tbuckley/cabot-search huggingface dataset:
Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy and Control of Immune-Mediated Inflammatory Diseases
Authors: Eugen Javor, Goran Hauser, Marko Skelin
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
Selection, Effectiveness, and Adverse Effects of Contraception—Reply
Authors: Stephanie Teal, Alison Edelman
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
HSF1 facilitates the multistep process of lymphatic metastasis in bladder cancer via a novel PRMT5‐WDR5‐dependent transcriptional program
Authors: Ming Huang, Wen Dong, Ruihui Xie, Jilin Wu, Qiao Su, Wuguo Li, Kai Yao, Yuelong Chen, Qianghua Zhou, Qiang Zhang, Wenwen Li, Liang Cheng, Shengmeng Peng, Siting Chen, Jian Huang, Xu Chen, Tianxin Lin
Journal: Cancer Communications (2022)

Abstract Background Lymphatic metastasis has been associated with poor prognosis in bladder cancer patients with limited therapeutic options. Emerging evidence shows that heat shock factor 1 (HSF1) drives diversified transcriptome to promote tumor growth and serves as a promising therapeutic target. However, the roles of HSF1 in lymphatic metastasis remain largely unknown. Herein, we aimed to illustrate the clinical roles and mechanisms of HSF1 in the lymphatic metastasis of bladder cancer and explore its therapeutic potential. Methods We screened the most relevant gene to lymphatic metastasis among overexpressed heat shock factors (HSFs) and heat shock proteins (HSPs), and analyzed its clinical relevance in three cohorts. Functional in vitro and in vivo assays were performed in HSF1‐silenced and ‐regained models. We also used Co‐immunoprecipitation to identify the binding proteins of HSF1 and chromatin immunoprecipitation and dual‐luciferase reporter assays to investigate the transcriptional program directed by HSF1. The pharmacological inhibitor of HSF1, KRIBB11, was evaluated in popliteal lymph node metastasis models and patient‐derived xenograft models of bladder cancer. Results HSF1 expression was positively associated with lymphatic metastasis status, tumor stage, advanced grade, and poor prognosis of bladder cancer. Importantly, HSF1 enhanced the epithelial‐mesenchymal transition (EMT) of cancer cells in primary tumor to initiate metastasis, proliferation of cancer cells in lymph nodes, and macrophages infiltration to facilitate multistep lymphatic metastasis. Mechanistically, HSF1 interacted with protein arginine methyltransferase 5 (PRMT5) and jointly induced the monomethylation of histone H3 at arginine 2 (H3R2me1) and symmetric dimethylation of histone H3 at arginine 2 (H3R2me2s). This recruited the WD repeat domain 5 (WDR5)/mixed‐lineage leukemia (MLL) complex to increase the trimethylation of histone H3 at lysine 4 (H3K4me3); resulting in upregulation of lymphoid enhancer‐binding factor 1 (LEF1), matrix metallopeptidase 9 (MMP9), C‐C motif chemokine ligand 20 (CCL20), and E2F transcription factor 2 (E2F2). Application of KRIBB11 significantly inhibited the lymphatic metastasis of bladder cancer with no significant toxicity. Conclusion Our findings reveal a novel transcriptional program directed by the HSF1‐PRMT5‐WDR5 axis during the multistep process of lymphatic metastasis in bladder cancer. Targeting HSF1 could be a multipotent and promising therapeutic strategy for bladder cancer patients with lymphatic metastasis.
Long Noncoding RNAs That Function in Nutrition: Lnc-ing Nutritional Cues to Metabolic Pathways
Authors: Claudia D. Lovell, Montserrat C. Anguera
Journal: Annual Review of Nutrition (2022)

