Using a clinical narrative-aware pre-trained language model for predicting emergency department patient disposition and unscheduled return visits.

The increasing prevalence of overcrowding in Emergency Departments (EDs) threatens the effective delivery of urgent healthcare. Mitigation strategies include the deployment of monitoring systems capable of tracking and managing patient disposition to facilitate appropriate and timely care, which subsequently reduces patient revisits, optimizes resource allocation, and enhances patient outcomes. This study used âˆ¼ 250,000 emergency department visit records from Taipei Medical University-Shuang Ho Hospital to develop a natural language processing model using BlueBERT, a biomedical domain-specific pre-trained language model, to predict patient disposition status and unplanned readmissions. Data preprocessing and the integration of both structured and unstructured data were central to our approach. Compared to other models, BlueBERT outperformed due to its pre-training on a diverse range of medical literature, enabling it to better comprehend the specialized terminology, relationships, and context present in ED data. We found that translating Chinese-English clinical narratives into English and textualizing numerical data into categorical representations significantly improved the prediction of patient disposition (AUROC = 0.9014) and 72-hour unscheduled return visits (AUROC = 0.6475). The study concludes that the BlueBERT-based model demonstrated superior prediction capabilities, surpassing the performance of prior patient disposition predictive models, thus offering promising applications in the realm of ED clinical practice.

Design and evaluation of oral formulation for apixaban.

Non-valvular atrial fibrillation (NVAF) is a common form of cardiac arrhythmia that affects 1-1.5% of adults and roughly 10% of elderly adults with dysphagia. Apixaban is an anticoagulant referred to as a factor Xa inhibitor, which has been shown to reduce the risk of stroke and systemic embolism in cases of NVAF. Our objective in the current study was to formulate an orally disintegrating film to facilitate the administration of apixaban to elderly patients who have difficulty swallowing. Researchers have used a wide variety of cellulose-based or non-cellulose-based polymers in a variety of combinations to achieve specific characteristics related to film formation, disintegration performance, drug content, in vitro drug release, and stability. One of the two formulations in this study was specify that bioequivalence criteria met with respect to Cmax of the reference drug (ELIQUIS®) in terms of pharmacokinetic profile. Further research will be required to assess the applicability of orodispersible films created using colloidal polymers of high and low molecular weights to other drugs with poor solubility in water.

Furanocoumarin Notopterol: Inhibition of Hepatocellular Carcinogenesis through Suppression of Cancer Stemness Signaling and Induction of Oxidative Stress-Associated Cell Death.

BACKGROUND: Hepatocellular carcinoma (HCC) remains an aggressive malignancy with a poor prognosis and a leading cause of cancer-related mortality globally. Cumulative evidence suggests critical roles for endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in chronic liver diseases. However, the role of ER stress in HCC pathogenesis, aggressiveness and therapy response remains unclear and understudied. OBJECTIVES: Against this background, the present study evaluated the therapeutic efficacy and feasibility of notopterol (NOT), a furanocoumarin and principal component of Notopterygium incisum, in the modulation of ER stress and cancer stemness, and the subsequent effect on liver oncogenicity. METHODS: An array of biomolecular methods including Western blot, drug cytotoxicity, cell motility, immunofluorescence, colony and tumorsphere formation, flow-cytometric mitochondrial function, GSH/GSSG ratio, and tumor xenograft ex vivo assays were used in the study. RESULTS: Herein, we demonstrated that NOT significantly suppresses the viability, migration, and invasion capacity of the human HCC HepJ5 and Mahlavu cell lines by disrupting ATF4 expression, inhibiting JAK2 activation, and downregulating the GPX1 and SOD1 expression in vitro. NOT also markedly suppressed the expression of vimentin (VIM), snail, b-catenin, and N-cadherin in the HCC cells, dose-dependently. Treatment with NOT significantly attenuated cancer stem cells (CSCs)-like phenotypes, namely colony and tumorsphere formation, with the concomitant downregulation of stemness markers OCT4, SOX2, CD133, and upregulated PARP-1 cleavage, dose-dependently. We also demonstrated that NOT anticancer activity was strongly associated with increased cellular reactive oxidative stress (ROS) but, conversely, reduced mitochondrial membrane potential and function in the HepJ5 and Mahlavu cells in vitro. Our tumor xenograft studies showed that compared with sorafenib, NOT elicited greater tumor growth suppression without adverse changes in mice body weights. Compared with the untreated control and sorafenib-treated mice, NOT-treated mice exhibited markedly greater apoptosis ex vivo, and this was associated with the co-suppression of stemness and drug-resistance markers OCT4, SOX2, ALDH1, and the upregulation of endoplasmic reticulum stress and oxidative stress factors PERK and CHOP. CONCLUSIONS: In summary, we demonstrated for the first time that NOT exhibits strong anticancer activity via the suppression of cancer stemness, enhanced endoplasmic reticulum stress and increased oxidative stress thus projecting NOT as a potentially effective therapeutic agent against HCC.

