tbuckley/cabot-search huggingface dataset:
Personal Exposure to Black Carbon at School and Levels of Fractional Exhaled Nitric Oxide in New York City
Authors: Kyung Hwa Jung, Kathleen E. Goodwin, Matthew S. Perzanowski, Steven N. Chillrud, Frederica P. Perera, Rachel L. Miller, Stephanie Lovinsky-Desir
Journal: Environmental Health Perspectives (2021)

Background: Schools are often located near traffic sources, leading to high levels of exposure to traffic-related air pollutants, including black carbon (BC). Thus, the school environment could play in a significant role in the adverse respiratory health of children. Objectives: Our objective was to determine associations between personal BC levels at school and airway inflammation [i.e., fractional exhaled nitric oxide (FeNO)] in school-age children. We hypothesized that higher school BC (SBC) would be associated with higher FeNO. Methods: Children 9–14 years of age in New York City (NYC) (n=114) wore BC monitors for two 24-h periods over a 6-d sampling period, repeated 6 months later. SBC was defined as the average personal BC concentrations measured during NYC school hours (i.e., 0830–1430 hours). FeNO was measured following each 24-h BC monitoring period. Multivariable linear regression in generalized estimating equation models were used to examine associations between SBC and FeNO. Results are presented as percentage difference (PD) in FeNO. Results: Personal BC at school was associated with higher FeNO (PD=7.47% higher FeNO per 1-μg/m3 BC (95% CI: 1.31, 13.9), p=0.02]. Compared with BC exposure during school, a smaller PD in FeNO was observed in association with BC exposure while commuting to and from school [PD=6.82% (95% CI: 0.70, 13.3), p=0.03]. Personal BC in non-school environments and residential BC were not associated with FeNO (p>0.05). A significant association between personal BC at school and FeNO was observed among children with seroatopy who did not have asthma [PD=21.5% (95% CI: 4.81, 40.9), p=0.01]. Discussion: Schools may be important sources of BC exposure that contribute to airway inflammation in school-age children. Our results provide rationale for interventions that target improved air quality in urban schools and classrooms. https://doi.org/10.1289/EHP8985
Patterns of Atopic Eczema Disease Activity From Birth Through Midlife in 2 British Birth Cohorts
Authors: Katrina Abuabara, Morgan Ye, David J. Margolis, Charles E. McCulloch, Amy R. Mulick, Richard J. Silverwood, Alice Sullivan, Hywel C. Williams, Sinéad M. Langan
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> Atopic eczema is characterized by a heterogenous waxing and waning course, with variable age of onset and persistence of symptoms. Distinct patterns of disease activity such as early-onset/resolving and persistent disease have been identified throughout childhood; little is known about patterns into adulthood. <h3>Objective</h3> This study aimed to identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, to examine whether early life risk factors and participant characteristics are associated with these subtypes, and to determine whether subtypes are associated with other atopic diseases and general health in mid-adulthood. <h3>Design, Setting, and Participants</h3> This study evaluated members of 2 population-based birth cohorts, the 1958 National Childhood Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Participant data were collected over the period between 1958 and 2016. Data were analyzed over the period between 2018 and 2020. <h3>Main Outcomes and Measures</h3> Subtypes of atopic eczema were identified based on self-reported atopic eczema period prevalence at multiple occasions. These subtypes were the outcome in models of early life characteristics and an exposure variable in models of midlife health. <h3>Results</h3> Latent class analysis identified 4 subtypes of atopic eczema with distinct patterns of disease activity among 15 939 individuals from the NCDS (51.4% male, 75.4% White) and 14 966 individuals from the BCS70 (51.6% male, 78.8% White): rare/no (88% to 91%), decreasing (4%), increasing (2% to 6%), and persistently high (2% to 3%) probability of reporting prevalent atopic eczema with age. Sex at birth and early life factors, including social class, region of residence, tobacco smoke exposure, and breastfeeding, predicted differences between the 3 atopic eczema subtypes and the infrequent/no atopic eczema group, but only female sex differentiated the high and decreasing probability subtypes (odds ratio [OR], 1.99; 95% CI, 1.66-2.38). Individuals in the high subtype were most likely to experience asthma and rhinitis, and those in the increasing subtype were at higher risk of poor self-reported general (OR, 1.29; 95% CI, 1.09-1.53) and mental (OR 1.45; 95% CI, 1.23-1.72) health in midlife. <h3>Conclusions and Relevance</h3> The findings of this cohort study suggest that extending the window of observation beyond childhood may reveal clear subtypes of atopic eczema based on patterns of disease activity. A newly identified subtype with increasing probability of activity in adulthood warrants additional attention given observed associations with poor self-reported health in midlife.
Incidence of Proliferative Diabetic Retinopathy and Other Neovascular Sequelae at 5 Years Following Diagnosis of Type 2 Diabetes
Authors: William S. Gange, Jennifer Lopez, Benjamin Y. Xu, Khristina Lung, Seth A. Seabury, Brian C. Toy
Journal: Diabetes Care (2021)

