tbuckley/cabot-search huggingface dataset:
MMS19 is required for NER and transcription in human cells
Authors: Yonghong Yang, Lurdes Queimado
Journal: Cancer Research (2008)

854  Yeast MMS19 encodes a polypeptide necessary for effective nucleotide excision repair (NER) and RNA polymerase II (Pol II) transcription. We have previously reported that human MMS19 is able to complement the NER and RNA Pol II transcription phenotypes of a yeast mms19 deleted strain. Human MMS19 associates with TFIIH by interacting with XPB and XPD, however, the precise functions of MMS19 in mammalian cells have not yet been established.  To determine the functions of MMS19 in mammalian cells we altered the levels of MMS19 in human normal cells by using short interfering RNA (siRNA). MMS19 expression was quantified by RT-PCR and western blotting. Cells expressing normal and low levels of MMS19 were exposed to ultraviolet (UV) radiation and high temperature. Cell viability after UV radiation and incubation at high temperature was analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. UV dose-dependent survival was measured by colony forming ability. The time required for the in vivo removal of UV-induced cyclobutane pyrimidine dimers (CPDs) after UV radiation was determined by NER immunoassay using monoclonal antibodies.  Our data show that human cells with siRNA-mediated depletion of MMS19 have significant decrease in cell viability after either UV radiation or incubation at high temperature. A significant decrease in the removal of CPDs after UV radiation was also observed in MMS19 knockdown cells.  These findings show for the first time that, in human cells, MMS19 protein is required for the effective removal of the UV-induced DNA damage and for efficient transcription at high temperature. Furthermore, our data suggests that the level of MMS19 expression might predict the ability of human cells to survive stress such as exposure to DNA damaging agents and high temperature. These findings might have important implications from human aging to cancer therapy.
Gonadotropin-Secreting Pituitary Macroadenoma Complicated With Hemorrhagic Apoplexy in 18F-FDG PET/CT
Authors: Sebastien Dejust, Benedicte Decoudier, Brigitte Higel, Claude-Fabien Litre, David Morland
Journal: Clinical Nuclear Medicine (2021)

We report the case of 69-year-old man referred for a stage IV pulmonary adenocarcinoma and presenting a decrease in visual acuity. An 18F-FDG PET/CT showed an intense and heterogeneous uptake of a mass in the sellar region. An MRI showed a pituitary macroadenoma associated with a large cyst on the left side, with necrosis zones and fluid level, compressing the optic chiasma. Endocrine testing showed a panhypopituitarism, and pathology confirmed a pituitary apoplexy in a gonadotropin-secreting macroadenoma. No malignant cells were detected. Molecular imaging could have an important role in the detection and characterization of pituitary tumors.
Remote Monitoring for Patients After Ambulatory Surgery—Is It Ready for Prime Time?
Authors: Andrea L. Pusic, Pete Stetson, Larissa Temple
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Abstract 1995: Six-month Clinical Outcome Of Elderly Patients With St-elevation MI According To Reperfusion: Data From The French FAST-MI Registry
Authors: Nicolas Boudou, Vincent Bataille, Tabassome Simon, Georges Amat, Pierre Bareiss, Chu Hautepierre, Jean-Pierre Cambou, Didier Carrié, Nicolas Danchin
Journal: Circulation (2007)

Background: Demographic changes in Western countries’ population have resulted in an increase in the number of elderly patients hospitalized for STEMI. There is a wide gap between the proportion of...
Inadequate Dosage of Mycophenolate Mofetil Is Likely to Yield Substandard Trial Results and Substandard Patient Care—Reply
Authors: Andrea Angeletti, Pietro Ravani, Gian Marco Ghiggeri
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
OP0024 DECREASED LEVELS OF T FOLLICULAR HELPER (CD4+CXCR5+) CELLS AND CD27+CD38+ AND CD27+CD38- B CELLS IN ANKYLOSING SPONDYLITIS PATIENTS CORRELATE WITH MARKER OF INFLAMMATION
Authors: H. Forsblad-D’elia, U. Hellman, A. Kumar, K. Lejon
Journal: Annals of the Rheumatic Diseases (2021)

