tbuckley/cabot-search huggingface dataset:
Group 1 innate lymphoid-cell-derived interferon-γ maintains anti-viral vigilance in the mucosal epithelium
Authors: John P. Shannon, Sophia M. Vrba, Glennys V. Reynoso, Erica Wynne-Jones, Olena Kamenyeva, Courtney S. Malo, Christian R. Cherry, Daniel T. McManus, Heather D. Hickman
Journal: Immunity (2021)
A modular and controllable T cell therapy platform for acute myeloid leukemia
Authors: Mohamed-Reda Benmebarek, Bruno L. Cadilha, Monika Herrmann, Stefanie Lesch, Saskia Schmitt, Stefan Stoiber, Abbass Darwich, Christian Augsberger, Bettina Brauchle, Lisa Rohrbacher, Arman Oner, Matthias Seifert, Melanie Schwerdtfeger, Adrian Gottschlich, Felicitas Rataj, Nadja C. Fenn, Christian Klein, Marion Subklewe, Stefan Endres, Karl-Peter Hopfner, Sebastian Kobold
Journal: Leukemia (2021)

Abstract Targeted T cell therapy is highly effective in disease settings where tumor antigens are uniformly expressed on malignant cells and where off-tumor on-target-associated toxicity is manageable. Although acute myeloid leukemia (AML) has in principle been shown to be a T cell-sensitive disease by the graft-versus-leukemia activity of allogeneic stem cell transplantation, T cell therapy has so far failed in this setting. This is largely due to the lack of target structures both sufficiently selective and uniformly expressed on AML, causing unacceptable myeloid cell toxicity. To address this, we developed a modular and controllable MHC-unrestricted adoptive T cell therapy platform tailored to AML. This platform combines synthetic agonistic receptor (SAR) -transduced T cells with AML-targeting tandem single chain variable fragment (scFv) constructs. Construct exchange allows SAR T cells to be redirected toward alternative targets, a process enabled by the short half-life and controllability of these antibody fragments. Combining SAR-transduced T cells with the scFv constructs resulted in selective killing of CD33 + and CD123 + AML cell lines, as well as of patient-derived AML blasts. Durable responses and persistence of SAR-transduced T cells could also be demonstrated in AML xenograft models. Together these results warrant further translation of this novel platform for AML treatment.
Time-Restricted Salutary Effects of Blood Flow Restoration on Venous Thrombosis and Vein Wall Injury in Mouse and Human Subjects
Authors: Wenzhu Li, Chase W. Kessinger, Makoto Orii, Hang Lee, Lang Wang, Ido Weinberg, Michael R. Jaff, Guy L. Reed, Peter Libby, Ahmed Tawakol, Peter K. Henke, Farouc A. Jaffer
Journal: Circulation (2021)

Up to 50% of patients with proximal deep vein thrombosis (DVT) will develop the postthrombotic syndrome characterized by limb swelling and discomfort, hyperpigmentation, skin ulcers, and impaired quality of life. Although catheter-based interventions enabling the restoration of blood flow (RBF) have demonstrated little benefit on postthrombotic syndrome, the impact on the acuity of the thrombus and mechanisms underlying this finding remain obscure. In experimental and clinical studies, we examined whether RBF has a restricted time window for improving DVT resolution.
Covid-19: GPs can limit routine work to focus on vaccination, says NHS England
Authors: Gareth Iacobucci
Journal: BMJ (2021)

General practices can suspend some non-essential work to allow them to focus on delivering covid-19 vaccinations, NHS England has said.

In a letter to general practitioners and local commissioners sent on 7 January, NHS England set out measures designed to reduce practices’ workloads while protecting their income to help them deliver covid-19 vaccinations.1 The letter urged local commissioners to “take a supportive and pragmatic approach to minimise local contract enforcement across routine care, with attention and support focused on the core areas.” But it stressed that GPs should ensure that “general practice remains fully and safely open for patients, including maintenance of appointments.”

