tbuckley/cabot-search huggingface dataset:
Smoking and Complications After Cancer Surgery
Authors: Clement Wong, Siti Khadijah Binti Mohamad Asfia, Paul S. Myles, John Cunningham, Elizabeth M. Greenhalgh, Emma Dean, Sally Doncovio, Lisa Briggs, Nicholas Graves, Nikki McCaffrey
Journal: JAMA Network Open (2025)

Surgical cancer treatments may be delayed for patients who smoke over concerns for increased risk of complications. Quantifying risks for people who had recently smoked can inform any trade-offs of delaying surgery. To investigate the association between smoking status or smoking cessation time and complications after cancer surgery. Embase, CINAHL, Medline COMPLETE, and Cochrane Library were systematically searched for studies published from January 1, 2000, to August 10, 2023. Observational and interventional studies comparing the incidence of complications in patients undergoing cancer surgery who do and do not smoke. Two reviewers screened results and extracted data according to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Data were pooled with a random-effects model and adjusted analysis was performed. The odds ratio (OR) of postoperative complications (of any type) for people who smoke currently vs in the past (4-week preoperative cutoff), currently smoked vs never smoked, and smoked within shorter (2-week cutoff) and longer (1-year cutoff) time frames. The meta-analyses across 24 studies with a pooled sample of 39 499 participants indicated that smoking within 4 weeks preoperatively was associated with higher odds of postoperative complications compared with ceasing smoking for at least 4 weeks (OR, 1.31 [95% CI, 1.10-1.55]; n = 14 547 [17 studies]) and having never smoked (OR, 2.83 [95% CI, 2.06-3.88]; n = 9726 [14 studies]). Within the shorter term, there was no statistically significant difference in postoperative complications between people who had smoked within 2 weeks preoperatively and those who had stopped between 2 weeks and 3 months in postoperative complications (OR, 1.19 [95% CI, 0.89-1.59]; n = 5341 [10 studies]), although the odds of complications among people who smoked within a year of surgery were higher compared with those who had quit smoking for at least 1 year (OR, 1.13 [95% CI, 1.00-1.29]; N = 31 238 [13 studies]). The results from adjusted analyses were consistent with the key findings. In this systematic review and meta-analysis of smoking cessation and complications after cancer surgery, people with cancer who had stopped smoking for at least 4 weeks before surgery had fewer postoperative complications than those smoking closer to surgery. High quality, intervention-based evidence is needed to identify the optimal cessation period and inform clinicians on the trade-offs of delaying cancer surgery.
Strategies to Assess Risk for Hereditary Cancer in Primary Care Clinics
Authors: Elizabeth M. Swisher, Heather M. Harris, Sarah Knerr, Tesla N. Theoryn, Barbara M. Norquist, Jeannine Brant, Brian H. Shirts, Faith Beers, DaLaina Cameron, Emerson J. Dusic, Laurie A. Riemann, Beth Devine, Michael L. Raff, Rabindra Kadel, Howard J. Cabral, Catharine Wang
Journal: JAMA Network Open (2025)

Best practices for improving access to assessment of hereditary cancer risk in primary care are lacking. To compare 2 population-based engagement strategies for identifying primary care patients with a family or personal history of cancer and offering eligible individuals genetic testing for cancer susceptibility. The EDGE (Early Detection of Genetic Risk) clinical trial cluster-randomized 12 clinics from 2 health care systems in Montana, Wyoming, and Washington state to 1 of 2 engagement approaches for assessment of hereditary cancer risk in primary care. The study population included 95 623 English-speaking patients at least 25 years old with a primary care visit during the recruitment window between April 1, 2021, and March 31, 2022. The intervention comprised 2 risk assessment engagement approaches: (1) point of care (POC), conducted by staff immediately preceding clinical appointments, and (2) direct patient engagement (DPE), where letter and email outreach facilitated at-home completion. Patients who completed risk assessment and met prespecified criteria were offered genetic testing via a home-delivered saliva testing kit at no cost. Primary outcomes were the proportion of patients with a visit who (1) completed the risk assessment and (2) completed genetic testing. Logistic regression models were used to compare the POC and DPE approaches, allowing for overdispersion and including clinic as a design factor. An intention-to-treat analysis was used to evaluate primary outcomes. Over a 12-month window, 95 623 patients had a primary care visit across the 12 clinics. Those who completed the risk assessment (n = 13 705) were predominately female (64.7%) and aged between 65 and 84 years (39.6%). The POC approach resulted in a higher proportion of patients completing risk assessment than the DPE approach (19.1% vs 8.7%; adjusted odds ratio [AOR], 2.68; 95% CI, 1.72-4.17; P < .001) but a similar proportion completing testing (1.5% vs 1.6%; AOR, 0.96; 95% CI, 0.64-1.46; P = .86). Among those eligible for testing, POC test completion was approximately half of that for the DPE approach (24.7% vs 44.7%; AOR, 0.49; 95% CI, 0.37-0.64; P < .001). The proportion of tested patients identified with an actionable pathogenic variant was significantly lower for the POC approach than the DPE approach (3.8% vs 6.6%; AOR, 0.61; 95% CI, 0.44-0.85; P = .003). In this cluster randomized clinical trial of risk assessment delivery, POC engagement resulted in a higher rate of assessment of hereditary cancer risk than the DPE approach but a similar rate of genetic testing completion. Using a combination of engagement strategies may be the optimal approach for greater reach and impact. ClinicalTrials.gov Identifier: NCT04746794.
Direct Exposure to Mass Shootings Among US Adults
Authors: David C. Pyrooz, James A. Densley, Jillian K. Peterson
Journal: JAMA Network Open (2025)

