tbuckley/cabot-search huggingface dataset:
Racial and ethnic disparities in early treatment with immunotherapy for advanced HCC in the United States
Authors: Joseph C. Ahn, Marie Lauzon, Michael Luu, Mazen Noureddin, Walid Ayoub, Alexander Kuo, Vinay Sundaram, Kambiz Kosari, Nicholas Nissen, Jun Gong, Andrew Hendifar, Lewis R. Roberts, Ghassan K. Abou‐Alfa, Amit G. Singal, Ju Dong Yang
Journal: Hepatology (2022)

Abstract Background and Aims Immunotherapy has emerged as an effective treatment for patients with advanced‐stage HCC. We aimed to investigate the efficacy of immunotherapy for advanced HCC in a nationwide cohort and racial and ethnic disparities in access to immunotherapy. Approach and Results We used the US National Cancer Database to identify patients with tumor‐node‐metastasis stage 3 or 4 HCC between 2017 and 2018. We performed multivariable Cox regression to identify factors associated with overall survival (OS) and logistic regression to identify factors associated with receipt of immunotherapy. Of the 3,990 patients treated for advanced HCC, 3,248 (81.4%) patients received chemotherapy and 742 (18.6%) patients received immunotherapy as a first‐line treatment. Immunotherapy was associated with improved OS compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65–0.88) after adjusting for covariates. There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46–0.83) and Black patients (aOR: 0.71, 95% CI: 0.54–0.89) less likely to receive immunotherapy compared with White patients. There was a significant interaction between race‐ethnicity and facility type, with higher disparity observed in nonacademic centers (interaction p = 0.004). Conclusions Immunotherapy was associated with improved OS compared with chemotherapy in advanced HCC. There are significant disparities in early access to immunotherapy, likely due to differential access to clinical trials and experimental therapies. A comprehensive approach to monitoring and eliminating racial‐ethnic disparities in the management of advanced HCC is urgently needed.
Knife-Cut Ulcers in Crohn’s Disease
Authors: Rohit Kothari, Deepak Vashisht
Journal: New England Journal of Medicine (2022)

A 30-year-old man with Crohn’s disease presented with multiple painful ulcers in his groin and perineal area. Physical examination of the skin showed deep, linear erosions. Skin swabs were negative for bacterial, fungal, herpes simplex viral, and tubercular infections.
Add-On Prostaglandin E<sub>1</sub> in Venovenous Extracorporeal Membrane Oxygenation: A Randomized, Double-Blind, Placebo-controlled Pilot Trial
Authors: Nina Buchtele, Christian Schörgenhofer, Michael Schwameis, Bernd Jilma, Peter Schellongowski, Harald Herkner, Katharina Riss, Monika Schmid, Alexander Hermann, Oliver Robak, Bernhard Nagler, Ludwig Traby, Andja Bojic, Thomas Staudinger
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Prostaglandin E1 (alprostadil; PGE1), in addition to low-dose unfractionated heparin, increases the biocompatibility of extracorporeal systems and enhances the efficacy of artificial organs without increasing bleeding risk. Objectives: We investigated the safety and efficacy of PGE1 in adults receiving venovenous extracorporeal membrane oxygenation (ECMO). Methods: This study was a randomized, double-blind, placebo-controlled phase II pilot trial at two medical intensive care units at the Medical University of Vienna, Austria. Adults with venovenous ECMO were randomly assigned to receive an intravenous infusion of 5 ng/kg/min PGE1 or placebo (0.9% saline) in addition to standard anticoagulation with unfractionated heparin. Measurements and Main Results: The primary outcome was the rate of transfused packed red blood cells per ECMO day. Secondary outcomes were the incidence of and time to clinically overt bleeding and thromboembolic events. A post hoc subgroup analysis included only patients with coronavirus disease (COVID-19). Between September 2016 and April 2021, of 133 screened patients, 50 patients were randomized, of whom 48 received the assigned study medication (24 per group). The transfusion rate was similar between groups (0.41 vs. 0.39; P = 0.733). PGE1 was associated with fewer thromboembolic events (7 vs. 16; P = 0.020) and longer thromboembolism-free time (hazard ratio [HR], 0.302; P = 0.01), fewer clinically overt bleeding events (2 vs. 11; P = 0.017), and longer bleeding-free time (HR, 0.213; P = 0.047). In patients with COVID-19 (n = 25), the HRs for clinically overt bleeding and thromboembolism were 0.276 (95% confidence interval, 0.035–2.186) and 0.521 (95% confidence interval, 0.149–1.825), respectively. Conclusions: Add-on treatment with PGE1 was safe but did not meet the primary endpoint of reducing the rate of red blood cell transfusions in patients receiving venovenous ECMO. Larger studies need to evaluate the safety and efficacy of additional PGE1 in ECMO. Clinical trial registered with EudraCT (2015-005014-30) and www.clinicaltrials.gov (NCT02895373).
Investigation and management of Wilson's disease: a practical guide from the British Association for the Study of the Liver
Authors: Samuel Shribman, Thomas Marjot, Abubakar Sharif, Sunitha Vimalesvaran, Aftab Ala, Graeme Alexander, Anil Dhawan, James Dooley, Godfrey T Gillett, Deirdre Kelly, Alisdair McNeill, Thomas T Warner, Valerie Wheater, William Griffiths, Oliver Bandmann
Journal: The Lancet. Gastroenterology & hepatology (2022)
N6-methyladenosine modification of CENPK mRNA by ZC3H13 promotes cervical cancer stemness and chemoresistance
Authors: Xian Lin, Feng Wang, Jian Chen, Jing Liu, Yi-Bin Lin, Li Li, Chuan-Ben Chen, Qin Xu
Journal: Military Medical Research (2022)

