tbuckley/cabot-search huggingface dataset:
Bedaquiline Monotherapy for Multibacillary Leprosy
Authors: Jaison Barreto, Patricia Sammarco Rosa, Linda Adams, Zuleima Aguilar, Nyasha Bakare, Sandra R Chaplan, Ruxandra Draghia Akli, Etienne Ernault, Sarah Kulke, Nacer Lounis, Dawn Millington, James A Palmer, Bart Remmerie, Miao Wang, Stephanie Young, Richard Truman, Paula Frassinetti Bessa Rebello
Journal: New England Journal of Medicine (2024)

Standard multidrug therapy for leprosy may be associated with severe side effects, which add to the stigma and discrimination that affect persons with the disease. In addition, the threat posed by drug-resistant leprosy shows the need for alternative drug combinations and shorter, safer regimens of multidrug therapy.
Single-cell epigenetic and clonal analysis decodes disease progression in pediatric acute myeloid leukemia
Authors: Boyu Cui, Lanlan Ai, Minghui Lei, Yongjuan Duan, Chao Tang, Jingliao Zhang, Yan Gao, Xuan Li, Caiying Zhu, Yingchi Zhang, Xiaofan Zhu, Tomoya Isobe, Wenyu Yang, Berthold Gottgens, Ping Zhu
Journal: Blood (2024)

Pediatric acute myeloid leukemia (pAML) is a clonal disease with recurrent genetic alterations that affect epigenetic states. However, the implications of epigenetic dysregulation in disease progression remain unclear. Here, we interrogated single-cell and clonal level chromatin accessibility of bone marrow samples from 28 pAML patients representing multiple subtypes using mtscATAC-seq, which revealed distinct differentiation hierarchies and abnormal chromatin accessibility in a subtype-specific manner. Innate immune signaling was commonly enhanced across subtypes and related to improved advantage of clonal competition and unfavorable prognosis, with further reinforcement in a relapse-associated leukemia stem cell-like population. We identified a panel of 31 innate immunity related genes to improve the risk classification of pAML patients. By comparing paired diagnosis and post-chemotherapy relapse samples, we showed that primitive cells significantly reduced MHC class II signaling, suggesting an immune evasion mechanism to facilitate their expansion at relapse. Key regulators orchestrating cell cycle dysregulation were identified to contribute to pAML relapse in drug-resistant clones. Our work establishes the single-cell chromatin accessibility landscape at clonal resolution and reveals the critical involvement of epigenetic disruption, offering insights into classification and targeted therapies of pAML patients.
Phase II Trial of Nivolumab Plus Doxorubicin, Vinblastine, Dacarbazine as Frontline Therapy in Older Adults With Hodgkin Lymphoma
Authors: Pallawi Torka, Tatyana Feldman, Kerry J. Savage, Nivetha Ganesan, Esther Drill, Helen Hancock, Theresa Davey, Leslie Perez, Charisse Capadona, Sarima Subzwari, Natasha Galasso, Jinshu Yang, Michelle Post, Alexander Boardman, Philip Caron, Kevin David, Zachary Epstein-Peterson, Lorenzo Falchi, Paola Ghione, Paul Hamlin, Steven M. Horwitz, Andrew M. Intlekofer, William Johnson, Anita Kumar, Jennifer Lue, Ariela Noy, Colette Owens, M. Lia Palomba, Gilles A. Salles, Raphael Steiner, Robert Stuver, Santosha Vardhana, Joachim Yahalom, Ahmet Dogan, Andrew D. Zelenetz, Heiko Schöder, Alison J. Moskowitz
Journal: Journal of Clinical Oncology (2024)

