tbuckley/cabot-search huggingface dataset:
Organ Donation After Euthanasia—Reply
Authors: Jan Bollen, Ernst van Heurn, Walther van Mook
Journal: JAMA (2017)

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Gene editing technique successfully corrects mutation in human embryos
Authors: Jacqui Wise
Journal: BMJ (2017)

Researchers in the United States have successfully used a gene editing technique in early stage human embryos to correct a mutation that causes hypertrophic cardiomyopathy, a report in Nature has confirmed.1

The embryos in the study were not allowed to develop for more than a few days and were never intended to be implanted into a womb. Further research is needed to establish the safety of the method before it can be adopted clinically. However, if the technique proves to be safe, it could potentially be used for other genetic disorders such as cystic fibrosis or Huntington’s disease.

Hypertrophic cardiomyopathy is a common inherited condition affecting one in 500 people, and it is the most common cause of sudden death in otherwise healthy young athletes. In 40% of families with hypertrophic cardiomyopathy it is caused by a single copy of a mutant MYBPC3 gene.

The research team produced zygotes by fertilising healthy …
WHAT PRE-PARTICIPATION HEALTH COMPLAINTS AND ATHLETE CHARACTERISTICS PREDICT INJURY AND ILLNESS AT MAJOR ATHLETICS CHAMPIONSHIPS? COHORT STUDY AT THE BEIJING 2015 IAAF WORLD CHAMPIONSHIPS
Authors: Toomas Timpka, Jenny Jacobsson, Victor Bargoria, Julien Periard, Sébastien Racinais, Ola Ronsen, Karin Halje, Christer Andersson, Örjan Dahlström, Armin Spreco, Pascal Edouard, Juan Manuel Alonso
Journal: British Journal of Sports Medicine (2017)

Background During the month before world championships in individual sports, about one-third of athletes are disturbed by injury complaints. Athletics athletes reporting a pre-championship gradual-onset injury complaint are known to be at increased risk to sustain an injury at the upcoming competitions. Predictors for in-championship illness and the predictive value of anxiety associated with pre-participation injury and illness complaints have not been investigated. Objective To determine pre-participation predictors of injury and illness at a major Athletics championship. Design Prospective cohort study. Setting The 2015 IAAF World Championships in Athletics. Participants 307 (32.1%) of 957 athletes in 50 national teams that accepted to participate. Assessment of Risk Factors Sex, age, home continent, event category and pre-participation health complaints with qualifiers (injury or illness complaint, onset type (injury complaints only), reduction in participation, severity estimated by duration of time loss, associated anxiety, expected performance impact, etc.). Main Outcome Measurements In-championship injury and in-championship illness. Results 116 athletes (38.3%) of the participating athletes reported an injury complaint during the month before the championships, while 40 athletes (13%) reported an illness complaint. Twenty athletes (6.5%) sustained an injury or illness during the championships. Endurance athletes were almost tenfold more likely to sustain an in-championship illness than speed/power athletes (OR, 9.88; 95% CI, 1.20–81.31; P =0.033). Participants reporting a pre-participation gradual-onset injury complaint were three times more likely (OR, 3.09; 95% CI, 1.08–8.79; P =0.035) and those reporting an illness complaint causing anxiety were fivefold more likely (OR, 5.56; 95% CI, 1.34–23.15; P =0.018) to sustain an in-championship injury. Conclusions Endurance athletes require particular clinical attention at major Athletics championships. Pre-participation complaints causing anxiety are interesting predictors for in-championship health problems. Diagnostic criteria for different types of exertion-related illness and the clinical and educational services provided to athletes preparing for championships in individual sports warrant further study.
Isolated and unilateral facial angiofibromas revealing a type 1 segmental postzygotic mosaicism of tuberous sclerosis complex with c.4949_4982del <i> <scp>TSC</scp> 2 </i> mutation
Authors: D. Bessis, M.‐C. Malinge, C. Girard
Journal: British Journal of Dermatology (2017)
Human infection with a novel H7N9 avian influenza virus in Yunnan, China
Authors: Yue Feng, Li Gao, Jing Miao, Mi Zhang, Chunyue Zhang, Xicheng Wang, Yuejuan Zhao, Jianrong Zhao, Haiyan Min, Xingqi Dong, Xueshan Xia
Journal: Journal of Infection (2017)
炎症:IFNλ4ではなく,IFN‐λ3がIFNL3‐IFNL4ハプロタイプ依存的に肝臓の炎症および線維症を仲介すると考えられる
Authors: Eslam Mohammed, Kelaeng Kebitsaone Simon, Thabet Khaled, Douglas Mark W, Liddle Christopher, George Jacob, Metwally Mayada, White Rose, Leung Reynold, Rahme Antony, Asimakopoulos Anastasia, Mcleod Duncan, Mahajan Hema, Mahajan Neha, Mangia Alessandra, Santoro Rosanna, Berg Thomas, Fischer Janett, Malik Barbara, Irving William L, Dore Gregory J, Matthews Gail, Applegate Tanya, Grebely Jason, Jonsson Julie R, Sheridan David, Bassendine Margaret, Gronbaek Henning, Abate Maria Lorena, Bugianesi Elisabetta, Rosso Chiara, Mezzabotta Lavinia, Hartmann Rune, Spengler Ulrich, Nattermann Jacob, Fragomeli Vincenzo, Rojas Angela, Romero‐Gomez Manuel, Gallego‐Duran Rocio, Booth David R, Weltman Martin, Mollison Lindsay, Cheng Wendy, Riordan Stephen, Powell Elizabeth
Journal: Nature Genetics (2017)
Customized positive PEG linkers for the delivery of antisense molecules
Authors: Hong Zhao, Prasanna Reddy, Jing Xia, Syed Ali, Maoliang Wang, Puja Sapra, david Filpula, Chalres Conover, Lee Greenberger, Ivan Horak
Journal: Cancer Research (2007)

