bluuebunny/crossref_metadata_2025 huggingface dataset:
Incretin‐based medications for type 2 diabetes: an overview of reviews
Authors: Gamble J.‐M. , Clarke A. , Myers K. J. , Agnew M. D. , Hatch K. , Snow M. M. , Davis E. M.
Published: March 2015

Aims

To summarize evidence from and assess the quality of published systematic reviews evaluating the safety, efficacy and effectiveness of incretin‐based medications used in the treatment of type 2 diabetes.

Methods

We identified systematic reviews of randomized controlled trials or observational studies published in any language that evaluated the safety and/or effectiveness of glucagon‐like peptide‐1 (GLP‐1) receptor agonists or dipeptidyl‐peptidase‐4 (DPP‐4) inhibitors. Data sources used include the Cochrane Library, PubMed, EMBASE, Web of Science, International Pharmaceutical Abstracts, table of contents of diabetes journals, and hand‐searching of reference lists and clinical practice guidelines. The methodological quality of systematic reviews was independently assessed by two reviewers using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist. Our study protocol was registered with PROSPERO (2013:CRD42013005149). The primary outcomes were pooled treatment effect estimates for glycaemic control, macrovascular and microvascular complications, and hypoglycaemic events.

Results

We identified 467 unique citations of which 84 systematic reviews met our inclusion criteria. There were 51 reviews that evaluated GLP‐1 receptor agonists and 64 reviews that evaluated DPP‐4 inhibitors. The median (interquartile range) AMSTAR score was 6 (3) out of 11 for quantitative and 1 (1) for non‐quantitative reviews. Among the 66 quantitative systematic reviews, there were a total of 718 pooled treatment effect estimates reported for our primary outcomes and 1012 reported pooled treatment effect estimates for secondary outcomes.

Conclusions

Clinicians and policy makers, when using the results of systematic reviews to inform decision‐making with regard to round clinical care or healthcare policies for incretin‐based medications, should consider the variability in quality of reviews.
The anticonvulsant retigabine is a subtype selective modulator of GABAA receptors
Authors: Treven Marco , Koenig Xaver , Assadpour Elham , Gantumur Enkhbileg , Meyer Christiane , Hilber Karlheinz , Boehm Stefan , Kubista Helmut
Published: March 2015

Objective

Within its range of therapeutic plasma concentrations, the anticonvulsant retigabine (ezogabine) is believed to selectively act on Kv7 channels. Here, the contribution of specific γ‐aminobutyric acid (GABA)A receptor subtypes to the antiseizure effects of retigabine was investigated.

Methods

Using patch‐clamp recordings, seizure‐like activity, tonic currents, and GABA‐induced currents in hippocampal neurons were tested for their sensitivity toward retigabine, as were recombinant GABAA receptors expressed in tsA 201 cells.

Results

Retigabine reduced seizure‐like activity elicited by low Mg2+ in a concentration‐dependent manner with half maximal inhibition at 1 μm. Seizure‐like activity triggered by blocking either Kv7 channels or GABAA receptors was equally reduced by retigabine, but when these channels/receptors were blocked simultaneously, the inhibition was lost. Retigabine (10 μm) enhanced bicuculline‐sensitive tonic currents in hippocampal neurons, but failed to affect GABA‐evoked currents. However, when receptors involved in phasic GABAergic inhibition were blocked by penicillin, retigabine did enhance GABA‐evoked currents. In tsA 201 cells expressing various combinations of GABAA receptor subunits, 10 μm retigabine enhanced currents through α1β2δ, α4β2δ, α4β3δ, and α6β2δ receptors, but left currents through α1β2γ2S, α4β3γ2S, α5β3γ2S, and α6β2γ2S receptors unaltered. With αβ receptors, retigabine diminished currents through α1β2 and α4β3, but increased currents through α6β2 receptors. The enhancement of currents through α1β2δ receptors by retigabine was concentration dependent and became significant at 1 μm.

Significance

These results demonstrate that retigabine is a subtype selective modulator of GABAA receptors with preference for extrasynaptic δ‐containing receptors; this property may contribute to its broad antiepileptic effectiveness and explain its lack of effect on absence seizures.
Fatigue after Stroke – Perspectives and Future Directions
Authors: Kutlubaev Mansur A. , Mead Gillian E. , Lerdal Anners
Published: March 2015

Fatigue is a common consequence of stroke and adversely affects long-term outcomes. It is associated with a number of psychological and biological factors. Nevertheless, its mechanisms are not well understood. There may be subtypes of post-stroke fatigue e.g. primary and secondary, subjective fatigue and activity-dependent fatigability – but further research is needed to determine whether such subtypes exist. There is very limited evidence for treatment of fatigue after stroke. Psychosocial treatments and physical activity are promising method for its management. Other potentially effective treatment options include mind-body interventions, and use of psychostimulants. More research is needed in this area.
Individual differences in responses to workplace stress: the contribution of attachment theory
Authors: Johnstone Melissa , Feeney Judith A.
Published: March 2015

