tbuckley/cabot-search huggingface dataset:
Sodium Reduction Legislation and Urinary Sodium and Blood Pressure in South Africa
Authors: Thomas Gaziano, David Kapaon, Jacques D. du Toit, Nigel J. Crowther, Alisha N. Wade, June Fabian, Carlos Riumallo-Herl, F. Carla Roberts-Toler, Xavier Gómez-Olivé, Stephen Tollman
Journal: JAMA Cardiology (2025)

Importance Reductions in dietary salt are associated with blood pressure reductions; however, national governments that have passed laws to reduce sodium intake have not measured these laws’ impact. Objective To determine if South African regulations restricting sodium content in processed foods were associated with reductions in sodium consumption and blood pressure. Design, Setting, and Participants The HAALSI (Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa) study is a population-based cohort study among adults aged 40 years or older randomly selected from individuals living in rural Mpumalanga Province in South Africa. This study incorporated 3 waves of data (2014/2015, 2018/2019, and 2021/2022) from the HAALSI study to examine how 24-hour urine sodium (24HrNa) excretion changed among a population-based cohort following mandatory sodium regulations. Spot urine samples were collected across 3 waves, and data analysis was performed from 2023 to 2024. Exposures South African regulations introduced in 2013 that reduced levels for the maximum amount of sodium in milligrams per 100 mg of food product by 25% to 80% across 13 processed food categories by 2019. Main Outcomes and Measures 24HrNa was estimated using the INTERSALT equation, and generalized estimating equations were used to assess changes in sodium excretion and blood pressure. Results Among 5059 adults 40 years or older, mean (SD) age was 62.43 years (13.01), and 2713 participants (53.6%) were female. Overall mean (SD) estimated 24HrNa excretion at baseline was 3.08 g (0.78). There was an overall reduction in mean 24HrNa excretion of 0.22 g (95% CI, −0.27 to −0.17; P &amp;amp;lt; .001) between the first 2 waves and a mean reduction of 0.23 g (95% CI, −0.28 to −0.18; P &amp;amp;lt; .001) between the first and third waves. The reductions were larger when analysis was restricted to those with samples in all 3 waves (−0.26 g for both waves 2 and 3 compared to wave 1). Every gram of sodium reduction was associated with a −1.30 mm Hg reduction (95% CI, 0.65-1.96; P = .00) in systolic blood pressure. The proportion of the study population that achieved ideal sodium consumption (&amp;amp;lt;2 g per day) increased from 7% to 17%. Conclusion and Relevance In this cohort study, following South African regulations limiting sodium in 13 categories of processed foods, there was a significant reduction in 24HrNa excretion among this rural South African population, which was sustained with reductions in blood pressure consistent with levels of sodium excreted. These results support the potential health effects anticipated by effective implementation of population-based salt reformulation policies.
Response to “A commentary on ‘Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery’”
Authors: Jindong Xie, Xinpei Deng, Anli Yang, Shaoquan Zheng, Yuhui Tang, Yi Xie, Junsheng Zhang, Hailin Tang, Wenkuan Chen, Yutian Zou, Xiaoming Xie
Journal: International Journal of Surgery (2025)

Xie, Jindong; Deng, Xinpei; Yang, Anli; Zheng, Shaoquan; Tang, Yuhui; Xie, Yi; Zhang, Junsheng; Tang, Hailin; Chen, Wenkuan; Zou, Yutian PhD, MD; Xie, Xiaoming Author Information
Socioeconomic and Geographic Differences in Mammography Trends Following the 2009 USPSTF Policy Update
Authors: Jason Semprini, Loren Saulsberry, Olufunmilayo I. Olopade
Journal: JAMA Network Open (2025)

