tbuckley/cabot-search huggingface dataset:
26204 Hematology laboratory shift based on common terminology criteria in patients with advanced basal cell carcinoma receiving sonidegib 200 mg daily: Results from the 42-month BOLT study
Authors: Michael Migden, Karl Lewis, Alexander Guminski, Ralf Gutzmer, Carmen Loquai, Nicholas Squittieri, Peter Foley
Journal: Journal of the American Academy of Dermatology (2021)
John D Williams
Authors: Michael Lancaster-Smith, Lesley Williams
Journal: BMJ (2021)

John Desmond Williams was born in Dover, the only son of Jack, a local businessman, and Alice (Carey), and brother to three older sisters. In 1940 his education at Dover Grammar School was interrupted by evacuation to south Wales, where he was billeted with a retired miner’s family for two years. Having left school after the lower sixth, he completed his education at the Royal College of Science, now Imperial College London. He originally intended to read chemistry, but sharing digs in Notting Hill with two medical students led to a change of direction and a successful application to study medicine at Guy’s Hospital Medical School.

After his studies and house posts at Guy’s, John was called for …
28575 Caring for skin during a pandemic: Acute facial skin changes following mask-wearing
Authors: Rachel Elsanadi, Fiore Casale, Niki Nourmohammadi, Katerina Yale, Cristina Nguyen, Vardit Eckhouse, Yoav Cohen, Natasha Atanaskova Mesinkovska
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 122: Adenylate Kinase Isoform Network and AMP Metabolic Signaling in Heart Regeneration
Authors: Song Zhang, Petras Dzeja
Journal: Circulation Research (2017)

Metabolic signaling mechanisms of tissue regeneration is still an enigma. Energy state and metabolite signals regulate cell commitment to self-renewal, lineage specification, differentiation and regeneration. In a favorable metabolic environment, cells can grow and proliferate, however when energy is low - metabolic monitoring system sends signals to cell cycle checkpoint to halt cell division and preserve fuel resources. We demonstrate that loss of heart regenerative capacity after birth in mice is associated with marked changes in metabolome, AK-catalyzed phosphotransfer flux (β-ATP[ 18 O]), ATP turnover (γ-ATP[ 18 O]) and AMP-AMPK signaling along with changes in expression levels of p21, cyclins A and E, pGSK3β and thymidine kinase. Marked reduction of thymidine phosphorylation capacity prevents DNA synthesis and cell proliferation. It emerges, that in adult heart augmented ATP turnover and AMP signal dynamics is misread by AMPK-sensor as "low energy" state inducing blockade of cell cycle metabolic checkpoint and cardiomyocyte proliferation and regeneration after injury. This occurs through augmented adenylate kinase (AK)-mediated AMP signaling which turns on AMPK consequently silencing p53/p21/cyclin cell cycle checkpoint. Changes in expression levels AK1, AK1β, AK2 and AK5 isoforms occur with arrest of heart regeneration. Protein knockdown using siRNA and CRISPR/Cas9 approach indicates that AK2 is critical for cardiomyocyte mitochondrial biogenesis and network formation. Furthermore, we have discovered that deficiency of the AK2 isoform, which is localized in mitochondria intermembrane-intra-cristae space, arrests developmental programming and is embryonically lethal in mice. The uncovered shift in metabolic signaling mechanisms opens new avenues for targeted regulation of heart regenerative potential critical for repair of injured hearts.
26291 Rapid skin improvement with ixekizumab treatment for pediatric patients with psoriasis: Results from IXORA-peds
Authors: Elizabeth Swanson, Lawrence Eichenfield, Claudia Rodriguez Capriles, Lingnan Li, Terri Ridenour, Alyssa Garrelts, Perla Lansang
Journal: Journal of the American Academy of Dermatology (2021)
Endoscopic management of a perforated gallbladder
Authors: Arvind J. Trindade, Mohammed Alshelleh, Nichol Martinez, Anam Rizvi, Petros C. Benias, Stephen Litvak
Journal: Endoscopy (2021)