Stemness and chemoresistance contribute to cervical cancer recurrence and metastasis. In the current study, we determined the relevant players and role of N6-methyladenine (m6A) RNA methylation in cervical cancer progression.The roles of m6A RNA methylation and centromere protein K (CENPK) in cervical cancer were analyzed using bioinformatics analysis. Methylated RNA immunoprecipitation was adopted to detect m6A modification of CENPK mRNA. Human cervical cancer clinical samples, cell lines, and xenografts were used for analyzing gene expression and function. Immunofluorescence staining and the tumorsphere formation, clonogenic, MTT, and EdU assays were performed to determine cell stemness, chemoresistance, migration, invasion, and proliferation in HeLa and SiHa cells, respectively. Western blot analysis, co-immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter, cycloheximide chase, and cell fractionation assays were performed to elucidate the underlying mechanism.Bioinformatics analysis of public cancer datasets revealed firm links between m6A modification patterns and cervical cancer prognosis, especially through ZC3H13-mediated m6A modification of CENPK mRNA. CENPK expression was elevated in cervical cancer, associated with cancer recurrence, and independently predicts poor patient prognosis [hazard ratio = 1.413, 95% confidence interval = 1.078 - 1.853, P = 0.012]. Silencing of CENPK prolonged the overall survival time of cervical cancer-bearing mice and improved the response of cervical cancer tumors to chemotherapy in vivo (P < 0.001). We also showed that CENPK was directly bound to SOX6 and disrupted the interactions of CENPK with β-catenin, which promoted β-catenin expression and nuclear translocation, facilitated p53 ubiquitination, and led to activation of Wnt/β-catenin signaling, but suppression of the p53 pathway. This dysregulation ultimately enhanced the tumorigenic pathways required for cell stemness, DNA damage repair pathways necessary for cisplatin/carboplatin resistance, epithelial-mesenchymal transition involved in metastasis, and DNA replication that drove tumor cell proliferation.CENPK was shown to have an oncogenic role in cervical cancer and can thus serve as a prognostic indicator and novel target for cervical cancer treatment.
Tumor Treating Fields: killing two birds with one stone
Authors: Juyeun Lee, Matthew M. Grabowski, Justin D. Lathia
Journal: Journal of Clinical Investigation (2022)

