tbuckley/cabot-search huggingface dataset:
Organophosphate Pesticide Metabolite Concentrations in Urine during Pregnancy and Offspring Nonverbal IQ at Age 6 Years
Authors: Todd A. Jusko, Michiel A. van den Dries, Anjoeka Pronk, Pamela A. Shaw, Mònica Guxens, Suzanne Spaan, Vincent W. Jaddoe, Henning Tiemeier, Matthew P. Longnecker
Journal: Environmental Health Perspectives (2019)

Background: Susceptibility to organophosphate (OP) pesticide neurotoxicity may be greatest during the prenatal period; however, previous studies have produced mixed findings concerning in utero OP pesticide exposure and child cognition. Objectives: Our objective was to determine whether maternal urinary concentrations of OP pesticide metabolites are inversely associated with child nonverbal IQ at 6 y of age and to examine potential effect measure modification by the PON1 gene. Methods: Data came from 708 mother–child pairs participating in the Generation R Study. Maternal urine concentrations of six dialkylphosphates (DAPs), collected at <18, 18–25, and >25 weeks of gestation, were determined. Child nonverbal IQ was measured at 6 y of age using the Mosaics and Categories subtests from the Snijders-Oomen Nonverbal Intelligence Test–Revised. PON1 was determined in cord blood for 474 infants. Multiple linear regression models were fit to estimate the DAP–IQ associations and PON1 interactions. Results: Overall, associations between child nonverbal IQ and maternal DAP concentrations were small and imprecise, and these associations were inconsistent across urine sampling periods. However, for a 10-fold difference in total DAP concentration for the >25 weeks of gestation samples, adjusted child nonverbal IQ was 3.9 points lower (95% CI: −7.5, −0.3). Heterogeneity in the DAP–IQ association by PON1 gene allele status was not observed (n=474). Conclusions: Consistent evidence of an association between higher maternal urinary DAP concentrations and lower child IQ scores at 6 y of age was not observed. There was some evidence for an inverse relation of child nonverbal IQ and late pregnancy urinary DAPs, but the estimated association was imprecise. https://doi.org/10.1289/EHP3024
Subgroup Analyses From the Phase 3 HELP Study of Lanadelumab for the Prevention of Hereditary Angioedema Attacks
Authors: Aleena Banerji, Michael E. Manning, Inmaculada Martinez-Saguer, Lawrence B. Schwartz, Andrew M. Smith, William H. Yang, Peng Lu, James Hao, Bruce L. Zuraw
Journal: Journal of Allergy and Clinical Immunology (2019)
Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study
Authors: Slavé Petrovski, Vimla Aggarwal, Jessica L Giordano, Melissa Stosic, Karen Wou, Louise Bier, Erica Spiegel, Kelly Brennan, Nicholas Stong, Vaidehi Jobanputra, Zhong Ren, Xiaolin Zhu, Caroline Mebane, Odelia Nahum, Quanli Wang, Sitharthan Kamalakaran, Colin Malone, Kwame Anyane-Yeboa, Russell Miller, Brynn Levy, David B Goldstein, Ronald J Wapner
Journal: The Lancet (2019)
Reply
Authors: Mary Drinane
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. In the letter by Kamar et al., advancements in our understanding of chronic hepatitis E infection in solid organ transplant patients over time are highlighted. They cite the 2019 publication on the importance of fecal hepatitis E PCR in determining clearance of chronic infection.1 However, our patient initially received ribavirin in 2013, with his second course in 2015, and his final treatment with ribavirin and sofosbuvir occurring in 2017. It must be noted that it was only in 2017 that a PCR test for hepatitis E became commercially available in the United States, where our patient was treated.2 PCRs that were obtained before 2017 were obtained by this patient's samples being used post hoc in the validation set for the commercial test. This case report was meant to provide contrast to the report by Donnelly et al., where sofosbuvir was used in combination with daclatasvir, but not ribavirin3 and foster further investigation of the role of sofosbuvir with ribavirin in management of hepatitis E. To clarify some points from the original case report, the patient was confirmed to be genotype 3. His second course of ribavirin in 2015 was discontinued when his hepatitis E levels were increasing despite being on 600 mg daily of ribavirin (recommended dosing at that time) because of concerns of lack of efficacy. In the final course of therapy, ribavirin was started at 1,200 mg daily because knowledge on dosing of ribavirin for treatment of hepatitis E had evolved. However, the dose of ribavirin was decreased to 800 mg daily 4 weeks into therapy because of anemia. Sofosbuvir was added to ribavirin to potentially obtain a synergist effect between the agents that had been previously noted in in vitro experiments.4 In summary, the field of hepatitis E has changed significantly over the time period our patient was treated. Our case highlights the opportunity to further investigate sofosbuvir in solid organ transplant patients, and in agreement with Kamar et al., we also welcome the community to investigate and provide additional data to its efficacy.
Antibiotic Treatment Drives the Diversification of the Human Gut Resistome
Authors: Jun Li, Elizabeth A. Rettedal, Eric van der Helm, Mostafa Ellabaan, Gianni Panagiotou, Morten O.A. Sommer
Journal: Genomics Proteomics & Bioinformatics (2019)

