tbuckley/cabot-search huggingface dataset:
Neutrophils infiltrate into the spiral ligament but not the stria vascularis in the cochlea during lipopolysaccharide-induced inflammation
Authors: Seong Hoon Bae, Jee Eun Yoo, Young Ho Choe, Sang Hyun Kwak, Jae Young Choi, Jinsei Jung, Young-Min Hyun
Journal: Theranostics (2021)

It has been challenging to apply intravital imaging for monitoring the inner ear, as the anatomical location and intricate structure hamper the access of imaging instruments to the inner ear of live mice.By employing intravital imaging of the cochlea in live mice with two-photon microscopy, we investigated neutrophil infiltration into the cochlea tissue and its characteristics under a lipopolysaccharide (LPS)-induced inflammatory state.Methods: Cochlea inflammation was induced by LPS injection to the middle ear.Using two-photon intravital microscopy with specifically designed surgical exteriorization of the cochlea in live mice, we investigated the dynamic features of neutrophils in the lateral wall of the cochlea.The molecular expression pattern of the cochlea lateral wall was also investigated during the LPS-induce inflammation.Results: Despite the contention of whether neutrophils are recruited to the spiral ligament (SL) during inflammation, we observed that LPS-induced inflammation of the middle ear, which mimics acute otitis media, triggered neutrophil migration to the SL in the lateral wall.Notably, massive neutrophil infiltration to the SL occurred 2 days after LPS inoculation, but there was no neutrophil infiltration into the stria vascularis (SV) region.At 1 day after LPS-induced cochlear inflammation, increased mRNA expression of interleukin-1β, interleukin-6 were identified in both the SL and SV, while the ICAM-1 mRNA expression increased only in the SL.The differential reactivity of ICAM-1 is likely responsible for the different neutrophil recruitment pattern in the cochlea.Conclusion: Intravital imaging of the cochlea revealed that neutrophil recruitment and infiltration during inflammation are spatially controlled and exclusively observed in the SL but not in the SV and organ of Corti.
Natural compounds in the regulation of proteostatic pathways: An invincible artillery against stress, ageing, and diseases
Authors: Arun Upadhyay
Journal: Acta Pharmaceutica Sinica B (2021)

Cells have different sets of molecules for performing an array of physiological functions. Nucleic acids have stored and carried the information throughout evolution, whereas proteins have been attributed to performing most of the cellular functions. To perform these functions, proteins need to have a unique conformation and a definite lifespan. These attributes are achieved by a highly coordinated protein quality control (PQC) system comprising chaperones to fold the proteins in a proper three-dimensional structure, ubiquitin-proteasome system for selective degradation of proteins, and autophagy for bulk clearance of cell debris. Many kinds of stresses and perturbations may lead to the weakening of these protective cellular machinery, leading to the unfolding and aggregation of cellular proteins and the occurrence of numerous pathological conditions. However, modulating the expression and functional efficiency of molecular chaperones, E3 ubiquitin ligases, and autophagic proteins may diminish cellular proteotoxic load and mitigate various pathological effects. Natural medicine and small molecule-based therapies have been well-documented for their effectiveness in modulating these pathways and reestablishing the lost proteostasis inside the cells to combat disease conditions. The present article summarizes various similar reports and highlights the importance of the molecules obtained from natural sources in disease therapeutics.
Endoscopic Cyanoacrylate Injection Versus Balloon‐Occluded Retrograde Transvenous Obliteration for Prevention of Gastric Variceal Bleeding: A Randomized Controlled Trial
Authors: Xuefeng Luo, Tong Xiang, Junchao Wu, Xiaoze Wang, Yongjun Zhu, Xiaotan Xi, Yuling Yan, Jinlin Yang, Juan Carlos García‐Pagán, Li Yang
Journal: Hepatology (2021)