We conducted a phase I/II study evaluating nivolumab plus doxorubicin, vinblastine, dacarbazine (N-AVD) as frontline therapy for treatment-naïve older adults (OA) with classical Hodgkin lymphoma (cHL; ClinicalTrials.gov identifier: NCT03033914). Patients age ≥60 years with newly diagnosed, any stage, cHL were treated with six cycles of AVD at standard doses plus nivolumab 240 mg intravenously once every 2 weeks (on days 1 and 15) of each cycle. A geriatric assessment was performed before therapy initiation. The primary end point was progression-free survival (PFS). Patient characteristics (N = 40) included median age of 66 years (range, 60-78 years) with 38% ≥70 years, 78% with stage III/IV disease, 68% with International Prognostic Score of ≥3, 82% dependent in ≥1 activities of daily living, 23% dependent in ≥1 instrumental activities of daily living, 50% with impaired timed up and go test, and 40% with polypharmacy. Among 37 response-evaluable patients, the median follow-up was 49 months and 3-year PFS and overall survival (OS) were 79% and 97%, respectively. Overall, 50% patients experienced grade 3/4 treatment-related adverse events (TRAEs), including febrile neutropenia in 8%. Four (10%) patients stopped therapy due to TRAEs. There was no correlation between baseline geriatric impairments and survival outcomes or toxicities. Positron emission tomography-2 was not predictive of PFS or OS. N-AVD is a highly effective and well-tolerated frontline regimen in OA with cHL across a wide range of geriatric impairments.
Body Weight Gain Associated With Alectinib in Patients With ALK+ Non–Small Cell Lung Cancer: Pooled Analysis of Individual Patient Data From Four Prospective Clinical Trials
Authors: Barend J. Sikkema, Sara J. Baart, Marthe S. Paats, Egbert F. Smit, Annemie M.W.J. Schols, Ron H.J. Mathijssen, Elisabeth F.C. van Rossum, Anne-Marie C. Dingemans
Journal: Journal of Clinical Oncology (2024)

Weight gain is a known adverse event (AE) of alectinib. This study evaluates the progression of actual weight gain over time and explores its association with baseline characteristics.
Development and Validation of a Smartphone Application for Neonatal Jaundice Screening
Authors: Alvin Jia Hao Ngeow, Aminath Shiwaza Moosa, Mary Grace Tan, Lin Zou, Millie Ming Rong Goh, Gek Hsiang Lim, Vina Tagamolila, Imelda Ereno, Jared Ryan Durnford, Samson Kei Him Cheung, Nicholas Wei Jie Hong, Ser Yee Soh, Yih Yann Tay, Zi Ying Chang, Ruiheng Ong, Li Ping Marianne Tsang, Benny K. L. Yip, Kuok Wei Chia, Kelvin Yap, Ming Hwee Lim, Andy Wee An Ta, Han Leong Goh, Cheo Lian Yeo, Daisy Kwai Lin Chan, Ngiap Chuan Tan, Woei Bing Poon, Selina Kah Ying Ho, Varsha Atul Shah, Sridhar Arunachalam, Kok Wooi Teoh, Sarah Hui Wen Yao, Usha Kunnumpurath Sivan, Amelia Suan-Lin Koe, Yoke Yen Lau, Kum Chue Khong, Audrey Wai Mei Seet, Sharon Kheng Lai Yam, Tianmin Lu, Subramanian Reena Chandhini, Jacqueline Su-Lin Teoh
Journal: JAMA Network Open (2024)

This diagnostic study describes the merger of domain knowledge (Kramer principle of dermal advancement of icterus) with current machine learning (ML) techniques to create a novel tool for screening of neonatal jaundice (NNJ), which affects 60% of term and 80% of preterm infants.
Melanoma Tumor Mutational Burden and Indoor Tanning Exposure
Authors: Grace B. Hanrahan, Anita Giobbie-Hurder, Blair Allais, Jayne Vogelzang, Christopher Fay, Hillary C. Tsibris
Journal: JAMA Dermatology (2024)

UV-induced mutagenesis leads to a higher tumor mutational burden (TMB) in cutaneous melanoma relative to other cancer types. TMB is an important prognostic marker in advanced melanoma; higher TMB is associated with greater clinical response to immune checkpoint inhibition and improved survival.
Pitavastatin, Procollagen Pathways, and Plaque Stabilization in Patients With HIV
Authors: Márton Kolossváry, Samuel R. Schnittman, Markella V. Zanni, Kathleen V. Fitch, Carl J. Fichtenbaum, Judith A. Aberg, Gerald S. Bloomfield, Carlos D. Malvestutto, Judith Currier, Marissa R. Diggs, Christopher deFilippi, Allison Ross Eckard, Adrian Curran, Murat Centinbas, Ruslan Sadreyev, Borek Foldyna, Thomas Mayrhofer, Julia Karady, Jana Taron, Sara McCallum, Michael T. Lu, Heather J. Ribaudo, Pamela S. Douglas, Steven K. Grinspoon
Journal: JAMA Cardiology (2024)

