tbuckley/cabot-search huggingface dataset:
Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts
Authors: Xinjia Cai, Heyu Zhang, Yanjin Wang, Jianyun Zhang, Tiejun Li
Journal: International Journal of Oral Science (2024)

Odontogenic keratocyst (OKC) is a common jaw cyst with a high recurrence rate. OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome. Moreover, OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts. Because of the different prognosis, differential diagnosis of several cysts can contribute to clinical management. We collected 519 cases, comprising a total of 2 157 hematoxylin and eosin-stained images, to develop digital pathology-based artificial intelligence (AI) models for the diagnosis and prognosis of OKC. The Inception_v3 neural network was utilized to train and test models developed from patch-level images. Finally, whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms. The AI models showed great performance in the diagnosis (AUC = 0.935, 95% CI: 0.898-0.973) and prognosis (AUC = 0.840, 95%CI: 0.751-0.930) of OKC. The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model. Furthermore, the study investigates the correlation between AI features generated by deep learning and pathological findings, highlighting the interpretative potential of AI models in the pathology. Here, we have developed the robust diagnostic and prognostic models for OKC. The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.
Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis
Authors: Xiao Yang, Hui Zhao, Rui Li, Yang Chen, Zhi Xu, Zhengjun Shang
Journal: International Journal of Oral Science (2024)

Abstract A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model, treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs) were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (vFAOs). Consistently, treatment with arecoline reduced the expression of CD31 in vFAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.
Centring the health of women across the HIV research continuum
Authors: Elizabeth Barr, Leslie J Marshall, Lauren F Collins, Catherine Godfrey, Noelle St Vil, Jamila K Stockman, Dvora L Joseph Davey, Krista Dong, Sarah M Temkin, Mary T Glenshaw, Corette Byrd, Janine A Clayton, Maureen M Goodenow
Journal: The Lancet HIV (2024)
A preoperative package of care for osteoarthritis, consisting of weight loss, orthotics, rehabilitation, and topical and oral analgesia (OPPORTUNITY): a two-centre, open-label, randomised controlled feasibility trial
Authors: A Hamish R W Simpson, Nicholas D Clement, Sharon A Simpson, Hemandt Pandit, Susie Smillie, Anthony R Leeds, Philip G Conaghan, Sarah R Kingsbury, David Hamilton, Peter Craig, David Ray, Catriona Keerie, Elaine Kinsella, Anna Bell-Higgs, Arlene McGarty, Christine Beadle, Colin R Howie, John Norrie
Journal: The Lancet Rheumatology (2024)
Effect of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on incidence of these infections in men who have sex with men and transgender women taking HIV pre-exposure prophylaxis (the Gonoscreen study): results from a randomised, multicentre, controlled trial
Authors: Thibaut Vanbaelen, Achilleas Tsoumanis, Eric Florence, Christophe Van Dijck, Diana Huis In 't Veld, Anne-Sophie Sauvage, Natacha Herssens, Irith De Baetselier, Anke Rotsaert, Veronique Verhoeven, Sophie Henrard, Yven Van Herrewege, Dorien Van den Bossche, Jean-Christophe Goffard, Elizaveta Padalko, Thijs Reyniers, Bea Vuylsteke, Marie-Pierre Hayette, Agnes Libois, Chris Kenyon
Journal: The Lancet HIV (2024)
The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline
Authors: Paula P. Schnurr, Jessica L. Hamblen, Jonathan Wolf, Rachael Coller, Claire Collie, Matthew A. Fuller, Paul E. Holtzheimer, Ursula Kelly, Ariel J. Lang, Kate McGraw, Joshua C. Morganstein, Sonya B. Norman, Katie Papke, Ismene Petrakis, David Riggs, James A. Sall, Brian Shiner, Ilse Wiechers, Marija S. Kelber
Journal: Annals of Internal Medicine (2024)

The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. This article summarizes the 2023 clinical practice guideline (CPG) and its development process, focusing on assessments and treatments for which evidence was sufficient to support a recommendation for or against.
Characterization of Tumor Responses in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib in the Phase 3 Randomized Trial: REFLECT
Authors: Richard S Finn, Shukui Qin, Fabio Piscaglia, Thomas R Jeffry Evans, Jennifer J Knox, Carlos López López, Zahra Ramji, Min Ren, Kalgi Mody, Arndt Vogel, Masatoshi Kudo
Journal: Liver Cancer (2024)

