bluuebunny/crossref_metadata_2025 huggingface dataset:
Fixed‐ratio combination of basal insulin and glucagon‐like peptide‐1 receptor agonists in the treatment of Japanese people with type 2 diabetes: An innovative solution to a complex therapeutic challenge
Authors: Kaneto Hideaki , Koshida Ryusuke , Baxter Mike
Published: May 2020

Over 10 million people in Japan have known or suspected type 2 diabetes (T2D), and this number is expected to rise. Although many people require therapy escalation because of the progressive nature of T2D, this appears to be suboptimal in Japanese real‐world clinical practice. Insulin therapy tends to be introduced only when glycaemic control is very poor (mean glycated haemoglobin >9%). Although basal insulin therapy is effective in reducing fasting plasma glucose (FPG), postprandial plasma glucose often remains uncontrolled. Basal‐bolus insulin regimens are complex and carry the risk of weight gain and hypoglycaemia. Recently, fixed‐ratio combinations (FRCs) of BI and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have shown efficacy in reducing both FPG and postprandial plasma glucose with a single injection and without increased risk of hypoglycaemia or weight gain. IDegLira, a titratable FRC of insulin degludec (100 U/mL) and liraglutide, is currently available in Japan and the United States/European Union at a ratio of 1 U (unit):0.036 mg. iGlarLixi (insulin glargine 100 U/mL and lixisenatide at a ratio of 1:1 (20 U/20 μg) has recently been approved in Japan. Phase 3 trials in Japan for IDegLira (DUAL Japan) and iGlarLixi (LixiLan JP) have shown that both FRCs are efficacious. This review provides an overview of IDegLira and iGlarLixi (Japanese formulation) and considers their potential use as new therapeutic options to address the clinical need for early glycaemic control in Japanese people with T2D.
Semantic Interaction Design: A powerful new UX synthesis approach
Authors: Rosenberg Daniel
Published: May 2020

Language is the basis for human conscious thought, independent of computer literacy level—in fact, independent of any literacy level.

What happens when user interface designers pay attention to techniques that minimize cognitive load? Just maybe, a little magic!
Designing for Better Care and Better Health
Authors: Ma Pauline , Bringas Deydra
Published: May 2020

Serendipitously, the very nature and construct of the way Johnson & Johnson's Credo is written aligns with design thinking—and it has influenced how Quinteros has transformed the development of his design team and their path forward within the company.

More than 70 years after it was crafted, Johnson & Johnson's timeless vision inspired its Chief Design Officer to assemble and guide the company's design team.
Mobile mural thrombus and spontaneous echo contrast in ascending aorta after postoperative adjuvant cisplatin‐based chemotherapy
Authors: Aoyama Yutaka , Harada Kenji , Yokoyama Yasuhiro , Ishiyama Yusuke , Komori Takahiro , Shimpo Masahisa , Kario Kazuomi
Published: May 2020

A 70‐year‐old asymptomatic male who had undergone a right nephrectomy for renal pelvic cancer was referred to us with a thrombus in the ascending aorta detected by contrast‐enhanced computed tomography after chemotherapy with gemcitabine/cisplatin. Transesophageal echocardiography revealed a 4‐cm mobile mural thrombus in the ascending aorta. An emergency thoracotomy for planned aortic root replacement was performed, but the intraoperative epi‐aortic ultrasound indicated that the thrombus had disappeared, and it showed prominent spontaneous‐echo contrast (SEC) in the ascending aorta. We speculate that vascular endothelium damage due to the cisplatin‐based chemotherapy induced the thrombus and SEC in the ascending aorta.
The distinct responses of bacteria and fungi in different‐sized soil aggregates under different management practices
Authors: Navas Mariela , Martín‐Lammerding Diana , Hontoria Chiquinquirá , Ulcuango Kelly , Mariscal‐Sancho Ignacio
Published: May 2020

Soil aggregates can be considered massive microbial incubators. Thus, the study of the bacteria and fungi colonizing different soil aggregate fractions helps to elucidate the factors influencing the associations between microhabitats in soil aggregates and microbial functioning. The main objective of this study was to evaluate the total bacterial and total fungal abundances and soil quality‐related parameters of four aggregate size fractions (>2 mm, 2–0.25 mm, 0.25–0.053 mm and <0.053 mm) at two depths (0–5 cm and 7–12 cm) under three different management regimes (no cultivation, direct seeding [DS] and traditional tillage [TT]). We analysed the pH, electrical conductivity and organic carbon (OC) and nitrogen (N) concentrations in both bulk soil samples and aggregate fractions. For DNA extracted from each aggregate fraction,we performed qPCR analysis of 16S rRNA (an estimate of bacterial abundance) and internal transcribed spacer (an estimate of fungal abundance). The TT decreased the proportion of macroaggregates (>2 mm), which constituted only 16.7% (with 0.17 OC/100 g soil) under this treatment at 0–5‐cm depth, compared with 50.7% (with 1.34 g OC/100 g soil) in uncultivated soil. The abundances of bacteria and fungi exhibited contrasting responses to soil management across aggregate fractions, which differed by depth. The abundance of bacteria, but not fungi, was closely related to OC and N concentrations, with higher values in macroaggregates than in microaggregates for TT and DS at 0–5 cm depth. Uncultivated soil showed no OC differences across aggregate fractions and the bacteria were distributed uniformly among them. Fungal abundance was higher in microaggregates, mainly in DS, concurrent with lower bacterial abundance. Therefore, bacteria and fungi responded differently to changes in properties at the aggregate scale induced by soil management within the soil surface horizon.

