bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into the involvement of spliceosomal mutations in myelodysplastic disorders from an analysis of SACY-1/DDX41 inCaenorhabditis elegans
Authors: Tsukamoto Tatsuya , Gearhart Micah D. , Kim Seongseop , Mekonnen Gemechu , Spike Caroline A. , Greenstein David
Published: December 2019

Mutations affecting spliceosomal proteins are frequently found in hematological malignancies, including myelodysplastic syndromes and acute myeloid leukemia. DDX41/Abstrakt is a metazoan-specific spliceosomal DEAD-box RNA helicase found to be recurrently mutated in inherited myelodysplastic syndromes and in relapsing cases of acute myeloid leukemia. The genetic properties and genomic impacts of disease-causing missense mutations in DDX41 and other spliceosomal proteins have been uncertain. Here we conduct a comprehensive molecular genetic analysis of theC. elegansDDX41 ortholog, SACY-1. Our results reveal general essential functions for SACY-1 in both the germline and the soma, as well as specific functions affecting germline sex determination and cell cycle control. Certainsacy-1/DDX41mutations, including the R525H human oncogenic variant, confer antimorphic activity, suggesting that they compromise the function of the spliceosome. Consistent with these findings,sacy-1exhibits synthetic lethal interactions with several spliceosomal components, and biochemical analyses suggest that SACY-1 is a component of theC. elegansspliceosome. We used the auxin-inducible degradation system to analyze the impact of SACY-1 on the transcriptome using RNA sequencing. SACY-1 depletion impacts the transcriptome through splicing-independent and splicing-dependent mechanisms. The observed transcriptome changes suggest that disruption of spliceosomal function induces a stress response. Altered 3’ splice site usage represents the predominant splicing defect observed upon SACY-1 depletion, consistent with a role for SACY-1 as a second-step splicing factor. Missplicing events appear more prevalent in the soma than the germline, suggesting that surveillance mechanisms protect the germline from aberrant splicing.

Author Summary

Mutations affecting spliceosomal proteins are frequently found in hematological malignancies. DDX41/Abstrakt is a metazoan-specific spliceosomal DEAD-box RNA helicase recurrently mutated in inherited and relapsing myelodysplastic syndromes and acute myeloid leukemia. The genetic properties and genomic impacts of disease-causing mutations in spliceosomal proteins have been uncertain. Here we conduct a comprehensive molecular genetic analysis of theC. elegansDDX41 ortholog, SACY-1. Our results reveal that multiplesacy-1/DDX41missense mutations, including the R525H human oncogenic variant, exhibit antimorphic activity that likely compromises the function of the spliceosome. The genomic consequences of SACY-1 depletion include splicing-splicing-independent and splicing-dependent alterations in the transcriptome.
Crystal engineering of exemestane to obtain a co-crystal with enhanced urease inhibition activity
Authors: Fatima Syeda Saima , Kumar Rajesh , Choudhary M. Iqbal , Yousuf Sammer
Published: December 2019

Co-crystallization is a phenomenon widely employed to enhance the physio-chemical and biological properties of active pharmaceutical ingredients (APIs). Exemestane, or 6-methylideneandrosta-1,4-diene-3,17-dione, is an anabolic steroid used as an irreversible steroidal aromatase inhibitor, which is in clinical use to treat breast cancer. The present study deals with the synthesis of co-crystals of exemestane with thiourea by liquid-assisted grinding. The purity and homogeneity of the exemestane–thiourea (1:1) co-crystal were confirmed by single-crystal X-ray diffraction followed by thermal stability analysis on the basis of differential scanning calorimetry and thermogravimetric analysis. Detailed geometric analysis of the co-crystal demonstrated that a 1:1 co-crystal stoichiometry is sustained by N—H...O hydrogen bonding between the amine (NH2) groups of thiourea and the carbonyl group of exemestane. The synthesized co-crystal exhibited potent urease inhibition activity in vitro (IC50 = 3.86 ± 0.31 µg ml−1) compared with the API (exemestane), which was found to be inactive, and the co-former (thiourea) (IC50 = 21.0 ± 1.25 µg ml−1), which is also an established tested standard for urease inhibition assays in vitro. The promising results of the present study highlight the significance of co-crystallization as a crystal engineering tool to improve the efficacy of pharmaceutical ingredients. Furthermore, the role of various hydrogen bonds in the crystal stability is successfully analysed quantitatively using Hirshfeld surface analysis.
Supply chain risk mitigation in South Africa: a case study of Eskom
Authors: Jonathan Ellsworth Chouncey , Mafini Chengedzai , Bhadury Joyendu
Published: December 2019

Purpose

Interferences to supply chains (SC), regardless of whether they are regular, unplanned or intentional, are progressively distorting SC execution. As such, risk mitigation in SCs has received sufficient attention in the academic literature. However, there is scant research done on this topic within the African context, and none on the SC of electrical energy on that continent. In an effort to address this gap, the purpose of this paper is to focus on the SC department of Eskom, the primary utility company of South Africa and one of the largest on the continent.

Design/methodology/approach

Adopting a non-probability sampling approach utilising the purposive sampling technique to choose the sampling components from the target population, data were collected through semi-structured interviews as well as additional documentation in various forms. Data interpretation and codification thereof were done using ATLAS.ti 8 from which ten themes emerged.

