tbuckley/cabot-search huggingface dataset:
Tracing local and regional clusters of carbapenemase-producing Klebsiella pneumoniae ST512 with whole genome sequencing, Finland, 2013 to 2018
Authors: Janko van Beek, Kati Räisänen, Markku Broas, Jari Kauranen, Arja Kähkölä, Janne Laine, Eeva Mustonen, Tuija Nurkkala, Teija Puhto, Jaana Sinkkonen, Senja Torvinen, Tarja Vornanen, Risto Vuento, Jari Jalava, Outi Lyytikäinen
Journal: Eurosurveillance (2019)

Background Two epidemiologically-unrelated clusters of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae were detected among several healthcare facilities (HCF) in Finland by routine surveillance using whole genome sequencing (WGS). Aim The objective was to investigate transmission chains to stop further spread of the responsible strain. Methods In this observational retrospective study, cases were defined as patients with K. pneumoniae KPC-3 sequence type (ST)512 strain detected in Finland from August 2013 to May 2018. Environmental specimens were obtained from surfaces, sinks and toilets in affected wards. WGS was performed on K. pneumoniae cultures using Illumina MiSeq platform and data were analysed using Ridom SeqShere software K. pneumoniae core genome multilocus sequence typing (cgMLST) scheme. Epidemiological information of the cases was provided by HCFs. Results We identified 20 cases in six HCFs: cluster 1 included 18 cases in five HCFs and cluster 2 two cases in one HCF. In cluster 1, a link with a foreign country was unclear, 6/18 cases without overlapping stay had occupied the same room in one of the five HCFs within &gt; 3 years. In cluster 2, the index case was transferred from abroad, both cases occupied the same room 8 months apart. A strain identical to that of the two cases in cgMLST was isolated from the toilet of the room, suggesting a clonal origin. Conclusions The clusters were mostly related to case transfer between facilities and likely involved environmental transmission. We show that CPE surveillance using WGS and collaboration between hospitals are crucial to identify clusters and trace transmission chains.
Lineage reprogramming of fibroblasts into induced cardiac progenitor cells by CRISPR/Cas9-based transcriptional activators
Authors: Jianglin Wang, Xueyan Jiang, Lixin Zhao, Shengjia Zuo, Xiantong Chen, Lingmin Zhang, Zhongxiao Lin, Xiaoya Zhao, Yuyan Qin, Xinke Zhou, Xi-Yong Yu
Journal: Acta Pharmaceutica Sinica B (2019)

Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types. Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs). CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity. Here we show lineage reprogramming to iCPCs through a dead Cas9 (dCas9)-based transcription activation system. Targeted and robust activation of endogenous cardiac factors, including GATA4, HAND2, MEF2C and TBX5 (G, H, M and T; GHMT), can reprogram human fibroblasts toward iCPCs. The iCPCs show potentials to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. Addition of MEIS1 to GHMT induces cell cycle arrest in G2/M and facilitates cardiac reprogramming. Lineage reprogramming of human fibroblasts into iCPCs provides a promising cellular resource for disease modeling, drug discovery and individualized cardiac cell therapy.
Abstract 14055: Trend and Predictors of Prolonged Length of Hospital Stay Following Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction in The United States: A 10 Year Perspective
Authors: Hemang B Panchal, Sreenivas P Veeranki, Samit Bhatheja, Ashraf Abusara, Timir Paul
Journal: Circulation (2015)