Clinical narrative-aware deep neural network for emergency department critical outcome prediction.

Since early identification of potential critical patients in the Emergency Department (ED) can lower mortality and morbidity, this study seeks to develop a machine learning model capable of predicting possible critical outcomes based on the history and vital signs routinely collected at triage. We compare emergency physicians and the predictive performance of the machine learning model. Predictors including patients' chief complaints, present illness, past medical history, vital signs, and demographic data of adult patients (aged ≥ 18 years) visiting the ED at Shuang-Ho Hospital in New Taipei City, Taiwan, are extracted from the hospital's electronic health records. Critical outcomes are defined as in-hospital cardiac arrest (IHCA) or intensive care unit (ICU) admission. A clinical narrative-aware deep neural network was developed to handle the text-intensive data and standardized numerical data, which is compared against other machine learning models. After this, emergency physicians were asked to predict possible clinical outcomes of thirty visits that were extracted randomly from our dataset, and their results were further compared to our machine learning model. A total of 4,308 (2.5 %) out of the 171,275 adult visits to the ED included in this study resulted in critical outcomes. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) of our proposed prediction model is 0.874 and 0.207, respectively, which not only outperforms the other machine learning models, but even has better sensitivity (0.95 vs 0.41) and accuracy (0.90 vs 0.67) as compared to the emergency physicians. This model is sensitive and accurate in predicting critical outcomes and highlights the potential to use predictive analytics to support post-triage decision-making.

Non-invasive ventilation for preoxygenation before general anesthesia: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Preoxygenation is crucial for providing sufficient oxygen reservoir to a patient before intubation and enables the extension of the period between breathing termination and critical desaturation (safe apnoea time). Conventionally, face mask ventilation is used for preoxygenation. Non-invasive ventilation is a new preoxygenation method. The study objective was to compare the outcomes of non-invasive ventilation and face mask ventilation for preoxygenation. METHOD: PubMed, Embase, Cochrane Library, and the ClinicalTrials.gov registry were searched for eligible studies published from database inception to September 2021. Individual effect sizes were standardized, and a meta-analysis was conducted using random effects models to calculate the pooled effect size. Inclusion criteria were randomised controlled trials of comparing the outcomes of non-invasive ventilation or face mask ventilation for preoxygenation in patients scheduled for surgeries. The primary outcome was safe apnea time, and the secondary outcomes were post-operative complications, number of patients who achieved the expired O2 fraction (FeO2) after 3 min of preoxygenation, minimal SpO2 during tracheal intubation, partial pressure of oxygen in the arterial blood (PaO2) and partial pressure of carbon dioxide (PaCO2) after preoxygenation, and PaO2 and PaCO2 after tracheal intubation. RESULTS: 13 trials were eligible for inclusion in this study. Significant differences were observed in safe apnoea time, number of patients who achieved FeO2 90% after preoxygenation for 3 min, and PaO2 and PaCO2 after preoxygenation and tracheal intubation. Only in the non-obese subgroup, no significant difference was observed in safe apnoea time (mean difference: 125.38, 95% confidence interval: - 12.26 to 263.03). CONCLUSION: Non-invasive ventilation appeared to be more effective than conventional methods for preoxygenation. We recommend non-invasive ventilation based on our results.

