bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of Disease Penetrance in PRPF31-Associated Retinopathy
Authors: McLenachan Samuel , Zhang Dan , Grainok Janya , Zhang Xiao , Huang Zhiqin , Chen Shang-Chih , Zaw Khine , Lima Alanis , Jennings Luke , Roshandel Danial , Moon Sang Yoon , Heath Jeffery Rachael C. , Attia Mary S. , Thompson Jennifer A. , Lamey Tina M. , McLaren Terri L. , De Roach John , Fletcher Sue , Chen Fred K.
Published: September 2021

Retinitis pigmentosa 11 (RP11) is caused by dominant mutations in PRPF31, however a significant proportion of mutation carriers do not develop retinopathy. Here, we investigated the relationship between CNOT3 polymorphism, MSR1 repeat copy number and disease penetrance in RP11 patients and non-penetrant carriers (NPCs). We further characterized PRPF31 and CNOT3 expression in fibroblasts from eight RP11 patients and one NPC from a family carrying the c.1205C>T variant. Retinal organoids (ROs) and retinal pigment epithelium (RPE) were differentiated from induced pluripotent stem cells derived from RP11 patients, an NPC and a control subject. All RP11 patients were homozygous for the 3-copy MSR1 repeat in the PRPF31 promoter, while 3/5 NPCs carried a 4-copy MSR1 repeat. The CNOT3 rs4806718 genotype did not correlate with disease penetrance. PRFP31 expression declined with age in adult cadaveric retina. PRPF31 and CNOT3 expression was reduced in RP11 fibroblasts, RO and RPE compared with controls. Both RP11 and NPC RPE displayed shortened primary cilia compared with controls, however a subpopulation of cells with normal cilia lengths was present in NPC RPE monolayers. Our results indicate that RP11 non-penetrance is associated with the inheritance of a 4-copy MSR1 repeat, but not with CNOT3 polymorphisms.
Detection of Del/Dup Inside SHOX/PAR1 Region in Children and Young Adults with Idiopathic Short Stature
Authors: Stritar Jera , Stavber Lana , Ficko Maja , Kotnik Primož , Battelino Tadej , Trebušak Podkrajšek Katarina , Hovnik Tinka
Published: September 2021

Short stature is a common growth disorder defined as a body height two standard deviations (SD) or more below the mean for a given age, gender, and population. A large part of the cases remains unexplained and is referred to as having idiopathic short stature (ISS). One of the leading genetic causes of short stature is variants of short stature homeobox-containing gene (SHOX) and is considered to be responsible for 2–15% of ISS. We aimed to analyse the regulatory and coding region of SHOX in Slovenian children and young adults with ISS and to investigate the pathogenicity of detected variants. Our cohort included 75 children and young adults with ISS. Multiplex ligation-dependent probe amplification (MLPA) was performed in all participants for the detection of larger copy number variations (CNVs). Sanger sequencing was undertaken for the detection of point variants, small deletions, and insertions. A total of one deletion and two duplications were discovered using the MLPA technique. Only one of these four variants was identified as disease-causing and occurred in one individual, which represents 1.3% of the cohort. With Sanger sequencing, two variants were discovered, but none of them appeared to have a pathogenic effect on height. According to the results, in the Slovenian population of children and young adults with ISS, SHOX deficiency is less frequent than expected considering existing data from other populations.
Associations between ALDH Genetic Variants, Alcohol Consumption, and the Risk of Nasopharyngeal Carcinoma in an East Asian Population
Authors: Liao Wen-Ling , Chan Fu-Chun , Chang Kai-Ping , Chang Ya-Wen , Chen Che-Hong , Su Wen-Hui , Chang Hen-Hong
Published: September 2021

Nasopharyngeal carcinoma (NPC) and alcohol flush syndrome are thought to be strongly influenced by genetic factors and are highly prevalent amongst East Asians. Diminished activity of aldehyde dehydrogenase (ALDH), a major enzyme in the alcohol-metabolizing pathway, causes the flushing syndrome associated with alcoholic consumption. The genetic effect of ALDH isoforms on NPC is unknown. We therefore investigated the association between the genetic polymorphisms of all 19 ALDH isoforms and NPC among 458 patients with NPC and 1672 age- and gender-matched healthy controls in Taiwan. Single-nucleotide polymorphisms (SNPs) located between the 40,000 base pairs upstream and downstream of the 19 ALDH isoform coding regions were collected from two genome-wise association studies conducted in Taiwan and from the Taiwan Biobank. Thirteen SNPs located on ALDH4A1, ALDH18A1, ALDH3B2, ALDH1L2, ALDH1A2, and ALDH2 Glu487Lys (rs671) were associated with NPC susceptibility. Stratification by alcohol status revealed a cumulative risk effect for NPC amongst drinkers and non-drinkers, with odds ratios of 4.89 (95% confidence interval 2.15–11.08) and 3.57 (1.97–6.47), respectively. A synergistic effect was observed between SNPs and alcohol. This study is the first to report associations between genetic variants in 19 ALDH isoforms, their interaction with alcohol consumption and NPC in an East Asian population.
Global Transcriptome Characterization and Assembly of the Thermophilic Ascomycete Chaetomium thermophilum
Authors: Singh Amit , Schermann Géza , Reislöhner Sven , Kellner Nikola , Hurt Ed , Brunner Michael
Published: September 2021

