tbuckley/cabot-search huggingface dataset:
Neonatal Colonization With Antibiotic-Resistant Pathogens in Low- and Middle-Income Countries
Authors: Anne-Lise Beaumont, Elsa Kermorvant-Duchemin, Sébastien Breurec, Bich-Tram Huynh
Journal: JAMA Network Open (2024)

Importance In low- and middle-income countries (LMICs), neonatal bacterial infections are mainly caused by Enterobacterales species and Staphylococcus aureus , which are also the leading causes of mortality directly attributable to antimicrobial resistance. As bacterial colonization often precedes infection, better knowledge of colonization is crucial to prevent antibiotic-resistant neonatal sepsis. Objective To synthesize current evidence on the prevalence of and factors associated with colonization with third-generation cephalosporin–resistant Enterobacterales (3GCRE), carbapenem-resistant Enterobacterales (CRE), and methicillin-resistant S aureus (MRSA) during the first 3 months of life in LMICs. Data Sources PubMed, Scopus, Web of Science, and the World Health Organization Global Index Medicus were searched for articles published from January 1, 2000, through July 29, 2024. Study Selection Included studies were conducted in LMICs and reported prevalence rates or factors associated with colonization with 3GCRE, CRE, or MRSA in neonates and infants up to 3 months of age. Outbreak reports were excluded. Data Extraction and Synthesis Data extraction and risk-of-bias assessment using a Joanna Briggs Institute tool were performed by 2 independent reviewers. Pooled prevalence for each pathogen was computed using a random-effects model. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Main Outcomes and Measures Prevalence of and factors associated with 3GCRE, CRE, and MRSA colonization. Results Of the 3147 articles identified in the search, 67 studies (51 for 3GCRE and CRE and 16 for MRSA) including 17 152 individuals were eligible. The pooled prevalence of 3GCRE colonization was 30.2% (95% CI, 21.4%-40.7%; τ 2 = 1.48; I 2 = 95.1%), varying from 18.2% (95% CI, 10.8%-29.1%) in nonhospitalized individuals to 48.2% (95% CI, 36.4%-60.2%) in hospitalized individuals. The prevalence of CRE colonization was 2.6% (95% CI, 0.7%-8.8%; τ 2 = 7.79; I 2 = 95.6%), while it was 2.7% (95% CI, 1.0%-6.7%; τ 2 = 2.58; I 2 = 93.5%) for MRSA. Increased risk of colonization with 3GCRE was associated with hospital birth (odds ratio [OR], 1.87; 95% CI, 1.33-2.64), neonatal antibiotic use (OR, 2.96; 95% CI, 1.43-6.11), and prolonged rupture of membranes (OR, 3.86; 95% CI, 2.19-6.84). Conclusions and Relevance In this systematic review and meta-analysis of antibiotic-resistant pathogen carriage in individuals aged 0 to 3 months, the pooled prevalence was substantial despite a limited exposure period. Although high heterogeneity between studies limited extrapolation of results, the findings highlight the need for further investigation to identify transmission routes and to design targeted and effective preventive measures.
Impact of active case finding for tuberculosis with mass chest X-ray screening in Glasgow, Scotland, 1950–1963: An epidemiological analysis of historical data
Authors: Peter MacPherson, Helen R. Stagg, Alvaro Schwalb, Hazel Henderson, Alice E. Taylor, Rachael M. Burke, Hannah M. Rickman, Cecily Miller, Rein M. G. J. Houben, Peter J. Dodd, Elizabeth L. Corbett
Journal: PLoS Medicine (2024)