Despite the documented antibiotic-induced disruption of the gut microbiota, the impact of antibiotic intake on strain-level dynamics, evolution of resistance genes, and factors influencing resistance dissemination potential remains poorly understood. To address this gap we analyzed public metagenomic datasets from 24 antibiotic treated subjects and controls, combined with an in-depth prospective functional study with two subjects investigating the bacterial community dynamics based on cultivation-dependent and independent methods. We observed that short-term antibiotic treatment shifted and diversified the resistome composition, increased the average copy number of antibiotic resistance genes, and altered the dominant strain genotypes in an individual-specific manner. More than 30% of the resistance genes underwent strong differentiation at the single nucleotide level during antibiotic treatment. We found that the increased potential for horizontal gene transfer, due to antibiotic administration, was ∼3-fold stronger in the differentiated resistance genes than the non-differentiated ones. This study highlights how antibiotic treatment has individualized impacts on the resistome and strain level composition, and drives the adaptive evolution of the gut microbiota.
A Novel α-Thalassemia Screening Scheme in Neonates with Higher Sensitivity and Specificity Using a Combination of Hb Bart's Quantity and Red Blood Cell Indices
Authors: Thidarat Suksangpleng, Suchada Riolueang, Jiraporn Korchuenjit, Supachai Ekwattanakit, Vip Viprakasit
Journal: Blood (2018)
Progressing rehabilitation after injury: consider the ‘control-chaos continuum’
Authors: Matt Taberner, Tom Allen, Daniel Dylan Cohen
Journal: British Journal of Sports Medicine (2019)

Early reintegration to training and match play following injury increases the risk of reinjury. However, having key players available benefits the team.1 Practitioners must balance these two components of the return to sport (RTS) process, combining evidence and clinical experience to estimate this risk, then plan and adapt RTS accordingly.1 Quantifying and monitoring training load is key in guiding this process while managing reinjury risk,2–4 and global positioning systems (GPS) provide a valid measure of external running loads.5 However, as practitioners, we should focus on both quantitative aspects of running load progression and qualitative characteristics of movement in competition. This includes highly variable, spontaneous and unanticipated movements (the conditions of ‘chaos’) reflecting the unpredictable nature of the sport.

In this editorial, we present the ‘control-chaos continuum’ (CCC) (figure 1), interlinking GPS variables, while progressively incorporating greater perceptual and reactive neurocognitive challenges.6 7 This framework moves from high control to high chaos, and is based on more than a decade of rehabilitation and RTS in the demanding setting of English Premier League football.