Findings

The ten themes that emerged from the analysis of data show that SC risks emanate from value streams, information and affiliations, SC activities and external situations. Furthermore, these are brought into relief within the African context through examples and quotes from Eskom managers.

Research limitations/implications

Based on the findings, the paper makes five major recommendations that would broadly apply not only to SC risk management (SCRM) in Eskom, but also other African utility companies.

Practical implications

Companies in emerging economies such as South Africa and other Sub-Saharan countries face a unique set of challenges with regards to SCRM. Some of these are identified in this paper and appropriate recommendations have been made.

Social implications

Being the largest utility provider in Africa, services offered by Eskom are vital for economic development of South Africa as well as neighbouring countries. As such, the findings of this paper as well as the recommendations have social implications for economic development in that country as well as the region.

Originality/value

While SC risk management has been studied extensively in the academic literature, to the best of the authors’ knowledge, this is the first paper that attempts to study it within the context of South Africa with focal emphasis on one of the largest corporations in that country.
Economic empowerment of Iranian women through the internet
Authors: Golzard Vahideh
Published: December 2019

Purpose

This paper aims to explore the extent to which the internet has created new opportunities for Iranian women in Tehran. It analyses both challenges and opportunities offered to Iranian women by the internet as a means of economic empowerment.

Design/methodology/approach

This paper adopts a qualitative approach and based on 13 semi-structured interviews with female internet users between the ages of 20 and 55 years. The qualitative data was collected through open-ended questions in face-to-face interviews. This study uses ethnography as a research tool to explore the question of whether the internet has made a difference in the economic lives of Iranian women.

Findings

Result reveals that the internet and working online have significant impact on the economic lives of Tehrani women by enabling them to engage in new forms of online business. This technology is being used for online advertising to attract more clients, to establish business contacts with peers and to manage households positively.

Research limitations/implications

The result of the research cannot be regarded as applicable to all women in Iran, as the opportunity to access online economic activities is only available to those women who are highly trained and well-educated. In addition, the result of the research may not reflect the barriers that women from different social classes and ethnic groups have faced in the achievement of economic empowerment online.

Practical implications

The study highlights that due to a generally lack of computer proficiency, women in these areas are unable to effectively maximise their participation in the online economic sphere. This barrier must be removed by enhancing women’s computer literacy and ICT (information, communication and technologies) and establishing development networking programme centres for internet skills training.

Originality/value

The internet has created opportunity for Iranian women to expand their participation in the online economic sphere. However, research in the field of online economic activities in Iran, especially concerning women working online, is scant. The key contribution of this paper is to fill the gap in this area of study, in particular offering insights into the ways in which women use the internet to overcome the boundaries of physical space and become empowered.
A model for promoting student participation in school governance
Authors: Cheng Eric C.K. , Leung Yan Wing , Yuen Wai Wa , Tang Hei Hang Hayes
Published: December 2019

Purpose

The purpose of this paper is to highlight the urgent need for a genuinely effective and attainable citizenship education model in Hong Kong’s schools, which focusses on promoting student participation in school governance. It is an empirical citizenship education management model for school leaders that illustrates the predictive effects of personally responsible, participatory, justice-oriented and patriotic citizenship, necessarily supported by school management practices, school ethos and teacher beliefs.

Design/methodology/approach

A total of 3,209 students from 51 secondary schools in Hong Kong participated in a quasi-experimental design questionnaire survey. A structural equation model (SEM) was applied to confirm the model.

Findings

The results of the SEM show that the values and cultural practices held by a school’s teachers drive the implementation of its citizenship education. Moreover, it is well known that organizational values can exert a powerful influence and it is the same within educational structures: management practices in schools have an impact on ethos, teachers’ beliefs and student participation in school governance.

Practical implications

The paper provides practical proposals for school leaders to create opportunities for student participation in school governance.

Originality/value

This study builds on existing literature and provides school leaders with a practical model for implementing student participation in school governance.
Examining the impact of perceived source credibility on attitudes and intentions towards taking advice from others on university choice
Authors: Wong Phoebe , Ng Peggy M.L. , Lee Daisy , Lam Regan
Published: December 2019

Purpose

Understanding the influences in the decision-making process of prospective students when choosing a university is crucial in student recruitment. The purpose of this paper is to investigate the impact of perceived source credibility on attitudes and intentions towards taking advice from significant others (e.g. parents, peers and teachers) on university choice.

Design/methodology/approach

In total, 626 samples from eight government-subsidised secondary schools were collected and tested using the component-based structural equation modelling of partial least squares.

Findings

The findings verified factors of source credibility that determine prospective students’ attitudes towards taking advice from others. Attitudes and subjective norms explained 49 per cent of the variance in intention to take advice from others on university choice. The findings of the present study provide practical marketing insights for enrolment and recruitment managers.

Originality/value

While most studies focus on students’ university choice in the recruitment process, studies on perceived source credibility of significant others in the university choice decision-making process are limited.
Fair-weather liberals and loyal conservatives
Authors: Soderberg Andrew T. , Zhang Teng , Lytle Brad
Published: December 2019

Purpose

Drawing on moral foundations theory, this paper aims to investigate the moral component of loyalty, a critical determinant of long-term organisational success.

Design/methodology/approach

This paper contains two studies using archival data gathered from the Major League Baseball and the National Basketball Association in the USA.

Findings

This paper finds empirical support for the “ideology-loyalty hypothesis” – namely, fans in more politically conservative communities are more loyal to their professional sports teams than those in more liberal ones.

