tbuckley/cabot-search huggingface dataset:
Risk, treatment duration, and recurrence risk of postpartum affective disorder in women with no prior psychiatric history: A population-based cohort study
Authors: Marie-Louise H. Rasmussen, Marin Strøm, Jan Wohlfahrt, Poul Videbech, Mads Melbye
Journal: PLoS Medicine (2017)

Some 5%-15% of all women experience postpartum depression (PPD), which for many is their first psychiatric disorder. The purpose of this study was to estimate the incidence of postpartum affective disorder (AD), duration of treatment, and rate of subsequent postpartum AD and other affective episodes in a nationwide cohort of women with no prior psychiatric history.Linking information from several Danish national registers, we constructed a cohort of 457,317 primiparous mothers with first birth (and subsequent births) from 1 January 1996 to 31 December 2013 (a total of 789,068 births) and no prior psychiatric hospital contacts and/or use of antidepressants. These women were followed from 1 January 1996 to 31 December 2014. Postpartum AD was defined as use of antidepressants and/or hospital contact for PPD within 6 months after childbirth. The main outcome measures were risk of postpartum AD, duration of treatment, and recurrence risk. We observed 4,550 (0.6%) postpartum episodes of AD. The analyses of treatment duration showed that 1 year after the initiation of treatment for their first episode, 27.9% of women were still in treatment; after 4 years, 5.4%. The recurrence risk of postpartum AD for women with a PPD hospital contact after first birth was 55.4 per 100 person-years; for women with postpartum antidepressant medication after first birth, it was 35.0 per 100 person-years. The rate of postpartum AD after second birth for women with no history of postpartum AD was 1.2 per 100 person-years. After adjusting for year of birth and mother's age, women with PPD hospital contact after first birth had a 46.4 times higher rate (95% CI 31.5-68.4) and women with postpartum antidepressant medication after their first birth had a 26.9 times higher rate (95% CI 21.9-33.2) of a recurrent postpartum episode after their second birth compared to women with no postpartum AD history. Limitations include the use of registry data to identify cases and limited confounder control.In this study, an episode of postpartum AD was observed for 0.6% of childbirths among women with no prior psychiatric history. The observed episodes were characterized by a relatively short treatment duration, yet the women had a notably high rate of later AD and recurrent episodes of postpartum AD. The recurrence risk of postpartum AD was markedly higher among women with PPD hospital contact after first birth compared to women with postpartum antidepressant medication after first birth. Our results underline the necessity of measures targeted at specific vulnerable groups, such as women who experience PPD as a first psychiatric episode.
Distinct epitope structures of defensin‐like proteins linked to proline‐rich regions give rise to differences in their allergenic activity
Authors: I. Pablos, S. Eichhorn, Y. Machado, P. Briza, A. Neunkirchner, B. Jahn‐Schmid, S. Wildner, W. T. Soh, C. Ebner, J.‐W. Park, W. F. Pickl, N. Arora, S. Vieths, F. Ferreira, G. Gadermaier
Journal: Allergy (2017)

Art v 1, Amb a 4, and Par h 1 are allergenic defensin-polyproline-linked proteins present in mugwort, ragweed, and feverfew pollen, respectively. We aimed to investigate the physicochemical and immunological features underlying the different allergenic capacities of those allergens.Recombinant defensin-polyproline-linked proteins were expressed in E. coli and physicochemically characterized in detail regarding identity, secondary structure, and aggregation status. Allergenic activity was assessed by mediator releases assay, serum IgE reactivity, and IgE inhibition ELISA using sera of patients from Austria, Canada, and Korea. Endolysosomal protein degradation and T-cell cross-reactivity were studied in vitro.Despite variations in the proline-rich region, similar secondary structure elements were observed in the defensin-like domains. Seventy-four percent and 52% of the Austrian and Canadian patients reacted to all three allergens, while Korean patients were almost exclusively sensitized to Art v 1. This was reflected by IgE inhibition assays demonstrating high cross-reactivity for Austrian, medium for Canadian, and low for Korean sera. In a subgroup of patients, IgE reactivity toward structurally altered Amb a 4 and Par h 1 was not changed suggesting involvement of linear epitopes. Immunologically relevant endolysosomal stability of the defensin-like domain was limited to Art v 1 and no T-cell cross-reactivity with Art v 125-36 was observed.Despite structural similarity, different IgE-binding profiles and proteolytic processing impacted the allergenic capacity of defensin-polyproline-linked molecules. Based on the fact that Amb a 4 demonstrated distinct IgE-binding epitopes, we suggest inclusion in molecule-based allergy diagnosis.
Antenatal screening for Down's syndrome.
Authors: K. Spencer
Journal: BMJ (1992)

