bluuebunny/crossref_metadata_2025 huggingface dataset:
Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single‐centre double‐blind randomised control study
Authors: Yap J , Slade D , Goddard H , Dawson C , Ganesan R , Velangi S , Sahu B , Kaur B , Hughes A  , Luesley D
Published: October 2020

Objective

To compare the safety and efficacy of 10% sinecatechins (Veregen®) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN).

Design

A Phase II double‐blind randomised control trial.

Setting

A tertiary gynaecological oncology referral centre.

Population

All women diagnosed with primary and recurrent uVIN.

Methods

Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks.

Main outcome measures

The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores.

Results

There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group.

Conclusion

Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study.

Tweetable abstract

A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.
Bioactive peptides from food fermentation: A comprehensive review of their sources, bioactivities, applications, and future development
Authors: Chai Kong Fei , Voo Amanda Ying Hui , Chen Wei Ning
Published: October 2020

Bioactive peptides (BPs) are specific protein fragments that exert various beneficial effects on human bodies and ultimately influence health, depending on their structural properties and amino acid composition and sequences. By offering promising solutions to solve diverse health issues, the production, characterization, and applications of food‐derived BPs have drawn great interest in the current literature and are of particular interest to the food and pharmaceutical industries. The microbial fermentation of protein from various sources is indubitably a novel way to produce BPs with numerous beneficial health effects. Apart from its lower cost as compared to enzymes, the BPs produced from microbial fermentation can be purified without further hydrolysis. Despite these features, current literature shows dearth of information on the BPs produced from food via microbial fermentation. Hence, there is a strong necessity to explore the BPs obtained from food fermentation for the development of commercial nutraceuticals and functional foods. As such, this review focuses on the production of BPs from different food sources, including the extensively studied milk and milk products, with emphasis on microbial fermentation. The structure–activity (antihypertensive, antioxidant, antimicrobial, opiate‐like, anti‐inflammatory, anticancer/antiproliferative, antithrombotic, hypolipidemic, hypocholesterolemic, and mineral binding) relationship, potential applications, future development, and challenges of BPs obtained from food fermentation are also discussed.
Antioxidant and cytoprotective effects of enzyme‐extracted constituents of Protaetia brevitarsis seulensis powder
Authors: Choi In‐Hag , Choi Sung‐Up , Son Jin‐Sung , Jang Woo‐Whan , Chung Tae‐Ho
Published: October 2020

This study was aimed to compare the antioxidant and cytoprotective effects of hot‐water and enzyme‐extracted constituents of Protaetia brevitarsis seulensis powder. The products of enzymatic extraction had 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH)‐radical‐scavenging activity, cytotoxic effects, and provided cytoprotection against H2O2 and intracellular reactive oxygen species. Enzymatic extraction improved DPPH‐radical‐scavenging activity relative to hot‐water extraction (P < 0.05), with inhibition rates of 33% at 500 μg/mL and 35% at 1000 μg/mL. Cell viability ranged from 100 to 122%, and was higher for hot‐water than for enzymatic extraction (P > 0.05). Hot‐water extraction achieved greater cytoprotection against H2O2 than enzymatic extraction. However, enzymatic extraction achieved greater antioxidant and cytoprotective activity against reactive oxygen species than hot‐water extraction. These results provide evidence of the antioxidant and cytoprotective effects produced by enzymatic extraction of the active ingredients from Protaetia brevitarsis seulensis powder.
Association between maternal prepregnancy body mass index and risk of preterm birth in more than 1 million Asian American mothers
Authors: Gao Rui , Liu Buyun , Yang Wenhan , Wu Yuxiao , Snetselaar Linda G. , Santillan Mark K. , Bao Wei
Published: October 2020

Background

Asian Americans are among the fastest growing subpopulations in the United States. However, evidence about maternal prepregnancy body mass index (BMI) and preterm birth among Asian Americans is lacking.

Methods

This population‐based study used nationwide birth certificate data from the US National Vital Statistics System 2014 to 2018. All Asian American mothers who had a singleton live birth were included. According to Asian‐specific cutoffs, maternal prepregnancy BMI was classified into underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5‐22.9 kg/m2), overweight (BMI 23.0‐27.4 kg/m2), class I obesity (BMI 27.5‐32.4 kg/m2), class II obesity (BMI 32.5‐37.4 kg/m2), and class III obesity (BMI ≥37.5 kg/m2). Preterm birth was defined as gestational age less than 37 weeks. Multivariable logistic regression models were used to estimate the odds ratio (OR) of preterm birth.

Results

We included 1 081 341 Asian American mother‐infant pairs. The rate of preterm birth was 6.51% (n = 70 434). The rate of maternal prepregnancy overweight and obesity was 46.80% (n = 506 042). Compared with mothers with normal weight, the adjusted OR of preterm delivery was 1.04 (95% CI, 1.01‐1.07) for underweight mothers, 1.18 (95% CI, 1.16‐1.20) for overweight mothers, 1.41 (95% CI, 1.37‐1.44) for mothers with class I obesity, 1.69 (95% CI, 1.63‐1.76) for mothers with class II obesity, and 1.78 (95% CI, 1.66‐1.90) for mothers with class III obesity. Similar patterns of associations were observed in Asian American mothers across different country origins.

