tbuckley/cabot-search huggingface dataset:
Enhanced Mutation Rate, Relaxed Selection, and the “Domino Effect” are associated with Gene Loss in <i>Blattabacterium</i>, A Cockroach Endosymbiont
Authors: Yukihiro Kinjo, Nathan Lo, Paula Villa Martín, Gaku Tokuda, Simone Pigolotti, Thomas Bourguignon
Journal: Molecular Biology and Evolution (2021)

Intracellular endosymbionts have reduced genomes that progressively lose genes at a timescale of tens of million years. We previously reported that gene loss rate is linked to mutation rate in Blattabacterium, however, the mechanisms causing gene loss are not yet fully understood. Here, we carried out comparative genomic analyses on the complete genome sequences of a representative set of 67 Blattabacterium strains, with sizes ranging between 511 and 645 kb. We found that 200 of the 566 analyzed protein-coding genes were lost in at least one lineage of Blattabacterium, with the most extreme case being one gene that was lost independently in 24 lineages. We found evidence for three mechanisms influencing gene loss in Blattabacterium. First, gene loss rates were found to increase exponentially with the accumulation of substitutions. Second, genes involved in vitamin and amino acid metabolism experienced relaxed selection in Cryptocercus and Mastotermes, possibly triggered by their vertically inherited gut symbionts. Third, we found evidence of epistatic interactions among genes leading to a "domino effect" of gene loss within pathways. Our results highlight the complexity of the process of genome erosion in an endosymbiont.
Associations of Systolic Blood Pressure and Diastolic Blood Pressure With the Incidence of Coronary Artery Disease or Cerebrovascular Disease According to Glucose Status
Authors: Mayuko Harada Yamada, Kazuya Fujihara, Satoru Kodama, Takaaki Sato, Taeko Osawa, Yuta Yaguchi, Masahiko Yamamoto, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Hiroyasu Seida, Wataru Ogawa, Hirohito Sone
Journal: Diabetes Care (2021)

OBJECTIVE To determine associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with new-onset coronary artery disease (CAD) or cerebrovascular disease (CVD) according to glucose status. RESEARCH DESIGN AND METHODS Examined was a nationwide claims database from 2008 to 2016 on 593,196 individuals. A Cox proportional hazards model identified risks of CAD and CVD events among five levels of SBP and DBP. RESULTS During the study period 2,240 CAD and 3,207 CVD events occurred. Compared with SBP ≤119 mmHg, which was the lowest quintile of SBP, hazard ratios (95% CI) for CAD/CVD in the 4 higher quintiles (120–129, 130–139, 140–149, ≥150 mmHg) gradually increased from 2.10 (1.73–2.56)/1.46 (1.27–1.68) in quintile 2 to 3.21 (2.37–4.34)/4.76 (3.94–5.75) in quintile 5 for normoglycemia, from 1.39 (1.14–1.69)/1.70 (1.44–2.01) in quintile 2 to 2.52 (1.95–3.26)/4.12 (3.38–5.02) in quintile 5 for borderline glycemia, and from 1.50 (1.19–1.90)/1.72 (1.31–2.26) in quintile 2 to 2.52 (1.95–3.26)/3.54 (2.66–4.70) in quintile 5 for diabetes. A similar trend was observed for DBP across 4 quintiles (75–79, 80–84, 85–89, and ≥90 mmHg) compared with ≥74 mmHg, which was the lowest quintile. CONCLUSIONS Results indicated that cardiovascular risks gradually increased with increases in SBP and DBP regardless of the presence of and degree of a glucose abnormality. Further interventional trials are required to apply findings from this cohort study to clinical practice.
AB0019 TREATMENT OF AUTOIMMUNE AND INFLAMMATORY SKIN DISEASES USING SKIN-TARGETING BIFUNCTIONAL ANTIBODIES: A LOCALIZED IMMUNOMODULATION APPROACH
Authors: S. Borthakur, P. Mande, D. Rios, P. Halvey, A. Boisvert, M. Rowe, A. Agrawal, M. Borah, M. Cianci, J. L. Viney, K. Kis-Toth, K. L. Otipoby, I. Mascanfroni, N. Higginson-Scott
Journal: Annals of the Rheumatic Diseases (2021)

