tbuckley/cabot-search huggingface dataset:
Utility of Diabetes Type–Specific Genetic Risk Scores for the Classification of Diabetes Type Among Multiethnic Youth
Authors: Richard A. Oram, Seth A. Sharp, Catherine Pihoker, Lauric Ferrat, Giuseppina Imperatore, Adrienne Williams, Maria J. Redondo, Lynne Wagenknecht, Lawrence M. Dolan, Jean M. Lawrence, Michael N. Weedon, Ralph D’Agostino, William A. Hagopian, Jasmin Divers, Dana Dabelea
Journal: Diabetes Care (2022)

Genetic risk scores (GRS) aid classification of diabetes type in White European adult populations. We aimed to assess the utility of GRS in the classification of diabetes type among racially/ethnically diverse youth in the U.S.We generated type 1 diabetes (T1D)- and type 2 diabetes (T2D)-specific GRS in 2,045 individuals from the SEARCH for Diabetes in Youth study. We assessed the distribution of genetic risk stratified by diabetes autoantibody positive or negative (DAA+/-) and insulin sensitivity (IS) or insulin resistance (IR) and self-reported race/ethnicity (White, Black, Hispanic, and other).T1D and T2D GRS were strong independent predictors of etiologic type. The T1D GRS was highest in the DAA+/IS group and lowest in the DAA-/IR group, with the inverse relationship observed with the T2D GRS. Discrimination was similar across all racial/ethnic groups but showed differences in score distribution. Clustering by combined genetic risk showed DAA+/IR and DAA-/IS individuals had a greater probability of T1D than T2D. In DAA- individuals, genetic probability of T1D identified individuals most likely to progress to absolute insulin deficiency.Diabetes type-specific GRS are consistent predictors of diabetes type across racial/ethnic groups in a U.S. youth cohort, but future work needs to account for differences in GRS distribution by ancestry. T1D and T2D GRS may have particular utility for classification of DAA- children.
Serology Test Results and Other Important Characteristics of Patients With Persistent COVID-19 Symptoms—Reply
Authors: Cédric Lemogne, Joane Matta, Olivier Robineau
Journal: JAMA Internal Medicine (2022)

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A Female Career in Research
Authors: Katherine M. Flegal
Journal: Annual Review of Nutrition (2022)

After a long career at the National Center for Health Statistics, I retired and joined the Stanford Prevention Research Center as an unpaid associate. I was once described by a former US Food and Drug Administration commissioner as “one of the great epidemiologists.” The chair of the Harvard nutrition department, speaking on National Public Radio, once described my research as “rubbish.” Both may be exaggerations. Here I address some of the events that led to these contrasting descriptions. I also address the extent to which the so-called Matilda effect may have influenced my career. Are women in science on an equal footing with men? The Matilda effect suggests not. Unlike the Matthew effect for scientists, whereby those of higher prestige accrue a disproportionate share of recognition and rewards, the Matilda effect proposes that women scientists are systematically undervalued and underrecognized. I could never get a faculty job and was often treated like an underling. Nonetheless I persevered to publish highly cited research on several high-profile and sometimes controversial topics. Though overt sexism in science and workplaces has diminished over the course of my career, progress toward eliminating unconscious bias has been slower. The Matthew and Matilda effects are still powerful forces that distort incentives and rewards in science.
Complementary Utility of Dopamine Transporter and Tau PET Imaging in the Diagnosis of Progressive Supranuclear Palsy
Authors: Chenhao Jia, Meiqi Wu, Tzu-Chen Yen, Yanfeng Li, Ruixue Cui
Journal: Clinical Nuclear Medicine (2022)

