tbuckley/cabot-search huggingface dataset:
Autoimmunity in Acute Poststreptococcal GN: A Neglected Aspect of the Disease
Authors: Bernardo Rodriguez-Iturbe
Journal: Journal of the American Society of Nephrology (2021)

Acute poststreptococcal GN (APSGN) is the prototype of immune complex GN and is associated with manifestations of autoimmune reactivity that have been neglected as epiphenomena. Recently, studies have demonstrated transient antifactor B autoantibodies that activate the alternative complement pathway, bringing self-immunity to a central position in the pathogenesis of APSGN. Therefore, examining other manifestations of autoimmunity that have been reported in association with poststreptococcal GN is of interest. This article reviews the renal and extrarenal manifestations of autoimmune reactivity in APSGN and considers their potential relevance in modifying the usually benign clinical course of the disease. It also discusses related aspects of the nephritogenic antigens, complement activation, and genetic elements associated with immune reactivity and their potential relevance to the familial incidence of the disease.
Insight Into The Molecular Basis Of The Anti‑Hyperglycemic Activity Of Ra‑3 In Type 2 Diabetic Rats And Its Cardioprotective Potential In Cultured Cardiomyoblasts
Authors: R.A. Mosa, S.E. Mabhida, N.F. Sangweni, P.V. Dludla, A.R. Opoku, R. Johnson
Journal: Metabolism (2021)
Engraftment and SDF-1/CXCR4 Signaling in Human CD34+ Hematopoietic Stem/Progenitor Cells Are Regulated By R4 Rgs Subfamily Proteins
Authors: Tsin Sik Wong, Kathy Yuen Yee Chan, Karen Li, Xiao-Bing Zhang, Ting Fan Leung, Chi Kong Li, Kam Tong Leung
Journal: Blood (2017)
Impact of 18F-FDG PET, PET/CT, and PET/MRI on Staging and Management as an Initial Staging Modality in Breast Cancer
Authors: Sangwon Han, Joon Young Choi
Journal: Clinical Nuclear Medicine (2021)

Objectives We performed a systematic review and meta-analysis to evaluate the impact of 18 F-FDG PET, PET/CT, and PET/MRI on staging and management during the initial staging of breast cancer. Methods We searched the PubMed, Embase, Cochrane Library, and KoreaMed databases until March 2020 to identify studies that reported the proportion of breast cancer patients whose clinical stage or management were changed after PET scans. The proportion of changes was pooled using a random-effects model. Subgroup and metaregression analyses were performed to explore heterogeneity. Results We included 29 studies (4276 patients). The pooled proportions of changes in stage and management were 25% (95% confidence interval [CI], 21%–30%) and 18% (95% CI, 14%–23%), respectively. When stage changes were stratified according to initial stage, the pooled proportions were 11% (95% CI, 3%–22%) in stage I, 20% (95% CI, 16%–24%) in stage II, and 34% (95% CI, 27%–42%) in stage III. The relative proportions of intermodality and intention-to-treat changes were 74% and 70%, respectively. Using metaregression analyses, the mean age and the proportion of initial stage III to IV and histologic grade II to III were significant factors affecting the heterogeneity in changes in stage or management. Conclusions Currently available literature suggests that the use of 18 F-FDG PET, PET/CT, or PET/MRI leads to significant modification of staging and treatment in newly diagnosed breast cancer patients. Therefore, there may be a role for routine clinical use of PET imaging for the initial staging of breast cancer.
Improving Glycemic Control in Patients With COVID-19 : A Quality Improvement Project
Authors: N.A. Jadoon, S. Noor, M. Iqbal, N. Pervez
Journal: Metabolism (2021)