In a mechanistic substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) randomized clinical trial, pitavastatin reduced noncalcified plaque (NCP) volume, but specific protein and gene pathways contributing to changes in coronary plaque remain unknown.
Selective vs Routine Cholangiography Across a Health Care Enterprise
Authors: Abby Gross, Sayf Al-deen Said, Chase J. Wehrle, Hanna Hong, Joseph Quick, Sarah Larson, Mir Shanaz Hossain, Samer Naffouje, R. Matthew Walsh, Toms Augustin
Journal: JAMA Surgery (2024)

There is sparse literature on whether routine cholangiography (RC) vs selective cholangiography (SC) during cholecystectomy is associated with improved perioperative outcomes, regardless of whether an intraoperative cholangiogram (IOC) is performed.
Improving Diversity in a Novel Psoriasis Study
Authors: Andrew Alexis, Amy McMichael, Neelam Vashi, Tina Bhutani, Adrian O. Rodriguez, Jensen Yeung, Olivia Choi, Daphne Chan, Theodore Alkousakis, Denise N. Bronner, Laura Park-Wyllie, Long-Long Gao, Pearl Grimes, Mona Shahriari, Geeta Yadav, Chesahna Kindred, Susan C. Taylor, Seemal R. Desai
Journal: JAMA Dermatology (2024)

Diverse racial and ethnic representation in clinical trials has been limited, not representative of the US population, and the subject of pending US Food and Drug Administration guidance. Psoriasis presentation and disease burden can vary by skin pigmentation, race and ethnicity, and socioeconomic differences. Overall, there are limited primary data on clinical response, genetics, and quality of life in populations with psoriasis and skin of color (SoC). The Varying Skin Tones in Body and Scalp Psoriasis: Guselkumab Efficacy and Safety trial (VISIBLE) is underway and uses strategies aimed at addressing this persistent gap.
Risk of Death Due to Melanoma and Other Causes in Patients With Thin Cutaneous Melanomas
Authors: Serigne N. Lo, Gabrielle J. Williams, Anne E. Cust, David W. Ollila, Alexander H. R. Varey, Sydney Ch’ng, Richard A. Scolyer, John F. Thompson
Journal: JAMA Dermatology (2024)

Most patients who present with primary cutaneous melanomas have thin tumors (≤1.0 mm in Breslow thickness, ie, pT1a and pT1b). Although their prognosis is generally considered to be excellent, there is limited precise information on the association of risk of death with specific Breslow measurements in thin lesions.
Safety and Efficacy of Anti–IL-23 Monoclonal Antibody QX004N for Patients With Psoriasis
Authors: Xiaojiao Li, Bing Li, Deming Yang, Meng Wang, Qianqian Li, Nan Wang, Min Fang, Jingrui Liu, Hong Zhang, Min Wu, Cuiyun Li, Xiaoxue Zhu, Yanhua Ding, Shanshan Li
Journal: JAMA Dermatology (2024)

