DigitalCommons@The Texas Medical Center
Not a member yet
41791 research outputs found
Sort by
COVID-19 Booster Vaccine Messaging in Emergency Departments: A Cluster Randomized Clinical Trial
No full textImportance: Patient uptake of updated COVID-19 vaccines is crucial for reducing severe outcomes, yet national uptake remains low.
Objective: To determine if tailored messaging or simple inquiry about vaccine acceptance increases 30-day uptake of updated COVID-19 vaccines among emergency department (ED) patients.
Design, setting, and participants: This 3-arm, cluster randomized clinical trial conducted from January 29 to June 18, 2024, enrolled adult ED patients who had not received a COVID-19 vaccine in the prior 6 months across 6 EDs in San Francisco, California; Philadelphia, Pennsylvania; Houston, Texas; and Durham, North Carolina.
Interventions: Intervention M involved tailored messaging about updated COVID-19 vaccines and inquiry about vaccine acceptance. Intervention Q involved only inquiry about vaccine acceptance. Usual care (no messaging or vaccine acceptance questions) served as the control.
Main outcomes and measures: The primary outcome was updated COVID-19 vaccine receipt within 30 days of the ED visit, assessed via electronic health record review and follow-up telephone calls. Secondary outcomes included vaccine acceptance and vaccination during the ED visit. Outcomes were also compared between study sites that had the updated COVID-19 vaccine available and those that did not.
Results: Of 852 participants (median age, 47 years [IQR, 33-63 years]; 464 [54.5%] women), 247 (29.0%) were in the intervention M group, 273 (32.0%) in the intervention Q group, and 332 (39.0%) in the control group. Vaccine uptake at 30 days was not significantly higher in either the intervention M group compared with control (14 participants [5.7%] vs 10 [3.0%]; absolute difference, 2.7 percentage points [pp] [95% CI, -0.8 to 6.3 pp]) or the intervention Q group compared with control (11 [4.0%] vs 10 [3.0%]; absolute difference, 1.0 pp [95% CI, -2.0 to 4.2 pp]). However, at sites where vaccines were available, the intervention M group had higher uptake compared with control (13 of 132 [9.8%] vs 5 of 150 [3.3%]; absolute difference, 6.5 pp [95% CI, 0.5-12.5 pp]).
Conclusions and relevance: In this cluster randomized clinical trial of adult ED patients, tailored messaging and simple inquiry alone did not significantly increase 30-day updated COVID-19 vaccine uptake among patients. The slight increase in uptake among participants in the EDs that had access to the updated COVID-19 vaccines suggested that vaccine availability was an effect modifier, underscoring the importance of opportunity and convenience in vaccine delivery.
Trial registration: ClinicalTrials.gov Identifier: NCT06156215
Digital Commons Reaches 3 Million Downloads
No full textSince its first article was deposited in 2005, has grown to include over 38,500 items accessed by users in over 170 countries and 1,000 institutions, with an average of 100,000 downloads each month. DigitalCommons@TMC
For additional information visit the library blog
Automated Assignment Grading With Large Language Models: Insights From a Bioinformatics Course
No full textMotivation: Providing students with individualized feedback through assignments is a cornerstone of education that supports their learning and development. Studies have shown that timely, high-quality feedback plays a critical role in improving learning outcomes. However, providing personalized feedback on a large scale in classes with large numbers of students is often impractical due to the significant time and effort required. Recent advances in natural language processing and large language models (LLMs) offer a promising solution by enabling the efficient delivery of personalized feedback. These technologies can reduce the workload of course staff while improving student satisfaction and learning outcomes. Their successful implementation, however, requires thorough evaluation and validation in real classrooms.