Given its aggressive natural history and immunosuppressive nature, glioblastoma (GBM) remains difficult to treat. Tumor Treating Fields (TTFields) are a promising treatment for GBM patients, yet the entirety of their antitumor action has not been fully elucidated. In a recent issue of the JCI, Chen et al. explored the effect of TTFields in reinvigorating immune responses. By elegant step-by-step approaches, the authors demonstrated that TTFields promote the production of immune-stimulating proinflammatory and interferon type 1 cytokines in tumor cells in a cGAS/STING- and AIM2 inflammasome–dependent mechanism, thereby activating the immune system. The findings show that TTFields not only directly inhibit tumor cell growth, as previously reported, but enhance antitumor immunity, suggesting TTFields can be used as an immune-modulating approach in GBM.
Advancing Health Equity Efforts to Reduce Obesity: Changing the Course
Authors: Shiriki K. Kumanyika
Journal: Annual Review of Nutrition (2022)

Population-based solutions are needed to stabilize and then reverse the continued upward trends in obesity prevalence in the US population and worldwide. This review focuses on the related, urgent issue of disparities in obesity prevalence affecting US racial/ethnic minority and other socially marginalized populations. The review provides background on these disparities from a health equity perspective and highlights evidence of progress in equity-focused obesity efforts. Five recommendations for advancing equity efforts are offered as potential approaches to build on progress to date: (
CT Imaging-Derived Anatomy Predicts Complexity and Hemodynamic Impact of Transcatheter Edge-to-Edge Mitral Valve Repair
Authors: Frank Meijerink, Iris Wolsink, Abdelhak El Bouziani, R.Nils Planken, Daniëlle Robbers-Visser, S. Matthijs Boekholdt, Marcel A.M. Beijk, Robbert J. de Winter, Jan Baan, Berto J. Bouma
Journal: JACC. Cardiovascular imaging (2022)
CS1 CAR-T targeting the distal domain of CS1 (SLAMF7) shows efficacy in high tumor burden myeloma model despite fratricide of CD8+CS1 expressing CAR-T cells
Authors: Julie O’Neal, Julie K. Ritchey, Matthew L. Cooper, Jessica Niswonger, L. Sofía González, Emily Street, Michael P. Rettig, Susan W. Gladney, Leah Gehrs, Ramzi Abboud, Julie L. Prior, Gabriel J. Haas, Reyka G. Jayasinghe, Li Ding, Armin Ghobadi, Ravi Vij, John F. DiPersio
Journal: Leukemia (2022)

