tbuckley/cabot-search huggingface dataset:
Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking
Authors: Man-Xiu Xie, Ren-Chun Lai, Yi-Bin Xiao, Xi Zhang, Xian-Ying Cao, Xiao-Yu Tian, An-Nan Chen, Zi-Yi Chen, Yan Cao, Xiao Li, Xiao-Long Zhang
Journal: Military Medical Research (2024)

Abstract Background Tactile and mechanical pain are crucial to our interaction with the environment, yet the underpinning molecular mechanism is still elusive. Endophilin A2 (EndoA2) is an evolutionarily conserved protein that is documented in the endocytosis pathway. However, the role of EndoA2 in the regulation of mechanical sensitivity and its underlying mechanisms are currently unclear. Methods Male and female C57BL/6 mice (8–12 weeks) and male cynomolgus monkeys (7–10 years old) were used in our experiments. Nerve injury-, inflammatory-, and chemotherapy-induced pathological pain models were established for this study. Behavioral tests of touch, mechanical pain, heat pain, and cold pain were performed in mice and nonhuman primates. Western blotting, immunostaining, co-immunoprecipitation, proximity ligation and patch-clamp recordings were performed to gain insight into the mechanisms. Results The results showed that EndoA2 was primarily distributed in neurofilament-200-positive (NF200 + ) medium-to-large diameter dorsal root ganglion (DRG) neurons of mice and humans. Loss of EndoA2 in mouse NF200 + DRG neurons selectively impaired the tactile and mechanical allodynia. Furthermore, EndoA2 interacted with the mechanically sensitive ion channel Piezo2 and promoted the membrane trafficking of Piezo2 in DRG neurons. Moreover, as an adaptor protein, EndoA2 also bound to kinesin family member 5B (KIF5B), which was involved in the EndoA2-mediated membrane trafficking process of Piezo2. Loss of EndoA2 in mouse DRG neurons damaged Piezo2-mediated rapidly adapting mechanically activated currents, and re-expression of EndoA2 rescued the MA currents. In addition, interference with EndoA2 also suppressed touch sensitivity and mechanical hypersensitivity in nonhuman primates. Conclusions Our data reveal that the KIF5B/EndoA2/Piezo2 complex is essential for Piezo2 trafficking and for sustaining transmission of touch and mechanical hypersensitivity signals. EndoA2 regulates touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking in sensory neurons. Our findings identify a potential new target for the treatment of mechanical pain.
Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?
Authors: Silvia Uccella
Journal: Endocrine Pathology (2024)

Abstract In the last two decades, the increasing availability of technologies for molecular analyses has allowed an insight in the genomic alterations of neuroendocrine neoplasms (NEN) of the gastrointestinal tract and pancreas. This knowledge has confirmed, supported, and informed the pathological classification of NEN, clarifying the differences between neuroendocrine carcinomas (NEC) and neuroendocrine tumors (NET) and helping to define the G3 NET category. At the same time, the identification genomic alterations, in terms of gene mutation, structural abnormalities, and epigenetic changes differentially involved in the pathogenesis of NEC and NET has identified potential molecular targets for precision therapy. This review critically recapitulates the available molecular features of digestive NEC and NET, highlighting their correlates with pathological aspects and clinical characteristics of these neoplasms and revising their role as predictive biomarkers for targeted therapy. In this context, the feasibility and applicability of a molecular classification of gastrointestinal and pancreatic NEN will be explored.
Sorafenib vs. Lenvatinib in advanced hepatocellular carcinoma after atezolizumab/bevacizumab failure: A real-world study
Authors: Young Eun Chon, Dong Yun Kim, Mi Na Kim, Beom Kyung Kim, Seung Up Kim, Jun Yong Park, Sang Hoon Ahn, Yeonjung Ha, Joo Ho Lee, Kwan Sik Lee, Beodeul Kang, Jung Sun Kim, Hong Jae Chon, Do Young Kim
Journal: Clinical and Molecular Hepatology (2024)

