tbuckley/cabot-search huggingface dataset:
Evaluation of large language models in breast cancer clinical scenarios: a comparative analysis based on ChatGPT-3.5, ChatGPT-4.0, and Claude2
Authors: Linfang Deng, Tianyi Wang, None Yangzhang, Zhenhua Zhai, Wei Tao, Jincheng Li, Yi Zhao, Shaoting Luo, Jinjiang Xu
Journal: International Journal of Surgery (2024)

Background Large language models (LLMs) have garnered significant attention in the AI domain owing to their exemplary context recognition and response capabilities. However, the potential of LLMs in specific clinical scenarios, particularly in breast cancer diagnosis, treatment, and care, has not been fully explored. This study aimed to compare the performances of three major LLMs in the clinical context of breast cancer. Methods In this study, clinical scenarios designed specifically for breast cancer were segmented into five pivotal domains (nine cases): assessment and diagnosis, treatment decision-making, postoperative care, psychosocial support, and prognosis and rehabilitation. The LLMs were used to generate feedback for various queries related to these domains. For each scenario, a panel of five breast cancer specialists, each with over a decade of experience, evaluated the feedback from LLMs. They assessed feedback concerning LLMs in terms of their quality, relevance, and applicability. Results There was a moderate level of agreement among the raters ( Fleiss’ kappa =0.345, P &lt;0.05). Comparing the performance of different models regarding response length, GPT-4.0 and GPT-3.5 provided relatively longer feedback than Claude2. Furthermore, across the nine case analyses, GPT-4.0 significantly outperformed the other two models in average quality, relevance, and applicability. Within the five clinical areas, GPT-4.0 markedly surpassed GPT-3.5 in the quality of the other four areas and scored higher than Claude2 in tasks related to psychosocial support and treatment decision-making. Conclusion This study revealed that in the realm of clinical applications for breast cancer, GPT-4.0 showcases not only superiority in terms of quality and relevance but also demonstrates exceptional capability in applicability, especially when compared to GPT-3.5. Relative to Claude2, GPT-4.0 holds advantages in specific domains. With the expanding use of LLMs in the clinical field, ongoing optimization and rigorous accuracy assessments are paramount.
An Efficient Closed-Loop Adaptive Controller for a Small-Sized Quadruped Robotic Rat
Authors: Xiaolong Quan, Rongjie Du, Ruochao Wang, Zhenshan Bing, Qing Shi
Journal: Cyborg and Bionic Systems (2024)

Large quadruped robots have shown potential for a wide range of everyday tasks due to their superior terrain adaptation. However, small-scale quadruped robots have limited payloads and thus cannot carry sufficient sensing and computational resources, which imposes limitations on their environmental adaptability. To address this challenge, we proposed an efficient closed-loop adaptive controller by simplified pose estimation and control strategy that utilizes only inertial measurement unit sensors, which drastically reduces the control computation. Accordingly, we integrated this control system into a small-scale quadruped robot, SQuRo, and conducted a series of experiments to verify the environmental adaptation performance of SQuRo. The results demonstrated that SQuRo has achieved 6 kinds of robust motion: slope stabilization motion, linear tracking motion, autonomous fall recovery motion, uneven terrain walk, slope walk, and obstacle avoidance. This work paves the way for small-scale quadruped robots to autonomously perform tasks in challenging environments.
Pediatric Cholestatic Diseases: Common and Unique Pathogenic Mechanisms
Authors: Harry Sutton, Saul J. Karpen, Binita M. Kamath
Journal: Annual Review of Pathology Mechanisms of Disease (2024)

Cholestasis is the predominate feature of many pediatric hepatobiliary diseases. The physiologic flow of bile requires multiple complex processes working in concert. Bile acid (BA) synthesis and excretion, the formation and flow of bile, and the enterohepatic reuptake of BAs all function to maintain the circulation of BAs, a key molecule in lipid digestion, metabolic and cellular signaling, and, as discussed in the review, a crucial mediator in the pathogenesis of cholestasis. Disruption of one or several of these steps can result in the accumulation of toxic BAs in bile ducts and hepatocytes leading to inflammation, fibrosis, and, over time, biliary and hepatic cirrhosis. Biliary atresia, progressive familial intrahepatic cholestasis, primary sclerosing cholangitis, and Alagille syndrome are four of the most common pediatric cholestatic conditions. Through understanding the commonalities and differences in these diseases, the important cellular mechanistic underpinnings of cholestasis can be greater appreciated.
Re: Pramit Khetrapal, Joanna Kae Ling Wong, Wei Phin Tan, et al. Robot-assisted Radical Cystectomy Versus Open Radical Cystectomy: A Systematic Review and Meta-analysis of Perioperative, Oncological, and Quality of Life Outcomes Using Randomized Controlled Trials. Eur Urol 2023;84:393–405
Authors: Philipp Dahm, Onuralp Ergun, Niranjan Sathianathen
Journal: European Urology (2024)
Advancing equity in human genomics through tissue-specific multi-ancestry molecular data
Authors: Ana Luiza Arruda, Andrew P. Morris, Eleftheria Zeggini
Journal: Cell Genomics (2024)

