tbuckley/cabot-search huggingface dataset:
The Purinoreceptor P2X7 in Extracellular ATP-Mediated Inflammation through the Spectrum of Kidney Diseases and Kidney Transplantation
Authors: Juan Miguel Téllez Garcia, Thei Steenvoorden, Frederike Bemelman, Marc Hilhorst, Alessandra Tammaro, Liffert Vogt
Journal: Journal of the American Society of Nephrology (2025)

Abstract Extracellular purines play a critical role in maintaining a balanced inflammatory response, but may also trigger disproportionate inflammation in various kidney pathologies. Extracellular ATP is the most well-characterized inflammatory purine, that serves as a potent extracellular DAMP (i.e., danger-associated molecular pattern). It signals through the P2 purinoreceptors, during both acute and chronic kidney damage. The purinoreceptor P2X7 (P2X7R) has been extensively studied in kidney disease due to its potent ability to enhance inflammation by activating the NLRP3 inflammasome in both immune and parenchymal tubular cells and potential role in immunometabolic reprogramming. We will explore how, following a primary insult to the kidney, disturbance of purinergic balance characterized by extracellular ATP-mediated P2X7R activation exacerbates acute kidney injury. Secondly, we will describe how persistent purinergic disbalance promotes a P2X7R-mediated protracted inflammatory reaction leading to the progression of chronic kidney disease of different etiologies. Lastly, we will also highlight the relevant and emerging role of P2X7R signaling in both antigen presenting cells and adaptive immune cells to modulate cellular and humoral immune responses in kidney transplantation and hypertension. This review underscores that ATP-P2X7R axis is a key driver of pathological purinergic signaling, representing a largely unexplored but highly promising clinical target against a wide spectrum of kidney diseases.
HSR25-169: Sociodemographic Disparities in Survival Outcomes Among Adolescent and Young Adult Patients With Lung Cancer: Insights From a SEER Database Analysis
Authors: Olanipekun Lanny Ntukidem, Oboseh John Ogedegbe, Ayobami Gbenga Olafimihan, Sakshi Bai, Inimfon Jackson
Journal: Journal of the National Comprehensive Cancer Network (2025)

"HSR25-169: Sociodemographic Disparities in Survival Outcomes Among Adolescent and Young Adult Patients With Lung Cancer: Insights From a SEER Database Analysis" published on 28 Mar 2025 by National Comprehensive Cancer Network.
Immunogenomic cancer evolution: A framework to understand cancer immunosuppression
Authors: Shogo Kumagai, Yusaku Momoi, Hiroyoshi Nishikawa
Journal: Science Immunology (2025)

The process of tumor development involves tumor cells eluding detection and suppression of immune responses, which can cause decreased tumor cell antigenicity, expression of immunosuppressive molecules, and immunosuppressive cell recruitment to the tumor microenvironment (TME). Immunologically and genomically integrated analysis (immunogenomic analysis) of patient specimens has revealed that oncogenic aberrant signaling is involved in both carcinogenesis and immune evasion. In noninflamed cancers such as epidermal growth factor receptor ( EGFR )–mutated lung cancers, genetic abnormalities in cancer cells contribute to the formation of an immunosuppressive TME by recruiting immunosuppressive cells, which cannot be fully explained by the cancer immunoediting hypothesis. This review summarizes the latest findings regarding the links between cancer genetic abnormalities and immunosuppression causing clinical resistance to immunotherapy. We propose the concepts of immunogenomic cancer evolution, in which cancer cell genomic evolution shapes the immunosuppressive TME, and immunogenomic precision medicine, in which cancer immunotherapy can be combined with molecularly targeted reagents that modulate the immunosuppressive TME.
Asymptomatic Hemorrhagic Events and Functional Outcomes in Acute Stroke
Authors: Rundong Chen, Weilong Hua, Yilei Zhang, Yongxin Zhang, Hongjian Zhang, Yongwei Zhang, Jianmin Liu, Pengfei Yang, Xiaoxi Zhang, Lei Zhang
Journal: JAMA Network Open (2025)