Atezolizumab plus bevacizumab (ATE+BEV) therapy has become the recommended first-line therapy for patients with unresectable hepatocellular carcinoma (HCC) because of favorable treatment responses. However, there is a lack of data on sequential regimens after ATE+BEV treatment failure. We aimed to investigate the clinical outcomes of patients with advanced HCC who received subsequent systemic therapy for disease progression after ATE+BEV. This multicenter, retrospective study included patients who started second-line systemic treatment with sorafenib or lenvatinib after HCC progressed on ATE+BEV between August 2019 and December 2022. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.). Clinical features of the two groups were balanced through propensity score (PS) matching. This study enrolled 126 patients, 40 (31.7%) in the lenvatinib group, and 86 (68.3%) in the sorafenib group. The median age was 63 years, and males were predominant (88.1%). In PS-matched cohorts (36 patients in each group), the objective response rate was similar between the lenvatinib- and sorafenib-treated groups (5.6% vs. 8.3%; P=0.643), but the disease control rate was superior in the lenvatinib group (66.7% vs. 22.2%; P<0.001). Despite the superior progression- free survival (PFS) in the lenvatinib group (3.5 vs. 1.8 months, P=0.001), the overall survival (OS, 10.3 vs. 7.5 months, P=0.353) did not differ between the two PS-matched treatment groups. In second-line therapy for unresectable HCC after ATE+BEV failure, lenvatinib showed better PFS and comparable OS to sorafenib in a real-world setting. Future studies with larger sample sizes and longer follow-ups are needed to optimize second-line treatment.
Impact of clonal hematopoiesis of indeterminate potential on hepatocellular carcinoma in individuals with steatotic liver disease
Authors: Alfredo Marchetti, Serena Pelusi, Alessio Marella, Francesco Malvestiti, Antony Ricchiuti, Luisa Ronzoni, Marta Lionetti, Vittoria Moretti, Elisabetta Bugianesi, Luca Miele, Umberto Vespasiani-Gentilucci, Paola Dongiovanni, Alessandro Federico, Giorgio Soardo, Roberta D’Ambrosio, Misti V. McCain, Helen L. Reeves, Vincenzo La Mura, Daniele Prati, Niccolò Bolli, Luca Valenti
Journal: Hepatology (2024)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global epidemic and is the most rapidly rising cause of HCC. Clonal hematopoiesis of indeterminate potential (CHIP) contributes to neoplastic and cardiometabolic disorders and is considered a harbinger of tissue inflammation. CHIP was recently associated with increased risk of liver disease. The aim of this study was to examine whether CHIP is associated with HCC development in patients with SLD.
Epstein-Barr virus gp42 antibodies reveal sites of vulnerability for receptor binding and fusion to B cells
Authors: Wei Bu, Ashish Kumar, Nathan L. Board, JungHyun Kim, Kennichi Dowdell, Shu Zhang, Yona Lei, Anna Hostal, Tammy Krogmann, Yanmei Wang, Stefania Pittaluga, Joseph Marcotrigiano, Jeffrey I. Cohen
Journal: Immunity (2024)
TRIM29 facilitates gemcitabine resistance via MEK/ERK pathway and is modulated by circRPS29/miR-770–5p axis in PDAC
Authors: Wenjie Huang, Xiaojun Hu, Xiang He, Dongyue Pan, Zhaorong Huang, Zhanfeng Gu, Guobing Huang, Ping Wang, Chunhui Cui, Yingfang Fan
Journal: Drug Resistance Updates (2024)
Systematic endoscopic staging of mediastinum to guide radiotherapy planning in patients with locally advanced non-small-cell lung cancer (SEISMIC): an international, multicentre, single-arm, clinical trial
Authors: Daniel P Steinfort, Gargi Kothari, Neil Wallace, Nicholas Hardcastle, Kanishka Rangamuwa, Edith M T Dieleman, Percy Lee, Peixuan Li, Julie A Simpson, Shaun Yo, Farzad Bashirdazeh, Phan Nguyen, Barton R Jennings, David Fielding, Laurence Crombag, Louis B Irving, Kazuhiro Yasufuku, Jouke T Annema, David E Ost, Shankar Siva
Journal: The Lancet Respiratory Medicine (2024)
The Difference Between Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rate and Risk of Diabetic Microvascular Complications Among Adults With Diabetes: A Population-Based Cohort Study
Authors: Daijun He, Bixia Gao, Jinwei Wang, Chao Yang, Ming-Hui Zhao, Luxia Zhang
Journal: Diabetes Care (2024)