There is a pressing need to generate molecular data from diverse tissues across global populations. These currently missing data are necessary to resolve genome-wide association study loci, identify effector genes, and move the translational genomics needle beyond European-ancestry individuals and the minority of diseases for which blood is the relevant tissue.
Parallel control of cold-triggered adipocyte thermogenesis by UCP1 and CKB
Authors: Janane F. Rahbani, Jakub Bunk, Damien Lagarde, Bozena Samborska, Anna Roesler, Haopeng Xiao, Abhirup Shaw, Zafir Kaiser, Jessica L. Braun, Mia S. Geromella, Val A. Fajardo, Robert A. Koza, Lawrence Kazak
Journal: Cell Metabolism (2024)
Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy
Authors: Serena Jasmine Aleo, Valentina Del Dotto, Martina Romagnoli, Claudio Fiorini, Giada Capirossi, Camille Peron, Alessandra Maresca, Leonardo Caporali, Mariantonietta Capristo, Concetta Valentina Tropeano, Claudia Zanna, Fred N. Ross-Cisneros, Alfredo A. Sadun, Maria Gemma Pignataro, Carla Giordano, Chiara Fasano, Andrea Cavaliere, Anna Maria Porcelli, Gaia Tioli, Francesco Musiani, Alessia Catania, Costanza Lamperti, Stefania Bianchi Marzoli, Annamaria De Negri, Maria Lucia Cascavilla, Marco Battista, Piero Barboni, Michele Carbonelli, Giulia Amore, Chiara La Morgia, Dmitrii Smirnov, Catalina Vasilescu, Aiman Farzeen, Beryll Blickhaeuser, Holger Prokisch, Claudia Priglinger, Bettina Livonius, Claudia B. Catarino, Thomas Klopstock, Valeria Tiranti, Valerio Carelli, Anna Maria Ghelli
Journal: Cell Reports Medicine (2024)

Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% of patients, but we can neither predict nor understand the non-responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound heterozygous. This hampers idebenone reduction. In its oxidized form, idebenone inhibits complex I, decreasing respiratory function in cells. By retrospectively analyzing a large cohort of idebenone-treated LHON patients, classified by their response to therapy, we show that patients with homozygous or compound heterozygous NQO1 variants have the poorest therapy response, particularly if carrying the m.3460G>A/MT-ND1 LHON mutation. These results suggest consideration of patient NQO1 genotype and mitochondrial DNA mutation in the context of idebenone therapy.
Tetrahedral DNA loaded siCCR2 restrains M1 macrophage polarization to ameliorate pulmonary fibrosis in chemoradiation-induced murine model
Authors: Chen Li, Xiaorong Feng, Songhang Li, Xing He, Zeli Luo, Xia Cheng, Jie Yao, Jie Xiao, Xiaofei Wang, Dingke Wen, Duanya Liu, Yanfei Li, Hong Zhou, Lu Ma, Tongyu Lin, Xiaoxiao Cai, Yunfeng Lin, Lu Guo, Mu Yang
Journal: Molecular Therapy (2024)

