tbuckley/cabot-search huggingface dataset:
Serum Protein Exposure Activates a Core Regulatory Program Driving Human Proximal Tubule Injury
Authors: Kevin A. Lidberg, Selvaraj Muthusamy, Mohamed Adil, Anish Mahadeo, Jade Yang, Ranita S. Patel, Lu Wang, Theo K. Bammler, Jonathan Reichel, Catherine K. Yeung, Jonathan Himmelfarb, Edward J. Kelly, Shreeram Akilesh
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement Whether kidney tubules exposed to nephrotic-range serum protein levels during glomerular filtration are injured remains controversial. This is important because acutely injured tubules can trigger inflammation and fibrosis that can lead to irreversible injury and CKD. Using human kidney tubule 3D microphysiologic systems and orthogonal epigenomic approaches, we found that serum, but not its major protein component albumin, directly induces tubular injury and secretion of proinflammatory components. Similar changes were observed in preclinical models and patients with proteinuric kidney disease. Taken together, our results demonstrate a causal role for serum proteins in tubular injury and identify regulatory mechanisms and novel pathways for intervention. Background The kidneys efficiently filter waste products while retaining serum proteins in the circulation. However, numerous diseases compromise this barrier function, resulting in spillage of serum proteins into the urine (proteinuria). Some studies of glomerular filtration suggest that tubules may be physiologically exposed to nephrotic-range protein levels. Therefore, whether serum components can directly injure the downstream tubular portions of the kidney, which in turn can lead to inflammation and fibrosis, remains controversial. Methods We tested the effects of serum protein exposure in human kidney tubule microphysiologic systems and with orthogonal epigenomic approaches since animal models cannot directly assess the effect of serum components on tubules. Results Serum, but not its major protein component albumin, induced tubular injury and secretion of proinflammatory cytokines. Epigenomic comparison of serum-injured tubules and intact kidney tissue revealed canonical stress-inducible regulation of injury-induced genes. Concordant transcriptional changes in microdissected tubulointerstitium were also observed in an independent cohort of patients with proteinuric kidney disease. Conclusions Our results demonstrate a causal role for serum proteins in tubular injury and identify regulatory mechanisms and novel pathways for intervention.
Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trial
Authors: Carlo Scognamiglio Renner Araujo, Ana Cristina Medeiros-Ribeiro, Carla G S Saad, Karina Rossi Bonfiglioli, Diogo Souza Domiciano, Andrea Yukie Shimabuco, Matheus Santos Rodrigues Silva, Emily Figueiredo Neves Yuki, Sandra Gofinet Pasoto, Tatiana Pedrosa, Leonard de Vinci Kanda Kupa, Gioanna Zou, Rosa M R Pereira, Clóvis Artur Silva, Nádia Emi Aikawa, Eloisa Bonfa
Journal: Annals of the Rheumatic Diseases (2022)

Objective To evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA). Methods This was a single-centre, prospective, randomised, investigator-blinded, intervention study ( NCT04754698 , CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) ≤10, prednisone ≤7.5 mg/day) randomised (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28 and D69. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI &gt;10) and did not withdraw MTX twice. Results Randomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group. Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%), p=0.848) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI &gt;10 at D28. At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%), p=0.019), with parallel augmentation in GMT (34.2 (25.2–46.4) vs 16.8 (11.9–23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI &gt;10 was more frequent in MTX-hold at D69 (p=0.024). Conclusion We provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.
Use of Ebola Vaccine: Expansion of Recommendations of the Advisory Committee on Immunization Practices To Include Two Additional Populations — United States, 2021
Authors: Jason H. Malenfant, Allison Joyce, Mary J. Choi, Caitlin M. Cossaboom, Amy N. Whitesell, Brian H. Harcourt, Robert L. Atmar, Julie M. Villanueva, Beth P. Bell, Christine Hahn, Jamie Loehr, Richard T. Davey, Armand Sprecher, Colleen S. Kraft, Trevor Shoemaker, Joel M. Montgomery, Rita Helfand, Inger K. Damon, Sharon E. Frey, Wilbur H. Chen
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