Despite improvement in treatment options for myeloma patients, including targeted immunotherapies, multiple myeloma remains a mostly incurable malignancy. High CS1 (SLAMF7) expression on myeloma cells and limited expression on normal cells makes it a promising target for CAR-T therapy. The CS1 protein has two extracellular domains - the distal Variable (V) domain and the proximal Constant 2 (C2) domain. We generated and tested CS1-CAR-T targeting the V domain of CS1 (Luc90-CS1-CAR-T) and demonstrated anti-myeloma killing in vitro and in vivo using two mouse models. Since fratricide of CD8 + cells occurred during production, we generated fratricide resistant CS1 deficient Luc90- CS1- CAR-T (ΔCS1-Luc90- CS1- CAR-T). This led to protection of CD8 + cells in the CAR-T cultures, but had no impact on efficacy. Our data demonstrate targeting the distal V domain of CS1 could be an effective CAR-T treatment for myeloma patients and deletion of CS1 in clinical production did not provide an added benefit using in vivo immunodeficient NSG preclinical models.
High-fat diet disrupts REG3γ and gut microbial rhythms promoting metabolic dysfunction
Authors: Katya Frazier, Amal Kambal, Elizabeth A. Zale, Joseph F. Pierre, Nathaniel Hubert, Sawako Miyoshi, Jun Miyoshi, Daina L. Ringus, Dylan Harris, Karen Yang, Katherine Carroll, Jake B. Hermanson, John S. Chlystek, Katherine A. Overmyer, Candace M. Cham, Mark W. Musch, Joshua J. Coon, Eugene B. Chang, Vanessa A. Leone
Journal: Cell Host & Microbe (2022)
A TCR mimic CAR T cell specific for NDC80 is broadly reactive with solid tumors and hematologic malignancies
Authors: Martin G. Klatt, Tao Dao, Zhiyuan Yang, Jianying Liu, Sung Soo Mun, Megan M. Dacek, Hanzhi Luo, Thomas J. Gardner, Christopher Bourne, Leila Peraro, Zita E. H. Aretz, Tanya Korontsvit, Michael Lau, Michael G. Kharas, Cheng Liu, David A. Scheinberg
Journal: Blood (2022)
The establishment of public health policies and the burden of non-alcoholic fatty liver disease in the Americas
Authors: Luis Antonio Díaz, Eduardo Fuentes-López, Gustavo Ayares, Francisco Idalsoaga, Jorge Arnold, Andrea Márquez-Lomas, Carolina A Ramírez, María Paz Medel, Francisca Viñuela, Lucas Lacalle, Juan Pablo Roblero, Catterina Ferreccio, Mariana Lazo, Mayur Brahmania, Ashwani K Singal, Melisa Dirchwolf, Nahum Méndez-Sánchez, Norberto Chavez-Tapia, Patricia Guerra, Juan Carlos Restrepo, Claudia P Oliveira, Julissa Lombardo, Abel Sánchez, Martín Elizondo, Martín Tagle, Martín Padilla, Marco Sánchez, Enrique Carrera, Marcos Girala, Omega Chery, Marlen Castellanos-Fernández, Francisco Barrera, Jeffrey V Lazarus, Patrick S Kamath, Ramon Bataller, Marco Arrese, Juan Pablo Arab
Journal: The Lancet. Gastroenterology & hepatology (2022)
Association of Psychiatric Disorders With Incidence of SARS-CoV-2 Breakthrough Infection Among Vaccinated Adults
Authors: Kristen Nishimi, Thomas C. Neylan, Daniel Bertenthal, Karen H. Seal, Aoife O’Donovan
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Psychiatric disorders may be associated with an increased risk for SARS-CoV-2 breakthrough infection after vaccination, but no studies have tested this hypothesis. <h3>Objective</h3> To evaluate whether past diagnoses of psychiatric disorders are associated with an increased incidence of SARS-CoV-2 breakthrough infection among fully vaccinated individuals. <h3>Design, Setting, and Participants</h3> This retrospective cohort study included data from the administrative and electronic health records of US Department of Veterans Affairs (VA) patients from February 20, 2020, to November 16, 2021. Participants included 263 697 patients who accessed VA health care during the study period, had at least 1 SARS-CoV-2 test recorded in the electronic health record, had no record of SARS-CoV-2 infection prior to vaccination, and had completed a full SARS-CoV-2 vaccination regimen 14 days or more prior. <h3>Exposures</h3> Psychiatric disorder diagnoses in the past 5 years, including depressive, posttraumatic stress, anxiety, adjustment, alcohol use, substance use, bipolar, psychotic, attention-deficit/hyperactivity, dissociative, and eating disorders. <h3>Main Outcomes and Measures</h3> SARS-CoV-2 breakthrough infections, defined as positive SARS-CoV-2 tests, among fully vaccinated individuals. <h3>Results</h3> Of 263 697 fully vaccinated VA patients (239 539 men [90.8%]; mean [SD] age, 66.2 [13.8] years), 135 481 (51.4%) had at least 1 psychiatric disorder diagnosis, and 39 109 (14.8%) developed a breakthrough infection. A diagnosis of any psychiatric disorder was associated with increased incidence of breakthrough infection, both in models adjusted for potential confounders (adjusted relative risk [aRR], 1.07; 95% CI, 1.05-1.09) and additionally adjusted for medical comorbidities and smoking (aRR, 1.03; 95% CI, 1.01-1.05). Most specific psychiatric disorder diagnoses were associated with an increased incidence of breakthrough infection, with the highest relative risk observed for adjustment disorder (aRR, 1.13; 95% CI, 1.10-1.16) and substance use disorders (aRR, 1.16; 95% CI, 1.12-1.21) in fully adjusted models. Stratifying the sample at 65 years of age revealed that associations between psychiatric diagnoses and incident breakthrough infection were present in both age groups but were stronger and robust to adjustment for medical comorbidities and smoking among older patients. <h3>Conclusions and Relevance</h3> This cohort study suggests that psychiatric disorder diagnoses were associated with an increased incidence of SARS-CoV-2 breakthrough infection among VA patients, with the strongest associations observed for older individuals. Individuals with psychiatric disorders may be at heightened risk for contracting COVID-19 even after vaccination, suggesting the need for targeted prevention efforts.
Editor's Note: miR-153 Supports Colorectal Cancer Progression via Pleiotropic Effects That Enhance Invasion and Chemotherapeutic Resistance
Authors: Lei Zhang, Karen Pickard, Veronika Jenei, Marc D. Bullock, Amanda Bruce, Richard Mitter, Gavin Kelly, Christos Paraskeva, John Strefford, John Primrose, Gareth J. Thomas, Graham Packham, Alex H. Mirnezami
Journal: Cancer Research (2022)

