tbuckley/cabot-search huggingface dataset:
Heavy Lifetime Cannabis Use and Mortality by Sex
Authors: Alexandre Vallée
Journal: JAMA Network Open (2024)

Importance The association between mortality and cannabis use remains unclear. Objective To examine sex-stratified associations of cumulative lifetime cannabis use with all-cause, cardiovascular disease (CVD), and cancer mortality in the UK Biobank population. Design, Setting, and Participants This cohort study used data from volunteers in the UK Biobank population. Participant monitoring for mortality in the UK Biobank study commenced from the point of their inclusion between 2006 and 2010 and continued until December 19, 2020. Data regarding the causes of death were sourced from the National Health Service Information Centre. Data were analyzed from inception of study inclusion to December 2020. Exposure Cannabis use status was assessed by questionnaire and categorized as heavy, moderate, low, and never. Main Outcomes and Measures The main outcomes were all-cause, CVD, and cancer mortality. Sex-stratified associations of cumulative lifetime cannabis use with mortality were estimated using Cox proportional hazards regression with adjustment for demographic and clinical variables. Results Among 121 895 participants (54.51% females with mean [SD] age of 55.15 [7.64] years; 45.49% males with mean [SD] age of 56.46 [7.79] years) during an overall median of 11.80 years (IQR, 10.53-13.22 years) of follow-up, 2375 total deaths occurred, including 1411 deaths from CVD and 440 from cancer. In males, after full adjustment, the hazard ratios (HRs) were 1.28 (95% CI, 0.90-1.81) for all-cause mortality, 0.98 (95% CI, 0.43-2.25) for CVD mortality, and 1.09 (95% CI, 0.71-1.67) for cancer mortality among heavy cannabis users compared with never users. In females, after full adjustment, the HRs were 1.49 (95% CI, 0.92-2.40) for all-cause mortality, 2.67 (95% CI, 1.19-4.32) for CVD mortality, and 1.61 (95% CI, 0.91-2.83) for cancer mortality among heavy cannabis users compared with never users. In female current tobacco users, after full adjustment, heavy cannabis use was associated with all-cause mortality (HR, 2.25; 95% CI, 1.12-4.53), CVD mortality (HR, 2.56; 95% CI, 1.43-15.36), and cancer mortality (HR, 3.52; 95% CI, 1.50-8.33) and among never tobacco users was associated with CVD mortality (HR, 2.98; 95% CI, 1.67-6.61). In male current tobacco users, heavy cannabis use was associated with cancer mortality (HR, 2.44; 95% CI, 1.14-5.23). Conclusions and Relevance In this study, a positive association between CVD mortality and heavy lifetime cannabis use was observed among females. Longitudinal studies are needed in general populations to investigate the potential effects of cannabis on mortality.
Comprehensive Audiologic Analyses After Cisplatin-Based Chemotherapy
Authors: Victoria A. Sanchez, Paul C. Dinh, Patrick O. Monahan, Sandra Althouse, Jennessa Rooker, Howard D. Sesso, M. Eileen Dolan, Mandy Weinzerl, Darren R. Feldman, Chunkit Fung, Lawrence H. Einhorn, Robert D. Frisina, Lois B. Travis
Journal: JAMA Oncology (2024)

Cisplatin is highly ototoxic but widely used. Evidence is lacking regarding cisplatin-related hearing loss (CRHL) in adult-onset cancer survivors with comprehensive audiologic assessments (eg, Words-in-Noise [WIN] tests, full-spectrum audiometry, and additional otologic measures), as well as the progression of CRHL considering comorbidities, modifiable factors associated with risk, and cumulative cisplatin dose.
Mental Health and Well-Being Among Home Health Aides
Authors: Melissa Yanez Hernandez, Elizabeth Fong-Chy Kuo, Yefrenia Henriquez Taveras, Ann Lee, Aida Ramos, Joanna Ringel, Susan Andreae, Emma Tsui, Monika M. Safford, Ariel C. Avgar, Megan J. Shen, Nicola Dell, Daniel Shalev, Catherine Riffin, Faith Wiggins, Elissa Kozlov, Nathalie Moise, Madeline R. Sterling
Journal: JAMA Network Open (2024)

