tbuckley/cabot-search huggingface dataset:
Down-regulation of AMPK/PPARδ signalling promotes endoplasmic reticulum stress-induced endothelial dysfunction in adult rat offspring exposed to maternal diabetes
Authors: Hao Luo, Cong Lan, Chao Fan, Xue Gong, Caiyu Chen, Cheng Yu, Jialiang Wang, Xiaoli Luo, Cuimei Hu, Pedro A Jose, Zaicheng Xu, Chunyu Zeng
Journal: Cardiovascular Research (2021)

Abstract Aims Exposure to maternal diabetes is associated with increased prevalence of hypertension in the offspring. The mechanisms underlying the prenatal programming of hypertension remain unclear. Because endoplasmic reticulum (ER) stress plays a key role in vascular endothelial dysfunction in hypertension, we investigated whether aberrant ER stress causes endothelial dysfunction and high blood pressure in the offspring of dams with diabetes. Methods and results Pregnant Sprague-Dawley rats were intraperitoneally injected with streptozotocin (35 mg/kg) or citrate buffer at Day 0 of gestation. Compared with control mother offspring (CMO), the diabetic mother offspring (DMO) had higher blood pressure and impaired endothelium-dependent relaxation in mesenteric arteries, accompanied by decreased AMPK phosphorylation and PPARδ expression, increased ER stress markers, and reactive oxygen species (ROS) levels. The inhibition of ER stress reversed these aberrant changes in DMO. Ex vivo treatment of mesenteric arteries with an AMPK agonist (A769662) or a PPARδ agonist (GW1516) improved the impaired EDR in DMO and reversed the tunicamycin-induced ER stress, ROS production, and EDR impairment in mesenteric arteries from CMO. The effects of A769662 were abolished by co-treatment with GSK0660 (PPARδ antagonist), whereas the effects of GW1516 were unaffected by Compound C (AMPK inhibitor). Conclusion These results suggest an abnormal foetal programming of vascular endothelial function in offspring of rats with maternal diabetes that is associated with increased ER stress, which can be ascribed to down-regulation of AMPK/PPARδ signalling cascade.
26259 Prurigo nodularis associated pruritus is a systemic process affecting both nodular and interlesional skin
Authors: Prachi Aggarwal, Justin Choi, Kyle A. Williams, Amy H. Huang, Youkyung S. Roh, Nishadh Sutaria, Rajeev Chavda, Sylvie Gabriel, Shawn G. Kwatra
Journal: Journal of the American Academy of Dermatology (2021)
A New Old Target: Androgen Receptor Signaling and Advanced Prostate Cancer
Authors: Daniel Westaby, Maria de Los Dolores Fenor de La Maza, Alec Paschalis, Juan M. Jimenez-Vacas, Jon Welti, Johann de Bono, Adam Sharp
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Owing to the development of multiple novel therapies, there has been major progress in the treatment of advanced prostate cancer over the last two decades; however, the disease remains invariably fatal. Androgens and the androgen receptor (AR) play a critical role in prostate carcinogenesis, and targeting the AR signaling axis with abiraterone, enzalutamide, darolutamide, and apalutamide has improved outcomes for men with this lethal disease. Targeting the AR and elucidating mechanisms of resistance to these agents remain central to drug development efforts. This review provides an overview of the evolution and current approaches for targeting the AR in advanced prostate cancer. It describes the biology of AR signaling, explores AR-targeting resistance mechanisms, and discusses future perspectives and promising novel therapeutic strategies.
26884 Ruxolitinib cream rapidly decreases pruritus in atopic dermatitis: Pooled results from two phase 3 studies
Authors: Andrew Blauvelt, Jacek C. Szepietowski, Kim Papp, Eric L. Simpson, Jonathan I. Silverberg, Brian S. Kim, Shawn G. Kwatra, Michael E. Kuligowski, May E. Venturanza, Kang Sun, Leon Kircik
Journal: Journal of the American Academy of Dermatology (2021)
Ultrasound‐Responsive Nanopeptisomes Enable Synchronous Spatial Imaging and Inhibition of Clot Growth in Deep Vein Thrombosis (Adv. Healthcare Mater. 16/2021)
Authors: Janna N. Sloand, Eric Rokni, Connor T. Watson, Michael A. Miller, Keefe B. Manning, Julianna C. Simon, Scott H. Medina
Journal: Advanced Healthcare Materials (2021)

