Miracle-dz/UniFAR-FTUs huggingface dataset:
Explainable Machine Learning to Bring Database to the Bedside

Objective: Exemplify an explainable machine learning framework to bring database to the bedside; develop and validate a point-of-care frailty assessment tool to prognosticate outcomes after injury. Background: A geriatric trauma frailty index that captures only baseline conditions, is readily-implementable, and validated nationwide remains underexplored. We hypothesized Trauma fRailty OUTcomes (TROUT) Index could prognosticate major adverse outcomes with minimal implementation barriers. Methods: We developed TROUT index according to Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis guidelines. Using nationwide US admission encounters of patients aged ≥65 years (2016–2017; 10% development, 90% validation cohorts), unsupervised and supervised machine learning algorithms identified baseline conditions that contribute most to adverse outcomes. These conditions were aggregated into TROUT Index scores (0–100) that delineate 3 frailty risk strata. After associative [between frailty risk strata and outcomes, adjusted for age, sex, and injury severity (as effect modifier)] and calibration analysis, we designed a mobile application to facilitate point-of-care implementation. Results: Our study population comprised 1.6 million survey-weighted admission encounters. Fourteen baseline conditions and 1 mechanism of injury constituted the TROUT Index. Among the validation cohort, increasing frailty risk (low=reference group, moderate, high) was associated with stepwise increased adjusted odds of mortality {odds ratio [OR] [95% confidence interval (CI)]: 2.6 [2.4–2.8], 4.3 [4.0–4.7]}, prolonged hospitalization [OR (95% CI)]: 1.4 (1.4–1.5), 1.8 (1.8–1.9)], disposition to a facility [OR (95% CI): 1.49 (1.4–1.5), 1.8 (1.7–1.8)], and mechanical ventilation [OR (95% CI): 2.3 (1.9–2.7), 3.6 (3.0–4.5)]. Calibration analysis found positive correlations between higher TROUT Index scores and all adverse outcomes. We built a mobile application (“TROUT Index”) and shared code publicly. Conclusion: The TROUT Index is an interpretable, point-of-care tool to quantify and integrate frailty within clinical decision-making among injured patients. The TROUT Index is not a stand-alone tool to predict outcomes after injury; our tool should be considered in conjunction with injury pattern, clinical management, and within institution-specific workflows. A practical mobile application and publicly available code can facilitate future implementation and external validation studies.
Approach to FNA of Thyroid Gland Cysts

Fine needle aspiration is a well-known procedure for the diagnosis and management of thyroid lesions, representing the first diagnostic tool for the definition of their nature. In clinical practice, a thyroid nodule can be classified as solid, cystic, and partially cystic based on its internal components. Different thyroid imaging reporting systems and cytologic diagnostic systems have focused their attention on solid nodules, which are more frequently linked with a malignant outcome. In fact, numerous papers demonstrated that nodules with microcalcifications, a taller-than-wide shape, hypoechogeneity, and irregular margins, are more likely to be malignant on histology. Nevertheless, according to the literature, the risk of malignancy in a partially cystic thyroid nodule ranges between 3.3 and 17-5%, including, for instance, the possible diagnosis of a cystic papillary thyroid carcinoma and other malignant entities. Therefore, in the current review article, we are going to discuss the approach to thyroid cystic lesions on fine needle aspiration cytology.
Bayesian adaptive clinical trial designs for respiratory medicine

The use of Bayesian adaptive designs for clinical trials has increased in recent years, particularly during the COVID‐19 pandemic. Bayesian adaptive designs offer a flexible and efficient framework for conducting clinical trials and may provide results that are more useful and natural to interpret for clinicians, compared to traditional approaches. In this review, we provide an introduction to Bayesian adaptive designs and discuss its use in recent clinical trials conducted in respiratory medicine. We illustrate this approach by constructing a Bayesian adaptive design for a multi‐arm trial that compares two non‐invasive ventilation treatments to standard oxygen therapy for patients with acute cardiogenic pulmonary oedema. We highlight the benefits and some of the challenges involved in designing and implementing Bayesian adaptive trials.
A comprehensive review of recent advances in the biological activities of quinazolines