Importance Home health aides and attendants (HHAs) provide essential care to older adults and those with chronic conditions in the home. However, some HHAs struggle with poor mood and stress, which may have been exacerbated by the COVID-19 pandemic. Objective To elicit HHAs’ perspectives toward mental health and well-being, including how their job influences both and how to better support the workforce in the future. Design, Setting, and Participants For this qualitative study, focus groups and interviews with HHAs were facilitated in English and Spanish from August 17, 2022, to February 9, 2023, in partnership with the 1199SEIU Training and Employment Fund, a benefit fund of the 1199SEIU United Healthcare Workers East and the largest health care union in the US. Included were HHAs at risk for poor mental health and well-being, which were defined as having at least mild or more symptoms on either the 8-item Personal Health Questionnaire depression scale, the 4-item Cohen Perceived Stress Scale, or the University of California, Los Angeles Loneliness Scale. Exposure Mental health and well-being of HHAs. Main Outcomes and Measures Focus groups and interviews were audio recorded, professionally transcribed, and translated. A thematic analysis was performed that was informed by Pender’s Health Promotion Model and the National Institute for Occupational Safety and Health’s Total Worker Health model. Results A total of 28 HHAs from 14 different agencies participated (mean [SD] age, 54.3 [10.8] years; 26 female [93%]). Seventeen participants (61%) spoke Spanish at home. Five key themes emerged: (1) HHAs’ attitudes toward mental health and well-being were influenced by a variety of personal and cultural factors; (2) HHAs’ relationships with their patients impacted their mood in both positive and negative ways; (3) structural and organizational aspects of the job, alongside the COVID-19 pandemic, impacted HHAs’ mood and stress levels; (4) HHAs used a variety of strategies to cope with their emotions; and (5) HHAs were eager for interventions that can improve their mood, particularly those that bring them closer to their colleagues. Conclusions and Relevance These findings suggest that HHAs’ mental health and well-being may be influenced by both personal and occupational factors. Interventions and policies to better support their emotional well-being on the job are warranted.
Safety and efficacy of trastuzumab deruxtecan for metastatic HER2+ and HER2-low breast cancer: An updated systematic review and meta-analysis of clinical trials.
Authors: Zaheer Qureshi, Faryal Altaf, Abdur Jamil, Rimsha Siddique
Journal: Journal of Clinical Oncology (2024)

1034 Background: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) that has shown promise in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis aimed to evaluate the safety and efficacy of T-DXd in this patient population, integrating data from the latest clinical trials. Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd’s efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data. Results: Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR 0.37, 95% CI 0.27–0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR 2.10, 95% CI 1.36–3.25), fatigue (OR 1.56, 95% CI 1.21–2.02), nausea (OR 6.42, 95% CI 4.37–9.42), vomiting (OR 6.21, 95% CI 3.14–12.25), constipation (OR 2.26, 95% CI 1.53–3.34), and notably, drug-related interstitial lung disease (ILD) (OR 10.89, 95% CI 3.81–31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis. Conclusions: T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring strategies to enhance safety profiles.
The tip of the iceberg: a plethora of lung nodules in the general population
Authors: Luis M. Seijo, Javier J. Zulueta
Journal: European Respiratory Journal (2024)

<h3>Shareable abstract</h3> <b>The widespread adoption of computed tomography in routine clinical practice combined with the advent of lung cancer screening has led to the detection of vast quantities of lung nodules in need of work-up and follow-up</b>https://bit.ly/4dE0KVG
<i>Notes from the Field:</i> Anthrax on a Sheep Farm in Winter — Texas, December 2023–January 2024
Authors: Julie M. Thompson, Kelly Spencer, Melissa Maass, Susan Rollo, Cari A. Beesley, Chung K. Marston, Alex R. Hoffmaster, William A. Bower, Maribel Gallegos Candela, John R. Barr, Anne E. Boyer, Zachary P. Weiner, María E. Negrón, Erin Swaney, Briana O’Sullivan
Journal: MMWR Morbidity and Mortality Weekly Report (2024)

