tbuckley/cabot-search huggingface dataset:
Hypoxia-induced feedback of HIF-1α and lncRNA-CF129 contributes to pancreatic cancer progression through stabilization of p53 protein
Authors: Mingliang Liu, Jianxin Zhong, Zhu Zeng, Kang Huang, Zeng Ye, Shijiang Deng, Hengyu Chen, Fengyu Xu, Qiang Li, Gang Zhao
Journal: Theranostics (2019)

Rationale: Emerging evidences have highlighted the critical roles of lncRNAs in human cancer development.The work sought to assess the biological role and potential underlying mechanisms of lncRNA-CF129 (CF129) which is significantly reduced in pancreatic cancer (PC).Methods: CF129 expression and its association with multiple clinicopathologic characteristics in PC specimens were analyzed.The role of CF129 both in vitro and in vivo was assessed, with RNA pull-down and immunoprecipitation assays being performed to detect the interaction between CF129 and p53 and E3 ligase MKRN1.Chromatin immunoprecipitation and luciferase assays were utilized to identify the interaction between p53 and FOXC2 promoter, HIF-1α/HDAC1 complex and CF129 promoter, FOXC2 and HIF-1α promoter, respectively.Results: CF129 levels were markedly lower in PC compared with paired non-tumor adjacent tissues.Low CF129 expression predicted short overall survival in PC patients.CF129 inhibited invasion and metastasis of PC cells in a FOXC2-dependent manner.In addition, CF129 regulates FOXC2 transcription through association with mutant p53.CF129 directly binds to p53 and E3 ligase MKRN1, and such an interaction leading to p53 protein ubiquitination and degradation.Furthermore, CF129 is a hypoxia-responsive lncRNA, which is transcriptionally downregulated by binding between HIF-1α/HDAC1 complex and CF129 promoter.Finally, it is revealed that HIF-1α is reciprocally regulated by FOXC2 in transcriptional level.Clinically, CF129 downregulation coordinates overexpression of FOXC2.Conclusions: Our study suggests that CF129 inhibits pancreatic cell proliferation and invasion by suppression of FOXC2 transcription, which depends on MKRN1-mediated ubiquitin-dependent p53 degradation.The HIF-1α/CF129/ p53/FOXC2 axis may function as a potential biomarker and therapeutic target.
Paracetamol absorption test to detect poor enteric absorption of oseltamivir in intensive care unit patients with severe influenza: a pilot study
Authors: Faten May, Gilles Peytavin, Slim Fourati, Claire Pressiat, Guillaume Carteaux, Keyvan Razazi, Armand Mekontso Dessap, Nicolas de Prost
Journal: Intensive Care Medicine (2019)
Individual differences, social attention, and the history of the social motivation hypotheses of autism
Authors: Peter C. Mundy
Journal: Behavioral and Brain Sciences (2019)

Abstract The stereotype of people with autism as unresponsive or uninterested in other people was prominent in the 1980s. However, this view of autism has steadily given way to recognition of important individual differences in the social-emotional development of affected people and a more precise understanding of the possible role social motivation has in their early development.
Antibiotics Prevented Maternal Infections After Vaginal Delivery
Authors: Anita Slomski
Journal: JAMA (2019)