Background: Current treatment approaches for autoimmune conditions comprise primarily of systemic immunosuppressants or cytokine blockade. The concentration of therapeutic molecules to the tissues that are the sites of autoimmune and inflammatory diseases is a promising approach with the potential to induce therapeutic benefit and avert risks associated with systemic immunotherapies. Pandion Therapeutics is developing a bifunctional antibody platform that can drive localized immune modulation by combining a “tether antibody” that targets a tissue of choice and “an effector end” that activates specific regulatory immune pathways to restore immune-homeostasis. Objectives: Here we report the engineering of a skin-tethered PD-1 agonist and a skin-tethered CD39 that inhibit T cell activation and function and deplete local ATP, respectively, modulating different arms of the immune system in a tissue specific manner. Methods: Biophysical assays were performed to characterize Skin-tethered immune effectors for drug-like properties and in vitro and in vivo assays for target binding, cellular activity and tissue specific-localization. Moreover, these bifunctionals were tested in pathway-relevant preclinical models such as Vitiligo and Contact Hypersensitivity. Results: Biophysical characterization of the bifunctional molecules showed desired drug like properties including specificity, stability, and manufacturability. The skin tethered bifunctionals showed effector activity in in vitro assays and selectively localized to the skin. Skin localization strikingly correlated with a tether-dependent efficacy compared to a non-tether control. Conclusion: We believe that this therapeutic approach has the potential to drive the resolution of cutaneous inflammation, providing an opportunity for developing new targeted therapies for autoimmune and inflammatory skin diseases. Disclosure of Interests: Susmita Borthakur Shareholder of: Pandion Therapeutics Inc., Employee of: Pandion therapeutics Inc., Purvi Mande: None declared, Daniel Rios: None declared, Patrick Halvey: None declared, Angela Boisvert: None declared, MIchael Rowe: None declared, Anisha Agrawal: None declared, Minasri Borah: None declared, Mike Cianci: None declared, Joanne L. Viney Shareholder of: Pandion therapeutics Inc., Consultant of: Harpoon, Finch, Quench, HotSpot, Employee of: Pandion Therapeutics Inc., Katalin Kis-Toth: None declared, Kevin L. Otipoby Shareholder of: Pandion Therapeutics Inc., Employee of: Pandion Therapeutics Inc., Ivan Mascanfroni: None declared, Nathan Higginson-Scott Shareholder of: Pandion Therapeutics Inc., Consultant of: Mediar Tx, Employee of: Pandion Therapeutics Inc.
Aging and CNS Myeloid Cell Depletion Attenuate Breast Cancer Brain Metastasis
Authors: Alex Man Lai Wu, Selamawit Gossa, Ramakrishna Samala, Monika A. Chung, Brunilde Gril, Howard H. Yang, Helen R. Thorsheim, Andy D. Tran, Debbie Wei, Esra Taner, Kristine Isanogle, Yuan Yang, Emma L. Dolan, Christina Robinson, Simone Difilippantonio, Maxwell P. Lee, Imran Khan, Quentin R. Smith, Dorian B. McGavern, Lalage M. Wakefield, Patricia S. Steeg
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Breast cancer diagnosed in young patients is often aggressive. Because primary breast tumors from young and older patients have similar mutational patterns, we hypothesized that the young host microenvironment promotes more aggressive metastatic disease. Experimental Design: Triple-negative or luminal B breast cancer cell lines were injected into young and older mice side-by-side to quantify lung, liver, and brain metastases. Young and older mouse brains, metastatic and naïve, were analyzed by flow cytometry. Immune populations were depleted using antibodies or a colony-stimulating factor-1 receptor (CSF-1R) inhibitor, and brain metastasis assays were conducted. Effects on myeloid populations, astrogliosis, and the neuroinflammatory response were determined. Results: Brain metastases were 2- to 4-fold higher in young as compared with older mouse hosts in four models of triple-negative or luminal B breast cancer; no age effect was observed on liver or lung metastases. Aged brains, naïve or metastatic, contained fewer resident CNS myeloid cells. Use of a CSF-1R inhibitor to deplete myeloid cells, including both microglia and infiltrating macrophages, preferentially reduced brain metastasis burden in young mice. Downstream effects of CSF-1R inhibition in young mice resembled that of an aged brain in terms of myeloid numbers, induction of astrogliosis, and Semaphorin 3A secretion within the neuroinflammatory response. Conclusions: Host microenvironmental factors contribute to the aggressiveness of triple-negative and luminal B breast cancer brain metastasis. CSF-1R inhibitors may hold promise for young brain metastasis patients.
Cognitive performance declines in older adults with type 1 diabetes: results from 32 years of follow-up in the DCCT and EDIC Study
Authors: Alan M Jacobson, Christopher M Ryan, Barbara H Braffett, Rose A Gubitosi-Klug, Gayle M Lorenzi, José A Luchsinger, Victoria R Trapani, Ionut Bebu, Naomi Chaytor, Susan M Hitt, Kaleigh Farrell, John M Lachin
Journal: The Lancet Diabetes & Endocrinology (2021)
An Introduction to Qualitative Inquiry
Authors: Catherine R. Butler, Ann M. O’Hare, Bryan R. Kestenbaum, George G. Sayre, Susan P.Y. Wong
Journal: Journal of the American Society of Nephrology (2021)