Conclusions

Among Asian American mothers, maternal prepregnancy overweight or obesity, defined by Asian‐specific, lower BMI cutoffs, was significantly associated with an increased risk of preterm birth. The risk of preterm birth increased with increasing obesity severity. These findings highlight the importance of using Asian‐specific BMI cutoffs in assessing risk of preterm birth among Asian American mothers.
Fibromyalgia in patients with psoriatic arthritis: Impact on disease activity indices, fatigue and health‐related quality of life
Authors: Elsawy Noha A. , Helal Abdel‐Moneim H. , Abd ElHamid Hala A. , Abdel‐Fattah Yousra Hisham
Published: October 2020

Objective

To assess the frequency of fibromyalgia (FM) in patients with psoriatic arthritis (PsA) and its impact on disease activity indices, fatigue and health‐related quality of life (QOL).

Methods

This cross‐sectional study randomly recruited patients with PsA attending an outpatient clinic between June 2017 and December 2018. Disease activity, functional ability, fatigue, and QOL were assessed for all patients. The recruited PsA patients were screened for concomitant FM, then classified into group Ι, patients with PsA only, and group ΙI, patients with FM‐PsA. The severity and impact of FM were assessed for group II patients.

Results

A total of 60 patients with PsA were assessed with a mean age of 49.30 ± 11.69 years, of which 43.3% were female. A total of 23 PsA patients had concomitant FM (38.3%). Patients with FM‐PsA showed a statistically higher disease activity in all aspects of PsA except for C‐reactive protein, swollen joint count (SJC) and dactylitis count. Patients in both groups had similar functional levels, while fatigue and QOL were statistically worse in patients with FM‐PsA than in patients with PsA only.

Conclusion

These results might highlight the importance of considering FM as a contextual factor in disease activity assessment in patients with PsA, especially in those with discrepancies in tender joint count/patient‐reported outcomes vs SJC/inflammatory markers and those with persistently high disease activity indices.
MiR‐133a acts as a tumor suppressor in lung cancer progression by regulating the LASP1 and TGF‐β/Smad3 signaling pathway
Authors: Shen Yuyao , Yang Yan , Li Yahua
Published: October 2020

Background

MiR‐133a has been confirmed to be involved in the development of multiple cancers including non‐small cell lung cancer (NSCLC). However, the precise molecular mechanism has not yet been fully elucidated. The purpose of this study was to investigate the functional role and underlying mechanism of miR‐133a in the progression of NSCLC.

Methods

Quantitative real‐time PCR (qRT‐PCR) was performed to measure miR‐133a and LASP1 expression in NSCLC tissues and cells. 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay was used to detect cell viability. The protein levels were measured by western blot. The tumor growth was measured by xenograft tumor formation assay.

Results

miR‐133a was significantly decreased while LASP1 was increased in NSCLC tissues and cells compared with control groups. Moreover, overexpression of miR‐133a suppressed cell viability, whereas miR‐133a knockdown enhanced the viability of A549 cells. More importantly, LASP1 was verified as a direct target of miR‐133a. Moreover, overexpression of miR‐133a inhibited the epithelial‐mesenchymal transition (EMT) and TGF‐β/Smad3 pathways by regulating LASP1 in vitro. In addition, miR‐133a mimic suppressed tumor growth by modulating the TGF‐β/Smad3 pathway in vivo.

Conclusions

In conclusion, miR‐133a acted as a tumor suppressor in lung cancer progression by regulating the LASP1 and TGF‐β/Smad3 signaling pathway.
Clinical T category for lung cancer staging: A pragmatic approach for real‐world practice
Authors: Choi Yeonu , Kim Sun‐Hyung , Kim Ki Hwan , Choi Yeonseok , Park Sung Goo , Sohn Insuk , Kim Hye Seung , Um Sang‐Won , Lee Ho Yun
Published: October 2020

Background

To determine which components should be measured and which window settings are appropriate for computerized tomography (CT) size measurements of lung adenocarcinoma (ADC) and to explore interobserver agreement and accuracy according to the eighth edition of TNM staging.

Methods

A total of 165 patients with surgically resected lung ADC earlier than stage 3A were included in this study. One radiologist and two pulmonologists independently measured the total and solid sizes of components of tumors on different window settings and assessed solidity. CT measurements were compared with pathologic size measurements.

Results

In categorizing solidity, 25% of the cases showed discordant results among observers. Measuring the total size of a lung adenocarcinoma predicted pathologic invasive components to a degree similar to measuring the solid component. Lung windows were more accurate (intraclass correlation [ICC] = 0.65–0.81) than mediastinal windows (ICC = 0.20–0.72) at predicting pathologic invasive components, especially in a part‐solid nodule. Interobserver agreements for measurement of solid components were good with little significant difference (lung windows, ICC = 0.89; mediastinal windows, ICC = 0.91). A high level of interobserver agreement was seen between the radiologist and pulmonologists and between residents (from the division of pulmonology and critical care) versus a fellow (from the division of pulmonology and critical care) on different windows.