Long noncoding RNAs (lncRNAs) are sensitive to changing environments and play key roles in health and disease. Emerging evidence indicates that lncRNAs regulate gene expression to shape metabolic processes in response to changing nutritional cues. Here we review various lncRNAs sensitive to fasting, feeding, and high-fat diet in key metabolic tissues (liver, adipose, and muscle), highlighting regulatory mechanisms that trigger expression changes of lncRNAs themselves, and how these lncRNAs regulate gene expression of key metabolic genes in specific cell types or across tissues. Determining how lncRNAs respond to changes in nutrition is critical for our understanding of the complex downstream cascades following dietary changes and can shape how we treat metabolic disease. Furthermore, investigating sex biases that might influence lncRNA-regulated responses will likely reveal contributions toward the observed disparities between the sexes in metabolic diseases.
A single-cell liver atlas of Plasmodium vivax infection
Authors: Liliana Mancio-Silva, Nil Gural, Eliana Real, Marc H. Wadsworth, Vincent L. Butty, Sandra March, Niketa Nerurkar, Travis K. Hughes, Wanlapa Roobsoong, Heather E. Fleming, Charlie A. Whittaker, Stuart S. Levine, Jetsumon Sattabongkot, Alex K. Shalek, Sangeeta N. Bhatia
Journal: Cell Host & Microbe (2022)

Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years and reactivate to cause recurrent blood-stage infection. Although they are an important target for malaria eradication, little is known about the molecular features of replicative and non-replicative intracellular liver-stage parasites and their host cell dependence. Here, we leverage a bioengineered human microliver platform to culture patient-derived P. vivax parasites for transcriptional profiling. Coupling enrichment strategies with bulk and single-cell analyses, we capture both parasite and host transcripts in individual hepatocytes throughout the course of infection. We define host- and state-dependent transcriptional signatures and identify unappreciated populations of replicative and non-replicative parasites that share features with sexual transmissive forms. We find that infection suppresses the transcription of key hepatocyte function genes and elicits an anti-parasite innate immune response. Our work provides a foundation for understanding host-parasite interactions and reveals insights into the biology of P. vivax dormancy and transmission.
opnMe.com: a digital initiative for sharing tools with the biomedical research community
Authors: Andreas Gollner, Markus Köster, Paul Nicklin, Thomas Trieselmann, Elliott Klein, Jaromir Vlach, Claudia Heine, Marc Grundl, Jürgen Ramharter, David Wyatt, Menorca Chaturvedi, Alessio Ciulli, Katharine C. Carter, Susanne Müller, Daniel Bischoff, Peter Ettmayer, Eric Haaksma, Jürgen Mack, Darryl McConnell, Dirk Stenkamp, Harald Weinstabl, Matthias Zentgraf, Clive R. Wood, Florian Montel
Journal: Nature Reviews Drug Discovery (2022)
Ultra-high drug loading improves nanoparticle efficacy against peritoneal mesothelioma
Authors: Robert C. Sabatelle, Rong Liu, Yin P. Hung, Eric Bressler, Eliza J. Neal, Andrew Martin, Iriny Ekladious, Mark W. Grinstaff, Yolonda L. Colson
Journal: Biomaterials (2022)

Peritoneal mesothelioma is an aggressive disease with a median survival of under three years, due to a lack of effective treatment options. Mesothelioma is traditionally considered a "chemoresistant" tumor; however, low intratumoral drug levels coupled with the inability to administer high systemic doses suggests that therapeutic resistance may be due to poor drug delivery rather than inherent biology. While patient survival may improve with repetitive local intraperitoneal infusions of chemotherapy throughout the perioperative period, these regimens carry associated toxicities and significant peri-operative morbidity. To circumvent these issues, we describe ultra-high drug loaded nanoparticles (NPs) composed of a unique poly(1,2-glycerol carbonate)-graft-succinate-paclitaxel (PGC-PTX + PTX) conjugate. PGC-PTX + PTX NPs are cytotoxic, localize to tumor in vivo, and improve survival in a murine model of human peritoneal mesothelioma after a single intraperitoneal (IP) injection compared to multiple weekly doses of the clinically utilized formulation PTX-C/E. Given their unique pharmacokinetics, a second intraperitoneal dose of PGC-PTX + PTX NPs one month later more than doubles the overall survival compared to the clinical control (122 versus 58 days). These results validate the clinical potential of prolonged local paclitaxel to treat intracavitary malignancies such as mesothelioma using a tailored polymer-mediated nanoparticle formulation.
Human performance and mental workload in augmented reality: brain computer interface advantages over gestures
Authors: Silvio Da Col, Eunsik Kim, Andrea Sanna
Journal: Brain-Computer Interfaces (2022)