Nanoparticle Theranostics The image describes the history of different anticoagulants and diagnostics for clotting disorders, highlighting several decades without innovation. In contrast, the right side of the image depicts the development of new precision strategies, like the nanoparticle theranostic paradigm. This latter work is highlighted in article 2100520 by Scott H. Medina and co-workers. Cover design by Daryl Branford.
Spatiotemporally co-delivery of triple therapeutic drugs via HA-coating nanosystems for enhanced immunotherapy
Authors: Chaoqun Ma, Yichao Duan, Chaohui Wu, Erjuan Meng, Pingping Li, Zhenzhong Zhang, Chunhua Zang, Xueling Ren
Journal: Asian Journal of Pharmaceutical Sciences (2021)

There is growing empirical evidence that certain types of chemotherapy and phototherapy trigger immunogenic cell death and enhance the therapeutic anticancer efficacy of genetic immunotherapy. However, the main challenge is spatiotemporally co-delivering different drugs to maximize the therapeutic index of the combination therapy. In this study, a drug delivery system (HTCP-Au/shPD-L1/DOX) was designed with a polysaccharide-wrapped shell and a condensed DNA core. To construct the HTCP-Au vector, dodecyl side chains with a polyethylenimine (PEI) head were grafted onto hyaluronic acid, and AuNPs were grafted via Au-S bonds. During drug loading, PEI arrested shRNA plasmid DNA targeting programmed cell death ligand 1 (shPD-L1) via electrostatic interactions. It also formed a PEI-DNA core that was automatically enclosed when aliphatic hydrocarbons pulled the hyaluronic acid backbone. A hydrophobic interlayer consisting of dodecyl bridge chains between the PEI-DNA core and the hyaluronic acid shell was required to accommodate hydrophobic doxorubicin. In vitro and in vivo assays demonstrated that this core-shell drug delivery system could efficiently load and transport three different drugs and effectively target tumors. Moreover, it could activate the immune system, thereby providing promising therapeutic efficacy against tumor growth and metastasis.
Diagnostic and drug release systems based on microneedle arrays in breast cancer therapy
Authors: Suliman Khan, Anwarul Hasan, Farnoosh Attar, Mohammad Mahdi Nejadi Babadaei, Hojjat Alizadeh Zeinabad, Majid Salehi, Morteza Alizadeh, Mahbub Hassan, Hossein Derakhshankhah, Michael R. Hamblin, Qian Bai, Majid Sharifi, Mojtaba Falahati, Timo L.M. ten Hagen
Journal: Journal of Controlled Release (2021)
Preventing Media-Based False Hopes
Authors: Lester Joe du Perron, Marleen Finoulst
Journal: JAMA Internal Medicine (2021)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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) 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 Internal Medicine journal
Self-reported Mental and Physical Health Among Norwegian Adolescents Before and During the COVID-19 Pandemic
Authors: Jasmina Burdzovic Andreas, Geir Scott Brunborg
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The COVID-19 pandemic and resulting conditions may negatively affect adolescents. <h3>Objective</h3> To examine aspects of self-reported mental and physical health among adolescents in Norway before and during the pandemic, including the role of pandemic-associated anxiety. <h3>Design, Setting, and Participants</h3> This cohort study examined a diverse nationwide sample of grade 11 students from the longitudinal MyLife study in Norway. The original study recruitment of all 8th, 9th, and 10th graders from the same middle schools facilitated identification of 2 sociodemographically comparable cohorts assessed in October to December 2018 and 2019, before the COVID-19 pandemic, and October to December 2020, during the pandemic. School entry and enrollment in Norway is determined by the birth year, and students usually start high school (11th grade) during the fall of the year of their 16th birthday. Data were analyzed from March to June 2021. <h3>Exposures</h3> The COVID-19 pandemic and associated conditions in Norway. <h3>Main Outcomes and Measures</h3> In grades 10 and 11, adolescents reported their depression symptoms using the Patient Health Questionnaire-9 (cutoff scores for moderate/severe depression, ≥15), number of close friends, physical health, and organized sports participation. Cohort differences were examined with a set of nested regression models, incrementally controlling for sociodemographic covariates and grade 10 outcomes. <h3>Results</h3> A sample of 2536 adolescents (1505 [59.4%] girls) was analyzed, including 1621 adolescents before the pandemic and 915 adolescents during the pandemic, of whom 158 adolescents (17.3%) reported high pandemic anxiety. The only significant difference in outcomes between the COVID-19 cohort and the pre–COVID-19 cohort were lower odds of organized sports participation (adjusted odds ratio [aOR], 0.69; 95% CI, 0.56-0.87). However, in subanalyses comparing adolescents with high anxiety during the COVID-19 pandemic with adolescents in the pre–COVID-19 cohort, adolescents with high pandemic anxiety were more likely to experience clinical-level depression symptoms (aOR, 2.17; 95% CI, 1.39-3.37) and poor physical health (aOR, 1.53; 95% CI, 1.01-2.31). <h3>Conclusions and Relevance</h3> In this cohort study of Norwegian adolescents, adolescents who started high school during the pandemic year had lower odds of organized sports participation in late 2020, but were otherwise comparable in terms of self-reported mental and physical health with their pre–COVID-19 counterparts. However, adolescents in the COVID-19 cohort experiencing high pandemic-related anxiety had significantly greater odds of poorer mental and physical health than adolescents in the pre–COVID-19 cohort. Strategies aiming to mitigate the impact of COVID-19 may benefit from identifying youth disproportionally affected by the pandemic conditions.
Pharmacovigilance Analysis of Cardiac Toxicities Associated With Targeted Therapies for Metastatic NSCLC
Authors: Sarah Waliany, Han Zhu, Heather Wakelee, Sukhmani K. Padda, Millie Das, Kavitha Ramchandran, Nathaniel J. Myall, Thomas Chen, Ronald M. Witteles, Joel W. Neal
Journal: Journal of Thoracic Oncology (2021)
Risk of hospital admission with covid-19 among teachers compared with healthcare workers and other adults of working age in Scotland, March 2020 to July 2021: population based case-control study
Authors: Lynda Fenton, Ciara Gribben, David Caldwell, Sam Colville, Jen Bishop, Martin Reid, Jane White, Marion Campbell, Sharon Hutchinson, Chris Robertson, Helen M Colhoun, Rachael Wood, Paul M McKeigue, David A McAllister
Journal: BMJ (2021)

