tbuckley/cabot-search huggingface dataset:
The Efficacy of Tradipitant in Patients With Diabetic and Idiopathic Gastroparesis in a Phase 3 Randomized Placebo-Controlled Clinical Trial
Authors: Jesse L. Carlin, Christos Polymeropoulos, Michael Camilleri, Anthony Lembo, Michaela Fisher, Caleigh Kupersmith, Darby Madonick, Paula Moszczynski, Sandra Smieszek, Changfu Xiao, Gunther Birznieks, Mihael H. Polymeropoulos
Journal: Clinical Gastroenterology and Hepatology (2024)

Neurokinin receptor 1 antagonists are effective in reducing nausea and vomiting in chemotherapy-induced emesis. We investigated the safety and efficacy of tradipitant, a neurokinin receptor 1 antagonist, in patients with idiopathic and diabetic gastroparesis.
Lysine acetyltransferase 6A maintains CD4+ T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity
Authors: Jia-Yao Fu, Shi-Jia Huang, Bao-Li Wang, Jun-Hao Yin, Chang-Yu Chen, Jia-Bao Xu, Yan-Lin Chen, Shuo Xu, Ting Dong, Hao-Nan Zhou, Xin-Yi Ma, Yi-Ping Pu, Hui Li, Xiu-Juan Yang, Li-Song Xie, Zhi-Jun Wang, Qi Luo, Yan-Xiong Shao, Lei Ye, Zi-Rui Zong, Xin-Di Wei, Wan-Wen Xiao, Shu-Tong Niu, Yi-Ming Liu, He-Ping Xu, Chuang-Qi Yu, Sheng-Zhong Duan, Ling-Yan Zheng
Journal: Cell Metabolism (2024)
Clinical features of rapid involuting congenital hemangioma: A prospective study
Authors: Tong Qiu, Zixin Zhang, Jiangyuan Zhou, Xue Gong, Xuepeng Zhang, Yuru Lan, Congxia Yang, YuJia Zhang, Zilong Zhou, Xian Jiang, Fan Hu, Wei Shan, Feiteng Kong, Yongbo Zhang, Qingxia Qiu, Siyuan Chen, Yi Ji
Journal: Journal of the American Academy of Dermatology (2024)
Potent antitumor activity of anti-HER2 antibody-topoisomerase I inhibitor conjugate based on self-immolative dendritic dimeric-linker
Authors: Yulia Liubomirski, Galia Tiram, Anna Scomparin, Samer Gnaim, Sayantan Das, Sachin Gholap, Liang Ge, Eilam Yeini, Omri Shelef, Arie Zauberman, Nir Berger, Doron Kalimi, Mira Toister-Achituv, Christian Schröter, Stephan Dickgiesser, Jason Tonillo, Min Shan, Carl Deutsch, Stanley Sweeney-Lasch, Doron Shabat, Ronit Satchi-Fainaro
Journal: Journal of Controlled Release (2024)
Policy solutions to eliminate racial and ethnic child health disparities in the USA
Authors: Monique Jindal, Elizabeth Barnert, Nathan Chomilo, Shawnese Gilpin Clark, Alyssa Cohen, Danielle M Crookes, Kiarri N Kershaw, Katy Backes Kozhimannil, Kamila B Mistry, Rebecca J Shlafer, Natalie Slopen, Shakira F Suglia, Max Jordan Nguemeni Tiako, Nia Heard-Garris
Journal: The Lancet Child & Adolescent Health (2024)
Racial and ethnic inequities in the quality of paediatric care in the USA: a review of quantitative evidence
Authors: Natalie Slopen, Andrew R Chang, Tiffani J Johnson, Ashaunta T Anderson, Aleha M Bate, Shawnese Clark, Alyssa Cohen, Monique Jindal, J'Mag Karbeah, Lee M Pachter, Naomi Priest, Shakira F Suglia, Nessa Bryce, Andrea Fawcett, Nia Heard-Garris
Journal: The Lancet Child & Adolescent Health (2024)
Patient-Specific Measurable Residual Disease Markers Predict Outcome in Patients With Myelodysplastic Syndrome and Related Diseases After Hematopoietic Stem-Cell Transplantation
Authors: Magnus Tobiasson, Tatjana Pandzic, Johanna Illman, Lars Nilsson, Simone Weström, Elisabeth Ejerblad, Gitte Olesen, Andreas Björklund, Astrid Olsnes Kittang, Olle Werlenius, Fryderyk Lorentz, Bengt Rasmussen, Jörg Cammenga, Duruta Weber, Carolin Lindholm, Joel Wiggh, Marios Dimitriou, Ann Elin Moen, Laimei Yip Lundström, Lena von Bahr, Karin Baltzer-Sollander, Martin Jädersten, Soili Kytölä, Gunilla Walldin, Per Ljungman, Kirsten Groenbaek, Stephan Mielke, Sten Eirik W. Jacobsen, Freja Ebeling, Lucia Cavelier, Lone Smidstrup Friis, Ingunn Dybedal, Eva Hellström-Lindberg
Journal: Journal of Clinical Oncology (2024)