In REFLECT, lenvatinib was noninferior to sorafenib in terms of overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC; median 13.6 vs. 12.3 months; HR 0.92, 95% CI 0.79-1.06). The objective response rate (ORR) with lenvatinib was 18.8% by blinded independent imaging review (IIR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); per modified RECIST (mRECIST), the ORR was 40.6%. We sought to further characterize these tumor responses and explore ORR's importance among outcomes for patients with HCC.
KIT ATP-Binding Pocket/Activation Loop Mutations in GI Stromal Tumor: Emerging Mechanisms of Kinase Inhibitor Escape
Authors: Thomas Mühlenberg, Johanna Falkenhorst, Tom Schulz, Benjamin S. Fletcher, Alina Teuber, Dawid Krzeciesa, Isabella Klooster, Meijun Lundberg, Lydia Wilson, Jonas Lategahn, Margaret von Mehren, Susanne Grunewald, Alicia Isabell Tüns, Eva Wardelmann, Jason K. Sicklick, Mehdi Brahmi, César Serrano, Hans-Ulrich Schildhaus, Sonja Sievers, Jürgen Treckmann, Michael C. Heinrich, Chandrajit P. Raut, Wen-Bin Ou, Adrian Marino-Enriquez, Suzanne George, Daniel Rauh, Jonathan A. Fletcher, Sebastian Bauer
Journal: Journal of Clinical Oncology (2024)

Imatinib resistance in GI stromal tumors (GISTs) is primarily caused by secondary
Meeting the Health and Social Needs of America’s Unhoused and Housing-Unstable Populations: A Position Paper From the American College of Physicians
Authors: Josh Serchen, David R. Hilden, Micah W. Beachy
Journal: Annals of Internal Medicine (2024)

Access to safe and stable housing has both a direct and indirect effect on health. Experiencing homelessness and housing instability can induce stress and trauma, worsening behavioral health and substance use. The absence of safe and stable living conditions can make it challenging to rest, recuperate, and recover from health ailments and can pose barriers to treatment adherence. Homelessness and housing instability is associated with high rates of numerous diseases and chronic conditions. Its cyclical relationship with other social drivers of health can exacerbate health disparities. As a result, unhoused persons experience unique health challenges and require a health care system and professionals designed to meet their distinct needs. Physicians and other health professionals have a role in educating themselves about the needs of unhoused patients as well as making themselves aware of community and government resources available to these populations. Policymakers must support health professionals in these efforts by supporting the data infrastructure needed to facilitate these referrals to resources, supporting research into best practices for caring for these populations, and investing in community-based organization capacity. Policy action is needed to address the underlying drivers of homelessness, including a dearth of affordable housing, while also addressing the short-term need for safe shelter now. In this position paper, the American College of Physicians (ACP) recognizes the need to address universal access to housing to fulfill one's right to health. ACP offers several recommendations to prevent homelessness and promote the necessary health care and social needs of unhoused populations.
A Risk Profile Using Simple Hematologic Parameters to Assess Benefits From Baricitinib in Patients Hospitalized With COVID-19: A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-2
Authors: Catharine I. Paules, Jing Wang, Kay M. Tomashek, Tyler Bonnett, Kanal Singh, Vincent C. Marconi, Richard T. Davey, David C. Lye, Lori E. Dodd, Otto O. Yang, Constance A. Benson, Gregory A. Deye, Sarah B. Doernberg, Noreen A. Hynes, Robert Grossberg, Cameron R. Wolfe, Seema U. Nayak, William R. Short, Jocelyn Voell, Gail E. Potter, Rekha R. Rapaka
Journal: Annals of Internal Medicine (2024)