Anthrax is a rare but serious infectious zoonotic disease caused by the spore-forming bacterium Bacillus anthracis.In North America, animal outbreaks typically occur during summer in hot, dry weather (1).Rare cases among humans usually follow direct contact with or processing of anthrax-infected animals or contanimated animal products such as hides, hair, or wool (1,2).In early 2024, an unusual case of confirmed cutaneous anthrax* acquired during the winter in a geographic region with enzootic anthrax occurred, and an investigation was undertaken.This activity was reviewed by CDC,
Exploring the potential of cell-derived vesicles for transient delivery of gene editing payloads
Authors: Kevin Leandro, David Rufino-Ramos, Koen Breyne, Emilio Di Ianni, Sara M. Lopes, Rui Jorge Nobre, Benjamin P. Kleinstiver, Pedro R.L. Perdigão, Xandra O. Breakefield, Luís Pereira de Almeida
Journal: Advanced Drug Delivery Reviews (2024)
ETV6::RUNX1 Acute Lymphoblastic Leukemia: how much therapy is needed for cure?
Authors: Anna Østergaard, Marta Fiocco, Hester de Groot-Kruseman, Anthony V. Moorman, Ajay Vora, Martin Zimmermann, Martin Schrappe, Andrea Biondi, Gabriele Escherich, Jan Stary, Chihaya Imai, Toshihiko Imamura, Mats Heyman, Kjeld Schmiegelow, Rob Pieters
Journal: Leukemia (2024)

Recent trials show 5-year survival rates >95% for ETV6::RUNX1 Acute Lymphoblastic Leukemia (ALL). Since treatment has many side effects, an overview of cumulative drug doses and intensities between eight international trials is presented to characterize therapy needed for cure. A meta-analysis was performed as a comprehensive summary of survival outcomes at 5 and 10 years. For drug dose comparison in non-high risk trial arms, risk group distribution was applied to split the trials into two groups: trial group A with ~70% (range: 63.5-75%) of patients in low risk (LR) (CCLSG ALL2004, CoALL 07-03, NOPHO ALL2008, UKALL2003) and trial group B with ~45% (range: 38.7-52.7%) in LR (AIEOP-BFM ALL 2000, ALL-IC BFM ALL 2002, DCOG ALL10, JACLS ALL-02). Meta-analysis did not show evidence of heterogeneity between studies in trial group A LR and medium risk (MR) despite differences in treatment intensity. Statistical heterogeneity was present in trial group B LR and MR. Trials using higher cumulative dose and intensity of asparaginase and pulses of glucocorticoids and vincristine showed better 5-year event-free survival but similar overall survival. Based on similar outcomes between trials despite differences in therapy intensity, future trials should investigate, to what extent de-escalation is feasible for ETV6::RUNX1 ALL.
Treatment of Hepatitis D — A Future Role for Combination Therapy
Authors: Norah Terrault
Journal: New England Journal of Medicine (2024)

Hepatitis D virus (HDV) infection is the most serious form of viral hepatitis, with an accelerated clinical course and heightened risks of cirrhosis and liver cancer.1 No therapies for HDV infection have been approved by the Food and Drug Administration (FDA), which has made the management of this disease challenging for decades. However, the tide has turned, with several new drugs under study. The goal of therapy is to achieve HDV eradication, with the very best treatment being one that would achieve clearance of both HDV and hepatitis B surface antigen (HBsAg), yielding a functional cure of both HDV and . . .
A commentary on “Single-cell and bulk RNA-sequence identified fibroblasts signature and CD8+ T cell - Fibroblast subtype predicting prognosis and immune therapeutic response of bladder cancer, based on machine-learning” (Int J Surg. 2024 May 17.)
Authors: Zhen Wang, Guolin Zhang, Xiaofeng Liu, Guang Tan
Journal: International Journal of Surgery (2024)

aDepartment of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116000, China bDepartment of Cardiology, The Second Hospital of Dalian Medical University, Dalian 116021, Liaoning, China cDepartment of Orthopaedics, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China Zhen Wang, Guolin Zhang These authors have contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author Address: . E-mail address: [email protected] (X. Liu). *Corresponding Author Address: The First Affiliated Hospital of Dalian Medical University CHINA. E-mail address: [email protected] (G. Tan). This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Prognostic utility of cardiopulmonary exercise testing with simultaneous exercise echocardiography in heart failure with preserved ejection fraction
Authors: Ayami Naito, Kazuki Kagami, Naoki Yuasa, Tomonari Harada, Hidemi Sorimachi, Fumitaka Murakami, Yuki Saito, Yuta Tani, Toshimitsu Kato, Naoki Wada, Takeshi Adachi, Hideki Ishii, Masaru Obokata
Journal: European Journal of Heart Failure (2024)
Mailed feedback to primary care physicians on antibiotic prescribing for patients aged 65 years and older: pragmatic, factorial randomised controlled trial
Authors: Kevin L Schwartz, Jennifer Shuldiner, Bradley J Langford, Kevin A Brown, Susan E Schultz, Valerie Leung, Nick Daneman, Mina Tadrous, Holly O Witteman, Gary Garber, Jeremy M Grimshaw, Jerome A Leis, Justin Presseau, Michael S Silverman, Monica Taljaard, Tara Gomes, Meagan Lacroix, Jamie Brehaut, Kednapa Thavorn, Sharon Gushue, Lindsay Friedman, Merrick Zwarenstein, Noah Ivers
Journal: BMJ (2024)

