tbuckley/cabot-search huggingface dataset:
Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer
Authors: Yadong Xie, Yifan Zhao, Lei Shi, Wei Li, Kun Chen, Min Li, Xia Chen, Haiwei Zhang, Tiantian Li, Yu Matsuzawa-Ishimoto, Xiaomin Yao, Dianhui Shao, Zunfu Ke, Jian Li, Yan Chen, Xiaoming Zhang, Jun Cui, Shuzhong Cui, Qibin Leng, Ken Cadwell, Xiaoxia Li, Hong Wei, Haibing Zhang, Huabin Li, Hui Xiao
Journal: Journal of Clinical Investigation (2020)

Although Western diet and dysbiosis are the most prominent environmental factors associated with inflammatory bowel diseases (IBDs), the corresponding host factors and cellular mechanisms remain poorly defined. Here we report that the TSC1/mTOR pathway in the gut epithelium represents a metabolic and innate immune checkpoint for intestinal dysfunction and inflammation. mTOR hyperactivation triggered by Western diet or Tsc1 ablation led to epithelium necroptosis, barrier disruption, and predisposition to dextran sulfate sodium-induced colitis and inflammation-associated colon cancer. Mechanistically, our results uncovered a critical role for TSC1/mTOR in restraining the expression and activation of RIPK3 in the gut epithelium through TRIM11-mediated ubiquitination and autophagy-dependent degradation. Notably, microbiota depletion by antibiotics or gnotobiotics attenuated RIPK3 expression and activation, thereby alleviating epithelial necroptosis and colitis driven by mTOR hyperactivation. mTOR primarily impinged on RIPK3 to potentiate necroptosis induced by TNF and by microbial pathogen-associated molecular patterns (PAMPs), and hyperactive mTOR and aberrant necroptosis were intertwined in human IBDs. Together, our data reveal a previously unsuspected link between the Western diet, microbiota, and necroptosis and identify the mTOR/RIPK3/necroptosis axis as a driving force for intestinal inflammation and cancer.
Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient
Authors: Naim Issa, Camden L. Lopez, Aleksandar Denic, Sandra J. Taler, Joseph J. Larson, Walter K. Kremers, Luisa Ricaurte, Massini A. Merzkani, Mariam Priya Alexander, Harini A. Chakkera, Mark D. Stegall, Joshua J. Augustine, Andrew D. Rule
Journal: Journal of the American Society of Nephrology (2020)

Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear.Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient.The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure.Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.
Cerebrospinal fluid immunoglobulins are increased in neonates exposed to Zika virus during foetal life
Authors: Gustavo C. Nascimento-Carvalho, Eduardo C. Nascimento-Carvalho, Martijn M. VanDuijn, Clara L. Ramos, Ana-Luisa Vilas-Boas, Otávio A. Moreno-Carvalho, Lona Zeneyedpour, Gerben Ferwerda, Ronald de Groot, Theo M. Luider, Cristiana M. Nascimento-Carvalho
Journal: Journal of Infection (2020)
Meningococcal B Vaccine and Meningococcal Carriage in Adolescents in Australia
Authors: Helen S. Marshall, Mark McMillan, Ann P. Koehler, Andrew Lawrence, Thomas R. Sullivan, Jenny M. MacLennan, Martin C.J. Maiden, Shamez N. Ladhani, Mary E. Ramsay, Caroline Trotter, Ray Borrow, Adam Finn, Charlene M. Kahler, Jane Whelan, Kumaran Vadivelu, Peter Richmond
Journal: New England Journal of Medicine (2020)

The meningococcal group B vaccine 4CMenB is a new, recombinant protein-based vaccine that is licensed to protect against invasive group B meningococcal disease. However, its role in preventing transmission and, therefore, inducing population (herd) protection is uncertain.
US cancer centre leaders secretly worked for China, internal report finds
Authors: Owen Dyer
Journal: BMJ (2020)

Six researchers who resigned last month from Florida’s Moffitt Cancer Center admitted to opening secret bank accounts in China to hide millions that they received from China’s Thousand Talents programme, say the preliminary findings of an internal investigation.

Among the six were Alan List, Moffitt’s president and chief executive officer, and the centre’s director, Thomas Sellers. They are the latest and most senior researchers to lose their jobs in a nationwide hunt for academics suspected of working for China, in what US authorities claim is an organised attempt to steal intellectual property.

