bluuebunny/crossref_metadata_2025 huggingface dataset:
Metropolitan Strategies and Climate Governance: Towards New Evaluative Approaches
Authors: Nguyen Thi Minh Phuong , Davidson Kathryn , Gleeson Brendan
Published: August 2018

In the new millennium, cities have become an emerging force among new forms of subnational climate governance. Of interest is how cities act unilaterally and directly in this new climate politics via the provision of relevant tools. Since metropolitan planning strategies have been considered as important mechanisms for achieving urban sustainability in this period, this research has sought to investigate the importance of these master plans in the delivery of urban responses to climate change. For this purpose, the study has employed a qualitative research methodology with the application of a comparative case study and the progression of a conceptual framework for evaluating climate policies in metropolitan plans of two selected cities—London and Melbourne. The study's results suggest that both the ‘London Plan’ and ‘Plan Melbourne’ incorporate critical elements to enhance climate governance, including the promotion of coordination principles, innovative technologies, a participatory planning approach and a long‐term planning scale. However, the review identified a consistent omission of key principles as identified through the proposed matrix for analysing the climate policies of a city's government, which include risk assessment tools, monitoring systems, distribution, impact frame and accountability. Moreover, the research also revealed the lack of vertical integration in policy formulation and implementation of ‘Plan Melbourne’. Our study suggests that a city's governance structure influences the way it undertakes its climate actions and the potential efficacy of these on a metropolitan scale.
Beneficial Effect of Intradialytic Electrical Muscle Stimulation in Hemodialysis Patients: A Randomized Controlled Trial
Authors: Suzuki Tadashi , Ikeda Masato , Minami Masayoshi , Matayoshi Yukiko , Nakao Masatsugu , Nakamura Takayoshi , Abo Masahiro
Published: August 2018

Many hemodialysis (HD) patients cannot perform self‐administered exercise training for their muscle wasting, weakness, and sarcopenia. Electrical muscle stimulation (EMS) has the advantages of easy application, and minimal risks for these patients. This study aimed to evaluate the effects of intradialytic EMS. This was a prospective, open‐label, randomized controlled trial. Twenty‐nine HD patients were randomly assigned to either the EMS group or the control (no training) group, and 13 patients in each group were eventually analyzed. The EMS group received intradialytic EMS over an 8‐week period. Measurement of isometric knee extensor strength using a handheld dynamometer, evaluation of the quadriceps cross‐sectional area (CSA) using magnetic resonance imaging (MRI), the Timed Up & Go Test (TUG) for physical function assessment, the Japanese version of the Short Form‐8 Health Survey (SF‐8), and blood tests were performed before and after the intervention period. The primary and secondary outcomes were improvement of quadriceps muscle strength and size, respectively. The EMS group demonstrated significant improvement compared with the control group in terms of knee extensor strength (right: 22.3 ± 12.8 vs. −10.8 ± 22.3 N, P < 0.001; left: 26.1 ± 29.7 vs. −8.3 ± 18.7 N, P < 0.001), quadriceps CSA at three positions, 25, 50, and 75% of the segment length from the greater trochanter to the inferior border of the lateral epicondyle of the femur (25% right: EMS group 1.7 ± 2.0 vs. Control group −0.4 ± 1.8cm2, P = 0.05; 25% left: EMS group 1.3 ± 1.1 vs. Control group −0.6 ± 1.8cm2, P = 0.01; 50% right: EMS group 2.0 ± 2.2 vs. Control group −0.7 ± 1.9cm2, P = 0.004; 50% left: EMS group 2.7 ± 2.1 vs. Control group −0.7 ± 1.6cm2, P = 0.001; 75% right: EMS group 1.8 ± 2.2 vs. Control group −0.7 ± 1.5cm2, P = 0.003; 75% left: EMS group 2.1 ± 1.9 vs. Control group −0.4 ± 1.5cm2, P = 0.003); and TUG time (–0.8 ± 0.6 vs. 0.2 ± 0.5s, P < 0.001). The EMS group showed improvement after intervention in all components of SF‐8, but these were not statistically significant. EMS could be an effective exercise training tool for HD patients with either muscle wasting, weakness, or sarcopenia.
Incidence, prevalence and clinical outcome of anaemia in inflammatory bowel disease: a population‐based cohort study
Authors: Eriksson Carl , Henriksson Ida , Brus Ole , Zhulina Yaroslava , Nyhlin Nils , Tysk Curt , Montgomery Scott , Halfvarson Jonas
Published: August 2018

Background

The incidence and short‐term outcome of anaemia in inflammatory bowel disease (IBD) are largely unknown.

Aim

To determine the incidence, prevalence and clinical outcome of anaemia in terms of resolution of anaemia within 12 months. We also planned to assess risk factors for anaemia in IBD.

Methods

A random sample of 342 patients was obtained from the population‐based IBD cohort of Örebro University Hospital, Sweden, consisting of 1405 patients diagnosed between 1963 and 2010. Haemoglobin measurements recorded from 1 January 2011 to 31 December 2013 were extracted from the Clinical Chemistry data system.

