bluuebunny/crossref_metadata_2025 huggingface dataset:
Stakeholder management in the alleviation of legal and regulatory disputes in public-private partnership projects in South Africa
Authors: Dithebe Khotso , Thwala Wellington Didibhuku Didibhuku , Aigbavboa Clinton Ohis , Edwards David J. , Hayhow Susan , Talebi Saeed
Published: October 2021

Purpose

The purpose of this paper is to introduce the use of critical success factors (CSFs) of stakeholder management as a possible solution to reduce disputes experienced because of legal and regulatory issues in public–private partnership (PPP) projects.

Design/methodology/approach

This paper’s epistemological positioning adopted positivism and deductive reasoning to investigate the dispute phenomena on PPP projects. A survey strategy was adopted using a structured questionnaire and closed-ended Likert scales to collate primary data. Questionnaires were distributed to South African construction professionals using both purposive and snowballing non-probability sampling techniques. Data was analysed using summary statistical analysis of the CSFs identified from literature.

Findings

This study revealed that among the 19 CSFs identified, five factors were highlighted that could contribute to the alleviation of disputes between stakeholders in PPP projects, namely, adequate project planning and control; effective leadership; appropriate strategies for the management of stakeholders; confirmation of clear goals and objectives of the project; and effective communication.

Originality/value

The strength of this study lies in the evaluation and use of CSFs of stakeholder management as a possible solution to minimise or even avoid disputes as a result of legal and regulatory issues in PPP projects. By integrating the CSFs, the legal and contractual misconceptions of the PPP initiative are clarified. Such work represents a novel contribution to procurement practice in South Africa and maybe to other countries internationally who are grappling with similar issues.
Prediction of recycled coarse aggregate concrete mechanical properties using multiple linear regression and artificial neural network
Authors: Patil Suhas Vijay , Balakrishna Rao K. , Nayak Gopinatha
Published: October 2021

Purpose

Recycling construction waste is a promising way towards sustainable development in construction. Recycled aggregate (RA) is obtained from demolished concrete structures, laboratory crushed concrete, concrete waste at a ready mix concrete plant and the concrete made from RA is known as RA concrete. The purpose of this study is to apply multiple linear regressions (MLRs) and artificial neural network (ANN) to predict the mechanical properties, such as compressive strength (CS), flexural strength (FS) and split tensile strength (STS) of concrete at the age of 28 days curing made completely from the recycled coarse aggregate (RCA).

Design/methodology/approach

MLR and ANN are used to develop a prediction model. The model was developed in the training phase by using data from a previously published research study and a developed model was further tested by obtaining data from laboratory experiments.

Findings

ANN shows more accuracy than MLR with an R2-value of more than 0.8 in the training phase and 0.9 in a testing phase. The high R2-value indicates strong relation between the actual and predicted values of mechanical properties of RCA concrete. These models will help construction professionals to save their time and cost in predicting the mechanical properties of RCA concrete at 28 days of curing.

Originality/value

ANN with rectified linear unit transfer function and backpropagation algorithm for training is used to develop a prediction model. The outcome of this study is the prediction model for CS, FS and STS of concrete at 28 days of curing.
Current trends in terrorist financing
Authors: Teichmann Fabian Maximilian
Published: October 2021

Purpose

The purpose of this paper is to illustrate how intelligent terrorist financiers avoid detection when acquiring and subsequently transferring financial assets to finance terrorism. Particular emphasis is placed on cryptocurrency.

Design/methodology/approach

A qualitative content analysis of 30 semi-standardised expert interviews with both criminals and prevention experts led to the identification of means for the circumvention of current combat the financing of terrorism (CFT) measures with a focus on cryptocurrency.

Findings

The findings illustrate, for the benefit of law enforcement agencies, investigators, regulating authorities and legislators, the specific low-risk methods that terrorist financiers use to generate and transfer assets. These findings help to develop more effective prevention methods.

Research limitations/implications

Qualitative findings from the analysis of semi-standardised interviews are limited to the 30 interviewees’ perspectives.

Practical implications

Identification of gaps in existing CFT mechanisms provides compliance officers, law enforcement agencies and legislators with valuable insights into how criminals operate.

Originality/value

The existing literature focuses on organisations that combat terrorist financing and the improvement of CFT measures. This article outlines how terrorist financiers avoid detection. Both preventative and criminal perspectives are considered.
Kinetic studies of photocatalytic degradation of an Azo dye by titania nanoparticles
Authors: Goyal Nidhi , Rastogi Deepali , Jassal Manjeet , Agrawal Ashwini K.
Published: October 2021

Purpose

Dyeing and printing are important steps in textile manufacturing. After the process completion, these dyes are released in the effluent. These dyes impart an unacceptable appearance but are also toxic to the soil and water bodies. The present research has been carried out to study the rate of photocatalytic degradation of an azo dye, namely, CI Direct Green 26, using titania nanoparticles under ultra violet (UV) irradiation as a function of temperature and time. Azo dyes account for the majority of all dyestuffs are produced and extensively used in the textile, paper, food, leather, cosmetics and pharmaceutical industries. Titania nanoparticles have been found to successfully degrade these dyes in the presence of UV light. The purpose of the present paper was to study the photodegradation of azo dyes using titania nanoparticles at different temperatures and time periods.

