tbuckley/cabot-search huggingface dataset:
Correction: Dose modification dynamics of ponatinib in patients with chronic-phase chronic myeloid leukemia (CP-CML) from the PACE and OPTIC trials
Authors: Elias Jabbour, Jane Apperley, Jorge Cortes, Delphine Rea, Michael Deininger, Elisabetta Abruzzese, Charles Chuah, Daniel J. DeAngelo, Andreas Hochhaus, Jeffrey H. Lipton, Michael Mauro, Franck Nicolini, Javier Pinilla-Ibarz, Gianantonio Rosti, Philippe Rousselot, Neil P. Shah, Moshe Talpaz, Alexander Vorog, Xiaowei Ren, Hagop Kantarjian
Journal: Leukemia (2024)
Body mass index and risk of over 100 cancer forms and subtypes in 4.1 million individuals in Sweden: the Obesity and Disease Development Sweden (ODDS) pooled cohort study
Authors: Ming Sun, Marisa da Silva, Tone Bjørge, Josef Fritz, Innocent B. Mboya, Mats Jerkeman, Pär Stattin, Jens Wahlström, Karl Michaëlsson, Bethany van Guelpen, Patrik K.E. Magnusson, Sven Sandin, Weiyao Yin, Ylva Trolle Lagerros, Weimin Ye, Bright Nwaru, Hannu Kankaanranta, Lena Lönnberg, Abbas Chabok, Karolin Isaksson, Nancy L. Pedersen, Sölve Elmståhl, Lars Lind, Linnea Hedman, Christel Häggström, Tanja Stocks
Journal: The Lancet Regional Health - Europe (2024)

Obesity, assessed by body mass index (BMI), is an established risk factor for 13 cancers. We aimed to identify further potential obesity-related cancers and to quantify their association with BMI relative to that of established obesity-related cancers.
Psychotropic drug prescribing before and during the COVID-19 pandemic among people with depressive and anxiety disorders: a multinational network study
Authors: Hao Luo, Yi Chai, Sijia Li, Wallis C Y Lau, Carmen Olga Torre, Joseph Hayes, Ivan C H Lam, Xiaoyu Lin, Can Yin, Stephen Fortin, Dave M Kern, Dong Yun Lee, Rae Woong Park, Jae-Won Jang, Celine S L Chui, Jing Li, Sarah Seager, Kenneth K C Man, Ian C K Wong
Journal: The Lancet Psychiatry (2024)
Multi-modal investigation of the bone micro- and ultrastructure, and elemental distribution in the presence of Mg-xGd screws at mid-term healing stages
Authors: Kamila Iskhakova, Hanna Cwieka, Svenja Meers, Heike Helmholz, Anton Davydok, Malte Storm, Ivo Matteo Baltruschat, Silvia Galli, Daniel Pröfrock, Olga Will, Mirko Gerle, Timo Damm, Sandra Sefa, Weilue He, Keith MacRenaris, Malte Soujon, Felix Beckmann, Julian Moosmann, Thomas O'Hallaran, Roger J Guillory, D C Florian Wieland, Berit Zeller-Plumhoff, Regine Willumeit-Römer
Journal: Bioactive Materials (2024)

Magnesium (Mg) - based alloys are becoming attractive materials for medical applications as temporary bone implants for support of fracture healing, e.g. as a suture anchor. Due to their mechanical properties and biocompatibility, they may replace titanium or stainless-steel implants, commonly used in orthopedic field. Nevertheless, patient safety has to be assured by finding a long-term balance between metal degradation, osseointegration, bone ultrastructure adaptation and element distribution in organs. In order to determine the implant behavior and its influence on bone and tissues, we investigated two Mg alloys with gadolinium contents of 5 and 10 wt percent in comparison to permanent materials titanium and polyether ether ketone. The implants were present in rat tibia for 10, 20 and 32 weeks before sacrifice of the animal. Synchrotron radiation-based micro computed tomography enables the distinction of features like residual metal, degradation layer and bone structure. Additionally, X-ray diffraction and X-ray fluorescence yield information on parameters describing the bone ultrastructure and elemental composition at the bone-to-implant interface. Finally, with element specific mass spectrometry, the elements and their accumulation in the main organs and tissues are traced. The results show that Mg-xGd implants degrade
Human cases of avian influenza A(H5) in the USA
Authors: Priya Venkatesan
Journal: The Lancet Microbe (2024)

