tbuckley/cabot-search huggingface dataset:
Precise Targeting Therapy of Orthotopic Gastric Carcinoma by siRNA and Chemotherapeutic Drug Codelivered in pH‐Sensitive Nano Platform
Authors: Quan Wang, Yu Tian, Lei Liu, Chuanrong Chen, Wei Zhang, Liting Wang, Qianqian Guo, Li Ding, Hao Fu, Hongjiang Song, Junyu Shi, Yourong Duan
Journal: Advanced Healthcare Materials (2021)

Abstract Gastric cancer is one of the most common malignant tumors, which remains as an obstacle to human health. Nowadays, targeted nanoparticles to gastric tumor tissues, provide new strategy for improved therapy but still remain challenging. The major hurdle of targeted therapeutic nanoparticles comes from the limited enrichment and poor selectivity of therapeutic agents in in situ tumor. Herein, a pH‐sensitive targeted nano platform coloaded As 2 O 3 and human epidermal growth factor receptor‐2 (HER2)‐siRNA (AH RNPs) is developed to achieve targeting therapy in orthotopic gastric carcinoma. AH RNPs can effectively prevent the degradation of siRNA and overcome the poor solubility of As 2 O 3 . In vitro studies show that AH RNPs could achieve synergistic inhibition of growth and metastasis on SGC7901 cells. Surprisingly, AH RNPs not only target gastric subcutaneous tumor, but also target in situ tumor, and express loaded genes in in situ tumor. Moreover, AH RNPs show excellent antitumor effect in orthotopic gastric tumor model and the anticancer mechanism is related about inhibiting the activation of ERK signal and downregulating the expression of cxc chemokine receptor 4 (CXCR4), HER2, MMP2, and MMP9 protein. This study provides a multi‐functional vector for precise targeting therapy of gastric cancer, which may serve as a potential clinical application for future gastric cancer.
Dangerous liaisons: Bacteria, antimicrobial therapies, and allergic diseases
Authors: Gerdien Tramper‐Stranders, Dominika Ambrożej, Alessandra Arcolaci, Marina Atanaskovic‐Markovic, Cristina Boccabella, Matteo Bonini, Aspasia Karavelia, Ervin Mingomataj, Liam O' Mahony, Milena Sokolowska, Eva Untersmayr, Wojciech Feleszko
Journal: Allergy (2021)

Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain-dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker-guided therapy, discerning those patients that might benefit from antibiotic therapy.
Prevention of NAFLD-associated HCC: Role of lifestyle and chemoprevention
Authors: Naomi F. Lange, Pompilia Radu, Jean-François Dufour
Journal: Journal of Hepatology (2021)

In many countries worldwide, the burden of hepatocellular carcinoma (HCC) associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) is increasing. Preventive strategies are needed to counteract this trend. In this review, we provide an overview of the evidence on preventive strategies in NAFLD-associated HCC. We consider the impact of lifestyle factors such as weight loss, physical activity, smoking, dietary patterns and food items, including coffee and alcohol, on both HCC and NAFLD/NASH. Furthermore, evidence on chemopreventive treatments, including aspirin, antidiabetic treatments and statins is summarised. The role of adjuvant therapies for tertiary prevention of HCC is briefly reviewed.
Reply to M. Ishida et al
Authors: Allison J. Applebaum, Erin E. Kent, Wendy G. Lichtenthal
Journal: Journal of Clinical Oncology (2021)