Background Community active case finding (ACF) for tuberculosis was widely implemented in Europe and North America between 1940 and 1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening. Methods and findings Case notifications for 1950 to 1963 were extracted from public health records and linked to demographic data. We fitted Bayesian multilevel regression models to estimate annual relative case notification rates (CNRs) during and after a mass screening intervention implemented over 5 weeks in 1957 compared to the counterfactual scenario where the intervention had not occurred. We additionally estimated case detection ratios and incidence. From 11 March 1957 to 12 April 1957, 714,915 people (622,349 of 819,301 [76.0%] resident adults ≥15 years) were screened with miniature chest X-ray; 2,369 (0.4%) were diagnosed with tuberculosis. Pre-intervention (1950 to 1956), pulmonary CNRs were declining at 2.3% per year from a CNR of 222/100,000 in 1950. With the intervention in 1957, there was a doubling in the pulmonary CNR (RR: 1.95, 95% uncertainty interval [UI] [1.81, 2.11]) and 35% decline in the year after (RR: 0.65, 95% UI [0.59, 0.71]). Post-intervention (1958 to 1963) annual rates of decline (5.4% per year) were greater (RR: 0.77, 95% UI [0.69, 0.85]), and there were an estimated 4,599 (95% UI [3,641, 5,683]) pulmonary case notifications averted due to the intervention. Effects were consistent across all city wards and notifications declined in young children (0 to 5 years) with the intervention. Limitations include the lack of data in historical reports on microbiological testing for tuberculosis, and uncertainty in contributory effects of other contemporaneous interventions including slum clearances, introduction of BCG vaccination programmes, and the ending of postwar food rationing. Conclusions A single, rapid round of mass screening with chest X-ray (probably the largest ever conducted) likely resulted in a major and sustained reduction in tuberculosis case notifications. Synthesis of evidence from other historical tuberculosis screening programmes is needed to confirm findings from Glasgow and to provide insights into ongoing efforts to successfully implement ACF interventions in today’s high tuberculosis burden countries and with new screening tools and technologies.
Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies
Authors: Kexin Ai, Bowen Liu, Xiaomei Chen, Chuxin Huang, liping Yang, Weiya Zhang, Jianyu Weng, Xin Du, Kongming Wu, Peilong Lai
Journal: Journal of Hematology & Oncology (2024)

Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application in solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address the challenges of sliding cytotoxicity in CAR-T cells. Despite improvements from fourth and next-generation CAR-T cells, new challenges include systemic toxicity from continuously secreted proteins, low productivity, and elevated costs. Recent research targets genetic modifications to boost killing potential, metabolic interventions to hinder tumor progression, and diverse combination strategies to enhance CAR-T cell therapy. Efforts to reduce the duration and cost of CAR-T cell therapy include developing allogenic and in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies and platforms enhance the potential of CAR-T cell therapy to overcome limitations in treating solid tumors. This review explores strategies to optimize CAR-T cell therapies for solid tumors, focusing on enhancing cytotoxicity and overcoming application restrictions. We summarize recent advances in T cell subset selection, CAR-T structural modifications, infiltration enhancement, genetic and metabolic interventions, production optimization, and the integration of novel technologies, presenting therapeutic approaches that could improve CAR-T cell therapy's efficacy and applicability in solid tumors.
Unveiling the complexity of G protein-coupled receptor heteromers: advances in live cell imaging technologies and biochemical methods
Authors: Hyunbin Kim, Huimin Lee, Jihye Seong
Journal: Med-X (2024)