13 human cases of highly pathogenic avian influenza (HPAI) A(H5) have been confirmed in the USA so far in 2024, as of July 26. All were mild illnesses occurring in farm workers exposed to infected dairy cattle or poultry. Although the current risk to the general public is low, increased vigilance and pandemic preparedness efforts have been encouraged by public health authorities.
Adiposity and Muscle Strength in Men With Prostate Cancer and Cardiovascular Outcomes
Authors: Darryl P. Leong, Vincent Fradet, Tamim Niazi, Joseph B. Selvanayagam, Robert Sabbagh, Celestia S. Higano, Steven Agapay, Sumathy Rangarajan, Rajibul Mian, Carlos A.K. Nakashima, Negareh Mousavi, Ian Brown, Felipe H. Valle, Luke T. Lavallée, Bobby Shayegan, Kelvin K.H. Ng, Darin D. Gopaul, Germano D. Cavalli, Sonia Saavedra, Jose P. Lopez-Lopez, Cristiano Freitas de Souza, Emmanuelle Duceppe, Lívia F. Avezum Oliveira, Avirup Guha, Juan Esteban Gomez-Mesa, Luis Eduardo Silva Móz, Philippe D. Violette, Álvaro Avezum, Gustavo B.F. Oliveira, Ariel G. Kann, Edilson Walter, Cesar O.L. Dusilek, Nicolas Villareal Trujillo, Patricia Beato, Ludhmila A. Hajjar, Patrick P.W. Luke, Eduardo Schlabendorff, David Sarid, Jehonathan Pinthus
Journal: JACC CardioOncology (2024)

There are limited data on the physical effects of androgen deprivation therapy (ADT) for prostate cancer (PC), and on the relationships of such measures of adiposity and strength to cardiovascular outcomes.
Rarefaction of Blood, But Not Lymphatic Capillaries, in Patients With Cardiac Amyloidosis
Authors: Alberto Aimo, Lucrezia Bonino, Vincenzo Castiglione, Veronica Musetti, Martina Rossetti, Alessandra Celi, Michele Coceani, Michele Emdin, Angela Pucci, Giuseppe Vergaro
Journal: JACC CardioOncology (2024)
Understanding and Overcoming Resistance to Selective FGFR inhibitors Across <i>FGFR2</i>-Driven Malignancies
Authors: Francesco Facchinetti, Yohann Loriot, Floriane Brayé, Damien Vasseur, Rastislav Bahleda, Ludovic Bigot, Rémy Barbé, Catline Nobre, David Combarel, Stefan Michiels, Antoine Italiano, Cristina Smolenschi, Lambros Tselikas, Jean-Yves Scoazec, Santiago Ponce-Aix, Benjamin Besse, Fabrice André, Ken A. Olaussen, Antoine Hollebecque, Luc Friboulet
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Understanding resistance to selective FGFR inhibitors is crucial to improve the clinical outcomes of patients with FGFR2-driven malignancies. Experimental Design: We analyzed sequential ctDNA, ± whole-exome sequencing, or targeted next-generation sequencing on tissue biopsies from patients with tumors harboring activating FGFR2 alterations progressing on pan-FGFR–selective inhibitors, collected in the prospective UNLOCK program. FGFR2::BICC1 Ba/F3 and patient-derived xenograft models were used for functional studies. Results: Thirty-six patients were included. In cholangiocarcinoma, at resistance to both reversible inhibitors (e.g., pemigatinib and erdafitinib) and the irreversible inhibitor futibatinib, polyclonal FGFR2 kinase domain mutations were frequent (14/27 patients). Tumors other than cholangiocarcinoma shared the same mutated FGFR2 residues, but polyclonality was rare (1/9 patients). At resistance to reversible inhibitors, 14 residues in the FGFR2 kinase domain were mutated—after futibatinib, only the molecular brake N550 and the gatekeeper V565. Off-target alterations in PI3K/mTOR and MAPK pathways were found in 11 patients, often together with on-target mutations. At progression to a first FGFR inhibitor, 12 patients received futibatinib or lirafugratinib (irreversible inhibitors), with variable clinical outcomes depending on previous resistance mechanisms. Two patients with TSC1 or PIK3CA mutations benefited from everolimus. In cell viability assays on Ba/F3 and in pharmacologic studies on patient-derived xenografts, irreversible inhibitors retained better activity against FGFR2 kinase domain mutations, with lirafugratinib active against the recalcitrant V565L/F/Y. Conclusions: At progression to FGFR inhibitors, FGFR2-driven malignancies are characterized by high intra- and interpatient molecular heterogeneity, particularly in cholangiocarcinoma. Resistance to FGFR inhibitors can be overcome by sequential, molecularly oriented treatment strategies across FGFR2-driven tumors.
Enhancing global sensitivity and uncertainty quantification in medical image reconstruction with Monte Carlo arbitrary-masked mamba
Authors: Jiahao Huang, Liutao Yang, Fanwen Wang, Yinzhe Wu, Yang Nan, Weiwen Wu, Chengyan Wang, Kuangyu Shi, Angelica I. Aviles-Rivero, Carola-Bibiane Schönlieb, Daoqiang Zhang, Guang Yang
Journal: Medical Image Analysis (2024)