Conclusions

A considerable percentage (25%) of discrepancies was encountered in categorizing the solidity of lesions, which may decrease the accuracy of measurements. Lung window settings may be superior to mediastinal windows for measuring lung ADCs, with comparable interobserver agreement and moderate accuracy for predicting pathologic invasive components.

Key points

Significant findings of the study

Lung window settings are better for evaluating part‐solid lung adenocarcinoma (ADC), with comparable interobserver agreement and moderate accuracy for predicting pathologic invasive components. The considerable percentage (25%) of discrepancies in categorizing solidity of the lesions may also have decreased the accuracy of measurements.

What this study adds

For accurate measurement and categorization of lung ADC, robust quantitative analysis is needed rather than a simple visual assessment.
Recognizing differentiating clinical signs of CLN3 disease (Batten disease) at presentation
Authors: Kuper Willemijn F. E. , Talsma Herman E. , van Schooneveld Mary J. , Pott Jan Willem R. , Huijgen Barbara C. H. , de Wit Gerard C. , van Hasselt Peter M. , van Genderen Maria M.
Published: October 2020

Purpose

To help differentiate CLN3 (Batten) disease, a devastating childhood metabolic disorder, from the similarly presenting early‐onset Stargardt disease (STGD1). Early clinical identification of children with CLN3 disease is essential for adequate referral, counselling and rehabilitation.

Methods

Medical chart review of 38 children who were referred to a specialized ophthalmological centre because of rapid vision loss. The patients were subsequently diagnosed with either CLN3 disease (18 patients) or early‐onset STGD1 (20 patients).

Results

Both children who were later diagnosed with CLN3 disease, as children who were later diagnosed with early‐onset STGD1, initially presented with visual acuity (VA) loss due to macular dystrophy at 5–10 years of age. VA in CLN3 disease decreased significantly faster than in STGD1 (p = 0.01). Colour vision was often already severely affected in CLN3 disease while unaffected or only mildly affected in STGD1. Optic disc pallor on fundoscopy and an abnormal nerve fibre layer on optical coherence tomography were common in CLN3 disease compared to generally unaffected in STGD1. In CLN3 disease, dark‐adapted (DA) full‐field electroretinogram (ERG) responses were either absent or electronegative. In early‐onset STGD1, DA ERG responses were generally unaffected. None of the STGD1 patients had an electronegative ERG.

Conclusion

Already upon presentation at the ophthalmologist, the retina in CLN3 disease is more extensively and more severely affected compared to the retina in early‐onset STGD1. This results in more rapid VA loss, severe colour vision abnormalities and abnormal DA ERG responses as the main differentiating early clinical features of CLN3 disease.
Frequency and coexistence of KRAS, NRAS, BRAF and PIK3CA mutations and occurrence of MMR deficiency in Danish colorectal cancer patients
Authors: Poulsen Tim Svenstrup , de Oliveira Douglas Vinicius Nogueira Perez , Espersen Maiken Lise Marcker , Klarskov Louise Laurberg , Skovrider‐Ruminski Wojciech , Hogdall Estrid
Published: October 2020

The MAPK signalling genes KRAS, NRAS and BRAF and the PIK3CA gene are routinely investigated for mutations in the diagnostic routine of colorectal cancer. Few studies have reported co‐existing mutations in these genes with clinical relevance, while some have been previously regarded as mutually exclusive. We set to investigate the frequency and co‐occurrent mutations in these targets, and the occurrence of mismatch repair deficiency (dMMR) in a large cohort of Danish colorectal cancers. 1000 colorectal tumours were sequenced as part of our diagnostic workflow for KRAS, NRAS, BRAF and PIK3CA mutations using next‐generation sequencing (NGS) and analysed by immunohistochemistry (IHC) for loss of the MMR proteins, MLH1, PMS2, MSH2 and MSH6. Co‐existing mutations in 12 patients (1.2%) occurred as multiple mutations in the same gene or spread across several genes (KRAS, NRAS and/or BRAF). The frequency of single mutations in the genes occurred with a frequency similar to previously reported, except for a higher frequency of BRAF mutations (18.0%). We found dMMR in 14.6% of the cases with a majority lacking expression of both MLH1 and PMS2. BRAF mutations were only present in dMMR cases involving MLH1 and/or PMS2. Our findings suggest that co‐existing mutations occur, except for the hotspot BRAF V600E, which is mutually exclusive with KRAS/NRAS mutations. Therefore, instead of single gene alterations from the MAPK signalling, assessing co‐occurrence of mutations within one or more of those genes should also be accounted. This may impact future oncological treatments and should be considered in the diagnostic workflow.
Culturally informed psychotherapy in Asian consultation‐liaison psychiatry
Authors: Della Constantine D. , Teo David Choon Liang , Agiananda Feranindhya , Nimnuan Chaichana
Published: October 2020

