tbuckley/cabot-search huggingface dataset:
Long-term behavioral symptom clusters among survivors of early-stage breast cancer. development and validation of a predictive model
Authors: Martina Pagliuca, Julie Havas, Emilie Thomas, Youenn Drouet, Davide Soldato, Maria Alice Franzoi, Joana Ribeiro, Camila K Chiodi, Emma Gillanders, Barbara Pistilli, Gwenn Menvielle, Florence Joly, Florence Lerebours, Olivier Rigal, Thierry Petit, Sylvie Giacchetti, Florence Dalenc, Johanna Wassermann, Olivier Arsene, Anne Laure Martin, Sibille Everhard, Olivier Tredan, Sandrine Boyault, Michelino De Laurentiis, Alain Viari, Jean Francois Deleuze, Aurelie Bertaut, Fabrice André, Ines Vaz-Luis, Antonio Di Meglio
Journal: JNCI Journal of the National Cancer Institute (2024)

Fatigue, cognitive impairment, anxiety, depression, and sleep disturbance are cancer-related behavioral symptoms (CRBS) that may persist years after early-stage breast cancer (BC), affecting quality of life. We aimed at generating a predictive model of long-term CRBS clusters among BC survivors four years post-diagnosis.
The National Cancer Institute Clinical Trials Planning Meeting to Address Gaps in Observational and Intervention Trials for Cancer-Related Cognitive Impairment
Authors: Michelle C Janelsins, Kathleen Van Dyk, Sheri J Hartman, Thuy T Koll, Christina K Cramer, Glenn J Lesser, Debra L Barton, Karen M Mustian, Lynne I Wagner, Patricia A Ganz, Peter D Cole, Alexis Bakos, James C Root, Kristina Hardy, Allison Magnuson, Robert J Ferguson, Brenna C McDonald, Andrew J Saykin, Brian D Gonzalez, Jeffrey S Wefel, David A Morilak, Saurabh Dahiya, Cobi J Heijnen, Yvette P Conley, Alicia K Morgans, Donald Mabbott, Michelle Monje, Stephen R Rapp, Vinai Gondi, Catherine Bender, Leanne Embry, Worta McCaskill Stevens, Judith O Hopkins, Diane St. Germain, Susan G Dorsey
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Cancer-related cognitive impairment is a broad term encompassing subtle cognitive problems to more severe impairment. The severity of this impairment is influenced by host, disease, and treatment factors, and the impairment affects patients before, during, and following cancer treatment. The National Cancer Institute (NCI) Symptom Management and Health-Related Quality of Life Steering Committee (SxQoL SC) convened a clinical trial planning meeting to review the state of the science on cancer-related cognitive impairment and develop phase II/III intervention trials aimed at improving cognitive function in cancer survivors with non–central nervous system disease and longitudinal studies to understand the trajectory of cognitive impairment and contributing factors. Participants included experts in the field of cancer-related cognitive impairment, members of the SxQoL SC, patient advocates, representatives from all 7 NCI Community Oncology Research Program research bases, and the NCI. Presentations focused on the following topics: measurement, lessons learned from pediatric and geriatric oncology, biomarker and mechanism endpoints, longitudinal study designs, and pharmacological and behavioral intervention trials. Panel discussions provided guidance on priority cognitive assessments, considerations for remote assessments, inclusion of relevant biomarkers, and strategies for ensuring broad inclusion criteria. Three clinical trial planning meeting working groups (longitudinal studies as well as pharmacological and behavioral intervention trials) convened for 1 year to discuss and report on top priorities and to design studies. The meeting experts concluded that sufficient data exist to advance phase II/III trials using selected pharmacological and behavioral interventions for the treatment of cancer-related cognitive impairment in the non–central nervous system setting, with recommendations included herein.
