tbuckley/cabot-search huggingface dataset:
The gut microbial metabolite formate exacerbates colorectal cancer progression
Authors: Dominik Ternes, Mina Tsenkova, Vitaly Igorevich Pozdeev, Marianne Meyers, Eric Koncina, Sura Atatri, Martine Schmitz, Jessica Karta, Maryse Schmoetten, Almut Heinken, Fabien Rodriguez, Catherine Delbrouck, Anthoula Gaigneaux, Aurelien Ginolhac, Tam Thuy Dan Nguyen, Lea Grandmougin, Audrey Frachet-Bour, Camille Martin-Gallausiaux, Maria Pacheco, Lorie Neuberger-Castillo, Paulo Miranda, Nikolaus Zuegel, Jean-Yves Ferrand, Manon Gantenbein, Thomas Sauter, Daniel Joseph Slade, Ines Thiele, Johannes Meiser, Serge Haan, Paul Wilmes, Elisabeth Letellier
Journal: Nature Metabolism (2022)

Abstract The gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the crosstalk between the gut microbiome and the host in relation to tumour cell metabolism remains largely unexplored. Here we show that formate, a metabolite produced by the CRC-associated bacterium Fusobacterium nucleatum , promotes CRC development. We describe molecular signatures linking CRC phenotypes with Fusobacterium abundance. Cocultures of F. nucleatum with patient-derived CRC cells display protumorigenic effects, along with a metabolic shift towards increased formate secretion and cancer glutamine metabolism. We further show that microbiome-derived formate drives CRC tumour invasion by triggering AhR signalling, while increasing cancer stemness. Finally, F. nucleatum or formate treatment in mice leads to increased tumour incidence or size, and Th17 cell expansion, which can favour proinflammatory profiles. Moving beyond observational studies, we identify formate as a gut-derived oncometabolite that is relevant for CRC progression.
American Board of Medical Specialties and New Standards for Continuing Certification
Authors: Richard E. Hawkins, Greg Ogrinc, Susan M. Ramin
Journal: JAMA (2022)

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
Correction: Pilot Phase II Trial of Neoadjuvant Immunotherapy in Locoregionally Advanced, Resectable Cutaneous Squamous Cell Carcinoma of the Head and Neck
Authors: Renata Ferrarotto, Moran Amit, Priyadharsini Nagarajan, M. Laura Rubin, Ying Yuan, Diana Bell, Adel K. El-Naggar, Jason M. Johnson, William H. Morrison, David I. Rosenthal, Bonnie S. Glisson, Faye M. Johnson, Charles Lu, Frank E. Mott, Bita Esmaeli, Eduardo M. Diaz, Paul W. Gidley, Ryan P. Goepfert, Carol M. Lewis, Randal S. Weber, Jennifer A. Wargo, Sreyashi Basu, Fei Duan, Shalini S. Yadav, Padmanee Sharma, James P. Allison, Jeffrey N. Myers, Neil D. Gross
Journal: Clinical Cancer Research (2022)

In the original version of this article (1), one patient's pathologic response was misclassified as partial instead of major. This error affects the data reported in Fig. 1A, in Supplementary Tables S3 and S4, and in the text of the Abstract, Results, and Discussion sections, but does not impact the primary endpoint. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret the error.
Influenza returns with a season dominated by clade 3C.2a1b.2a.2 A(H3N2) viruses, WHO European Region, 2021/22
Authors: Angeliki Melidou, Csaba Ködmön, Karen Nahapetyan, Annette Kraus, Erik Alm, Cornelia Adlhoch, Piers Mooks, Nishi Dave, Carlos Carvalho, Margaux MI Meslé, Rodney Daniels, Richard Pebody
Journal: Eurosurveillance (2022)