To evaluate whether providing family physicians with feedback on their antibiotic prescribing compared with that of their peers reduces antibiotic prescriptions. To also identify effects on antibiotic prescribing from case-mix adjusted feedback reports and messages emphasising antibiotic associated harms.
PROteolysis‐Targeting Chimeras (PROTACs) in leukemia: overview and future perspectives
Authors: André T. S. Vicente, Jorge A. R. Salvador
Journal: MedComm (2024)

Abstract Leukemia is a heterogeneous group of life‐threatening malignant disorders of the hematopoietic system. Immunotherapy, radiotherapy, stem cell transplantation, targeted therapy, and chemotherapy are among the approved leukemia treatments. Unfortunately, therapeutic resistance, side effects, relapses, and long‐term sequelae occur in a significant proportion of patients and severely compromise the treatment efficacy. The development of novel approaches to improve outcomes is therefore an unmet need. Recently, novel leukemia drug discovery strategies, including targeted protein degradation, have shown potential to advance the field of personalized medicine for leukemia patients. Specifically, PROteolysis‐TArgeting Chimeras (PROTACs) are revolutionary compounds that allow the selective degradation of a protein by the ubiquitin–proteasome system. Developed against a wide range of cancer targets, they show promising potential in overcoming many of the drawbacks associated with conventional therapies. Following the exponential growth of antileukemic PROTACs, this article reviews PROTAC‐mediated degradation of leukemia‐associated targets. Chemical structures, in vitro and in vivo activities, pharmacokinetics, pharmacodynamics, and clinical trials of PROTACs are critically discussed. Furthermore, advantages, challenges, and future perspectives of PROTACs in leukemia are covered, in order to understand the potential that these novel compounds may have as future drugs for leukemia treatment.
Exposure of benzo[a]pyrene induces HCC exosome‐circular RNA to activate lung fibroblasts and trigger organotropic metastasis
Authors: Wei Mu, Pengfei Gu, Huating Li, Jinjin Zhou, Yulun Jian, Weiping Jia, Yang Ge
Journal: Cancer Communications (2024)

Abstract Background Benzo[a]pyrene (B[a]P), a carcinogen pollutant produced by combustion processes, is present in the western diet with grilled meats. Chronic exposure of B[a]P in hepatocellular carcinoma (HCC) cells promotes metastasis rather than primary proliferation, implying an unknown mechanism of B[a]P‐induced malignancy. Given that exosomes carry bioactive molecules to distant sites, we investigated whether and how exosomes mediate cancer‐stroma communications for a toxicologically associated microenvironment. Method Exosomes were isolated from B[a]P stimulated BEL7404 HCC cells (7404‐100Bap Exo) at an environmental relevant dose (100 nmol/L). Lung pre‐education animal model was prepared via injection of exosomes and cytokines. The inflammatory genes of educated lungs were evaluated using quantitative reverse transcription PCR array. HCC LM3 cells transfected with firefly luciferase were next injected to monitor tumor burdens and organotropic metastasis. Profile of B[a]P‐exposed exosomes were determined by ceRNA microarray. Interactions between circular RNA (circRNA) and microRNAs (miRNAs) were detected using RNA pull‐down in target lung fibroblasts. Fluorescence in situ hybridization and RNA immunoprecipitation assay was used to evaluate the “on‐off” interaction of circRNA‐miRNA pairs. We further developed an adeno‐associated virus inhalation model to examine mRNA expression specific in lung, thereby exploring the mRNA targets of B[a]P induced circRNA‐miRNA cascade. Results Lung fibroblasts exert activation phenotypes, including focal adhesion and motility were altered by 7404‐100Bap Exo. In the exosome‐educated in vivo model, fibrosis factors and pro‐inflammatory molecules of are up‐regulated when injected with exosomes. Compared to non‐exposed 7404 cells, circ_0011496 was up‐regulated following B[a]P treatment and was mainly packaged into 7404‐100Bap Exo. Exosomal circ_0011496 were delivered and competitively bound to miR‐486‐5p in recipient fibroblasts. The down‐regulation of miR‐486‐5p converted fibroblast to cancer‐associated fibroblast via regulating the downstream of Twinfilin‐1 (TWF1) and matrix metalloproteinase‐9 (MMP9) cascade. Additionally, increased TWF1, specifically in exosomal circ_0011496 educated lungs, could promote cancer‐stroma crosstalk via activating vascular endothelial growth factor (VEGF). These modulated fibroblasts promoted endothelial cells angiogenesis and recruited primary HCC cells invasion, as a consequence of a pre‐metastatic niche formation. Conclusion We demonstrated that B[a]P‐induced tumor exosomes can deliver circ_0011496 to activate miR‐486‐5p/TWF1/MMP9 cascade in the lung fibroblasts, generating a feedback loop that promoted HCC metastasis.
LncRNA DCRT Protects Against Dilated Cardiomyopathy by Preventing NDUFS2 Alternative Splicing by Binding to PTBP1
Authors: Hengzhi Du, Yanru Zhao, Jianpei Wen, Beibei Dai, Guo Hu, Yufei Zhou, Zhongwei Yin, Nan Ding, Huaping Li, Jiahui Fan, Xiang Nie, Feng Wang, Qian Liu, Zheng Wen, Gang Xu, Dao Wen Wang, Chen Chen
Journal: Circulation (2024)