Deep learning has been extensively applied in medical image reconstruction, where Convolutional Neural Networks (CNNs) and Vision Transformers (ViTs) represent the predominant paradigms, each possessing distinct advantages and inherent limitations: CNNs exhibit linear complexity with local sensitivity, whereas ViTs demonstrate quadratic complexity with global sensitivity. The emerging Mamba has shown superiority in learning visual representation, which combines the advantages of linear scalability and global sensitivity. In this study, we introduce MambaMIR, an Arbitrary-Masked Mamba-based model with wavelet decomposition for joint medical image reconstruction and uncertainty estimation. A novel Arbitrary Scan Masking (ASM) mechanism "masks out" redundant information to introduce randomness for further uncertainty estimation. Compared to the commonly used Monte Carlo (MC) dropout, our proposed MC-ASM provides an uncertainty map without the need for hyperparameter tuning and mitigates the performance drop typically observed when applying dropout to low-level tasks. For further texture preservation and better perceptual quality, we employ the wavelet transformation into MambaMIR and explore its variant based on the Generative Adversarial Network, namely MambaMIR-GAN. Comprehensive experiments have been conducted for multiple representative medical image reconstruction tasks, demonstrating that the proposed MambaMIR and MambaMIR-GAN outperform other baseline and state-of-the-art methods in different reconstruction tasks, where MambaMIR achieves the best reconstruction fidelity and MambaMIR-GAN has the best perceptual quality. In addition, our MC-ASM provides uncertainty maps as an additional tool for clinicians, while mitigating the typical performance drop caused by the commonly used dropout.
Response by Kosiborod et al to Letter Regarding Article, “Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial”
Authors: Mikhail N. Kosiborod, Mark C. Petrie, Barry A. Borlaug
Journal: Circulation (2024)
Comparison of American and European Guideline Recommendations for Diagnostic Workup and Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack
Authors: Maxim J.H.L. Mulder, Tim Y. Cras, James Shay, Diederik W.J. Dippel, James F. Burke
Journal: Circulation (2024)