Background: The role of different lymphocyte subsets in ankylosing spondylitis (AS) is still to be elucidated. It has previously been reported contradictory data concerning the levels of T Follicular Helper (TFH) cells and differentiated B cells in peripheral blood of AS patients. In addition, the connection to disease related parameters is still to be fully revealed. Objectives: The purpose of this study was to investigate the level of CD4+TFH cells and CD27+CD38+/CD38- B cells in patients with AS from northern Sweden and to compare the levels with age and sex-matched controls. We also studied associations between these cell subsets and disease related factors. Methods: Peripheral blood mononuclear cells (PBMSc) from a cohort of 50 patients with AS from Region Västerbotten (mean age 52±9.1 years, 33 (66 %) men, 50 (100 %) HLAB27 positive) and 50 pair wise matched blood donor controls (mean age 54±8.8 years, 33 (66 %) men) were stained with a combination of antibodies allowing for the detection of CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analyzed by flow cytometry. In addition, the patient with AS were examined with spinal x-ray for radiographic alterations assessed with mSASSS. CRP and ESR were measured and physical function and disease activity were registered with BASMI and BASFI respectively ASDAS-CRP and BASDAI. Results: When comparing AS patients and controls pair wise, we observed on average a 50% reduction of TFH (CD3+CD4+CXCR5+) cells among CD45+ lymphocytes in PBMCs from patients (p=0,000008). Furthermore, a 20-30% reduction among memory/plasma cells (CD19+CD27+CD38+ and CD19+CD27+CD38-) among CD45+ lymphocytes in PBMCs from patients (p=0,002 and p=0,007 respectively). For female patients a correlation between TFH and ESR (R s =-0,551 p=0,022) was observed. Moreover, negative correlations between the two B cell subsets (CD19+CD27+CD38+ and CD19+CD27+CD38-) and ESR were observed for female patients (R s =–0,476 p=0,053 and R s =–0,522 p=0,032 respectively). Conclusion: TFH cells was reduced in AS patients and this reduction correlated with a reduction in differentiated (CD27+CD38+ and CD27+CD38-) B cells. In addition, the inflammation marker ESR was negatively correlated with TFH as well as with the differentiated B cell subsets in female patients. Our observations indicates a role of the humoral immune response in AS. Disclosure of Interests: None declared
Real-world prevalence across 159 872 patients with cancer supports the clinical utility of TMB-H to define metastatic solid tumors for treatment with pembrolizumab
Authors: D. Fabrizio, R. Cristescu, L. Albacker, A. Snyder, A. Ward, J. Lunceford, D. Aurora-Garg, F. Jin, J. Hopkins, E. Rubin, P. Hegde
Journal: Annals of Oncology (2021)
AB0796 THE EVALUATION OF LUNG DIAGNOSTIC PROCEDURE AT THE ONSET OF INFLAMMATORY RHEUMATIC DISEASES WITH INTERSTITIAL LUNG DISEASE
Authors: T. Hoffmann, P. Oelzner, F. Marcus, M. Förster, J. Böttcher, G. Wolf, A. Pfeil
Journal: Annals of the Rheumatic Diseases (2021)