Background: Length of hospital stay (LOS) following percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) significantly affects healthcare utilization and cost. There is paucity of data in the United States on the optimal LOS following PCI for STEMI. Our study objective is to assess the trend and predictors of prolonged LOS following PCI with stent placement for STEMI. Methods: Data were obtained from nationwide inpatient sample from 2003-2012, which is a 20% stratified probability sample of all non-federal acute care hospitalizations. Study outcome was prolonged LOS defined as stay in hospital for &gt;4 days following PCI for STEMI. Cochrane-Armitage trend test and multivariable logistic regression models were used to delineate the predictors of prolonged LOS which included patient’s demographics, baseline comorbidities, presenting illnesses and in-hospital complications following PCI for STEMI. Results: A total of 223,267 patients with STEMI underwent PCI with stent placement with a mean LOS of 3.3±3.3 days. There were 16.1% patients who had prolonged LOS. The trend analysis showed that incidence of prolonged LOS decreased from 17.1% in year 2003 to 14.3% in year 2012 (p&lt;0.05) (figure 1A). Pneumonia and peri-procedural intra-aortic balloon pump use were the strongest predictors for prolonged LOS. Other significant predictors for prolonged LOS following PCI for STEMI were history of congestive heart failure, anemia, respiratory failure requiring ventilator use; peri-procedural stroke and anemia or hemorrhage requiring blood transfusion (figure 1B). Conclusions: Incidence of prolonged LOS has consistently decreased over 10 years. Patient’s baseline comorbidities, illnesses at presentation and in-hospital complications can predict prolonged LOS following PCI for STEMI. Implementing an aggressive standard of care to prevent in-hospital complications can further shorten the LOS following PCI for STEMI.
Effect of Psychological Intervention on Fear of Cancer Recurrence: A Systematic Review and Meta-Analysis
Authors: Nina M. Tauber, Mia S. O’Toole, Andreas Dinkel, Jacqueline Galica, Gerry Humphris, Sophie Lebel, Christine Maheu, Gozde Ozakinci, Judith Prins, Louise Sharpe, Allan “Ben” Smith, Belinda Thewes, Sébastien Simard, Robert Zachariae
Journal: Journal of Clinical Oncology (2019)

Fear of cancer recurrence (FCR) is a significantly distressing problem that affects a substantial number of patients with and survivors of cancer; however, the overall efficacy of available psychological interventions on FCR remains unknown. We therefore evaluated this in the present systematic review and meta-analysis.We searched key electronic databases to identify trials that evaluated the effect of psychological interventions on FCR among patients with and survivors of cancer. Controlled trials were subjected to meta-analysis, and the moderating influence of study characteristics on the effect were examined. Overall quality of evidence was evaluated using the GRADE system. Open trials were narratively reviewed to explore ongoing developments in the field (PROSPERO registration no.: CRD42017076514).A total of 23 controlled trials (21 randomized controlled trials) and nine open trials were included. Small effects (Hedges's g) were found both at postintervention (g = 0.33; 95% CI, 0.20 to 0.46; P < .001) and at follow-up (g = 0.28; 95% CI, 0.17 to 0.40; P < .001). Effects at postintervention of contemporary cognitive behavioral therapies (CBTs; g = 0.42) were larger than those of traditional CBTs (g = 0.24; β = .22; 95% CI, .04 to .41; P = .018). At follow-up, larger effects were associated with shorter time to follow-up (β = -.01; 95% CI, -.01 to -.00; P = .027) and group-based formats (β = .18; 95% CI, .01 to .36; P = .041). A GRADE evaluation indicated evidence of moderate strength for effects of psychological intervention for FCR.Psychological interventions for FCR revealed a small but robust effect at postintervention, which was largely maintained at follow-up. Larger postintervention effects were found for contemporary CBTs that were focused on processes of cognition-for example, worry, rumination, and attentional bias-rather than the content, and aimed to change the way in which the individual relates to his or her inner experiences. Future trials could investigate how to further optimize and tailor interventions to individual patients' FCR presentation.
Near-simultaneous intensive care unit (ICU) admissions and all-cause mortality: a cohort study
Authors: Markos G. Kashiouris, Curtis N. Sessler, Rehan Qayyum, Venu Velagapudi, Christos Stefanou, Rahul Kashyap, Niall Crowley, Craig Daniels, Kianoush Kashani
Journal: Intensive Care Medicine (2019)
Global Action Needed to Protect Humanitarian Surgeons and Patients During Wars and Armed Conflicts
Authors: Rahul M. Jindal
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Short-term effects of multiple outdoor environmental factors on risk of asthma exacerbations: Age-stratified time-series analysis
Authors: Seung Won Lee, Dong Keon Yon, Chase C. James, Shinhae Lee, Hyun Yong Koh, Youn Ho Sheen, Jae-Won Oh, Man Yong Han, George Sugihara
Journal: Journal of Allergy and Clinical Immunology (2019)
Anticancer drug discovery by targeting cullin neddylation
Authors: Qing Yu, Yihan Jiang, Yi Sun
Journal: Acta Pharmaceutica Sinica B (2019)