A 50-year-old woman developed gait disturbances, tendency to fall backwards, bradykinesia, and memory loss over the previous 6 months. Brain 18F-FDG PET/CT was unable to distinguish among APSs (atypical parkinsonian syndromes); PET investigations of dopamine transporter (DAT) function (11C-CFT) and tau pathology (18F-APN-1607) were performed. 11C-CFT PET revealed severe loss of striatal DAT function, whereas significant tau accumulation was observed in the brainstem, basal ganglia, and globus pallidus on 18F-APN-1607 PET. Such finding suggested diagnosis of PSP (progressive supranuclear palsy). This case highlights the value of DAT and tau PET imaging in diagnosis of PSP and differential diagnosis ofAPSs.
Real-life performance of a COVID-19 rapid antigen detection test targeting the SARS-CoV-2 nucleoprotein for diagnosis of COVID-19 due to the Omicron variant
Authors: Paula de Michelena, Ignacio Torres, Ángela Ramos-García, Victoria Gozalbes, Nidia Ruiz, Ana Sanmartín, Pilar Botija, Sandrine Poujois, Dixie Huntley, Eliseo Albert, David Navarro
Journal: Journal of Infection (2022)
Association of SARS-CoV-2 Vaccination During Pregnancy With Pregnancy Outcomes
Authors: Maria C. Magnus, Anne K. Örtqvist, Elisabeth Dahlqwist, Rickard Ljung, Fredrik Skår, Laura Oakley, Ferenc Macsali, Björn Pasternak, Håkon K. Gjessing, Siri E. Håberg, Olof Stephansson
Journal: JAMA (2022)

Data about the safety of vaccines against SARS-CoV-2 during pregnancy are limited.To examine the risk of adverse pregnancy outcomes after vaccination against SARS-CoV-2 during pregnancy.This registry-based retrospective cohort study included 157 521 singleton pregnancies ending after 22 gestational weeks from January 1, 2021, until January 12, 2022 (Sweden), or January 15, 2022 (Norway). The Pregnancy Register in Sweden and the Medical Birth Registry of Norway were linked to vaccination and other registries for identification of exposure and background characteristics.Data on mRNA vaccines-BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)-and 1 viral vector vaccine-AZD1222 (AstraZeneca)-were collected from national vaccination registries.The risk of preterm birth and stillbirth was evaluated using Cox regression models, with gestational day as the time metric and vaccination as a time-dependent exposure variable. The risk of small for gestational age, low Apgar score, and neonatal care admission was evaluated using logistic regression. Random-effects meta-analysis was used to combine results between countries.Among the 157 521 singleton births included in the study (103 409 in Sweden and 54 112 in Norway), the mean maternal age at the time of delivery was 31 years, and 28 506 (18%) were vaccinated against SARS-CoV-2 (12.9% with BNT162b2, 4.8% with mRNA-1273, and 0.3% with AZD1222) while pregnant. A total of 0.7%, 8.3%, and 9.1% of individuals delivering were vaccinated during the first, second, and third trimester, respectively. Vaccination against SARS-CoV-2 was not significantly associated with increased risk of preterm birth (6.2 vs 4.9 per 10 000 pregnancy days; adjusted hazard ratio [aHR], 0.98 [95% CI, 0.91 to 1.05]; I2 = 0%; P for heterogeneity = .60), stillbirth (2.1 vs 2.4 per 100 000 pregnancy days; aHR, 0.86 [95% CI, 0.63 to 1.17]), small for gestational age (7.8% vs 8.5%; difference, -0.6% [95% CI, -1.3% to 0.2%]; adjusted OR [aOR], 0.97 [95% CI, 0.90 to 1.04]), low Apgar score (1.5% vs 1.6%; difference, -0.05% [95% CI, -0.3% to 0.1%]; aOR, 0.97 [95% CI, 0.87 to 1.08]), or neonatal care admission (8.5% vs 8.5%; difference, 0.003% [95% CI, -0.9% to 0.9%]; aOR, 0.97 [95% CI, 0.86 to 1.10]).In this population-based study conducted in Sweden and Norway, vaccination against SARS-CoV-2 during pregnancy, compared with no SARS-CoV-2 vaccination during pregnancy, was not significantly associated with an increased risk of adverse pregnancy outcomes. The majority of the vaccinations were with mRNA vaccines during the second and third trimesters of pregnancy, which should be considered in interpreting the findings.
Hepatic inflammation elicits production of proinflammatory netrin‐1 through exclusive activation of translation
Authors: Romain Barnault, Claire Verzeroli, Carole Fournier, Maud Michelet, Anna Rita Redavid, Ievgeniia Chicherova, Marie‐Laure Plissonnier, Annie Adrait, Olga Khomich, Fleur Chapus, Mathieu Richaud, Maëva Hervieu, Veronika Reiterer, Federica Grazia Centonze, Julie Lucifora, Birke Bartosch, Michel Rivoire, Hesso Farhan, Yohann Couté, Valbona Mirakaj, Thomas Decaens, Patrick Mehlen, Benjamin Gibert, Fabien Zoulim, Romain Parent
Journal: Hepatology (2022)

