tbuckley/cabot-search huggingface dataset:
Vitamin C Deficiency Causes Cell Type–Specific Epigenetic Reprogramming and Acute Tubular Necrosis in a Mouse Model
Authors: Zihui Yu, Ziying Xu, Yuan Liang, Pengbin Yin, Yue Shi, Jiayi Yu, Junfeng Hao, Ting Wang, Weimin Ci
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement Vitamin C levels decline in patients with various kidney diseases, but the role of the vitamin as an epigenetic regulator in the initiation and progression of kidney diseases has not been characterized. Using Gulo −/− mice, which, like humans, entirely depend on dietary vitamin C, we applied single-cell RNA sequencing, whole genome bisulfite sequencing, and methylated RNA immunoprecipitation sequencing to create the first comprehensive renal cell type–specific transcriptional and DNA/RNA methylation profiles. Vitamin C deficiency induced acute tubular necrosis (ATN) and remodeled DNA/RNA epigenetic modifications in a cell type–specific manner. Cisplatin-induced ATN and AKI had similar transcriptional profiles as Gulo −/− mice. An oxidation-resistant vitamin C derivative, APM, can prevent kidney injuries in cisplatin-induced ATN mice. These findings will aid development of vitamin C as an epigenetic therapy for kidney diseases. Background Vitamin C deficiency is found in patients with variable kidney diseases. However, the role of vitamin C as an epigenetic regulator in renal homeostasis and pathogenesis remains largely unknown. Methods We showed that vitamin C deficiency leads to acute tubular necrosis (ATN) using a vitamin C–deficient mouse model ( Gulo knock-out). DNA/RNA epigenetic modifications and injured S3 proximal tubule cells were identified in the vitamin C–deficient kidneys using whole-genome bisulfite sequencing, methylated RNA immunoprecipitation sequencing, and single-cell RNA sequencing. Results Integrated evidence suggested that epigenetic modifications affected the proximal tubule cells and fenestrated endothelial cells, leading to tubule injury and hypoxia through transcriptional regulation. Strikingly, loss of DNA hydroxymethylation and DNA hypermethylation in vitamin C–deficient kidneys preceded the histologic sign of tubule necrosis, indicating the causality of vitamin C–induced epigenetic modification in ATN. Consistently, prophylactic supplementation of an oxidation-resistant vitamin C derivative, ascorbyl phosphate magnesium, promoted DNA demethylation and prevented the progression of cisplatin-induced ATN. Conclusions Vitamin C played a critical role in renal homeostasis and pathogenesis in a mouse model, suggesting vitamin supplementation may be an approach to lower the risk of kidney injury.
Abstract P162: Cardiovascular Disease And Periodontal Disease In Type 1 Diabetes
Authors: Lauryn M Remmers, Janet Snell-bergeon
Journal: Circulation (2022)