4731   Introduction: Targeting genes has elicit significant effort over last two decades. Initial effort has focused on first generation of oligonucleotide based molecules as potential therapeutics for various human diseases. Recent progresses in oligonucleotide chemistry helped to introduce second and third generation antisense technology such as locked nucleic acid (LNA) and silencing RNA (siRNA). Effective systemic delivery of this type of molecules is still the biggest hurdle to fully realize their therapeutic potential in clinic. Short half-life and poor cellular uptake of highly negative charged feature of oligonucleotides has resulted suboptimal efficacy in xenograft models. To overcome these challenges, here we want to report the development of new Customized positively charged PEG linkers and their application to enhance the cellular uptake of antisense oligonucleotide, including LNA.  Procedure: Customized positively charged PEG linkers were made by incorporating either peptide fragments, or synthetic positive moieties into the backbone of PEG polymer. These PEG polymers were then converted to releasable, tail-free linkers using proprietary technologies before conjugated with antisense oligonucleotides. The PEG-oligo conjugates were tested for their stability in buffer and plasma. Subsequently, in vitro protein inhibition and target gene down-regulation studies were conducted using Western Blot and Real-Time PCR techniques in a panel of tumor cell lines with and without transfection agents.  Summary of Data: The PEG-oligo conjugates are stable under physiological buffer conditions and have shown greatly enhanced stability towards certain nucleases such as phosphodiesterase I (59-exonuclease), phosphodiesterase II (39-exonuclease), and nuclease P1 (endonuclease) in vitro. All the PEG-oligo conjugates have demonstrated a controlled release of native antisense molecule in rat plasma. More importantly, PEG-oligo conjugates have shown dose-dependent and specific target gene down-regulation documented by both Western blot and Real-Time PCR studies.  Conclusions: PEGylation of oligonucleotide using Customized positively charged PEG linkers has improved the in vitro stability of oligo molecules and released native antisense at different rates in plasma. The in vitro activity of PEG-oligo is dose dependent and more efficient than native molecule, especially in the absence of transfection agents. Safety, efficacy and down-modulation of target gene will be determined using PEG-oligo conjugates in preclinical models. Customized positively charged PEG linkers may provide a unique approach for the more efficient in vivo delivery of antisense molecules including LNA to fully realize its therapeutic potential.
BACK PAIN RISK FACTORS IN ADOLESCENT ATHLETES: SUITABILITY OF A BIOMECHANICAL SCREENING TOOL?
Authors: Steffen Mueller, Juliane Mueller, Josefine Stoll, Tilman Engel, Frank Mayer
Journal: British Journal of Sports Medicine (2017)