Results: We present the results of a practical evaluation of LLM-based graders for written assignments in the 2024/25 iteration of the Introduction to Bioinformatics course at the University of Ljubljana. Over the course of the semester, more than 100 students answered 36 text-based questions, most of which were automatically graded using LLMs. In a blind study, students received feedback from both LLMs and human teaching assistants (TAs) without knowing the source, and later rated the quality of the feedback. We conducted a systematic evaluation of six commercial and open-source LLMs and compared their grading performance with human TAs. Our results show that with well-designed prompts, LLMs can achieve grading accuracy and feedback quality comparable to human graders. Our results also suggest that open-source LLMs perform as well as commercial LLMs, allowing schools to implement their own grading systems while maintaining privacy
Characterization of Hepatic Pathology During Azoxymethane-Induced Acute Liver Failure
Get PDFBackground: Acute liver failure (ALF) is a loss of liver function due to a severe hepatic insult. Studies utilizing the azoxymethane (AOM) mouse model of ALF, which also generates hepatic encephalopathy, have primarily focused on development of neurological deficits. However, the molecular processes that generate liver damage have not been fully characterized. Therefore, a more comprehensive characterization of the hepatic consequences of AOM toxicity is needed to better understand this disease model.
Aim: To identify molecular pathology contributing to hepatic injury during the progression of AOM-induced ALF.
Methods: C57BL/6 mice were injected with AOM to produce ALF and hepatic encephalopathy. Tissue was collected at defined stages of neurological decline up to coma. Liver injury, CYP2E1 expression, oxidative stress, inflammation, apoptosis, necroptosis, and hepatocellular senescence were assessed.
Results: Increased hepatic necrosis and exacerbated liver injury were observed after AOM injection as mice progressed towards coma. CYP2E1 expression decreased in AOM-treated mice as liver injury progressed. Malondialdehyde, myeloperoxidase and other measures of oxidative stress were significantly increased during AOM-induced ALF. Hepatic CCL2 and tumor necrosis factor α expression increased as AOM-induced liver injury progressed. Mixed lineage kinase domain-like protein phosphorylation was increased early during the progression of AOM-induced liver injury. Measures of apoptosis and cellular senescence all increased as the time course of AOM progressed.
Conclusion: These data support that necrosis, oxidative stress, inflammation, apoptosis, and senescence were elevated in AOM-treated mice, with inflammation being the earliest significant change
Multiomic and Electrophysiologic Analyses Reveal That an Inherited MRC2 Variant Causes Fibroblast Dysfunction and Increased Atrial Fibrillation Susceptibility
No full textA recent study identified a rare variant in the mannose receptor C type 2 (MRC2) gene in individuals with familial reentrant supraventricular tachycardia, a Wolff-Parkinson-White (WPW) electrocardiogram pattern, and structurally normal hearts. WPW syndrome is associated with atrial fibrillation (AF), and MRC2 was recently proposed as a protective gene for AF. We determined whether the E990G-heterozygous (het) loss-of-function variant in Mrc2 increases AF susceptibility and identified aberrant cellular mechanisms resulting from Mrc2 deficiency in atrial cardiofibroblasts (ACFs) and atrial tissue in mice that may promote AF. Programmed electrical stimulation was performed to determine AF susceptibility in Mrc2 E990G-het mice and wild-type (WT) controls. ACFs were isolated from these mice and cultured, and transcriptomic profiling by RNA sequencing and secretomic/proteomic profiling by mass spectrometry were performed on ACFs and whole atrial tissue. E990G-het mice exhibited increased susceptibility to pacing-induced AF and had decreased atrioventricular effective refractory periods compared with WT controls. Transcriptomic, secretomic, and proteomic profiling of cultured ACFs and whole atrial tissue revealed differential expression of several fibrotic regulators in E990G-het versus WT mice, including decreased ACF expression of matrix metalloproteinase 13, which degrades collagen types I, II, and III; decreased ACF expression and secretion of matrix metalloproteinase 12, which degrades collagen types I, III, IV, elastin, and fibronectin; and increased tissue levels of cellular communication network factor 2/connective tissue growth factor, a profibrotic regulator. In conclusion, Mrc2 E990G-het mice exhibit increased AF susceptibility and differentially regulated fibrotic genes and proteins.
NEW & NOTEWORTHY Our study reveals a rare MRC2 gene variant (E990G) linked to familial supraventricular tachycardia and Wolff-Parkinson-White syndrome increases atrial fibrillation (AF) susceptibility in mice. The E990G-heterozygous variant disrupts atrial cardiofibroblast function, reducing protective matrix metalloproteinases (MMP-12 and MMP-13) and elevating profibrotic CCN2/CTGF levels, as shown through transcriptomic and proteomic profiling. This suggests that MRC2 deficiency promotes AF by altering fibrotic regulation in atrial tissue
Liver-specific Expression of HIV-1 Viral Protein R Causes Hepatic Steatosis and Glucose Intolerance in Male Mice
Get PDFBackground: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in people with HIV (PWH), with both HIV and antiretroviral therapy contributing to liver damage and glucose intolerance. However, the role of viral proteins derived from reservoirs in this process remains unclear.
