tbuckley/cabot-search huggingface dataset:
Tissue-specific reprogramming leads to angiogenic neutrophil specialization and tumor vascularization in colorectal cancer
Authors: Triet M. Bui, Lenore K. Yalom, Edward Ning, Jessica M. Urbanczyk, Xingsheng Ren, Caroline J. Herrnreiter, Jackson A. Disario, Brian Wray, Matthew J. Schipma, Yuri S. Velichko, David P. Sullivan, Kouki Abe, Shannon M. Lauberth, Guang-Yu Yang, Parambir S. Dulai, Stephen B. Hanauer, Ronen Sumagin
Journal: Journal of Clinical Investigation (2024)

Neutrophil (PMN) tissue accumulation is an established feature of ulcerative colitis (UC) lesions and colorectal cancer (CRC). To assess the PMN phenotypic and functional diversification during inflammatory ulceration to CRC transition we analyzed the transcriptomic landscape of blood and tissue PMNs. Transcriptional programs effectively separated PMNs based on their localization to peripheral blood, inflamed colon, and tumors. In silico pathway overrepresentation analysis, protein-network mapping, gene signature identification, and gene-ontology scoring revealed unique enrichment of angiogenic and vasculature development pathways in tumor-associated neutrophils (TANs). Functional studies utilizing ex vivo cultures, colitis-induced murine CRC, and patient-derived xenograft models demonstrated a critical role for TANs in promoting tumor vascularization. Spp1 (OPN) and Mmp14 (MT1-MMP) were identified by unbiased -omics and mechanistic studies to be highly induced in TANs, acting to critically regulate endothelial cell chemotaxis and branching. TCGA dataset and clinical specimens confirmed enrichment of SPP1 and MMP14 in high-grade CRC but not in UC patients. Pharmacological inhibition of TAN trafficking or MMP14 activity effectively reduced tumor vascular density, leading to CRC regression. Our findings, demonstrate a niche-directed PMN functional specialization, and identify TAN contributions to tumor vascularization, delineating a new therapeutic framework for CRC treatment focused on TAN angiogenic properties.
Severe Work-Related Injuries in the Oil and Gas Extraction Industry — 32 Federal Occupational Safety and Health Administration Jurisdictions, United States, January 2015–July 2022
Authors: Vidisha Parasram, Christina Socias-Morales, Audrey Reichard
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

The Occupational Safety and Health Administration (OSHA) severe injuries reports include work-related injuries from establishments under federal OSHA jurisdiction that result in an amputation, loss of an eye, or inpatient hospitalization.Data from 32 jurisdictions were examined to determine oil and gas extraction industry-specific severe industry trends during January 2015-July 2022, using the 2012 North American Industry Classification System (NAICS) codes for oil and gas extraction.During this period, a total of 2,101 severe work-related injuries were reported in this sector.Among these severe work-related injuries, well service contract workers' injuries included the highest number of amputations (417) and hospitalizations (1,194), accounting for 20% and 57%, respectively, of all severe injuries reported.Overall, 895 (43%) of all severe injuries reported involved upper extremities.Contract workers in the service and drilling subindustries (NAICS codes 213112 and 213111, respectively) experienced disproportionately more work-related injuries compared with those in the operation subindustry (NAICS code 211).These injuries could be preventable by including contractors in worksite safety plans that administer the hierarchy of controls, are within an effective safety management system, and provide consistent safety training on work equipment, personal protective equipment, and daily site safety meetings that increase safety culture.
Granular Hydrogels Improve Myogenic Invasion and Repair after Volumetric Muscle Loss
Authors: Gabrielle I. Tanner, Leia Schiltz, Niharika Narra, Marxa L. Figueiredo, Taimoor H. Qazi
Journal: Advanced Healthcare Materials (2024)