Most locally commissioned enhanced services should be suspended, except when these are specifically …
Abstract 15253: The Impact of Cancer Diagnosis on Mortality and Readmission Following Admission for Congestive Heart Failure
Authors: Javad Razjouyan, Aanand D Naik, Jacquelene Shahin, Molly J Horstman
Journal: Circulation (2018)

Introduction: The number of cancer survivors is rising in the United States. Lasting cardiovascular effects of cancer therapy may reduce cardiac compensatory reserve to acute clinical events. Limit...
Assessment of Advanced Glycation End Products and Receptors and the Risk of Dementia
Authors: Jinluan Chen, Sanne S. Mooldijk, Silvan Licher, Komal Waqas, M. Kamran Ikram, André G. Uitterlinden, M. Carola Zillikens, M. Arfan Ikram
Journal: JAMA Network Open (2021)

Advanced glycation end products (AGEs) and their receptor (RAGE) are implicated in the pathophysiological processes of dementia and potentially underlie the association of diabetes with neurodegeneration. However, longitudinal studies examining this association are lacking.To determine whether markers of the AGE-RAGE system are associated with prevalent and incident dementia and with cognition.In this population-based cohort study including participants from the prospective Rotterdam Study, extracellular newly identified RAGE binding protein (EN-RAGE) and soluble RAGE (S-RAGE) were measured in plasma collected between 1997 and 1999 in a random selection of participants, and additionally in participants with prevalent dementia. Participants without dementia were followed up for dementia until 2016. Skin AGEs, measured as skin autofluorescence, and cognition were measured between 2013 and 2016 in participants without dementia. Data analysis was performed from June 2019 to December 2019.EN-RAGE, S-RAGE, and skin autofluorescence.Prevalent and incident dementia and cognition, adjusted for potential confounders, including age, sex, diabetes, educational level, APOE ε4 carrier status, smoking, and estimated glomerular filtration rate.Of 3889 included participants (mean [SD] age, 72.5 [8.9] years; 2187 [56.2%] women), 1021 participants had data on plasma markers (mean [SD] age 73.6 [7.8] years; 564 [55.2%] women), 73 participants had dementia at baseline, and during 10 711 person-years of follow-up, 161 participants developed incident dementia. Compared with low levels, high EN-RAGE level was associated with a higher prevalence of dementia (odds ratio [OR], 3.68 [95% CI, 1.50-8.03]; P = .003), while high S-RAGE level was associated with a lower prevalence of dementia (OR, 0.37 [95% CI, 0.17-0.78]; P = .01). These associations attenuated in a longitudinal setting, with hazard ratios of 0.65 (95% CI, 0.42-1.01) for high EN-RAGE (P = .05) and 1.22 (95% CI, 0.82-1.81) for high S-RAGE (P = .33). Among 2890 participants without dementia (mean [SD] age, 72.5 [9.4] years; 1640 [57%] women), higher skin autofluorescence was associated with lower global cognitive function (adjusted difference in z score per 1-SD higher skin autofluorescence, -0.07 [95% CI, -0.11 to -0.04]), especially among carriers of the APOE ε4 allele (adjusted difference in z score per 1-SD higher skin autofluorescence, -0.15 [95% CI, -0.22 to -0.07]).These findings suggest that the AGE-RAGE system is associated with cognitive decline and dementia cross-sectionally but not longitudinally. This indicates either a short-term association or reverse causality. Findings of cross-sectional associations between higher skin autofluorescence and lower cognitive function and an association with APOE status also warrant replication and prospective studies.
Pharmaceutical Representatives and Resident Physicians
Authors: J. L. Glazer
Journal: JAMA (2002)

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
Delivery of single-domain antibodies into neurons using a chimeric toxin–based platform is therapeutic in mouse models of botulism
Authors: Shin-Ichiro Miyashita, Jie Zhang, Sicai Zhang, Charles B. Shoemaker, Min Dong
Journal: Science Translational Medicine (2021)

A detoxified chimeric toxin–based platform delivers therapeutics into neurons and has therapeutic effects in mouse models of botulism.
Abstract P274: Trans-generational Impact of Diet in Pregnancy: Maternal Dietary Intake of Grains During Pregnancy and Offspring Growth and Obesity From Birth Through Age of 7 Years
Authors: Yeyi Zhu, Sjurdur F Olsen, Pauline Mendola, Frank B Hu, Cuilin Zhang
Journal: Circulation (2016)