Mass shootings, defined as incidents where 4 or more people are shot with a firearm, have become a significant public health concern in the US. To estimate the prevalence of direct exposure to mass shootings among US adults and identify the sociodemographic groups most affected. A survey was administered in January 2024 to a sample of 10 000 respondents (18 years or older) designed to be representative of US adults using a multistage matched sampling design. In addition to exposure to mass shootings, the survey also collected sociodemographic information, including age, gender, self-reported race and ethnicity, and socioeconomic status. Survey respondents were asked about their lifetime presence at the scene of a mass shooting, any physical injuries sustained (including being shot or trampled or experiencing a related physical injury), and the features of such incidents. Multivariable logistic regression was used to generate adjusted odds ratios (AORs) of the associations between sociodemographic measures and being present on the scene of and injured in a mass shooting. All analyses undertaken to generate population and relational inferences were weighted to achieve representativeness of US adults. Of the 10 000 respondents included in the analysis, 51.34% (95% CI, 50.27%-52.40%) were female. In terms of race and ethnicity, 3.04% (95% CI, 2.71%-3.38%) were Asian, 12.46% (95% CI, 11.81%-13.12%) were Black, 16.04% (95% CI, 15.10%-16.98%) were Hispanic, 62.78% (95% CI, 61.73%-63.84%) were White, and 5.67% (95% CI, 5.23%-6.11%) were other race or ethnicity. The findings indicated that 6.95% (95% CI, 6.39%-7.50%) of respondents were present at the scene of a mass shooting, and 2.18% (95% CI, 1.85%-2.50%) sustained physical injuries, such as being shot or trampled, during such incidents. A total of 54.89% of mass shootings to which respondents were exposed occurred in 2015 or more recently, and 76.15% took place in respondents' local communities. Mass shootings were most likely to occur in neighborhoods. Younger individuals (eg, AOR for Baby Boomer and Silent generations vs Generation Z, 0.12; 95% CI, 0.09-0.18) and males (AOR, 1.55; 95% CI, 1.29-1.85) were more likely to report exposure compared with those from older generations or female individuals, respectively. Black respondents reported higher rates of being present at mass shootings (AOR, 1.87; 95% CI, 1.49-2.34), while Asian respondents reported lower rates (AOR, 0.36; 95% CI, 0.19-0.66), compared with White respondents, but there were no racial and ethnic differences in injuries sustained. The findings from this survey study of US adults underscore the extensive and often overlooked regular exposure to mass shootings in this country. The demographic disparities in exposure highlight the need for targeted interventions and support for the most affected groups, particularly younger generations and males. Understanding these patterns is essential for addressing the broader impacts of gun violence on public health and community well-being.
COVID-19 Outcomes Among Adults Receiving Electronic Nudges to Increase Influenza Vaccination
Authors: Niklas Dyrby Johansen, Ankeet S. Bhatt, Brian L. Claggett, Erica L. Dueger, Scott D. Solomon, Muthiah Vaduganathan, Tor Biering-Sørensen
Journal: JAMA Network Open (2025)

This secondary analysis of a randomized clinical trial investigates whether electronic nudging letters to increase influenza vaccination have an effect on COVID-19 vaccination, infection, and hospitalization.
Triclosan-Containing Sutures for the Prevention of Surgical Site Infection
Authors: Hasti Jalalzadeh, Allard S. Timmer, Dennis R. Buis, Yasmine E. M. Dreissen, Jon H. M. Goosen, Haitske Graveland, Mitchel Griekspoor, Frank F. A. IJpma, Maarten J. van der Laan, Roald R. Schaad, Patrique Segers, Wil C. van der Zwet, Stijn W. de Jonge, Niels Wolfhagen, Marja A. Boermeester
Journal: JAMA Network Open (2025)