Work stress is a major cause of physical and psychological distress, and both theory and research highlight the importance of individual differences in coping efforts. The present research clarifies the mechanisms linking attachment insecurities (anxiety and avoidance) to maladaptive coping; specifically, we tested an integrative model assessing stress appraisals as a mediator between attachment insecurities and coping strategies, together with mediating and moderating effects of coping resources (perceived self‐efficacy and social support). A community sample of 113 men and 115 women completed an online survey which incorporated a standardized vignette depicting workplace stress. The results supported stress appraisal as a mediator between attachment anxiety and less adaptive coping, and established both mediating and moderating effects of perceived coping resources. The effects support the relevance of attachment theory to the study of workplace stress.
First archaeogenetic results verify the mid‐Holocene occurrence of Dalmatian pelican Pelecanus crispus far out of present range
Authors: Nikulina Elena A. , Schmölcke Ulrich
Published: March 2015

The paper presents an evaluation of subfossil bird bones from archaeological and geological sites in Europe that shows that birds of the genus Pelecanus occurred far out of their present range between 7.4 and 5.0 ka BP in the Danish archipelago. Additionally, from other northwestern European regions mid‐Holocene records of pelicans are known. However, due to morphological similarities there are difficulties in species identification. In this paper ancient DNA barcoding techniques were used to clarify the species assignment of one of these records for the first time. Our results show that the bone derives from Dalmatian pelican Pelecanus crispus, a species that today breeds in 15 colonies in the eastern Mediterranean. This species identification is especially remarkable since the Dalmatian pelican is known to be less migratory. We demonstrate that the appearance and disappearance of pelicans in northwestern Europe coincide with climate parameters, since all records fall within warm periods. This applies for the larger group of Danish records during the Holocene thermal maximum in northern Europe as well as for two more groups of records from central Europe and Britain dating to 1.9 and 0.8 ka ago. Recent ecological research on the Dalmatian pelican shows that the species seems to profit from the modern climate changes and is starting to expand its range. Our paper documents that under special circumstances short‐distance migrant birds are also able to expand their ranges to areas far outside of the former distribution areas. Finally, the Dalmatian pelican is presented as an indicator species reflecting special climate conditions.

The present study demonstrates not only the possibility to recover avian DNA from at least 7 ka old bones, but the relevance of such genetic analysis in combination with archaeological data, particularly if bones could not be assigned to species level by morphological features. In such cases, aDNA is shown as a valuable tool for the reconstruction of the avifauna of the past.
Comparative safety study on severe anemia by simeprevir versus telaprevir‐based triple therapy for chronic hepatitis C
Authors: Ogawa Eiichi , Furusyo Norihiro , Kajiwara Eiji , Nomura Hideyuki , Kawano Akira , Takahashi Kazuhiro , Dohmen Kazufumi , Satoh Takeaki , Azuma Koichi , Nakamuta Makoto , Koyanagi Toshimasa , Kotoh Kazuhiro , Shimoda Shinji , Hayashi Jun ,   The Kyushu University Liver Disease Study (KULDS) Group
Published: March 2015

Background and Aim

The addition of hepatitis C virus (HCV) NS3/4A protease inhibitors to the pegylated interferon (PEG‐IFN) α and ribavirin combination regimen (triple therapy) has dramatically improved treatment outcome. Unfortunately, anemia remains a common adverse effect. This study was done to compare the development of severe anemia during simeprevir‐ or telaprevir‐based triple therapy.

Methods

This retrospective multicenter study consisted of 837 consecutive Japanese HCV genotype 1 patients treated in a real‐world clinical setting, 811 of whom were enrolled (simeprevir 281, telaprevir 530). The inosine triphosphate pyrophosphatase (ITPA) genotype at rs1127354 was determined for all studied patients. Logistic regression was done after propensity score matching to assess the risk of development of severe anemia.

Results

Propensity score matching of the entire study population yielded 266 matched pairs. Severe anemia (nadir hemoglobin < 9.0 g/dL) was developed during the treatment period by 81 (30.5%) and 144 (54.1%) patients treated with simeprevir and telaprevir, respectively. Treatment with simeprevir was independently associated with a lower risk of severe anemia (odds ratio 0.25, 95% confidence interval 0.16–0.38, P < 0.0001). Moreover, ITPA genotype, age, hemoglobin level, and estimated glomerular filtration rate at baseline were also independent factors associated with the development of severe anemia.

Conclusions

Patients treated with simeprevir‐based triple therapy have a lower risk of the development of severe anemia than those treated with telaprevir. Moreover, ITPA genotype and age may be useful for individualizing treatment to reduce the risk of anemia‐related adverse effects.
Aldehyde dehydrogenase 2 polymorphism for development to hepatocellular carcinoma in East Asian alcoholic liver cirrhosis
Authors: Abe Hiroshi , Aida Yuta , Seki Nobuyoshi , Sugita Tomonori , Tomita Yoichi , Nagano Tomohisa , Itagaki Munenori , Sutoh Satoshi , Nagatsuma Keisuke , Itoh Kyoko , Matsuura Tomokazu , Aizawa Yoshio
Published: March 2015

Background and Aim

We aimed to clarify the influences of aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) polymorphisms, and ethanol consumption profile to hepatocellular carcinoma (HCC) development in alcoholic liver cirrhosis without chronic hepatitis B and C virus infection (non‐B non‐C).

Methods

Of 236 freshly diagnosed non‐B non‐C alcoholic liver cirrhosis patients, 67 were diagnosed as HCC and the remaining 169 as not having HCC. The relationship between the genetic polymorphisms and development to HCC were evaluated in well‐matched patients with HCC (HCC group, n = 67) and without HCC (non‐HCC group, n = 67) using propensity scores in age, sex, and prevalence of diabetes mellitus.