Introduction: Emerging data from animal studies suggest that diet during pregnancy may affect fetal growth and metabolic programming of the offspring with long-term consequences. Epidemiologic data on transgenerational effects of maternal diet are sparse. Objective: We prospectively investigated the association of maternal diet, in particular, intake of grains during pregnancy with offspring growth and risk of obesity from birth through age 7 years among high risk populations, women complicated by gestational diabetes (GDM) and their children born from the index pregnancy. Methods: In the Danish National Birth Cohort (1996-2002), 918 women complicated by GDM and their singleton children were included in the study. Diet during pregnancy was measured by a validated food frequency questionnaire. Offspring body mass index z-scores (BMIZ) by WHO references were calculated using clinically measured weight and length/height at birth, 5 months, 12 months, and 7 years. Overweight/obese was defined by WHO cutoffs. Linear and Poisson regression with robust standard errors were applied, adjusting for maternal pre-pregnancy BMI and other demographic, lifestyle, and dietary factors. Results: Refined grain intake during pregnancy was significantly and positively associated with offspring growth at 7 years: adjusted β coefficient (95% CI) for a 1-serving per-day increment of refined grains associated with BMIZ at 7 years was 0.09 (0.02, 0.16). At 7 years, offspring born from women who consumed refined grains in the highest quartile (≥4.7 servings/day) experienced more than 1.7-fold increased risk of overweight/obesity as compared to those in the lowest quartile (&lt;2.2 servings/day) [adjusted relative risk (RR) (95% CI) = 1.74 (1.03, 2.93)]. Corresponding RR (95% CI) comparing the extremely high amount of refined grains (the highest 10th percentile, ≥5.9 servings/day) to the lowest quartile was 2.59 (1.28, 5.23). The associations appeared being modified by offspring diet and lifestyle factors during childhood: being more pronounced among children with less favorable lifestyle (i.e., who were breastfed &lt;6 months, physically inactive, or consumed more sugar sweetened beverages). Moreover, substitution of 1 serving/day of refined grains with an equal serving of whole grains among women was associated with an 11% (95% CI: 0.82, 0.98) reduced risk of overweight/obesity at 7 years among the offspring. Conclusions: Our findings suggest that higher intake of refined grains during pregnancy was significantly associated with greater offspring BMIZ and increased risk of overweight/obesity at 7 years. Such associations could be potentially modified by offspring diet and lifestyle factors during childhood.
Roles of piRNAs in transposon and pseudogene regulation of germline mRNAs and lncRNAs
Authors: Chen Wang, Haifan Lin
Journal: Genome biology (2021)

PIWI proteins, a subfamily of PAZ/PIWI Domain family RNA-binding proteins, are best known for their function in silencing transposons and germline development by partnering with small noncoding RNAs called PIWI-interacting RNAs (piRNAs). However, recent studies have revealed multifaceted roles of the PIWI-piRNA pathway in regulating the expression of other major classes of RNAs in germ cells. In this review, we summarize how PIWI proteins and piRNAs regulate the expression of many disparate RNAs, describing a highly complex global genomic regulatory relationship at the RNA level through which piRNAs functionally connect all major constituents of the genome in the germline.
Multiple Hepatic Aneurysm and Dry Gangrene of Fingertips in Eosinophilic Granulomatosis with Polyangiitis (EGPA)
Authors: Eun Sil Koh, Byung-Jae Lee, Jin-Young Lee, Noeul Kang, Jae Won Jeong, Sang-Hoon Kim, Dong-Chull Choi
Journal: Journal of Allergy and Clinical Immunology (2020)
Impact of Obesity on Measures of Cardiovascular and Kidney Health in Youth With Type 1 Diabetes as Compared With Youth With Type 2 Diabetes
Authors: Kalie L. Tommerdahl, Karl Baumgartner, Michal Schäfer, Petter Bjornstad, Isabella Melena, Shannon Hegemann, Amy D. Baumgartner, Laura Pyle, Melanie Cree-Green, Uyen Truong, Lorna Browne, Judith G. Regensteiner, Jane E.B. Reusch, Kristen J. Nadeau
Journal: Diabetes Care (2021)