Highlights

Management practices affect aggregate size distribution and their bacterial and fungal abundances

Tillage reduced the OC stored in macroaggregates >2 mm by 87% compared to uncultivated soil

Bacterial abundance was positively correlated with the C and N concentrations inside aggregates

Fungal abundance showed an important negative correlation with the bacterial abundance
High water use in desert plants exposed to extreme heat
Authors: Aparecido Luiza M. T. , Woo Sabrina , Suazo Crystal , Hultine Kevin R. , Blonder Benjamin
Published: May 2020

Many plant water use models predict leaves maximize carbon assimilation while minimizing water loss via transpiration. Alternate scenarios may occur at high temperature, including heat avoidance, where leaves increase water loss to evaporatively cool regardless of carbon uptake; or heat failure, where leaves non‐adaptively lose water also regardless of carbon uptake. We hypothesized that these alternative scenarios are common in species exposed to hot environments, with heat avoidance more common in species with high construction cost leaves. Diurnal measurements of leaf temperature and gas exchange for 11 Sonoran Desert species revealed that 37% of these species increased transpiration in the absence of increased carbon uptake. High leaf mass per area partially predicted this behaviour (r2 = 0.39). These data are consistent with heat avoidance and heat failure, but failure is less likely given the ecological dominance of the focal species. These behaviours are not yet captured in any extant plant water use model.
ogs5py: A Python‐API for the OpenGeoSys 5 Scientific Modeling Package
Authors: Müller Sebastian , Zech Alraune , Heße Falk
Published: May 2020

High‐performance numerical codes are an indispensable tool for hydrogeologists when modeling subsurface flow and transport systems. But as they are written in compiled languages, like C/C++ or Fortran, established software packages are rarely user‐friendly, limiting a wider adoption of such tools. OpenGeoSys (OGS), an open‐source, finite‐element solver for thermo‐hydro‐mechanical–chemical processes in porous and fractured media, is no exception. Graphical user interfaces may increase usability, but do so at a dramatic reduction of flexibility and are difficult or impossible to integrate into a larger workflow. Python offers an optimal trade‐off between these goals by providing a highly flexible, yet comparatively user‐friendly environment for software applications. Hence, we introduce ogs5py, a Python‐API for the OpenGeoSys 5 scientific modeling package. It provides a fully Python‐based representation of an OGS project, a large array of convenience functions for users to interact with OGS and connects OGS to the scientific and computational environment of Python.
Molecular and clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation
Authors: Yamashiro Yuya , Saito Tsuyoshi , Hayashi Takuo , Murakami Takashi , Yanai Yuka , Tsuyama Sho , Suehara Yoshiyuki , Takamochi Kazuya , Yao Takashi
Published: May 2020

Background

Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colorectal malignancy with expression of enteroblastic markers (glypican 3, SALL4, AFP); however, the clinicopathological and epidemiological features are not fully elucidated.

Aims

The aims of this study were to elucidate and establish the molecular and clinicopathological characteristics of CAED.

Materials and Methods

In addition to three cases recently diagnosed as CAED, colorectal carcinoma (CRC) with expression of enteroblastic markers were selected by using immunohistochemistry (IHC) on tissue microarrays of 988 advanced CRC. We employed next‐generation sequencing (NGS) and Sanger sequencing for the detection of genetic alterations. IHC for p53 and HER2, HER2‐FISH and MSI status was also investigated. Survival analyses for clinicopathological parameters were performed using Kaplan–Meier methods.

Results

Thirty‐nine cases (4.0%) were positive for at least one enteroblastic marker. Histological evaluation of the total of 42 cases revealed that 10 contained tumour cells with clear cytoplasm. Enteroblastic marker‐positive cases had aggressive behaviour and poor prognosis. NGS revealed TP53 as the most frequently mutated gene. The rate of HER2‐positive cases and MSI‐H cases was 9.5% (four of 42) and 12.2% (five of 41), respectively. Among these 42 cases, there were no molecular and clinicopathological differences according to the presence of tumour cells with clear cytoplasm.

Conclusions

Enteroblastic marker‐positive CRC could be grouped together as CAED regardless of clear cell cytoplasm. Using this definition, the frequency of CAED is 4.0% and has a poorer prognosis than that for conventional CRCs. HER2 targeted therapy would be a meaningful treatment for CAED, and CAEDs contain both MSI‐H and MSI‐stable CRCs, although the MSS phenotype is dominant.
Explorative behaviour is not associated with metabolism in the European Pied Flycatcher Ficedula hypoleuca
Authors: Poranen Oona , Ruuskanen Suvi
Published: May 2020