Results

In Crohn's disease, the incidence rate of anaemia was 19.3 (95% CI: 15.4‐23.7) per 100 person‐years and the prevalence was 28.7% (CI: 22.0‐36.2), compared with 12.9 (CI: 9.8‐16.5) and 16.5% (CI: 11.2‐22.9) for ulcerative colitis. Crohn's disease was associated with an increased incidence (OR = 1.60; CI: 1.02‐2.51) and prevalence of anaemia (OR = 2.04; CI: 1.20‐3.46) compared to ulcerative colitis. Stricturing disease phenotype in Crohn's disease (HR = 2.59; CI: 1.00‐6.79) and extensive disease in ulcerative colitis (HR = 2.40; CI: 1.10‐5.36) were associated with an increased risk of anaemia. Despite a higher probability of receiving specific therapy within 3 months from the diagnosis of anaemia, Crohn's disease patients had a worse outcome in terms of resolution of anaemia within 12 months (56% vs 75%; P = 0.03).

Conclusions

Anaemia is a common manifestation of IBD even beyond the first years after the diagnosis of IBD. Crohn's disease is associated with both an increased risk and a worse outcome.
Review article: treating‐to‐target for inflammatory bowel disease‐associated anaemia
Authors: Peyrin‐Biroulet Laurent , Lopez Anthony , Cummings J. R. Fraser , Dignass Axel , Detlie Trond Espen , Danese Silvio
Published: August 2018

Background

Iron deficiency has a high prevalence in inflammatory bowel disease (IBD) patients, with negative impact on quality of life and work capacity.

Aim

To propose an innovative approach based on early intervention, treating to target and tight monitoring in the management of iron deficiency in IBD patients.

Methods

We conducted a literature review on PubMed and Medline using pre‐defined keywords and terms to identify relevant studies on iron deficiency in IBD.

Results

Many physicians are focused on treating anaemia; however, anaemia is one of the consequences of iron deficiency. Hence, our therapeutic goal for these patients should evolve towards prevention of anaemia by screening and treating iron deficiency. Early diagnosis of iron deficiency is based on a combination of ferritin concentration and transferrin saturation. We consider that normalisation of these biomarkers reflects iron stores replenishment and should be considered as a major therapeutic goal. Treating iron deficiency regardless of the presence of anaemia seems to improve quality of life in several chronic conditions and should be considered as an innovative approach in IBD although strong evidence is still lacking. Tight monitoring is required to allow early detection of iron deficiency recurrence and to consider prompt additional iron supplementation.

Conclusion

We propose to extrapolate a three‐step strategy (early detection and intervention, treating‐to‐target and tight monitoring) to the management of iron deficiency in IBD patients. Universally applied, this proactive approach is expected to result in better outcomes in IBD patients.
Native‐born German and immigrant children's development of emotion knowledge: A latent growth curve analysis
Authors: Voltmer Katharina , von Salisch Maria
Published: August 2018

Young children in immigrant families tend to face more challenges and can often call upon fewer resources than their native‐born peers. This situation adversely affects their social–emotional development. In this study, the development of emotion knowledge of 576 immigrant and native‐born German children, aged 3–6 years, was compared at three time points over a 12‐month period by means of a latent growth curve analysis. Language abilities and behavioural self‐regulation were examined as mediators of the relation between immigration background and emotion knowledge. The immigrant children showed less emotion knowledge than did their native‐born peers at each point of measurement. These effects were partially mediated by their behavioural self‐regulation and their language abilities. How behavioural self‐regulation and language abilities affect the development of emotion knowledge and what this effect means for interventions are discussed.

Statement of contribution

What is already known on this subject?

Emotion knowledge develops rapidly between the ages of three and six.

Emotion knowledge develops similarly in different cultures.

What does this study adds?

This study compares the development of emotion knowledge between immigrant children and native‐born children.

It includes language skills as mediator on the development of emotion knowledge.

It also includes behavioural self‐regulation as mediator on the development of emotion knowledge.
Parental use of spatial language and gestures in early childhood
Authors: Kısa Yağmur Deniz , Aktan‐Erciyes Aslı , Turan Eylül , Göksun Tilbe
Published: August 2018

Parents’ use of spatial language and gestures is closely linked to children's spatial language development. Little is known about the quantity and quality of early spatial input and how infants’ individual characteristics may be related to the spatial input they receive. Here, we examine (1) the amount and type of spatial input 16‐ to 21‐month‐old Turkish‐learning children (n = 34) received in the context of a spatial activity (puzzle play) and (2) whether parental spatial input in the form of speech and gesture varies based on children's age, sex, and early spatial vocabulary comprehension assessed in an earlier session. Results of the regression analyses showed that parents’ use of spatial words was predicted by children's age over and beyond earlier spatial word comprehension and sex. In particular, parents used more spatial speech as their children got older even in this restricted age range. Children's early spatial word comprehension also correlated with parents’ spatial word production. Yet, parents’ overall gesture use and gestures with spatial words were not predicted by children's age, sex, or early spatial word comprehension. These findings suggest that in the spatial domain, early verbal input, but not gestural input, can change depending on children's age and children's spatial vocabulary comprehension may also be related to parental use of later spatial language.

Statement of contribution

What is already known on this subject?

Parents enhance their children's spatial skills using spatial language and gestures.

Parental spatial talk is related to children's later spatial skills.

What does this study add?

We assess both spatial talk and gesture in early childhood.

We examine the children's characteristics (age, sex) in relation to spatial talk and gesture.