Psychotherapy provides substantial benefits for patients with medical illness. Western‐based psychotherapies are commonly practiced by consultation‐liaison psychiatrists in Asia. Although such interventions benefit Asian patients, they are limited by their cultural applicability. Sociocultural factors shape the meaning, expression, and treatment of medical illnesses. In helping patients with medical problems, it is imperative that psychiatrists be mindful of the value of culture in their clinical work. The concept of the self, religion, spirituality, adaptation, coping, and defense mechanisms are all culturally determined. This article discusses how these concepts impact the practice of psychotherapy in the Asian consultation‐liaison psychiatry setting. Currently, there is a dearth of systematic research about this subject matter. Most studies describe the application of Western‐based psychotherapies for patients with medical illness with little input as to cultural modifications or implications of such interventions. The authors of this article identify culturally consonant psychotherapeutic techniques in the Asian consultation‐liaison psychiatry context. Furthermore, they also propose general guidelines in the cultural adaptation of psychotherapy interventions or development of indigenous psychotherapies.
Rhodes University through Henri Lefebvre’s spatial triad: How do “Rhodians” experience Rhodes University as place through its visual culture?
Authors: Mtolo Siyathokoza
Published: October 2020

This paper is about how people experience places through the visuals that populate the place. I interviewed people who are part of Rhodes University in South Africa. It is the case that people experience places in a highly targeted manner and that from this manner they fashion ideas about the place.
Dose individualisation in oncology using chemotherapy‐induced neutropenia: Example of docetaxel in non‐small cell lung cancer patients
Authors: Lombard Aurélie , Mistry Hitesh , Aarons Leon , Ogungbenro Kayode
Published: October 2020

Aims

Chemotherapy‐induced neutropenia has been associated with an increase in overall survival in non‐small cell lung cancer patients. Therefore, neutrophil counts could be an interesting biomarker for drug efficacy as well as linked directly to toxicity. For drugs where neutropenia is dose limiting, neutrophil counts might be used for monitoring drug effect and for dosing optimisation.

Methods

The relationship between drug effect on the first cycle neutrophil counts and patient survival was explored in a Phase III clinical trial where patients with non‐small cell lung cancer were treated with docetaxel. Once the association has been established, dosing optimisation was performed for patients with severe toxicities (neutropenia) without compromising drug efficacy (overall survival).

Results

After taking into account baseline prognostic factors, such as Eastern Cooperative Oncology Group performance status, smoking status, liver metastasis, tumour burden, neutrophil counts and albumin levels, a model‐predicted drug effect on the first cycle neutrophil counts was strongly associated with patient survival (P = .005). Utilising this relationship in a dose optimisation algorithm, 194 out of 366 patients would have benefited from a dose reduction after the first cycle of docetaxel. The simulated 1‐year survival probabilities associated with the original dose and the individualised dose were not different.

Conclusion

The strong relationship between drug effect on the first cycle neutrophil counts and patient survival suggests that this variable could be used to individualise dosing, possibly without needing pharmacokinetic samples. The algorithm highlights that doses could be reduced in case of severe haematological toxicities without compromising drug efficacy.
Incidence of Parkinson’s disease, dementia, cerebrovascular disease and stroke in bipolar disorder compared to other psychiatric disorders: An electronic health records network study of 66 million people
Authors: Harrison Paul J. , Luciano Sierra
Published: October 2020

Objectives

Bipolar disorder has been associated with an increased risk for neurodegenerative diseases, but uncertainties remain. The risk relative to other psychiatric disorders is not established.

Methods

We used a federated electronic health records network of 66 million people including over 700,000 with bipolar disorder. We assessed incidence of a first diagnosis of Parkinson's disease, dementia, cerebrovascular disease and stroke, in patients at least 1 year after diagnosis of bipolar disorder. Rates were compared to propensity score matched cohorts of subjects with mixed disorders, recurrent major depressive disorder (MDD) or schizophrenia.

Results

Parkinson's disease was commoner in bipolar disorder compared to all three cohorts (odds ratios [OR] ranging from 1.26 to 2.65). Dementia incidence was greater in bipolar disorder than in mixed disorders (OR = 1.61) or MDD (OR = 1.40), but not different from schizophrenia (OR = 0.96). Cerebrovascular disease and stroke were commoner in bipolar disorder than in schizophrenia (OR = 1.35) or mixed disorders (OR = 1.20) and equivocally raised compared to MDD. Results were robust to a wide range of confounding demographic, diagnostic and medication risk factors for neurodegenerative disorders.

Conclusions

Bipolar disorder confers an elevated risk for developing neurodegenerative disorders and cerebrovascular disease compared to other major adult psychiatric disorders. The results cannot be attributed to recognised confounders. The results are consistent with neuroprogressive views of bipolar disorder. The underlying mechanisms remain to be discovered.
New multivariate tests for assessing covariate balance in matched observational studies
Authors: Chen Hao , Small Dylan S.
Published: October 2020

We propose new tests for assessing whether covariates in a treatment group and matched control group are balanced in observational studies. The tests exhibit high power under a wide range of multivariate alternatives, some of which existing tests have little power for. The asymptotic permutation null distributions of the proposed tests are studied and theP‐values calculated through the asymptotic results work well in simulation studies, facilitating the application of the test to large data sets. The tests are illustrated in a study of the effect of smoking on blood lead levels. The proposed tests are implemented in anRpackageBalanceCheck.
Treatment progress of foster care adolescents with severe behavioural problems: Factors conditioning their performance in the residential treatment centres
Authors: Sabaté‐Tomas Marta , Sala‐Roca Josefina , Arnau Laura
Published: October 2020