OBJECTIVE Insulin resistance and obesity are independently associated with type 1 diabetes (T1D) and are known risk factors for cardiovascular and kidney diseases, the leading causes of death in T1D. We evaluated the effect of BMI on cardiovascular and kidney outcomes in youth with T1D versus control youth with normal weight or obesity and youth with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Pubertal youth (n = 284) aged 12–21 years underwent assessments of resting heart rate (RHR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), leptin, hs-CRP, adiponectin, ratio of urine albumin to creatinine, and estimated glomerular filtration rate. Participants with T1D underwent bicycle ergometry for VO2peak, monitoring for peripheral brachial artery distensibility (BAD), endothelial function testing for reactive hyperemic index, and aortic MRI for central arterial stiffness or shear. RESULTS In adolescents with T1D, RHR, SBP, DBP, mean arterial pressure, leptin, hs-CRP, and hypertension prevalence were significantly higher, and BAD, descending aorta pulse wave velocity, and VO2peak lower with an obese versus normal BMI. Although hypertension prevalence and RHR were highest in obese adolescents with T1D and adiponectin lowest in youth with T2D, other measures were similar between obese adolescents with T1D and those with T2D. CONCLUSIONS Obesity, now increasingly prevalent in people with T1D, correlates with a less favorable cardiovascular and kidney risk profile, nearly approximating the phenotype of youth with T2D. Focused lifestyle management in youth-onset T1D is critically needed to reduce cardiovascular risk.
Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function
Authors: Juan Huang, Jian Peng, James Alexander Pearson, Georgios Efthimiou, Youjia Hu, Ningwen Tai, Yanpeng Xing, Luyao Zhang, Jianlei Gu, Jianping Jiang, Hongyu Zhao, Zhiguang Zhou, F. Susan Wong, Li Wen
Journal: Cellular and Molecular Immunology (2021)

Abstract Innate immunity mediated by Toll-like receptors (TLRs), which can recognize pathogen molecular patterns, plays a critical role in type 1 diabetes development. TLR7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells; however, its role in type 1 diabetes development remains unclear. In our study, we discovered that Tlr7 -deficient ( Tlr7 −/− ) nonobese diabetic (NOD) mice, a model of human type 1 diabetes, exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7 -sufficient ( Tlr7 +/+ ) NOD mice. Mechanistic investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin production. Moreover, Tlr7 −/− NOD B cells were found to suppress diabetogenic CD4 + T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T cells. In addition, we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8 + T-cell activation by downregulating the expression of both nonclassical and classical MHC class I (MHC-I) molecules on B cells. Our data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T cells. Therefore, therapeutically targeting TLR7 may prove beneficial for disease protection.
Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish
Authors: Shuxian Lu, Zhaojie Lyu, Zhihao Wang, Yao Kou, Cong Liu, Shengyue Li, Mengyan Hu, Hongjie Zhu, Wenxing Wang, Ce Zhang, Yung-Shu Kuan, Yi-Wen Liu, Jianming Chen, Jing Tian
Journal: Theranostics (2021)

Lipin 1 is an intracellular protein acting as a phosphatidic acid phosphohydrolase enzyme controlling lipid metabolism. Human recessive mutations in LPIN1 cause recurrent, early-onset myoglobinuria, a condition normally associated with muscle pain and weakness. Whether and how lipin 1 deficiency in humans leads to peripheral neuropathy is yet unclear. Herein, two novel compound heterozygous mutations in LPIN1 with neurological disorders, but no myoglobinuria were identified in an adult-onset syndromic myasthenia family. The present study sought to explore the pathogenic mechanism of LPIN1 in muscular and neural development. Methods: The clinical diagnosis of the proband was compared to the known 48 cases of LPIN1 recessive homozygous mutations. Whole-exome sequencing was carried out on the syndromic myasthenia family to identify the causative gene. The pathogenesis of lipin 1 deficiency during somitogenesis and neurogenesis was investigated using the zebrafish model. Whole-mount in situ hybridization, immunohistochemistry, birefringence analysis, touch-evoke escape response and locomotion assays were performed to observe in vivo the changes in muscles and neurons. The conservatism of the molecular pathways regulated by lipin 1 was evaluated in human primary glioblastoma and mouse myoblast cells by siRNA knockdown, drug treatment, qRT-PCR and Western blotting analysis. Results: The patient exhibited adult-onset myasthenia accompanied by muscle fiber atrophy and nerve demyelination without myoglobinuria. Two novel heterozygous mutations, c.2047A>C (p.I683L) and c.2201G>A (p.R734Q) in LPIN1, were identified in the family and predicted to alter the tertiary structure of LPIN1 protein. Lipin 1 deficiency in zebrafish embryos generated by lpin1 morpholino knockdown or human LPIN1 mutant mRNA injections reproduced the myotomes defects, a reduction both in primary motor neurons and secondary motor neurons projections, morphological changes of post-synaptic clusters of acetylcholine receptors, and myelination defects, which led to reduced touch-evoked response and abnormalities of swimming behaviors. Loss of lipin 1 function in zebrafish and mammalian cells also exhibited altered expression levels of muscle and neuron markers, as well as abnormally enhanced Notch signaling, which was partially rescued by the specific Notch pathway inhibitor DAPT. Conclusions: These findings pointed out that the compound heterozygous mutations in human LPIN1 caused adult-onset syndromic myasthenia with peripheral neuropathy. Moreover, zebrafish could be used to model the neuromuscular phenotypes due to the lipin 1 deficiency, where a novel pathological role of over-activated Notch signaling was discovered and further confirmed in mammalian cell lines.
Combining IL-3 gene immunotherapy with radiotherapy for prostate cancer
Authors: Chi-Shiun Chiang, Chen-Ling Hsieh, Wei-Chung Liu, Young-Taek Oh, William H. McBride, Ji-Hong Hong
Journal: Cancer Research (2004)

