tbuckley/cabot-search huggingface dataset:
3D Printed Microheater Sensor‐Integrated, Drug‐Encapsulated Microneedle Patch System for Pain Management
Authors: Mengtian Yin, Li Xiao, Qingchang Liu, Sung‐Yun Kwon, Yi Zhang, Poonam R. Sharma, Li Jin, Xudong Li, Baoxing Xu
Journal: Advanced Healthcare Materials (2019)

Abstract Microneedle patch devices have been widely utilized for transdermal drug delivery in pain management, but is challenged by accurate control of drug release and subsequent diffusion to human body. The recent emerging wearable electronics that could be integrated with microneedle devices offer a facile approach to address such a challenge. Here a 3D‐printed microheater integrated drug‐encapsulated microneedle patch system for drug delivery is presented. The ink solution comprised polydimethylsiloxane (PDMS) and multiwalled carbon nanotubes (MWCNTs) with a mass concentration of up to 45% (≈10 times higher of existing ones) is prepared and used to print crack‐free stretchable microheaters on substrates with a broad range of materials and geometric curves. The adhesion strength of the printed microheater on the microneedle patch in elevated temperatures is measured to evaluate their integration performance. Assessments of encapsulated drug release into rat's skin are confirmed by examining degradation of microneedles, skin morphologies, and released fluorescent signals. Results and demonstrations established here creates a new opportunity for developing sensor controlled smart microneedle patch systems by integrating with wearable electronics, potentially useful in clinical and biomedical research.
The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients
Authors: Jill Hallin, Lars D. Engstrom, Lauren Hargis, Andrew Calinisan, Ruth Aranda, David M. Briere, Niranjan Sudhakar, Vickie Bowcut, Brian R. Baer, Joshua A. Ballard, Michael R. Burkard, Jay B. Fell, John P. Fischer, Guy P. Vigers, Yaohua Xue, Sole Gatto, Julio Fernandez-Banet, Adam Pavlicek, Karen Velastagui, Richard C. Chao, Jeremy Barton, Mariaelena Pierobon, Elisa Baldelli, Emanuel F. Patricoin, Douglas P. Cassidy, Matthew A. Marx, Igor I. Rybkin, Melissa L. Johnson, Sai-Hong Ignatius Ou, Piro Lito, Kyriakos P. Papadopoulos, Pasi A. Jänne, Peter Olson, James G. Christensen
Journal: Cancer Discovery (2019)

Despite decades of research, efforts to directly target KRAS have been challenging. MRTX849 was identified as a potent, selective, and covalent KRASG12C inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound KRASG12C, and inhibits KRAS-dependent signaling. MRTX849 demonstrated pronounced tumor regression in 17 of 26 (65%) KRASG12C-positive cell line- and patient-derived xenograft models from multiple tumor types, and objective responses have been observed in patients with KRASG12C-positive lung and colon adenocarcinomas. Comprehensive pharmacodynamic and pharmacogenomic profiling in sensitive and partially resistant nonclinical models identified mechanisms implicated in limiting antitumor activity including KRAS nucleotide cycling and pathways that induce feedback reactivation and/or bypass KRAS dependence. These factors included activation of receptor tyrosine kinases (RTK), bypass of KRAS dependence, and genetic dysregulation of cell cycle. Combinations of MRTX849 with agents that target RTKs, mTOR, or cell cycle demonstrated enhanced response and marked tumor regression in several tumor models, including MRTX849-refractory models. SIGNIFICANCE: The discovery of MRTX849 provides a long-awaited opportunity to selectively target KRASG12C in patients. The in-depth characterization of MRTX849 activity, elucidation of response and resistance mechanisms, and identification of effective combinations provide new insight toward KRAS dependence and the rational development of this class of agents.See related commentary by Klempner and Hata, p. 20.This article is highlighted in the In This Issue feature, p. 1.
Reconsidering the Optimal Immune Response to <i>Mycobacterium tuberculosis</i>
Authors: Liku B. Tezera, Salah Mansour, Paul Elkington
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Tuberculosis is unfortunately once again killing more people than any other infection.Despite global biomedical and public health efforts, standard interventions to control the pandemic have not advanced in most resource-poor settings, in contrast to other global diseases such as malaria and HIV infection.The authors propose that reconsidering concepts of the optimal host immune response to Mycobacterium tuberculosis is required to develop a paradigm that will inform novel interventions.The development of active tuberculosis associated with cancer treatment by immune checkpoint inhibition highlights that merely driving a stronger immune response may not improve control of the pathogen.Here, we present different models of the host-pathogen interaction that are consistent with the complexity of human infection.We consider both the protective and harmful components of the immune response in tuberculosis and develop a multiparameter framework that predicts disease risk.This novel conceptual model is important to inform emerging interventions to improve outcomes in tuberculosis by defining the ideal host response to target.
Targeting and microenvironment-improving of phenylboronic acid-decorated soy protein nanoparticles with different sizes to tumor
Authors: Xiaoping Qian, Lei Ge, Kangjun Yuan, Cheng Li, Xu Zhen, Weibo Cai, Rongshi Cheng, Xiqun Jiang
Journal: Theranostics (2019)