A correct genome annotation is fundamental for research in the field of molecular and structural biology. The annotation of the reference genome of Chaetomium thermophilum has been reported previously, but it is essentially limited to open reading frames (ORFs) of protein coding genes and contains only a few noncoding transcripts. In this study, we identified and annotated full-length transcripts of C. thermophilum by deep RNA sequencing. We annotated 7044 coding genes and 4567 noncoding genes. Astonishingly, 23% of the coding genes are alternatively spliced. We identified 679 novel coding genes as well as 2878 novel noncoding genes and corrected the structural organization of more than 50% of the previously annotated genes. Furthermore, we substantially extended the Gene Ontology (GO) and Enzyme Commission (EC) lists, which provide comprehensive search tools for potential industrial applications and basic research. The identified novel transcripts and improved annotation will help to understand the gene regulatory landscape in C. thermophilum. The analysis pipeline developed here can be used to build transcriptome assemblies and identify coding and noncoding RNAs of other species.
Non-Recombinogenic Functions of Rad51, BRCA2, and Rad52 in DNA Damage Tolerance
Authors: Prado Félix
Published: September 2021

The DNA damage tolerance (DDT) response is aimed to timely and safely complete DNA replication by facilitating the advance of replication forks through blocking lesions. This process is associated with an accumulation of single-strand DNA (ssDNA), both at the fork and behind the fork. Lesion bypass and ssDNA filling can be performed by translation synthesis (TLS) and template switching mechanisms. TLS uses low-fidelity polymerases to incorporate a dNTP opposite the blocking lesion, whereas template switching uses a Rad51/ssDNA nucleofilament and the sister chromatid to bypass the lesion. Rad51 is loaded at this nucleofilament by two mediator proteins, BRCA2 and Rad52, and these three factors are critical for homologous recombination (HR). Here, we review recent advances showing that Rad51, BRCA2, and Rad52 perform some of these functions through mechanisms that do not require the strand exchange activity of Rad51: the formation and protection of reversed fork structures aimed to bypass blocking lesions, and the promotion of TLS. These findings point to the central HR proteins as potential molecular switches in the choice of the mechanism of DDT.
Genetic and Molecular Evaluation: Reporting Three Novel Mutations and Creating Awareness of Pycnodysostosis Disease
Authors: Sayed Amr Khalda , El-Bassyouni Hala T. , Abdel Hady Sawsan , Mostafa Mostafa I. , Mehrez Mennat I. , Coviello Domenico , El-Kamah Ghada Y.
Published: September 2021

Pycnodysostosis is a rare autosomal recessive disorder with characteristic diagnostic manifestations. This study aims to phenotype and provide molecular characterization of Egyptian patients, with emphasis on identifying unusual phenotypes and raising awareness about pycnodysostosis with different presentations to avoid a mis- or under-diagnosis and consequent mismanagement. We report on 22 Egyptian pycnodysostosis patients, including 9 new participants, all descending from consanguineous families and their ages ranging from 6 to 15 years. In addition, prenatal diagnosis was performed in one family with affected siblings. They all presented with short stature, except for one patient who presented with pancytopenia as her primary complaint. Moreover, 41.2% of patients had sleep apnea, 14% presented with craniosynostosis, and 44.4% had failure of tooth development. Molecular analysis via direct exome sequencing of the cathepsin K gene revealed three novel mutations ((NM_000396.3) c.761_763delCCT, c.864_865delAA, and c.509G>T) as well as two previously reported mutations among nine new cases. The following is our conclusion: This study expands the molecular spectrum of pycnodysostosis by identifying three novel mutations and adds to the clinical and orodental aspects of the disease. The link between the CTSK gene mutations and the failure of tooth development has not been established, and further studies could help to improve our understanding of the molecular pathology.
A Comprehensive Examination of Severely Ill ME/CFS Patients
Authors: Chang Chia-Jung , Hung Li-Yuan , Kogelnik Andreas M. , Kaufman David , Aiyar Raeka S. , Chu Angela M. , Wilhelmy Julie , Li Peng , Tannenbaum Linda , Xiao Wenzhong , Davis Ronald W.
Published: September 2021

