bluuebunny/crossref_metadata_2025 huggingface dataset:
Math anxiety and its relationship with basic arithmetic skills among primary school children
Authors: Sorvo Riikka , Koponen Tuire , Viholainen Helena , Aro Tuija , Räikkönen Eija , Peura Pilvi , Dowker Ann , Aro Mikko
Published: March 2017

Background

Children have been found to report and demonstrate math anxiety as early as the first grade. However, previous results concerning the relationship between math anxiety and performance are contradictory, with some studies establishing a correlation between them while others do not. These contradictory results might be related to varying operationalizations of math anxiety.

Aims

In this study, we aimed to examine the prevalence of math anxiety and its relationship with basic arithmetic skills in primary school children, with explicit focus on two aspects of math anxiety: anxiety about failure in mathematics and anxiety in math‐related situations.

Sample

The participants comprised 1,327 children at grades 2–5.

Methods

Math anxiety was assessed using six items, and basic arithmetic skills were assessed using three assessment tasks.

Results

Around one‐third of the participants reported anxiety about being unable to do math, one‐fifth about having to answer teachers’ questions, and one tenth about having to do math. Confirmatory factor analysis indicated that anxiety about math‐related situations and anxiety about failure in mathematics are separable aspects of math anxiety. Structural equation modelling suggested that anxiety about math‐related situations was more strongly associated with arithmetic fluency than anxiety about failure. Anxiety about math‐related situations was most common among second graders and least common among fifth graders.

Conclusions

As math anxiety, particularly about math‐related situations, was related to arithmetic fluency even as early as the second grade, children's negative feelings and math anxiety should be identified and addressed from the early primary school years.
GABA‐ρ receptors: distinctive functions and molecular pharmacology
Authors: Naffaa Moawiah M , Hung Sandy , Chebib Mary , Johnston Graham A R , Hanrahan Jane R
Published: March 2017

The homomeric GABA‐ρ ligand‐gated ion channels (also known as GABAC or GABAA‐ρ receptors) are similar to heteromeric GABAA receptors in structure, function and mechanism of action. However, their distinctive pharmacological properties and distribution make them of special interest. This review focuses on GABA‐ρ ion channel structure, ligand selectivity toward ρ receptors over heteromeric GABAA receptor sub‐types and selectivity between different homomeric ρ sub‐type receptors. Several GABA analogues show selectivity at homomeric GABA‐ρ receptors over heteromeric GABAA receptors. More recently, some synthetic ligands have been found to show selectivity at receptors formed from one ρ subtype over others. The unique pharmacological profiles of these agents are discussed in this review. The classical binding site of GABA within the orthosteric site of GABA‐ρ homomeric receptors is discussed in detail regarding the loops and residues that constitute the binding site. The ligand‐residue interactions in this classical binding and those of mutant receptors are discussed. The structure and conformations of GABA are discussed in regard to its flexibility and molecular properties. Although the binding mode of GABA is difficult to predict, several interactions between GABA and the receptor assist in predicting its potential conformation and mode of action. The structure–activity relationships of GABA and structurally key ligands at ρ receptors are described and discussed.
Innovations in practice: group mindfulness for adolescent anxiety – results of an open trial
Authors: Crowley Michael J. , Nicholls Sarah S. , McCarthy Deborah , Greatorex Kate , Wu Jia , Mayes Linda C.
Published: March 2017

Background

Group Mindfulness Therapy (GMT) is a program tailored for adolescents that targets anxiety with mindfulness skills including present moment awareness, mindfulness in everyday life (breathing, eating, walking), body scan, loving‐kindness, and self‐acceptance. Youth with anxiety may benefit from mindfulness exercises precisely because they learn to redirect their mind, and presumably their attention, away from wandering in the direction of worry and negative self‐appraisals and toward greater acceptance of internal states. This open trial assessed the feasibility and initial effectiveness of GMT in a school setting.

Method

Twelve 6th and 7th grade adolescents with elevated anxiety [Screen for Child Anxiety Disorders (SCARED) ≥ 30] participated in GMT after school. Youth completed measures of anxiety and perceived stress and their parents completed measures of internalizing and externalizing behavior problems at pretreatment and posttreatment. We hypothesized that GMT would significantly reduce youth anxiety and stress.

Results

Significant improvements were observed in anxiety, internalizing, stress, and attention, with effect sizes ranging from .88 to 1.34.

Conclusions

We demonstrate that GMT is feasible and acceptable to adolescents presenting with anxiety as a primary concern. We provide further support for the use of a mindfulness‐based intervention for anxiety reduction. The group format suggests a cost‐effective way to deliver services in a school setting.
Developing Mathematics Knowledge
Authors: Rittle‐Johnson Bethany
Published: March 2017

Developing strong knowledge about mathematics is important for success academically, economically, and in life, but many children fail to become proficient in math. Research on the developmental relations between conceptual and procedural knowledge of math provides insights into the development of knowledge about math. First, competency in math requires children to develop conceptual knowledge, procedural knowledge, and procedural flexibility. Second, conceptual and procedural knowledge often develop in a bidirectional, iterative fashion, with improvements in one type of knowledge‐supporting improvements in the other, as well as procedural flexibility. Third, learning techniques such as comparing, explaining, and exploring promote more than one type of knowledge about math, indicating that each is an important learning process. Researchers need to develop and validate measurement tools, devise more comprehensive theories of math development, and build more bridges between research and educational practice.
Assessment of in vivo mast cell reactivity in patients with systemic mastocytosis
Authors: Gülen T. , Möller Westerberg C. , Lyberg K. , Ekoff M. , Kolmert J. , Bood J. , Öhd J. , James A. , Dahlén S.‐E. , Nilsson G. , Dahlén B.
Published: March 2017

Background

Patients with systemic mastocytosis (SM) have clinical signs of mast cell (MC) activation and increased levels of MC mediators. It is unclear whether the increased mediator levels are caused by increased numbers of tissue MCs, or whether these cells in affected individuals have a hyperactive phenotype.

