tbuckley/cabot-search huggingface dataset:
Association of opioid and benzodiazepine coprescribing with adverse events among older adults with cancer
Authors: Devon K Check, Samir Soneji, Harvey Jay Cohen, Andrea Des Marais, Katie F Jones, Charles E Gaber, Jessica S Merlin, Amy O’Regan, Nicole Fergestrom, Lauren E Wilson, Aaron N Winn
Journal: JNCI Journal of the National Cancer Institute (2025)

Abstract Background Many older adults with cancer are coprescribed opioids/benzodiazepines; evidence on harms is lacking. Methods Using SEER-Medicare (2012-2019), we identified patients with breast, colorectal, or lung cancer. Cox proportional hazards models estimated the adjusted hazard ratios (HR) of coprescribing (measured from claims, at the day level) with the immediate risk of overdose, fall/fracture, and all-cause hospitalization. In a secondary analysis, models were stratified by ≥ 90 days of continuous medication supply. Results In our cohort of 107,288 patients, compared to those prescribed neither medication, those prescribed benzodiazepines had an increase in the immediate risk of falls/fractures (HR: 1.17, 95% CI: 1.02-1.34) and all-cause hospitalizations (HR: 1.08, 95% CI: 1.04-1.12). Patients prescribed opioids had an increase in the immediate risk of overdose (HR: 5.62, 95% CI: 4.86, 5.62), falls/fractures (HR: 1.56, 95% CI: 1.41, 1.73), and all-cause hospitalizations (HR: 1.26, 95% CI: 1.23, 1.30). HRs were similar for patients coprescribed opioids/benzodiazepines. For patients without continuous exposure to one or both medications, effects were larger for coprescribed opioids/benzodiazepines vs opioids for overdose (HR: 15.22, 95% CI: 8.79-26.35 vs HR: 6.85, 95% CI: 6.85- 26.35) and all-cause hospitalization (HR: 3.21, 95% CI: 2.60-3.96 vs HR: 1.98, 95% CI: 1.87- 2.10). Conclusions Overall, compared to no prescribing, benzodiazepine prescribing and opioid prescribing were each associated with an increase in the immediate risk of adverse events. Effects were similar for those prescribed opioids and those coprescribed opioids/benzodiazepines. For patients with intermittent vs long-term medication exposure, coprescribing additionally increased the risk of overdose and all-cause hospitalization.
ATLANTIC DIP, Changing the Landscape for Better Maternal and Infant Health: The 2024 Norbert Freinkel Award Lecture
Authors: Fidelma Dunne
Journal: Diabetes Care (2025)

The Norbert Freinkel Award recognizes contribution of research, clinical practice, and advocacy to improving pregnancy outcomes for women with diabetes. This award honors a man of outstanding achievements. Norbert was a forward-thinking investigator, a concise and precise writer, and a gifted clinical practitioner. His philosophy stated that a research question should be framed around an unsolved patient problem, a solution should be sought at several levels and across several disciplines, and the solution should be shared and applied to the problem. The Atlantic Diabetes in Pregnancy (ATLANTIC DIP) network has followed this philosophy. Women now achieve better pregnancy preparation and have lower blood glucose and lower glycated hemoglobin with improved pregnancy outcomes. Screening and follow-up for gestational diabetes mellitus (GDM) is consistent. The trial on early metformin in addition to usual care in the reduction of GDM effects (A Randomized Placebo-Controlled Trial of the Effectiveness of Metformin in Addition to Usual Care in the Reduction of Gestational Diabetes Mellitus Effects [EMERGE]) provides evidence for metformin use in pregnancies complicated by GDM as an alternative to insulin. Learnings and evidence from ATLANTIC DIP have shaped national policy and guidelines and have contributed to global knowledge in this area. We continue to strive for excellence and equity of care and normalization of perinatal outcomes.
Management of Diabetes and Hyperglycemia in the Hospital: A Systematic Review of Clinical Practice Guidelines
Authors: Linnea M. Wilson, Shoshana J. Herzig, Edward R. Marcantonio, Michael A. Steinman, Mara A. Schonberg, Brianna X. Wang, Ella Hileman-Kaplan, Timothy S. Anderson
Journal: Diabetes Care (2025)