One in four myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients are estimated to be severely affected by the disease, and these house-bound or bedbound patients are currently understudied. Here, we report a comprehensive examination of the symptoms and clinical laboratory tests of a cohort of severely ill patients and healthy controls. The greatly reduced quality of life of the patients was negatively correlated with clinical depression. The most troublesome symptoms included fatigue (85%), pain (65%), cognitive impairment (50%), orthostatic intolerance (45%), sleep disturbance (35%), post-exertional malaise (30%), and neurosensory disturbance (30%). Sleep profiles and cognitive tests revealed distinctive impairments. Lower morning cortisol level and alterations in its diurnal rhythm were observed in the patients, and antibody and antigen measurements showed no evidence for acute infections by common viral or bacterial pathogens. These results highlight the urgent need of developing molecular diagnostic tests for ME/CFS. In addition, there was a striking similarity in symptoms between long COVID and ME/CFS, suggesting that studies on the mechanism and treatment of ME/CFS may help prevent and treat long COVID and vice versa.
Nutritional Health Education in Pregnant Women in a Rural Health Centre: Results in Spanish and Foreign Women
Authors: Dios-Aguado Mercedes de , Agulló-Ortuño María Teresa , Ugarte-Gurrutxaga María Idoia , Yañez-Araque Benito , Molina-Gallego Brígida , Gómez-Cantarino Sagrario
Published: September 2021

The dietary behaviour of pregnant women, as well as the socio-cultural conditions in which pregnancy takes place, influence obstetric outcomes. To analyse the influence of socioeconomic factors and dietary habits on obstetric outcomes in Spanish and foreign pregnant women living in a rural environment, a population-based, prospective-observational study in a cohort of Spanish and foreign pregnant women in the town of Yepes, in the province of Toledo, Spain was conducted. Foreign pregnant women are ecodependent on their partners, have secondary education and low socioeconomic level. Spanish pregnant women have secondary education, a medium socio-economic level, live with their partners and are economically independent. Moreover, 85% of Spanish pregnant women gave birth at term and reached a gestational age of 40 ± 1.83 weeks. However, only 55% of foreign pregnant women reached a gestational age of 39.72 ± 2.28 weeks. Through health education, pregnant women in this geographical area of Castilla la Mancha, Spain, adopted bicultural dietary patterns, thus reaching the prescribed diet of 2000 Kcal. Through this diet, both Spanish and foreign pregnant women maintained albumin and plasma protein levels within the established range, with no significant differences in obstetric outcomes among pregnant women in the study.
Doctors’ Views on How to Improve Communication and Quality of Care for Patients Experiencing End-of-Life: A Qualitative Descriptive Study
Authors: McCormack Fiona , Hopley Rachel , Kurth Judith , Iqbal Zafar
Published: September 2021

(1) Background: There remains a lack of sufficient progress in enhancing quality of care for patients experiencing end-of-life. This study aimed to better understand the views of doctors on how to improve end-of-life healthcare, in light of existing challenges and processes. (2) Methods: This qualitative descriptive study used semi-structured individual interviews. Through purposive sampling, sixteen doctors from primary care (three general practices) or acute care (one National Health Service hospital trust) participated. Interviews were audio-recorded, transcribed and thematic analysis conducted. (3) Results: Two main themes were identified: First, planning for patient-centred care—conversations about end-of-life care should take place earlier to allow for care that is planned and personalised. The need for more training and improvements to documenting patient wishes were highlighted. Second, delivering on patients’ wishes: improvements to the healthcare system—the importance of a record of patient wishes that can be shared across the system was identified. Improved utilisation of available resources is also needed to better deliver quality patient-centred care. (4) Conclusion: More effective communication and coordination across acute and primary care settings is needed. The importance of patient wishes and advance care planning was emphasised. More guidance at a strategic level may help provide clarity about expectations, roles and responsibilities.
From Discovery to Public Consumption: The Process of Mapping and Evaluating Underwater Cultural Heritage in Malta
Authors: Gambin Timmy , Bravo-Morata Rodríguez Alberto , Sausmekat Maja
Published: September 2021

The in situ promotion and preservation of underwater cultural heritage sites is one of the main ideas of the UNESCO Convention on the Protection of Underwater Cultural Heritage. Currently, most shipwrecks are found in water shallower than the 50 m contour. The continued technological advances and increases in technical diving and deep-water exploration point towards a shift in this statistic, which is set to increase exponentially in the not-too-distant future. Thus, it is imperative to look at ways in which such directives can be implemented. This paper will highlight the synergy between existing remote sensing technologies and the management of underwater cultural heritage with examples of on-going research projects, such as Malta’s approach to surveying and implementing a scoring system for historic wreck sites based on local and global considerations of historic and natural conditions of site elements. Such an approach allows for the scaling of sites based on a number of parameters and provides instructive information for the creation of management strategies. The intention here is to demonstrate how large-scale remote sensing surveys can make major contributions to site management, which, in turn, facilitates the decision-making process in terms of how and what information is transmitted to divers and members of the public.
Nutraceutical and Functional Properties of Peel, Pulp, and Seed Extracts of Six ‘Köhnü’ Grape Clones
Authors: Kupe Muhammed , Karatas Neva , Unal Mehmet Settar , Ercisli Sezai , Baron Mojmir , Sochor Jiri
Published: September 2021