OBJECTIVE To determine the incidence and risk factors for developing proliferative diabetic retinopathy (PDR), tractional retinal detachment (TRD), and neovascular glaucoma (NVG) at 5 years after the initial diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS Insured patients aged ≥18 years with newly diagnosed type 2 diabetes and 5 years of continuous enrollment were identified from a nationwide commercial claims database containing data from 2007 to 2015. The incidences of PDR, TRD, and NVG were computed at 5 years following the index diagnosis of type 2 diabetes. Associations between these outcomes and demographic, socioeconomic, and medical factors were tested with multivariable logistic regression. RESULTS At 5 years following the initial diagnosis of type 2 diabetes, 1.74% (1,249 of 71,817) of patients had developed PDR, 0.25% of patients had developed TRD, and 0.14% of patients had developed NVG. Insulin use (odds ratio [OR] 3.59, 95% CI 3.16–4.08), maximum HbA1c &amp;gt;9% or &amp;gt;75 mmol/mol (OR 2.10, 95% CI 1.54–2.69), renal disease (OR 2.68, 95% CI 2.09–3.42), peripheral circulatory disorders (OR 1.88, 95% CI 1.25–2.83), neurological disease (OR 1.62, 95% CI 1.24–2.11), and older age (age 65–74 years) at diagnosis (OR 1.62, 95% CI 1.28–2.03) were identified as risk factors for development of PDR at 5 years. Young age (age 18–23 years) at diagnosis (OR 0.46, 95% CI 0.29–0.74), Medicare insurance (OR 0.60, 95% CI 0.70–0.76), morbid obesity (OR 0.72, 95% CI 0.59–0.87), and smoking (OR 0.84, 95% CI 0.70–1.00) were identified as protective factors. CONCLUSIONS A subset of patients with type 2 diabetes develop PDR and other neovascular sequelae within the first 5 years following the diagnosis with type 2 diabetes. These patients may benefit from increased efforts for screening and early intervention.
Mortality trends over five decades in adult transgender people receiving hormone treatment: a report from the Amsterdam cohort of gender dysphoria
Authors: Christel JM de Blok, Chantal M Wiepjes, Daan M van Velzen, Annemieke S Staphorsius, Nienke M Nota, Louis JG Gooren, Baudewijntje PC Kreukels, Martin den Heijer
Journal: The Lancet Diabetes & Endocrinology (2021)
Convalescent plasma associates with reduced mortality and improved clinical trajectory in patients hospitalized with COVID-19
Authors: Shanna A. Arnold Egloff, Angela Junglen, Joseph S.A. Restivo, Marjorie Wongskhaluang, Casey Martin, Pratik Doshi, Daniel Schlauch, Gregg Fromell, Lindsay E. Sears, Mick Correll, Howard A. Burris, Charles F. LeMaistre
Journal: Journal of Clinical Investigation (2021)