On December 19, 2019, the Food and Drug Administration (FDA) approved rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO, Merck) for the prevention of Ebola virus disease (EVD) caused by infection with Ebola virus, species Zaire ebolavirus, in adults aged ≥18 years. In February 2020, the Advisory Committee on Immunization Practices (ACIP) recommended preexposure vaccination with ERVEBO for adults aged ≥18 years in the United States who are at highest risk for potential occupational exposure to Ebola virus because they are responding to an outbreak of EVD, work as health care personnel at federally designated Ebola treatment centers in the United States, or work as laboratorians or other staff members at biosafety level 4 facilities in the United States (1).
Sale of UK’s Vaccine Manufacturing and Innovation Centre
Authors: Rebecca E Glover, Adam P Roberts, Andrew C Singer, Claas Kirchhelle
Journal: BMJ (2022)

Amidst the Omicron coronavirus variant, revelations about high profile breaches of pandemic restrictions, and deepening tensions between Ukraine and Russia, a puzzling announcement has escaped the attention of many commentators-the UK government has put its Vaccine Manufacturing Innovation Centre (VMIC) up for sale.
CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4
Authors: Peng Liao, Weimin Wang, Weichao Wang, Ilona Kryczek, Xiong Li, Yingjie Bian, Amanda Sell, Shuang Wei, Sara Grove, Jeffrey K Johnson, Paul D Kennedy, Miguel Gijón, Yatrik M Shah, Weiping Zou
Journal: Cancer Cell (2022)
Black patients with multiple myeloma have better survival than white patients when treated equally: a matched cohort study
Authors: Jing Dong, Zhuping Garacci, Christopher Staffi Buradagunta, Anita D’Souza, Meera Mohan, Ashley Cunningham, Siegfried Janz, Binod Dhakal, Aaron P. Thrift, Parameswaran Hari
Journal: Blood Cancer Journal (2022)

Abstract We assessed differences in survival between non-Hispanic black (NHB) and non-Hispanic white (NHW) patients with multiple myeloma (MM), and the sequential effects of patient characteristics, and diagnosis and treatment-related factors on the survival disparity using data from 3319 NHB and 20,831 NHW MM patients in the SEER-Medicare (1999–2017) database. Four sets of 3319 NHWs were matched sequentially to the same set of 3319 NHBs, based on demographics (age, sex, year of diagnosis, marital status, and SEER site), socioeconomic status (SES, demographics plus SES), presentation factors (SES variables plus comorbidity), and treatment factors (presentation variables plus antimyeloma therapies). We found NHBs were less likely to receive treatment than NHWs even among patients matched for demographics, SES, and comorbidities. The absolute difference in 5-year survival between NHBs and NHWs was not significant in the demographics match (0.6%; P = 0.30) and remained non-significant after matching for SES (1.4%, P = 0.17). When matching for presentation, NHBs had significantly longer 5-year survival than NHWs (absolute difference = 3.8%, P = 0.003). Additional matching on treatment-related factors further enlarged the racial difference in 5-year survival to 4.6% ( P &lt; 0.001). Our findings reinforce the importance of equitable access to effective treatment modalities to further improve the survival of NHB patients with MM.
Sputum cell counts in COPD patients who use electronic cigarettes
Authors: Andrew Higham, Augusta Beech, Natalie Jackson, Simon Lea, Dave Singh
Journal: European Respiratory Journal (2022)

COPD is caused by the inhalation of noxious particles, commonly from cigarette smoking [1]. Smoking cessation is an important part of COPD management. Electronic cigarettes (e-cigarettes) are used by COPD patients to facilitate cigarette smoking cessation [2]. E-cigarettes contain multiple chemicals that can cause inflammation and toxicity [3]. The potential harm caused by long term e-cigarette use in COPD patients is unknown. Electronic cigarette use in COPD ex-smokers causes increased sputum neutrophils <https://bit.ly/3HPIisR> A. Beech and D. Singh are supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). This research was supported by the North West Lung Centre Charity, Manchester. This report is independent research and the views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Minority Enrollment in Phase II and III Clinical Trials in Urologic Oncology
Authors: Jeunice Owens-Walton, Cheyenne Williams, Alexis Rompré-Brodeur, Peter A. Pinto, Mark W. Ball
Journal: Journal of Clinical Oncology (2022)