Abstract Background and Aims Netrin‐1 displays protumoral properties, though the pathological contexts and processes involved in its induction remain understudied. The liver is a major model of inflammation‐associated cancer development, leading to HCC. Approach and Results A panel of cell biology and biochemistry approaches (reverse transcription quantitative polymerase chain reaction, reporter assays, run‐on, polysome fractionation, cross linking immunoprecipitation, filter binding assay, subcellular fractionation, western blotting, immunoprecipitation, stable isotope labeling by amino acids in cell culture) on in vitro–grown primary hepatocytes, human liver cell lines, mouse samples and clinical samples was used. We identify netrin‐1 as a hepatic inflammation‐inducible factor and decipher its mode of activation through an exhaustive eliminative approach. We show that netrin‐1 up‐regulation relies on a hitherto unknown mode of induction, namely its exclusive translational activation. This process includes the transfer of NTN1 (netrin‐1) mRNA to the endoplasmic reticulum and the direct interaction between the Staufen‐1 protein and this transcript as well as netrin‐1 mobilization from its cell‐bound form. Finally, we explore the impact of a phase 2 clinical trial‐tested humanized anti‐netrin‐1 antibody (NP137) in two distinct, toll‐like receptor (TLR) 2/TLR3/TLR6‐dependent, hepatic inflammatory mouse settings. We observe a clear anti‐inflammatory activity indicating the proinflammatory impact of netrin‐1 on several chemokines and Ly6C+ macrophages. Conclusions These results identify netrin‐1 as an inflammation‐inducible factor in the liver through an atypical mechanism as well as its contribution to hepatic inflammation.
Relevance of polyp size for primary endoscopic full-thickness resection of suspected T1 colorectal cancers
Authors: Paul Didden, Rixta A. H. van Eijck van Heslinga, Matthijs P. Schwartz, L. R. Arensman, Frank P. Vleggaar, Wilmar de Graaf, Arjun D. Koch, Michael Doukas, Miangela M. Lacle, Leon M. G. Moons
Journal: Endoscopy (2022)

En bloc local excision of suspected T1 colorectal cancer (CRC) provides optimal tumor risk assessment with curative intent. Endoscopic full-thickness resection (eFTR) with an over-the-scope device has emerged as a local excision technique for T1 CRCs, but data on the upper size limit for achieving a histological complete (R0) resection are lacking. We aimed to determine the influence of polyp size on the R0 rate.eFTR procedures for suspected T1 CRCs performed between 2015 and 2021 were selected from the endoscopy databases of three tertiary centers. The main outcome was R0 resection, defined as tumor- and dysplasia-free margins (≥ 0.1 mm) for both the deep and lateral resection margins. Regression analysis was performed to identify risk factors for R1/Rx resection, mainly focusing on endoscopically estimated polyp size.136 patients underwent eFTR for suspected T1 CRC (median size 15 mm [IQR 13-18 mm]; 83.1 % cancer). The rates of technical success and R0 resection were 87.5 % (119/136; 95 %CI 80.9 %-92.1 %) and 79.7 % (106/136; 95 %CI 72.1 %-85.7 %), respectively. Increasing polyp size was significantly associated with R1/Rx resection (risk ratio 2.35 per 5-mm increase, 95 %CI 1.80-3.07; P < 0.001). The R0 rate was 89.9 % (80/89) for polyps ≤ 15 mm, 71.4 % (25/35) for 16-20 mm, and 11.1 % (1/9) for those > 20 mm.eFTR is associated with a 90 % R0 rate for T1 CRCs of ≤ 15 mm. Performing eFTR for polyps 16-20 mm should depend on access, their mobility, and the availability of alternative resection techniques. eFTR for > 20-mm polyps results in a high R1 rate and should not be recommended.
Abstract PD7-07: Surgical management and contralateral breast cancer risk in women with a history of radiation therapy for Hodgkin lymphoma: Results from a population-based cohort
Authors: Elisheva R Eisenberg, Anna Weiss, Ipshita Prakash, Sonia Skamene, Mark Basik, Jean Francois Boileau, Lissa Ajjamada, Michael Pollak, Stephanie M Wong
Journal: Cancer Research (2022)

