tbuckley/cabot-search huggingface dataset:
A novel stratification scheme combined with internal arteries in CT imaging for guiding postoperative adjuvant transarterial chemoembolization in hepatocellular carcinoma: a retrospective cohort study
Authors: Xinming Li, Xiangjing Liang, Zhipeng Li, Jianye Liang, Zhendong Qi, Liming Zhong, Zhijun Geng, Wen Liang, Xianyue Quan, Changhong Liang, Zaiyi Liu
Journal: International Journal of Surgery (2024)

Background: Although postoperative adjuvant transarterial chemoembolization (PA-TACE) improves survival outcomes in a subset of patients with resected hepatocellular carcinoma (HCC), the lack of reliable biomarkers for patient selection remains a significant challenge. The present study aimed to evaluate whether computed tomography (CT) imaging can provide more value for predicting benefits from PA-TACE and to establish a new scheme for guiding PA-TACE benefits. Methods: In this retrospective study, patients with HCC who had undergone preoperative contrast-enhanced CT and curative hepatectomy were evaluated. Inverse probability of treatment weight was performed to balance the difference of baseline characteristics. Cox models were used to test the interaction among PA-TACE, imaging features and pathological indicators. An HCC imaging and pathological classification (HIPC) scheme incorporating these imaging and pathological indicators was established. Results: This study included 1,488 patients (median age, 52 y [IQR, 45–61 y]; 1,309 male). Microvascular invasion (MVI) positive, and diameter&gt;5 cm tumors achieved a higher recurrence-free survival (RFS), and overall survival (OS) benefit, respectively, from PA-TACE than MVI negative, and diameter ≤5 cm tumors. Patients with internal arteries (IA) positive benefited more than those with IA negative in terms of RFS ( P =0.016) and OS ( P =0.018). PA-TACE achieved significant RFS and OS improvements in HIPC3 (IA present and diameter, or two or three tumors) patients but not in HIPC1 (diameter ≤5 cm, MVI negative) and HIPC2 (other single tumor) patients. Our scheme may decrease the number of patients receiving PA-TACE by approximately 36.5% compared to the previous suggestion. Conclusions: IA can provide more value for predicting the benefit of PA-TACE treatment. The proposed HIPC scheme can be used to stratify patients with and without survival benefits from PA-TACE.
Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation
Authors: Eric A. Thim, Lydia E. Kitelinger, Fátima Rivera-Escalera, Alexander S. Mathew, Michael R. Elliott, Timothy N. J. Bullock, Richard J. Price
Journal: Theranostics (2024)

Background: Boiling histotripsy (BH), a mechanical focused ultrasound ablation strategy, can elicit intriguing signatures of anti-tumor immunity.However, the influence of BH on dendritic cell function is unknown, compromising our ability to optimally combine BH with immunotherapies to control metastatic disease.Methods: BH was applied using a sparse scan (1 mm spacing between sonications) protocol to B16F10-ZsGreen melanoma in bilateral and unilateral settings.Ipsilateral and contralateral tumor growth was measured.Flow cytometry was used to track ZsGreen antigen and assess how BH drives dendritic cell behavior.Results: BH monotherapy elicited ipsilateral and abscopal tumor control in this highly aggressive model.Tumor antigen presence in immune cells in the tumor-draining lymph nodes (TDLNs) was ~3-fold greater at 24h after BH, but this abated by 96h.B cells, macrophages, monocytes, granulocytes, and both conventional dendritic cell subsets (i.e.cDC1s and cDC2s) acquired markedly more antigen with BH.BH drove activation of both cDC subsets, with activation being dependent upon tumor antigen acquisition.Our data also suggest that BH-liberated tumor antigen is complexed with damage-associated molecular patterns (DAMPs) and that cDCs do not traffic to the TDLN with antigen.Rather, they acquire antigen as it flows through afferent lymph vessels into the TDLN.Conclusion: When applied with a sparse scan protocol, BH monotherapy elicits abscopal melanoma control and shapes dendritic cell function through several previously unappreciated mechanisms.These results offer new insight into how to best combine BH with immunotherapies for the treatment of metastatic melanoma.
Adaptive Selection of Cis-regulatory Elements in the Han Chinese
Authors: Shuai Liu, Huaxia Luo, Peng Zhang, Yanyan Li, Di Hao, Sijia Zhang, Tingrui Song, Tao Xu, Shunmin He
Journal: Molecular Biology and Evolution (2024)

