tbuckley/cabot-search huggingface dataset:
Abstract 049: De Novo Postpartum Hypertension In A Safety-net Hospital: Incidence And Risk Factors
Authors: Samantha E Parker, Ayodele Ajayi, Christina Yarrington
Journal: Circulation (2021)

Introduction: Postpartum hypertension can be persistent, following a pregnancy complicated by hypertension, or new onset ( de novo ), following a normotensive pregnancy. The postpartum period is traditionally defined as six weeks after delivery, yet accruing evidence shows that hypertension underlies the majority of severe maternal morbidity events through a year postpartum. While guidelines for enhanced monitoring of women at risk of persistent postpartum hypertension exist, less is known about risk factors for de novo postpartum hypertension. The aim of this study is to estimate the incidence of and identify risk factors for de novo postpartum hypertension among a diverse safety-net hospital population through the entire year postpartum. Hypothesis: We assessed the hypothesis that women with de novo postpartum hypertension share similar demographic and reproductive characteristics to women at increased risk of cardiovascular related maternal morbidity. Methods: We conducted a cohort study of 8,531 deliveries at Boston Medical Center from 2016-2018. Data on demographics, reproductive history, and labor and delivery were obtained from medical records. All documented blood pressure measures from pregnancy through 12 months postpartum were extracted. Women with chronic hypertension or hypertensive disorders of pregnancy were excluded. De novo postpartum hypertension was defined as two separate blood pressure readings with systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg at least 48 hours after delivery. Severe de novo hypertension was defined using criteria of SBP ≥160 and/or DPB ≥110. We examined the distribution of demographic and pregnancy characteristics among women with and without de novo postpartum hypertension. Secondary analyses restricting to women with healthcare visits after six weeks postpartum were also conducted. Results: Among the 6,631 women without a history of hypertension, 10% (n=660) developed de novo postpartum hypertension; a third of whom had severe hypertension (n=225). Compared to women without de novo hypertension; cases were more likely to be non-Hispanic Black; delivered via cesearean section; have had a preterm delivery; and be multiparous. In analyses restricted to women with visits extending past six weeks postpartum (n=3,272), the incidence of de novo postpartum hypertension was 16.6%. Approximately 30% of these cases were diagnosed after the traditionally used six week period. Conclusion: In conclusion, 1 in 10 women with normotensive pregnancies experience de novo hypertension in the year after delivery, with a third of these cases developing after six weeks. Opportunities to monitor and manage women at the highest risk of de novo hypertension throughout the entire year postpartum could mitigate cardiovascular related maternal morbidity.
Removing Race From Kidney Function Estimates—Reply
Authors: James A. Diao, Neil R. Powe, Arjun K. Manrai
Journal: JAMA (2021)

In Reply In response to our study on the implications of removing race from eGFR,1 Ms van der Burgh and colleagues describe advantages of eGFRcys, including potentially improved prediction of cardiovascular events and mortality in patients with CKD.
151P Impact of germline BRCA (gBRCA) mutation (m) status on clinical characteristics and patterns of care among women with early breast cancer (eBC): An analysis of the observational prospective CANTO cohort
Authors: A. Bertaut, J. Blanc, B. Pistilli, A. Dhaini Merimeche, O. Rigal, C. Coutant, M. Fournier, C.C. Jouannaud, P. Soulie, F. Lerebours, P.H. Cottu, O. Tredan, L. Vanlemmens, C. Levy, M-A. Mouret-Reynier, M. Campone, A-L. Martin, A. Jacquet Jacquet, N. Briot, I. Vaz-Luis
Journal: Annals of Oncology (2021)
Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review
Authors: Christoph U. Correll, Samuele Cortese, Giovanni Croatto, Francesco Monaco, Damir Krinitski, Gonzalo Arrondo, Edoardo G. Ostinelli, Caroline Zangani, Michele Fornaro, Andrés Estradé, Paolo Fusar‐Poli, Andre F. Carvalho, Marco Solmi
Journal: World Psychiatry (2021)

