating under field conditions, with shelf-stable reaction kits which require a minimum of liquid handling skills. Comparison of the assay performance with an established laboratory based real-time reverse transcriptase PCR (rRT-PCR) test targeting the 3D region of FMD virus (Tetracore Inc, USA) was investigated. LAMP has the potential to complement current laboratory diagnostics, such as rRT-PCR, as a preliminary tool in the investigation of FMD. We describe a strategic approach to validation of the test for use in the field using extracted RNA samples of various serotypes from Thailand and then finally unextracted field samples collected from FMD suspected animals (primarily oral lesion swabs) from Bhutan and Australia. The statistical approach to validation was performed by Frequentist and Bayesian latent class methods, which both confirmed this new RT-LAMP-FMDV test as fit-for-purpose as a herd diagnostic tool with diagnostic specificity >99% and sensitivity 79% (95% Bayesian credible interval: 65, 90%) on unextracted field samples (oral swabs).
Active Multilabel Crowd Consensus

Crowdsourcing is an economic and efficient strategy aimed at collecting annotations of data through an online platform. Crowd workers with different expertise are paid for their service, and the task requester usually has a limited budget. How to collect reliable annotations for multilabel data and how to compute the consensus within budget are an interesting and challenging, but rarely studied, problem. In this article, we propose a novel approach to accomplish active multilabel crowd consensus (AMCC). AMCC accounts for the commonality and individuality of workers and assumes that workers can be organized into different groups. Each group includes a set of workers who share a similar annotation behavior and label correlations. To achieve an effective multilabel consensus, AMCC models workers’ annotations via a linear combination of commonality and individuality and reduces the impact of unreliable workers by assigning smaller weights to their groups. To collect reliable annotations with reduced cost, AMCC introduces an active crowdsourcing learning strategy that selects sample–label–worker triplets. In a triplet, the selected sample and label are the most informative for the consensus model, and the selected worker can reliably annotate the sample at a low cost. Our experimental results on multilabel data sets demonstrate the advantages of AMCC over state-of-the-art solutions on computing crowd consensus and on reducing the budget by choosing cost-effective triplets.
Optimizing Resources in Children’s Surgical Care: An Update on the American College of Surgeons' Verification Program

Surgical procedures are performed in the United States in a wide variety of clinical settings and with variation in clinical outcomes. In May 2012, the Task Force for Children’s Surgical Care, an ad hoc multidisciplinary group comprising physicians representing specialties relevant to pediatric perioperative care, was convened to generate recommendations to optimize the delivery of children’s surgical care. This group generated a white paper detailing the consensus opinions of the involved experts. Following these initial recommendations, the American College of Surgeons (ACS), Children’s Hospital Association, and Task Force for Children’s Surgical Care, with input from all related perioperative specialties, developed and published specific and detailed resource and quality standards designed to improve children’s surgical care (https://www.facs.org/quality-programs/childrens-surgery/childrens-surgery-verification). In 2015, with the endorsement of the American Academy of Pediatrics (https://pediatrics.aappublications.org/content/135/6/e1538), the ACS established a pilot verification program. In January 2017, after completion of the pilot program, the ACS Children’s Surgery Verification Quality Improvement Program was officially launched. Verified sites are listed on the program Web site at https://www.facs. org/quality-programs/childrens-surgery/childrens-surgery-verification/centers, and more than 150 are interested in verification. This report provides an update on the ACS Children’s Surgery Verification Quality Improvement Program as it continues to evolve.
Prevalence of Continuous Pulse Oximetry Monitoring in Hospitalized Children With Bronchiolitis Not Requiring Supplemental Oxygen.

Importance US national guidelines discourage the use of continuous pulse oximetry monitoring in hospitalized children with bronchiolitis who do not require supplemental oxygen. Objective Measure continuous pulse oximetry use in children with bronchiolitis. Design, Setting, and Participants A multicenter cross-sectional study was performed in pediatric wards in 56 US and Canadian hospitals in the Pediatric Research in Inpatient Settings Network from December 1, 2018, through March 31, 2019. Participants included a convenience sample of patients aged 8 weeks through 23 months with bronchiolitis who were not receiving active supplemental oxygen administration. Patients with extreme prematurity, cyanotic congenital heart disease, pulmonary hypertension, home respiratory support, neuromuscular disease, immunodeficiency, or cancer were excluded. Exposures Hospitalization with bronchiolitis without active supplemental oxygen administration. Main Outcomes and Measures The primary outcome, receipt of continuous pulse oximetry, was measured using direct observation. Continuous pulse oximetry use percentages were risk standardized using the following variables: nighttime (11 pm to 7 am), age combined with preterm birth, time after weaning from supplemental oxygen or flow, apnea or cyanosis during the present illness, neurologic impairment, and presence of an enteral feeding tube. Results The sample included 3612 patient observations in 33 freestanding children's hospitals, 14 children's hospitals within hospitals, and 9 community hospitals. In the sample, 59% were male, 56% were white, and 15% were black; 48% were aged 8 weeks through 5 months, 28% were aged 6 through 11 months, 16% were aged 12 through 17 months, and 9% were aged 18 through 23 months. The overall continuous pulse oximetry monitoring use percentage in these patients, none of whom were receiving any supplemental oxygen or nasal cannula flow, was 46% (95% CI, 40%-53%). Hospital-level unadjusted continuous pulse oximetry use ranged from 2% to 92%. After risk standardization, use ranged from 6% to 82%. Intraclass correlation coefficient suggested that 27% (95% CI, 19%-36%) of observed variation was attributable to unmeasured hospital-level factors. Conclusions and Relevance In a convenience sample of children hospitalized with bronchiolitis who were not receiving active supplemental oxygen administration, monitoring with continuous pulse oximetry was frequent and varied widely among hospitals. Because of the apparent absence of a guideline- or evidence-based indication for continuous monitoring in this population, this practice may represent overuse.
Triptolide suppresses IDH1-mutated malignancy via Nrf2-driven glutathione metabolism