An 88-year-old woman with obesity (body mass index 40 kg/m2), diabetes, and heart failure presented with acute cholecystitis. Computed tomography (CT) showed a distended gallbladder with a large stone ([Fig. 1]). She was started on intravenous fluids and antibiotics. After 5 hours into her admission, she began to become lethargic and had increasing tachycardia. The patient was deemed a nonsurgical candidate owing to her comorbidities and age. Given the recent evidence [1], the patient was referred for endoscopic ultrasound (EUS)-guided drainage after multidisciplinary discussion.
Association of Age and Pediatric Household Transmission of SARS-CoV-2 Infection
Authors: Lauren A. Paul, Nick Daneman, Kevin L. Schwartz, Michelle Science, Kevin A. Brown, Michael Whelan, Ellen Chan, Sarah A. Buchan
Journal: JAMA Pediatrics (2021)

As a result of low numbers of pediatric cases early in the COVID-19 pandemic, pediatric household transmission of SARS-CoV-2 remains an understudied topic.
IL-17A–producing sinonasal MAIT cells in patients with chronic rhinosinusitis with nasal polyps
Authors: Min-Seok Rha, Young Hoon Yoon, June-Young Koh, Jae Hyung Jung, Ha Seok Lee, Soo Kyoung Park, Su-Hyung Park, Yong Min Kim, Ki-Sang Rha, Eui-Cheol Shin
Journal: Journal of Allergy and Clinical Immunology (2021)
A soft neuroprosthetic hand providing simultaneous myoelectric control and tactile feedback
Authors: Guoying Gu, Ningbin Zhang, Haipeng Xu, Shaoting Lin, Yang Yu, Guohong Chai, Lisen Ge, Houle Yang, Qiwen Shao, Xinjun Sheng, Xiangyang Zhu, Xuanhe Zhao
Journal: Nature Biomedical Engineering (2021)
Surmounting structural barriers to tackle endemic infectious diseases
Authors: Felix Calderón, Alan H. Fairlamb, Mike Strange, Pauline Williams, Carl F. Nathan
Journal: The Journal of Experimental Medicine (2021)

A unique experiment in bringing academic and industrial scientists together to tackle endemic infectious diseases has proved a success. The Tres Cantos Open Lab Foundation, guided and advised by independent experts, funds extended stays of academics at the campus of a pharmaceutical company, where they access the firm’s resources in partnership with company scientists. Progress in tackling tuberculosis, protozoal infections, and enteric bacterial diseases has sustained the decade-long evolution of the model, whose distinctive features complement other public–private partnerships with similar goals.
The Cancer Microbiome: Recent Highlights and Knowledge Gaps
Authors: Reece J. Knippel, Julia L. Drewes, Cynthia L. Sears
Journal: Cancer Discovery (2021)