The ACTT risk profile, which was developed from ACTT-1 (Adaptive COVID-19 Treatment Trial-1), demonstrated that hospitalized patients with COVID-19 in the high-risk quartile (characterized by low absolute lymphocyte count [ALC], high absolute neutrophil count [ANC], and low platelet count at baseline) benefited most from treatment with the antiviral remdesivir. It is unknown which patient characteristics are associated with benefit from treatment with the immunomodulator baricitinib. To apply the ACTT risk profile to the ACTT-2 cohort to investigate potential baricitinib-related treatment effects by risk quartile. Post hoc analysis of ACTT-2, a randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04401579). Sixty-seven trial sites in 8 countries. Adults hospitalized with COVID-19 (n = 999; 85% U.S. participants). Baricitinib+remdesivir versus placebo+remdesivir. Mortality, progression to invasive mechanical ventilation (IMV) or death, and recovery, all within 28 days; ALC, ANC, and platelet count trajectories. In the high-risk quartile, baricitinib+remdesivir was associated with reduced risk for death (hazard ratio [HR], 0.38 [95% CI, 0.16 to 0.86]; P = 0.020), decreased progression to IMV or death (HR, 0.57 [CI, 0.35 to 0.93]; P = 0.024), and improved recovery rate (HR, 1.53 [CI, 1.16 to 2.02]; P = 0.002) compared with placebo+remdesivir. After 5 days, participants receiving baricitinib+remdesivir had significantly larger increases in ALC and significantly larger decreases in ANC compared with control participants, with the largest effects observed in the high-risk quartile. Secondary analysis of data collected before circulation of current SARS-CoV-2 variants. The ACTT risk profile identifies a subgroup of hospitalized patients who benefit most from baricitinib treatment and captures a patient phenotype of treatment response to an immunomodulator and an antiviral. Changes in ALC and ANC trajectory suggest a mechanism whereby an immunomodulator limits severe COVID-19. National Institute of Allergy and Infectious Diseases.
Outcomes of a Dietary Intervention to Reduce Bladder Cancer Recurrence and Progression in Survivors of Non–Muscle-Invasive Bladder Cancer
Authors: Karen H. Kim Yeary, Han Yu, Margaret Gates Kuliszewski, Qiang Li, Susan E. McCann, Rachel Pratt, Frances G. Saad-Harfouche, Zinian Wang, Nikia Clark, Chong Wang, Elizabeth DiCarlo, Li Tang
Journal: Journal of the National Comprehensive Cancer Network (2024)

As one of the 10 most common cancers in the United States, bladder cancer is the most expensive cancer to treat. Most bladder cancers (70%-80%) are diagnosed at early stages as non-muscle-invasive bladder cancer (NMIBC), which can be removed. However, 50% to 80% of NMIBC recurs within 5 years, and 15% to 30% progresses with poor survival. Besides life-long surveillance, current treatment is limited. Preclinical and epidemiologic evidence suggest that dietary isothiocyanates (ITCs) in cruciferous vegetables (Cruciferae) could be a noninvasive and cost-effective strategy to improve NMIBC prognosis. Yet, a Cruciferae intervention that increases ITC exposure in NMIBC survivors has not been tested. Thus, the primary aim of this study was to test the effect of a Cruciferae intervention on urinary ITC levels and Cruciferae intake in NMIBC survivors.
A Versatile Chitosan‐Based Hydrogel Accelerates Infected Wound Healing via Bacterial Elimination, Antioxidation, Immunoregulation, and Angiogenesis
Authors: Ye Zhang, Sinan Chen, Xian Qin, Ai Guo, Kai Li, Lixue Chen, Weiwei Yi, Zhongliang Deng, Franklin R. Tay, Wenbo Geng, Li Miao, Yang Jiao, Bailong Tao
Journal: Advanced Healthcare Materials (2024)