Augmented reality (AR) technologies have been introduced in manufacturing planning functions. Working in augmented environments, users usually select virtual objects with hand gestures that are associated with arm fatigue. In this paper, a Steady-State Visual Evoked Potentials (SSVEP) Brain-Computer Interface (BCI) for 'hologram' selection in AR is proposed. The BCI and hand gesture performances, workload, and usability have been measured for 4 different tasks. Although the results showed that BCI were on average 2.52 seconds slower than hand gestures, the BCI was more precise than hand gestures, with accuracies close to 100%. The BCI had an overall workload of 38.52, that resulted to be lower than the hand gestures' one of 52.40. Finally, the BCI's System Usability Scale of 77.8 overcame the hand gestures one of 11.3 points. These results highlighted the potential of coupling together BCI and AR, demonstrating a possible future application of these technologies in industrial settings.
Non-communicable diseases in older people living with HIV in four African countries: a cohort study
Authors: David Chang, Allahna Esber, Nicole Dear, Michael Iroezindu, Emmanuel Bahemana, Hannah Kibuuka, John Owuoth, Jonah Maswai, Trevor Crowell, Christina Polyak, Joseph S Cavanaugh, Julie A Ake, Catherine Godfrey
Journal: The Lancet HIV (2022)
Machine learning approaches to predicting no-shows in pediatric medical appointment
Authors: Dianbo Liu, Won-Yong Shin, Eli Sprecher, Kathleen Conroy, Omar Santiago, Gal Wachtel, Mauricio Santillana
Journal: npj Digital Medicine (2022)

Abstract Patients’ no-shows, scheduled but unattended medical appointments, have a direct negative impact on patients’ health, due to discontinuity of treatment and late presentation to care. They also lead to inefficient use of medical resources in hospitals and clinics. The ability to predict a likely no-show in advance could enable the design and implementation of interventions to reduce the risk of it happening, thus improving patients’ care and clinical resource allocation. In this study, we develop a new interpretable deep learning-based approach for predicting the risk of no-shows at the time when a medical appointment is first scheduled. The retrospective study was conducted in an academic pediatric teaching hospital with a 20% no-show rate. Our approach tackles several challenges in the design of a predictive model by (1) adopting a data imputation method for patients with missing information in their records (77% of the population), (2) exploiting local weather information to improve predictive accuracy, and (3) developing an interpretable approach that explains how a prediction is made for each individual patient. Our proposed neural network-based and logistic regression-based methods outperformed persistence baselines. In an unobserved set of patients, our method correctly identified 83% of no-shows at the time of scheduling and led to a false alert rate less than 17%. Our method is capable of producing meaningful predictions even when some information in a patient’s records is missing. We find that patients’ past no-show record is the strongest predictor. Finally, we discuss several potential interventions to reduce no-shows, such as scheduling appointments of high-risk patients at off-peak times, which can serve as starting point for further studies on no-show interventions.
Lack of VMP1 impairs hepatic lipoprotein secretion and promotes non-alcoholic steatohepatitis
Authors: Xiaoxiao Jiang, Sam Fulte, Fengyan Deng, Shiyuan Chen, Yan Xie, Xiaojuan Chao, Xi C. He, Yuxia Zhang, Tiangang Li, Feng Li, Colin McCoin, E. Matthew Morris, John Thyfault, Wanqing Liu, Linheng Li, Nicholas O. Davidson, Wen-Xing Ding, Hong-Min Ni
Journal: Journal of Hepatology (2022)