PURPOSE Clinical relapse is the major threat for patients with myelodysplastic syndrome (MDS) undergoing hematopoietic stem-cell transplantation (HSCT). Early detection of measurable residual disease (MRD) would enable preemptive treatment and potentially reduced relapse risk. METHODS Patients with MDS planned for HSCT were enrolled in a prospective, observational study evaluating the association between MRD and clinical outcome. We collected bone marrow (BM) and peripheral blood samples until relapse, death, or end of study 24 months after HSCT. Patient-specific mutations were identified with targeted next-generation sequencing (NGS) panel and traced using droplet digital polymerase chain reaction (ddPCR). RESULTS Of 266 included patients, estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD results were available for 221 patients. Relapse was preceded by positive BM MRD in 42/44 relapses with complete MRD data, by a median of 71 (23-283) days. Of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD–, and five were MRD+ at last sampling. Estimated 1 year-RFS after first positive MRD was 49%, 39%, and 30%, using cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), WHO subgroup AML (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute GVHD grade III-IV (HR, 4.13) were associated with shorter RFS. MRD+ was also independently associated with shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32). CONCLUSION Assessment of individualized MRD using NGS + ddPCR is feasible and can be used for early detection of relapse. Positive MRD is associated with shorter RFS and OS (ClinicalTrials.gov identifier: NCT02872662 ).
Device-assisted enteroscopy: take-home messages and open issues from everyday clinical practice
Authors: Emanuele Rondonotti
Journal: Endoscopy (2024)

Over the last two decades, technological innovations have completely changed the diagnostic and therapeutic work-up of several diseases involving the small bowel. The introduction of small-bowel capsule endoscopy (SBCE) first, and later of device-assisted enteroscopy (DAE), has not only allowed a direct and accurate study of the small-bowel mucosa, but also enabled the implementation of effective endoscopic therapy.
Lumen-apposing metal stents for the treatment of pancreatic and peripancreatic fluid collections and bleeding risk: a propensity matched study
Authors: Benedetto Mangiavillano, Sundeep Lakhtakia, Jayanta Samanta, Francesco Auriemma, Jorge Vargas-Madrigal, Paolo Giorgio Arcidiacono, Carmelo Barbera, Hazem Ashhab, Tae Jun Song, Khanh Do-Kong Pham, Anthony Y.B. Teoh, Jong Ho Moon, Stefano Francesco Crinò, Pradermchai Kongkam, Giovanni Aragona, Mark A. De Lusong, Jahnvi Dhar, Andrew Ofosu, Agostino Ventra, Danilo Paduano, Gianluca Franchellucci, Alessandro Repici, Alberto Larghi, Antonio Facciorusso
Journal: Endoscopy (2024)

Introduction Endoscopic ultrasound (EUS)-guided drainage of symptomatic pancreatic fluid collections (PFCs) using the Hot-Axios device has recently been associated with a significant risk of bleeding. This adverse event (AE) seems to occur less frequently with the use of a different device, the Spaxus stent. The aim of the current study was to compare the rates of bleeding between the two stents. Methods Patients admitted for treatment of PFCs by EUS plus lumen-apposing metal stent in 18 endoscopy referral centers between 10 July 2019 and 28 February 2022 were identified and their outcomes compared using a propensity-matching analysis. Results 363 patients were evaluated. After a 1-to-1 propensity score match, 264 patients were selected (132 per group). The technical and clinical success rates were comparable between the two groups. Significantly more bleeding requiring transfusion and/or intervention occurred in the Hot-Axios group than in the Spaxus group (6.8% vs. 1.5%; P = 0.03); stent type was a significant predictor of bleeding in both univariate and multivariate regression analyses (P = 0.03 and 0.04, respectively). Bleeding necessitating arterial embolization did not however differ significantly between the two groups (3.0% vs. 0%; P = 0.12). In addition, the Hot-Axios was associated with a significantly higher rate of overall AEs compared with the Spaxus stent (9.8% vs. 3.0%; P = 0.04). Conclusion Our study showed that, in patients with PFCs, bleeding requiring transfusion and/or intervention occurred significantly more frequently with use of the Hot-Axios stent than with the Spaxus stent, although this was not the case for bleeding requiring embolization.
Triggering receptor expressed on myeloid cells 2 (TREM2) regulates phagocytosis in glioblastoma
Authors: Mekenzie M Peshoff, Pravesh Gupta, Shivangi Oberai, Rakesh Trivedi, Hiroshi Katayama, Prashanth Chakrapani, Minghao Dang, Simona Migliozzi, Joy Gumin, Divya B Kadri, Jessica K Lin, Nancy K Milam, Mark E Maynard, Brian D Vaillant, Brittany Parker-Kerrigan, Frederick F Lang, Jason T Huse, Antonio Iavarone, Linghua Wang, Karen Clise-Dwyer, Krishna P Bhat
Journal: Neuro-Oncology (2024)