Importance Asymptomatic hemorrhagic infarction (HI) and subarachnoid hemorrhage (SAH) after endovascular treatment (EVT) for acute ischemic stroke are commonly considered low risk, but their long-term impact on functional outcomes is unclear. Objective To determine whether asymptomatic HI and SAH are associated with worse 90-day functional recovery in patients with acute ischemic stroke treated with EVT. Design, Setting, and Participants This is a secondary analysis of the DIRECT-MT randomized clinical trial, which compared intravenous thrombolysis prior to EVT with EVT alone. The multicenter study was conducted at tertiary hospitals in China between 2016 and 2019 with 90-day follow-up. Trial patients with asymptomatic HI, SAH, or no hemorrhage were included in the present analysis, which was performed in December 2024. Exposure Asymptomatic HI and SAH detected on follow-up imaging. Main Outcomes and Measures The primary outcome was the score on the modified Rankin scale (mRS) assessed at 90 days. Secondary analyses categorized mRS scores into thresholds of 0 to 1, 0 to 2, and 0 to 3, representing excellent, good, and favorable recovery, respectively. Results A total of 490 patients were included (median [IQR] age, 70 [60-76] years; 210 [42.9%] female), with 133 (27.1%) in the asymptomatic HI and SAH group and 357 (72.9%) in the no hemorrhage group. After propensity score matching, the odds ratio of having a worse mRS scores at 90 days in the asymptomatic HI and SAH group compared with the no hemorrhage group was 2.59 (95% CI, 1.45-4.63; P = .001). For binary outcomes, asymptomatic HI and SAH were consistently associated with worse recovery across mRS score thresholds of 0 to 1 and 0 to 2 in all models. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, asymptomatic HI and SAH were associated with worse 90-day functional outcomes in patients with acute ischemic stroke treated with EVT. These findings emphasize the need for close monitoring and tailored management strategies in patients with asymptomatic hemorrhagic events following thrombectomy. Trial Registration ClinicalTrials.gov Identifier: NCT03469206
Discrimination, Depression, and Anxiety Among US Adults
Authors: Monica L. Wang, Marie-Rachelle Narcisse
Journal: JAMA Network Open (2025)