Design/methodology/approach

Titania nanoparticle concentration of 0.1% (w/v) was dispersed in distilled water by sonication for 1 h in sonication bath. The of rate of degradation of Direct Green 26 dye in the titania nanoparticle dispersion, under UV-A exposure was studied at different temperatures ranging from 25°C to 65 °C for time periods ranging from 1 h to 6 h. Photocatalytic degradation tests were performed in a specially designed UV reactor chamber. Raman spectroscopy of Titania nanoparticles, dye and titania/dye mixture before and after UV exposure was carried out using Confocal Laser Dispersion Raman Microscope (Renishaw, UK) with 785 nm excitation laser.

Findings

Titanium dioxide is an efficient photocatalyst for decolourisation of direct dye. The photodegradation of the direct Green dye was found to follow the pseudo first-order reaction. The Arrhenius activation energy was found to be 24.8 kJ/mol with A value of 0.0013 for the photocatalytic degradation of the dye. Raman spectroscopy also confirmed the adsorption of dye on titania nanoparticle and its complete degradation on exposure to UV light.

Practical implications

This research highlights the application of titania nanoparticles for the effective degradation of dye in the effluent from textiles, clothing, paper and any kind of dyeing process. Azo dyes account for the majority of all dyestuffs are produced and extensively used in the textile, paper, food, leather, cosmetics and pharmaceutical industries. Titania nanoparticles have been found to successfully degrade these dyes in the presence of UV light which can be very beneficial for the effluent treatment plants in textile and other industries.

Originality/value

Azo dyes are one of the harmful pollutants released in textile waste water. The degradation and removal of the coloured waste in the textile effluent is an important environmental concern and needs to be investigated. The research is one of the first to investigate and understand the mechanism of the degradation of an azo dye in the presence of titania nanoparticles by Raman spectroscopy.
Coupling additive manufacturing and low-temperature sintering: a fast processing route of silicate glassy matrix
Authors: Tang Danna , Wang Yushen , Li Zheng , Li Yan , Hao Liang
Published: October 2021

Purpose

The low-temperature sintering of silica glass combined with additive manufacturing (AM) technology has brought a revolutionary change in glass manufacturing. This study aims to carry out in an attempt to achieve precious manufacturing of silicate glassy matrix through the method of slurry extrusion.

Design/methodology/approach

A low-cost slurry extrusion modelling technology is used to extrude silicate glassy matrix inks, composed of silicate glass powder with different amounts of additives. Extrudability of the inks, their printability window and the featuring curves of silicate glassy matrix are investigated. In addition, the properties of the low-temperature sintering green part as a functional part are explored and evaluated from morphology, hardness and colour.

Findings

The results showed that the particle size was mainly distributed from 1.4 µm to 5.3 µm, showing better slurry stability and print continuity. The parameters were set to 8 mm/s, 80% and 0.4 mm, respectively, to achieve better forming of three-dimensional (3D) samples. Besides, the organic binder removal step was concentrated on 200°C–300°C and 590°C–650°C was the fusion bonding temperature of the powder. The hardness values of 10 test samples ranged from 588 HL to 613 HL, which met the requirements of hard stones with super-strong mechanical strength. In addition, the mutual penetration of elements caused by temperature changes may lead to a colourful appearance.

Originality/value

The custom continuous AM technology enables the fabrication of a glass matrix with 3D structural features. The precise positioning technology of the glass matrix is expected to be applied more widely in functional parts.
Mechanical properties and crystallinity of polypropylene injection molded in polyjet and aluminum tooling
Authors: Mendible Gabriel Antonio , Saleh Nabil , Barry Carol , Johnston Stephen P.
Published: October 2021

Purpose

Rapid tooling has numerous advantages when prototyping injection molded components, but the effects of the tooling on the resulting part properties are often overlooked. The purpose of this paper is to consider the effect of tooling on the final part properties and morphology.

Design/methodology/approach

Digital polyacrylonitrile-butadiene-styrene (ABS) tooling and aluminum tooling were used to mold test specimens from isotatic polypropylene (iPP). Tensile behavior, impact strength, shrinkage, surface roughness and porosity were evaluated for both sets of samples. Additionally, differential scanning calorimeter (DSC) and wide-angle X-ray scattering (WAXS) were used to assess the crystallinity of the samples.

Findings

Characterization of the molded parts showed that slower cooling rates in the Digital ABS inserts promoted the formation of ß-PP, while this crystal structure was not found in the parts molded using aluminum tooling. Additionally, parts molded on the digital ABS inserts exhibited higher mold shrinkage and SEM images identified microscopic shrinkage voids within the material. The change in morphology and the presence of voids significantly affected the tensile behavior with the parts molded in Digital ABS, which broke with little cold drawing and exhibited higher tensile moduli and higher yield strengths.

Practical implications

The results show that the choice of rapid tooling technique plays an important role on determining the properties of the final parts.

Originality/value

Previous studies have not characterized the effect of rapid tooling on the morphology of the molded articles fully or over a variety of processing conditions. This study builds on prior work by using both WAXS and DSC to characterize morphological changes over a wide range of processing conditions and comparing results to mechanical property and shrinkage data.
Combined effect of shape distortion and bend angle on collapse load of pipe bends under in-plane closing bending moment and internal pressure
Authors: Silambarasan R. , Veerappan A.R. , Shanmugam S.
Published: October 2021

Purpose

The purpose of this paper is to quantify the combined effect of shape distortion and bend angle on the collapse loads of pipe bends exposed to internal pressure and in-plane closing bending moment. Non-linear finite element analysis with large displacement theory was performed considering the pipe bend material to be elastic perfectly plastic.