Figure 1 
Return to sport framework - the control-chaos continuum. Control=high level of structure on behaviour/actions/movement, that is, controlled situation. Chaos=unpredictable behaviour/actions/movement, as to appear random/reactive, that is, chaotic situation. Green represents high control (low intensity) moving towards high chaos (high intensity). Model can be adjusted according to specific injury diagnosis, estimated tissue healing times and expected return to training. Acc/Dec Magnitude =rate of change in velocity, for example, 3 ms−2.**Game load adjustable dependent on injury type/severity. ACC, accelerations; BW, bodyweight; COD, change of direction; DEC, decelerations; Exp-D, explosive distance (accelerating/decelerating from 2 to 4 ms−1  5.5 ms−1); MS, maximal speed; MAXHR, maximal heart rate; PR, passive recovery; SPR, sprint distance (>7 ms−1); TD, total distance.



Using retrospective player chronic running loads (GPS) in …
Comparison of Two Different Therapeutic Regimens with Azacitidine and Lenalidomide (Combined versus Sequential) in Higher-Risk Myelodysplastic Syndromes. Update of Long-Term Results of a Randomized Phase II Multicenter Study
Authors: Carlo Finelli, Cristina Clissa, Matilde Y Follo, Sarah Parisi, Miriam Fogli, Sara Mongiorgi, Isabella Capodanno, Costanza Bosi, Barbara Castagnari, Anna Candoni, Monica Crugnola, Maria Benedetta Giannini, Marco Gobbi, Giovanna Leonardi, Gian Matteo Rigolin, Domenico Russo, Patrizia Tosi, Andrea Pellagatti, Jacqueline Boultwood, Lucio Cocco, Michele Cavo
Journal: Blood (2018)
银屑病患者的血清同型半胱胺酸、叶酸和维生素 B12 水平:系统性综述和荟萃分析
Authors: T.‐Y. Tsai, H. Yen, Y.‐C. Huang
Journal: British Journal of Dermatology (2019)

银屑病患者发生冠心病和中风的风险增大。目前已有研究表明,银屑病会引起血液内的同型半胱胺酸水平升高。同型半胱胺酸水平高与动脉粥样硬化(动脉“生垢”)有关联。同型半胱胺酸的分解依赖于叶酸和维生素 B12。血液叶酸水平低已在银屑病患者中有报告,这部分归因于皮肤内细胞周转率增加导致叶酸消耗量增大,也部分归因于叶酸在肠道内的吸收量减少。来自中国台湾的作者评论了现已发表的多项研究,并证实银屑病患者的血液同型半胱胺酸水平的确高于对照(无银屑病人群),血液叶酸水平的确低于对照。银屑病患者和对照在血液维生素 B12 水平方面没有差别。作者认为对此应该谨慎解读,因为还有其他许多混杂因素可能会影响结果。然而,他们建议检测银屑病患者的血液同型半胱胺酸水平,以识别出心血管病高风险者。建议开展进一步的研究,特别是应研究使用叶酸或维生素 B12 是否能够降低这些并发症的发病风险。
The Anti-Tumor Effect of the Ubiquitin-Activating Enzyme (UAE) Inhibitor TAK-243 on Pre-Clinical Models of Multiple Myeloma
Authors: Junling Zhuang, Hans Lee, Isere Kuiatse, Hua Wang, Fazal Shirazi, Allison Berger, Marc Hyer, Nibedita Chattopadhyay, Sakeena Syed, Judy Qiuju Shi, Jie Yu, Vaishali Shinde, Anna Kreshock, Stephen Tirrell, Saurabh Menon, Richard Julian Jones, Robert Z. Orlowski
Journal: Blood (2016)
Suboptimalities for sure: Arguments from evolutionary theory
Authors: Rob Withagen, John van der Kamp, Matthieu de Wit
Journal: Behavioral and Brain Sciences (2018)

Abstract Rahnev &amp; Denison (R&amp;D) addressed the issue of (sub)optimalities in perception but only made a passing reference to evolutionary thinking. In our commentary, we concur with the authors’ claim that evolution does not work toward optimalities, but argue that an evolutionary perspective on perception questions the Bayesian approach that the authors adopted.
Combined tract segmentation and orientation mapping for bundle-specific tractography
Authors: Jakob Wasserthal, Peter F. Neher, Dusan Hirjak, Klaus H. Maier-Hein
Journal: Medical Image Analysis (2019)

