tbuckley/cabot-search huggingface dataset:
Emergency Department Care for Children During the 2022 Viral Respiratory Illness Surge
Authors: Alexander T. Janke, Courtney W. Mangus, Christopher M. Fung, Neil Kamdar, Michelle L. Macy, Michele M. Nypaver, Keith E. Kocher
Journal: JAMA Network Open (2023)

Importance Pediatric readiness is essential for all emergency departments (EDs). Children’s experience of care may differ according to operational challenges in children’s hospitals, community hospitals, and rural EDs caused by recurring and sometimes unpredictable viral illness surges. Objective To describe wait times, lengths of stay (LOS), and ED revisits across diverse EDs participating in a statewide quality collaborative during a surge in visits in 2022. Design, Setting, and Participants This retrospective cohort study included 25 EDs from the Michigan Emergency Department Improvement Collaborative data registry from January 1, 2021, through December 31, 2022. Pediatric (patient age &amp;amp;lt;18 years) encounters for viral and respiratory conditions were analyzed, comparing wait times, LOS, and ED revisit rates for children’s hospital, urban pediatric high-volume (≥10% of overall visits), urban pediatric low-volume (&amp;amp;lt;10% of overall visits), and rural EDs. Exposures Surge in ED visit volumes for children with viral and respiratory illnesses from September 1 through December 31, 2022. Main Outcomes and Measures Prolonged ED visit wait times (arrival to clinician assigned, &amp;amp;gt;4 hours), prolonged LOS (arrival to departure, &amp;amp;gt;12 hours), and ED revisit rate (ED discharge and return within 72 hours). Results A total of 2 761 361 ED visits across 25 EDs in 2021 and 2022 were included. From September 1 to December 31, 2022, there were 301 688 pediatric visits for viral and respiratory illness, an increase of 71.8% over the 4 preceding months and 15.7% over the same period in 2021. At children’s hospitals during the surge, 8.0% of visits had prolonged wait times longer than 4 hours, 8.6% had prolonged LOS longer than 12 hours, and 42 revisits occurred per 1000 ED visits. Prolonged wait times were rare among other sites. However, prolonged LOS affected 425 visits (2.2%) in urban high-pediatric volume EDs, 133 (2.6%) in urban pediatric low-volume EDs, and 176 (3.1%) in rural EDs. High visit volumes were associated with increased ED revisits across sites. Conclusions and Relevance In this cohort study of more than 2.7 million ED visits, a pediatric viral illness surge was associated with different pediatric acute care across EDs in the state. Clinical management pathways and quality improvement efforts may more effectively mitigate dangerous clinical conditions with strong collaborative relationships across EDs and setting of care.
<i>QuickStats:</i> Average Number of Stroke* Deaths per Day, by Month and Sex — National Vital Statistics System, United States, 2021
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Deaths attributed to stroke were identified using International Classification of Diseases, Tenth Revision underlying cause of death codes I60-I69.In 2021, the average number of stroke deaths per day was highest in January (275 for females and 212 for males) and then declined to a monthly low in June (235 for females and 180 for males).Beginning in July, the average number of stroke deaths per day increased for each successive month through the end of the year among both males and females, with the average number of stroke deaths higher among females than males for every month.
A Nationwide Comparative Analysis of Temperature-Related Mortality and Morbidity in Japan
Authors: Lei Yuan, Lina Madaniyazi, Ana M. Vicedo-Cabrera, Yasushi Honda, Chris Fook Sheng Ng, Kayo Ueda, Kazutaka Oka, Aurelio Tobias, Masahiro Hashizume
Journal: Environmental Health Perspectives (2023)

The impact of temperature on morbidity remains largely unknown. Moreover, extensive evidence indicates contrasting patterns between temperature–mortality and temperature–morbidity associations. A nationwide comparison of the impact of temperature on mortality and morbidity in more specific subgroups is necessary to strengthen understanding and help explore underlying mechanisms by identifying susceptible populations.
