tbuckley/cabot-search huggingface dataset:
Arcuate Nucleus-Dependent Regulation of Metabolism—Pathways to Obesity and Diabetes Mellitus
Authors: Alexander Jais, Jens C Brüning
Journal: Endocrine Reviews (2021)

Abstract The central nervous system (CNS) receives information from afferent neurons, circulating hormones, and absorbed nutrients and integrates this information to orchestrate the actions of the neuroendocrine and autonomic nervous systems in maintaining systemic metabolic homeostasis. Particularly the arcuate nucleus of the hypothalamus (ARC) is of pivotal importance for primary sensing of adiposity signals, such as leptin and insulin, and circulating nutrients, such as glucose. Importantly, energy state–sensing neurons in the ARC not only regulate feeding but at the same time control multiple physiological functions, such as glucose homeostasis, blood pressure, and innate immune responses. These findings have defined them as master regulators, which adapt integrative physiology to the energy state of the organism. The disruption of this fine-tuned control leads to an imbalance between energy intake and expenditure as well as deregulation of peripheral metabolism. Improving our understanding of the cellular, molecular, and functional basis of this regulatory principle in the CNS could set the stage for developing novel therapeutic strategies for the treatment of obesity and metabolic syndrome. In this review, we summarize novel insights with a particular emphasis on ARC neurocircuitries regulating food intake and glucose homeostasis and sensing factors that inform the brain of the organismal energy status.
A phase 2 study of carfilzomib, cyclophosphamide and dexamethasone as frontline treatment for transplant-eligible MM with high-risk features (SGH-MM1)
Authors: Yunxin Chen, Sathish Kumar Gopalakrishnan, Melissa Ooi, Rehena Sultana, Li Hui Lim, Nicholas Grigoropoulos, Shin Yeu Ong, Mingge Xu, Ee Mei Teh, Melinda Tan, Lawrence Ng, Yuh Shan Lee, Colin Phipps, Francesca Lorraine W. Y. Lim, William Hwang, Wee Joo Chng, Yeow Tee Goh, Chandramouli Nagarajan
Journal: Blood Cancer Journal (2021)
The UK's contribution to cancer control in low-income and middle-income countries
Authors: Susannah Stanway, Mark Lodge, Richard Sullivan, Kim Diprose, Annie M Young, Nigel Crisp, Philippa Lewis, Tim Eden, Ajay Aggarwal, Amanda Nadin, Frank Chinegwundoh, Bhawna Sirohi, Ged Byrne, Richard Cowan
Journal: The Lancet Oncology (2021)
Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0–17 Years — United States, August 2020–August 2021
Authors: David A. Siegel, Hannah E. Reses, Andrea J. Cool, Craig N. Shapiro, Joy Hsu, Tegan K. Boehmer, Cheryl R. Cornwell, Elizabeth B. Gray, S. Jane Henley, Kimberly Lochner, Amitabh B. Suthar, B. Casey Lyons, Linda Mattocks, Kathleen Hartnett, Jennifer Adjemian, Katharina L. van Santen, Michael Sheppard, Karl A. Soetebier, Pamela Logan, Michael Martin, Osatohamwen Idubor, Pavithra Natarajan, Kanta Sircar, Eghosa Oyegun, Joyce Dalton, Cria G. Perrine, Georgina Peacock, Beth Schweitzer, Sapna Bamrah Morris, Elliot Raizes
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Although COVID-19 generally results in milder disease in children and adolescents than in adults, severe illness from COVID-19 can occur in children and adolescents and might require hospitalization and intensive care unit (ICU) support (1-3). It is not known whether the B.1.617.2 (Delta) variant,* which has been the predominant variant of SARS-CoV-2 (the virus that causes COVID-19) in the United States since late June 2021,† causes different clinical outcomes in children and adolescents compared with variants that circulated earlier. To assess trends among children and adolescents, CDC analyzed new COVID-19 cases, emergency department (ED) visits with a COVID-19 diagnosis code, and hospital admissions of patients with confirmed COVID-19 among persons aged 0-17 years during August 1, 2020-August 27, 2021. Since July 2021, after Delta had become the predominant circulating variant, the rate of new COVID-19 cases and COVID-19-related ED visits increased for persons aged 0-4, 5-11, and 12-17 years, and hospital admissions of patients with confirmed COVID-19 increased for persons aged 0-17 years. Among persons aged 0-17 years during the most recent 2-week period (August 14-27, 2021), COVID-19-related ED visits and hospital admissions in the states with the lowest vaccination coverage were 3.4 and 3.7 times that in the states with the highest vaccination coverage, respectively. At selected hospitals, the proportion of COVID-19 patients aged 0-17 years who were admitted to an ICU ranged from 10% to 25% during August 2020-June 2021 and was 20% and 18% during July and August 2021, respectively. Broad, community-wide vaccination of all eligible persons is a critical component of mitigation strategies to protect pediatric populations from SARS-CoV-2 infection and severe COVID-19 illness.
Targeting NRF2 and Its Downstream Processes: Opportunities and Challenges
Authors: Laura Torrente, Gina M. DeNicola
Journal: The Annual Review of Pharmacology and Toxicology (2021)

