bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the impact of the National Department of Health’s National Adherence Guidelines for Chronic Diseases in South Africa using routinely collected data: a cluster-randomised evaluation
Authors: Fox Matthew P , Pascoe Sophie J , Huber Amy N , Murphy Joshua , Phokojoe Mokgadi , Gorgens Marelize , Rosen Sydney , Wilson David , Pillay Yogan , Fraser-Hurt Nicole
Published: January 2018

Introduction

In 2016, South Africa’s National Department of Health (NDOH) launched the National Adherence Guidelines for Chronic Diseases for phased implementation throughout South Africa. Early implementation of a ‘minimum package’ of eight interventions in the Adherence Guidelines for patients with HIV is being undertaken at 12 primary health clinics and community health centres in four provinces. NDOH and its partners are evaluating the impact of five of the interventions in four provinces in South Africa.

Methods and analysis

The minimum package is being delivered at the 12 health facilities under NDOH guidance and through local health authorities. The five evaluation interventions are: (1) fast track initiation counselling for patients eligible for antiretroviral therapy (ART); (2) adherence clubs for stable ART patients; (3) decentralised medication delivery for stable ART patients; (4) enhanced adherence counselling for unstable ART patients; and (5) early tracing of patients who miss an appointment by ≥5 days. For evaluation, NDOH matched the 12 intervention clinics with 12 comparison clinics and randomly allocated one member of each pair to intervention or comparison (standard of care) status within pairs, allowing evaluation of the interventions using a matched cluster-randomised design. The evaluation uses data routinely collected by the clinics, with no study interaction with subjects to prevent influencing the primary outcomes. Enrolment began on 20 June 2016 and was completed on 16 December 2016. A total of 3456 patients were enrolled and will now be followed for 14 months to estimate effects on short-term and final outcomes. Primary outcomes include viral suppression, retention and medication pickups, evaluated at two time points during follow-up.

Ethics and dissemination

The study received approval from the University of Witwatersrand Human Research Ethics Committee and Boston University Institutional Review Board. Results will be presented to key stakeholders and at international conferences and published in peer-reviewed journals.

Trial registration number

NCT02536768; Pre-results.
Roles of mothers and fathers in supporting child physical activity: a cross-sectional mixed-methods study
Authors: Solomon-Moore Emma , Toumpakari Zoi , Sebire Simon J , Thompson Janice L , Lawlor Deborah A , Jago Russell
Published: January 2018

Objectives

Examine the extent that parent gender is associated with supporting children’s physical activity.

Design

Cross-sectional mixed-methods study.

Setting

47 primary schools located in Bristol (UK).

Participants

944 children aged 8–9 years and one of their parents provided quantitative data; 51 parents (20 fathers) were interviewed.

Methods

Children wore an accelerometer, and mean minutes of moderate-to-vigorous physical activity (MVPA) per day, counts per minute (CPM) and achievement of national MVPA guidelines were derived. Parents reported who leads in supporting child activity during the week and weekend. Linear and logistic regression examined the association between gender of parent who supports child activity and child physical activity. For the semistructured telephone interviews, inductive and deductive content analyses were used to explore the role of gender in how parents support child activity.

Results

Parents appeared to have a stronger role in supporting boys to be more active, than girls, and the strongest associations were when they reported that both parents had equal roles in supporting their child. For example, compared with the reference of female/mother support, equal contribution from both parents during the week was associated with boys doing 5.9 (95% CI 1.2 to 10.6) more minutes of MVPA per day and more CPM when both parents support on weekday and weekends (55.1 (14.3 to 95.9) and 52.8 (1.8 to 103.7), respectively). Associations in girls were weaker and sometimes in the opposite direction, but there was no strong statistical evidence for gender interactions. Themes emerged from the qualitative data, specifically; parents proactively supporting physical activity equally, mothers supporting during the week, families getting together at weekends, families doing activities separately due to preferences and parents using activities to bond one-to-one with children.

Conclusions

Mothers primarily support child activity during the week. Children, possibly more so boys, are more active if both parents share the supporting role.
Comparative efficacy and acceptability of interventions for major depression in older persons: protocol for Bayesian network meta-analysis
Authors: Liew Tau Ming , Lee Cia Sin
Published: January 2018

Introduction

Major depression is a leading cause of disability and has been associated with adverse effects in older persons. While many pharmacological and non-pharmacological interventions have been shown to be effective to address major depression in older persons, there has not been a meta-analysis that consolidates all the available interventions and compare the relative benefits of these available interventions. In this study, we aim to conduct a systematic review and network meta-analysis to compare the efficacy and acceptability of all the known pharmacological and non-pharmacological interventions for major depression in older persons.

Methods and analysis

We will search Medline, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials and references of other review articles for articles related to the keywords of ‘randomised trial’, ‘major depression’, ‘older persons’ and ‘treatments’. Two reviewers will independently select the eligible articles. For each included article, the two reviewers will independently extract the data and assess the risk of bias using the Cochrane revised tool for risk of bias. Bayesian network meta-analyses will be conducted to pool the depression scores (based on standardised mean difference) and the all-cause discontinuation across all included studies. The ranking probabilities for all interventions will be estimated and the hierarchy of each intervention will be summarised as surface under the cumulative ranking curve (SUCRA). Meta-regression and sub-group analyses will also be performed to evaluate the effect of study-level covariates. The quality of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Ethics and dissemination

The results will be disseminated through conference presentations and peer-reviewed publications. They will provide the consolidated evidence to inform clinicians on the best choice of intervention to address major depression in older persons.