Type 1 diabetes (T1D) is a condition in which the body’s immune system destroys insulin-producing beta cells, resulting in hyperglycemia. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in those with T1D. Periodontal disease (PD) is the 6th major complication of T1D. Oral bacteria have been detected in atherosclerotic plaques. Thus, oral bacteria may play a causal role in cardiovascular disease. The aims of this study are to determine how subclinical measures of cardiovascular disease differ by diabetes status and how they are related to the extent of periodontal disease. It is hypothesized that people with T1D will have stiffer vessels with higher pulse wave velocity (PWV), lower brachial artery distensibility (BrachD), and higher carotid intima-media thickness (cIMT) compared to non-diabetic controls. It is also hypothesized that people with T1D will have a higher prevalence of PD compared to non-diabetic controls. Study visits were performed to assess cardiovascular and periodontal outcomes in people with T1D (n=144) and non-diabetic controls (n=147). Univariate analysis was performed using t-test and chi-square to test for significant differences in vascular measures and periodontal status between T1D and controls. Age and sex-adjusted multivariate linear and logistic regression was used to further examine differences in vascular measures and periodontal disease by diabetes status. PWV was significantly higher in people with T1D compared to controls (8.390 +/- 0.111 vs. 7.822 +/- 0.108, p=0.0003). BrachD was significantly lower in people with T1D compared to controls (5.795 +/- 0.095 vs. 6.413 +/- 0.094, p&lt;0.0001). cIMT was significantly higher in people with T1D compared to controls (0.679 +/- 0.009 vs. 0.626 +/- 0.009, p&lt;0.0001). Adults with T1D were significantly more likely to have moderate to severe PD compared to controls (OR = 2.759, 95% CI [1.310-5.811], p=0.0076). Adults with T1D have worse cardiovascular health as measured by stiffer central vessels, more subclinical atherosclerosis, and lower peripheral vessel distensibility. Adults with T1D had almost 3-fold higher risk of moderate to severe PD compared to non-diabetic adults. The relationship between PD and the increased CVD risk in people with T1D warrants further examination.
Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk
Authors: Yu Tian, Andre E Kim, Stephanie A Bien, Yi Lin, Conghui Qu, Tabitha A Harrison, Robert Carreras-Torres, Virginia Díez-Obrero, Niki Dimou, David A Drew, Akihisa Hidaka, Jeroen R Huyghe, Kristina M Jordahl, John Morrison, Neil Murphy, Mireia Obón-Santacana, Cornelia M Ulrich, Jennifer Ose, Anita R Peoples, Edward A Ruiz-Narvaez, Anna Shcherbina, Mariana C Stern, Yu-Ru Su, Franzel J B van Duijnhoven, Volker Arndt, James W Baurley, Sonja I Berndt, D Timothy Bishop, Hermann Brenner, Daniel D Buchanan, Andrew T Chan, Jane C Figueiredo, Steven Gallinger, Stephen B Gruber, Sophia Harlid, Michael Hoffmeister, Mark A Jenkins, Amit D Joshi, Temitope O Keku, Susanna C Larsson, Loic Le Marchand, Li Li, Graham G Giles, Roger L Milne, Hongmei Nan, Rami Nassir, Shuji Ogino, Arif Budiarto, Elizabeth A Platz, John D Potter, Ross L Prentice, Gad Rennert, Lori C Sakoda, Robert E Schoen, Martha L Slattery, Stephen N Thibodeau, Bethany Van Guelpen, Kala Visvanathan, Emily White, Alicja Wolk, Michael O Woods, Anna H Wu, Peter T Campbell, Graham Casey, David V Conti, Marc J Gunter, Anshul Kundaje, Juan Pablo Lewinger, Victor Moreno, Polly A Newcomb, Bens Pardamean, Duncan C Thomas, Konstantinos K Tsilidis, Ulrike Peters, W James Gauderman, Li Hsu, Jenny Chang-Claude
Journal: JNCI Journal of the National Cancer Institute (2022)

The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk.
18F-Labeled WBC PET/CT Scan in a Case of Recurrent Glioblastoma Multiforme, Presented as Pyrexia of Unknown Origin
Authors: Subha Shankar Das, Dharmender Malik, Gaurav Khanna, Ishita Bharat Sen, Rana Patir
Journal: Clinical Nuclear Medicine (2022)

Abstract Neoplastic causes account for approximately 10% to 20% cases of PUO (pyrexia of unknown origin). The mechanisms by which malignancies induce fever are not fully understood. The release of pyrogenic cytokines either directly from tumor cells or from macrophages responding to tumor are likely to play a major role, which acts on the hypothalamus, causing a change in the thermostatic set point. We present a case of recurrent glioblastoma multiforme, who presented with PUO. 18 F-FDG–labeled leukocyte PET/CT scan done for localization of infective focus demonstrated significant tracer accumulation at the periphery of the recurrent brain lesion. Subsequent excisional biopsy from the lesion was suggestive of noninfected recurrent glioblastoma multiforme.
Early Treatment for Covid-19 with SARS-CoV-2 Neutralizing Antibody Sotrovimab
Authors: Anil Gupta, Yaneicy Gonzalez-Rojas, Erick Juarez, Manuel Crespo Casal, Jaynier Moya, Diego R. Falci, Elias Sarkis, Joel Solis, Hanzhe Zheng, Nicola Scott, Andrea L. Cathcart, Christy M. Hebner, Jennifer Sager, Erik Mogalian, Craig Tipple, Amanda Peppercorn, Elizabeth Alexander, Phillip S. Pang, Almena Free, Cynthia Brinson, Melissa Aldinger, Adrienne E. Shapiro
Journal: New England Journal of Medicine (2021)

