tbuckley/cabot-search huggingface dataset:
Abstract 16974: Augmentation of Vasoactive Intestinal Peptide Signaling Prevents the Development of Duchenne Muscular Dystrophy-Associated Cardiomyopathy Through Inhibition of NF-κB Signaling
Authors: Jian Huang, Terry Gemelli, Xuan Jiang, Yunbeen Bae, Tara Tassin, John Shelton, Bret Evers, Sue Arnold, John Lee, Pradeep P Mammen
Journal: Circulation (2020)

Duchenne muscular dystrophy (DMD) is a recessive X-linked neuromuscular disorder characterized by progressive muscle degeneration with DMD-associated cardiomyopathy being the primary mode of death. Vasoactive intestinal peptide (VIP) is a 28 amino acid neuropeptide with biological effects mediated by G protein-coupled receptors. Utilizing a genetically modified form of VIP (PB1046) targeting cardiomyocytes, we hypothesized that augmentation of VIP signaling prevents the development of DMD-associated cardiomyopathy through inhibition of NF-κB. Either PB1046 (1.5 mg/kg) or a Placebo (saline) was injected subcutaneously every other day in three mouse models: DMD mdx:Utr+/- , DMD mdx , and wild type mice starting at 4 weeks of age for a total of 8 weeks. Cardiac function was assessed by weekly echocardiography. The cardiac tissues were collected at 14 weeks of age for histological and molecular analyses. Drug-treated DMD mdx:Utr+/- mice showed preservation of cardiac function (fractional shortening 61%±0.4 vs 45%±1.3, p &lt;0.01; n=8-12) and a marked reduction in myocardial fibrosis (2.92%±0.13 vs 6.42% ±0.39, p &lt;0.01; n=3) compared with controls. Hydroxyproline levels within drug-treated DMD mdx:Utr+/- mice was decreased compared with controls (44.6±5.3 vs 64.3±6.9 nmol/100mg heart weight, p &lt;0.05, n=6). RNA-Seq data revealed an upregulation of cAMP signaling with downregulation of NF-kB signaling in isolated cardiac myocytes from drug-treated DMD mdx:Utr+/- mice as compared to controls (n=3). Western blot analyses revealed increased phosphorylation of CREB (1.97±0.02 vs 1.00±0.06, p &lt;0.05, n=5-9) with decreased phosphorylation of p65 in drug-treated DMD cardiac nuclei as compared to controls (0.62±0.06 vs 1.00±0.09, p &lt;0.05, n=3). Collectively, the data revealed augmentation of VIP signaling prevents the development of DMD-associated cardiomyopathy in DMD mdx:Utr+/- mice. The molecular mechanism underlying the benefits of VIP signaling suggests an upregulation of cAMP-CREB signaling with downregulation of NF-kB signaling leading to inhibition of inflammation and fibrosis within drug-treated DMD hearts. VIP signaling in DMD may serve as a new therapeutic target for the treatment of DMD-associated cardiomyopathy.
CD33/CD3-Bispecific T-Cell Engaging (BiTE®) Antibody Constructs Efficiently Target Monocytic CD14+ hla-DRlow IDO+ aml-MDSCs
Authors: Dimitrios Mougiakakos, Domenica Saul, Martina Braun, Sehmus Tohumeken, Roman Kischel, Lutteropp Michael, Cedric E. Dos Santos, Regina Jitschin, Andreas Mackensen
Journal: Blood (2017)
Better Hypertension Control With Digital Self-monitoring
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
Retrospective serosurveillance for anti-SARS-CoV-2 immunoglobulin during a time of low prevalence: A cautionary tale
Authors: Paul William Bird, Christopher Holmes, Oliver Fletcher, Vinay Badhwar, Oliver Toovey, Julian Wei-Tze Tang
Journal: Journal of Infection (2021)

We performed a retrospective screening of 428 serum samples for anti-SARS-CoV-2 immunoglobulin during a period of low prevalence. Employing two different serological tests yielded discrepant results for 10 samples; highlighting an increased risk of potential false positive results and the need for further confirmatory testing before publication of data.
Refugee Mental Health—An Urgent Call for Research and Action
Authors: Altaf Saadi, Tala Al-Rousan, Rawan AlHeresh
Journal: JAMA Network Open (2021)