We present how children's earlier vocabulary competence relates to parental input.
Increased β2-adrenoceptor phosphorylation in airway smooth muscle in severe asthma: possible role of mast cell-derived growth factors
Authors: Chachi L , Alzahrani A , Koziol-White C , Biddle M , Bagadood R , Panettieri R A , Bradding P , Amrani Y
Published: August 2018

The purpose of this study was to investigate whether growth factors produced by activated human lung mast cells (HLMCs) impair β2-adrenoceptor (β2-AR) function in human airway smooth muscle (ASM) cells. Protein array analysis confirmed the presence of various growth factors, including transforming growth factor (TGF)-β1, in the supernatants of high-affinity IgE receptor (FcεRI)-activated HLMCs which, when applied to ASM cells, impaired albuterol-induced cyclic adenosine monophosphate (cAMP) production, an effect that was prevented following neutralization of TGF-β1. This blunted β2-AR response was reproduced by treating ASM cells with TGF-β1 or fibroblast growth factor (FGF)-2, which induced β2-AR phosphorylation at tyrosine residues Tyr141 and Tyr350, and significantly reduced the maximal bronchorelaxant responses to isoproterenol in human precision cut lung slices (PCLS). Finally, ASM cells isolated from severe asthmatics displayed constitutive elevated β2-AR phosphorylation at both Tyr141 and Tyr350 and a reduced relaxant response to albuterol. This study shows for the first time that abnormal β2-AR phosphorylation/function in ASM cells that is induced rapidly by HLMC-derived growth factors, is present constitutively in cells from severe asthmatics.
Effect of vitamin D supplementation on free and total vitamin D: A comparison of Asians and Caucasians
Authors: Gopal‐Kothandapani Jaya Sujatha , Evans Lucy Faith , Walsh Jennifer S. , Gossiel Fatma , Rigby Alan S. , Eastell Richard , Bishop Nick J.
Published: August 2018

Objectives

It is well established that UK Asians typically have lower vitamin D levels than Caucasians. It is also known that vitamin D binding protein (DBP) is lower in some races than Caucasians. To investigate how ethnicity, skin colour and genetic variation affect the response to vitamin D (15000 IU) administered to young Asian and Caucasian men.

Design

Prospective, single‐centre clinical trial.

Participants

Sixty young men (18‐25 year) of Asian (n = 30) and Caucasian (n = 30) origin.

Measurements

We measured serum calcium, phosphate, magnesium, alkaline phosphatase, albumin, parathyroid hormone; total 25 hydroxyvitamin D (25OHD); calculated and directly measured free 25OHD; DBP at baseline and 4 weeks; DBP genotype, skin colour (Fitzpatrick scale), dietary vitamin D and calcium intake at baseline; and urine calcium:creatinine ratio at baseline, 1 and 4 weeks.

Results

At baseline, Asians had lower serum total 25OHD (26.4 [13.7] vs 34.1 [12.3] nmol/L P = 0.0272) and DBP (6.7 [3.4] vs 9.6 [4.4] nmol/L; P = 0.0065) but similar free 25OHD (16.7 [10.4] vs 17.8 [7.5] pmol/L P = 0.6530). After dosing, total 25OHD rose similarly in each group (≈56 nmol/L), but measured free 25OHD rose more in Asians (18.1 [9.4] vs 12.2 [13.3] pmol/L P = 0.0464). Lower DBP at baseline, possibly reflecting genotype differences, was associated with a greater change in measured free 25OHD in Caucasians, but not in Asians.

Conclusions

Asian compared with Caucasian males had a larger increment in measured free 25OHD following 150 000 units vitamin D3, possibly reflecting differences in DBP affinity for 25OHD. Ethnicity should be considered when devising guidelines for the treatment of vitamin D deficiency.
Measuring photostability through glass: the application of microfading testing to the study of framed pastel artworks
Authors: del Hoyo‐Meléndez Julio M. , Świt Paweł , Sobczyk Joanna
Published: August 2018

Paper‐based heritage objects on exhibition are typically framed using a transparent glazing material such as glass or acrylic. This often makes the task of measuring their light fastness a difficult one since cultural institutions may have unframing restrictions, especially for large‐format objects. However, a testing programme recently conducted at the National Museum in Krakow has revealed that in certain cases it is possible to obtain colorant stability information directly from a framed object. Microfading testing results are reliable if the distance from the object to the protective glazing is adequate to allow proper illumination and collection of reflected light. This paper presents a case study of six large‐format pastels on paper by Stanisław Wyspiański, one of the most outstanding and versatile artists at the turn of the twentieth century in Poland. Some of the orange and pink areas showed higher sensitivity to light with fading rates that remain within the Blue Wool 1–2 range. The objects have been classified according to the light sensibility of their colorants, and this information has allowed development and implementation of exhibition guidelines that serve to minimise the degradation associated with museum illumination. In addition, scientific imaging, microfading data and computer analysis of the images have allowed virtual representation of the potential colour changes that these artworks may experience as a result of uncontrolled and long exposure to gallery illumination.
2‐(2‐nitrobenzylidene) indolin‐3‐one compound inhibits transmembrane prostate androgen‐induced protein (TMEPAI) expression and cancer cell proliferation
Authors: Li Yuyin , Wang Jianjun , Song Ning , Zeng Feihong , Zhao Miaomiao , Wang Ali , Chen Yue , Jing Lei , Yu Peng , Diao Aipo
Published: August 2018

Objectives

The transmembrane prostate androgen‐induced protein (TMEPAI) is aberrantly expressed in many cancer and plays a crucial role in tumourigenesis, which makes it a potential cancer therapeutic target for drug discovery.