Multiomic profiling reveals metabolic alterations mediating aberrant platelet activity and inflammation in myeloproliferative neoplasms
Authors: Fan He, Angelo B.A. Laranjeira, Tim Kong, Shuyang Lin, Katrina J. Ashworth, Alice Liu, Nina M. Lasky, Daniel A.C. Fisher, Maggie J. Cox, Mary C. Fulbright, Lilian Antunes-Heck, LaYow Yu, Molly Brakhane, Bei Gao, Stephen M. Sykes, Angelo D’Alessandro, Jorge Di Paola, Stephen T. Oh
Journal: Journal of Clinical Investigation (2023)

Platelets from patients with myeloproliferative neoplasms (MPNs) exhibit a hyperreactive phenotype. Here, we found elevated P-selectin exposure and platelet-leukocyte aggregates indicating activation of platelets from essential thrombocythemia (ET) patients. Single-cell RNA-seq analysis of primary samples revealed significant enrichment of transcripts related to platelet activation, mTOR, and oxidative phosphorylation in ET patient platelets. These observations were validated via proteomic profiling. Platelet metabolomics revealed distinct metabolic phenotypes consisting of elevated ATP generation accompanied by increases in the levels of multiple intermediates of the tricarboxylic acid cycle, but lower α-ketoglutarate (α-KG) in MPN patients. Inhibition of PI3K/AKT/mTOR signaling significantly reduced metabolic responses and hyperreactivity in MPN patient platelets, while α-KG supplementation markedly reduced oxygen consumption and ATP generation. Ex vivo incubation of platelets from both MPN patients and Jak2 V617F-knockin mice with α-KG supplementation significantly reduced platelet activation responses. Oral α-KG supplementation of Jak2 V617F mice decreased splenomegaly and reduced hematocrit, monocyte, and platelet counts. Finally, α-KG treatment significantly decreased proinflammatory cytokine secretion from MPN CD14+ monocytes. Our results reveal a previously unrecognized metabolic disorder in conjunction with aberrant PI3K/AKT/mTOR signaling that contributes to platelet hyperreactivity in MPN patients.
Use of Inactivated Polio Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices — United States, 2023
Authors: Sarah Kidd, Thomas Clark, Janell Routh, Sybil Cineas, Lynn Bahta, Oliver Brooks
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Poliovirus can cause poliomyelitis and lifelong paralysis. Although wild poliovirus types 2 and 3 have been eradicated, wild poliovirus type 1 and vaccine-derived polioviruses are still circulating in multiple countries worldwide. In 2022, a case of paralytic polio caused by vaccine-derived poliovirus type 2 was identified in an unvaccinated young adult in New York. This case and subsequent detection of community transmission underscored the ongoing risk for importation of poliovirus into the United States and risk for poliomyelitis among unvaccinated persons. However, previous Advisory Committee on Immunization Practices (ACIP) recommendations for adult polio vaccination were limited to adults known to be at increased risk for exposure. During October 2022-June 2023, the ACIP Polio Vaccine Work Group reviewed data on poliovirus surveillance and epidemiology, safety and effectiveness of inactivated poliovirus vaccine (IPV), and other considerations outlined in the ACIP Evidence to Recommendations Framework. On June 21, 2023, ACIP voted to recommend that all U.S. adults aged ≥18 years who are known or suspected to be unvaccinated or incompletely vaccinated against polio complete a primary polio vaccination series with IPV. This report summarizes evidence considered for this recommendation and provides clinical guidance for the use of IPV in adults.