BACKGROUNDEvidence supporting convalescent plasma (CP), one of the first investigational treatments for coronavirus disease 2019 (COVID-19), has been inconclusive, leading to conflicting recommendations. The primary objective was to perform a comparative effectiveness study of CP for all-cause, in-hospital mortality in patients with COVID-19.METHODSThe multicenter, electronic health records-based, retrospective study included 44,770 patients hospitalized with COVID-19 in one of 176 HCA Healthcare-affiliated community hospitals. Coarsened exact matching (1:k) was employed, resulting in a sample of 3774 CP and 10,687 comparison patients.RESULTSExamination of mortality using a shared frailty model, controlling for concomitant medications, date of admission, and days from admission to transfusion, demonstrated a significant association of CP with lower mortality risk relative to the comparison group (adjusted hazard ratio [aHR] = 0.71; 95% CI, 0.59-0.86; P < 0.001). Examination of patient risk trajectories, represented by 400 clinico-demographic features from our real-time risk model (RTRM), indicated that patients who received CP recovered more quickly. The stratification of days to transfusion revealed that CP within 3 days after admission, but not within 4 to 7 days, was associated with a significantly lower mortality risk (aHR = 0.53; 95% CI, 0.47-0.60; P < 0.001). CP serology level was inversely associated with mortality when controlling for its interaction with days to transfusion (HR = 0.998; 95% CI, 0.997-0.999; P = 0.013), yet it did not reach univariable significance.CONCLUSIONSThis large, diverse, multicenter cohort study demonstrated that CP, compared with matched controls, is significantly associated with reduced risk of in-hospital mortality. These observations highlight the utility of real-world evidence and suggest the need for further evaluation prior to abandoning CP as a viable therapy for COVID-19.FUNDINGThis research was supported in whole by HCA Healthcare and/or an HCA Healthcare-affiliated entity, including Sarah Cannon and Genospace.
PHF6 and JAK3 mutations cooperate to drive T-cell acute lymphoblastic leukemia progression
Authors: Shengnan Yuan, Xiaomin Wang, Shuaibing Hou, Tengxiao Guo, Yanjie Lan, Shuang Yang, Fei Zhao, Juan Gao, Yuxia Wang, Yajing Chu, Jun Shi, Tao Cheng, Weiping Yuan
Journal: Leukemia (2021)

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a malignant hematologic disease caused by gene mutations in T-cell progenitors. As an important epigenetic regulator, PHF6 mutations frequently coexist with JAK3 mutations in T-ALL patients. However, the role(s) of PHF6 mutations in JAK3-driven leukemia remain unclear. Here, the cooperation between JAK3 activation and PHF6 inactivation is examined in leukemia patients and in mice models. We found that the average survival time is shorter in patients with JAK/STAT and PHF6 comutation than that in other patients, suggesting a potential role of PHF6 in leukemia progression. We subsequently found that Phf6 deficiency promotes JAK3 M511I -induced T-ALL progression in mice by inhibiting the Bai1-Mdm2-P53 signaling pathway, which is independent of the JAK3/STAT5 signaling pathway. Furthermore, combination therapy with a JAK3 inhibitor (tofacitinib) and a MDM2 inhibitor (idasanutlin) reduces the Phf6 KO and JAK3 M511I leukemia burden in vivo. Taken together, our study suggests that combined treatment with JAK3 and MDM2 inhibitors may potentially increase the drug benefit for T-ALL patients with PHF6 and JAK3 comutation.
Assessment of an Exhaled Breath Test Using High-Pressure Photon Ionization Time-of-Flight Mass Spectrometry to Detect Lung Cancer
Authors: Shushi Meng, Qingyun Li, Zuli Zhou, Hang Li, Xianping Liu, Shuli Pan, Mingru Li, Lei Wang, Yanqing Guo, Mantang Qiu, Jun Wang
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Exhaled breath is an attractive option for cancer detection. A sensitive and reliable breath test has the potential to greatly facilitate diagnoses and therapeutic monitoring of lung cancer. <h3>Objective</h3> To investigate whether the breath test is able to detect lung cancer using the highly sensitive high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). <h3>Design, Setting, and Participants</h3> This diagnostic study was conducted with a prospective-specimen collection, retrospective-blinded evaluation design. Exhaled breath samples were collected before surgery and detected by HPPI-TOFMS. The detection model was constructed by support vector machine (SVM) algorithm. Patients with pathologically confirmed lung cancer were recruited from Peking University People's Hospital, and healthy adults without pulmonary noncalcified nodules were recruited from Aerospace 731 Hospital. Data analysis was performed from August to October 2020. <h3>Exposures</h3> Breath testing and SVM algorithm. <h3>Main Outcomes and Measures</h3> The detection performance of the breath test was measured by sensitivity, specificity, accuracy, and area under the receiver-operating characteristic curve (AUC). <h3>Results</h3> Exhaled breath samples were from 139 patients with lung cancer and 289 healthy adults, and all breath samples were collected and tested. Of all participants, 228 (53.27%) were women and the mean (SD) age was 57.0 (11.4) years. After clinical outcomes were ascertained, all participants were randomly assigned into the discovery data set (381 participants) and the blinded validation data set (47 participants). The discovery data set was further broken into a training set (286 participants) and a test set (95 participants) to construct and test the detection model. The detection model reached a mean (SD) of 92.97% (4.64%) for sensitivity, 96.68% (2.21%) for specificity, and 95.51% (1.93%) for accuracy in the test set after 500 iterations. In the blinded validation data set (47 participants), the model revealed a sensitivity of 100%, a specificity of 92.86%, an accuracy of 95.74%, and an AUC of 0.9586. <h3>Conclusions and Relevance</h3> This diagnostic study's results suggest that a breath test with HPPI-TOFMS is feasible and accurate for lung cancer detection, which may be useful for future lung cancer screenings.
CircMYH9 drives colorectal cancer growth by regulating serine metabolism and redox homeostasis in a p53-dependent manner
Authors: Xin Liu, Yunze Liu, Zhao Liu, Changwei Lin, Fanchao Meng, Lei Xu, Xiuzhong Zhang, Chong Zhang, Penbo Zhang, Shuai Gong, Nai Wu, Zeqiang Ren, Jun Song, Yi Zhang
Journal: Molecular Cancer (2021)