BACKGROUND: Dilated cardiomyopathy is characterized by left ventricular dilation and continuous systolic dysfunction. Mitochondrial impairment is critical in dilated cardiomyopathy; however, the underlying mechanisms remain unclear. Here, we explored the cardioprotective role of a heart-enriched long noncoding RNA, the dilated cardiomyopathy repressive transcript (DCRT), in maintaining mitochondrial function. METHODS: The DCRT knockout (DCRT −/− ) mice and DCRT knockout cells were developed using CRISPR-Cas9 technology. Cardiac-specific DCRT transgenic mice were generated using α-myosin heavy chain promoter. Chromatin coimmunoprecipitation, RNA immunoprecipitation, Western blot, and isoform sequencing were performed to investigate the underlying mechanisms. RESULTS: We found that the long noncoding RNA DCRT was highly enriched in the normal heart tissues and that its expression was significantly downregulated in the myocardium of patients with dilated cardiomyopathy. DCRT −/− mice spontaneously developed cardiac dysfunction and enlargement with mitochondrial impairment. DCRT transgene or overexpression with the recombinant adeno-associated virus system in mice attenuated cardiac dysfunction induced by transverse aortic constriction treatment. Mechanistically, DCRT inhibited the third exon skipping of NDUFS2 (NADH dehydrogenase ubiquinone iron-sulfur protein 2) by directly binding to PTBP1 (polypyrimidine tract binding protein 1) in the nucleus of cardiomyocytes. Skipping of the third exon of NDUFS2 induced mitochondrial dysfunction by competitively inhibiting mitochondrial complex I activity and binding to PRDX5 (peroxiredoxin 5) and suppressing its antioxidant activity. Furthermore, coenzyme Q10 partially alleviated mitochondrial dysfunction in cardiomyocytes caused by DCRT reduction. CONCLUSIONS: Our study revealed that the loss of DCRT contributed to PTBP1-mediated exon skipping of NDUFS2, thereby inducing cardiac mitochondrial dysfunction during dilated cardiomyopathy development, which could be partially treated with coenzyme Q10 supplementation.
Comparison of venovenous extracorporeal membrane oxygenation, prone position and supine mechanical ventilation for severely hypoxemic acute respiratory distress syndrome: a network meta-analysis
Authors: Sachin Sud, Eddy Fan, Neill K. J. Adhikari, Jan O. Friedrich, Niall D. Ferguson, Alain Combes, Claude Guerin, Gordon Guyatt
Journal: Intensive Care Medicine (2024)
Genome-Wide Methylation Analysis Reveals a <i>KCNK3</i> -Prominent Causal Cascade on Hypertension
Authors: Dandan Huang, Wenlong Shang, Mengtong Xu, Qiangyou Wan, Jin Zhang, Xiaofeng Tang, Yujun Shen, Yan Wang, Ying Yu
Journal: Circulation Research (2024)

Despite advances in understanding hypertension's genetic structure, how noncoding genetic variants influence it remains unclear. Studying their interaction with DNA methylation is crucial to deciphering this complex disease's genetic mechanisms.