Erratum: “Urinary Glyphosate, 2,4-D and DEET Biomarkers in Relation to Neurobehavioral Performance in Ecuadorian Adolescents in the ESPINA Cohort”
Authors: Briana N.C. Chronister, Kun Yang, Audrey R. Yang, Tuo Lin, Xin M. Tu, Dolores Lopez-Paredes, Harvey Checkoway, Jose Suarez-Torres, Sheila Gahagan, Danilo Martinez, Dana Barr, Raeanne C. Moore, Jose R. Suarez-Lopez
Journal: Environmental Health Perspectives (2023)
Circulating Tumor DNA Enables Sensitive Detection of Actionable Gene Fusions and Rearrangements Across Cancer Types
Authors: Pashtoon M. Kasi, Jessica K. Lee, Lincoln W. Pasquina, Brennan Decker, Pierre Vanden Borre, Dean C. Pavlick, Justin M. Allen, Christine Parachoniak, Julia C. F. Quintanilha, Ryon P. Graf, Alexa B. Schrock, Geoffrey R. Oxnard, Christine M. Lovly, Hanna Tukachinsky, Vivek Subbiah
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Genomic rearrangements can generate potent oncogenic drivers or disrupt tumor suppressor genes. This study examines the landscape of fusions and rearrangements detected by liquid biopsy (LBx) of circulating tumor DNA (ctDNA) across different cancer types. Experimental Design: LBx from 53,842 patients with 66 solid tumor types were profiled using FoundationOneLiquid CDx, a hybrid-capture sequencing platform that queries 324 cancer-related genes. Tissue biopsies (TBx) profiled using FoundationOneCDx were used as a comparator. Results: Among all LBx, 7,377 (14%) had ≥1 pathogenic rearrangement detected. A total of 3,648 (6.8%) LBx had ≥1 gain-of-function (GOF) oncogene rearrangement, and 4,428 (8.2%) LBx had ≥1 loss-of-function rearrangement detected. Cancer types with higher prevalence of GOF rearrangements included those with canonical fusion drivers: prostate cancer (19%), cholangiocarcinoma (6.4%), bladder (5.5%), and non–small cell lung cancer (4.4%). Although the prevalence of driver rearrangements was lower in LBx than TBx overall, the frequency of detection was comparable in LBx with a tumor fraction (TF) ≥1%. Rearrangements in FGFR2, BRAF, RET, and ALK, were detected across cancer types, but tended to be clonal variants in some cancer types and potential acquired resistance variants in others. Conclusions: In contrast to some prior literature, this study reports detection of a wide variety of rearrangements in ctDNA. The prevalence of driver rearrangements in tissue and LBx was comparable when TF ≥1%. LBx presents a viable alternative when TBx is not available, and there may be less value in confirmatory testing when TF is sufficient.
PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti–PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients
Authors: Thomas Denize, Opeyemi A. Jegede, Sayed Matar, Nourhan El Ahmar, Destiny J. West, Emily Walton, Aseman Sheshdeh Bagheri, Varunika Savla, Yasmin Nabil Laimon, Saurabh Gupta, Sai Vikram Vemula, David A. Braun, Kelly P. Burke, Paul J. Catalano, Gordon J. Freeman, Robert J. Motzer, Michael B. Atkins, David F. McDermott, Arlene H. Sharpe, Toni K. Choueiri, Sabina Signoretti
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Programmed cell death protein 1 (PD-1) expression on CD8+TIM-3−LAG-3− tumor-infiltrating cells predicts positive response to PD-1 blockade in metastatic clear-cell renal cell carcinoma (mccRCC). Because inhibition of PD-1 signaling in regulatory T cells (Treg) augments their immunosuppressive function, we hypothesized that PD-1 expression on tumor-infiltrating Tregs would predict resistance to PD-1 inhibitors. Experimental Design: PD-1+ Tregs were phenotyped using multiparametric immunofluorescence in ccRCC tissues from the CheckMate-025 trial (nivolumab: n = 91; everolimus: n = 90). Expression of CD8, PD-1, TIM-3, and LAG-3 was previously determined (Ficial and colleagues, 2021). Clinical endpoints included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Results: In the nivolumab (but not everolimus) arm, high percentage of PD-1+ Tregs was associated with shorter PFS (3.19 vs. 5.78 months; P = 0.021), shorter OS (18.1 vs. 27.7 months; P = 0.013) and marginally lower ORR (12.5% vs. 31.3%; P = 0.059). An integrated biomarker (PD-1 Treg/CD8 ratio) was developed by calculating the ratio between percentage of PD-1+Tregs (marker of resistance) and percentage of CD8+PD-1+TIM-3−LAG-3− cells (marker of response). In the nivolumab (but not everolimus) arm, patients with high PD-1 Treg/CD8 ratio experienced shorter PFS (3.48 vs. 9.23 months; P &amp;lt; 0.001), shorter OS (18.14 vs. 38.21 months; P &amp;lt; 0.001), and lower ORR (15.69% vs. 40.00%; P = 0.009). Compared with the individual biomarkers, the PD-1 Treg/CD8 ratio showed improved ability to predict outcomes to nivolumab versus everolimus. Conclusions: PD-1 expression on Tregs is associated with resistance to PD-1 blockade in mccRCC, suggesting that targeting Tregs may synergize with PD-1 inhibition. A model that integrates PD-1 expression on Tregs and CD8+TIM-3−LAG-3− cells has higher predictive value.