whole screened population the number of babies with Down's syndrome was 25.With Wald and colleagues' screening test, the number of Down's syndrome babies detected was 12.With screening by maternal age > 37 years alone, the number detected could have been 7 out of 25.These proportions are not significantly different (Fisher's exact test p=0-24; odds ratio 2-37; 95% confidence interval 0 73 to 7 68).Even with the different uptake of amniocentesis in the two groups-that is, 75% for all ages and 63% for those ¢ 37 years- there was still no significant difference in the result (p=0-2; odds ratio 2-95 (0 77 to 11-3)).Only 4 9% of women were aged ¢ 37 years; the confidential enquiries into maternal deaths in the United Kingdom 1985-7 reported that 8% of pregnant women were over 352 and in our hospital in 1991 the proportion ¢ 37 years was 9-2%.This proportion is likely to rise as women delay their families for personal and financial reasons, and as this proportion rises the detection rates from the triple test and from maternal age alone will become even more similar.In any particular district the cost of introducing this programme will depend on the proportion of women ¢ 37 years; in addition, many authorities (including our own) have now abandoned co fetoprotein testing, relying for neural tube defect screening on ultrasonography alone, and the cost of reintroducing this test would need to be accounted for in the calculations.
Binding of FUN14 Domain Containing 1 With Inositol 1,4,5-Trisphosphate Receptor in Mitochondria-Associated Endoplasmic Reticulum Membranes Maintains Mitochondrial Dynamics and Function in Hearts in Vivo
Authors: Shengnan Wu, Qiulun Lu, Qilong Wang, Ye Ding, Zejun Ma, Xiaoxiang Mao, Kai Huang, Zhonglin Xie, Ming-Hui Zou
Journal: Circulation (2017)

Background: FUN14 domain containing 1 (FUNDC1) is a highly conserved outer mitochondrial membrane protein. The aim of this study is to examine whether FUNDC1 modulates the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), mitochondrial morphology, and function in cardiomyocytes and intact hearts. Methods: The impacts of FUNDC1 on MAMs formation and cardiac functions were studied in mouse neonatal cardiomyocytes, in mice with cardiomyocyte-specific Fundc1 gene knockout ( Fundc1 f/Y /Cre αMyHC+/− ), and in the cardiac tissues of the patients with heart failure. Results: In mouse neonatal cardiomyocytes and intact hearts, FUNDC1 was localized in MAMs by binding to ER-resided inositol 1,4,5-trisphosphate type 2 receptor (IP 3 R2). Fundc1 ablation disrupted MAMs and reduced the levels of IP 3 R2 and Ca 2+ in both mitochondria and cytosol, whereas overexpression of Fundc1 increased the levels of IP 3 R2 and Ca 2+ in both mitochondria and cytosol. Consistently, Fundc1 ablation increased Ca 2+ levels in ER, whereas Fundc1 overexpression lowered ER Ca 2+ levels. Further, Fundc1 ablation in cardiomyocytes elongated mitochondria and compromised mitochondrial functions. Mechanistically, we found that Fundc1 ablation-induced reduction of intracellular Ca 2+ levels suppressed mitochondrial fission 1 protein ( Fis1 ) expression and mitochondrial fission by reducing the binding of the cAMP response element binding protein (CREB) in the Fis1 promoter. Fundc1 f/Y /Cre αMyHC+/− mice but not their littermate control mice ( Fundc1 wt/Y /Cre αMyHC+/− ) exhibited cardiac dysfunction. The ligation of the left ventricle artery of Fundc1 f/Y /Cre αMyHC+/− mice caused more severe cardiac dysfunction than those in sham-treated Fundc1 f/Y /Cre αMyHC+/− mice. Finally, we found that the FUNDC1/MAMs/CREB/Fis1 signaling axis was significantly suppressed in patients with heart failure. Conclusions: We conclude that FUNDC1 binds to IP 3 R2 to modulate ER Ca 2+ release into mitochondria and cytosol. Further, a disruption of the FUNDC1 and IP 3 R2 interaction lowers the levels of Ca 2+ in mitochondria and cytosol, both of which instigate aberrant mitochondrial fission, mitochondrial dysfunction, cardiac dysfunction, and heart failure.
Abstract 16972: Premature Ventricular Complex Characteristics Are Associated With Sudden Cardiac Death: the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS)
Authors: David M German, Muammar M Kabir, Jason Thomas, Jonathan W Waks, Colleen M Sitlani, Mary L Biggs, Nona Sotoodehnia, David S Siscovick, Elsayed Z Soliman, Charles A Henrickson, Tor Biering-Sorensen, Scott D Solomon, Wendy S Post, Alfred E Buxton, Mark E Josephson, Larisa G Tereshchenko
Journal: Circulation (2016)