Abstract G protein-coupled receptors (GPCRs), crucial for diverse physiological responses, have traditionally been investigated in their monomeric form. However, some GPCRs can form heteromers, revealing complexity in their functional characteristics such as ligand binding properties, downstream signaling pathways, and trafficking. Understanding GPCR heteromers is crucial in both physiological contexts and drug development. Here, we review the methodologies for investigating physical interactions in GPCR heteromers, including co-immunoprecipitation, proximity ligation assays, interfering peptide approaches, and live cell imaging techniques based on resonance energy transfer and bimolecular fluorescence complementation. In addition, we discuss recent advances in live cell imaging techniques for exploring functional features of GPCR heteromers, for example, circularly permuted fluorescent protein-based GPCR biosensors, TRUPATH, and nanobody-based GPCR biosensors. These advanced biosensors and live cell imaging technologies promise a deeper understanding of GPCR heteromers, urging a reassessment of their physiological importance and pharmacological relevance. Graphical Abstract
Pilot Trial of Perampanel on Peritumoral Hyperexcitability in Newly Diagnosed High-grade Glioma
Authors: Steven Tobochnik, Michael S. Regan, Maria K.C. Dorotan, Dustine Reich, Emily Lapinskas, Md Amin Hossain, Sylwia Stopka, David M. Meredith, Sandro Santagata, Melissa M. Murphy, Omar Arnaout, Wenya Linda Bi, E. Antonio Chiocca, Alexandra J. Golby, Michael A. Mooney, Timothy R. Smith, Keith L. Ligon, Patrick Y. Wen, Nathalie Y.R. Agar, Jong Woo Lee
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Glutamatergic neuron–glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the targeted AMPA receptor antagonist perampanel on peritumoral hyperexcitability. Experimental Design: An open-label trial was performed comparing perampanel with standard of care (SOC) in patients undergoing resection of newly diagnosed radiologic high-grade glioma. Perampanel was administered as a preoperative loading dose followed by maintenance therapy until progressive disease or up to 12 months. SOC treatment involved levetiracetam for 7 days or as clinically indicated. The primary outcome of hyperexcitability was defined by intraoperative electrocorticography high-frequency oscillation (HFO) rates. Seizure freedom and overall survival were estimated by the Kaplan–Meier method. Tissue concentrations of perampanel, levetiracetam, and correlative biomarkers were measured by mass spectrometry. Results: HFO rates were similar between patients treated with perampanel and levetiracetam. The trial was terminated early after a planned interim analysis, and outcomes assessed in 11 patients (seven perampanel treated; four treated with SOC). Over a median 281 days of postenrollment follow-up, 27% of patients had seizures, including 14% maintained on perampanel and 50% treated with SOC. Overall survival in perampanel-treated patients was similar to that in a glioblastoma reference cohort. Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations. Conclusions: Glioma peritumoral glutamate concentrations correlated with high-gamma oscillation rates. Targeting glutamatergic activity with perampanel achieved similar electrocorticographic hyperexcitability levels as in levetiracetam-treated patients.
External Validation of an Electronic Health Record–Based Diagnostic Model for Histological Acute Tubulointerstitial Nephritis
Authors: Dennis G. Moledina, Kyra Shelton, Steven Menez, Abinet M. Aklilu, Yu Yamamoto, Bashar A. Kadhim, Melissa Shaw, Candice Kent, Amrita Makhijani, David Hu, Michael Simonov, Kyle O’Connor, Jack Bitzel, Heather Thiessen-Philbrook, F. Perry Wilson, Chirag R. Parikh
Journal: Journal of the American Society of Nephrology (2024)

Background: Accurate diagnosis of acute tubulointerstitial nephritis (AIN) often requires a kidney biopsy. We previously developed a diagnostic statistical model for predicting biopsy-confirmed AIN by combining four laboratory tests after evaluating over 150 potential predictors from the electronic health record. Here, we validate this diagnostic model in two biopsy-based cohorts at Johns Hopkins Hospital (JHH) and Yale, which were geographically and temporally distinct from the development cohort, respectively. Methods: We analyzed patients who underwent kidney biopsy at JHH and Yale University (2019-2023). We assessed discrimination (AUC) and calibration using previously derived model coefficients and recalibrated the model using an intercept correction factor that accounted for differences in baseline prevalence of AIN between development and validation cohorts. Results: We included 1982 participants: 1454 at JHH and 528 at Yale. JHH (5%) and Yale (17%) had lower proportions of biopsies with AIN than the development set (23%). The AUC was 0.73 (0.66-0.79) at JHH and 0.73 (0.67-0.78) at Yale, similar to the development set (0.73 (0.64-0.81)). Calibration was imperfect in validation cohorts, particularly at JHH, but improved with application of an intercept correction factor. The model increased AUC of clinicians' prebiopsy suspicion for AIN by 0.10 to 0.77 (0.71-0.82). Conclusions: An AIN diagnostic model retained discrimination in two validation cohorts but needed recalibration to account for local AIN prevalence. The model improved clinicians’ ability to predict AIN.
Is IgA Class Switching Epigenetically Wired?
Authors: Ghazal Z. Quinn, Katalin Susztak
Journal: Journal of the American Society of Nephrology (2024)

Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania Correspondence: Dr. Katalin Susztak, email: [email protected] See related article, "B-Cell Epigenetic Modulation of IgA Response by 5-Azacytidine and IgA Nephropathy," on pages 1686–1701.
Unveiling the hidden impact: Scope 3 emissions in endoscopy
Authors: Lyndon V. Hernandez
Journal: Endoscopy (2024)

The study by López-Muñoz et al. published in this issue of Endoscopy provides a critical analysis of the carbon footprint associated with single-use duodenoscopes (SUDs) and reusable duodenoscopes (RUDs), offering valuable insights into the broader environmental impact of medical equipment [1]. By modeling three distinct clinical scenarios, the authors highlight the substantial difference in carbon emissions between the approaches, emphasizing particularly the environmental benefits of reusable devices; however, the study also brings to light an often underestimated aspect of environmental impact in healthcare: Scope 3 emissions.
Can we improve the endoscopic resection of dysplastic lesions in colonic inflammatory bowel diseases?
Authors: Nicholas Burr
Journal: Endoscopy (2024)