Abstract Background Diabetes has emerged as an important risk factor for severe illness and death from COVID-19. Reports have shown that diabetes is common among patients hospitalized in the United Kingdom with COVID-19 illness. Despite a preponderance of evidence that diabetes is associated with poor COVID-19 outcomes, there is a paucity of information on inpatient glycemic control among patients with diabetes and acute hyperglycemia hospitalized with COVID-19. Aim This quality improvement project was conducted to evaluate the current practice of glycemic management in hospitalized COVID patients and improve the glycemic control in these patients. Method 2 PDSA cycles were conducted with inability to continue further due to reduction in incidence of disease. This involved data collection regarding glycemic control in COVID-19 patients with diabetes on wards, focusing on the referral to DSN(Diabetes Specialist Nurses) , monitoring of blood glucose levels, management in case blood glucose levels were out of range. Data was also collected about the characteristics of patients. Results First PDSA showed that although in most cases, there were timely referrals to DSN in many cases, the monitoring and management of glycemic excursions was suboptimal in all cases. Blood glucose monitoring was also variable. In the second PDSA cycle, awareness sessions were conducted around glycemic management among medical and nursing staff. A two page document based on local guidance and recommendations of Association of British Clinical Diabetologists was prepared, and posted in the ward. It was also discussed in the handovers for wards. Results are shown in attached graph. Discussion In conclusion, awareness exercise and provision of guideline summary led to some improvement in glycemic control of these patients. Further PDSA cycles could not be done due to decrease in number of admissions. References 1. Docherty A, Harrison E, Green C, Hardwick H, Pius R, Norman L et al. Features of 20133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020;:m1985. 2. Bode B, Garrett V, Messler J, McFarland R, Crowe J, Booth R et al. Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States. Journal of Diabetes Science and Technology. 2020;14(4):813-821. Keywords: Diabetes, COVID-19, Glycemic control Funding and Conflicts of Interest: None
Deaths from alcohol hit record high during 2020, show figures
Authors: Matthew Limb
Journal: BMJ (2021)

An urgent inquiry is needed to understand why deaths from alcohol hit record levels in England and Wales in the first nine months of 2020, experts have said.

Provisional data from the Office for National Statistics (ONS) covers the period during and after the first lockdown last year.1 These show there were 5460 deaths related to alcohol specific causes registered between January and September 2020—a 16.4% increase compared with the same nine month period in 2019 (4689 deaths). Three quarters of these deaths (79.8%) were caused by alcoholic liver disease.

A peak alcohol specific death rate of 12.8 deaths per 100 000 people was …
A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity
Authors: Kenta Matsuda, Stephen A. Migueles, Jinghe Huang, Lyuba Bolkhovitinov, Sarah Stuccio, Trevor Griesman, Alyssa A. Pullano, Byong H Kang, Elise Ishida, Matthew Zimmerman, Neena Kashyap, Kelly M. Martins, Daniel Stadlbauer, Jessica Pederson, Andy Patamawenu, Nathaniel Wright, Tulley Shofner, Sean Evans, C. Jason Liang, Julián Candia, Angelique Biancotto, Giovanna Fantoni, April Poole, Jon Smith, Jeff Alexander, Marc Gurwith, Florian Krammer, Mark Connors
Journal: Journal of Clinical Investigation (2021)

BACKGROUNDTo understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray.METHODSViral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays.RESULTSAd4-H5-Vtn DNA was shed from most upper respiratory tract-immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine.CONCLUSIONReplicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets.TRIAL REGISTRATIONClinicalTrials.gov NCT01443936 and NCT01806909.FUNDINGIntramural and Extramural Research Programs of the NIAID, NIH (U19 AI109946) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSN272201400008C).
High-throughput assay for measuring p53 ubiquitylation by MDM2.
Authors: Ilia V. Davydov, John H. Kenten, Yassamin J. Safiran, Pankaj Oberoi, Hans A. Biebuyck, Jacob N. Wohlstadter
Journal: Cancer Research (2004)

2077  The activity of p53 tumor suppressor protein is regulated by MDM2, which targets p53 for ubiquitylation and subsequent degradation by proteasomes. MDM2 represents an attractive target for anti-cancer drug development. Inhibition of MDM2 ubiquitin ligase activity is expected to lead to increased growth arrest and apoptosis of p53-positive cancer cells resulting from metabolic stabilization of p53. We developed an in vitro assay for measuring MDM2-catalyzed ubiquitylation of p53 from human recombinant enzymes. Ubiquitylated p53 was detected using electrochemiluminescence on MSD’s SectorHTS™ Reader and Multi-Array Plates. The assay was formatted for high-throughput screening for potential MDM2 inhibitors in 384-well plates.
Harnessing machine learning for development of microbiome therapeutics
Authors: Laura E. McCoubrey, Moe Elbadawi, Mine Orlu, Simon Gaisford, Abdul W. Basit
Journal: Gut Microbes (2021)