Importance In 2024, the US Preventive Services Task Force (USPSTF) reversed a 2009 policy recommending only females aged 50 to 74 years complete a biennial mammogram. Understanding whether females facing heterogeneous breast cancer risks responded to the 2009 guidance may illuminate how they may respond to the latest policy update. Objective To evaluate whether the 2009 policy was associated with changes in mammography screening in females no longer recommended to complete a biennial mammogram and whether these changes varied by factors associated with breast cancer risk. Design, Setting, and Participants The difference-in-differences design compared biennial mammogram trends in the exposed groups (aged 40-49 and ≥75 years) with trends of the unexposed groups (aged 50-64 and 65-74 years), before and after the 2009 update. Population-based, repeated cross-sectional survey data came from the Behavioral Risk Factor Surveillance System (BRFSS) biennial cancer screening module (2000-2018). The sample was restricted to females between ages 40 and 84 years. Data were analyzed from March 1 to June 30, 2024. Main Outcomes and Measures The outcome was a binary variable indicating whether the respondent reported a mammogram in the past 2 years (biennial). After 2009, females aged 40 to 49 and 75 or older years were exposed to the policy update, as a complete biennial mammogram was recommended. Subgroup analyses included race and ethnicity, educational level, household income, smoking history, current binge drinking status, and state of residence. Results The sample included 1 594 834 females; 75% reported a biennial mammogram. In those aged 40 to 49 years, the USPSTF update was associated with a 1.1 percentage-point (95% CI, −1.8% to −0.3 percentage points) decrease in the probability of a biennial mammogram, with the largest decreases in the non-Hispanic Black population (−3.0 percentage points; 95% CI, −5.5% to −0.5 percentage points). In the aged 75 years or older group, the USPSTF update was associated with a 4.8 percentage-point decrease (95% CI, −6.3% to −3.5 percentage points) in the probability of a biennial mammogram, with significant heterogeneity by race and ethnicity, binge drinking status, and state residence. Conclusions and Relevance In this study, socioeconomic factors were associated with differences in how females responded to the 2009 USPSTF mammography recommendation. Whether the 2024 update considered such differences is unclear. These findings suggest that including risk assessment into future USPSTF policy updates may improve adoption of risk-reducing interventions and shorten the time to diagnosis and treatment for high-risk patients.
Exploring genes associated with metabolic dysfunction as therapeutic targets for head and neck cancers: a novel strategy
Authors: Si-Yue Yin, Yu-Chen Liu, Yi-Pin Yang, Bing-Yu Liang, Zi-Yue Fu, Min Fan, Yu-Chen Zhang, Zi-Hui Xie, Ke Han, Jian-Peng Wang, Lei Zhang, Liang Zhang, Bu-Sheng Tong, Yan-Xun Han, Cong-Jun Zhang
Journal: International Journal of Surgery (2025)

Evidence suggests a potential link between metabolic dysfunction and head and neck cancer (HNC). This study investigates the potential causal relationships between metabolic dysfunction and HNC using genetic data. While no significant causal associations were identified between metabolic indicators and HNC risk, the research revealed that inhibition of certain genes could reduce cancer risk. Specifically, inhibiting SLC5A2 was associated with a decreased risk of HNC and oropharyngeal cancer (OPC), while KCNJ11 inhibition was linked to a reduced risk of oral cavity cancer (OCC). Additionally, inhibiting SLC5A1 and CACNB2 showed a connection to lower OPC risk. These findings suggest that targeting these genes could offer promising therapeutic strategies for preventing and treating HNC, as well as improving both preoperative and postoperative management in affected patients.
Predicting futile outcomes following deceased donor liver transplantation in non-Hcc patients with MELD-Na score above 30: a retrospective international multicenter cohort study
Authors: Hye-Sung Jo, Young-in Yoon, Ki-Hun Kim, Parissa Tabrizian, Rebecca Marino, Pedro Marin-Castro, Wellington Andraus, Jongman Kim, Gyu-Seong Choi, Deok-Gie Kim, Dong Jin Joo, Carlos Florez-Zorrilla, Deniz Balci, Henrik Petrowsky, Karim J Halazun, Dong-Sik Kim
Journal: International Journal of Surgery (2025)