We appreciate Ishida and Onishi's correspondence 1 on our commentary. 2We clarify here that we propose that having a separate repository of documentation of caregiver services and support be a standard in the provision of family-centered oncology care delivery.This might be considered complementary to Ishida and Onishi's proposal for a communication and referral system that is bidirectional, allowing both clinicians and caregivers to maintain communication and services.Indeed, Ishida and Onishi raise an important issue.For example, web-based patientcentered communication systems, which are becoming more and more commonly implemented, are used by caregivers to communicate with the health care team.Creating a separate but connected communication system for caregivers might not only facilitate private communication about patient care but also more comprehensively address the growing supportive care needs of cancer caregivers, including initiating caregiver-specific referrals.Such a system would also allow for continuity of communication and care into bereavement.It could mitigate feelings of abandonment among bereaved caregivers that result from the closing of communication portals at the time of patients' deaths and could facilitate the provision of bereavement support.We are grateful for Ishida and Onishi's comments that amplify the point that documenting caregivers is a fundamental step toward creating access and fostering communication among clinicians and caregivers.
31 MONOCYTE/MACROPHAGE PERIBILIARY RECRUITMENT BY PKHD1-DEFECTIVE CHOLANGIOCYTES INDUCES EXPRESSION OF αvβ6 INTEGRIN ON BILIARY CYSTS VIA TGF-β1 AND TNF-α IN CONGENITAL HEPATIC FIBROSIS
Authors: L. Fabris, L. Locatelli, C. Spirlì, M. Cadamuro, S. Lecchi, C. Morell, Y. Popov, D. Schuppan, M. Strazzabosco
Journal: Journal of Hepatology (2012)
Abstract 18271: Usefulness of the Synthesized 18-Lead Electrocardiogram in the Diagnosis of Acute Posterior Wall Infarction
Authors: Tsukasa Yagi, Eizo Tachibana, Tadashi Ashida, Keiichiro Kuronuma, Wataru Atsumi, Tsuyoshi Kawamorita, Satoshi Kunimoto, Shigemasa Tani, Naoya Matsumoto, Ken Nagao, Atsushi Hirayama
Journal: Circulation (2017)

Introduction: The synthesized 18-lead electrocardiogram (ECG) (Nihon koden Co. Ltd.) has been reported to be useful. Recording of the posterolateral leads (V7 to V9 leads) is useful for making the ...
In adults with overweight or obesity, continued weekly semaglutide after a 20-wk run-in improved weight loss
Authors: Darren Lau, Raj Padwal
Journal: Annals of Internal Medicine (2021)

Source Citation Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325:1414-25. 33755728
Midodrine for the Prevention of Vasovagal Syncope
Authors: Robert Sheldon, Peter Faris, Anthony Tang, Felix Ayala-Paredes, Juan Guzman, Manlio Marquez, Carlos A. Morillo, Andrew D. Krahn, Teresa Kus, Debbie Ritchie, Shahana Safdar, Connor Maxey, Satish R. Raj
Journal: Annals of Internal Medicine (2021)

Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope.To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions.Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481).25 university hospitals in Canada, the United States, Mexico, and the United Kingdom.Patients with recurrent vasovagal syncope and no serious comorbid conditions.Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months.The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up.The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups.Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center.Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden.The Canadian Institutes of Health Research.
Photothermal therapy with regulated Nrf2/NF-κB signaling pathway for treating bacteria-induced periodontitis
Authors: Yujuan Tian, Ying Li, Jialin Liu, Yi Lin, Jian Jiao, Bo Chen, Wanmeng Wang, Shuilin Wu, Changyi Li
Journal: Bioactive Materials (2021)

Periodontitis is an inflammatory disease initiated by bacterial infection, developed by excessive immune response, and aggravated by high level of reactive oxygen species (ROS). Hence, herein, a versatile metal-organic framework (MOF)-based nanoplatform is prepared using mesoporous Prussian blue (MPB) nanoparticles to load BA, denoted as MPB-BA. The established MPB-BA nanoplatform serves as a shelter and reservoir for vulnerable immunomodulatory drug BA, which possesses antioxidant, anti-inflammatory and anti-bacterial effects. Thus, MPB-BA can exert its antioxidant, anti-inflammatory functions through scavenging intracellular ROS to switch macrophages from M1 to M2 phenotype so as to relieve inflammation. The underlying molecular mechanism lies in the upregulation of phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2) to scavenge ROS and subsequently inhibit the nuclear factor kappa-B (NF-κB) signal pathway. Moreover, MPB-BA also exhibited efficient photothermal antibacterial activity against periodontal pathogens under near-infrared (NIR) light irradiation. In vivo RNA sequencing results revealed the high involvement of both antioxidant and anti-inflammatory pathways after MPB-BA application. Meanwhile, micro-CT and immunohistochemical staining of p-Nrf2 and p-P65 further confirmed the superior therapeutic effects of MPB-BA than minocycline hydrochloride. This work may provide an insight into the treatment of periodontitis by regulating Nrf2/NF-κB signaling pathway through photothermal bioplatform-assisted immunotherapy.
Overcoming microenvironmental resistance to PD-1 blockade in genetically engineered lung cancer models
Authors: Amaia Martinez-Usatorre, Ece Kadioglu, Gael Boivin, Chiara Cianciaruso, Alan Guichard, Bruno Torchia, Nadine Zangger, Sina Nassiri, Ioanna Keklikoglou, Martina Schmittnaegel, Carola H. Ries, Etienne Meylan, Michele De Palma
Journal: Science Translational Medicine (2021)