Results

Daily amount of ethanol consumption was significantly lower (P = 0.005), and consumptive period was significantly longer (P = 0.003) in HCC group than non‐HCC group. Of 134 well‐matched patients, 113 (84.3%) had ALDH2*1/*1 genotype and 21 (15.7%) had ALDH2*1/*2 genotype. In HCC development, consumptive long period (P = 0.007) and carrying ALDH2*1/*2 genotype (P = 0.026) were identified as significant factors independently participated, while there was no relation to ADH1B polymorphism. In addition, consumptive period was significantly longer in HCC group than non‐HCC group in ALDH2*1/*1 genotype patients (P = 0.0005), while there was no difference in profile of ethanol consumption in ALDH2*1/*2 genotype patients. Among HCC group, daily (P = 3.78 × 10−6) and cumulative amount (P = 4.89 × 10−6) of ethanol consumption were significantly higher in ALDH2*1/*1 genotype patients than ALDH2*1/*2 genotype patients.

Conclusion

In alcoholic liver cirrhosis, investigations of ALDH2 polymorphism and ethanol consumption profile are useful for prediction of HCC development.
Randomized study comparing vitamin D3 and 1α‐Hydroxyvitamin D3 in combination with pegylated interferon/ribavirin therapy for chronic hepatitis C
Authors: Omori‐Mizuno Yoshie , Nakayama Nobuaki , Inao Mie , Funyu Junji , Asabe Shinichi , Tomita Kengo , Nishikawa Kou , Hosoda Yasuo , Tanaka Masahiko , Hashimoto Yoshiaki , Yakabi Koji , Koshima Yohei , Mochida Satoshi
Published: March 2015

Background and Aim

An intention‐to‐treat prospective randomized study was carried out to compare the potentiation of antiviral efficacies between cholecalciferol, non‐activated vitamin D3 supplement, and alfacalcidol, activated 1α‐Hydroxyvitamin D3 [1α (OH)‐vitamin D3].

Methods

Chronic hepatitis patients with genotype 1b hepatitis C virus (HCV) infection showing serum HCV‐RNA levels greater than 5 Log IU/mL received oral administration of cholecalciferol (2000 IU/day) or alfacalcidol (0.5 μg/day) for 4 weeks, and then they were given pegylated interferon (Peg‐IFN)‐α2a plus ribavirin therapy in combination with either vitamin D3 for 48 or 72 weeks according to the response‐guided manner.

Results

A total of 36 patients were evaluated. Serum 25‐hydroxyvitamin D3 [25(OH)‐D3] levels were increased only in patients in the cholecalciferol group during the lead‐in vitamin D administration, and the levels at 4 weeks were higher in these patients than in those in the alfacalcidol group (P < 0.001), while serum 1α,25‐dihydroxyvitamin D3 [1α,25(OH)2‐D3] levels were not different between both groups. Rapid virological response was obtained in six (33%) patients in the cholecalciferol group; the ratio was higher than that in the alfacalcidol group (one patient; 6%, P < 0.05). Serum HCV‐RNA level decline at 4 weeks of combined Peg‐IFN‐α2a plus ribavirin therapy compared with the baseline levels were greater in the cholecalciferol group (4.6 Log IU/mL) than in the alfacalcidol group (3.5 Log IU/mL) (P < 0.05), when four patients showing null response to the therapy was excluded. However, both complete early virological response and sustained viral response rates were not different between both groups.

Conclusion

Cholecalciferol produced superior potentiation of the antiviral activity than alfacalcidol only during the initial periods of combined Peg‐IFN‐α2a plus ribavirin therapy through upregulation of serum 25(OH)‐D3 levels.
Empathic Accuracy and Aggression in Couples: Individual and Dyadic Links
Authors: Cohen Shiri , Schulz Marc S. , Liu Sabrina R. , Halassa Muhannad , Waldinger Robert J.
Published: March 2015

The authors examined links between intimate partner aggression and empathic accuracy—how accurately partners can read one another's emotions—during highly affective moments from couples' (N = 109) video recall of laboratory‐based discussions of upsetting events. Less empathic accuracy between partners was generally related to higher levels of aggression by both partners. More specific patterns emerged based on the type of aggression and emotion being expressed. Women's poorer ability to read their partners' vulnerable and positive emotions was linked to both men's and women's greater physical and psychological aggression. Moreover, women's inaccuracy in reading their partner's hostility was linked to women's greater psychological aggression toward the men. Men's inaccuracy in reading their partner's hostility was linked to women's (not men's) greater physical and psychological aggression. The results suggest important nuances in the links between empathic inaccuracy and aggression, and implications for prevention and treatment of partner aggression are discussed.
Intergenerational Exchanges of Middle‐Aged Adults With Their Parents and Parents‐In‐Law in Korea
Authors: Kim Kyungmin , Zarit Steven H. , Fingerman Karen L. , Han Gyounghae
Published: March 2015

The authors investigated patterns of support exchanges between Korean adult children and their parents and parents‐in‐law, gender differences in these patterns, and implications of children's marital quality for exchange patterns. Data were from a nationally representative sample of married adults (N = 920, age 30–59 years) with at least 1 living parent and 1 living parent‐in‐law. Latent class analysis was applied to 12 indicators of exchanges (financial, instrumental, emotional support given to and received from parents and parents‐in‐law). Five classes of exchanges were identified, 3 showing balanced patterns of exchanges with parents and parents‐in‐law across three types of support and 2 classes with unbalanced patterns (e.g., giving instrumental and financial but not emotional support). The findings revealed variability in intergenerational exchange patterns, with a mix of patrilineal traditional and balanced patterns. Significant associations of exchange patterns with adult children's marital quality suggest the importance of balanced exchanges with parents for marriage.
Coparenting and Nonresident Fathers' Monetary Contributions to Their Children
Authors: Goldberg Julia S.
Published: March 2015

