tbuckley/cabot-search huggingface dataset:
Influence of gender modality on the delivery of breast cancer care from diagnosis to treatment: a systematic review
Authors: Retaj Ramadan, Sophia Tan, A.J. Lowik, Kathryn V. Isaac
Journal: International Journal of Transgender Health (2024)

Background: Breast cancer is a global health burden. Although screening and treatment programs have improved breast cancer survival for Canadians, it is unclear if there is a disparity in cancer burden and care received by transgender and Two-Spirit patients due to the general paucity of research concerning breast cancer care of these individuals. Objective/Aims: A systematic review was conducted to examine the burden of breast cancer in transgender and Two-Spirit populations, identify how gender modality/identity may impact the delivery of breast cancer care, and develop actionable recommendations for the provision of more inclusive, high-quality cancer care. Methods: A comprehensive search of PubMed/MEDLINE (OVID), Embase (OVID), and Web of Science databases was conducted using keywords and based on the PRISMA framework. Two independent reviewers performed selection and data extraction of studies that met inclusion criteria related to breast cancer in adult transgender and/or Two-Spirit patients. Results: Of 7,402 articles screened, 61 studies were included, the majority of which focused on binary-identified trans people, with none addressing Two-Spirit people's experiences of cancer care. Findings determined no clear association between gender affirming hormone therapy and risk of breast cancer in transgender populations. Additionally, the burden of breast cancer could be identified for transgender and/or Two-Spirit patients. Patient-provider and system barriers in the delivery of breast cancer care were identified, including lack of trust and knowledge, discrimination, and insufficient population-wide data collection and research. Conclusion: Significant gaps in literature regarding the experiences, barriers and needs of transgender and/or Two-Spirit patients with breast cancer exist. Developing effective guidelines and clinical practices that encompass all gender identities and expanding the depth and scope of research is crucial toward fostering diverse, inclusive, and equitable healthcare.
Impact of tricuspid regurgitation on right ventricular function and clinical outcomes in pulmonary arterial hypertension: food for thought
Authors: Thenappan Thenappan
Journal: European Respiratory Journal (2024)

Right ventricular (RV) function is the linchpin in the natural history of pulmonary arterial hypertension (PAH) [1]. Patients with PAH feel well, function better and live longer if RV function is preserved [1]. The RV initially adapts to the increased afterload in the pulmonary circulation by hypertrophy and increased contractility, which maintains stroke volume. This is called the homeometric adaptation or the Anrep effect [1]. Eventually when the homeometric adaption is not enough to maintain cardiac output, the RV dilates, which maintains stroke volume by increasing the RV end-diastolic volume based on the Starling principle, which is referred to as the heterometric adaption [1]. Progressive RV dilation can lead to dilatation of the tricuspid valve annulus, malcoaptation of the tricuspid valve leaflets, and ultimately tricuspid regurgitation [2]. Tricuspid regurgitation in PAH: food for thought <https://bit.ly/3ylWgmm> The author would like to acknowledge E.K. Weir from the University of Minnesota for scientific review of this editorial.
Utility of methylated DNA markers for the diagnosis of malignant biliary strictures
Authors: Matthew A. Cooley, Amber R. Schneider, Emily G. Barr Fritcher, Dragana Milosevic, Michael J. Levy, Amber R. Bridgeman, John A. Martin, Bret T. Petersen, Barham K. Abu Dayyeh, Andrew C. Storm, Ryan J. Law, Eric J. Vargas, Vishal Garimella, Tyler Zemla, Sarah M. Jenkins, Jun Yin, Gregory J. Gores, Lewis R. Roberts, Benjamin R. Kipp, Vinay Chandrasekhara
Journal: Hepatology (2024)