It is essential for nanoparticles to delivery drugs accurately and penetrate deeply to tumor.However, complicated tumor microenvironment such as elevated tumor interstitial fluid pressure (IFP) and solid stress reduces the transport efficiency of nanomedicines in tumor.Methods: We herein report a drug delivery system of phenylboronic acid-decorated soy protein nanoparticles with the size of 30 nm, 50 nm and 150 nm.In vitro examinations including cytotoxicity, cellular uptake and penetration in multicellular tumor spheroids and in vivo observations including IFP and tumor solid stress measurements and antitumor activity were performed.Results: It was found that phenylboronic acid moiety could endow the nanoparticles actively targeting affinity to sialic acid (SA) which overexpressed in tumor cells.Simultaneously soy protein could improve tumor microenvironment such as reduction of IFP and tumor stress.Among the soy protein nanoparticles with different sizes, 30 nm-sized nanoparticles showed the best cellular uptake and highest cytotoxicity in vitro after loading doxorubicin (DOX).In vivo, 30 nm-sized nanoparticles showed the best tumor microenvironment improvement efficiency, leading to the enhanced drug accumulation and antitumor efficiency when combination with DOX.Conclusion: Our study introduces a bioactive nanoparticulate design strategy to actively target and significantly improve tumor microenvironment for enhanced cancer therapy.
Medical Students Around the World Poorly Trained in Nutrition
Authors: Jennifer Abbasi
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Epidemiologic Trends in <i>Clostridioides difficile</i> Infections in a Regional Community Hospital Network
Authors: Nicholas A. Turner, Steven C. Grambow, Christopher W. Woods, Vance G. Fowler, Rebekah W. Moehring, Deverick J. Anderson, Sarah S. Lewis
Journal: JAMA Network Open (2019)

