RefAI: a GPT-powered retrieval-augmented generative tool for biomedical literature recommendation and summarization.

OBJECTIVES: Precise literature recommendation and summarization are crucial for biomedical professionals. While the latest iteration of generative pretrained transformer (GPT) incorporates 2 distinct modes-real-time search and pretrained model utilization-it encounters challenges in dealing with these tasks. Specifically, the real-time search can pinpoint some relevant articles but occasionally provides fabricated papers, whereas the pretrained model excels in generating well-structured summaries but struggles to cite specific sources. In response, this study introduces RefAI, an innovative retrieval-augmented generative tool designed to synergize the strengths of large language models (LLMs) while overcoming their limitations. MATERIALS AND METHODS: RefAI utilized PubMed for systematic literature retrieval, employed a novel multivariable algorithm for article recommendation, and leveraged GPT-4 turbo for summarization. Ten queries under 2 prevalent topics ("cancer immunotherapy and target therapy" and "LLMs in medicine") were chosen as use cases and 3 established counterparts (ChatGPT-4, ScholarAI, and Gemini) as our baselines. The evaluation was conducted by 10 domain experts through standard statistical analyses for performance comparison. RESULTS: The overall performance of RefAI surpassed that of the baselines across 5 evaluated dimensions-relevance and quality for literature recommendation, accuracy, comprehensiveness, and reference integration for summarization, with the majority exhibiting statistically significant improvements (P-values <.05). DISCUSSION: RefAI demonstrated substantial improvements in literature recommendation and summarization over existing tools, addressing issues like fabricated papers, metadata inaccuracies, restricted recommendations, and poor reference integration. CONCLUSION: By augmenting LLM with external resources and a novel ranking algorithm, RefAI is uniquely capable of recommending high-quality literature and generating well-structured summaries, holding the potential to meet the critical needs of biomedical professionals in navigating and synthesizing vast amounts of scientific literature.

Effectiveness of interventions to improve drinking water, sanitation, and handwashing with soap on risk of diarrhoeal disease in children in low-income and middle-income settings: a systematic review and meta-analysis.

BACKGROUND: Estimates of the effectiveness of water, sanitation, and hygiene (WASH) interventions that provide high levels of service on childhood diarrhoea are scarce. We aimed to provide up-to-date estimates on the burden of disease attributable to WASH and on the effects of different types of WASH interventions on childhood diarrhoea in low-income and middle-income countries (LMICs). METHODS: In this systematic review and meta-analysis, we updated previous reviews following their search strategy by searching MEDLINE, Embase, Scopus, Cochrane Library, and BIOSIS Citation Index for studies of basic WASH interventions and of WASH interventions providing a high level of service, published between Jan 1, 2016, and May 25, 2021. We included randomised and non-randomised controlled trials conducted at household or community level that matched exposure categories of the so-called service ladder approach of the Sustainable Development Goal (SDG) for WASH. Two reviewers independently extracted study-level data and assessed risk of bias using a modified Newcastle-Ottawa Scale and certainty of evidence using a modified Grading of Recommendations, Assessment, Development, and Evaluation approach. We analysed extracted relative risks (RRs) and 95% CIs using random-effects meta-analyses and meta-regression models. This study is registered with PROSPERO, CRD42016043164. FINDINGS: 19 837 records were identified from the search, of which 124 studies were included, providing 83 water (62 616 children), 20 sanitation (40 799 children), and 41 hygiene (98 416 children) comparisons. Compared with untreated water from an unimproved source, risk of diarrhoea was reduced by up to 50% with water treated at point of use (POU): filtration (n=23 studies; RR 0·50 [95% CI 0·41-0·60]), solar treatment (n=13; 0·63 [0·50-0·80]), and chlorination (n=25; 0·66 [0·56-0·77]). Compared with an unimproved source, provision of an improved drinking water supply on premises with higher water quality reduced diarrhoea risk by 52% (n=2; 0·48 [0·26-0·87]). Overall, sanitation interventions reduced diarrhoea risk by 24% (0·76 [0·61-0·94]). Compared with unimproved sanitation, providing sewer connection reduced diarrhoea risk by 47% (n=5; 0·53 [0·30-0·93]). Promotion of handwashing with soap reduced diarrhoea risk by 30% (0·70 [0·64-0·76]). INTERPRETATION: WASH interventions reduced risk of diarrhoea in children in LMICs. Interventions supplying either water filtered at POU, higher water quality from an improved source on premises, or basic sanitation services with sewer connection were associated with increased reductions. Our results support higher service levels called for under SDG 6. Notably, no studies evaluated interventions that delivered access to safely managed WASH services, the level of service to which universal coverage by 2030 is committed under the SDG. FUNDING: WHO, Foreign, Commonwealth & Development Office, and National Institute of Environmental Health Sciences.

