tbuckley/cabot-search huggingface dataset:
Abstract 17601: The Relationship of Serum Potassium Level and the Survival Outcomes in Out-of-hospital Cardiac Arrest Patients
Authors: Dongsun Choi, Young Sun Ro, Sang Do Shin
Journal: Circulation (2016)

Introduction:  Potassium has essential role in cellular function. The aim of this study was to evaluate the relationship of serum potassium level and the survival outcomes for out-of-hospital cardiac arrest (OHCA) patients   Methods:  This study is prospective study, We used CAPTURES database, which is OHCA cohort of 27 Emergency Department (ED) in Korea , consist of 5 Level 1 ED and 22 Level 2 ED, from February 2014 to January 2015. The inclusion criteria were all OHCA patients in cohort who receive cardiopulmonary resuscitation (CPR) in ED. Patients were excluded if they were transferred from another hospital or had pre-hospital return of spontaneous circulation (ROSC), If the Initial potassium level and clinical outcome data is missing or not captured. Main exposure was Serum potassium concentration on arrival. According to the serum potassium level, Patients were devided into hypokalemia group (K+   Results:  During study period, 1,616 patients with CAPTURES cohort, 792 patietns were included in analysis. 40 (5.1%) patients were hypokalemia, 318(40.2%) patients were normokalemia, 434(54.8%) patients were hyperkalemia. In hyperkalmia group have significantly lower ratio of good neurologic outcome (1.6%) than normokalemia group (6.2%). And Hypokalemia group have significantly higher ratio of good neurologic outcome (30%). After adjusting covariables, The neurologic outcome of Hyperkalmia group is significantly lower than normokalmia (OR 0.45 95% CI 0.32 - 0.86). And the neurologic outcome of hypokalemia group is significantly higher than normokalemia group (OR 2.8 95% CI 1.08 - 7.22)   Conclusions:  In OHCA patients, Hyperkalemia had significant relationship with poor neurologic outcome. And Hypokalmia had relationship with good neurologic outcome.
Cryj 1, a major allergen of Japanese cedar pollen, up-regulates the effector functions of eosinophils
Authors: Takehito Kobayashi, Kazuyuki Nakagome, Sachiko Miyauchi, Toru Noguchi, Kouhei Saitou, Tomoyuki Soma, Hidetomo Nakamoto, Makoto Nagata
Journal: Journal of Allergy and Clinical Immunology (2018)
Sucrase-isomaltase 15Phe IBS risk variant in relation to dietary carbohydrates and faecal microbiota composition
Authors: Louise Thingholm, Malte Rühlemann, Jun Wang, Matthias Hübenthal, Wolfgang Lieb, Matthias Laudes, Andre Franke, Mauro D’Amato
Journal: Gut (2018)

Recently in Gut , a coding sucrase-isomaltase ( SI ) variant (15Phe at single nucleotide polymorphism rs9290264) with 35% reduced disaccharidase activity was reported to increase IBS risk and to correlate with more frequent stools. These observations were not assessed in relation to key dietary factors including carbohydrate (ie, SI substrates) consumption.1 

Here, we studied two large German population-based cross-sectional cohorts, namely PopGen (n=639; average age 61.4; 44.8% female) and FoCus (n=759; average age 53.0; 58.5% female), with available genotype (genome-wide arrays), dietary (12-month food frequency questionnaire, FFQ), faecal microbiota (16S sequencing) and IBS status (self-reported from questionnaire) data, as previously described in detail.2–4 

In a combined age/sex/body mass index (BMI)-adjusted logistic regression analysis of the two data sets, carriers of the 15Phe variant (52.86%) reported IBS significantly more often than non-carriers (3.69% vs 1.84%, respectively; P=0.044, OR=2.04), thus replicating and extending previous findings.1 When taking into account the consumption of SI substrate carbohydrates (polysaccharides and disaccharides; g/day) estimated from FFQ, this association appeared strongest for individuals with lowest intake (not shown). In particular, as illustrated in figure 1, starch was the individual carbohydrate component where the largest difference in IBS prevalence …
Abstract 11678: Tricuspid Valve Repair Versus Replacement for Very Severe Functional Tricuspid Regurgitation
Authors: Duk-Hyun Kang, Jeong Yoon Jang, Ran Heo, Sahmin Lee, Jong-Min Song, Kee-Joon Choi, Jae-Kwan Song, Jae-Won Lee, Joo-Hee Zo
Journal: Circulation (2016)