The optimal treatment for gastric varices (GVs) is a topic that remains open for study. This study compared the efficacy and safety of endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous obliteration (BRTO) to prevent rebleeding in patients with cirrhosis and GVs after primary hemostasis.Patients with cirrhosis and history of bleeding from gastroesophageal varices type 2 or isolated gastric varices type 1 were randomized to cyanoacrylate injection (n = 32) or BRTO treatment (n = 32). Primary outcomes were gastric variceal rebleeding or all-cause rebleeding. Patient characteristics were well balanced between two groups. Mean follow-up time was 27.1 ± 12.0 months in a cyanoacrylate injection group and 27.6 ± 14.3 months in a BRTO group. Probability of gastric variceal rebleeding was higher in the cyanoacrylate injection group than in the BRTO group (P = 0.024). Probability of remaining free of all-cause rebleeding at 1 and 2 years for cyanoacrylate injection versus BRTO was 77% versus 96.3% and 65.2% versus 92.6% (P = 0.004). Survival rates, frequency of complications, and worsening of esophageal varices were similar in both groups. BRTO resulted in fewer hospitalizations, inpatient stays, and lower medical costs.BRTO is more effective than cyanoacrylate injection in preventing rebleeding from GVs, with similar frequencies of complications and mortalities.
MO01.41 Using an Exploratory Composite Endpoint to Evaluate the Myelopreservation Benefits of Trilaciclib in Patients with Small Cell Lung Cancer
Authors: J. Subramanian, J. Jaal, I. Kudaba, K. Nikolov, D. Radosavljevic, T. Csőszi, J. Xiao, J. Horton, R.K. Malik, M.D. Gómez
Journal: Journal of Thoracic Oncology (2021)
Low-dose colchicine reduced risk for cardiovascular events in chronic coronary disease
Authors: Jay N. Cohn
Journal: Annals of Internal Medicine (2021)

ACP Journal ClubJanuary 2021Low-dose colchicine reduced risk for cardiovascular events in chronic coronary diseaseJay N. Cohn, MDJay N. Cohn, MDUniversity of Minnesota Medical School, Minneapolis, Minnesota, USA (J.N.C.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202101190-008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationNidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020;383:1838-47. https://pubmed.ncbi.nlm.nih.gov/32865380Clinical Impact RatingsGIM/FP/GP: Cardiology: Reference1 Hennekens CH, Lopez-Sendon J. Overview of the prevention of cardiovascular disease events in those with established disease (secondary prevention) or at high risk. In: Cannon CP, Kaski JC, eds. UpToDate. 2020. Accessed at www.uptodate.com/contents/overview-of-the-prevention-of-cardiovascular-disease-events-in-those-with-established-disease-secondary-prevention-or-at-high-risk on 1 Nov 2020. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Minnesota Medical School, Minneapolis, Minnesota, USA (J.N.C.)Disclosures: The commentator has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7312.This article was published at Annals.org on 5 January 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPrecision Medicine Approaches to Vascular Disease January 2021Volume 174, Issue 1Page: JC8KeywordsAngiographyAtherosclerosisCardiovascular disease riskCardiovascular diseasesColchicineDrugsMortalityMyocardial infarctionStable coronary artery diseaseStatins ePublished: 5 January 2021 Issue Published: January 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
SARS-CoV-2 antibody response after COVID-19 in patients with rheumatic disease
Authors: Kristin M D’Silva, Naomi Serling-Boyd, Tiffany Y-T Hsu, Jeffrey A Sparks, Zachary S Wallace
Journal: Annals of the Rheumatic Diseases (2021)

