tbuckley/cabot-search huggingface dataset:
Tumor Cell Escape from Therapy-Induced Senescence as a Model of Disease Recurrence after Dormancy
Authors: Tareq Saleh, Liliya Tyutyunyk-Massey, David A. Gewirtz
Journal: Cancer Research (2019)

Senescence, a durable form of growth arrest, represents a primary response to numerous anticancer therapies. Although the paradigm that senescence is "irreversible" has largely withstood the findings of tumor cell recovery from what has been termed "pseudo-senescence" or "senescence-like arrest," a review of the literature suggests that therapy-induced senescence in tumor cells is not obligatorily a permanent cell fate. Consequently, we propose that senescence represents one avenue whereby tumor cells evade the direct cytotoxic impact of therapy, thereby allowing for prolonged survival in a dormant state, with the potential to recover self-renewal capacity and contribute to disease recurrence.
Adolescent Suicide as a Failure of Acute Stress-Response Systems
Authors: Adam Bryant Miller, Mitchell J. Prinstein
Journal: Annual Review of Clinical Psychology (2019)

Suicide is the second leading cause of death worldwide for adolescents. Despite decades of research on correlates and risk factors for adolescent suicide, we know little about why suicidal ideation and behavior frequently emerge in adolescence and how to predict, and ultimately prevent, suicidal behavior among youths. In this review, we first discuss knowledge regarding correlates, risk factors, and theories of suicide. We then review why adolescence is a period of unique vulnerability, given changing biology and social network reorganization. Next, we present a conceptual model through which to interpret emerging findings in adolescent suicide research. We suggest that a promising area for future research is to examine adolescent suicide as a failure of biological responses to acute stress in the proximal moments of a suicidal crisis. After reviewing initial evidence for this conceptualization, we review future directions for studies on adolescent suicide.
Talimogene laherparepvec (T‐ <scp>VEC</scp> ) in advanced melanoma: complete response in a heart and kidney transplant patient. A case report
Authors: J. Ressler, R. Silmbrod, A. Stepan, F. Tuchmann, A. Cicha, K. Uyanik‐Ünal, C. Hoeller
Journal: British Journal of Dermatology (2019)

Talimogene laherparepvec (T-VEC) is a intralesional oncolytic virotherapy, licensed in the European Union for locoregional advanced melanoma of American Joint Committee on Cancer stages IIIB, IIIC and IVM1a. Organ transplant recipients are currently excluded from all clinical trials dealing with immunotherapies due to the risk of transplant rejection. A 58-year-old white man with a history of heart and kidney transplantation in 2014 was diagnosed with melanoma (Breslow thickness 1·6 mm, stage pT2a) on the left arm in September 2015. In March 2016 he developed in transit metastases, and local therapy with a combination of topical imiquimod (5%) and cryotherapy of individual lesions was initiated. However, in November 2016 therapy was stopped following local progression of the metastases. An interdisciplinary decision to treat the patient with T-VEC was taken. After 11 cycles of T-VEC, the patient showed a complete response. As of June 2018, 11 months after the last treatment cycle of T-VEC, the patient continues to be tumour free. The patient tolerated the therapy well with only mild adverse events and did not show any sign of graft rejection or loss of function of the transplanted organs. We conclude that T-VEC can be a potentially effective and safe treatment in patients with a history of organ transplantation. Nevertheless, due to this special situation, the risks and benefits should always be discussed with an interdisciplinary tumour board.
Association of Delirium Response and Safety of Pharmacological Interventions for the Management and Prevention of Delirium
Authors: Yi-Cheng Wu, Ping-Tao Tseng, Yu-Kang Tu, Chung-Yao Hsu, Chih-Sung Liang, Ta-Chuan Yeh, Tien-Yu Chen, Che-Sheng Chu, Yutaka J. Matsuoka, Brendon Stubbs, Andre F. Carvalho, Saho Wada, Pao-Yen Lin, Yen-Wen Chen, Kuan-Pin Su
Journal: JAMA Psychiatry (2019)