Top‐tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this jour­nal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial inter­ventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta‐analyses (NMAs) and meta‐analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co‐primary outcomes were disease‐specific symptom reduction and all‐cause discontinuation (“acceptability”). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co‐primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta‐analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention‐deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive‐compulsive disorder; CBT in post‐traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence‐based information for clinical decision making.
만성 B형 간염에서 알파 인터페론 치료에 대한 반응과 B형 간염 바이러스 core 유전자 변이와의 상관 관계
Authors: 유병철, Kim Hyung Joon, 도재혁, 박실무
Journal: Clinical and Molecular Hepatology (2002)

목적: B형 간염 바이러스 core 유전자 변이는 세포독성 T 임파구가 바이러스에 간염된 간세포를 인지하는 것을 방해하여 면역제거로부터의 회피를 유도하는 인터페론의 치료 반응에 영향을 미칠 수 있는 것으로 알려져 있다. 본 연구는 HBV core 유전자의 변이가 알파 인터페론 치료의 비반응과 연관이 있는 지를 규명하고자 하였으며 또한 치료에 반응 후 재발된 경우에서 재발이 HBV core 유전자 변이종의 출현에 의한 것인지를 알아보고자 하였다. 대상과 방법: 만성 B형 간염으로 알파 인터페론 치료를 받은 환자중 HbeAg, HBV DNA가 소실되고 생화학검사상, ALT치도 정상을 유지하 반응군 10예, 치료에 반응하지 않은 비반응군 10예, 치료 후 반응을 보인후 다시 HbeAg과 HBV DNA가 양전되고 ALT치가 상승한 재발군 10예를 대상으로 치료 전과 재발 후의 혈청에서 HBV DNA를 추출하여 중합효소연쇄반응 후 core 유전자의 염기서열을 분석하였다. 결과: 반응군에서는 7개의 과오 돌연변이와 71개의 침묵 돌연변이가 관찰되었으나 비반응군에서는 43개의 과오 돌연변이와 109개의 침묵 돌연변이가 관찰되어 비반응군에서 유의하게 core유전자 변이의 빈도가 높았다. 재발군에서는 8개의 과오 돌연변이와 74개의 침묵 돌연변이가 관찰 되었으며 치료 전과 비교한 재발 후의 염기서열에서는 6개의 핵산 치환이 관찰되었으나 모두 침묵 돌연변이이었다. 과오 돌연변이가 집중적으로 발생한 부의는 codon 30-50 사이와 codon 80-100사이였다. 결론: HBV core 유전자의 변이는 알파 인터페론의 치료 반응에 영향을 미치는 요소의 하나로 생가된다. 그러나 치료 후 재발의 원인은 알파 인터페론 치료중 core 유저자 변이혀의 발생에 의한 것은 아니며 숙주 바이러스 관계에서의 다른 요인이 있을 것으로 생각된다.
Bcr-Abl expression induces redox imbalance with a preferential increase in hydrogen peroxide
Authors: Hui Zhang, Geetha Achanta, Li Feng, Ralph B. Arlinghaus, Peng Huang
Journal: Cancer Research (2006)