A Practical Guide to Using Oral JAK Inhibitors for Atopic Dermatitis from the International Eczema Council
Authors: Carter Haag, Andrew Alexis, Valeria Aoki, Robert Bissonnette, Andrew Blauvelt, Raj Chovatiya, Michael J Cork, Simon G Danby, Lawrence Eichenfield, Kilian Eyerich, Melinda Gooderham, Emma Guttman-Yassky, Dirk-Jan Hijnen, Alan Irvine, Norito Katoh, Dedee F Murrell, Yael A Leshem, Adriane Levin, Ida Vittrup, Jill I Olydam, Raquel L Orfali, Amy Paller, Yael Renert-Yuval, David Rosmarin, Jonathan Silverberg, Jacob Thyssen, Sonja Ständer, Nick Stefanovic, Gail Todd, JiaDe Yu, Eric Simpson
Journal: British Journal of Dermatology (2024)

Janus kinase inhibitors (JAKinibs) have the potential to dramatically alter the landscape of atopic dermatitis (AD) management due to their promising efficacy results from phase 3 trials and rapid onset of action. However, JAKinibs are not without risk, and their use is not appropriate for all AD patients, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD.
Lower survival for surgical treatment of HPV-related oropharynx cancer at community cancer centers
Authors: Danielle R Trakimas, Wojciech K Mydlarz, Leila J Mady, Christine G Gourin, Wayne Koch, Nyall R London, Harry Quon, Ana P Kiess, Tanguy Y Seiwert, Carole Fakhry
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background The rate of primary surgery for human papillomavirus-related oropharynx cancer (HPVOPC) has recently declined, while utilization of transoral robotic surgery (TORS) has lagged at community cancer centers (CCs). We hypothesize that differences in overall survival (OS) exist between patients undergoing surgery for HPVOPC at CCs and low (&amp;lt;15 TORS/year; LVACs) and high (≥15 TORS/year; HVACS) TORS volume academic centers. Methods Cases from the US National Cancer Database with a diagnosis of HPVOPC from 2010-2019 that underwent primary surgical treatment were included. Trends in TORS utilization, rates of positive surgical margins (PMs), quality of adjuvant treatment and 5-year OS were compared between CCs, LVACs and HVACs. Results 5,406 cases met study criteria. A significantly lower proportion of cases at CCs utilized TORS than at LVACs or HVACs (26.2% vs 44.0% vs 73.9%, respectively, p &amp;lt; .001). The rate of PMs was significantly higher at CCs than at LVACs or HVACs (25.7% vs 15.3% vs 9.2%, p &amp;lt; .001). A greater proportion of cases undergoing adjuvant radiotherapy (RT) received prolonged courses (23.6% vs 13.1% vs 8.8%, p &amp;lt; .001) or excessive doses (16.5% vs 11.5% vs 8.7%, p &amp;lt; .001) of RT at CCs than at LVACs or HVACs, respectively. 5-year OS was lowest at CCs (85.2%, 95%CI: 81.7-88.2%), intermediate at LVACs (88.9%, 95%CI: 87.2-90.4%), and highest at HVACs (91.4%, 95%CI: 89.5-92.9%; pLR&amp;lt;0.01). Conclusions Significant differences in the type and quality of surgical and adjuvant treatment for HPVOPC exist between facility types based on TORS volume. Overall survival was lowest at CCs, intermediate at LVACs and highest at HVACs.