Significance IDH1 mutation is a common genetic abnormality in human malignancies, whereas selective therapeutics for IDH1-mutated malignancies remain unavailable. Our present study reveals that IDH1-mutated cancer cells exhibit addiction to Nrf2-governed antioxidative pathways. Blockade of Nrf2 transcriptional activity achieved synergistic lethality with a neomorphic IDH1 mutation. We also showed that triptolide serves as a potent Nrf2 inhibitor, which inhibited Nrf2 transcriptional activity and led to apoptotic changes in IDH1-mutated cells via redox catastrophe. We believe that our findings highlight the broad scope and significance of Nrf2 blockade as a therapeutic strategy and provide an actionable strategy for IDH1-mutated malignancies. Isocitrate dehydrogenase (IDH) mutation is a common genetic abnormality in human malignancies characterized by remarkable metabolic reprogramming. Our present study demonstrated that IDH1-mutated cells showed elevated levels of reactive oxygen species and higher demands on Nrf2-guided glutathione de novo synthesis. Our findings showed that triptolide, a diterpenoid epoxide from Tripterygium wilfordii, served as a potent Nrf2 inhibitor, which exhibited selective cytotoxicity to patient-derived IDH1-mutated glioma cells in vitro and in vivo. Mechanistically, triptolide compromised the expression of GCLC, GCLM, and SLC7A11, which disrupted glutathione metabolism and established synthetic lethality with reactive oxygen species derived from IDH1 mutant neomorphic activity. Our findings highlight triptolide as a valuable therapeutic approach for IDH1-mutated malignancies by targeting the Nrf2-driven glutathione synthesis pathway.
Evolution of viscoelastic coagulation testing

ABSTRACT Introduction The methods of viscoelastic coagulation testing (VCT) have evolved since the original invention of thrombelastography over 60 years ago, and new generations of devices are clinically used to guide hemostatic interventions at bedside. The utility of VCTs has been demonstrated in several clinical trials, but diagnostic performance of VCT may vary between devices, various transfusion algorithms, and patient populations. Areas covered Working principles and currently available data on the evolving VCTs for coagulation monitoring in acute care settings are reviewed. The PubMed database was used to search pertinent retrospective, prospective, and meta-analysis data on VCTs. Expert opinion Point-of-care VCTs provide clinically useful information on platelet count, fibrin polymerization, and other procoagulant factor activities in acute bleeding due to trauma or major surgery, and antithrombotic therapy. The addition of fibrin-specific VCT channel has brought renewed attention to early correction of fibrinogen deficiency using fibrinogen-rich component therapy, and stabilization of fibrin with antifibrinolytic agents. Normal reference ranges vary between devices, and diagnostic and treatment algorithms should be specifically established for each device and indication. There is interest in utilizing VCTs in complex coagulation management relating to hemophilia with inhibitors, but the standardized protocol has not been established.
Role of genetics and epigenetics in male infertility

Male infertility is a complex condition with a strong genetic and epigenetic background. This review discusses the importance of genetic and epigenetic factors in the pathophysiology of male infertility. The interplay between thousands of genes, the epigenetic control of gene expression, and environmental and lifestyle factors, which influence genetic and epigenetic variants, determines the resulting male infertility phenotype. Currently, karyotyping, Y‐chromosome microdeletion screening and CFTR gene mutation tests are routinely performed to investigate a possible genetic aetiology in patients with azoospermia and severe oligozoospermia. However, current testing is limited in its ability to identify a variety of genetic and epigenetic conditions that might be implicated in both idiopathic and unexplained infertility. Several epimutations of imprinting genes and developmental genes have been postulated to be candidate markers for male infertility. As such, development of novel diagnostic panels is essential to change the current landscape with regard to prevention, diagnosis and management. Understanding the underlying genetic mechanisms related to the pathophysiology of male infertility, and the impact of environmental exposures and lifestyle factors on gene expression might aid clinicians in developing individualised treatment strategies.
Characterization of a novel shell matrix protein with vWA domain from Mytilus coruscus

ABSTRACT Mollusk shell is a product of biomineralization with excellent mechanical properties, and the shell matrix proteins (SMPs) have important functions in shell formation. A vWA domain-containing protein (VDCP) was identified from the shell of Mytilus coruscus as a novel shell matrix protein. The VDCP gene is expressed at a high level in specific locations in the mantle and adductor muscle. Recombinant VDCP (rVDCP) showed abilities to alter the morphology of both calcite and aragonite, induce the polymorph change of calcite, bind calcite, and decrease the crystallization rate of calcite. In addition, immunohistochemistry analyses revealed the specific location of VDCP in the mantle, the adductor muscle, and the myostracum layer of the shell. Furthermore, a pull-down analysis revealed eight protein interaction partners of VDCP in shell matrices and provided a possible protein–protein interaction network of VDCP in the shell. GRAPHICAL ABSTRACT Sequence characterization, recombinant expression, biomineralization-related function, and localization of a vWA domain-containing protein (VDCP) identified from Mytilus corusus shell.