Lung cancer resistance to PD-1 inhibition can be overcome by targeting tumor-associated macrophages in mouse models.
Temporal variation in association between short-term exposure to fine particulate matter and hospitalisations in older adults in the USA: a long-term time-series analysis of the US Medicare dataset
Authors: Chen Chen, Jason A Warrington, Francesca Dominici, Roger D Peng, Daniel C Esty, Jennifer F Bobb, Michelle L Bell
Journal: The Lancet Planetary Health (2021)

Short-term exposure to fine particulate matter (PM2·5) is associated with increased risk of hospital admissions and mortality, and health risks differ by the chemical composition of PM2·5. Policies to control PM2·5 could change its chemical composition and total mass concentration, leading to change in the subsequent health impact. However, there is little ence on whether associations between PM2·5 and health exhibit temporal variation. We investigated whether risks of hospitalisations from short-term exposure to PM2·5 varied over time in the USA.We did a time-series analysis using a national dataset comprising daily circulatory and respiratory hospitalisation rates of Medicare beneficiaries (age ≥65 years) and PM2·5 in 173 US counties from 1999 to 2016. We fitted modified quasi-Poisson models to estimate temporal trends of associations within a county, and pooled county-level estimates using Bayesian hierarchical modelling to generate an overall estimate.The study included 10 559 654 circulatory and 3 027 281 respiratory hospitalisations. We identified changes in the national average association between previous-day PM2·5 and respiratory hospitalisation over time, with a U-shape that is robust under stratification, linear, and non-linear models. The change in risk of respiratory hospitalisation per 10 μg/m3 increase in previous-day PM2·5 decreased from 0·75% (95% posterior credible interval 0·05 to 1·46) in 1999 to -0·28% (-0·79 to 0·23) in 2008, and then increased to 1·44% (0·00 to 2·91) in 2016. No statistically significant temporal change was observed for associations between same-day PM2·5 and circulatory hospitalisation.Hospitalisation risk from PM2·5 changes over time and has increased over the past 7 years in study, especially in northeastern USA. The temporal trend differs by cause of hospitalisation. This study emphasises the necessity of evaluating temporal heterogeneity in health impacts of PM2·5 and suggests caution in applying association estimates to a different time period.US Environmental Protection Agency and Yale Institute for Biospheric Studies.
Is Dapagliflozin Cost-effective for Treating Heart Failure?
Authors: Anita Slomski
Journal: JAMA (2021)

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
The Beneficial Effects of Earlier Versus Later Implementation of Intensive Therapy in Type 1 Diabetes
Authors: John M. Lachin, Ionut Bebu, David M. Nathan
Journal: Diabetes Care (2021)

OBJECTIVE The principal aim is to estimate the benefits of earlier versus later implementation of intensive therapy in type 1 diabetes with respect to the long-term risks of progression of a renal (microvascular) and cardiovascular (macrovascular) complication in the Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH DESIGN AND METHODS Cox proportional hazards regression models estimated the 20-year cumulative incidence (absolute risk) and the 20-year relative risk of cardiovascular disease (CVD) and reduced estimated glomerular filtration rate (eGFR) over the first 20 years of EDIC follow-up as a function of the mean HbA1c. RESULTS A hypothetical patient treated earlier with 10 years of intensive therapy and a mean HbA1c of 7% (53 mmol/mol) followed by 10 years with a mean of 9% (75 mmol/mol) would have a 33% reduction in the risk of CVD and a 52% reduction in reduced eGFR compared with a patient with a mean HbA1c of 9% (75 mmol/mol) over the first 10 years followed by later intensive therapy over 10 years with an HbA1c of 7% (53 mmol/mol). Despite both patients having the same average glycemic exposure over the 20 years, the patient with the lower HbA1c over the first 10 years had a lower risk of progression of complications over the 20 years than the patient who had the higher value initially. CONCLUSIONS While implementation of intensive therapy at any time in type 1 diabetes will be beneficial, within the 20-year period modeled, earlier relative to later implementation is associated with a greater reduction in the risks of kidney and cardiovascular complications.
Accelerated COVID-19 vaccine development: milestones, lessons, and prospects
Authors: Karin Bok, Sandra Sitar, Barney S. Graham, John R. Mascola
Journal: Immunity (2021)