Materials and methods

Here, we employed a firefly luciferase reporter driven by the TMEPAI gene promoter to screen for compound capable of inhibiting the expression of TMEPAI, and the effects of TMEPAI inhibitor on cancer cell proliferation were evaluated using the colony formation assay, cell cycle analysis, Ki‐67 immunofluorescence assay and EdU incorporation assay.

Results

2‐(2‐nitrobenzylidene) indolin‐3‐one (JHY‐A007‐50) was identified and shown to effectively inhibit the TMEPAI promoter activity. Further studies revealed that JHY‐A007‐50 specifically inhibited the expression of TMEPAI at both the mRNA and protein levels. Moreover, we found that JHY‐A007‐50 could inhibit cell proliferation and induce cell cycle arrest at the G1 phase. Our results showed that overexpression of TMEPAI decreased the inhibitory effects of JHY‐A007‐50 on cancer cell proliferation, and JHY‐A007‐50 did not affect the cell viability of HeLa cells knocked down of TMEPAI.

Conclusions

Taken together, these results suggest that compound JHY‐A007‐50 mediates the downregulation of TMEPAI expression and inhibits cell proliferation in cancer cells.
A novel inhibitor of ADAM17 sensitizes colorectal cancer cells to 5‐Fluorouracil by reversing Notch and epithelial‐mesenchymal transition in vitro and in vivo
Authors: Li Dan‐Dan , Zhao Chang‐Hao , Ding Huai‐Wei , Wu Qiong , Ren Tian‐Shu , Wang Jian , Chen Cong‐Qin , Zhao Qing‐Chun
Published: August 2018

Objectives

Colorectal cancer is one of the most common malignancies both in men and women. Owing to metastasis and resistance, the prognosis of colorectal cancerCRC patients remains extremely poor with chemotherapy. A disintegrin and metalloproteinase 17 (ADAM17) induces the activation of Notch pathway and contributes to the chemoresistance. This study aimed to discover a novel ADAM17 inhibitor and investigate the chemosensitization effect.

Materials and methods

Pharmacophore model, western blot and enzymatic assay were used to discover ZLDI‐8. Cell proliferation was determined by MTT and colony formation assay. Cell migratory and invasive ability were determined by wound healing scratch and transwell assay. Immunofluorescence images and western blot analysed the expression of Notch or epithelial‐mesenchymal transition (EMT) pathway markers. Xenografts were employed to evaluate the chemosensitization effect of ZLDI‐8 in vivo.

Results

We found that ZLDI‐8 cell‐specifically inhibited the proliferation of CRC, and this effect was due to abrogation of ADAM17 and Notch pathway. Meanwhile, we reported for the first time that ZLDI‐8 synergistically improved the anti‐tumour and anti‐metastasis activity of 5‐fluorouracil or irinotecan by reversing Notch and EMT pathways. Interestingly, in vivo studies further demonstrated that ZLDI‐8 promoted the anti‐tumour effect of 5‐fluorouracil through Notch and EMT reversal.

Conclusions

A novel ADAM17 inhibitor ZLDI‐8 may be a potential chemosensitizer which sensitized CRC cells to 5‐fluorouracil or irinotecan by reversing Notch and EMT pathways.
Oestrogen receptor α regulates the odonto/osteogenic differentiation of stem cells from apical papilla via ERK and JNK MAPK pathways
Authors: Wang Yanqiu , Lu Yadie , Li Zehan , Zhou Yixiang , Gu Yongchun , Pang Xiyao , Wu Jintao , Gobin Romila , Yu Jinhua
Published: August 2018

Objectives

Oestrogen receptor (ER) is a common nucleus receptor that is essential for the regulation of cell growth, proliferation and differentiation. This study was to examine whether ERα can affect the proliferation and odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs).

Materials and Methods

Stem cells from apical papillas were isolated, purified and then transfected with ERα lentiviruses. The proliferation capacity was investigated by cell counting kit‐8 (CCK‐8) assay and flow cytometry. The odonto/osteogenic differentiation ability was analysed by alkaline phosphatase (ALP) activity, alizarin red staining, western blot assay (WB) and real‐time RT‐PCR. MAPK pathway and its downstream transcriptional factors were explored by WB assay.

Results

As indicated by CCK‐8 assay and flow cytometry, ERα had no significant effect on the proliferation of SCAPs. When ERα was overexpressed, the ALP activity and the formation of calcified nodules were significantly enhanced in SCAPs. Moreover, the odonto/osteogenic markers (DMP1/DMP1, DSPP/DSP, RUNX2/RUNX2, OCN/OCN) in SCAPs were significantly up‐regulated at both mRNA and protein levels. On the contrary, the odonto/osteogenic differentiation ability of SCAPs was remarkably inhibited after suppression of ERα. Mechanistically, the protein levels of phosphorylated ERK and JNK significantly increased after ERα overexpression. Moreover, some downstream transcriptional factors of MAPK pathway were simultaneously activated by ERα overexpression.

Conclusions

Together, the data accumulated here indicated that ERα can enhance the odonto/osteogenic differentiation of SCAPs via ERK and JNK MAPK pathways.
A novel radiographic projection for the detection of sagittal plane slab fracture of the equine third carpal bone
Authors: Ramzan P. H. L.
Published: August 2018

Background

Some sagittal plane fractures of the equine third carpal bone are difficult to detect with conventional radiographic projections.