The transcription factor NRF2 coordinates the expression of a vast array of cytoprotective and metabolic genes in response to various stress inputs to restore cellular homeostasis. Transient activation of NRF2 in healthy tissues has been long recognized as a cellular defense mechanism and is critical to prevent cancer initiation by carcinogens. However, cancer cells frequently hijack the protective capability of NRF2 to sustain the redox balance and meet their metabolic requirements for proliferation. Further, aberrant activation of NRF2 in cancer cells confers resistance to commonly used chemotherapeutic agents and radiotherapy. During the last decade, many research groups have attempted to block NRF2 activity in tumors to counteract the survival and proliferative advantage of cancer cells and reverse resistance to treatment. In this review, we highlight the role of NRF2 in cancer progression and discuss the past and current approaches to disable NRF2 signaling in tumors.
Huge Tumor Thrombus of Chondrosarcoma on FDG PET/CT
Authors: 許正男(Cheng-Nan Hsu), 陳潓誼(Hui-Yi Chen), 吳昱 (Yu-Chin Wu), 楊淳帆(Chun-Fan Yang), 謝德鈞(Te-Chun Hsieh)
Journal: Clinical Nuclear Medicine (2011)
LARP7 Suppresses Endothelial-to-Mesenchymal Transition by Coupling With TRIM28
Authors: Xiaodong Liang, Shuo Wu, Zilong Geng, Li Liu, Shasha Zhang, Shiyan Wang, Yan Zhang, Yu Huang, Bing Zhang
Journal: Circulation Research (2021)

Rationale: Endothelial-to-mesenchymal transition (EndMT) is a fundamental biological process in which endothelial cells lose their endothelial characteristics and acquire mesenchymal properties. EndMT contributes to physiological organ development such as valvulogenesis and is associated with a number of deleterious pathologies such as organ fibrosis. Several signaling pathways of TGF-β (transforming growth factor β), BMP (bone morphogenetic protein) and inflammation have been shown to regulate EndMT. However, the transcriptional and epigenetic programs governing EndMT remains largely unclarified. Objective: To identify the transcriptional or epigenetic mechanisms underlying EndMT and EndMT-associated formation of cardiac valves. Methods and Results: We identified the LARP7 (La ribonucleoprotein domain family member 7), a RNAPII (RNA-binding protein regulating RNA polymerase II) pausing, was downregulated in 2 cytokine-induced EndMT models. LARP7 depletion with lentivirus-mediated shRNA transformed endothelial cells to mesenchymal morphology and induced the expression of the EndMT key regulator, SLUG. Specific deletion of LARP7 in the endocardium in inducible CDH5 CreERT2 ;LARP7 f/f mouse enhanced EndMT in the atrioventricular and outflow tract cushion as revealed by lineage tracing approach. ChIP-seq analysis showed LARP7 and TRIM28 (tripartite motif containing 28) which is an epigenetic repressor were colocalized at SLUG promoter. LARP7 directly interacted with TRIM28 and facilitated it loading to SLUG promoter and repressed its transcription through deacetylating the histones. More importantly, inducible knockout of LARP7 or TRIM28 in the endocardium accelerated EndMT, leading to the valvular hyperplasia, which was further aggravated by the double knockout of these 2 genes. Conclusions: The present study uncovers an orchestrated transcriptional and epigenetic mechanism by which LARP7 cooperates with TRIM28 to govern the EndMT and valvulogenesis.
Controlling diabetes and hypertension in sub-Saharan Africa: lessons from HIV programmes
Authors: Shabbar Jaffar, Kaushik Ramaiya, Catherine Karekezi, Nelson Sewankambo, Shabbar Jaffar, Kaushik Ramaiya, Catherine Karekezi, Anne Ruhweza Katahoire, Christian Kraef, Gerald Mutungi, Joshua Musinguzi, Josephine Birungi, Anupam Garrib, Joseph Okebe, James A Prior, Katie Bates, Jeffrey V Lazarus, Marie-Claire Van Hout, Max Bachmann, Mbiydzenyuy Ferdinant, Beatrice Gachambi, George Msengi, Gerald Yonga, Janet Lutale, Jean Claude Mbanya, Sayoki Mfinanga, Moffat J Nyirenda, Geoff Gill, Peter G Smith, Nelson Sewankambo
Journal: The Lancet (2021)
A Tale of 2 Epidemics—Reply
Authors: A. Mark Clarfield
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
Covid-19: Infection increases the risk of kidney disease even in mild cases, finds study
Authors: Ingrid Torjesen
Journal: BMJ (2021)