Background Back pain (BP) is already a relevant injury site in adolescent athletes. A valid screening is essential for BP prevention. Objective To investigate whether a biomechanical screening tool (BST) is suitable to predict BP in adolescent athletes. Design Longitudinal analysis with 1.9±1.0 yrs between both measurement days. Setting Medical center of the German Olympic Sports Federation . BST was implemented in the annual (pre-participation) examination of elite athletes. Patients (or Participants) 343 athletes (195 males/148 females, 13±1 yrs, 164±12 cm, 53±13 kg, 5±3 training years, 8±6 training hours per week) out of 20 sport disciplines were included in the study. Interventions (or Assessment of Risk Factors) Subjective BP was assessed using a faces-pain-scale (FPS 1–5: 1=no pain; 2–5=slight- to maximum pain). In addition, postural control (one-legged stance), jumping performance (counter movement/drop jump), and maximum isokinetic trunk extension/flexion strength (60°/sec) was assessed for all athletes. Main Outcome Measurements Athletes were classified into 4 groups with respect to the course of back pain [(A) no BP (n=206); (B) BP-developers (n=34); (C) persisting BP (n=71); (D) diminishing BP (n=32)]. Outcomes included center of pressure displacement COP [mm], jump height [cm], peak jumping force [N], contact time [ms] and peak torque for trunk extension/flexion [Nm]. Descriptive analysis was followed by two-way ANOVA (repeated measures; α=0.05). Results Overall, the athletes enhanced trunk strength, jump performance and postural control across the evaluation period. Pain free athletes (A) showed statistically significant higher trunk strength gains (extension/flexion: +45/+37%) compared to athletes developing BP (B: +20/+9%; p&lt;0.05). No differences were observed for jump performance and postural control (p&gt;0.05). Conclusions Analysing biomechanical variables is valid to identify significantly impaired trunk strength development in athletes with BP incidence. In contrast, jump performance and postural control are of minor relevance. Therefore, poor trunk strength development could serve as back pain risk factor in athletes. Trunk strength training interventions should be recommended.
Cyclophilin A Maintains Glioma-Initiating Cell Stemness by Regulating Wnt/β-Catenin Signaling
Authors: Guangzhi Wang, Jia Shen, Jiahang Sun, Zhenfeng Jiang, Jiabing Fan, Hongjun Wang, Shan Yu, Yu Long, Yi Liu, Hongbo Bao, Kelvin Xi Zhang, Ke Han, Minwei Zhu, Yongri Zheng, Zhiguo Lin, Chuanlu Jiang, Mian Guo
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Glioma-initiating cells (GIC) are glioma stem–like cells that contribute to glioblastoma (GBM) development, recurrence, and resistance to chemotherapy and radiotherapy. They have recently become the focus of novel treatment strategies. Cyclophilin A (CypA) is a cytosolic protein that belongs to the peptidyl–prolyl isomerase (PPIase) family and the major intracellular target of the immunosuppressive drug cyclosporin A (CsA). In this study, we investigate the functions of CypA and its mechanism of action in GICs' development. Experimental Design: We analyzed differences in CypA expression between primary tumors and neurospheres from the GDS database, both before and after GIC differentiation. A series of experiments was conducted to investigate the role of CypA in GIC stemness, self-renewal, proliferation, radiotherapy resistance, and mechanism. We then designed glutathione S-transferase (GST) pulldown and coimmunoprecipitation assays to detect signaling activity. Results: In this study, we demonstrated that CypA promotes GIC stemness, self-renewal, proliferation, and radiotherapy resistance. Mechanistically, we found that CypA binds β-catenin and is recruited to Wnt target gene promoters. By increasing the interaction between β-catenin and TCF4, CypA enhances transcriptional activity. Conclusions: Our results demonstrate that CypA enhances GIC stemness, self-renewal, and radioresistance through Wnt/β-catenin signaling. Due to its promotive effects on GICs, CypA is a potential target for future glioma therapy. Clin Cancer Res; 23(21); 6640–9. ©2017 AACR.
The Histone Deacetylase 1 and 2 (HDAC1/2) Inhibitor ACY-957: Impact of Dosing Schedule on Pharmacokinetics (PK), Pharmacodynamics (PD), Hematopoietic Toxicity, and Gamma Globin (HBG, ɣ) Expression in Monkey
Authors: Apurva Chonkar, Matthew Jarpe, Kailash Bhol, Simon S Jones, Jeffrey R Shearstone
Journal: Blood (2016)
Acute Flaccid Myelitis Among Children — Washington, September<b>–</b>November 2016
Authors: Jesse Bonwitt, Amy Poel, Chas DeBolt, Elysia Gonzales, Adriana Lopez, Janell Routh, Krista Rietberg, Natalie Linton, James Reggin, James Sejvar, Scott Lindquist, Catherine Otten
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