<h3>Importance</h3> <i>Clostridioides difficile</i>infection (CDI) remains a leading cause of health care facility–associated infection. A greater understanding of the regional epidemiologic profile of CDI could inform targeted prevention strategies. <h3>Objectives</h3> To assess trends in incidence of health care facility–associated and community-acquired CDI among hospitalized patients over time and to conduct a subanalysis of trends in the NAP1 strain of CDI over time. <h3>Design, Setting, and Participants</h3> This long-term multicenter cohort study reviewed records of patients (N = 2 025 678) admitted to a network of 43 regional community hospitals primarily in the southeastern United States from January 1, 2013, through December 31, 2017. Generalized linear mixed-effects models were used to adjust for potential clustering within facilities and changing test method (nucleic acid amplification testing or toxin enzyme immunoassay) over time. <h3>Main Outcomes and Measures</h3> <i>Clostridioides difficile</i>infection incidence rates were counted as cases per 1000 admissions for community-acquired and total CDI cases or cases per 10 000 patient-days for health care facility–associated CDI. Long-term trends in the proportion of cases acquired in the community and in NAP1 strain incidence were also evaluated. <h3>Results</h3> A total of 2 025 678 admissions and 21 254 CDI cases were included (12 678 [59.6%] female; median [interquartile range] age, 69 [55-80] years). Median (interquartile range) total CDI incidence increased slightly from 7.9 (3.5-12.4) cases per 1000 admissions in 2013 to 9.3 (4.9-13.7) cases per 1000 admissions in 2017. After adjustment, the overall incidence of health care facility–associated CDI declined (incidence rate ratio [IRR], 0.995; 95% CI, 0.990-0.999;<i>P</i> = .03), whereas insufficient evidence was found for either an increase or a decrease in community-acquired CDI (IRR, 1.004; 95% CI, 0.999-1.009;<i>P</i> = .14). The proportion of cases classified as community acquired increased over time from a mean (SD) of 0.49 (0.28) in 2013 to 0.61 (0.26) in 2017 (odds ratio, 1.010 per month; 95% CI, 1.006-1.015;<i>P</i> &lt; .001). Rates of the NAP1 strain of CDI varied widely between facilities, with no statistically significant change in NAP1 strain incidence over time in the community setting (IRR, 1.007; 95% CI, 0.994-1.021) or health care facility setting (IRR, 1.011; 95% CI, 0.990-1.032). <h3>Conclusions and Relevance</h3> The findings suggest that, despite the modest improvement in health care facility–associated CDI rates, a better understanding of community-acquired CDI incidence is needed for future infection prevention efforts.
Shotgun metagenomics reveals an enrichment of potentially cross-reactive bacterial epitopes in ankylosing spondylitis patients, as well as the effects of TNFi therapy upon microbiome composition
Authors: Jian Yin, Peter Richard Sternes, Mingbang Wang, Jing Song, Mark Morrison, Ting Li, Ling Zhou, Xin Wu, Fusheng He, Jian Zhu, Matthew A Brown, Huji Xu
Journal: Annals of the Rheumatic Diseases (2019)

Diverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome.The stools from a case-control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray.Previous reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients.These findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.
Characterization of High Mortality Probability Operations at National Surgical Quality Improvement Program Hospitals
Authors: Benjamin J. Resio, Alexander S. Chiu, Yawei Zhang, Kevin Y. Pei
Journal: JAMA Surgery (2019)