Abstract Cis-regulatory elements have an important role in human adaptation to the living environment. However, the lag in population genomic cohort studies and epigenomic studies, hinders the research in the adaptive analysis of cis-regulatory elements in human populations. In this study, we collected 4,013 unrelated individuals and performed a comprehensive analysis of adaptive selection of genome-wide cis-regulatory elements in the Han Chinese. In total, 12.34% of genomic regions are under the influence of adaptive selection, where 1.00% of enhancers and 2.06% of promoters are under positive selection, and 0.06% of enhancers and 0.02% of promoters are under balancing selection. Gene ontology enrichment analysis of these cis-regulatory elements under adaptive selection reveals that many positive selections in the Han Chinese occur in pathways involved in cell–cell adhesion processes, and many balancing selections are related to immune processes. Two classes of adaptive cis-regulatory elements related to cell adhesion were in-depth analyzed, one is the adaptive enhancers derived from neanderthal introgression, leads to lower hyaluronidase level in skin, and brings better performance on UV-radiation resistance to the Han Chinese. Another one is the cis-regulatory elements regulating wound healing, and the results suggest the positive selection inhibits coagulation and promotes angiogenesis and wound healing in the Han Chinese. Finally, we found that many pathogenic alleles, such as risky alleles of type 2 diabetes or schizophrenia, remain in the population due to the hitchhiking effect of positive selections. Our findings will help deepen our understanding of the adaptive evolution of genome regulation in the Han Chinese.
Spirohypertones A and B as potent antipsoriatics: Tumor necrosis factor-α inhibitors with unprecedented chemical architectures
Authors: Yulin Duan, Weiguang Sun, Yongqi Li, Zhengyi Shi, Lanqin Li, Yeting Zhang, Kun Huang, Zhiping Zhang, Changxing Qi, Yonghui Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

Tumor necrosis factor-α (TNF-α) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A (1) and B (2), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from Hypericum patulum. The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism calculations. Importantly, 2 showed remarkable TNF-α inhibitory activity, which could protect L929 cells from death induced by co-incubation with TNF-α and actinomycin D. It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α. Notably, in an imiquimod-induced psoriasis murine model, 2 restrained symptoms of epidermal hyperplasia associated with psoriasis, presenting anti-inflammatory and antiproliferative effects. This discovery positions 2 as a potent TNF-α inhibitor, providing a promising lead compound for developing an antipsoriatic agent.
Colibactin-producing <i>Escherichia coli</i> enhance resistance to chemotherapeutic drugs by promoting epithelial to mesenchymal transition and cancer stem cell emergence
Authors: Guillaume Dalmasso, Antony Cougnoux, Tiphanie Faïs, Virginie Bonnin, Benoit Mottet-Auselo, Hang TT Nguyen, Pierre Sauvanet, Nicolas Barnich, Marine Jary, Denis Pezet, Julien Delmas, Richard Bonnet
Journal: Gut Microbes (2024)