Behavioural problems are a recurring issue in the child welfare system population. Normative residential centres do not have the characteristics to address the specific needs of these adolescents, so they are usually treated at therapeutic residential centres. In Catalonia (Spain), these cases are treated in intensive educational residential centres (CREIs), a variant of therapeutic residential care (TRC) facilities. This exploratory study seeks to understand the treatment progress of adolescents with severe behavioural problems who were placed in the CREIs, a variant of TRC facilities. Data from 206 cases, the totality of population under treatment in the CREIs, were collected using a questionnaire administered to the treating team. A cross‐sectional design was used, applying quantitative methods to analyse the incidence and interrelation of a series of variables related to the progress of adolescents in the CREIs. Significant differences among profiles by sex, place of origin, criminal offences, substance abuse and mental health disorders were found. Furthermore, adolescents who performed a positive treatment progress according to the professional staff arrived at the CREI at an earlier age and had longer stays than the group with an unremarkable progress. Logistic regression indicated that duration of stay in the centre and runaways predict the adolescents' treatment progress. This treatment is working well with the milder cases; however, it does not tend to be successful for adolescents with greater difficulties. It is recommended that interventions focus on factors that engage the adolescents in their own rehabilitation process, include substance abuse programmes and consider the gender perspective.
Efficient energy consumption system using heuristic renewable demand energy optimization in smart city
Authors: Shu Ming , Wu Shizhong , Wu Tong , Qiao Zhonglin , Wang Nai , Xu Fei , Shanthini A. , Muthu Bala Anand
Published: October 2020

The rapid growth of urban development in recent years required reliable as well as realistic smart solutions to transport, system infrastructure, environmental conditions, and quality of life in smart cities. Furthermore, several innovative and comprehensive applications for smart cities are accessible through the Internet of Things that plays a significant role in reducing the utilization of energy requirements and other environmental effects. Based on the demands in reducing energy consumption, this article designed and developed a combined heat and power design based on the renewable energy system and energy storage system, which helps to minimize the utilization of energy consumption in smart cities. In these concerns, a standardized heuristic renewable demand energy optimization in the smart city (HRDEOSC) architecture is presented, where the smart area domain is distributed into a wide area network. In comparison with the overall domestic energy consumption of electricity and transport, the energy demand for desalination processes is very small and it has been achieved by HRDEOSC. Here, the designed computational model demonstrate that the developed system contributes significantly to our challenges and proved to be an economical approach for the development of the smart structural design which helps to reduce the energy consumption of smart cities.
Self‐Regulation Deficiency in Predicting Problematic Use of Mobile Social Networking Apps: The Role of Media Dependency*
Authors: Liu Zilong , Lin Xiaolin , Wang Xuequn , Wang Tianhua
Published: October 2020

The problematic use of mobile social networking apps (SNAs) is an increasing issue in various places where people live and work. For example, employees’ use of mobile SNAs at work can result in significant loss of productivity. The literature has mainly focused on the etiology of problematic behavior with a focus on human psychological characteristics, whereas few studies have examined the role of technology media and problematic behavior. By integrating self‐regulation deficiency and media system dependency, this study investigates the drivers of problematic use of mobile SNAs by exploring users’ self‐regulation deficiency and its antecedents from a media dependency perspective. Data were collected from Chinese mobile SNA users via longitudinal surveys. The results show that self‐ and social‐oriented SNA dependency positively affect cognitive preoccupation and perceived irreplaceability, which in turn lead to users’ problematic use. We also compare the effect of SNA dependency across genders in the post‐hoc analysis. In the female group, self‐ and social‐oriented SNA dependency influenced problematic use through cognitive preoccupation and perceived irreplaceability. In the male group, self‐ and social‐oriented SNA dependency influenced problematic use only through their cognitive preoccupation. Implications for theory and practice are discussed.
Efficacy and safety of once‐weekly semaglutide versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30‐week, double‐blind, phase 3a, randomized trial
Authors: Ji Linong , Dong Xiaolin , Li Yiming , Li Yufeng , Lim Soo , Liu Ming , Ning Zu , Rasmussen Søren , Skjøth Trine Vang , Yuan Guoyue , Eliaschewitz Freddy G.
Published: October 2020

Aim

To evaluate the efficacy and safety of once‐weekly subcutaneous semaglutide, a glucagon‐like peptide‐1 (GLP‐1) analogue, versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes (T2D) in a multiregional clinical trial.

Materials and Methods

In the 30‐week, randomized, double‐blind, double‐dummy, active comparator SUSTAIN China trial, 868 adults with T2D inadequately controlled on metformin (HbA1c 7.0%‐10.5%) were randomized to receive once‐weekly semaglutide 0.5 mg (n = 288), semaglutide 1.0 mg (n = 290) or once‐daily sitagliptin 100 mg (n = 290). The primary and confirmatory secondary endpoints were change from baseline to week 30 in HbA1c and body weight, respectively.