Background: In the current “sickest first” allocation policy for limited deceased liver grafts, identifying patients “too sick to transplant” before transplantation is crucial to optimize outcomes. This study aimed to predict futile outcomes following deceased donor liver transplantation (DDLT) in patients with Model for End-Stage Liver Disease-Sodium (MELD-Na) scores ≥30. Methods: This international multicenter study was conducted as part of the International Society of Liver Surgeons. We collected data from patients with a MELD-Na score ≥30 who underwent DDLT. A total of 994 patients were enrolled between 2010–2021, including 654 from the Republic of Korea, 224 from the US, and 116 from other regions. Futility was defined as death within three months or during the hospital stay following a DDLT. After exclusion, 160 (16.6%) patients were classified into a futile group and 803 (83.4%) into a non-futile group. Results: The MELD-Na scores collected at three time points (listing, matching, and transplantation) were comparable between the groups (P = 0.442, P = 0.180, and P = 0.554, respectively). Regarding concomitant organ failure factors, the futile group showed a higher incidence of organ dysfunction across all measured parameters, including the use of mechanical ventilators, continuous renal replacement therapy (CRRT), pneumonia, bacteremia, and vasopressor use (all P&lt;0.01). Independent risk factors for futile outcome were recipient age (≥65 years), body mass index (&lt;18.5 kg/m 2 ), mechanical ventilator use, CRRT (≥1 week), and prolonged ICU stay before transplantation (≥2 weeks). The futility rate was 53.3% in patients with ≥3 risk factors (P&lt;0.001). We developed a nomogram to predict futility after DDLT based on multivariate regression analysis, which showed a better predictive power than previous models. Conclusions: The risk factors and new nomogram, which adequately reflect concomitant organ failure before liver transplantation, could effectively predict the risk of futile outcomes after DDLT and contribute to decision-making regarding transplantation eligibility in clinical practice.
Effects of Clazakizumab on Anemia and Iron Metabolism in Patients with Kidney Failure
Authors: Brendon L. Neuen, Benjamin Catanese, Annamarie Chang, Mark Heise, Pierluigi Tricoci, G. Michael Felker, Kenneth W. Mahaffey, Myles Wolf, Glenn M. Chertow
Journal: Journal of the American Society of Nephrology (2025)

Neuen, Brendon L.; Catanese, Benjamin; Chang, Annamarie; Heise, Mark; Tricoci, Pierluigi; Felker, G. Michael; Mahaffey, Kenneth W.; Wolf, Myles; Chertow, Glenn M.; the POSIBIL6ESKD Investigators Author Information
Cognitive Processing Therapy for Posttraumatic Stress Disorder in Japan
Authors: Masaya Ito, Akiko Katayanagi, Mitsuhiro Miyamae, Tamae Inomata, Yuriko Takagishi, Akiko Kikuchi, Miyuki Makino, Yoko Matsuda, Keiko Yamaguchi, Chiaki Nakayama, Kyosuke Kaneko, Chika Yokoyama, Fumi Imamura, Ayako Kanie, Mari Oba, Satoshi Tanaka, Satomi Nakajima, Tomomi Narisawa, Kyoko Akutsu, Rieko Konno, Yuki Oe, Naotsugu Hirabayashi, Toshi A. Furukawa, Patricia A. Resick, Masaru Horikoshi
Journal: JAMA Network Open (2025)