Covid-19: Infection increases the risk of kidney disease even in mild cases, finds study Ingrid TorjesenPeople who have recovered from covid-19 have a greater risk of kidney disease, even if they only experienced mild to moderate covid-19 symptoms and were not admitted to hospital, shows a study published in the
Practice-Changing Opportunity to Reduce Disparities in Screening Mammography—Implementation of Risk Assessment in Primary Care
Authors: Elizabeth M. Valencia, Sandhya Pruthi
Journal: JAMA Network Open (2021)

Candice Schwartz, MD; Ifeanyi Beverly Chukwudozie, MPH, MBA; Silvia Tejeda, PhD; Ganga Vijayasiri, PhD; Ivy Abraham, MD; Mylene Remo, MD; Hiral A. Shah, MD; Maria Rojas, BS; Alicia Carillo, MA; Loraine Moreno, RN; Richard B. Warnecke, PhD; Kent F. Hoskins, MD
Moving Toward Fully Blended Collaborative Care
Authors: Christopher M. Callahan
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 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) 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
Targeting Hsp90 using EC154, a novel synthetic Hsp90 inhibitor, impairs multiple oncogenic signaling pathways in human gastric and pancreatic cancer cells and reduces tumor growth in vivo
Authors: Christian Moser, Sven Lang, Karen Lundgren, Hans Schlitt, Edward Geissler, Hong Zhang, Francis Burrows, Oliver Stoeltzing
Journal: Cancer Research (2008)

1181  Background: Hsp90 has been identified to be crucial for stability and functionality of oncogenic signaling molecules, including EGFR, Her-2, Akt, Erk, and various transcription factors. We recently demonstrated that gastric and pancreatic cancer harbors multiple such targets, which can effectively be inhibited by geldanamycin derivates, and leading to significant growth inhibition. We now followed-up on this aspect by investigating effects of a novel synthetic Hsp90 inhibitor (EC154) ingastrointestinal cancers. Methods: Human pancreatic cancer cells, gastric cancer cells, and endothelial cells were employed. Cytotoxic effects were assessed by MTT analyses. Effects of Hsp90 blockade on signaling pathways were investigated by Western blotting. The impact of EC154 on cell migration was evaluated in modified Boyden chambers. Effects of EC154 tumor growth and vascularization were investigated in subcutaneous xenograft models. Mice received either EC154 (25 mg/kg, 50 mg/kg; 2x/week) or vehicle by intraperitoneal injections. Tumor volumes were measured every other day. Tissue was harvested for immunohistochemical analyses and Western blotting. Results: The drug dose-dependently reduced proliferation of gastric and pancreatic cancer cells in vitro and Western blot analyses showed that EC154 effectively blocked STAT3, Akt and Erk activation in cancer cells, in addition to down-regulating EGFR and IGF-IR. Furthermore, EC154 led to marked inhibition of tumor cell migration in vitro (P
Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa
Authors: Brianna Caldwell, Anne R Meyer, Jared A Weis, Amy C Engevik, Eunyoung Choi
Journal: Gut (2021)

Metaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar cells, proliferating cells and spasmolytic polypeptide-expressing metaplasia (SPEM) cells, a key metaplastic cell population. Zymogen-secreting chief cells are long-lived cells in the stomach mucosa and have been considered the origin of SPEM cells; however, a conflicting paradigm has proposed isthmal progenitor cells as an origin for SPEM.Gastric intrinsic factor (GIF) is a stomach tissue-specific gene and exhibits protein expression unique to mature mouse chief cells. We generated a novel chief cell-specific driver mouse allele, GIF-rtTA. GIF-GFP reporter mice were used to validate specificity of GIF-rtTA driver in chief cells. GIF-Cre-RnTnG mice were used to perform lineage tracing during homoeostasis and acute metaplasia development. L635 treatment was used to induce acute mucosal injury and coimmunofluorescence staining was performed for various gastric lineage markers.We demonstrated that mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, we observed long-term label-retaining chief cells at 1 year after the GFP labelling in chief cells. However, only a very small subset of the long-term label-retaining chief cells displayed the reprogramming ability in homoeostasis. In contrast, we identified chief cell-originating SPEM cells as contributing to lineages within foveolar cell hyperplasia in response to the acute mucosal injury.Our study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development.
Local delivery of mRNA-encoded cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models
Authors: Christian Hotz, Timothy R. Wagenaar, Friederike Gieseke, Dinesh S. Bangari, Michelle Callahan, Hui Cao, Jan Diekmann, Mustafa Diken, Christian Grunwitz, Andy Hebert, Karl Hsu, Marie Bernardo, Katalin Karikó, Sebastian Kreiter, Andreas N. Kuhn, Mikhail Levit, Natalia Malkova, Serena Masciari, Jack Pollard, Hui Qu, Sue Ryan, Abderaouf Selmi, Julia Schlereth, Kuldeep Singh, Fangxian Sun, Bodo Tillmann, Tatiana Tolstykh, William Weber, Lena Wicke, Sonja Witzel, Qunyan Yu, Yu-An Zhang, Gang Zheng, Joanne Lager, Gary J. Nabel, Ugur Sahin, Dmitri Wiederschain
Journal: Science Translational Medicine (2021)

Local immunotherapy with an mRNA mixture encoding four cytokines mobilizes a systemic antitumor response and promotes tumor eradication.
Tumor-draining lymph nodes: At the crossroads of metastasis and immunity
Authors: Haley du Bois, Taylor A. Heim, Amanda W. Lund
Journal: Science Immunology (2021)

Early engagement of the lymphatic system by solid tumors in peripheral, nonlymphoid tissues is a clinical hallmark of cancer and often forecasts poor prognosis. The significance of lymph node metastasis for distant spread, however, has been questioned by large-scale lymph node dissection trials and the likely prevalence of direct hematogenous metastasis. Still, an emerging appreciation for the immunological role of the tumor-draining lymph node has renewed interest in its basic biology, role in metastatic progression, antitumor immunity, and patient outcomes. In this review, we discuss our current understanding of the early mechanisms through which tumors engage lymphatic transport and condition tumor-draining lymph nodes, the significance of these changes for both metastasis and immunity, and potential implications of the tumor-draining lymph node for immunotherapy.
Weight changes according to treatment in a diverse cohort of breast cancer patients.
Authors: Jami Aya Fukui, Kami White, Timothy Frankland, Caryn Oshiro, Lynne Wilkens
Journal: Journal of Clinical Oncology (2021)