International guidelines recommend the use of triclosan-containing sutures for the prevention of surgical site infections. However, controversy still remains about triclosan-containing suture use in clinical practice since several new randomized clinical trials (RCTs) have shown contradicting results. To update a previous systematic review and meta-analysis of the association of triclosan-containing sutures with surgical site infections and explore the potential added value of new RCTs. PubMed, Embase, and Cochrane CENTRAL databases were searched from January 1, 2015, to March 14, 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. Published RCTs comparing triclosan-containing sutures with similar sutures without triclosan for the prevention of surgical site infections in any type of surgery were included. Two authors (H.J. and A.S.T.) independently extracted and pooled data in a random-effects (Mantel-Haenszel) model. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach, and trial sequential analysis was used to estimate whether further studies would reveal different outcomes. The primary outcome was the incidence of surgical site infections, expressed as relative risk (RRs) and corresponding 95% CIs. Secondary outcomes were the incidence of surgical site infections according to depth (superficial incisional, deep incisional, and organ/space) and adverse events related to triclosan-containing sutures. The systematic review yielded 15 additional RCTs compared with a previous published review in 2017. A meta-analysis of 31 studies including 17 968 participants (62% male) undergoing various types of surgery was performed. Use of triclosan-containing sutures was associated with fewer surgical site infections compared with sutures without triclosan (RR, 0.75; 95% CI, 0.65-0.86). The certainty of evidence was moderate after downgrading for heterogeneity (τ2 = 0.04; I2 = 43%). In the trial sequential analysis of all trials and a sensitivity analysis excluding studies with a high risk of bias, the cumulative z curve crossed the trial sequential monitoring boundary for benefit, confirming the robustness of the summary effect estimate. This updated meta-analysis found moderate-certainty evidence that wound closure with triclosan-containing sutures was associated with a lower risk of surgical site infections. The trial sequential analysis suggests that future trials that would change these findings are improbable.
Enhancing PD-1 blockade in NSCLC: Reprogramming tumor immune microenvironment with albumin-bound statins targeting lipid rafts and mitochondrial respiration
Authors: Na Chen, Zhanfeng Li, Heyuan Liu, Aimin Jiang, Liqiang Zhang, Siqi Yan, Wangxiao He, Jingyue Yang, Tianya Liu
Journal: Bioactive Materials (2025)
Accelerating adoption of new approach methodologies in regulatory decision making: an industry perspective
Authors: Andrew S. Robertson, Nahid Latif, Imein Bousnina, Donna Boyce, Kevin Carl, Sean P. Curtis, Jennifer Dudinak, Carlos O. Garner, Michael Garvin, Sabine Luik, Koen Nauwelaerts, Eddie Reilly, Michelle Rohrer, Katrin Rupalla, Jacintha Shenton, Jerry Stewart, Mark Taisey, Axel Vicart, Raymond C. Votzmeyer, Matthew P. Wagoner, Max Wegner, Kathy Williams
Journal: Nature Reviews Drug Discovery (2025)
Disruption of the sorcin‒PAX5 protein‒protein interaction induces ferroptosis by promoting the FBXL12-mediated ubiquitination of ALDH1A1 in pancreatic cancer
Authors: Yahui Ding, Yongping Bai, Tianyang Chen, Sisi Chen, Wanjing Feng, Shuoqian Ma, Quan Zhang
Journal: Journal of Hematology & Oncology (2025)
Survival trends in patients with chronic thromboembolic pulmonary hypertension: An observational study
Authors: Takatoyo Kiko, Ryotaro Asano, Yusuke Yoshikawa, Hiroyuki Endo, Shinya Fujisaki, Ryo Takano, Mitsumasa Akao, Naruhiro Nishi, Hiroya Hayashi, Soshiro Ogata, Akiyuki Kotoku, Hiroki Horinouchi, Yosuke Inoue, Jin Ueda, Yoshimasa Seike, Akihiro Tsuji, Tetsuya Fukuda, Kunihiro Nishimura, Hitoshi Matsuda, Takeshi Ogo
Journal: European Respiratory Journal (2025)