Although several pharmacological interventions for delirium have been investigated, their overall benefit and safety remain unclear.To evaluate evidence regarding pharmacological interventions for delirium treatment and prevention.PubMed, Embase, ProQuest, ScienceDirect, Cochrane Central, Web of Science, ClinicalKey, and ClinicalTrials.gov from inception to May 17, 2018.Randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention.To extract data according to a predetermined list of interests, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines were applied, and all meta-analytic procedures were conducted using a random-effects model.The primary outcomes were treatment response in patients with delirium and the incidence of delirium in patients at risk of delirium.A total of 58 RCTs were included, in which 20 RCTs with 1435 participants (mean age, 63.5 years; 65.1% male) compared the outcomes of treatment and 38 RCTs with 8168 participants (mean age, 70.2 years; 53.4% male) examined the prevention of delirium. A network meta-analysis demonstrated that haloperidol plus lorazepam provided the best response rate for delirium treatment (odds ratio [OR], 28.13; 95% CI, 2.38-333.08) compared with placebo/control. For delirium prevention, the ramelteon, olanzapine, risperidone, and dexmedetomidine hydrochloride groups had significantly lower delirium occurrence rates than placebo/control (OR, 0.07; 95% CI, 0.01-0.66 for ramelteon; OR, 0.25; 95% CI, 0.09-0.69 for olanzapine; OR, 0.27; 95% CI, 0.07-0.99 for risperidone; and OR, 0.50; 95% CI, 0.31-0.80 for dexmedetomidine hydrochloride). None of the pharmacological treatments were significantly associated with a higher risk of all-cause mortality compared with placebo/control.This network meta-analysis demonstrated that haloperidol plus lorazepam might be the best treatment and ramelteon the best preventive medicine for delirium. None of the pharmacological interventions for treatment or prophylaxis increased the all-cause mortality.
Prediction of functional microRNA targets by integrative modeling of microRNA binding and target expression data
Authors: Weijun Liu, Xiaowei Wang
Journal: Genome biology (2019)

We perform a large-scale RNA sequencing study to experimentally identify genes that are downregulated by 25 miRNAs. This RNA-seq dataset is combined with public miRNA target binding data to systematically identify miRNA targeting features that are characteristic of both miRNA binding and target downregulation. By integrating these common features in a machine learning framework, we develop and validate an improved computational model for genome-wide miRNA target prediction. All prediction data can be accessed at miRDB ( http://mirdb.org ).
Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial
Authors: Yi Wan, Fenglei Wang, Jihong Yuan, Jie Li, Dandan Jiang, Jingjing Zhang, Hao Li, Ruoyi Wang, Jun Tang, Tao Huang, Jusheng Zheng, Andrew J Sinclair, Jim Mann, Duo Li
Journal: Gut (2019)

Objective To investigate whether diets differing in fat content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with cardiometabolic risk factors in healthy adults whose diet is in a transition from a traditional low-fat diet to a diet high in fat and reduced in carbohydrate. Methods In a 6-month randomised controlled-feeding trial, 217 healthy young adults (aged 18–35 years; body mass index &lt;28 kg/m 2 ; 52% women) who completed the whole trial were included. All the foods were provided during the intervention period. The three isocaloric diets were: a lower-fat diet (fat 20% energy), a moderate-fat diet (fat 30% energy) and a higher-fat diet (fat 40% energy). The effects of the dietary interventions on the gut microbiota, faecal metabolomics and plasma inflammatory factors were investigated. Results The lower-fat diet was associated with increased α-diversity assessed by the Shannon index (p=0.03), increased abundance of Blautia (p=0.007) and Faecalibacterium (p=0.04), whereas the higher-fat diet was associated with increased Alistipes (p=0.04), Bacteroides (p&lt;0.001) and decreased Faecalibacterium (p=0.04). The concentration of total short-chain fatty acids was significantly decreased in the higher-fat diet group in comparison with the other groups (p&lt;0.001). The cometabolites p-cresol and indole, known to be associated with host metabolic disorders, were decreased in the lower-fat diet group. In addition, the higher-fat diet was associated with faecal enrichment in arachidonic acid and the lipopolysaccharide biosynthesis pathway as well as elevated plasma proinflammatory factors after the intervention. Conclusion Higher-fat consumption by healthy young adults whose diet is in a state of nutrition transition appeared to be associated with unfavourable changes in gut microbiota, faecal metabolomic profiles and plasma proinﬂammatory factors, which might confer adverse consequences for long-term health outcomes. Trial registration number NCT02355795 ; Results.
Enhancement of high-LET radiation-induced lung cancer cell apoptosis by Antennapedia proteins (ANTP)-SmacN7
Authors: Y. Xie
Journal: Annals of Oncology (2019)