Abstract Drug‐resistant bacterial infection of cutaneous wounds causes great harm to the human body. These infections are characterized by a microenvironment with recalcitrant bacterial infections, persistent oxidative stress, imbalance of immune regulation, and suboptimal angiogenesis. Treatment strategies available to date are incapable of handling the healing dynamics of infected wounds. A Schiff base and borate ester cross‐linked hydrogel, based on phenylboronic acid‐grafted chitosan (CS‐PBA), dibenzaldehyde‐grafted poly(ethylene glycol), and tannic acid (TA), is fabricated in the present study. Customized phenylboronic acid‐modified zinc oxide nanoparticles (ZnO) are embedded in the hydrogel prior to gelation. The CPP@ZnO‐P‐TA hydrogel effectively eliminates methicillin‐resistant Staphylococcus aureus (MRSA) due to the pH‐responsive release of Zn 2+ and TA. Killing is achieved via membrane damage, adenosine triphosphate reduction, leakage of intracellular components, and hydrolysis of bacterial o ‐nitrophenyl‐β‐ d ‐galactopyranoside. The CPP@ZnO‐P‐TA hydrogel is capable of scavenging reactive oxygen and nitrogen species, alleviating oxidative stress, and stimulating M2 polarization of macrophages. The released Zn 2+ and TA also induce neovascularization via the PI3K/Akt pathway. The CPP@ZnO‐P‐TA hydrogel improves tissue regeneration in vivo by alleviating inflammatory responses, stimulating angiogenesis, and facilitating collagen deposition. These findings suggest that this versatile hydrogel possesses therapeutic potential for the treatment of MRSA‐infected cutaneous wounds.
RNA Therapeutics for the Cardiovascular System
Authors: Victor J. Dzau, Conrad P. Hodgkinson
Journal: Circulation (2024)

RNA therapeutics hold significant promise in the treatment of cardiovascular diseases. RNAs are biologically diverse and functionally specific and can be used for gain- or loss-of-function purposes. The effectiveness of mRNA-based vaccines in the recent COVID-19 pandemic has undoubtedly proven the benefits of an RNA-based approach. RNA-based therapies are becoming more common as a treatment modality for cardiovascular disease. This is most evident in hypertension where several small interfering RNA–based drugs have proven to be effective in managing high blood pressure in several clinical trials. As befits a rapidly burgeoning field, there is significant interest in other classes of RNA. Revascularization of the infarcted heart through an mRNA drug is under clinical investigation. mRNA technology may provide the platform for the expression of paracrine factors for myocardial protection and regeneration. Emergent technologies on the basis of microRNAs and gene editing are tackling complex diseases in a novel fashion. RNA-based gene editing offers hope of permanent cures for monogenic cardiovascular diseases, and long-term control of complex diseases such as essential hypertension, as well. Likewise, microRNAs are proving effective in regenerating cardiac muscle. The aim of this review is to provide an overview of the current landscape of RNA-based therapies for the treatment of cardiovascular disease. The review describes the large number of RNA molecules that exist with a discussion of the clinical development of each RNA type. In addition, the review also presents a number of avenues for future development.
68Ga-RM2 PET–MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial
Authors: Heying Duan, Farshad Moradi, Guido A Davidzon, Tie Liang, Hong Song, Andreas M Loening, Shreyas Vasanawala, Sandy Srinivas, James D Brooks, Steven Hancock, Andrei Iagaru
Journal: The Lancet Oncology (2024)
Effect of BCG vaccination against Mycobacterium tuberculosis infection in adult Brazilian health-care workers: a nested clinical trial
Authors: Paulo Cesar Pereira dos Santos, Nicole Louise Messina, Roberto Dias de Oliveira, Patricia Vieira da Silva, Marco Antonio Moreira Puga, Margareth Dalcolmo, Glauce dos Santos, Marcus Vinícius Guimarães de Lacerda, Bruno Araújo Jardim, Fernando Fonseca de Almeida e Val, Nigel Curtis, Jason R Andrews, Julio Croda
Journal: The Lancet Infectious Diseases (2024)

The effectiveness of BCG vaccine for adult pulmonary tuberculosis remains uncertain. In this study, we aimed to evaluate the effect of vaccination with BCG-Denmark to prevent initial and sustained interferon-γ release assay conversion in Brazilian health-care workers.
Opportunities and challenges for innovative and equitable healthcare
Authors: David J. Ecker, Clarice D. Aiello, Joseph R. Arron, C. Frank Bennett, Amy Bernard, Xandra O. Breakefield, Timothy J. Broderick, Shawneequa L. Callier, Barry Canton, Janice S. Chen, C. Simone Fishburn, Banning Garrett, Sidney M. Hecht, Tobias Janowitz, Melinda Kliegman, Adrian Krainer, Chrystal U. Louis, Christopher Lowe, Alfica Sehgal, Yesim Tozan, Kevin J. Tracey, Fyodor Urnov, Daniel Wattendorf, Thomas W. Williams, Xuanhe Zhao, Michael R. Hayden
Journal: Nature Reviews Drug Discovery (2024)
Summary of WHO infection prevention and control guideline for Ebola and Marburg disease: a call for evidence based practice
Authors: Victoria Willet, Devika Dixit, Dale Fisher, Daniel G Bausch, Folasade Ogunsola, Joanne Khabsa, Elie A Akl, April Baller
Journal: BMJ (2024)