Background: Interstitial lung disease (ILD) in inflammatory rheumatic diseases (IRD) is associated with increased mortality. Moreover, the lung is one of the most effected organs on IRD. Consequently, screening methods were required to the detect ILD in IRD. Objectives: The objective of the following study is to evaluate the diagnostic value of lung function test, chest x-ray and HR-CT of the lung in the detection of ILD at the onset of IRD. Methods: The study is designed as a case-control study and includes 126 patients with a newly diagnosed IRD. It was matched by gender, age and the performance of lung function test and chest x-ray. The sensitivity and specificity were verified by crosstabs and receiver operating characteristic (ROC) curve analysis. The study cohort was divided in two groups (ILD group: n = 63 and control group: n = 63). If possible, all patients received a lung function test and optional a chest x-ray. Patients with pathological findings in the screening tests (chest x-ray or reduced diffusing capacity for carbon monoxide (DLCO) &lt; 80 %) maintained a high-resolution computer tomography (HR-CT) of the lung. Additionally, an immunological bronchioalveolar lavage was performed in the ILD group as gold standard for the detection of ILD. Results: The DLCO (&lt; 80 %) revealed a sensitivity of 83.6 % and specificity of 45.8 % for the detection of ILD. Other examined parameter of lung function test showed no sufficient sensitivity as screening test (FVC = Forced Vital Capacity, FEV1 = Forced Expiratory Volume in 1 second, TLC = Total Lung Capacity, TLCO = Transfer factor of the Lung for carbon monoxide). Also, a combination of different parameter did not increase the sensitivity. The sensitivity and specificity of chest x-ray for the verification of ILD was 64.2 % versus 73.6 %. The combination of DLCO (&lt; 80 %) and chest x-ray showed a sensitivity with 95.2 % and specificity with 38.7 %. The highest sensitivity (95.2 %) and specificity (77.4 %) was observed for the combination of DLCO (&lt; 80 %) and HR-CT of the lung. Conclusion: The study highlighted that a reduced DLCO in lung function test is associated with a lung involvement in IRD. DLCO represented a potential screening parameter for lung manifestation in IRD. Especially patients with suspected vasculitis should receive an additional chest x-ray. Based on the high sensitivity of DLCO in combination with chest x-ray or HR-CT for the detection of ILD in IRD, all patients with a reduced DLCO (&lt; 80%) should obtained an imaging of the lung. Disclosure of Interests: None declared
Treatment failure in giant cell arteritis
Authors: Sebastian H Unizony, Min Bao, Jian Han, Yves Luder, Andrey Pavlov, John H Stone
Journal: Annals of the Rheumatic Diseases (2021)

Objective Identify predictors of treatment failure in patients with giant cell arteritis (GCA) receiving tocilizumab in combination with glucocorticoids and in patients with GCA receiving only glucocorticoids. Methods Posthoc analysis of the Giant-Cell Arteritis Actemra trial including 250 patients who received tocilizumab every week plus a 26-week prednisone taper (n=100), tocilizumab every-other-week plus a 26-week prednisone taper (n=49) or placebo plus a 26-week (n=50) or 52-week (n=51) prednisone taper in the intention-to-treat population. Responders for this analysis were patients who maintained remission (no GCA signs/symptoms and no erythrocyte sedimentation rate elevation) through week 52. Treatment failure was defined as inability to achieve remission by week 12 or relapse between weeks 12 and 52. Predictors investigated in univariate and multivariable analyses included patient characteristics, disease-related and treatment-related factors and patient-reported outcomes (PROs). Results 149 patients received tocilizumab plus prednisone (TCZ/PDN) and 101 received placebo plus prednisone (PBO+PDN). After adjustment for confounders, treatment failure was significantly less likely in the TCZ/PDN group than the PBO/PDN group (OR, 0.2; 95% CI, 0.1 to 0.3; p&lt;0.0001). Risk for treatment failure was significantly higher in women than men in the PBO/PDN group (OR, 5.2; 95% CI, 1.6 to 17.2; p=0.007) but not in the TCZ/PDN group. Predictors of treatment failure in the TCZ/PDN group included lower baseline prednisone doses and worse PROs at baseline. Conclusion The strongest risk factors for treatment failure in GCA are treatment with prednisone alone and female sex. Lower starting prednisone doses and impaired PROs are associated with failure to respond to tocilizumab. Trial registration number NCT01791153 .
An enhanced method for nucleic acid detection with CRISPR-Cas12a using phosphorothioate modified primers and optimized gold-nanopaticle strip
Authors: Jiaojiao Gong, Lijuan Kan, Xiuming Zhang, Ying He, Jiaqiang Pan, Liping Zhao, Qianyun Li, Menghao Liu, Jie Tian, Sili Lin, Zhouyu Lu, Liang Xue, Chaojun Wang, Guanghui Tang
Journal: Bioactive Materials (2021)