Grape production has a long history in the Elazig province and surrounding vicinity and produced grapes have been used for table consumption and also processed into traditional beverages, Şıra (special non-alcoholic grape juice) and wine. In the Elazig province, the main grape cultivars are ‘Ağın Beyazı’, ‘Öküzgözü’, ‘Boğazkere’, ‘Şilfoni’, ‘Tahannebi’, and ‘Köhnü’. Among them, ‘Köhnü’ cultivar is highly preferred by consumers due to its black color and perfect berry characteristics. The cultivar has grown for centuries in different parts of Elazig and shows a great variability for most of its morphological and biochemical characteristics. In the present study, we aimed to determine morphological and biochemical traits in six ‘Köhnü’ clones sampled from Elazığ. The cluster weight of six clones was found between 334–394 g. The highest total phenolic content was observed in seeds followed by peel and pulp samples. The seed extract of Clone 2 had the highest total phenolic content at 254 mg gallic acid equivalent/100 g fresh weight. The results also showed that peel, pulp, and seed samples of ‘Köhnü’ grape clones had considerable amounts of antioxidant components determined by DPPH (1,1-Diphenyl-2-picryl-hydrazyl), FRAP (ferric reducing antioxidant power), and TEAC assays and might be rich sources of natural antioxidants. Among the six ‘Köhnü’ clones, Clone 3, and Clone 6 differed from the others in respect to the highest cluster weight, the highest concentrations of total phenolic content, and antioxidant activity. The results also implied that all clones could be used potentially as a readily accessible source of natural antioxidants and as a possible pharmaceutical supplement.
Human Biomonitoring of Environmental and Occupational Exposures by GC-MS and Gas Sensor Systems: A Systematic Review
Authors: Longo Valentina , Forleo Angiola , Giampetruzzi Lucia , Siciliano Pietro , Capone Simonetta
Published: September 2021

Environmental chemicals and contaminants coming from multiple external sources enter the human body, determining a potential risk for human health. Human biomonitoring (HBM), measuring the concentrations of biomarkers in human specimens, has become an emerging approach for assessing population-wide exposure to hazardous chemicals and health risk through large-scale studies in many countries. However, systematic mapping of HBM studies, including their characteristics, targeted hazardous pollutants, analytical techniques, and sample population (general population and occupationally exposed workers), has not been done so far. We conducted a systematic review of the literature related to airborne hazardous pollutants in biofluids to answer the following questions: Which main chemicals have been included in the literature, which bodily fluids have been used, and what are the main findings? Following PRISMA protocol, we summarized the publications published up to 4 February 2021 of studies based on two methods: gas-chromatography/mass spectrometry (GC/MS) and electronic noses (e-noses). We screened 2606 records and 117 publications were included in the analysis, the most based on GC/MS analysis. The selected HBM studies include measurements of biomarkers in different bodily fluids, such as blood, urine, breast milk, and human semen as well as exhaled air. The papers cover numerous airborne hazardous pollutants that we grouped in chemical classes; a lot of hazardous and noxious compounds, mainly persistent organic pollutants (POPs) and volatile organic compounds (VOCs), have been detected in biological fluids at alarming levels. The scenario that emerged from this survey demonstrates the importance of HBM in human exposure to hazardous pollutants and the need to use it as valid tool in health surveillance. This systematic review represents a starting point for researchers who focus on the world of pollutant biomonitoring in the human body and gives them important insights into how to improve the methods based on GC/MS. Moreover, it makes a first overview of the use of gas sensor array and e-noses in HBM studies.
Oral Health Knowledge Gaps and Their Impact on the Role of Pediatricians: A Multicentric Study
Authors: Alrashdi Murad , Limaki Maria-Eleni , Alrashidi Abdualelah
Published: September 2021

Purpose: This study aimed to evaluate the current level of pediatricians to promote oral health. In particular, the study sought to determine whether years of experience were associated with the dentistry knowledge of pediatricians. Materials and Methods: Online recruitment was used to obtain a sample of pediatricians from the United States of America, Greece, and Saudi Arabia. These three countries are the participants in this research project. The participants completed an anonymous, online, self-administered questionnaire. This questionnaire is available upon request. The differences in responses to knowledge questions, attitude questions, and solution questions were examined with respect to years of experience. Poisson regression models were used to examine whether these differences were statistically significant. Results: A total of 313 pediatricians participated in the study. The study found moderate levels of dental knowledge among pediatricians. A total of 53.4% reported that they had adequate knowledge to make the right recommendations on oral health for patients and parents. Compared to the participants in a residency program, the participants with 5 to 10 years of experience were over 2.72 times as likely to report adequate knowledge, and participants with 10 years of experience or more were nearly 1.98 times as likely to report adequate knowledge. There was a significant association between dentistry knowledge questions and attitude. Conclusion: The current level of influence of pediatricians in promoting pediatric oral health is limited to moderate. The gaps in oral health knowledge remain an issue, even among a broad sample of pediatricians from Greece, Saudi Arabia, and the United States, particularly pediatricians with less work experience.
An Exploratory Study among Intellectual Disability Physicians on the Care and Coercion Act and the Use of Psychotropic Drugs for Challenging Behaviour
Authors: bij de Weg Janouk C. , Honingh Aline K. , Teeuw Marieke , Sterkenburg Paula S.
Published: September 2021