Objectives

To describe a novel radiographic projection for the detection of sagittal plane slab fractures of the equine third carpal bone.

Study design

Retrospective study of radiological records.

Methods

From a first opinion Thoroughbred racehorse caseload, cases were included for analysis if sagittal fracture of the third carpal bone was evident on a dorsoproximal lateral‐palmarodistal medial oblique (DPrL‐PDiMO) projection of the distal row of carpal bones and not visible on the standard dorsoproximal‐dorsodistal oblique (DPr‐DDiO) projection.

Results

Eight cases in which radiological identification of fracture was dependent on theDPrL‐PDiMOprojection were identified from August 2013 to August 2017.

Main limitations

Unblinded study.

Conclusions

Conventional radiographic projections can fail to detect some serious fractures of the equine third carpal bone. TheDPrL‐PDiMOprojection has a role in the investigation of suspected carpal injury in racehorses.
Status quo and perspectives of biogas production for energy and material utilization
Authors: Bahrs Enno , Angenendt Elisabeth
Published: August 2018

Biogas is in many respects a serious alternative to other fossil resources and complements other renewable energy sources from wind and sun. Biogas can be produced in many places decentrally. Its energy potential is high, and it is widely used in the EU and all over the world. With more than 16,000 ktoe of oil equivalent in the EU in 2016, it corresponds to approximately 8% of the total primary energy produced by renewable energies in the EU, produced with nearly 17,000 biogas plants. Nevertheless, the production costs of biogas and its products like energy, heat, and fuel are still too high. Kost et al. (2018) show a comparison of electricity generation costs of different renewable energies and their future potentials. While electricity from huge biogas plants offers generation costs from 10 to 15 ct/kWh, electricity from onshore wind and huge solar systems offers generation costs from 4 to 8 ct/kWh. Although substantial progress has been made with regard to substrate use, production techniques and market designs, many more innovations are needed throughout the biogas value chain for it to be competitive in energy markets without high subsidies. As several papers in the special issue on biogas show, there are numerous innovations and product designs with regard to energy and material uses that could maintain or even increase the importance of biogas production both within and outside of the EU. There are many potential benefits of biogas, as it offers high shares of produced renewable energies as well as large amounts of material products like digestates and in future maybe products of higher value such as proteins or lactic acids.
Sensitivity of Simulated Hyporheic Exchange to River Bathymetry: The Steinlach River Test Site
Authors: Chow Reynold , Wu Hao , Bennett Jeremy P. , Dugge Jürnjakob , Wöhling Thomas , Nowak Wolfgang
Published: August 2018

This study determines the aspects of river bathymetry that have the greatest influence on the predictive biases when simulating hyporheic exchange. To investigate this, we build a highly parameterized HydroGeoSphere model of the Steinlach River Test Site in southwest Germany as a reference. This model is then modified with simpler bathymetries, evaluating the changes to hyporheic exchange fluxes and transit time distributions. Results indicate that simulating hyporheic exchange with a high‐resolution detailed bathymetry using a three‐dimensional fully coupled model leads to nested multiscale hyporheic exchange systems. A poorly resolved bathymetry will underestimate the small‐scale hyporheic exchange, biasing the simulated hyporheic exchange towards larger scales, thus leading to overestimates of hyporheic exchange residence times. This can lead to gross biases in the estimation of a catchment's capacity to attenuate pollutants when extrapolated to account for all meanders along an entire river within a watershed. The detailed river slope alone is not enough to accurately simulate the locations and magnitudes of losing and gaining river reaches. Thus, local bedforms in terms of bathymetric highs and lows within the river are required. Bathymetry surveying campaigns can be more effective by prioritizing bathymetry measurements along the thalweg and gegenweg of a meandering channel. We define the gegenweg as the line that connects the shallowest points in successive cross‐sections along a river opposite to the thalweg under average flow conditions. Incorporating local bedforms will likely capture the nested nature of hyporheic exchange, leading to more physically meaningful simulations of hyporheic exchange fluxes and transit times.
PD‐L1 and IDO expression in cervical and vulvar invasive and intraepithelial squamous neoplasias: implications for combination immunotherapy
Authors: Chinn Zachary , Stoler Mark H , Mills Anne M
Published: August 2018

Aims

The immunoregulatory enzyme indoleamine dioxygenase 2,3 (IDO) has been implicated in cervical and vulvar squamous carcinomas (SCC) and may represent a mechanism of resistance to anti‐PD‐1/anti‐PD‐L1 therapy. However, the relationship between IDO and PD‐L1 has not been well‐investigated.

Methods and results

Sixty‐five cases of cervical and vulvar intraepithelial neoplasia and SCC were assessed for IDO and PD‐L1 expression. Overall, tumoral PD‐L1 expression was seen in 72% of SCC, while 50% expressed IDO; co‐expression was seen in 42%. Using the combined positive score (CPS) threshold of 1 to account for both tumoral and immune staining, 83% of SCC expressed PD‐L1, 61% expressed IDO and 53% showed co‐expression. Cervical SCCs were significantly more likely than human papillomavirus (HPV)‐related vulvar SCCs to express tumoral IDO (75% versus 13%, P < 0.001) and demonstrate an IDO CPS ≥ 1 (88% versus 25%, P < 0.001); no significant differences were seen for PD‐L1. Additionally, there were no significant differences in IDO and PD‐L1 expression in dVIN‐associated versus HPV‐associated vulvar SCC. In contrast to SCC, the majority of intraepithelial lesions were entirely negative for tumoral PD‐L1 and IDO and had a CPS score of <1.