Functional Contribution and Clinical Implication of Cancer-Associated Fibroblasts in Glioblastoma
Authors: Phillip M. Galbo, Anne Tranberg Madsen, Yang Liu, Mou Peng, Yao Wei, Michael J. Ciesielski, Robert A. Fenstermaker, Sarah Graff, Cristina Montagna, Jeffrey E. Segall, Simone Sidoli, Xingxing Zang, Deyou Zheng
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The abundance and biological contribution of cancer-associated fibroblasts (CAF) in glioblastoma (GBM) are poorly understood. Here, we aim to uncover its molecular signature, cellular roles, and potential tumorigenesis implications. Experimental Design: We first applied single-cell RNA sequencing (RNA-seq) and bioinformatics analysis to identify and characterize stromal cells with CAF transcriptomic features in human GBM tumors. Then, we performed functional enrichment analysis and in vitro assays to investigate their interactions with malignant GBM cells. Results: We found that CAF abundance was low but significantly correlated with tumor grade, poor clinical outcome, and activation of extracellular matrix remodeling using three large cohorts containing bulk RNA-seq data and clinical information. Proteomic analysis of a GBM-derived CAF line and its secretome revealed fibronectin (FN1) as a critical candidate factor mediating CAF functions. This was validated using in vitro cellular models, which demonstrated that CAF-conditioned media and recombinant FN1 could facilitate the migration and invasion of GBM cells. In addition, we showed that CAFs were more abundant in the mesenchymal-like state (or subtype) than in other states of GBMs. Interestingly, cell lines resembling the proneural state responded to the CAF signaling better for the migratory and invasive phenotypes. Conclusions: Overall, this study characterized the molecular features and functional impacts of CAFs in GBM, alluding to novel cell interactions mediated by CAFs in the GBM microenvironment.
GLP-1 Receptor Agonists and Colorectal Cancer Risk in Drug-Naive Patients With Type 2 Diabetes, With and Without Overweight/Obesity
Authors: Lindsey Wang, William Wang, David C. Kaelber, Rong Xu, Nathan A. Berger
Journal: JAMA Oncology (2023)

This cohort study compares glucagon-like peptide 1 receptor agonists (GLP-1RAs) with 7 non–GLP-1RA antidiabetics among drug-naive patients with type 2 diabetes.