Importance Cognitive processing therapy (CPT) is an evidence-based treatment for posttraumatic stress disorder (PTSD). However, there is little evidence on the efficacy of CPT in East Asia. Objective To evaluate whether CPT is effective in treating PTSD among outpatients in a Japanese medical setting. Design, Setting, and Participants This randomized clinical trial used a 16-week, single-center, assessor-blinded, parallel-group superiority design to examine the efficacy of CPT in conjunction with treatment as usual (CPT-TAU) vs waiting list with TAU (WL-TAU) from April 2016 through December 2022. The trial included adult patients with PTSD at a national psychiatric referral hospital in Tokyo, Japan. Analysis was based on intention to treat and per protocol and was performed from February 1 to April 30, 2024. Interventions Participants were randomized 1:1 to CPT-TAU (n = 29), which consisted of 12 weekly individual CPT sessions, or WL-TAU (n = 31), which consisted of clinical monitoring and/or pharmacotherapy. Main Outcomes and Measures The primary outcome was the Clinician-Administered PTSD Scale (CAPS-5) score for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) at 17 weeks. Secondary outcomes included self-reported PTSD symptoms assessed by the PTSD Checklist–5 and responder status at 17 weeks. Adverse events were evaluated using the Japanese version of the Common Terminology Criteria for Adverse Events, version 4.0. Results Among 60 eligible participants (all included in the intention-to-treat analysis), mean (SD) age was 36.9 (9.9) years; 54 (90.0%) were women. The CPT-TAU group showed a mean (SE) reduction in CAPS-5 scores of 14.00 (1.92) points, with a low dropout rate (2 of 29 [6.9%]). Patients in the CPT-TAU group showed superiority in all secondary and other outcomes. The mean change difference was observed in depression (8.83; 95% CI, 6.00-11.66), suicidal ideation (6.73; 95% CI, 1.25-12.22), disability (8.16; 95% CI, 3.90-12.43), clinical global impression (0.84; 95% CI, 0.41-1.26), and loss of principal PTSD diagnosis (59.09; 95% CI, 37.19-81.00). There were no serious adverse events in the CPT-TAU group and 3 serious adverse events in the WL-TAU group during the intervention period. Conclusions and Relevance In this randomized clinical trial of CPT-TAU vs WL-TAU, CPT was superior in reducing PTSD symptoms. These results strengthen the evidence for use of CPT in East Asian populations. Trial Registration Umin.Uc.Jp/Ctr Identifier: UMIN000021670
Employer-Sponsored Digital Health Platforms for Mental Wellness—A Good Investment
Authors: Molly Candon, Rebecca E. Stewart
Journal: JAMA Network Open (2025)

Matt Hawrilenko, PhD; Casey Smolka, MAAA; Emily Ward, PhD; Geetu Ambwani, MSc; Millard Brown, MD; Anita Mohandas, MSc, MHP; Martin Paulus, PhD; John Krystal, MD; Adam Chekroud, PhD
Multicenter, retrospective GUIDANCE001 study comparing transarterial chemoembolization with or without tyrosine kinase and immune checkpoint inhibitors as conversion therapy to treat unresectable hepatocellular carcinoma: Survival benefit in intermediate or advanced, but not early, stages
Authors: Da-Long Yang, Lin Ye, Fan-Jian Zeng, Jie Liu, Hong-Bing Yao, Jun-Liang Nong, Shao-Ping Liu, Ning Peng, Wen-Feng Li, Pei-Sheng Wu, Chuang Qin, Ze Su, Jun-Jie Ou, Xiao-Feng Dong, Yi-He Yan, Teng-Meng Zhong, Xian-Shuang Mao, Ming-Song Wu, Yao-Zhi Chen, Guo-Dong Wang, Mian-Jing Li, Xue-Yao Wang, Fu-Quan Yang, Yong-Rong Liang, Shu-Chang Chen, Yong-Yu Yang, Kang Chen, Fu-Xin Li, Yong-Cheng Lai, Qing-Qing Pang, Xiu-Mei Liang, Xue-Mei You, Bang-De Xiang, Ya-Qun Yu, Liang Ma, Jian-Hong Zhong
Journal: Hepatology (2025)