Abstract Skeletal muscle injuries including volumetric muscle loss (VML) lead to excessive tissue scarring and permanent functional disability. Despite its high prevalence, there is currently no effective treatment for VML. Bioengineering interventions such as biomaterials that fill the VML defect to support cell and tissue growth are a promising therapeutic strategy. However, traditional biomaterials developed for this purpose lack the pore features needed to support cell infiltration. The present study investigates for the first time, the impact of granular hydrogels on muscle repair – hypothesizing that their flowability will permit conformable filling of the defect site and their inherent porosity will support the invasion of native myogenic cells, leading to effective muscle repair. Small and large microparticle fragments are prepared from photocurable hyaluronic acid polymer via extrusion fragmentation and facile size sorting. In assembled granular hydrogels, particle size and degree of packing significantly influence pore features, rheological behavior, and injectability. Using a mouse model of VML, it is demonstrated that, in contrast to bulk hydrogels, granular hydrogels support early‐stage (satellite cell invasion) and late‐stage (myofiber regeneration) muscle repair processes. Together, these results highlight the promising potential of injectable and porous granular hydrogels in supporting endogenous repair after severe muscle injury.
The gap between real‐world and guidelines in the use of sodium–glucose cotransporter 2 inhibitors for heart failure patients with reduced ejection fraction: Is it underestimated or overestimated? Letter regarding the article ‘Real‐world use of sodium–glucose cotransporter 2 inhibitors in patients with heart failure and reduced ejection fraction: Data from the Swedish Heart Failure Registry’
Authors: Yuqin Zhao, Jun Sun, Cheng Xie
Journal: European Journal of Heart Failure (2024)
Selection of Antibiotics as Prophylaxis for Close Contacts of Patients with Meningococcal Disease in Areas with Ciprofloxacin Resistance — United States, 2024
Authors: Isha Berry, Amy B. Rubis, Rebecca L. Howie, Shalabh Sharma, Daya Marasini, Henju Marjuki, Samuel Crowe, Lucy A. McNamara
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Meningococcal disease, caused by the bacterium Neisseria meningitidis, is a rare but life-threatening illness that requires prompt antibiotic treatment for patients and antibiotic prophylaxis for their close contacts.Historically, N. meningitidis isolates in the United States have been largely susceptible to the antibiotics recommended for prophylaxis, including ciprofloxacin.Since 2019, however, the number of meningococcal disease cases caused by ciprofloxacin-resistant strains has increased.Antibiotic prophylaxis with ciprofloxacin in areas with ciprofloxacin resistance might result in prophylaxis failure.Health departments should preferentially consider using antibiotics other than ciprofloxacin as prophylaxis for close contacts when both of the following criteria have been met in a local catchment area during a rolling 12-month period: 1) the reporting of two or more invasive meningococcal disease cases caused by ciprofloxacin-resistant strains, and 2) ≥20% of all reported invasive meningococcal disease cases are caused by ciprofloxacin-resistant strains.Other than ciprofloxacin, alternative recommended antibiotic options include rifampin, ceftriaxone, or azithromycin.Ongoing monitoring for antibiotic resistance of meningococcal isolates through surveillance and health care providers' reporting of prophylaxis failures will guide future updates to prophylaxis considerations and recommendations.
Atypical Diabetes: What Have We Learned and What Does the Future Hold?
Authors: Stephen I. Stone, Ashok Balasubramanyam, Jennifer E. Posey
Journal: Diabetes Care (2024)