At least 200 people are being investigated at 71 US hospitals, universities, and research institutions. Most of these investigations began when letters arrived from the US …
The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria
Authors: Alexander Röth, Jun-ichi Nishimura, Zsolt Nagy, Julia Gaàl-Weisinger, Jens Panse, Sung-Soo Yoon, Miklos Egyed, Satoshi Ichikawa, Yoshikazu Ito, Jin Seok Kim, Haruhiko Ninomiya, Hubert Schrezenmeier, Simona Sica, Kensuke Usuki, Flore Sicre de Fontbrune, Juliette Soret, Alexandre Sostelly, James Higginson, Andreas Dieckmann, Brittany Gentile, Judith Anzures-Cabrera, Kenji Shinomiya, Gregor Jordan, Marta Biedzka-Sarek, Barbara Klughammer, Angelika Jahreis, Christoph Bucher, Régis Peffault de Latour
Journal: Blood (2020)
The β3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans
Authors: Brian S. Finlin, Hasiyet Memetimin, Beibei Zhu, Amy L. Confides, Hemendra J. Vekaria, Riham H. El Khouli, Zachary R. Johnson, Philip M. Westgate, Jianzhong Chen, Andrew J. Morris, Patrick G. Sullivan, Esther E. Dupont-Versteegden, Philip A. Kern
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Beige adipose tissue is associated with improved glucose homeostasis in mice. Adipose tissue contains β3-adrenergic receptors (β3-ARs), and this study was intended to determine whether the treatment of obese, insulin-resistant humans with the β3-AR agonist mirabegron, which stimulates beige adipose formation in subcutaneous white adipose tissue (SC WAT), would induce other beneficial changes in fat and muscle and improve metabolic homeostasis.
Perinatal management for premature babies should be multidisciplinary and personalised
Authors: E J Verweij, I K M Reiss
Journal: BMJ (2020)

We read the new framework from the British Association of Perinatal Medicine1 and The BMJ ’s related news story2 with interest. This is a big step forward in perinatal management for extremely premature neonates. We agree with the risk assessment proposed but would like it to be more individualised. 

As …
Pseudomyogenic Hemangioendothelioma
Authors: Yiyan Liu
Journal: Clinical Nuclear Medicine (2019)

Abstract Pseudomyogenic hemangioendothelioma is a rare vascular tumor described as a fibroma-like variant of epithelioid sarcoma. There were scant publications about FDG PET/CT findings of pseudomyogenic hemangioendothelioma. A 20-year-old man with biopsy-confirmed pseudomyogenic hemangioendothelioma of the left tibia had FDG PET/CT for evaluation of the lesion extent and metastasis, which demonstrated numerous, multilayer FDG-avid lesions of the left lower extremity below the knee. Although pathologic examination is mandatory for diagnosis, FDG PET/CT of the case showed distinctive image finding of pseudomyogenic hemangioendothelioma: multifocal and multilayer lesions in a single distal lower extremity.
Recent Trends in the Incidence and Survival of Stage 1A Pancreatic Cancer: A Surveillance, Epidemiology, and End Results Analysis
Authors: Amanda L Blackford, Marcia Irene Canto, Alison P Klein, Ralph H Hruban, Michael Goggins
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Rapid access to pancreatic imaging and regular pancreatic surveillance may help identify stage I pancreatic cancer. We investigated recent trends in the stage of newly diagnosed pancreatic ductal adenocarcinoma (PDACs), age at diagnosis, and survival. Methods Trends in age-adjusted incidence of stage IA PDAC between 2004 and 2016 were determined from the National Cancer Institute’s Surveillance, Epidemiology and End Results database. All tests were two-sided. Results The incidence of stage IA PDAC cases diagnosed increased statistically significantly from 2004 to 2016 (annual percent change = 14.5, 95% confidence interval [CI] = 11.4 to 17.7; P &amp;lt; .001). During the study period, average age at diagnosis for stage IA and IB casesAQ3 declined by 3.5 years (95% CI = 1.2 to 5.9; P = .004) and 5.5 years (95% CI = 3.4 to 7.6; P &amp;lt; .001), whereas average age increased for higher-stage cases (by 0.6 to 1.4 years). Among stage IA cases, the proportion of blacks was smaller (10.2% vs 12.5%), and the proportion of other non-Caucasians was higher compared with higher-stage cases (11.9% vs 8.4%; P &amp;lt; .001). Stage IA cases were more likely to carry insurance (vs Medicaid or none) than higher-stage cases (cases aged younger than 65 years; odds ratio = 2.45, 95% CI = 1.96 to 3.06; P &amp;lt; .001). The 5-year overall survival for stage IA PDAC improved from 44.7% (95% CI = 31.4 to 63.7) in 2004 to 83.7% (95% CI = 78.6% to 89.2%) in 2012; 10-year survival improved from 36.7% (95% CI = 24.1 to 55.8) in 2004 to 49.0% (95% CI = 37.2% to 64.6%) in 2007. Conclusions In recent years, the proportion of patients diagnosed with stage IA PDAC has increased, their average age at diagnosis has decreased, and their overall survival has improved. These trends may be the result of improved early diagnosis and early detection.
<i>Helicobacter pylori</i> antibiotic eradication coupled with a chemically defined diet in INS-GAS mice triggers dysbiosis and vitamin K deficiency resulting in gastric hemorrhage
Authors: Lisa Quinn, Alexander Sheh, Jessie L Ellis, Donald E Smith, Sarah L Booth, Xueyan Fu, Sureshkumar Muthupalani, Zhongming Ge, Dylan A Puglisi, Timothy C Wang, Tamas A Gonda, Hilda Holcombe, James G Fox
Journal: Gut Microbes (2020)