Methods: Adeno-associated virus (AAV) constructs encoding a control protein or HIV-1 viral protein R (Vpr) driven by the thyroxine-binding globulin promoter were administered to male mice (n = 5 per group) fed regular chow or a high-fat diet (HFD). Young adult mice underwent intraperitoneal glucose tolerance testing and magnetic resonance imaging, followed by euthanasia. Liver and adipose tissues were analyzed for mRNA expression, lipid levels, and fat content and plasma samples for triglycerides and liver function.
Results: AAV-Vpr mice on HFD developed exacerbated hepatic steatosis, glucose intolerance, and systemic inflammation compared to AAV-green fluorescent protein control mice. Gene expression indicated enhanced de novo lipogenesis, diminished lipid oxidation and insulin resistance in the liver. These effects were distinct from those observed with HFD alone, confirming a Vpr-specific contribution.
Conclusion: Vpr upregulates the hepatic synthesis of fatty acids and downregulates their oxidation and export as triglycerides. The liver-specific activity of Vpr is sufficient, in synergy with a HFD, to cause hepatic steatosis and impaired glucose tolerance. These findings define a tissue-autonomous role for Vpr in mediating hepatic steatosis in mice, with implications for MASLD development and its complications in PWH
Single Balloon Enteroscopy in the Elderly
Get PDFBackground: Single-balloon enteroscopy (SBE) is a minimally invasive procedure to assess and treat small bowel pathologies. The most common use is to detect suspected small bowel bleeding: Insignificant gastrointestinal (GI) bleeding or iron deficiency anaemia (IDA). The safety and feasibility of SBE in the elderly has not been adequately studied.
Aim: To assess the safety and feasibility of both antegrade and retrograde SBE in elderly patients.
Methods: We performed a retrospective cohort study of all antegrade and retrograde SBE done at our center from March 2011 through May 2020. We collected patient\u27s data including demographics, indications, findings, therapeutic interventions, and complications. The cohort was divided into 3 groups: Patients younger than 65 years (group 1), patients 65-75 years (group 2), and patients older than 75 years (group 3). We used 1-way one way analysis of variance, a χ 2 test, and logistic regression to compare study outcomes. The primary aim was to assess diagnostic yield, therapeutic yield and rates of complications from SBE among study groups.
Results: A total of 284 SBE were performed in 227 patients. In the 227 patients, we analyzed 194 antegrade (19 in gastric bypass patients) and 33 retrograde procedures. Mean age was 62.0 (SD: 16.7), 130 patients were women (57.3%), 98 were Hispanic (43.4%), and mean body mass index was 28 (SD: 6.3). The number of patients in each group were: Group 1 (117, 51.3%), group 2 (57, 25.0%) and group 3 (53, 23.7%). Gender, ethnicity, body mass index and proportions of antegrade and retrograde were comparable between age groups. The most common indications for procedure were: Obscure GI bleeding (48%), IDA (48%), abdominal pain (14%), and others (abnormal capsule, 43%; abnormal imaging, 9.7%; diarrhea 5.3%). The elderly (group 3) were more likely to have GI bleed as the indication (42.7%, 40.4%, 67.9%, P = 0.004) without difference in IDA (44.4%, 56.1%, 47.2%, P = 0.35). Diagnostic yield was significantly higher in the elderly group (48.2%, 53.7%, 68.0%), particularly in antegrade (48.5%, 53.3%, 72.1%, P = 0.033). Angioectasias were the most common finding (21.0%) and present more often in the elderly (10.9%, 20.4%, 44%) (P \u3c 0.001). Therapeutic interventions were also more in the elderly group (35.0%, 33.3%, 58.5%, P = 0.007). There were only 2 (0.9%) complications, including minor oropharyngeal hemorrhage and esophageal trauma and no deaths, with no difference among groups.