Design/methodology/approach

One half of the pipe bend model was built in ABAQUS. Shape distortion, namely, ovality (Co) and thinning (Ct), were each varied from 0% to 20% in steps of 5% and bend angle was varied from 30° to 180° in steps of 30°.

Findings

The findings show that ovality has a significant impact on collapse load. The effect of ovality decreases with an increase in bend angle for small thickness. The opposite effect was observed for large thickness pipe bends. The influence of ovality was more for higher bend angles. Ovality impact was almost negligible at certain internal pressure denoted as nullifying point (NP). The latter increased with an increase in pipe bend thickness and decreased with increase in pipe bend radius. For small bend angles one NP was observed where ovality impact is negligible and beyond this point the ovality effect increased. Two NPs were observed for large bend angles and ovality effect was maximum between the two NPs. Thinning yielded a minimal effect on collapse load except for small bend angles and bend radii. The influence of internal pressure on thinning was also negligible.

Originality/value

Influence of shape distortions and bend angle on collapse load of pipe bend exposed to internal pressure and in-plane closing bending has been not revealed in existing literature.
A bioinformatic toolkit to simultaneously identify sex and sex‐linked regions
Authors: Darolti Iulia , Mank Judith E.
Published: October 2021

Sex chromosomes are strange things, and often exhibit unusual patterns of diversity, rates of evolution, and gene regulation (Bachtrog et al., 2011, Mank, 2013). These unique features mean that although sex chromosomes are often a relatively small proportion of the genome, they are best identified and assessed separately from the autosomal majority when carrying out genomic analyses. However, identifying and partitioning genomic regions into sex‐linked and autosomal in non‐model species can often be quite difficult. In this issue of Molecular Ecology Resources, Nursyifa et al. (2021) provide a useful method that combines sequencing depth information with clustering models to assign sex to samples at the same time as identifying sex‐linked scaffolds. This method gives robust results even with more challenging or low‐quality data, and thus is particularly promising in studies of non‐model organisms.
Trimodality therapy for esophageal cancer: The role of surgical and radiation treatment parameters in the development of anastomotic complications
Authors: Alfaifi Salem , Chu Robert , Hui Xuan , Broderick Stephen , Hooker Craig , Brock Malcolm , Bush Errol , Hales Russell , Anderson Lori , Hoff Jeffrey , Friedes Cole , Han‐Oh Sarah , Mcnutt Todd , Ha Jinny , Yang Stephen , Battafarano Richard , Feliciano Joy , Voong K. Ranh
Published: October 2021

Background

Here, we investigated the relationship between clinical parameters, including the site of surgical anastomosis and radiation dose to the anastomotic region, and anastomotic complications in esophageal cancer patients treated with trimodality therapy.

Methods

Between 2007 and 2016, esophageal cancer patients treated with trimodality therapy at a tertiary academic cancer center were identified. Patient, treatment, and outcome parameters were collected. Radiation dose to the gastric regions were extracted. Anastomotic complication was defined as leak and/or stricture. We used Fisher's exact and Wilcoxon rank‐sum tests to compare the association between clinical parameters and anastomotic complications.

Results

Of 89 patients identified, the median age was 63 years, 82% (n = 73) were male, and 82% had distal (n = 47) or gastroesophageal junction (n = 26) tumors. Median follow‐up was 25.8 months. Esophagectomies were performed with cervical (65%, n = 58) or thoracic anastomoses (35%, n = 31). Anastomotic complications developed in 60% (n = 53). Cervical anastomosis was associated with anastomotic complications (83%, n = 44/53, p < 0.01). Radiation to any gastric substructure was not associated with anastomotic complications (p > 0.05). In the subset of patients with distal/gastroesophageal junction tumors undergoing esophagectomy with cervical anastomosis where radiation was delivered to the future neoesophagus, 80% (n = 35/44) developed anastomotic complications. In this high‐risk subgroup, radiation was not associated with anastomotic complications (p > 0.05).

Conclusions

Our analysis did not demonstrate an association between radiation dose to gastric substructures and anastomotic complications. However, it showed an association between esophagectomy with cervical anastomosis and anastomotic complications. Patients with distal/gastroesophageal junction tumors who undergo esophagectomy with cervical anastomosis have higher rates of anastomotic complications unrelated to radiation to gastric substructures.
Navigating the temporal continuum of effective population size
Authors: Nadachowska‐Brzyska Krystyna , Konczal Mateusz , Babik Wieslaw
Published: October 2021

Effective population size, Ne, is a key evolutionary parameter that determines the levels of genetic variation and efficacy of selection. Estimation and interpretation of Ne are essential in diverse areas of evolutionary and conservation biology, ranging from assessing the evolutionary potential or extinction risk to empowering research on the genomic basis of adaptation.

The diverse applications of the Ne concept resulted in largely independent methodological developments using different Ne definitions and focusing on the estimation of either contemporary or long‐term Ne. Recently, several novel approaches appeared that allow the estimation of temporal Ne trends at various parts of the temporal Ne continuum.

Here, we provide an overview of the temporal aspects of Ne, asking whether the existing methods and available data provide Ne estimates for the entire temporal continuum. We outline the apparent division into contemporary and long‐term Ne existing in the literature, review Ne estimation methods across the temporal continuum and navigate the reader through it pointing to the important biological and methodological limitations inherent to the estimation procedures. Finally, we provide examples of recent research and future perspectives.