While the major white matter tracts are of great interest to numerous studies in neuroscience and medicine, their manual dissection in larger cohorts from diffusion MRI tractograms is time-consuming, requires expert knowledge and is hard to reproduce. In previous work we presented tract orientation mapping (TOM) as a novel concept for bundle-specific tractography. It is based on a learned mapping from the original fiber orientation distribution function (FOD) peaks to tract specific peaks, called tract orientation maps. Each tract orientation map represents the voxel-wise principal orientation of one tract. Here, we present an extension of this approach that combines TOM with accurate segmentations of the tract outline and its start and end region. We also introduce a custom probabilistic tracking algorithm that samples from a Gaussian distribution with fixed standard deviation centered on each peak thus enabling more complete trackings on the tract orientation maps than deterministic tracking. These extensions enable the automatic creation of bundle-specific tractograms with previously unseen accuracy. We show for 72 different bundles on high quality, low quality and phantom data that our approach runs faster and produces more accurate bundle-specific tractograms than 7 state of the art benchmark methods while avoiding cumbersome processing steps like whole brain tractography, non-linear registration, clustering or manual dissection. Moreover, we show on 17 datasets that our approach generalizes well to datasets acquired with different scanners and settings as well as with pathologies. The code of our method is openly available at https://github.com/MIC-DKFZ/TractSeg.
The Dangerous Flavors of E-Cigarettes
Authors: Jeffrey M. Drazen, Stephen Morrissey, Edward W. Campion
Journal: New England Journal of Medicine (2019)

Nicotine is amazingly addictive. About 20 years ago, researchers in a nearby laboratory were studying the effects of cigarette smoke on lung function in mice. To expose a mouse to cigarette smoke, the mouse is placed in a plastic tube, head out. The tube is positioned in a stream of smoke, which the mouse then breathes. On the day of the first exposure, it is difficult to get the mouse to enter the tube. But on the second exposure, most mice run right into the tube. In contrast, mice not exposed to tobacco smoke on the first day continue to . . .
Author Correction: Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism
Authors: Michelle Luciano, Saskia P. Hagenaars, Gail Davies, W. David Hill, Toni-Kim Clarke, Masoud Shirali, Sarah E. Harris, Riccardo E. Marioni, David C. Liewald, Chloe Fawns-Ritchie, Mark J. Adams, David M. Howard, Cathryn M. Lewis, Catharine R. Gale, Andrew M. McIntosh, Ian J. Deary
Journal: Nature Genetics (2019)
Alternative RNA Splicing as a Potential Major Source of Untapped Molecular Targets in Precision Oncology and Cancer Disparities
Authors: Timothy J. Robinson, Jennifer A. Freedman, Muthana Al Abo, April E. Deveaux, Bonnie LaCroix, Brendon M. Patierno, Daniel J. George, Steven R. Patierno
Journal: Clinical Cancer Research (2019)

Studies of alternative RNA splicing (ARS) have the potential to provide an abundance of novel targets for development of new biomarkers and therapeutics in oncology, which will be necessary to improve outcomes for patients with cancer and mitigate cancer disparities. ARS, a key step in gene expression enabling individual genes to encode multiple proteins, is emerging as a major driver of abnormal phenotypic heterogeneity. Recent studies have begun to identify RNA splicing-related genetic and genomic variation in tumors, oncogenes dysregulated by ARS, RNA splice variants driving race-related cancer aggressiveness and drug response, spliceosome-dependent transformation, and RNA splicing-related immunogenic epitopes in cancer. In addition, recent studies have begun to identify and test, preclinically and clinically, approaches to modulate and exploit ARS for therapeutic application, including splice-switching oligonucleotides, small molecules targeting RNA splicing or RNA splice variants, and combination regimens with immunotherapies. Although ARS data hold such promise for precision oncology, inclusion of studies of ARS in translational and clinical cancer research remains limited. Technologic developments in sequencing and bioinformatics are being routinely incorporated into clinical oncology that permit investigation of clinically relevant ARS events, yet ARS remains largely overlooked either because of a lack of awareness within the clinical oncology community or perceived barriers to the technical complexity of analyzing ARS. This perspective aims to increase such awareness, propose immediate opportunities to improve identification and analysis of ARS, and call for bioinformaticians and cancer researchers to work together to address the urgent need to incorporate ARS into cancer biology and precision oncology.
Total neoadjuvant therapy compared with standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis.
Authors: Sashidhar Manthravadi, Weijing Sun, Anwaar Saeed, Joaquina Celebre Baranda, Anup Kasi
Journal: Journal of Clinical Oncology (2019)