Guidelines help to facilitate treatment decisions based on available evidence, and also to provide recommendations in areas of uncertainty. In this paper, we compare the recommendations for stroke workup and secondary prevention of ischemic stroke and transient ischemic attack of the American Heart Association (AHA)/American Stroke Association (ASA) with the European Stroke Organization (ESO) guidelines. The primary aim of this paper is to offer clinicians guidance by identifying areas where there is consensus and where consensus is lacking, in the absence or presence of high-level evidence. We compared AHA/ASA with the ESO guideline recommendations for 7 different topics related to diagnostic stroke workup and secondary prevention. We categorized the recommendations based on class and level of evidence to determine whether there were relevant differences in the ratings of evidence that the guidelines used for its recommendations. Finally, we summarized major topics of agreement and disagreement, while also prominent knowledge gaps were identified. In total, we found 63 ESO and 82 AHA/ASA recommendations, of which 38 were on the same subject. Most recommendations are largely similar, but not all are based on high-level evidence. For many recommendations, AHA/ASA and ESO assigned different levels of evidence. For the 10 recommendations with Level A evidence (high quality) in AHA/ASA, ESO only labeled 4 of these as high quality . There are many remaining issues with either no or insufficient evidence, and some topics that are not covered by both guidelines. Most ESO and AHA/ASA Guideline recommendations for stroke workup and secondary prevention were similar. However not all were based on high-level evidence and the appointed level of evidence often differed. Clinicians should not blindly follow all guideline recommendations; the accompanying level of evidence informs which recommendations are based on robust evidence. Topics with lower levels of evidence, or those with recommendations that disagree or are missing, may be an incentive for further clinical research.
Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease Codes in Patient Records
Authors: Virginia H. Sun, Julius C. Heemelaar, Ibrahim Hadzic, Vineet K. Raghu, Chia-Yun Wu, Leyre Zubiri, Azin Ghamari, Nicole R. LeBoeuf, Osama Abu-Shawer, Kenneth L. Kehl, Shilpa Grover, Prabhsimranjot Singh, Giselle A. Suero-Abreu, Jessica Wu, Ayo S. Falade, Kelley Grealish, Molly F. Thomas, Nora Hathaway, Benjamin D. Medoff, Hannah K. Gilman, Alexandra-Chloe Villani, Jor Sam Ho, Meghan J. Mooradian, Meghan E. Sise, Daniel A. Zlotoff, Steven M. Blum, Michael Dougan, Ryan J. Sullivan, Tomas G. Neilan, Kerry L. Reynolds
Journal: Journal of Clinical Oncology (2024)

PURPOSE Current approaches to accurately identify immune-related adverse events (irAEs) in large retrospective studies are limited. Large language models (LLMs) offer a potential solution to this challenge, given their high performance in natural language comprehension tasks. Therefore, we investigated the use of an LLM to identify irAEs among hospitalized patients, comparing its performance with manual adjudication and International Classification of Disease (ICD) codes. METHODS Hospital admissions of patients receiving immune checkpoint inhibitor (ICI) therapy at a single institution from February 5, 2011, to September 5, 2023, were individually reviewed and adjudicated for the presence of irAEs. ICD codes and an LLM with retrieval-augmented generation were applied to detect frequent irAEs (ICI-induced colitis, hepatitis, and pneumonitis) and the most fatal irAE (ICI-myocarditis) from electronic health records. The performance between ICD codes and LLM was compared via sensitivity and specificity with an α = .05, relative to the gold standard of manual adjudication. External validation was performed using a data set of hospital admissions from June 1, 2018, to May 31, 2019, from a second institution. RESULTS Of the 7,555 admissions for patients on ICI therapy in the initial cohort, 2.0% were adjudicated to be due to ICI-colitis, 1.1% ICI-hepatitis, 0.7% ICI-pneumonitis, and 0.8% ICI-myocarditis. The LLM demonstrated higher sensitivity than ICD codes (94.7% v 68.7%), achieving significance for ICI-hepatitis ( P &lt; .001), myocarditis ( P &lt; .001), and pneumonitis ( P = .003) while yielding similar specificities (93.7% v 92.4%). The LLM spent an average of 9.53 seconds/chart in comparison with an estimated 15 minutes for adjudication. In the validation cohort (N = 1,270), the mean LLM sensitivity and specificity were 98.1% and 95.7%, respectively. CONCLUSION LLMs are a useful tool for the detection of irAEs, outperforming ICD codes in sensitivity and adjudication in efficiency.
Loss of p53 and SMAD4 induces adenosquamous subtype pancreatic cancer in the absence of an oncogenic KRAS mutation
Authors: Daowei Yang, Xinlei Sun, Rohan Moniruzzaman, Hua Wang, Citu Citu, Zhongming Zhao, Ignacio I. Wistuba, Huamin Wang, Anirban Maitra, Yang Chen
Journal: Cell Reports Medicine (2024)