Treatment options for patients with chronic thromboembolic hypertension (CTEPH) have increased over the past decade. However, it is unknown whether the outcomes of patients with CTEPH have changed as well. This retrospective study analysed the data of 834 patients with CTEPH, categorised into early (April 1980-December 1999), middle (January 2000-September 2010), and current (October 2010-December 2023) eras. The primary endpoint was all-cause mortality. Multivariable Cox proportional hazards models were used to assess changes in all-cause mortality after adjusting for confounding variables. Ninety-five, 210, and 529 patients were from the early, middle, and current eras, respectively. The proportion of patients who did not receive CTEPH therapy decreased from 65% in the early era to 36% and 3% in the middle and current eras, respectively. Meanwhile, the adoption of multimodal treatment increased from 0% to 58% over time. The Kaplan-Meier analysis revealed significant improvements in overall survival (log-rank p<0.001). The 5-year survival rates improved from 68% in the early era to 85% and 93% in the middle and current eras, respectively. The adjusted hazard ratios for mortality were 0.291 (95% confidence interval [CI]: 0.154-0.550; p<0.001) for the early versus middle era, 0.447 (95% CI: 0.249-0.804; p=0.007) for the middle versus current era, and 0.130 (95% CI: 0.067-0.254; p<0.001) for the early versus current era. The long-term prognosis of patients with CTEPH has significantly improved in recent decades.
DAGIP: alleviating cell-free DNA sequencing biases with optimal transport
Authors: Antoine Passemiers, Stefania Tuveri, Tatjana Jatsenko, Adriaan Vanderstichele, Pieter Busschaert, An Coosemans, Dirk Timmerman, Sabine Tejpar, Peter Vandenberghe, Diether Lambrechts, Daniele Raimondi, Joris Robert Vermeesch, Yves Moreau
Journal: Genome biology (2025)

Cell-free DNA (cfDNA) is a rich source of biomarkers for various pathophysiological conditions. Preanalytical variables, such as the library preparation protocol or sequencing platform, are major confounders of cfDNA analysis. We present DAGIP, a novel data correction method that builds on optimal transport theory and deep learning, which explicitly corrects for the effect of such preanalytical variables and can infer technical biases. Our method improves cancer detection and copy number alteration analysis by alleviating the sources of variation that are not of biological origin. It also enhances fragmentomic analysis of cfDNA. DAGIP allows the integration of cohorts from different studies.
Regulation of LEAP2 by insulin and glucagon in mice and humans
Authors: Valdemar Brimnes Ingemann Johansen, Anna Katrina Jógvansdóttir Gradel, Stephanie Kjærulff Holm, Joyceline Cuenco, Christoffer Merrild, Natalia Petersen, Damien Demozay, Bharath Kumar Mani, Malte Palm Suppli, Magnus F.G. Grøndahl, Asger Bach Lund, Filip Krag Knop, Cesar A. Prada-Medina, Wouter Frederik Johan Hogendorf, Jens Lykkesfeldt, Myrte Merkestein, Kei Sakamoto, Birgitte Holst, Christoffer Clemmensen
Journal: Cell Reports Medicine (2025)

Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous antagonist and inverse agonist of the ghrelin receptor, countering ghrelin's effects on cell signaling and feeding. However, despite an emerging interest in LEAP2's physiology and pharmacology, its endocrine regulation remains unclear. Here, we report that plasma LEAP2 levels decrease significantly upon glucagon infusions during somatostatin clamps in humans. This effect is preserved in patients with obesity and type 2 diabetes while diminished following a hypercaloric diet and a sedentary lifestyle for 2 weeks. Additionally, insulin receptor antagonism offsets the upregulation of LEAP2 during the postprandial state in mice. Finally, insulin and glucagon receptor-expressing hepatocytes are the primary source of hepatic LEAP2 expression, coinciding with a putative enhancer-like signature bound by insulin- and glucagon-regulated transcription factors at the LEAP2 locus. Collectively, our findings implicate insulin and glucagon in regulating LEAP2 and warrant further investigations into the exact mechanisms orchestrating this endocrine axis.
Contract to kill: GNAS mutation
Authors: Pratima Raut, Poompozhil Mathivanan, Surinder K. Batra, Moorthy P. Ponnusamy
Journal: Molecular Cancer (2025)