BackgroundCoronavirus disease 2019 (Covid-19) disproportionately results in hospitalization or death in older patients and those with underlying conditions. Sotrovimab is a pan-sarbecovirus monoclonal antibody that was designed to prevent progression of Covid-19 in high-risk patients early in the course of disease.MethodsIn this ongoing, multicenter, double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, nonhospitalized patients with symptomatic Covid-19 (≤5 days after the onset of symptoms) and at least one risk factor for disease progression to receive a single infusion of sotrovimab at a dose of 500 mg or placebo. The primary efficacy outcome was hospitalization (for >24 hours) for any cause or death within 29 days after randomization.Download a PDF of the Research Summary.ResultsIn this prespecified interim analysis, which included an intention-to-treat population of 583 patients (291 in the sotrovimab group and 292 in the placebo group), 3 patients (1%) in the sotrovimab group, as compared with 21 patients (7%) in the placebo group, had disease progression leading to hospitalization or death (relative risk reduction, 85%; 97.24% confidence interval, 44 to 96; P=0.002). In the placebo group, 5 patients were admitted to the intensive care unit, including 1 who died by day 29. Safety was assessed in 868 patients (430 in the sotrovimab group and 438 in the placebo group). Adverse events were reported by 17% of the patients in the sotrovimab group and 19% of those in the placebo group; serious adverse events were less common with sotrovimab than with placebo (in 2% and 6% of the patients, respectively).ConclusionsAmong high-risk patients with mild-to-moderate Covid-19, sotrovimab reduced the risk of disease progression. No safety signals were identified. (Funded by Vir Biotechnology and GlaxoSmithKline; COMET-ICE ClinicalTrials.gov number, NCT04545060.) Quick Take Sotrovimab for Early Covid-19 1m 56s
Pituitary Metastasis of Renal Cell Carcinoma Characterized by 18F–Prostate-Specific Membrane Antigen–1007 PET/CT
Authors: Arsalan Tariq, Vignesh Raman, Hamish Alexander, Matthew J. Roberts, Paul Thomas
Journal: Clinical Nuclear Medicine (2022)

Renal cell carcinoma (RCC) is one of the most common oncological diagnoses worldwide. Accurate staging and restaging imaging continue to be a priority in clinical practice as 20% to 30% of patients present with advanced metastatic disease at diagnosis, and 20% to 30% develop recurrence after surgical resection. We present a case of a 71-year-old man presenting with an isolated pituitary RCC metastasis accurately defined on 18F-prostate-specific membrane antigen-1007 masquerading as a macroadenoma on conventional imaging (CT and MRI). This demonstrates the potential utility of 18F-prostate-specific membrane antigen-1007 in characterizing RCC brain metastasis.
Correction: Metastasis-Associated Protein 2 Represses NF-κB to Reduce Lung Tumor Growth and Inflammation
Authors: Nefertiti El-Nikhely, Annika Karger, Poonam Sarode, Indrabahadur Singh, Andreas Weigert, Astrid Wietelmann, Thorsten Stiewe, Reinhard Dammann, Ludger Fink, Friedrich Grimminger, Guillermo Barreto, Werner Seeger, Soni S. Pullamsetti, Ulf R. Rapp, Rajkuma Savai
Journal: Cancer Research (2022)

In the original version of this article (1), there was an error in Fig. 4A. Specifically, the image used to show the LLC1 control H&amp;E staining was the same as the image used in Fig. 2G to show the Sftpc-IKK2CA control H&amp;E staining. The correct image has been provided, and the error has been corrected in the latest online HTML and PDF version of the article. The authors regret this error.
Authors’ Reply
Authors: Andrew J.B. Watts, Keith H. Keller, Astrid Weins
Journal: Journal of the American Society of Nephrology (2022)

We are excited by the renewed focus on diffuse podocytopathies that our discoveries are eliciting in the field.1 We agree that gaining a more precise mechanistic understanding of disease pathogenesis is crucial, and that developing a new classification for diffuse podocytopathies on the basis of autoantibodies is important for guiding precision medicine strategies to treat these diseases.2 We strongly encourage contributions from all groups in the field, together with independent validation of all of the proposed factors, to ensure the pathogenic significance of diffuse podocytopathies is confirmed. Disclosures A. Weins reports having consultancy agreements with Goldfinch Bio, Inc. All remaining authors have nothing to disclose. Funding None.
Multicentre evaluation of two multiplex PCR platforms for the rapid microbiological investigation of nosocomial pneumonia in UK ICUs: the INHALE WP1 study
Authors: Virve I Enne, Alp Aydin, Rossella Baldan, Dewi R Owen, Hollian Richardson, Federico Ricciardi, Charlotte Russell, Brenda O Nomamiukor-Ikeji, Ann-Marie Swart, Juliet High, Antony Colles, Julie Barber, Vanya Gant, David M Livermore, Justin O’Grady
Journal: Thorax (2022)