Early versus delayed feeding after therapeutic endoscopic procedures: Meta-analysis of randomized controlled trials.

INTRODUCTION: Early feeding was previously considered to increase the risk of postprocedural bleeding. However, many trials have demonstrated the benefits of early feeding after therapeutic endoscopic procedures. We conducted a meta-analysis of randomized controlled trials to evaluate the safety and outcomes between early feeding and delayed feeding after therapeutic endoscopic procedures. METHODS: Medline (PubMed), Embase, Google Scholar, the Cochrane Library, and clinicaltrials.gov were searched to identify randomized controlled trials that met our inclusion criteria. The pooled data for the mortality rate, postprocedural bleeding rate, and length of hospital stay were analyzed. RESULTS: A total of seven trials consisting of 717 patients were reviewed. These seven trials examined various therapeutic endoscopic procedures. Three trials included patients undergoing endoscopic hemostasis for upper gastrointestinal bleeding, two included patients undergoing esophageal variceal ligation, and two included patients with gastric neoplasm treated with endoscopic submucosal dissection. Although no significant differences were observed in the postprocedural bleeding rate or the mortality rate between patients who received early feeding and those who received delayed feeding, early feeding resulted in shorter hospital stays (weighted mean difference -1.04, 95% confidence interval -1.45 to 0.63). CONCLUSION: Early feeding appears to be a safe management method for patients undergoing therapeutic endoscopic procedures. Therefore, we recommend early feeding for these patients.

Association between Sleep Deprivation in Caregivers and Risk of Injury among Toddlers: A Propensity Score Analysis.

INTRODUCTION: Unintentional injury remains the leading cause of death in children worldwide. Adequate parental supervision is a crucial strategy for preventing injury. Many factors, such as a large family size, poor socioeconomic status, and the caregiver being a single mother, contribute to unintentional injury in children. In addition, sleep deprivation in caregivers might be associated with injury in children because sleep deprivation causes impaired daytime cognitive function, wake-state instability, and negative moods, thereby impairing caregiver supervision. Therefore, this study determines the association between injury in children and the sleep quality of their primary caregivers. METHOD: This is a retrospective case-control study on unintentional injury in children aged 0 to 4 years who visited the emergency department (case group) and an age- and sex-matched control group. Sleep quality in caregivers was assessed using the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was used to evaluate the association between aspects of the PSQI and injury. A propensity score model was used to generate a quasirandomized design. RESULTS: This case-control study recruiting 277 injured and 274 noninjured children was conducted in Taiwan. There was no statistically significant difference in child's age and primary caregiver's age between the injured and noninjured groups. The primary outcome, Pittsburgh sleep quality index, was not significantly different between the two groups. The average scores of sleep duration and habitual sleep efficiency in the control group were higher than those in the case group. However, there was no difference between the two groups after adjusting via a propensity score model, including the following potential confounders, child's age, child's sex, number of previous injury, caregiver mental status, caregiver's sex and caregiver's age, and the number of children living together. CONCLUSION: Our study was the first to examine the association between injury in children and the sleep quality of their primary caregivers. We observed that no PSQI component significantly affected the risk of injury among children.

Long-term in vitro degradation behavior and biocompatibility of polycaprolactone/cobalt-substituted hydroxyapatite composite for bone tissue engineering.