Ahmed Hossain, PhD; Redwan Bin Abdul Baten, MPH; Zeeba Zahra Sultana, MPH; Taifur Rahman, MPH; Mirza Asif Adnan, MPH; Moynul Hossain, MPH; Taifur Aziz Khan, MPH; Muzakkir Kamar Uddin, MPH
The high prevalence of <i>Clostridioides difficile</i> among nursing home elders associates with a dysbiotic microbiome
Authors: John P. Haran, Doyle V. Ward, Shakti K. Bhattarai, Ethan Loew, Protiva Dutta, Amanda Higgins, Beth A. McCormick, Vanni Bucci
Journal: Gut Microbes (2021)

Clostridioides difficile disproportionally affects the elderly living in nursing homes (NHs). Our objective was to explore the prevalence of C. difficile in NH elders, over time and to determine whether the microbiome or other clinical factors are associated with C. difficile colonization.We collected serial stool samples from NH residents. C. difficile prevalence was determined by quantitative polymerase-chain reaction detection of Toxin genes tcdA and tcdB; microbiome composition was determined by shotgun metagenomic sequencing. We used mixed-effect random forest modeling machine to determine bacterial taxa whose abundance is associated with C. difficile prevalence while controlling for clinical covariates including demographics, medications, and past medical history.We enrolled 167 NH elders who contributed 506 stool samples. Of the 123 elders providing multiple samples, 30 (24.4%) elders yielded multiple samples in which C. difficile was detected and 78 (46.7%) had at least one C. difficile positive sample. Elders with C. difficile positive samples were characterized by increased abundances of pathogenic or inflammatory-associated bacterial taxa and by lower abundances of taxa with anti-inflammatory or symbiotic properties. Proton pump inhibitor (PPI) use is associated with lower prevalence of C. difficile (Odds Ratio 0.46; 95%CI, 0.22-0.99) and the abundance of bacterial species with known beneficial effects was higher in PPI users and markedly lower in elders with high C. difficile prevalence.C. difficile is prevalent among NH elders and a dysbiotic gut microbiome associates with C. difficile colonization status. Manipulating the gut microbiome may prove to be a key strategy in the reduction of C. difficile in the NH.
All-trans retinoic acid and 13-cis retinoic acid differentiated rat C6 glioblastoma cells and decreased telomerase activity leading to increased sensitivity to IFN-γ and taxol for apoptosis
Authors: Arabinda Das, Surajit Karmakar, Sunil J. Patel, Naren L. Banik, Swapan K. Ray
Journal: Cancer Research (2005)