Background and Aims: Various conversion therapy options have become available to patients with unresectable HCC, but which conversion therapy is optimal for which type of patient is controversial. This study compared the efficacy and safety of TACE alone or combined with immune checkpoint and tyrosine kinase inhibitors. Approach and Results: Data were retrospectively compared for patients with initially unresectable HCC who underwent conversion therapy consisting of TACE alone (n=459) or combined with immune checkpoint and tyrosine kinase inhibitors (n=343). Compared to the group that received TACE alone, the group that received triple conversion therapy showed significantly higher rates of overall survival (HR 0.43, 95%CI 0.35–0.53). In addition, triple therapy was associated with significantly longer median progression-free survival (15.9 vs. 8.0 mo, p &lt;0.001). These results were confirmed in matched subsets of patients from each group. However, subgroup analysis confirmed the results only for patients with HCC in intermediate or advanced stages, not in an early stage. Those who received triple conversion therapy had a significantly higher rate of hepatectomy after conversion therapy (36.4 vs. 23.5%, p &lt;0.001). Among those who underwent hepatectomy after conversion therapy, triple therapy was associated with a significantly higher rate of complete tumor response (32.1 vs. 11.1%, p &lt;0.001). However, it was also associated with a significantly higher frequency of serious adverse events (35.6 vs. 27.0%, p =0.009). Conclusions: Combining TACE with immune checkpoint and tyrosine kinase inhibitors was associated with significantly better survival and conversion efficacy than TACE alone among patients with intermediate or advanced unresectable HCC.
<i>Pseudomonas aeruginosa</i> infection induces intragraft lymphocytotoxicity that triggers lung transplant antibody-mediated rejection
Authors: Fuyi Liao, Dequan Zhou, Marlene Cano, Zhiyi Liu, Davide Scozzi, Laneshia K. Tague, Derek E. Byers, Wenjun Li, Jothilingam Sivapackiam, Vijay Sharma, Alexander S. Krupnick, Dara W. Frank, Daniel Kreisel, Hrishikesh S. Kulkarni, Ramsey R. Hachem, Andrew E. Gelman
Journal: Science Translational Medicine (2025)

How pathogens inhibit transplant tolerance remains unclear. Here, we found that Pseudomonas aeruginosa infection, but not other common bacterial respiratory infections, increases antibody-mediated rejection (AMR) risk in recipients of lung transplants. To explore this relationship, we performed orthotopic lung transplants in mice, infected recipients with P. aeruginosa , and observed for the development of AMR. Intravital two-photon microscopy showed that P. aeruginosa rapidly invaded bronchial-associated lymphoid tissues, which resulted in acute lymphocytotoxicity, including the death of forkhead box P3 (Foxp3) + CD4 + T cells that are required to suppress AMR. P. aeruginosa –mediated AMR required expression of the type III secretion system (T3SS), which injects exotoxins into the cell cytoplasm. Through a combination of mutagenesis and epitope tagging experiments, we revealed that T3SS exotoxin T ADP ribosyl-transferase activity was sufficient for graft-resident Foxp3 + CD4 + T cell apoptosis, leading to myeloid differentiation primary response 88 (Myd88)–dependent generation of T-box expressed in T cells (T-bet)– and C-X-C motif chemokine receptor 3 (CXCR3)–positive germinal center and memory B cells with high donor antigen avidity. We also found that T-bet + and CXCR3 + B cells were elevated in biopsies from recipients of lung transplants who were diagnosed with AMR. In mice, CXCR3 deficiency restricted to B cells or CXCR3 blockade prevented AMR despite P. aeruginosa infection. Our work has identified a previously unrecognized role of bacterial virulence in lung allograft rejection and suggests potential strategies to prevent AMR for those at high risk of P. aeruginosa infection after transplant.
Translocating gut pathobiont <i>Enterococcus gallinarum</i> induces T <sub>H</sub> 17 and IgG3 anti-RNA–directed autoimmunity in mouse and human
Authors: Konrad Gronke, Mytien Nguyen, Helen Fuhrmann, Noemi Santamaria de Souza, Julia Schumacher, Márcia S. Pereira, Ulrike Löschberger, Anna Brinkhege, Nathalie J. Becker, Yi Yang, Nicole Sonnert, Shana Leopold, Anjelica L. Martin, Lilly von Münchow-Klein, Cecilia Pessoa Rodrigues, Dilay Cansever, Remy Hallet, Kirsten Richter, David A. Schubert, Guillaume M. Daniel, David Dylus, Marianne Forkel, Dorothee Schwinge, Christoph Schramm, Sylvio Redanz, Kara G. Lassen, Silvio Manfredo Vieira, Luca Piali, Noah W. Palm, Christoph Bieniossek, Martin A. Kriegel
Journal: Science Translational Medicine (2025)