Background: The aim of the present study was to investigate the mechanisms underlying the radiation-sensitising effect from antennapedia proteins (ANTP)-SmacN7 on induction of apoptosis in lung cancer cells irradiated with high-LET ionizing irradiation (IR) from accelerated carbon and iron particles. Methods: Two cultured human non-small lung cancer (NSCLC) cell lines, A549 and NCI-H460, were irradiated with low-LET X-irradiations or high-LET IR with or without treatment of ANTP-SmacN7. Change of cell survival, induction of apoptosis and cell cycle progression, and alterations in both death and survival signals for apoptosis, were studied by colony formation assay, flowcytometry, and Western blot analysis, respectively. Results: Showed that at the LD50 for clonogenic cell killing by high-LET iron particles, compared to the low-LET X-rays irradiations, high-LET IR was more efficient for clonogenic cell killing and induction of apoptosis, which was correlated with cell G2/M phase progression. In addition, ANTP-SmacN7 markedly promoted apoptotic cell killing through inhibition of X-linked inhibitor of apoptosis protein (XIAP) and activation of caspase-3 and 9. Furthermore, both antiapoptotic and proapoptotic molecular response was correlated with the apoptotic cell killing and in accordance with the results of clonogenic cell killing. Conclusions: These findings provide useful information to contribute to the improvement of high-LET clinical radiotherapy for NSCLC from the point of view of pharmaceutical radio-sensitization. Legal entity responsible for the study: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PRC. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.
A2.31 Braf (v raf murine sarcoma viral oncogene homologue B1) mutations in rheumatoid arthritis patients
Authors: F Arnoux, N Lambert, F Fina, M Martin, S Kanaan, N Balandraud, I Auger, J Roudier
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by excessive immune responses resulting in inflammation of the joints. Braf (v raf murine sarcoma viral oncogene homologue B1), a kinase of the mitogen-activated protein (MAP) kinase cascade known to regulate cell activation, may be involved in inflammation. By using an assay capable to detect one mutated cell out of 1000, we found that BRAF is mutated in 1% of peripheral blood cells of 23/45 RA patients. In most patients the valine residue at position 600 is substituted by an alanine (V600A). In this study, we evaluated the frequency of V600A mutation in RA patients and controls and its effect on Braf kinase activity. <h3>Materials and methods</h3> A digital droplet polymerase chain reaction (0.001% sensitivity) was used to detect V600A mutation in 110 RA patients and 127 controls including 43 healthy controls, 31 patients with other autoimmune diseases (lupus and scleroderma) and 53 patients with other inflammatory diseases (spondylitis ankylosing and psoriatic arthritis). To test whether V600A influences Braf kinase activity, we developed an <i>in vitro</i> phosphorylation assay of MEK1 (mitogen extracellular regulated kinase), a major Braf substrate. MEK1 phosphorylation was tested in presence of wild type or mutated recombinant Braf proteins. <h3>Results</h3> We found that 54% of patients with RA have a V600A BRAF mutation versus 26% of controls (p = 0.00001). When we looked at the number of mutated cells it appeared that patients with RA had more V600A mutated cells than controls. Moreover, we found that V600A activates <i>in vitro</i> phosphorylation of MEK1. <h3>Conclusions</h3> Most RA patients have V600A mutation in BRAF gene. This mutation is a strong enhancer of Braf kinase activity. V600A mutation could activate the MAP kinase pathway through Braf, leading to pro inflammatory cytokine production and joint inflammation.
Association of Missense Polymorphism in<i>HSD3B1</i>With Outcomes Among Men With Prostate Cancer Treated With Androgen-Deprivation Therapy or Abiraterone
Authors: Masaki Shiota, Shintaro Narita, Shusuke Akamatsu, Naohiro Fujimoto, Takayuki Sumiyoshi, Maki Fujiwara, Takeshi Uchiumi, Tomonori Habuchi, Osamu Ogawa, Masatoshi Eto
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Recently, genetic polymorphism in<i>HSD3B1</i>encoding 3β-hydroxysteroid dehydrogenase-1 has been shown to be associated with oncological outcome when treated with androgen-deprivation therapy (ADT) for prostate cancer. Upfront abiraterone combined with ADT has proved survival benefit. However, its effect on oncological outcome among different ethnicities and in abiraterone treatment remain unclear. <h3>Objective</h3> To investigate the significance of missense polymorphism in<i>HSD3B1</i>gene among men treated with primary ADT or abiraterone. <h3>Design, Setting, and Participants</h3> This prognostic study included Japanese patients with metastatic hormone-sensitive prostate cancer between June 1993 and July 2005 and with castration-resistant prostate cancer between September 2014 and February 2018. Genome DNA was obtained from patient whole blood samples, and genotyping on<i>HSD3B1</i>(rs1047303, 1245C) was performed by Sanger sequencing. <h3>Exposures</h3> Primary ADT for metastatic hormone-sensitive prostate cancer and abiraterone for castration-resistant prostate cancer. <h3>Main Outcomes and Measures</h3> The association of genotype in<i>HSD3B1</i>with clinicopathological parameters and oncological outcome, including prostate-specific antigen response, progression-free survival, treatment failure–free survival, and overall survival was examined. <h3>Results</h3> Of 203 men, 104 were in the primary ADT cohort (median [interquartile range] age, 72 [67-76] years) and 99 men were in the abiraterone group (median [interquartile range] age, 74 [67-80] years). Most patients carried metastatic lesions in each cohort. Among the cohort of primary ADT, men carrying heterozygous and homozygous variant types in<i>HSD3B1</i>gene showed higher progression risk (hazard ratio [HR], 2.34; 95% CI, 1.08-4.49;<i>P</i> = .03) but not any-caused death risk (HR, 1.36; 95% CI, 0.52-2.92;<i>P</i> = .50), compared with men carrying homozygous wild type. In contrast, among the abiraterone cohort, men carrying variant type in<i>HSD3B1</i>gene showed lower progression risk (HR, 0.32; 95% CI, 0.12-0.69;<i>P</i> = .006) and lower all-cause mortality risk (HR, 0.40; 95% CI, 0.13-0.94;<i>P</i> = .04) compared with men carrying homozygous wild type. <h3>Conclusions and Relevance</h3> This study showed that<i>HSD3B1</i>genetic variant is distinctly associated with oncological outcome between primary ADT and abiraterone in Japanese men, suggesting universal significance among different ethnicities in primary ADT, as well as promise as a predictive biomarker of ADT and abiraterone.
Classification of Donor KIR-Genotype Information to Predict Outcome after Unrelated Hematopoietic Stell Cell Transplantation: The Jury Is Still out
Authors: Johannes Schetelig, Henning Baldauf, Carolin Massalski, Sandra Frank, Jürgen Sauter, Matthias Stelljes, Francis A. Ayuk, Armin Gerbitz, Wolfgang Bethge, Gesine Bug, Stefan A Klein, Sarah Wendler, Falk Heidenreich, Julia Luedemann, Vinzenz Lange, Liesbeth C. de Wreede, Daniel Fürst, Alexander H. Schmidt, Guido Kobbe, Hellmut Dietmar Ottinger, Carlheinz Mueller, Dietrich W. Beelen, Joannis Mytilineos, Katharina Fleischhauer, Martin Bornhäuser
Journal: Blood (2018)
The “Hemolyzed” Physical Examination—Situational Challenges to Accurate Bedside Diagnosis
Authors: Zaven Sargsyan
Journal: JAMA Internal Medicine (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 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
Preventing Dogma from Driving Practice
Authors: Patricia A. Kritek, Andrew M. Luks
Journal: New England Journal of Medicine (2019)