BACKGROUND Inpatient hyperglycemia is common among adults, and management varies. PURPOSE To systematically identify guidelines on inpatient hyperglycemia management. DATA SOURCES MEDLINE, Guidelines International Network, and specialty society websites were searched from 1 January 2010 to 14 August 2024. STUDY SELECTION Clinical practice guidelines pertaining to blood glucose management in hospitalized adults were included. DATA EXTRACTION Two authors screened articles and extracted data, and three assessed guideline quality. Recommendations on inpatient monitoring, treatment targets, medications, and care transitions were collected. DATA SYNTHESIS Guidelines from 10 organizations met inclusion criteria, and 5 were assessed to be of high quality per the Appraisal of Guidelines for REsearch &amp; Evaluation II (AGREE II) instrument. All guidelines recommended monitoring blood glucose for patients with diabetes and nine for admission hyperglycemia. Eight guidelines recommended an upper blood glucose target of 180 mg/dL, five with a lower limit of 100 mg/dL and three of 140 mg/dL. Guidelines were in agreement on using capillary blood glucose monitoring, and three guidelines included discussion of continuous monitoring. Hyperglycemia treatment with basal-bolus insulin alone (n = 3) or with correction (n = 5) was most commonly recommended, while sliding scale insulin was advised against (n = 5). Guidance on use of oral diabetes medications was inconsistent. Five guidelines included discussion of transitioning to home medications. Recommendations for hypoglycemia management and diabetes management in older adults were largely limited to outpatient guidance. LIMITATIONS Non-English-language guidelines were excluded. CONCLUSIONS While there is consensus on inpatient blood glucose monitoring and use of basal-bolus insulin, there is disagreement on treatment targets and use of home medications and little guidance on how to transition treatment at discharge.
Enhancing human NK cell antitumor function by knocking out SMAD4 to counteract TGFβ and activin A suppression
Authors: Anna Rea, Sara Santana-Hernández, Javier Villanueva, Marta Sanvicente-García, Mariona Cabo, Jesús Suarez-Olmos, Fabricio Quimis, Mengjuan Qin, Eduard Llorens, Sandra Blasco-Benito, Lamberto Torralba-Raga, Lorena Perez, Bishan Bhattarai, Elisenda Alari-Pahissa, Anna-Maria Georgoudaki, Francesc Balaguer, Manel Juan, Julián Pardo, Toni Celià-Terrassa, Ana Rovira, Nina Möker, Congcong Zhang, Marco Colonna, Jan Spanholtz, Karl-Johan Malmberg, Clara Montagut, Joan Albanell, Marc Güell, Miguel López-Botet, Aura Muntasell
Journal: Nature Immunology (2025)

Transforming growth factor beta (TGFβ) and activin A suppress natural killer (NK) cell function and proliferation, limiting the efficacy of adoptive NK cell therapies. Inspired by the partial resistance to TGFβ of NK cells with SMAD4 haploinsufficiency, we used CRISPR–Cas9 for knockout of SMAD4 in human NK cells. Here we show that SMAD4KO NK cells were resistant to TGFβ and activin A inhibition, retaining their cytotoxicity, cytokine secretion and interleukin-2/interleukin-15-driven proliferation. They showed enhanced tumor penetration and tumor growth control, both as monotherapy and in combination with tumor-targeted therapeutic antibodies. Notably, SMAD4KO NK cells outperformed control NK cells treated with a TGFβ inhibitor, underscoring the benefit of maintaining SMAD4-independent TGFβ signaling. SMAD4KO conferred TGFβ resistance across diverse NK cell platforms, including CD19-CAR NK cells, stem cell-derived NK cells and ADAPT-NK cells. These findings position SMAD4 knockout as a versatile and compelling strategy to enhance NK cell antitumor activity, providing a new avenue for improving NK cell-based cancer immunotherapies. The authors show that knocking out SMAD4, human NK cells resist TGFβ and activin A suppression and demonstrate that SMAD4 knockout enhances the antitumor function of several NK cell products in clinical development.
Genomic introgression and adaptation of southern seabird species facilitate recent polar colonization
Authors: Josefina Jorquera, Lucila Morales, Elize Y X Ng, Daly Noll, Luis R Pertierra, Patricio Pliscoff, Ulises Balza, Thierry Boulinier, Amandine Gamble, Tatiana Kasinsky, Julie C McInnes, Juan Carlos Marín, Silvia Olmastroni, Pierre Pistorius, Richard A Phillips, Jacob González-Solís, Louise Emmerson, Elie Poulin, Rauri C K Bowie, Christopher P Burridge, Juliana A Vianna
Journal: Molecular Biology and Evolution (2025)