PROSPERO registration number

CRD42017075756.
Symptom-Disease Pair Analysis of Diagnostic Error (SPADE): a conceptual framework and methodological approach for unearthing misdiagnosis-related harms using big data
Authors: Liberman Ava L , Newman-Toker David E
Published: January 2018

Background

The public health burden associated with diagnostic errors is likely enormous, with some estimates suggesting millions of individuals are harmed each year in the USA, and presumably many more worldwide. According to the US National Academy of Medicine, improving diagnosis in healthcare is now considered ‘a moral, professional, and public health imperative.’ Unfortunately, well-established, valid and readily available operational measures of diagnostic performance and misdiagnosis-related harms are lacking, hampering progress. Existing methods often rely on judging errors through labour-intensive human reviews of medical records that are constrained by poor clinical documentation, low reliability and hindsight bias.

Methods

Key gaps in operational measurement might be filled via thoughtful statistical analysis of existing large clinical, billing, administrative claims or similar data sets. In this manuscript, we describe a method to quantify and monitor diagnostic errors using an approach we call ‘Symptom-Disease Pair Analysis of Diagnostic Error’ (SPADE).

Results

We first offer a conceptual framework for establishing valid symptom-disease pairs illustrated using the well-known diagnostic error dyad of dizziness-stroke. We then describe analytical methods for both look-back (case–control) and look-forward (cohort) measures of diagnostic error and misdiagnosis-related harms using ‘big data’. After discussing the strengths and limitations of the SPADE approach by comparing it to other strategies for detecting diagnostic errors, we identify the sources of validity and reliability that undergird our approach.

Conclusion

SPADE-derived metrics could eventually be used for operational diagnostic performance dashboards and national benchmarking. This approach has the potential to transform diagnostic quality and safety across a broad range of clinical problems and settings.
Understanding cardiac troponin part 2: early rule out of acute coronary syndrome
Authors: Carlton Edward , Body Richard
Published: January 2018

Chest pain of suspected cardiac origin is a very common emergency department presentation. Over the past decade, there has been an exponential growth in strategies that promote blood sampling at earlier and earlier time points after presentation to facilitate the rule out of acute coronary syndrome.

In part 2 of this series, we examine key concepts from the recent literature with the aim of improving clinicians’ understanding of the rule-out strategies available to them and provide a structured overview of strategies that facilitate discharge with blood testing over <3 hours.
Tumours composed of fat are no longer a simple diagnosis: an overview of fatty tumours with a spindle cell component
Authors: McCarthy Aoife J , Chetty Runjan
Published: January 2018

This is a review of the morphological spectrum of fatty tumours containing a component of spindle cells, highlighting the immunohistochemical and cytogenetic workup that is now mandatory for accurate diagnosis, with the goal of providing a practical approach for practising surgical pathologists. There have been significant advances in recent years in classifying and understanding the pathogenesis of fatty tumours with spindle cells, based on the correlation of histological, immunohistochemical and cytogenetic/molecular findings. In spite of this, morphological diagnosis and accurate classification of fatty tumours with spindle cells can be challenging to diagnostic pathologists. A group of three lesions: spindle cell lipoma, mammary-type myofibroblastoma and cellular angiofibroma share morphological features and are united by retinoblastoma protein (pRb) loss. Closely allied to these lesions, especially spindle cell lipoma is the newly designated atypical spindle cell lipomatous tumour, which shares morphological, immunohistochemical and cytogenetic features with the trio of tumours lacking nuclear pRb. All of these lesions lackMDM2andCDK4amplification as well and separation is based on clinical features, principally location. Atypical lipomatous tumour or well-differentiated liposarcoma shows retention of pRb but overexpression and amplification of MDM2. Fatty tumours with spindle cells need to be extensively sampled, with careful attention paid to cellular atypia and location, and they need to have immunohistochemical workup with pRb, MDM2, desmin, CD34 and p16. In addition, cytogenetic analysis forMDM2andCDK4amplification has become crucial for the proper identification of these lesions.
FAM46Amutations are responsible for autosomal recessive osteogenesis imperfecta
Authors: Doyard Mathilde , Bacrot Séverine , Huber Céline , Di Rocco Maja , Goldenberg Alice , Aglan Mona S , Brunelle Perrine , Temtamy Samia , Michot Caroline , Otaify Ghada A , Haudry Coralie , Castanet Mireille , Leroux Julien , Bonnefont Jean-Paul , Munnich Arnold , Baujat Geneviève , Lapunzina Pablo , Monnot Sophie , Ruiz-Perez Victor L , Cormier-Daire Valérie
Published: January 2018

Background

Stüve-Wiedemann syndrome (SWS) is characterised by bowing of the lower limbs, respiratory distress and hyperthermia that are often responsible for early death. Survivors develop progressive scoliosis and spontaneous fractures. We previously identifiedLIFRmutations in most SWS cases, but absence ofLIFRpathogenic changes in five patients led us to perform exome sequencing and to identify homozygosity for aFAM46Amutation in one case [p.Ser205Tyrfs*13]. The follow-up of this case supported a final diagnosis of osteogenesis imperfecta (OI), based on vertebral collapses and blue sclerae.

Methods and results

This prompted us to screenFAM46Ain 25 OI patients with no known mutations.

We identified a homozygous deleterious variant inFAM46Ain two affected sibs with typical OI [p.His127Arg]. Another homozygous variant, [p.Asp231Gly], also classed as deleterious, was detected in a patient with type III OI of consanguineous parents using homozygosity mapping and exome sequencing.