The percentage of children in the United States living apart from their biological father has increased, while public assistance for single mothers has diminished. This has resulted in a need to better understand and promote nonresident fathers' economic support of their children. In the present study the author used data from the Fragile Families and Child Wellbeing Study (N = 1,752) to examine how coparenting—the degree to which parents are mutually supportive and cooperative in raising their child—is related to nonresident fathers' monetary contributions. Results from pooled regression and fixed effects models indicate that coparenting is positively associated with fathers' likelihood of paying formal and informal child support and the amount of these payments. Findings from cross‐lagged structural equation models suggest that the association between coparenting and fathers' payments is reciprocal but that coparenting has a stronger effect on fathers' payments than fathers' payments do on coparenting.
Red and far‐red fluorescent dyes for the characterization of head and neck cancer at the cellular level
Authors: Abbaci Muriel , Casiraghi Odile , Temam Stephane , Ferchiou Malek , Bosq Jacques , Dartigues Peggy , De Leeuw Frederic , Breuskin Ingrid , Laplace‐Builhé Corinne
Published: March 2015

Background

Primary upper aerodigestive tract malignancy remains a cancer having a poor prognosis, despite current progress in treatment, due to a generally late diagnosis. Objectives: We conducted a preliminary assessment of five dyes approved for human use for the imaging of head and neck tissues at the cellular level, which could be considered for clinical examination.

Methods

We investigated fluorescence endomicroscopic images on fresh samples obtained from head and neck surgeries after staining with hypericin, methylene blue, toluidine blue, patent blue or indocyanine green to provide a preliminary consideration as to whether these images contain enough information for identification of non‐pathologic and pathologic tissues. The distribution pattern of dye has been examined using probe‐based confocal laser endomicroscopy (pCLE) in ex vivo specimens and compared with corresponding histology.

Results

In most samples, the image quality provided by pCLE with both dyes allowed pathologists to recognize histological characteristics to identify the tissues.

Conclusion

The combination of pCLE imaging with these dyes provides interpretable images close to conventional histology; a promising clinical tool to assist physicians in examination of upper aerodigestive tract, as long as depth imaging issues can be overcome.
The Impact of Sleep on Female Sexual Response and Behavior: A Pilot Study
Authors: Kalmbach David A. , Arnedt J. Todd , Pillai Vivek , Ciesla Jeffrey A.
Published: March 2015

Introduction

The etiological role of sleep disturbance in sexual difficulties has been largely overlooked. Research suggests that short sleep duration and poor sleep quality lead to poor female sexual response. However, prior research consists of cross-sectional studies, and the influence of sleep on sexual functioning and behavior has not been prospectively examined.

Aim

We sought to examine the influence of nightly sleep duration, sleep quality, and sleep onset latency on daily female sexual response and activity.

Methods

This study used a longitudinal design to study 171 women free of antidepressants and with reliable Internet access who were recruited from a university setting in the United States. Participants first completed baseline measures in a laboratory, and then completed web-delivered surveys at their habitual wake time for 14 consecutive days.

Main Outcome Measures

All outcome measures were modified for daily recall. Participants completed the Profile of Female Sexual Function's desire, subjective arousal, and orgasmic functioning scales and the Female Sexual Function Index's genital arousal scale, and indicated whether they engaged in partnered sexual activity or self-stimulation in response to dichotomous items.

Results

Analyses revealed that longer sleep duration was related to greater next-day sexual desire (b = 0.32, P = 0.02), and that a 1-hour increase in sleep length corresponded to a 14% increase in odds of engaging in partnered sexual activity (odds ratio = 1.14, P < 0.05). In contrast, sleeping longer predicted poorer next-day genital arousal (b = −0.19, P < 0.01). However, results showed that women with longer average sleep duration reported better genital arousal than women with shorter average sleep length (b = 0.54, P = 0.03).

Conclusions

Obtaining sufficient sleep is important to the promotion of healthy sexual desire and genital response, as well as the likelihood of engaging in partnered sexual activity. These relationships were independent of daytime affect and fatigue. Future directions may investigate sleep disorders as risk factors for sexual dysfunction.
The effect of enalapril on furosemide‐activated renin–angiotensin–aldosterone system in healthy dogs
Authors: Lantis A. C. , Ames M. K. , Werre S. , Atkins C. E.
Published: March 2015