Background and Aims: Early identification of malignant biliary strictures (MBSs) is challenging, with up to 20% classified as indeterminants after preliminary testing and tissue sampling with endoscopic retrograde cholangiopancreatography. We aimed to evaluate the use of methylated DNA markers (MDMs) from biliary brushings to enhance MBS detection in a prospective cohort. Approach: Candidate MDMs were evaluated for their utility in MBS diagnosis through a series of discovery and validation phases. DNA was extracted from biliary brushing samples, quantified, bisulfite-converted, and then subjected to methylation-specific droplet digital polymerase chain reaction. Patients were considered to have no malignancy if the sampling was negative and there was no evidence of malignancy after 1 year or definitive negative surgical histopathology. Results: Fourteen candidate MDMs were evaluated in the discovery phase, with top-performing and new markers evaluated in the technical validation phase. The top 4 MDMs were TWIST1, HOXA1, VSTM2B, and CLEC11A, which individually achieved AUC values of 0.82, 0.81, 0.83, and 0.78, respectively, with sensitivities of 59.4%, 53.1%, 62.5%, and 50.0%, respectively, at high specificities for malignancy of 95.2%–95.3% for the final biologic validation phase. When combined as a panel, the AUC was 0.86, achieving 73.4% sensitivity and 92.9% specificity, which outperformed cytology and fluorescence in situ hybridization (FISH). Conclusions: The selected MDMs demonstrated improved performance characteristics for the detection of MBS compared to cytology and FISH. Therefore, MDMs should be considered viable candidates for inclusion in diagnostic testing algorithms.
The Bioinformatic Applications of Hi-C and Linked Reads
Authors: Libo Jiang, Michael A Quail, Jack Fraser-Govi1, Haipeng Wang, Xuequn Shi, Karen Oliver, Esther Mellado Gomez, Fengtang Yang, Zemin Ning
Journal: Genomics Proteomics & Bioinformatics (2024)

Long-range sequencing grants insight into additional genetic information beyond what can be accessed by both short reads and modern long-read technology. Several new sequencing technologies, such as "Hi-C" and "Linked Reads", produce long-range datasets for high-throughput and high-resolution genome analyses, which are rapidly advancing the field of genome assembly, genome scaffolding, and more comprehensive variant identification. In this review, we focused on five major long-range sequencing technologies: high-throughput chromosome conformation capture (Hi-C), 10X Genomics Linked Reads, haplotagging, transposase enzyme linked long-read sequencing (TELL-seq), and single- tube long fragment read (stLFR). We detailed the mechanisms and data products of the five platforms and their important applications, evaluated the quality of sequencing data from different platforms, and discussed the currently available bioinformatics tools. This work will benefit the selection of appropriate long-range technology for specific biological studies.
Entering a New Era in Sleep-Apnea Treatment
Authors: Sanjay R Patel
Journal: New England Journal of Medicine (2024)

Obstructive sleep apnea is one of the most common respiratory disorders worldwide. Persons with obstructive sleep apnea can have loud snoring that is detrimental to social relationships and have breathing problems that result in recurrent nocturnal awakenings, unrefreshing sleep, and excessive daytime sleepiness — effects that together can substantially impair quality of life. Excess weight is the most important risk factor for obstructive sleep apnea; it is responsible for approximately 60% of moderate-to-severe cases of obstructive sleep apnea in the United States.1 Clinical guidelines therefore recommend evidence-based weight-loss strategies as part of the comprehensive management of obstructive sleep apnea.2 Unfortunately, . . .
Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity
Authors: Atul Malhotra, Ronald R Grunstein, Ingo Fietze, Terri E Weaver, Susan Redline, Ali Azarbarzin, Scott A Sands, Richard J Schwab, Julia P Dunn, Sujatro Chakladar, Mathijs C Bunck, Josef Bednarik
Journal: New England Journal of Medicine (2024)

BackgroundObstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment.MethodsWe conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity. Participants who were not receiving treatment with positive airway pressure (PAP) at baseline were enrolled in trial 1, and those who were receiving PAP therapy at baseline were enrolled in trial 2. The participants were assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary end point was the change in the apnea–hypopnea index (AHI, the number of apneas and hypopneas during an hour of sleep) from baseline. Key multiplicity-controlled secondary end points included the percent change in AHI and body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure.ResultsAt baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was −25.3 events per hour (95% confidence interval [CI], −29.3 to −21.2) with tirzepatide and −5.3 events per hour (95% CI, −9.4 to −1.1) with placebo, for an estimated treatment difference of −20.0 events per hour (95% CI, −25.8 to −14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was −29.3 events per hour (95% CI, −33.2 to −25.4) with tirzepatide and −5.5 events per hour (95% CI, −9.9 to −1.2) with placebo, for an estimated treatment difference of −23.8 events per hour (95% CI, −29.6 to −17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary end points were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal in nature and mostly mild to moderate in severity.ConclusionsAmong persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes. (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.)
Natural MOF‐Like Photocatalytic Nanozymes Alleviate Tumor Pressure for Enhanced Nanodrug Penetration
Authors: Anshuo Li, Yifei Li, Yanmin Jia, Yuchu He, Meng Yuan, Zining Hao, Yaqian He, Yihan Fu, Jinhui Zhang, Dawei Gao, Xuwu Zhang, Xinquan Jiang, Wenkang Tu
Journal: Advanced Healthcare Materials (2024)