FAM46A is a member of the superfamily of nucleotidyltransferase fold proteins but its exact function is presently unknown. Nevertheless, there are lines of evidence pointing to a relevant role of FAM46A in bone development. By RT-PCR analysis, we detected specific expression ofFAM46Ain human osteoblasts andinterestingly, a nonsense mutation inFam46ahas been recently identified in an ENU-derived (N-ethyl-N-nitrosourea) mouse model characterised by decreased body length, limb, rib, pelvis, and skull deformities and reduced cortical thickness in long bones.

Conclusion

We conclude thatFAM46Amutations are responsible for a severe form of OI with congenital bowing of the lower limbs and suggest screening this gene in unexplained OI forms.
High predictive value of brain MRI imaging in primary mitochondrial respiratory chain deficiency
Authors: de Beaurepaire Isaure , Grévent David , Rio Marlène , Desguerre Isabelle , de Lonlay Pascale , Levy Raphaël , Dangouloff-Ros Volodia , Bonnefont Jean-Paul , Barcia Giulia , Funalot Benoit , Besmond Claude , Metodiev Metodi D , Ruzzenente Benedetta , Assouline Zahra , Munnich Arnold , Rötig Agnès , Boddaert Nathalie
Published: January 2018

Background

Because the mitochondrial respiratory chain (RC) is ubiquitous, its deficiency can theoretically give rise to any symptom in any organ or tissue at any age with any mode of inheritance, owing to the twofold genetic origin of respiratory enzyme machinery, that is, nuclear and mitochondrial. Not all respiratory enzyme deficiencies are primary and secondary or artefactual deficiency is frequently observed, leading to a number of misleading conclusions and inappropriate investigations in clinical practice. This study is aimed at investigating the potential role of brain MRI in distinguishing primary RC deficiency from phenocopies and other aetiologies.

Methods

Starting from a large series of 189 patients (median age: 3.5 years (8 days–56 years), 58% males) showing signs of RC enzyme deficiency, for whom both brain MRIs and disease-causing mutations were available, we retrospectively studied the positive predictive value (PPV) and the positive likelihood ratio (LR+) of brain MRI imaging and its ability to discriminate between two groups: primary deficiency of the mitochondrial RC machinery and phenocopies.

Results

Detection of (1) brainstem hyperintensity with basal ganglia involvement (P≤0.001) and (2) lactate peak with either brainstem or basal ganglia hyperintensity was highly suggestive of primary RC deficiency (P≤0.01). Fourteen items had a PPV>95% and LR+ was greater than 9 for seven signs. Biallelic SLC19A3 mutations represented the main differential diagnosis. Non-significant differences between the two groups were found for cortical/subcortical atrophy, leucoencephalopathy and involvement of caudate nuclei, spinothalamic tract and corpus callosum.

Conclusion

Based on these results and owing to invasiveness of skeletal muscle biopsies and cost of high-throughput DNA sequencing, we suggest giving consideration to brain MRI imaging as a diagnostic marker and an informative investigation to be performed in patients showing signs of RC enzyme deficiency.
Risk factors for oropharyngeal gonorrhoea in men who have sex with men: an age-matched case–control study
Authors: Cornelisse Vincent J , Walker Sandra , Phillips Tiffany , Hocking Jane S , Bradshaw Catriona S , Lewis David A , Prestage Garrett Paul , Grulich Andrew E , Fairley Christopher K , Chow Eric P F
Published: January 2018

Objectives

Oropharyngeal gonorrhoea is common among men who have sex with men (MSM). We aimed to clarify which oral sex practices were independent risk factors for oropharyngeal gonorrhoea: tongue kissing, receptive oro-penile sex (fellatio) or insertive oro-anal sex (rimming), and whether daily use of mouthwash and recent antibiotic use was protective.

Methods

In 2015, we conducted an age-matched case–control study of MSM who attended the Melbourne Sexual Health Centre. Cases had tested positive for oropharyngeal gonorrhoea by nucleic acid amplification testing, and controls had tested negative. Questionnaire items included tongue kissing, oral sex practices, condom use, recent antibiotic use, mouthwash use and alcohol consumption.

Results

We identified 177 cases, age matched to 354 controls. In univariable analyses, cases were 1.90 times (95% CI 1.13 to 3.20) more likely than controls to have had casual sexual partners (CSP) in the preceding 3 months, were 2.17 times (95% CI 1.31 to 3.59) more likely to have kissed CSP and were 2.04 times (95% CI 1.26 to 3.30) more likely to have had receptive oro-penile sex with CSP. Oropharyngeal gonorrhoea was not associated with insertive oro-anal sex or mouthwash use. The number of CSP for tongue kissing and receptive oral sex and total CSP were highly correlated, and in multivariable analysis neither kissing nor receptive oro-penile sex was significantly associated with having oropharyngeal gonorrhoea, after adjusting for total number of CSP.

Conclusions

The finding that oropharyngeal gonorrhoea was associated with a higher number of sexual partners but not specific sexual practices highlights the need for further research in the area of gonorrhoea transmission to define the probability of transmission from specific sex acts.
Genetic diversity of K-antigen gene clusters ofEscherichia coliand their molecular typing using a suspension array
Authors: Yang Shuang , Xi Daoyi , Jing Fuyi , Kong Deju , Wu Junli , Feng Lu , Cao Boyang , Wang Lei
Published: January 2018