Vacuole membrane protein 1 (VMP1) is an endoplasmic reticulum (ER) transmembrane protein that regulates the formation of autophagosomes and lipid droplets. Recent evidence suggests that VMP1 plays a critical role in lipoprotein secretion in zebra fish and cultured cells. However, the pathophysiological roles and mechanisms by which VMP1 regulates lipoprotein secretion and lipid accumulation in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are unknown.Liver-specific and hepatocyte-specific Vmp1 knockout mice as well as Vmp1 knock-in mice were generated by crossing Vmp1flox or Vmp1KI mice with albumin-Cre mice or by injecting AAV8-TBG-cre, respectively. Lipid and energy metabolism in these mice were characterized by metabolomic and transcriptome analyses. Mice with hepatic overexpression of VMP1 who were fed a NASH diet were also characterized.Hepatocyte-specific deletion of Vmp1 severely impaired VLDL secretion resulting in massive hepatic steatosis, hepatocyte death, inflammation and fibrosis, which are hallmarks of NASH. Mechanistically, loss of Vmp1 led to decreased hepatic levels of phosphatidylcholine and phosphatidylethanolamine as well as to changes in phospholipid composition. Deletion of Vmp1 in mouse liver also led to the accumulation of neutral lipids in the ER bilayer and impaired mitochondrial beta-oxidation. Overexpression of VMP1 ameliorated steatosis in diet-induced NASH by improving VLDL secretion. Importantly, we also showed that decreased liver VMP1 is associated with NAFLD/NASH in humans.Our results provide novel insights on the role of VMP1 in regulating hepatic phospholipid synthesis and lipoprotein secretion in the pathogenesis of NAFLD/NASH.Non-alcoholic fatty liver disease and its more severe form, non-alcoholic steatohepatitis, are associated with a build-up of fat in the liver (steatosis). However, the exact mechanisms that underly steatosis in patients are not completely understood. Herein, the authors identified that the lack of a protein called VMP1 impairs the secretion and metabolism of fats in the liver and could therefore contribute to the development and progression of non-alcoholic fatty liver disease.
In ischemic stroke upon wakening, IV thrombolysis or EVT improves functional outcome at 90 d
Authors: Katie Lin, Eddy Lang
Journal: Annals of Internal Medicine (2022)

Roaldsen MB, Lindekleiv H, Mathiesen EB. Intravenous thrombolytic treatment and endovascular thrombectomy for ischaemic wake-up stroke. Cochrane Database Syst Rev. 2021;12:CD010995. 34850380.
Racial and Ethnic Disparities in the Management of Postdural Puncture Headache With Epidural Blood Patch for Obstetric Patients in New York State
Authors: Allison Lee, Jean Guglielminotti, Anne-Sophie Janvier, Guoha Li, Ruth Landau
Journal: JAMA Network Open (2022)

Characterizing and addressing racial and ethnic disparities in peripartum pain assessment and treatment is a national priority.To evaluate the association of race and ethnicity with the provision and timing of an epidural blood patch (EBP) for management of postdural puncture headache in obstetric patients.This cross-sectional study used New York State hospital discharge records from January 1, 1998, to December 31, 2016, from mothers 15 to 49 years of age with a postdural puncture headache after neuraxial analgesia or anesthesia for childbirth. Statistical analysis was performed from February 2020 to February 2022.Patients' race and ethnicity (reported as provided by each participating hospital; the method of determining race and ethnicity [ie, self-reported or not] cannot be determined from the data) were categorized into non-Hispanic White (reference group), non-Hispanic Black, Hispanic, and other race and ethnicity (including Asian and Pacific Islander, American Indian, Alaskan Native, and other).The primary outcome was the rate of EBP use. The secondary outcome was the interval (days) between hospital admission and provision of EBP. Odds ratios (ORs) and 95% CIs of EBP use associated with race and ethnicity were estimated using mixed-effect logistic regression models, adjusting for patient and hospital characteristics.During the study period, 8921 patients (mean [SD] age, 30 [6] years; 1028 [11.5%] Black; 1301 [14.6%] Hispanic; 4960 [55.6%] White; and 1359 [15.2%] other race and ethnicity) with postdural puncture headache were identified among 1.9 million deliveries with a neuraxial procedure. Of these 8921 patients, 4196 (47.0%; 95% CI, 46.0%-48.1%) were managed with an EBP. A total of 2650 White patients (53.4%; 95% CI, 52.0%-54.8%) used an EBP; this rate was significantly higher than that among Hispanic patients (41.7% [543]; 95% CI, 39.9%-44.5%), Black patients (35.7% [367]; 95% CI, 32.8%-38.7%), or patients of other race and ethnicity (35.2% [478]; 95% CI, 32.6%-37.8%). Timing of EBP was at a median of 2 days (IQR, 2-3 days) after hospital admission for White patients compared with a median of 3 days (IQR, 2-4 days) for Hispanic patients, Black patients, and patients of other race and ethnicity (P < .001 for the comparison with White patients). After adjustment for patient and hospital characteristics, the EBP rate was not different between White and Hispanic patients (adjusted OR, 1.11; 95% CI, 0.94-1.30). It was significantly lower for Black patients (adjusted OR, 0.80; 95% CI, 0.67-0.94) and patients of other races and ethnicities (adjusted OR, 0.85; 95% CI, 0.73-0.99).In this study, significant racial and ethnic disparities in the management of postdural puncture headache with EBP were observed, with both lower rates and delayed timing, which may be associated with long-term adverse effects.
Cholesterol Microdomain Enhances the Biofilm Eradication of Antibiotic Liposomes (Adv. Healthcare Mater. 8/2022)
Authors: Jianjun Xie, Zhiping Meng, Xingxing Han, Sipan Li, Xinai Ma, Xuanyu Chen, Yinmei Liang, Xiaomin Deng, Kexin Xia, Yue Zhang, Huaxu Zhu, Tingming Fu
Journal: Advanced Healthcare Materials (2022)