Psoriasis is a chronic, immune-mediated skin disease with an unmet need for biologic treatment options. To assess the safety, pharmacokinetics, and efficacy of QX004N in healthy individuals and patients with moderate to severe plaque psoriasis in China. This randomized clinical trial was composed of 2 parts. Part 1 was a first-in-human, single-ascending-dose, phase 1a clinical trial conducted from November 2, 2021, to January 16, 2023. Part 2 was a double-blind, multiple dose-escalation, phase 1b clinical trial conducted from February 15, 2023, to January 5, 2024, at 5 clinical centers in China, involving patients with moderate to severe plaque psoriasis. In part 1, healthy participants in each cohort were assigned in a 4:1 ratio to receive a single subcutaneous injection of QX004N (ranging from 10 mg to 600 mg) or placebo. In part 2, patients in each cohort were assigned in a 4:1 ratio to receive QX004N or placebo at doses of 150 mg, 300 mg, and 600 mg once every 2 weeks. For part 1, the primary outcome was the safety of a single dose of QX004N in healthy participants, and the secondary outcome was the pharmacokinetic profile. For part 2, the primary efficacy end point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) by week 12; other efficacy end points were considered secondary. The phase 1a clinical trial (part 1) enrolled 55 healthy participants (mean [SD] age, 35.9 [6.0] years; 30 [54.5%] female), and the phase 1b clinical trial (part 2) enrolled 30 patients with moderate to severe plaque psoriasis. The mean (SD) age of QX004N-treated participants in part 2 was 41.4 (7.5) years, and 19 of 24 QX004N-treated participants (79.2%) were male. The mean (SD) age of the placebo cohort in part 2 was 35.3 (8.4) years, and 5 of 6 placebo-treated participants (83.3%) were male. QX004N exhibited linear pharmacokinetics and was tolerated well in both healthy participants and patients with psoriasis. Most adverse events were mild to moderate in severity, with no drug-related serious adverse events reported. The proportion of patients receiving QX004N who achieved PASI 75 at week 12 and PASI 90 (90% improvement in PASI) at week 16 in the 150-mg, 300-mg, and 600-mg cohorts was 100%, significantly higher than that in the placebo cohorts (33.3%). The maximum proportion of patients achieving Investigator's Global Assessment score of 0 or 1 was 100% in the 3 QX004N cohorts. In this randomized clinical trial, QX004N was well tolerated and demonstrated superior efficacy compared to placebo in patients with moderate to severe plaque psoriasis. Chinese Clinical Trial Registry Identifier: CTR20212313 and CTR20223457.
Angiotensin Receptor-Neprilysin Inhibitor Prescribing Patterns in Patients Hospitalized for Heart Failure
Authors: Pratyaksh K. Srivastava, Alexandra M. Klomhaus, Stephen J. Greene, Paul Heidenreich, Sabra C. Lewsey, Clyde W. Yancy, Gregg C. Fonarow
Journal: JAMA Cardiology (2024)

Angiotensin receptor-neprilysin inhibition (ARNI) improves mortality among patients with heart failure with reduced ejection fraction (HFrEF), ie, those with an EF of 40% or less.
Use of Biologic and Biosynthetic Mesh for Ventral Hernia Repair in Current Practice
Authors: Cody L. Mullens, Leah Schoel, Michael F. McGee, Anne P. Ehlers, Dana Telem, Ryan Howard
Journal: JAMA Surgery (2024)

Originally developed for use in contaminated fields, there is growing evidence against the use of biologic and biosynthetic mesh in ventral hernia repair. However, its prevalence and patterns of use in current practice are largely unknown.
Genotype and Associated Cancer Risk in Individuals With Telomere Biology Disorders
Authors: Marena R. Niewisch, Jung Kim, Neelam Giri, Judith C. Lunger, Lisa J. McReynolds, Sharon A. Savage
Journal: JAMA Network Open (2024)

Telomere biology disorders (TBDs) are inherited cancer-prone bone marrow failure syndromes with differences in morbidity and mortality based on mode of inheritance.
Use of Promotional Language in Grant Applications and Grant Success
Authors: Huilian Sophie Qiu, Hao Peng, Henrik Barslund Fosse, Teresa K. Woodruff, Brian Uzzi
Journal: JAMA Network Open (2024)

Scientific writing is critical for successfully showing the merits of innovative ideas to funding agencies, colleagues, and practitioners, and it has evolved over time, particularly in the increased use of promotional words.
Linking Genome-Wide Association Studies to Pharmacological Treatments for Psychiatric Disorders
Authors: Aurina Arnatkeviciute, Alex Fornito, Janette Tong, Ken Pang, Ben D. Fulcher, Mark A. Bellgrove
Journal: JAMA Psychiatry (2024)