Originality/value

These findings contribute to a growing literature on the moral roots of organisational phenomena by providing evidence of community-level effects of political ideology on loyalty. Based on these findings, this paper suggests that when making strategic decisions (e.g. expansion into a new market), organisations need to pay attention to the political climate of the communities in which they operate (or intend to operate) to achieve and sustain organisational success.
Design, fabrication and characterization of LTCC micro-hotplates for gas-sensing application
Authors: Kulhari Lokesh , Chandran Achu , Ray Kanad , Khanna P.K.
Published: December 2019

Purpose

Low temperature co-fired ceramics (LTCC) technology-based micro-hotplates are of immense interest owing to their ruggedness, high temperature stability and reliability. The purpose of this paper is to study the role of thermal mass of LTCC-based micro-hotplates on the power consumption and temperature for gas-sensing applications.

Design/methodology/approach

The LTCC micro-hotplates with different thicknesses are designed and fabricated. The role of thermal mass on power consumption and temperature of these hotplates are simulated and experimentally studied. Also, a comparison study on the performance of LTCC and alumina-based hotplates of equivalent thickness is done. A thick film-sensing layer of tin oxide is coated on LTCC micro-hotplate and demonstrated for the sensing of commercial liquefied petroleum gas.

Findings

It is found from both simulation and experimental studies that the power consumption of LTCC hotplates was decreasing with the decrease in thermal mass to attain the same temperature. Also, the LTCC hotplates are less power-consuming than alumina-based one, owing to their superior thermal characteristics (low thermal conductivity, 3.3 W/ [m-K]).

Originality/value

This study will be beneficial for designing hotplates based on LTCC technology with low power consumption and better stability for gas-sensing applications.
Analysis of haemodynamics and angiogenic response to ischaemia in the obese type 2 diabetic model Spontaneously Diabetic Torii Leprfa (SDT fatty) rats
Authors: Murai Yasutaka , Sasase Tomohiko , Tadaki Hironobu , Heitaku Shiro , Imagawa Naoya , Yamada Takahisa , Ohta Takeshi
Published: December 2019

Peripheral artery disease (PAD) is defined as peripheral blood flow impairment, especially in the legs, caused by atherosclerotic stenosis. The disease decreases quality of life because of intermittent claudication or necrosis of the leg. The hindlimb ischaemia model, in which ischaemia is induced by femoral artery ligation, is often utilized as a PAD model. In the hindlimb ischaemia model, nonmetabolic syndrome animals are mainly used. In this study, we investigated the usefulness of Spontaneously Diabetic Torii Leprfa (SDT fatty) rats, a new model for obese type 2 diabetes, as a new PAD animal model. We found that hindlimb blood flow in SDT fatty rats was significantly lower than that in Sprague–Dawley (SD) rats under nonischaemic conditions. Furthermore, SDT fatty rats showed a significantly higher plasma nitrogen oxide level, shorter prothrombin time, and shorter activated partial thromboplastin time than SD rats. In addition, we found that the change in blood flow 7 days after induction of hindlimb ischaemia and the number of Von Willebrand factor‐positive vessels in gastrocnemius muscles were significantly lower in SDT fatty rats than in SD rats. These results suggest that excess production of reactive oxygen species and coagulation activation could be involved in lower blood flow in non‐ischaemic rats and that decreased angiogenesis could be involved in the poor recovery of blood flow in SDT fatty rats with hindlimb ischaemia. Taken together, our results suggest that SDT fatty rats might be useful as a new model for PAD with metabolic syndrome.
Postmortem Diagnosis of Fatal Hypothermia by Fourier Transform Infrared Spectroscopic Analysis of Edema Fluid in Formalin‐Fixed, Paraffin‐Embedded Lung Tissues
Authors: Lin Hancheng , Guo Xiangshen , Luo Yiwen , Chen Yijiu , Zhao Rui , Guan Dawei , Wang Zhenyuan , Huang Ping
Published: December 2019

The goal of this study was to investigate whether pulmonary edema could become a specific diagnostic marker for fatal hypothermia using Fourier transform infrared (FTIR) spectroscopy in combination with chemometrics. The spectral profile analysis indicated that hypothermia fatalities associated with pulmonary edema fluid contained more β‐sheet protein conformational structures than the control causes of death, which included sudden cardiac death, brain injury, cerebrovascular disease, mechanical asphyxiation, intoxication, and drowning. Subsequently, the results of principal component analysis (PCA) further revealed that the content of β‐sheet protein conformational structures in the pulmonary edema fluid was the main discriminatory marker between fatal hypothermia and the other causes of death. Ultimately, a robust postmortem diagnostic model for fatal hypothermia using a partial least‐squares discriminant analysis (PLS‐DA) algorithm was constructed. Pulmonary edema fluid spectra collected from eight new forensic autopsy cases that did not participate in the construction of the diagnostic model were predicted using the model. The results showed the causes of death of all these eight cases were correctly classified. In conclusion, this preliminary study demonstrates that FTIR spectroscopy in combination with chemometrics could be a promising approach for the postmortem diagnosis of fatal hypothermia.
Improving emergency department transfer for patients arriving by ambulance: A retrospective observational study
Authors: Crilly Julia , Johnston Amy NB , Wallis Marianne , O'Dwyer John , Byrnes Joshua , Scuffham Paul , Zhang Ping , Bosley Emma , Chaboyer Wendy , Green David
Published: December 2019

Objective

Extended delays in the transfer of patients from ambulance to ED can compromise patient flow. The present study aimed to describe the relationship between the use of an Emergency Department Ambulance Off‐Load Nurse (EDAOLN) role, ED processes of care and cost effectiveness.