Berberine Liposomes In article number 2101745 by Yue Zhang, Tingming Fu, and co-workers, an engineered liposome containing cholesterol microdomain and berberine hydrochloride is developed for the eradication of Staphylococcus aureus biofilm. Liposomes with cholesterol microdomains significantly inhibit the growth of S. aureus, remove the bacterial biofilm, and lead to an almost complete recovery of rats with pulmonary infection. In addition, liposomes fuse better with bacterial cell membranes and have a stronger affinity for bacterial virulence factors, indicating that the tailored liposomes can combat bacterial biofilms and reduce tissue damage caused by toxins during bacterial eradication.
Cost-effectiveness of Robotic-Assisted Radical Prostatectomy for Localized Prostate Cancer in the UK
Authors: Muhieddine Labban, Prokar Dasgupta, Chao Song, Russell Becker, Yanli Li, Usha Seshadri Kreaden, Quoc-Dien Trinh
Journal: JAMA Network Open (2022)

<h3>Importance</h3> The cost-effectiveness of different surgical techniques for radical prostatectomy remains a subject of debate. Emergence of recent critical clinical data and changes in surgical equipment costs due to their shared use by different clinical specialties necessitate an updated cost-effectiveness analysis in a centralized, largely government-funded health care system such as the UK National Health Service (NHS). <h3>Objective</h3> To compare robotic-assisted radical prostatectomy (RARP) with open radical prostatectomy (ORP) and laparoscopic-assisted radical prostatectomy (LRP) using contemporary data on clinical outcomes, costs, and surgical volumes in the UK. <h3>Design, Setting, and Participants</h3> This economic analysis used a Markov model developed to compare the cost-effectiveness of RARP, LRP, and ORP to treat localized prostate cancer. The model was constructed from the perspective of the UK NHS. The model simulated 65-year-old men who underwent radical prostatectomy for localized prostate cancer and were followed up for a 10-year period. Data were analyzed from May 1, 2020, to July 31, 2021. <h3>Exposures</h3> Robotic-assisted radical prostatectomy, LRP, and ORP. <h3>Main Outcomes and Measures</h3> Quality-adjusted life-years (QALYs), costs (direct medical costs and costs outside the NHS), and incremental cost-effectiveness ratios (ICERs). <h3>Results</h3> Compared with LRP, RARP cost £1785 (US $2350) less and had 0.24 more QALYs gained; thus, RARP was a dominant option compared with LRP. Compared with ORP, RARP had 0.12 more QALYs gained but cost £526 (US $693) more during the 10-year time frame, resulting in an ICER of £4293 (US $5653)/QALY. Because the ICER was below the £30 000 (US $39 503) willingness-to-pay threshold, RARP was more cost-effective than ORP in the UK. The most sensitive variable influencing the cost-effectiveness of RARP was the lower risk of biochemical recurrence (BCR). Scenario analysis indicated RARP would remain more cost-effective than ORP as long as the BCR hazard ratios comparing RARP vs ORP were less than 0.99. <h3>Conclusions and Relevance</h3> These findings suggest that in the UK, RARP has an ICER lower than the willingness-to-pay threshold and thus is likely a cost-effective surgical treatment option for patients with localized prostate cancer compared with ORP and LRP. The results were mainly driven by the lower risk of BCR for RARP. These findings may differ in other health care settings where different thresholds and costs may apply.