Abstract Genomic adaptation and introgression can occur during the speciation process, enabling species to diverge in their frequencies of adaptive alleles or acquire new alleles that may promote adaptation to environmental changes. There is limited information on introgression in organisms from extreme environments and their responses to climate change. To address these questions, we focused on the three southern skua species, selected for their widespread distribution across the Southern Hemisphere and their complex history of speciation and introgression events. Our genomic data reveal that these skuas underwent diversification around the Penultimate Glacial Period, followed by subsequent demographic expansion. We identified a geographic region of introgression among species that followed a directional pattern sourced from the Antarctic continent, South America, and east to west in subantarctic islands, all converging towards the Antarctic Peninsula. The three skua species and admixed individuals exhibited a unique pattern of putative genes under selection, allowing adaptation to extreme conditions. Individuals with a higher proportion of brown skua ancestry showed signs of selection on genes related to reproductive isolation, while admixed individuals with a higher proportion of South Polar Skua ancestry displayed patterns resembling those of the South Polar Skua. Introgression may be a key mechanism of adaptation for many species that may help buffer against the ongoing climate change.
Detection of circulating tumor DNA using a tissue-free epigenomic assay is a highly prognostic biomarker in early-stage triple negative breast cancer
Authors: Foluso O. Ademuyiwa, Cynthia X. Ma, Katherine Weilbaecher, Rama Suresh, Lindsay L. Peterson, Ron Bose, Nusayba Bagegni, Caron E. Rigden, Ashley Frith, Katherine Clifton, Derek Dustin, Mingyang Cai, Liyang Xiong, Sai Chen, Andrew Davis
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Clinical tools to monitor treatment response and metastatic risk could improve early-stage triple-negative breast cancer (TNBC) care. While molecular residual disease (MRD) assays show promise, their use in the neoadjuvant setting requires rapid turnaround times. Tissue-informed approaches may be challenging for patients with limited biopsy samples. The objectives were to determine the surveillance sensitivity for detecting metastatic recurrence and evaluate the ctDNA response to neoadjuvant therapy using a tissue-free epigenomic assay. Patients and Methods: Patients with stage II or III TNBC undergoing neoadjuvant docetaxel and carboplatin chemotherapy on a clinical trial (NCT02124902) followed by surgery with or without adjuvant therapy were included in this study. Blood samples were prospectively collected prior to, during, and after completion of neoadjuvant therapy (NAT), and after surgery at pre-specified surveillance time points. Plasma samples were analyzed by Guardant Reveal. Results: A total of 119 TNBC patients were included in the analysis. ctDNA was detected in the post-surgical setting in 8.9% (7/79) of patients, with an 83% (5/6) patient-level surveillance sensitivity for metastatic recurrence and 99.5% (197/198) sample-level specificity. Post-surgical ctDNA detection was prognostic for shorter recurrence-free interval (RFI; HR 37.7, p&amp;lt;0.0001). ctDNA detection at the post-NAT pre-surgical time point was also associated with shorter RFI in patients with residual disease at surgery (HR 28.2, p&amp;lt;0.0001). Conclusions: In early-stage TNBC patients, a tissue-free, epigenomic assay and demonstrated high specificity and sensitivity for metastatic recurrence. ctDNA detection in the neoadjuvant setting indicated poor prognosis, highlighting its potential role across breast cancer care.
Global profiling of CPL3-mediated alternative splicing reveals regulatory mechanisms of DGK5 in plant immunity and phosphatidic acid homeostasis
Authors: Sung-Il Kim, Xiyu Ma, Liang Kong, Wenbin Guo, Lahong Xu, Libo Shan, Runxuan Zhang, Ping He
Journal: Genome biology (2025)