Introduction: The optimal decision regarding whether to repair or replace the tricuspid valve (TV) remains controversial in patients with very severe functional tricuspid regurgitation (TR). Objectives: We sought to compare clinical outcomes of TV repair versus replacement for very severe TR associated with severe TV tethering. Methods: We included 96 consecutive patients (20 men, 58±11 years of age) who had both severe tethering of TV and very severe functional TR, and consequently underwent TV surgery during left-sided valve surgery. TV repair was performed on 79 patients (repair group), whereas 17 patients underwent TV replacement (replacement group). The primary end-point of the study was defined as the composite of operative mortality, cardiac death, repeat TV surgery and hospitalization due to congestive heart failure during follow-up. Results: The two groups had similar baseline clinical, echocardiographic and operative characteristics, but operative mortality was significantly higher in the replacement group than in the repair group (P=0.008). During a median follow-up of 87 months, 19 (24%) patients in the repair group and 8 (47%) in the replacement group attained the composite end point, and the estimated 10-year event-free survival rate was significantly higher in the repair group (75 ± 6%) than in the replacement group (43 ± 2%) (P = 0.019). TV replacement was independently associated with end points in the Cox proportional hazards analysis after adjustment with propensity score (hazard ratio, 4.033; 95% CI, 1.470 to 11.071; P=0.007). Conclusions: Compared with TV repair, replacement was associated with higher operative mortality and worse long-term clinical outcomes in patients with very severe functional TR. Repair should be the preferred surgical option even for severe TR associated with more advanced tethering and right ventricular dilatation.
Countrywide demonstration of adult protection derived from infant immunisation
Authors: Carlos G Grijalva
Journal: Thorax (2018)

Humans, especially young children, are considered the only reservoir of Streptococcus pneumoniae . Pneumococcal nasopharyngeal colonisation is very common and usually asymptomatic, but it also represents the primordial step in the development of pneumococcal diseases.1 Nasopharyngeal colonisation is very prevalent among young children but appears to be much less common among adults. Yet, adults, especially older adults, are disproportionally affected by pneumococcal diseases. Close interaction with young children is a recognised source of exposure to pneumococcus among adults, and previous studies have documented the associations with colonisation and also disease among exposed adults.2–4 

The chain of transmission of pneumococcal colonisation and its connection with disease has been drastically transformed with the introduction of the pneumococcal conjugate vaccines. Unlike non-conjugated polysaccharide vaccines, pneumococcal conjugate vaccines elicit a strong immune response in vaccinated young children and provide protection against colonisation with serotypes included in the vaccine. This leads not only to protection of vaccinated children, but by targeting the main reservoir of transmission, vaccination also prevents transmission of pneumococcus to others in contact with vaccinated children. Indeed, widespread vaccination of infants with conjugate vaccines has led first to reductions and ultimately to virtual elimination of the circulation of serotypes included in the vaccines.5–8

Routine vaccination of infants with pneumococcal conjugate vaccines has led to profound changes in the ecology of S. pneumoniae and the distribution of related infections. As the circulation of vaccine serotypes was reduced due to the powerful biological pressure of the vaccine, disease caused by those retreating vaccine serotypes has declined in both vaccinated and unvaccinated …
Analysis of DNA Methylation in Young People: Limited Evidence for an Association Between Victimization Stress and Epigenetic Variation in Blood
Authors: Sarah J. Marzi, Karen Sugden, Louise Arseneault, Daniel W. Belsky, Joe Burrage, David L. Corcoran, Andrea Danese, Helen L. Fisher, Eilis Hannon, Terrie E. Moffitt, Candice L. Odgers, Carmine Pariante, Richie Poulton, Benjamin S. Williams, Chloe C.Y. Wong, Jonathan Mill, Avshalom Caspi
Journal: American Journal of Psychiatry (2018)

Objective: DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become “embedded” in the genome and alter transcriptional processes to compromise health. The authors sought to investigate whether early-life victimization stress is associated with genome-wide DNA methylation. Method: The authors tested the hypothesis that victimization is associated with DNA methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994–1995 birth cohort of 2,232 twins born in England and Wales and assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms of victimization were ascertained in childhood and adolescence (including physical, sexual, and emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber-victimization; and crime). Results: Epigenome-wide analyses of polyvictimization across childhood and adolescence revealed few significant associations with DNA methylation in peripheral blood at age 18, but these analyses were confounded by tobacco smoking and/or did not survive co-twin control tests. Secondary analyses of specific forms of victimization revealed sparse associations with DNA methylation that did not replicate across different operationalizations of the same putative victimization experience. Hypothesis-driven analyses of six candidate genes in the stress response (NR3C1, FKBP5, BDNF, AVP, CRHR1, SLC6A4) did not reveal predicted associations with DNA methylation in probes annotated to these genes. Conclusions: Findings from this epidemiological analysis of the epigenetic effects of early-life stress do not support the hypothesis of robust changes in DNA methylation in victimized young people. We need to come to terms with the possibility that epigenetic epidemiology is not yet well matched to experimental, nonhuman models in uncovering the biological embedding of stress.
UN pledges to tackle environmental health risks
Authors: Anne Gulland
Journal: BMJ (2018)