It was found that precipitation in phosphate buffer solutions was mainly caused by formation of aluminum phosphate and calcium phosphate, which was attributed to the reaction between Ca(II) and Al(III)from pH-adjusting agents such as alkali hydroxides or carbonates and phosphate. In the present experiment, a model system of Ca(II)-phosphate was established and optimal conditions for prevention of the precipitate or stabilization in buffer solutions were investigated on the basis of the precipitation-prevention factor, Rca [a molar ratio of complexed Ca(II) to additive at a complete dissolution point of Ca(II), and the stability constant for the 1:1 Ca complex presumed. EDTA was the most favorable for complexation of Ca(II) in phosphate buffer solutions (pH 6-9), but the complexation of Ca(II) with other additives generally became weak with increasing pH and temperature. The complexation of Ca(II) with condensed phosphates was relatively strong, followed by that with citric acid. In the case of other carboxylic acids, high concentrations were required for complexation of Ca(II). On the basis of the complex stability constants calculated, it was found that complexation of Ca(II) with additives was remarkably inhibited by the presence of phosphate buffer.
Combined chemotherapy and endoscopic ultrasound-guided intratumoral 32P implantation for locally advanced pancreatic adenocarcinoma: a pilot study
Authors: Jeevinesh Naidu, Dylan Bartholomeusz, Joshua Zobel, Romina Safaeian, William Hsieh, Benjamin Crouch, Karen Ho, Deborah Calnan, Nimit Singhal, Andrew Ruszkiewicz, John W. Chen, Chuan Ping Tan, Paul Dolan, Nam Q. Nguyen
Journal: Endoscopy (2021)

Abstract Background This study evaluated clinical outcomes of combined chemotherapy and endoscopic ultrasound (EUS)-guided intratumoral radioactive phosphorus-32 (32P) implantation in locally advanced pancreatic adenocarcinoma (LAPC). Methods Consecutive patients with newly diagnosed LAPC were recruited over 20 months. Baseline computed tomography and 18F-2-fluoro-2-deoxy-D-glucose (18FDG) positron emission tomography–computed tomography were performed and repeated after 12 weeks to assess treatment response. Following two cycles of conventional chemotherapy, patients underwent EUS-guided 32P implantation followed by six chemotherapy cycles. Results 12 patients with LAPC (median age 69 years [interquartile range 61.5–73.3]; 8 male) completed treatment. Technical success was 100 % with no procedural complications. At 12 weeks, median reduction in tumor volume was 8.2 cm3 (95 % confidence interval 4.95–10.85; P = 0.003), with minimal or no 18FDG uptake in nine patients (75 %). Tumor downstaging was achieved in six patients (50 %), leading to successful resection in five (42 %), including four R0 resections (80 %). Conclusions EUS-guided 32P implantation was feasible, well tolerated, and resulted in a 42 % surgical resection rate. Further evaluation in a larger randomized multicenter trial is warranted.
Steroid-refractory PD-(L)1 pneumonitis: incidence, clinical features, treatment, and outcomes
Authors: Aanika Balaji, Melinda Hsu, Cheng Ting Lin, Josephine Feliciano, Kristen Marrone, Julie R Brahmer, Patrick M Forde, Christine Hann, Lei Zheng, Valerie Lee, Peter B Illei, Sonye K Danoff, Karthik Suresh, Jarushka Naidoo
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune-checkpoint inhibitor (ICI)-pneumonitis that does not improve or resolve with corticosteroids and requires additional immunosuppression is termed steroid-refractory ICI-pneumonitis. Herein, we report the clinical features, management and outcomes for patients treated with intravenous immunoglobulin (IVIG), infliximab, or the combination of IVIG and infliximab for steroid-refractory ICI-pneumonitis. Methods Patients with steroid-refractory ICI-pneumonitis were identified between January 2011 and January 2020 at a tertiary academic center. ICI-pneumonitis was defined as clinical or radiographic lung inflammation without an alternative diagnosis, confirmed by a multidisciplinary team. Steroid-refractory ICI-pneumonitis was defined as lack of clinical improvement after high-dose corticosteroids for 48 hours, necessitating additional immunosuppression. Serial clinical, radiologic (CT imaging), and functional features (level-of-care, oxygen requirement) were collected preadditional and postadditional immunosuppression. Results Of 65 patients with ICI-pneumonitis, 18.5% (12/65) had steroid-refractory ICI-pneumonitis. Mean age at diagnosis of ICI-pneumonitis was 66.8 years (range: 35–85), 50% patients were male, and the majority had lung carcinoma (75%). Steroid-refractory ICI-pneumonitis occurred after a mean of 5 ICI doses from PD-(L)1 start (range: 3–12 doses). The most common radiologic pattern was diffuse alveolar damage (DAD: 50%, 6/12). After corticosteroid failure, patients were treated with: IVIG (n=7), infliximab (n=2), or combination IVIG and infliximab (n=3); 11/12 (91.7%) required ICU-level care and 8/12 (75%) died of steroid-refractory ICI-pneumonitis or infectious complications (IVIG alone=3/7, 42.9%; infliximab alone=2/2, 100%; IVIG + infliximab=3/3, 100%). All five patients treated with infliximab (5/5; 100%) died from steroid-refractory ICI-pneumonitis or infectious complications. Mechanical ventilation was required in 53% of patients treated with infliximab alone, 80% of those treated with IVIG + infliximab, and 25.5% of those treated with IVIG alone. Conclusions Steroid-refractory ICI-pneumonitis constituted 18.5% of referrals for multidisciplinary irAE care. Steroid-refractory ICI-pnuemonitis occurred early in patients’ treatment courses, and most commonly exhibited a DAD radiographic pattern. Patients treated with IVIG alone demonstrated an improvement in both level-of-care and oxygenation requirements and had fewer fatalities (43%) from steroid-refractory ICI-pneumonitis when compared to treatment with infliximab (100% mortality).
Reforms to Mental Health Act aim to tackle poor care and racial inequalities
Authors: Clare Dyer
Journal: BMJ (2021)