The incidence of colonic inflammatory bowel disease (IBD) is increasing globally, with prevalence rates of approximately 1 in 200 adults in the highest-risk populations [1]. One of the consequences of longstanding colonic inflammation is the potential development of premalignant lesions and colorectal cancer (CRC). Although the risk of CRC in IBD is declining, the cumulative risk is estimated to be 1%, 2%, and 5% after 10, 20, and >20 years of disease, respectively [2].
Genome-first determination of the prevalence and penetrance of eight germline myeloid malignancy predisposition genes: a study of two population-based cohorts
Authors: Rachel M. Hendricks, Jung Kim, Jeremy S. Haley, Mark Louie Ramos, Uyenlinh L. Mirshahi, David J. Carey, Douglas R. Stewart, Lisa J. McReynolds
Journal: Leukemia (2024)

Abstract It is estimated that 10% of individuals with a myeloid malignancy carry a germline susceptibility. Using the genome-first approach, in which individuals were ascertained on genotype alone, rather than clinical phenotype, we quantified the prevalence and penetrance of pathogenic germline variants in eight myeloid malignancy predisposition (gMMP) genes. ANKRD26 , CEBPA, DDX41, MECOM, SRP72, ETV6, RUNX1 and GATA2 , were analyzed from the Geisinger MyCode DiscovEHR ( n = 170,503) and the United Kingdom Biobank (UKBB, n = 469,595). We identified a high risk of myeloid malignancies (MM) (odds ratio[OR] all genes: DiscovEHR, 4.6 [95% confidential interval (CI) 2.1–9.7], p &lt; 0.0001; UKBB, 6.0 [95% CI 4.3–8.2], p = 3.1 × 10 -27 ), and decreased overall survival (hazard ratio [HR] DiscovEHR, 1.8 [95% CI 1.3–2.6], p = 0.00049; UKBB, 1.4 [95% CI 1.2–1.8], p = 8.4 × 10 -5 ) amongst heterozygotes. Pathogenic DDX41 variants were the most commonly identified, and in UKBB showed a significantly increased risk of MM (OR 5.7 [95% CI 3.9–8.3], p = 6.0 × 10 -20 ) and increased all-cause mortality (HR 1.35 [95% CI 1.1–1.7], p = 0.0063). Through a genome-first approach, this study genetically ascertained individuals with a gMMP and determined their MM risk and survival.
Effects of a coal to clean heating policy on acute myocardial infarction in Beijing: a difference-in-differences analysis
Authors: Martha Lee, Jie Chang, Qiuju Deng, Piaopiao Hu, Honor Bixby, Sam Harper, Guofeng Shen, Shu Tao, Moning Guo, Feng Lu, Jill Baumgartner, Jing Liu
Journal: The Lancet Planetary Health (2024)
Removing lead from the global economy
Authors: Stephen P Luby, Jenna E Forsyth, Zafar Fatmi, Mahbubur Rahman, Jesmin Sultana, Erica L Plambeck, N Grant Miller, Eran Bendavid, Peter J Winch, Howard Hu, Bruce Lanphear, Philip J Landrigan
Journal: The Lancet Planetary Health (2024)

Lead, an element toxic to countless biological processes, occurs naturally in the earth's lithosphere and is geologically sequestered from the biosphere at the earth's surface. When humans remove lead from the lithosphere and distribute it throughout the economy, its toxic effects impact throughout the web of life. Lead mining and manufacturing is a small industry that generates enormous harms. Lead impairs the growth, development, and reproduction of microbes, insects, plants, and animals. The annual human costs of lead exposure include 5·5 million premature adult deaths from cardiovascular disease and US$1·4 trillion in losses to the global economy from lead impairing children's cognitive development. Although the lead industry touts lead as the most recycled metal, most recycling occurs within countries that are incapable of enforcing environmental regulations. Millions of metric tonnes of lead are dispersed into the environment each year, disproportionately in low-income and middle-income countries. Substitutes for lead in the economy are available and we should act in the best interests of the planet and human health by eliminating lead from the global economy by 2035.
A qualitative exploration of barriers, enablers, and implementation strategies to replace disposable medical devices with reusable alternatives
Authors: Jessica F Davies, Forbes McGain, Evelyn Sloan, Jill Francis, Stephanie Best
Journal: The Lancet Planetary Health (2024)