OBJECTIVE The impact of the difference between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFRdiff) on diabetic microvascular complications (DMCs) remains unknown. We investigated the associations of eGFRdiff with overall DMCs and subtypes, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic neuropathy (DN). RESEARCH DESIGN AND METHODS This prospective cohort study included 25,825 participants with diabetes free of DMCs at baseline (2006 to 2010) from the UK Biobank. eGFRdiff was calculated using both absolute difference (eGFRabdiff) and the ratio (eGFRrediff) between cystatin C- and creatinine-based calculations. Incidence of DMCs was ascertained using electronic health records. Cox proportional hazards regression models were used to evaluate the associations of eGFRdiff with overall DMCs and subtypes. RESULTS During a median follow-up of 13.6 years, DMCs developed in 5,753 participants, including 2,752 cases of DR, 3,203 of DKD, and 1,149 of DN. Each SD decrease of eGFRabdiff was associated with a 28% higher risk of overall DMCs, 14% higher risk of DR, 56% higher risk of DKD, and 29% higher risk of DN. For each 10% decrease in eGFRrediff, the corresponding hazard ratios (95% CIs) were 1.16 (1.14, 1.18) for overall DMCs, 1.08 (1.05, 1.11) for DR, 1.29 (1.26, 1.33) for DKD, and 1.17 (1.12, 1.22) for DN. The magnitude of associations was not materially altered in any of the sensitivity analyses. CONCLUSIONS Large eGFRdiff was independently associated with risk of DMCs and its subtypes. Our findings suggested monitoring eGFRdiff in the diabetes population has potential benefit for identification of high-risk patients.
Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS
Authors: Changchang Xu, Lin Zhang, Shaoyu Xu, Zichen Wang, Qi Han, Ying Lv, Xingfang Wang, Xiangxin Zhang, Qingju Zhang, Ying Zhang, Simeng He, Qiuhuan Yuan, Yuan Bian, Chuanbao Li, Jiali Wang, Feng Xu, Yihai Cao, Jiaojiao Pang, Yuguo Chen
Journal: Cellular and Molecular Immunology (2024)
Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy
Authors: Jonathan E. Rosenberg, Ronac Mamtani, Guru P. Sonpavde, Yohann Loriot, Ignacio Duran, Jae-Lyun Lee, Nobuaki Matsubara, Christof Vulsteke, Daniel Castellano, Srikala S. Sridhar, Helle Pappot, Howard Gurney, Jens Bedke, Michiel S. van der Heijden, Luca Galli, Bhumsuk Keam, Naoya Masumori, Johannes Meran, Peter H. O'Donnell, Se Hoon Park, Enrique Grande, Lisa Sengeløv, Hiroji Uemura, Konstantina Skaltsa, Mary Campbell, Maria Matsangou, Chunzhang Wu, Zsolt Hepp, Caroline McKay, Thomas Powles, Daniel P. Petrylak
Journal: European Urology (2024)