We conclude that the entire temporal Ne continuum can now be inferred using several complementary approaches, bringing together contemporary and long‐term perspectives. Further rapid progress in the field is expected from the wide adoption of machine learning and transition to haplotype‐resolved population genomic data. The expected progress notwithstanding, interpretational difficulties are likely to remain, emphasising the need for a thorough understanding of the Ne theory behind the methods, their assumptions and inherent limitations.
On the recent developments of mutual funds with fixed‐income holdings: a systematic review
Authors: Hejri Abbas
Published: October 2021

Bond funds and money market funds hold a sizable portion of fixed‐income securities and have experienced considerable growth over the recent decades. Moreover, the global financial crisis (GFC) was a turning point in identifying the hidden risks associated with these mutual funds. Nevertheless, and despite their significance, these funds are dwarfed by numerous studies on equity mutual funds. This paper conducts a systematic review and explores the primary research streams and emerging themes during the GFC and post‐GFC. Four main genealogies are identified: performance persistency and active management, green funds, ’funds’ flow and flow‐performance, and money market funds and financial crisis.
The effect of intraperitoneal ropivacaine on post‐operative pain and recovery after diagnostic laparoscopy and hysteroscopy: A randomised double‐blind placebo‐controlled trial
Authors: Frawley Natasha , Jones Richard , Pearce Dora , Vollenhoven Beverley
Published: October 2021

Background

Intraperitoneal local anaesthetic has shown benefit in operative laparoscopy; however, no randomised controlled trial has been reported with patients having diagnostic laparoscopy.

Aims

To determine the effect of intraperitoneal ropivacaine on post‐operative analgesic requirements, pain, nausea scores and recovery following gynaecological diagnostic laparoscopy and hysteroscopy.

Materials and Methods

Randomised double‐blind placebo‐controlled trial. Well women aged 18–50 years, undergoing day case hysteroscopy and diagnostic laparoscopy for gynaecological indications were randomised to 20 mL of 150 mg intraperitoneal ropivacaine diluted in saline, or 20 mL normal saline instillation (placebo) at the end of the procedure. Women were followed up until eight hours post‐discharge.

Results

Slower than anticipated recruitment meant that the study was finished before the sample size of 100 patients was achieved. Fifty‐nine patients were included for analysis. Thirty‐one patients were randomised to ropivacaine and 28 patients to control. Sixty‐one percent of patients in both arms required opioid medication in recovery. The total median equivalent morphine dose was significantly higher in the patients randomised to control (11.7 mg) vs ropivacaine (6.7 mg), P = 0.03. Time to discharge was 20 min faster in patients randomised to ropivacaine, but this finding did not reach significance. Overall pain and nausea scores in the first eight hours showed no significant differences.

Conclusion

There was significantly reduced opioid use in recovery when using intraperitoneal ropivacaine compared to placebo, in this randomised placebo‐controlled trial on women undergoing day case diagnostic laparoscopy and hysteroscopy.
The impact of IBD medications on risk of pneumonia and pneumonia‐related hospitalisation: a nationwide cohort study of 56 410 IBD patients
Authors: Khan Nabeel , Patel Dhruvan , Trivedi Chinmay , Pernes Tyler , Kavani Himanshu , Xie Dawei , Yang Yu‐Xiao
Published: October 2021

Background

There are limited data on the incidence of pneumonia and pneumonia‐related hospitalisation in the IBD population, and on any association of IBD medications with such outcomes.

Aims

To evaluate the impact of IBD medications on the risk of pneumonia, pneumonia‐related hospitalisations and death.

Methods

We conducted a retrospective cohort study of IBD patients from the nationwide Veteran Affairs (VA) dataset. The exposure of interest was different IBD medication groups. We estimated the incidence rate of pneumonia, pneumonia‐related hospitalisation and mortality based on IBD medication subgroups. We used a multivariable Cox regression to estimate the adjusted hazard ratios (AHR) and 95% confidence intervals (CIs) for these outcomes.

Results

Out of 56 410 patients with IBD, 3759 developed pneumonia, 1489 were hospitalised, and 248 died within 30 days of their pneumonia diagnosis. The crude incidence rates of pneumonia, pneumonia‐related hospitalisation and pneumonia‐related mortality were 6.47, 2.52 and 0.43, respectively, per 1000 person‐years. In multivariable Cox regression analysis, compared to 5‐ASA alone, anti‐TNF medication was associated with an increased risk of pneumonia (AHR 1.39; 95% CI 1.22‐1.59) and hospitalisation (AHR 1.61; 95% CI 1.31‐1.98). Use of prednisone in the prior 30 days was associated with increased risk of pneumonia (AHR 2.14; 95% CI 1.92‐2.38) and hospitalisation (AHR 2.44; 95% CI 2.08‐2.88).

Conclusion

Anti‐TNF medications and prednisone use may be associated with increased risk of developing pneumonia and pneumonia‐related hospitalisation. Physicians should evaluate the risk–benefit ratio of IBD medications, especially in the elderly population.
A graph theory‐based whole brain approach to assess mood state differences in adolescents and young adults with bipolar disorder
Authors: Goldman Danielle A. , Sankar Anjali , Colic Lejla , Villa Luca , Kim Jihoon A. , Pittman Brian , Constable R. Todd , Scheinost Dustin , Blumberg Hilary P.
Published: October 2021

Objectives

Identifying hubs of brain dysfunction in adolescents and young adults with Bipolar I Disorder (BDAYA) could provide targets for early detection, prevention, and treatment. Previous neuroimaging studies across mood states of BDAYA are scarce and often examined limited brain regions potentially prohibiting detection of other important regions. We used a data‐driven whole‐brain Intrinsic Connectivity Distribution (ICD) approach to investigate dysconnectivity hubs across mood states in BDAYA.