PURPOSE Proportionate minority representation in clinical trials is an important step toward addressing health care inequities. Given the paucity of data on this topic in urologic oncology, we sought to quantify the enrollment of minority patients in clinical trials studying prostate, kidney, and bladder/urothelial cancers. METHODS The ClincialTrials.gov database was queried for completed phase II and III interventional trials in prostate, kidney, and bladder cancers. The SEER database was used to calculate the US prevalence of these genitourinary cancers. Representation quotients (RQ) were calculated to describe the relative proportion of each racial/ethnic group enrolled in clinical trials over the proportion of persons from each group among national cancer cases by cancer type. RESULTS Of 341 trials that met initial eligibility criteria, only 169 (49.7%) reported data on race or ethnicity. Aggregate RQs from 2000 to 2017 showed that White patients were continually over-represented in trials for all cancer types. Black and Asian patients were poorly represented across all cancer types. When stratified by 3-year increments, the RQs remained stable for all races, from 2000 to 2017. When stratified by ethnicity, Hispanic patients were under-represented across all cancer types in the study period. When examining representation by funding source, we found that US government–funded clinical trials proportionally enroll the most diverse patient populations over those funded by academic institutions and industry. Interestingly, more than 50% of the trials examined did not report race nor ethnicity, highlighting a crucial flaw in investigator compliance with federal clinical trial mandates. CONCLUSION Clinical trials targeting prostate, kidney, and bladder cancers continue to under-represent racial/ethnic minority patients. On the basis of the incidence of these cancers within minority populations, efforts should focus on creating racially and ethnically inclusive cancer research.
Respiratory and allergic outcomes among 5-year-old children exposed to pesticides
Authors: Jessica Y Islam, Jane Hoppin, Ana M Mora, Manuel E Soto-Martinez, Leonel Córdoba Gamboa, Jorge Ernesto Peñaloza Castañeda, Brian Reich, Christian Lindh, Berna van Wendel de Joode
Journal: Thorax (2022)

Background Little is known about the effects of pesticides on children’s respiratory and allergic outcomes. We evaluated associations of prenatal and current pesticide exposures with respiratory and allergic outcomes in children from the Infants’ Environmental Health Study in Costa Rica. Methods Among 5-year-old children (n=303), we measured prenatal and current specific gravity-corrected urinary metabolite concentrations of insecticides (chlorpyrifos, pyrethroids), fungicides (mancozeb, pyrimethanil, thiabendazole) and 2,4-D. We collected information from caregivers on respiratory (ever doctor-diagnosed asthma and lower respiratory tract infections (LRTI), wheeze and cough during last 12 months) and allergic (nasal allergies, itchy rash, ever eczema) outcomes. We fitted separate multivariable logistic regression models for high (≥75th percentile (P75)) vs low (&lt;P75) metabolite concentrations with respiratory and allergic outcomes. We also ran models including metabolite concentrations as continuous exposure variables. Results Children’s respiratory outcomes were common (39% cough, 20% wheeze, 12% asthma, 5% LRTI). High current pyrethroid metabolite concentrations (∑pyrethroids) were associated with wheeze (OR=2.37, 95% CI 1.28 to 4.34), itchy rash (OR=2.74, 95% CI 1.33 to 5.60), doctor-diagnosed asthma and LRTI. High current ethylene thiourea (ETU) (specific metabolite of mancozeb) was somewhat associated with LRTI (OR=2.09, 95% CI 0.68 to 6.02). We obtained similar results when modelling ∑pyrethroids and ETU as continuous variables. We saw inconsistent or null associations for other pesticide exposures and health outcomes. Conclusions Current pyrethroid exposure may affect children’s respiratory and allergic health at 5 years of age. Current mancozeb exposure might contribute to LRTI. These findings are important as pyrethroids are broadly used in home environments and agriculture and mancozeb in agriculture.
Nontuberculous Mycobacteria in Portugal: Trends from the last decade
Authors: A. Santos, S. Carneiro, A. Silva, J.P. Gomes, R. Macedo
Journal: Pulmonology (2022)