382  The Bcr-Abl fusion protein is generated through the t(9;22) chromosome translocation, and is manifested in most patients with chronic myelogenous leukemia (CML) and in a sub-group of patients with acute lymphocytic leukemia (ALL). Previous studies have observed an increased ROS generation in cells expressing Bcr-Abl. However, the specific type of reactive oxygen species and the mechanisms by which Bcr-Abl induces ROS generation remain unclear. The current study was undertaken to examine the correlation between Bcr-Abl expression, ROS production and the down-stream cellular responses, and to investigate the mechanistic basis for Bcr-Abl induced cellular redox imbalance. The murine Da-1-3b cell line generated by stable transfection of bcr/abl into the parental Da-1 cells, and the tetracycline-inducible bcr/abl-transfected cell lines TonB210 and 32D were used for this study. We demonstrated that the levels of Bcr-Abl expression were correlated with a significant increase in intracellular hydrogen peroxide production. Interestingly, there was only a minimum increase in superoxide levels without significant change in the antioxidant enzyme MnSOD expression, suggesting that the increase of hydrogen peroxide in Bcr-Abl expressing cells was unlikely from the conversion of superoxide to hydrogen peroxide by MnSOD in the mitochondria. Analysis of cellular morphology showed that there was an increase in cell volume in association with Bcr-Abl protein expression. Immunoblot analysis demonstrated that induction of Bcr-Abl protein resulted in a rise in mitochondrial Hsp60 expression, and Bcr-Abl appeared to be translocated to mitochondria. Our data suggest that expression of Bcr-Abl causes redox imbalance in the cells with a preferential increase of hydrogen peroxide, and is apparently associated with mitochondrial stress. Experiments are currently being conducted to determine the mechanism by which Bcr-Abl protein expression induces ROS production, the sites of ROS generation, and the relevant biological consequences.
ヘモグロビンE βサラセミアにおけるメトヘモグロビン血症およびアスコルビン酸欠乏: 代謝的および臨床的意義
Authors: Allen Angela, Fisher Christopher, Premawardhena Anuja, Bandara Dayananda, Perera Ashok, Allen Stephen, Pierre Timothy St, Olivieri Nancy, Weatherall David
Journal: Blood (2012)
Abstract 15339: Prediction of Severe Right Ventricular Failure After Left Ventricle Assist Device Using Echocardiographic Right Ventricular Dp/dt
Authors: Dan L Li, Vineet Agrawal, Gabriel Hernandez, Emily M Sandhaus, Sara Womack, Eun-jeong Kim, Evan Brittain, Ashish S Shah, Lisa Mendes, Sandip K Zalawadiya, Joann Lindenfeld
Journal: Circulation (2020)

Introduction: Right ventricular failure (RVF) remains a major cause of morbidity and mortality after continuous flow Left Ventricle Assist Device (CF-LVAD) implantation. Previous risk assessments using pre-operative data to predict RVF have performed only modestly well. Methods: We retrospectively studied the potential of echocardiographic RV dP/dt - a non-invasive measure of right ventricular contractility derived from the Doppler signal of tricuspid regurgitation, to predict post-LVAD RVF in patients who were inotrope-independent and those who were on inotropic therapy prior to LVAD. Sixty-five consecutive CF-LVAD recipients at Vanderbilt University Medical Center from 2013-2019 who had a baseline echocardiogram without inotrope support within 3 months prior to LVAD implantation were included. Forty patients from the cohort were started on inotropes prior to LVAD implantation. Baseline off-inotrope and on-inotrope RV dP/dt data were analyzed. Severity of post-LVAD RVF was defined by INTERMACS criteria. Results: Of the 65 studied patients, 30 patients had none or mild RVF, 17 had moderate RVF, and 18 had severe RVF. Patients with severe RVF had markedly poorer survival outcome than no/mild and moderate RVF patients. Baseline RV dP/dt was significantly lower in patients who developed post-LVAD severe RVF. A baseline off-inotrope, or on-inotrope RV dP/dt ≥ 300 mmHg/s predicted a low risk of severe RVF with high sensitivity (89% and 80%, respectively) and negative predictive value (91% and 88% respectively); while the presence of both off-inotrope and on-inotrope RV dP/dt &lt; 300 mmHg/s was associated with a high likelihood of post-LVAD RVF (OR 10.5, 95% 1.8-59.4 compared to the rest of the cohort on inotrope therapy). Conclusion: Echocardiographic RV dP/dt may be a valuable adjunct tool for prediction of post-LVAD severe RVF in patients undergoing evaluation for LVAD implantation.
Effectiveness of a Vaping Cessation Text Message Program Among Young Adult e-Cigarette Users
Authors: Amanda L. Graham, Michael S. Amato, Sarah Cha, Megan A. Jacobs, Mia M. Bottcher, George D. Papandonatos
Journal: JAMA Internal Medicine (2021)