The last twenty years of seminal microbiome research has uncovered microbiota's intrinsic relationship with human health. Studies elucidating the relationship between an unbalanced microbiome and disease are currently published daily. As such, microbiome big data have become a reality that provide a mine of information for the development of new therapeutics. Machine learning (ML), a branch of artificial intelligence, offers powerful techniques for big data analysis and prediction-making, that are out of reach of human intellect alone. This review will explore how ML can be applied for the development of microbiome-targeted therapeutics. A background on ML will be given, followed by a guide on where to find reliable microbiome big data. Existing applications and opportunities will be discussed, including the use of ML to discover, design, and characterize microbiome therapeutics. The use of ML to optimize advanced processes, such as 3D printing and in silico prediction of drug-microbiome interactions, will also be highlighted. Finally, barriers to adoption of ML in academic and industrial settings will be examined, concluded by a future outlook for the field.
Prevention of influenza during mismatched seasons in older adults with an MF59-adjuvanted quadrivalent influenza vaccine: a randomised, controlled, multicentre, phase 3 efficacy study
Authors: Jiří Beran, Humberto Reynales, Airi Poder, Charles Y Yu, Punnee Pitisuttithum, Lee Li Yuan, Wim Vermeulen, Carole Verhoeven, Brett Leav, Bin Zhang, Daphne Sawlwin, Esther Hamers-Heijnen, Jonathan Edelman, Igor Smolenov
Journal: The Lancet Infectious Diseases (2021)
PD-L1 on mast cells suppresses effector CD8+ T-cell activation in the skin in murine contact hypersensitivity
Authors: Tomoko Hirano, Tetsuya Honda, Shuto Kanameishi, Yuki Honda, Gyohei Egawa, Akihiko Kitoh, Saeko Nakajima, Atsushi Otsuka, Takashi Nomura, Teruki Dainichi, Tomonori Yaguchi, Takashi Inozume, Tatsuki R. Kataoka, Koji Tamada, Kenji Kabashima
Journal: Journal of Allergy and Clinical Immunology (2021)
Long-Term Efficacy of Dupilumab in Patients With Asthma With an Allergic Phenotype Rolled Over From LIBERTY ASTHMA QUEST: LIBERTY ASTHMA TRAVERSE Study
Authors: Lawrence Sher, Jonathan Corren, Ian Pavord, Nadia Daizadeh, Benjamin Ortiz, Michel Djandji, Yamo Deniz, Paul Rowe
Journal: Journal of Allergy and Clinical Immunology (2021)
Assessment of Anxiety, Depression and Resilience in Food-Allergic Adolescents and Primary Caregivers During the COVID-19 Pandemic
Authors: Ashton Rogers, Emily Seminara, Caitlan Murphy, Diana Munoz-Mendoza, Amika Sood, Ellen Manegold, Brandi Whitaker, Stacie Jones, Amy Scurlock
Journal: Journal of Allergy and Clinical Immunology (2021)
The complement system drives local inflammatory tissue priming by metabolic reprogramming of synovial fibroblasts
Authors: Jasna Friščić, Martin Böttcher, Christiane Reinwald, Heiko Bruns, Benjamin Wirth, Samantha-Josefine Popp, Kellie Irene Walker, Jochen A. Ackermann, Xi Chen, Jason Turner, Honglin Zhu, Lisa Seyler, Maximilien Euler, Philipp Kirchner, René Krüger, Arif B. Ekici, Triin Major, Oliver Aust, Daniela Weidner, Anita Fischer, Fabian T. Andes, Zeljka Stanojevic, Vladimir Trajkovic, Martin Herrmann, Adelheid Korb-Pap, Isabel Wank, Andreas Hess, Johnathan Winter, Viktor Wixler, Jörg Distler, Günter Steiner, Hans P. Kiener, Benjamin Frey, Lasse Kling, Karim Raza, Silke Frey, Arnd Kleyer, Tobias Bäuerle, Timothy R. Hughes, Anika Grüneboom, Ulrike Steffen, Gerhard Krönke, Adam P. Croft, Andrew Filer, Jörg Köhl, Kerstin Klein, Christopher D. Buckley, Georg Schett, Dimitrios Mougiakakos, Markus H. Hoffmann
Journal: Immunity (2021)
The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment
Authors: Hong Zhang, Liwu Fu
Journal: Acta Pharmaceutica Sinica B (2021)

A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2). The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported. Either low or high ALDH2 expression contributes to tumor progression and varies among different tumor types. Furthermore, the ALDH2∗2 polymorphism (rs671) is the most common single nucleotide polymorphism (SNP) in Asia. Epidemiological studies associate ALDH2∗2 with tumorigenesis and progression. This study summarizes the essential functions and potential ALDH2 mechanisms in the occurrence, progression, and treatment of tumors in various types of cancer. Our study indicates that ALDH2 is a potential therapeutic target for cancer therapy.
Systemic inflammatory syndromes with immunodysregulatory phenotype: clinical characteristics, genetic findings and therapeutic response
Authors: Grazielly Pereira Pereira GF, Alex Prado, Jaqueline Brandão Brandão, JC, Francine Zanetti Zanetti, FA, Nazoneth Alberto, None Samucanda alberto, NE, Jorge Kalil, Luiz Fonseca, Fabio Castro Castro, FF, Myrthes Toledo-Barros, Barros, Leonardo Mendonça Mendonça, LO
Journal: Journal of Allergy and Clinical Immunology (2021)
Home insulation also saves lives by reducing wood stove pollution
Authors: Dorothy L Robinson
Journal: BMJ (2021)