Nontuberculous mycobacteria (NTM) are opportunistic human pathogens found in the environment. The transmission seems to be associated with inhalation of aerosol droplets, ingestion or trauma events. Recent studies indicate that NTM disease is increasing worldwide, however, the true clinical impact of NTM infections is difficult to determine due to challenges in discriminating between disease and colonization as they are ubiquitous in the environment. In addition, understanding the epidemiology of NTM is difficult and has not yet been established. In this work, we used a country NTM representative collection from the National Reference Laboratory for Tuberculosis (NRL-TB) of the National Institute of Health (INSA), to characterize the circulation trends of NTM species in Portugal and the most affected regions, contributing to a better understanding of the NTM epidemiology. We conducted a nationwide retrospective study where all individuals with positive NTM cultures at the NRL-TB of the INSA from 2014 to December 2020 were included. Positive cultures were identified using GenoType Mycobacterium CM/AS® (Hain Lifescience) according to manufacturer's instructions, or hsp65 DNA sequencing as previously described. Social-demographic data from patients were also analyzed and patients classified into 3 groups according only to microbiological data, “definite NTM disease”, “NTM colonization” and, “possible NTM disease”. In the period 2014-2020, the NRL-TB performed 50397 cultures. Among these, 1118 cultures were NTM positive retrieved from 944. Most of our cases were in patients whose mean age was 64±15.9 years, and no significant differences between gender was observed, although more frequent in male patients. Overall, from the 944 cases, we were able to identified 93 “definite NTM disease” cases and 79 “possible NTM disease”. Mycobacterium avium complex (MAC) (40,8%), Mycobacterium abscessus-chelonae complex (MABC) (9,6%) and Mycobacterium fortuitum (6,3%) were responsible for most of the infections. The geographical distribution of NTM cases varied significantly and was possible to observe that was independent of population density. The region were most cases occurred was Lisbon Metropolitan Area (31,9%), followed by North (25,3%) and Centre (24,4%), however North region has the highest number of “definite NTM disease” cases (n=33). This is the first national wide epidemiological study on this subject, contributing to a better understanding of NTM dynamics in Portugal. MAC was the NTM species responsible for the majority of infections and, LMA the region with the highest number of cases. It was also possible to conclude that the number of NTM isolates is independent of the demography of the region.
Clonal relations in the mouse brain revealed by single-cell and spatial transcriptomics
Authors: Michael Ratz, Leonie von Berlin, Ludvig Larsson, Marcel Martin, Jakub Orzechowski Westholm, Gioele La Manno, Joakim Lundeberg, Jonas Frisén
Journal: Nature Neuroscience (2022)