Methods

Functional magnetic resonance imaging whole‐brain ICD data were investigated for differences across four groups: BDAYA‐depressed (n = 22), BDAYA‐euthymic (n = 45), BDAYA‐elevated (n = 24), and healthy controls (HC, n = 111). Clusters of ICD differences were assessed for regional dysconnectivity and mood symptom relationships. Analyses were also performed for BDAYA overall (vs. HC) ICD differences persisting across mood states.

Results

ICD was higher in the BDAYA‐ depressed group than other groups in bilateral ventral/rostral/dorsal prefrontal cortex (PFC) and right lenticular nucleus (LN) (pcorrected <0.05). In BDAYA‐depressed, functional connectivity (FC) was increased between these regions with their contralateral homologues and PFC‐medial temporal FC was more negative (p < 0.005). PFC‐related findings correlated with depression scores (p < 0.05). The overall BDAYA group showed ICD increases in more ventral left PFC and right cerebellum, present across euthymia and acute mood states.

Conclusions

This ICD approach supports a PFC hub of inter‐ and intra‐hemispheric frontotemporal dysconnectivity in BDAYA with potential trait features and disturbances of higher magnitude during depression. Hubs were also revealed in LN and cerebellum, less common foci of BD research. The hubs are potential targets for early interventions to detect, prevent, and treat BD.
Decreasing rate of inpatient pediatric bipolar disorder diagnosis in the US between 2004 and 2010
Authors: Sherwood Samantha N. , Carlson Gabrielle A. , Freeman Andrew J.
Published: October 2021

Objectives

Diagnosis of bipolar disorder (BD) increased substantially among youth between the mid‐1990s and mid‐2000s in the United States. This dramatic increase in diagnosis resulted in concern regarding the potential for misdiagnosis of BD among youth. However, the rate of BD diagnosis in the United States had not been evaluated nationally since the mid‐2000s. It was unclear whether changes in diagnostic rates continued to occur. Therefore, the present study aimed to assess the pattern of longitudinal trends in the rate of national inpatient BD diagnosis subsequent to 2004.

Methods

Data included a nationally representative dataset of inpatient hospitalizations between 1996 and 2010. De‐identified data were obtained from the National Hospital Discharge Survey (NHDS) conducted annually by the National Center for Health Statistics.

Results

The proportion of BD diagnoses relative to all psychiatric diagnoses increased between 1996 and 2004 among children and adolescents. The proportion of BD diagnoses then decreased between 2004 and 2010 among children but continued to increase for adolescents. However, population‐adjusted rates of BD diagnosis per 10,000 individuals in the general population initially increased until the mid‐2000s and then decreased until 2010 for both children and adolescents.

Conclusions

Rates of BD diagnosis substantially decreased for youth between the mid‐2000s and 2010. This decline coincided with recommendations for more conservative diagnostic practices due to concerns about overdiagnosis and increasing awareness of the side effects of front‐line medications used to treat BD in youth. Findings provide insight into changing trends in inpatient service utilization for BD in the United States.
Successful endoscopic submucosal dissection of a laterally spreading tumor involving a diverticulum assisted by a traction device
Authors: Yoshikawa Takaaki , Yamauchi Atsushi , Yazumi Shujiro
Published: October 2021

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‘Increasing value and reducing waste’ in paediatric neurological research
Authors: Becker‐Barroso Elena
Published: October 2021

This commentary is on the original article by Diskin et al. on pages 200–208 of this issue.
Neonatal diabetes caused by disrupted pancreatic and β‐cell development
Authors: De Franco Elisa
Published: October 2021

Neonatal diabetes is diagnosed before the age of 6 months and is usually caused by single‐gene mutations. More than 30 genetic causes of neonatal diabetes have been described to date, resulting in severely reduced β‐cell number or function. Seven of these genes are known to cause neonatal diabetes through disrupted development of the whole pancreas, resulting in diabetes and exocrine pancreatic insufficiency. Pathogenic variants in five transcription factors essential for β‐cell development cause neonatal diabetes without other pancreatic phenotypes. However, additional extra‐pancreatic features are common. This review will focus on the genes causing neonatal diabetes through disrupted β‐cell development, discussing what is currently known about the genetic and phenotypic features of these genetic conditions, and what discoveries may come in the future.
Structural insights reveal the second base catalyst of isomaltose glucohydrolase
Authors: Tagami Takayoshi , Chen Minghao , Furunaga Yuta , Kikuchi Asako , Sadahiro Juri , Lang Weeranuch , Okuyama Masayuki , Tanaka Yoshikazu , Iwasaki Tomohito , Yao Min , Kimura Atsuo
Published: October 2021