Human colorectal cancers (CRCs) are readily colonized by colibactin-producing E. coli (CoPEC). CoPEC induces DNA double-strand breaks, DNA mutations, genomic instability, and cellular senescence. Infected cells produce a senescence-associated secretory phenotype (SASP), which is involved in the increase in tumorigenesis observed in CRC mouse models infected with CoPEC. This study investigated whether CoPEC, and the SASP derived from CoPEC-infected cells, impacted chemotherapeutic resistance. Human intestinal epithelial cells were infected with the CoPEC clinical 11G5 strain or with its isogenic mutant, which is unable to produce colibactin. Chemotherapeutic resistance was assessed in vitro and in a xenograft mouse model. Expressions of cancer stem cell (CSC) markers in infected cells were investigated. Data were validated using a CRC mouse model and human clinical samples. Both 11G5-infected cells, and uninfected cells incubated with the SASP produced by 11G5-infected cells exhibited an increased resistance to chemotherapeutic drugs in vitro and in vivo. This finding correlated with the induction of the epithelial to mesenchymal transition (EMT), which led to the emergence of cells exhibiting CSC features. They grew on ultra-low attachment plates, formed colonies in soft agar, and overexpressed several CSC markers (e.g. CD133, OCT-3/4, and NANOG). In agreement with these results, murine and human CRC biopsies colonized with CoPEC exhibited higher expression levels of OCT-3/4 and NANOG than biopsies devoid of CoPEC. Conclusion: CoPEC might aggravate CRCs by inducing the emergence of cancer stem cells that are highly resistant to chemotherapy.
Abortion Restrictions and the Child Welfare System
Authors: Feng Li, Kai Liu
Journal: JAMA Pediatrics (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Ultrasensitive Detection of Circulating Tumour DNA enriches for Patients with a Greater Risk of Recurrence of Clinically Localised Prostate Cancer
Authors: Bernard Pope, Gahee Park, Edmund Lau, Jelena Belic, Radoslaw Lach, Anne George, Patrick McCoy, Anne Nguyen, Corrina Grima, Bethany Campbell, Chol-hee Jung, Emma-Jane Ditter, Hui Zhao, David C. Wedge, Daniel S. Brewer, Andy G. Lynch, Harveer Dev, Vincent J. Gnanpragasam, Nitzan Rosenfeld, Christopher M. Hovens, Niall M. Corcoran, Charles E. Massie
Journal: European Urology (2024)
Ethics and Terminology for Opting In and Out
Authors: Malea Joyce, Mark S. Segal, Ashutosh M. Shukla
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Probiotic <i>Lactobacillus</i> spp. improves <i>Drosophila</i> memory by increasing lactate dehydrogenase levels in the brain mushroom body neurons
Authors: Shuk-Man Ho, Wan-Hua Tsai, Chih-Ho Lai, Meng-Hsuan Chiang, Wang-Pao Lee, Hui-Yu Wu, Pei-Yi Bai, Tony Wu, Chia-Lin Wu
Journal: Gut Microbes (2024)

Probiotics are live microorganisms that offer potential benefits to their hosts and can occasionally influence behavioral responses. However, the detailed mechanisms by which probiotics affect the behavior of their hosts and the underlying biogenic effects remain unclear. Lactic acid bacteria, specifically Lactobacillus spp. are known probiotics. Drosophila melanogaster, commonly known as the fruit fly, is a well-established model organism for investigating the interaction between the host and gut microbiota in translational research. Herein, we showed that 5-day administration of Lactobacillus acidophilus (termed GMNL-185) or Lacticaseibacillus rhamnosus (termed GMNL-680) enhances olfactory-associative memory in Drosophila. Moreover, a combined diet of GMNL-185 and GMNL-680 demonstrated synergistic effects on memory functions. Live brain imaging revealed a significant increase in calcium responses to the training odor in the mushroom body β and γ lobes of flies that underwent mixed feeding with GMNL-185 and GMNL-680. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and whole-mount brain immunohistochemistry revealed significant upregulation of lactate dehydrogenase (LDH) expression in the fly brain following the mixed feeding. Notably, the genetic knockdown of Ldh in neurons, specifically in mushroom body, ameliorated the beneficial effects of mixed feeding with GMNL-185 and GMNL-680 on memory improvement. Altogether, our results demonstrate that supplementation with L. acidophilus and L. rhamnosus enhances memory functions in flies by increasing brain LDH levels.
Automated cardiac arrest detection using a photoplethysmography wristband: algorithm development and validation in patients with induced circulatory arrest in the DETECT-1 study
Authors: Roos Edgar, Niels T B Scholte, Kambiz Ebrahimkheil, Marc A Brouwer, Rypko J Beukema, Masih Mafi-Rad, Kevin Vernooy, Sing-Chien Yap, Eelko Ronner, Nicolas van Mieghem, Eric Boersma, Peter C Stas, Niels van Royen, Judith L Bonnes
Journal: The Lancet Digital Health (2024)