In October 2016, Seattle Children's Hospital notified the Washington State Department of Health (DOH) and CDC of a cluster of acute onset of limb weakness in children aged ≤14 years. All patients had distinctive spinal lesions largely restricted to gray matter detected by magnetic resonance imaging (MRI), consistent with acute flaccid myelitis (AFM). On November 3, DOH issued a health advisory to local health jurisdictions requesting that health care providers report similar cases. By January 24, 2017, DOH and CDC had confirmed 10 cases of AFM and excluded two suspected cases among residents of Washington during September-November 2016. Upper respiratory tract, stool, rectal, serum, buccal, and cerebrospinal fluid (CSF) specimens were tested for multiple pathogens. Hypothesis-generating interviews were conducted with patients or their parents to determine commonalities between cases. No common etiology or source of exposure was identified. Polymerase chain reaction (PCR) testing detected enterovirus D68 (EV-D68) in nasopharyngeal swabs of two patients, one of whom also tested positive for adenovirus by PCR, and detected enterovirus A71 (EV-A71) in the stool of a third patient. Mycoplasma spp. immunoglobulin M (IgM) titer was elevated in two patients, but both had upper respiratory swabs that tested negative for Mycoplasma spp. by PCR. Clinicians should maintain vigilance for AFM and report cases as soon as possible to state or local health departments.
02.48 Inhibition of in vitro b cell maturation and igg secretion by new chemical probes in assays using blood cells from patients with sle and iim
Authors: Yvonne Sundström, Filip Bergqvist, Michael Sundström, Elena Ossipova, Johan Lengqvist, Iva Gunnarsson, Ingrid Lundberg, Per-Johan Jakobsson, Louise Berg
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic inflammatory diseases, such as systemic lupus erythematosus (SLE) and idiopathic inflammatory myositis (IIM), have largely unknown aetiology and represent a disease area with major unmet medical needs. Treatment often give a clinical effect, but not in all patients; and symptoms often remain. In collaboration with the Structural Genomics Consortium (SGC), we have investigated <i>in vitro</i> B-cell effects of about 50 different chemical probes which bind and inhibit epigenetic enzymes and regulators, such as bromodomains and histone methyltransferases, as well as kinases and other intracellular protein targets. These probes are small molecules that can enter cells and selectively inhibit potential new drug-targets at therapeutically relevant doses. The read out are expression of molecules which have been shown to be of pathological relevance in systemic inflammatory diseases. <h3>Materials and methods</h3> Peripheral blood mononuclear cells (PBMC) from patients with SLE or IIM and healthy controls were incubated in presence of different chemical probes at 1 or 0,1 uM for 6 days in culture medium containing B-cell stimulating factors; IL4, IL10, IL21, sCD40L and CpG2006. Cell viability was determined by flow cytometry using the live/dead marker viability IR<sup>®</sup> and B-cell maturation was investigated using markers for memory B cells (CD27), plasmablasts (CD38) and surface IgG. Secretion of IgG was quantified by ELISA. <h3>Results</h3> The percentage of memory B cells, plasmablasts and IgG-expressing B cells, as well as IgG secretion, was induced by the B-cell stimulating factors. These parameters were suppressed by a set of the epigenetic probes, as well as by some of the probes targeting other intracellular proteins. A few of the probes decreased cell viability. Both B cells from SLE and IIM were affected. <h3>Conclusions</h3> We have found a set of chemical probes, with documented target selectivity and potent inhibitory effects of these targets, which affect <i>in vitro</i> B-cell maturation and secretion of IgG. Further analysis is required to better understand the pathways that are affected.
PTH-002 Survival after upper gi stent insertion: a retrospective audit from a single centre
Authors: H Smart, C Cooper, C Carr, N Haslam, P O’Toole, A Moore, J Ramesh, S Sarkar
Journal: Endoscopy (2017)