In the WHO European Region, COVID-19 non-pharmaceutical interventions continued slowing influenza circulation in the 2021/22 season, with reduced characterisation data. A(H3) predominated and, in some countries, co-circulated with A(H1)pdm09 and B/Victoria viruses. No B/Yamagata virus detections were confirmed. Substantial proportions of characterised circulating virus subtypes or lineages differed antigenically from their respective northern hemisphere vaccine components. Appropriate levels of influenza virus characterisations should be maintained until the season end and in future seasons, when surveillance is adapted to integrate SARS-CoV-2.
Management of Complicated Appendicitis During Pregnancy in the US
Authors: Matthew Ashbrook, Vincent Cheng, Kulmeet Sandhu, Koji Matsuo, Morgan Schellenberg, Kenji Inaba, Kazuhide Matsushima
Journal: JAMA Network Open (2022)

Data are sparse regarding the optimal treatment for complicated appendicitis during pregnancy.To compare nonoperative and operative management in complicated appendicitis during pregnancy.This cohort study was conducted using National Inpatient Sample data from between January 2003 and September 2015. This database approximates a 20% stratified sample of US inpatient hospital discharges. Included individuals were pregnant women discharged with the diagnosis of complicated appendicitis. Data were analyzed from February 2020 through February 2022.Study patients were categorized into 3 groups: those with successful nonoperative management, failed nonoperative management with delayed operation, or immediate operation for complicated appendicitis.Clinical outcomes, including maternal infectious complications and perinatal complications, hospital length of stay, and total hospital charges.Among 8087 pregnant women with complicated appendicitis (median [IQR] age, 27 [22-32] years), nonoperative management of complicated appendicitis was successful among 954 patients (11.8%) and failed among 2646 patients (32.7%), who underwent delayed operation; 4487 patients (55.5%) underwent immediate operation. In multivariate analysis, successful nonoperative management was associated with higher odds of amniotic infection (odds ratio [OR], 4.35; 95% CI, 2.22-8.53; P < .001) and sepsis (OR, 1.52; 95% CI, 1.10-2.11; P = .01) compared with immediate operation, while there was no significant difference in preterm delivery, preterm labor, or abortion. However, failed nonoperative management that required delayed operation was associated with higher odds of preterm delivery, preterm labor, or abortion compared with immediate operation (OR, 1.45; 95% CI, 1.24-1.68; P < .001). Immediate operation was associated with decreased hospital charges compared with nonoperative management that was successful (regression coefficient [RC], 0.09; 95% CI, 0.07-0.11; P < .001) and that failed (RC, 0.12; 95% CI: 0.11-0.14; P < .001). In subgroup multivariate logistic regression analysis, each day in delay to surgery was associated with an increase in odds of preterm delivery, preterm labor, or abortion by 23% (OR, 1.23; 95% CI, 1.18-1.29; P < .001).This study found that immediate operation for complicated appendicitis in pregnant women was associated with lower odds of maternal infectious complications without higher odds of perinatal or other maternal complications compared with successful nonoperative management. Failed nonoperative management was associated with worse clinical outcomes.
3D Upconversion Barcodes for Combinatory Wireless Neuromodulation in Behaving Animals
Authors: Xudong Lin, Tianying Sun, Minghui Tang, Anqi Yang, Richard Yan‐Do, Da Chen, Yaobin Gao, Xin Duan, Ji‐Jung Kai, Feng Wang, Peng Shi
Journal: Advanced Healthcare Materials (2022)