709 Background: Standard therapy of locally advanced rectal cancer (LARC) includes concurrent chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy (CT). An alternative strategy known as Total Neoadjuvant Therapy (TNT) involves administration of CRT and CT prior to surgery with the goal of delivering uninterrupted systemic therapy to eradicate micrometastases. A comparison of these two approaches has not been reviewed previously. Methods: Following PRISMA guidelines, a systematic review of PubMed and Web of Science was performed from inception through September 2018 to identify studies which compared TNT with CRT in LARC. The outcomes of interest were pathologic complete response rates (PCR), sphincter-preserving surgery rates, ileostomy rates, disease-free survival (DFS) and overall survival (OS). Summary hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a random effects model and heterogeneity was estimated using the inconsistency index (I 2 ). Results: After reviewing 2,163 reports, 5 studies which compared CRT and TNT were selected for inclusion. These were reported from Europe and the United States and included a total of 1,134 patients of whom 552 received TNT. The pooled prevalence of PCR was 32.4% (range 17-28%) in the TNT group and 22.3% (range 4-21%) in the CRT group. In a meta-analysis of five studies, TNT was associated with a higher chance of achieving a pathologic complete response (OR 1.92; 95% CI 1.44- 2.57, I 2 = 22%). Recipients of TNT also had higher odds of receiving sphincter-sparing surgery (5 studies, OR 1.92; 95% CI 1.44- 2.57, I 2 = 0%) and lower odds of requiring an ileostomy (2 studies, OR 0.72; 95% CI 0.54- 0.96, I 2 = 0%). Only one study presented data on DFS and noted improved DFS in patients who received TNT (OR 0.72; 95% CI 0.54- 0.96). The impact of TNT relative to standard therapy on overall survival was not reported. Conclusions: Total Neoadjuvant Therapy is a promising strategy in locally advanced rectal cancer, with superior PCR rates compared to standard therapy. However, the long term impact on disease recurrence and overall survival remain unclear. These are best be studied in a prospective randomized clinical trial.
Chronic virus infection compromises memory bystander T cell function in an IL-6/STAT1-dependent manner
Authors: Isabel Barnstorf, Mariana Borsa, Nicolas Baumann, Katharina Pallmer, Alexander Yermanos, Nicole Joller, Roman Spörri, Suzanne P.M. Welten, Nike J. Kräutler, Annette Oxenius
Journal: The Journal of Experimental Medicine (2019)