Quinazoline heterocycles are critical in the development of medications. Quinazoline derivatives have been intensively researched, providing a wide range of compounds with diverse biological roles. The quinazoline nucleus has garnered a lot of attention in medical chemistry in recent years. It was assumed to be a pharmacophore component in the development of physiologically interesting drugs. This review is an attempt to increase the potential of quinazoline by highlighting a wide range of advancements demonstrated by numerous derivatives of the quinazoline moiety, as well as focusing on diverse pharmacological actions of the quinazoline moiety. This review compiles recent studies on the quinazoline moiety described in the literature by researchers.
Challenges in the delivery of sex education for people with intellectual disabilities: A Chinese cultural‐contextual analysis

Abstract Background Staff members' views can have a significant impact on sexuality issues of people with intellectual disabilities. Research on the impact of sociocultural factors in this area in the Chinese context is sparse. Methods Semi‐structured interviews were conducted with seven professionals (social worker, nurse, life skills trainer and manager) to explore their experiences of and attitudes towards the sexual needs of people with intellectual disabilities by applying interpretative phenomenological analysis. Results The study identified two major themes, each with two sub‐themes: 1. Professional handling of the sexual needs of people with intellectual disabilities (sex education and intervention); 2. Barriers (incompatible approaches and parental resistance). Participants also experienced feelings of resignation facing the barriers they encountered. Collectivism and cultural view about sex are potentially the influencing factors. Conclusion This study highlights the need to adopt an evidence‐based sex education programme whose content and delivery should take account of cultural factors.
Comment on: Real-life comparison of three intravitreal antibiotic drug regimens in endophthalmitis

Dear Editor, We went through the article titled “Real-life comparison of three intravitreal antibiotic drug regimens in endophthalmitis” by Bari et al.[1] The authors have done a commendable job with their work on endophthalmitis. We have a few observations. It seems that the authors have followed the guidelines of the Endophthalmitis Vitrectomy Study and intravitreal antibiotics were the initial line of treatment in majority of patients. The authors have mentioned that the presenting vision was hand movements (HM) in majority of cases and 97% of cases had to undergo vitrectomy after the initial treatment. In real-life scenario, the threshold for performing vitrectomies in endophthalmitis cases has decreased and vitrectomy should be tried as the initial management, especially in cases with vision around HM and no view of fundus. Improved quality of instrumentation and upgraded training of ophthalmic surgeons in performing vitrectomy have helped in achieving good anatomical and functional outcomes in such cases. There are also reports available in the literature which have stated that initial vitrectomy had achieved better outcomes compared to performing initial tap and injecting antibiotics. [2,3]
Tumor suppressor genes are reactivated by miR-26A1 via enhancer reprogramming in NSCLC

Abstract Non-small cell lung cancer (NSCLC) is one of the most malignant epithelial tumors. Studies have suggested that DNA hypermethylation of promoters and abnormal histone modifications could induce tumor suppressor genes (TSGs) downregulation in NSCLC. However, the exact mechanism of TSGs downregulation remains unclear. In this study, we found that there is no difference in the regions of most TSGs promoters in NSCLC. Moreover, we found that there is no DNA methylation difference in the region of VILL promoter in NSCLC compared with adjacent tissue samples by pyrosequencing. We further demonstrated that VILL was markedly reactivated in A549 and H1703 cells infected with miR-26A1 lentivirus while this activation was inhibited by JQ1, an enhancer inhibitor. In addition, we identified that miR-26A1 could function as a tumor suppressor to inhibit proliferation and metastasis of NSCLC cells. Chromatin immunoprecipitation assays revealed that overexpression of miR-26A1 could significantly induce the enrichment of H3K27ac at the enhancer regions in A549 cells. To sum up, our findings revealed that enhancer-mediated TSGs regulation occured in NSCLC, suggesting that miR-26A1 could serve as a key regulator and may be a potential therapeutic target for NSCLC.
Commentary: Usage of intravitreal steroids in endophthalmitis: Horns of a dilemma

The usage of steroids intravitreally along with antimicrobials for endophthalmitis management has been marred with controversy for decades. To a large extent, management of endophthalmitis has been based on physician discretion and has a lot of variability between cases. The rationale behind steroids/anti-inflammatory agents is that endophthalmitis leads to severe inflammation and bystander damage to intraocular tissues, especially the neurosensory retina, resulting in irreversible functional changes. Suppressing this inflammation may help reduce the irreversible damage and shorten the overall disease course. It is not well understood whether the damage to the visual function is due to the infectious agent or the immune response developed by the host in response to it.
Development of categorical speech perception in Mandarin‐speaking children and adolescents