Large-scale genome-wide association studies (GWAS) should ideally inform the development of pharmacological treatments, but whether GWAS-identified mechanisms of disease liability correspond to the pathophysiological processes targeted by current pharmacological treatments is unclear.
Rethinking ARDS classification: oxygenation impairment fails to predict VILI risk
Authors: Giulia Catozzi, Tommaso Pozzi, Domenico Nocera, Beatrice Donati, Stefano Giovanazzi, Valentina Ghidoni, Mauro Galizia, Rosanna D’Albo, Mattia Busana, Federica Romitti, Alessandro Gatta, Onnen Moerer, Konrad Meissner, Michael Quintel, Peter Herrmann, Davide Chiumello, Luigi Camporota, Luciano Gattinoni
Journal: Intensive Care Medicine (2024)

The selection and intensity of respiratory support for ARDS are guided by PaO
Frailty in Long-Term Prostate Cancer Survivors and Its Association With Quality of Life and Emotional Health
Authors: Valentin H. Meissner, Kolja Imhof, Matthias Jahnen, Lukas Lunger, Andreas Dinkel, Stefan Schiele, Donna P. Ankerst, Jürgen E. Gschwend, Kathleen Herkommer
Journal: Journal of the National Comprehensive Cancer Network (2024)

Frailty is emerging as an important determinant for quality of life (QoL) and emotional health in older patients with cancer, and specifically in long-term prostate cancer survivors, but quantitative studies are lacking. The current study assesses the prevalence of frailty and its association with QoL and emotional health in long-term prostate cancer survivors after radical prostatectomy.
Definitive Radiotherapy for Oligometastatic and Oligoprogressive Thyroid Cancer: A Potential Strategy for Systemic Therapy Deferral
Authors: Stephanie O. Dudzinski, Maria E. Cabanillas, Sarah Hamidi, Vicente R. Marczyk, Naifa L. Busaidy, Ramona Dadu, James Welsh, Mimi I. Hu, G. Brandon Gunn, Chenyang Wang, Steven G. Waguespack, Jack Phan, Thomas H. Beckham, Joe Y. Chang, Steven I. Sherman, Jay P. Reddy, Anita K. Ying, Michael S. O’Reilly, Aileen Chen, Anna Lee, Saumil J. Gandhi, Zhongxing Liao, Ethan B. Ludmir, Quynh-Nhu Nguyen, Steven H. Lin, Mark E. Zafereo, Matthew S. Ning
Journal: Journal of the National Comprehensive Cancer Network (2024)

Definitive radiotherapy (dRT) has been shown to be an effective option for patients with oligometastatic and oligoprogressive cancers; however, this approach has not been well-studied in metastatic thyroid cancer.
Agonism of the glutamate receptor GluK2 suppresses dermal mast cell activation and cutaneous inflammation
Authors: Youran R. Zhang, Swapnil Keshari, Kazuo Kurihara, James Liu, Lindsay M. McKendrick, Chien-Sin Chen, Yufan Yang, Louis D. Falo, Jishnu Das, Tina L. Sumpter, Daniel H. Kaplan
Journal: Science Translational Medicine (2024)

Activation of dermal mast cells through the Mas-related G protein-coupled receptor B2 receptor (MrgprB2 in mice and MrgprX2 in humans) is a key component of numerous inflammatory skin diseases, including dermatitis and rosacea. Sensory neurons actively suppress mast cell activation through the regulated release of glutamate, resulting in reduced expression of
Development of a fibrin-targeted theranostic for gastric cancer
Authors: Shadi A. Esfahani, Li Ma, Shriya Krishna, Hua Ma, Shvan J. Raheem, Sergey Shuvaev, Nicholas J. Rotile, Jonah Weigand-Whittier, Avery T. Boice, Nicholas Borges, Constantina A. Treaba, Caitlin Deffler, Himashinie Diyabalanage, Valerie Humblet, David E. Sosnovik, Umar Mahmood, Pedram Heidari, Angela Shih, Ciprian Catana, Matthew R. Strickland, Samuel J. Klempner, Peter Caravan
Journal: Science Translational Medicine (2024)