Studies in our laboratory have revealed that furosemide‐induced RAAS activation, evaluated via the urine aldosterone‐to‐creatinine ratio (UAldo:C), was not attenuated by the coadministration of benazepril, while enalapril successfully suppressed amlodipine‐induced urinary aldosterone excretion. This study was designed to evaluate the efficacy of enalapril in suppressing ACE activity and furosemide‐induced circulating RAAS activation. Failure to do so would suggest that this failure may be a drug class effect. We hypothesized that enalapril would suppress ACE activity and furosemide‐induced circulating RAAS activation. Sixteen healthy hound dogs. The effect of furosemide (2 mg/kg PO, q12 h; Group F) and furosemide plus enalapril (0.5 mg/kg PO, q12 h; Group FE) on circulating RAAS was determined by plasma ACE activity, 4–6 h post‐treatment, and urinary A:C on days −1, −2, 1, 4, and 7. There was a significant increase in the average urine aldosterone‐to‐creatinine ratio (UAldo:C) after administration of furosemide (P < 0.05). Enalapril inhibited ACE activity (P < 0.0001) but did not significantly reduce aldosterone excretion. A significant (P < 0.05) increase in the UAldo:C was maintained for the 7 days of the study in both groups. Enalapril decreased plasma ACE activity; however, it did not suppress furosemide‐induced RAAS activation, as determined by the UAldo:C. While enalapril blunts ACE activity, the absence of circulating RAAS suppression may be due to angiotensin II reactivation, alternative RAAS pathways, and furosemide overriding concurrent ACE inhibition, all indicating the existence of aldosterone breakthrough (ABT). Along with similar findings with benazepril, it appears that failure to suppress aldosterone suppression with furosemide stimulation may be a drug class effect. The discrepancy between the current data and the documented benefits of enalapril likely reflects the efficacy of this ACE inhibitor in suppressing tissue RAAS, variable population responsiveness to ACE‐inhibition, and/or providing additional survival benefits, possibly through as yet unknown mechanisms.
Prevalence, awareness and treatment of chronic kidney disease among middle‐aged and elderly: The China Health and Retirement Longitudinal Study
Authors: Wang Shengfeng , Chen Ru , Liu Qing , Shu Zheng , Zhan Siyan , Li Liming
Published: March 2015

Aim

To provide reliable estimates of the prevalence, awareness, and treatment of chronic kidney disease (CKD), and their distribution and related influencing factors in middle‐aged and elderly population in China.

Methods

A cross‐sessional survey called the China Health and Retirement Longitudinal Study (CHARLS) was conducted in 2011–2012 in Chinese people aged 45 years or older. This was to evaluate the prevalence of CKD, disease awareness compared to other chronic diseases in the population, and whether they were being treated for their CKD. Estimated GFR (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration eGFR creatinine‐cystatin C (eGFRcreat‐cys) equation. CKD was defined as eGFR less than 60 mL/min per 1.73 m2. Multivariable logistic regressions were used to estimate odds ratios (ORs) for the risk factors.

Results

The overall prevalence of CKD was 11.5% (95%CI: 10.1% ∼ 12.8%). It was higher in urban than rural population (13.0% vs 10.0%, P < 0.05). Among all patients with CKD, only 8.7% were aware of the diagnosis. 4.9% of the patients were receiving treatment. The proportion of those aware of their condition and those who were treated decreased with age in both sexes. Of those aware (8.9%), 55.9% were treated. 31.4% of the treated patients took Chinese traditional medicine.

Conclusions

There is a surprising prevalence of CKD in the Chinese middle‐aged and elderly population, with disproportionately low awareness and treatment. A comprehensive strategy toward prevention, screening, treatment and control of CKD is needed to slow the epidemic of CKD.
Traditional Uses of Medicinal Plants from the Canadian Boreal Forest for the Management of Chronic Pain Syndromes
Authors: Uprety Yadav , Lacasse Anaïs , Asselin Hugo
Published: March 2015

Objective

Chronic pain is more prevalent in indigenous populations who often prefer traditional remedies over allopathic drugs. Our objective was to investigate the traditional uses of medicinal plants from the Canadian boreal forest for the management of chronic pain syndromes.

Methods

We reviewed the most extensive database on medicinal plants used by aboriginal people of the Canadian boreal forest to investigate the plants used in the management of 3 of the most common chronic pain syndromes: arthritis/rheumatism; back pain; and headache/migraine. We also reviewed the pharmacology and phytochemistry literature to investigate concordance with indigenous knowledge.

Results

A total of 114 medicinal plant species were reported, of which 27 (23.5%) were used to treat more than 1 chronic pain syndrome. Pharmacological or phytochemical evidence to explain plant function as chronic pain remedy was available in the literature for only 38 species (33%), with several species reported to have anti‐inflammatory and analgesic properties effective in treating chronic pain syndromes.

Conclusions

Our study showed the potential of boreal plants as alternative and complementary medicines for the treatment of chronic pain syndromes that could be enhanced by further research on efficacy and safety issues.
EjAP2‐1, an AP2/ERF gene, is a novel regulator of fruit lignification induced by chilling injury, via interaction with EjMYB transcription factors
Authors: Zeng Jiao‐ke , Li Xian , Xu Qian , Chen Jian‐ye , Yin Xue‐ren , Ferguson Ian B. , Chen Kun‐song
Published: March 2015