Safety, Tolerability, and Biologic Activity of AXA1125 and AXA1957 in Subjects With Nonalcoholic Fatty Liver Disease.

INTRODUCTION: AXA1125 and AXA1957 are novel, orally administered endogenous metabolic modulator compositions, specifically designed to simultaneously support multiple metabolic and fibroinflammatory pathways associated with nonalcoholic fatty liver disease (NAFLD). This study assessed safety, tolerability, and biologic activity of AXA1125 and AXA1957 in NAFLD. METHODS: In this multicenter, 16-week, placebo-controlled, single-blind, randomized clinical study in subjects with NAFLD stratified by type 2 diabetes, AXA1125 24 g, AXA1957 13.5 g or 20.3 g, or placebo was administered twice daily. Key metabolism (MRI-proton density fat fraction [MRI-PDFF] and homeostasis model assessment of insulin resistance [HOMA-IR]) and fibroinflammation markers (alanine aminotransferase [ALT], corrected T1 [cT1], keratin-18 [K-18] M65, and N-terminal type III collagen propeptide [Pro-C3]) were evaluated. Safety outcomes included adverse events and standard laboratory assessments. RESULTS: Baseline characteristics of the 102 enrolled subjects, including 40 with type 2 diabetes, were consistent with presumed nonalcoholic steatohepatitis. AXA1125 showed consistently greater biologic activity than AXA1957 or placebo. Week 16 changes from baseline with AXA1125 vs placebo: MRI-PDFF -22.9% vs -5.7%, HOMA-IR -4.4 vs +0.7, ALT -21.9% vs -7.2%, K-18 M65 -13.6% vs +20.1%, cT1 -69.6 vs +18.3 ms (P < 0.05), and Pro-C3 -13.6% vs -3.6%. Week 16 changes from baseline with AXA1957 20.3 g: MRI-PDFF -8.1%, HOMA-IR +8.4, ALT -20.7%, K-18 M65 6.6%, cT1 -34.7 ms, and Pro-C3 -15.6%. A greater proportion of subjects treated with AXA1125 achieved clinically relevant thresholds: ≥30% MRI-PDFF, ≥17-IU/L ALT, and ≥80-ms cT1 reductions at week 16. Study products were safe and well tolerated with stable lipid and weight profiles. DISCUSSION: Both compositions showed multitargeted activity on relevant NAFLD pathways. AXA1125 demonstrated the greatest activity over 16 weeks, warranting continued clinical investigation in nonalcoholic steatohepatitis subjects.

Identification of MicroRNA-Related Tumorigenesis Variants and Genes in the Cancer Genome Atlas (TCGA) Data.