Protein neddylation is a post-translational modification which transfers the ubiquitin-like protein NEDD8 to a lysine residue of the target substrate through a three-step enzymatic cascade. The best-known substrates of neddylation are cullin family proteins, which are the core component of Cullin-RING E3 ubiquitin ligases (CRLs). Given that cullin neddylation is required for CRL activity, and CRLs control the turn-over of a variety of key signal proteins and are often abnormally activated in cancers, targeting neddylation becomes a promising approach for discovery of novel anti-cancer therapeutics. In the past decade, we have witnessed significant progress in the field of protein neddylation from preclinical target validation, to drug screening, then to the clinical trials of neddylation inhibitors. In this review, we first briefly introduced the nature of protein neddylation and the regulation of neddylation cascade, followed by a summary of all reported chemical inhibitors of neddylation enzymes. We then discussed the structure-based targeting of protein-protein interaction in neddylation cascade, and finally the available approaches for the discovery of new neddylation inhibitors. This review will provide a focused, up-to-date and yet comprehensive overview on the discovery effort of neddylation inhibitors.
NHS England explores funding options for cystic fibrosis drug
Authors: Deborah Cohen
Journal: BMJ (2019)

NHS England is “committed to exploring and developing alternative routes” to enable people with cystic fibrosis to access Orkambi (ivacaftor-lumacaftor) on the NHS if Vertex, the US company that markets it, does not price the drug “fairly and responsibly,” a spokesperson has said.

The statement comes after the Scottish government agreed a deal with Vertex to provide around 400 people with cystic fibrosis access to Orkambi and Symkevi (ivacaftor-tezacaftor).1

There are several options open to the NHS if it fails to reach an agreement with Vertex.

These include suspending the patent and proceeding with a crown use licence—meaning that another company can manufacture the drug. Or NHS England could avoid the patent by using a research exemption to import an existing generic version of Orkambi to use in a clinical trial.

The UK has …
Growth Suppressing Activity of Lhx2 in Human T Cell Acute Lymphoblastic Leukemia (T-ALL)-Derived Cells and Large-Scale Screening of a Lead Compounds Targeting T-ALL
Authors: Kazuya Miyashita, Noritaka Kagaya, Miho Izumikawa, Kenji Kitajima, Kyoko Watakabe-Inamoto, Yuho Najima, Noriko Doki, Takeshi Kobayashi, Kazuhiko Kakihana, Susumu Goyama, Toshio Kitamura, Kazuteru Ohashi, Kazuo Shin-ya, Takahiko Hara
Journal: Blood (2016)
Response by Thiruganasambandamoorthy et al to Letters Regarding Article, “Duration of Electrocardiographic Monitoring of Emergency Department Patients With Syncope”
Authors: Venkatesh Thiruganasambandamoorthy, Brian H. Rowe, Marco L.A. Sivilotti, Andrew D. McRae, Kirtana Arcot, Marie-Joe Nemnom, Longlong Huang, Muhammad Mukarram, Andrew D. Krahn, George A. Wells, Monica Taljaard
Journal: Circulation (2019)
Regulation of hepatic mitochondrial oxidation by glucose-alanine cycling during starvation in humans
Authors: Kitt Falk Petersen, Sylvie Dufour, Gary W. Cline, Gerald I. Shulman
Journal: Journal of Clinical Investigation (2019)

In order to determine whether the glucose-alanine cycle regulates rates of hepatic mitochondrial oxidation in humans, we applied positional isotopomer NMR tracer analysis (PINTA) to assess rates of hepatic mitochondrial oxidation and pyruvate carboxylase flux in healthy volunteers following both an overnight (12 hours) and a 60-hour fast. Following the 60-hour fast, rates of endogenous glucose production and mitochondrial oxidation decreased, whereas rates of hepatic pyruvate carboxylase flux remained unchanged. These reductions were associated with reduced rates of alanine turnover, assessed by [3-13C]alanine, in a subgroup of participants under similar fasting conditions. In order to determine whether this reduction in alanine turnover was responsible for the reduced rates of hepatic mitochondrial oxidation, we infused unlabeled alanine into another subgroup of 60-hour fasted subjects to increase rates of alanine turnover, similar to what was measured after a 12-hour fast, and found that this perturbation increased rates of hepatic mitochondrial oxidation. Taken together, these studies demonstrate that 60 hours of starvation induce marked reductions in rates of hepatic mitochondrial oxidation, which in turn can be attributed to reduced rates of glucose-alanine cycling, and reveal a heretofore undescribed role for glucose-alanine in the regulation of hepatic mitochondrial oxidation in humans.
Labour pledges to increase GP training places to 5000 and scrap prescription charges
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The Labour Party has said that it will increase the number of GP trainees in England by around 43%—from 3500 to 5000 places—in order to relieve the strain on surgeries and reduce GP burnout, if elected.