Pancreatic cancer is associated with an oncogenic KRAS mutation in approximately 90% of cases. However, a non-negligible proportion of pancreatic cancer cases harbor wild-type KRAS (KRAS-WT). This study establishes genetically engineered mouse models that develop spontaneous pancreatic cancer in the context of KRAS-WT. The Trp53
Pathogenesis, Diagnostics, and Therapeutics for Alzheimer's Disease: Breaking the Memory Barrier
Authors: Pushpa Tryphena Kamatham, Rashi Shukla, Dharmendra Kumar Khatri, Lalitkumar K. Vora
Journal: Ageing Research Reviews (2024)

Alzheimer's disease (AD) is the most common cause of dementia and accounts for 60-70 % of all cases. It affects millions of people worldwide. AD poses a substantial economic burden on societies and healthcare systems. AD is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. As the prevalence of AD continues to increase, understanding its pathogenesis, improving diagnostic methods, and developing effective therapeutics have become paramount. This comprehensive review delves into the intricate mechanisms underlying AD, explores the current state of diagnostic techniques, and examines emerging therapeutic strategies. By revealing the complexities of AD, this review aims to contribute to the growing body of knowledge surrounding this devastating disease.
Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology
Authors: Thomas A. Wadden, Gregory K. Brown, Christina Egebjerg, Ofir Frenkel, Bryan Goldman, Robert F. Kushner, Barbara McGowan, Maria Overvad, Anders Fink-Jensen
Journal: JAMA Internal Medicine (2024)