Abstract In oncological nanomedicine, overcoming the dual‐phase high interstitial pressure in the tumor microenvironment is pivotal for enhancing the penetration and efficacy of nanotherapeutics. The elevated tumor interstitial solid pressure (TISP) is largely attributed to the overaccumulation of collagen in the extracellular matrix, while the increased tumor interstitial fluid pressure (TIFP) stems from the accumulation of fluid due to the aberrant vascular architecture. In this context, metal–organic frameworks (MOFs) with catalytic efficiency have shown potential in degrading tumor interstitial components, thereby reducing interstitial pressure. However, the potential biotoxicity of the organic components of MOFs limits their clinical translation. To circumvent this, a MOF‐like photocatalytic nanozyme, RPC@M, using naturally derived cobalt phytate (CoPA) and resveratrol (Res) is developed. This nanozyme not only facilitates the decomposition of water in the tumor interstitium under photoactivation to reduce TIFP, but also generates an abundance of reactive oxygen species through its peroxidase‐like activity to exert cytotoxic effects on tumor cells. Moreover, Res contributes to the reduction of collagen deposition, thereby lowering TISP. The concurrent diminution of both TISP and TIFP by RPC@M leads to enhanced tumor penetration and potent antitumor activity, presenting an innovative approach in constructing tumor therapeutic nanozymes from natural products.
Bioorthogonal targeted cell membrane vesicles/cell-sheet composites reduce postoperative tumor recurrence and scar formation of melanoma
Authors: Xinrui Yang, Zhanxue Xu, Fan Shu, Jiangwei Xiao, Yuqing Zeng, Xingyu Lu, Fei Yu, Lifang Xi, Fang Cheng, Botao Gao, Hongbo Chen
Journal: Journal of Controlled Release (2024)
Understanding the complex links between social media and health behaviour
Authors: Fabiana Zollo, Andrea Baronchelli, Cornelia Betsch, Marco Delmastro, Walter Quattrociocchi
Journal: BMJ (2024)

Fabiana Zollo and colleagues call for comprehensive, robust research on the influence of social media on health behaviour in order to improve public health responses ### Key messages Over 90% of people connected to the internet are active on social media, with a total of 4.76 billion users worldwide in January 2023.1 The digital revolution has reshaped the news landscape and changed the way users interact with information. Social media's targeted communication rapidly reaches vast audiences, who in turn actively participate in shaping and engaging with content. This marks a departure from the more passive consumption patterns associated with traditional media. Over the past few years, social media have emerged as a primary source of news for many people, despite widespread user concerns about potential misinformation (box 1) and the necessity to discern between reliable and untrustworthy information.4 Data from six continents also indicate a preference among users for content that reflects their reading or viewing history, rather than content selected by journalists, suggesting a shift towards personalised and user driven content curation. In this evolving landscape, celebrities, influencers, and social media personalities are increasingly assuming roles as news sources, especially on platforms such as TikTok, Instagram, and Snapchat. Box 1 ### What is misinformation?RETURN TO TEXT
Characterization of adverse cutaneous effects in the setting of enfortumab vedotin for metastatic urothelial carcinoma: A retrospective review
Authors: Rhea Malik, David H Xiang, Grant J Riew, Stephanie Sanchez-Melendez, Shawn Afvari, Nicole R LeBoeuf, Vinod E Nambudiri
Journal: Journal of the American Academy of Dermatology (2024)
STELLAR-303: A randomized phase 3 study of zanzalintinib (XL092) plus atezolizumab versus regorafenib in previously treated metastatic colorectal cancer.
Authors: Anwaar Saeed, Josep Tabernero, Guan Wang, Xia Ma, Robina Smith, J. Randolph Hecht
Journal: Journal of Clinical Oncology (2024)