Clinicians generally know that many practices persist in medicine without clear evidence to support them. One such example is the approach to endotracheal intubation of critically ill patients in the intensive care unit (ICU), where intubation is typically fraught with substantially more risk than in the controlled setting of the operating room. Patients in the ICU are often far less clinically stable, and other forms of less invasive support have failed. These patients have a lack of physiological reserve and, as a result, are prone to rapid decompensation in the peri-intubation period. Equally important, they may not be fasting at . . .
Changing Prevalence of Lower Airway Infections in Young Children with Cystic Fibrosis
Authors: Oded Breuer, Andre Schultz, Lidija Turkovic, Nicholas de Klerk, Anthony D. Keil, Siobhain Brennan, Joanne Harrison, Colin Robertson, Philip J. Robinson, Peter D. Sly, Sarath Ranganathan, Stephen M. Stick, Daan Caudri
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Historical studies suggest that airway infection in cystic fibrosis initiates with Staphylococcus aureus and Haemophilus influenzae, with later emergence of Pseudomonas aeruginosa. Aspergillus species are regarded as relatively infrequent, late-occurring infections.Objectives: To assess the prevalence and change in prevalence of early lower airway infections in a modern cohort of children with cystic fibrosis.Methods: All infants diagnosed with cystic fibrosis after newborn screening participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) cohort study between 2000 and 2018 were included. Participants prospectively underwent BAL at 3–6 months, 1 year, and annually up to 6 years of age. Lower airway infection prevalence was described. Changes in prevalence patterns were assessed longitudinally using generalized estimating equations controlling for age and repeated visits.Measurements and Main Results: A total of 380 infants underwent 1,759 BALs. The overall prevalence and median age of first acquisition of the most common infections were as follows: S. aureus, 11%, 2.5 years; P. aeruginosa, 8%, 2.4 years; Aspergillus species, 11%, 3.2 years; and H. influenzae, 9%, 3.1 years. During the study, a significant decrease in prevalence of P. aeruginosa (P < 0.001) and S. aureus (P < 0.001) was observed with a significant change toward more aggressive treatment. Prevalence of Aspergillus infections did not significantly change (P = 0.669).Conclusions: Aspergillus species and P. aeruginosa are commonly present in the lower airways from infancy. The decrease in prevalence of P. aeruginosa and S. aureus since 2000, coinciding with a more aggressive therapeutic approach, has resulted in Aspergillus becoming the most commonly isolated pathogen in young children. Further research is warranted to understand the implication of these findings.
SP0100 How to select the most appropriate capillaroscopic device: pros and cons
Authors: W Hermann
Journal: Annals of the Rheumatic Diseases (2017)