4671  This study aimed to test the hypothesis that the expression of IL-3 gene within a prostate cancer could enhance its response to radiation therapy. To this aim, we employed a murine model of prostate cancer (TRAMP-C1 and TRAMP-C2) and retroviral and adenoviral vectors to express IL-3 intratumorally. The combining effects of IL-3 gene expression and radiation therapy were evaluated by in vitro colony assay and in vivo tumor growth delay. The nature of the intratumoral host cell infiltrate and the level of systemic immunity that was generated were measured by flow cytometry and ELISPOT, respectively. The results show that transfection of Adv-IL3 into TRAMP cells does not alter their intrinsic radiosensitivity, but it increases the time of growth delay following a single dose of 35 Gy or fractionation dose of 3 x 10 Gy radiation. Flow cytometry shows that the major change of cellular components within MoMuLV-IL3 transfected tumors prior to irradiation is recruitment of Mac-1 and F4/80 positive cells with enhanced expression of MHC II molecules five days after 35 Gy of radiation. The TRAMP specific splenic immune response was measured by ELISPOT. The result showed that IL3 gene expression activates IL-4 producing lymphocytes (Th2 response). However following radiotherapy, the response there was a shift to a Th1 response with more IFN-γ than IL-4 producing cells. The study proves the hypothesis that IL-3 gene transfection can enhance prostate cancer response to radiotherapy. It also demonstrates that the effect of IL-3 is mainly through the induction of immunity and infiltrating cells into the tumor. Moreover, this study shows that combining IL-3 gene immunotherapy with radiotherapy can switch the anti-tumor immune response from a Th2 to a Th1 response. Exploration of the mechanism responsible for this shift is underway.
OA03.07 Pembrolizumab for Advanced Mesothelioma: Results from the Phase 2 KEYNOTE-158 Study
Authors: T.A. Yap, K. Nakagawa, N. Fujimoto, K. Kuribayashi, T. Guren, L. Calabrò, R.S. Frommer, B. Gao, S. Kao, I. Matos, D. Planchard, A. Chatterjee, F. Jin, K. Norwood, H.L. Kindler
Journal: Journal of Thoracic Oncology (2021)
Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020
Authors: Kathy Leung, Marcus HH Shum, Gabriel M Leung, Tommy TY Lam, Joseph T Wu
Journal: Eurosurveillance (2021)

Two new SARS-CoV-2 lineages with the N501Y mutation in the receptor-binding domain of the spike protein spread rapidly in the United Kingdom. We estimated that the earlier 501Y lineage without amino acid deletion Δ69/Δ70, circulating mainly between early September and mid-November, was 10% (6–13%) more transmissible than the 501N lineage, and the 501Y lineage with amino acid deletion Δ69/Δ70, circulating since late September, was 75% (70–80%) more transmissible than the 501N lineage.
Covid-19: Government uses lateral flow tests to keep children in schools against regulator’s advice
Authors: Jacqui Wise
Journal: BMJ (2021)

Covid-19: Government uses lateral flow tests to keep children in schools against regulator's advice Jacqui WiseThe UK government has confirmed that it is using daily contact testing in schools as an alternative to self-isolation as part of an "ongoing evaluation," even though the UK regulator has not approved antigen lateral flow devices to be used this way.