1734  Glioblastoma is the deadliest and most prevalent brain tumor. It is considered to be a death sentence as the glioblastoma patients hardly survive more than 1 year following diagnosis. There is no effective therapeutic strategy for the treatment of glioblastoma. So, new and innovative therapeutic strategies need to be devised for the treatment of this deadly disease. In this investigation, we used rat C6 glioblastoma cells to examine the efficacy of a combination of a retinoid and a cytotoxic cytokine or cytostatic agent for controlling their growth. The malignant property of glioblastoma is often potentiated by the activation of telomerase activity. We hypothesized that retinoid induced differentiation of C6 glioblastoma cells and down regulation of telomerase activity would decrease the proliferative potential and increase drug sensitivity for apoptosis. Treatment of C6 cells with 1 μM all-trans retinoic acid (ATRA) or 1 μM 13-cis retinoic acid (13-CRA) for 14 days induced astrocytic differentiation morphologically and biochemically, and also down regulated telomerase activity. Differentiated C6 cells decreased proliferation and increased sensitivity to interferon-gamma (IFN-γ) and taxol (TXL) for apoptosis. Wright staining and ApopTag assay identified, respectively, morphological and biochemical features of apoptosis in C6 cells following exposure to 500 units/ml IFN-γ for 48 h or 0.1 μM TXL for 24 h. Fura-2 assay detected an increase in intracellular free Ca2+ in apoptotic C6 cells, indicating involvement of Ca2+-dependent events in apoptosis. Western blot analyses showed an increase in Bax:Bcl-2 ratio, cytochrome c release from mitochondria, conversion of pro-caspase-9 to active caspase-9, and overexpression and activation of calpain and caspase-3 to cleave 270 kD α-spectrin at specific sites for generation of 145 kD and 120 kD spectrin break down products (SBDPs), respectively, in course of apoptosis. Activation of caspase-3 was also confirmed in the increased generation of 20 kD and 12 kD fragments. Following exposure to IFN-γ or TXL, apoptosis related events were found to be highly prominent in the differentiated C6 cells. Moreover, treatment of undifferentiated and differentiated C6 cells with TXL caused the phosphorylation of Bcl-2 and thus inactivated its anti-apoptotic property, further promoting the commitment of cells to apoptosis. Taken together, all the results of this investigation suggested that first retinoid induced astrocytic differentiation with down regulation of telomerase activity and then induction of apoptosis with a cytotoxic or a cytostatic agent could be an effective combination therapeutic strategy for controlling the growth of glioblastoma cells. This investigation was supported in part by the R01 grants from the NCI and NINDS of the NIH, and also a grant from the State of SC.
P45.04 Radiologic and Clinical Features of Screening-Detected Pulmonary Invasive Mucinous Adenocarcinoma
Authors: D.H. Kim, S.Y. Bae, K.J. Na, S. Park, H.J. Lee, C.H. Kang, Y.T. Kim, I.K. Park
Journal: Journal of Thoracic Oncology (2021)
P76.25 Radiation Pneumonitis in NSCLC Patients Receiving EGFR-TKI and Once-Daily Thoracic RT: Predicting Values of Clinical and DVH Parameters
Authors: X. Yang, T. Mei, Y. Xu, L. Zhou, X. Zhou, J. Xue, Y. Liu, B. Zou, Y. Wang, J. Wang, Y. Lu, Y. Gong
Journal: Journal of Thoracic Oncology (2021)
Abstract 13084: Increasing Engagement in the Electronic Framingham Heart Study (eFHS): A Factorial Randomized Trial
Authors: Ludovic Trinquart, David D McManus, Christopher Nowak, Vik Kheterpal, Emily S Manders, Kelsey Fusco, Honghuang Lin, Nicole L Spartano, Chunyu Liu, Belinda Borrelli, Emelia J Benjamin, Joanne Murabito
Journal: Circulation (2019)

Background: Smartphone apps and mHealth devices offer innovative ways to collect cardiovascular data. However, maintaining engagement is challenging. We assessed the effect of interventions to enha...
P89.13 Real-World Experience of NGS-Based Molecular Profiling in ‘Triple-Negative’ (EGFR/ALK/ROS1) Advanced NSCLC: Should we keep Testing Smokers?
Authors: F. Simionato, L. Calvetti, F. Pancheri, S. Scarparo, P. Frugoni, C. Marco, A.G. Menin, S. Ave, A. Lupi, G. Aprile
Journal: Journal of Thoracic Oncology (2021)
Coffee Consumption and Colorectal Cancer Prognosis
Authors: Shunan Wang, Zhixin Zhang, Wenquan Niu
Journal: JAMA Oncology (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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Risk of COVID‐19 infection in adult patients with atopic eczema and psoriasis: a single‐centre cross‐sectional study
Authors: Z.Z.N. Yiu, G. Harding‐Oredugba, C.E.M. Griffiths, R.B. Warren, E. McMullen, H.J.A. Hunter
Journal: British Journal of Dermatology (2021)