Objective

To determine reactivity of the skin and the airways to directly acting mediators and indirectly acting mast cell secretagogues in subjects with SM.

Methods

Skin reactivity to morphine and histamine, and airway responsiveness to mannitol and methacholine, was assessed in 15 patients with SM, 11 patients with allergic asthma (A) and 13 healthy controls (HC). Serum tryptase and urinary metabolites of the MC mediators histamine and prostaglandin D2 were measured, as well as ex vivo basophil histamine release.

Results

Mast cell mediators in the blood and urine were significantly higher in patients with SM than in HC and A controls. Responsiveness to local activation of skin MCs (by morphine) and airway MCs (by mannitol) was similar in SM and HC groups. Likewise, end‐organ responsiveness in the skin to histamine, and in the airways to methacholine, was similar in all three subject groups. There was no evidence of increased basophil reactivity in SM patients.

Conclusions and Clinical Relevance

Mast cells in the skin and airways of subjects with SM do not exhibit hyper‐reactivity towards the MC‐activating stimuli morphine and mannitol, respectively. Therefore, the highly elevated baseline levels of MC mediators in SM are most likely due to increased MC numbers, rather than altered MC responsiveness. The underlying mechanisms could involve leakage of MC mediators, or dysfunctions in mediator synthesis, storage and release. One clinical implication of our study is that there is no contraindication to perform skin tests using morphine in subjects with mastocytosis.
Trans‐oral robotic assisted tongue base mucosectomy for investigation of cancer of unknown primary in the head and neck region. The UK experience
Authors: Winter S.C. , Ofo E. , Meikle D. , Silva P. , Fraser L. , O'Hara J. , Kim D. , Robinson M. , Paleri V.
Published: March 2017

Objectives

The diagnosis of cancer of unknown primary (CUP) in head and neck occurs when the treating clinicians have utilised all available diagnostic tests and failed to identify the origin of the disease. There is no agreed consensus on which diagnostic investigations to use, or the order in which to use them in, although broad recommendations exist. Small tumours arising in the tongue base can be below the limits of resolution of conventional diagnostic techniques. Given the difficulty in targeting the tongue base, current practice involves blind random biopsies, which leads to a variable detection rate. Robotically assisted surgical removal of the tongue base, tongue base mucosectomy (TBM) has been shown to improve diagnostic yield. This study reports the diagnostic hit rate for tongue base primaries using this technique.

Design

Retrospective case review.

Setting

UK Head and Neck Centres.

Participants

Patients presenting as an unknown primary, investigated with clinical examination, PET‐CT and palatine tonsillectomy.

Main Outcome Measures

The detection of a primary site of head and neck cancer in the otherwise unknown primary tumour.

Results

The primary tumour site was identified in the tongue base in 53% (n=17) of patients. In 15 patients the tumour was in the ipsliateral tongue base (88%) while in two cases (12%) the tumour was located in contra lateral tongue base.

Conclusions

Trans‐oral robotic assisted TBM raises the possibility of identifying over 50% of tumours that would otherwise be classified as CUP. Identifying these in the contralateral tongue base has implications for treatment planning and outcome.
Intracorporeal anastomoses in emergency laparoscopic colorectal surgery from a series of 59 cases: where and how to do it – a technical note and video
Authors: Di Saverio S. , Birindelli A. , Mandrioli M. , Podda M. , Binda G. A.
Published: March 2017

Aim

Laparoscopy offers the benefits of minimally invasive surgery and faster recovery. Acute surgical patients may potentially benefit from the great advantages of emergency laparoscopy, which is more clinically relevant in acute than elective patients. Fashioning a laparoscopic intracorporeal anastomosis (ICA) after emergent colorectal resection, whenever technically feasible and not contraindicated by the patient's general and haemodynamic condition, is a most challenging technical skill.

Method

During the period 2010–2016, 59 patients underwent a laparoscopic procedure for colorectal emergency in an acute care setting by a single operating surgeon with advanced laparoscopic skills and specific expertise in both colorectal surgery and acute care surgery. This series includes 32 laparoscopic right colectomies (12 for obstruction and 20 for perforation/peritonitis) and 27 left colectomies (6 for obstruction and 21 for perforation/peritonitis). Twenty‐eight ileocolic side‐to‐side ICA, and 27 left colonic ICA (3 colocolic, 24 colorectal) were performed.

Results

Reasonably good postoperative outcomes were observed in the entire series of 59 laparoscopic colectomies performed in an urgent setting. Overall, the major morbidity rate in the entire group was 16.9% (10/59) with an incidence of intra‐abdominal abscess of 11.8% (7/59); the overall leak rate was 3.4% (2/59). The re‐operation rate was 3.4% (2/59). A video included in the Supporting Information shows five different sites and techniques for ICA and describes technical details with tips and tricks. All patients shown in the video had an uneventful postoperative recovery and were managed postoperatively according to enhanced recovery after surgery protocols.