Capsular polysaccharides (CPSs), or K-antigens, are the major surface antigens of Escherichia coli. More than 80 serologically unique K-antigens are classified into 4 groups (Groups 1–4) of capsules. Groups 1 and 4 contain the Wzy-dependent polymerization pathway and the gene clusters are in the order galF to gnd; Groups 2 and 3 contain the ABC-transporter-dependent pathway and the gene clusters consist of 3 regions, regions 1, 2 and 3. Little is known about the variations among the gene clusters. In this study, 9 serotypes of K-antigen gene clusters (K2ab, K11, K20, K24, K38, K84, K92, K96, and K102) were sequenced and correlated with their CPS chemical structures. On the basis of sequence data, a K-antigen-specific suspension array that detects 10 distinct CPSs, including the above 9 CPSs plus K30, was developed. This is the first report to catalog the genetic features of E. coli K-antigen variations and to develop a suspension array for their molecular typing. The method has a number of advantages over traditional bacteriophage and serum agglutination methods and lays the foundation for straightforward identification and detection of additional K-antigens in the future.
Observational constraints on the generalized α attractor model
Authors: Shahalam M. , Myrzakulov Ratbay , Myrzakul Shynaray , Wang Anzhong
Published: January 2018

We study the generalized [Formula: see text] attractor model in the context of the late time cosmic acceleration. The model interpolates between the scaling freezing and thawing dark energy models. In the slow roll region, the original potential is modified whereas the modification ceases in the asymptotic region and the effective potential behaves as the quadratic one. In our setting, the field rolls slowly around the present epoch and mimics the scaling behavior in the future. We obtain observational constraints on the model parameters by using an integrated database (SN+Hubble+BAO+CMB).
Ergodic BSDEs driven by G-Brownian motion and applications
Authors: Hu Mingshang , Wang Falei
Published: January 2018

This paper considers a new kind of backward stochastic differential equations (BSDEs) driven by [Formula: see text]-Brownian motion, which is called ergodic [Formula: see text]-BSDEs. Firstly, the well-posedness of [Formula: see text]-BSDEs with infinite horizon is given by combining a new linearization method with the argument of Briand and Hu [4]. Then, in view of [Formula: see text]-stochastic calculus approach the Feynman–Kac formula for fully nonlinear elliptic partial differential equations (PDEs) is established. Finally, with the help of the aforementioned results we obtain the existence of solution to [Formula: see text]-EBSDE and some applications are also stated.
Adaptive Speculation for Efficient Internetware Application Execution in Clouds
Authors: Ouyang Xue , Garraghan Peter , Primas Bernhard , Mckee David , Townend Paul , Xu Jie
Published: January 2018

Modern Cloud computing systems are massive in scale, featuring environments that can execute highly dynamic Internetware applications with huge numbers of interacting tasks. This has led to a substantial challenge—the straggler problem, whereby a small subset of slow tasks significantly impede parallel job completion. This problem results in longer service responses, degraded system performance, and late timing failures that can easily threaten Quality of Service (QoS) compliance. Speculative execution (or speculation) is the prominent method deployed in Clouds to tolerate stragglers by creating task replicas at runtime. The method detects stragglers by specifying a predefined threshold to calculate the difference between individual tasks and the average task progression within a job. However, such a static threshold debilitates speculation effectiveness as it fails to capture the intrinsic diversity of timing constraints in Internetware applications, as well as dynamic environmental factors, such as resource utilization. By considering such characteristics, different levels of strictness for replica creation can be imposed to adaptively achieve specified levels of QoS for different applications. In this article, we present an algorithm to improve the execution efficiency of Internetware applications by dynamically calculating the straggler threshold, considering key parameters including job QoS timing constraints, task execution progress, and optimal system resource utilization. We implement this dynamic straggler threshold into the YARN architecture to evaluate it’s effectiveness against existing state-of-the-art solutions. Results demonstrate that the proposed approach is capable of reducing parallel job response time by up to 20% compared to the static threshold, as well as a higher speculation success rate, achieving up to 66.67% against 16.67% in comparison to the static method.
An Online Algorithm for Task Offloading in Heterogeneous Mobile Clouds
Authors: Zhou Bowen , Dastjerdi Amir Vahid , Calheiros Rodrigo N. , Buyya Rajkumar
Published: January 2018

Mobile cloud computing is emerging as a promising approach to enrich user experiences at the mobile device end. Computation offloading in a heterogeneous mobile cloud environment has recently drawn increasing attention in research. The computation offloading decision making and tasks scheduling among heterogeneous shared resources in mobile clouds are becoming challenging problems in terms of providing global optimal task response time and energy efficiency. In this article, we address these two problems together in a heterogeneous mobile cloud environment as an optimization problem. Different from conventional distributed computing system scheduling problems, our joint offloading and scheduling optimization problem considers unique contexts of mobile clouds such as wireless network connections and mobile device mobility, which makes the problem more complex. We propose a context-aware mixed integer programming model to provide off-line optimal solutions for making the offloading decisions and scheduling the offloaded tasks among the shared computing resources in heterogeneous mobile clouds. The objective is to minimize the global task completion time (i.e., makespan). To solve the problem in real time, we further propose a deterministic online algorithm—the Online Code Offloading and Scheduling (OCOS) algorithm—based on the
rent/buy
problem and prove the algorithm is 2-competitive. Performance evaluation results show that the OCOS algorithm can generate schedules that have around two times shorter makespan than conventional independent task scheduling algorithms. Also, it can save around 30% more on makespan of task execution schedules than conventional offloading strategies, and scales well as the number of users grows.
A Novel l-Asparaginase with low l-Glutaminase Coactivity Is Highly Efficacious against Both T- and B-cell Acute Lymphoblastic Leukemias In Vivo
Authors: Nguyen Hien Anh , Su Ying , Zhang Jenny Y. , Antanasijevic Aleksandar , Caffrey Michael , Schalk Amanda M. , Liu Li , Rondelli Damiano , Oh Annie , Mahmud Dolores L. , Bosland Maarten C. , Kajdacsy-Balla Andre , Peirs Sofie , Lammens Tim , Mondelaers Veerle , De Moerloose Barbara , Goossens Steven , Schlicht Michael J. , Kabirov Kasim K. , Lyubimov Alexander V. , Merrill Bradley J. , Saunthararajah Yogen , Van Vlierberghe Pieter , Lavie Arnon
Published: January 2018

Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer, although about 4 of every 10 cases occur in adults. The enzyme drug l-asparaginase serves as a cornerstone of ALL therapy and exploits the asparagine dependency of ALL cells. In addition to hydrolyzing the amino acid l-asparagine, all FDA-approved l-asparaginases also have significant l-glutaminase coactivity. Since several reports suggest that l-glutamine depletion correlates with many of the side effects of these drugs, enzyme variants with reduced l-glutaminase coactivity might be clinically beneficial if their antileukemic activity would be preserved. Here we show that novel low l-glutaminase variants developed on the backbone of the FDA-approved Erwinia chrysanthemi l-asparaginase were highly efficacious against both T- and B-cell ALL, while displaying reduced acute toxicity features. These results support the development of a new generation of safer l-asparaginases without l-glutaminase activity for the treatment of human ALL.

Significance: A new l-asparaginase–based therapy is less toxic compared with FDA-approved high l-glutaminase enzymes Cancer Res; 78(6); 1549–60. ©2018 AACR.
Total Nut, Tree Nut, Peanut, and Peanut Butter Consumption and the Risk of Pancreatic Cancer in the Netherlands Cohort Study
Authors: Nieuwenhuis Lisette , van den Brandt Piet A.
Published: January 2018

Background: Nut intake has been associated with decreased cancer-related mortality, but few studies have examined the potential of nuts in the chemoprevention of pancreatic cancer. We prospectively investigated the association of total nut, tree nut, peanut, and peanut butter consumption with pancreatic cancer risk.

Methods: In the Netherlands Cohort Study, 120,852 men and women completed a baseline questionnaire, including a food frequency questionnaire, in 1986. After 20.3 years of follow-up, 583 incident pancreatic cancer cases, including 349 microscopically confirmed pancreatic cancer (MCPC) cases, were included in multivariable case–cohort analyses.

Results: Increased total nut consumption was associated with a nonsignificantly decreased MCPC risk in men [HR (95% confidence interval) for 10+ g/d vs. nonconsumers = 0.72 (0.47–1.11), Ptrend = 0.163]. No clear association was found in women. For tree nut and peanut consumption, nonsignificant inverse associations were observed in men. In women, no or unclear associations were found for tree nut and peanut consumption. Peanut butter intake was related to a significantly reduced risk of MCPC in men [HR (95% confidence interval) for 5+ g/d vs. nonconsumers = 0.53 (0.28–1.00), Ptrend = 0.047], but this relation was not clear in women. Evidence for a nonlinear dose–response relation with MCPC was found for tree nut intake only. The associations were weaker when looking at total pancreatic cancer.

Conclusions: Our results suggest that nuts and peanut butter might reduce pancreatic cancer risk in men. In women, no or unclear associations were found.

Impact: Nut consumption might reduce the risk of pancreatic cancer in men. Cancer Epidemiol Biomarkers Prev; 27(3); 274–84. ©2018 AACR.
Marine ω-3 Polyunsaturated Fatty Acid and Fish Intake after Colon Cancer Diagnosis and Survival: CALGB 89803 (Alliance)
Authors: Van Blarigan Erin L. , Fuchs Charles S. , Niedzwiecki Donna , Ye Xing , Zhang Sui , Song Mingyang , Saltz Leonard B. , Mayer Robert J. , Mowat Rex B. , Whittom Renaud , Hantel Alexander , Benson Al , Atienza Daniel , Messino Michael , Kindler Hedy , Venook Alan , Ogino Shuji , Giovannucci Edward L. , Meyerhardt Jeffrey A.
Published: January 2018

Background: Marine ω-3 polyunsaturated fatty acids (PUFAs), primarily found in dark fish, may prevent colorectal cancer progression, in part through inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2). However, data in humans are limited.

Methods: We examined marine ω-3 PUFAs and fish intake and survival among 1,011 colon cancer patients enrolled in Cancer and Leukemia Group B 89803 between 1999 and 2001 and followed through 2009. Diet was assessed during and 6 months after chemotherapy. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free (DFS), recurrence-free (RFS), and overall survival (OS).

Results: We observed 343 recurrences and 305 deaths (median follow-up: 7 years). Patients in the highest vs. lowest quartile of marine ω-3 PUFA intake had an HR for DFS of 0.72 (95% CI, 0.54–0.97; Ptrend = 0.03). Individuals who consumed dark fish ≥1/week versus never had longer DFS (HR 0.65; 95% CI, 0.48–0.87; P-value = 0.007), RFS (HR 0.61; 95% CI, 0.46–0.86; Ptrend = 0.007), and OS (HR 0.68; 95% CI, 0.48–0.96; Ptrend = 0.04). In a subset of 510 patients, the association between marine ω-3 PUFA intake and DFS appeared stronger in patients with high PTGS2 expression (HR 0.32; 95% CI, 0.11–0.95; Ptrend = 0.01) compared with patients with absent/low PTGS2 expression (HR 0.78; 95% CI, 0.48–1.27; Ptrend = 0.35; Pinteraction = 0.19).

Conclusions: Patients with high intake of marine ω-3 PUFAs and dark fish after colon cancer diagnosis may have longer DFS.