e-Cigarettes are the most commonly used tobacco product among young adults (YAs). Despite the harms of nicotine exposure among YAs, there are few, if any, empirically tested vaping cessation interventions available. To determine the effectiveness of a text message program for vaping cessation among YAs vs assessment-only control. A parallel, 2-group, double-blind, individually randomized clinical trial was conducted from December 2019 to November 2020 among YA e-cigarette users. Eligible individuals were US residents aged 18 to 24 years who owned a mobile phone with an active text message plan, reported past 30-day e-cigarette use, and were interested in quitting in the next 30 days. Participants were recruited via social media ads, the intervention was delivered via text message, and assessments were completed via website or mobile phone. Follow-up was conducted at 1 and 7 months postrandomization; follow-up data collection began January 2020 and ended in November 2020. The study was prespecified in the trial protocol. All participants received monthly assessments via text message about e-cigarette use. The assessment-only control arm (n = 1284) received no additional intervention. The active intervention arm (n = 1304) also received This is Quitting, a fully automated text message program for vaping cessation that delivers social support and cognitive and behavioral coping skills training. The primary outcome was self-reported 30-day point prevalence abstinence (ppa) at 7 months analyzed under intention-to-treat analysis, which counted nonresponders as vaping. Secondary outcomes were 7-day ppa under intention-to-treat analysis and retention weighted complete case analysis of 30-day and 7-day ppa. Of the 2588 YA e-cigarette users included in the trial, the mean (SD) age was 20.4 (1.7) years, 1253 (48.4%) were male, 2159 (83.4%) were White, 275 (10.6%) were Hispanic, and 493 (19.0%) were a sexual minority. Most participants (n = 2129; 82.3%) vaped within 30 minutes of waking. The 7-month follow-up rate was 76.0% (n = 1967), with no differential attrition. Abstinence rates were 24.1% (95% CI, 21.8%-26.5%) among intervention participants and 18.6% (95% CI, 16.7%-20.8%) among control participants (odds ratio, 1.39; 95% CI, 1.15-1.68; P < .001). No baseline variables moderated the treatment-outcome relationship, including nicotine dependence. Results of this randomized clinical trial demonstrated that a tailored and interactive text message intervention was effective in promoting vaping cessation among YAs. These results establish a benchmark of intervention effectiveness. ClinicalTrials.gov Identifier: NCT04251273.
Interference of methylenetetrahydrofolate reductase expression alters cell cycle and cellular folate metabolism in vitro
Authors: EnPei Isabel Chiang, Ming-Tzun Wu, Yi-Cheung Wang, Yu-Wen Chen
Journal: Cancer Research (2008)

5084  Genetic predisposition plays a significant role in tumorigenesis and cancer prevention. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR) is associated with altered risk of diseases including cancer. Low-activity genotype of MTHFR was found to be associated with a trend of reduction in risk of hepatocellular carcinoma, yet the mechanism remained to be determined. In the present study we established in vitro cell models for disrupted MTHFR by RNA interference, to investigate the impacts of MTHFR suppression in hepatic cellular folate metabolism, and further test the hypothesis that in liver, individuals with reduced MTHFR activity are less susceptible to chromosome damage during folate deficiency. Folate depletion induced chromosome damage, reduced cells of G1 phase and subsequently resulted in accumulation in S-G2/M. Furthermore, folate deficiency induced micronuclei in cells in a dose dependent manner. Supplementation of folate or MTHFR knockdown in HepG2 cells reduced the occurrence of this phenomenon. MTHFR suppression HepG2 cells decreased total number of micronuclei under sufficient folate condition compared to wild type cells. We suggest that suppression of MTHFR may be potentially protective against DNA damage caused by folate deficiency in liver by increasing the abundance of nucleotide for DNA repair. These cell-lines could be potential models for studying the consequences of human genetic variation in MTHFR and their relationship to pathways involved in cancer pathogenesis or progression (NSC-2320-005-008 MY3).
Multicentre derivation and validation of a colitis-associated colorectal cancer risk prediction web tool
Authors: Kit Curtius, Misha Kabir, Ibrahim Al Bakir, Chang Ho Ryan Choi, Juanda L Hartono, Michael Johnson, James E East, James O Lindsay, Roser Vega, Siwan Thomas-Gibson, Janindra Warusavitarne, Ana Wilson, Trevor A Graham, Ailsa Hart
Journal: Gut (2021)