The United Nations and World Health Organization are to work together to tackle environmental health risks such as air pollution and vector borne diseases.

WHO and UN Environment signed an agreement in Nairobi, Kenya on 10 January for closer collaboration and will establish a joint programme as well as an annual high level meeting to curb the environmental risks that are linked to around 12.6 million deaths each year, mainly in lower and middle income countries.

Although the two agencies already collaborate, they say this is the most …
Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling
Authors: Takashi Kanaya, Sayuri Sakakibara, Toshi Jinnohara, Masami Hachisuka, Naoko Tachibana, Shinya Hidano, Takashi Kobayashi, Shunsuke Kimura, Toshihiko Iwanaga, Tomoo Nakagawa, Tatsuro Katsuno, Naoya Kato, Taishin Akiyama, Toshiro Sato, Ifor R. Williams, Hiroshi Ohno
Journal: The Journal of Experimental Medicine (2018)

M cells are located in the follicle-associated epithelium (FAE) that covers Peyer’s patches (PPs) and are responsible for the uptake of intestinal antigens. The differentiation of M cells is initiated by receptor activator of NF-κB. However, the intracellular pathways involved in M cell differentiation are still elusive. In this study, we demonstrate that the NF-κB pathway activated by RANK is essential for M cell differentiation using in vitro organoid culture. Overexpression of NF-κB transcription factors enhances the expression of M cell–associated molecules but is not sufficient to complete M cell differentiation. Furthermore, we evaluated the requirement for tumor necrosis factor receptor–associated factor 6 (TRAF6). Conditional deletion of TRAF6 in the intestinal epithelium causes a complete loss of M cells in PPs, resulting in impaired antigen uptake into PPs. In addition, the expression of FAE-associated genes is almost silenced in TRAF6-deficient mice. This study thus demonstrates the crucial role of TRAF6-mediated NF-κB signaling in the development of M cells and FAE.
Critical roles of αII spectrin in brain development and epileptic encephalopathy
Authors: Yu Wang, Tuo Ji, Andrew D. Nelson, Katarzyna Glanowska, Geoffrey G. Murphy, Paul M. Jenkins, Jack M. Parent
Journal: Journal of Clinical Investigation (2018)

The nonerythrocytic α-spectrin-1 (SPTAN1) gene encodes the cytoskeletal protein αII spectrin. Mutations in SPTAN1 cause early infantile epileptic encephalopathy type 5 (EIEE5); however, the role of αII spectrin in neurodevelopment and EIEE5 pathogenesis is unknown. Prior work suggests that αII spectrin is absent in the axon initial segment (AIS) and contributes to a diffusion barrier in the distal axon. Here, we have shown that αII spectrin is expressed ubiquitously in rodent and human somatodendritic and axonal domains. CRISPR-mediated deletion of Sptan1 in embryonic rat forebrain by in utero electroporation caused altered dendritic and axonal development, loss of the AIS, and decreased inhibitory innervation. Overexpression of human EIEE5 mutant SPTAN1 in embryonic rat forebrain and mouse hippocampal neurons led to similar developmental defects that were also observed in EIEE5 patient-derived neurons. Additionally, patient-derived neurons displayed aggregation of spectrin complexes. Taken together, these findings implicate αII spectrin in critical aspects of dendritic and axonal development and synaptogenesis, and support a dominant-negative mechanism of SPTAN1 mutations in EIEE5.
EMA calls for hydroxyethyl starch solutions to be taken off market
Authors: Deborah Cohen
Journal: BMJ (2018)

Hydroxyethyl starch (HES) solutions for infusion should be removed from the market across Europe because they carry “serious risks,” the European Medicines Agency (EMA) has said.

Hydroxyethyl starch solutions are colloids used for plasma volume replacement following acute blood loss. They have been used instead of crystalloids—such as saline—to prevent shock.