RBM25 is required to restrain inflammation via ACLY RNA splicing-dependent metabolism rewiring
Authors: Yunkai Zhang, Ying Gao, Yujia Wang, Yuyu Jiang, Yan Xiang, Xiaohui Wang, Zeting Wang, Yingying Ding, Huiying Chen, Bing Rui, Wanwan Huai, Boyu Cai, Xiaomeng Ren, Feng Ma, Sheng Xu, Zhenzhen Zhan, Xingguang Liu
Journal: Cellular and Molecular Immunology (2024)
Central role for cholangiocyte pathobiology in cholestatic liver diseases
Authors: Nidhi Jalan-Sakrikar, Maria Eugenia Guicciardi, Steven P. O’Hara, Adiba Azad, Nicholas F. LaRusso, Gregory J. Gores, Robert C. Huebert
Journal: Hepatology (2024)

Cholangiopathies comprise a spectrum of chronic intra- and extrahepatic biliary tract disorders culminating in progressive cholestatic liver injury, fibrosis and often cirrhosis and its sequela. Treatment for these diseases is limited and collectively they are one of the therapeutic “black boxes” in clinical hepatology. The etiopathogenesis of the cholangiopathies likely includes disease-specific mediators, but also common cellular and molecular events driving disease progression (e.g., cholestatic fibrogenesis, inflammation, and duct damage). The common pathways involve cholangiocytes, the epithelial cells lining the intrahepatic and extrahepatic bile ducts, which are central to the pathogenesis of these disorders. Current information suggests that cholangiocytes function as a signaling “hub” in biliary tract-associated injury. Herein, we review the pivotal role of cholangiocytes in cholestatic fibrogenesis, focusing on crosstalk between cholangiocytes and portal fibroblasts and hepatic stellate cells. The proclivity of these cells to undergo a senescence-associated secretory phenotype which is pro-inflammatory and –fibrogenic, and the intrinsic intracellular activation pathways resulting in secretion of cytokines and chemokines is reviewed. The crosstalk between cholangiocytes and cells of the innate (neutrophils and macrophages), and adaptive (T-cells and B-cells) immune systems is also examined in detail. The information will help consolidate information on this topic, guide further research and potential therapeutic strategies for these diseases.
Author Correction: Harnessing the power of longitudinal medical imaging for eye disease prognosis using Transformer-based sequence modeling
Authors: Gregory Holste, Mingquan Lin, Ruiwen Zhou, Fei Wang, Lei Liu, Qi Yan, Sarah H Van Tassel, Kyle Kovacs, Emily Y Chew, Zhiyong Lu, Zhangyang Wang, Yifan Peng
Journal: npj Digital Medicine (2024)
Efficacy and safety of infliximab in patients with autoimmune hepatitis
Authors: Cumali Efe, Ellina Lytvyak, Tuğçe Eşkazan, Rodrigo Liberal, Theodoros Androutsakos, Dilara Turan Gökçe, Benedetta Terziroli Beretta-Piccoli, Maciej Janik, Christine Bernsmeier, Pinelopi Arvaniti, Piotr Milkiewicz, Ersin Batibay, Osman Yüksekyayla, Ilkay Ergenç, Çiğdem Arikan, Albert F. Stättermayer, Sezgin Barutçu, Mustafa Cengiz, Özlem Gül, Alexandra Heurgue, Michael A. Heneghan, Sumita Verma, Tuğrul Purnak, Murat Törüner, Meral Akdogan Kayhan, Ibrahim Hatemi, Kalliopi Zachou, Guilherme Macedo, Joost P. H. Drenth, Einar Björnsson, Aldo J. Montano-Loza, Staffan Wahlin, Fatima Higuera-de la Tijera
Journal: Hepatology (2024)

Background and Aims: A limited number of drugs are used as standard or alternative therapies in autoimmune hepatitis (AIH). No specific recommendations are available for patients failing to respond to these therapies. We analyzed the efficacy and safety of infliximab in patients with AIH. Approach and Results: We performed a retrospective study of 42 patients with AIH who received infliximab at 21 liver centers in 12 countries. Patients were categorized according to the reason for infliximab therapy. Patients in group 1 (n=20) had failed standard, second-line (mycophenolate mofetil and 6-mercaptopurine) or third-line (tacrolimus or cyclosporine) therapy. In group 2 (n=22), infliximab was given for treatment of concomitant extrahepatic autoimmune diseases. Patients received a median of 17 (range: 3–104) infliximab infusions. Complete biochemical response (CR) was achieved or maintained in 33 (78%) patients during infliximab therapy. In group 1, infliximab induced CR in 11 of 20 (55%) patients. In group 2, 16 patients with CR prior to infliximab maintained remission, and the remaining 6 patients with active AIH (5 on standard and 1 on both second-line and third-line therapy) showed CR following infliximab therapy. Infliximab led to CR in 75% (6/8) of nonresponders to second-line and in 46% (6/13) of failing third-line therapy. Overall, 65% (17/26) of the patients with active AIH achieved CR on infliximab. Infliximab was discontinued in 3 patients of group 1. One patient had a severe allergic reaction and 2 developed anti-infliximab autoantibodies. Conclusions: Our study suggests that infliximab may be an effective and safe rescue therapy in AIH.