Unwitnessed out-of-hospital cardiac arrest is associated with low survival chances because of the delayed activation of the emergency medical system in most cases. Automated cardiac arrest detection and alarming using biosensor technology would offer a potential solution to provide early help. We developed and validated an algorithm for automated circulatory arrest detection using wrist-derived photoplethysmography from patients with induced circulatory arrests.
Optimal strategies to improve uptake of and adherence to HIV prevention among young people at risk for HIV acquisition in the USA (ATN 149): a randomised, controlled, factorial trial
Authors: Dallas Swendeman, Mary Jane Rotheram-Borus, Elizabeth Mayfield Arnold, Maria Isabel Fernández, Walter Scott Comulada, Sung-Jae Lee, Manuel A Ocasio, Kelsey Ishimoto, William Gertsch, Naihua Duan, Cathy J Reback, Debra A Murphy, Katherine A Lewis, Sue Ellen Abdalian, Robert Bolan, Yvonne Bryson, Ruth Cortado, Risa Flynn, Tara Kerin, Jeffrey Klausner, Marguerita Lightfoot, Norweeta Milburn, Karin Nielsen, Wilson Ramos, Wenze Tang, Panteha Hayati Rezvan, Robert E. Weiss
Journal: The Lancet Digital Health (2024)

Pre-exposure prophylaxis (PrEP), condom use, post-exposure prophylaxis (PEP), and sexual partner reduction help to prevent HIV acquisition but have low uptake among young people. We aimed to assess the efficacy of automated text messaging and monitoring, online peer support, and strengths-based telehealth coaching to improve uptake of and adherence to PrEP, condom use, and PEP among adolescents aged 12-24 years at risk of HIV acquisition in Los Angeles, CA, USA, and New Orleans, LA, USA.
Clinical Interviewing: An Essential but Neglected Method of Medicine
Authors: Giovanni A Fava, Nicoletta Sonino, David C Aron, Richard Balon, Carmen Berrocal Montiel, Jianxin Cao, John Concato, Ajandek Eory, Ralph I Horwitz, Chiara Rafanelli, Ulrich Schnyder, Hongxing Wang, Thomas N Wise, Jesse H Wright, Stephan Zipfel, Chiara Patierno
Journal: Psychotherapy and Psychosomatics (2024)

Clinical interviewing is the basic method to understand how a person feels and what are the presenting complaints, obtain medical history, evaluate personal attitudes and behavior related to health and disease, give the patient information about diagnosis, prognosis, and treatment, and establish a bond between patient and physician that is crucial for shared decision making and self-management. However, the value of this basic skill is threatened by time pressures and emphasis on technology. Current health care trends privilege expensive tests and procedures and tag the time devoted to interaction with the patient as lacking cost-effectiveness. Instead, the time spent to inquire about problems and life setting may actually help to avoid further testing, procedures, and referrals. Moreover, the dialogue between patient and physician is an essential instrument to increase patient's motivation to engage in healthy behavior. The aim of this paper was to provide an overview of clinical interviewing and its optimal use in relation to style, flow and hypothesis testing, clinical domains, modifications according to settings and goals, and teaching. This review points to the primacy of interviewing in the clinical process. The quality of interviewing determines the quality of data that are collected and, eventually, of assessment and treatment. Thus, interviewing deserves more attention in educational training and more space in clinical encounters than it is currently receiving.
PABPC1L Induces IDO1 to Promote Tryptophan Metabolism and Immune Suppression in Renal Cell Carcinoma
Authors: Guannan Shu, Minyu Chen, Wuyuan Liao, Liangmin Fu, Mingjie Lin, Chengpeng Gui, Junjie Cen, Jun Lu, Zhenhua Chen, Jinhuan Wei, Wei Chen, Yinghan Wang, Jiangquan Zhu, Tianxin Zhao, Xiaonan Liu, Jiajia Jing, Guo-chang Liu, Yihui Pan, Junhang Luo, Jiaxing Zhang
Journal: Cancer Research (2024)