The development of effective vaccines to combat infectious diseases is a complex multi-year and multi-stakeholder process. To accelerate the development of vaccines for coronavirus disease 2019 (COVID-19), a novel pathogen emerging in late 2019 and spreading globally by early 2020, the United States government (USG) mounted an operation bridging public and private sector expertise and infrastructure. The success of the endeavor can be seen in the rapid advanced development of multiple vaccine candidates, with several demonstrating efficacy and now being administered around the globe. Here, we review the milestones enabling the USG-led effort, the methods utilized, and ensuing outcomes. We discuss the current status of COVID-19 vaccine development and provide a perspective for how partnership and preparedness can be better utilized in response to future public-health pandemic emergencies.
Long‐term extension study of tofacitinib in refractory dermatomyositis
Authors: Julie J. Paik, Matthew Shneyderman, Laura Gutierrez‐Alamillo, Jemima Albayda, Eleni Tiniakou, Jamie Perin, Grazyna Purwin, Sherry Leung, Doris Leung, Livia Casciola‐Rosen, Andrew S. Koenig, Lisa Christopher‐Stine
Journal: Arthritis & Rheumatology (2021)

We previously demonstrated that tofacitinib was effective in treating skin-predominant refractory dermatomyositis (DM) at 12 weeks in a prospective open label clinical trial, Study of Tofacitinib In Refractory dermatomyositis (STIR) (1). Here, we report the long-term extension results of up to 96 weeks to investigate the treatment durability of tofacitinib in refractory DM. Inclusion criteria and outcome measures were the same as the parent study (1). Assessments were conducted at weeks 20, 72, and 96. The baseline demographic features of all 10 trial patients were reported previously (1).
Little Evidence the Standard Genetic Code Is Optimized for Resource Conservation
Authors: Hana Rozhoňová, Joshua L Payne
Journal: Molecular Biology and Evolution (2021)

Selection for resource conservation can shape the coding sequences of organisms living in nutrient-limited environments. Recently, it was proposed that selection for resource conservation, specifically for nitrogen and carbon content, has also shaped the structure of the standard genetic code, such that the missense mutations the code allows tend to cause small increases in the number of nitrogen and carbon atoms in amino acids. Moreover, it was proposed that this optimization is not confounded by known optimizations of the standard genetic code, such as for polar requirement or hydropathy. We challenge these claims. We show the proposed optimization for nitrogen conservation is highly sensitive to choice of null model and the proposed optimization for carbon conservation is confounded by the known conservative nature of the standard genetic code with respect to the molecular volume of amino acids. There is therefore little evidence the standard genetic code is optimized for resource conservation. We discuss our findings in the context of null models of the standard genetic code.
A manganese (II)-based coordinative dendrimer with robust efficiency in intracellular peptide delivery
Authors: Lanfang Ren, Yang Gao, Yiyun Cheng
Journal: Bioactive Materials (2021)

Peptides have gained increasing interests as drug candidates in modern pharmaceutical industry, however, the development of peptide drugs acting on intracellular targets is limited due to their membrane impermeability. Here, we reported the use of metal-terpyridine based coordinative dendrimer for cytosolic peptide delivery. Among the investigated transition metal ions, Mn2+-coordinated polymer showed the highest delivery efficiency due to balanced peptide binding and release. It showed robust efficiency in the delivery of peptides with different charge property and hydrophobicity into various primary cells. The efficiency of Mn2+-terpyridine based polymer is superior to cell penetrating peptides such as oligoarginines. The material also delivered an autophagy-inducing peptide derived from Beclin-1 into cells and efficiently induced autophagy in the cells. This study provides a promising alternative to cell penetrating peptides for cytosolic peptide delivery.
Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease
Authors: Kevin Mulder, Amit Ashok Patel, Wan Ting Kong, Cécile Piot, Evelyn Halitzki, Garett Dunsmore, Shabnam Khalilnezhad, Sergio Erdal Irac, Agathe Dubuisson, Marion Chevrier, Xiao Meng Zhang, John Kit Chung Tam, Tony Kiat Hon Lim, Regina Men Men Wong, Rhea Pai, Ahmed Ibrahim Samir Khalil, Pierce Kah Hoe Chow, Suny Z. Wu, Ghamdan Al-Eryani, Daniel Roden, Alexander Swarbrick, Jerry Kok Yen Chan, Salvatore Albani, Lisa Derosa, Laurence Zitvogel, Ankur Sharma, Jinmiao Chen, Aymeric Silvin, Antonio Bertoletti, Camille Blériot, Charles-Antoine Dutertre, Florent Ginhoux
Journal: Immunity (2021)