Lignin biosynthesis is regulated by many transcription factors, such as those of the MYB and NAC families. However, the roles of AP2/ERF transcription factors in lignin biosynthesis have been rarely investigated. Eighteen EjAP2/ERF genes were isolated from loquat fruit (Eriobotrya japonica), which undergoes postharvest lignification during low temperature storage. Among these, expression of EjAP2‐1, a transcriptional repressor, was negatively correlated with fruit lignification. The dual‐luciferase assay indicated that EjAP2‐1 could trans‐repress activities of promoters of lignin biosynthesis genes from both Arabidopsis and loquat. However, EjAP2‐1 did not interact with the target promoters (Ej4CL1). Yeast two‐hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays indicated protein–protein interactions between EjAP2‐1 and lignin biosynthesis‐related EjMYB1 and EjMYB2. Furthermore, repression effects on the Ej4CL1 promoter were observed with the combination of EjAP2‐1 and EjMYB1 or EjMYB2, while EjAP2‐1 with the EAR motif mutated (mEjAP2‐1) lost such repression, although mEjAP2‐1 still interacted with EjMYB protein. Based on these results, it is proposed that EjAP2‐1 is an indirect transcriptional repressor on lignin biosynthesis, and the repression effects were manifested by EAR motifs and were conducted via protein–protein interaction with EjMYBs.
Risk factors and antibiotic therapy in P. aeruginosa community‐acquired pneumonia
Authors: Sibila Oriol , Laserna Elena , Maselli Diego Jose , Fernandez Juan Felipe , Mortensen Eric M. , Anzueto Antonio , Waterer Grant , Restrepo Marcos I.
Published: March 2015

Background and objective

Current guidelines recommend empirical treatment against Pseudomonas aeruginosa in community‐acquired pneumonia (CAP) patients with specific risk factors. However, evidence to support these recommendations is limited. We evaluate the risk factors and the impact of antimicrobial therapy in patients hospitalized with CAP due to P. aeruginosa.

Methods

We performed a retrospective population‐based study of >150 hospitals. Patients were included if they had a diagnosis of CAP and P. aeruginosa was identified as the causative pathogen. Univariate and multivariate analyses were performed using the presence of risk factors and 30‐day mortality as the dependent measures.

Results

Seven hundred eighty‐one patients with P. aeruginosa pneumonia were identified in a cohort of 62 689 patients with pneumonia (1.1%). Of these, 402 patients (0.6%) were included in the study and 379 (0.5%) were excluded due to health care‐associated pneumonia or immunosuppression. In patients with CAP due to P. aeruginosa, 272 (67.8%) had no documented risk factors. These patients had higher rates of dementia and cerebrovascular disease. Empirical antibiotic therapy against P. aeruginosa within the first 48 h of presentation was independently associated with lower 30‐day mortality in patients with CAP due to P. aeruginosa (hazard ratio (HR) 0.42, 95% confidence interval (CI): 0.23–0.76) and in patients without risk factors for P. aeruginosa CAP (HR 0.40, 95% CI: 0.21–0.76).

Conclusions

Risk factor recommended by current guidelines only detect one third of the patients admitted with CAP due to P. aeruginosa. Risk factors did not define the whole benefit observed due to empirical therapy covering P. aeruginosa.
Millennial‐scale stratigraphy of a tide‐dominated incised valley during the last 14 kyr: Spatial and quantitative reconstruction in the Tokyo Lowland, central Japan
Authors: Tanabe Susumu , Nakanishi Toshimichi , Ishihara Yoshiro , Nakashima Rei
Published: March 2015

Spatial and quantitative analysis of infilling processes of the tide‐dominated incised valleys beneath the Tokyo Lowland during the last 14 kyr was undertaken by using data from 18 sediment cores, 467 radiocarbon dates and 6100 borehole logs. The post‐Last Glacial Maximum valley fills consist of braided river, meandering river, estuary, spit and delta systems in ascending order. The boundary between the estuary and delta systems is regarded as the maximum flooding surface. The maximum flooding surface beneath the Tokyo Lowland is dated at 8 ka in the Arakawa Valley and 7 ka in the Nakagawa Valley. This age difference is due to the migration of the Tone River from the Arakawa Valley to the Nakagawa Valley at 5 ka, and suggests that the widely held view that the global initiation of deltas coincided with the abrupt rise of sea‐level at 9 to 8 ka is true only where there has been steady sediment supply from major rivers. The meandering river system is dominated by sheet‐like sands that were deposited during lateral migration of channels during the Younger Dryas and isolated vertical sands within muds that reflect vertical aggradation of channels before and after the Younger Dryas. The transition between these channel geometries is controlled by a threshold sea‐level rise of 4 to 7 mm yr−1. Before migration of the Tone River at 5 ka, the tide‐dominated bay in the Nakagawa Valley was filled by upward‐fining laterally accreting muds. The muds accreted from the margin to the axis of the bay. Such lateral accretion of suspended particles derived from outside the bay has been documented in other tide‐dominated coastal environments and is probably common in other similar settings. After the migration of the Tone River, the bay was filled by upward‐coarsening deltaic sediments.
Evaluating the Impact of a Working Time Regulation on Capital Operating Time: The French 35‐hour Work Week Experience
Authors: Gilles Fabrice
Published: March 2015

In this article, we evaluate the impact of diminishing weekly working hours on capital operating time using the French 35‐hour working week experience. We merge the French survey on Capital Operating Time (COT, Banque de France, Central Bank of France; 1989–2004) and administrative Working Time Reduction agreements files (WTR, DARES, French Ministry of Labour; May 2003). We construct shift‐work‐based capital operating time indicators. Using differences‐in‐differences econometric models, we show that the implementation of the 35‐hour work week did not induce any reduction in COT. Hence, firms increased shift‐work to compensate for the decrease in working hours.
An Exploration of Future Patterns of the Contributions to OpenStreetMap and Development of a Contribution Index
Authors: Arsanjani Jamal Jokar , Mooney Peter , Helbich Marco , Zipf Alexander
Published: March 2015