To determine the risk of hospital admission with covid-19 and severe covid-19 among teachers and their household members, overall and compared with healthcare workers and adults of working age in the general population.
Association of the Frequency and Quantity of Alcohol Consumption With Gastrointestinal Cancer
Authors: Jung Eun Yoo, Dong Wook Shin, Kyungdo Han, Dahye Kim, Su-Min Jeong, Hye Yeon Koo, Su Jong Yu, Jinsung Park, Kui Son Choi
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Although total alcohol consumption is a known risk factor for gastrointestinal (GI) cancers, few studies have attempted to assess the pattern of alcohol drinking in association with GI cancers. <h3>Objective</h3> To evaluate the relative association of the frequency of drinking vs the amount of alcohol consumed per occasion with the development of GI cancers. <h3>Design, Setting, and Participants</h3> A population-based retrospective cohort study used data from the Korean National Health Insurance System database on 11 737 467 participants without cancer who underwent a national health screening program from January 1, 2009, to December 31, 2010. Participants were followed up from the year after their health screening date until they received a diagnosis of GI cancer, death, or December 31, 2017. The median follow-up duration was 6.4 years (interquartile range, 6.4-7.4 years). Statistical analysis was performed from January 1, 2019, to March 31, 2020. <h3>Exposures</h3> Weekly alcohol consumption (nondrinker [0 g/week], mild drinker [0-104 g/week], moderate drinker [105-209 g/week], and heavy drinker [≥210 g/week]), drinking frequency, and amount per occasion. <h3>Main Outcomes and Measures</h3> Incident GI cancers at 6 specific sites (esophagus, stomach, colorectal, liver, biliary, and pancreas). <h3>Results</h3> Among 11 737 467 participants (6 124 776 women [52.2%]; mean [SD] age, 54.6 [10.4] years), 319 202 (2.7%) developed GI cancer. Compared with nondrinkers, the risk of GI cancer was higher for mild drinkers (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29). The risk of GI cancer increased linearly with the frequency of drinking in a dose-dependent manner (aHR, 1.39; 95% CI, 1.36-1.41 for individuals who drink every day). In contrast, the risk of GI cancer appeared to increase with consumption up to 5 to 7 units per occasion (aHR, 1.15; 95% CI, 1.14-1.16), and then the HRs were no higher for those with a higher intake per session than 5 to 7 units (8-14 units per occasion: aHR, 1.11; 95% CI, 1.09-1.12; &gt;14 units per occasion: aHR, 1.11; 95% CI, 1.08-1.14). Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion. Risk patterns for 6 specific cancers were generally similar to that of all GI cancers. <h3>Conclusions and Relevance</h3> In this cohort study, frequent drinking was a more important risk factor for incident GI cancers than the amount of alcohol consumed per occasion. Individuals should be cautioned about regular consumption of small amounts of alcohol in addition to the total amount of alcohol consumption or amount per occasion.
BT18: A new era for teledermatology in the COVID‐19 pandemic
Journal: British Journal of Dermatology (2021)