Abstract Background Glioblastomas (GBMs) are central nervous system tumors that resist standard-of-care interventions and even immune checkpoint blockade. Myeloid cells in the tumor microenvironment can contribute to GBM progression; therefore, emerging immunotherapeutic approaches include reprogramming these cells to achieve desirable antitumor activity. Triggering receptor expressed on myeloid cells 2 (TREM2) is a myeloid signaling regulator that has been implicated in a variety of cancers and neurological diseases with contrasting functions, but its role in GBM immunopathology and progression is still under investigation. Methods Our reverse translational investigations leveraged single-cell RNA sequencing and cytometry of human gliomas to characterize TREM2 expression across myeloid subpopulations. Using 2 distinct murine glioma models, we examined the role of Trem2 on tumor progression and immune modulation of myeloid cells. Furthermore, we designed a method of tracking phagocytosis of glioma cells in vivo and employed in vitro assays to mechanistically understand the influence of TREM2 signaling on tumor uptake. Results We discovered that TREM2 expression does not correlate with immunosuppressive pathways, but rather showed strong a positive association with the canonical phagocytosis markers lysozyme (LYZ) and macrophage scavenger receptor (CD163) in gliomas. While Trem2 deficiency was found to be dispensable for gliomagenesis, Trem2+ myeloid cells display enhanced tumor uptake compared to Trem2- cells. Mechanistically, we demonstrate that TREM2 mediates phagocytosis via Syk signaling. Conclusions These results indicate that TREM2 is not associated with immunosuppression in gliomas. Instead, TREM2 is an important regulator of phagocytosis that may be exploited as a potential therapeutic strategy for brain tumors.
SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma
Authors: Mohammad Hamdy Abdelrazak Morsy, Ingrid Lilienthal, Martin Lord, Magali Merrien, Agata Magdalena Wasik, Marta Sureda-Gómez, Virginia Amador, Henrik J. Johansson, Janne Lehtiö, Beatriz Garcia-Torre, Jose Ignacio Martin-Subero, Nikolaos Tsesmetzis, Sijia Tao, Raymond F. Schinazi, Baek Kim, Agnes L. Sorteberg, Malin Wickström, Devon Sheppard, Georgios Z. Rassidakis, Ian A. Taylor, Birger Christensson, Elias Campo, Nikolas Herold, Birgitta Sander
Journal: Blood (2024)