Conclusion

This case series illustrates all possible sites and techniques for colonic ICA in an emergency setting. All colorectal and acute care surgeons should have laparoscopic suturing skills.
Surgical and not analgesic technique affects postoperative inflammation following colorectal cancer surgery: a prospective, randomized study
Authors: Siekmann W. , Eintrei C. , Magnuson A. , Sjölander A. , Matthiessen P. , Myrelid P. , Gupta A.
Published: March 2017

Aim

Epidural analgesia reduces the surgical stress response. However, its effect on pro‐ and anti‐inflammatory cytokines in the genesis of inflammation following major abdominal surgery remains unclear. Our main objective was to elucidate whether perioperative epidural analgesia prevents the inflammatory response following colorectal cancer surgery.

Methods

Ninety‐six patients scheduled for open or laparoscopic surgery were randomized to epidural analgesia (group E) or patient‐controlled intravenous analgesia (group P). Surgery and anaesthesia were standardized in both groups. Plasma cortisol, insulin and serum cytokines [interleukin 1β (IL‐1β), IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, tumour necrosis factor α, interferon γ, granulocyte‐macrophage colony‐stimulating factor, prostaglandin E2 and vascular endothelial growth factor] were measured preoperatively (T0), 1–6 h postoperatively (T1) and 3–5 days postoperatively (T2). Mixed model analysis was used, after logarithmic transformation when appropriate, for analyses of cytokines and stress markers.

Results

>There were no significant differences in any serum cytokine concentration between groups P and E at any time point except for IL‐10 which was 87% higher in group P [median and range 4.1 (2.3–9.2) pg/ml] compared to group E [2.6 (1.3–4.7) pg/ml] (P = 0.002) at T1. There was no difference in plasma cortisol and insulin between the groups at any time point after surgery. A significant difference in median serum cytokine concentration was found between open and laparoscopic surgery with higher levels of IL‐6, IL‐8 and IL‐10 at T1 in patients undergoing open surgery compared to laparoscopic surgery. No difference in serum cytokine concentration was detected between the groups or between the surgical technique at T2.

Conclusions

Open surgery, compared to laparoscopic surgery, has greater impact on these inflammatory mediators than epidural analgesia vs intravenous analgesia.
Benchmarking recent national practice in rectal cancer treatment with landmark randomized controlled trials
Authors:   Dutch Snapshot Research Group
Published: March 2017

Aim

A Snapshot study design eliminates changes in treatment and outcome over time. This population based Snapshot study aimed to determine current practice and outcome of rectal cancer treatment with published landmark randomized controlled trials as a benchmark.

Method

In this collaborative research project, the dataset of the Dutch Surgical Colorectal Audit was extended with additional treatment and long‐term outcome data. All registered patients who underwent resection for rectal cancer in 2011 were eligible. Baseline characteristics and outcome were evaluated against the results of the Dutch TME trial and the COLOR II trial from which the original datasets were obtained.

Results

A total of 71 hospitals participated, and data were completed for 2102 out of the potential 2633 patients (79.8%). Median follow‐up was 41 (interquartile range 25–47) months. Overall circumferential resection margin (CRM) involvement was 9.3% in the Snapshot cohort and 18.5% in the Dutch TME trial. CRM positivity after laparoscopic resection was 7.8% in the Snapshot and 9.5% in the COLOR II trial. Three‐year overall local recurrence rate in the Snapshot was 5.9%, with a disease‐free survival of 67.1% and overall survival of 79.5%. Benchmarking with the randomized controlled trials revealed an overall favourable long‐term outcome of the Snapshot cohort.

Conclusion

This study showed that current rectal cancer care in a large unselected Dutch population is of high quality, with less positive CRM since the TME trial and oncologically safe implementation of minimally invasive surgery after the COLOR II trial.
Endoscopic ultrasonography diagnosis of subepithelial lesions
Authors: Kida Mitsuhiro , Kawaguchi Yusuke , Miyata Eiji , Hasegawa Rikiya , Kaneko Toru , Yamauchi Hiroshi , Koizumi Shuko , Okuwaki Kosuke , Miyazawa Shiro , Iwai Tomohisa , Kikuchi Hidehiko , Watanabe Maya , Imaizumi Hiroshi , Koizumi Wasaburo
Published: March 2017

Using endoscopic ultrasonography (EUS), it is practicable to diagnose subepithelial lesions (SEL) with originating layer, echo level, and internal echo pattern etc. Lipoma, lymphangioma, and cyst have characteristic features; therefore, there is no need for endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA). Ectopic pancreas and glomus tumors, which originate from the third and fourth layers, are frequently seen in the antrum. However, ectopic pancreas located in the fundus or body is large and originates from the third and fourth layers (thickening of fourth layer). Each subepithelial lesion has characteristic findings. However, imaging differentiation of tumors originating from the fourth layer is very difficult, even if contrast echo is used. Therefore, EUS‐FNA should be done in these tumors, but the diagnostic yield for small lesions is not sufficient for clinical demands. Generally, those tumors, including small ones, should be first followed up in 6 months, then yearly follow up in cases of no significant change in size and features. When those tumors become larger than 1–2 cm, EUS‐FNA is recommended. Furthermore, unusual SEL and SEL with malignant findings such as nodular, heterogeneous, anechoic area, and ulceration indicate EUS‐FNA. Cap‐attached forward‐viewing echoendoscope is very helpful for EUS‐FNA of small SEL.
The Mahatma Gandhi National Rural Employment Guarantee Scheme: A Policy Solution to Rural Poverty in India?
Authors: Breitkreuz Rhonda , Stanton Carley‐Jane , Brady Nurmaiya , Pattison‐Williams John , King E.D. , Mishra Chudhury , Swallow Brent
Published: March 2017

The Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) was developed by the Indian government to reduce rural poverty through 100 days of guaranteed employment per year. Using focus group methods, we explore whether this scheme has provided rights' based social protection through guaranteed employment for Scheduled Castes, Scheduled Tribes and women in Kerala, Tamil Nadu and Odisha. We found that the experiences of participating in MGNREGA varied depending on how MGNREGA wages compared to market wages in the region, as well as local implementation of the program. Although MGNREGA offered some basic employment for marginalized groups, it did not provide substantial help to the most vulnerable. However, there was some evidence of small but significant shifts in labour relations. Higher wages, more opportunities for work, better implementation and a greater recognition of the caregiving responsibilities of women will be required for this policy to fully meet its goals.
Disentangling the pathways of land use impacts on the functional structure of fish assemblages in Amazon streams
Authors: Leitão Rafael P. , Zuanon Jansen , Mouillot David , Leal Cecília G. , Hughes Robert M. , Kaufmann Philip R. , Villéger Sébastien , Pompeu Paulo S. , Kasper Daniele , de Paula Felipe R. , Ferraz Silvio F. B. , Gardner Toby A.
Published: March 2017

Agricultural land use is a primary driver of environmental impacts on streams. However, the causal processes that shape these impacts operate through multiple pathways and at several spatial scales. This complexity undermines the development of more effective management approaches, and illustrates the need for more in‐depth studies to assess the mechanisms that determine changes in stream biodiversity. Here we present results of the most comprehensive multi‐scale assessment of the biological condition of streams in the Amazon to date, examining functional responses of fish assemblages to land use. We sampled fish assemblages from two large human‐modified regions, and characterized stream conditions by physical habitat attributes and key landscape‐change variables, including density of road crossings (i.e. riverscape fragmentation), deforestation, and agricultural intensification. Fish species were functionally characterized using ecomorphological traits describing feeding, locomotion, and habitat preferences, and these traits were used to derive indices that quantitatively describe the functional structure of the assemblages. Using structural equation modeling, we disentangled multiple drivers operating at different spatial scales, identifying causal pathways that significantly affect stream condition and the structure of the fish assemblages. Deforestation at catchment and riparian network scales altered the channel morphology and the stream bottom structure, changing the functional identity of assemblages. Local deforestation reduced the functional evenness of assemblages (i.e. increased dominance of specific trait combinations) mediated by expansion of aquatic vegetation cover. Riverscape fragmentation reduced functional richness, evenness and divergence, suggesting a trend toward functional homogenization and a reduced range of ecological niches within assemblages following the loss of regional connectivity. These results underscore the often‐unrecognized importance of different land use changes, each of which can have marked effects on stream biodiversity. We draw on the relationships observed herein to suggest priorities for the improved management of stream systems in the multiple‐use landscapes that predominate in human‐modified tropical forests.
Association between regional heterogeneity in the mid‐facial bone micro‐architecture and increased fragility along Le Fort lines
Authors: Janovic Aleksa , Milovanovic Petar , Hahn Michael , Rakocevic Zoran , Amling Michael , Busse Bjoern , Dimitrijevic Milovan , Djuric Marija
Published: March 2017

Background/Aim

Le Fort lines have traditionally been considered as zones of weakness in the mid‐facial skeleton although the structural basis of increased bone fragility at these sites has not yet been investigated. Considering recent findings of occlusal loading‐related regional heterogeneity in the mid‐facial bone micro‐architecture, the aim of this study was to explore whether such heterogeneity in cortical and cancellous bone micro‐architecture may contribute to increased fragility at Le Fort fracture sites.

Materials and Methods

Twenty‐five cortical and thirteen cancellous bone specimens were harvested from a dry skull and analyzed by micro‐CT. Specimens were classified into Le Fort or Non‐Le Fort groups based on their location in the mid‐facial skeleton.

Results

Cortical bone along Le Fort lines showed tendencies toward lower thickness (1.5±0.63 vs 1.75±0.79; P=.39) and greater porosity (11.48±5.67 vs 10.28±5.28; P=.59). A significant difference was detected in the trabecular degree of anisotropy which was higher in cancellous bone from Le Fort fracture sites (2.14±0.69 vs 1.58±0.34; P=.02).

Conclusions

Regional heterogeneity in cortical bone micro‐architecture could not fully explain increased fragility of the mid‐facial skeleton at the Le Fort lines. However, regional differences in trabecular bone anisotropy may contribute to increased bone fragility.
Trans‐generational plasticity in response to immune challenge is constrained by heat stress
Authors: Roth Olivia , Landis Susanne H.
Published: March 2017