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
Letter to the Editor: Liver Transplantation for Acute Liver Failure Because of Dengue Fever: First Successful Reported Case Worldwide
Authors: Narendra S. Choudhary, Sanjiv Saigal, Arvinder S. Soin
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: Fever with jaundice and acute liver failure (ALF)‐like presentation may occur because of several infectious agents in addition to hepatotropic viruses; the list includes dengue virus, malaria, enteric fever, leptospirosis, and scrub typhus. Generally, ALF is part of systemic infections in these infections. The dengue virus is a nonhepatotropic virus; liver dysfunction is frequently present and ranges from transaminitis to ALF.1 Liver transplantation for ALF associated with systemic diseases is generally not recommended as stated by European Association for the Study of the Liver (EASL) clinical practical guidelines for ALF, 2017. Galante et al. have reported the first case of liver transplantation for dengue‐related ALF.2 The report raises some important questions. First, dengue‐related ALF is not rare, as stated by the researchers; several series from tropical countries have shown that dengue‐related ALF contributes to a meaningful number of cases with ALF1; in fact, liver transplantation is not done for dengue‐related ALF because it is a systemic infection and may cause shock syndrome. Second, ALF attributed to dengue may have better outcomes than viral hepatitis ALF, as shown by Tan et al.3 Third, dengue is a systemic infection; neurological manifestations of dengue include encephalitis, meningitis, myelitis, and neuromuscular complications,4 and it is difficult to differentiate these manifestations from hepatic encephalopathy in an ALF setting. Fourth, dengue may cause graft dysfunction in the post–liver transplant period as shown by us earlier.5 Although the researchers have reported a successful case, we believe that liver transplantation for dengue‐related ALF should be done only in exceptional circumstances. The article should not convey a message that liver transplantation should be done for dengue‐related ALF routinely.
Eligibility and subsequent burden of cardiovascular disease of four strategies for blood pressure-lowering treatment: a retrospective cohort study
Authors: Emily Herrett, Sarah Gadd, Rod Jackson, Krishnan Bhaskaran, Elizabeth Williamson, Tjeerd van Staa, Reecha Sofat, Adam Timmis, Liam Smeeth
Journal: The Lancet (2019)

Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example.
Nab-Paclitaxel plus Durvalumab as Second- or Third-Line Treatment of Advanced NSCLC: Results from ABOUND.2L+
Authors: R Govindan, M C Dols, S Aix, P E Postmus, C Lewanski, J Bennouna, J Fischer, O Vidal, D Stewart, A Ardizoni, J Weaver, M Wolfsteiner, M Reck, D Talbot, D Morgensztern, T J Ong
Journal: Journal of Thoracic Oncology (2017)
Biomimetic open porous structured core-shell microtissue with enhanced mechanical properties for bottom-up bone tissue engineering
Authors: Chao Luo, Huimin Fang, Muran Zhou, Jialun Li, Xinyue Zhang, Shaokai Liu, Chuchao Zhou, Jinfei Hou, Huan He, Jiaming Sun, Zhenxing Wang
Journal: Theranostics (2019)

Background: Microtissues constructed with hydrogels promote cell expansion and specific differentiation by mimicking the microarchitecture of native tissues. However, the suboptimal mechanical property and osteogenic activity of microtissues fabricated by natural polymers need further improvement for bone reconstruction application. Core-shell designed structures are composed of an inner core part and an outer part shell, combining the characteristics of different materials, which improve the mechanical property of microtissues. Methods: A micro-stencil array chip was used to fabricate an open porous core-shell micro-scaffold consisting of gelatin as shell and demineralized bone matrix particles modified with bone morphogenetic protein-2 (BMP-2) as core. Single gelatin micro-scaffold was fabricated as a control. Rat bone marrow mesenchymal stem cells (BMSCs) were seeded on the micro-scaffolds, after which they were dynamic cultured and osteo-induced in mini-capsule bioreactors to fabricate microtissues. The physical characteristics, biocompatibility, osteo-inducing and controlled release ability of the core-shell microtissue were evaluated in vitro respectively. Then microtissues were tested in vivo via ectopic implantation and orthotopic bone implantation in rat model. Results: The Young's modulus of core-shell micro-scaffold was nearly triple that of gelatin micro-scaffold, which means the core-shell micro-scaffolds have better mechanical property. BMSCs rapidly proliferated and retained the highest viability on core-shell microtissues. The improved osteogenic potential of core-shell microtissues was evidenced by the increased calcification based on von kossa staining and osteo-relative gene expression. At 3months after transplantation, core-shell microtissue group formed the highest number of mineralized tissues in rat ectopic subcutaneous model, and displayed the largest amount of new bony tissue deposition in rat orthotopic cranial defect. Conclusion: The novel core-shell microtissue construction strategy developed may become a promising cell delivery platform for bone regeneration.
Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis
Authors: Nan Chen, Chuanming Hao, Bi-Cheng Liu, Hongli Lin, Caili Wang, Changying Xing, Xinling Liang, Gengru Jiang, Zhengrong Liu, Xuemei Li, Li Zuo, Laimin Luo, Jianqin Wang, Ming-hui Zhao, Zhihong Liu, Guang-Yan Cai, Li Hao, Robert Leong, Chunrong Wang, Cameron Liu, Thomas Neff, Lynda Szczech, Kin-Hung P. Yu
Journal: New England Journal of Medicine (2019)

Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis.
Comparing apples to apples
Authors: Jaroslaw Regula, Michal F. Kaminski
Journal: Endoscopy (2019)

In the current issue of Endoscopy, Pedersen et al. [1] present data on the risk of post-colonoscopy colorectal cancer (PCCRC) in Denmark and we congratulate the authors for their interesting and very valuable study. They used near-perfect Danish registries to obtain very meaningful data. These registries included The Danish Cancer Registry, which contains coded information about every Danish cancer patient with histology and TNM classification, the Danish National Patient Registry, and the Danish National Prescription Registry, which contains information about every contact with the public health care service including dates, diagnoses, treatments, and procedures.
An Unusual Case of Abdominal Pain
Authors: Russell Goodman, Anand Vaidya, Paul Dellaripa
Journal: New England Journal of Medicine (2013)

A 41-year-old man presented to the emergency department with abdominal pain. He described the pain as the most excruciating he had ever had. It developed suddenly, without warning, 1 hour before presentation. The pain was located in the right lower quadrant and radiated to his right flank and groin. It was slightly alleviated when he was lying supine. He reported nausea and one episode . . .
Abstract 19974: Medicalized Prehospital Care in the Elderly: Facing Age Discrimination
Authors: Eric Wiel, Nicolas Segal, Christophe Di Pompéo, Jean-Baptiste Marc, Carine Vanderstraeten, Mathieu Doukhan, Joséphine Escutnaire, Pierre-Yves Gueugniaud, Hervé Hubert
Journal: Circulation (2015)

Introduction: Few studies report results on cardiac arrests (CA) care in the elderly. Even if age is not considered as an essential prognostic factor some studies questioned if cardiopulmonary resuscitation (CPR) in the elderly could be futile. Nevertheless in daily clinical practice, age seems to be an important factor conditioning CA care. Hypothesis: The aim of this case-control study was to compare out of hospital cardiac arrest care and outcome between young (&lt;65 years old) and elderly patients. Methods: We performed a prospective case-control study based on data extracted from the French National CA registry. All adult patients (&gt;18 years old) with CA recorded between July 2011 and May 2014 were included. Each elderly (&gt;=65 years old) patient (case) was matched on 3 criteria: sex, initial cardiac rhythm, and the no-flow duration. Results: We studied 4,347 pairs. We significantly found less BLS starting, ACLS duration, mobile medical team (MMT) automated chest compression, MMT ventilation and MMT epinephrine injection in the elderly. Statistical differences were also observed for return of spontaneous circulation (ROSC) (OR=0.84[0.77-0.92]), transport to hospital (OR=0.58[0.51-0.61]), vital status at hospital admission (OR=0.55[0.50-0.60]), vital status at Day 30 (OR=0.42[0.35-0.50]), and Cerebral Performance Category (CPC) at Day 30 (OR=0.44[0.37-0.53]). Conclusions: All CA guidelines, ethical statement, clinical procedures do not propose age as a discrimination criterion in OHCA care. However, our study shows that with similar CA conditions, elderly patients are victims of medical discrimination by a shorter duration and less intensive care leading to a lower survival rate compared to young people.
Діагностика мінімальної печінкової енцефалопатії за допомогою нейропсихометричних тестів
Authors: V.B. Yahmur, S.L. Melanich, N.V. Nedzvetska
Journal: GASTROENTEROLOGY (2020)