Labour’s shadow health secretary Jonathan Ashworth announced the promise at the party conference on 22 September, saying that it would help ease the burden on GPs and stop so many leaving the profession.

The party also announced it would scrap prescription charges, a move that the BMA has said will stop people having to “choose between paying a bill and buying food or paying for their prescription.”

Speaking at the conference, Ashworth said, “If you want to resolve the crisis in our …
Response to: ‘Anti-Ku syndrome with elevated CK: association with myocardial involvement in systemic sclerosis’ by Campochiaro <i>et al</i>
Authors: Lionel Spielmann, François Séverac, Alain Meyer
Journal: Annals of the Rheumatic Diseases (2019)

Result of meta-analysis are in bold.*For each definition, the highest prevalence reported was taken into account.†Sample numbers are derived from the 10% prevalence in the whole cohort.‡Sample numbers are derived from the 90% prevalence in the whole cohort).§Result of the random effect (with a constant continuity correction of 0.5 for analysis of proportions and "treatment arm" continuity correction for pooling ORs).CMR, cardiac magnetic resonance; CTD, connective tissue disoders; LVEF, left ventricular ejection fraction ;SSc, systemic sclerosis .
Abstract 16703: Regulation of Cell Proliferation in Renal Injury by Dopamine D2 Receptors
Authors: Megha Kumar, Laureano Asico, Prasad Konkalmatt, Zachary Freyberg, Pedro A Jose, Ines Armando
Journal: Circulation (2018)

Introduction: Genetic factors contribute to the susceptibility to chronic renal disease associated with essential hypertension. The renal dopamine D2 receptor (D2R) has a significant role in blood pressure (BP) control and in negative regulation of the development of inflammation and injury. Several common single nucleotide polymorphisms of the human DRD2 gene are associated with decreased D2R expression and function. Impaired D2R function results in renal inflammation and end-organ damage. Injury to the kidney triggers a cell proliferation response that can be either adaptive, leading to repair of the tubular epithelium, or maladaptive, leading to fibrosis and chronic kidney disease. Hypothesis: We tested the role of renal D2Rs in the cell proliferation response Methods: We used models of renal injury in mice and human renal proximal tubule cells (hRPTCs) Results: Renal selective silencing of the D2R in mice resulted in an increase in the mRNA expression of the proliferation marker Ki-67 (2.8±0.8 vs 1.0±0.1 fold; qRT-PCR; P&lt;0.05; n=4-5), along with an increase in the number of proliferating cells in renal cortical slices determined by nuclear Ki-67 staining (36±3 vs 6±1; positive cells/field; P&lt;0.05), in comparison with mice with no silencing. Renal tubule-selective rescue of D2R function in these mice by the ureteral infusion of AAV carrying D2R reduced the expression of cortical Ki-67 mRNA (42±3 vs 100±5 %; P&lt;0.05; n=4) and the number of positive cells/field (16±2 vs 32±5; P&lt;0.05), in comparison with mice treated with a control AAV. In mice subjected to renal ischemia reperfusion Ki-67 mRNA expression was higher (1.5±0.03 vs 1.0±0.05 fold; P&lt;0.05; n=3-4) than in mice with sham operation. Renal tubule treatment with AAV carrying D2R after ischemic injury reduced Ki-67 expression (0.65±0.05 vs 1±0.1; P&lt;0.05) and the number of Ki-67 positive cells in kidney sections. Rescue of function or renal tubule-selective D2R overexpression reduced tissue damage, fibrosis and the increase in BP in these models. Treatment of hRPTCs with the nephrotoxic, aristolochic acid (5 μg/ml, 24h), increased mRNA Ki-67 (2.8±0.2 fold; P&lt;0.05; n=4-5) in comparison with cells treated with vehicle while the presence of a D2R agonist, quinpirole (1μM, 24h), in the medium reduced the increase by 42% and also reduced the increase in fibronectin 1 and collagen 1a1 elicited by aristolochic acid Conclusions: Our data suggest that regulation of cell proliferation is one of the mechanisms involved in the protective effect of D2R function on renal inflammation and injury.
Out of Pocket Diabetes-Related Medical Expenses for Adolescents and Young Adults With Type 1 Diabetes: The SEARCH for Diabetes in Youth Study
Authors: Lina Merjaneh, Catherine Pihoker, Jasmin Divers, Nora Fino, Georgeanna Klingensmith, Sundar S. Shrestha, Sharon Saydah, Elizabeth J. Mayer-Davis, Dana Dabelea, Jeffrey Powell, Jean M. Lawrence, Lawrence M. Dolan, Davene R. Wright
Journal: Diabetes Care (2019)