Patients with advanced gastric cancer (GCa) have limited treatment options, and alternative treatment approaches are necessary to improve their clinical outcomes. Because fibrin is abundant in gastric tumors but not in healthy tissues, we hypothesized that fibrin could be used as a high-concentration depot for a high-energy beta-emitting cytotoxic radiopharmaceutical delivered to tumor cells. We showed that fibrin is present in 64 to 75% of primary gastric tumors and 50 to 100% of metastatic gastric adenocarcinoma cores. First-in-human 64 Cu-FBP8 fibrin–targeted positron emission tomography (PET) imaging in seven patients with gastric or gastroesophageal junction cancer showed high probe uptake in all target lesions with tumor-to-background (muscle) uptake ratios of 9.9 ± 6.6 in primary ( n = 7) and 11.2 ± 6.6 in metastatic ( n = 45) tumors. Using two mouse models of human GCa, one fibrin-high (SNU-16) and one fibrin-low (NCI-N87), we showed that PET imaging with a related fibrin-specific peptide, CM500, labeled with copper-64 ( 64 Cu-CM500) specifically bound to and precisely quantified tumor fibrin in both models. We then labeled the fibrin-specific peptide CM600 with yttrium-90 and showed that 90 Y-CM600 effectively decreased tumor growth in these mouse models. Mice carrying fibrin-high SNU-16 tumors experienced tumor growth inhibition and prolonged survival in response to either a single high dosage or fractionated lower dosage of 90 Y-CM600, whereas mice carrying fibrin-low NCI-N87 tumors experienced prolonged survival in response to a fractionated lower dosage of 90 Y-CM600. These results lay the foundation for a fibrin-targeted theranostic that may expand options for patients with advanced GCa.
ABCG1 orchestrates adipose tissue macrophage plasticity and insulin resistance in obesity by rewiring saturated fatty acid pools
Authors: Veronica D. Dahik, Pukar KC, Clément Materne, Canelle Reydellet, Marie Lhomme, Céline Cruciani-Guglielmacci, Jessica Denom, Eric Bun, Maharajah Ponnaiah, Florence Deknuydt, Eric Frisdal, Lise M. Hardy, Hervé Durand, Isabelle Guillas, Philippe Lesnik, Ivan Gudelj, Gordan Lauc, Maryse Guérin, Anatol Kontush, Antoine Soprani, Christophe Magnan, Marc Diedisheim, Olivier Bluteau, Nicolas Venteclef, Wilfried Le Goff
Journal: Science Translational Medicine (2024)

The mechanisms governing adipose tissue macrophage (ATM) metabolic adaptation during diet-induced obesity (DIO) are poorly understood. In obese adipose tissue, ATMs are exposed to lipid fluxes, which can influence the activation of specific inflammatory and metabolic programs and contribute to the development of obesity-associated insulin resistance and other metabolic disorders. In the present study, we demonstrate that the membrane ATP-binding cassette g1 (Abcg1) transporter controls the ATM functional response to fatty acids (FAs) carried by triglyceride-rich lipoproteins, which are abundant in high-energy diets. Mice genetically lacking Abcg1 in the myeloid lineage presented an ameliorated inflammatory status in adipose tissue and reduced insulin resistance. Abcg1-deficient ATMs exhibited a less inflammatory phenotype accompanied by a low bioenergetic profile and modified FA metabolism. A closer look at the ATM lipidome revealed a shift in the handling of FA pools, including a redirection of saturated FAs from membrane phospholipids to lipid droplets, leading to a reduction in membrane rigidity and neutralization of proinflammatory FAs. ATMs from human individuals with obesity presented the same reciprocal relationship between ABCG1 expression and this inflammatory and metabolic status. Abolition of this protective, anti-inflammatory phenotype in Abcg1-deficient ATMs was achieved through restoration of lipoprotein lipase (Lpl) activity, thus delineating the importance of the Abcg1/Lpl axis in controlling ATM metabolic inflammation. Overall, our study identifies the rewiring of FA pools by Abcg1 as a major pathway orchestrating ATM plasticity and insulin resistance in DIO.