Conclusions

In summary, IDO and PD‐L1 co‐expression is common in cervical SCCs and, to a lesser extent, vulvar SCCs. These data suggest a role for combination immunotherapy in a subset of cervical SCCs as well as select vulvar SCCs. Expression for both markers is less common in intraepithelial lesions, providing no strong support for this form of immunotherapy in the absence of invasion.
Critical appraisal of methodological quality of Systematic Reviews and Meta‐analysis in Paediatric Dentistry journals
Authors: Jayaraman Jayakumar , Nagendrababu Venkateshbabu , Pulikkotil Shaju Jacob , Innes Nicola P.
Published: August 2018

Objective

To systematically assess the methodological quality of Systematic Reviews (SRs) and Meta‐Analyses (MA) published in Paediatric Dentistry journals and to analyse the relationship between the authors, journals, country, review topic, and the year of publication to the methodological quality of SRs and MA.

Design

Paediatric Dentistry journals ranked in the top five of the h5 index of Google Scholar Metrics were selected. SRs with MA were searched independently by two reviewers using PubMed and Scopus databases until December 2017. Methodological quality was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool. Statistical significance was set at P < 0.05 and Mann‐Whitney U test and Kruskal‐Wallis test was employed for comparing the AMSTAR score with the journal characteristics.

Results

Finally, 24 SRs with MA were included. The overall AMSTAR score of SRs and MA published in paediatric dentistry journals was 7.08 ± 2.41. No statistically significant differences were found between the country, journal or focus of study to the quality of SRs except the number of authors and the year of publication (P < 0.05).

Conclusions

The quality of SRs and MA in leading Paediatric Dentistry journals were evaluated with AMSTAR tool and areas where quality could be improved were identified.
Systematic review of the real‐world evidence of adalimumab safety in psoriasis registries
Authors: Strober B. , Crowley J. , Langley R.G. , Gordon K. , Menter A. , Leonardi C. , Arikan D. , Valdecantos W.C.
Published: August 2018

Long‐term safety of adalimumab in psoriasis clinical studies has been established. The objective of this research was to review real‐world evidence of adalimumab safety from registries of adult patients with psoriasis treated in clinical practice. Databases (BIOSIS Previews, Current Contents Search, Derwent Drug File, EMBASE, EMBASE Alert, EMCare, MEDLINE, SciSearch) were searched for psoriasis registries with adalimumab safety data. Eligible papers were English language manuscripts (conference abstracts excluded) from psoriasis registries presenting safety data for adult patients with psoriasis receiving adalimumab. The incidence and rate (events/100 patient‐years [PY]) of adverse events (AEs), serious AEs (SAEs) and AEs of special interest are reported. Abstracts of 425 publications were screened, and 401 publications excluded (208 conference abstracts; 193 papers). Remaining manuscripts were fully screened; 14 were excluded (no adalimumab data, n = 10; no safety data, n = 2; no on‐treatment data, n = 1; not English, n = 1), and 10 selected. Overall rates of AEs (4273 [22.2/100PY]) and SAEs (827 [4.3/100PY]) were reported in the ESPRIT registry (N = 6059). Rates of infections (7.7–14.7/100PY) and serious infections (<0.6–2.0/100PY) were reported in four studies. Cardiovascular‐related events were reported in three studies: ≤0.1/100PY per major cardiac event in ESPRIT, <0.5/100PY major cardiac events in PsoBest and serious cardiovascular events in two patients (<1%) in DERMBIO. Malignancies were reported in three studies (any malignancy, 0.9/100PY; malignancies excluding non‐melanoma skin cancer [NMSC], <0.6/100PY; NMSC, 0.6–<0.5/100PY). These findings suggest that real‐world safety of adalimumab is consistent across different psoriasis registries, which supports the existing long‐term safety profile of adalimumab from clinical studies.
The impact of major dietary patterns on glycemic control, cardiovascular risk factors, and weight loss in patients with type 2 diabetes: A network meta‐analysis
Authors: Pan Bei , Wu Yiting , Yang Qingxia , Ge Long , Gao Caiyun , Xun Yangqin , Tian Jinhui , Ding Guowu
Published: August 2018

Objective

To comprehensively compare the differences between major dietary patterns in improving glycemic control, cardiovascular risk, and weight loss for patients with type 2 diabetes.

Method

We systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) that compared the efficacy of Mediterranean, low‐carbohydrate, and/or low‐fat dietary patterns for patients with type 2 diabetes. Studies that compared any one of those diets with regular diet were also included. The risk of bias in eligible RCTs was evaluated according to the Cochrane Handbook. The primary outcome was glycemic control. Secondary outcomes included weight loss and cardiovascular risk factors. A network meta‐analysis was performed using R‐3.3.2.