Impact: Randomized controlled trials examining dark fish and/or marine ω-3 PUFA supplements and colon cancer recurrence/survival are needed. Cancer Epidemiol Biomarkers Prev; 27(4); 438–45. ©2018 AACR.
Ginsenoside Rb1 Protects the Brain from Damage Induced by Epileptic Seizure via Nrf2/ARE Signaling
Authors: Shi Yunbo , Miao Wang , Teng Junfang , Zhang Lingli
Published: January 2018

Background/Aims: Ginsenoside Rb1 (Rb1) has been reported to have varieties of neuroprotective effects. This study aimed to evaluate the effects of Rb1 on pentylenetetrazol (PTZ)-induced rat brain injury and Mg2+ free-induced neuron injury and analyzed the detailed molecular mechanisms in vivo and in vitro. Methods: Seizure duration and latency were measured in epilepsy kindled rat. The cognitive impairment was assessed by Morris water maze (MWM) test. Oxidative stress parameters, malondialdehyde (MDA) and glutathione (GSH) were measured by the 2-thiobarbituric acid methods and the DTNB-GSSG reductase recycling methods. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Neuronal apoptosis was measured by Annexin V-FITC and propidium iodide (PI) staining. Immunohistochemistry and immunofluorescence staining were performed to evaluate Nrf2 and HO-1 expressions. Expression of Nrf2, HO-1, Bcl-2, iNOS and LC3 were evaluated by western blot. Results: The PTZ-injured rats presented longer seizure duration and shorter seizure latency. Rb1 ameliorated these effects, as well as the cognitive deficits caused by PTZ exposure. Besides, Rb1 dose-dependently increased GSH levels, decreased MDA levels and alleviated neuronal damage in PTZ-treated rats. In vitro, Rb1 increased cell viability and decreased neuronal apoptosis in a dose-dependent manner under Mg2+ free condition. Moreover, in vivo and in vitro, Rb1 enhanced both the Nrf2 and HO-1 expressions. Furthermore, upregulation of the expression of Bcl-2 and downregulation of the expression of iNOS and LC3 were observed. However, knockdown of Nrf2 adversely affected the protective effects of Rb1 in epileptic hippocampal neurons. Conclusion: Rb1 conferred neuroprotective effects against PTZ-induced brain damage and Mg2+ free-induced neuron injury by activating Nrf2/ARE signaling.
Hypoxia Suppresses TGF-B1-Induced Cardiac Myocyte Myofibroblast Transformation by Inhibiting Smad2/3 and Rhoa Signaling Pathways
Authors: Yan Zhankui , Shen Daifei , Liao Jilin , Zhang Yanmei , Chen Yicun , Shi Ganggang , Gao Fenfei
Published: January 2018

Background/Aims: Hypoxia modulation of transforming growth factor (TGF)- β-induced signaling during myofibroblast transformation is dependent on the specific cell type. The purpose of this study was to explore the effects of hypoxia on myofibroblast transformation of TGF-β1-induced cardiomyocyte H9c2 cells. Methods: H9c2 cells were cultured for intermittent hypoxia treatment and TGF-β1 treatment. α-Smooth muscle actin (α-SMA) expression was examined by western blotting and immunofluorescence after treatment. To further explore the possible mechanism for this effect, the effects of hypoxia on three early TGF-β-dependent signaling pathways, i.e. the Smad2/3, RhoA and mitogen-activated protein kinase (MAPK) pathways, were screened by western blotting. Results: Intermittent hypoxia induced TGF-β1 expression, but had no effect on α-SMA expression. Exogenous TGF-β1 alone upregulated α-SMA expression in H9c2 cells in a concentration- and time-dependent manner. α-SMA expression declined with the duration of hypoxia after intermittent hypoxia and exogenous TGF-β1 co-treatment. Phospho-JNK and phospho-p38 levels were not significantly altered after TGF-β1 and hypoxia treatment. However, levels of phospho-ERK increased after TGF-β1 treatment and continued to increase after hypoxia co-treatment. The activation of phospho-Smad2/3 and phospho-RhoA induced by TGFβ1 was significantly reduced after hypoxia co-treatment. Conclusion: Hypoxia can inhibit TGF-β1-induced H9c2 myofibroblast transformation, based on inhibition of α-SMA expression by suppressing signaling downstream of TGF-β1, Smad2/3 and RhoA. It suggested that TGF-β-mediated cardiomyocyte transformation is not involved in hypoxia-mediated fibrosis.
E2F1 Suppresses Oxidative Metabolism and Endothelial Differentiation of Bone Marrow Progenitor Cells
Authors: Xu Shiyue , Tao Jun , Yang Liu , Zhang Eric , Boriboun Chan , Zhou Junlan , Sun Tianjiao , Cheng Min , Huang Kai , Shi Jiawei , Dong Nianguo , Liu Qinghua , Zhao Ting C. , Qiu Hongyu , Harris Robert A. , Chandel Navdeep S. , Losordo Douglas W. , Qin Gangjian
Published: January 2018

Rationale:

The majority of current cardiovascular cell therapy trials use bone marrow progenitor cells (BM PCs) and achieve only modest efficacy; the limited potential of these cells to differentiate into endothelial-lineage cells is one of the major barriers to the success of this promising therapy. We have previously reported that the E2F transcription factor 1 (E2F1) is a repressor of revascularization after ischemic injury.

Objective:

We sought to define the role of E2F1 in the regulation of BM PC function.

Methods and Results:

Ablation of E2F1 (E2F1 deficient) in mouse BM PCs increases oxidative metabolism and reduces lactate production, resulting in enhanced endothelial differentiation. The metabolic switch in E2F1-deficient BM PCs is mediated by a reduction in the expression of pyruvate dehydrogenase kinase 4 and pyruvate dehydrogenase kinase 2; overexpression of pyruvate dehydrogenase kinase 4 reverses the enhancement of oxidative metabolism and endothelial differentiation. Deletion of E2F1 in the BM increases the amount of PC-derived endothelial cells in the ischemic myocardium, enhances vascular growth, reduces infarct size, and improves cardiac function after myocardial infarction.