Abstract Knowledge of the human microbiome, which is likely a critical factor in the initiation, progression, and prognosis of multiple forms of cancer, is rapidly expanding. In this review, we focus on recent investigations to discern putative, causative microbial species and the microbiome composition and structure currently associated with procarcinogenesis and tumorigenesis at select body sites. We specifically highlight forms of cancer, gastrointestinal and nongastrointestinal, that have significant bacterial associations and well-defined experimental evidence with the aim of generating directions for future experimental and translational investigations to develop a clearer understanding of the multifaceted mechanisms by which microbiota affect cancer formation. Significance: Emerging and, for some cancers, strong experimental and translational data support the contribution of the microbiome to cancer biology and disease progression. Disrupting microbiome features and pathways contributing to cancer may provide new approaches to improving cancer outcomes in patients.
Reverse Myocardial Remodeling Following Valve Repair in Patients With Chronic Severe Primary Degenerative Mitral Regurgitation
Authors: Boyang Liu, Desley A H Neil, Moninder Bhabra, Ramesh Patel, Thomas A Barker, Nicolas Nikolaidis, J Stephen Billing, Manvir Hayer, Shanat Baig, Anna M Price, Ravi Vijapurapu, Thomas A Treibel, Nicola C Edwards, Richard P Steeds
Journal: JACC. Cardiovascular imaging (2021)
Cancer immunotherapy with PI3K and PD-1 dual-blockade via optimal modulation of T cell activation signal
Authors: Sho Isoyama, Shigeyuki Mori, Daisuke Sugiyama, Yasuhiro Kojima, Yasuko Tada, Kohei Shitara, Kunihiko Hinohara, Shingo Dan, Hiroyoshi Nishikawa
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune checkpoint blockade (ICB) induces durable clinical responses in patients with various types of cancer. However, its limited clinical efficacy requires the development of better approaches. In addition to immune checkpoint molecules, tumor-infiltrating immunosuppressive cells including regulatory T cells (Tregs) play crucial roles in the immune suppressive tumor microenvironment. While phosphatidylinositol 3-kinase (PI3K) inhibition as a Treg-targeted treatment has been implicated in animal models, its effects on human Tregs and on the potential impairment of effector T cells are required to be clarified for successful cancer immunotherapy. Methods The impact of a selective-PI3K inhibitor ZSTK474 with or without anti-programmed cell death 1 (PD-1) monoclonal antibody on Tregs and CD8 + T cells were examined with in vivo animal models and in vitro experiments with antigen specific and non-specific fashions using peripheral blood from healthy individuals and cancer patients. Phenotypes and functions of Tregs and effector T cells were examined with comprehensive gene and protein expression assays. Results Improved antitumor effects by the PI3K inhibitor in combination with ICB, particularly PD-1 blockade, were observed in mice and humans. Although administration of the PI3K inhibitor at higher doses impaired activation of CD8 + T cells as well as Tregs, the optimization (doses and timing) of this combination treatment selectively decreased intratumoral Tregs, resulting in increased tumor antigen-specific CD8 + T cells in the treated mice. Moreover, on the administration of the PI3K inhibitor with the optimal dose for selectively deleting Tregs, PI3K signaling was inhibited not only in Tregs but also in activated CD8 + T cells, leading to the enhanced generation of tumor antigen-specific memory CD8 + T cells which contributed to durable antitumor immunity. These opposing outcomes between Tregs and CD8 + T cells were attributed to the high degree of dependence on T cell signaling in the former but not in the latter. Conclusions PI3K inhibitor in the combination with ICB with the optimized protocol fine-tuned T cell activation signaling for antitumor immunity via decreasing Tregs and optimizing memory CD8 + T cell responses, illustrating a promising combination therapy.
Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes
Authors: Clair Crewe, Jan-Bernd Funcke, Shujuan Li, Nolwenn Joffin, Christy M. Gliniak, Alexandra L. Ghaben, Yu A. An, Hesham A. Sadek, Ruth Gordillo, Yucel Akgul, Shiuhwei Chen, Dmitri Samovski, Pamela Fischer-Posovszky, Christine M. Kusminski, Samuel Klein, Philipp E. Scherer
Journal: Cell Metabolism (2021)
Retraction Note to: Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF
Authors: Thomas R. Johnson, Sweaty Koul, Binod Kumar, Lakshmipathi Khandrika, Sarah Venezia, Paul D. Maroni, Randall B. Meacham, Hari K. Koul
Journal: Molecular Cancer (2021)

Prostate-derived Ets factor (PDEF) is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF) in prostate cancer. We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression and increased MMP9 expression during the transition to aggressive prostate cancer. These studies demonstrate for the first time negative regulation of MMP9 expression by PDEF, and that PDEF expression was lost in aggressive prostate cancer and was inversely associated with MMP9 expression in clinical samples of prostate cancer. Based on these exciting results, we propose that loss of PDEF along with increased MMP9 expression should serve as novel markers for early detection of aggressive prostate cancer.
Neonatal exposure to a wild-derived microbiome protects mice against diet-induced obesity
Authors: Benedikt Hild, Matthew S. Dreier, Ji Hoon Oh, John A. McCulloch, Jonathan H. Badger, Juen Guo, Claire E. Thefaine, Regina Umarova, Kevin D. Hall, Oksana Gavrilova, Stephan P. Rosshart, Giorgio Trinchieri, Barbara Rehermann
Journal: Nature Metabolism (2021)
Reporting of Race and Ethnicity in Medical and Scientific Journals
Authors: Khadijah K. Breathett, Erica S. Spatz, Brahmajee K. Nallamothu
Journal: JAMA (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 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
Fifty years of clinical and research studies for childhood renal tumors within the International Society of Pediatric Oncology (SIOP)
Authors: N. Graf, C. Bergeron, J. Brok, B. de Camargo, T. Chowdhury, R. Furtwängler, M. Gessler, J. Godzinski, K. Pritchard-Jones, G.L. Ramirez-Villar, C. Rübe, B. Sandstedt, J.-P. Schenk, F. Spreafico, H. Sudour-Bonnange, H. van Tinteren, A. Verschuur, G. Vujanic, M.M. van den Heuvel-Eibrink
Journal: Annals of Oncology (2021)
Clinical Images: Extranodal Natural Killer/T Cell Lymphoma As a Rare Mimicker of Granulomatosis With Polyangiitis
Authors: Jennifer Strouse, Anand Rajan, He B. Chang, Mohamad D. Dimachkie, Christopher Halbur, Brittany Bettendorf
Journal: Arthritis & Rheumatology (2021)