Trans‐generational plasticity (TGP) is the adjustment of phenotypes to changing habitat conditions that persist longer than the individual lifetime. Fitness benefits (adaptiveTGP) are expected upon matching parent–offspring environments. In a global change scenario, several performance‐related environmental factors are changing simultaneously. This lowers the predictability of offspring environmental conditions, potentially hampering the benefits of TGP. For the first time, we here explore how the combination of an abiotic and a biotic environmental factor in the parental generation plays out as trans‐generational effect in the offspring. We fully reciprocally exposed the parental generation of the pipefishSyngnathus typhleto an immune challenge and elevated temperatures simulating a naturally occurring heatwave. Upon mating and male pregnancy, offspring were kept in ambient or elevated temperature regimes combined with a heat‐killed bacterial epitope treatment. Differential gene expression (immune genes andDNA‐ and histone‐modification genes) suggests that the combined change of an abiotic and a biotic factor in the parental generation had interactive effects on offspring performance, the temperature effect dominated over the immune challenge impact. The benefits of certain parental environmental conditions on offspring performance did not sum up when abiotic and biotic factors were changed simultaneously supporting that available resources that can be allocated to phenotypic trans‐generational effects are limited. Temperature is the master regulator of trans‐generational phenotypic plasticity, which potentially implies a conflict in the allocation of resources towards several environmental factors. This asks for a reassessment of TGP as a short‐term option to buffer environmental variation in the light of climate change.
Estimating stock depletion level from patterns of catch history
Authors: Zhou Shijie , Punt André E , Ye Yimin , Ellis Nick , Dichmont Cathy M , Haddon Malcolm , Smith David C , Smith Anthony DM
Published: March 2017

The degree to which a stock is depleted is one of the most important quantities in fisheries management because it is used to quantify the success of management and to inform management responses. However, stock depletion is extremely difficult to estimate, particularly with limited data. Using the RAM Legacy database, we developed a boosted regression tree (BRT) model to correlate depletion with a range of predictors calculated from catch data, making the model usable for many fisheries worldwide. The most important predictors were found to be catch trends obtained from linear regressions of scaled catch on time, including regression coefficients for the whole catch time series, the subseries before and after the maximum catch, and in recent years. Eight predictors explain about 80% of variation in depletion. There is a correlation of .5 between measured levels of depletion and the predictions of the BRT model. Predictions are less biased when the stock is fished down below half of the carrying capacity. The BRT model outperforms comparable existing catch‐based depletion estimators and could be used to provide priors for depletion for data‐poor stock assessment methods, or used more directly to provide estimates of the probability that depletion is below a given threshold value.
Effect of dementia on receipt of influenza vaccine: a cohort study in French older adults using administrative data: 2007–2012
Authors: Gallini Adeline , Coley Nicola , Andrieu Sandrine , Lapeyre‐Mestre Maryse , Gardette Virginie
Published: March 2017

Despite guidelines stating the vaccine benefit in this population, older adults with dementia may be less likely to receive influenza vaccine than cognitively intact older adults. But no study has yet reported on vaccine uptake in patients newly diagnosed with dementia or whether years since dementia diagnosis influences vaccine uptake. We conducted a cohort study in the French Health Insurance database (Echantillon Généraliste de Bénéficiaires) which contains hospital data and claims for a 1/97th random sample of the French population. Diseased subjects were ≥65 years and had a new record of dementia diagnosis between September 1, 2007, and August 31, 2008. Vaccine receipt was measured via influenza vaccine dispensing in community pharmacies. We described influenza vaccination rates up to 2011–2012 and estimated adjusted relative risks (aRR) for vaccine receipt each year using multivariate modified Poisson models controlling for sociodemographics, comorbidities, and health resources use. Four hundred and seven subjects with dementia (mean age 81.8 years, 69.3% females) and 4862 subjects (mean age 75.2 years, 61.3% females) without dementia were included. In 2008–2009, influenza vaccination prevalence was 70.0% (95% CI = [65.3–74.4]) and 70.2% (95% CI = [68.9–71.4]) in subjects with and without dementia, respectively (aRR = 0.93; 95% CI = [0.87–1.00]). In 2009–2010, the aRR was of the same magnitude (aRR = 0.96, 95% CI = [0.90–1.03]), but in 2010–2011 and 2011–2012, the aRR was 1.02 (95% CI = [0.94–1.11]) and 1.05 (95% CI = [0.96–1.14]), respectively. Subjects with dementia had a slightly nonsignificant lower receipt of influenza vaccine in the year following dementia diagnosis than subjects without dementia. In subsequent years, divergent trends were observed in vaccine uptake according to dementia status.
Non‐alcoholic fatty liver disease phosphoproteomics: A functional piece of the precision puzzle
Authors: Wattacheril Julia , Rose Kristie L. , Hill Salisha , Lanciault Christian , Murray Clark R. , Washington Kay , Williams Brandon , English Wayne , Spann Matthew , Clements Ronald , Abumrad Naji , Flynn Charles Robb
Published: March 2017

Background

Molecular signaling events associated with the necroinflammatory changes in nonalcoholic steatohepatitis (NASH) are not well understood.

Aims

To understand the molecular basis of NASH, we evaluated reversible phosphorylation events in hepatic tissue derived from Class III obese subjects by phosphoproteomic means with the aim of highlighting key regulatory pathways that distinguish NASH from non‐alcoholic fatty liver disease (also known as simple steatosis; SS).

Materials & Methods

Class III obese subjects undergoing bariatric surgery underwent liver biopsy (eight normal patients, eight with simple steatosis, and eight NASH patients). Our strategy was unbiased, comparing global differences in liver protein reversible phosphorylation events across the 24 subjects.

Results

Of the 3078 phosphorylation sites assigned (2465 phosphoserine, 445 phosphothreonine, 165 phosphotyrosine), 53 were altered by a factor of 2 among cohorts, and of those, 12 were significantly increased or decreased by ANOVA (P < 0.05).