Circular RNAs (circRNAs) play important roles in cancer progression and metabolism regulation. Serine/glycine metabolism supports the growth of cancer cells by contributing to their anabolic demands and epigenome as well as by regulating their redox state. However, the role of circRNA in the regulation of serine/glycine metabolism has not been well elucidated.Microarray analysis was used to screen differentially expressed novel circRNAs. qRT-PCR and FISH were utilized to analyzed the expression of circMYH9. CCK8, colony formation and FACS were used to analyze proliferation of colorectal cancer (CRC) cells. Xenograft experiments were used to analyze tumor growth in vivo. RNA-sequencing, immunoblot and LC-MS were used to identify the downstream metabolic pathway of circMYH9. ChIRP, Mass Spectrometry, RIP and RNA pulldown were utilized to test the interaction between circMYH9, hnRNPA2B1 and p53 pre-mRNA. ChIP-qPCR was used to analyze the binding sites of HIF-1α. Chemically-induced CRC mice were generated to evaluate the role of circMYH9 in tumorigenesis.We identified an intron-derived circRNA, circMYH9, which was significantly upregulated in CRC tissues. A higher circMYH9 level correlated with shorter relapse-free survival and overall survival of CRC patients. CircMYH9 promoted serine/glycine metabolism, the NAD + /NADH ratio, and glutathione recycling and inhibited reactive oxygen species (ROS) in a p53-dependent manner, impacting tumour growth. Mechanistically, circMYH9 destabilized the pre-mRNA of p53 by recruiting hnRNPA2B1 in the nucleus. hnRNPA2B1 bound to N6-methyladenosine sites on the 3' untranslated region of p53 pre-mRNA and maintained its stability. Moreover, a lack of amino acids led to an elevated level of ROS, resulting in increased HIF1α, which promoted circMYH9 expression by binding to the promoter region. Furthermore, in vivo AAV9-mediated transfection of circMYH9 could drive chemically-induced carcinogenesis by suppressing p53 in mice.The overexpression of circMYH9 promotes CRC proliferation though modulating serine/glycine metabolism and redox homeostasis in a p53-dependent manner, and targeting circMYH9 and its pathway may be an effective strategy for the treatment of CRC.
The Bloody Mystery of Glomerular Tuft Development
Authors: Denise K. Marciano
Journal: Journal of the American Society of Nephrology (2021)