Results

Ten RCTs involving five dietary patterns met the eligibility criteria. The findings revealed that compared to low‐fat diet, Mediterranean diet showed beneficial effects in glycemic control (HbA1c [%]: MD = –0.45, 95% CI = –0.55 to –0.34; fasting plasma glucose [mmol/L]: MD = –1.24 95% CI = –1.57 to –0.91, respectively; weight loss [kg]: MD =–1.18, 95% CI = –1.99 to –0.37; waist circumference [cm]: MD = –0.73, 95% CI = –1.26 to –0.19), and cardiovascular risk factors (HDL‐cholesterol [mmol/L]: MD = 0.07, 95% CI = 0.04 to 0.11; total cholesterol [mmol/L]: MD = –0.17, 95% CI = –0.26 to –0.08; triglycerides [mmol/L]: MD = –0.21, 95% CI = –0.27 to –0.16). Network meta‐analysis showed that high‐carbohydrate diet improved HDL‐cholesterol (mmol/l) (MD = 1.04, 95% CI = 0.39 to 1.68) when compared with regular diet. The differences were not statistically significant in other indirect comparison groups for other outcomes.

Conclusions

A mediterranean diet showed beneficial improvements in glycemic control, weight loss, and cardiovascular risk factors in people with type 2 diabetes.
Value capture in hierarchically organized value chains
Authors: Henkel Joachim , Hoffmann Alexander
Published: August 2018

We study how the structure of negotiations in a value chain affects the distribution of value among its members. To this end, we generalize the Shapley value and the core to hierarchical bargaining situations. While the core yields no concrete predictions, the Shapley value analysis suggests that positions most conducive to value capture are those that allow to realize large complementarity gains. If the game exhibits “supercomplementarity,” then it is advantageous if a firm's negotiation partners are grouped into clusters. Using examples from the aircraft and white goods industries, we assess whether the firms’ actions are consistent with model predictions.
Age and growth of black seabream Acanthopagrus schlegelii (Sparidae) in Hong Kong and adjacent waters of the northern South China Sea
Authors: Law Calton S. W. , Sadovy de Mitcheson Yvonne
Published: August 2018

Age and growth of the black seabream Acanthopagrus schlegelii (family Sparidae) from the northern South China Sea (NSCS) were studied by reading growth rings in sectioned sagittal otoliths. Ring formation frequency was determined to be annual by using marginal increment analysis. The von Bertalanffy growth function parameters were estimated as: L∞ = 43.7 cm LS; K =0.22 year; t0 = −1.59 years. Functional males are significantly younger than functional females, with sexually transitional individuals between the modal ages of males and females supporting protandry in this species. Males become sexually mature within 1 year and 50% age at sex change is at 2 years. The maximum age recorded for both males and females sampled was 9 years which is lower than for conspecifics elsewhere and may reflect high fishing pressure in the study area when compared with conspecifics in other areas or could reflect latitudinal effects. Otolith mass was significantly and positively related to age, providing a cheap and quick alternative method for approximating age. Acanthopagrus schlegelii is a relatively fast‐growing and rapidly maturing species attaining a similar asymptotic length to conspecifics. A need for fishery management is indicated to protect both young juveniles and older adults, especially females, to increase reproductive output and safeguard fishery production.
Over‐the‐scope clip system: A review of 1517 cases over 9 years
Authors: Kobara Hideki , Mori Hirohito , Nishiyama Noriko , Fujihara Shintaro , Okano Keiichi , Suzuki Yasuyuki , Masaki Tsutomu
Published: August 2018

Rescue therapy for gastrointestinal (GI) refractory bleeding, perforation, and fistula has traditionally required surgical interventions owing to the limited performance of conventional endoscopic instruments and techniques. An innovative clipping system, the over‐the‐scope clip (OTSC), may play an important role in rescue therapy. This innovative device is proposed as the final option in endoscopic treatment. The device presents several advantages including having a powerful sewing force for closure of GI defects using a simple mechanism and also having an innovative feature, whereby a large defect and fistula can be sealed using accessory forceps. Consequently, it is able to provide outstanding clinical effects for rescue therapy. This review clarifies the current status and limitations of OTSC according to different indications of GI refractory disease, including refractory bleeding, perforation, fistula, and anastomotic dehiscence. An extensive literature search identified studies reported 10 or more cases in which the OTSC system was applied. A total of 1517 cases described in 30 articles between 2010 and 2018 were retrieved. The clinical success rates and complications were calculated overall and for each indication.

The average clinical success rate was 78% (n = 1517) overall, 85% for bleeding (n = 559), 85% (n = 351) for perforation, 52% (n = 388) for fistula, 66% (n = 97) for anastomotic dehiscence, and 95% (n = 122) for other conditions, respectively. The overall and severe OTSC‐associated complications were 1.7% (n = 23) and 0.59% (n = 9), respectively.

This review concludes that the OTSC system may serve as a safe and productive device for GI refractory diseases, albeit with limited success for fistula.
Clinical, endoscopic, and histological differentiation between celiac disease and tropical sprue: A systematic review
Authors: Sharma Pragya , Baloda Vandana , Gahlot Gaurav PS , Singh Alka , Mehta Ritu , Vishnubathla Sreenivas , Kapoor Kulwant , Ahuja Vineet , Gupta Siddhartha Datta , Makharia Govind K , Das Prasenjit
Published: August 2018

Background and Aim

While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS.

Methods

Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis.

Results

Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D‐xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia.