Abstract Background: Women with a history of chest radiation for Hodgkin lymphoma are at an increased risk of developing breast cancer. Although mastectomy has historically been recommended for surgical treatment of breast cancers in women with prior radiation exposure, surgical management trends and contralateral breast cancer risk in this population remain undefined. Methods: We performed a population-based retrospective study using the Surveillance, Epidemiology, and End Results (SEER) database from 1990-2016. Our cohort included women who received radiation for Hodgkin lymphoma prior to 30 years old and were diagnosed with a subsequent breast cancer. We evaluated trends in local therapy including rates of breast conserving surgery (BCS) and mastectomy. In those undergoing unilateral surgery, the Kaplan-Meier method was used to estimate the 5- and 10-year cumulative incidence of contralateral breast cancer. Results: Our final cohort included 295 women with a median age of 22 years (range, 8-30 years) at Hodgkin lymphoma diagnosis, and 42 years (range, 22-65 years) at breast cancer diagnosis. Of these patients, 263 (89.2%) presented with unilateral breast cancer, while 32 (10.8%) presented with synchronous bilateral breast cancer. Overall, BCS was performed in 17.3% of patients and mastectomy was performed in 82.7%. In the 263 patients presenting with unilateral breast cancer, 50 (19.0%) underwent BCS and 213 (81.0%) underwent mastectomy. Subgroup analysis of mastectomy patients with surgical laterality information available demonstrated a 40.5% bilateral mastectomy rate. In the entire cohort, the 5-year incidence of contralateral breast cancer in women who underwent unilateral surgery was 9.4% (95% CI, 5.6-15.4), increasing to 20.2% (95% CI, 13.7-29.2) at 10-years of follow up. Hormone receptor status of the index breast cancer was not associated with significant differences in the incidence of contralateral breast cancer (p=0.13). Conclusions: Women with a history of prior chest radiation for Hodgkin Lymphoma with a diagnosis with breast cancer have a 10-year contralateral breast cancer risk of 20%. These findings support consideration of contralateral prophylactic mastectomy during surgical decision-making in this high-risk patient population. Citation Format: Elisheva R Eisenberg, Anna Weiss, Ipshita Prakash, Sonia Skamene, Mark Basik, Jean Francois Boileau, Lissa Ajjamada, Michael Pollak, Stephanie M Wong. Surgical management and contralateral breast cancer risk in women with a history of radiation therapy for Hodgkin lymphoma: Results from a population-based cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-07.
Treating Gestational Diabetes Reduces Birth Weight but Does Not Affect Infant Adiposity Across the 1st Year of Life
Authors: Ravi Retnakaran, Chang Ye, Anthony J. Hanley, Philip W. Connelly, Mathew Sermer, Bernard Zinman, Jill K. Hamilton
Journal: Diabetes Care (2022)