As our understanding of the pathophysiology of diabetes evolves, we increasingly recognize that many patients may have a form of diabetes that does not neatly fit with a diagnosis of either type 1 or type 2 diabetes. The discovery and description of these forms of “atypical diabetes” have led to major contributions to our collective understanding of the basic biology that drives insulin secretion, insulin resistance, and islet autoimmunity. These discoveries now pave the way to a better classification of diabetes based on distinct endotypes. In this review, we highlight the key biological and clinical insights that can be gained from studying known forms of atypical diabetes. Additionally, we provide a framework for identification of patients with atypical diabetes based on their clinical, metabolic, and molecular features. Helpful clinical and genetic resources for evaluating patients suspected of having atypical diabetes are provided. Therefore, appreciating the various endotypes associated with atypical diabetes will enhance diagnostic accuracy and facilitate targeted treatment decisions.
Disentangling Computed Tomography Pattern and Extent to Estimate Prognosis in Fibrosing Interstitial Lung Diseases
Authors: Joseph Jacob, Chad A. Newton
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Disentangling CT Pattern and Extent to Estimate Prognosis in Fibrosing Interstitial Lung Diseases." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Genetic, immunologic, and clinical features of 830 patients with Mendelian susceptibility to mycobacterial diseases (MSMD): A systematic review
Authors: Armin Khavandegar, Seyed Alireza Mahdaviani, Majid Zaki-Dizaji, Fereshteh Khalili-Moghaddam, Sarina Ansari, Saba Alijani, Nooshin Taherzadeh-Ghahfarrokhi, Davood Mansouri, Jean-Laurent Casanova, Jacinta Bustamante, Mahnaz Jamee
Journal: Journal of Allergy and Clinical Immunology (2024)
Epidemiology and Prognostic Implications of Coronary Artery Calcium in Asymptomatic Individuals With Prediabetes: A Multicohort Study
Authors: Mahmoud Al Rifai, Mouaz H. Al-Mallah, Michael J. Blaha, Jaideep Patel, John W. McEvoy, Khurram Nasir, Izza Shahid, Kershaw V. Patel, Garima Sharma, Jaume Marrugat, Helena Tizon-Marcos, Raimund Erbel, Andreas Stang, Karl-Heinz Jöckel, Nils Lehmann, Sara Schramm, Börge Schmidt, Roger S. Blumenthal, Salim S. Virani, Vijay Nambi, Miguel Cainzos-Achirica
Journal: Diabetes Care (2024)

OBJECTIVE To describe the epidemiology and prognostic value of coronary artery calcium (CAC) in individuals with prediabetes. RESEARCH DESIGN AND METHODS We pooled participants free of clinical atherosclerotic cardiovascular disease (ASCVD) from four prospective cohorts: the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100 to &amp;lt;126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7% to &amp;lt;6.5%, if available, and no glucose-lowering medications) and restrictive (FPG ≥110 to &amp;lt;126 mg/dL and HbA1c ≥5.7% to &amp;lt;6.5%, if available, among participants not taking glucose-lowering medications). RESULTS The study included 13,376 participants (mean age 58 years; 54% women; 57% White; 27% Black). The proportions with CAC ≥100 were 17%, 22%, and 37% in those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th–75th percentile) follow-up time of 14.6 (interquartile range 7.8–16.4) years, individuals with prediabetes and CAC ≥100 had a higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared with euglycemia, the hazard ratios (HRs) for ASCVD were 0.79 (95% CI 0.62, 1.01) for prediabetes and CAC 0, 0.70 (0.54, 0.89) for prediabetes and CAC 1–99, 1.54 (1.27, 1.88) for prediabetes and CAC ≥100, and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC ≥100. CONCLUSIONS CAC ≥100 is frequent among individuals with prediabetes and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to that in individuals with diabetes.
Chatting with the King about cancer
Authors: Richard Smith
Journal: BMJ (2024)

King: Good morning.This King Charles.I'm sorry to ring so early, and I'm sure that you're surprised to hear from me.You'll know probably that I've had cancer diagnosed, and by a strange coincidence while I was waiting in the hospital an aide brought to my attention the blog you posted yesterday about the meaning of cancer. 1 As you may guess, I'm a man who likes to think about the big picture of everything, including cancer.
Anomaly guided segmentation: Introducing semantic context for lesion segmentation in retinal OCT using weak context supervision from anomaly detection
Authors: Philipp Seeböck, José Ignacio Orlando, Martin Michl, Julia Mai, Ursula Schmidt-Erfurth, Hrvoje Bogunović
Journal: Medical Image Analysis (2024)