Background Culture-based microbiological investigation of hospital-acquired or ventilator-associated pneumonia (HAP or VAP) is insensitive, with aetiological agents often unidentified. This can lead to excess antimicrobial treatment of patients with susceptible pathogens, while those with resistant bacteria are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship. Methods Surplus routine lower respiratory tract samples were collected from intensive care unit patients about to receive new or changed antibiotics for hospital-onset lower respiratory tract infections at 15 UK hospitals. Testing was performed using the BioFire FilmArray Pneumonia Panel (bioMérieux) and Unyvero Pneumonia Panel (Curetis). Concordance analysis compared machine and routine microbiology results, while Bayesian latent class (BLC) analysis estimated the sensitivity and specificity of each test, incorporating information from both PCR panels and routine microbiology. Findings In 652 eligible samples; PCR identified pathogens in considerably more samples compared with routine microbiology: 60.4% and 74.2% for Unyvero and FilmArray respectively vs 44.2% by routine microbiology. PCR tests also detected more pathogens per sample than routine microbiology. For common HAP/VAP pathogens, FilmArray had sensitivity of 91.7%–100.0% and specificity of 87.5%–99.5%; Unyvero had sensitivity of 50.0%–100.0%%, and specificity of 89.4%–99.0%. BLC analysis indicated that, compared with PCR, routine microbiology had low sensitivity, ranging from 27.0% to 69.4%. Interpretation Conventional and BLC analysis demonstrated that both platforms performed similarly and were considerably more sensitive than routine microbiology, detecting potential pathogens in patient samples reported as culture negative. The increased sensitivity of detection realised by PCR offers potential for improved antimicrobial prescribing.
Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression
Authors: Mu-Hong Chen, Chih-Sung Liang, Kuan-Pin Su
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
32P Impact of smoking status on the relative efficacy of the EGFR TKI/angiogenesis inhibitor combination therapy in advanced NSCLC: A systematic review and meta-analysis
Authors: U. Dafni, R.A. Soo, S. Peters, Z. Tsourti, K. Vervita, J-Y. Han, J. De Castro, L. Coate, M. Früh, S.M.S. Hashemi, E. Nadal, E. Carcereny, M. Angeles Sala González, R. Bernabé Caro, M. Provencio Pulla, S. Cuffe, B. Ruepp, H. Roschitzki-Voser, R. Rosell, R.A. Stahel
Journal: Annals of Oncology (2022)
Measures of differentiation and integration: One step closer to consciousness
Authors: Marcello Massimini, Simone Sarasso, Silvia Casarotto, Mario Rosanova
Journal: Behavioral and Brain Sciences (2022)

Interpreting empirical measures of integration and differentiation as indices of cortical performance and memory consolidation during wakefulness rather than consciousness per se is inconsistent with the literature. Recent studies show that these theory-inspired measures can dissociate from such processes and reliably index the brain's capacity for experience. We consider this as a positive trend in consciousness research.
Numb and Numblike regulate sarcomere assembly and maintenance
Authors: Baolei Wang, Min Yang, Shujuan Li
Journal: Journal of Clinical Investigation (2022)

A sarcomere is the contractile unit of the myofibril in striated muscles such as cardiac and skeletal muscles. The assembly of sarcomeres depends on multiple molecules that serve as raw materials and participate in the assembly process. However, the mechanism of this critical assembly process remains largely unknown. Here, we found that the cell fate determinant Numb and its homolog Numblike regulated sarcomere assembly and maintenance in striated muscles. We discovered that Numb and Numblike are sarcomeric molecules that were gradually confined to the Z-disc during striated muscle development. Conditional knockout of Numb and Numblike severely compromised sarcomere assembly and its integrity and thus caused organelle dysfunction. Notably, we identified that Numb and Numblike served as sarcomeric α-Actin-binding proteins (ABPs) and shared a conserved domain that can bind to the barbed end of sarcomeric α-Actin. In vitro fluorometric α-Actin polymerization assay showed that Numb and Numblike also played a role in the sarcomeric α-Actin polymerization process. Last, we demonstrate that Numb and Numblike regulate sarcomeric α-Actinin-dependent (ACTN-dependent) Z-disc consolidation in the sarcomere assembly and maintenance. In summary, our studies show that Numb and its homolog Numblike regulate sarcomere assembly and maintenance in striated muscles, and demonstrate a molecular mechanism by which Numb/Numblike, sarcomeric α-Actin, and ACTN cooperate to control thin filament formation and Z-disc consolidation.
Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: a single-arm, single-centre, feasibility, phase 2 trial
Authors: Chad Tang, Pavlos Msaouel, Kieko Hara, Haesun Choi, Venus Le, Amishi Y Shah, Jennifer Wang, Eric Jonasch, Seungtaek Choi, Quynh-nhu Nguyen, Prajnan Das, Surendra Prajapati, Zhiqian Yu, Khaja Khan, Steven Powell, Ravi Murthy, Kanishka Sircar, Nizar M Tannir
Journal: The Lancet Oncology (2021)
LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance
Authors: Sijia He, Jiyoon Ryu, Juanhong Liu, Hairong Luo, Ying Lv, Paul R. Langlais, Jie Wen, Feng Dong, Zhe Sun, Wenjuan Xia, Jane L. Lynch, Ravindranath Duggirala, Bruce J. Nicholson, Mengwei Zang, Yuguang Shi, Fang Zhang, Feng Liu, Juli Bai, Lily Q. Dong
Journal: Journal of Clinical Investigation (2021)