Methods

This was a retrospective observational study over three periods of before (T1), during (T2) and after (T3) the introduction of the EDAOLN role in 2012. Ambulance, ED and cost data were linked and used for analysis. Processes of care measures analysed included: time to be seen by a doctor from ED arrival (primary outcome), ambulance‐ED offload compliance, proportion of patients seen within recommended triage timeframe, ED length of stay (LoS), proportion of patients transferred, admitted or discharged from the ED within 4 h and cost effectiveness.

Results

A total of 6045 people made 7010 presentations to the ED by ambulance over the study period. Several measures improved significantly between T1 and T2 including offload compliance (T1: 58%; T2: 63%), time to be seen (T1: 31 min; T2: 28 min), ED LoS (T1: 335 min; T2: 306 min), ED LoS <4 h (T1: 31%; T2: 33%). Some measures carried over into T3, albeit to a lesser extent. Post‐hoc analyses showed that outcomes improved most for less urgent patients. The annualised net cost of the EDAOLN (if funded from additional resources) of $130 721 could result in an annualised reduction of approximately 3912 h in waiting time to be seen by a doctor.

Conclusion

With the EDAOLN role in place, slight outcome improvements in several key ambulance and ED efficiency criteria were noted. During times of ED crowding, the EDAOLN role may be one cost‐effective strategy to consider.
Purification of the Cry1Ac protein of Bacillus thuringiensis and assessment against the Plutella xylostella and soil microbial community
Authors: Jung Young Jun , Yoo Su‐Hyang , Choi Wonkyun , Lee Jung Ro , Moon Jeong Chan
Published: December 2019

The insecticidal toxin gene of Bacillus thuringiensis (Bt) is the most commonly used to develop insect‐resistant living modified organisms (LMOs). Insecticidal proteins produced in transgenic plants are released into the soil from the roots. In this study, possible effects of crystal 1Ac (Cry1Ac) protein on the soil microbial community in Korea were studied. To purify the insoluble Cry1Ac protein expressing Escherichia coli cells, we performed repeated sonication and PBS washing of the insoluble part and Cry1Ac protein was isolated in soluble form from the insoluble form using 100 mM Na2CO3 buffer (pH 9.6) without affinity bead. Also, size‐exclusion chromatography (SEC) was performed to increase the purity of the isolated Cry1Ac protein. The final protein product was identified as Cry1Ac protein through MALDI‐TOF. Insecticidal activity of Cry1Ac protein was demonstrated through the death of Plutella xylostella treated with Cry1Ac protein. Purely isolated Cry1Ac protein showed the same insecticidal activity as Cry1Ac expressed in LM crops. To investigate the change of soil microbial distribution using maize field soils treated with Cry1Ac protein, we isolated high quality metagenomic DNAs from buffer‐ and Cry1Ac protein‐treated soil groups, and analyzed the distribution of soil microorganisms through next‐generation sequencing (NGS) analysis. NGS results showed a similar microbial distribution in both buffer‐ and Cry1Ac protein‐treated samples. These results suggest a useful risk assessment method for domestic targeted insect and soil microorganisms using the Cry1Ac protein.
Effect of pretreatment with paste and sauce extract made using Tenebrio molitor larvae on ethanol‐damaged HepG2 cells
Authors: Hwang Dooseon , Lee Woo Seok , Goo Tae‐Won , Park Seung‐Won , Yun Eun‐Young
Published: December 2019

In this study, we made koji using protein‐rich Tenebrio molitor larvae (TML) inoculated with Aspergillus oryzae, and then used the koji to prepare a paste and a sauce. The TML koji showed the highest amino nitrogen, protease activity, and free amino acids content when it was fermented for 72 h after inoculation with 0.8% A. oryzae. The koji was aged in 20% saltwater for 50 days, and then the paste and sauce were separated. To evaluate the effect of TML paste and sauce on ethanol (EtOH)‐damaged hepatocytes, aspartate aminotransferase (AST) and alanine aminotransaminase (ALT) were measured in EtOH‐treated HepG2 cells after pretreatment with TML paste and sauce extract. As a result, we confirmed that TML paste and sauce extracts lowered the AST and ALT content in the medium, compared to soybean sauce and paste extracts. TML paste and sauce extract significantly reduced the expression of tumor necrosis factor (TNF)‐α and interleukin (IL)‐6, a biomarker of inflammation, and significantly increased the activity of the antioxidants superoxide dismutase (SOD) and reduced glutathione (GSH) in proportion to the amount of TML added to the paste and sauce. These results suggest that the intake of TML paste and sauce, a new type of fermented food made from insects, may provide effective protection to the liver against hepatocyte injury by EtOH via anti‐inflammatory and antioxidative effects.
The silver tsunami: an enquiry into the financial needs, preferences and behaviours of retirees
Authors: Chambers Barbara , Walker Ruth , Feng Jun , Gu Yuanyuan
Published: December 2019