Abstract Background Alternative splicing of precursor mRNAs serves as a crucial mechanism to enhance gene expression plasticity for organismal adaptation. However, the precise regulation and function of alternative splicing in plant immune gene regulation remain elusive. Results Here, by deploying in-depth transcriptome profiling with deep genome coverage coupled with differential expression, differential alternative splicing, and differential transcript usage analysis, we reveal profound and dynamic changes in alternative splicing following treatment with microbial pattern flg22 peptides in Arabidopsis . Our findings highlight RNA polymerase II C-terminal domain phosphatase-like 3 (CPL3) as a key regulator of alternative splicing, preferentially influencing the splicing patterns of defense genes rather than their expression levels. CPL3 mediates the production of a flg22-induced alternative splicing variant, diacylglycerol kinase 5α (DGK5α), which differs from the canonical DGK5β in its interaction with the upstream kinase BIK1 and subsequent phosphorylation, resulting in reduced flg22-triggered production of phosphatidic acid and reactive oxygen species. Furthermore, our functional analysis suggests that DGK5β, but not DGK5α, contributes to plant resistance against virulent and avirulent bacterial infections. Conclusions These findings underscore the role of CPL3 in modulating alternative splicing dynamics of defense genes and DGK5 isoform-mediated phosphatidic acid homeostasis, shedding light on the intricate mechanisms underlying plant immune gene regulation.
Assessment of Pulmonary Perfusion in a Pediatric Patient with Acute Hypoxic Respiratory Failure Using Electrical Impedance Tomography
Authors: Glasiele C Alcala, Giovanni M Bruno, Marcus Victor, Alex Blanchette, Lorenzo Berra, Ryan W. Carroll
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"Assessment of Pulmonary Perfusion in a Pediatric Patient with Acute Hypoxic Respiratory Failure Using Electrical Impedance Tomography." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Application of Kirchhoff’s Laws to pharmacologic and pharmacokinetic analyses
Authors: Leslie Z Benet, Jasleen K Sodhi, Markus Ville Tiitto, Yue Xiang
Journal: Pharmacological Reviews (2025)

Recently, we introduced a straightforward approach to derive clearance and rate constant equations, without relying on differential equations, utilizing Kirchhoff's Laws, a well known physics methodology used to describe rate-defining processes either in series or parallel. Manuscripts from our laboratory have re-examined published experimental data, demonstrating that the Kirchhoff's Laws methodology can explain data previously considered anomalous, such as the following: (1) all experimental perfused liver clearance data conforming to the equation once thought to represent the unphysiological well stirred model, (2) instances where linear pharmacokinetic systemic bioavailability determinations exceed unity, (3) renal clearance being influenced by drug input processes, (4) statistically significant differences in bioavailability measures between urinary excretion and systemic concentration measurements, and (5) how the long-accepted steady-state clearance approach used in pharmacokinetics for the past half-century leads to unrealistic conclusions about the relationship between liver-to-blood Kpuu and hepatic availability FH. These findings demonstrate the potential for errors in pharmacokinetic evaluations that rely on differential equations. The Kirchhoff's Laws approach is applicable to all pharmacokinetic analyses of quality experimental data, both those that align with present pharmacokinetic theory, and those that do not. Although 3 publications have attempted to rebut our position, they fail to address unexplained experimental data, and we detail here why these analyses are invalid. Our discoveries are ongoing. Additionally, we briefly discuss the application of Kirchoff's Laws to saturable nonlinear kinetics, explaining increased pharmacodynamic response for extended vs immediate release dosage forms, as well as the advantages of successfully formulating high hepatic extraction drugs. SIGNIFICANCE STATEMENT: The Kirchhoff's Laws approach to deriving clearance equations for linear systems in parallel or in series, independent of differential equations, successfully describes anomalous published pharmacokinetic data that have previously been unexplained. We review 9 experimental outcomes in humans that are newly explained using the Kirchhoff's Laws approach, including the extension to deriving nonlinear saturable clearance relationships.
Insights from ADPedKD, ERKReg and RaDaR registries provide a multi-national perspective on the presentation of childhood autosomal dominant polycystic kidney disease in high- and middle-income countries.
Authors: Charlotte Gimpel, Steffen Fieuws, Jonas Hofstetter, David Pitcher, Lotte Vanmeerbeek, Stefanie Haeberle, Angélique Dachy, Laura Massella, Tomas Seeman, Bruno Ranchin, Lise Allard, Justine Bacchetta, Umut S Bayrakci, Francesca Becherucci, Victor Perez-Beltran, Martine Besouw, Hanna Bialkevich, Olivia Boyer, Nur Canpolat, Dominique Chauveau, Neslihan Çiçek, Peter J Conlon, Olivier Devuyst, Claire Dossier, Marc Fila, Hana Flögelová, Astrid Godron-Dubrasquet, Ibrahim Gokce, Elsa Gonzalez Nguyen-Tang, Juan David González-Rodríguez, Anne Guffens, Giuseppe Grandaliano, Laurence Heidet, Augustina Jankauskiene, Tanja Kersnik Levart, Bertrand Knebelmann, Jens Christian König, Claudio La Scola, Valentina Fanny Leone, Valérie Leroy, Mieczyslaw Litwin, Laura Lucchetti, Adrian C Lungu, Pierluigi Marzuillo, Antonio Mastrangelo, Monika Miklaszewska, Giovanni Montini, François Nobili, Lukasz Obrycki, Svetlana Papizh, Aleksandra Paripović, Dušan Paripović, Licia Peruzzi, Ann Raes, Seha Saygili, Brankica Spasojević, Thomas Simon, Maria Szczepańska, Francesco Trepiccione, Nataša Marčun Varda, Rik Westland, Selcuk Yüksel, Iga Zaluska- Lesniewska, Julie Tenebaum, Reem Mustafa, Andrew J Mallett, Lisa M Guay-Woodford, Daniel P Gale, Detlef Böckenhauer, Max C Liebau, Franz Schaefer, Djalila Mekahli
Journal: Kidney International (2025)
Consensus recommendations to inform an update of the NCAA Mental Health Best Practices
Authors: Emily Kroshus-Havril, Carey Wheelhouse, James Houle, Jessica Bartley, Darcy Gruttadaro, Casey Pick, Ashwin L Rao, Alicia Fine, Jean Merrill, Deena Casiero, Brian Hainline
Journal: British Journal of Sports Medicine (2025)