CRISPR-Cas12a system has been shown promising for nucleic acid diagnostics due to its rapid, portable and accurate features. However, cleavage of the amplicons and primers by the cis- and trans-activity of Cas12a hinders the attempts to integrate the amplification and detection into a single reaction. Through phosphorothioate modification of primers, we realized onepot detection with high sensitivity using plasmids of SARS-CoV-2, HPV16 and HPV18. We also identified the activated Cas12a has a much higher affinity to C nucleotide-rich reporter than others. By applying such reporters, the reaction time required for a lateral-flow readout was significantly reduced. Furthermore, to improve the specificity of the strip-based assay, we created a novel reporter and, when combined with a customized gold-nanopaticle strip, the readout was greatly enhanced owing to the elimination of the nonspecific signal. This established system, termed Targeting DNA by Cas12a-based Eye Sight Testing in an Onepot Reaction (TESTOR), was validated using clinical cervical scrape samples for human papillomaviruses (HPVs) detection. Our system represents a general approach to integrating the nucleic acid amplification and detection into a single reaction in CRISPR-Cas systems, highlighting its potential as a rapid, portable and accurate detection platform of nucleic acids.
GPs are at “breaking point”—how can retired GPs help?
Authors: David M Lewis
Journal: BMJ (2021)

Iacobucci reports that “GPs are at ‘breaking point’ because of the ‘intense’ workload facing doctors and staff.”1 I am a recently retired GP, and this made me feel uncomfortable. As a youthful 61 year old, I feel guilty that those who were so recently colleagues are struggling with this overwork, and those who were so recently patients are not receiving the care they need. …
Editorial: Drowning: a seasonal disease
Authors: R. H. Moser
Journal: JAMA (1974)

The blaze of summer is upon us with all its attendant joys and woes. Despite the charm of warmth and sun after the dreary winter, I am always reminded of a tragedy that occurred one sun-swept day in June, a few years back. I recounted this incident once before,<sup>1</sup>but it bears repetition before a larger audience. One brisk Sunday morning, three teaching sisters of the Third Order of St. Francis were exploring the sea cliffs on an isolated beach on the south shore of Maui. It was a high-surf day and waves charged into the<i>pali</i>in a spectacular show of spray and sound. The youngest, more adventurous sister, a 29-year-old teacher, scrambled down the rocky surface to a vantage point about six feet above the sea. Suddenly a giant wave swept in, engulfed her, and carried her out into the rough water of the cove. One of
OP0311 THE ROLE OF COMORBID PATHOLOGY IN THE PROGRESSIVE COURSE OF ANCA-ASSOCIATED SYSTEMIC VASCULITIS
Authors: A. Chudinov, I. Belyaeva, V. Mazurov, O. Inamova
Journal: Annals of the Rheumatic Diseases (2021)

Background: ANCA-associated systemic vasculitis (AAV) is characterized by a high incidence of complications and high damage index. Comorbid pathology at the onset can significantly worsen the prognosis AAV. The most significant comorbid conditions in patients with AAV are coronary artery disease, hypertension and dyslipidemia. Objectives: The aim of this study was to determine the role of comorbid pathology in the progressive course in patients with AAV. Methods: Patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA) were observed during the first 3 years of the disease and included in this study between 2010 and 2018. At the onset of AAV 75% of patients had significant comorbidities (coronary artery disease, hypertension, dyslipidemia, chronic obstructive pulmonary disease, peptic ulcer, diabetes mellitus, autoimmune thyroiditis and others). Results: In total 209 (165 [79%] female and mean age 51.8 ± 13.2 years) AAV patients (94 GPA; 46 MPA; and 69 EGPA) were included in the analysis. Formation of chronic kidney disease was significantly more frequent in the group of AAV patients with hypertension at the onset, than in patients without hypertension (respectively 37% and 23.6%, p=0.041). Development of thromboembolic complications was significantly more frequent in the group of AAV patients with coronary artery disease at the onset of AAV, than in patients without coronary artery disease (respectively 34% and 14.8%, p=0.034). Dyslipidemia also was risk factor for cardiovascular complications (OR – 3.81, 95% CI (2.43; 8.2) p=0.009). Presence of diabetes mellitus in the AAV onset was risk factor for infectious complications (OR – 1.77, 95% CI (1.14; 3.45) p=0.038). Conclusion: Our study has shown that comorbid pathology increase risk of serious complications and can significantly worsen the prognosis AAV. Prevention of development of comorbid conditions and control of lipid levels, hypertension levels are necessary to prevent the formation of irreversible organ damage. Disclosure of Interests: None declared.
Live-attenuated RNA hybrid vaccine technology provides single-dose protection against Chikungunya virus
Authors: Emily A. Voigt, Jasmine Fuerte-Stone, Brian Granger, Jacob Archer, Neal Van Hoeven
Journal: Molecular Therapy (2021)