Major reforms have been announced to mental health laws in England and Wales that aim to ensure parity with physical health services, put patients’ views at the centre of their care, and tackle racial inequalities.1

The far reaching proposals come in a government white paper building on reforms recommended by a review of the 1983 Mental Health Act two years ago by Simon Wessely, former president of the Royal College of Psychiatrists.2 The Department of Health and Social Care has promised that changes requiring legislation will be incorporated in a draft Mental Health Bill for consultation next year.

The Wessely review was set up by the government to find the …
Thirty-Year Trends in Complications in U.S. Adults With Newly Diagnosed Type 2 Diabetes
Authors: Michael Fang, Elizabeth Selvin
Journal: Diabetes Care (2021)

OBJECTIVE To assess the prevalence of and trends in complications among U.S. adults with newly diagnosed diabetes. RESEARCH DESIGN AND METHODS We included 1,486 nonpregnant adults (aged ≥20 years) with newly diagnosed diabetes (diagnosed within the past 2 years) from the 1988–1994 and 1999–2018 National Health and Nutrition Examination Survey. We estimated trends in albuminuria (albumin-to-creatinine ratio ≥30 mg/g), reduced estimated glomerular filtration rate (eGFR &amp;lt;60 mL/min/1.73 m2), retinopathy (any retinal microaneurysms or blot hemorrhages), and self-reported cardiovascular disease (history of congestive heart failure, heart attack, or stroke). RESULTS From 1988–1994 to 2011–2018, there was a significant decrease in the prevalence of albuminuria (38.9 to 18.7%, P for trend &amp;lt;0.001) but no change in the prevalence of reduced eGFR (7.5 to 9.9%, P for trend = 0.30), retinopathy (1988–1994 to 1999–2008 only; 13.2 to 12.1%, P for trend = 0.86), or self-reported cardiovascular disease (19.0 to 16.5%, P for trend = 0.64). There were improvements in glycemic, blood pressure, and lipid control in the population, and these partially explained the decline in albuminuria. Complications were more common at the time of diabetes diagnosis for adults who were older, lower income, less educated, and obese. CONCLUSIONS Over the past three decades, there have been encouraging reductions in albuminuria and risk factor control in adults with newly diagnosed diabetes. However, the overall burden of complications around the time of the diagnosis remains high.
Rethinking How to Persuade More Parents From Diverse or Disadvantaged Backgrounds to Enroll Infants in Neonatal Clinical Trials
Authors: Heather H. Burris, Andrea F. Duncan
Journal: JAMA Network Open (2021)