Glycoside hydrolase family 15 (GH15) inverting enzymes contain two glutamate residues functioning as a general acid catalyst and a general base catalyst, for isomaltose glucohydrolase (IGHase), Glu178 and Glu335, respectively. Generally, a two‐catalytic residue‐mediated reaction exhibits a typical bell‐shaped pH–activity curve. However, IGHase is found to display atypical non‐bell‐shaped pH‐kcat and pH‐kcat/Km profiles, theoretically better‐fitted to a three‐catalytic residue‐associated pH–activity curve. We determined the crystal structure of IGHase by the single‐wavelength anomalous dispersion method using sulfur atoms and the cocrystal structure of a catalytic base mutant E335A with isomaltose. Although the activity of E335A was undetectable, the electron density observed in its active site pocket did not correspond to an isomaltose but a glycerol and a β‐glucose, cryoprotectant, and hydrolysis product. Our structural and biochemical analyses of several mutant enzymes suggest that Tyr48 acts as a second catalytic base catalyst. Y48F mutant displayed almost equivalent specific activity to a catalytic acid mutant E178A. Tyr48, highly conserved in all GH15 members, is fixed by another Tyr residue in many GH15 enzymes; the latter Tyr is replaced by Phe290 in IGHase. The pH profile of F290Y mutant changed to a bell‐shaped curve, suggesting that Phe290 is a key residue distinguishing Tyr48 of IGHase from other GH15 members. Furthermore, F290Y is found to accelerate the condensation of isomaltose from glucose by modifying a hydrogen‐bonding network between Tyr290‐Tyr48‐Glu335. The present study indicates that the atypical Phe290 makes Tyr48 of IGHase unique among GH15 enzymes.
Hematopoietic PBX‐interacting protein is a novel regulator of mammary epithelial cell differentiation
Authors: Dwivedi Anju , Padala Chiranjeevi , Kumari Anita , Khumukcham Saratchandra Singh , Penugurti Vasudevarao , Ghosh Sinjini , Mazumder Aprotim , Goffin Vincent , Manavathi Bramanandam
Published: October 2021

Hematopoietic PBX‐interacting protein (HPIP, also known as PBXIP1) is an estrogen receptor (ER) interacting protein that regulates estrogen‐mediated breast cancer cell proliferation and tumorigenesis. However, its functional significance in the context of mammary gland development is unexplored. Here, we report that HPIP is required for prolactin (PRL)‐induced lactogenic differentiation in vitro. Molecular analysis of HPIP expression in mice revealed its induced expression at pregnancy and lactation stages of mammary gland. Moreover, PRL is a lactogenic hormone that controls pregnancy as well as lactation and induces Hpip/Pbxip1 expression in a signal transducer and activator of transcription 5a‐dependent manner. Using mammary epithelial and lactogenic‐competent cell lines, we further show that HPIP plays a regulatory role in PRL‐mediated mammary epithelial cell differentiation, which is measured by acini formation, β‐casein synthesis, and lipid droplet formation. Further mechanistic studies using pharmacological inhibitors revealed that HPIP modulates PRL‐induced β‐casein synthesis via phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) activation. This study also identified HPIP as a critical regulator of autocrine PRL signaling as treatment with the PRL receptor antagonist Δ1‐9‐G129R‐hPRL restrained HPIP‐mediated PRL synthesis, AKT activation, and β‐casein synthesis in cultured HC11 cells. Interestingly, we also uncovered that microRNA‐148a (miR‐148a) antagonizes HPIP‐mediated mammary epithelial cell differentiation. Together, our study identified HPIP as a critical regulator of PRL signaling and revealed a novel molecular circuitry involving PRL, HPIP, PI3K/AKT, and miR‐148a that controls mammary epithelial cell differentiation in vitro.
Improving primary health care quality for refugees and asylum seekers: A systematic review of interventional approaches
Authors: P. Iqbal Maha , Walpola Ramesh , Harris‐Roxas Ben , Li Jiadai , Mears Stephen , Hall John , Harrison Reema
Published: October 2021

Background

It has been widely acknowledged that refugees are at risk of poorer health outcomes, spanning mental health and general well‐being. A common point of access to health care for the migrant population is via the primary health care network in the country of resettlement. This review aims to synthesize the evidence of primary health care interventions to improve the quality of health care provided to refugees and asylum seekers.

Methods

A systematic review was undertaken, and 55 articles were included in the final review. The Preferred Reporting Items for Systematic Reviews was used to guide the reporting of the review, and articles were managed using a reference‐management software (Covidence). The findings were analysed using a narrative empirical synthesis. A quality assessment was conducted for all the studies included.

Results

The interventions within the broad primary care setting could be organized into four categories, that is, those that focused on developing the skills of individual refugees/asylum seekers and their families; skills of primary health care workers; system and/or service integration models and structures; and lastly, interventions enhancing communication services. Promoting effective health care delivery for refugees, asylum seekers and their families is a complex challenge faced by primary care professionals, the patients themselves and the communication between them.

Conclusion

This review highlights the innovative interventions in primary care promoting refugee health. Primary care interventions mostly focused on upskilling doctors, with a paucity of research exploring the involvement of other health care members. Further research can explore the involvement of interprofessional team members in providing effective refugee/migrant health.