Abstract The mammalian brain contains many specialized cells that develop from a thin sheet of neuroepithelial progenitor cells. Single-cell transcriptomics revealed hundreds of molecularly diverse cell types in the nervous system, but the lineage relationships between mature cell types and progenitor cells are not well understood. Here we show in vivo barcoding of early progenitors to simultaneously profile cell phenotypes and clonal relations in the mouse brain using single-cell and spatial transcriptomics. By reconstructing thousands of clones, we discovered fate-restricted progenitor cells in the mouse hippocampal neuroepithelium and show that microglia are derived from few primitive myeloid precursors that massively expand to generate widely dispersed progeny. We combined spatial transcriptomics with clonal barcoding and disentangled migration patterns of clonally related cells in densely labeled tissue sections. Our approach enables high-throughput dense reconstruction of cell phenotypes and clonal relations at the single-cell and tissue level in individual animals and provides an integrated approach for understanding tissue architecture.
Enhancer retargeting of <i>CDX2</i> and <i>UBTF::ATXN7L3</i> define a subtype of high-risk B-progenitor acute lymphoblastic leukemia
Authors: Shunsuke Kimura, Lindsey Montefiori, Ilaria Iacobucci, Yaqi Zhao, Qingsong Gao, Elisabeth M. Paietta, Claudia Haferlach, A. Douglas Laird, Paul E. Mead, Zhaohui Gu, Wendy Stock, Mark Litzow, Jacob M. Rowe, Selina M. Luger, Stephen P. Hunger, Georgina L. Ryland, Breon Schmidt, Paul G. Ekert, Alicia Oshlack, Sean M. Grimmond, Jacqueline Rehn, James Breen, David Yeung, Deborah L. White, Ibrahim Aldoss, Elias J. Jabbour, Ching-Hon Pui, Manja Meggendorfer, Wencke Walter, Wolfgang Kern, Torsten Haferlach, Samuel Brady, Jinghui Zhang, Kathryn G. Roberts, Piers Blombery, Charles G. Mullighan
Journal: Blood (2022)
Reply to: Cause or consequence?
Authors: Eric D. Bateman, David B. Price, Hao-Chien Wang, Patricia Schonffeldt, Angelina Catanzariti, Ralf J.P. van der Valk, Maarten J.H.I. Beekman
Journal: European Respiratory Journal (2022)

<b>SABINA III shows associations between SABA prescriptions and poor asthma outcomes and does not imply causation. However, implying that high SABA use is simply a “consequence” of poor asthma control is also an oversimplification of a complex issue.</b>https://bit.ly/3rXKSGm
Current Cigarette Smoking Among Adults — United States, 2016
Authors: Ahmed Jamal, Elyse Phillips, Andrea S. Gentzke, David M. Homa, Stephen D. Babb, Brian A. King, Linda J. Neff
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Tobacco use remains the single largest preventable cause of death and disease in the United States. According to the 2010 U.S. Surgeon General's report, approximately 443,000 U.S. adults die from smoking-related illnesses each year. In addition, smoking has been estimated to cost the United States $96 billion in direct medical expenses and $97 billion in lost productivity annually. To assess progress toward the Healthy People 2020 (HP2020) objective to reduce cigarette smoking by adults (objective TU-1.1),* CDC's Office on Smoking and Health used data from the 2011 National Health Interview Survey (NHIS) to estimate current national cigarette smoking prevalence. The findings indicate that 19.0% of adults smoked cigarettes in 2011 and no statistically significant change in current adult smoking prevalence occurred from 2010 (19.3%) to 2011 (19.0%). Among daily smokers, the proportion who smoked ≥30 cigarettes per day (CPD) declined significantly, from 12.6% in 2005 to 9.1% in 2011, whereas the proportion of those who smoked 1-9 CPD increased significantly, from 16.4% to 22.0%. To help reduce the national prevalence of cigarette smoking among adults to the HP2020 target of 12%, population-based prevention strategies (e.g., increasing prices of tobacco products, antitobacco media campaigns featuring graphic personal stories on the adverse health impact of smoking, smoke-free laws for workplaces and public places, and barrier-free access to help quitting) will need to be implemented more extensively. Such evidence-based tobacco control interventions can help adults quit and prevent the initiation of tobacco use.
A New Departure in British Medical Education.
Authors: None W. H.
Journal: JAMA (1899)

London, N. W., Jan. 5, 1899. <h3>To the Editor:</h3> —The medical year in England has been marked by three most significant developments. They may indeed be described as epoch-making, although they will scarcely even be mentioned in the "Annus Medicus" or the year books. First and most important is the founding of the London Polyclinic and Medical Graduates' College; second, the establishment by the Government of the School for Tropical Diseases, and third, the magnificent gift of $1,250,000 by Lord Iveagh to the Jenner Institute of Preventive Medicine (videJournal, January 21, p. 146). These are not only important in themselves, but significant of profound changes in public opinion. The Polyclinic is the first formal and adequate recognition on the part of the profession of the value of post graduate instruction in English medical education. The School of Tropical Medicine is a partial recognition of the long ignored duty of