Automated lesion detection in retinal optical coherence tomography (OCT) scans has shown promise for several clinical applications, including diagnosis, monitoring and guidance of treatment decisions. However, segmentation models still struggle to achieve the desired results for some complex lesions or datasets that commonly occur in real-world, e.g. due to variability of lesion phenotypes, image quality or disease appearance. While several techniques have been proposed to improve them, one line of research that has not yet been investigated is the incorporation of additional semantic context through the application of anomaly detection models. In this study we experimentally show that incorporating weak anomaly labels to standard segmentation models consistently improves lesion segmentation results. This can be done relatively easy by detecting anomalies with a separate model and then adding these output masks as an extra class for training the segmentation model. This provides additional semantic context without requiring extra manual labels. We empirically validated this strategy using two in-house and two publicly available retinal OCT datasets for multiple lesion targets, demonstrating the potential of this generic anomaly guided segmentation approach to be used as an extra tool for improving lesion detection models.
Characteristics of Alcohol, Marijuana, and Other Drug Use Among Persons Aged 13–18 Years Being Assessed for Substance Use Disorder Treatment — United States, 2014–2022
Authors: Sarah Connolly, Taryn Dailey Govoni, Xinyi Jiang, Andrew Terranella, Gery P. Guy, Jody L. Green, Christina Mikosz
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Substance use often begins during adolescence, placing youths at risk for fatal overdose and substance use disorders (SUD) in adulthood.Understanding the motivations reported by adolescents for using alcohol, marijuana, and other drugs and the persons with whom they use these substances could guide strategies to prevent or reduce substance use and its related consequences among adolescents.A cross-sectional study was conducted among adolescents being assessed for SUD treatment in the United States during 2014-2022, to examine self-reported motivations for using substances and the persons with whom substances were used.The most commonly reported motivation for substance use was "to feel mellow, calm, or relaxed" (73%), with other stress-related motivations among the top reasons, including "to stop worrying about a problem or to forget bad memories" (44%) and "to help with depression or anxiety" (40%); one half (50%) reported using substances "to have fun or experiment."The majority of adolescents reported using substances with friends (81%) or using alone (50%).These findings suggest that interventions related to reducing stress and addressing mental health concerns might reduce these leading motivations for substance use among adolescents.Education for adolescents about harm reduction strategies, including the danger of using drugs while alone and how to recognize and respond to an overdose, can reduce the risk for fatal overdose.
Comparison of Administration of 8-Milligram and 4-Milligram Intranasal Naloxone by Law Enforcement During Response to Suspected Opioid Overdose — New York, March 2022–August 2023
Authors: Emily R. Payne, Sharon Stancliff, Kirsten Rowe, Jason A. Christie, Michael W. Dailey
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

This report describes real-world comparisons of survival, the average number of doses administered, the presence of postnaloxone signs and symptoms, and hospital transport refusal among people receiving 8-mg and 4-mg intranasal naloxone.
<i>QuickStats:</i> Percentage* of Children and Adolescents Aged 5–17 Years Who Had Ever Received a Diagnosis of Attention-Deficit/Hyperactivity Disorder,† by Urbanization Level§ and Age Group — National Health Interview Survey, United States, 2020–2022¶
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Total Large central metropolitan areas Large fringe metropolitan areas Medium and small metropolitan areas Nonmetropolitan areas Support Width OptionsPage wide = 7.5" QuickStats = 5.0" 1½ columns = 4.65" 1 column = 3.
Biomarkers Associated with Lung Function Decline and Dupilumab Response in Patients with Asthma
Authors: Ian D. Pavord, Lucia De Prado Gómez, Guy Brusselle, Daniel J. Jackson, Christopher E. Brightling, Alberto Papi, Jorge F. Maspero, Klaus F. Rabe, Stephanie Korn, Mei Zhang, Xavier Soler, Juby A. Jacob-Nara, Megan Hardin, Nami Pandit-Abid, Paul J. Rowe, Amr Radwan, Yamo Deniz
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Biomarkers Associated with Lung Function Decline and Dupilumab Response in Patients with Asthma." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Faecal microbial transfer and complex carbohydrates mediate protection against COPD
Authors: Kurtis F Budden, Shakti D Shukla, Kate L Bowerman, Annalicia Vaughan, Shaan L Gellatly, David L A Wood, Nancy Lachner, Sobia Idrees, Saima Firdous Rehman, Alen Faiz, Vyoma K Patel, Chantal Donovan, Charlotte A Alemao, Sj Shen, Nadia Amorim, Rajib Majumder, Kanth S Vanka, Jazz Mason, Tatt Jhong Haw, Bree Tillet, Michael Fricker, Simon Keely, Nicole Hansbro, Gabrielle T Belz, Jay Horvat, Thomas Ashhurst, Caryn van Vreden, Helen McGuire, Barbara Fazekas de St Groth, Nicholas J C King, Ben Crossett, Stuart J Cordwell, Lorenzo Bonaguro, Joachim L Schultze, Emma E Hamilton‐Williams, Elizabeth Mann, Samuel C Forster, Matthew A Cooper, Leopoldo N Segal, Sanjay H Chotirmall, Peter Collins, Rayleen Bowman, Kwun M Fong, Ian A Yang, Peter A B Wark, Paul G Dennis, Philip Hugenholtz, Philip M Hansbro
Journal: Gut (2024)