Understanding the financial needs and preferences of retirees is critical for retirement income policy and product design. Today, Australian retirees are accumulating record levels of retirement savings in order to generate retirement income. Using qualitative and quantitative research methods, we find that retirees value leisure spending, but do not plan for long‐term health and care needs. Moreover, retirees value risk protection but are unwilling to forgo potential investment gains. The differing levels of importance that retirees attach to aspects of retirement, health, intergenerational planning and family dynamics suggest that retirement income products cannot be ‘one‐size‐fits‐all’.
Income inequality and interpersonal trust in China
Authors: Yang Zhixu , Xin Ziqiang
Published: December 2019

Two studies investigated the cross‐temporal and cross‐sectional associations between income inequality and interpersonal trust in China. In Study 1, a cross‐temporal meta‐analysis involving 141 studies (N = 64,853) found that Chinese college students’ scores on the Interpersonal Trust Scale (Rotter, 1967) decreased 0.54 SD from 1998 to 2016, and that the decline in interpersonal trust across birth cohorts was explained by earlier income inequality index in China. In Study 2, a cross‐regional analysis showed that Chinese citizens in provinces with more income inequality (vs. less inequality) perceived the local government to be less trustworthy and, in turn, reported lower levels of interpersonal trust. These findings contribute to the understanding of the rising income inequality as an explanation for the waning interpersonal trust in China, and point to a crucial channel connecting income inequality with interpersonal trust.
Choice of local anaesthetic for epidural caesarean section: a Bayesian network meta‐analysis
Authors: Reschke M. M. , Monks D. T. , Varaday S. S. , Ginosar Y. , Palanisamy A. , Singh P. M.
Published: December 2019

Rapid‐onset epidural local anaesthesia can avoid general anaesthesia for caesarean delivery. We performed a Bayesian network meta‐analysis of direct and indirect comparisons to rank speed of onset of the six local anaesthetics most often used epidurally for surgical anaesthesia for caesarean delivery. We searched Google Scholar, PubMed, EMBASE, Ovid, CINAHL and CENTRAL to June 2019. We analysed 24 randomised controlled trials with 1280 women. The mean (95%CrI) onset after bupivacaine 0.5% was 19.8 (17.3–22.4) min, compared with which the mean (95%CrI) speed of onset after lidocaine 2% with bicarbonate, 2‐chloroprocaine 3% and lidocaine 2% was 6.4 (3.3–9.6) min faster, 5.7 (3.0–8.3) min faster and 3.9 (1.8–6.0) min faster, respectively. Speed of onset was similar to bupivacaine 0.5% after ropivacaine 0.75% and l‐bupivacaine 0.5%: 1.6 (−1.4 to 4.8) min faster and 0.4 (−2.2 to 3.0) min faster, respectively. The rate (95%CrI) of intra‐operative hypotension was least after l‐bupivacaine 0.5%, 315 (236–407) per 1000, and highest after 2‐chloroprocaine 3%, 516 (438–594) per 1000. The rate (CrI) of intra‐operative supplementation of analgesia was least after ropivacaine 0.75% 48 (19–118) per 1000 and highest after 2‐chloroprocaine 3%, 250 (112–569) per 1000.
A clinical decision support tool may help to optimise vedolizumab therapy in Crohn’s disease
Authors: Dulai Parambir S. , Amiot Aurelien , Peyrin‐Biroulet Laurent , Jairath Vipul , Serrero Melanie , Filippi Jerome , Singh Siddharth , Pariente Benjamin , Loftus Edward V. , Roblin Xavier , Kane Sunanda , Buisson Anthony , Siegel Corey A. , Bouhnik Yoram , Sandborn William J. , Lasch Karen , Rosario Maria , Feagan Brian G. , Bojic Daniela , Trang‐Poisson Caroline , Shen Bo , Altwegg Romain , Sands Bruce E. , Colombel Jean‐Frederic , Carbonnel Franck ,   the GETAID OBSERV‐IBD, VICTORY Cohorts Collaboration*
Published: December 2019

Background

A clinical decision support tool (CDST) has been validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn’s disease.

Aim

To assess the utility of this CDST for predicting exposure‐efficacy and disease outcomes.

Methods

Using data from three independent datasets (GEMINI, GETAID and VICTORY), we assessed clinical remission rates and measured VDZ exposure, rapidity of onset of action, response to dose optimisation and progression to surgery by CDST‐defined response groups (low, intermediate and high).

Results

A linear relationship existed between CDST‐defined groups, measured VDZ exposure, rapidity of onset of action and efficacy in GEMINI through week 52 (P < 0.001 at all time points across three CDST‐defined groups). In GETAID, CDST predicted differences in clinical remission at week 14 (AUC = 0.68) and rapidity of onset of action (P = 0.04) between probability groups. The high‐probability patients did not benefit from shortening of infusion intervals, and differences in onset of action between the high‐intermediate and low‐probability groups within GETAID were no longer significant when including low‐probability patients who received a week 10 infusion. CDST predicted a twofold increase in surgery risk over 12 months of VDZ therapy among low‐ to intermediate‐probability vs high‐probability patients (adjusted HR 2.06, 95% CI 1.33‐3.21).

