tbuckley/cabot-search huggingface dataset:
Core elements of national policy for digital health technology evidence and access
Authors: Megan Coder, Lacey McBride, Samantha McClenahan
Journal: npj Digital Medicine (2024)

Digital health technologies (DHT) offer the ability to deliver personalized care, lower barriers to access, and positively impact health outcomes. However, DHT utilization is impacted by insufficient market access pathways. A policy "full-stack"—including regulatory authorization, product value assessment, pricing and reimbursement, and patient access infrastructure—offers a framework for DHT integration into national healthcare ecosystems. Consistent clinical evidence requirements across national jurisdictions will further increase DHT scalability.
The Neurodevelopmental Protein POGZ Suppresses Metastasis in Triple Negative Breast Cancer by Attenuating TGFβ Signaling
Authors: John Heath, Caitlynn Mirabelli, Matthew G. Annis, Valerie Sabourin, Steven Hebert, Steven Findlay, HaEun Kim, Michael Witcher, Claudia L. Kleinman, Peter M. Siegel, Alexandre Orthwein, Josie Ursini-Siegel
Journal: Cancer Research (2024)

The pogo transposable element-derived zinc finger protein, POGZ, is notably associated with neurodevelopmental disorders through its role in gene transcription. Many proteins involved in neurological development are often dysregulated in cancer, suggesting a potential role for POGZ in tumor biology. Here, we provided experimental evidence that POGZ influences the growth and metastatic spread of triple-negative breast cancers (TNBC). In well-characterized models of TNBC, POGZ exerted a dual role, both as a tumor promoter and metastasis suppressor. Mechanistically, loss of POGZ potentiated TGFβ pathway activation to exert cytostatic effects while simultaneously increasing the mesenchymal and migratory properties of breast tumors. Although POGZ levels are elevated in human breast cancers, the most aggressive forms of TNBC tumors, including those with increased mesenchymal and metastatic properties, exhibit dampened POGZ levels, and low POGZ expression was associated with inferior clinical outcomes in these tumor types. Taken together, these data suggest that POGZ is a critical suppressor of the early stages of the metastatic cascade. Significance: The POGZ neurodevelopmental protein plays dual functions in triple-negative breast cancers as a tumor promoter and metastasis suppressor, inhibiting TGFβ-regulated EMT to limit breast cancer metastatic progression.
Glomerular filtration rate estimation in transgender adults using gender-affirming hormone therapy: an exploratory cross-sectional study
Authors: Keila Turino Miranda, Sandra M Dumanski, Nathalie Saad, Lesley A Inker, Christine A White, Pierre Delanaye, David Collister, Dina N Greene, Cameron T Whitley, Tyrone G Harrison, Chantal L Rytz, Lindsay Peace, Darlene Y Sola, Sofia B Ahmed
Journal: Kidney International (2024)
First-Line Nivolumab Plus Relatlimab Versus Nivolumab Plus Ipilimumab in Advanced Melanoma: An Indirect Treatment Comparison Using RELATIVITY-047 and CheckMate 067 Trial Data
Authors: Georgina V. Long, Evan J. Lipson, F. Stephen Hodi, Paolo A. Ascierto, James Larkin, Christopher Lao, Jean-Jacques Grob, Flavia Ejzykowicz, Andriy Moshyk, Viviana Garcia-Horton, Zheng-Yi Zhou, Yiqiao Xin, Jennell Palaia, Laura McDonald, Sarah Keidel, Anthony Salvatore, Divya Patel, Leon A. Sakkal, Hussein Tawbi, Dirk Schadendorf
Journal: Journal of Clinical Oncology (2024)