previously shared pictures for new users.Despite some limitations, the Pando app has immensely improved patient safety and proved to be invaluable for our joint dermatology and plastic surgery interactions.However, there is an unmet need for a system with the ability to instantly transfer pictures to PACS and patient electronic records, to improve things further.
The Evolving Post-PCI Antithrombotic Therapies
Authors: E. Magnus Ohman
Journal: New England Journal of Medicine (2021)

Prolonged dual antiplatelet therapy is the treatment of choice for patients with an acute coronary syndrome who have undergone percutaneous coronary intervention (PCI) with a drug-eluting stent.1,2 The rationale is anchored in the understanding that drug-eluting stents impair the vascular healing process, because exposure of the metal in the stent serves as a nidus for stent thrombosis.2,3 The technology for drug-eluting stents has evolved from early devices, which were associated with heightened thrombotic risk, to third- and fourth-generation devices.2,4 These newer stents have been modified to retain their anti-restenosis properties while shortening their drug-eluting properties to minimize the exposure of . . .
Cardiac CIP protein regulates dystrophic cardiomyopathy
Authors: Xin He, Jianming Liu, Fei Gu, Jinghai Chen, Yao Wei Lu, Jian Ding, Haipeng Guo, Mao Nie, Masaharu Kataoka, Zhiqiang Lin, Xiaoyun Hu, Huaqun Chen, Xinxue Liao, Yugang Dong, Wang Min, Zhong-Liang Deng, William T. Pu, Zhan-Peng Huang, Da-Zhi Wang
Journal: Molecular Therapy (2021)

Heart failure is a leading cause of fatality in Duchenne muscular dystrophy (DMD) patients. Previously, we discovered that cardiac and skeletal-muscle-enriched CIP proteins play important roles in cardiac function. Here, we report that CIP, a striated muscle-specific protein, participates in the regulation of dystrophic cardiomyopathy. Using a mouse model of human DMD, we found that deletion of CIP leads to dilated cardiomyopathy and heart failure in young, non-syndromic mdx mice. Conversely, transgenic overexpression of CIP reduces pathological dystrophic cardiomyopathy in old, syndromic mdx mice. Genome-wide transcriptome analyses reveal that molecular pathways involving fibrogenesis and oxidative stress are affected in CIP-mediated dystrophic cardiomyopathy. Mechanistically, we found that CIP interacts with dystrophin and calcineurin (CnA) to suppress the CnA-Nuclear Factor of Activated T cells (NFAT) pathway, which results in decreased expression of Nox4, a key component of the oxidative stress pathway. Overexpression of Nox4 accelerates the development of dystrophic cardiomyopathy in mdx mice. Our study indicates CIP is a modifier of dystrophic cardiomyopathy and a potential therapeutic target for this devastating disease.
Contemporary Management of Thyroid Nodules
Authors: Kristen Kobaly, Caroline S. Kim, Susan J. Mandel
Journal: Annual Review of Medicine (2021)