Conclusion: In a retrospective analysis of SBE, we found this procedure safe and feasible in the elderly. SBE has higher diagnostic and therapeutic yields in the elderly vs the other age groups, mainly because of the increased small bowel angioectasias
Genome-Wide Association Studies of Down Syndrome Associated Congenital Heart Defects Suggests a Genetically Heterogeneous Risk for CHD in DS
No full textCongenital heart defects (CHDs) are the most common structural birth defect and are present in 40-50% of children born with Down syndrome (DS). To characterize the genetic architecture of DS-associated CHD, we sequenced genomes of a multiethnic group of children with DS and a CHD (n=886: atrioventricular septal defects (AVSD), n=438; atrial septal defects (ASD), n=122; ventricular septal defects (VSD), n=170; other types of CHD, n=156) and DS with a structurally normal heart (DS+NH, n=572). We performed four GWAS for common variants (MAF\u3e0.05) comparing DS with CHD, stratified by CHD-subtype, to DS+NH controls. Although no SNP achieved genome-wide significance, multiple loci in each analysis achieved suggestive significance (p\u3c 2x10−6). Of these, the 1p35.1 locus (near RBBP4) was specifically associated with ASD risk and the 5q35.2 locus (near MSX2) was associated with any type of CHD. Each of the suggestive loci contained one or more plausible candidate genes expressed in the developing heart. While no SNP replicated (p\u3c 2x10−6) in an independent cohort of DS+CHD (DS+CHD: n=229; DS+NH: n=197), most SNPs that were suggestive in our GWASs remained suggestive when meta-analyzed with the GWASs from the replication cohort. These results build on previous work to identify genetic modifiers of DS-associated CHD
Unexpected Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy After Routine Preoperative Evaluation Leads to Life-Saving Intervention
No full textBackground: A healthy 44-year-old woman presented for preoperative evaluation of planned bunionectomy. Electrocardiogram showed T-wave inversions in leads V1 to V5 and epsilon waves in precordium prompting further evaluation.
Case summary: Imaging studies and genetic testing revealed diagnosis of arrhythmogenic right ventricular cardiomyopathy. Patient met Class IIb indication for primary prevention with implantable cardioverter-defibrillator (ICD). Despite weak guideline indication, shared decision-making with the patient led to ICD implantation. Six months later, she had a ventricular tachycardia arrest resulting in ICD shock and return to sinus rhythm.
Discussion: Routine preoperative evaluation led to the diagnosis of a rare pathology. Prompt evaluation and intervention using shared decision-making led to a life-saving intervention.
Take-home messages: Utilization of guidelines in conjunction with patient-centered therapy is the best approach to provide optimal care and prevent mortality in rare instances like this case for ICD placement after arrhythmogenic right ventricular cardiomyopathy diagnosis
Blue-Shifted Ancyromonad Channelrhodopsins for Multiplex Optogenetics
Get PDFLight-gated ion channels from protists (channelrhodopsins or ChRs) are optogenetic tools widely used for controlling neurons and cardiomyocytes. Multiplex optogenetic applications require spectrally separated molecules, which are difficult to engineer without disrupting channel function. Scanning numerous sequence databases, we identified three naturally blue-shifted ChRs from ancyromonads. They form a separate branch on the phylogenetic tree and contain residue motifs characteristic of anion ChRs (ACRs). However, only two conduct chloride, whereas the closely related Nutomonas longa homolog generates inward cation currents in mammalian cells under physiological conditions, significantly exceeding those by previously known tools with similar spectral maxima (peak absorption at ~440 nm). Measurements of transient absorption changes and pH titration of purified proteins combined with mutant analysis revealed the roles of the residues in the photoactive site. Ancyromonad ChRs could be activated by near-infrared two-photon illumination, a technique that enables the deeper-tissue optogenetic activation of specific neurons in three dimensions. Both ancyromonad ACRs allowed optogenetic silencing of mouse cortical neurons in brain slices. Ancyromonas sigmoides ACR (AnsACR) expression in cholinergic neurons enabled photoinhibition of pharyngeal muscle contraction in live worms. Overall, our results deepen the mechanistic understanding of light-gated channel function and expand the optogenetic toolkit with potent, blue-shifted ChRs