TPS3634 Background: Metastatic colorectal cancer (mCRC) has seen increased rates in overall survival (OS) as novel targeted agents have become available. Unfortunately, the median OS is still less than 2 years, and the 5-year survival rate is only about 16%. This underscores an unmet need in this population that necessitates finding therapeutic options to enhance treatment outcomes. As monotherapy, immune checkpoint inhibitors (ICIs) have shown limited efficacy in non–microsatellite instability-high (non–MSI-H) mCRC, which represents a majority of mCRC cases. However, addition of tyrosine kinase inhibitors (TKIs) to ICIs has demonstrated encouraging efficacy in mCRC, particularly in patients without liver metastases (LM). Clinical data suggest synergy whereby TKIs may increase sensitivity to ICIs by promoting an immune-permissive tumor microenvironment. Zanzalintinib is a novel TKI targeting VEGFR, MET, and the TAM kinases (TYRO3, AXL, MER), which are involved in tumor angiogenesis, metastasis, and immunosuppression. In a phase 1 study, zanzalintinib in combination with atezolizumab (an anti–PD-L1 ICI) showed antitumor activity and a manageable safety profile across multiple tumor types, including mCRC. The present study, STELLAR-303, was designed to evaluate the efficacy and safety of zanzalintinib + atezolizumab in patients with non–MSI-H mCRC. Methods: STELLAR-303 (NCT05425940) is a global, randomized, open-label, phase 3 study. Patients must be aged ≥18 years and have non–MSI-H/non-mismatch repair deficient disease, with documented RAS status by tissue-based analysis, measurable disease per RECIST v1.1, and ECOG performance status of 0–1. Patients must have had intolerance to, or radiographic progression during/after, standard-of-care treatments for mCRC. Patients previously treated with regorafenib, trifluridine/tipiracil, or PD-L1/PD-1 ICIs are excluded. Patients with or without active LM at baseline are eligible; those with definitively treated LM (including surgical resection, microwave/radiofrequency ablation, or stereotactic body radiation therapy, but not yttrium-90 or chemoembolization alone) are considered to have non-active LM if treated ≥6 months before enrollment with no evidence of radiologic progression on subsequent imaging. Patients are randomized 1:1 to receive either zanzalintinib + atezolizumab, or regorafenib alone. Planned enrollment is 874 patients, and the number of patients with/without LM will be capped to ensure relevance to the real-world mCRC population. The primary endpoint is OS in patients without LM, while OS in all randomized patients is the key secondary endpoint. A hierarchical testing strategy will be employed for primary and key secondary endpoints. Safety will also be assessed. STELLAR-303 enrollment is ongoing in the US, Europe, and Asia-Pacific region. Clinical trial information: NCT05425940 .
Recompensation in MASLD-related cirrhosis via metabolic bariatric surgery
Authors: Gong Feng, Yu Han, Wah Yang, Scott Shikora, Kamal Mahawar, Tan To Cheung, Giovanni Targher, Christopher D. Byrne, Virginia Hernandez-Gea, Herbert Tilg, Ming-Hua Zheng
Journal: Trends in Endocrinology and Metabolism (2024)
Comparative effectiveness of NALIRIFOX vs. FOLFIRINOX in pancreatic cancer.
Authors: Xiayu Jiao, Afsaneh Barzi
Journal: Journal of Clinical Oncology (2024)