Idiopathic pulmonary fibrosis (IPF) is a chronic lethal disease in the absence of demonstrated efficacy for preventing progression. Although macrophage-mediated alveolitis is determined to participate in myofibrotic transition during disease development, the paradigm of continuous macrophage polarization is still under-explored due to lack of proper animal models. Here, by integrating 2.5 U/kg intratracheal Bleomycin administration and 10 Gy thorax irradiation at day 7, we generated a murine model with continuous alveolitis-mediated fibrosis, which mimics most of the clinical features of our involved IPF patients. In combination with data from scRNA-seq of patients and a murine IPF model, a decisive role of CCL2/CCR2 axis in driving M1 macrophage polarization was revealed, and M1 macrophage was further confirmed to boost alveolitis in leading myofibroblast activation. Multiple sticky-end tetrahedral framework nucleic acids conjunct with quadruple ccr2-siRNA (FNA-siCCR2) was synthesized in targeting M1 macrophages. FNA-siCCR2 successfully blocked macrophage accumulation in pulmonary parenchyma of the IPF murine model, thus preventing myofibroblast activation and leading to the disease remitting. Overall, our studies lay the groundwork to develop a novel IPF murine model, reveal M1 macrophages as potential therapeutic targets, and establish new treatment strategy by using FNA-siCCR2, which are highly relevant to clinical scenarios and translational research in the field of IPF.
Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study
Authors: Amin H. Nassar, So Yeon Kim, Jacqueline V. Aredo, Jamie Feng, Frances Shepherd, Chao Xu, David Kaldas, Jhanelle E. Gray, Thomas J. Dilling, Joel W. Neal, Heather A. Wakelee, Yufei Liu, Steven H. Lin, Tariq Abuali, Arya Amini, Yunan Nie, Tejas Patil, Anastasiya Lobachov, Jair Bar, Bailey Fitzgerald, Yu Fujiwara, Thomas U. Marron, Rohit Thummalapalli, Helena Yu, Dwight H. Owen, John Sharp, Saira Farid, Pedro Rocha, Edurne Arriola, Angelica D’Aiello, Haiying Cheng, Ryan Whitaker, Kaushal Parikh, Yash Ashara, Luxi Chen, Kamya Sankar, Jeremy P. Harris, Misako Nagasaka, Adanma Ayanambakkam, Ana I. Velazquez, Meera Ragavan, Jessica J. Lin, Zofia Piotrowska, Molly Wilgucki, Joshua Reuss, Heike Luders, Christian Grohe, Javier Baena Espinar, Ella Feiner, Salman R. Punekar, Shruti Gupta, Ticiana Leal, David J. Kwiatkowski, Raymond H. Mak, Elio Adib, Abdul Rafeh Naqash, Sarah B. Goldberg
Journal: Journal of Thoracic Oncology (2024)
Long-Term Efficacy and Tolerability of PCSK9 Targeted Therapy: A Review of the Literature
Authors: Willemijn A. M. Schonck, Erik S. G. Stroes, G. Kees Hovingh, Laurens F. Reeskamp
Journal: Drugs (2024)

Increased plasma levels of low-density lipoprotein cholesterol (LDL-C) are causally associated with atherosclerotic cardiovascular disease (ASCVD), and statins that lower LDL-C have been the cornerstone of ASCVD prevention for decades. However, guideline-recommended LDL-C targets are not achieved in about 60% of statin users. Proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapy effectively lowers LDL-C levels and has been shown to reduce ASCVD risk. A growing body of scientific and clinical evidence shows that PCSK9-targeted therapy offers an excellent safety and tolerability profile with a low incidence of side effects in the short term. In this review, we present and discuss the current clinical and scientific evidence pertaining to the long-term efficacy and tolerability of PCSK9-targeted therapy.
Diurnal Rhythms in the Red Seaweed <i>Gracilariopsis chorda</i> are Characterized by Unique Regulatory Networks of Carbon Metabolism
Authors: JunMo Lee, Ji Hyun Yang, Andreas P M Weber, Debashish Bhattacharya, Woe-Yeon Kim, Hwan Su Yoon
Journal: Molecular Biology and Evolution (2024)

Cellular and physiological cycles are driven by endogenous pacemakers, the diurnal and circadian rhythms. Key functions such as cell cycle progression and cellular metabolism are under rhythmic regulation, thereby maintaining physiological homeostasis. The photoreceptors phytochrome and cryptochrome, in response to light cues, are central input pathways for physiological cycles in most photosynthetic organisms. However, among Archaeplastida, red algae are the only taxa that lack phytochromes. Current knowledge about oscillatory rhythms is primarily derived from model species such as Arabidopsis thaliana and Chlamydomonas reinhardtii in the Viridiplantae, whereas little is known about these processes in other clades of the Archaeplastida, such as the red algae (Rhodophyta). We used genome-wide expression profiling of the red seaweed Gracilariopsis chorda and identified 3,098 rhythmic genes. Here, we characterized possible cryptochrome-based regulation and photosynthetic/cytosolic carbon metabolism in this species. We found a large family of cryptochrome genes in G. chorda that display rhythmic expression over the diurnal cycle and may compensate for the lack of phytochromes in this species. The input pathway gates regulatory networks of carbon metabolism which results in a compact and efficient energy metabolism during daylight hours. The system in G. chorda is distinct from energy metabolism in most plants, which activates in the dark. The green lineage, in particular, land plants, balance water loss and CO2 capture in terrestrial environments. In contrast, red seaweeds maintain a reduced set of photoreceptors and a compact cytosolic carbon metabolism to thrive in the harsh abiotic conditions typical of intertidal zones.
mRNA-based precision targeting of neoantigens and tumor-associated antigens in malignant brain tumors
Authors: Vrunda Trivedi, Changlin Yang, Kelena Klippel, Oleg Yegorov, Christina von Roemeling, Lan Hoang-Minh, Graeme Fenton, Elizabeth Ogando-Rivas, Paul Castillo, Ginger Moore, Kaytora Long-James, Kyle Dyson, Bently Doonan, Catherine Flores, Duane A. Mitchell
Journal: Genome Medicine (2024)