e12513 Background: Weight changes are common among breast cancer patients. The majority of studies to date have focused on weight gain after a breast cancer diagnosis and its implications on health in survivors. Fewer studies have examined weight loss and its related characteristics. Weight changes have been reported to be influenced by several factors such as age, treatment, stage and pre-diagnostic weight. We evaluated weight changes during key treatment time points in early stage breast cancer patients. Methods: We characterized 389 female patients diagnosed in Hawaii with early stage breast cancer from 2003-2017 in the Multiethnic Cohort (MEC) linked with Kaiser Permanente Hawaii electronic medical record data. We evaluated weight changes from surgery to 4 years post-diagnosis with six time points along a patient’s treatment trajectory (chemotherapy, radiation, endocrine, or surgery alone) and annually thereafter, adjusting for age, race/ethnicity and initial body mass index (BMI). Results: We found key time points of significant weight change for breast cancer patients according to their adjuvant treatment. In patients who had surgery alone (S), surgery-radiation (SR), or surgery-endocrine therapy (SE), the percentage of patients with stable weight, while generally comprising the majority, consistently decreased over time. However, the percentages of patients with weight loss and weight gain during this time steadily increased up to 4 years after initial surgery. Weight loss was more common than weight gain by about 2 fold in these treatment groups (weight loss 33.2%-42% vs weight gain 11.6%-21.4%). For patients with surgery-chemotherapy (SC), there was significant increase in patients with weight loss seen within the first 3 months after surgery (16.2% to 43.7%), during the time when patients receive chemotherapy. And this weight loss trend persisted until year 4. Weight gain was less commonly seen in this treatment group. Conclusions: We identified key time points during breast cancer treatment that may provide a therapeutic window to positively influence outcomes. Tailored weight management interventions should be utilized to promote overall health and long term survivorship.
A retrospective case series of paediatric Stevens–Johnson syndrome and toxic epidermal necrolysis: evaluation of practice using the British Association of Dermatology’s National Guidelines for children and young people
Authors: J. Forsyth, E. Russell, T. McPherson
Journal: British Journal of Dermatology (2021)

The recent publication of the first national guidelines for paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in your journal is a valuable step towards building a focussed understanding of paediatric SJS/TEN (1). The recommended audit points are essential for facilitating a national standard of care.
Women’s Experiences of Promotion and Tenure in Academic Medicine and Potential Implications for Gender Disparities in Career Advancement
Authors: Marie Murphy, Jacquelyn K. Callander, Daniel Dohan, Jennifer R. Grandis
Journal: JAMA Network Open (2021)

Gender disparities in career advancement in academic medicine have persisted despite gender parity in medical school matriculation. Although numerous explanations for this gap exist, little is known about women's experiences of promotion and tenure in academic medicine.To examine women's experiences of promotion and tenure in academic medicine to uncover mechanisms associated with the gender disparity in career advancement.In this qualitative study, 52 in-depth, semistructured interviews with women academic medicine faculty members were conducted in 2019. The 52 participants were drawn from 16 medical schools across the US. Institutions were selected using a purposive sampling strategy to seek diversity of geography and ownership (private or public). Within institutions, purposive and snowball sampling were used to seek diversity with respect to respondents' degree type (MD, PhD, and MD and PhD), age, and career stage. Interview transcripts were analyzed using qualitative thematic analysis. Data analysis was performed from March to December 2020.Themes and subthemes in participants' experiences of promotion and tenure.The 52 women in this study ranged in age from 34 to 82 years (mean [SD] age, 54.0 [10.7] years). Eighteen respondents (34.6%) held an MD, 4 (7.7%) held both an MD and PhD, and 30 (57.7%) held a PhD. Fourteen respondents (26.9%) were assistant professors at the time of the study, 8 (15.4%) were associate professors, and 30 (57.7%) were full professors. Four main themes within participants' experiences of promotion and tenure that pertain to gender inequities were identified: ambiguous or inconsistent criteria for promotion or tenure; lack of standard processes for reviewing applications and making decisions; vulnerability to malicious behavior of senior faculty, department chairs, and division chiefs; and women seeing men have different experiences of advancement.The respondents' experiences of promotion and tenure suggest that promotion and tenure processes may be characterized by inconsistency and a lack of oversight, which have the potential to contribute to well-documented patterns of gender disparities in career advancement in academic medicine.