<h3>Introduction</h3> The insertion of self-expanding metal mesh stents (SEMS) is often employed in the palliation of upper GI malignancy or in patients with benign disease who are unfit for more aggressive intervention. Technical and clinical outcomes are usually predictable and good. It is more difficult to predict patient survival; this audit was undertaken to address this outcome. <h3>Method</h3> Patients undergoing upper GI SEMS insertion between 1<sup>st</sup> January and 31<sup>st</sup> December 2016 were identified from an endoscopy software system (Unisoft). Patients' demographic data and outcome was obtained by interrogation of the hospital computerised laboratory records system (ICE), Somerset Cancer Registry (SCR) and pathological records. <h3>Results</h3> 76 upper GI SEMS were inserted in 59 patients between 1<sup>st</sup> January and 31<sup>st</sup> December 2016. There were 42 men and 17 women. The mean age of the group was 68.5 (range 41–89) years. <b>SEMS insertion</b> – This was undertaken by experienced endoscopists utilising fluoroscopy in all cases. Oesophageal SEMS used were all fully covered, either Wallflex Oesophageal (Boston Scientific) or Niti-S Double (Taewoong) and inserted using the over-the-wire technique. Gastric outflow SEMS were either Evolution Duodenal uncovered (Cook Medical) or Niti-S S pyloric/duodenal fully covered (Taewoong). These were inserted using the through-the-scope method. <b>Oesophageal SEMS insertion</b> – This was undertaken in 49 patients; 46 had oesophageal or oesophago-gastric junctional cancer, 2 extrinsic compression from lung cancer and 1 benign post-operative anastomotic stricture. 1 or more repeat interventions were required in a total of 17 (35%) patients. This included 17 repeat SEMS insertions, 5 reposition of SEMS, 1 removal for pain and 1 argon plasma coagulation recanalisation of hyperplastic overgrowth. 37 patients (75%) died after a median follow up of 99 (range 3–485) days. The median survival was 89 (range 3–485) days. <b>Gastric outflow SEMS insertion</b> – This was performed in 10 patients; 5 had pancreatic cancer, 2 post-operative recurrence of oesophago-gastric cancer, 1 gastric cancer, 1 post-operative anastomotic stricture (Whipple's procedure) and 1 chronic pancreatitis. 2 patients (20%) had repeat intervention; 1 removal (benign disease) and 1 stent dilatation. 7 patients (70%) died after a median follow up of 80 (range 8–232) days. The median survival was 56 (range 8–110) days. <h3>Conclusion</h3> We know that upper GI SEMS insertion produces palliation of distressing symptoms in patients with advanced disease. In this audit we have defined that between 20%–35% of patients require an endoscopic re-intervention to their SEMS. Survival in both patient groups is limited, with a median survival of between 2 and 3 months. This data should inform discussion in patients regarding end of life planning. <h3>Disclosure of Interest</h3> None Declared
Edible Electrochemistry: Food Materials Based Electrochemical Sensors
Authors: Jayoung Kim, Itthipon Jeerapan, Bianca Ciui, Martin C. Hartel, Aida Martin, Joseph Wang
Journal: Advanced Healthcare Materials (2017)

This study demonstrates the first example of completely food-based edible electrochemical sensors. The new edible composite electrodes consist of food materials and supplements serving as the edible conductor, corn, and olive oils as edible binders, vegetables as biocatalysts, and food-based packing sleeves. These edible composite electrodes are systematically characterized for their attractive electrochemical properties, such as potential window, capacitance, redox activity using various electrochemical techniques. The sensing performance of the edible carbon composite electrodes compares favorably with that of "traditional" carbon paste electrodes. Well defined voltammetric detection of catechol, uric acid, ascorbic acid, dopamine, and acetaminophen is demonstrated, including sensitive measurements in simulated saliva, gastric fluid, and intestinal fluid. Furthermore, successful biosensing applications are realized by incorporating a mushroom and horseradish vegetable tissues with edible carbon pastes for imparting biocatalytic activity toward the biosensing of phenolic and peroxide compounds. The attractive sensing performance of the new edible sensors indicates considerable promise for physiological monitoring applications and for developing edible and ingestible devices for diverse biomedical applications.