Introduction: The prognostic impact of premature ventricular complexes (PVCs) is debated, and features of PVCs which associated with risk for sudden cardiac death (SCD) remain poorly described. Hyp...
Reverse bougienage of the major papilla via the minor papilla followed by conventional sphincterotomy
Authors: Martin Goetz
Journal: Endoscopy (2017)

I read with great interest the paper and skillful E-video by Chavan et al. on “Reverse sphincterotomy of the minor papilla via the major papilla for chronic pancreatitis with incomplete pancreas divisum” [1]. I would like to highlight a slightly different approach in a similar patient who was admitted for management of suspected necrotizing pancreatitis (confirmed by endoscopic ultrasound) in incomplete pancreas divisum with chronic pancreatitis (these data have not been published previously).
Are Current Advances of Compression Algorithms for Capsule Endoscopy Enough? A Technical Review
Authors: Mohammad Wajih Alam, Md. Mehedi Hasan, Shahed Khan Mohammed, Farah Deeba, Khan A. Wahid
Journal: IEEE Reviews in Biomedical Engineering (2017)

The recent technological advances in capsule endoscopy system have revolutionized the healthcare system by introducing new techniques and functionalities to diagnose gastrointestinal tract. These techniques improve diagnostic accuracy and reduce the risk of hospitalization. Although many benefits of capsule endoscopy are known, there are still limitations including lower battery life, higher bandwidth, poor image quality and lower frame rate, which have restricted its wide use. In order to solve these limitations, the importance of a low-cost compression algorithm, that produces higher frame rate with better image quality and yet consumes lower bandwidth and transmission power, is paramount. While several review papers have been published describing the capability of capsule endoscope in terms of its functionality and emerging features, an extensive review on the compression algorithms from past and for future applications is still of great interest. Hence, in this review, we aim to address the issue by exploring the characteristics of endoscopic images, analyzing the strengths and weaknesses of useful compression techniques, and making suggestions for possible future adaptation.
Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens
Authors: Romualdo Barroso-Sousa, William T. Barry, Ana C. Garrido-Castro, F. Stephen Hodi, Le Min, Ian E. Krop, Sara M. Tolaney
Journal: JAMA Oncology (2017)