Conclusion:

Our results suggest a novel mechanism by which E2F1 mediates the metabolic control of BM PC differentiation, and strategies that inhibit E2F1 or enhance oxidative metabolism in BM PCs may improve the effectiveness of cell therapy.
Standardized Definition of Structural Valve Degeneration for Surgical and Transcatheter Bioprosthetic Aortic Valves
Authors: Dvir Danny , Bourguignon Thierry , Otto Catherine M. , Hahn Rebecca T. , Rosenhek Raphael , Webb John G. , Treede Hendrik , Sarano Maurice E. , Feldman Ted , Wijeysundera Harindra C. , Topilsky Yan , Aupart Michel , Reardon Michael J. , Mackensen G. Burkhard , Szeto Wilson Y. , Kornowski Ran , Gammie James S. , Yoganathan Ajit P. , Arbel Yaron , Borger Michael A. , Simonato Matheus , Reisman Mark , Makkar Raj R. , Abizaid Alexandre , McCabe James M. , Dahle Gry , Aldea Gabriel S. , Leipsic Jonathon , Pibarot Philippe , Moat Neil E. , Mack Michael J. , Kappetein A. Pieter , Leon Martin B.
Published: January 2018

Bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. A significant challenge when comparing the durability of different types of bioprostheses is the lack of a standardized terminology for the definition of a degenerated valve. This issue becomes especially important when we try to compare the degeneration rate of surgically inserted and transcatheter bioprosthetic valves. This document, by the VIVID (Valve-in-Valve International Data), proposes practical and standardized definitions of valve degeneration and provides recommendations for the timing of clinical and imaging follow-up assessments accordingly. Its goal is to improve the quality of research and clinical care for patients with deteriorated bioprostheses by providing objective and strict criteria that can be utilized in future clinical trials. We hope that the adoption of these criteria by both the cardiological and surgical communities will lead to improved comparability and interpretation of durability analyses.
Divided the genus Tachycines Adelung (Orthoptera, Rhaphidophoridae: Aemodogryllinae; Aemodogryllini) from China
Authors: QIN YANYAN , WANG HANQIANG , LIU XIANWEI , LI KAI
Published: January 2018

This work involves revised analysis of Karny’s classification system in 1934 of the genus Tachycines Adelung, 1902 including the two subgenera: Tachycines (Tachycines) s. str. Adelung, 1902 and Tachycines (Gymnaeta) Adelung, 1902. We also describe 11 new species of Tachycines (Tachycines): Tachycines (Tachycines) karnyi sp. nov., Tachycines (Tachycines) maximus sp. nov., Tachycines (Tachycines) multispinosus sp. nov., Tachycines (Tachycines) xiai sp. nov., Tachycines (Tachycines) bilobatus sp. nov., Tachycines (Tachycines) trilobatus sp. nov., Tachycines (Tachycines) transversus sp. nov., Tachycines (Tachycines) incisus sp. nov., Tachycines (Tachycines) yanlingensis sp. nov., Tachycines (Tachycines) baiyunjianensis sp. nov., Tachycines (Tachycines) sichuanensis sp. nov.. A key to the subgenera of Tachycines Adelung, 1902 and a key to the species of Tachycines (Tachycines) are provided.
Morphological and molecular review of Jacob’s Mountain Stream Keelback Opisthotropis jacobi Angel & Bourret, 1933 (Squamata: Natricidae) with description of a sibling species from northern Vietnam
Authors: ZIEGLER THOMAS , DAVID PATRICK , ZIEGLER TIM N. , PHAM CUONG T. , NGUYEN TRUONG Q. , LE MINH D.
Published: January 2018

New morphological data including hemipenis morphology is provided for Opisthotropis jacobi, a poorly known Mountain Stream Keelback from Vietnam and China, based on three newly collected individuals from Sa Pa (Lao Cai Province) and Tam Dao (Vinh Phuc Province) in northern Vietnam. In addition, morphological data from Vietnam is summarized based on the original description (Angel & Bourret 1933), on the overview book by Bourret (1936) and on a number of smaller, little-known contributions by the latter author along with re-examination of specimens deposited in the herpetological collection of the Muséum national d’Histoire naturelle, Paris. We also sequenced a fragment of the mitochondrial cytochrome b from the newly collected specimens of the Jacob’s Mountain Stream Keelback and performed molecular analyses of new and existing data of the genus. A recently discovered Opisthotropis population from Tay Yen Tu Nature Reserve in Bac Giang Province, northern Vietnam, which at the first glance resembled O. jacobi morphologically, is shown to diverge both genetically and morphologically from the existing species and is herein described as a new species. Opisthotropis voquyi sp. nov. is characterized by the combination of the following characters: internasal not in contact with loreal; one preocular; usually two postoculars; one anterior temporal; one posterior temporal; 7 or 8, rarely 9 supralabials; 25 maxillary teeth; subcaudals 74–86; 15 dorsal scale rows at neck, at midbody and before vent; body scales smooth or only with few faint keels; and dorsal scales being greyish, greyish-brown or brown in preservative, posteriorly more or less edged with pale greyish-brown. Phylogenetically, the new species is supported as a sister taxon to O. jacobi, but the two taxa are approximately 10% divergent based on cytochrome b data.
The cave-dwelling false scorpion genus Pseudoblothrus Beier, 1931 (Arachnida: Pseudoscorpiones: Syarinidae) in the Crimean Peninsula
Authors: KOLESNIKOV VASILIY B. , TURBANOV ILYA S.
Published: January 2018