MicroRNAs (miRNAs) are a class of small non-coding RNA that can down-regulate their targets by selectively binding to the 3' untranslated region (3'UTR) of most messenger RNAs (mRNAs) in the human genome. Single nucleotide variants (SNVs) located in miRNA target sites (MTS) can disrupt the binding of targeting miRNAs. Anti-correlated miRNA-mRNA pairs between normal and tumor tissues obtained from The Cancer Genome Atlas (TCGA) can reveal important information behind these SNVs on MTS and their associated oncogenesis. In this study, using previously identified anti-correlated miRNA-mRNA pairs in 15 TCGA cancer types and publicly available variant annotation databases, namely dbNSFP (database for nonsynonymous SNPs' functional predictions) and dbMTS (database of miRNA target site SNVs), we identified multiple functional variants and their gene products that could be associated with various types of cancers. We found two genes from dbMTS and 33 from dbNSFP that passed our stringent filtering criteria (e.g., pathogenicity). Specifically, from dbMTS, we identified 23 candidate genes, two of which (BMPR1A and XIAP) were associated with diseases that increased the risk of cancer in patients. From dbNSFP, we identified 65 variants located in 33 genes that were likely pathogenic and had a potential causative relationship with cancer. This study provides a novel way of utilizing TCGA data and integrating multiple publicly available databases to explore cancer genomics.

Global Access to Handwashing: Implications for COVID-19 Control in Low-Income Countries.

BACKGROUND: Low-income countries have reduced health care system capacity and are therefore at risk of substantially higher COVID-19 case fatality rates than those currently seen in high-income countries. Handwashing is a key component of guidance to reduce transmission of the SARS-CoV-2 virus, responsible for the COVID-19 pandemic. Prior systematic reviews have indicated the effectiveness of handwashing to reduce transmission of respiratory viruses. In low-income countries, reduction of transmission is of paramount importance, but social distancing is challenged by high population densities and access to handwashing facilities with soap and water is limited. OBJECTIVES: Our objective was to estimate global access to handwashing with soap and water to inform use of handwashing in the prevention of COVID-19 transmission. METHODS: We utilized observational surveys and spatiotemporal Gaussian process regression modeling in the context of the Global Burden of Diseases, Injuries, and Risk Factors Study to estimate access to a handwashing station with available soap and water for 1,062 locations from 1990 to 2019. RESULTS: Despite overall improvements from 1990 {33.6% [95% uncertainty interval (UI): 31.5, 35.6] without access} to 2019, globally in 2019, 2.02 (95% UI: 1.91, 2.14) billion people, 26.1% (95% UI: 24.7, 27.7) of the global population, lacked access to handwashing with available soap and water. More than 50% of the population in sub-Saharan Africa and Oceania were without access to handwashing in 2019, and in eight countries, 50 million or more persons lacked access. DISCUSSION: For populations without handwashing access, immediate improvements in access or alternative strategies are urgently needed, and disparities in handwashing access should be incorporated into COVID-19 forecasting models when applied to low-income countries. https://doi.org/10.1289/EHP7200.

Targeting of rifamycin SV to the colon for treatment of travelers' diarrhea: a randomized, double-blind, placebo-controlled phase 3 study.

BACKGROUND: Rifamycin SV is under development for treatment of travelers' diarrhea (TD) in a new oral formulation, Rifamycin SV MMX (RIF-MMX; Santarus Inc., San Diego, CA, USA), which targets its delivery to the colon, making it a unique rifamycin drug. METHODS: This was a randomized, double-blind, phase 3 study of adult travelers to Mexico or Guatemala experiencing acute diarrhea. A total of 264 patients received RIF-MMX (2 × 200 mg twice daily for 3 days, n = 199) or placebo (n = 65) in a 3 : 1 ratio. The primary endpoint was the length of time between the administration of first dose of study drug and passage of the last unformed stool (TLUS; after which clinical cure was declared). Other endpoints included eradication of pathogens from the stools, pathogen minimum inhibitory concentration (MIC), and adverse events (AEs). RESULTS: TLUS was significantly shorter in the RIF-MMX group (median: 46.0 hours) compared with placebo (median: 68.0 hours; p = 0.0008) and a larger percentage of RIF-MMX treated patients (81.4%) achieved clinical cure compared with placebo patients (56.9%). TLUS was significantly shorter in the subgroups of patients with enteroaggregative, enterotoxigenic, or diffusely adherent Escherichia coli infections (p = 0.0035) with nonsignificant activity against invasive bacteria (p = 0.3804). Overall pathogen eradication rates were numerically higher in the RIF-MMX group (67.0%) compared with placebo (54.8%) but the difference did not reach significance (p = 0.0836). In vitro resistance to rifamycin SV was observed in some bacteria remaining after treatment of patients with RIF-MMX but was not associated with lower efficacy in them. AEs appeared to be more frequent with placebo (38.5%) than with RIF-MMX (29.6%). CONCLUSIONS: RIF-MMX shortened the duration of TD in patients with a broad range of pathogens and was well tolerated. The unique pharmacokinetic properties of the drug offer evidence that TD pathogens work at the level of the colon.