Many aspects of care for people with kidney disease cannot be meaningfully understood in numerical terms, and benefit from a qualitative approach to inquiry. Qualitative methodologies were originally developed in the social sciences, but are increasingly used in medical research to address questions
Correspondence on ‘Concomitant use of oral glucocorticoids and proton pump inhibitors and risk of osteoporotic fractures among patients with rheumatoid arthritis: a population-based cohort study’
Authors: Zhen Gong, Fangjie Zhang
Journal: Annals of the Rheumatic Diseases (2021)

We read with deep interest the article by Abtahi et al 1; their study was aimed at investigating the concomitant use of oral glucocorticoids (GCs) and proton pump inhibitors (PPIs) and risk of osteoporotic fractures among patients with rheumatoid arthritis (RA). The authors concluded that there was an interaction between the risk of osteoporotic fractures and concomitant use of oral GCs and PPIs.

However, we noticed that among the disease severity indicators of RA described in the manuscript, the authors did not use any of the following disease activity measures: disease activity score in 28 joints with the erythrocyte sedimentation rate or C reactive protein level, clinical disease activity index, simplified disease activity index, routine assessment of patient index data 3 and patient activity …
AB0754 THE INFLUENCE OF PHYSICAL ACTIVITY ON BODY COMPOSITION AND SELF-ESTEEM IN ADULTS WITH JUVENIL IDIOPATHIC ARTHRITIS
Authors: R. De Oliveira, P. Julio, P. Fernandes, R. Marini, S. Appenzeller
Journal: Annals of the Rheumatic Diseases (2021)

Background: With improvement of treatment, long-term factors influencing quality of life have to be addressed in the care of juvenile idiopathic arthritis (JIA) patients. Objectives: To compare body composition, level of physical activity and self-esteem of adult patients with JIA with control group (CG). Methods: The levels of physical activity were analyzed using the International Physical Activity Questionnaire (IPAQ) short version. The body composition data were collected using the Omrom HBF 514 C vertical electric bioimpedance device. The Rosenberg Self-Esteem Scale was used to assess positive and negative attitude and feelings about themselves, where the lower the score, the higher the individual’s self-esteem. For the statistical analysis of the data, the IBM SPSS software was used with a significance index of p &lt;0.05. Results: We included 81 individuals &gt;18 years, 38 with JIA and 43 healthy people. The female sex was the largest participant in this research, being. There was no significant difference regarding sex [female =28 (73.7%) in JIA and 26 (60.5%) in CG] and age of the groups (29.39 ± 7.6 vs. 31.1 ± 3.1, p = 0.18). The CG showed greater height and body weight (163.5 ± 9.8 vs. 169.6 ± 8.0, p&lt;0.001; 63.07 ± 16.65 vs. 69.33 ± 6.88, p = 0.003, respectively), but no difference in Body Mass Index (BMI) was observed (24.32 ± 4.9 vs. 24.12 ± 2.09, p = 0.8). JIA had a higher percentage of total fat mass (31.65 ± 10.20 vs. 28.47 ± 4.9, p = 0.07), while the CG had a higher percentage of total muscle mass (29.7 ± 6.5 vs. 35.86 ± 6.05, p&lt;0.001). The self-esteem of JIA patients was lower than in the CG (21 ± 3.9 vs. 16.26 ± 4.3, p&lt;0.001). In the IPAQ classifications, JIA patients were classified as less physically active than the CG (2.63% vs. 20.93%, p = 0.022), less irregularly active (5.26% vs. 23.25, p = 0.023) and a higher level of sedentary lifestyle (65.78% vs. 25.58%, p&lt;0.001). A higher percentage of muscle mass was associated with greater self-esteem (r=-0.3; p=0.01). Conclusion: The low practice of physical activities by patients with JIA seems to directly influence both, their body composition and their self-esteem. These patients should be encouraged to increase physical activity from an early age by a multiprofessional healthcare team to seek improvement their quality of life. Disclosure of Interests: None declared
An MRI-trackable therapeutic nanovaccine preventing cancer liver metastasis
Authors: Bing Xiao, Dongdong Li, Hongxia Xu, Xiaoxuan Zhou, Xiaodan Xu, Yue Qian, Feidan Yu, Hongjie Hu, Zhuxian Zhou, Xiangrui Liu, Jianqing Gao, Nigel K.H. Slater, Youqing Shen, Jianbin Tang
Journal: Biomaterials (2021)
Covid-19: PM’s former chief aide accuses health secretary of lying over PPE and access to treatment
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The prime minister’s former chief adviser Dominic Cummings has launched an incendiary attack on England’s health secretary’s handling of the covid-19 pandemic, accusing Matt Hancock of “lying to everybody on multiple occasions.”