Based on morphological and molecular studies of material from caves in three karst regions of Crimea, the small, apparently relictual, Euro-Mediterranean and Macaronesian false scorpion genus Pseudoblothrus Beier, 1931 is shown to contain only one troglobiont species there, P. roszkovskii (Redikorzev, 1918), of which P. ljovuschkini Krumpál, 1984 and Obisium tauricum Lebedev, 1927 are junior subjective synonyms. A detailed redescription of the adults and tritonymph of P. roszkovskii is provided, together with phylogenetic and zoogeographical analyses.
A new species of fan-throated lizard of the genus Sitana Cuvier, 1829 from coastal Kerala, southern India
Authors: SADASIVAN KALESH , RAMESH M. B. , PALOT MUHAMED JAFER , AMBEKAR MAYURESH , MIRZA ZEESHAN A.
Published: January 2018

We here describe Sitana attenboroughii sp. nov., a new species of fan-throated lizard of the genus Sitana Cuvier, 1829 from coastal Kerala in southern India. The new species morphologically is closer to Sitana visiri Deepak, 2016 (in Deepak et al. 2016a), however, differs in having higher numbers of ventral scales and a comparatively short but richly colored dewlap. Genetically the new species shows affinity to Sitana marudhamneydhal Deepak, Khandekar, Varma & Chaitanya, 2016 from which it differs in an uncorrected pairwise sequence divergence of 2.2% for a fragment of mitochondrial Nicotinamide adenine dinucleotide dehydrogenase (NADH) subunit 2 gene.
A new species of Misetus Wesmael, 1845 (Hymenoptera, Ichneumonidae, Ichneumoninae, Phaeogenini) from Italy, with updated key to the females of Palaearctic species
Authors: GIOVANNI FILIPPO DI , SCARAMOZZINO PIER LUIGI , DILLER ERICH
Published: January 2018

A new species, Misetus strumiai sp. n., from the island of Montecristo (Italy, Tuscany) is described and illustrated. The new species is characterized by having the clypeus with a small median tooth, metasomal tergite II almost entirely smooth and polished, and extensively red body color (except for black head). A comparative diagnosis is provided in order to distinguish the new taxon from the other known species of the genus Misetus Wesmael, 1845.
Enhanced Adaptive Inflation Algorithm for Ensemble Filters
Authors: El Gharamti Mohamad
Published: January 2018

Spatially and temporally varying adaptive inflation algorithms have been developed to combat the loss of variance during the forecast due to various model and sampling errors. The adaptive Bayesian scheme of Anderson uses available observations to update the Gaussian inflation distribution assigned for every state variable. The likelihood function of the inflation is computed using model-minus-data innovation statistics. A number of enhancements for this inflation scheme are proposed. To prevent excessive deflation, an inverse gamma distribution for the prior inflation is considered. A non-Gaussian distribution offers a flexible framework for the inflation variance to evolve during the update. The innovations are assumed random variables, and a correction term is added to the mode of the likelihood distribution such that the observed inflation is slightly larger. This modification improves the stability of the adaptive scheme by limiting the occurrence of negative and physically intolerable inflations. The enhanced scheme is compared to the original one in twin experiments using the Lorenz-63 model, the Lorenz-96 model, and an idealized, high-dimensional atmospheric model. Results show that the proposed enhancements are capable of generating accurate and consistent state estimates. Allowing moderate deflation is shown to be useful.
Antimicrobial Activity of a Colloidal AgNP Suspension Demonstrated In Vitro against Monoculture Biofilms: Toward a Novel Tooth Disinfectant for Treating Dental Caries
Authors: Schwass D.R. , Lyons K.M. , Love R. , Tompkins G.R. , Meledandri C.J.
Published: January 2018

A novel silver nanoparticle (AgNP) formulation was developed as a targeted application for the disinfection of carious dentine. Silver nitrate (AgNO3) was chemically reduced using sodium borohydrate (NaBH4) in the presence of sodium dodecyl sulfate (SDS) to form micelle aggregate structures containing monodisperse 6.7- to 9.2-nm stabilized AgNPs. AgNPs were characterized by measurement of electrical conductivity and dynamic light scattering, scanning electron microscopy, transmission electron microscopy, and inductively coupled plasma mass spectrometry. Antimicrobial activity of AgNPs was tested against planktonic cultures of representative gram-positive and gram-negative oral bacteria using well diffusion assays on tryptic soy broth media and monoculture biofilms grown with brain heart infusion ± sucrose anaerobically at 37°C on microtiter plates. Biofilm mass was measured by crystal violet assay. Effects were compared to silver diamine fluoride and chlorhexidine (negative controls) and 70% isopropanol (positive control) exposed cultures. In the presence of AgNPs, triplicate testing against Streptococcus gordonii DL1, C219, G102, and ATCC10558 strains; Streptococcus mutans UA159; Streptococcus mitis I18; and Enterococcus faecalis JH22 for planktonic bacteria, the minimum inhibitory concentrations were as low as 7.6 µg mL–1 and the minimum bacteriocidal concentrations as low as 19.2 µg mL–1 silver concentration. Microplate readings detecting crystal violet light absorption at 590 nm showed statistically significant differences between AgNP-exposed biofilms and where no antimicrobial agents were used. The presence of sucrose did not influence the sensitivity of any of the bacteria. By preventing in vitro biofilm formation for several Streptococcus spp. and E. faecalis, this AgNP formulation demonstrates potential for clinical application inhibiting biofilms.