Dysregulation in adipokine biosynthesis and function contributes to obesity-induced metabolic diseases. However, the identities and functions of many of the obesity-induced secretory molecules remain unknown. Here, we report the identification of leucine-rich alpha-2-glycoprotein 1 (LRG1) as an obesity-associated adipokine that exacerbates high fat diet–induced hepatosteatosis and insulin resistance. Serum levels of LRG1 were markedly elevated in obese humans and mice compared with their respective controls. LRG1 deficiency in mice greatly alleviated diet-induced hepatosteatosis, obesity, and insulin resistance. Mechanistically, LRG1 bound with high selectivity to the liver and promoted hepatosteatosis by increasing de novo lipogenesis and suppressing fatty acid β-oxidation. LRG1 also inhibited hepatic insulin signaling by downregulating insulin receptor substrates 1 and 2. Our study identified LRG1 as a key molecule that mediates the crosstalk between adipocytes and hepatocytes in diet-induced hepatosteatosis and insulin resistance. Suppressing LRG1 expression and function may be a promising strategy for the treatment of obesity-related metabolic diseases.
CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigen-negative variants of acute lymphoblastic leukemia
Authors: Xiuli Wang, Zhenyuan Dong, Dennis Awuah, Wen-Chung Chang, Wesley A. Cheng, Vibhuti Vyas, Soung-Chul Cha, Aaron J. Anderson, Tiantian Zhang, Zhe Wang, Szymon J. Szymura, Benjamin Z. Kuang, Mary C. Clark, Ibrahim Aldoss, Stephen J. Forman, Larry W. Kwak, Hong Qin
Journal: Leukemia (2022)
Abstract P023: A Scoring Tool For Identifying Hispanics/latinos With Chronic Kidney Disease: Hispanic Community Health Study/study Of Latinos
Authors: Celestin Missikpode, Amber Pirzada, Jiehuan Sun, Ramon Durazo-Arvizu, Nora Franceschini, Daniela Sotres-Alvarez, Gregory A Talavera, Ana Ricardo, James Lash, Martha L Daviglus
Journal: Circulation (2022)

Introduction: Despite the high prevalence of chronic kidney disease (CKD) in the Hispanic/Latino population, most Hispanic/Latino adults with CKD are not aware. This study aims to develop a tool for the Hispanic/Latino population to determine whether an individual has CKD. Methods: Baseline (2008-2011) data on 13,636 participants (aged 18 – 74 years; 60.8% female) from the Hispanic Community Health Study/Study of Latinos were analyzed to develop a tool using routinely available information to identify individuals with an increased likelihood of having CKD. CKD was defined as a low eGFR (&lt;60 ml/min per 1.73 m 2 ) or the presence of albuminuria [urine albumin to creatinine ratio (UACR)≥30 mg/g]. Based on prior literature, several CKD risk factors were examined using several prediction algorithms (RIDGE regression, LASSO regression, classification and regression tree, and random forest). Results: A total of 364 (2.7%) individuals had low eGFR and 1346 (10.1%) had albuminuria. The LASSO model was selected due to its greater accuracy and parsimony. Variables predictive of CKD were weighted to develop a model-based numeric scoring system. Age, self-reported health conditions (i.e., hypertension, diabetes, prevalent coronary heart disease/stroke, balloon angioplasty/stent/bypass surgery), physical functioning limitations, and having health insurance were predictive of low eGFR (Table). Diabetes, hypertension, and pulse were predictive of albuminuria (Table). Multivariate models were internally validated using 10-fold cross-validation (area under the receiver operating characteristic curve of 0.87 and 0.70 for low eGFR and albuminuria, respectively). A score of ≥9 on the eGFR model yielded sensitivity (SN) of 84%, specificity (SP) of 78%, positive predictive value (PPV) of 9%, and negative predictive value (NPV) of 99%. A score of ≥4 on the albuminuria model yielded SN of 62%, SP of 67%, PPV of 18%; and NPV of 94%. Conclusion: This community tool may facilitate the identification of undiagnosed CKD in Hispanics/Latinos.