Elliott Mark Weiss, MD, MSME; Aleksandra E. Olszewski, MD; Katherine F. Guttmann, MD, MBE; Brooke E. Magnus, PhD; Sijia Li, BS; Anita R. Shah, MD, MPH; Sandra E. Juul, MD, PhD; Yvonne W. Wu, MD, MPH; Kaashif A. Ahmad, MD, MSc; Ellen Bendel-Stenzel, MD; Natalia A. Isaza, MD; Andrea L. Lampland, MD; Amit M. Mathur, MD; Rakesh Rao, MD; David Riley, MD; David G. Russell, JD; Zeynep N. I. Salih, MD; Carrie B Torr, MD; Joern-Hendrik Weitkamp, MD; Uchenna E. Anani, MD; Taeun Chang, MD; Juanita Dudley, BSN; John Flibotte, MD; Erin M. Havrilla, MSN; Charmaine M. Kathen, DNP; Alexandra C. O’Kane, MS; Krystle Perez, MD, MPH; Brenda J. Stanley, MSN; Benjamin S. Wilfond, MD; Seema K. Shah, JD
MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice
Authors: Wei Ying, Hong Gao, Felipe Castellani Gomes Dos Reis, Gautam Bandyopadhyay, Jachelle M. Ofrecio, Zhenlong Luo, Yudong Ji, Zhongmou Jin, Crystal Ly, Jerrold M. Olefsky
Journal: Cell Metabolism (2021)
TS01.07 Genomic HLA as a Predictive Biomarker for Survival Among Non-Small Cell Lung Cancer Patient Treated with Single Agent Immunotherapy.
Authors: A. Abed, L. Calapre, J. Lo, M.S. Correia, S. Bowyer, A. Chopra, M. Watson, A. Khattak, M. Millward, E. Gray
Journal: Journal of Thoracic Oncology (2021)
Children’s centres are the foundation of social regeneration
Authors: Sebastian Kraemer
Journal: BMJ (2021)

Aynsley-Green praises the last Labour government’s Every Child Matters policy,1 which included the ambitious Sure Start programme, a massive financial and organisational investment in child health and development.2 Its founders’ vision was to strengthen communities around young children in areas of social deprivation,3 but the focus was blurred when Treasury funding was dispersed to local authorities, soon compounded by the financial …
Abstract 19286: Sleep Duration and Subclinical Measures of Atherosclerosis in a Bi-racial Cohort: The Bogalusa Heart Study
Authors: Patrick Stuchlik, Benjamin Pollock, Wei Chen, Emily Harville, Lydia Bazzano
Journal: Circulation (2017)

Introduction: The association of cardiovascular (CV) disease with inadequate sleep is well-documented, with evidence pointing toward a J-shaped curve, where the worst CV risk is found at both extre...
MO01.46 Tepotinib Activity in Brain Metastases (BM): Preclinical Models and Clinical Data from MET Exon 14 (METex14) Skipping NSCLC
Authors: S. Viteri, J. Mazieres, R. Veillon, E. Felip, X. Le, M. Garassino, T. Stanton, M. Morise, J.-S. Lee, S. Matsumoto, F. De Marinis, T. Wehler, A. Clark, M. Friese-Hamim, C. Stroh, R. Bruns, G. Otto, P. Paik
Journal: Journal of Thoracic Oncology (2021)
Do ‘pathologic’ cardiac murmurs in adolescents identify structural heart disease? An evaluation of 15 141 active adolescents for conditions that put them at risk of sudden cardiac death
Authors: Ashley V Austin, David S Owens, Jordan M Prutkin, Jack C Salerno, Brian Ko, Hank F Pelto, Ashwin L Rao, David M Siebert, Jennifer S Carrol, Kimberly G Harmon, Jonathan A Drezner
Journal: British Journal of Sports Medicine (2021)