Importance Examining how discrimination is associated with mental health across different demographic groups can guide efforts to improve mental well-being. Objectives To analyze associations between discrimination and mental health and explore how these associations may vary by race and ethnicity and sex. Design, Setting, and Participants Cross-sectional data of 29 522 adults weighted to represent a population of 258 237 552 US adults from the 2023 US National Health Interview Survey were analyzed. Exposures Exposure to discrimination was measured using the Everyday Discrimination Scale, which assesses frequency of being treated with less courtesy, receiving poor service, being treated as not smart, being feared, and experiencing harassment. A summative scale and a nominal variable (none, low, and high) measured degree and levels of discrimination exposure. Main Outcomes and Measures Outcomes included depression (measured with the Patient Health Questionnaire-2 scale) and anxiety (measured with the Generalized Anxiety Disorder-2 scale), with scores of 3 or greater indicating positive screening results for each scale. Multinomial logistic regression analyses examined associations of interest and tests of interaction explored effect modification by race and ethnicity and sex. Results Among a sample of 29 522 adults weighted to represent a population of 258 237 552 US adults (mean age, 48.1 years [95% CI, 47.8-48.4 years]; 51.1% female; 17.5% Hispanic or Latino, 2.5% multiracial or other, 6.2% non-Hispanic Asian, 11.6% non-Hispanic or non-Latino Black, and 62.2% non-Hispanic or non-Latino White), each unit increase in exposure to discrimination was associated with increased odds of positive screening results for depression (odds ratio [OR], 1.15 [95% CI, 1.12-1.17]), anxiety (OR, 1.14 [95% CI, 1.12-1.16]), and both depression and anxiety (OR, 1.19 [95% CI, 1.16-1.21]). Compared with no exposure to discrimination, low and high exposure to discrimination were associated with increased odds of positive screening results for depression (low exposure: OR, 2.20 [95% CI, 1.77-2.72]; high exposure: OR, 5.39 [95% CI, 3.61-8.04]), anxiety (low exposure: OR, 1.97 [95% CI, 1.66-2.33]; high exposure: OR, 4.98 [95% CI, 3.59-6.91]), and both depression and anxiety (low exposure: OR, 2.60 [95% CI, 2.13-3.18]; high exposure: OR, 8.84 [95% CI, 6.44-12.14]). Associations between discrimination and positive screening results for depression alone ( F 4,607 = 3.35; P = .01) and between discrimination and positive screening results for both depression and anxiety ( F 4,607 = 2.80; P = .03) varied by race and ethnicity. Associations of interest did not differ by sex. Conclusions and Relevance Findings of this cross-sectional study suggest an association between discrimination and mental health across US adults, emphasizing the need for further evaluation and increased awareness of how these associations may vary across different demographic groups.
Development of a New Longitudinal Ordinal Outcome for Clinical Trials in ECMO Patients
Authors: Ary Serpa Neto, Lisa Higgins, Elizabeth Lorenzi, Lindsay Berry, Elizabeth Ryan, Stephane Heritier, Shannah Anderson, Judit Orosz, Aidan Burrell, Zoe McQuilten, Priya Nair, Carol L. Hodgson
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Rationale: Randomised clinical trials in intensive care often prioritize disease-focused outcomes rather than patient-centred outcomes. Objective: To report and evaluate the 'Daily Organ Support for patients on extracorporeal membrane oxygenation (ECMO)', the DOSE outcome. This is a new longitudinal ordinal outcome for clinical trials in patients receiving ECMO. Methods: Prospective, multicentre study in 28 hospitals in Australia and New Zealand. Adult patients admitted to a participating ICU between February 2019 and September 2023 and who underwent any type of ECMO were included. The DOSE outcome was created considering: 1) death; 2) on ECMO; 3) ventilated not on ECMO; 4) in ICU but not ventilated; 5) in hospital ward; and 6) discharged from the hospital. DOSE was developed in collaboration with consumers and other stakeholders, and validated against death and new disability at six months. Simulations were performed to compare the power obtained against 28-day mortality alone. Measurements and Main Results: Among 1375 patients who received ECMO (median age, 52 years; 34% female), at day 90, 42%, 29% and 66% of the patients receiving VA-, VV-ECMO, or eCPR were deceased, respectively. DOSE accurately predicted death and new disability at six months (area under the curve [AUC] > 0.800). With a sample size of 400 per arm and an odds ratio of 1.20, DOSE provided 56% more power than an analysis considering 28-day mortality alone (36% vs. 91%) in simulations of a two-arm clinical trial. Conclusions: The DOSE outcome performed well compared to a patient-centred outcome. Compared to 28-day mortality, DOSE provided more statistical power in a simulated two-arm clinical trial.
Coming Full Circle with Preventive Pulmonary Practice: The American Thoracic Society Vaccine Initiative
Authors: Robert Stansbury, George Su, Amy Stern, Anna Hrovat, Sairam Parthasarathy
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"Coming Full Circle with Preventive Pulmonary Practice: The American Thoracic Society Vaccine Initiative." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
YIA25-001: Molecular Residual Disease (MRD) Guided Adjuvant Therapy In Renal Cell Carcinoma (RCC) - The MRD GATE RCC Study
Authors: Arnab Basu, Fady Sidhom, Caleb Hwang, James Ferguson, Charles Peyton, Sejong Bae, Deepak Kilari, Arpita Desai, Soroush Rais-Bahrami
Journal: Journal of the National Comprehensive Cancer Network (2025)
TIP25-247: A Randomized Controlled Trial to Assess the Impact of Omission of 5-Fluorouracil Bolus Among Stage 2 and 3 Gastrointestinal Cancer Patients
Authors: Mahima Prakash, Kiran P.K.
Journal: Journal of the National Comprehensive Cancer Network (2025)