The new Dutch Care and Coercion Act aims to better regulate the use of psychotropic drugs for challenging behaviour in people with an intellectual disability. This study explores experiences of intellectual disability physicians (IDPs) in prescribing psychotropic drugs and investigates how the Act and the new multidisciplinary guideline on challenging behaviour affects their practice. A qualitative study was conducted, consisting of nine semi-structured in-depth interviews with IDPs, followed by a thematic analysis. It was found that IDPs experienced the new Act and guideline as supportive of their work as guardians of the appropriate use of psychotropic drugs. The multidisciplinary character of the guideline was experienced positively. However, IDPs are faced with organisational barriers and time constraints, as such, they question the feasibility of implementing the Act. Based on these findings, it can be concluded that the Care and Coercion Act may support the existing shift towards the appropriate use of psychotropic drugs if required conditions can be met.
Exploring the Influencing Factors of the Recreational Utilization and Evaluation of Urban Ecological Protection Green Belts for Urban Renewal: A Case Study in Shanghai
Authors: Zhao Weiqi , Wang Yun , Chen Dan , Wang Ling , Tang Xiaomin
Published: September 2021

With the continuous expansion of urban construction land, the green belts aiming for ecological protection have ensured a sustainable and effective function of regional ecosystem services. At the same time, these ecological green belts are expected to develop their compound service potentials with the development of cities. In order to meet the increasing demand of urban residents for the recreational utilization of urban green space, the primary function of the ecological green belts has transformed from being purely ecological to a combination of being ecological and recreational. Based on social media data, which has the characteristics of a large amount of accessible geographic information, this study used multiple regression models to analyze the recreational utilization intensity of ecological protection green belts with a case study in the green belt of Shanghai, China. The research results showed that the internal elements (total external area, water area, etc.) of the Shanghai green belt have positive correlations with its recreational utilization. The impact of external factors was inconclusive on the recreational utilization of the outer forest belt (the number of subway stations in accessibility factors was negatively correlated; the number of cultural facilities and the number of restaurants in the surrounding service facilities were positively related). Combined with the “Shanghai City Master Plan (2017–2035)”, this study suggests potential zones for the recreational transformation of the Shanghai green belt, provides a theoretical and practical basis for improving the recreational utilization of an urban ecological protection green belt and contributes to the sustainable development of ecological protection green belts in high-density cities.
Psychological Distress, Dental Health, and Dental Fear among Finnish University Students: A National Survey
Authors: Pohjola Vesa , Kunttu Kristina , Virtanen Jorma I.
Published: September 2021

The aim of this study was to investigate the association between dental fear, psychological distress, and perceived symptoms of teeth controlled for age, gender, educational sector, and tobacco use. The data from the Finnish University Student Health Survey 2016 targeting students (n = 10,000) of academic universities and universities of applied sciences were used. Psychological distress was measured with the Clinical Outcomes in Routine Evaluation 10 (CORE-10) and the General Health Questionnaire 12 (GHQ-12) and dental fear with the question ‘Do you feel scared about receiving dental care?’. The study included 3110 students. In logistic regression analyses those with psychological distress (measured with CORE-10 and GHQ-12) and those reporting teeth-related symptoms were more likely than their counterparts to have high dental fear. In gender-specific analyses men with psychological distress (measured with CORE-10) and women with teeth-related symptoms were more likely to have high levels of dental fear. Finnish university students with psychological distress and teeth-related symptoms were more likely to experience higher levels of dental fear than their counterparts were. The results of this study support possible common vulnerability factors that dental fear and other psychological disorders may share.
Risk Modifying Factors of Anxiety and Depressive Disorders, Using the Example of a Population Study in the Żywiec District
Authors: Lubecka Bogumiła , Lubecki Marek , Kasperczyk Janusz , Jośko-Ochojska Jadwiga , Pudlo Robert
Published: September 2021

The aim of this study was the identification of the risk modifying factors of anxiety and depressive disorders based on a population study. This study was conducted in a randomly selected group of 1659 adult inhabitants of the Żywiec district. Anonymous questionnaires consisting of a proprietary questionnaire and the Hospital Anxiety and Depression Scale (HADS) were used to collect the data. The conducted analysis revealed that the factors increasing the risk of depressive disorders in the studied population were female gender, age over 60, retirement period, primary and vocational education, unemployment, mental work and absolute lack of physical activity, but also daily and intensive sports, heavy smoking, chronic somatic diseases and misuse of sleeping pills and over-the-counter sedatives. Anxiety disorders occurred more often in the group of unemployed, self-employed or retired people. They also occurred more often in the group of people who do not perform any physical activity and use alcohol every day, but also among those who maintain abstinence, regularly smoke tobacco and use stimulants, suffer from somatic diseases and overuse sleeping drugs. Disease preventive factors for anxiety disorders and depression were a constant form of employment, moderate and regular physical activity, avoiding the use of psychoactive substances and the regular treatment of comorbid somatic diseases and insomnia.
Predicting Future Geographic Hotspots of Potentially Preventable Hospitalisations Using All Subset Model Selection and Repeated K-Fold Cross-Validation
Authors: Tuson Matthew , Turlach Berwin , Murray Kevin , Kok Mei Ruu , Vickery Alistair , Whyatt David
Published: September 2021