Abstract Sterile alpha motif and histidine-aspartate (HD) domain–containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several hematological malignancies. Targeting SAMHD1’s ara-CTPase activity has recently been demonstrated to enhance ara-C efficacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMG-box containing protein 11 (SOX11) as a novel direct binding partner and first known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Coimmunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identified SAMHD1 as the top SOX11 interaction partner, which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar affinity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara-C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identified SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its first known endogenous inhibitor with potentially important implications for clinical therapy stratification.
ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy
Authors: María-Eva Mingot-Castellano, Faustino García-Candel, Jorge Martínez-Nieto, José García-Arroba, Javier de la Rubia-Comos, Inés Gómez-Seguí, María-Liz Paciello-Coronel, David Valcárcel-Ferreiras, Moraima Jiménez, Joan Cid, Miquel Lozano, José-María García-Gala, Sonia Angós-Vazquez, Miriam Vara-Pampliega, Luisa Guerra-Domínguez, Laura-Francisca Ávila-Idrobo, Ana Oliva-Hernandez, Saioa Zalba-Marcos, Inmaculada Tallón-Ruiz, Sandra Ortega-Sánchez, Rosa Goterris-Viciedo, Gemma Moreno-Jiménez, Lourdes Domínguez-Acosta, María Araiz-Ramírez, Luis Hernández-Mateos, Elena Flores-Ballesteros, Julio del Río-Garma, Cristina Pascual-Izquierdo
Journal: Blood (2024)
Low ectonucleotidase activity and increased neutrophil-platelet aggregates in patients with antiphospholipid syndrome
Authors: Somanathapura K. NaveenKumar, Ajay Tambralli, Bruna Mazetto Fonseca, Srilakshmi Yalavarthi, Wenying Liang, Claire K. Hoy, Cyrus Sarosh, Christine E. Rysenga, Caroline H. Ranger, Caroline E. Vance, Jacqueline A. Madison, Fernanda A. Orsi, Suman L. Sood, Jordan K. Schaefer, Yu Zuo, Jason S. Knight
Journal: Blood (2024)
Reply to: Asthma–Chronic Obstructive Pulmonary Disease Overlap versus Chronic Obstructive Pulmonary Disease: Comparing Apples and Oranges
Authors: Emily Gerstein, Jared Bierbrier, G. Alex Whitmore, Shawn D. Aaron
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Reply to: ACO vs. COPD: Comparing Apples and Oranges." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Reply to: Identification of AAT-Deficient Subjects with Normal Spirometry Who May Benefit from AAT Replacement
Authors: Daniel D. Fraughen, Auyon J. Ghosh, Tomás P. Carroll, Noel G. McElvaney
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Reply to: Identification of AAT-Deficient Subjects with Normal Spirometry Who May Benefit from AAT Replacement ." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Asthma–Chronic Obstructive Pulmonary Disease Overlap versus Chronic Obstructive Pulmonary Disease: Comparing Apples and Oranges
Authors: Guisheng Xian, Zhiwei Long, Yan Wang
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"ACO vs. COPD: Comparing Apples and Oranges." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Association Between Age at Diabetes Diagnosis and Subsequent Incidence of Cancer: A Longitudinal Population-Based Cohort
Authors: Yanyun Li, Jingyan Tian, Tianzhichao Hou, Kai Gu, Qinghua Yan, Siming Sun, Jiange Zhang, Jiao Sun, Lili Liu, Chang-Sheng Sheng, Yi Pang, Minna Cheng, Chunxiao Wu, Katie Harris, Yan Shi, Zachary T. Bloomgarden, John Chalmers, Chen Fu, Guang Ning
Journal: Diabetes Care (2024)

OBJECTIVE Diabetes presenting at a younger age has a more aggressive nature. We aimed to explore the association of age at type 2 diabetes mellitus (T2DM) diagnosis with subsequent cancer incidence in a large Chinese population. RESEARCH DESIGN AND METHODS The prospective population-based longitudinal cohort included 428,568 newly diagnosed T2DM patients from 2011 to 2018. Participants were divided into six groups according to their age at diagnosis: 20–54, 55–59, 60–64, 65–69, 70–74, and ≥75 years. The incidence of overall and 14 site-specific cancers was compared with the Shanghai general population including 100,649,346 person-years. RESULTS A total of 18,853 and 582,643 overall cancer cases were recorded in the T2DM cohort and the general population. The age-standardized rate of overall cancer in T2DM patients was 501 (95% CI: 491, 511) per 100,000 person-years, and the standardized incidence ratio (SIR) was 1.10 (1.09, 1.12). Younger age at T2DM diagnosis was associated with higher incidence of overall and site-specific cancers. SIRs for overall cancer with T2DM diagnosis at ages 20–54, 55–59, 60–64, 65–69, 70–74, and ≥75 years were 1.48 (1.41, 1.54), 1.30 (1.25, 1.35), 1.19 (1.15, 1.23), 1.16 (1.12, 1.20), 1.06 (1.02, 1.10), and 0.86 (0.84, 0.89), respectively. Similar trends were observed for site-specific cancers, including respiratory, colorectum, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancer and lymphoma among both males and females. CONCLUSIONS Our findings highlight the necessity of stratifying management for T2DM according to age of diagnosis. As with a range of vascular outcomes, age-standardized cancer risks are greater in earlier compared with later onset T2DM.
Human T-lymphotropic virus type 1 and antiretroviral therapy: practical considerations for pre-exposure and post-exposure prophylaxis, transmission prevention, and mitigation of severe disease
Authors: Jake S O’Donnell, Noushin Jaberolansar, Keith J Chappell
Journal: The Lancet Microbe (2024)