Health-Related quality of life (HRQL) assessments in a 52-Week, Double-Blind, randomized, Placebo-Controlled phase 3 study of resmetirom (MGL-3196) in patients with metabolic dysfunction associated steatohepatitis (MASH) and fibrosis
Authors: Zobair M. Younossi, Maria Stepanova, Andrei Racila, Linda Henry, Dominic Labriola, Rebecca Taub, Fatema Nader
Journal: Hepatology (2024)

Background/Aims: Resmetirom, liver directed thyroid-hormone receptor-β agonist, received approval for MASH treatment. We assessed HRQL in MASH patients treated with resmetirom. Methods: Non-cirrhotic MASH/NASH patients with confirmed/suspected fibrosis were enrolled in a 54-month double-blind randomized placebo-controlled Phase 3 clinical trial with serial biopsy assessments (MAESTRO-NASH, NCT03900429) at baseline and Week 52. HRQL was assessed using Chronic Liver Disease Questionnaire-NASH (CLDQ-NAFLD) and Liver Disease Quality of Life (LDQOL). Baseline HRQL score changes by treatment group (resmetirom 80 mg, resmetirom 100 mg or placebo) and histological response (improvement of fibrosis without worsening of NAS or resolution of MASH/NASH without worsening of fibrosis) were compared after 52 weeks. Results: Included were 966 ITT patients: 323 received resmetirom 100 mg, 322 resmetirom 80 mg, 321 placebo. By weeks 24 and 52, patients receiving 80 or 100 mg resmetirom experienced HRQL improvement CLDQ-NAFLD worry domain (mean +0.21 to +0.24, p &lt;0.05). At week 52, subjects who met histologic endpoints after treatment with resmetirom (100 mg and 80 mg pooled) experienced HRQL improvement in CLDQ-NAFLD Worry +0.46 (41% met MCID), LDQOL domains: Role Emotional +3.0 (28% met MCID), Health Distress +8.1 (38% MCID), Stigma +3.5 (39% MCID) and total LDQOL +2.2 (35% MCID) (all p &lt;0.05). Similar improvements noted in histologic responders from 100 mg or 80 mg resmetirom groups when separated- no improvements in placebo or nonresponders. Baseline F3 histologic responders had similar/more pronounced HRQL improvements. Conclusions: MASH/NASH patients with fibrosis improvement or resolution of MASH with resmetirom experienced clinically meaningful and statistically significant HRQL improvements.
Stretch-induced hepatic endothelial mechanocrine promotes hepatocyte proliferation
Authors: Yi Wu, Linda Li, Wang Li, Ning Li, Xiaoyu Zhang, Lu Zheng, Shaoyu Zhong, Shouqin Lü, Xinyu Shu, Jin Zhou, Ding Ai, Ming Gao, Sijin Liu, Dongyuan Lü, Mian Long
Journal: Hepatology (2024)

Background &amp; Aims: Partial hepatectomy (PHx)-induced liver regeneration causes the increase in relative blood flow rate within the liver, which dilates hepatic sinusoids and applies mechanical stretch on liver sinusoidal endothelial cells (LSECs). Heparin-binding EGF-like growth factor (HB-EGF) is a crucial growth factor during liver regeneration. We aimed to investigate whether this sinusoidal dilation-induced stretch promotes HB-EGF secretion in LSECs and what the related molecular mechanism is. Approach &amp; Results: In vivo PHx, ex vivo liver perfusion and in vitro LSEC mechanical stretch were applied to detect HB-EGF expression in LSECs and hepatocyte proliferation. Knockdown or inhibition of mechanosensitive proteins were used to unravel the molecular mechanism in response to stretch. This stretch triggers amplitude- and duration-dependent HB-EGF up-regulation in LSECs, which is mediated by Yes-associated protein (YAP) nuclear translocation and binding to TEAD. This YAP translocation is achieved in two ways: On one hand, F-actin polymerization-mediated expansion of nuclear pores promotes YAP entry into nucleus passively. On the other hand, F-actin polymerization up-regulates the expression of BAG family molecular chaperone regulator 3 (BAG-3), which binds with YAP to enter nucleus cooperatively. In this process, β1-integrin serves as a target mechanosensory in stretch-induced signaling pathways. This HB-EGF secretion-promoted liver regeneration after 2/3 PHx is attenuated in endothelial cell-specific Yap1 -deficient mice. Conclusions: Our findings indicate that mechanical stretch-induced HB-EGF up-regulation in LSECs via YAP translocation can promote the hepatocyte proliferation during liver regeneration through a mechanocrine manner, which deepens the understanding of the mechanical-biological coupling in liver regeneration.