Disclosureform Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Covid-19: US hospitals are overwhelmed as cases rise at “alarming rate”
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

Covid-19: US hospitals are overwhelmed as cases rise at "alarming rate" Janice Hopkins TanneThe representative body of more than 5000 hospitals in the US has appealed to the federal government to release more than $48bn (£35.1bn;€40.9bn) to help them cope with a 43% increase in covid-19 hospital admissions over the past two weeks, which are especially affecting poorly vaccinated southern states.
Abstract 9893: Preoperative Lower Cholesterol Level is the Independent Risk Factor of Severe Postoperative Mortality in Patients With Ruptured Abdominal Aortic Aneurysm
Authors: Atsuko Nakayama, Hiroyuki Morita, Tetsuro Miyata, Masatoshi Nagayama, Tetsuya Sumiyoshi, Ryozo Nagai
Journal: Circulation (2012)

Background: Hypocholesterolemia is reported to be the critical risks of hemorrhagic stroke, but the influence of hypocholesterolemia on large vessels such as abdominal aortic aneurysm (AAA) is unknown. Methods: We conducted a retrospective cohort study on 1053 consecutive patients receiving the surgical repair for infrarenal AAA in multicenter in Tokyo from 2003 through 2011. Laboratory data including total cholesterol levels were measured immediately before surgery. Cox hazards model were used to evaluate the risk factors for the postoperative mortality as well as major adverse cardiac events (MACE; composite of cardiovascular death without postoperative in-hospital death, acute coronary syndrome, cerebrovascular disorder). Results: The average follow-up period was 2.5 ± 2.1 years. In the multiple Cox analysis adjusted for age, gender, aneurysm size, smoking, hypertension, diabetes, past history of coronary disease, past history of chronic obstructive pulmonary disease, anemia, shock, statin use, β-blocker use and angiotensin II receptor blocker use, anemia (hemoglobin level &lt; 10 g/dl), shock and hypocholesterolemia (total cholesterol level &lt; 120 mg/dl) before surgery were found to be the risk factors of all postoperative death in patients with ruptured AAA (HR3.3; 95%CI 2.0-5.3, HR2.5; 95%CI 2.0-4.7, HR;5.4 CI 3.0-9.7, respectively, n=183). Meanwhile, there found to be no risk factor of all death in non-ruptured AAA (n=870). Furthermore, the mortality of patients with each total cholesterol level 120 - 140, 140 - 160, and 160 - 180 mg/dl was higher than that of total cholesterol level &gt; 180 mg/dl (HR3.2; 95%CI 1.9-5.2, HR2.7; 95%CI 1.6-4.4, HR1.8; 95%CI 1.0-3.2, respectively). Receiver operator characteristic (ROC) curve analysis showed hypocholesterolemia is the most significant predictor of postoperative in-hospital death in patients with ruptured AAA (the area under the ROC curve = 0.77). The risk factor of MACE was identified to be the existence of preoperative coronary artery disease. Conclusions: The risk factors of poor mortality in patients with ruptured AAA were anemia, shock and hypocholesterolemia. The lower total cholesterol level indicated the more severe mortality of ruptured AAA.
Small spleen peptides prevent development of psoriatic arthritis via restoration of peripheral tolerance
Authors: Viktor Wixler, Igor Z Zaytsev, Rafael Leite Dantas, Tanja Schied, Yvonne Boergeling, Veronika Lührmann, Georg Varga, Dörthe Masemann, Stephan Ludwig
Journal: Molecular Therapy (2021)