Thyroid nodules are common in the general population, with higher prevalence in women and with advancing age. Approximately 5% of thyroid nodules are malignant; the majority of this subset represents papillary thyroid cancer. Ultrasonography is the standard technique to assess the underlying thyroid parenchyma, characterize the features of thyroid nodules, and evaluate for abnormal cervical lymphadenopathy. Various risk stratification systems exist to categorize the risk of malignancy based on the ultrasound appearance of a thyroid nodule. Nodules are selected for fine-needle aspiration biopsy on the basis of ultrasound features, size, and high-risk clinical history. Cytology results are classified by the Bethesda system into six categories ranging from benign to malignant. When cytology is indeterminate, molecular testing can further risk-stratify patients for observation or surgery. Surveillance is indicated for nodules with benign cytology, indeterminate cytology with reassuring molecular testing, or non-biopsied nodules without a benign sonographic appearance.
<i>CTLA4</i>promoter hypomethylation is a negative prognostic biomarker at initial diagnosis but predicts response and favorable outcome to anti-PD-1 based immunotherapy in clear cell renal cell carcinoma
Authors: Niklas Klümper, Damian J Ralser, Romina Zarbl, Katrin Schlack, Andres Jan Schrader, Marc Rehlinghaus, Michèle J Hoffmann, Günter Niegisch, Annemarie Uhlig, Lutz Trojan, Julie Steinestel, Konrad Steinestel, Ralph M Wirtz, Danijel Sikic, Markus Eckstein, Glen Kristiansen, Marieta Toma, Michael Hölzel, Manuel Ritter, Sebastian Strieth, Jörg Ellinger, Dimo Dietrich
Journal: Journal for ImmunoTherapy of Cancer (2021)

In metastatic clear cell renal cell carcinoma (ccRCC), different combination therapies, each including anti-PD-1 immune checkpoint blockade (ICB), are applied as first-line treatment. Robust predictive biomarkers for rational upfront therapy decisions are lacking, although they are urgently needed. Recently, we showed that
Black oesophagus in an adolescent with type 2 diabetes
Authors: Paolo Quitadamo, Flora Caruso, Cristina Bucci, Casimiro Del Monaco, Alessandra Verde, Angela Zanfardino, Caterina Strisciuglio, Alessia Piscopo, Dario Iafusco, Augusto Mastrominico, Mariano Caldore
Journal: The Lancet Diabetes & Endocrinology (2021)
26588 Patient-reported outcomes from a large, North American-based cohort, highlight a greater disease burden for generalized pustular psoriasis vs plaque psoriasis: Real-world evidence from the Corrona Psoriasis Registry
Authors: Bruce Strober, Nirali Kotowsky, Rose A. Medeiros, Nicole Foster, Judson Janak, Wendell C. Valdecantos, Mary Flack, Amanda K. Golembesky, Mark Lebwohl
Journal: Journal of the American Academy of Dermatology (2021)
Intradermal covid-19 vaccination could solve supply problems
Authors: Martin Schweiger
Journal: BMJ (2021)

Covid-19 vaccines save lives and mitigate illness, but there is simply not an adequate supply to reach everyone who should be immunised.1 Vaccine supply has been a limiting factor in the UK roll out, but this is much more of a problem globally.

One solution would be switching to intradermal vaccination because it uses a much smaller volume of vaccine. But there have not yet been …
Intussusception in the Peutz–Jeghers Syndrome
Authors: Khalid Akbari, Bruno Sgromo
Journal: New England Journal of Medicine (2021)

A 26-year-old woman with the Peutz–Jeghers syndrome presented with abdominal pain and vomiting. Computed tomography of the abdomen revealed multiple gastric polyps and gastrogastric intussusception.
Erratum to “Ultrasound-mediated delivery enhances therapeutic efficacy of MMP sensitive liposomes” [Journal of Controlled Release, Volume 325 (10 September 2020) 121–134]
Authors: Marieke Olsman, Viktoria Sereti, Kristine Andreassen, Sofie Snipstad, Annemieke van Wamel, Rasmus Eliasen, Sigrid Berg, Andrew J. Urquhart, Thomas L. Andresen, Catharina de Lange Davies
Journal: Journal of Controlled Release (2021)