We present a live-attenuated RNA hybrid vaccine technology that uses an RNA vaccine delivery vehicle to deliver in vitro-transcribed, full-length, live-attenuated viral genomes to the site of vaccination. This technology allows ready manufacturing in a cell-free environment, regardless of viral attenuation level, and it promises to avoid many safety and manufacturing challenges of traditional live-attenuated vaccines. We demonstrate this technology through development and testing of a live-attenuated RNA hybrid vaccine against Chikungunya virus (CHIKV), comprised of an in vitro-transcribed, highly attenuated CHIKV genome delivered by a highly stable nanostructured lipid carrier (NLC) formulation as an intramuscular injection. We demonstrate that single-dose immunization of immunocompetent C57BL/6 mice results in induction of high CHIKV-neutralizing antibody titers and protection against mortality and footpad swelling after lethal CHIKV challenge.
AB0003 HLA-ALLELES IN SUSCEPTIBILITY TO SYSTEMIC AND OLIGOARTICULAR JUVENILE IDIOPATHIC ARTHRITIS IN THE BELARUSIAN POPULATION
Authors: H. Yatskiu, A. Sukalo, R. Goncharova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Juvenile idiopathic arthritis (JIA) is a complex trait, the most common rheumatic disease in children. Considering clinical heterogeneity of the disease, the genetic background of particular JIA subtypes may also vary significantly. Objectives: This work was aimed to reveal characteristic patterns of HLA associations within 11 loci for two clinically different forms of JIA in the Belarusian population. Methods: 24 patients diagnosed with systemic JIA, 24 patients with oligoarticular JIA and 24 healthy controls were included into the study. The JIA patients were divided into subgroups according to IIAR classification criteria. High-throughput HLA typing was performed using TruSight HLA v2 Sequencing Panel (Illumina) on MiSeq system. Sample analysis was performed using Assign TruSight HLA v2.0 software. Results: DQA1* 05:01:01 and DQB1* 02:01:01 alleles showed protective effect against both systemic (p = 0.007; OR=0.08; 95% CI=[0.009–0.65] and p = 0.01; OR=0.09; 95% CI=[0.01–0.83]) and oliarticular JIA (p = 0.026; OR=0.16; 95% CI=[0.03–0.79] and p = 0.046; OR=0.2; 95% CI=[0.04–1.00], while for DRB1 *03:01 negative association was revealed only for systemic JIA (p = 0.03; OR=0.11; 95% CI=[0.01–0.88]). At the same time the DQB1* 04:02:01 (p=0.026; OR=5.88; 95% CI=[1.20–28.72]) and DRB1* 08:01:01 (p=0.07; OR=3.94; 95% CI=[1.01–15.39]) allele frequencies were significantly higher in patients with oligoarthritis but not systemic JIA when compared with controls. Conclusion: High-throughput HLA typing revealed distinct HLA-alleles associated with different JIA subtypes in the Belarusian population as well as some alleles protective both for oligoartricular and systemic JIA. Disclosure of Interests: None declared
Do monogenic inborn errors of immunity cause susceptibility to severe COVID-19?
Authors: Chris Cotsapas, Janna Saarela, Jocelyn R. Farmer, Vinod Scaria, Roshini S. Abraham
Journal: Journal of Clinical Investigation (2021)

The SARS-CoV-2 virus, which causes COVID-19, has been associated globally with substantial morbidity and mortality. Numerous reports over the past year have described the clinical and immunological profiles of COVID-19 patients, and while some trends have emerged for risk stratification, they do not provide a complete picture. Therefore, efforts are ongoing to identify genetic susceptibility factors of severe disease. In this issue of the JCI, Povysil et al. performed a large, multiple-country study, sequencing genomes from patients with mild and severe COVID-19, along with population controls. Contrary to previous reports, the authors observed no enrichment of predicted loss-of-function variants in genes in the type I interferon pathway, which might predispose to severe disease. These studies suggest that more evidence is needed to substantiate the hypothesis for a genetic immune predisposition to severe COVID-19, and highlights the importance of considering experimental design when implicating a monogenic basis for severe disease.