Progress in Immunization Safety Monitoring — Worldwide, 2020–2022
Authors: Erin F. Blau, Madhava Ram Balakrishnan, Helena Sköld, Ravi Shankar Santhana Gopala Krishnan, Pinelopi Lundquist, Shanthi Pal, Jane F. Gidudu
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Effective surveillance of adverse events following immunization (AEFIs) primarily relies on the collaboration of two partners: national regulatory authorities (NRAs) and national expanded programs on immunization (EPIs). In December 2020, the World Health Organization (WHO) Global Advisory Committee for Vaccine Safety recommended a new case-based indicator of national capacity to monitor immunization safety: at least one serious AEFI reported per 1 million total population per year. To achieve this indicator, WHO-affiliated countries and territories (WHO countries) rely upon data generated from functional AEFI surveillance systems. This report describes 2020-2022 global, regional, and national progress in use of the newly introduced immunization safety monitoring indicator and progress on joint AEFI reporting from national EPIs and NRAs. Among WHO countries, 51 (24%) of 214 implemented the new indicator in 2020, 111 (52%) of 214 implemented it in 2021, and 92 (43%) of 215 in 2022. In 2020, 41 (19%) WHO countries reported AEFI data jointly from EPIs and NRAs; this increased to 55 (26%) in 2021 and 57 (27%) in 2022. These findings, resulting in part from the intensified support for COVID-19 vaccination, demonstrate that national AEFI surveillance systems increasingly support the timely use and sharing of case-based immunization safety data, but work is still needed to strengthen global vaccine safety monitoring.
First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results
Authors: Peter Schmid, Nicholas C. Turner, Carlos H. Barrios, Steven J. Isakoff, Sung-Bae Kim, Marie-Paule Sablin, Shigehira Saji, Peter Savas, Gregory A. Vidal, Mafalda Oliveira, Joyce O'Shaughnessy, Antoine Italiano, Enrique Espinosa, Valentina Boni, Shane White, Beatriz Rojas, Ruffo Freitas-Junior, Yeesoo Chae, Igor Bondarenko, Jieun Lee, Cesar Torres Mattos, Jorge Luis Martinez Rodriguez, Lisa H. Lam, Surai Jones, Sarah-Jayne Reilly, Xiayu Huang, Kalpit Shah, Rebecca Dent
Journal: Clinical Cancer Research (2023)

Abstract Purpose: To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer (mTNBC). Patients and Methods: The single-arm CO40151 phase Ib study (NCT03800836), the single-arm signal-seeking cohort of IPATunity130 (NCT03337724), and the randomized phase III IPATunity170 trial (NCT04177108) enrolled patients with previously untreated mTNBC. Triplet therapy comprised intravenous atezolizumab 840 mg (days 1 and 15), oral ipatasertib 400 mg/day (days 1–21), and intravenous paclitaxel 80 mg/m2 (or nab-paclitaxel 100 mg/m2; days 1, 8, and 15) every 28 days. Exploratory translational research aimed to elucidate mechanisms and molecular markers of sensitivity and resistance. Results: Among 317 patients treated with the triplet, efficacy ranged across studies as follows: median progression-free survival (PFS) 5.4 to 7.4 months, objective response rate 44% to 63%, median duration of response 5.6 to 11.1 months, and median overall survival 15.7 to 28.3 months. The safety profile was consistent with the known toxicities of each agent. Grade ≥3 adverse events were more frequent with the triplet than with doublets or single-agent paclitaxel. Patients with PFS &amp;gt;10 months were characterized by NF1, CCND3, and PIK3CA alterations and increased immune pathway activity. PFS &amp;lt;5 months was associated with CDKN2A/CDKN2B/MTAP alterations and lower predicted phosphorylated AKT-S473 levels. Conclusions: In patients with mTNBC receiving an ipatasertib/atezolizumab/taxane triplet regimen, molecular characteristics may identify those with particularly favorable or unfavorable outcomes, potentially guiding future research efforts.
Population Attributable Risk of Advanced-Stage Breast Cancer by Race and Ethnicity
Authors: Karla Kerlikowske, Shuai Chen, Michael C. S. Bissell, Christoph I. Lee, Jeffrey A. Tice, Brian L. Sprague, Diana L. Miglioretti
Journal: JAMA Oncology (2023)

Advanced-stage breast cancer rates vary by race and ethnicity, with Black women having a 2-fold higher rate than White women among regular screeners. Clinical risk factors that explain a large proportion of advanced breast cancers by race and ethnicity are unknown.