The major challenge in the treatment of autoimmune diseases is the restoration of the impaired peripheral immune tolerance that always accompanies the development of such diseases. Here, we show that small splenic peptides (SSPs) of whole spleen extract efficiently suppress the development of psoriatic arthritis in vivo, even in the presence of sustained levels of pro-inflammatory cytokines. SSPs target dendritic cells (DCs) and convert them into tolerogenic cells, which in turn differentiate naive CD4+ cells into Foxp3-expressing T regulatory cells (Tregs). The latter requires direct contact between SSP-activated DCs and naive CD4+ T cells via PD-1 and CTLA4 immune checkpoint receptors of T cells. Finally, depletion of Foxp3+ Tregs in vivo abrogated the protective effect of SSPs on psoriatic arthritis development. We hypothesize that SSPs represent an intrinsic component of the adaptive immune system responsible for the physiological maintenance of peripheral tolerance and that therapeutically administered SSPs are able to restore imbalanced peripheral tolerance in autoimmune diseases.
Emergence of SARS-CoV-2 Alpha (B.1.1.7) variant, infection rates, antibody seroconversion and seroprevalence rates in secondary school students and staff: Active prospective surveillance, December 2020 to March 2021, England
Authors: Shamez N. Ladhani, Georgina Ireland, Frances Baawuah, Joanne Beckmann, Ifeanyichukwu O Okike, Shazaad Ahmad, Joanna Garstang, Andrew J Brent, Bernadette Brent, Felicity Aiano, Zahin Amin-Chowdhury, Meaghan Kall, Ray Borrow, Ezra Linley, Maria Zambon, John Poh, Lenesha Warrener, Angie Lackenby, Joanna Ellis, Gayatri Amirthalingam, Kevin E Brown, Mary E Ramsay
Journal: Journal of Infection (2021)

We assessed SARS-CoV-2 infection, seroprevalence and seroconversion in students and staff when secondary schools reopened in March 2021.We initiated SARS-CoV-2 surveillance in 18 secondary schools across six regions in September 2020. Participants provided nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term and at the start of the spring term (March 2021).In March 2021, 1895 participants (1100 students:795 staff) were tested; 5.6% (61/1094) students and 4.4% (35/792) staff had laboratory-confirmed SARS-CoV-2 infection from December 2020-March 2021. Nucleoprotein-antibody seroprevalence was 36.3% (370/1018) in students and 31.9% (245/769) in staff, while spike-antibody prevalence was 39.5% (402/1018) and 59.8% (459/769), respectively, similar to regional community seroprevalence. Between December 2020 and March 2021, 14.8% (97/656; 95%CI: 12.2-17.7) students and 10.0% (59/590; 95%CI: 7.7-12.7) staff seroconverted. Weekly seroconversion rates were similar from September to December 2020 (8.0/1000) and from December 2020 to March 2021 (7.9/1000; students: 9.3/1,000; staff: 6.3/1,000).By March 2021, a third of secondary school students and staff had evidence of prior infection based on N-antibody seropositivity, and an additional third of staff had evidence of vaccine-induced immunity based on S-antibody seropositivity.
原発性消化管間質腫瘍切除後にアジュバント療法を施した患者の長期転帰は病理学的および分子的特性に相関する: ACOSOG Z9001試験
Authors: L Corless Christopher, V Ballman Karla, R Antonescu Cristina, Kolesnikova Violetta, G Maki Robert, W T Pisters Peter, E Blackstein Martin, D Blanke Charles, D Demetri George, C Heinrich Michael, Von Mehren Margaret, Patel Shreyaskumar, D Mccarter Martin, Owzar Kouros, P Dematteo Ronald
Journal: Journal of Clinical Oncology (2014)