OBJECTIVE The continuum of maternal glycemia in pregnancy shows continuous associations with both 1) neonatal birth weight at delivery and 2) subsequent adiposity later in childhood. While treating gestational diabetes mellitus (GDM) can lower birth weight and thereby disrupt the former association, it is unclear if such treatment reduces childhood adiposity. Thus, we sought to compare anthropometry across the 1st year of life between infants born to women who were treated for GDM and those with lesser degrees of gestational dysglycemia (untreated). RESEARCH DESIGN AND METHODS Anthropometric measurements were performed at 3 months and 12 months of life in 567 infants born to women comprising the following four gestational glucose tolerance groups: 1) women with normoglycemia on both glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy; 2) women with an abnormal GCT but normal OGTT; 3) those with mild gestational impaired glucose tolerance; and 4) women treated for GDM. RESULTS Birth weight progressively increased across the three untreated groups but was lowest in women treated for GDM (P = 0.0004). Similarly, women treated for GDM had the lowest rate of macrosomia (P = 0.02). Conversely, however, there were no differences among the four groups in weight z score, length z score, weight-for-length z score, or BMI z score at either 3 months or 12 months (all P values = NS). Similarly, there were no differences among the groups in triceps/biceps/subscapular/suprailiac skinfold thickness or sum of skinfolds at either 3 months or 12 months (all P values = NS). CONCLUSIONS Despite reducing birth weight and macrosomia, the treatment of GDM does not have analogous effects on infant adiposity across the 1st year of life.
Incidence and Characteristics of Remission of Type 2 Diabetes in England: A Cohort Study Using the National Diabetes Audit
Authors: Naomi Holman, Sarah H. Wild, Kamlesh Khunti, Peter Knighton, Jackie O’Keefe, Chirag Bakhai, Bob Young, Naveed Sattar, Jonathan Valabhji, Edward W. Gregg
Journal: Diabetes Care (2022)