Discussion

Statistical analyses of canonical signaling pathways identified carbohydrate metabolism and RNA post‐transcriptional modification among the most over‐represented networks.

Conclusion

Collectively, these results raise the possibility of abnormalities in carbohydrate metabolism as an important trigger for the development of NASH, in parallel with already established abnormalities in lipid metabolism.
Impact of hepatitis C virus recombinant form RF1_2k/1b on treatment outcomes within the Georgian national hepatitis C elimination program
Authors: Karchava Marine , Chkhartishvili Nikoloz , Sharvadze Lali , Abutidze Akaki , Dvali Natia , Gatserelia Lana , Dzigua Lela , Bolokadze Natalia , Dolmazashvili Ekaterine , Kotorashvili Adam , Imnadze Paata , Gamkrelidze Amiran , Tsertsvadze Tengiz
Published: March 2017

Aim

Hepatitis C virus (HCV) recombinant form RF1_2k/1b is common in ethnic Georgians. This chimera virus contains genomic fragments of genotype 2 and genotype 1 and is misclassified as genotype 2 by standard genotyping. We aimed to identify RF1_2k/1b strains among genotype 2 patients and assess its impact on treatment outcomes.

Methods

The study included 148 patients with HCV genotype 2 as determined by 5‐untranslated region/core genotyping assay. RF1_2k/1b was identified by sequencing the non‐structural protein 5B region. Patients were treated within the national hepatitis C elimination program with sofosbuvir/ribavirin (SOF/RBV), interferon (IFN)/SOF/RBV, or ledipasvir (LDV)/SOF/RBV.

Results

Of 148 patients, 103 (69.5%) had RF1_ 2k/1b. Sustained virologic response (SVR) data was available for 136 patients (RF1_ 2k/1b, n = 103; genotype 2, n = 33). Sustained virologic response was achieved in more genotype 2 patient than in RF1_2k/1b patients (97.0% vs. 76.7%, P = 0.009). Twelve weeks of LDV/SOF/RBV treatment was highly effective (100% SVR) in both genotypes. Among RF1_2k/1b patients, LDV/SOF/RBV for 12 weeks was superior (100% SVR) to SOF/RBV for 12 weeks (56.4%, P < 0.0001) or 20 weeks (79.2%, P = 0.05). Twelve weeks of IFN/SOF/RBV also showed better response than SOF/RBV for 12 weeks (88.9% vs. 56.4%, P = 0.02) in these patients.

Conclusions

High prevalence of the RF1_2k/1b strain can significantly affect treatment outcomes. Treatment with IFN/SOF/RBV and especially LDV/SOF/RBV ensured significantly higher SVR in patients infected with RF1_2k/1b strain compared to standard HCV genotype 2 treatment with SOF/RBV. There is a need to reassess existing methods for the management of HCV genotype 2 infections, especially in areas with high prevalence of the RF1_2k/1b strain.
Electric field‐assisted ion exchange strengthening of borosilicate and soda lime silicate glass
Authors: Talimian Ali , Mariotto Gino , Sglavo Vincenzo M.
Published: March 2017

In this study, we investigate the effects of electric field‐assisted ion exchange (EF‐IE) on potassium for sodium ion exchanges of soda borosilicate and soda lime silicate glasses. The results show that applying an electric field (E‐field) with the intensity of 1000 V cm−1 for few minutes produces an exchanged layer with a thickness comparable to the conventional chemical strengthening for 4 hours. There is a critical E‐field that increases the mobility and, therefore, the diffusion coefficient of the potassium ions in the glasses. The increase is, perhaps, related to the evolution of the glass structure due to the penetration of potassium ions under an E‐field. Vickers indentations showed that strong compression is generated in the glass by EF‐IE; however, the bending strength improvement is limited because of the presence of large surface defects and the stress distribution inhomogeneity.
Methylprednisolone aceponate for atopic dermatitis
Authors: Torrelo Antonio
Published: March 2017

Background

The 4th generation topical corticosteroids (TCS) have demonstrated a most favorablerisk–benefit ratio. Methylprednisolone aceponate (MPA) is a non‐halogenated corticosteroid with a methyl group at C6, which confers higher intrinsic activity. MPA is included in the group of potent TCS (category III/IV).

Methods

A literature review is carried out of the clinical efficacy, pharmacokinetics, and adverse effects of MPA, especially for the treatment of atopic dermatitis (AD).

Results

Several clinical studies support the use of MPA in infants and children, with minimal local or systemic adverse effects reported. The pharmacokinetic profile and the low rate of adverse effects of MPA are most suitable for the treatment of atopic dermatitis (AD), a chronic disease with frequent flaring that can involve extensive areas of the skin.

Conclusions

Most patients with AD can be easily brought into control with the use of only TCS. Achieving a complete healing of eczema is key in AD, and once the skin is clinically healthy, emollients can be used according to the physician and patient preferences. Physicians should be trained in the recognition of early or subtle manifestations of active eczema that are most suitably treated with topical TCS to achieve a most rapid and satisfactory control of the disease. If the whole area with eczema is not treated, active eczema will remain and treatment will be ineffective. Insufficient use of TCS will lead to inefficiency and frustration.
Comparison of quantitative and qualitative tests for glucose‐6‐phosphate dehydrogenase deficiency in the neonatal period
Authors: Keihanian F. , Basirjafari S. , Darbandi B. , Saeidinia A. , Jafroodi M. , Sharafi R. , Shakiba M.
Published: March 2017

Introduction

Considering the high prevalence of glucose‐6‐phosphate dehydrogenase (G6PD) deficiency among newborns, different screening methods have been established in various countries. In this study, we aimed to assess the prevalence of G6PD deficiency among newborns in Rasht, Iran, and compare G6PD activity in cord blood samples, using quantitative and qualitative tests.