Conclusions

We further extended the clinical utility of a previously validated VDZ CDST, which accurately predicts at baseline exposure‐efficacy relationships and rapidity of onset of action and could be used to help identify patients who would most benefit from interval shortening and those most likely to require surgery while on active therapy.
United in Fight against prOstate cancer (UFO) registry: first results from a large, multi‐centre, prospective, longitudinal cohort study of advanced prostate cancer in Asia
Authors: Uemura Hirotsugu , Ye Dingwei , Kanesvaran Ravindran , Chiong Edmund , Lojanapiwat Bannakij , Pu Yeong‐Shiau , Rawal Sudhir Kumar , Abdul Razack Azad Hassan , Zeng Hao , Chung Byung Ha , Md Yusoff Noor Ashani , Ohyama Chikara , Kim Choung Soo , Leewansangtong Sunai , Tsai Yuh‐Shyan , Liu Yanfang , Liu Weiping , van Kooten Losio Maximiliano , Asinas‐Tan Marxengel
Published: December 2019

Objectives

To document the management of advanced prostate cancer including diagnosis, prognosis, treatment, and care, in real‐world practice in Asia using the United in Fight against prOstate cancer (UFO) registry.

Patients and Methods

We established a multi‐national, longitudinal, observational registry of patients with prostate cancer presenting to participating tertiary care hospitals in eight Asian countries. A total of 3636 eligible patients with existing or newly diagnosed high‐risk localised prostate cancer (HRL), non‐metastatic biochemically recurrent prostate cancer (M0), or metastatic prostate cancer (M1), were consecutively enrolled and are being followed‐up for 5 years. Patient history, demographic and disease characteristics, treatment and treatment decisions, were collected at first prostate cancer diagnosis and at enrolment. Patient‐reported quality of life was prospectively assessed using the European Quality of Life‐five Dimensions, five Levels (EQ‐5D‐5L) and Functional Assessment of Cancer Therapy for Prostate Cancer questionnaires. In the present study, we report the first interim analysis of 2063 patients enrolled from study start (15 September 2015) until 18 May 2017.

Results

Of the 2063 enrolled patients, 357 (17%), 378 (19%), and 1328 (64%) had HRL, M0 or M1 prostate cancer, respectively. The mean age at first diagnosis was similar in each group, 56% of all patients had extracapsular extension of their tumour, 28% had regional lymph node metastasis, and 53% had distant metastases. At enrolment, 62% of patients had at least one co‐morbidity (mainly cardiovascular disease or diabetes), 91.8% of M1 patients had an Eastern Cooperative Oncology Group performance score of <2 and the mean EQ‐5D‐5L visual analogue score was 74.6–79.6 across cohorts. Treatment of M1 patients was primarily with combined androgen blockade (58%) or androgen‐deprivation therapy (either orchidectomy or luteinising hormone‐releasing hormone analogues) (32%). Decisions to start therapy were mainly driven by treatment guidelines and disease progression. Decision to discontinue therapy was most often due to disease progression (hormonal drug therapy) or completion of therapy (chemotherapy).

Conclusion

In the UFO registry of advanced prostate cancer in Asia, regional differences exist in prostate cancer treatment patterns that will be explored more deeply during the follow‐up period; prospective follow‐up is ongoing. The UFO registry will provide valuable descriptive data on current disease characteristics and treatment landscape amongst patients with prostate cancer in Asia.
Parents' perspectives on participation of young children with attention deficit hyperactivity disorder, developmental coordination disorder, and/ or autism spectrum disorder: A systematic scoping review
Authors: Coussens Marieke , Van Driessen Evy , De Baets Stijn , Van Regenmortel Jasmine , Desoete Annemie , Oostra Ann , Vanderstraeten Guy , Waelvelde Hilde Van , Van de Velde Dominique
Published: December 2019

Background

During the early years of a child's life, participation is essential for learning and development. Children with disabilities are at risk for decreased participation. The interplay between environment and participation is identified as one of the most important factors influencing successful participation. The objective of this scoping review was to synthesize peer‐reviewed literature about barriers and facilitators of participation according to the perspective of parents of children younger than 6 years with Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and/ or Developmental Coordination Disorder (DCD).

Methods

The scoping review followed Arksey and O'Malley's framework. Relevant studies were identified by a comprehensive search of scientific databases (PubMed and Web of Science). Studies describing perspectives of parents regarding their child's participation, written in English, and published between 2001 and September 2017 were included.

Results

A total of 854 articles were retrieved, with 13 meeting the criteria. Elements contributing to perceived barriers and facilitators were identified and organized according to the International Classification of Functioning, Child–Youth framework. Concepts contained in these studies were linked to “activities and participation” (general tasks and demands, such as bedtime and dinner routines, and social, civic life, such as play and leisure). Environment‐focused factors identified were situated on “support and relationships, ” “attitudes, ” and “services, systems, and policies.”

Conclusion

The review revealed guidelines focusing on family‐centred care, communication with, and providing information to parents with young children with developmental disabilities (ADHD, DCD, and/ or ASD).
Unilateral primary aldosteronism as an independent risk factor for vertebral fracture
Authors: Yokomoto‐Umakoshi Maki , Sakamoto Ryuichi , Umakoshi Hironobu , Matsuda Yayoi , Nagata Hiromi , Fukumoto Tazuru , Ogata Masatoshi , Ogawa Yoshihiro ,   the Q‐AND‐A study group
Published: December 2019

Context

Primary aldosteronism (PA) is known to increase vertebral fracture (VF), although the detailed mechanism remains to be elucidated. We hypothesized that the PA subtype is associated with VF.

Objective

To evaluate whether unilateral PA is associated with the prevalence of VF.

Design

This was a retrospective cross‐sectional study in a single referral centre.