In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL). For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation. We analyzed the QLQ-C30 change from baseline to week 12, the confirmed improvement rate, and the time to improvement or deterioration. Baseline PRO compliance rates were 91% for the EV arm (n = 301) and 89% for the chemotherapy arm (n = 307); the corresponding average rates from baseline to week 12 were 70% and 67%. Patients receiving EV versus chemotherapy had reduced pain (difference in change from baseline to week 12: −5.7, 95% confidence interval [CI] −10.8 to −0.7; p = 0.027) and worsening appetite loss (7.3, 95% CI 0.90–13.69; p = 0.026). Larger proportions of patients in the EV arm reported HRQoL improvement from baseline than in the chemotherapy arm; the odds of a confirmed improvement across ten QLQ-C30 function/symptom scales were 1.67 to 2.76 times higher for EV than for chemotherapy. Patients in the EV arm had a shorter time to first confirmed improvement in global health status (GHS)/QoL, fatigue, pain, and physical, role, emotional, and social functioning (all p < 0.05). EV delayed the time to first confirmed deterioration in GHS/QoL (p = 0.027), but worsening appetite loss occurred earlier (p = 0.009) in comparison to chemotherapy. HRQoL with EV was maintained, and deterioration in HRQoL was delayed with EV in comparison to chemotherapy. Better results with EV were reported for some scales, with the greatest difference observed for pain. These findings reinforce the EV safety and efficacy outcomes and benefits observed in EV-301. Patients with previously treated advanced cancer of the urinary tract receiving the drug enfortumab vedotin maintained their HRQoL in comparison to patients treated with chemotherapy. The EV-301 trial is registered on ClinicalTrials.gov as NCT03474107 and on EudraCT as 2017-003344-21.
Retrospective analysis of multiple myeloma drug use in cutaneous toxicity of monoclonal gammopathy of undetermined significance
Authors: Emily R. Gordon, Caroline Chen, Oluwaseyi Adeuyan, Brigit A. Lapolla, Megan H. Trager, Lauren M. Fahmy, Celine M. Schreidah, David A. Wetter, Larisa J. Geskin
Journal: Journal of the American Academy of Dermatology (2024)
Why are not all eligible chronic myeloid leukemia patients willing to attempt tyrosine kinase inhibitor discontinuation? A Czech nationwide analysis related to the TKI stopping trial HALF
Authors: Daniela Žáčková, Lukáš Semerád, Edgar Faber, Hana Klamová, Lukáš Stejskal, Petra Bělohlávková, Michal Karas, Eduard Cmunt, Olga Černá, Jiřina Procházková, Petra Čičátková, Anežka Kvetková, Tomáš Horňák, Ivana Skoumalová, Dana Srbová, Cyril Šálek, David Buffa, Jaroslava Voglová, Tomáš Jurček, Adam Folta, Ivana Ježíšková, Hana Žižková, Kateřina Machová Poláková, Tomáš Papajík, Pavel Žák, Pavel Jindra, Adam Svobodník, Radka Štěpánová, Jiří Mayer
Journal: Leukemia (2024)
Allogeneic haematopoietic cell transplantation for advanced systemic mastocytosis: Best practice recommendations on behalf of the EBMT Practice Harmonisation and Guidelines Committee
Authors: Donal P. McLornan, Tomasz Czerw, Gandhi Damaj, Mark Ethell, Carmelo Gurnari, Juan Carlos Hernández-Boluda, Nicola Polverelli, Juliana Schwaab, Katja Sockel, Greco Raffaella, Francesco Onida, Isabel Sánchez-Ortega, Giorgia Battipaglia, Chiara Elena, Jason Gotlib, Andreas Reiter, Julien Rossignol, Celalettin Ustun, Peter Valent, Ibrahim Yakoub-Agha, Deepti H. Radia
Journal: Leukemia (2024)
Compression from a retroperitoneal schwannoma presenting as a subepithelial lesion of the gastric fundus
Authors: Xue-Mei Lin, Juan Liu, Chun-Hui Xi, Jun Wang, Guo-Dong Yang, Xian-Fei Wang, Cong Yuan
Journal: Endoscopy (2024)