In 2013, the EMA said that the products should not be used to treat critically ill patients or patients with sepsis, after trials found an increased risk …
Skin Conformal Polymer Electrodes for Clinical ECG and EEG Recordings
Authors: Flurin Stauffer, Moritz Thielen, Christina Sauter, Séverine Chardonnens, Simon Bachmann, Klas Tybrandt, Christian Peters, Christofer Hierold, Janos Vörös
Journal: Advanced Healthcare Materials (2018)

Abstract Preparation‐free and skin compliant biopotential electrodes with high recording quality enable wearables for future healthcare and the Internet of Humans. Here, super‐soft and self‐adhesive electrodes are presented for use on dry and hairy skin without skin preparation or attachment pressure. The electrodes show a skin‐contact impedance of 50 kΩ cm 2 at 10 Hz that is comparable to clinical standard gel electrodes and lower than existing dry electrodes. Microstructured electrodes inspired by grasshopper feet adhere repeatedly to the skin with a force of up to 0.1 N cm −2 without further attachment even during strong movement or deformation of the skin. Skin compliance and adhesive properties of the electrodes result in reduction of noise and motion artifacts superior to other dry electrodes reaching the performance of commercial gel electrodes. The signal quality is demonstrated by recording a high‐fidelity electrocardiograms of a swimmer in water. Furthermore, an electrode with soft macropillars is used to detect alpha activity in the electroencephalograms from the back of the head through dense hair. Compared to gel electrodes, the soft biopotential electrodes are nearly imperceptible to the wearer and cause no skin irritations even after hours of application. The electrodes presented here could combine unobtrusive and long‐term biopotential recordings with clinical‐grade signal performance.
Significant comorbidity of necrotizing enterocolitis with non-IgE-mediated gastrointestinal food allergy in non-premature babies
Authors: Yumiko Miyaji, Tatsuki Fukuie, Masami Narita, Yukihiro Ohya, Kenji Matsumoto, Ichiro Nomura
Journal: Journal of Allergy and Clinical Immunology (2018)
Impact of a five-dimensional framework on R&amp;D productivity at AstraZeneca
Authors: Paul Morgan, Dean G. Brown, Simon Lennard, Mark J. Anderton, J. Carl Barrett, Ulf Eriksson, Mark Fidock, Bengt Hamrén, Anthony Johnson, Ruth E. March, James Matcham, Jerome Mettetal, David J. Nicholls, Stefan Platz, Steve Rees, Michael A. Snowden, Menelas N. Pangalos
Journal: Nature Reviews Drug Discovery (2018)
Abstract 11944: Association of Heavy Alcohol Consumption With Risk of Heart Failure Stratified by Patient Characteristics
Authors: Isaac R Whitman, Vratika Agarwal, Jonathan W Dukes, Eric Vittinghoff, Thomas A Dewland, Gregory M Marcus
Journal: Circulation (2015)

Introduction: While cardiac systolic dysfunction secondary to chronic abuse of alcohol is well described, some evidence suggests a cardiovascular benefit of moderate alcohol consumption. It remains unclear if heavy alcohol consumption predicts congestive heart failure (CHF) in the general population. In addition, the patient characteristics that might influence this relationship remain unknown. Methods and Results: We randomly selected 1 million adults from the California Healthcare Cost and Utilization Project database (capturing all emergency department, ambulatory procedural, and inpatient healthcare encounters) from January 1, 2005 to December 31, 2009. After exclusions for missing demographic information (N=72,301, 7%) and prevalent CHF at study entry (N=69,512, 7%), 858,187 patients were included in the analysis. Analysis variables were defined using ICD-9 codes. During study follow-up, 4% (N=33,046) were coded with alcohol abuse and 12% (N=106,655) developed incident CHF. The mean age was 52 ± 21 years, 35% (N=299,884) were men, and 45% (N=384,204) were white. After adjustment for age, gender, race, hypertension, diabetes, coronary artery disease, chronic kidney disease, valvular heart disease, dyslipidemia, smoking, obesity, obstructive sleep apnea, and income, alcohol abuse was associated with a 70% increased risk of incident CHF (hazard ratio 1.69, 95%CI 1.49-1.91, P&lt;0.001). This relationship was especially strong among younger individuals and those without hypertension ( Figure ). Conclusions: Alcohol abuse was associated with incident CHF in this diverse, population-based cohort. Interaction analyses suggest that the mechanism linking alcohol abuse to development of heart failure may resemble those intrinsic to age related comorbidities and hypertension. Younger individuals and those without hypertension may be disproportionately prone to the myocardial toxic effects of alcohol.
Asthma-COPD overlap: A Portuguese survey
Authors: E. Padrão, D. Araújo, A. Todo Bom, C. Robalo Cordeiro, J. Correia de Sousa, J. Cardoso, M. Morais-Almeida, R. Costa, F. Pavão, R.B. Leite, A. Marques
Journal: Pulmonology (2018)