The tumor microenvironment (TME) in renal cell carcinomas (RCC) is marked by substantial immunosuppression and immune resistance despite having extensive T-cell infiltration. Elucidation of the mechanisms underlying immune evasion could help identify therapeutic strategies to boost the efficacy of immune checkpoint blockade (ICB) in RCC. This study uncovered a mechanism wherein the polyadenylate-binding protein PABPC1L modulates indoleamine 2,3-dioxygenase 1 (IDO1), a prospective target for immunotherapy. PABPC1L was markedly upregulated in RCC, and high PABPC1L expression correlated with unfavorable prognosis and resistance to ICB. PABPC1L bolstered tryptophan metabolism by upregulating IDO1, inducing T-cell dysfunction and Treg infiltration. PABPC1L enhanced the stability of JAK2 mRNA, leading to increased JAK2-STAT1 signaling that induced IDO1 expression. Additionally, PABPC1L-induced activation of the JAK2-STAT1 axis created a positive feedback loop to promote PABPC1L transcription. Conversely, loss of PABPC1L diminished IDO1 expression, mitigated cytotoxic T-cell suppression, and enhanced responsiveness to anti-PD-1 therapy in patient-derived xenograft models. These findings reveal the crucial role of PABPC1L in facilitating immune evasion in RCC and indicate that inhibiting PABPC1L could be a potential immunotherapeutic approach in combination with ICB to improve patient outcomes.
Advancing Second-Line Treatment for Primary Biliary Cholangitis
Authors: David N Assis
Journal: New England Journal of Medicine (2024)

Primary biliary cholangitis is a chronic cholestatic, autoimmune disease characterized by the destruction of small, intrahepatic biliary epithelial cells.1 If left untreated, primary biliary cholangitis can result in liver failure and death. Patients with primary biliary cholangitis also have debilitating symptoms, notably pruritus and fatigue. Effective treatment is essential to prevent disease progression and, ideally, also improve quality of life. The number of patients with primary biliary cholangitis on transplantation waiting lists has decreased by half over the past two decades,2 owing mainly to the use of ursodeoxycholic acid, which remains the first-line treatment for this disease. Treatment success is . . .
Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera
Authors: Marina Kremyanskaya, Andrew T Kuykendall, Naveen Pemmaraju, Ellen K Ritchie, Jason Gotlib, Aaron Gerds, Jeanne Palmer, Kristen Pettit, Uttam K Nath, Abdulraheem Yacoub, Arturo Molina, Samuel R Saks, Nishit B Modi, Frank H Valone, Sarita Khanna, Suneel Gupta, Srdan Verstovsek, Yelena Z Ginzburg, Ronald Hoffman
Journal: New England Journal of Medicine (2024)

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown.
CD19 CAR T-Cell Therapy in Autoimmune Disease — A Case Series with Follow-up
Authors: Fabian Müller, Jule Taubmann, Laura Bucci, Artur Wilhelm, Christina Bergmann, Simon Völkl, Michael Aigner, Tobias Rothe, Ioanna Minopoulou, Carlo Tur, Johannes Knitza, Soraya Kharboutli, Sascha Kretschmann, Ingrid Vasova, Silvia Spoerl, Hannah Reimann, Luis Munoz, Roman G. Gerlach, Simon Schäfer, Ricardo Grieshaber-Bouyer, Anne-Sophie Korganow, Dominique Farge-Bancel, Dimitrios Mougiakakos, Aline Bozec, Thomas Winkler, Gerhard Krönke, Andreas Mackensen, Georg Schett
Journal: New England Journal of Medicine (2024)

Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission.
A Prospective, Single-Arm, Phase 2 Study of Modified Transarterial Chemoembolization Using Low-Dose Chemotherapy with Blank Microspheres Plus Low-Dose Lenvatinib and Microwave Ablation in Patients with Large (≥7 cm) Unresectable Hepatocellular Carcinoma: The TALEM Trial
Authors: Zhi-Mei Huang, Xue Han, Jian Wang, Ling Gu, Lu Tang, Shao-Yong Wu, Tian Di, Ying-Wen Hou, Wan Yee Lau, Yi-Quan Jiang, Jin-Hua Huang
Journal: Liver Cancer (2024)

For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (cTACE) remains suboptimal. This study investigated the efficacy and safety of modified TACE using low-dose chemotherapy with blank microspheres (BMS-TACE) plus low-dose lenvatinib (LD-LEN) and microwave ablation (MWA) in patients with large unresectable HCC.