Abstract Background Despite advancements in the successful use of immunotherapy in treating a variety of solid tumors, applications in treating brain tumors have lagged considerably. This is due, at least in part, to the lack of well-characterized antigens expressed within brain tumors that can mediate tumor rejection; the low mutational burden of these tumors that limits the abundance of targetable neoantigens; and the immunologically “cold” tumor microenvironment that hampers the generation of sustained and productive immunologic responses. The field of mRNA-based therapeutics has experienced a boon following the universal approval of COVID-19 mRNA vaccines. mRNA-based immunotherapeutics have also garnered widespread interest for their potential to revolutionize cancer treatment. In this study, we developed a novel and scalable approach for the production of personalized mRNA-based therapeutics that target multiple tumor rejection antigens in a single therapy for the treatment of refractory brain tumors. Methods Tumor-specific neoantigens and aberrantly overexpressed tumor-associated antigens were identified for glioblastoma and medulloblastoma tumors using our cancer immunogenomics pipeline called O pen R eading Frame A ntigen N etwork (O.R.A.N). Personalized tumor antigen-specific mRNA vaccine was developed for each individual tumor model using selective gene capture and enrichment strategy. The immunogenicity and efficacy of the personalized mRNA vaccines was evaluated in combination with anti-PD-1 immune checkpoint blockade therapy or adoptive cellular therapy with ex vivo expanded tumor antigen-specific lymphocytes in highly aggressive murine GBM models. Results Our results demonstrate the effectiveness of the antigen-specific mRNA vaccines in eliciting robust anti-tumor immune responses in GBM hosts. Our findings substantiate an increase in tumor-infiltrating lymphocytes characterized by enhanced effector function, both intratumorally and systemically, after antigen-specific mRNA-directed immunotherapy, resulting in a favorable shift in the tumor microenvironment from immunologically cold to hot. Capacity to generate personalized mRNA vaccines targeting human GBM antigens was also demonstrated. Conclusions We have established a personalized and customizable mRNA-therapeutic approach that effectively targets a plurality of tumor antigens and demonstrated potent anti-tumor response in preclinical brain tumor models. This platform mRNA technology uniquely addresses the challenge of tumor heterogeneity and low antigen burden, two key deficiencies in targeting the classically immunotherapy-resistant CNS malignancies, and possibly other cold tumor types.
Predictors of persistent pain after extracorporeal shockwave lithotripsy for painful chronic calcific pancreatitis
Authors: Nitish Gurav, Nitin Jagtap, Vinod Koppoju, Kiran Sekhramantri, Shujaath Asif, Manu Tandan, Sundeep Lakhtakia, Rakesh Kalapala, Mohan Ramchandani, Rupjyoti Talukdar, Jahangeer Basha, Zaheer Nabi, Sana Fatima Memon, Santosh Darisetty, Guduru Venkat Rao, D. Nageshwar Reddy
Journal: Endoscopy (2024)

Abstract Background Extracorporeal shockwave lithotripsy (ESWL) and/or endoscopic retrograde cholangiopancreatography (ERCP) are recommended as first-line therapy for painful uncomplicated chronic pancreatitis with obstructed main pancreatic duct (MPD) in the pancreas head/body. However, predictors of pain relief after ESWL are unknown. We evaluated independent predictors of persistent pain in patients who underwent ESWL for chronic pancreatitis. Methods 640 consecutive adult patients with chronic pancreatitis, who underwent successful ESWL with ERCP and pancreatic duct (PD) stent placement, were followed for 12 months. The pain was assessed at baseline and at 12 months using the Izbicki Pain Score, with a score decrease of &gt;50% considered pain relief. Independent predictors of pain relief were derived from logistic regression analysis. Results Of 640 patients (mean age 36.71 [SD 12.19] years; 60.5% men), 436 (68.1%) had pain relief and 204 (31.9%) had persistent pain. On univariate analysis, older age, male sex, alcohol and tobacco intake, longer duration of symptoms, dilated MPD and MPD stricture were associated with persistent pain at 12 months (P&lt;0.05). Consumption of alcohol (odds ratio [OR] 1.93, 95%CI 1.26–2.97), tobacco (OR 4.09, 95%CI 2.43–6.90), duration of symptoms (OR 1.02, 95%CI 1.01–1.04), MPD size (OR 1.22, 95%CI 1.11–1.33), and MPD stricture (OR 8.50, 95%CI 5.01–14.42) were independent predictors of persistent pain. Conclusions Alcohol, tobacco, duration of symptoms, MPD size and stricture were independent predictors of persistent pain after successful ESWL. A multidisciplinary team approach that includes behavioral therapy and surgical options should be considered for such patients.
High Diagnostic Yield of Abnormal Endoscopic Findings in the Evaluation of Laryngopharyngeal Reflux
Authors: Amanda J. Krause, Dustin A. Carlson, Walter W. Chan, Chien-Lin Chen, C. Prakash Gyawali, Madeline Greytak, Alexander M. Kaizer, Andrew Jenkins, John E. Pandolfino, Vinathi Polamraju, Ming-Wun Wong, Rena Yadlapati
Journal: Clinical Gastroenterology and Hepatology (2024)