Chronic viral infections are widespread among humans, with ∼8–12 chronic viral infections per individual, and there is epidemiological proof that these impair heterologous immunity. We studied the impact of chronic LCMV infection on the phenotype and function of memory bystander CD8+ T cells. Active chronic LCMV infection had a profound effect on total numbers, phenotype, and function of memory bystander T cells in mice. The phenotypic changes included up-regulation of markers commonly associated with effector and exhausted cells and were induced by IL-6 in a STAT1-dependent manner in the context of chronic virus infection. Furthermore, bystander CD8 T cell functions were reduced with respect to their ability to produce inflammatory cytokines and to undergo secondary expansion upon cognate antigen challenge with major cell-extrinsic contributions responsible for the diminished memory potential of bystander CD8+ T cells. These findings open new perspectives for immunity and vaccination during chronic viral infections.
A Neuroethics Framework for the Australian Brain Initiative
Authors: Adrian Carter, Linda J. Richards, Deborah Apthorp, Mostafa Rahimi Azghadi, David R. Badcock, Bernard Balleine, John M. Bekkers, Michael Berk, James A. Bourne, Andrew P. Bradley, Michael Breakspear, Alan Brichta, Olivia Carter, Anne Castles, Khaled Chakli, Sarah Cohen-Woods, Simon J. Conn, Jennifer Cornish, Kim Cornish, Greg de Zubicaray, Gary F. Egan, Peter G. Enticott, Bernadette M. Fitzgibbon, Cynthia Forlini, Alex Fornito, Lyn Griffiths, Judith Gullifer, Wayne Hall, Glenda Halliday, Anthony J. Hannan, Stefan Harrer, Alan Harvey, Chris Hatherly, Ian B. Hickie, Jeanette Kennett, Matthew Kiernan, Trevor Kilpatrick, Isabell Kiral-Kornek, Mayuresh S. Korgaonkar, Andrew J. Lawrence, Rick Leventer, Neil Levy, Julio Licinio, Nigel Lovell, Geoff Mackellar, Lynne Malcolm, Alice Mason, Jason B. Mattingley, Sarah E. Medland, Patricia T. Michie, Jess Nithianantharajah, John Parker, Jonathan M. Payne, Laura Poole-Warren, Pankaj Sah, Zoltan Sarnyai, Peter R. Schofield, Olga Shimoni, David H.K. Shum, Tim Silk, Mark Slee, Ashleigh E. Smith, Tina Soulis, Sharath Sriram, Greg J. Stuart, Jonathan Tapson, Matthew B. Thompson, André van Schaik, Nicole A. Vincent, Bryce Vissel, Allison Waters
Journal: Neuron (2019)
The Portuguese version of Rhinitis and Asthma Patient's Perspective (RAPP): Validation and assessment
Authors: A. Todo-Bom, F. Braido, G. Molinengo, C. Loureiro, G.W. Canonica, I. Baiardini
Journal: Pulmonology (2019)

Allergic rhinitis (AR) and asthma are two common chronic diseases that often coexist. There is a need for a validated tool to evaluate HRQoL of Portuguese speakers with asthma and/or rhinitis patients in clinical practice. To adapt and validate RhinAsthma Patient Perspective (RAPP) in Portuguese. The RAPP questionnaire was translated into Portuguese. Asthmatics with comorbidities and rhinitis attending the allergy department of Coimbra University Hospital were asked to complete the Portuguese translation of RAPP, in addition to the SF-12, ACT, and a Symptomatologic VAS twice, with a 4-week interval between visits. During Visit 2, a Global Rating Scale (GRS) was completed to assess any change in health status. Scale dimensions, internal consistency and convergent validity, reliability, discriminant ability and responsiveness to change, as well as Minimal Clinical Difference were assessed. Factor and confirmatory analysis confirm the unidimensional structure of the questionnaire. Internal consistency has been shown to be satisfactory (0.82 visit 1 and 0.86 at visit 2). The tool is able to discriminate between patients on the basis of asthma severity, asthma control level, and rhinitis severity; convergent validity showed a significant correlation with SF-2 Physical component (r = −0.46 and 0.42, p at Visits 1 and 2). An ICC of 0.97 and a CCC = 0.94 indicate that the tool is highly reliable. Responsiveness was shown in detecting a significant association with GRS changes (r = 0.41, p < 0.01) and ACT (r = −0.47, p < 0.01) but not with VAS. (r = .14, n.s.). MID value was 2 points. The Portuguese version of RAPP has been demonstrated to have good measurement properties and sensitivity to health changes, which will provide a valid, reliable and standardized HRQoL measurement in patients with asthma and comorbid allergic rhinitis in clinical practice.
Epinephrine dispensings, allergy hospitalizations and the elimination of co‐payments in Sweden
Authors: Jennifer L. P. Protudjer, Roelinde Middelveld, Natalia Ballardini, Hay Mar Wai, Staffan Ahlstedt, Lennart Nilsson, Juho E. Kivistö
Journal: Allergy (2019)

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