Gastric subepithelial lesions (SELs) are frequently incidental findings encountered during endoscopy. The lesions may originate from any layer of the gastric wall and sometimes arise from compression by extraluminal structures [1]. Schwannomas are nerve sheath tumors that seldom occur in the retroperitoneal region, comprising only 4% of all retroperitoneal tumors and 3% of all schwannomas [2]. Herein, we present a case of retroperitoneal schwannoma compressing the gastric fundus and presenting as a protruding subepithelial mass.
Endoscopic repair of duodenal fistula occurring as a rare complication of abdominal drainage following partial hepatectomy
Authors: Ruide Liu, Xianglei Yuan, Xinyue Zhou, Qianyi Deng, Bing Hu
Journal: Endoscopy (2024)

The placement of abdominal drainage tubes is a standard procedure following abdominal surgery [1] [2]. Here, we present a case of duodenal fistula caused by drainage tubes following partial hepatectomy.
Patient, family caregiver, and economic outcomes of an integrated screening and novel stepped collaborative care intervention in the oncology setting in the USA (CARES): a randomised, parallel, phase 3 trial
Authors: Jennifer L Steel, Charles J George, Lauren Terhorst, Jonathan G Yabes, Vincent Reyes, Dan P Zandberg, Marci Nilsen, Gauri Kiefer, Jonas Johnson, Christopher Marsh, Jason Bierenbaum, Nishant Tageja, Michal Krauze, Robert VanderWeele, Gaurav Goel, Gopala Ramineni, Michael Antoni, Yoram Vodovotz, Jon Walker, Samer Tohme, Timothy Billiar, David A Geller
Journal: The Lancet (2024)
The gout epidemic in French Polynesia: a modelling study of data from the Ma’i u’u epidemiological survey
Authors: Tristan Pascart, Kaja A Wasik, Cristian Preda, Valérie Chune, Jérémie Torterat, Nicolas Prud’homme, Maryline Nassih, Agathe Martin, Julien Le Masson, Vahinetua Rodière, Sylvain Frogier, Georges Canova, Jean-Paul Pescheux, Charles Shan Sei Fan, Charlotte Jauffret, Patrick Claeys, Sarah LeBaron von Baeyer, Stephane E Castel, Anne-Katrin Emde, Laura Yerges-Armstrong, Keolu Fox, Megan Leask, Jean-Jacques Vitagliano, Sahara Graf, Laurène Norberciak, Jacques Raynal, Nicola Dalbeth, Tony Merriman, Thomas Bardin, Erwan Oehler
Journal: The Lancet Global Health (2024)

Gout is the most common cause of inflammatory arthritis worldwide, particularly in Pacific regions. We aimed to establish the prevalence of gout and hyperuricaemia in French Polynesia, their associations with dietary habits, their comorbidities, the prevalence of the HLA-B*58:01 allele, and current management of the disease.
Aminoglycosides, deafness, and non-tuberculous mycobacteria
Authors: Francis Drobniewski, Marcia Ashmi, Changchunzi He, Jamie Cheong, Anand Shah
Journal: The Lancet Global Health (2024)