"TIP25-247: A Randomized Controlled Trial to Assess the Impact of Omission of 5-Fluorouracil Bolus Among Stage 2 and 3 Gastrointestinal Cancer Patients" published on 28 Mar 2025 by National Comprehensive Cancer Network.
Mortality Classification for Deaths With Nonfirearm Force by Police, 2012-2021
Authors: Justin Michael Feldman, Tracey Lloyd, Phillip Atiba Solomon
Journal: JAMA Network Open (2025)

Importance For deaths preceded by nonfirearm force by law enforcement officers, mortality classification has potential implications for public accountability and epidemiologic surveillance. Objective To characterize the proportion of in-custody deaths for which cause and manner of death reflected the use of nonfirearm force by police officers and to assess factors associated with mortality classification. Design, Setting, and Participants This cross-sectional study examined national data from the Associated Press’s Lethal Restraint database. The analysis included deaths that occurred in 2012 to 2021 following the use of nonfirearm force by state or local police officers and that did not occur in prisons or jails. Exposures Death investigation system (medical examiner, coroner, or sheriff-coroner), racial and ethnic bias, and county political context (percentage of Republican presidential votes). Main Outcomes and Measures Manner of death classification (homicide vs accident, undetermined, natural, suicide, and any manner), mention of force-related injuries or conditions in the cause-of-death statement (yes vs no), and mention of any force in the cause-of-death statement (yes vs no) were assessed using logistic regression models. Results A total of 940 decedents (mean [SD] age, 39 [11] years; 909 men [97.0%]; 297 identified as Black [32.4%], 179 as Hispanic or Latinx [19.6%], 401 as White [43.9%], and 37 as other [4.0%] race and ethnicity) were included. Of the 940 deaths, 268 (28.5%) were classified as homicide, and 155 (16.5%) were mentioned as a force-related injury or condition and 400 (42.6%) as any force in the cause-of-death statement. In contrast, 695 cause-of-death statements (73.9%) mentioned drugs. Unadjusted results showed that homicide classification increased from 25.0% (66 of 264 deaths) during 2012-2014 to 32.2% (123 of 382 deaths) during 2018-2021. Models estimating adjusted prevalence differences showed that compared with medical examiner jurisdictions, coroners (−0.19; 95% CI, −0.31 to −0.06) and sheriff-coroners (−0.17; 95% CI, −0.28 to −0.05) were less likely to classify deaths as homicides. Model results also showed that classifications for incidents occurring in counties with the lowest percentage of Republican voters were the most likely to reflect force across all 3 manner and cause outcomes (0.17 [95% CI, 0.05-0.28] for homicide, 0.22 [95% CI, 0.06-0.38] for any mention of force, and 0.14 [95% CI, 0.023-0.26] for force-related injuries or conditions). Conclusions and Relevance In this cross-sectional study of deaths following use of nonfirearm force by police officers, nonhomicide classifications and cause-of-death statements making no mention of force were widespread. These findings suggest that inconsistent classification of the cause and manner of deaths that follow nonfirearm force by police officers is an issue of public safety and health with profound social implications.
HSR25-180: Real-World (rw) Characteristics, Treatment (tx) Patterns and Clinical Outcomes in Patients (pts) With Limited-Stage Small-Cell Lung Cancer (LS-SCLC) Who Received Chemoradiotherapy (CRT)
Authors: Puneeth Iyengar, Doreen A. Kahangire, Alice Wang, Kristin Hsieh, Natalia Donner, Iqra Syed, Daniel Simmons, Anne C. Chiang
Journal: Journal of the National Comprehensive Cancer Network (2025)