Methods

This cross‐sectional, prospective study was performed at five largest hospitals in Rasht, Guilan Province, Iran. The screening tests were performed for all the newborns, referred to these hospitals. Specimens were characterized in terms of G6PD activity under ultraviolet light, using the kinetic method and the qualitative fluorescent spot test (FST). We also determined the sensitivity, specificity, negative predictive value, and positive predictive value of the qualitative assay.

Results

Blood samples were collected from 1474 newborns. Overall, 757 (51.4%) subjects were male. As the findings revealed, 1376 (93.4%) newborns showed normal G6PD activity, while 98 (6.6%) had G6PD deficiency. There was a significant difference in the mean G6PD level between males and females (P = 0.0001). Also, a significant relationship was detected between FST results and the mean values obtained in the quantitative test (P < 0.0001).

Conclusion

According to the present study, FST showed acceptable sensitivity and specificity for G6PD activity, although it appeared inefficient for diagnostic purposes in some cases.
Intravesical liposome therapy for interstitial cystitis
Authors: Tyagi Pradeep , Kashyap Mahendra , Majima Tsuyoshi , Kawamorita Naoki , Yoshizawa Tsuyoshi , Yoshimura Naoki
Published: March 2017

Over the past two decades, there has been lot of interest in the use of liposomes as lipid‐based biocompatible carriers for drugs administered by the intravesical route. The lipidic bilayer structure of liposomes facilitates their adherence to the apical membrane surface of luminal cells in the bladder, and their vesicular shape allows them to co‐opt the endocytosis machinery for bladder uptake after instillation. Liposomes have been shown to enhance the penetration of both water‐soluble and insoluble drugs, toxins, and oligonucleotides across the bladder epithelium. Empty liposomes composed entirely of the endogenous phospholipid, sphingomyelin, could counter mucosal inflammation and promote wound healing in patients suffering from interstitial cystitis. Recent clinical studies have tested multilamellar liposomes composed entirely of sphingomyelin as a novel intravesical therapy for interstitial cystitis. In addition, liposomes have been used as a delivery platform for the instillation of botulinum toxin in overactive bladder patients. The present review discusses the properties of liposomes that are important for their intrinsic therapeutic effect, summarizes the recently completed clinical studies with intravesical liposomes and covers the latest developments in this field.
Difference in toxicity reporting between patients and clinicians during systemic chemotherapy in patients with urothelial carcinoma
Authors: Fukushi Ken , Narita Takuma , Hatakeyama Shingo , Yamamoto Hayato , Tobisawa Yuki , Yoneyama Tohru , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Ohyama Chikara
Published: March 2017

Objectives

To compare toxicity reporting between patients and clinicians in the case of systemic chemotherapy for urothelial carcinoma.

Methods

Between June 2013 and March 2016, 100 urothelial carcinoma patients received two courses of chemotherapy of gemcitabine plus cisplatin or gemcitabine plus carboplatin, and they were prospectively enrolled in the present study. During chemotherapy, patients answered European Organization for the Research and Treatment of Cancer Quality‐of‐Life Questionnaire C30 quality‐of‐life questionnaires, including four toxicity‐related symptoms (appetite loss, nausea, constipation and diarrhea). Clinicians evaluated adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Differences of toxicity reporting were compared between patients and clinicians. Logistic regression analyses were carried out to investigate potential factors for underreporting by clinicians.

Results

Toxicity underreporting was most frequently for diarrhea (44%), followed by appetite loss (39%), constipation (33%) and nausea (22%). In total, toxicity underreporting was observed in 72% of patients. Background‐adjusted logistic regression analyses showed pretreatment quality‐of‐life items of global, symptomatic scores to be predictors for toxicity underreporting by clinicians. The limitations of the present study included its retrospective nature and small sample size.

Conclusions

Toxicity underreporting by clinicians is frequent in urothelial carcinoma patients receiving systemic chemotherapy. Pretreatment quality‐of‐life evaluation is essential not only for quality‐of‐life evaluation, but also to identify potential individuals at risk for toxicity underreporting.
TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy
Authors: Dougall William C. , Kurtulus Sema , Smyth Mark J. , Anderson Ana C.
Published: March 2017

While therapies targeting the co‐inhibitory or immune checkpoint receptors PD‐1 and CTLA‐4 have shown remarkable success in many cancers, not all patients benefit from these therapies. This has catalyzed enormous interest in the targeting of other immune checkpoint receptors. In this regard, TIGIT and CD96 have recently entered the limelight as novel immune checkpoint receptor targets. TIGIT and CD96 together with the co‐stimulatory receptor CD226 form a pathway that is analogous to the CD28/CTLA‐4 pathway, in which shared ligands and differential receptor:ligand affinities fine‐tune the immune response. Although the roles of TIGIT and CD96 as immune checkpoint receptors in T cell and natural killer cell biology are just beginning to be uncovered, accumulating data support the targeting of these receptors for improving anti‐tumor immune responses. A clear understanding of the immune cell populations regulated by TIGIT and CD96 is key to the design of immunotherapies that target these receptors in combination with other existing immune checkpoint blockade therapies.
LAG3 (CD223) as a cancer immunotherapy target
Authors: Andrews Lawrence P. , Marciscano Ariel E. , Drake Charles G. , Vignali Dario A. A.
Published: March 2017