Long-term future prediction of geographic areas with high rates of potentially preventable hospitalisations (PPHs) among residents, or “hotspots”, is critical to ensure the effective location of place-based health service interventions. This is because such interventions are typically expensive and take time to develop, implement, and take effect, and hotspots often regress to the mean. Using spatially aggregated, longitudinal administrative health data, we introduce a method to make such predictions. The proposed method combines all subset model selection with a novel formulation of repeated k-fold cross-validation in developing optimal models. We illustrate its application predicting three-year future hotspots for four PPHs in an Australian context: type II diabetes mellitus, heart failure, chronic obstructive pulmonary disease, and “high risk foot”. In these examples, optimal models are selected through maximising positive predictive value while maintaining sensitivity above a user-specified minimum threshold. We compare the model’s performance to that of two alternative methods commonly used in practice, i.e., prediction of future hotspots based on either: (i) current hotspots, or (ii) past persistent hotspots. In doing so, we demonstrate favourable performance of our method, including with respect to its ability to flexibly optimise various different metrics. Accordingly, we suggest that our method might effectively be used to assist health planners predict excess future demand of health services and prioritise placement of interventions. Furthermore, it could be used to predict future hotspots of non-health events, e.g., in criminology.
The Effect of Concurrent Resistance Training on Upper Body Strength, Sprint Swimming Performance and Kinematics in Competitive Adolescent Swimmers. A Randomized Controlled Trial
Authors: Amara Sofiene , Barbosa Tiago M. , Negra Yassine , Hammami Raouf , Khalifa Riadh , Chortane Sabri Gaied
Published: September 2021

This study aimed to examine the effect of 9 weeks of concurrent resistance training (CRT) between resistance on dry land (bench press (BP) and medicine ball throw) and resistance in water (water parachute and hand paddles) on muscle strength, sprint swimming performance and kinematic variables compared by the usual training (standard in-water training). Twenty-two male competitive swimmers participated in this study and were randomly allocated to two groups. The CRT group (CRTG, age = 16.5 ± 0.30 years) performed a CRT program, and the control group (CG, age = 16.1 ± 0.32 years) completed their usual training. The independent variables were measured pre- and post-intervention. The findings showed that the one-repetition maximum bench press (1RM BP) was improved only after a CRT program (d = 2.18; +12.11 ± 1.79%). Moreover, all sprint swimming performances were optimized in the CRT group (d = 1.3 to 2.61; −4.22 ± 0.18% to −7.13 ± 0.23%). In addition, the findings revealed an increase in velocity and stroke rate (d = 1.67, d = 2.24; 9.36 ± 2.55%, 13.51 ± 4.22%, respectively) after the CRT program. The CRT program improved the muscle strength, which, in turn, improved the stroke rate, with no change in the stroke length. Then, the improved stroke rate increased the swimming velocity. Ultimately, a faster velocity leads to better swim performances.
Safe Debonding of Fixed Appliances: A Comparison of Traditional Techniques and LODI Devices on Different Bracket Types in Terms of Enamel Cracks, Site of Bond Failure, and Bracket Reusability
Authors: Gibas-Stanek Marta , Pihut Małgorzata
Published: September 2021

The objective of this study was to compare the effects of the debonding of three different bracket types by means of three popular debonding methods. A total of 180 human third molars was divided into six groups, consisting of 20 teeth each. Three bracket types were bonded to the enamel (metal brackets with an integral base and a foil mesh base, and ceramic brackets) and three methods of bracket debonding were employed (bracket removal pliers, Weingart pliers, and Lift-Off Debonding Instrument). The samples were examined with scanning electron microscopy to assess the number of enamel cracks, measure the area of adhesive remaining on the enamel, and calculate the adhesive remnant index (ARI). There were no statistically significant differences between the groups in terms of the number of enamel cracks after bracket debonding. The amount of adhesive remaining on the teeth after the brackets were removed was significantly different between the groups. LODI and Weingart pliers are considered to be the safest methods of debonding brackets with an integral base, while LODI is the best tool for brackets with foil mesh. Bracket removal pliers are considered to be the preferred method for ceramic bracket debonding.
Topology Conflict Detection Considering Incremental Updating of Multi-Scale Road Networks
Authors: Zhang Jianchen , Wang Jiayao , Li Heying
Published: September 2021