The pace‐of‐life syndrome hypothesis (POLS) represents an attractive theoretical framework suggesting that physiological and behavioural traits have evolved together with environmental conditions and life‐history strategies. POLS predicts that metabolic differences covary with behavioural variation such that high metabolic rate is associated with risk‐prone behaviour and a faster pace‐of‐life, whereas a low metabolic rate is associated with risk‐averse behaviour and a slower pace‐of‐life. We tested the POLS hypothesis in captive European Pied Flycatchers during their first year by examining the relationship between explorative behaviour and basal metabolic rate. Our results are inconsistent with POLS. The positive association of explorative behaviour with basal metabolic rate was not recovered for either sex, possibly due to foraging conditions in the aviaries where control and trial groups were fed twice a day, the birds' young age, developmental plasticity, or a non‐existent syndrome.
Effect of high‐energy ball milling on the microstructure and properties of ultrafine gradient cemented carbides
Authors: Zhou Xiangkui , Wang Renru , Li Chensi , Wang Xiaobin , Wang Kai , Wang Qiang
Published: May 2020

Planetary low‐temperature high‐energy ball mill was used for preparing the mixed powders with different particle sizes by adjusting the milling time. The ultrafine grain gradient cemented carbides were prepared by sinter‐HIP treatment. The effects of milling time on the gradient formation, grain growth, and mechanical properties of ultrafine grain gradient cemented carbides were investigated. The results show that the high‐energy ball milling cannot effectively reduce the particle size of mixed powder with short milling time. In addition, the particle size of the mixed powder is significantly reduced, while the specific surface area is significantly increased when the ball milling time exceeds 25 hours. The gradient layer thickness and the grain size increase at the beginning and then decrease when the mixed powder particle size was decreased. Simultaneously, the density, hardness, and fracture toughness of the alloy increase gradually. On the contrary, the number of WC with abnormal grain growth is significantly increased. The thickness of the gradient layer reached 32 μm, and the mean WC grain size is 314 nm. Based on the analyzed results, an optimized gradient layer thickness, grain size, density, and hardness can be obtained when the ball milling time is 35 hours.
High prevalence of autosomal recessive congenital ichthyosis in a Mexican population caused by a new mutation in the TGM1 gene: epidemiological evidence of a founder effect
Authors: González‐Del Carmen Manuel , Montaño Sarita , Reyes‐Hernández Octavio D. , Vizcaíno‐Dorado Pablo A. , Leyva‐García Norberto , Morales‐Morfín Juan C. , Diaz‐Beltran Wendy , Quinto‐Santiago Edna , Cariño‐Calvo Lizbeth , Magaña Jonathan J. , Leyva‐Gómez Gerardo , Cortés Hernán
Published: May 2020

Background

Autosomal recessive congenital ichthyoses (ARCI) are inherited disorders produced by mutations in essential genes for the skin function. A low prevalence of this disease has been resported worldwide; however, in a recent study, we identified a large cluster of ARCI families who resided in the High Mountains Region from the Veracruz State, Mexico. Thus, we aimed to identify the causative mutation of ARCI and describe the high prevalence of this disease in this region.

Methods

We selected seven familiar trios and performed whole‐exome sequencing to identify the mutation associated with ARCI. To validate the identified mutation, we performed Sanger sequencing in 62 patients, 30 unaffected relatives, and 100 healthy volunteers. Finally, we performed molecular modeling to investigate the possible functional consequences produced by the mutation.

Results

We identified a novel homozygous mutation (c.1054C>G [p.Pro352Ala]) in the exon 7 of the TGM1 gene in all the patients. We calculated a prevalence rate of ARCI of 74:100,000 (1:1,348) in the studied communities. Molecular modeling revealed that the mutation leads to a nonconservative amino acid substitution, which is very probably damaging to the protein structure/function.

Conclusions

We report a novel mutation in the TGM1 gene in 62 Mexican patients. The unusually high frequency of this mutation suggests a founder effect; however, further haplotype analysis is necessary to corroborate this hypothesis. In this respect, to our knowledge, the prevalence of ARCI found in the studied communities is the highest observed worldwide.
Social support, role clarity and job satisfaction: a successful combination for nurses
Authors: Orgambídez Alejandro , Almeida Helena
Published: May 2020

Aim

To analyse the moderating effect of role clarity on the relationship between social support (supervisor and colleagues) and job satisfaction.

Background

The social support of supervisors and co‐workers and the clarity of roles are important antecedents of job satisfaction. According to the Conservation of Resources theory, the interaction of the instrumental nature of role clarity and social support would result in higher levels of job satisfaction in nursing.

Methods

Through a convenience sample, a final sample of 191 participants (64.92% registered nurses, 35.08% nursing assistants) was obtained from a private hospital complex in Portugal. Hierarchical linear regression models were carried out to check the moderating function of role clarity.

Results

Regression models showed the moderating effect of role clarity. Nursing staff with high social support from their supervisors and peers showed higher scores in job satisfaction when role clarity was high.

Conclusion

An adequate description of roles, through clear and detailed information regarding expected functions, responsibilities and behaviour, allows the effect of social support from supervisors and co‐workers on job satisfaction to be stronger.

Implications for nursing practice

Strategies such as defining responsibilities, setting clear expectations and role analysis allow a reduction in sources of uncertainty in jobs. Training in communication and feedback skills would improve the social support given by supervisors and colleagues.