Patient or Public Contribution

Patient and public involvement was explored in terms of interventions designed to improve health care delivery for the humanitarian migrant population, that is, specifically refugees and asylum seekers.
Mass spectrometric study of the laser‐evaporated Fe–Zr–O system up to 3300 K
Authors: Sheindlin Michael , Frolov Alexander , Petukhov Sergei , Bottomley David , Masaki Kurata , Manara Dario , Costa Davide
Published: October 2021

Material systems such as U–Zr–O, Fe–Zr–O, and Zr–O have been recognized as fundamental for the analysis of in‐vessel nuclear fuel debris behavior during a severe meltdown accident. In the present work, the evaporation behavior of ZrO2 and Zr–Fe–O systems are investigated using heating with laser pulses of millisecond duration and time‐of‐flight mass spectrometry. The relative partial pressures of main species of vapor over ZrO2 and ZrO2–FeO systems were measured at temperatures above 2750 K. The temperature dependence of O/Zr atomic ratio in vapor over zirconia was analyzed: it turned out that evaporation occurs in a noncongruent mode at temperatures above 3000 K. Evaporation of the Zr–Fe–O system was greatly affected by the fast evaporation of FeO, implying that the atomic Zr/Fe ratio, less than 0.1 below 3000 K, significantly increased with temperature. Moreover, the ratios of main vapor components were defined only by the surface temperature, independent of the zirconia sample origin.
Cytokine profiles and the dynamic of gingivitis development in humans
Authors: Leite Fábio R. M. , Nascimento Gustavo G. , Møller Holger J. , Belibasakis Georgios N. , Bostanci Nagihan , Smith Patricio C. , López Rodrigo
Published: October 2021

Aim

To investigate the relationship between cytokine profiles and “fast” and “slow” patterns of gingival inflammation development.

Materials and Methods

Forty‐two adults participated in an experimental gingivitis study, comprising a 2‐week hygiene phase (clinical examination and professional cleaning); a 3‐week induction phase (absence of oral hygiene); and a 2‐week resolution phase (re‐establishment of oral hygiene). Plaque and gingival inflammation scores were assessed. Interferon‐gamma (IFN‐γ), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, and tumour necrosis factor‐alpha (TNF‐α) from gingival crevicular fluid were collected and measured by multiplex ELISA. Group‐based‐trajectory‐modelling (GBTM) was used to model cytokine profiles over the induction phase. The effect of gingival inflammation on cytokine levels over time was estimated with mixed‐effects modelling.

Results

GBTM analysis revealed two cytokine profiles, “non‐organized response” (IL‐4, IL‐6, IL‐8, IL‐12, and IL‐13) and “organized response” (IL‐2, IL‐10, and TNF‐α). Among the “slow” responders, neither cytokine profile was associated with gingivitis. In contrast, a “fast” response was associated with a higher “non‐organized response” factor (coef. 0.14) and a lower “organized response” factor (coef. −0.03).

Conclusion

A “fast” gingivitis development was associated with a higher “non‐organized response” and a lower “organized response”, which may elucidate the role of individual variability in gingivitis susceptibility.
Prenatal androgenization causes expression changes of progesterone and androgen receptor mRNAs in the arcuate nucleus of female mice across development
Authors: Watanabe Yugo , Prescott Melanie , Campbell Rebecca E. , Jasoni Christine L.
Published: October 2021

Prenatal exposure to excess androgens is associated with the development of polycystic ovary syndrome (PCOS). In prenatally androgenised (PNA) mice, a model of PCOS, progesterone receptor (PR) protein expression is reduced in arcuate nucleus (ARC) GABA neurons. This suggests a mechanism for PCOS‐related impaired steroid hormone feedback and implicates androgen excess with respect to inducing transcriptional repression of the PR‐encoding gene Pgr in the ARC. However, the androgen sensitivity of ARC neurons and the relative gene expression of PRs over development and following prenatal androgen exposure remain unknown. Here, we used a quantitative reverse transcriptase‐polymerase chain reaction (RT‐qPCR) of microdissected ARC to determine the relative androgen receptor (Ar) and progesterone receptor (Pgr) gene expression in PNA and control mice at five developmental timepoints. In a two‐way analysis of variance, none of the genes examined showed expression changes with a statistically significant interaction between treatment and age, although PgrA showed a borderline interaction. For all genes, there was a statistically significant main effect of age on expression levels, reflecting a general increase in expression with increasing age, regardless of treatment. For PgrB and Ar, there was a statistically significant main effect of treatment, indicating a change in expression following PNA (increased for PgrB and decreased for Ar), regardless of age. For PgrA, there was a borderline main effect of treatment, suggesting a possible change in expression following PNA, regardless of age. PgrAB gene expression changes showed no significant main effect of treatment. We additionally examined androgen and progesterone responsiveness specifically in P60 ARC GABA neurons using RNAScope® (Advanced Cell Diagnostics, Inc.) in situ hybridization. This analysis revealed that Pgr and Ar were expressed in the majority of ARC GABA neurons in normal adult females. However, our RNAScope® analysis did not show significant changes in Pgr or Ar expression within ARC GABA neurons following PNA. Lastly, because GABA drive to gonadotropin‐releasing hormone neurons is increased in PNA, we hypothesised that PNA mice would show increased expression of glutamic acid decarboxylase (GAD), the rate‐limiting enzyme in GABA production. However, the RT‐qPCR showed that the expression of GAD encoding genes (Gad1 and Gad2) was unchanged in adult PNA mice compared to controls. Our findings indicate that PNA treatment can impact Pgr and Ar mRNA expression in adulthood. This may reflect altered circulating steroid hormones in PNA mice or PNA‐induced epigenetic changes in the regulation of Pgr and Ar gene expression in ARC neurons.
Role of adenosine signaling in preeclampsia
Authors: Iriyama Takayuki , Sayama Seisuke , Osuga Yutaka
Published: October 2021