We sought to generate consensus-based recommendations to inform updates to the National Collegiate Athletic Association (NCAA) Mental Health Best Practices. A two-phase modified Delphi consensus process was used to identify foundational premises and actionable recommendations for NCAA member schools. Participants were members of the NCAA's Mental Health Advisory Group (n=31), including student-athletes, representatives from leading national organisations involved in college student or athlete mental health and higher education, and licensed mental health providers who work with student-athletes. The consensus process produced 11 foundational premises and 36 recommendation statements that were considered useful and feasible for NCAA member schools. Foundational premises addressed multiple levels of risk factors that may adversely impact student-athlete mental health. Recommendations for member schools were broadly grouped into (1) creating healthy environments that support mental health and promote well-being; (2) developing procedures for identifying student-athletes with mental health symptoms and disorders, including the use of validated mental health screening tools; (3) establishing mental health action plans that outline referral pathways of student-athletes to licensed mental health providers; and (4) ensuring licensure of providers who oversee and manage student-athlete mental healthcare. These premises and recommendations provide guidance for understanding and supporting student-athlete mental health needs.
Risk of Herpes Zoster and Postherpetic Neuralgia in Patients with Psoriasis Treated with Biologics: A nationwide study using target trial emulation framework
Authors: Chaw-Ning Lee, Miyuki Hsing-Chun Hsieh, Che-Yu Chen, Chao-Chun Yang, Tzu-Chi Liao, Edward Chia-Cheng Lai
Journal: British Journal of Dermatology (2025)

Patients with psoriasis have a higher baseline risk of herpes zoster (HZ) than the general population. This has raised concerns that TNF-α inhibitor use may be associated with an increased risk of HZ. However, the risk profiles for newer biologics, including IL-17 inhibitor (IL-17i), IL-12/23 inhibitor (IL-12/23i) and IL-23 inhibitor (IL-23i), remain uncertain. To compare HZ and postherpetic neuralgia (PHN) risks among different biologics, including ustekinumab, secukinumab, ixekizumab, guselkumab, etanercept and adalimumab, with traditional systemic treatments (TST). We conducted a retrospective cohort study by analyzing data from Taiwan's National Health Insurance Research Database (NHIRD 2011-2021). We included patients with psoriasis or psoriatic arthritis aged 20 years and above who had been treated with biologics or TST for at least six months. We classified patients by individual biologics or TST and followed them up for 2.5 years from drug initiation until the occurrence of outcome events or death. The primary outcome was the diagnosis of HZ. We used inverse probability of treatment weighting (IPTW) to adjust for covariates, including patient age, sex, comorbidities and co-medications. We used Cox proportional hazards models to evaluate the risk of HZ among different biologics. In total, we identified 815, 1870, 1095, 2327, 261, 303 and 98 patients with psoriasis receiving etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, brodalumab and guselkumab, respectively. Compared to patients receiving TST, for those receiving ustekinumab and guselkumab the risk of HZ trended lower (weighted HR: 0.82, 95% CI: 0.61-1.11; 0.48, 0.22-1.02), while for those receiving adalimumab it was statistically significantly higher (weighted HR: 1.63, 95% CI: 1.22-2.18). Additionally, ustekinumab was associated with a reduced risk of PHN (HR: 0.22, 95% CI: 0.08-0.64). There were no significant differences in the risk of HZ between TST and either etanercept, secukinumab, ixekizumab or brodalumab. The findings suggested ustekinumab and guselkumab may be associated with a reduced risk of HZ and PHN, compared to TST. This study could have significance for real-world practice.