Results

The trial enrolled ~70% (605/868) of the patients in China, and the remaining patients from four other countries, including the Republic of Korea. Both doses of semaglutide were superior to sitagliptin in reducing HbA1c and body weight after 30 weeks of treatment. The odds of achieving target HbA1c of less than 7.0% (53 mmol/mol), weight loss of 5% or higher, or 10% or higher, and the composite endpoint of HbA1c less than 7.0% (53 mmol/mol) without severe or blood glucose‐confirmed symptomatic hypoglycaemia no weight gain, were all significantly higher with both semaglutide doses compared with sitagliptin. The safety profile for semaglutide was consistent with the known class effects of GLP‐1 receptor agonists (RAs). Consistent efficacy and safety findings were seen in the Chinese subpopulation.

Conclusions

Once‐weekly semaglutide was superior to sitagliptin in improving glycaemic control and reducing body weight in patients with T2D inadequately controlled on metformin. The safety and tolerability profiles were consistent with those of semaglutide and other GLP‐1 RAs. Semaglutide is an effective once‐weekly treatment option for the Chinese population.
COST PASS‐THROUGH IN COMMERCIAL AVIATION: THEORY AND EVIDENCE
Authors: Gayle Philip G. , Lin Ying
Published: October 2020

The significant worldwide decline in crude oil price beginning in mid‐2014 through to 2015, which resulted in substantial fuel expense reductions for airlines, but no apparent commensurate reductions in industry average airfares has caused much public debate. This paper examines the market mechanisms through which crude oil price may influence airfare. Interestingly, and new, our analysis reveals that the crude oil price‐airfare pass‐through relationship can be either positive or negative, depending on various market and airline‐specific characteristics. We find evidence that airline‐specific jet fuel hedging strategy and market origin–destination distance contribute significantly to pass‐through rates being negative. (JEL L93, L13, Q40)
Increased susceptibility to acoustic trauma in a mouse model of non‐syndromic sensorineural deafness, DFNB91
Authors: Tan Justin , Kaiserman Dion , O'Leary Stephen J. , Bird Phillip I.
Published: October 2020

Inactivating mutations of SERPINB6 in humans result in progressive hearing loss starting in early adulthood (DFNB91). We have previously shown that C57BL/6J mice lacking the orthologous gene, Serpinb6a, exhibit progressive hearing loss, which is associated with progressive loss of distinct cell types in the organ of Corti beginning with outer hair cells (OHCs). However, deafness in these animals occurs much earlier than expected, possibly because C57BL/6J mice also carry an age‐related hearing loss mutation in the cadherin 23 gene (Cdh23ahl) that causes late onset hearing loss. The CBA/CaH strain of mice does not carry Cdh23ah/ahl and may represent a better model of the human DFNB91 patients. Here, we show that transfer of the mutant Serpinb6a allele onto the Cdh23 normal CBA/CaH background markedly delays onset of hearing loss, more closely phenocopying DFNB91, without altering the pattern of cellular loss. Young, pre‐symptomatic mice of this genotype exposed to acoustic trauma exhibit permanent hearing loss, compared to controls, associated with the disappearance of OHCs. We conclude that Serpinb6 helps to maintain hearing by protecting hair cells from stress.
Gadamer's Phenomenological Ethics
Authors: DaVia Carlo
Published: October 2020

Hans‐Georg Gadamer held that the chief task of philosophy today is to defend practical reason against the encroachments of techno‐scientific rationality and thereby to ground the possibility for a philosophical ethics. Although this is well‐known and much discussed in the secondary literature, there is curiously sparse discussion of just what Gadamer took ethical inquiry to be. The little discussion that exists tends either to neglect Gadamer's distinction between practical reasoning and philosophical ethics, or it accuses Gadamer himself of conflating the two. This paper provides a sketch of Gadamer's understanding of ethics in a way that makes clear how it differs from practical reasoning.
Fretting‐fatigue analysis of shot‐peened aluminium and titanium test specimens
Authors: Vantadori Sabrina , Zanichelli Andrea
Published: October 2020

In the last decades, many alleviation measures were proposed in order to improve the life of fretting fatigue‐affected components. In such a context, the shot peening treatment is worth noting. Therefore, in the present paper, the fatigue life of shot‐peened aluminium and titanium alloy specimens, subject to fretting fatigue under partial slip regime, is assessed by means of the Carpinteri et al. criterion for fretting fatigue. First, according to the superposition principle, the relaxed residual stresses (due to the shot peening treatment) are combined with the stress components due to fretting fatigue loading. Then fretting fatigue assessment is performed. In such a context, a novel theoretical law for the relaxed residual stress field is here proposed, the implementation of which shows very promising results in terms of fretting fatigue life estimation of the shot‐peened specimens examined.
Beyond ecosystem modeling: A roadmap to community cyberinfrastructure for ecological data‐model integration
Authors: Fer Istem , Gardella Anthony K. , Shiklomanov Alexey N. , Campbell Eleanor E. , Cowdery Elizabeth M. , De Kauwe Martin G. , Desai Ankur , Duveneck Matthew J. , Fisher Joshua B. , Haynes Katherine D. , Hoffman Forrest M. , Johnston Miriam R. , Kooper Rob , LeBauer David S. , Mantooth Joshua , Parton William J. , Poulter Benjamin , Quaife Tristan , Raiho Ann , Schaefer Kevin , Serbin Shawn P. , Simkins James , Wilcox Kevin R. , Viskari Toni , Dietze Michael C.
Published: October 2020