ctDNA dynamics and mechanisms of acquired resistance in patients treated with osimertinib with or without bevacizumab from the randomised phase II ETOP-BOOSTER trial
Authors: Ross A. Soo, Urania Dafni, Ji-Youn Han, Byoung Chul Cho, Ernest Nadal, Chong Ming Yeo, Enric Carcereny, Javier de Castro, Maria Angeles Sala, Linda Coate, Mariano Provencio, Christian Britschgi, Patrick Vagenknecht, Georgia Dimopoulou, Roswitha Kammler, Stephen P. Finn, Solange Peters, Rolf A. Stahel
Journal: Clinical Cancer Research (2024)

Abstract Background: ETOP 10-16 BOOSTER study was a randomised phase II trial of osimertinib and bevacizumab versus osimertinib in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously. Methods: Next generation sequencing (Guardant360®) was conducted in serial plasma samples. The association between ctDNA and efficacy outcomes was explored and molecular alterations at progression were described. Results: 136 patients (88% of 155 randomised) had plasma samples at baseline (68 per arm), 110 (71%) at week 9 and 65 (42%) at progression. In a multivariable model for progression-free survival (PFS), the treatment effect was found different by smoking status (interaction p=0.046), with the effect of smoking also different by baseline EGFR T790M (interaction p=0.033), while both TP53 at baseline and tissue EGFR Exon 21 L858R mutation were significantly associated with worse PFS outcome. Smokers (current/former) without baseline EGFR T790M showed a significant improvement in PFS under combination treatment, albeit with small numbers (p=0.015). Week-9 EGFR T790M clearance was associated with improved PFS in the osimertinib arm (p=0.0097). Acquired EGFR C797S mutations were detected in 22% and 13% of patients in the combination and osimertinib arm, respectively. Conclusions: The differential effect of treatment by smoking was not explained by TP53 mutation or other molecular alterations examined. Molecular mechanisms of acquired resistance were detected but no novel molecular alterations were identified in the combination arm.
HKDC1 promotes liver cancer stemness under hypoxia through stabilizing β-catenin
Authors: Li Fan, Cheng Tian, Wentao Yang, Xiaoli Liu, Yogesh Dhungana, Wenjian Yang, Haiyan Tan, Evan S. Glazer, Jiyang Yu, Junmin Peng, Lichun Ma, Min Ni, Liqin Zhu
Journal: Hepatology (2024)

Background and Aims: Hexokinases (HKs), a group of enzymes catalyzing the first step of glycolysis, have been shown to play important roles in liver metabolism and tumorigenesis. Our recent studies identified hexokinase domain containing 1 (HKDC1) as a top candidate associated with liver cancer metastasis. We aimed to compare its cell-type specificity with other HKs upregulated in liver cancer and investigate the molecular mechanisms underlying its involvement in liver cancer metastasis. Approach and Results: We found that, compared to HK1 and HK2, the other 2 commonly upregulated HKs in liver cancer, HKDC1 was most strongly associated with the metastasis potential of tumors and organoids derived from 2 liver cancer mouse models we previously established. RNA in situ hybridization and single-cell RNA-seq analysis revealed that HKDC1 was specifically upregulated in malignant cells in HCC and cholangiocarcinoma patient tumors, whereas HK1 and HK2 were widespread across various tumor microenvironment lineages. An unbiased metabolomic profiling demonstrated that HKDC1 overexpression in HCC cells led to metabolic alterations distinct from those from HK1 and HK2 overexpression, with HKDC1 particularly impacting the tricarboxylic acid cycle. HKDC1 was prometastatic in HCC orthotopic and tail vein injection mouse models. Molecularly, HKDC1 was induced by hypoxia and bound to glycogen synthase kinase 3β to stabilize β-catenin, leading to enhanced stemness of HCC cells. Conclusions: Overall, our findings underscore HKDC1 as a prometastatic HK specifically expressed in the malignant compartment of primary liver tumors, thereby providing a mechanistic basis for targeting this enzyme in advanced liver cancer.