The overlap between asthma and chronic obstructive pulmonary disease (COPD) (ACO) has been discussed for many years but clinical recommendations for this entity have been diverse. This study is intended to reach a consensus on diagnosis, treatment and patient orientation for ACO, within the Portuguese medical community. This study was conducted by a multidisciplinary panel of experts from three distinct medical specialties (Pulmonology, Family Medicine and Immunoallergology). This panel selected a total of 190 clinicians, based on their expertise in obstructive airway diseases, to participate in a Delphi structured survey with three rounds of questionnaires. These results were ultimately discussed, in a meeting with the panel of experts and some of the study participants, and consensus was reached in terms of classification criteria, treatment and orientation of ACO patients. The majority of clinicians (87.2%) considered relevant the definition of an overlap entity between asthma and COPD. A consensus was achieved on the diagnosis of ACO – presence of simultaneous clinical characteristics of asthma and COPD together with a fixed airflow obstruction (FEV1/FVC < 0.7) associated with 2 major criteria (previous history of asthma; presence of a previous history of smoking exposure and/or exposure to biomass combustion; positive bronchodilation test (increase in FEV1 of at least 200 mL and 12%) on more than 1 occasion) plus 1 minor criteria (history of atopy; age ≥40 years; peripheral eosinophilia (>300 eosinophils/μL or >5% of leukocytes); elevation of specific IgEs or positive skin tests for common allergens). A combination of inhaled corticosteroid (ICS) with long-acting beta2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) was considered as first line pharmacological treatment. Triple therapy with ICS plus LABA and LAMA should be used in more severe or symptomatic cases. Non-pharmacological treatment, similar to what is recommended for asthma and COPD, was also considered highly important. A hospital referral of ACO patients should be made in symptomatic or severe cases or when there is a lack of diagnostic resources. This study highlights the relevance of defining ACO, within the Portuguese medical community, and establishes diagnostic criteria that are important for future interventional studies. Recommendations on treatment and patient's orientation were also achieved.
N6-methyladenosine RNA modification regulates embryonic neural stem cell self-renewal through histone modifications
Authors: Yang Wang, Yue Li, Minghui Yue, Jun Wang, Sandeep Kumar, Robert J. Wechsler-Reya, Zhaolei Zhang, Yuya Ogawa, Manolis Kellis, Gregg Duester, Jing Crystal Zhao
Journal: Nature Neuroscience (2018)

Internal N
Mutations in DNMT3A, U2AF1, and EZH2 identify intermediate-risk acute myeloid leukemia patients with poor outcome after CR1
Authors: Caner Saygin, Cassandra Hirsch, Bartlomiej Przychodzen, Mikkael A. Sekeres, Betty K. Hamilton, Matt Kalaycio, Hetty E. Carraway, Aaron T. Gerds, Sudipto Mukherjee, Aziz Nazha, Ronald Sobecks, Christopher Goebel, Donna Abounader, Jaroslaw P. Maciejewski, Anjali S. Advani
Journal: Blood Cancer Journal (2018)

Intermediate-risk acute myeloid leukemia (IR-AML) is a clinically heterogeneous disease, for which optimal post-remission therapy is debated. The utility of next-generation sequencing information in decision making for IR-AML has yet to be elucidated. We retrospectively studied 100 IR-AML patients, defined by European Leukemia Net classification, who had mutational information at diagnosis, received intensive chemotherapy and achieved complete remission (CR) at Cleveland Clinic (CC). The Cancer Genome Atlas (TCGA) data were used for validation. In the CC cohort, median age was 58.5 years, 64% had normal cytogenetics, and 31% required >1 induction cycles to achieve CR1. In univariable analysis, patients carrying mutations in DNMT3A, U2AF1, and EZH2 had worse overall and relapse-free survival. After adjusting for other variables, the presence of these mutations maintained an independent effect on survival in both CC and TCGA cohorts. Patients who did not have the mutations and underwent hematopoietic cell transplant (HCT) had the best outcomes. HCT improved outcomes for patients who had these mutations. RUNX1 or ASXL1 mutations did not predict survival, and performance of HCT did not confer a significant survival benefit. Our results provide evidence of clinical utility in considering mutation screening to stratify IR-AML patients after CR1 to guide therapeutic decisions.