The editors are publishing this note to alert readers to a concern about this article (1). In Fig. 2F, we detected that the graph of flow cytometry data for untransfected SW480 cells without cisplatin treatment was duplicated for the miR-153–transfected SW480 cells without cisplatin treatment.
<i>QuickStats</i>: Age-Adjusted Death Rates* of Heart Disease and Cancer, by Sex — United States, 2010–2020
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

ICD-10 = International Classification of Diseases, Tenth Revision.* Age-adjusted rates are heart disease and cancer deaths per 100,000 standard population.Heart disease deaths were identified using ICD-10 codes I00-I09, I11, I13, and I20-I51; cancer deaths were identified using ICD-10 codes C00-C97.Age-adjusted cancer and heart disease death rates for both males and females declined steadily from 2010 to 2019.Cancer death rates continued to decline for both males and females during 2019-2020 to 170.3 per 100,000 population (males) and 124.5 (females) in 2020.The pattern was different for deaths caused by heart disease for both males and females.Heart disease death rates increased during 2019-2020 to 214.2 (males) and 130.2 (females) in 2020.During 2010-2020, higher death rates were reported for males than females for both heart disease and cancer, with the cancer death rate for males exceeding the heart disease death rate for females.
Urticaria 12 Days After COVID-19 mRNA Booster Vaccination
Authors: Anna R. Wolfson, Esther E. Freeman, Kimberly G. Blumenthal
Journal: JAMA (2022)

A healthy 27-year-old woman received a COVID-19 mRNA booster vaccine (Moderna) on December 7, 2021.She had not experienced adverse effects after the first 2 vaccine doses on January 17 and February 5, 2021.Twelve days after the booster vaccination, she developed pruritic wheals on her face and bilateral, transient eyelid swelling.Over the next week, a pruritic rash spread over her neck, chest, trunk, and arms; each lesion faded without scarring within 24 hours.She did not experience lip, tongue, or neck swelling; shortness of breath; wheezing; chest pain; or palpitations.Application of pressure to her forearm in a circular motion using a pen cap elicited wheal and flare lesions (Figure, left panel).On physical examination, performed 17 days after the onset of rash, her vital signs were normal.She had no tongue, lip, or throat swelling, and her lungs were clear to auscultation bilaterally.Wheal and flare lesions developed on her upper eyelids during the examination and resolved after approximately 30 minutes (Figure, right panel).Light pressure applied to her skin with a tongue depressor elicited wheal and flare lesions within 3 to 5 minutes.The patient had no history of atopy, urticaria, angioedema, or food or drug allergy and no recent infections.She took no prescription medications and reported no recent use of over-the-counter medications, including nonsteroidal anti-inflammatory drugs.She had no recent travel, exposure to animals, or use of new personal care products. Diagnosis
Reply
Authors: Jennifer R. Kramer, Yamini Natarajan, Jianliang Dai, Xian Yu, Liang Li, Hashem B. El‐Serag, Fasiha Kanwal
Journal: Hepatology (2022)