which affects the start codon of SNRPE.This variant was associated with HHS in our original study. 3 The fact that we identified mutations in three ethnically diverse families suggests that mutations in SNRPE are a relatively frequent occurrence.It is thus surprising that no additional cases have been reported since our original publication. 3 As also observed in the cases at that time, there was wide phenotypic variation in the present ones.Concerning the splice site mutation, c.54+2T>A directly affects one of the most conserved nucleotides of the 5 0 splice site of intron 1.As the newly activated splice site donor, which allows exon 1 skipping, was found in the vector sequence, we cannot exclude the possibility that another mechanism is taking place in vivo.However, if the described aberrant transcript were to be produced, it may be either subjected to RNA decay or, more likely, allow the production of an in-frame 52 amino acid-long protein corresponding to a different small nuclear ribonucleoprotein polypeptide E (SNRPE) isoform (ENST00000 367208Á1).We suggest that the lower expression of wildtype protein, or the imbalance between the two isoforms, impacts on SNRPE function with respect to hair growth/ development. 3 Interestingly, a mutation in SNRPE was recently identified in a patient with primary microcephaly and intellectual disability. 2 None of the present cases showed either clinical feature.This study identified two novel heterozygous mutations, and one known mutation, in SNRPE.This expands the mutational and ethnic spectrum of HHS.
P35.03 Methylation Signatures Associated with T790M Status in Progressive NSCLC
Authors: G. O'Kane, A. Leon, M. Shabir, J. Law, P. Bradbury, G. Liu, A. Sacher, F. Shepherd, D. Torti, T. Stockley, M. Tsao, T. Pugh, N. Leighl
Journal: Journal of Thoracic Oncology (2021)
P-0224 Addition of Cetuximab to Oxaliplatin-Based Chemotherapy on Liver and Spleen Size and Thrombocytopenia in Patients with Metastatic Colorectal Cancer
Authors: Victor Lee, Weijia Fang, K.O. Lam, Cheukwai Choi, Sherry Ng, Garrett Ho, Thomas Cheng, Rico Liu, T.W. Leung, D.L.W. Kwong, Shusen Zheng
Journal: Annals of Oncology (2012)
FP14.06 Multicenter Analysis of Mechanisms of Resistance to Osimertinib (O) in EGFR Mutated NSCLC: An ATOMIC Registry Study
Authors: J.M. Bauml, R. Mick, C. Mccoach, J. Weiss, K. Marrone, J. Nieva, L. Villaruz, B. Levy, R. Moreno, R. Murkherji, F. Sun, W. Schwartzman, K. Shaverdashvili, X. Wang, M. Shah, J. Woodley, N. Miller, C. Succe, T. Ullah, C. Lovly, R. Doebele, W. Iams, L. Horn, J. Dowell, G. Liu, N. Leighl, T. Patil, S. Liu, V. Velcheti, D. Aisner, R. Camidge
Journal: Journal of Thoracic Oncology (2021)
Heterogeneity of IFN-Mediated Responses and Tumor Immunogenicity in Patients with Cervical Cancer Receiving Concurrent Chemoradiotherapy
Authors: Jianzhou Chen, Chuangzhen Chen, Yizhou Zhan, Li Zhou, Jie Chen, Qingxin Cai, Yanxuan Wu, Zhihan Sui, Chengbing Zeng, Xiaolong Wei, Ruth Muschel
Journal: Clinical Cancer Research (2021)

Abstract Purpose: To ask whether the expression of immune markers and IFN signaling in tumor biopsies changes during concurrent chemoradiotherapy (CCRT). Experimental Design: Tumor biopsies and peripheral mononuclear blood cells (PMBC) before and immediately after 20 Gy/10 fractions (F) of radiation treatment (RT) from 30 patients with cervical cancer receiving CCRT were evaluated by IHC and qRT-PCR for immune markers and correlated with the short-term response. Results: Tumor immune response to radiation before and after 10F RT as reflected by CD8+ T-cell infiltration had substantial heterogeneity with increases, decreases, and no change all evident. Increases in CD8+ T cells during CCRT correlated with the presence of nuclear IRF1 in tumor cells (r = 0.68, P &amp;lt; 0.0001) and the patient short-term response (P &amp;lt; 0.01). Similarly, in a subset of patients (∼40%) PD-L1 positivity in tumor cells increased, which also correlated with nuclear IRF1 staining (r = 0.48, P &amp;lt; 0.01). Patients with augmented PMBC IFN signature expression after 10F had a significantly higher probability of PD-L1 induction (83% vs. 7%, P &amp;lt; 0.0001). Most patients exhibited abundant expression of SERPINB9 and CD47 in tumor cells, and tumor infiltration by CD68+ cells. SERPINB9 expression correlated with STAT1 signaling in tumor cells. Conclusions: CCRT leads to differential tumor immunogenicity and IFN signaling in patients with cervical cancer, suggesting radiation induction of immunity is limited to a subset of patients and may reflect the heterogeneity of intratumoral induction of IFNs. See related commentary by Mondini and Deutsch, p. 3815
MA05.10 Performance of Draft 2020 USPSTF Lung-Cancer Screening Guidelines and Potential for use of Risk Models to Reduce Racial/Ethnic Disparities
Authors: R. Landy, C. Young, M. Skarzynski, L. Cheung, C. Berg, M.P. Rivera, H. Robbins, A. Chaturvedi, H. Katki
Journal: Journal of Thoracic Oncology (2021)
Therapeutic Ultrasound Triggered Silk Fibroin Scaffold Degradation
Authors: Megan K. DeBari, Xiaodan Niu, Jacqueline V. Scott, Mallory D. Griffin, Sean R. Pereira, Keith E. Cook, Bin He, Rosalyn D. Abbott
Journal: Advanced Healthcare Materials (2021)