Patients

We identified 210 hypertensive patients whose clinical data were available for case‐detection results. One hundred and fifty‐two patients were diagnosed with PA using captopril challenge tests.

Measurements

We measured the prevalence of VF, according to PA subtype.

Results

One hundred thirteen patients with PA were subtype classified by adrenal vein sampling. Of these, 37 patients had unilateral PA, 76 patients had bilateral PA, 58 patients had non‐PA; 39 patients with PA were not subtype‐classified. Patients with PA had a higher prevalence of VF (29%, 44/152) than those with non‐PA (12%, 7/58; P = .011). Moreover, unilateral PA had a higher prevalence of VF (46%, 17/37) than bilateral PA (20%, 15/76; P = .021). There was no significant difference in the prevalence of VF between bilateral PA and non‐PA. Unilateral PA was an independent risk factor for VF after adjusting for age and sex (OR: 3.16, 95% confidence interval: 1.12‐8.92; P = .017). Among patients with unilateral PA, serum cortisol concentrations after 1‐mg dexamethasone suppression test were higher in those with VF (1.32 ± 0.67 g/dL) than those without (0.96 ± 0.33 g/dL; P = .048).

Conclusions

Unilateral PA is an independent risk factor for VF.
Economic impact of keratoconus using a health expenditure questionnaire: A patient perspective
Authors: Chan Elsie , Baird Paul N. , Vogrin Sara , Sundararajan Vijaya , Daniell Mark D. , Sahebjada Srujana
Published: December 2019

Importance

This is the first study to estimate the lifetime costs associated with keratoconus based on a questionnaire completed by patients and highlights the significant economic burden of the disease. As keratoconus affects individuals from a young age, the study highlights keratoconus as a public health concern.

Background

Keratoconus is a disorder characterized by corneal steepening and thinning, leading to reduced visual acuity. To date, there have been no studies evaluating the economic costs of keratoconus from a patient's perspective.

Design

A randomized cross‐sectional study undertaken in Australia where keratoconus subjects were recruited from public and private ophthalmology and optometry clinics.

Participants

A total of 100 participants completed the questionnaire: median age was 31 years and 57% were males.

Methods

A keratoconus health expenditure questionnaire was designed to assess direct and indirect expenditures for each individual.

Main Outcome Measures

Total direct and indirect costs associated with the condition were calculated along with the estimated lifetime per capita costs.

Results

The total cost related to direct and indirect care was estimated to be AUD 3365. By applying our cost data to keratoconus prevalence data for the Australian population, the total cost is estimated to be approximately AUD 44.7 million per year in Australia.

Conclusions and Relevance

Our results show that the costs associated with the diagnosis and management of keratoconus represent a significant cost to patients. An understanding of this is important not only to individuals and their families, but also health care providers, health insurers and the wider health system.
Incidence and characteristics of cataract surgery in South Korea from 2011 to 2015: A nationwide population‐based study
Authors: Ryu Sun Young , Kim Jiwon , Hong Jung Hwa , Chung Eun Jee
Published: December 2019

Importance

Detailed incidence data for cataract surgery in the general population are limited, yet important for determining the surgical needs of the community and formulation of healthcare policies.

Background

To report incidence rates of cataract surgery in South Korea.

Design

Nationwide, retrospective population‐based study.

Participants

This study involved the entire population of South Korea (n = 47 990 761); 2 236 107 eyes of 1 591 176 patients confirmed as having cataract surgery from 1 January 2011 to 31 December 2015 were included.

Methods

Data for all patients who underwent primary cataract surgery in South Korea were retrieved using Korean Electronic Data Interchange and Korean Standard Classification of Diseases‐7 codes. Annual incidence rates were calculated and adjusted to the national population data for the corresponding year.

Main Outcome Measures

The average incidence of cataract surgery during the 5‐year study period was estimated using population data from the 2010 Korean census.

Results

The incidence of cataract surgery increased from 8.54/1000 person‐years in 2011 to 9.67/1000 person‐years in 2015. The probability of second‐eye surgery within 12 months after the first‐eye surgery increased from 42.98% in 2011 to 48.01% in 2015. In total, 85.72% of surgeries were performed in non‐rural areas: 43.18% in individuals with a higher household income and 76.65% in primary healthcare centres. The rate of vitrectomy for posterior capsular rupture was 0.72%.

Conclusions and Relevance

The incidence of cataract surgery in South Korea is increasing over time. Our findings are expected to aid in the formulation of future healthcare policies concerning cataract surgery in South Korea.
Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice
Authors: de Munter Johannes P.J.M. , Shafarevich Igor , Liundup Alexei , Pavlov Dmitrii , Wolters Erik Ch , Gorlova Anna , Veniaminova Ekaterina , Umriukhin Aleksei , Kalueff Allan , Svistunov Andrei , Kramer Boris W. , Lesch Klaus‐Peter , Strekalova Tatyana
Published: December 2019

Aims

Mutations in DNA/RNA‐binding factor (fused‐in‐sarcoma) FUS and superoxide dismutase‐1 (SOD‐1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD‐1‐G93A (SOD‐1) and new FUS[1‐359]‐transgenic (FUS‐tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti‐inflammatory treatments were investigated using these mutants.

Methods

FUS‐tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti‐inflammatory drug a selective blocker of cyclooxygenase‐2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro‐Cells (a preparation of 1.39 × 106mesenchymal and hemopoietic human stem cells, containing 5 × 105of CD34+cells), which showed anti‐inflammatory properties. SOD‐1 mice received i.c.v.‐administration of Neuro‐Cells or vehicle.