The significant increase in the complexity of diabetes care over the last two decades is associated with a high economic burden (1), with almost one-quarter of adults with diabetes burdened with significant out of pocket expenses (OOPEs) (2). Little is known about the OOPEs for families of adolescents and young adults with type 1 diabetes. We therefore report the diabetes-related OOPEs for these families from the SEARCH for Diabetes in Youth (SEARCH) study and their association with demographic, socioeconomic, clinical, and health care characteristics.

A detailed description of the SEARCH study methods has previously been published (3). Participants had a baseline visit shortly after diabetes diagnosis and one or more follow-up visits; this report includes data from a follow-up visit between November 2011 and July 2015, at which time participants’ diabetes duration was >5 years. Participants ≥18 years old or a parent/guardian of participants <18 years old completed surveys, including questions about sociodemographics, diabetes treatment, health insurance, and OOPEs. The primary outcome was OOPEs in a typical month. Monthly OOPEs were captured in intervals of unequal lengths expressed in 2013 U.S. dollars as $0, $1–19, $20–49, $50–99, $100–199, and ≥$200.

Descriptive analyses were based on the midpoint of each interval. The midpoint of the last interval (≥$200) was estimated at $278, based on MarketScan data (4). Interval-censored regression models were fit assuming a Weibull distribution to evaluate the association between categories of OOPEs and covariates. The relationship between OOPEs and each covariate was assessed after adjustment for nonmodifiable characteristics (model 1), modifiable clinical factors (model 2), and health insurance categories (model 3). SAS 9.4 was used for analyses. …
Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation
Authors: Tawnie J Braaten, Julie R Brahmer, Patrick M Forde, Dung Le, Evan J Lipson, Jarushka Naidoo, Megan Schollenberger, Lei Zheng, Clifton O Bingham, Ami A Shah, Laura C Cappelli
Journal: Annals of the Rheumatic Diseases (2019)

Objective We sought to investigate the long-term outcomes of patients who develop immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA), to define factors associated with IA persistence after ICI cessation, the need for immunosuppressants and the impact of these medications on underlying malignancies. Methods We conducted a prospective observational study of patients referred for IA associated with ICIs. Patients were recruited from June 2015 to December 2018. Information was obtained at the baseline visit, and follow-up visits occurred at varying intervals for up to 24 months from ICI cessation. Kaplan-Meier curves were developed to characterise IA persistence. Cox proportional hazards models were used to assess the influence of various factors on IA persistence. Logistic regression was used to evaluate the impact of IA treatment on tumour response. Results Sixty patients were monitored with a median follow-up after ICI cessation of 9 months. A majority (53.3%) had active IA at their most recent follow-up. IA was less likely to improve in those with longer duration of ICI use, in those receiving combination ICI therapy, and in patients with multiple other immune-related adverse events. Tumour response did not appear to be impacted by immunosuppression. Although not statistically significant, persistent IA was correlated with a better tumour response (complete or partial response). Conclusion ICI-induced IA can become a long-term disease necessitating management by rheumatology for immunomodulatory treatment. Importantly, the use of immunomodulatory treatment has not been shown to impact cancer outcomes in this study.