Implications for nursing policy

Hospital boards and nurse managers should be aware of the importance of clarifying roles, responsibilities, and functions of each professional category and hierarchical level for the provision of adequate quality of care.
Lurking in plain sight: Hypertension awareness and treatment among New York City taxi/for‐hire vehicle drivers
Authors: Narang Bharat , Mirpuri Sheena , Kim Soo Young , Jutagir Devika R. , Gany Francesca
Published: May 2020

Hypertension is a risk factor for cardiovascular disease, which is the leading cause of death in the United States. Taxi and for‐hire vehicle (FHV) drivers, a largely male, immigrant and medically underserved population, are at increased risk of cardiovascular disease, in part due to the nature of their work. This study examined demographic and lifestyle predictors of hypertension diagnosis awareness, objectively measured blood pressure (hypertensive‐range vs non‐hypertensive‐range readings), medication use, and hypertension control. A cross‐sectional assessment was conducted with 983 male taxi/FHV drivers who attended health fairs in New York City from 2010 to 2017. Twenty‐three percent self‐reported a hypertension history and 46% had hypertensive‐range BP readings. Approximately, half the drivers lacked health insurance (47%) and a usual care source (46%). Thirty percent did not self‐report hypertension and had hypertensive‐range BP readings. Medication use was reported by 69% of hypertension‐aware drivers, and being older and having health care access (insurance, a usual care source, and seeing a doctor in the past year) was significantly associated with medication use. Hypertension‐unaware drivers with hypertensive‐range BP readings were less likely to have a usual care source. Over 60% of drivers who were hypertension‐aware and on medication had hypertensive‐range readings. There is a need for community‐based and workplace driver and provider interventions to address BP awareness and management and to provide health care navigation for vulnerable populations such as taxi/FHV vehicle drivers.
SP1‐induced SNHG14 aggravates hypertrophic response in in vitro model of cardiac hypertrophy via up‐regulation of PCDH17
Authors: Long Yadong , Wang Lin , Li Zhiqiang
Published: May 2020

Cardiac hypertrophy (CH) is a common cardiac disease and is closely associated with heart failure. Protocadherin 17 (PCDH17) was reported to aggravate myocardial infarction. Present study was designed to illustrate the impact of PCDH17 and the mechanism of PCDH17 expression regulation in CH. CH model in vivo and in vitro was established by transverse aortic constriction (TAC) and Ang‐II treatment. Hypertrophy was evaluated in PMC and H9c2 cells by examining cell surface area and hypertrophic markers. Results demonstrated that PCDH17 was up‐regulated in CH in vivo and in vitro. PCDH17 knock‐down alleviated hypertrophic response in Ang‐II‐induced cardiomyocytes. By means of ENCORI database and a series of mechanism assays, miR‐322‐5p and miR‐384‐5p were identified to interact with and inhibit PCDH17. Next, lncRNA SNHG14 (small nucleolar RNA host gene 14) was validated to sponge both miR‐322‐5p and miR‐384‐5p to elevate PCDH17 level. The subsequent rescue assays revealed that miR‐322‐5p and miR‐384‐5p restored SNHG14 depletion‐mediated suppression on hypertrophy in Ang‐II‐induced cardiomyocytes. Besides, Sp1 transcription factor (SP1) was verified as the transcription factor activating both SNHG14 and PCDH17. Both SNHG14 and PCDH17 reversed SP1 knock‐down‐mediated repression on hypertrophy in Ang‐II‐induced cardiomyocytes. Together, present study first uncovered ceRNA network of SNHG14/miR‐322‐5p/miR‐384‐5p/PCDH17 in Ang‐II‐induced cardiomyocytes.
A Tale of (almost) 1001 Coefficients: The Deep and Heterogeneous Effects of the EU‐Turkey Customs Union
Authors: Larch Mario , Schmeißer Aiko F. , Wanner Joschka
Published: May 2020

In view of the deferred start of negotiations for the modernization of the customs union between the EU and Turkey (CU‐EUT), we looked back and analysed the ex post trade consequences of the CU‐EUT. Employing up‐to‐date econometric best practices for regional integration agreements, we quantified both the total and the heterogeneous trade effects of the CU‐EUT. In contrast with most previous studies, our results indicate that the CU‐EUT made a significantly positive, large and robust impact, implying there was an additional increase in EU‐Turkey trade in manufacturing by 55–65 per cent compared with that during the previously active Ankara Agreement. We also provide evidence that the CU‐EUT significantly increased Turkey's trade with non‐member countries of the CU‐EUT. Additionally, a substantial heterogeneity in the CU‐EUT effect was found across different industries as well as for each of its member countries and the direction of trade. We linked the heterogeneity of up to 911 coefficient estimates to the differences in initial trade costs and show that it cannot be ascribed to reductions in bilateral tariff rates.
Collagen supplementation for skin health: A mechanistic systematic review
Authors: Barati Meisam , Jabbari Masoumeh , Navekar Roya , Farahmand Fariba , Zeinalian Reihaneh , Salehi‐Sahlabadi Ammar , Abbaszadeh Nasrin , Mokari‐Yamchi Amin , Davoodi Sayed Hossein
Published: May 2020

Background

Over the last decade, many researchers tried to evaluate the effects of collagen supplements on skin aging and surprisingly revealed that the interventions improved skin aging parameters without any inconsistency.

Aim

This systematic review assesses the literature regarding the effects of collagen supplements on skin health parameters in healthy and patient subjects, focusing on mechanisms of action.