Targeting Fibrinolytic Inhibition for Venous Thromboembolism Treatment: Overview of an Emerging Therapeutic Approach
Authors: Satish Singh, Pardeep Kumar, Yogendra S. Padwad, Farouc A. Jaffer, Guy L. Reed
Journal: Circulation (2024)

Venous thrombosis and pulmonary embolism (venous thromboembolism) are important causes of morbidity and mortality worldwide. In patients with venous thromboembolism, thrombi obstruct blood vessels and resist physiological dissolution (fibrinolysis), which can be life threatening and cause chronic complications. Plasminogen activator therapy, which was developed &gt;50 years ago, is effective in dissolving thrombi but has unacceptable bleeding risks. Safe dissolution of thrombi in patients with venous thromboembolism has been elusive despite multiple innovations in plasminogen activator design and catheter-based therapy. Evidence now suggests that fibrinolysis is rigidly controlled by endogenous fibrinolysis inhibitors, including α2-antiplasmin, plasminogen activator inhibitor-1, and thrombin-activable fibrinolysis inhibitor. Elevated levels of these fibrinolysis inhibitors are associated with an increased risk of venous thromboembolism in humans. New therapeutic paradigms suggest that accelerated and effective fibrinolysis may be achieved safely by therapeutically targeting these fibrinolytic inhibitors in venous thromboembolism. In this article, we discuss the role of fibrinolytic components in venous thromboembolism and the current status of research and development targeting fibrinolysis inhibitors.
Effects of a self-guided digital mental health self-help intervention for Syrian refugees in Egypt: A pragmatic randomized controlled trial
Authors: Sebastian Burchert, Mhd Salem Alkneme, Ammar Alsaod, Pim Cuijpers, Eva Heim, Jonas Hessling, Nadine Hosny, Marit Sijbrandij, Edith Van't Hof, Pieter Ventevogel, Christine Knaevelsrud
Journal: PLoS Medicine (2024)

Digital mental health interventions for smartphones, such as the World Health Organization (WHO) Step-by-Step (SbS) program, are potentially scalable solutions to improve access to mental health and psychosocial support in refugee populations. Our study objective was to evaluate the effectiveness of SbS as self-guided intervention with optional message-based contact-on-demand (COD) support on reducing psychological distress, functional impairment, symptoms of posttraumatic stress disorder (PTSD), and self-identified problems in a sample of Syrian refugees residing in Egypt.
Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial
Authors: Baohui Han, Trevor Feinstein, Yuankai Shi, Gongyan Chen, Yu Yao, Chunhong Hu, Jianhua Shi, Jifeng Feng, Huijuan Wu, Ying Cheng, Qi-Sen Guo, Zhijun Jie, Feng Ye, Yiping Zhang, Zhihua Liu, Weidong Mao, Liangming Zhang, Junguo Lu, Jun Zhao, Lyudmila Bazhenova, Jimmy Ruiz, Goetz H Kloecker, Kalmadi R Sujith, Ira A Oliff, Matthew Wong, Bin Liu, Yanping Wu, Lan Huang, Yan Sun
Journal: The Lancet Respiratory Medicine (2024)