If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown.To compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens.A PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," "MDX-010," "nivolumab," "BMS-963558," "pembrolizumab," "MK-3475," "atezolizumab," "MPDL3280A," and "phase."Thirty-eight randomized clinical trials evaluating the usage of these ICIs for treatment of advanced solid tumors were identified, resulting in a total of 7551 patients who were eligible for a meta-analysis. Regimens were categorized by class into monotherapy with a PD-1 (programmed cell death protein 1) inhibitor, a CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) inhibitor, or a PD-L1 (programmed cell death 1 ligand 1) inhibitor, and combination therapy with PD-1 plus CTLA-4 inhibitors.The data were extracted by 1 primary reviewer (R.B.-S.) and then independently reviewed by 2 secondary reviewers (W.T.B. and A.C.G.-C.) following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inferences on the incidence of AEs were made using log-odds random effects models.Incidence of all-grade hypothyroidism, hyperthyroidism, hypophysitis, primary adrenal insufficiency, and insulin-deficient diabetes.Overall, 38 randomized clinical trials comprising 7551 patients were included in this systematic review and meta-analysis. The incidence of both hypothyroidism and hyperthyroidism was highest in patients receiving combination therapy. Patients on the combination regimen were significantly more likely to experience hypothyroidism (odds ratio [OR], 3.81; 95% CI, 2.10-6.91, P < .001) and hyperthyroidism (OR, 4.27; 95% CI, 2.05-8.90; P = .001) than patients on ipilimumab. Compared with patients on ipilimumab, those on PD-1 inhibitors had a higher risk of developing hypothyroidism (OR, 1.89; 95% CI, 1.17-3.05; P = .03). The risk of hyperthyroidism, but not hypothyroidism, was significantly greater with PD-1 than with PD-L1 inhibitors (OR, 5.36; 95% CI, 2.04-14.08; P = .002). While patients who received PD-1 inhibitors were significantly less likely to experience hypophysitis than those receiving ipilimumab (OR, 0.29; 95% CI, 0.18-0.49; P < .001), those who received combination therapy were significantly more likely to develop it (OR, 2.2; 95% CI, 1.39-3.60; P = .001). For primary adrenal insufficiency and insulin-deficient diabetes no statistical inferences were made due to the smaller number of events.Our study provides more precise data on the incidence of endocrine dysfunctions among patients receiving ICI regimens. Patients on combination therapy are at increased risk of thyroid dysfunction and hypophysitis.
Societal perspectives analysis for evaluating direct‐acting antiviral affordability while awaiting liver transplant
Authors: Xibei Liu, Yousif Elmofti, Catherine Kulaga, Brandon Gisi, Ji Won Yoo
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the study by Ahmed et al.1 identifying the cost‐effectiveness of all direct‐acting antivirals (DAAs) for patients with hepatitis C virus (HCV) awaiting liver transplant (LT) in the United States. A few things should be considered before applying the findings of Ahmed et al.1 to clinical practice. There are possible selection biases in the base case scenario, for example, the ASTRAL‐4 cohort,2 which may not reflect the full spectrum of the US population. The ASTRAL‐4 study2 included a predominantly white population (90%) compared to patients on the actual United Network of Organ Sharing waitlist (white 70%) in year 2012.3 According to Beckman et al.4, <1% of inmates with HCV were treated with DAAs. This inequality in DAAs for HCV treatment is not limited to the United States and is a common dilemma in other developed countries even under universal health care systems such as those of the United Kingdom and Korea.5 Kieslich et al.5 identified the limitations of payers' perspectives that were applied by Ahmed et al.,1 which might not fully reflect vulnerable populations as stated above. According to the United Network of Organ Sharing database in year 2016, approximately 20% of LT waitlist cases resulted in death or removal from the waitlist. The proportion of DAA users among HCV patients awaiting LT is largely unknown. Uncertainty remains regarding the Trump administration's actions on DAA coverage for patients with HCV waiting LT. In these contexts, Kieslich et al.5 suggested that both the patient and the public should be proactively engaged to promote DAA coverage for HCV treatment as an urgent agenda for the media and policymakers. Simultaneously, newer cost‐effectiveness analyses of DAA coverage should be tested again, ideally by two reference case perspectives—the societal and payers' perspectives—and should be put forward to identify the most affordable ways to cover DAAs for US patients with HCV awaiting LT.6
Pharmacokinetics (PK) and exposure-response (ER) of rilotumumab (Rmab) in patients (pts) with small-cell lung cancer (SCLC).
Authors: Yilong Zhang, Jenny Zheng, Rui Tang, Elwyn Loh, Sarita Dubey, Min Zhu
Journal: Journal of Clinical Oncology (2014)

7593 Background: Rmab is a fully human monoclonal antibody against hepatocyte growth factor that was evaluated as a first-line treatment for extensive-stage SCLC in a phase 1b/2 trial (J Thorac Oncol. 2013;8(S2):O21.05). That trial did not show meaningful improvements in progression-free survival (PFS) or overall survival (OS). We characterized Rmab PK in pts with SCLC and performed an ER analysis that related PK to tumor size (TS), PFS, and OS. Methods: Rmab population PK (PPK) and ER were assessed in 132 pts with SCLC who were randomized 1:1 to receive either Rmab (15 mg/kg) or placebo, with etoposide plus carboplatin/cisplatin every 3 weeks (Q3W). A PPK model was developed using data from phase 1 and earlier phase 2 studies. TS vs time was characterized using a tumor dynamic model, and time to tumor growth (TTG) and TS ratios (the ratios of TS at 6, 9, or 12 weeks to TS at baseline) were derived from this model. The relationships between PFS/OS and baseline pt characteristics, exposure metrics, and tumor response metrics were evaluated using Cox proportional hazards and parametric survival models. Pts were divided into high- and low-exposure groups based on median Rmab trough concentration at steady state (Cminss). Survival analyses were performed with R, and PPK and tumor dynamic analyses were performed with NONMEM. Results: Rmab PK was well characterized by a two-compartment PK model. Body weight (WT) affected clearance (CL) and central volume of distribution (Vc): a 10% increase in WT increased CL by 6% and Vc by 7%. Chemotherapy reduced TS, but Rmab did not have an additional effect on TS. OS was best described by a log-logistic distribution. Rmab improved OS relative to placebo in the high-exposure group (Cminss > 155 mg/mL) but not in the low-exposure group (Cminss ≤ 155 mg/mL). Univariate analysis suggested that favorable predictive factors of OS included higher Rmab exposure, female sex, and longer TTG. There was no apparent PK-PFS relationship. Conclusions: High Rmab exposure was associated with improved OS in this ER analysis, but further studies will be needed to determine whether this association is causative and whether a combination of chemotherapy and Rmab at a dose > 15 mg/kg Q3W leads to improved OS.
Result of the feasibility study of lidocaine (LDC) for peripheral venous pain induced by oxaliplatin (L-OHP).
Authors: Daisuke Sakai, Miwako Uemori, Takashi Sugiura, Toshihiro Kudo, Miwa Boku, Keiko Tanizaki, Aya Kato, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori, Taroh Satoh, Taro Hayashi
Journal: Journal of Clinical Oncology (2017)