We assessed whether the presence and character of a cardiac murmur in adolescents were associated with structural heart disease that confers risk of sudden cardiac death (SCD).We performed a retrospective analysis of 15 141 adolescents age 12-19 who underwent a heart screen with history, physical examination and ECG. Participants with any screening abnormality underwent an echocardiogram for the assessment of structural heart disease. Murmurs were classified as physiological or pathological according to standard clinical criteria, and participants with murmurs were compared with a comparison group without murmurs. The primary outcome was echocardiogram-detected structural heart disease associated with SCD.905 participants with a cardiac murmur (mean age 15.8; 58% male) and 4333 participants without a murmur (comparison group; mean age 15.8; 55% male) had an echocardiogram to detect structural heart disease. 743 (82%) murmurs were described as physiological and 162 (18%) as pathological. Twenty-five (2.8%) participants with murmurs and 61 (1.4%) participants without murmurs had structural heart disease. Three (0.3%) participants in the murmur group were diagnosed with hypertrophic cardiomyopathy (HCM) which was the only identified condition associated with SCD. Two participants with HCM had physiological murmurs, one had a pathological murmur, and all three had an abnormal ECG. The most common minor structural heart disease was bicuspid aortic valve in both the murmur (7; 0.8%) and comparison (20; 0.5%) groups. The positive predictive value of physiological versus pathological murmurs for identifying any structural heart disease was 2.4% versus 4.3% (p=0.21), respectively. The positive predictive value of having any murmur versus no murmur for identifying structural heart disease was 2.8% versus 1.4% (p=0.003), respectively.In adolescents, the traditional classification of cardiac murmurs as 'physiologic' or 'pathologic' does not differentiate for structural heart disease that puts individuals at risk for SCD. We recommend ECG evaluation in all patients with a cardiac murmur found during preparticipation screening to increase detection of HCM.
Management of Cardiogenic Shock During COVID-19
Authors: Carolyn M. Rosner, Behnam N. Tehrani, Alexander G. Truesdell, Shashank S. Sinha, Ramesh Singh, Mehul Desai, Erik Osborn, Shashank Desai, Daniel Tang, Wayne B. Batchelor
Journal: Journal of the American College of Cardiology (2021)
Evaluation of Internet-Based Crowdsourced Fundraising to Cover Health Care Costs in the United States
Authors: Suveen Angraal, Arun George Zachariah, Raaisa Raaisa, Rohan Khera, Praveen Rao, Harlan M. Krumholz, John A. Spertus
Journal: JAMA Network Open (2021)

This serial cross-sectional study examines online crowdsourced fundraising for US health care costs from 2010 to 2018 and evaluates whether there are trends by medical condition and geographic distribution.
Integration of CMR Scar Imaging and Electroanatomic Mapping: The Future of VT Ablation?⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Kenneth C. Bilchick
Journal: JACC. Cardiovascular imaging (2012)
The Future of Drug-Pricing Transparency
Authors: William B. Feldman, Benjamin N. Rome, Jerry Avorn, Aaron S. Kesselheim
Journal: New England Journal of Medicine (2021)

Interview with Dr. William Feldman on a new federal price-transparency rule and legal challenges to efforts to increase access to pricing information. (11:54)Download A federal "Transparency in Coverage" rule requires insurers to disclose list prices and historical net prices for medications and to give patients personalized cost-sharing estimates. Despite industry opposition, the rule may endure under the Biden administration.
Changes in Abortion in Texas Following an Executive Order Ban During the Coronavirus Pandemic
Authors: Kari White, Bhavik Kumar, Vinita Goyal, Robin Wallace, Sarah C. M. Roberts, Daniel Grossman
Journal: JAMA (2021)

This study assesses changes in abortions performed and at what gestational age following a Texas order postponing non–medically necessary surgeries due to the COVID-19 pandemic compared with abortions performed during the same months in 2019.