Methods

At the first step of search in the databases, 9057 items were obtained. After removal of duplicate items, 6531 publications remained. Further screening by title and/or abstract resulted in removal of 6500 items. Finally, full texts of the 31 remained items were assessed for eligibility and 10 publications were included in this review.

Results

The evidences obtained from these systematic reviews indicated that oral administration of intact or hydrolyzed collagen improves clinical manifestation of skin health. Almost all of the included studies reported the beneficial effects of collagen supplementation, and no inconsistencies have been seen in this regard between studies.

Conclusions

In this systematic review, three different mechanisms of action were clarified for the intervention. Direct effects of collagen peptides on fibroblasts, M2‐like macrophages, and oral tolerance‐related mechanisms are the possible mechanisms for the beneficial effects of collagen supplementation.
The Causal Effect of Limits to Arbitrage on Asset Pricing Anomalies
Authors: CHU YONGQIANG , HIRSHLEIFER DAVID , MA LIANG
Published: May 2020

We examine the causal effect of limits to arbitrage on 11 well‐known asset pricing anomalies using the pilot program of Regulation SHO, which relaxed short‐sale constraints for a quasi‐random set of pilot stocks, as a natural experiment. We find that the anomalies became weaker on portfolios constructed with pilot stocks during the pilot period. The pilot program reduced the combined anomaly long–short portfolio returns by 72 basis points per month, a difference that survives risk adjustment with standard factor models. The effect comes only from the short legs of the anomaly portfolios.
Picking 'winners' in space: Impact of spatial targeting on firm performance in China
Authors: Howell Anthony
Published: May 2020

This paper examines the spatial patterns of China's industrial encouragement policy and its distributional impact on firm productivity. To this end, I develop separate proxies to measure three popular policy instruments (subsidies, tax holidays, and preferential access to loans). I first show that China's industrial support policies tend to exhibit a prominent spatial feature of targeting firms located in lagging cities with lower density. Taking into account potential endogeneity of industrial policy, unobserved heterogeneity and firm dynamics, quantile regression techniques show that more intense industrial support leads to: (a) a reduction in the productivity of lower‐performing firms, especially in denser cities; and (b) a small productivity gain for better performing firms but only in denser cities. Counterfactual analysis further reveals that pursuing an alternative, space‐neutral industrial encouragement policy would increase average productivity by 14–16%, in aggregate, but also contribute to significantly higher regional inequality.
Clinical features and outcomes of lymphadenopathy in a tertiary children's hospital
Authors: Venturini Elisabetta , Grillandini Chiara , Bianchi Leila , Montagnani Carlotta , Chiappini Elena , Galli Luisa
Published: May 2020

Aim

The aim of the present study is to describe the clinical features and outcomes of childhood lymphadenopathy and to define factors able to predict neoplastic aetiology or may improve its prognosis.

Methods

All children evaluated for lymphadenopathy in our tertiary children's hospital and who underwent their first examination between 1 January, 2015 and 31 December, 2017 were enrolled in this retrospective observational study. Data were analysed using SPSS.Statistics, 24.0.

Results

A total of 322 children, aged between 0 and 18 years (median 4.5; interquartile range 2.5–9), were enrolled. A specific diagnosis was achieved in almost half of the cases (n = 159, 49.4%) by using one or more methods, including serological, microbiological, biomolecular or histological investigations on surgical samples. Epstein Barr virus and non‐tuberculous mycobacteria were the most common etiological agents among acute/sub‐acute and chronic lymphadenopathy, respectively. At the end of the study period, two‐thirds (210, 65.2%) of enrolled patients were successfully treated. Malignancies and non‐tuberculous mycobacteria infections had the longest time to resolution.

Conclusions

Our data suggest that lymphadenopathy is a benign condition in most cases. Of note in our study, 2.5% of lymphadenopathy cases were found to be due to oncologic conditions. The most frequent infective causes were Epstein Barr virus, bacteria and non‐tuberculous mycobacteria infections. No haematic or ultrasonographic features were independently able to provide sufficient evidence for a conclusive diagnosis. However, utilising these findings alongside evaluation for clinical criteria can guide decision‐making for physicians. Lymphadenectomy is the most appropriate process to follow in the event of chronic lymphadenopathy with undefined diagnosis.
A validation study of the Ursodeoxycholic Acid Response Score in Japanese patients with primary biliary cholangitis
Authors: Yagi Minami , Matsumoto Kosuke , Komori Atsumasa , Abe Masanori , Hashimoto Naoaki , Inao Mie , Namisaki Tadashi , Kawata Kazuhito , Ninomiya Masashi , Fujii Hideki , Takahashi Atsushi , Kang Jong‐Hon , Takamura Masaaki , Arakawa Mie , Joshita Satoru , Sato Ken , Itakura Jun , Nomura Takako , Kakisaka Keisuke , Kaneko Akira , Tamura Yamato , Miura Ryo , Aiso Mitsuhiko , Arizumi Toshihiko , Asaoka Yoshinari , Kikuchi Kentaro , Takikawa Yasuhiro , Masaki Tsutomu , Umemura Takeji , Honda Akira , Ohira Hiromasa , Kawada Norifumi , Yoshiji Hitoshi , Mochida Satoshi , Takikawa Hajime , Tanaka Atsushi ,   Japan PBC Study Group (JPBCSG)
Published: May 2020

Background/Purpose

Although ursodeoxycholic acid (UDCA) is a first‐line treatment for primary biliary cholangitis (PBC), 20%‐30% of patients with PBC exhibit an incomplete response to UDCA. Recently, the UDCA Response Score was proposed for predicting response to UDCA using pretreatment parameters in patients with PBC. We aimed to validate the UDCA Response Score in Japanese patients with PBC.