Chronic autoimmune diseases often lead to long-term sequelae and require lifelong immunosuppression because of an incomplete understanding of the triggers and drivers in genetically predisposed patients. Gut bacteria that escape the gut barrier, known as translocating gut pathobionts, have been implicated as instigators and perpetuators of extraintestinal autoimmune diseases in mice. The gut microbial contributions to autoimmunity in humans remain largely unclear, including whether specific pathological human adaptive immune responses are triggered by such pathobionts. Here, we show that the translocating pathobiont Enterococcus gallinarum can induce both human and mouse interferon-γ + T helper 17 (T H 17) differentiation and immunoglobulin G3 (IgG3) subclass switch of anti– E. gallinarum RNA antibodies, which correlated with anti-human RNA autoantibody responses in patients with systemic lupus erythematosus (SLE) and autoimmune hepatitis, two extraintestinal autoimmune diseases. E. gallinarum RNA, but not human RNA, triggered Toll-like receptor 8 (TLR8), and TLR8-mediated human monocyte activation promoted human T H 17 induction by E. gallinarum . Translocation of the pathobiont triggered increased anti-RNA autoantibody titers that correlated with renal autoimmune pathophysiology in murine gnotobiotic lupus models and with disease activity in patients with SLE. These studies elucidate cellular mechanisms of how a translocating gut pathobiont induces systemic human T cell– and B cell–dependent autoimmune responses and provide a framework for developing host- and microbiota-derived biomarkers and targeted therapies in autoimmune diseases.
Selective abrogation of S6K2 identifies lipid homeostasis as a survival vulnerability in MAPK inhibitor–resistant <i>NRAS</i> -mutant melanoma
Authors: Brittany Lipchick, Adam N. Guterres, Hsin-Yi Chen, Delaine M. Zundell, Segundo Del Aguila, Patricia I. Reyes-Uribe, Yulissa Tirado, Subhasree Basu, Xiangfan Yin, Andrew V. Kossenkov, Yiling Lu, Gordon B. Mills, Qin Liu, Aaron R. Goldman, Maureen E. Murphy, David W. Speicher, Jessie Villanueva
Journal: Science Translational Medicine (2025)

Although oncogenic NRAS activates mitogen-activated protein kinase (MAPK) signaling, inhibition of the MAPK pathway is not therapeutically efficacious in NRAS -mutant ( NRAS MUT ) tumors. Here, we report that selectively silencing the ribosomal protein S6 kinase 2 (S6K2) while preserving the activity of S6K1 perturbs lipid metabolism, enhances fatty acid unsaturation, and triggers lethal lipid peroxidation in NRAS MUT melanoma cells that are resistant to MAPK inhibition. S6K2 depletion induces endoplasmic reticulum stress and peroxisome proliferator–activated receptor α (PPARα) activation, triggering cell death selectively in MAPK inhibitor–resistant melanoma. We found that combining PPARα agonists and polyunsaturated fatty acids phenocopied the effects of S6K2 abrogation, blocking tumor growth in both patient-derived xenografts and immunocompetent murine melanoma models. Collectively, our study establishes S6K2 and its effector subnetwork as promising targets for NRAS MUT melanomas that are resistant to global MAPK pathway inhibitors.