Infection with Helicobacter pylori causes chronic inflammation and is a risk factor for gastric cancer. Antibiotic treatment or increased dietary folate prevents gastric carcinogenesis in male INS-GAS mice. To determine potential synergistic effects, H. pylori-infected male INS-GAS mice were fed an amino acid defined (AAD) diet with increased folate and were treated with antibiotics after 18 weeks of H. pylori infection. Antibiotic therapy decreased gastric pathology, but dietary folate had no effect. However, the combination of antibiotics and the AAD diet induced anemia, gastric hemorrhage, and mortality. Clinical presentation suggested hypovitaminosis K potentially caused by dietary deficiency and dysbiosis. Based on current dietary guidelines, the AAD diet was deficient in vitamin K. Phylloquinone administered subcutaneously and via a reformulated diet led to clinical improvement with no subsequent mortalities and increased hepatic vitamin K levels. We characterized the microbiome and menaquinone profiles of antibiotic-treated and antibiotic-free mice. Antibiotic treatment decreased the abundance of menaquinone producers within orders Bacteroidales and Verrucomicrobiales. PICRUSt predicted decreases in canonical menaquinone biosynthesis genes, menA and menD. Reduction of menA from Akkermansia muciniphila, Bacteroides uniformis, and Muribaculum intestinale were confirmed in antibiotic-treated mice. The fecal menaquinone profile of antibiotic-treated mice had reduced MK5 and MK6 and increased MK7 and MK11 compared to antibiotic-free mice. Loss of menaquinone-producing microbes due to antibiotics altered the enteric production of vitamin K. This study highlights the role of diet and the microbiome in maintaining vitamin K homeostasis.
Attenuated Mitral Leaflet Enlargement Contributes to Functional Mitral Regurgitation After Myocardial Infarction
Authors: Ons Marsit, Marie-Annick Clavel, Claudia Côté-Laroche, Sandra Hadjadj, Marc-André Bouchard, Mark D. Handschumacher, Marine Clisson, Marie-Claude Drolet, Marie-Chloé Boulanger, Dae-Hee Kim, J. Luis Guerrero, Philipp Emanuel Bartko, Jacques Couet, Marie Arsenault, Patrick Mathieu, Philippe Pibarot, Elena Aïkawa, Joyce Bischoff, Robert A. Levine, Jonathan Beaudoin
Journal: Journal of the American College of Cardiology (2020)
Evidence too weak to guide surgical treatment decisions for anterior cruciate ligament injury: a systematic review of the risk of new meniscal tears after anterior cruciate ligament injury
Authors: Guri Ranum Ekås, Clare L Ardern, Hege Grindem, Lars Engebretsen
Journal: British Journal of Sports Medicine (2020)

Objective To investigate the risk of new meniscal tears after treatment for anterior cruciate ligament (ACL) injury, in children and adults with and without ACL reconstruction. Design Prognosis systematic review (PROSPERO registration number CRD42016036788). Methods We searched Embase, Ovid Medline, Cochrane, CINAHL, SPORTDiscus, PEDro and Google Scholar from inception to 3rd May 2018. Eligible articles included patients with ACL injury (diagnosis confirmed by MRI and/or diagnostic arthroscopy), reported the number of meniscal tears at the time of ACL injury diagnosis/start of treatment and reported the number of new meniscal tears that subsequently occurred. Articles with fewer than 20 patients at follow-up, and articles limited to ACL revision surgery or multi-ligament knee injuries were excluded. Two independent reviewers screened articles, assessed eligibility, assessed risk of bias and extracted data. We judged the certainty of evidence using the Grading of Recommendations Assessment Development and Evaluation (GRADE) working group methodology. Results Of 75 studies included in the systematic review, 54 studies with 9624 patients and 501 new meniscal tears were appropriate for quantitative analysis. Heterogeneity precluded data pooling. The risk of new meniscal tears was 0%–21% when follow-up was &lt;2 years, 0%–29% when follow-up was 2 to 5 years, 5%–52% when follow-up was 5 to 10 years and 4%–31% when follow-up was longer than 10 years. The proportion of studies with high risk of selection, misclassification and detection bias was 84%, 69% and 68%, respectively. Certainty of evidence was very low. Conclusion New meniscal tears occurred in 0%–52% of patients between 4 months and 20 years (mean 4.9±4.4 years) following treatment for ACL injury. The certainty of evidence was too low to guide surgical treatment decisions. This review cannot conclude that the incidence of new meniscal tears is lower if ACL injury is treated with surgery compared with treatment with rehabilitation only.
RICTOR/mTORC2 affects tumorigenesis and therapeutic efficacy of mTOR inhibitors in esophageal squamous cell carcinoma
Authors: Zhaoming Lu, Xiaojing Shi, Fanghua Gong, Shenglei Li, Yang Wang, Yandan Ren, Mengyin Zhang, Bin Yu, Yan Li, Wen Zhao, Jianying Zhang, Guiqin Hou
Journal: Acta Pharmaceutica Sinica B (2020)