OBJECTIVE: Currently, infections due to foreign-body reactions caused by bacteria or implant materials at the wound site are one of the major reasons for the failure of guided tissue regeneration (GTR) and guided bone regeneration (GBR) in clinical applications. The purpose of this study was to develop regeneration membranes with localized cobalt ion release to reduce infection and inflammation by polycaprolactone (PCL)/cobalt-substituted hydroxyapatite (CoHA). METHODS: The PCL composite membrane containing 20 wt% CoHA powders was prepared by solvent casting. The surface morphology, crystal structure, chemical composition and thermal properties of PCL composite membranes were characterized. The biocompatibility, osteogenic differentiation and antibacterial properties of composite membrane were also investigated. Then, in biodegradability was assessed by immersing phosphate buffer solution (PBS) for 6 months. RESULTS: Physicochemical analyses revealed that CoHA is evenly mixed in the membranes and assistance reduce the crystallinity of PCL for getting more degradation amounts than PCL membrane. Osteoblast cells culture on the membrane showed that the CoHA significantly increases cell proliferation and found the calcium deposition production increased over 90% compared with PCL after 7 days of culture. A good antibacterial effect was achieved by the addition of CoHA powder. The results were confirmed by 2.4 times reduction of proliferation of Escherichia coli (E. coli) seeded on the composite membrane after 24 h. Immersing in PBS for 6 months indicated that PCL-CoHA composite membrane has improved biodegradation and can continuously remove free radicals to reduce the inflammatory response. SIGNIFICANCE: The PCL-CoHA composite membrane with suitable releasing of cobalt ion can be considered as a potential choice for bone tissue regeneration.

Cardioprotective Efficacy of Red Wine Extract of Onion in Healthy Hypercholesterolemic Subjects.

The objective of this study was to evaluate the efficacy of the red wine extract of onion (RO) and red wine (RW) on alleviating the risk factors of cardiovascular disease. During in vitro studies, various antioxidant activities [trolox equivalent antioxidant capacity (TEAC), DPPH, and H2 O2 scavenging ability] of RO and RW group were evaluated. Both RO and RW showed the maximum antioxidant capacity. During in vivo studies, 23 healthy hypercholesterolemic volunteers were randomly selected and assigned into two groups, who drunk 250 mL of RO (n = 11) or RW (n = 10) for 10 weeks. No significant changes were observed in anthropometric parameters (body weight, height, body mass, and BMI) in each group. Both RW and RO extracts elevated (p < 0.05) antioxidant activity and thereby prolonging the lag time of low-density lipoprotein oxidation. However, RO extract intake substantially suppressed (p < 0.05) the total cholesterol and low-density lipoprotein cholesterol levels when equivalence with RW thus, indicating its additional hypocholesterolemic effect. The inflammatory markers such as factor VII were also positively modulated by RO extract. Results indicated that RO extract consumption rendered better cardio protective effect than RW by altering cholesterol, improving antioxidation and suppressing inflammatory marker levels and thereby, attenuating the cardiovascular disease incidence.

Sleep duration and sleep quality following acute mild traumatic brain injury: a propensity score analysis.

INTRODUCTION: Mild traumatic brain injury (mTBI) has been widely studied and the effects of injury can be long term or even lifelong. This research aims to characterize the sleep problems of patients following acute mTBI. METHODS: A total of 171 patients with mTBI within one month and 145 non-mTBI controls were recruited in this study. The questionnaire, Pittsburgh Sleep Quality Index (PSQI), was used to evaluate seven aspects of sleep problems. A propensity score method was used to generate a quasirandomized design to account for the background information, including gender, age, Beck's Anxiety Index, Beck's Depression Index, and Epworth Sleepiness Scale. The effect was evaluated via cumulative logit regression including propensity scores as a covariate. RESULTS: Before adjustment, about 60% mTBI patients and over three quarters of control subjects had mild sleep disturbance while one third mTBI patients had moderate sleep disturbance. After adjusting by the propensity scores, the scores of sleep quality and duration were significant between mTBI and control groups. CONCLUSION: Our study supports that sleep problem is common in mTBI group. After adjusting the confounders by propensity score, sleep duration and subjective sleep quality are the most frequently reported problems in mTBI patients within one month after the injury.