"HSR25-180: Real-World (rw) Characteristics, Treatment (tx) Patterns and Clinical Outcomes in Patients (pts) With Limited-Stage Small-Cell Lung Cancer (LS-SCLC) Who Received Chemoradiotherapy (CRT)" published on 28 Mar 2025 by National Comprehensive Cancer Network.
Towards Precision Treatment of COPD Exacerbations: The Role of Specialized Pro-Resolving Mediators
Authors: Jessica Bon, Steven Bozinovski
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"Towards Precision Treatment of COPD Exacerbations: The Role of Specialized Pro-Resolving Mediators." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Somatic uniparental disomy of PTEN in endothelial cells causes vascular malformations in patients with PTEN Hamartoma Tumor Syndrome
Authors: Sandra D. Castillo, Xabier Perosanz, Andrew K. Ressler, Marta Ivars, Jairo Rodriguez, Carlota Rovira, Emanuele M. Nola, Judith Llena, Joaquim Grego-Bessa, Monica Roldan, Raquel Arnau, Anabel Martínez-Romero, Ignasi Barber, Miguel Bejarano, Asuncion Vicente, Veronica Celis, Héctor Salvador, Jaume Mora, Douglas A. Marchuk, Eulalia Baselga, Mariona Graupera
Journal: Cancer Discovery (2025)

Abstract PTEN Hamartoma Tumor Syndrome (PHTS) is a rare tumor risk disorder caused by germline loss-of-function mutations in PTEN. Half of these patients develop vascular malformations, a hamartoma characterized by overgrowth of vessels. Here, we harness biopsies and patient-derived endothelial cells (ECs) to study the genetic etiology of PHTS-related vascular malformations. We discover that these lesions are generated by the somatic loss of the PTEN wild-type allele through copy-neutral loss of heterozygosity, leading to somatic uniparental disomy of the PTEN mutated allele in ECs. We established a mouse model of PHTS-related vascular malformations and identified that the mTOR inhibitor rapamycin and AKT inhibitor capivasertib block vascular lesion growth. As proof-of-concept for clinical activity, off-label treatment with rapamycin of two patients with PHTS reduced vascular overgrowth and abrogated lesion-associated pain. Overall, our results uncover the genetic cause of vascular malformations in patients with PHTS and open new avenues for therapeutic intervention.
Circulating MicroRNAs: functional biomarkers for melanoma prognosis and treatment
Authors: Su Yin Lim, Suzanah C. Boyd, Russell J. Diefenbach, Helen Rizos
Journal: Molecular Cancer (2025)

MicroRNAs (miRNAs) hold significant promise as circulating cancer biomarkers and unlike many other molecular markers, they can provide valuable insights that extend beyond tumour biology. The expression of circulating miRNAs may parallel the cellular composition and dynamic activity within the tumour microenvironment and reveal systemic immune responses. The functional complexity of miRNAs-where a single miRNA can regulate multiple messenger RNAs (mRNAs) to fine tune fundamental processes, and a single mRNA can be targeted by multiple miRNAs-underscores their broad significance and impact. However, this complexity poses significant challenges for translating miRNA research into clinical practice. In melanoma, specific miRNA signatures have shown notable diagnostic, prognostic and predictive value, with lineage-specific and immune-related miRNAs frequently identified as valuable markers. In this review, we explore the role of circulating miRNAs as potential biomarkers in melanoma, and highlight the current status and advances required to translate miRNA research into therapeutic opportunities.
Synergistic effects of electrical and chemical cues with biodegradable scaffolds for large peripheral nerve defect regeneration
Authors: Rosalie Bordett, Sama Abdulmalik, Allen Zennifer, Suranji Wijekoon, Sai Sadhananth Srinivasan, Ergin Coskun, Yeshavanth Kumar Banasavadi Siddegowda, Xiaojun Yu, Sangamesh G Kumbar
Journal: Bioactive Materials (2025)
A phase 1, first-in-human, dose-escalation, expansion trial of cytokine encoding synthetic mRNA-mixture alone or with cemiplimab in advanced solid tumors
Authors: Oliver Bechter, Carmen Loquai, Stephane Champiat, Jean-Francois Baurain, Jean-Jacques Grob, Jochen Utikal, Sylvie Rottey, Alfonso Berrocal, Jessica C. Hassel, Ana Arance, Miguel F. Sanmamed, Marye Boers-Sonderen, Brian Gastman, Christoffer Gebhardt, Brant Delafontaine, Ugur Sahin, Özlem Türeci, Patrick Brueck, Giovanni Abbadessa, Rahul Marpadga, Helen Lee, Yue Yang, Barbara Buday, Gianfranco Di Genova, Hong Wang, Binfeng Xia, Joon Sang Lee, Céleste Lebbe
Journal: Clinical Cancer Research (2025)