To assess the incidence of remission of type 2 diabetes in routine care settings.People with type 2 diabetes (HbA1c ≥48 mmol/mol [6.5%] or <48 mmol/mol [6.5%] with a prescription for glucose-lowering medications) alive on 1 April 2018 were identified from a national collation of health records in England and followed until 31 December 2019. Remission was defined as two HbA1c measurements of <48 mmol/mol (6.5%) at least 182 days apart, with no prescription for glucose-lowering medications 90 days before these measurements.In 2,297,700 people with type 2 diabetes, the overall incidence of remission per 1,000 person-years was 9.7 (95% CI 9.6-9.8) and 44.9 (95% CI 44.0-45.7) in 75,610 (3.3%) people who were diagnosed <1 year. In addition to shorter duration of diagnosis, baseline factors associated with higher odds of remission were no prescription for glucose-lowering medication, lower HbA1c and BMI, BMI reduction, White ethnicity, female sex, and lower socioeconomic deprivation. Among 8,940 (0.4%) with characteristics associated with remission (diagnosed <2 years, HbA1c <53 mmol/mol [7.0%], prescribed metformin alone or no glucose-lowering medications, BMI reduction of ≥10%), incidence of remission per 1,000 person-years was 83.2 (95% CI 78.7-87.9).Remission of type 2 diabetes was generally infrequent in routine care settings but may be a reasonable goal for a subset of people who lose a significant amount of weight shortly after diagnosis. Policies that encourage intentional remission of type 2 diabetes should seek to reduce the ethnic and socioeconomic inequalities identified.
T-cell exhaustion and residency dynamics inform clinical outcomes in hepatocellular carcinoma
Authors: Maryam Barsch, Henrike Salié, Alexandra Emilia Schlaak, Zhen Zhang, Moritz Hess, Lena Sophie Mayer, Catrin Tauber, Patricia Otto-Mora, Takuya Ohtani, Tobias Nilsson, Lara Wischer, Frances Winkler, Sasikant Manne, Andrew Rech, Annette Schmitt-Graeff, Peter Bronsert, Maike Hofmann, Christoph Neumann-Haefelin, Tobias Boettler, Stefan Fichtner-Feigl, Florian van Boemmel, Thomas Berg, Lorenza Rimassa, Luca Di Tommaso, Anwaar Saeed, Antonio D’Alessio, David J. Pinato, Dominik Bettinger, Harald Binder, E. John Wherry, Michael Schultheiss, Robert Thimme, Bertram Bengsch
Journal: Journal of Hepatology (2022)
CHARACTERISTICS AND SURVIVAL OUTCOMES IN PRIMARY MALIGNANT CARDIAC TUMORS BASED ON HISTOLOGY: INSIGHTS FROM THE SEER DATABASE
Authors: Sanskriti Shrivastava, Mark M Aloysius, Raza Naseer, Hamza Hanif, Chaitanya Rojulpote, Ayla Benge, Milos Babic, Pranjal Kumar Boruah
Journal: Journal of the American College of Cardiology (2022)
Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study
Authors: James Welker, Juan D Pulido, Andrew T Catanzaro, Carlos D Malvestutto, Zihai Li, Jonathan B Cohen, Eric D Whitman, Dana Byrne, Olivia K Giddings, Jordan E Lake, Joel V Chua, Ella Li, Jian Chen, Xiang Zhou, Kun He, Davis Gates, Amarjot Kaur, Jamie Chen, Hung-Yen Chou, Martin Devenport, Raymond Touomou, Shyamasundaran Kottilil, Yang Liu, Pan Zheng, Pan Zheng, Yang Liu, Martin Devenport, Raymond Touomou, Hung-Yen Chou, Jai Thakor, Imaan Khan, Nicole Do, Josephine Faragalla, Andrea Hook, Sarah Kern, Janira V. Ramos, Jason Ward, Jamie Chen, John Higson, Meena Dam, Dawn Serkin, Pooja Karloopia, Wendy Moore, Mark Scofield, David Jeffery Childers, Jeffrey S. Cantrell, Millie Corgan, Ella Li, Jian Chen, Xiang Zhou, Jing Liu, Denise Redvers-Higgins, Hua Han, Jiyun Hou, Yudi Pan, Karyn Tucker, Xiaoyan Zhang, Shyamasundaran Kottilil, Joel V. Chua, Jennifer Husson, Shivakumar Narayanan, Jaqueline Bran, Ka Wing Joyce Lam, Alicia Jeffrey, Olivia K. Giddings, Jennie Pexa, Mario Becerra, James Welker, Kathleen W. Gray, Nicole Richmond, Chukwuemeka Nzelibe, Carlos D. Malvestutto, Susan Koletar, Mahdee Sobhanie, Jan Clark, Zihai Li, Kelsi Reynolds, Karthik Chakravarthy, Kevin Weller, Mohamed Yusuf, Jennifer Severing, Kelley Barley, Juan D. Pulido, Jennifer C. Fulton, William Gil, M.D. Jeanine, Richmond R.N., Sandy Jones, Kristina Clemmer, Dana Byrne, Lisa Pedroza, Emily Nicole Davidson, Amanda Logan, Katie Grant, Eric D. Whitman, Jason Kessler, Robert Roland, Rosemary Stefiniw, Molly Maurer, Salome Geene, Christopher F. Buck, Debra Connolly, Patrice Light, Sunanda Baviskar, Yee Won Low, Kyra Michalski, Pamela Giordano, Jennifer Chao, Michelle Williams, Amulya Makkapati, Andrew T. Catanzaro, Jonathan B. Cohen, Mehad Musbah, Pramila Jaladanki, Ying Yuan, Shilpa Rele, Desirae Stewart, Starlet Lewis, Ian Sankar, Nabulungi Kasumba, Kaylia Biney, Elham Hekmat, Jordan E. Lake, Bindu Akkanti, Melissa J. Reimer-McAtee, Marisel Negret Hernandez
Journal: The Lancet Infectious Diseases (2022)

Non-antiviral therapeutic options are required for the treatment of hospitalised patients with COVID-19. CD24Fc is an immunomodulator with potential to reduce the exaggerated inflammatory response to tissue injuries. We aimed to evaluate the safety and efficacy of CD24Fc in hospitalised adults with COVID-19 receiving oxygen support.
DECLINING TREND OF TRANSAPICAL ACCESS FOR TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH AORTIC STENOSIS: AN ANALYSIS OF NATIONAL INPATIENT SAMPLE FROM 2011-2017.
Authors: Sumit Sohal, Harsh Mehta, Krishna Prasad Kurpad, Rajiv Tayal, Gautam Karteek Visveswaran, Najam Wasty, Sergio Waxman, Marc Cohen
Journal: Journal of the American College of Cardiology (2022)