Clinical results of revision shoulder arthroplasty using the reverse prosthesis.

BACKGROUND: Success of revision shoulder arthroplasty using an unconstrained prosthesis depends on an intact rotator cuff and satisfactory bone quantity. However, the reverse shoulder arthroplasty can stabilize a glenohumeral joint even in patients with rotator cuff deficiency and bone deficits, resulting in improved outcomes. MATERIALS AND METHODS: Thirty shoulders in 28 patients with a failed arthroplasty were investigated consecutively between 2005 and 2008. All shoulders had significant rotator cuff deficiency without glenoid bone loss. Revision arthroplasty using the reverse prosthesis was performed with a minimum of 2 years of follow-up. Concomitant glenoid reconstructions with tricortical iliac crest bone grafting were necessary in 12 shoulders. RESULTS: The average adjusted Constant score improved from 24% to 65% and the American Shoulder and Elbow Surgeons (ASES) score improved from 55 to 72 (P < .0001). Average active forward flexion increased from 42° to 106° (P < .0001). The average ASES pain score improved from 6.6 to 1.6 (P < .0001). The overall complication rate was 50%, and 7 patients (23%) required reoperation. Overall, 24 of 30 shoulders (80%) were very satisfied or satisfied. CONCLUSION: Reverse shoulder arthroplasty can be an efficacious salvage procedure in the management of failed arthroplasty due to rotator cuff-related instability or bone defects, or both. Structural bone grafting on the glenoid side is successful at managing large defects, producing similar or better clinical outcomes compared with patients without bone loss. Although the operation is associated with a considerable complication rate, 80% of patients were satisfied with the results of the procedure, and 29 of 30 shoulders had a stable prosthesis.

Predictive capability of historical data for diagnosis of dizziness.

OBJECTIVE: The study examines categorical responses to questions on a comprehensive dizziness questionnaire, to find the overall predictive power of the questionnaire, and to identify which question(s) are most predictive of each diagnosis. STUDY DESIGN: Retrospective chart review. SETTING: Specialized dizziness and balance center at a tertiary care hospital. PATIENTS: A total of 619 patients (aged 19-89 yr, of whom 60% are women and 40% are men) diagnosed with 1 of 23 types of dizziness or postural instability. INTERVENTION: All patients were administered a standard 163-item dizziness questionnaire (including 77 review of systems items). OUTCOME MEASURES: Predicted diagnoses from the questionnaire, as determined by binary and multinomial logistic regressions, are compared with an ultimate clinical diagnosis made by an expert neurotologist based on full interview, examination, and clinical tests. RESULTS: Significant question groupings exist for each of the main diagnoses. A subset of 47 questions under multinomial logistic regression gave high predictive accuracies for migraine (92%), benign paroxysmal positional vertigo (90%) and Ménière's disease (86%), and fair predictive power for vestibular neuritis (63%), contributing to an overall predictive accuracy of 84%. A smaller subset of 32 questions gave an overall predictive accuracy of 71%. CONCLUSION: The capability of historical data to accurately predict the ultimate diagnosis for dizziness emphasizes the importance of a structured questionnaire in the evaluation of such patients. Future developments include the formulation of a computer-based program to generate a differential diagnosis for the practitioner to consider.