We appreciate the insightful comments made by our colleagues, Zhou et al., with regard to our article entitled, “Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease.” In response to your first point regarding HBV, we agree that there may be some patients in our NAFLD cohort who—although negative for HBsAg—could have had occult HBV infection. However, we believe this number was negligible in our population of U.S. veterans who are mostly White or African American and hence unlikely to impact on our results. We also agree that our cohort included patients with varying degrees of severity of diabetes, and this may explain some of our findings. However, we adjusted for glycemic control using percentage of time with hemoglobin A1c < 7 over the study period. We also adjusted for diabetes complications. These variables should ameliorate some, but perhaps not all, of the effects of disease severity. Finally, we agree that our findings may not be generalizable to Asians or patients of other races/ethnicities, and future multicenter studies are needed to confirm our findings. CONFLICT OF INTEREST Nothing to report.
<i>Bifidobacterium infantis</i> treatment promotes weight gain in Bangladeshi infants with severe acute malnutrition
Authors: Michael J. Barratt, Sharika Nuzhat, Kazi Ahsan, Steven A. Frese, Aleksandr A. Arzamasov, Shafiqul Alam Sarker, M. Munirul Islam, Parag Palit, Md Ridwan Islam, Matthew C. Hibberd, Swetha Nakshatri, Carrie A. Cowardin, Janaki L. Guruge, Alexandra E. Byrne, Siddarth Venkatesh, Vinaik Sundaresan, Bethany Henrick, Rebbeca M. Duar, Ryan D. Mitchell, Giorgio Casaburi, Johann Prambs, Robin Flannery, Mustafa Mahfuz, Dmitry A. Rodionov, Andrei L. Osterman, David Kyle, Tahmeed Ahmed, Jeffrey I. Gordon
Journal: Science Translational Medicine (2022)

Disrupted development of the gut microbiota is a contributing cause of childhood malnutrition.
Aberrant miR-339-5p/neuronatin signaling causes prodromal neuronal calcium dyshomeostasis in mutant presenilin mice
Authors: Hao-Yu Zou, Lin Guo, Bei Zhang, Si Chen, Xin-Rong Wu, Xian-Dong Liu, Xin-Yu Xu, Bin-Yin Li, Shengdi Chen, Nan-Jie Xu, Suya Sun
Journal: Journal of Clinical Investigation (2022)

Mushroom spine loss and calcium dyshomeostasis are early hallmark events of age-related neurodegeneration, such as Alzheimer's disease (AD), that are connected with neuronal hyperactivity in early pathology of cognitive brain areas. However, it remains elusive how these key events are triggered at the molecular level for the neuronal abnormality that occurs at the initial stage of disease. Here, we identify downregulated miR-339-5p and its upregulated target protein, neuronatin (Nnat), in cortex neurons from the presenilin-1 M146V knockin (PSEN1-M146V KI) mouse model of familial AD (FAD). Inhibition of miR-339-5p or overexpression of Nnat recapitulates spine loss and endoplasmic reticulum calcium overload in cortical neurons with the PSEN1 mutation. Conversely, either overexpression of miR-339-5p or knockdown of Nnat restores spine morphogenesis and calcium homeostasis. We used fiber photometry recording during the object-cognitive process to further demonstrate that the PSEN1 mutant causes defective habituation in neuronal reaction in the retrosplenial cortex and that this can be rescued by restoring the miR-339-5p/Nnat pathway. Our findings thus reveal crucial roles of the miR-339-5p/Nnat pathway in FAD that may serve as potential diagnostic and therapeutic targets for early pathogenesis.