Despite the impressive impact of CTLA4 and PD1‐PDL1‐targeted cancer immunotherapy, a large proportion of patients with many tumor types fail to respond. Consequently, the focus has shifted to targeting alternative inhibitory receptors (IRs) and suppressive mechanisms within the tumor microenvironment. Lymphocyte activation gene‐3 (LAG3) (CD223) is the third IR to be targeted in the clinic, consequently garnering considerable interest and scrutiny. LAG3 upregulation is required to control overt activation and prevent the onset of autoimmunity. However, persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression, contributing to a state of exhaustion manifest in impaired proliferation and cytokine production. The exact signaling mechanisms downstream of LAG3 and interplay with other IRs remain largely unknown. However, the striking synergy between LAG3 and PD1 observed in multiple settings, coupled with the contrasting intracellular cytoplasmic domain of LAG3 as compared with other IRs, highlights the potential uniqueness of LAG3. There are now four LAG3‐targeted therapies in the clinic with many more in preclinical development, emphasizing the broad interest in this IR. Given the translational relevance of LAG3 and the heightened interest in the impact of dual LAG3/PD1 targeting in the clinic, the outcome of these trials could serve as a nexus; significantly increasing or dampening enthusiasm for subsequent targets in the cancer immunotherapeutic pipeline.
Tim‐3 and its role in regulating anti‐tumor immunity
Authors: Das Madhumita , Zhu Chen , Kuchroo Vijay K.
Published: March 2017

Immunotherapy is being increasingly recognized as a key therapeutic modality to treat cancer and represents one of the most exciting treatments for the disease. Fighting cancer with immunotherapy has revolutionized treatment for some patients and therapies targeting the immune checkpoint molecules such as CTLA‐4 and PD‐1 have achieved durable responses in melanoma, renal cancer, Hodgkin's diseases and lung cancer. However, the success rate of these treatments has been low and a large number of cancers, including colorectal cancer remain largely refractory to CTLA‐4 and PD‐1 blockade. This has provided impetus to identify other co‐inhibitory receptors that could be exploited to enhance response rates of current immunotherapeutic agents and achieve responses to the cancers that are refectory to immunotherapy. Tim‐3 is a co‐inhibitory receptor that is expressed on IFN‐g‐producing T cells, FoxP3+ Treg cells and innate immune cells (macrophages and dendritic cells) where it has been shown to suppress their responses upon interaction with their ligand(s). Tim‐3 has gained prominence as a potential candidate for cancer immunotherapy, where it has been shown that in vivo blockade of Tim‐3 with other check‐point inhibitors enhances anti‐tumor immunity and suppresses tumor growth in several preclinical tumor models. This review discusses the recent findings on Tim‐3, the role it plays in regulating immune responses in different cell types and the rationale for targeting Tim‐3 for effective cancer immunotherapy.
The third group of the B7‐CD28 immune checkpoint family: HHLA2, TMIGD2, B7x, and B7‐H3
Authors: Janakiram Murali , Shah Urvi A. , Liu Weifeng , Zhao Aimin , Schoenberg Mark P. , Zang Xingxing
Published: March 2017

The B7‐CD28 family of ligands and receptors play important roles in T‐cell co‐stimulation and co‐inhibition. Phylogenetically they can be divided into three groups. The recent discovery of the new molecules (B7‐H3 [CD276], B7x [B7‐H4/B7S1], and HHLA2 [B7H7/B7‐H5]/TMIGD2 [IGPR‐1/CD28H]) of the group III has expanded therapeutic possibilities for the treatment of human diseases. In this review, we describe the discovery, structure, and function of B7‐H3, B7x, HHLA2, and TMIGD2 in immune regulation. We also discuss their roles in important pathological states such as cancers, autoimmune diseases, transplantation, and infection. Various immunotherapeutical approaches are emerging including antagonistic monoclonal antibodies and agonistic fusion proteins to inhibit or potentiate these molecules and pathways in cancers and autoimmune diseases.
TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy
Authors: Akalu Yemsratch T. , Rothlin Carla V. , Ghosh Sourav
Published: March 2017

Cancer immunotherapy utilizing T‐cell checkpoint inhibitors has shown tremendous clinical success. Yet, this mode of treatment is effective in only a subset of patients. Unresponsive patients tend to have non‐T‐cell‐inflamed tumors that lack markers associated with the activation of adaptive anti‐tumor immune responses. Notably, elimination of cancer cells by T cells is critically dependent on the optimal activity of innate immune cells. Therefore, identifying new targets that regulate innate immune cell function and promote the engagement of adaptive tumoricidal responses is likely to lead to the development of improved therapies against cancer. Here, we review the TAM receptor tyrosine kinases—TYRO3, AXL, and MERTK—as an emerging class of innate immune checkpoints that participate in key steps of anti‐tumoral immunity. Namely, TAM‐mediated efferocytosis, negative regulation of dendritic cell activity, and dysregulated production of chemokines collectively favor the escape of malignant cells. Hence, disabling TAM signaling may promote engagement of adaptive immunity and complement T‐cell checkpoint blockade.