Methods

Registry data of Japanese patients (n = 873) were collected. Patients with data on all clinical parameters required for calculating the UDCA Response Score were selected. The endpoint was UDCA response, defined as alkaline phosphatase <1.67 times the upper limit of the normal value after 12 months of UDCA treatment.

Results

All parameters were available in 804 patients (male/female = 120/684, age 58.9 [interquartile range 51.1‐66.9] years). Bezafibrate was commenced within 12 months of UDCA in 78 patients (9.7%) because of the lack of an early response. We found that the endpoint was not reached in these 78 patients, and the area under the receiver operating characteristic curve (AUROC) of the score was 0.74 (95% confidence interval [CI] 0.70‐0.79). The AUROC was 0.77 (95% CI 0.70‐0.83) in patients undergoing UDCA monotherapy (n = 726). Finally, the AUROC of the modified UDCA Response Score using only data from the treatment start date was 0.80 (95% CI 0.70‐0.90) in patients receiving a combination therapy of UDCA and bezafibrate (n = 160).

Conclusion

The validity of the UDCA Response Score was acceptable in Japanese patients; this score will be informative in patients treated with a combination therapy of UDCA and bezafibrate.
Enhancing variety through gamified, interactive learning experiences
Authors: Moro Christian , Stromberga Zane
Published: May 2020

With this issue we conclude the print publication of responses received to our call for Medical Education Adaptations: Lessons learned from educators' experiences rapidly transforming practice on account of COVID‐19 related disruption.
Sandfly surveillance and investigation of Leishmania spp. DNA in sandflies in Kosovo
Authors: Vaselek S. , Oguz G. , Ayhan N. , Ozbel Y. , Kadriaj P. , Ćupina A. I. , Velo E. , Muja N. , Baymak D. , Alishani M. , Toz S. , Nalcaci M. , Sherifi K. , Charrel R. , Alten B. , Petrić D.
Published: May 2020

In the past decade, leishmaniasis seems to be re‐emerging in Balkan countries. There are serious implications that Kosovo is a visceral leishmaniasis endemic region with autochthonous transmission; nevertheless, surveillance of vectors, reservoirs or the disease is not yet established. Gaining knowledge about sandfly vector species is a prerequisite for the development of a monitoring and control plan in the future. After a long gap in research of over 70 years, sandfly studies in Kosovo were resumed in 2014. During this presence/absence study, nine sandfly species were detected: Phlebotomus papatasi, Ph. perfiliewi, Ph. tobbi, Ph. neglectus, Ph. simici, Ph. balcanicus, Ph. alexandri, Ph. mascittii and Sergentomyia minuta. Three species are new with regard to the fauna of Kosovo – Ph. alexandri, Ph. balcanicus and Ph. mascittii. Besides increased diversity, changes in the number of collected specimens and distribution range of species were recorded, with Ph. neglectus being the most dominant species with the widest distribution. Testing of randomly chosen females for Leishmania spp. DNA resulted the in detection of L. tropica in a specimen of Ph. neglectus. The presence of numerous vector species in the sandfly fauna of Kosovo pose a threat for the re‐emergence of vector‐borne diseases. Therefore, continuous surveillance is recommended with regular updates on vector distribution and abundance.
Scleral lens wear following penetrating keratoplasty: changes in corneal curvature and optics
Authors: Kumar Mukesh , Shetty Rohit , Lalgudi Vaitheeswaran G , Vincent Stephen J
Published: May 2020

Purpose

Visual rehabilitation following penetrating keratoplasty is the primary indication for approximately 15% of all scleral lens fittings. Since corneal biomechanics are altered following penetrating keratoplasty, the aim of this study was to quantify changes in anterior corneal optics following short‐term scleral lens wear in eyes with corneal grafts.

Methods

Scheimpflug images were obtained before and after a period of scleral lens wear (mean 6.3 ± 1.4 h), from eyes that had previously undergone penetrating keratoplasty (10 eyes of nine participants, mean age 31 ± 9 years). Corneal power and thickness data were examined over the central 6 mm, including regional analyses of the central (0–3 mm) and the mid‐peripheral cornea (3–6 mm annulus) using customised software to deterime corneal power vectors M (best fit sphere), J0 (90/180 astigmatism) and J45 (45/135 astigmatism). Anterior corneal aberrations were extracted using corneal elevation data.

Results

Corneal power vector J45 increased following lens wear (by 0.22 ± 0.05 D, p = 0.003) across the central 6 mm, while M displayed regional variations following lens wear indicating larger changes further from the corneal centre (p = 0.004). The change in corneal power vector M was also correlated with the magnitude of central corneal swelling (r = 0.65, p = 0.04). The anterior corneal aberration terms of oblique astigmatism, hoirzontal coma, and spherical aberration also varied following lens wear (all p ≤ 0.01). The mean change in the corneal spherocylinder derived from the elevation data following lens wear was +0.14/−0.54 × 44 for a 6 mm corneal diameter.