The mutation in Gsα-coding GNAS exons, popular as gsp oncogene, is the most frequent mutation across all heterotrimeric G proteins involved in oncogenesis. GNAS R201, the most frequently mutated, followed by Q227, are found predominantly across various neoplasms and cancers such as IPMN, pituitary, thyroid, appendiceal, colorectal, etc. This review emphasizes the pivotal significance of the gsp oncogene and its ramifications underpinning the sustained addiction to GNAS mutation. Recent studies delineating the mechanistic intricacies that provide solid evidence of the profound impact of oncogenic GNAS on tumor formation, progression, and maintenance are highlighted. We have leveraged the discoveries of Gsα as an ideal neoantigen candidate for vaccine therapy, allele-specific inhibitors, and cyclic peptide-based small molecular inhibitors for G proteins and explored the therapeutic potential to target oncogenic GNAS directly. Alternative therapeutic modalities and patient-centric studies to mitigate the impact of GNAS mutations are also discussed. The exposition of novel studies and strategies designed to address the potential challenges inherent in these approaches of targeting the activating mutations of GNAS, along with probable avenues for further investigation, are highlighted. This review aims to reverberate the current understanding of the oncogenic potential of GNAS, the genomic and biological landscape of GNAS-driven neoplasms and cancers, and potential therapeutic strategies against them.
Hot and Cold Fibrosis: The Role of Serum Biomarkers to assess the Immune Mechanisms and ECM-Cell Interactions in Human Fibrosis
Authors: A Zawadzki, D J Leeming, A J Sanyal, Q M Anstee, J M Schattenberg, S L Friedman, S D Schuppan, M A Karsdal
Journal: Journal of Hepatology (2025)

Fibrosis is a pathological condition characterized by excessive accumulation of extracellular matrix (ECM) components, particularly collagens, leading to tissue scarring and organ dysfunction. In fibrosis, an imbalance between collagen synthesis (fibrogenesis) and degradation (fibrolysis) results in the deposition of fibrillar collagens disrupting the structural integrity of the ECM and, consequently, the tissue architecture. Fibrosis is associated with a wide range of chronic diseases, including liver cirrhosis, kidney fibrosis, pulmonary fibrosis, and autoimmune diseases. Recently, the concept of "hot" and "cold" fibrosis has emerged, referring to the immune status within fibrotic tissues and the nature of fibrogenic signaling. Hot fibrosis is characterized by active immune cell infiltration and inflammation, while cold fibrosis is associated with auto- and paracrine myofibroblast activation, immune cell exclusion and quiescence. This article aims to explore the relationship between hot and cold fibrosis, the role of various types of collagens and their biologically active fragments in modulating the immune system, and how serological ECM biomarkers can help the understanding of the disease-relevant interactions between immune and mesenchymal cells in fibrotic tissues. Additionally, we draw lessons from immuno-oncology research in solid tumors to shed light on potential strategies for fibrosis treatment and highlight the advantage of having a "hot fibrotic environment" to treat fibrosis by enhancing collagen degradation through modulation of the immune system.
Ultra-sensitive detection of transposon insertions across multiple families by transposable element display sequencing
Authors: Pol Vendrell-Mir, Basile Leduque, Leandro Quadrana
Journal: Genome biology (2025)

Mobilization of transposable elements (TEs) can generate large effect mutations. However, due to the difficulty of detecting new TE insertions in genomes and the typically rare occurrence of transposition, the actual rate, distribution, and population dynamics of new insertions remain largely unexplored. We present a TE display sequencing approach that leverages target amplification of TE extremities to detect non-reference TE insertions with high specificity and sensitivity, enabling the detection of insertions at frequencies as low as 1 in 250,000 within a DNA sample. Moreover, this method allows the simultaneous detection of insertions for distinct TE families, including both retrotransposons and DNA transposons, enhancing its versatility and cost-effectiveness for investigating complex "mobilomes." When combined with nanopore sequencing, this approach enables the identification of insertions using long-read information and achieves a turnaround time from DNA extraction to insertion identification of less than 24 h, significantly reducing the time-to-answer. By analyzing a population of Arabidopsis thaliana plants undergoing a transposition burst, we demonstrate the power of the multiplex TE display sequencing to analyze "evolve and resequence" experiments. Notably, we find that 3–4% of de novo TE insertions exhibit recurrent allele frequency changes indicative of either positive or negative selection. TE display sequencing is an ultra-sensitive, specific, simple, and cost-effective approach for investigating the rate and landscape of new TE insertions across multiple families in large-scale population experiments. We provide a step-by-step experimental protocol and ready-to-use bioinformatic pipelines to facilitate its straightforward implementation.
Mesenchymal stromal/stem cell spheroid-derived extracellular vesicles advance the therapeutic efficacy of 3D-printed vascularized artificial liver lobules in liver failure treatment
Authors: Jiabin Zhang, Xiaodie Chen, Yurong Chai, Yuanyuan Jin, Fenfang Li, Chenya Zhuo, Yanteng Xu, Haixia Wang, Enguo Ju, Yeh-Hsing Lao, Xi Xie, Mingqiang Li, Yu Tao
Journal: Bioactive Materials (2025)