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with substantial risk of secondary (often life-threatening) disease for the estimated 10 million to 20 million people infected globally. Despite a clear need, no HTLV-1-specific vaccine or antiretroviral therapy has been developed to date. Instead, existing public and primary health-care interventions inadequately focus on infection prevention and management of secondary diseases. In this Personal View, we discuss the evidence that exists to support the sensitivity of HTLV-1 to antiretroviral therapies approved by the US Food and Drug Administration for the treatment of HIV-1, how this sensitivity is affected by clinically relevant virological and immunological features, and additional practical considerations for the use of antiretroviral therapies in the context of HTLV-1.
Interleukin-6, Diabetes, and Metabolic Syndrome in a Biracial Cohort: The Reasons for Geographic and Racial Differences in Stroke Cohort
Authors: Brittney J. Palermo, Katherine S. Wilkinson, Timothy B. Plante, Charles D. Nicoli, Suzanne E. Judd, Debora Kamin Mukaz, D. Leann Long, Nels C. Olson, Mary Cushman
Journal: Diabetes Care (2024)

OBJECTIVE Black Americans have a greater risk of type 2 diabetes than White Americans. The proinflammatory cytokine interleukin-6 (IL-6) is implicated in diabetes pathogenesis, and IL-6 levels are higher in Black individuals. This study investigated associations of IL-6 with incident diabetes and metabolic syndrome in a biracial cohort. RESEARCH DESIGN AND METHODS The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White adults age ≥45 years in 2003–2007, with a follow-up ∼9.5 years later. Baseline plasma IL-6 was measured in 3,399 participants at risk of incident diabetes and 1,871 at risk of metabolic syndrome. Relative risk (RR) by IL-6 was estimated with modified Poisson regression for both groups. RESULTS Incident diabetes occurred in 14% and metabolic syndrome in 20%; both rates rose across IL-6 quartiles. There was a three-way interaction of IL-6, race, and central adiposity for incident diabetes (P = 8 × 10−5). In Black participants with and without central adiposity, RRs were 2.02 (95% CI 1.00–4.07) and 1.66 (1.00–2.75) for the fourth compared with first IL-6 quartile, respectively. The corresponding RRs were 1.73 (0.92–3.26) and 2.34 (1.17–4.66) in White participants. The pattern was similar for IL-6 and metabolic syndrome. CONCLUSIONS Although IL-6 was higher in Black than in White participants and those with central adiposity, the association of IL-6 with diabetes risk was statistically significant only among White participants without central adiposity. The association with metabolic syndrome risk was similarly stronger in low-risk groups. The results support the concept of interventions to lower inflammation in diabetes prevention, but to reduce race disparities, better biomarkers are needed.
Technological determinants of health: a looming apocalypse
Authors: Kamran Abbasi
Journal: BMJ (2024)

Perhaps nobody predicted the damaging dysfunction of a health service and the collapse of society as we know it because of a decision to withdraw an instant messaging service, but it may be about to happen.Regulation of WhatsApp and similar technologies, specifically by allowing access to messages to investigate crimes such as terrorism, could lead to them being unavailable in the UK.
The Specialist Treatment of Inpatients: Caring for Diabetes in Surgery (STOIC-D Surgery) Trial: A Randomized Controlled Trial of Early Intervention With an Electronic Specialist-Led Model of Diabetes Care
Authors: Rahul D. Barmanray, Mervyn Kyi, Peter G. Colman, Lois Rowan, Mayurapriya Raviskanthan, Lucy Collins, Laura Donaldson, Stephanie Montalto, Joshua Tsan, Emily Sun, Minh Le, Leon J. Worth, Benjamin Thomson, Spiros Fourlanos
Journal: Diabetes Care (2024)

To investigate the effect of early intervention with an electronic specialist-led "proactive" model of care on glycemic and clinical outcomes.
Tumor-associated macrophage (TAM)-secreted CCL22 confers cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells via regulating the activity of diacylglycerol kinase α (DGKα)/NOX4 axis
Authors: Jie Chen, Di Zhao, Lingyuan Zhang, Jing Zhang, Yuanfan Xiao, Qingnan Wu, Yan Wang, Qimin Zhan
Journal: Drug Resistance Updates (2024)
Use of nitrogen in US execution may constitute torture, warns human rights agency
Authors: Jacqui Wise
Journal: BMJ (2024)

The UN human rights office has called on authorities in the US state of Alabama to halt the planned execution of a man by nitrogen hypoxia saying the "novel and untested method" could amount to torture under international human rights law. 1 Kenneth Eugene Smith, aged 57, was convicted for a murder for hire committed in 1988.He is scheduled to be executed by nitrogen hypoxia on 25 January.He survived a botched attempt to execute him by lethal injection in 2022 after staff failed to establish a proper intravenous line. 1 OHCHR.Execution by nitrogen asphyxiation in Alabama.January 2024.www.ohchr.