PURPOSE Nivolumab plus relatlimab and nivolumab plus ipilimumab have been approved for advanced melanoma on the basis of the phase II/III RELATIVITY-047 and phase III CheckMate 067 trials, respectively. As no head-to-head trial comparing these regimens exists, an indirect treatment comparison was conducted using patient-level data from each trial. METHODS Inverse probability of treatment weighting (IPTW) adjusted for baseline characteristic differences. Minimum follow-ups (RELATIVITY-047, 33 months; CheckMate 067, 36 months) were selected to best align assessments. Outcomes included progression-free survival (PFS), confirmed objective response rate (cORR), and melanoma-specific survival (MSS) per investigator; overall survival (OS); and treatment-related adverse events (TRAEs). A Cox regression model compared PFS, OS, and MSS. A logistic regression model compared cORRs. Subgroup analyses were exploratory. RESULTS After IPTW, key baseline characteristics were balanced for nivolumab plus relatlimab (n = 339) and nivolumab plus ipilimumab (n = 297). Nivolumab plus relatlimab demonstrated similar PFS (hazard ratio [HR], 1.08 [95% CI, 0.88 to 1.33]), cORR (odds ratio, 0.91 [95% CI, 0.73 to 1.14]), OS (HR, 0.94 [95% CI, 0.75 to 1.19]), and MSS (HR, 0.86 [95% CI, 0.67 to 1.12]) to nivolumab plus ipilimumab. Subgroup comparisons showed larger numerical differences favoring nivolumab plus ipilimumab with acral melanoma, BRAF -mutant melanoma, and lactate dehydrogenase &gt;2 × upper limit of normal, but were limited by small samples. Nivolumab plus relatlimab was associated with fewer grade 3-4 TRAEs (23% v 61%) and any-grade TRAEs leading to discontinuation (17% v 41%). CONCLUSION Nivolumab plus relatlimab demonstrated similar efficacy to nivolumab plus ipilimumab in the overall population, including most—but not all—subgroups, and improved safety in patients with untreated advanced melanoma. Results should be interpreted with caution.
Nanoplastics in the Human Respiratory System
Authors: Chenghui Zhong, Meiqi Lan, Changli Tu, Wenfeng Lu, Yuewei Liu, Xiaoliang Li, Cuiyan Tan, Jing Liu, Yun Zhou
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Nanoplastics in the Human Respiratory System." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Erratum: Busulfan Plus Fludarabine Compared With Busulfan Plus Cyclophosphamide for AML Undergoing HLA-Haploidentical Hematopoietic Cell Transplantation: A Multicenter Randomized Phase III Trial
Authors: Yiwen Ling, Li Xuan, Na Xu, Fen Huang, Zhiping Fan, Ziwen Guo, Xiaojun Xu, Hui Liu, Ren Lin, Sijian Yu, Haiyan Zhang, Hua Jin, Meiqing Wu, Can Liu, Xinquan Liang, Ruiming Ou, Yuping Zhang, Xiaodan Liu, Hong Qu, Xiao Zhai, Jing Sun, Ying Zhao, Qifa Liu
Journal: Journal of Clinical Oncology (2024)
Progressive Early Interstitial Lung Abnormalities in Persons At-Risk for Familial Pulmonary Fibrosis: A Prospective Cohort Study
Authors: Margaret L Salisbury, Cheryl Markin, Tisra Fadely, Adam R. Guttentag, Stephen M Humphries, David A. Lynch, Jonathan A Kropski, Timothy S Blackwell
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Relatives of patients with familial pulmonary fibrosis (FPF) are at increased risk to develop FPF. Interstitial lung abnormalities (ILAs) are a radiologic biomarker of subclinical disease, but the implications of very mild abnormalities remain unclear.
Clinical characteristics and risk factors for secondary lymphoedema in hidradenitis suppurativa
Authors: Patricia Garbayo-Salmons, Aida Lara-Moya, Sofía Haselgruber, Eva Vilarrasa, Antonio Martorell, Marta Gamissans, Inés Gracia-Darder, Rafael S Aguayo-Ortiz, Cristina Ciudad, Raquel Rivera-Díaz, Veronica Mora-Fernandez, Jorge Romaní, Joan Garcias-Ladaria, Rosa Fornons-Servent, Diana Fuertes Bailón, Alejandro Molina-Leyva
Journal: British Journal of Dermatology (2024)

Lymphoedema – a chronic inflammatory disorder associated with hidradenitis suppurativa (HS) – significantly impairs function and patients’ quality of life. Herein, we present a retrospective review of a multicentre cohort of patients with HS with secondary lymphoedema.
Gender, age, and longitudinal measurement invariance of child and adolescent depression scales: A systematic review
Authors: Pascal Schlechter, Mona Hillmann, Sharon A.S. Neufeld
Journal: Clinical Psychology Review (2024)