In an era of rapid global change, our ability to understand and predict Earth's natural systems is lagging behind our ability to monitor and measure changes in the biosphere. Bottlenecks to informing models with observations have reduced our capacity to fully exploit the growing volume and variety of available data. Here, we take a critical look at the information infrastructure that connects ecosystem modeling and measurement efforts, and propose a roadmap to community cyberinfrastructure development that can reduce the divisions between empirical research and modeling and accelerate the pace of discovery. A new era of data‐model integration requires investment in accessible, scalable, and transparent tools that integrate the expertise of the whole community, including both modelers and empiricists. This roadmap focuses on five key opportunities for community tools: the underlying foundations of community cyberinfrastructure; data ingest; calibration of models to data; model‐data benchmarking; and data assimilation and ecological forecasting. This community‐driven approach is a key to meeting the pressing needs of science and society in the 21st century.
Handling missing values in trait data
Authors: Johnson Thomas F. , Isaac Nick J. B. , Paviolo Agustin , González‐Suárez Manuela
Published: October 2020

Aim

Trait data are widely used in ecological and evolutionary phylogenetic comparative studies, but often values are not available for all species of interest. Traditionally, researchers have excluded species without data from analyses, but estimation of missing values using imputation has been proposed as a better approach. However, imputation methods have largely been designed for randomly missing data, whereas trait data are often not missing at random (e.g., more data for bigger species). Here, we evaluate the performance of approaches for handling missing values when considering biased datasets.

Location

Any.

Time period

Any.

Major taxa studied

Any.

Methods

We simulated continuous traits and separate response variables to test the performance of nine imputation methods and complete‐case analysis (excluding missing values from the dataset) under biased missing data scenarios. We characterized performance by estimating the error in imputed trait values (deviation from the true value) and inferred trait–response relationships (deviation from the true relationship between a trait and response).

Results

Generally, Rphylopars imputation produced the most accurate estimate of missing values and best preserved the response–trait slope. However, estimates of missing data were still inaccurate, even with only 5% of values missing. Under severe biases, errors were high with every approach. Imputation was not always the best option, with complete‐case analysis frequently outperforming Mice imputation and, to a lesser degree, BHPMF imputation. Mice, a popular approach, performed poorly when the response variable was excluded from the imputation model.

Main conclusions

Imputation can handle missing data effectively in some conditions but is not always the best solution. None of the methods we tested could deal effectively with severe biases, which can be common in trait datasets. We recommend rigorous data checking for biases before and after imputation and propose variables that can assist researchers working with incomplete datasets to detect data biases and minimize errors.
Modification of pork‐skin jelly by enzymatic cross‐linking: melting resistance and quality improvement
Authors: Liu Qiong , Zhang Min , Bhandari Bhesh , Yang Chaohui
Published: October 2020

Improvements of melting resistance and quality by modification of pork‐skin jelly through enzymatic cross‐linking were studied, and the mechanism of quality improvement was discussed in this work. Gel strength, springiness and chewiness of modified gel increased significantly (P < 0.05). Transglutaminase (TGase) also improved the viscoelasticity, stability and melting resistance of gel system, as proved by rheological analysis. Sensory evaluation showed that increase in texture need to be moderate and the utilisation of 0.6% TGase was the most appropriate for pork‐skin jelly. Significant effects of TGase on inducing protein cross‐link and aggregation were confirmed by determining rheology during enzyme treatment and cross‐linking extent of pork‐skin soup. Correlation analysis showed TGase could improve melting temperature and texture by facilitating cross‐linking. Covalent interaction based on ε‐(γ‐glutamyl)‐lysine induced by TGase could play the main role in these improvements. This study suggested that TGase could be applied to design gelatin‐based food for tailored quality properties through enzymatic cross‐linking.
Small carnivorans, museums and zoos
Authors: Kitchener A. C.
Published: October 2020

Small carnivorans are generally poorly represented in zoos, probably because they are small, mostly nocturnal and solitary hunters. However, there is limited knowledge about the ecology and behaviour of a large number of these and many species are threatened with extinction or their conservation status is poorly known or even unknown. Although rare in zoos, there are good opportunities for zoos and museums to cooperate to ensure that when animals die, they are subjected to careful post‐mortem examinations, and preserved for research into anatomy and functional morphology. In turn museum collections are rich stores of specimens that assist zoos in identification, and provide veterinarians with access to animal remains and their anatomy to facilitate treatment and surgery. New techniques, such as computerized tomography (CT) and magnetic resonance imaging (MRI) scanning, plus the establishment of biobanks allow new ways of capturing vital information about small carnivorans for a wide range of research, including taxonomy and systematics, archaeology and palaeontology, anatomy, pathology and conservation science. Most importantly museum collections of zoo specimens allow the impacts of captivity, such as diet and activity levels, to be investigated. However, the development of this research resource relies on closer cooperation between zoos and museums. As wild and captive populations are increasingly managed under the International Union for Conservation of Nature’s Conservation Planning Specialist Group One Plan approach, it will also be increasingly important for zoos and museums to work together to benefit the conservation of threatened small carnivorans.
Perceptions of the rights and capabilities of people with intellectual disability in the United States
Authors: McConkey Roy , Slater Paul , Smith Ashlyn , Dubois Lindsay , Shellard Amy
Published: October 2020

Background

The United States has yet to ratify the UN Convention on the Rights of Persons with Disabilities. The extent of public support in the United States for the rights of persons with intellectual disability is not known.