In an evidence session before MPs from the health and science select committees on 26 June, Cummings claimed that Hancock, under pressure to explain the shortage of personal protective equipment (PPE) last April, had falsely accused NHS England’s chief Simon Stevens and the Treasury of blocking orders.

Cummings said a subsequent investigation by the now former cabinet secretary Mark Sedwill found this to be false, prompting both Cummings and Sedwill to urge the prime minister to remove Hancock from his post.

Cummings said, “The secretary of state for health should have been fired for at least 15 to 20 things, including lying to everybody on multiple occasions in meeting after …
scGRNom: a computational pipeline of integrative multi-omics analyses for predicting cell-type disease genes and regulatory networks
Authors: Ting Jin, Peter Rehani, Mufang Ying, Jiawei Huang, Shuang Liu, Panagiotis Roussos, Daifeng Wang
Journal: Genome Medicine (2021)

Abstract Understanding cell-type-specific gene regulatory mechanisms from genetic variants to diseases remains challenging. To address this, we developed a computational pipeline, scGRNom ( s ingle- c ell G ene R egulatory N etwork prediction from multi- om ics), to predict cell-type disease genes and regulatory networks including transcription factors and regulatory elements. With applications to schizophrenia and Alzheimer’s disease, we predicted disease genes and regulatory networks for excitatory and inhibitory neurons, microglia, and oligodendrocytes. Further enrichment analyses revealed cross-disease and disease-specific functions and pathways at the cell-type level. Our machine learning analysis also found that cell-type disease genes improved clinical phenotype predictions. scGRNom is a general-purpose tool available at https://github.com/daifengwanglab/scGRNom .
POS0297 HOSPITAL ADMISSIONS FOR PATIENTS WITH RHEUMATOID ARTHRITIS IN WESTERN AUSTRALIA HOSPITALS HAVE DECLINED OVER TIME
Authors: K. Almutairi, J. Nossent, D. Preen, H. Keen, C. Inderjeeth
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) represents a substantial burden on patients and society in terms of morbidity, enduring disability, and medical expenses (1). RA prevalence is poorly described in Australia, and linked health datasets can provide a more meaningful picture for RA epidemiology in the Australian population. Objectives: To describe the period prevalence rate of RA patients per 1000 hospital separations coded as RA primary or secondary diagnosis in Western Australia (WA) hospitals between 1995 and 2014. Methods: We extracted data on all patients identified in the WA Hospital Morbidity Data Collection between 1995 and 2014, with the International Classification of Diseases (ICD) codes for RA (ICD 10 M05.00–M06.99, and the corresponding ICD 9 codes). We estimated period prevalence rates per 1000 hospital separations and annual average percentage changes, with the total number of hospital separations each year. Results: A total of 17,125 patients were admitted to WA hospitals with a diagnostic code for RA over the study period (1995-2014). The total number of hospital separations for RA patients was 50,353, indicating an average of three hospital separations per patient over twenty years. The RA prevalence was 3.4 per 1000 separations over the study period, with a -2.89% annual average decrease since 1995. Conclusion: These data demonstrate that hospitalisation for RA has decreased considerably in WA over the last two decades. As this decrease roughly coincides with the introduction of biological drug treatment for RA, the reduced need for hospital admission is likely due to improvements in RA management. References: [1]Uhlig T, Moe RH, Kvien TK (2014) The burden of disease in rheumatoid arthritis. Pharmacoeconomics 32:841-851. doi:10.1007/s40273-014-0174-6 Acknowledgements: Khalid Almutairi was supported by an Australian Government Research Training Program PhD Scholarship at the University of Western Australia. Disclosure of Interests: Khalid Almutairi: None declared, Johannes Nossent Speakers bureau: Janssen, David Preen: None declared, Helen Keen Speakers bureau: Pfizer Australia, Abbvie Australia, Charles Inderjeeth Speakers bureau: Eli Lilly
POS0796 SURVIVAL OF GIANT CELL ARTERITIS PATIENTS IN SLOVENIA
Authors: A. Hočevar, A. Viršček, R. Jese, M. Tomsic, Z. Rotar
Journal: Annals of the Rheumatic Diseases (2021)