Incremental updating is an important technical method used to maintain the data of road networks. Topology conflict detection of multiscale road networks in incremental updating is an important link. Most of the previous algorithms focus on a single scale road network, which cannot be applied to topology conflict detection for different scale road networks during incremental updating. Therefore, this study proposes a topology conflict detection algorithm that considers the incremental updating of multiscale networks. The algorithm designs a K-order topological neighborhood to judge incremental neighborhood links and builds a topology refinement model based on geometric measurement. Furthermore, we propose a network topology conflict detection rule considering the influence of cartographic generalization operator and use the improved topological distance to detect topology conflicts. The experimental results show that (1) the overall accuracy and recall rate of the proposed method are more than 90%; (2) after considering the topology conflict caused by cartography generalization, the accuracy was increased by 29.2%; and (3) the value of average path length of a network can be used as the basis for setting the best K value.
SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification
Authors: Bellchambers Helen M. , Barratt Kristen S. , Diamand Koula E. M. , Arkell Ruth M.
Published: September 2021

The mechanisms of neural crest cell induction and specification are highly conserved among vertebrate model organisms, but how similar these mechanisms are in mammalian neural crest cell formation remains open to question. The zinc finger of the cerebellum 1 (ZIC1) transcription factor is considered a core component of the vertebrate gene regulatory network that specifies neural crest fate at the neural plate border. In mouse embryos, however, Zic1 mutation does not cause neural crest defects. Instead, we and others have shown that murine Zic2 and Zic5 mutate to give a neural crest phenotype. Here, we extend this knowledge by demonstrating that murine Zic3 is also required for, and co-operates with, Zic2 and Zic5 during mammalian neural crest specification. At the murine neural plate border (a region of high canonical WNT activity) ZIC2, ZIC3, and ZIC5 function as transcription factors to jointly activate the Foxd3 specifier gene. This function is promoted by SUMOylation of the ZIC proteins at a conserved lysine immediately N-terminal of the ZIC zinc finger domain. In contrast, in the lateral regions of the neurectoderm (a region of low canonical WNT activity) basal ZIC proteins act as co-repressors of WNT/TCF-mediated transcription. Our work provides a mechanism by which mammalian neural crest specification is restricted to the neural plate border. Furthermore, given that WNT signaling and SUMOylation are also features of non-mammalian neural crest specification, it suggests that mammalian neural crest induction shares broad conservation, but altered molecular detail, with chicken, zebrafish, and Xenopus neural crest induction.
Antifungal Activity of Bacillus velezensis CE 100 against Anthracnose Disease (Colletotrichum gloeosporioides) and Growth Promotion of Walnut (Juglans regia L.) Trees
Authors: Choub Vantha , Ajuna Henry B. , Won Sang-Jae , Moon Jae-Hyun , Choi Su-In , Maung Chaw Ei Htwe , Kim Chul-Woo , Ahn Young Sang
Published: September 2021

Walnut anthracnose caused by Colletotrichum gloeosporioides is a deleterious disease that severely affects the production of walnut (Juglans regia L.). The aim of this study was to assess the antifungal and growth promotion activities of Bacillus velezensis CE 100 as an alternative to chemical use in walnut production. The crude enzyme from B. velezensis CE 100 exhibited chitinase, protease, and β-l,3-glucanase activity and degraded the cell wall of C. gloeosporioides, causing the inhibition of spore germination and mycelial growth by 99.3% and 33.6% at 100 µL/mL, respectively. The field application of B. velezensis CE 100 culture broth resulted in a 1.3-fold and 6.9-fold decrease in anthracnose disease severity compared to the conventional and control groups, respectively. Moreover, B. velezensis CE 100 produced indole-3-acetic acid (up to 1.4 µg/mL) and exhibited the potential for ammonium production and phosphate solubilization to enhance the availability of essential nutrients. Thus, field inoculation of B. velezensis CE 100 improved walnut root development, increased nutrient uptake, enhanced chlorophyll content, and consequently improved total biomass by 1.5-fold and 2.0-fold compared to the conventional and control groups, respectively. These results demonstrate that B. velezensis CE 100 is an effective biocontrol agent against anthracnose disease and a potential plant growth-promoting bacteria in walnut tree production.
B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy
Authors: Alam Manzar , Ali Sabeeha , Mohammad Taj , Hasan Gulam Mustafa , Yadav Dharmendra Kumar , Hassan Md. Imtaiyaz
Published: September 2021