Abstract Although children develop categorical speech perception at a very young age, the maturation process remains unclear. A cross‐sectional study in Mandarin‐speaking 4‐, 6‐, and 10‐year‐old children, 14‐year‐old adolescents, and adults (n = 104, 56 males, all Asians from mainland China) was conducted to investigate the development of categorical perception of four Mandarin phonemic contrasts: lexical tone contrast Tone 1‐2, vowel contrast /u/−/i/, consonant aspiration contrast /p/−/ph/, and consonant formant transition contrast /p/−/t/. The results indicated that different types of phonemic contrasts, and even the identification and discrimination of the same phonemic contrast, matured asynchronously. The observation that tone and vowel perception are achieved earlier than consonant perception supports the phonological saliency hypothesis.
Interaction between Hyperuricemia and Admission Lactate Increases the Risk of Acute Kidney Injury in Patients with ST-Segment Elevation Myocardial Infarction

Background and Objective: Acute kidney injury (AKI) is a common complication associated with adverse outcomes among patients with ST-segment elevation myocardial infarction (STEMI). This is conflicting information about the relationship between hyperuricemia and AKI in STEMI. This work aimed to investigate the effect of the interaction between hyperuricemia and lactate on the risk of AKI. Methods: We analyzed 2,008 consecutive STEMI patients between January 2014 and January 2019. Hyperuricemia was defined as a serum uric acid level >7 mg/dL for males and >6 mg/dL for females. AKI was defined based on the Kidney Disease: Improving Global Outcomes (KDIGO). Logistic regression models were applied to establish the relationship between hyperuricemia and AKI in the overall population and subgroups stratified as per lactate levels at admission (≤2.2 mmol/L or >2.2 mmol/L). Results: In total, we included 1,887 STEMI patients. Multivariate analysis showed that hyperuricemia is associated with the risk of AKI (OR: 1.34; 95% CI: 1.01–1.77; p = 0.045). Nonetheless, the predictive effect of hyperuricemia was only observed in patients with lactate level >2.2 mmol/L (OR: 2.05; 95% CI: 1.36–3.10; p < 0.001), but not in those with lactate level ≤2.2 mmol/L (OR: 0.86, 95% CI: 0.56–1.32; p = 0.493). The interaction between hyperuricemia and lactate levels demonstrated a significant effect on AKI. Conclusions: In summary, hyperuricemia increases the risk of AKI in STEMI patients with lactate levels> 2.2 mmol/L, but not in those with lactate levels ≤2.2 mmol/L.
Prevalence of respiratory viruses among paediatric patients in acute respiratory illnesses in Malaysia

Objectives Acute respiratory infections (ARIs) are one of the leading causes of childhood morbidity and mortality worldwide. However, there is limited surveillance data on the epidemiological burden of respiratory pathogens in tropical countries like Malaysia. This study aims to estimate the prevalence of respiratory pathogens causing ARIs among children aged <18 years old in Malaysia and their epidemiological characteristics. Methods Nasopharyngeal swab specimens received at 12 laboratories located in different states of Malaysia from 2015–2019 were studied. Detection of 18 respiratory pathogens were performed using multiplex PCR. Results Data from a total of 23,306 paediatric patients who presented with ARI over a five-year period was studied. Of these, 18538 (79.5%) were tested positive. The most prevalent respiratory pathogens detected in this study were enterovirus/ rhinovirus (6837/ 23000; 29.7%), influenza virus (5176/ 23000; 22.5%) and respiratory syncytial virus (RSV) (3652/ 23000; 15.9%). Throughout the study period, RSV demonstrated the most pronounce seasonality; peak infection occurred during July to September. Whereas the influenza virus was detected year-round in Malaysia. No seasonal variation was noted in other respiratory pathogens. The risk of RSV hospitalisation was found to be significantly higher in children aged less than two years old, whereas hospitalisation rates for the influenza virus peaked at children aged between 3–6 years old. Conclusion This study provides insight into the epidemiology and the seasonality of the causative pathogens of ARI among the paediatric population in Malaysia. Knowledge of seasonal respiratory pathogens epidemiological dynamics will facilitate the identification of a target window for vaccination.
Developmental neurotoxicity of silver nanoparticles: the current state of knowledge and future directions