Upconversion techniques offer all-optical wireless alternatives to modulate targeted neurons in behaving animals, but most existing upconversion-based optogenetic devices show prefixed emission that is used to excite just one channelrhodopsin at a restricted brain region. Here, a hierarchical upconversion device is reported to enable spatially selective and combinatory optogenetics in behaving rodent animals. The device assumes a multiarrayed optrode format containing engineered upconversion nanoparticles (UCNPs) to deliver dynamic light palettes as a function of excitation wavelength. Three primary emissions at 477, 540, and 654 nm are selected to match the absorption of different channelrhodopsins. The UCNPs are barcode assembled to multiple nanomachined optical pinholes in a microscale pipette device to allow remotely addressable, spectrum programmable, and spatially selective optical interrogation of complex brain circuits. Using the unique device, the basolateral amygdala and caudoputamen circuits are selectively modulated and the associated fear or anxiety behavior in freely behaving rodents is successfully differentiated. It is believed that the 3D barcode upconversion device would be a great supplement to current optogenetic toolsets and opens up new possibilities for sophisticated neural control.
Clinical Utility Assessment of Gonadotropin-Releasing Hormone Analogs Among Women Younger Than 35 Years—Reply
Authors: Yang Yu, Xiangyun Zong
Journal: JAMA Oncology (2022)

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 Oncology 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 Oncology journal
Cost-effectiveness of artificial intelligence for screening colonoscopy: a modelling study
Authors: Miguel Areia, Yuichi Mori, Loredana Correale, Alessandro Repici, Michael Bretthauer, Prateek Sharma, Filipe Taveira, Marco Spadaccini, Giulio Antonelli, Alanna Ebigbo, Shin-ei Kudo, Julia Arribas, Ishita Barua, Michal F Kaminski, Helmut Messmann, Douglas K Rex, Mário Dinis-Ribeiro, Cesare Hassan
Journal: The Lancet Digital Health (2022)

Artificial intelligence (AI) tools increase detection of precancerous polyps during colonoscopy and might contribute to long-term colorectal cancer prevention. The aim of the study was to investigate the incremental effect of the implementation of AI detection tools in screening colonoscopy on colorectal cancer incidence and mortality, and the cost-effectiveness of such tools.We conducted Markov model microsimulation of using colonoscopy with and without AI for colorectal cancer screening for individuals at average risk (no personal or family history of colorectal cancer, adenomas, inflammatory bowel disease, or hereditary colorectal cancer syndrome). We ran the microsimulation in a hypothetical cohort of 100 000 individuals in the USA aged 50-100 years. The primary analysis investigated screening colonoscopy with versus without AI every 10 years starting at age 50 years and finishing at age 80 years, with follow-up until age 100 years, assuming 60% screening population uptake. In secondary analyses, we modelled once-in-life screening colonoscopy at age 65 years in adults aged 50-79 years at average risk for colorectal cancer. Post-polypectomy surveillance followed the simplified current guideline. Costs of AI tools and cost for downstream treatment of screening detected disease were estimated with 3% annual discount rates. The main outcome measures included the incremental effect of AI-assisted colonoscopy versus standard (no-AI) colonoscopy on colorectal cancer incidence and mortality, and cost-effectiveness of screening projected for the average risk screening US population.In the primary analyses, compared with no screening, the relative reduction of colorectal cancer incidence with screening colonoscopy without AI tools was 44·2% and with screening colonoscopy with AI tools was 48·9% (4·8% incremental gain). Compared with no screening, the relative reduction in colorectal cancer mortality with screening colonoscopy with no AI was 48·7% and with screening colonoscopy with AI was 52·3% (3·6% incremental gain). AI detection tools decreased the discounted costs per screened individual from $3400 to $3343 (a saving of $57 per individual). Results were similar in the secondary analyses modelling once-in-life colonoscopy. At the US population level, the implementation of AI detection during screening colonoscopy resulted in yearly additional prevention of 7194 colorectal cancer cases and 2089 related deaths, and a yearly saving of US$290 million.Our findings suggest that implementation of AI detection tools in screening colonoscopy is a cost-saving strategy to further prevent colorectal cancer incidence and mortality.European Commission and Japan Society of Promotion of Science.
Malic Enzyme 1 Absence in Synovial Sarcoma Shifts Antioxidant System Dependence and Increases Sensitivity to Ferroptosis Induction with ACXT-3102
Authors: Caitlyn B. Brashears, Bethany C. Prudner, Richa Rathore, Katharine E. Caldwell, Carina A. Dehner, Jane L. Buchanan, Sara E.S. Lange, Neal Poulin, Jennifer K. Sehn, Jason Roszik, Dirk Spitzer, Kevin B. Jones, Regis O'Keefe, Torsten O. Nielsen, Eric B. Taylor, Jason M. Held, William Hawkins, Brian A. Van Tine
Journal: Clinical Cancer Research (2022)