on behalf of the Guideline Development Group Outbreaks of Ebola and Marburg disease have continued to occur since the Zaire ebolavirus outbreak in West Africa 2014-16.In response, the World Health Organisation (WHO) published a new infection prevention and control (IPC) guideline for both diseases in August 2023, 1 which replaces those issued in 2014 and 2016. 2 -4 This article summarises the process involved in developing the updated guideline and includes an infographic (fig 1) to highlight key IPC recommendations from the guideline, following the patient care pathway from the community to a healthcare facility to discharge.The full guideline is available as a downloadable PDF on both the WHO website (Infection prevention and control guideline for Ebola and Marburg disease, August 2023, who.int) and the web based MAGICapp platform.
Genetic associations with ratios between protein levels detect new pQTLs and reveal protein-protein interactions
Authors: Karsten Suhre
Journal: Cell Genomics (2024)

Protein quantitative trait loci (pQTLs) are an invaluable source of information for drug target development because they provide genetic evidence to support protein function, suggest relationships between cis- and trans-associated proteins, and link proteins to disease endpoints. Using Olink proteomics data for 1,463 proteins measured in over 54,000 samples of the UK Biobank, we identified 4,248 associations with 2,821 ratios between protein levels (rQTLs). rQTLs were 7.6-fold enriched in known protein-protein interactions, suggesting that their ratios reflect biological links between the implicated proteins. Conducting a GWAS on ratios increased the number of discovered genetic signals by 24.7%. The approach can identify novel loci of clinical relevance, support causal gene identification, and reveal complex networks of interacting proteins. Taken together, our study adds significant value to the genetic insights that can be derived from the UKB proteomics data and motivates the wider use of ratios in large-scale GWAS.
Alistipes indistinctus-derived hippuric acid promotes intestinal urate excretion to alleviate hyperuricemia
Authors: Ying-Xi Xu, Lu-Di Liu, Jiang-Yuan Zhu, Shan-Shan Zhu, Bing-Qi Ye, Jia-Lu Yang, Jing-Yi Huang, Zhi-Hao Huang, Yi You, Wen-Kang Li, Jia-Lin He, Min Xia, Yan Liu
Journal: Cell Host & Microbe (2024)
Impaired cerebellar plasticity hypersensitizes sensory reflexes in SCN2A-associated ASD
Authors: Chenyu Wang, Kimberly D. Derderian, Elizabeth Hamada, Xujia Zhou, Andrew D. Nelson, Henry Kyoung, Nadav Ahituv, Guy Bouvier, Kevin J. Bender
Journal: Neuron (2024)

Children diagnosed with autism spectrum disorder (ASD) commonly present with sensory hypersensitivity or abnormally strong reactions to sensory stimuli. Such hypersensitivity can be overwhelming, causing high levels of distress that contribute markedly to the negative aspects of the disorder. Here, we identify a mechanism that underlies hypersensitivity in a sensorimotor reflex found to be altered in humans and in mice with loss of function in the ASD risk-factor gene SCN2A. The cerebellum-dependent vestibulo-ocular reflex (VOR), which helps maintain one's gaze during movement, was hypersensitized due to deficits in cerebellar synaptic plasticity. Heterozygous loss of SCN2A-encoded Na
Management of chronic pancreatitis
Authors: O Joe Hines, Stephen J Pandol
Journal: BMJ (2024)

ABSTRACT Chronic pancreatitis results from repeated episodes of pancreatic inflammation and associated fibrosis leading to the loss of functional exocrine and endocrine pancreatic function. The disease is manifested by abdominal pain, deterioration in quality of life, food maldigestion and malabsorption, diabetes, and an increased risk for pancreatic adenocarcinoma. This review summarizes the latest evidence on the diagnosis and management of chronic pancreatitis and its manifestations. In particular, this review discusses advances in understanding of the role of genetic disorders in the mechanisms of the disease and surgical options for patients refractory to medical therapy. Furthermore, clinical trials are under way to develop medical therapeutics.