Conclusions

Clinically significant alterations in anterior corneal topography and higher order aberrations were observed following short‐term scleral lens wear in eyes that had undergone penetrating keratoplasty. Spherocylindrical changes were approximately double the magnitude and more oblique in orientation compared to previous reports of healthy eyes. Changes in corneal power vector M may be related to epithelial corneal oedema.
Allergen Immunotherapy in Children User’s Guide
Authors: Alvaro‐Lozano Montserrat , Akdis Cezmi A. , Akdis Mubeccel , Alviani Cherry , Angier Elisabeth , Arasi Stefania , Arzt‐Gradwohl Lisa , Barber Domingo , Bazire Raphaëlle , Cavkaytar Ozlem , Comberiati Pasquale , Dramburg Stephanie , Durham Stephen R. , Eifan Aarif O. , Forchert Leandra , Halken Susanne , Kirtland Max , Kucuksezer Umut C. , Layhadi Janice A. , Matricardi Paolo Maria , Muraro Antonella , Ozdemir Cevdet , Pajno Giovanni Battista , Pfaar Oliver , Potapova Ekaterina , Riggioni Carmen , Roberts Graham , Rodríguez del Río Pablo , Shamji Mohamed H. , Sturm Gunter J. , Vazquez‐Ortiz Marta
Published: May 2020

Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well‐defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.
Intravenous dexmedetomidine sedation for magnetoencephalography: A retrospective study
Authors: Tewari Anurag , Mahmoud Mohamed , Rose Douglas , Ding Lili , Tenney Jeffrey
Published: May 2020

Background

Magnetoencephalography (MEG) plays a preponderant role in the preoperative assessment of patients with drug‐resistant epilepsy (DRE). However, the magnetoencephalography of patients with drug‐resistant epilepsy can be difficult without sedation and/or general anesthesia. Our objective is to describe our experience with intravenous dexmedetomidine as sedation for magnetoencephalography and its effect, if any, on the ability to recognize epileptic spikes.

Methods

In this retrospective study, we reviewed the records of 89 children who presented for Magnetoencephalography/electroencephalography (EEG) scans between August of 2008 and May of 2015. Data analyzed included demographics and the frequency of epileptic spikes. Sedated magnetoencephalography recordings were compared to nonsedated video‐electroencephalography (vEEG) recordings in the same patients to determine the impact of dexmedetomidine.

Results

Spike frequency between magnetoencephalography with sedation and video‐electroencephalography without sedation was compared in 85 patients. Magnetoencephalography and video‐electroencephalography were considered clinically concordant in 80 patients (94.1%) and discordant in 5 patients (5.9%), all with less spikes during Magnetoencephalography. The median (range) bolus dose of dexmedetomidine was 2 (1‐2) mcg/kg. The median (range) infusion rate of dexmedetomidine was 2 (0.5‐4) mcg/kg/h. All patients experienced reductions in heart rate after administration of dexmedetomidine; these reductions were statistically, but not clinically, significant.

Conclusions

Our results suggest that dexmedetomidine‐based protocol provides reliable sedation in children undergoing MEG scanning because of the high success rate, limited interictal artifacts, and minimal impacts on spike frequency.
Trauma‐focused imaginal exposure for auditory hallucinations: A case series
Authors: Brand Rachel M. , Bendall Sarah , Hardy Amy , Rossell Susan L. , Thomas Neil
Published: May 2020

Objective

There is mounting evidence that traumatic life events play a role in auditory hallucinations (AH). Theory suggests that some AH are decontextualized trauma memory intrusions. Exposure‐based trauma‐focused therapies that target trauma memory intrusions may therefore be a promising new treatment. We aimed to assess the feasibility and acceptability of a standard protocol trauma‐focused imaginal exposure intervention for trauma‐related AH and to provide initial proof of concept regarding potential effects on AH.

Design

We conducted a single‐arm case series of a six session (90 min per session) imaginal exposure intervention for trauma‐related AH with assessments at baseline, post‐therapy, and one‐month follow‐up.

Results

Fifteen people were recruited and eligible to start the intervention. Participants reported high levels of satisfaction; however, temporary distress and symptom exacerbation were common and contributed to discontinuation. There was a large reduction in AH severity at one‐month follow‐up (adjusted d = 0.99), but individual response was highly variable. There were also large reductions in post‐traumatic stress disorder symptoms and the intrusiveness of the trauma memory.

Conclusions

Imaginal exposure for trauma‐related AH is generally acceptable and may have large effects on AH severity for some people. However, temporary distress and symptom exacerbation are common and can lead to discontinuation. Low referral rates and uptake also suggest feasibility issues for standalone imaginal exposure for AH. The intervention may be more feasible and acceptable in the context of a broader trauma‐focused therapy. Well‐powered trials are needed to determine efficacy and factors that impact on acceptability and therapy response.

Practitioner points

Some AH can be understood as trauma memory intrusions that lack temporal and spatial contextualization and are therefore experienced without autonoetic awareness.

Imaginal exposure to trauma memories associated with AH may be an effective intervention for some people.