OpenStreetMap (OSM) represents one of the most well‐known examples of a collaborative mapping project. Major research efforts have so far dealt with data quality analysis but the modality of OSM's evolution across space and time has barely been noted. This study aims to analyze spatio‐temporal patterns of contributions in OSM by proposing a contribution index (CI) in order to investigate the dynamism of OSM. The CI is based on a per cell analysis of the node quantity, interactivity, semantics, and attractivity (the ability to attract contributors). Additionally this research explores whether OSM has been constantly attracting new users and contributions or if OSM has experienced a decline in its ability to attract continued contributions. Using the Stuttgart region of Germany as a case study the empirical findings of the CI over time confirm that since 2007, OSM has been constantly attracting new users, who create new features, edit the existing spatial objects, and enrich them with attributes. This rate has been dramatically growing since 2011. The utilization of a Cellular Automata‐Markov (CA‐Markov) model provides evidence that by the end of 2016 and 2020, the rise of CI will spread out over the study area and only a few cells without OSM features will remain.
Independent Analysis of Real-Time, Measured Performance Data From Microcogenerative Fuel Cell Systems Installed in Buildings
Authors: Dillon Heather E. , Colella Whitney G.
Published: March 2015

Pacific Northwest National Laboratory (PNNL) is working with industry to independently monitor up to 15 distinct 5 kW-electric (kWe) combined heat and power (CHP) high temperature (HT) proton exchange membrane (PEM) fuel cell systems (FCSs) installed in light commercial buildings. This research paper discusses an evaluation of the first six months of measured performance data acquired at a 1 s sampling rate from real-time monitoring equipment attached to the FCSs at building sites. Engineering performance parameters are independently evaluated. Based on an analysis of the first few months of measured operating data, FCS performance is consistent with manufacturer-stated performance. Initial data indicate that the FCSs have relatively stable performance and a long-term average production of about 4.57 kWe of power. This value is consistent with, but slightly below, the manufacturer's stated rated electric power output of 5 kWe. The measured system net electric efficiency has averaged 33.7%, based on the higher heating value (HHV) of natural gas fuel. This value, also, is consistent with, but slightly below, the manufacturer's stated rated electric efficiency of 36%. The FCSs provide low-grade hot water to the building at a measured average temperature of about 48.4 °C, lower than the manufacturer's stated maximum hot water delivery temperature of 65 °C. The uptime of the systems is also evaluated. System availability can be defined as the quotient of total operating time compared to time since commissioning. The average values for system availability vary between 96.1 and 97.3%, depending on the FCS evaluated in the field. Performance at rated value for electrical efficiency (PRVeff) can be defined as the quotient of the system time operating at or above the rated electric efficiency and the time since commissioning. The PRVeff varies between 5.6% and 31.6%, depending on the FCS field unit evaluated. Performance at rated value for electrical power (PRVp) can be defined as the quotient of the system time operating at or above the rated electric power and the time since commissioning. PRVp varies between 6.5% and 16.2%. Performance at rated value for electrical efficiency and power (PRVt) can be defined as the quotient of the system time operating at or above both the rated electric efficiency and the electric power output compared to the time since commissioning. PRVt varies between 0.2% and 1.4%. Optimization to determine the manufacturer rating required to achieve PRVt greater than 80% has been performed based on the collected data. For example, for FCS Unit 130 to achieve a PRVt of 95%, it would have to be down-rated to an electrical power output of 3.2 kWe and an electrical efficiency of 29%. The use of PRV as an assessment metric for FCSs has been developed and reported for the first time in this paper. For FCS Unit 130, a maximum decline in electric power output of approximately 18% was observed over a 500 h period in Jan. 2012.
Damage Identification Based on the Proper Orthogonal Mode Energy Curvature
Authors: Lee Eun-Taik , Eun Hee-Chang
Published: March 2015

The evaluation of the structural performance and durability using only measurement data without any baseline data is practical. One measurement data type is the frequency response function (FRF) data set, which does not provide enough information about the health state because of the noise included in the data. Proper orthogonal modes (POMs) extracted from the FRF data in a prescribed frequency range are utilized as an index to recognize the existence of damage. The POMs represent the principal axes of inertia formed by the distribution of data on the modal coordinate curve. This work proposes a damage detection method to trace damage based on the POM energy curvature at the element of the finite element model. The validity of the proposed method is illustrated by a numerical experiment and an experimental test.
Stability Analysis and Improvement of Uncertain Disk Brake Systems With Random and Interval Parameters for Squeal Reduction
Authors: Lü Hui , Yu Dejie
Published: March 2015

Stability analysis and improvement of disk brake systems for squeal reduction have been investigated by automotive manufacturers for decades. However, most of the researches have not considered uncertainties. For this case, a practical approach for analyzing and improving the stability of uncertain disk brake systems is proposed in this paper. In the proposed approach, a hybrid uncertain model with random and interval parameters is introduced to deal with the uncertainties existing in a disk brake system. The parameters of brake pressure, densities of component materials, and thickness of back plate are treated as random variables; whereas the parameters of frictional coefficient and Young's modulus of component materials are treated as interval variables. Attention is focused on stability analysis of the disk brake system for squeal reduction, and the stability is investigated via complex eigenvalue analysis (CEA). The dominant unstable mode is extracted by performing CEA based on a linear finite element (FE) model, and the negative damping ratio corresponding to the dominant unstable mode is selected as the indicator of system stability. To improve the efficiency of analysis, response surface methodology (RSM) is used to replace the time-consuming FE simulations. Based on RSM and CEA, the stability analysis model of the disk brake system is constructed, in which reliability analysis, hybrid uncertain analysis and sensitivity analysis are applied to deal with the uncertain problems. The analysis results of a numerical example demonstrate the effectiveness of the proposed approach, and show that the stability and robustness of the uncertain disk brake system can be improved effectively by increasing the stiffness of back plate.
Zombie Bible: Stant Litore's Strangers in the Land and the Conditions of Bibleness
Authors: Meredith Christopher
Published: March 2015