Abstract The increasing production and use of silver nanoparticles (AgNPs) as an antimicrobial agent in an array of medical and commercial products, including those designed for infants and children, poses a substantial risk of exposure during the developmental period. This review summarizes current knowledge on developmental neurotoxicity of AgNPs in both pre- and post-natal stages with a focus on the biological specificity of immature organisms that predisposes them to neurotoxic insults as well as the molecular mechanisms underlying AgNP-induced neurotoxicity. The current review revealed that AgNPs increase the permeability of the blood–brain barrier (BBB) and selectively damage neurons in the brain of immature rats exposed pre and postnatally. Among the AgNP-induced molecular mechanisms underlying toxic insult is cellular stress, which can consequently lead to cell death. Glutamatergic neurons and NMDAR-mediated neurotransmission also appear to be a target for AgNPs during the postnatal period of exposure. Collected data indicate also that our current knowledge of the impact of AgNPs on the developing nervous system remains insufficient and further studies are required during different stages of development with investigation of environmentally-relevant doses of exposure.
Design, synthesis, extra-precision docking, and molecular dynamics simulation studies of pyrrolidin-2-one derivatives as potential acetylcholinesterase inhibitors

Abstract Inhibition of acetylcholinesterase (AChE) has been widely explored to develop novel molecules for management of Alzheimer's disease. In past research finding reported molecule 3-(4-(4-fluorobenzoyl)piperidin-1-yl)-1-(4-methoxybenzyl)pyrrolidin-2-one displayed a spectrum of anti-Alzheimer’s properties herein, we report a library of 18 novel molecules that were rationally designed and synthesized employing known literature to mimic and explore the novel chemical space around the lead compound 6e and donepezil. All the compounds were docked in extra-precision mode with AChE (PDB ID 4EY7) using the Glide module. Molecular dynamics (MD) simulation studies were carried out for 100 ns along with MM-PBSA studies of the trajectory frames generated post-MD simulations. Docking and MD simulation studies suggested that the synthesized compounds showed a good binding affinity with AChE. and might form stable complexes. 3-(4-(benzyl(methyl)amino)piperidin-1-yl)-1-(3,4-dimethoxybenzyl)pyrrolidin-2-one (14a; docking score: −18.59) and 1-(3,4-dimethoxybenzyl)-3-(4-(methyl(thiazol-2-ylmethyl)amino)piperidin-1-yl)pyrrolidin-2-one (14d; docking score: −18.057) showed higher docking score than donepezil (docking score: −17.257) while most of the compounds had docking score >-10.0. ADMET study predicted these compounds to be CNS active and most of the compounds were drug-like molecules with no HERG blockade and good to excellent oral absorption. We developed an atom-based 3 D-QSAR model with R^2 and Q^2 values of 0.9639 and 0.8779 to predict the activity of the synthesized compounds. The model predicted these compounds to be potent AChE inhibitors with IC50 values in the lower micromolar range. Based on the in silico findings, we report these newly synthesized compounds 3-(4-(benzyl(methyl)amino)piperidin-1-yl)-1-(3,4-dimethoxybenzyl)pyrrolidin-2-one (14a) and 7-(2,6-difluorobenzyl)-2-(4-methoxybenzyl)-2,7-diazaspiro[4.5]decan-1-one (20 b) as potential AChE inhibitors. Communicated by Ramaswamy H. Sarma
Allele-specific alternative splicing of Drosophila Ribosomal protein S21 suppresses a lethal mutation in the Phosphorylated adaptor for RNA export (Phax) gene