Understanding developmental trajectories and gender differences in depressive symptoms is clinically relevant. Discerning true differences across gender, age groups, and time is based on the often-neglected premise of measurement invariance (MI) of child and adolescent depression scales. In this systematic review, we assessed available evidence for MI across gender, age groups, and time for depression scales validated in children and adolescents, in studies with at least one assessment under age 18. A literature search using Medline, PsychInfo, Scopus, Web of Science, and Google Scholar databases identified 42 studies that examined MI. MI of eleven scales was tested in 1–9 studies per scale. Conclusions are hampered by different factor solutions tested within some scales. All included questionnaires showed preliminary evidence for MI across gender. Across some studies, crying had higher factor loadings in females compared to males, indicating that crying may be differently related to depression across gender. MI evidence was preliminary in just four scales across time, mostly confined to ages 13–17. One study showed developmental conclusions differed when non-invariance is not accounted for in observed scores. Overall, evidence for MI in child and adolescent depression scales is currently limited.
B Cell Epigenetic Modulation of IgA Response by 5-Azacytidine and IgA Nephropathy
Authors: Shanshan Yu, Xiang Li, Ting Wang, Jingyi Li, Hongzhi Li, Ying Xu, Yanling Hu, Fubin Zhu, Jinwei Wang, Tianhe Wang, Bin Zhu, Xu-jie Zhou, Hong Zhang, Jicheng Lv, Jonathan Barratt, Binghai Zhao
Journal: Journal of the American Society of Nephrology (2024)

Key Points Dysregulated IgA production plays a key role in the pathogenesis of IgA nephropathy. Increased 5-methylcytosine modification, an epigenetic regulatory mechanism, exaggerated IgA nephropathy phenotype in mice. Conversely, inhibition of 5-methylcytosine modification ameliorated progression of IgA nephropathy–like kidney disease in mice. Background IgA nephropathy is an important global cause of kidney failure. Dysregulation of IgA production is believed to play a key role in IgA nephropathy pathogenesis; however, little is known about the epigenetic mechanisms, such as RNA 5-methylcytosine (5mC) modification, in regulating IgA synthesis. Methods To decipher the role of RNA 5mC in regulation of IgA class switch, the microRNA (miR)-23b −/− and Lactobacillus casei (Chinese Industrial Microbial Culture Collection Center) cell wall extract–induced Kawasaki disease mice were treated with 5-azacytidine. Trdmt1 −/− and double Trdmt1 −/− / miR-23b −/− mice and Aid −/− mice or Aid −/− / miR-23b −/− mice were also used. Results We showed that miR-23b downregulated expression of Transfer RNA Aspartic Acid Methyltransferase 1 and consequently reduced 5mC (m 5 C) RNA modification and IgA synthesis in B cells. Inhibition of m 5 C RNA modification normalized serum IgA levels and ameliorated progression of the IgA nephropathy–like kidney disease in miR-23b −/− and Kawasaki disease mice, while mesangial IgA and C3 deposition failed to develop in Trdmt1 −/− miR-23b −/− mice. By contrast, increased m 5 C RNA modification resulted in an exaggerated IgA nephropathy phenotype. miR-23b regulation of serum IgA levels and the development of an IgA nephropathy–like kidney disease in miR-23b −/− and Kawasaki disease mice is likely mediated through TRDMT1-driven 5mC RNA modification in B cells, resulting in impaired activation-induced cytidine deaminase activity and IgA class switch recombination. Conclusions This study revealed TRDMT1-induced RNA 5mC methylation regulated IgA class switch, and inhibition of RNA 5mC by 5-azacytidine ameliorated progression of IgA nephropathy.
Navigating Renin-Angiotensin System Inhibitors in Patients with Declines in eGFR
Authors: Rachel Shulman, Jordana B. Cohen
Journal: Journal of the American Society of Nephrology (2024)

1Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 2Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania Correspondence: Dr. Jordana B. Cohen, email: [email protected] See related articles, "Association between Acute Declines in eGFR during Renin-Angiotensin System Inhibition and Risk of Adverse Outcomes," and "Estimated Effect of Restarting Renin-Angiotensin System Inhibitors after Discontinuation on Kidney Outcomes and Mortality," on pages XXX–XXX and XXX–XXX, respectively.
Neuro-mesenchymal interaction mediated by a β2 adrenergic-nerve growth factor feedforward loop promotes colorectal cancer progression.
Authors: Hiroki Kobayashi, Tadashi Iida, Yosuke Ochiai, Ermanno Malagola, Xiaofei Zhi, Ruth A. White, Jin Qian, Feijing Wu, Quin T. Waterbury, Ruhong Tu, Biyun Zheng, Jonathan S. LaBella, Leah B. Zamechek, Atsushi Ogura, Susan L. Woods, Daniel L. Worthley, Atsushi Enomoto, Timothy C. Wang
Journal: Cancer Discovery (2024)