Abstract Purpose: To investigate the metabolism of synovial sarcoma (SS) and elucidate the effect of malic enzyme 1 absence on SS redox homeostasis. Experimental Design: ME1 expression was measured in SS clinical samples, SS cell lines, and tumors from an SS mouse model. The effect of ME1 absence on glucose metabolism was evaluated utilizing Seahorse assays, metabolomics, and C13 tracings. The impact of ME1 absence on SS redox homeostasis was evaluated by metabolomics, cell death assays with inhibitors of antioxidant systems, and measurements of intracellular reactive oxygen species (ROS). The susceptibility of ME1-null SS to ferroptosis induction was interrogated in vitro and in vivo. Results: ME1 absence in SS was confirmed in clinical samples, SS cell lines, and an SS tumor model. Investigation of SS glucose metabolism revealed that ME1-null cells exhibit higher rates of glycolysis and higher flux of glucose into the pentose phosphate pathway (PPP), which is necessary to produce NADPH. Evaluation of cellular redox homeostasis demonstrated that ME1 absence shifts dependence from the glutathione system to the thioredoxin system. Concomitantly, ME1 absence drives the accumulation of ROS and labile iron. ROS and iron accumulation enhances the susceptibility of ME1-null cells to ferroptosis induction with inhibitors of xCT (erastin and ACXT-3102). In vivo xenograft models of ME1-null SS demonstrate significantly increased tumor response to ACXT-3102 compared with ME1-expressing controls. Conclusions: These findings demonstrate the translational potential of targeting redox homeostasis in ME1-null cancers and establish the preclinical rationale for a phase I trial of ACXT-3102 in SS patients. See related commentary by Subbiah and Gan, p. 3408
Intervertebral Disc Degeneration: Biomaterials and Tissue Engineering Strategies toward Precision Medicine
Authors: Isma Liza Mohd Isa, Sabarul Afian Mokhtar, Sunny A. Abbah, Mh Busra Fauzi, Aiden Devitt, Abhay Pandit
Journal: Advanced Healthcare Materials (2022)

Abstract Intervertebral disc degeneration is a common cause of discogenic low back pain resulting in significant disability. Current conservative or surgical intervention treatments do not reverse the underlying disc degeneration or regenerate the disc. Biomaterial‐based tissue engineering strategies exhibit the potential to regenerate the disc due to their capacity to modulate local tissue responses, maintain the disc phenotype, attain biochemical homeostasis, promote anatomical tissue repair, and provide functional mechanical support. Despite preliminary positive results in preclinical models, these approaches have limited success in clinical trials as they fail to address discogenic pain. This review gives insights into the understanding of intervertebral disc pathology, the emerging concept of precision medicine, and the rationale of personalized biomaterial‐based tissue engineering tailored to the severity of the disease targeting early, mild, or severe degeneration, thereby enhancing the efficacy of the treatment for disc regeneration and ultimately to alleviate discogenic pain. Further research is required to assess the relationship between disc degeneration and lower back pain for developing future clinically relevant therapeutic interventions targeted towards the subgroup of degenerative disc disease patients.
Review of Jennifer S. Blumenthal-Barby, <i>Good Ethics and Bad Choices: The Relevance of Behavioral Economics for Medical Ethics</i>
Authors: Sven Nyholm
Journal: The American Journal of Bioethics (2022)