Objective Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. Design Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. Results FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. Conclusion The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.
Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies
Authors: Lena Allweiss, Annika Volmari, Vithika Suri, Jeffrey J. Wallin, John F. Flaherty, Dmitry Manuilov, Bryan Downie, Marc Lütgehetmann, Jan-Hendrik Bockmann, Stephan Urban, Heiner Wedemeyer, Maura Dandri
Journal: Journal of Hepatology (2024)

Background & AimsBulevirtide (BLV) is a first-in-class entry inhibitor and the only approved treatment for patients chronically infected with HDV in Europe. We aimed to investigate the efficacy of BLV treatment in paired liver biopsies obtained at baseline and after 24 or 48 weeks of treatment.MethodsWe performed a combined analysis of 126 paired liver biopsies derived from 3 clinical trials. In the phase 2 clinical trial MYR202, patients with chronic hepatitis D were randomised to receive 24 weeks of BLV at 2mg, 5mg or 10mg/day. Patients in MYR203 (phase 2) and MYR301 (phase 3) received 48 weeks of 2mg or 10mg/day BLV. Tenofovir disoproxil fumarate monotherapy or delayed treatment served as comparator. Virological parameters and infection-related host genes were assessed by qPCR and immunohistochemistry.ResultsAt week 24, median intrahepatic HDV RNA decline from baseline was 0.9Log10 with 2mg (n=7), 1.1Log10 with 5mg (n=5) and 1.4Log10 with 10mg (n=7). At week 48, median reductions were 2.2Log10 with 2mg (n=27) and 2.7Log10 with 10mg (n=37), while HDV RNA levels did not change in the comparator arms. Notably, a drastic decline in the number of hepatitis delta antigen positive hepatocytes and a concomitant decrease of transcriptional levels of inflammatory chemokines and interferon-stimulated genes was determined in all BLV-treatment arms. Despite the abundance of HBsAg-positive hepatocytes, replication and covalently closed circular DNA (cccDNA) levels of the helper virus HBV were low and remained unaffected by BLV treatment.ConclusionBlocking viral entry diminishes signs of liver inflammation and promotes a strong reduction of HDV infection within the liver, thus suggesting that some patients may achieve HDV cure with long-term treatment.Impact and implicationsChronic infection with the hepatitis delta virus causes the most severe form of viral hepatitis affecting approximately 12 million people worldwide. The entry inhibitor bulevirtide (BLV) is the only recently approved anti-HDV drug, which has proven efficacious and safe in clinical trials and real-word data. Here, we investigated paired liver biopsies at baseline and after 24 or 48 weeks of treatment from three clinical trials to understand the effect of the drug on viral and host parameters in the liver, the site of viral replication. We found that BLV treatment strongly reduces the number of HDV-infected cells and signs of liver inflammation. This data implies that blocking viral entry ameliorates liver inflammation and that prolonged treatment regimens might lead to HDV cure in some patients. This concept will inform further developments of therapeutic strategies and combination treatments in CHD patients.
Mutant p53 Gain-of-Function in the Spotlight: Are We Suffering a GOF Delusion?
Authors: David P. Lane
Journal: Cancer Discovery (2024)

Summary: Mutant p53 proteins are often highly expressed in human cancers and have been thought to have oncogenic driver gain-of-function (GOF) properties. Wang and colleagues show, surprisingly, that this is not the case because removing the TP53-mutant gene from human and mouse cancer cells using CRISPR technology has no effect on cancer cell growth in vitro or in vivo. See related article by Wang et al., p. 362 (10) .