Objective Patients with ulcerative colitis (UC) diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN: high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in patients with UC with LGD and create a visual web tool to effectively communicate the risk. Design In our retrospective multicentre validated cohort study, adult patients with UC with an index diagnosis of LGD, identified from four UK centres between 2001 and 2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from three external centres (n=198). The validated model was embedded in a web tool to calculate patient-specific risk. Results Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD &gt;1 cm (HR 2.7; 95% CI 1.2 to 5.9), unresectable or incomplete endoscopic resection (HR 3.4; 95% CI 1.6 to 7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR 3.1; 95% CI 1.5 to 6.7) and multifocality (HR 2.9; 95% CI 1.3 to 6.2). In the validation cohort, this four-variable model accurately predicted future AN cases with overall calibration Observed/Expected=1.01 (95% CI 0.64 to 1.52), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up. Conclusion Multicohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator ( www.UC-CaRE.uk ) can support treatment decision-making.
Research, Practice, and Policy Implications of Adverse Childhood Events
Authors: Edward L. Machtinger, Alicia Lieberman, Marguerita Lightfoot
Journal: JAMA Pediatrics (2021)

To the Editor We read with great interest the article by Baldwin et al,1 which contributes to a substantial body of research describing the staggering population-level effects of adverse childhood experiences (ACEs) on many of the most common causes of adult illness, death, and health disparities.2
Recombinant Avian Orthoavulavirus-1 Engineered to Express Variants of the SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Immune Responses
Authors: J. Yates, R. C. Mould, L. Chan, J. P. Knapp, Y. Mehrani, Y. L. Pei, P. H. Pham, A. Leacy, L. A. Santry, B. A. McBey, P. P. Major, B. W. Bridle, L. Susta, S. K. Wootton
Journal: Molecular Therapy (2021)
Augmentation of Stimulator of Interferon Genes–Induced Type I Interferon Production in COPA Syndrome
Authors: Takashi Kato, Masaki Yamamoto, Yoshitaka Honda, Takashi Orimo, Izumi Sasaki, Kohei Murakami, Hiroaki Hemmi, Yuri Fukuda‐Ohta, Kyoichi Isono, Saki Takayama, Hidenori Nakamura, Yoshiro Otsuki, Toshiaki Miyamoto, Junko Takita, Takahiro Yasumi, Ryuta Nishikomori, Tadashi Matsubayashi, Kazushi Izawa, Tsuneyasu Kaisho
Journal: Arthritis & Rheumatology (2021)

Coatomer subunit alpha (COPA) syndrome, also known as autoinflammatory interstitial lung, joint, and kidney disease, is caused by heterozygous mutations in COPA. We identified a novel COPA variant in 4 patients in one family. We undertook this study to elucidate whether and how the variant causes manifestations of COPA syndrome by studying these 4 patients and by analyzing results from a gene-targeted mouse model.We performed whole-exome sequencing in 7 family members and measured the type I interferon (IFN) signature of the peripheral blood cells. We analyzed the effects of COPA variants in in vitro experiments and in Copa mutant mice that were generated.We identified a heterozygous variant of COPA (c.725T>G, p.Val242Gly) in the 4 affected members of the family. The IFN score was high in the members carrying the variant. In vitro analysis revealed that COPA V242G, as well as the previously reported disease-causing variants, augmented stimulator of interferon genes (STING)-induced type I IFN promoter activities. CopaV242G/+ mice manifested interstitial lung disease and STING-dependent elevation of IFN-stimulated gene expression. In CopaV242G/+ dendritic cells, the STING pathway was not constitutively activated but was hyperactivated upon stimulation, leading to increased type I IFN production.V242G, a novel COPA variant, was found in 4 patients from one family. In gene-targeted mice with the V242G variant, interstitial lung disease was recapitulated and augmented responses of the STING pathway, leading to an increase in type I IFN production, were demonstrated.
Early Intervention in Cerebral Palsy and Beyond
Authors: Abdellah Tebani, Stéphane Marret
Journal: JAMA Pediatrics (2021)

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