Methods

Online public opinion polls were conducted nationally and in eight selected cities in 2017 and repeated in 2018 with 26,876 respondents in total.

Results

Support for rights was high: notably in accessing healthcare, schooling, playing sports and getting married. However, less support was evident for the rights of people who were perceived as less capable. Respondents with prior frequent personal contact and who had an engagement with Special Olympics were those most likely to support the rights and capabilities of persons with intellectual disability.

Conclusions

Public support for the ratification of the UN Convention seems likely. Further longitudinal research could identify successful strategies for implementing the rights of disabled persons locally and nationally.
EBV–encoded miRNAs can sensitize nasopharyngeal carcinoma to chemotherapeutic drugs by targeting BRCA1
Authors: Lung Raymond Wai‐Ming , Tong Joanna Hung‐Man , Ip Lok‐Man , Lam Ka‐Hei , Chan Anthony Wing‐Hung , Chak Wing‐Po , Chung Lau‐Ying , Yeung Walter Wai , Hau Pok‐Man , Chau Shuk‐Ling , Tsao Sai‐Wah , Lau Kin‐Mang , Lo Kwok‐Wai , To Ka‐Fai
Published: October 2020

Nasopharyngeal carcinoma (NPC) is an Epstein‐Barr virus (EBV)‐associated epithelial malignancy. The high expression of BART‐miRNAs (miR‐BARTs) during latent EBV infection in NPC strongly supports their pathological importance in cancer progression. Recently, we found that several BART‐miRNAs work co‐operatively to modulate the DNA damage response (DDR) by reducing Ataxia‐telangiectasia‐mutated (ATM) activity. In this study, we further investigated the role of miR‐BARTs on DDR. The immunohistochemical study showed that the DNA repair gene, BRCA1, is consistently down‐regulated in primary NPCs. Using computer prediction programs and a series of reporter assays, we subsequently identified the negative regulatory role of BART2‐3p, BART12, BART17‐5p and BART19‐3p in BRCA1 expression. The ectopic expression of these four miR‐BARTs suppressed endogenous BRCA1 expression in EBV‐negative epithelial cell lines, whereas BRCA1 expression was enhanced by repressing endogenous miR‐BARTs activities in C666‐1 cells. More importantly, suppressing BRCA1 expression in nasopharyngeal epithelial cell lines using miR‐BART17‐5p and miR‐BART19‐3p mimics reduced the DNA repair capability and increased the cell sensitivity to the DNA‐damaging chemotherapeutic drugs, cisplatin and doxorubicin. Our findings suggest that miR‐BARTs play a novel role in DDR and may facilitate the development of effective NPC therapies.
Simple risk score to screen for prediabetes: A cross‐sectional study from the Qatar Biobank cohort
Authors: Abbas Mostafa , Mall Raghvendra , Errafii Khaoula , Lattab Abdelkader , Ullah Ehsan , Bensmail Halima , Arredouani Abdelilah
Published: October 2020

Aims/Introduction

The progression from prediabetes to type 2 diabetes is preventable by lifestyle intervention and/or pharmacotherapy in a large fraction of individuals with prediabetes. Our objective was to develop a risk score to screen for prediabetes in the Middle East, where diabetes prevalence is one of the highest in the world.

Materials and Methods

In this cross‐sectional, case–control study, we used data of 4,895 controls and 2,373 prediabetic adults obtained from the Qatar Biobank cohort. Significant risk factors were identified by logistic regression and other machine learning methods. The receiver operating characteristic was used to calculate the area under curve, cut‐off point, sensitivity, specificity, positive and negative predictive values. The prediabetes risk score was developed from data of Qatari citizens, as well as long‐term (≥15 years) residents.

Results

The significant risk factors for the Prediabetes Risk Score in Qatar were age, sex, body mass index, waist circumference and blood pressure. The risk score ranges from 0 to 45. The area under the curve of the score was 80% (95% confidence interval 78–83%), and the cut‐off point of 16 yielded sensitivity and specificity of 86.2% (95% confidence interval 82.7–89.2%) and 57.9% (95% confidence interval 65.5–71.4%), respectively. Prediabetes Risk Score in Qatar performed equally in Qatari nationals and long‐term residents.

Conclusions

Prediabetes Risk Score in Qatar is the first prediabetes screening score developed in a Middle Eastern population. It only uses risk factors measured non‐invasively, is simple, cost‐effective, and can be easily understood by the general public and health providers. Prediabetes Risk Score in Qatar is an important tool for early detection of prediabetes, and can help tremendously in curbing the diabetes epidemic in the region.