As well as creating warmer, healthier homes,1 improved insulation saves lives by reducing wood heater pollution, which is responsible for 56% of the health costs of man made air pollution in New Zealand—NZ$4425 (£2322; €2643; $3200) per wood heater per year.2

Nick Hopkinson, medical director of the British Lung Foundation and Asthma UK, warning of similar problems emerging in the UK, …
Disability, the communication of physical activity and sedentary behaviour, and ableism: a call for inclusive messages
Authors: Brett Smith, Kamran Mallick, Javier Monforte, Charlie Foster
Journal: British Journal of Sports Medicine (2021)

This editorial is a call for action to make physical activity and sedentary behaviour messages inclusive. It focuses on disability. Numerous definitions of disability and ways of identifying as disabled exist across the globe. For example, some people, cultures, organisations and governments prefer for certain reasons to use the term ‘disabled people’, whereas others prefer ‘people with disabilities’ or ‘people with an impairment’.1 Respecting difference in terminology used around the world,1 we align with the social model and thus use the term ‘disabled people’ throughout this editorial. Disability refers to people who have long-term physical (eg, spinal cord injury), sensory (eg, visual impairment), cognitive (eg, learning difficulties) and/or mental impairments (eg, depression), which in interaction with various barriers may hinder their full and effective participation in society on an equal basis with others.2

Despite the benefits of physical activity, many disabled people live insufficiently active lifestyles. They are also more likely to be inactive when compared with non-disabled people.2 Recent UK physical activity guidelines for disabled people recommended doing strength activities on 2 or more days a week and at least 150 min of moderate-intensity aerobic physical activity each week for substantial health gains.2–4 It was also stressed in the UK guidelines that some physical activity is better than nothing as small amounts bring health benefits and the 150-min message alone can be daunting, especially for disabled adults who are mostly inactive.1–4 The new WHO global guidelines for physical activity and disability5 echoed the UK guidelines, providing support for its recommendations.

To maximise the impact of national and global physical activity guidelines, and reduce participation inequalities, inclusive and effective communication …
European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance
Authors: Martin Aringer, Ralph Brinks, Thomas Dörner, David Daikh, Marta Mosca, Rosalind Ramsey-Goldman, Josef S Smolen, David Wofsy, Dimitrios T Boumpas, Diane L Kamen, David Jayne, R Cervera, Nathalie Costedoat-Chalumeau, Betty Diamond, Dafna D Gladman, Bevra Hahn, Falk Hiepe, Søren Jacobsen, Dinesh Khanna, Kirsten Lerstrøm, Elena Massarotti, Joseph McCune, Guillermo Ruiz-Irastorza, Jorge Sanchez-Guerrero, Matthias Schneider, Murray Urowitz, George Bertsias, Bimba F Hoyer, Nicolai Leuchten, Gabriela Schmajuk, Chiara Tani, Sara K Tedeschi, Zahi Touma, Branimir Anic, Florence Assan, Tak Mao Chan, Ann Elaine Clarke, Mary K Crow, László Czirják, Andrea Doria, Winfried Graninger, Bernadett Halda-Kiss, Sarfaraz Hasni, Peter M Izmirly, Michelle Jung, Gábor Kumánovics, Xavier Mariette, Ivan Padjen, José M Pego-Reigosa, Juanita Romero-Diaz, Íñigo Rúa-Figueroa, Raphaèle Seror, Georg H Stummvoll, Yoshiya Tanaka, Maria G Tektonidou, Carlos Vasconcelos, Edward M Vital, Daniel J Wallace, Sule Yavuz, Pier Luigi Meroni, Marvin J Fritzler, Ray Naden, Karen Costenbader, Sindhu R Johnson
Journal: Annals of the Rheumatic Diseases (2021)

Background/objectives The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. Methods We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. Results Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia &lt;4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. Conclusions Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of &gt;80% for all items, explaining the higher overall specificity of the criteria set.
Covid-19: Children less likely to report fever, persistent cough, or appetite loss, large UK study finds
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: Children less likely to report fever, persistent cough, or appetite loss, large UK study finds Elisabeth MahaseYoung people aged five to 17 with covid-19 are less likely to report fever, persistent cough, or appetite loss than adults, according to a UK study of more than a million people.1