Ann Robinson’s research reviews—7 December 2023
Authors: Ann Robinson
Journal: BMJ (2023)

hormonal resuscitation is associated with more hearts and other organs being suitable for transplantation.This randomised study of 838 brain-dead donors compared outcomes with thyroid versus saline infusions.There was no significant difference in the percentage who went on to donate their heart (54.9 v 53.2%), and graft survival at 30 days was extremely high and the same in both groups (>95%).Furthermore, the levothyroxine group had more cases of severe hypertension and tachycardia than the saline group.
PD-1H/VISTA mediates immune evasion in acute myeloid leukemia
Authors: Tae Kon Kim, Xue Han, Qianni Hu, Esten N. Vandsemb, Carly M. Fielder, Junshik Hong, Kwang Woon Kim, Emily F. Mason, R. Skipper Plowman, Jun Wang, Qi Wang, Jian-Ping Zhang, Ti Badri, Miguel F. Sanmamed, Linghua Zheng, Tianxiang Zhang, Jude Alawa, Sang Won Lee, Amer M. Zeidan, Stephanie Halene, Manoj M. Pillai, Namrata S. Chandhok, Jun Lu, Mina L. Xu, Steven D. Gore, Lieping Chen
Journal: Journal of Clinical Investigation (2023)

Acute myeloid leukemia (AML) presents a pressing medical need in that it is largely resistant to standard chemotherapy as well as modern therapeutics such as targeted therapy and immunotherapy, including anti-PD therapy. We demonstrate that Programmed Death-1 Homolog (PD-1H), an immune co-inhibitory molecule is highly expressed in blasts from the bone marrow of AML patients, while normal myeloid cell subsets and T cells have the expression of PD-1H. In studies employing syngeneic and humanized AML mouse models, overexpression of PD-1H promoted the growth of AML cells, mainly by evading T cell-mediated immune responses. Importantly, ablation of AML cell surface PD-1H by antibody blockade or genetic targeting significantly inhibited AML progression by promoting T cell activity. In addition, the genetic deletion of PD-1H from host normal myeloid cells inhibited AML progression as well and the combination of PD-1H blockade with PD-1 blockade conferred a synergistic anti-leukemia effect. Our findings provide the basis for PD-1H as an attractive therapeutic target to treat human AML.
The BMJ Appeal 2023-24: The Syrian health workers pulling 24 hour shifts to keep their maternity hospital open
Authors: Jane Feinmann
Journal: BMJ (2023)

a 22 year old midwife, works a 9 am to 4 pm shift in an antenatal clinic at the Ain Al Bayda Hospital in northwest Syria.She's responsible for monthly check-ups on patients who live in one of the 58 neighbouring camps for internally displaced people, who have been unable to leave through a decade of barbaric civil war."The biggest danger to pregnant women here is anaemia caused by malnutrition," she says.When her shift has finished Ghufran moves to the obstetric wing, where she works for the remaining hours of the day.She's on duty as one of six midwives working in a rota along with a surgical team and nursing staff.These gruelling working hours are the only way to provide essential care given the scarcity of available medical staff, says Waseem Bakir, health coordinator of Violet, a Syrian non-governmental organisation."There's a constant risk that pregnant women won't find the medical care they need," says Bakir.
B3GALT6 promotes dormant breast cancer cell survival and recurrence by enabling heparan sulfate-mediated FGF signaling
Authors: Amulya Sreekumar, Michelle Lu, Biswa Choudhury, Tien-chi Pan, Dhruv K. Pant, Matthew R. Lawrence-Paul, Christopher J. Sterner, George K. Belka, Takashi Toriumi, Brian A. Benz, Matias Escobar-Aguirre, Francesco E. Marino, Jeffrey D. Esko, Lewis A. Chodosh
Journal: Cancer Cell (2023)
Organizational Strategies to Promote Well‐Being and Combat Burnout in Rheumatology: Comment on the article by Calabrese et al
Authors: Priyanka Iyer, Bharat Kumar
Journal: Arthritis & Rheumatology (2023)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.