Печінкова енцефалопатія є загрозливим ускладненням як гострої, так і хронічної печінкової недостатності. Мінімальна печінкова енцефалопатія є початковим етапом розвитку енцефалопатії, що не має неврологічних симптомів із маніфестацією когнітивних порушень, у зв’язку з чим є достатньо складною для діагностики. Ознаки мінімальної енцефалопатії присутні приблизно у 70 % хворих із цирозом печінки та діагностуються лише при проведенні психометричних тестів. У роботі проведено обстеження 40 хворих на хронічний вірусний гепатит С та 30 хворих на цироз печінки, асоційований з вірусом С, з використанням флікер-тесту та тесту зв’язку чисел. Проведення цих тестів дозволило встановити мінімальну печінкову енцефалопатію у 50 % хворих І групи та 44,8 % — ІІ групи та визначити подальшу лікувальну тактику.
Coinfection With <i>Talaromyces marneffei</i> and Other Pathogens Associated With Acquired Immunodeficiency
Authors: Nana Shi, Jinliang Kong, Ke Wang, Cunwei Cao
Journal: JAMA Dermatology (2019)

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The role of the skin microbiota in acne pathophysiology
Authors: S. Ramasamy, E. Barnard, T.L. Dawson, H. Li
Journal: British Journal of Dermatology (2019)

The role of skin microbiota in acne remains to be fully elucidated. Initial culture‐based investigations were hampered by growth rate and selective media bias. Even with less biased genomic methods, sampling, lysis and methodology, the task of describing acne pathophysiology remains challenging. Acne occurs in sites dominated by Cutibacterium acnes (formerly Propionibacterium acnes) and Malassezia species, both of which can function either as commensal or pathogen. This article aims to review the current state of the art of the microbiome and acne. The literature regarding the microbiome and acne was reviewed. It remains unclear whether there is a quantitative difference in microbial community distribution, making it challenging to understand any community shift from commensal to pathogenic nature. It is plausible that acne involves (i) change in the distribution of species/strains, (ii) stable distribution with pathogenic alteration in response to internal (intermicrobe) or external stimuli (host physiology or environmental) or (iii) a combination of these factors. Understanding physiological changes in bacterial species and strains will be required to define their specific roles, and identify any potential intervention points, in acne pathogenesis and treatment. It will also be necessary to determine whether any fungal species are involved, and establish whether they play a significant role. Further investigation using robust, modern analytic tools in longitudinal studies with a large number of participants, may make it possible to determine whether the microbiota plays a causal role, is primarily involved in exacerbation, or is merely a bystander. It is likely that the final outcome will show that acne is the result of complex microbe–microbe and community–host interplay.
WNT16, a new biomarker of senescence involved in lung tumorigenesis
Authors: Romuald Binet, Damien Ythier, Damien Nissou, Christian Brambilla, Elisabeth Brambilla, Curtis Harris, Remy Pedeux
Journal: Cancer Research (2008)

1844  Lung cancer incidence increases exponentially with aging. Because senescent cells accumulate with age and are able to secrete a lot of factors modifying the microenvironment and allowing tumor cell growth (enzymes, cytokines, growth factors), recent studies have suggested that cellular senescence could be the link between cancer and aging. In this context, our study aims to identify and characterize new secreted markers of senescence that are involved in lung tumor promotion and progression.  Using MRC5 lung fibroblasts, we identified a new pathway activated in replicative senescence. By DNA-protein array, we showed that p300, an important regulatory protein in p53-mediated replicative senescence, can form a complex with Pbx1 to activate WNT16 expression. In microarrays, we observed that WNT16 is the most overexpressed gene in replicatively senescent MRC5, and this result was confirmed by Real-Time PCR and Western blot. WNT16 is a member of the WNT family of secreted proteins, and although its function is still unknown, WNT16 protein was previously described as a survival factor in leukemia cells and a proliferation enhancer in keratinocytes. In order to validate WNT16 as a marker of replicative senescence, we reverted senescence in two ways: by degrading p53 or by expression of the catalytic subunit of the human telomerase. In these two models, WNT16 expression is reduced.  To establish the interest of WNT16 as a marker not only of replicative senescence but of cellular senescence, we tested WNT16 expression in three models of SIPS (Stress-Induced Premature Senescence): oxidative stress, DNA damage induced by radiation exposure and oncogenic activation through H-RasV12 expression. In these three SIPS models, WNT16 RNA and protein expression increased compared to dividing fibroblasts.  WNT known properties (proliferation, migration, motility) and role in colon and lung cancers suggest that WNT16 secreted protein could play a dual role in the microenvironment and in tumor cells. By performing growth curves and colony formation assays, we showed that WNT16 overexpression can increase proliferation of transformed CALU-6 lung cancer cell line. Overall, our study shows that WNT16 is a new biomarker of fibroblast cellular senescence that can also be involved in lung tumorigenesis.
Abstract 11863: The Effect of Dapagliflozin Treatment on Epicardial Adipose Tissue Volume and P-Wave Dispersion
Authors: Takao Sato, Yuta Sakaguchi, Yuji Taya, Sho Yuasa, Masaaki Okabe, Yoshifusa Aizawa
Journal: Circulation (2018)