Abstract A patient's capacity for tissue regeneration varies based on age, nutritional status, disease state, lifestyle, and gender. Because regeneration cannot be predicted prior to biomaterial implantation, there is a need for responsive biomaterials with adaptive, personalized degradation profiles to improve regenerative outcomes. This study reports a new approach to use therapeutic ultrasound as a means of altering the degradation profile of silk fibroin biomaterials noninvasively postimplantation. By evaluating changes in weight, porosity, surface morphology, compressive modulus, and chemical structure, it is concluded that therapeutic ultrasound can trigger enhanced degradation of silk fibroin scaffolds noninvasively. By removing microbubbles on the scaffold surface, it is found that acoustic cavitation is the mechanism responsible for changing the degradation profile. This method is proved to be safe for human cells with no negative effects on cell viability or metabolism. Sonication through human skin also effectively triggers scaffold degradation, increasing the clinical relevance of these results. These findings suggest that silk is an ultrasound‐responsive biomaterial, where the degradation profile can be adjusted noninvasively to improve regenerative outcomes.
Risk of Suicide Attempt in Patients With Recent Diagnosis of Mild Cognitive Impairment or Dementia
Authors: Mia Maria Günak, Deborah E. Barnes, Kristine Yaffe, Yixia Li, Amy L. Byers
Journal: JAMA Psychiatry (2021)

<h3>Importance</h3> Little is known about the association between mild cognitive impairment (MCI) and suicide. Most studies have focused on dementia and suicidal behavior, with inconsistent results. <h3>Objectives</h3> To examine the association between diagnoses of MCI and dementia and suicide attempt and explore potential psychiatric moderators and to assess whether the association differs based on recency of diagnosis. <h3>Design, Setting, and Participants</h3> This nationwide cohort study integrated 5 national databases from the Department of Veterans Affairs (VA) and Centers for Medicare &amp; Medicaid Services and included all VA medical centers in the US. US veterans 50 years or older with MCI diagnoses at baseline (October 1, 2011, to September 30, 2013) or earlier (October 1, 2007, to September 30, 2011) were propensity matched 1:3 with (1) patients with dementia diagnoses and (2) patients without either diagnosis based on demographic characteristics and the Charlson Comorbidity Index. Diagnoses of MCI or dementia were defined as recent if there were no diagnosis codes before baseline. Data were analyzed from March 16, 2020, to January 15, 2021. <h3>Main Outcomes and Measures</h3> Information on suicide attempts through December 31, 2016, provided by the National Suicide Prevention Applications Network (nonfatal) and Mortality Data Repository (fatal). <h3>Results</h3> The study population of 147 595 participants included 21 085 patients with MCI, 63 255 with dementia, and 63 255 in the propensity-matched comparison group. Participants had a mean (SD) age of 74.7 (10.3) years, 143 353 (97.1%) were men, 4242 (2.9%) were women, and 127 065 (86.1%) were non-Hispanic White. A total of 138 patients with MCI (0.7%) and 400 patients with dementia (0.6%) attempted suicide during follow-up, compared with 253 patients without MCI or dementia (0.4%). Exploratory analyses revealed that no psychiatric comorbidity moderated the association between MCI or dementia and suicide attempt. After adjustment for demographic details and medical and psychiatric comorbidities, risk of suicide attempt was consistently highest for patients with a recent MCI or dementia diagnosis, with adjusted hazard ratios (HRs) of 1.73 (95% CI, 1.34-2.22;<i>P</i> &lt; .001) for recent MCI and 1.44 (95% CI, 1.17-1.77;<i>P</i> = .001) for recent dementia. Risk associated with prior diagnosis was not significant (HR for prior MCI, 1.03 [95% CI, 0.78-1.36;<i>P</i> = .84]; HR for prior dementia, 1.14 [95% CI, 0.95-1.36;<i>P</i> = .15]). <h3>Conclusions and Relevance</h3> This study found that older adults with recent MCI or dementia diagnoses were at increased risk of attempting suicide. These findings suggest that involvement of supportive services at the time of or soon after diagnoses of MCI or dementia may help mitigate risk of suicide attempts.