Temporary distress and symptom exacerbation may be common when using standard trauma‐focused imaginal exposure for AH. This can impact on the acceptability of the therapy and should be considered in future development and delivery.
Cytosolic malate dehydrogenase 4 modulates cellular energetics and storage reserve accumulation in maize endosperm
Authors: Chen Yongqiang , Fu Zhiyuan , Zhang Hui , Tian Runmiao , Yang Huili , Sun Canran , Wang Lulin , Zhang Wen , Guo Zhanyong , Zhang Xuehai , Tang Jihua
Published: May 2020

Cytosolic malate dehydrogenase (MDH) is a key enzyme that regulates the interconversion between malate and oxaloacetate (OAA). However, its role in modulating storage compound accumulation in maize endosperm is largely unknown. Here, we characterized a novel naturally occurring maize mdh4‐1 mutant, which produces small, opaque kernels and exhibits reduced starch but enhanced lysine content. Map‐based cloning, functional complementation and allelism analyses identified ZmMdh4 as the causal gene. Enzymatic assays demonstrated that ZmMDH4 predominantly catalyses the conversion from OAA to malate. In comparison, the activity of the mutant enzyme, which lacks one glutamic acid (Glu), was completed abolished, demonstrating that the Glu residue was essential for ZmMDH4 function. Knocking down ZmMdh4 in vivo led to a substantial metabolic shift towards glycolysis and a dramatic disruption in the activity of the mitochondrial complex I, which was correlated with transcriptomic alterations. Taken together, these results demonstrate that ZmMdh4 regulates the balance between mitochondrial respiration and glycolysis, ATP production and endosperm development, through a yet unknown feedback regulatory mechanism in mitochondria.
Therapeutic coil embolization of dominant shunt in hepatopulmonary syndrome enhances post‐liver transplant respiratory recovery
Authors: Sonavane Amey D. , Bagde Abhijit , Raut Vikram , Marar Shaji , Sawant Ambreen , Shah Ketul , Raj Amruth , Thorat Ashok , Chaksota Harshit , Biradar Vishnu , Vasanth Suresh , Nagral Aabha , Mirza Darius
Published: May 2020

Coil embolization of the atypical enlarged pulmonary artery/arteriole with visible shunting may improve hypoxemia in patients with hepatopulmonary syndrome (HPS). When used selectively in cases with large shunts, either pre‐ or post‐liver transplantation (LT), it can aid an early recovery and reduce morbidity. We present a case where a large intrapulmonary shunt was embolized preoperatively to improve hypoxemia associated with HPS and enhance post‐operative recovery.
The influence of facial expression at perceptual threshold on electrodermal activity and social comfort distance
Authors: Cartaud Alice , Ott Laurent , Iachini Tina , Honoré Jacques , Coello Yann
Published: May 2020

Interpersonal distance, an essential component of social interaction, is modulated by the emotion conveyed by others and associated physiological response. However, in modern societies with overcrowded and hyperstimulating environments, we can only surreptitiously glimpse the faces of others in order to quickly make behavioral adjustments. How this impacts social interactions is not yet well understood. In the present study, we investigated this issue by testing whether facial expressions that are difficult to identify modify the physiological response (Electrodermal Activity, EDA) and subsequent judgment of interpersonal comfort distance. We recorded participants’ EDA while they provided comfort judgments to interpersonal distances with a Point‐Light Walker (PLW). The PLW, with an emotionally neutral gait, moved toward and crossed participants at various distances after the latter were exposed to a negative (anger), positive (happiness) or neutral facial expression presented at the perceptual threshold. Bayesian analyses of the data revealed an increase versus decrease of interpersonal comfort distance with the PLW depending on the negative versus positive emotional valence of the facial expression. They also showed an increase in EDA when the approaching PLW violated interpersonal comfort distance after participants were exposed to an angry facial expression. These effects correlated with the subjective assessment of the arousal of facial expressions. Thus, previous exposure to barely visible facial expressions can alter the representation of social comfort space and the physiological response associated with a violation of interpersonal comfort distances, depending on the valence and arousal of the emotional social stimuli.
Optimization of carbon stock models to local conditions using farmers' soil tests: A case study with AMGv2 for a cereal plain in central France
Authors: Nowak Benjamin , Marliac Gaëlle
Published: May 2020

Soil organic carbon (SOC) is associated with environmental benefits and crop productivity; therefore, monitoring of SOC stocks is important when assessing the sustainability of agricultural systems. This study applied a hybrid method and the results of on‐farm soil tests to calibrate the AMGv2 model and adapt it to local conditions. The method was applied to soils in the Limagne plain (France), which shifted to cereal production since the 1960s. Based on analysing 988 soil test data, covering the period from 1954 to 2019, it was found that SOC stocks showed a significant decrease in the three main soil types of the study area. An optimization procedure estimated that the initial ratios of stable to total carbon fall in the ranges 0.42 and 0.46 for vertisols, 0.48 and 0.52 for calcisols, and 0.56 and 0.60 for fluvisols. Simulations using these values estimated that SOC stocks declined between 1960 and 2018 by between −31 and −17%, depending on soil type. The optimized model was used to forecast the evolution of SOC stocks up to 2050. These simulations showed a further decline in SOC stocks with continuation of current practices, even assuming a 15% increase in crop yields. They indicated that stopping straw exports would stabilize stocks, while a systematic introduction of cover crops would increase stocks about 3.8% over the period considered. It is concluded that this hybrid procedure can improve the adaptation of predictive models to local conditions.