Importance Obesity is associated with numerous psychosocial complications, making psychiatric safety a consideration for treating people with obesity. Few studies have investigated the psychiatric safety of newly available antiobesity medications. Objective To evaluate the psychiatric safety of subcutaneous semaglutide, 2.4 mg, once weekly in people without known major psychopathology. Design, Setting, and Participants This post hoc analysis of pooled data from the randomized, double-blind, placebo-controlled, multicenter phase 3a STEP 1, 2, and 3 trials (68 weeks; 2018-2020) and phase 3b STEP 5 trial (104 weeks; 2018-2021) included adults with overweight or obesity; STEP 2 participants also had type 2 diabetes. Trial designs have been published previously. Interventions Semaglutide, 2.4 mg, vs placebo. Main Outcomes and Measures Depressive symptoms and suicidal ideation/behavior were assessed using the Patient Health Questionnaire (PHQ-9) and Columbia–Suicide Severity Rating Scale, respectively. Psychiatric and nervous system disorder adverse events were investigated. Results This analysis included 3377 participants in the STEP 1, 2, and 3 trials (2360 women [69.6%]; mean [SD] age, 49 [13] years) and 304 participants in STEP 5 (236 women [77.6%]; mean [SD] age, 47 [11] years). In the STEP 1, 2, and 3 trials, mean (SD) baseline PHQ-9 scores for the semaglutide, 2.4 mg, and placebo groups were 2.0 (2.3) and 1.8 (2.3), respectively, indicating no/minimal symptoms of depression. PHQ-9 scores at week 68 were 2.0 (2.9) and 2.4 (3.3), respectively; the estimated treatment difference (95% CI) between groups was −0.56 (−0.81 to −0.32) ( P &amp;amp;lt; .001). Participants treated with semaglutide vs placebo were less likely to shift (from baseline to week 68) to a more severe category of PHQ-9 depression (odds ratio, 0.63; 95% CI, 0.50-0.79; P &amp;amp;lt; .001). Based on the Columbia–Suicide Severity Rating Scale, 1% or fewer of participants reported suicidal ideation/behavior during treatment, with no differences between semaglutide, 2.4 mg, and placebo. Psychiatric disorder adverse events were generally balanced between groups. Similar results were observed in STEP 5. Conclusions and Relevance The results of this post hoc analysis suggest that treatment with semaglutide, 2.4 mg, did not increase the risk of developing symptoms of depression or suicidal ideation/behavior vs placebo and was associated with a small but statistically significant reduction in depressive symptoms (not considered clinically meaningful). People with obesity should be monitored for mental health concerns so they can receive appropriate support and care. Trial Registration ClinicalTrials.gov Identifiers: STEP 1 ( NCT03548935 ), 2 ( NCT03552757 ), 3 ( NCT03611582 ), and 5 ( NCT03693430 )
GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant
Authors: Ilon Liu, Gustavo Alencastro Veiga Cruzeiro, Lynn Bjerke, Rebecca F. Rogers, Yura Grabovska, Alexander Beck, Alan Mackay, Tara Barron, Olivia A. Hack, Michael A. Quezada, Valeria Molinari, McKenzie L. Shaw, Marta Perez-Somarriba, Sara Temelso, Florence Raynaud, Ruth Ruddle, Eshini Panditharatna, Bernhard Englinger, Hafsa M. Mire, Li Jiang, Andrezza Nascimento, Jenna LaBelle, Rebecca Haase, Jacob Rozowsky, Sina Neyazi, Alicia-Christina Baumgartner, Sophia Castellani, Samantha E. Hoffman, Amy Cameron, Murry Morrow, Quang-De Nguyen, Giulia Pericoli, Sibylle Madlener, Lisa Mayr, Christian Dorfer, Rene Geyeregger, Christopher Rota, Gerda Ricken, Keith L. Ligon, Sanda Alexandrescu, Rodrigo T. Cartaxo, Benison Lau, Santhosh Uphadhyaya, Carl Koschmann, Emelie Braun, Miri Danan-Gotthold, Lijuan Hu, Kimberly Siletti, Erik Sundström, Rebecca Hodge, Ed Lein, Sameer Agnihotri, David D. Eisenstat, Simon Stapleton, Andrew King, Cristina Bleil, Angela Mastronuzzi, Kristina A. Cole, Angela J. Waanders, Angel Montero Carcaboso, Ulrich Schüller, Darren Hargrave, Maria Vinci, Fernando Carceller, Christine Haberler, Irene Slavc, Sten Linnarsson, Johannes Gojo, Michelle Monje, Chris Jones, Mariella G. Filbin
Journal: Cancer Cell (2024)

Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, we delineate a cellular hierarchy along the interneuron lineage development continuum, revealing that DHG-H3G34 mirror spatial patterns of progenitor streams surrounding interneuron nests, as seen during human brain development. Integrating these findings with genome-wide CRISPR-Cas9 screens identifies genes upregulated in interneuron lineage progenitors as major dependencies. Among these, CDK6 emerges as a targetable vulnerability: DHG-H3G34 tumor cells show enhanced sensitivity to CDK4/6 inhibitors and a CDK6-specific degrader, promoting a shift toward more mature interneuron-like states, reducing tumor growth, and prolonging xenograft survival. Notably, a patient with progressive DHG-H3G34 treated with a CDK4/6 inhibitor achieved 17 months of stable disease. This study underscores interneuronal progenitor-like states, organized in characteristic niches, as a distinct vulnerability in DHG-H3G34, highlighting CDK6 as a promising clinically actionable target.