Placenta‐specific molecular basis that is responsible for the pathophysiology of preeclampsia (PE) remains to be fully understood. Adenosine, an endogenous nucleoside, is a signaling molecule that is induced under pathological conditions such as hypoxia and is involved in various diseases. Recent evidence on humans and animal models has demonstrated that enhanced placental adenosine signaling contributes to the development of PE. This review is to summarize current progress and discuss the significance of adenosine signaling in the pathophysiology of PE and future perspectives of therapeutic possibilities targeting adenosine signaling.
The prognosis of “sandwich” mode of postoperative chemotherapy and radiation in patients with locally advanced cervical cancer
Authors: Geng Yuning , Wang Ming , Yang Shuli , Zhao Hui , Wu Yumei
Published: October 2021

Objective

This study aims to evaluate the survival outcome between different postoperative radiation and chemotherapy modes in locally advanced cervical cancer (LACC).

Methods

This study is a retrospective cohort study. A total of 150 patients with LACC underwent radical hysterectomy combined with postoperative radiation and /or chemotherapy from October 2009 to October 2019. Of those, 101 patients who received “sandwich” adjuvant chemotherapy and radiation (SCR) were enrolled into group A and 49 patients who received simple radiation were enrolled into group B. The primary outcome was the rates of progression‐free survival (PFS) and overall survival (OS).

Results

Of 150 patients, 95.3% (143/150) patients complete the study. The rates of deep myometrial invasion (92% and 72.9%, p = 0.007), lymph vascular invasion positive (74.3% and 26.5%, p = 2.59 × 10−8), positive surgical margin (11.9% and 0%, p = 0.012), and lymph‐node involvement (40.6% vs. 4.1%, p = 4.0 × 10−6) at baseline were higher in the group A than group B. There was no difference between the follow‐up time of group A and group B (45.81 ± 16.83 vs. 45.81 ± 16.84 months, p = 0.665). After the postoperative adjuvant, group A achieved the comparable PFS to group B [p = 0.40; hazard ratio (HR), 1.45; 95% CI, 0.62–3.38]. The cumulative rate of OS in group A was comparable in group B (p = 0.31; HR, 1.53; 95% CI, 0.68–3.45).

Conclusions

Postoperative ‘sandwich’ chemotherapy and radiation could yield a similar survival rate to radiation alone in LACC women with high‐risk factors such as deep interstitial infiltration, lymphatic vascular space infiltration, positive resection margin, and lymph‐node metastasis.
Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells
Authors: Silva Luan César , Borgato Gabriell Bonifácio , Wagner Vivian Petersen , Martins Manoela Domingues , Rocha Guilherme Zweig , Lopes Márcio Ajudarte , Santos‐Silva Alan Roger , de Castro Júnior Gilberto , Kowalski Luiz Paulo , Nor Jacques E. , Squarize Cristiane H. , Castilho Rogerio Moraes , Vargas Pablo Agustin
Published: October 2021

Aim

To evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands.

Material and Methods

UM‐HMC‐1, UM‐HMC‐2, and UM‐HMC‐3A MEC cell lines were used to establish the effects of Cephaeline over tumor viability determined by MTT assay. In vitro wound healing scratch assays were performed to address cellular migration while immunofluorescence staining for histone H3 lysine 9 (H3k9ac) was used to identify the acetylation status of tumor cells upon Cephaeline administration. The presence of cancer stem cells was evaluated by the identification of ALDH enzymatic activity by flow cytometry and through functional assays using in vitro tumorsphere formation.

Results

A single administration of Cephaeline resulted in reduced viability of MEC cells along with the halt on tumor growth and cellular migration potential. Administration of Cephaeline resulted in chromatin histone acetylation as judged by the increased levels of H3K9ac and disruption of tumorspheres formation. Interestingly, ALDH levels were increased in UM‐HMC‐1 and UM‐HMC‐3A cell lines, while UM‐HMC‐2 showed a reduced enzymatic activity.

Conclusion

Cephaeline has shown anti‐cancer properties in all MEC cell lines tested by regulating tumor cells’ viability, migration, proliferation, and disrupting the ability of cancer cells to generate tumorspheres.
Serotonin Receptor (HTR2A) Gene Polymorphism Modulates Social Sharing of Happiness in Both American and Japanese Adults
Authors: Matsunaga Masahiro , Ohtsubo Yohsuke , Masuda Takahiko , Noguchi Yasuki , Yamasue Hidenori , Ishii Keiko
Published: October 2021

A single nucleotide polymorphism in the serotonin 2A receptor gene (HTR2Ars6311 guanine [G] vs. adenine [A]) appears associated with positive emotional contagion (social sharing of happiness) in Japanese people. However, it remains unknown whether theHTR2Apolymorphism also impacts the social sharing of happiness in Western cultures. The present study thus compared 207 Japanese university students and 200 American adults (including non‐students). Social sharing of happiness was examined using a vignette‐based questionnaire. Participants were asked to imagine that they were experiencing an emotionally neutral event. At the same time, they were asked to imagine that a friend was experiencing a positive valence event (presence condition), whereas in the other condition such information was not presented (absence condition). Results showed that the G allele carriers felt happier in the presence than in the absence of the friend compared with participants with the AA genotype. Although we did not specifically consider comparability between the two samples, the findings suggest that the effect ofHTR2Apolymorphisms on social sharing of happiness observed in Japanese populations may be applicable to American populations.