One of the most important indications for performing capillaroscopy is to differentiate between primary and secondary Raynaud9s syndrome. Different kinds of microscopes are at hand and generally vary in terms of picture quality or price. Before purchasing a microscope and capillaroscopy software, several considerations about the required standards of examination should be made; some of which are summarized as follows: The region of interest (ROI). Normal capillaries have a mean diameter of about 8 μm. For an accurate assessment a magnification of 100–200x is recommended, for an overview the magnification of 50x is sufficient. Measurement. Beside qualitative measures like changes in vessel architecture, there should be the possibility of quantifying the number of capillaries/mm or vessel diameters. Documentation. All parts of the examination have to be stored and assigned to patient and case. Practical aspects and handling of the device. Different kinds of microscopes are on the market of which three will be discussed in detail. Briefly summarized: Stereo microscopes. Advantages: Very good image quality, zooming in and out without problems, relatively easy to use. Disadvantages: device is not mobile, in patients with finger contractures examinations are difficult to perform, relatively high costs. Videocapillaroscopes: Advantages: Very good image quality, easy to use, "gold standard" for capillaroscopy. Disadvantages: No overview, zooming in and out not applicable (change of lenses required), relatively high costs. USB microscopes: Advantages: low costs, zooming in and out without problems, easy to use. Disadvantages: limited picture quality, documentation laborious. Selecting a capillaroscopic device depends on the conditions of use ("quick look" vs. "academic evaluation and follow up"), which should be clarified before buying a device. The price range is significant and usually differs between 100€ for USB microscopes and up to 10,000€ for stereo and videocapillaroscopes <h3>Literature</h3> Cutolo M et al. How to perform and interpret capillaroscopy. Best Pract Res Clin Rheumatol. 2013;27(2):237–48. Cutolo M et al. State of the art on nailfold capillaroscopy: a reliable diagnostic tool and putative biomarker in rheumatology? Rheumatology (Oxford). 2013;52(11):1933–40. <h3>Disclosure of Interest</h3> None declared