level was measured using a colorimetric assay (reference, 8.60-10.00mg/dL [to convert to millimoles per liter, multiply by 0.25]).Also, the surgeon scored the macroscopic appearance of the parathyroid glands as 0, nonfunctioning gland; 1, uncertain; and 2, functioning gland, always before ICG.The primary end point was the need for calcium supplementation.Criteria for the administration of calcium were the presence of symptoms of hypocalcemia or calcium levels less than 7.20 mg/dL in asymptomatic patients.Results | Fifty patients (33 women [66%]) with a mean (SD) age of 52 (12.9) years diagnosed as having thyroid cancer (n = 35 [70%]), multinodular goiter (n = 13 [26%]), and Graves disease (n = 2 [4%]) underwent total thyroidectomy, associated with central neck dissection in 30.Calcium supplements were needed by 11 patients (22%) postoperatively.Differences in baseline data between patients with and without hypocalcemia were not found.Results of ioPTH levels, ICG angiography, and surgeon's evaluation of glands viability are shown in Table 1.Of the 39 patients (78%) who did not require calcium supplementation, ioPTH correctly identified 32 of them (64%) and ICG correctly identified 37 (74%).As shown in Table 2, the diagnostic accuracy of ICG angiography and ioPTH was similar.Discussion | Prevention of the parathyroid function during thyroidectomy is clinically relevant owing to serious adverse effects of permanent hypoparathyroidism.Reported studies of PTH levels measured at different times during or after thyroidectomy have shown controversial results. 1,2Indocyanine green angiography has been proposed as a useful technique for evaluation of the viability status of the glands, with encouraging results.However, the first reported studies 3,4 failed to identify all parathyroid gland tissue, and therefore, these missing glands could be responsible for a positive outcome.On the contrary, here we identified all parathyroid glands.In our study, the diagnostic accuracy of ICG angiography and ioPTH were similar to predict hypocalcemia, but this may be a type II error, and a larger sample size would find that ICG angiography could be superior to ioPTH.With all the parathyroid tissue identified, it seems that visualization of at least 1 well-perfused gland on ICG angiography is highly suggestive of normocalcemia in the immediate postoperative period.Also, ICG angiography would allow immediate decision-making without the need of waiting for ioPTH measurement, although a learning curve to score gland vascularization is needed.
Long-Term Outcomes after Severe Traumatic Brain Injury in Older Adults. A Registry-based Cohort Study
Authors: Matthew J. Maiden, Peter A. Cameron, Jeffrey V. Rosenfeld, D. James Cooper, Susan McLellan, Belinda J. Gabbe
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients.Objectives: To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates.Methods: This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI. Functional status was assessed with Glasgow Outcome Scale Extended (GOSE) 6, 12, and 24 months after injury. Cohort subgroups were defined by admission to an ICU. Features associated with functional outcome were assessed from the ICU subgroup.Measurements and Main Results: The study included 540 older adults who had been hospitalized with severe TBI over the 10-year period; 428 (79%) patients died in hospital, and 456 (84%) died 6 months after injury. There were 277 patients who had not been admitted to an ICU; at 6 months, 268 (97%) had died, 8 (3%) were dependent (GOSE 2-4), and 1 (0.4%) was functionally independent (GOSE 5-8). There were 263 patients who had been admitted to an ICU; at 6 months, 188 (73%) had died, 39 (15%) were dependent, and 32 (12%) were functionally independent. These proportions did not change over longer follow-up. The only clinical features associated with a lower rate of functional independence were Injury Severity Score ≥25 (adjusted odds ratio, 0.24 [95% confidence interval, 0.09-0.67]; P = 0.007) and older age groups (P = 0.017).Conclusions: Severe TBI in older adults is a condition with very high mortality, and few recover to functional independence.
Single-Arm Phase II Trials of Combination Therapies: A Review of the CTEP Experience 2008–2017
Authors: Jared C Foster, Boris Freidlin, Charles A Kunos, Edward L Korn
Journal: JNCI Journal of the National Cancer Institute (2019)

Designing and interpreting single-arm phase II trials of combinations of agents is challenging because it can be difficult, based on historical data, to identify levels of activity for which the combination would be worth pursuing. We identified Cancer Therapy Evaluation Program single-arm combination trials that were activated in 2008-2017 and tabulated their design characteristics and results. Positive trials were evaluated as to whether they provided credible evidence that the combination was better than its constituents. A total of 125 trials were identified, and 120 trials had results available. Twelve had designs where eligible patients were required to be resistant or refractory to all but one element of the combination. Only 17.8% of the 45 positive trials were deemed to provide credible evidence that the combination was better than its constituents. Of the 10 positive trials with observed rates 10 percentage points higher than their upper (alternative hypothesis) targets, only five were deemed to provide such credible evidence. Many trials were definitively negative, with observed clinical activity at or below their lower (null hypothesis) targets. Ideally, use of single-arm combination trials should be restricted to settings where each agent is known to have minimal monotherapy activity (and a randomized trial is infeasible). In these settings, an observed signal is attributable to synergy and thus could be used to decide whether the combination is worth pursuing. In other settings, credible evidence can still be obtained if the observed activity is much higher than expected, but experience suggests that this is a rare occurrence.
Redefining Hypoglycemia in Clinical Trials: Validation of Definitions Recently Adopted by the American Diabetes Association/European Association for the Study of Diabetes
Authors: Simon R. Heller, John B. Buse, Robert Ratner, Elizabeth Seaquist, Lars Bardtrum, Charlotte Thim Hansen, Deniz Tutkunkardas, Alan C. Moses
Journal: Diabetes Care (2019)