Dysregulation of mTORC1/mTORC2 pathway is observed in many cancers and mTORC1 inhibitors have been used clinically in many tumor types; however, the mechanism of mTORC2 in tumorigenesis is still obscure. Here, we mainly explored the potential role of mTORC2 in esophageal squamous cell carcinoma (ESCC) and its effects on the sensitivity of cells to mTOR inhibitors. We demonstrated that RICTOR, the key factor of mTORC2, and p-AKT (Ser473) were excessively activated in ESCC and their overexpression is related to lymph node metastasis and the tumor-node-metastasis (TNM) phase of ESCC patients. Furthermore, we found that mTORC1/ mTORC2 inhibitor PP242 exhibited more efficacious anti-proliferative effect on ESCC cells than mTORC1 inhibitor RAD001 due to RAD001-triggered feedback activation of AKT signal. Another, we demonstrated that down-regulating expression of RICTOR in ECa109 and EC9706 cells inhibited proliferation and migration as well as induced cell cycle arrest and apoptosis. Noteworthy, knocking-down stably RICTOR significantly suppresses RAD001-induced feedback activation of AKT/PRAS40 signaling, and enhances inhibition efficacy of PP242 on the phosphorylation of AKT and PRAS40, thus potentiates the antitumor effect of RAD001 and PP242 both in vitro and in vivo. Our findings highlight that selective targeting mTORC2 could be a promising therapeutic strategy for future treatment of ESCC.
Healthy and Climate-Friendly Eating Patterns in the New Zealand Context
Authors: Jonathan Drew, Cristina Cleghorn, Alexandra Macmillan, Anja Mizdrak
Journal: Environmental Health Perspectives (2020)

Background: The global food system is driving both the climate crisis and the growing burden of noncommunicable disease. International research has highlighted the climate and health co-benefit opportunity inherent in widespread uptake of plant-based diets. Nevertheless, uncertainty remains as to what constitutes healthy and climate-friendly eating patterns in specific world regions. Objectives: Using New Zealand as a case study, this research investigates the extent to which potential contextual differences may affect the local applicability of international trends. It further examines the potential for demand-end avenues to support a transition toward a healthier, more climate-friendly food system in New Zealand. Methods: A New Zealand-specific life-cycle assessment (LCA) database was developed by modifying cradle to point-of-sale reference emissions estimates according to the New Zealand context. This food emissions database, together with a New Zealand-specific multistate life-table model, was then used to estimate climate, health, and health system cost impacts associated with shifting current consumption to align with dietary scenarios that conform to the New Zealand dietary guidelines (NZDGs). Results: Whole plant foods, including vegetables, fruits, legumes, and whole grains were substantially less climate-polluting (1.2–1.8 kgCO2e/kg) than animal-based foods, particularly red and processed meats (12–21 kgCO2e/kg). Shifting population-level consumption to align with the NZDGs would confer diet-related emissions savings of 4–42%, depending on the degree of dietary change and food waste minimization pursued. NZDG-abiding dietary scenarios, when modeled out over the lifetime of the current New Zealand population, would also confer large health gains (1.0–1.5 million quality-adjusted life-years) and health care system cost savings (NZ$14–20 billion). Discussion: Guideline-abiding dietary scenarios, particularly those that prioritize plant-based foods, have the potential to confer substantial climate and health gains. This research shows that major contextual differences specific to New Zealand's food system do not appear to cause notable deviation from global trends, reinforcing recent international research. https://doi.org/10.1289/EHP5996
Long-Term Efficacy and Safety of Copanlisib in Multiply Relapsed or Refractory Patients with Marginal Zone Lymphoma
Authors: Martin Dreyling, Panayiotis Panayiotidis, George A Follows, Luigina Mollica, Arnon Nagler, Muhit Özcan, Armando Santoro, Don Stevens, David Trevarthen, Florian Hiemeyer, Li Liu, Jose Garcia-Vargas, Barrett H Childs, Pier Luigi Zinzani
Journal: Blood (2019)
Hydroxyethyl Starch for Fluid Replacement Therapy in High-Risk Surgical Patients
Authors: Fernando G. Zampieri, Alexandre B. Cavalcanti
Journal: JAMA (2020)

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