"Review of Jennifer S. Blumenthal-Barby, Good Ethics and Bad Choices: The Relevance of Behavioral Economics for Medical Ethics." The American Journal of Bioethics, 22(5), pp. W4–W5
The Shorter, the Better: Can We Improve Efficiency of Idiopathic Pulmonary Fibrosis Trials?
Authors: Giacomo Sgalla, Marlies S. Wijsenbeek, Luca Richeldi
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

hypertension (16).A more precise assessment of donor smoke exposure, passive or active, may provide more information for safer donor-recipient matching.Overall, this study provides guidance for the design of future ARDS therapeutic drug trials.This study adds to the preponderance of evidence suggesting that clinical trials must begin to integrate precise phenotyping of ARDS patients into patient selection, including their tobacco exposure, to identify effective patient-specific therapeutics for ARDS.Finally, and perhaps most importantly, ongoing public health efforts to highlight the profound impact of tobacco smoke exposure on ARDS risks are integral to decreasing the population-based risk of a syndrome with high morbidity, mortality, and societal cost.
No sex-related differences in infarct size, no-reflow, and protection by ischaemic pre-conditioning in Göttingen minipigs
Authors: Petra Kleinbongard, Helmut Lieder, Andreas Skyschally, Gerd Heusch
Journal: Cardiovascular Research (2022)

Female sex has been proposed to be cardioprotective per se. Studies with myocardial ischaemia/reperfusion and infarct size as endpoint have demonstrated cardioprotection in female, castrated male, and male pigs. These studies are difficult to compare, given the different pig strains, models, durations of ischaemia, and methods of infarct size quantification. The few studies using both female and male pigs reported no differences in infarct size and cardioprotection. We, therefore, prospectively compared infarct size in Göttingen minipigs undergoing ischaemia/reperfusion (I/R) without and with ischaemic pre-conditioning (IPC) between female, castrated male, and male pigs.In a prospective, randomized approach, 28 Göttingen open-chest, anaesthetized minipigs underwent 60 min ischaemia by distal left anterior descending artery (LAD) occlusion and 180 min reperfusion without and with IPC by three cycles of 5 min LAD occlusion/10 min reperfusion. Infarct size with I/R was not different between female, castrated male, and male pigs (45 ± 8 vs. 45 ± 13 vs. 41 ± 9% area at risk), as was the reduction in infarct size with IPC (25 ± 11 vs. 30 ± 8 vs. 19 ± 10% area at risk). In addition, the area of no-reflow was not different between female, castrated male, and male pigs with I/R (57 ± 13 vs. 35 ± 7 vs. 47 ± 26% infarct size) or IPC (4 ± 10 vs.12 ± 20 vs. 0 ± 0% infarct size). Phosphorylation of signal transducer and activator of transcription 3 was increased at 10 min reperfusion by IPC but not by I/R to the same extent in female, castrated male, and male pigs (198 ± 30 vs. 230 ± 165 vs. 179 ± 107% of baseline).Our data do not support the notion of sex- or castration-related differences in infarct size, coronary microvascular injury, and cardioprotection by IPC.The translation of successful preclinical studies on cardioprotection to the benefit of patients with reperfused myocardial infarction has been difficult. The difficulties have been attributed to confounders such as co-morbidities and co-medications which patients typically have but animals don´t, but also to age and sex. Notably, female sex has been considered as protective per se. We have now, using our established and clinically relevant pig model of reperfused acute myocardial infarction and ischaemic preconditioning as the most robust cardioprotective intervention looked for sex-related differences of infarct size, no-reflow and cardioprotection by ischaemic preconditioning in a prospectively powered approach but found none such difference.
Laboratory Diagnosis of Creutzfeldt–Jakob Disease
Authors: Inga Zerr
Journal: New England Journal of Medicine (2022)

The diagnosis of Creutzfeldt–Jakob disease has advanced from detection of characteristic EEG and MRI features to include the detection in CSF of 14-3-3 protein and, with the use of RT-QuIC assays, of abnormally folded prion protein, with close to 100% sensitivity and specificity.