4160 Background: Metastatic pancreatic cancer is associated with limited survival, poor quality of life, and limited treatment options. FOLFIRINOX and gemcitabine/nab-paclitaxel (GNP) are associated with survival gain compared to gemcitabine and NALIRIFOX is associated with survival improvement compared to GNP. NALIRIFOX and FOLFIRINOX are not directly compared to each other. We conducted an analysis of oncologic benefits and costs of NALIRIFOX vs. FOLFIRINOX. Methods: A cost-effectiveness model was developed using partitioned survival analysis with three health states: progression-free, progression, and death. Data on overall survival and progression-free survival were derived from PRODIGE and NAPOLI-3 published data to reconstruct the states in the model. The time horizon of the model was set to 36 months. Costs included treatment costs and adverse event management as well as supportive care cost. We used Veteran Affair’s data for unit cost of each agent. To calculate the cost of treatment we assumed the average body surface area to be 1.79. Five adverse events (AEs) were included in the cost analysis: neutropenia, febrile neutropenia, anemia, diarrhea, and thrombocytopenia. We used the utility of 0.80 during PFS and 0.73 during progression for assessment of Quality Adjusted Life Year (QALY). The benefits and costs of treatment was calculated and used to estimate the incremental cost-effectiveness ratio (ICER) of NALIRIFOX compared with FOLFIRINOX. Results: The calculated PFS for FOLFIRINOX was 6.8 months and for NALIRIFOX was 8.9 months. Compared to FOLFIRINOX, NALIRIFOX was associated with an improvement in life year gain (11.97 months vs. 10.95 months). The monthly acquisition cost for NALIRIFOX was $13,610 and for FOLFIRINOX $5,501. Based on the probabilities of selected AEs, the monthly cost of AE management for NALIRIFOX was $5,589 and for FOLFIRINOX was $ 15,511. QALY for NALIRIFOX was 10.23 and for FOLFIRINOX was 9.59 months. The incremental cost effectiveness ratio for NALIRIFOX vs. FOLFIRINOX was $1,368,937. Conclusions: In this modeling analysis, NALIRIFOX is associated with improvement in PFS and QALY. The analysis highlights the importance of AE management for improving quality of life and cost in the recipients of FOLFIRINOX. The economic value for use of NALIRIFOX is very high and outside of any conventional boundary of acceptable value threshold for treatment.
Long-term cardiovascular, cerebrovascular, and thrombotic complications after SARS-CoV-2-Omicron infection: a retrospective cohort study
Authors: Liang En Wee, Jue Tao Lim, An Ting Tay, Deanette Pang, Calvin J. Chiew, Yew Woon Chia, Shir Lynn Lim, Jonathan Yap, Benjamin Ong, David Chien Boon Lye, Kelvin Bryan Tan
Journal: Clinical Microbiology and Infection (2024)
Corrigendum to ‘Engineered multilayer ovarian tissue that secretes sex steroids and peptide hormones in response to gonadotropins’ [Biomaterials 34/10 (2013) 2412–2420].
Authors: Sivanandane Sittadjody, Justin M. Saul, Sunyoung Joo, James J. Yoo, Anthony Atala, Emmanuel C. Opara
Journal: Biomaterials (2024)
Establishment and Validation of an Extracellular Volume Model Without Blood Sampling in STEMI Patients
Authors: Lei Chen, Zeqing Zhang, Xinjia Du, Jiahua Liu, Zhongxiao Liu, Wensu Chen, Wenliang Che
Journal:  (2024)

Recent studies have shown that extracellular volume (ECV) can also be obtained without blood sampling by the linear relationship between haematocrit (HCT) and blood pool R1 (1/T1). However, whether this relationship holds for patients with myocardial infarction is still unclear. This study established and validated an ECV model without blood sampling in ST-segment elevation myocardial infarction (STEMI) patients.
Transepithelial transport of nanoparticles in oral drug delivery: From the perspective of surface and holistic property modulation
Authors: Yaxian Zheng, Shiqin Luo, Min Xu, Qin He, Jiang Xie, Jiawei Wu, Yuan Huang
Journal: Acta Pharmaceutica Sinica B (2024)

Despite the promising prospects of nanoparticles in oral drug delivery, the process of oral administration involves a complex transportation pathway that includes cellular uptake, intracellular trafficking, and exocytosis by intestinal epithelial cells, which are necessary steps for nanoparticles to enter the bloodstream and exert therapeutic effects. Current researchers have identified several crucial factors that regulate the interaction between nanoparticles and intestinal epithelial cells, including surface properties such as ligand modification, surface charge, hydrophilicity/hydrophobicity, intestinal protein corona formation, as well as holistic properties like particle size, shape, and rigidity. Understanding these properties is essential for enhancing transepithelial transport efficiency and designing effective oral drug delivery systems. Therefore, this review provides a comprehensive overview of the surface and holistic properties that influence the transepithelial transport of nanoparticles, elucidating the underlying principles governing their impact on transepithelial transport. The review also outlines the chosen of parameters to be considered for the subsequent design of oral drug delivery systems.