Results

All FUS‐tg‐treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS‐tg‐vehicle‐treated mice. Neuro‐Cell‐treated mutants had reduced muscle atrophy and lumbar motor neuron degeneration. This group but not celecoxib‐FUS‐tg‐treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium‐binding adapter molecule‐1 (Iba‐1), and glycogen‐synthase‐kinase‐3ß (GSK‐3ß). The Neuro‐Cells‐treated‐SOD‐1 mice showed better motor functions than vehicle‐treated‐SOD‐1 group.

Conclusion

The neuropathology in FUS‐tg mice is sensitive to standard ALS treatments and Neuro‐Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation.
The informational and decisional preferences of patients undergoing surgery for Crohn’s anal fistula: a qualitative study
Authors: Lee M. J. , Marshall J. H. , Jones G. L. , Lobo A. J. , Brown S. R.
Published: December 2019

Aim

One in three patients with Crohn’s disease will develop a perianal fistula, but only a few achieve long‐term healing. Treatment is both medical and surgical. Since there is no ‘best’ surgical procedure, patient preference is important in selecting the appropriate treatment for this condition. The aim of this study was to investigate the informational and decisional preferences of patients when surgical treatment is being considered.

Method

Patients who had undergone surgery for Crohn's anal fistula underwent face‐to‐face semi‐structured interviews. These explored the experience of treatments for fistula, of receiving information and of participation in decision‐making. Transcripts were analysed by two investigators through inductive thematic analysis. Saturation was assessed for at 12 interviews and then after each subsequent interview.

Results

Seventeen patients completed interviews, and saturation was achieved. Five themes were identified, of which two (desired information and decision‐making) were relevant to this study. Other themes included experience of Crohn’s disease, experience of receiving information and procedure‐specific comments. Participants wanted to have information on any risks, high‐level outcomes (e.g. success), impact on day‐to‐day life and aftercare. Participants felt they did not always receive the information they needed to select the best treatment option. Participants felt uninvolved in treatment decisions and would have liked to trade off operations to reach their treatment goal.

Conclusion

Information provided to patients about surgical treatment of Crohn’s perianal fistula does not meet their needs. Clinicians should address aftercare, impact on quality of life and the risks and benefits of the any proposed procedure.
Activating Semantic Knowledge During Spoken Words and Environmental Sounds: Evidence From the Visual World Paradigm
Authors: Toon Josef , Kukona Anuenue
Published: December 2019

Two visual world experiments investigated the activation of semantically related concepts during the processing of environmental sounds and spoken words. Participants heard environmental sounds such as barking or spoken words such as “puppy” while viewing visual arrays with objects such as a bone (semantically related competitor) and candle (unrelated distractor). In Experiment 1, a puppy (target) was also included in the visual array; in Experiment 2, it was not. During both types of auditory stimuli, competitors were fixated significantly more than distractors, supporting the coactivation of semantically related concepts in both cases; comparisons of the two types of auditory stimuli also revealed significantly larger effects with environmental sounds than spoken words. We discuss implications of these results for theories of semantic knowledge.
Heart‐lung transplantation: A viable option for connective tissue diseases
Authors: Stern Lily K. , Selby Van N. , Kolaitis Nicholas A. , Boin Francesco , Aras Mandar , Klein Liviu , De Marco Teresa
Published: December 2019

Background

While lung transplantation (LTx) has been effective for connective tissue disease (CTD) patients with pulmonary involvement, outcomes for heart‐lung transplantation (HLTx) are less defined. The aim of this study is to evaluate HLTx in CTD patients utilizing the UNOS database.

Methods

HLTx patients with CTD (HLTx‐CTD) were compared to both LTx patients with CTD (LTx‐CTD) and HLTx patients with all other indications (HLTx‐OI) from 1999 to 2018. Primary outcome was 1‐ and 5‐year graft survival. Secondary outcomes included freedom from first‐year rejection and outcomes prior to transplant discharge.

Results

1143/29 323 adults received first‐time HLTx or LTx for CTD. Seventeen were HLTx‐CTD (3.3% of total HLTx) and 1126 were LTx‐CTD (3.9% of total LTx). There were 492 HLTx‐OI. Transplant hemodynamic values including cardiac output, pulmonary capillary wedge pressure, and calculated pulmonary vascular resistance were significantly worse for HLTx‐CTD vs LTx‐CTD (4.2 vs 5.4 L/min, P = .005; 14 vs 10 mm Hg, P = .009; 439 vs 267 dynes, P = .007, respectively). Cardiac status 1 was more common for HLTx‐CTD vs HLTx‐OI (94% vs 56%, P < .001). HLTx‐CTD 1 and 5‐year graft survival was similar compared to LTx‐CTD and HLTx‐OI.

Conclusion

HLTx‐CTD is a valid option for carefully selected patients with CTD cardiac and pulmonary involvement with similar morbidity and mortality compared to LTx‐CTD and HLTx‐OI.
Sputum cytology: Fungus‐like elements in an immunocompromised patient
Authors: Martínez‐Girón Rafael , Martínez‐Torre Cristina
Published: December 2019

The presence of a contaminant fresh water algae mimicking a fungus in a sputum smear from an HIV + patient is reported.