Hospitals use many single-use devices that produce more waste and greenhouse gas emissions than reusable devices; operating theatres alone are responsible for up to a third of hospital waste. We explored barriers and enablers to replacing disposable devices with reusable alternatives in operating theatres by use of interviews, the Theoretical Domains Framework, and theory-informed behaviour change techniques. 19 stakeholders were interviewed at a large tertiary hospital in Melbourne, Australia, and 53 barriers and 44 experience-based or intuition-based enablers were identified. 30 strategies were identified across six topics: external purchasing (two strategies); internal purchasing (seven strategies); incentivisation and standardised environmental decision making (three strategies); successful practical introduction of reusable devices (five strategies); identification of goals and facilitation of leadership (two strategies); and a community of practice and knowledge building (11 strategies). We present these 30 implementation strategies, from the individual to the policy level, which consist of evidence-based behaviour change techniques aimed at addressing the identified barriers to replacing single-use devices with reusable alternatives.
Nurturing nature
Authors: None The Lancet Planetary Health
Journal: The Lancet Planetary Health (2024)

At the time that North America was first colonised by Europeans, Passenger pigeons were the most numerous birds on the continent. Numbers were estimated to be in the billons with commentators describing the flocks as "infinite multitudes". A description that proved to be inaccurate and perhaps also revealed something about the prevailing attitudes which lead to their ultimate demise. The combination of commercial scale harvesting for meat and habitat destruction resulted in rapid population decline, and despite efforts to conserve the species, including attempts at captive breeding, the last bird (named Martha) died in captivity in 1914.
Responding to heat-related health risks: the urgency of an equipoise between emergency and equity
Authors: Purnamita Dasgupta, Vikram Dayal, Rajib Dasgupta, Kristie L Ebi, Clare Heaviside, William Joe, Rupa Kumar Kolli, Meeta Keswani Mehra, Arabinda Mishra, Pankaja Raghav
Journal: The Lancet Planetary Health (2024)

In the summer of 2024, there were higher temperatures than usual in several parts of India. Temperatures in Delhi, a huge city with millions of residents, broke several previous records. Low-income households have dwellings that do not offer much protection from the heat, and individuals struggle to access basic amenities, such as water. With accumulating evidence on consequent impacts for mortality and morbidity, governance structures are seeking to respond in a timely and efficient manner. There is a need to recognise that heat-related illnesses and deaths are not best addressed merely as an acute disaster but as public health and economic challenges that require planned responses. Responses that are sustainable and equitable combine long-term structural efforts at resilience building with emergency preparedness and prove to be most effective in averting the largely preventable deaths, morbidities, and economic shocks arising from heat-related health risks among exposed and vulnerable communities. Joint action on climate and health enhances achievement of multiple developmental goals with multistakeholder participation. Diverse sectors, including medical care, surveillance, risk communication, disaster preparedness, livelihoods and jobs, and adaptation and urban planning, are needed to raise public awareness and engagement, induce behavioural change, and focus resources for the much-needed structural changes in urban planning and health systems that can save lives and avert damages. To reduce heat-related health risks, vulnerability, inequity, and climate action in the Indian context must be urgently addressed.
Effects of fine particulate matter from wildfire and non-wildfire sources on emergency-department visits in people who were housed and unhoused in San Diego County (CA, USA) during 2012–20: a time-stratified case–crossover study
Authors: Lara Schwarz, Andrew Nguyen, Emilie Schwarz, Edward M Castillo, Jesse J Brennan, Theodore C Chan, Rosana Aguilera, Alexander Gershunov, Tarik Benmarhnia
Journal: The Lancet Planetary Health (2024)

Being unhoused can increase vulnerability to adverse health effects due to air pollution. We aimed to quantify changes in emergency-department visits during and after exposure to wildfire-specific and non-wildfire particulate matter 2·5 μm or less in diameter (PM
Feasibility and acceptability of the Problem Management for Moms programme for improving maternal mental health in Zambia: an open-label trial
Authors: Günther Fink, Maria Melero-Dominguez, Mpela Chembe, Daniela de Vernisy-Romero, Thandiwe Tembo, Tamara Billima, Ravi Paul, Margarita Alegria, Doug Parkerson, Peter C Rockers, Zaliwe Banda, Gabriel Lungu, Dorothy Sikazwe, Irene Falgas-Bague
Journal: The Lancet Psychiatry (2024)