e21624 Background: For the patients with colorectal cancer, CapeOx or SOX, combination of L-OHP with oral fluoropyrimidines Capecitabine or S-1, is commonly used in clinical practice. These regimens, different from FOLFOX, do not necessarily require central venous port placement and can be administered via peripheral vein. However, peripheral vascular pain induced by administration of L-OHP was discussed. Methods: LDC was concomitantly administered through the lateral duct of drip route from 30 minutes before to end of L-OHP administration, to patients with colorectal cancer who are to be administered L-OHP (100 mg/m2 or more) via the peripheral vein for the first time. LDC dose was set at two levels of 0.5 (Level 1) and 1.5 (Level 2) mg / kg / Hr. Safety, symptoms of pain and pharmacokinetics of LDC were evaluated. The DLT criteria were (1) an allergic reaction of Grade 2 or higher, (2) non-hematological toxicity of Grade 3 or more related to LDC, (3) cessation of administration of L-OHP or LDC, (4) higher than 5 mcg / mL of blood concentration of LDC. Results: A total of nine patients were enrolled (Level 1: 3, Level 2: 6). No DLTs were observed. The average Cmax of LDC was 0.4 (range: 0.3 - 0.5) mcg/ml at Level 1 and 1.3 (0.5 - 2.3) mcg / ml at Level 2. In the pain assessment (VAS score), in Level 1, 2 cases did not feel pain, 1 case was 3/10. In Level 2, there were no pain in 4 cases and 2/10 in the remaining 2 cases. Conclusions: To alleviate vascular pain caused by peripheral intravenous administration of L-OHP, concomitant administration of LDC could be safe and effective. Clinical trial information: UMIN000011393.
Statistical Package for Growth Rates Made Easy
Authors: Portia Mira, Miriam Barlow, Juan C Meza, Barry G Hall
Journal: Molecular Biology and Evolution (2017)

Growth rates are an important tool in microbiology because they provide high throughput fitness measurements. The release of GrowthRates, a program that uses the output of plate reader files to automatically calculate growth rates, has facilitated experimental procedures in many areas. However, many sources of variation within replicate growth rate data exist and can decrease data reliability. We have developed a new statistical package, CompareGrowthRates (CGR), to enhance the program GrowthRates and accurately measure variation in growth rate data sets. We define a metric, Variability-score (V-score), that can help determine if variation within a data set might result in false interpretations. CGR also uses the bootstrap method to determine the fraction of bootstrap replicates in which a strain will grow the fastest. We illustrate the usage of CGR with growth rate data sets similar to those in Mira, Meza, et al. (Adaptive landscapes of resistance genes change as antibiotic concentrations change. Mol Biol Evol. 32(10): 2707-2715). These statistical methods are compatible with the analytic methods described in Growth Rates Made Easy and can be used with any set of growth rate output from GrowthRates.
Gene Expression Signatures and Immunohistochemical Subtypes Add Prognostic Value to Each Other in Breast Cancer Cohorts
Authors: Arian Lundberg, Linda S. Lindström, J. Chuck Harrell, Claudette Falato, Joseph W. Carlson, Paul K. Wright, Theodoros Foukakis, Charles M. Perou, Kamila Czene, Jonas Bergh, Nicholas P. Tobin
Journal: Clinical Cancer Research (2017)

Gene signatures and Ki67 stratify the same breast tumor into opposing good/poor prognosis groups in approximately 20% of patients. Given this discrepancy, we hypothesized that the combination of a clinically relevant signature and IHC markers may provide more prognostic information than either classifier alone.
TP53 Mutations Determine Outcome of Patients (pts) with High-Risk Myelodysplastic Syndrome (HRMDS) and Acute Myelogenous Leukemia (AML) Regardless of Karyotype and ELN Risk Stratification
Authors: James K. McCloskey, Marshall McKenna, Jamie L. Koprivnikar, Samantha Depadova, Genique Stanislaus, Stuart L. Goldberg, Stefan Faderl
Journal: Blood (2016)