Esophagogastroduodenoscopy (EGD) is recommended in patients with typical gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation, chest pain) in the setting of proton pump inhibitor (PPI) nonresponse. EGD evaluates for erosive disease, assesses antireflux barrier integrity, excludes non-GERD conditions, and, in the absence of erosive findings, is followed by reflux testing.
Coconut Water Induces Clinical Remission in Mild to Moderate Ulcerative Colitis: Double-blind Placebo-controlled Trial
Authors: Saurabh Kedia, Shubi Virmani, Aditya Bajaj, Manasvini Markandey, Neha Singh, Divya Madan, Kanav Kaushal, Pabitra Sahu, Sudheer Kumar Vuyyuru, Bhaskar Kante, Peeyush Kumar, David Mathew Thomas, Sandeep Kumar Mundhra, Mukesh Kumar Singh, Mahak Verma, Raju Sharma, Prasenjit Das, Nihar Ranjan Dash, Nitika Monga, Amit Awasthi, Govind Makharia, Vineet Ahuja
Journal: Clinical Gastroenterology and Hepatology (2024)
Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes
Authors: Michalis Georgiou, Anthony G. Robson, Kaoru Fujinami, Thales A.C. de Guimarães, Yu Fujinami-Yokokawa, Malena Daich Varela, Nikolas Pontikos, Angelos Kalitzeos, Omar A. Mahroo, Andrew R. Webster, Michel Michaelides
Journal: Progress in Retinal and Eye Research (2024)
Infant Ustekinumab Clearance, Risk of Infection, and Development After Exposure During Pregnancy
Authors: Mette Julsgaard, Jantien W. Wieringa, Simon M.D. Baunwall, Bo M. Bibby, Gertjan J.A. Driessen, Linda Kievit, Jacob B. Brodersen, Anja Poulsen, Jens Kjeldsen, Mette M. Hansen, Hai Q. Tang, Christina L. Balmer, Henning Glerup, Jakob B. Seidelin, Kent V. Haderslev, Lise Svenningsen, Signe Wildt, Mie A. Juel, Anders Neumann, Jens Fuglsang, Tine Jess, Anne-Mette Haase, Christian L. Hvas, Jens Kelsen, C. Janneke van der Woude, Julie Korgaard, Thea Vestergaard, Uffe Lund Lystbæk, Anne Berg, Anette Tyrsted Mikkelsen, Anne Marie Holm, Annebirthe Bo Hansen, Ole Mathiesen, Jette Krüger Jensen, Lone Neumann, Jane Boris, Marianne Lemming, Marianne Rahbek, Heidi Gram Søresen, Marie Højriis Storkholm, Jeanette Ziska, Else Marie Vestergaard, Sidsel Elisabeth Bøggild Ipsen, Jørgen Gram, Gunhild Brixen, Hanne Brix Westergaard, Lennart Jan Friis-Hansen, Bettina Friis Olsen, Heidi Fischer, Poul Jannik Bjerrum, Anne Haahr Ibsen, Vibeke Jaeger, Jesper Clausager Madsen, Lars Alling Møller, Karen Søeby, Jane Hansen Damm, Linda Hilsted, Lone Christiansen, Heidi Sharif, Britt Strøm Johansen, Karina Mattebjerg Dahl, Ebbe Langholz, Pia R. Kamstrup, Anja Jochumsen, Lene Drasbek Huusom, Lise Bathum, Charlotte Wilken-Jensen
Journal: Clinical Gastroenterology and Hepatology (2024)

Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life.