Conclusions

Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests.
Cytochrome P450 4A11 expression in tumor cells: A favorable prognostic factor for hepatocellular carcinoma patients
Authors: Eun Hyuk Soo , Cho Sang Yeon , Lee Byung Seok , Kim Sup , Song In‐Sang , Chun Kwangsik , Oh Cheong‐Hae , Yeo Min‐Kyung , Kim Seok Hyun , Kim Kyung‐Hee
Published: August 2018

Background and Aim

Elevated cytochrome p450 (CYP) 4A gene expression has been linked to the aggravation of various cancers and affects various regulated metabolites. In hepatocellular carcinoma (HCC), the clinicopathological value of CYP4A has not yet been explored, although CYP4A is expressed at high levels in the liver. The goal of this study was to evaluate the clinicopathological value of CYP4A11 expression in HCC.

Methods

We performed immunohistochemical analysis of CYP4A11 and correlated the results with clinicopathological features of HCC (n = 155). Western blotting and reverse transcription–polymerase chain reaction against CYP4A11 and CYP4A22 were also performed for 15 and 20 pairs of fresh‐frozen primary HCC and non‐neoplastic liver tissue, respectively. Moreover, we analyzed the underlying mechanism by comparing the high and low CYP4A11 mRNA expression groups using gene set enrichment analysis.

Results

CYP4A11 expression level was higher in non‐neoplastic hepatocytes than those in HCC cells (P < 0.001), and CYP4A11 expression positively correlated with favorable prognostic factors, including tumor size, histological grade, and pathological tumor stage (P = 0.007, P = 0.005, and P = 0.007). Multivariate analysis revealed that CYP4A11 expression was an independent prognostic factor of overall and disease‐free survival (P = 0.002 and P = 0.033). Based on gene set enrichment analysis, high CYP4A11 mRNA expression negatively correlated with the expression of cell cycle‐related genes.

Conclusion

These findings support the notion that CYP4A11 expression is a favorable prognostic factor of HCC and suggest potential predictive diagnostic and prognostic roles of CYP4A11 expression in HCC.
Mandating nerve biopsy: A step towards personalizing therapy in pure neuritic leprosy
Authors: Kulshreshtha Dinkar , Malhotra Kiran Preet , Malhotra Hardeep Singh , Thacker Anup Kumar , Garg Ravindra Kumar , Singh Ajai Kumar , Maurya Pradeep Kumar
Published: August 2018

Pure neuritic leprosy (PNL) accounts for 5% to 10% of leprosy patients who usually present with asymmetrical neuropathy in the absence of lepra bacilli on slit‐skin smears. However, nerve biopsies in PNL lack appropriate categorization in current immunologic terms. We aimed to classify nerve biopsies according to the immune spectrum of leprosy and assess the role of histologic classification of nerve biopsies in treating PNL. Patients from two tertiary care referral centres were enrolled in this incident case study. Patients presenting with mononeuropathy and multiple mononeuropathies presumably with leprosy, without skin lesions, underwent nerve biopsy and slit‐skin smear examination. Amongst 78 patients with mononeuropathy, 38 were diagnosed with leprosy on nerve biopsy. Leprosy was classified as tuberculoid in 16, lepromatous in 5 and borderline in 17 patients. Lepra bacilli were present in 15 biopsies. On comparing histologic subtypes with number of nerves involved clinically, a significant number of cases with single nerve involvement showed multibacillary (BB, BL or LL) histology and vice versa. Nerve biopsy helps in diagnosing patients presenting with PNL and aids in classifying it to customize the treatment for best results. Current treatment recommendations for PNL from WHO and National Leprosy Eradication Program are based on clinical assessment only, which are likely to result in inconsistent treatment and possibly relapse in cases where histomorphology shows disparity. Inclusion of nerve biopsy to guide therapy in patients with PNL is suggested.
Lesional and circulating levels of interleukin‐17 and 25‐hydroxycholecalciferol in active acne vulgaris: Correlation to disease severity
Authors: Abd‐Elmaged Wafaa M. , Nada Essam A. , Hassan Mohammed H. , Elsadek Bakheet E. M. , Abdelrahim Eman A. , Ahmed Nagwa S. , Toghan Rana , Ahmed Heba T. I.
Published: August 2018

Objectives

The immunological aspects of inflammatory acne are still incompletely understood, so this study aimed to investigate the possible role of IL‐17 and 25 hydroxycholecalciferol (25(OH)D3) in the disease pathogenesis and progression.

Materials and Methods

Across‐sectional study has been conducted on 135 patients with active acne vulgaris of various severities and 150 matched controls. ELISA assays of serum and tissue levels of IL‐17 and 25(OH)D3, also immunohistochemical and Western blotting demonstration of the expression patterns of lesional IL‐17 in comparison with control group, were performed.

Results

The mean serum levels of IL‐17 were 544.2 pg/mL ± 477.4 SD and 42.2 pg/mL ± 8.1 SD for acne patients and controls, respectively, with significantly higher levels among the patient group (P < 0.05). Higher IL‐17 expression levels in active acne lesions when compared with its level in healthy skin of the controls. The mean serum levels of 25(OH)D3 among patients and controls were 33.3 ng/mL ± 9.7 SD and 51.7 ng/mL ± 2.7 SD, respectively, with significantly lower levels among the patient group (P < 0.05). There were significantly negative correlations between IL‐17 and 25(OH)D3 levels (P < 0.001 for both).

Conclusions

Deficiency of vitamin D3 accompanied with higher IL‐17 in an inverse pattern may have a possible role in active acne vulgaris.