Kavita Prasad and colleagues' study1 addressing the global burden of deafness is very timely, particularly preventable causes related to anti-infective therapies (32·4 million cases per annum). Appropriate aminoglycoside prescribing is essential for individual clinical benefit, to reduce ototoxicity and, more broadly, to reduce the development of antimicrobial resistance.
Prevalence of subclinical pulmonary tuberculosis in adults in community settings: an individual participant data meta-analysis
Authors: Logan Stuck, Eveline Klinkenberg, Nahid Abdelgadir Ali, Egbal Ahmed Basheir Abukaraig, Yaw Adusi-Poku, Zeleke Alebachew Wagaw, Razia Fatima, Nathan Kapata, Pascalina Kapata-Chanda, Bruce Kirenga, Llang B Maama-Maime, Sayoki G Mfinanga, Sizulu Moyo, Lindiwe Mvusi, Ndahafa Nandjebo, Hai Viet Nguyen, Hoa Binh Nguyen, Joshua Obasanya, Bashorun Adedapo Olufemi, Philip Patrobas Dashi, Thato J Raleting Letsie, Nunurai Ruswa, Elizeus Rutebemberwa, Mbazi Senkoro, Tieng Sivanna, Huot Chan Yuda, Irwin Law, Ikushi Onozaki, Edine Tiemersma, Frank Cobelens, Jane Ruth Aceng, Ifedayo Adetifa, Phonaly Chittamani, Donekham Inthavong, Farzanah Ismail, Moses Joloba, Simon Kasozi, Harriet Kisembo, Martie Van der Merwe, Nkateko Mkhondo, Joanita Nalunjogi, Sakhone Sutepmani
Journal: The Lancet Infectious Diseases (2024)
Mortality in patients admitted to hospital with heart failure in China: a nationwide Cardiovascular Association Database-Heart Failure Centre Registry cohort study
Authors: Hua Wang, Yingying Li, Ke Chai, Zheng Long, Zhikai Yang, Minghui Du, Shengfeng Wang, Siyan Zhan, Yujia Liu, Yuhao Wan, Fang Wang, Peng Yin, Weimin Li, Yuhua Liao, Yugang Dong, Xinli Li, Jingmin Zhou, Kai-Hang Yiu, Maigeng Zhou, Yong Huo, Jiefu Yang
Journal: The Lancet Global Health (2024)

BackgroundChina has the largest burden of heart failure worldwide. However, large-scale studies on heart failure mortality are scarce. We aimed to investigate mortality and identify risk factors for mortality among patients with heart failure in China.MethodsThis prospective cohort study used data from the China Cardiovascular Association (CCA) Database-Heart Failure Centre Registry, which were linked to the National Mortality Registration Information Management System by the Chinese Centre for Disease Control and Prevention. We included patients enrolled from Jan 1, 2017, to Dec 31, 2021, across 572 CCA Database-Heart Failure Centre certified hospitals in 31 provinces of mainland China. Eligible patients were aged 18 years or older (younger than 100 years) with a principal discharge diagnosis of heart failure based on Chinese heart failure guidelines. All-cause mortality at 30 days, 1 year, and 3 years for patients with heart failure were calculated and the causes of death were recorded. Multivariable analysis was used to analyse factors associated with all-cause mortality and cardiovascular mortality. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2200066305.FindingsOf the 327 477 patients in the registry, 230 637 eligible adults with heart failure were included in our analyses. Participant mean age was 69·3 years (SD 13·2), 94 693 (41·1%) participants were female, and 135 944 (58·9%) were male. The median follow-up time was 531 days (IQR 251–883). Post-discharge all-cause mortality of patients with heart failure at 30 days was 2·4% (95% CI 2·3–2·5), at 1 year was 13·7% (13·5–13·9), and at 3 years was 28·2% (27·7–28·6). Cardiovascular death accounted for 32 906 (71·5%) of 46 006 all-cause deaths. Patients with heart failure with reduced ejection fraction had the highest all-cause mortality. A lower guideline adherence score was independently associated with the increase of all-cause and cardiovascular mortality.InterpretationIn China, mortality for patients with heart failure is still high, especially in patients with reduced ejection fraction. Our findings suggest that guideline-directed medical therapy needs to be improved.FundingNational High Level Hospital Clinical Research Funding, the Capital's Funds for Health Improvement and Research, and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences.TranslationFor the Chinese translation of the abstract see Supplementary Materials section.
Outcomes of heart failure: gaps in knowledge and needs for action
Authors: Yi Wu, Xi Li
Journal: The Lancet Global Health (2024)

Heart failure is a substantial health concern, affecting 64 million people globally.1 In China, it is estimated that the number of patients with heart failure has reached 8·9 million.2 Furthermore, the burden of heart failure is expected to increase as a result of the rapidly ageing population and the growing prevalence of cardiometabolic disorders. Therefore, it is crucial to have a comprehensive understanding of the health outcomes of heart failure and the factors that influence them.