Cancer-associated fibroblasts (CAFs) and nerves, components of the tumor microenvironment, have each been shown to directly promote gastrointestinal cancers. However, it remains unknown whether these cells interact with each other to regulate cancer progression. We found that in colorectal cancer (CRC) norepinephrine induces ADRB2-dependent nerve growth factor (NGF) secretion from CAFs, which in turn increases intra-tumor sympathetic innervation and norepinephrine accumulation. Adrenergic stimulation accelerates CRC growth through ADRA2A/Gi-mediated activation of Yes-Associated Protein (YAP). NGF from CAFs directly enhances CRC cell growth via the PI3K/AKT pathway. Treatment with a tropomyosin receptor kinase (Trk) inhibitor decreased YAP and AKT activation and CRC progression in mice. In human CRC, high NGF expression is associated with the mesenchymal-like tumor subtype and poor patient survival. These findings suggest a central role for reciprocal CAF-nerve crosstalk in promoting CRC progression. Blocking this feedforward loop with a Trk inhibitor may represent a potential therapeutic approach for CRC.
Nanoengineered mitochondria enable ocular mitochondrial disease therapy via the replacement of dysfunctional mitochondria
Authors: Yi Wang, Nahui Liu, Lifan Hu, Jingsong Yang, Mengmeng Han, Tianjiao Zhou, Lei Xing, Hulin Jiang
Journal: Acta Pharmaceutica Sinica B (2024)

Leber's hereditary optic neuropathy (LHON) is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I, which is an important contributor to blindness among young adults across the globe. However, the disorder has no available cures, since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them. Herein, PARKIN mRNA-loaded nanoparticle (mNP)-engineered mitochondria (mNP-Mito) were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria, normalizing the function of complex I for treating LHON. The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer, along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process. In a mouse model induced with a complex I inhibitor (rotenone, Rot), mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity (76.5%) compared to the group exposed to Rot damage (29.5%), which greatly promoted the restoration of ATP generation and mitigation of ocular mitochondrial disease-related phenotypes. This study highlights the significance of nanoengineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.
Oral resveratrol in adults with knee osteoarthritis: A randomized placebo-controlled trial (ARTHROL)
Authors: Christelle Nguyen, Emmanuel Coudeyre, Isabelle Boutron, Gabriel Baron, Camille Daste, Marie-Martine Lefèvre-Colau, Jérémie Sellam, Jennifer Zauderer, Francis Berenbaum, François Rannou
Journal: PLoS Medicine (2024)

Background Resveratrol is a natural compound found in red wine. It has demonstrated anti-inflammatory properties in preclinical models. We compared the effect of oral resveratrol in a new patented formulation to oral placebo for individuals with painful knee osteoarthritis. Methods and findings ARTHROL was a double-blind, randomized, placebo-controlled, Phase 3 trial conducted in 3 tertiary care centers in France. We recruited adults who fulfilled the 1986 American College of Rheumatology criteria for knee osteoarthritis and reported a pain intensity score of at least 40 on an 11-point numeric rating scale (NRS) in 10-point increments (0, no pain, to 100, maximal pain). Participants were randomly assigned (1:1) by using a computer-generated randomization list with permuted blocks of variable size (2, 4, or 6) to receive oral resveratrol (40 mg [2 caplets] twice a day for 1 week, then 20 mg [1 caplet] twice a day; resveratrol group) or matched oral placebo (placebo group) for 6 months. The primary outcome was the mean change from baseline in knee pain on a self-administered 11-point pain NRS at 3 months. The trial was registered at ClinicalTrials.gov : (NCT02905799). Between October 20, 2017 and November 8, 2021, we assessed 649 individuals for eligibility, and from November 9, 2017, we recruited 142 (22%) participants (mean age 61.4 years [standard deviation (SD) 9.6] and 101 [71%] women); 71 (50%) were randomly assigned to the resveratrol group and 71 (50%) to the placebo group. At baseline, the mean knee pain score was 56.2/100 (SD 13.5). At 3 months, the mean reduction in knee pain was −15.7 (95% confidence interval (CI), −21.1 to −10.3) in the resveratrol group and −15.2 (95% CI, −20.5 to −9.8) in the placebo group (absolute difference −0.6 [95% CI, −8.0 to 6.9]; p = 0.88). Serious adverse events (not related to the interventions) occurred in 3 (4%) in the resveratrol group and 2 (3%) in the placebo group. Our study has limitations in that it was underpowered and the effect size, estimated to be 0.55, was optimistically estimated. Conclusions In this study, we observed that compared with placebo, oral resveratrol did not reduce knee pain in people with painful knee osteoarthritis. Trial registration ClinicalTrials.gov ID: NCT02905799 .
Safety and efficacy of odronextamab in patients with relapsed or refractory follicular lymphoma
Authors: T.M. Kim, M. Taszner, S. Novelli, S-G. Cho, J.C. Villasboas, M. Merli, A. Jiménez-Ubieto, B. Tessoulin, L.M. Poon, D. Tucker, J. Walewski, S. Yi, Y. Song, G. Chong, E. Bachy, S. Guidez, A. Alonso, D. Jagadeesh, W. Zhang, L. Magnano, E. Iskierka-Jażdżewska, M. Tani, B. Shen, A. Uppala, M. Zhu, S. Shariff, J. Brouwer-Visser, A. Chaudhry, H. Mohamed, S. Ambati, S. Luminari
Journal: Annals of Oncology (2024)