Abstract Purpose: We investigated SAR441000 (mixture of four mRNAs encoding interleukin [IL]-12, single chain interferon [IF]-α-2b, granulocyte-macrophage colony-stimulating factor, and IL-15 sushi domain) alone or in combination with cemiplimab in patients with advanced solid tumors. Patients and Methods: SAR441000 was intratumorally administered weekly in a 4-week cycle in monotherapy and in a 3-week cycle at a pre-defined dose level (DL) with 350 mg cemiplimab (intravenously) every 3 weeks in combination therapy. The primary objective was to determine maximum tolerated or maximum administered dose (MAD), overall safety, tolerability, and objective response rate of SAR441000. Results: We enrolled 77 patients previously treated with anti-cancer therapies (escalation monotherapy: N=21; escalation combination: N=15; and expansion combination [PD-1 refractory melanoma]: N=41). MAD at DL8 was 4000 µg. The most common Grade ≥3 treatment-related adverse event was fatigue in escalation phase (monotherapy: 28.6%; combination therapy: 66.7%) and injection-site pain (31.7%) in expansion phase. In combination therapy, one patient in escalation and two in expansion phase achieved partial responses. At 4000 μg (highest dose) across all cohorts, the maximum fold change in plasma cytokine concentration was the highest and lowest for IFN-α-2 (74.9-folds) and IL-15 (1.96-folds), respectively. Increased blood IFN-γ and IP-10 levels were observed for most patients. Conclusions: Intratumoral administration of SAR441000 in combination with cemiplimab, was generally well tolerated with anti-tumor activity in loco-regional disease setting. Anecdotal evidence of pharmacodynamic immune-modulatory effect and distant non-injected lesion anti-tumor response was observed, without significant effect in patients with advanced solid tumors previously treated with anti-PD1 therapies.
Reply to Hsiao and Chen: Refining the Concept of Disease Stability in COPD: Bridging Complexity and Clinical Practice
Authors: Dave Singh
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"Reply to Hsiao and Chen: Refining the Concept of Disease Stability in COPD: Bridging Complexity and Clinical Practice." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Epilepsy in the Indigenous peoples in Canada, Australia, New Zealand, and the USA: a systematic scoping review
Authors: Ngaire F Keenan, Sean G Aitchison, Nathalie Jetté, Karen L Parko, Pamela Roach, Angela Dos Santos, John Archer, Erik Andersen, Jeannine L Stairmand, James Stanley, Lynette G Sadleir
Journal: The Lancet Global Health (2025)
Cost-effectiveness of intrapartum azithromycin to prevent maternal infection, sepsis, or death in low-income and middle-income countries: a modelling analysis of data from a randomised, multicentre, placebo-controlled trial
Authors: Jackie K Patterson, Simon Neuwahl, Sydney Kirsch, Janet L Moore, Alan T N Tita, Waldemar A Carlo, Adrien Lokangaka, Antoinette Tshefu, Musaku Mwenechanya, Elwyn Chomba, Avinash Kavi, Mrityunjay C Metgud, Shivaprasad S Goudar, Richard J Derman, Poonam Shivkumar, Manju Waikar, Archana Patel, Patricia L Hibberd, Paul Nyongesa, Fabian Esamai, Osa A Ekhaguere, Sherri Bucher, Saleem Jessani, Shiyam S Tikmani, Sarah Saleem, Blair J Wylie, Robert L Goldenberg, Sk Masum Billah, Ruth Lennox, Rashidul Haque, William A Petri, Manolo Mazariegos, Nancy F Krebs, Jennifer J Hemingway-Foday, Denise Babineau, Marion Koso-Thomas, Elizabeth M McClure, Melissa Bauserman
Journal: The Lancet Global Health (2025)