Stant Litore’s Strangers in the Land represents a very canny fusion of apocalyptic zombie literature and the biblical story of Deborah from Judg 4–5. This article examines the way Litore redeploys the zombie sub-genre to put otherwise obscured aspects of the Judges story on full display.  Thinking through the Zombie in relation to the process of Kristevan abjection, the article also explores the ways in which the novel presents the so-called 'real' Bible as an already-zombified cultural phenomenon. Is the undead corpse a useful emblem through which we can explore the functioning of the social idea called 'The Bible' in all its gory detail?
Continuous liquid interface production of 3D objects
Authors: Tumbleston John R. , Shirvanyants David , Ermoshkin Nikita , Janusziewicz Rima , Johnson Ashley R. , Kelly David , Chen Kai , Pinschmidt Robert , Rolland Jason P. , Ermoshkin Alexander , Samulski Edward T. , DeSimone Joseph M.
Published: March 2015

Fast, continuous, 3D printing

Although three-dimensional (3D) printing is now possible using relatively small and low-cost machines, it is still a fairly slow process. This is because 3D printers require a series of steps to cure, replenish, and reposition themselves for each additive cycle. Tumbleston
et al.
devised a process to effectively grow solid structures out of a liquid bath. The key to the process is the creation of an oxygen-containing “dead zone” between the solid part and the liquid precursor where solidification cannot occur. The precursor liquid is then renewed by the upward movement of the growing solid part. This approach made structures tens of centimeters in size that could contain features with a resolution below 100 µm.

Science
, this issue p.
1349
Activation of A2b adenosine receptor regulates ovarian cancer cell growth: involvement of Bax/Bcl-2 and caspase-3
Authors: Hajiahmadi Sima , Panjehpour Mojtaba , Aghaei Mahmoud , Shabani Mahdi
Published: March 2015

A2b adenosine receptor (A2bAR) acts as a potent regulator of cell growth in various cell lines. The present study was designed to understand the controlling mechanism of A2bAR agonist (NECA)-induced apoptosis in ovarian cancer cells. Real-time PCR and western blotting assays were used to evaluate the gene and protein expression profiles of A2bAR, respectively. MTT assay was used to study the cell proliferation effect of A2bAR agonist (NECA). Detection of apoptosis was conducted using annexin V-FITC/PI staining, caspase-3 activation assay, and the expression of Bax and Bcl-2 proteins analysis. The mitochondrial membrane potential (ΔΨM) was analyzed by employing JC-1 prob. The mRNA and protein expression levels of A2bAR in ovarian cancer cells were detected. NECA significantly reduced cell viability in a dose-dependent manner in OVCAR-3 and Caov-4 cell lines. The growth inhibition effect of NECA was related to the induction of cell apoptosis, which was manifested by annexin V-FITC staining, activation of caspase-3, and loss of mitochondrial membrane potentials (ΔΨm). In addition, downregulation of the regulatory protein Bcl-2 and upregulation of Bax protein by NECA were also observed. These findings demonstrated that NECA induces apoptosis via the mitochondrial signaling pathway. Thus, A2bAR agonists may be a potential agent for induction of apoptosis in ovarian cancer cells.
The α-effect in the SNAr reaction of 1-(4-nitrophenoxy)-2,4-dinitrobenzene with anionic nucleophiles: effects of solvation and polarizability on the α-effect
Authors: Um Ik-Hwan , Kim Min-Young , Cho Hyo-Jin , Dust Julian M. , Buncel Erwin
Published: March 2015

A kinetic study on SNAr reactions of 1-(4-nitrophenoxy)-2,4-dinitrobenzene (1a) with various anionic nucleophiles in 80 mol% water – 20 mol% DMSO at 25.0 °C is reported. The Brønsted-type plot for the reaction of 1a with a series of substituted phenoxides and HOO− results in an excellent linear correlation with βnuc = 1.17. However, OH− exhibits dramatic negative deviation from the Brønsted-type plot, while N3−, C6H5S−, and butane-2,3-dione monoximate (Ox−) deviate positively from linearity. HOO− is 680-fold more reactive than OH− but does not exhibit the α-effect. In contrast, Ox− is 166-fold more reactive than isobasic 4-Cl−C6H4O− and exhibits the α-effect. Differential solvation effects have been suggested to be responsible for the α-effect in this study, i.e., Ox− exhibits the α-effect, since it is 5.7 kcal/mol less strongly solvated than 4-Cl−C6H4O− in the reaction medium, while HOO− does not show the α-effect due to a strong requirement for partial desolvation before nucleophilic attack. The highly enhanced reactivity of polarizable N3− and C6H5S− and extremely decreased reactivity of nonpolarizable OH− are in accord with the hard–soft acid and base principle.