To determine if the International Hypoglycaemia Study Group (IHSG) level 2 low glucose definition can identify clinically relevant hypoglycemia in clinical trials and offer value as an end point for future trials.
Pheromones Modulate Learning by Regulating the Balanced Signals of Two Insulin-like Peptides
Authors: Taihong Wu, Fengyun Duan, Wenxing Yang, He Liu, Antonio Caballero, Diana Andrea Fernandes de Abreu, Abdul Rouf Dar, Joy Alcedo, QueeLim Ch’ng, Rebecca A. Butcher, Yun Zhang
Journal: Neuron (2019)
Comparative effectiveness of school-based interventions to prevent anxiety and depression in children and young people: Systematic review and network meta-analysis
Authors: Deborah M Caldwell, Sarah R Davies, Sarah Hetrick, Jennifer C Palmer, Paola Caro, Jose Lopez-Lopez, David Gunnell, Judi L Kidger, James Thomas, Clare E French, Emily Stockings, Rona M Campbell, Nicky J Welton
Journal: The Lancet Psychiatry (2019)
Drug policy in UK has regressed in past decade, says former chief adviser
Authors: Jacqui Wise
Journal: BMJ (2019)

The UK’s drugs policy has “gone backwards” in the past 10 years, representing a “litany of failure,” a former chief adviser to the government has said.

David Nutt was speaking at an event to mark the 10th anniversary of his dismissal as chair of the Advisory Council on the Misuse of Drugs. Nutt, professor of neuropsychopharmacology at Imperial College London, was sacked after stating that ecstasy and LSD were less dangerous than alcohol.1

His dismissal led to several other council members resigning and …
Exercise alone and exercise combined with education both prevent episodes of low back pain and related absenteeism: systematic review and network meta-analysis of randomised controlled trials (RCTs) aimed at preventing back pain
Authors: Rongzhong Huang, Jie Ning, Vivienne H Chuter, Jeffrey Bruce Taylor, Demoulin Christophe, Zengdong Meng, Yu Xu, Lihong Jiang
Journal: British Journal of Sports Medicine (2019)

Objectives We aimed to investigate which prevention strategies for low back pain (LBP) are most effective. Design We completed a Bayesian network meta-analysis to summarise the comparative effectiveness of LBP prevention strategies. The primary outcomes were an episode of LBP and LBP-associated work absenteeism represented as ORs with associated 95% credibility intervals (CrIs). We ranked all prevention strategies with surface under the cumulative ranking curve (SUCRA) analysis. Data sources PubMed, EMBASE and CENTRAL databases were searched along with manual searches of retrieved articles. We only included randomised controlled trials (RCTs) that reported an episode of LBP and/or LBP-associated work absenteeism evaluating LBP prevention strategies were included. Eligibility criteria for selecting studies Data were independently extracted by two investigators, and RCT quality was assessed using the Cochrane Risk of Bias tool. Results and summary Forty RCTs were included. Exercise combined with education (OR: 0.59, CrI: 0.41 to 0.82) and exercise alone (OR: 0.59, CrI: 0.36 to 0.92) both prevented LBP episodes; exercise combined with education and education alone both had large areas under the curve (SUCRA: 81.3 and 79.4, respectively). Additionally, exercise (OR: 0.04, CrI: 0.00 to 0.34) prevented LBP-associated work absenteeism, with exercise and the combination of exercise and education ranking highest (SUCRA: 99.0 and 60.2, respectively). Conclusions Exercise alone and exercise combined with education can prevent episodes of LBP and LBP-related absenteeism. Trial registration number PROSPERO 42017056884.