Abstract Genetic disruptions to the biogenesis of spliceosomal small-nuclear ribonucleoproteins in Drosophila cause wide-spread alternative splicing changes, including changes to the splicing of pre-mRNA for Ribosomal protein S21 (RpS21). Using a transposon mutant for the Phosphorylated adaptor for RNA export (Phax) gene, we demonstrate that changes in the splicing of RpS21 transcripts have a strong influence on the developmental progression of PhaxSH/SH mutants. Different alleles of the Drosophila RpS21 gene are circulating in common laboratory strains and cell lines. These alleles exhibit differences in RpS21 intron retention and splicing efficiency. Differences in the splicing of RpS21 transcripts account for prior conflicting observations of the phenotypic severity of PhaxSH/SH mutant stocks. The alleles uncover a strong splicing enhancer in RpS21 transcripts that can fully suppress the larval lethality and partially suppress the pupal lethality exhibited by PhaxSH/SH mutant lines. In the absence of the splicing enhancer, the splicing of RpS21 transcripts can be modulated in trans by the SR-rich B52 splicing factor. As PhaxSH/SH mutants exhibit wide-spread splicing changes in transcripts for other genes, findings here establish the importance of a single alternative splicing event, RpS21 splicing or intron retention, to the developmental progression of Drosophila.
Circ‐CBFB exacerbates hypoxia/reoxygenation‐triggered cardiomyocyte injury via regulating miR‐495‐3p in a VDAC1‐dependent manner

A large body of literature has identified that circular RNAs play critical roles in regulating the occurrence and development of cardiovascular disease. In the present study, we intended to provide new ideas and perspectives on the functional role of circ‐CBFB in hypoxia/reoxygenation (H/R)‐injured cardiomyocytes. We observed that circ‐CBFB expression was enhanced which was accompanied by a miR‐495‐3p reduction in response to H/R exposure. Functionally, deletion of circ‐CBFB obviously potentiated cell viability and restrained cell apoptosis, which was accompanied by a remarkable elevation of antiapoptotic Bcl‐2 but the repression of proapoptotic Bax and cleaved caspase‐3 in response to H/R. Additionally, the absence of circ‐CBFB dramatically prohibited H/R‐evoked cardiomyocyte oxidative stress, as revealed by a decrease in reactive oxygen species overproduction, diminution in MAD content, and enhancement in SOD, CAT, and GSH‐Px activities. Moreover, elimination of circ‐CBFB resulted in improvement of mitochondrial dysfunction, as assessed by mitochondrial membrane potential, adenosine triphosphate production, and the release of cyto‐c. Interestingly, circ‐CBFB inversely regulated miR‐495‐3p expression via acting as a competing endogenous RNA. VDAC1 was identified to be a functional target of miR‐495‐3p and positively modulated by circ‐CBFB. Mechanically, dissipation of miR‐495‐3p or augmentation of VDAC1 manifestly counteracted the beneficial effects of circ‐CBFB knockdown on H/R‐elicited cardiomyocyte insult. Collectively, these observations demonstrated that absence of circ‐CBFB offered cardio‐protection against H/R‐triggered cardiomyocyte injury by relieving apoptosis, oxidative stress, and mitochondria dysfunction through miR‐495‐3p/VDAC1 axis. This work unveiled an innovative axis of circ‐CBFB/miR‐495‐3p/VDAC1 in H/R‐challenged cardiomyocyte damage, exerting its potential in providing new thoughts in acute myocardial infarction management.
Robust muscle force prediction using NMFSEMD denoising and FOS identification

In this paper, an aliasing noise restraint technique and a system identification-based surface electromyography (sEMG)-force prediction model are proposed to realize a type of robust sEMG and muscle force prediction. For signal denoising, a novel non-negative matrix factorization screening empirical mode decomposition (NMFSEMD) and a fast orthogonal search (FOS)-based muscle force prediction model are developed. First, the NMFSEMD model is used to screen the empirical mode decomposition (EMD) results into the noisy intrinsic mode functions (IMF). Then, the noise matrix is computed using IMF translation and superposition, and the matrix is used as the input of NMF to obtain the denoised IMF. Furthermore, the reconstruction outcome of the NMFSEMD method can be used to estimate the denoised sEMG. Finally, a new sEMG muscle force prediction model, which considers a kind of candidate function in derivative form, is constructed, and a data-training-based linear weighted model is obtained. Extensive experimental results validate the suggested method’s correction: after the NMFSEMD denoising of raw sEMG signal, the signal-noise ratio (SNR) can be improved by about 15.0 dB, and the energy percentage (EP) can be greater than 90.0%. Comparing with the muscle force prediction models using the traditional pretreatment and LSSVM, and the NMFSEMD plus LSSVM-based method, the mean square error (MSE) of our approach can be reduced by at least 1.2%.