In the kidney, the glomerular tuft is an intricate plexus of anastomosing capillaries that acts in concert with podocytes and mesangial cells to form a functional filtration unit. Despite its importance, the cellular and molecular mechanisms that drive glomerular capillary formation, maintenance,
O-5 Frequency of minimal residual disease as measured by ctDNA in mismatch repair deficient tumors following curative resection
Authors: Y. Janjigian, M. Lumish, G. Jayakumaran, M. Fox, S. Sabwa, A. Cercek, Z. Stadler, G. Ku, N. Segal, E. Won, S. Maron, T. Troso-Sandoval, M. Segal, V. Strong, D. Molena, M. Weiser, D. Jones, A. Zehir, M. Berger, L. Diaz
Journal: Annals of Oncology (2021)
COVID-19 and immune-mediated inflammatory diseases: effect of disease and treatment on COVID-19 outcomes and vaccine responses
Authors: Filippo Fagni, David Simon, Koray Tascilar, Verena Schoenau, Michael Sticherling, Markus F Neurath, Georg Schett
Journal: The Lancet Rheumatology (2021)

At the beginning of the COVID-19 pandemic, patients with immune-mediated inflammatory diseases were considered to be at high risk for SARS-CoV-2 infection and the development of severe COVID-19. Data collected over the past year, however, suggest that a diagnosis of inflammatory arthritis, psoriasis, or inflammatory bowel diseases does not increase risk for SARS-CoV-2 infection or severe COVID-19 compared with people without these diseases. Furthermore, substantial data suggest that certain medications frequently used in patients with immune-mediated inflammatory diseases, in particular cytokine inhibitors, might even lower the risk for severe COVID-19. Conversely, glucocorticoids and potentially B-cell-depleting treatments seem to worsen COVID-19 outcomes. Additionally, the first data on SARS-CoV-2 vaccination in patients with these diseases suggest that tolerability of vaccination in patients with immune-mediated inflammatory diseases is good, although the immune response to vaccination can be somewhat reduced in this patient group, particularly those taking methotrexate or CD20-targeted treatment.
Changes in maternal risk factors and their association with changes in cesarean sections in Norway between 1999 and 2016: A descriptive population-based registry study
Authors: Ingvild Hersoug Nedberg, Marzia Lazzerini, Ilaria Mariani, Kajsa Møllersen, Emanuelle Pessa Valente, Erik Eik Anda, Finn Egil Skjeldestad
Journal: PLoS Medicine (2021)

Background Increases in the proportion of the population with increased likelihood of cesarean section (CS) have been postulated as a driving force behind the rise in CS rates worldwide. The aim of the study was to assess if changes in selected maternal risk factors for CS are associated with changes in CS births from 1999 to 2016 in Norway. Methods and findings This national population-based registry study utilizes data from 1,055,006 births registered in the Norwegian Medical Birth Registry from 1999 to 2016. The following maternal risk factors for CS were included: nulliparous/≥35 years, multiparous/≥35 years, pregestational diabetes, gestational diabetes, hypertensive disorders, previous CS, assisted reproductive technology, and multiple births. The proportion of CS births in 1999 was used to predict the number of CS births in 2016. The observed and predicted numbers of CS births were compared to determine the number of excess CS births, before and after considering the selected risk factors, for all births, and for births stratified by 0, 1, or &gt;1 of the selected risk factors. The proportion of CS births increased from 12.9% to 16.1% (+24.8%) during the study period. The proportion of births with 1 selected risk factor increased from 21.3% to 26.3% (+23.5%), while the proportion with &gt;1 risk factor increased from 4.5% to 8.8% (+95.6%). Stratification by the presence of selected risk factors reduced the number of excess CS births observed in 2016 compared to 1999 by 67.9%. Study limitations include lack of access to other important maternal risk factors and only comparing the first and the last year of the study period. Conclusions In this study, we observed that after an initial increase, proportions of CS births remained stable from 2005 to 2016. Instead, both the size of the risk population and the mean number of risk factors per birth continued to increase. We observed a possible association between the increase in size of risk population and the additional CS births observed in 2016 compared to 1999. The increase in size of risk population and the stable CS rate from 2005 and onward may indicate consistent adherence to obstetric evidence-based practice in Norway.
Replication Studies for Database Research
Authors: Christopher P. Childers, Melinda Maggard-Gibbons
Journal: JAMA Surgery (2021)

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