Background: Recent meta-analysis reported no difference in the long-term mortality of GCA patients at a population level, but an increased mortality in hospital-based cohorts 1 . Objectives: The aim of our study was to evaluate for the first time the survival of GCA patients in Slovenia. Methods: We included patients with clinical diagnosis of GCA supported by histology or imaging diagnosed between September 2011 and December 2019 and prospectively followed at our secondary/tertiary rheumatology center. To evaluate mortality the censor date of 24. June 2020 was used. Kaplan–Meier analysis was used to analyze mortality. Standardized mortality ratio (SMR) was calculated using data of age matched Slovenian population as the reference. Results: Between September 2011 and December 2019 we identified 309 new GCA patients (203 (65.7%) females, median (IQR) age 74.9 (67.7–80.1.7), range 53.7 to 97.5 years). Patients were followed (until death or censor date) of a median (IQR) 33.3 (17.5-60.8) months. Until the censor date 51 (16.5%) GCA patients died (24 females, 27 males). We found no significant sex related differences in the net survival estimates during the first five years of follow up (p=0.68). Figure 1 shows the survival curve of GCA patients and general population as a comparator according to Kaplan–Meier analysis. In the first year following GCA diagnosis the mortality rate was 1.9 times higher compared to general Slovenian population (95% CI 1.19 - 2.88, p=0.03). For patients who survived the first year after diagnosis the mortality was comparable to the general population (Table 1). Figure 1. Survival curve according to Kaplan–Meier analysis in GCA Table 1. Standardized mortality ratios of patients who survived the first year after diagnosing GCA (ie. were followed at least one year) compared to the general population Years of FU Observed deaths Expected deaths SMR (95%CI) P-value 2 11 9.7 1.14 (0.57-2.03) 0.753 3 14 16.5 0.85 (0.46-1.43) 0.626 4 21 21.6 0.97 (0.60-1.49) 0.987 5 25 25.0 1.00 (0.65-1.48) 0.921 6 26 27.6 0.94 (0.61-1.38) 0.831 Legend: FU follow up; SMR Standardized mortality ratios; CI confidence interval Conclusion: GCA patients had an increased risk of death in the first year from the GCA diagnosis. References: [1]Hill CL, et al. Semin Arthritis Rheum . 2017;46(4):513-9. Disclosure of Interests: None declared
Abstract 16893: Mortality Benefit Associated With Catheter Ablation of Ventricular Tachycardia in Non-ischemic Cardiomyopathy: A Propensity Score-Matched Analysis of In-hospital Outcomes in the United States
Authors: David F Briceno Gomez, Tanush Gupta, Jorge Romero, Dhaval Kolte, Sahil Khera, Pedro A Villablanca, An Tran, Chintan Trivedi, Carola Gianni, Sanghamitra Mohanty, Prasant Mohanty, Mario Garcia, Gregg C Fonarow, Deepak L Bhatt, Andrea Natale, Luigi Di Biase
Journal: Circulation (2017)

Background: Monomorphic ventricular tachycardia (VT) is an important cause of morbidity and mortality. Use and outcome data on mortality benefit of catheter ablation for VT in non-ischemic cardiomy...
Genomic survey of SARS-CoV-2 vaccine breakthrough infections in healthcare workers from Kerala, India
Authors: Beena Philomina J, Bani Jolly, Neethu John, Rahul C. Bhoyar, Nisha Majeed, Vigneshwar Senthivel, Fairoz CP, Mercy Rophina, Bindhu Vasudevan, Mohamed Imran, Prasanth Viswanathan, V.R. Arvinden, Anoop Joseph, Mohit Kumar Divakar, Priyanka R Nair, Afra Shamnath, P. Jayesh Kumar, Abhinav Jain, P. Geetha, Anjali Bajaj, Samatha Mathew, Vishu Gupta, Srashti Jyoti Agrawal, Vinod Scaria, Sridhar Sivasubbu, Chandni Radhakrishnan
Journal: Journal of Infection (2021)
Reporting of Sociodemographic Variables in Randomized Clinical Trials, 2014-2020
Authors: Aaron M. Orkin, Gina Nicoll, Navindra Persaud, Andrew D. Pinto
Journal: JAMA Network Open (2021)

This cross-sectional study assesses the frequency and thoroughness of reporting of sociodemographic variables in randomized clinical trials published in 5 high-impact health journals from January 2014 to July 2020.