Introduction: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors has been reported to reduce the risk of cardiovascular event. Epicardial adipose tissue (EAT) is a pathogenic fat depot that may be associated with coronary atherosclerosis as well as atrial fibrillation (AF). P-wave dispersion and P-wave variation are predictors of AF development. So, the present study is to aim the impact of SGLT-2 inhibitor on EAT volume and AF predictors. Methods: 40 diabetes mellitus patients with coronary artery disease (10 women; mean age 67±5) were prospectively enrolled, which were classified into the dapagliflozin group (DG) (n=20) and conventional therapy group (CTG) (n=20) during a six-month period. EAT was defined as any pixel that had CT attenuation of -150 to -30 Hounsfield units within the pericardial sac. Using 12-leads of surface electrocardiogram, the P-wave dispersion was defined as the difference between the longest and shortest P-wave durations, and P-wave variation was also defined as the standard dev...
Deviation from the Proportional Hazards Assumption in Randomized Phase 3 Clinical Trials in Oncology: Prevalence, Associated Factors, and Implications
Authors: Rifaquat Rahman, Geoffrey Fell, Steffen Ventz, Andrea Arfé, Alyssa M. Vanderbeek, Lorenzo Trippa, Brian M. Alexander
Journal: Clinical Cancer Research (2019)

Deviations from proportional hazards (DPHs), which may be more prevalent in the era of precision medicine and immunotherapy, can lead to underpowered trials or misleading conclusions. We used a meta-analytic approach to estimate DPHs across cancer trials, investigate associated factors, and evaluate data-analysis approaches for future trials.Experimental Design: We searched PubMed for phase III trials in breast, lung, prostate, and colorectal cancer published in a preselected list of journals between 2014 and 2016 and extracted individual patient-level data (IPLD) from Kaplan-Meier curves. We re-analyzed IPLD to identify DPHs. Potential efficiency gains, when DPHs were present, of alternative statistical methods relative to standard log-rank based analysis were expressed as sample-size requirements for a fixed power level.From 152 trials, we obtained IPLD on 129,401 patients. Among 304 Kaplan-Meier figures, 75 (24.7%) exhibited evidence of DPHs, including eight of 14 (57%) KM pairs from immunotherapy trials. Trial type [immunotherapy, odds ratio (OR), 4.29; 95% confidence interval (CI), 1.11-16.6], metastatic patient population (OR, 3.18; 95% CI, 1.26-8.05), and non-OS endpoints (OR, 3.23; 95% CI, 1.79-5.88) were associated with DPHs. In immunotherapy trials, alternative statistical approaches allowed for more efficient clinical trials with fewer patients (up to 74% reduction) relative to log-rank testing.DPHs were found in a notable proportion of time-to-event outcomes in published clinical trials in oncology and was more common for immunotherapy trials and non-OS endpoints. Alternative statistical methods, without proportional hazards assumptions, should be considered in the design and analysis of clinical trials when the likelihood of DPHs is high.