miR-31 is upregulated in oral premalignant epithelium and contributes to the immortalization of normal oral keratinocytes.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. MicroRNAs are short non-coding RNAs that regulate gene expression and are crucial for tumorigenesis. Previously, we have identified that miR-31 is frequently upregulated in OSCC and that this miR-31 increase, together with downstream effector modulation, enhances oral carcinogenesis. We have identified higher levels of miR-31 expression in oral potential malignant disorder (OPMD) tissues compared with normal oral mucosa. Exogenous miR-31 and human telomerase reverse transcriptase (hTERT) expression were introduced into cultured normal oral keratinocytes (NOKs), which led to the immortalization; these lines were designated M31OK1 and M31OK3. These immortalized lines maintained the capability to undergo squamous differentiation. In addition, migration by both cell lines was attenuated by hTERT and miR-31 knockdown. M31OK1 carries a p53 gene mutation at codon 273. A serum-tolerant subline, M31OK1-D, exhibits potent anchorage-independent growth that is attenuated by knockdown of both hTERT and miR-31. miR-31-targeted factors inhibiting HIF (FIH), which upregulated vascular endothelial growth factor (VEGF), was found crucial for oral tumorigenesis. The proliferation, migration and epithelial-mesenchymal transition of M31OK1-D are associated with downregulation of FIH and upregulation of VEGF, which require miR-31 expression. High miR-31 expression is correlated with higher VEGF expression and lower E-cadherin expression in OPMD tissue. It can be concluded that miR-31 collaborates with hTERT to immortalize NOKs and that this may contribute to early stage oral carcinogenesis. The targeting of downstream factors by miR-31 may further advance the neoplastic progression of immortalized NOKs, allowing them to become malignant.

Malate dehydrogenase is negatively regulated by miR-1 in Trichomonas vaginalis.

MicroRNAs are highly conserved small noncoding RNAs that can suppress protein translation through complementary binding to target mRNAs. We used a novel approach to identify miRNA targets in the protist Trichomonas vaginalis by comparing the levels of differentially expressed proteins and genes in the trophozoite and amoeboid stages. We observed that the T. vaginalis malate dehydrogenase (Tv_MDH) gene was upregulated 20-fold in the amoeboid stage, but the protein level was reduced by 4.5-fold. Bioinformatics analysis revealed that the Tv_MDH mRNA contains putative target sites of the miR-1 family. The expression level of endogenous tva-miR-1 in the amoeboid stage was 50-fold higher than in the trophozoite stage. Transfection of trophozoites with tva-miR-1 mimics reduced Tv_MDH protein expression by 60%. Based on these experimental data, we conclude that Tv_MDH is negatively regulated by tva-miR-1. The results of this study demonstrate that a combination of proteomic and transcriptomic approaches is a powerful tool for identifying miRNA targets.

Ovarian cyst torsion in a toddler.

Acute abdominal pain in children is encountered frequently, and the differential diagnosis is extensive. Acute ovarian torsion in children is rare, especially at a very young age, and a difficult diagnosis to make. Infarction caused by ovarian torsion will result if the twist is not unwound spontaneously or surgically in a timely fashion. We presented a case of acute ovarian cyst torsion in a 2-year-old girl who originally presented to the emergency department with abdominal pain and vomiting. Ultimately, she was found to have a 2-cm cyst of the right ovary with concomitant torsion. Because acute ovarian torsion in a very young child is not encountered frequently, timely diagnosis is required to prevent mortality and minimize morbidity. It is important to keep ovarian torsion in the differential of any female children with acute abdominal pain. Emergency physicians should be aware that the potential of acute ovarian torsion in a very young child has a high index of suspicion and seek early operative intervention.

Identification of microRNA in the protist Trichomonas vaginalis.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that have important regulatory roles in multicellular organisms. However, miRNA has never been identified experimentally in protist. Direct cloning of 438 expressed miRNA tags by microRNA serial analysis of gene expression from the parasitic protist Trichomonas vaginalis identified nine candidate miRNAs. Bioinformatics analysis of the corresponding genomic region revealed that these miRNA candidates contain a classical stem-loop-stem structure of pre-microRNAs. Analysis of the 20 nt long mature tva-miR-001 showed that it is an intergenic miRNA located at the scaffold DS113596. Tva-miR-001 was differentially expressed in the trophozoite, pseudocyst and amoeboid stages. Based on the experimental results of the present study, we provided solid evidence that protist possesses a miRNA regulating network comparable with multicellular organisms for the first time.