<h3>Background</h3> Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. <h3>Patients and methods</h3> This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma after two or more lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in cycle 1 to help mitigate the risk of cytokine release syndrome, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by independent central review. <h3>Results</h3> Among 128 patients evaluated, 95% completed cycle 1, and 85% completed four or more cycles. At 20.1 months' efficacy follow-up, objective response rate was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events occurred in 16% of patients. The most common treatment-emergent adverse events were cytokine release syndrome [56%; grade ≥3 1.7% (1/60) with 0.7/4/20 mg step-up], neutropenia (39%), and pyrexia (38%). <h3>Conclusions</h3> Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma.
Real-time platelet P2Y12 receptor occupancy as a promising pharmacodynamics biomarker for bridging the gap between PK/PD of clopidogrel therapy
Authors: Haipeng Li, Yueming Gu, Yumeng Zhao, Aiyun Xu, Dong Sun, Jingkai Gu
Journal: Acta Pharmaceutica Sinica B (2024)

Clopidogrel effectively inhibits platelet aggregation in response to ADP by irreversibly binding to the platelet P2Y12 receptor through its active metabolite. However, the observed discrepancies between the pharmacokinetics (PK) and pharmacodynamics (PD) of clopidogrel present substantial challenges in individualizing of antiplatelet therapy. To address these challenges, a robust liquid chromatography-tandem mass spectrometry method has been developed to facilitate the real-time assessment of platelet P2Y12 receptor occupancy. This method has been validated in animal models, providing a reliable link between individual PK profiles and PD effects. Target receptor occupancy offers a comprehensive overview of interindividual variations in clopidogrel metabolism, regulation of P2Y12 receptor expression, and platelet turnover. Moreover, it directly correlates with the inhibitory effect on platelet aggregation. The levels of platelet P2Y12 occupancy accurately reflect the extent of clinical factors influencing the PD of clopidogrel, including dosage, drug-drug interactions (DDI), and type 2 diabetes mellitus (T2DM). As a normalized metric, platelet P2Y12 occupancy not only serves potential as a diagnostic tool for personalized clopidogrel therapy but also aids in elucidating the role of the P2Y12 signaling pathway in cases of abnormal on-treatment platelet reactivity.
Lessons learned from an unsuccessful decentralized clinical trial in Oncology
Authors: Antonis Valachis, Henrik Lindman
Journal: npj Digital Medicine (2024)

Decentralized clinical trials have gained in popularity over the last years due to their advantages related to broadening recruitment strategies and resource saving possibilities. As more clinical trials adopt decentralized strategies, it is essential to share the knowledge about both successful and unsuccessful efforts in the research community. In the present commentary, we explore potential reasons that led to early termination of a decentralized clinical trial in Oncology.
The Role of Artificial Intelligence in Nephrology Clinical Trials
Authors: Lili Chan, Girish N. Nadkarni
Journal: Journal of the American Society of Nephrology (2024)

1The Charles Bronfman Institute of Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 2The Division of Data Driven and Digital Medicine (D3M), Icahn School of Medicine at Mount Sinai, New York, NY 3The Barbara T Murphy Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY aCorresponding Author: Girish N Nadkarni, MD, MPH, One Gustave L Levy Place, Box 1003, New York, NY-10029. [email protected]
Frailty and Prehabilitation
Authors: Danielle L. Kirkman, Jason M. Kidd, Salvatore Carbone, Vasco M. Pontinha, Bekir Tanriover, Dhiren Kumar, Gaurav Gupta
Journal: Journal of the American Society of Nephrology (2024)

Kirkman, Danielle L.; Kidd, Jason M.; Carbone, Salvatore; Pontinha, Vasco M.; Tanriover, Bekir; Kumar, Dhiren; Gupta, Gaurav Author Information