Defects in the apoptosis mechanism stimulate cancer cell growth and survival. B cell lymphoma 2 (Bcl-2) is an anti-apoptotic molecule that plays a central role in apoptosis. Bcl-2 is the founding constituent of the Bcl-2 protein family of apoptosis controllers, the primary apoptosis regulators linked with cancer. Bcl-2 has been identified as being over-expressed in several cancers. Bcl-2 is induced by protein kinases and several signaling molecules which stimulate cancer development. Identifying the important function played by Bcl-2 in cancer progression and development, and treatment made it a target related to therapy for multiple cancers. Among the various strategies that have been proposed to block Bcl-2, BH3-mimetics have appeared as a novel group of compounds thanks to their favorable effects on many cancers within several clinical settings. Because of the fundamental function of Bcl-2 in the regulation of apoptosis, the Bcl-2 protein is a potent target for the development of novel anti-tumor treatments. Bcl-2 inhibitors have been used against several cancers and provide a pre-clinical platform for testing novel therapeutic drugs. Clinical trials of multiple investigational agents targeting Bcl-2 are ongoing. This review discusses the role of Bcl-2 in cancer development; it could be exploited as a potential target for developing novel therapeutic strategies to combat various types of cancers. We further highlight the therapeutic activity of Bcl-2 inhibitors and their implications for the therapeutic management of cancer.
Role of Pannexin 1 ATP-Permeable Channels in the Regulation of Signaling Pathways during Skeletal Muscle Unloading
Authors: Zaripova Ksenia A. , Kalashnikova Ekaterina P. , Belova Svetlana P. , Kostrominova Tatiana Y. , Shenkman Boris S. , Nemirovskaya Tatiana L.
Published: September 2021

Skeletal muscle unloading results in atrophy. We hypothesized that pannexin 1 ATP-permeable channel (PANX1) is involved in the response of muscle to unloading. We tested this hypothesis by blocking PANX1, which regulates efflux of ATP from the cytoplasm. Rats were divided into six groups (eight rats each): non-treated control for 1 and 3 days of the experiments (1C and 3C, respectively), 1 and 3 days of hindlimb suspension (HS) with placebo (1H and 3H, respectively), and 1 and 3 days of HS with PANX1 inhibitor probenecid (PRB; 1HP and 3HP, respectively). When compared with 3C group there was a significant increase in ATP in soleus muscle of 3H and 3HP groups (32 and 51%, respectively, p < 0.05). When compared with 3H group, 3HP group had: (1) lower mRNA expression of E3 ligases MuRF1 and MAFbx (by 50 and 38% respectively, p < 0.05) and MYOG (by 34%, p < 0.05); (2) higher phosphorylation of p70S6k and p90RSK (by 51 and 35% respectively, p < 0.05); (3) lower levels of phosphorylated eEF2 (by 157%, p < 0.05); (4) higher level of phosphorylated GSK3β (by 189%, p < 0.05). In conclusion, PANX1 ATP-permeable channels are involved in the regulation of muscle atrophic processes by modulating expression of E3 ligases, and protein translation and elongation processes during unloading.
The Crucial Role of NLRP3 Inflammasome in Viral Infection-Associated Fibrosing Interstitial Lung Diseases
Authors: Effendi Wiwin Is , Nagano Tatsuya
Published: September 2021

Idiopathic pulmonary fibrosis (IPF), one of the most common fibrosing interstitial lung diseases (ILD), is a chronic-age-related respiratory disease that rises from repeated micro-injury of the alveolar epithelium. Environmental influences, intrinsic factors, genetic and epigenetic risk factors that lead to chronic inflammation might be implicated in the development of IPF. The exact triggers that initiate the fibrotic response in IPF remain enigmatic, but there is now increasing evidence supporting the role of chronic exposure of viral infection. During viral infection, activation of the NLRP3 inflammasome by integrating multiple cellular and molecular signaling implicates robust inflammation, fibroblast proliferation, activation of myofibroblast, matrix deposition, and aberrant epithelial-mesenchymal function. Overall, the crosstalk of the NLRP3 inflammasome and viruses can activate immune responses and inflammasome-associated molecules in the development, progression, and exacerbation of IPF.
Exploring Aβ Proteotoxicity and Therapeutic Candidates Using Drosophila melanogaster
Authors: Elovsson Greta , Bergkvist Liza , Brorsson Ann-Christin
Published: September 2021

Alzheimer’s disease is a widespread and devastating neurological disorder associated with proteotoxic events caused by the misfolding and aggregation of the amyloid-β peptide. To find therapeutic strategies to combat this disease, Drosophila melanogaster has proved to be an excellent model organism that is able to uncover anti-proteotoxic candidates due to its outstanding genetic toolbox and resemblance to human disease genes. In this review, we highlight the use of Drosophila melanogaster to both study the proteotoxicity of the amyloid-β peptide and to screen for drug candidates. Expanding the knowledge of how the etiology of Alzheimer’s disease is related to proteotoxicity and how drugs can be used to block disease progression will hopefully shed further light on the field in the search for disease-modifying treatments.
Diosmin Inhibits Glioblastoma Growth through Inhibition of Autophagic Flux
Authors: Chang Yung-Lung , Li Yao-Feng , Chou Chung-Hsing , Huang Li-Chun , Wu Yi-Ping , Kao Ying , Tsai Chia-Kuang
Published: September 2021

Diosmin, a natural flavone glycoside acquired through dehydrogenation of the analogous flavanone glycoside hesperidin, is plentiful in many citrus fruits. Glioblastoma multiforme (GBM) is the most malignant primary brain tumor; the average survival time of GBM patients is less than 18 months after standard treatment. The present study demonstrated that diosmin, which is able to cross the blood–brain barrier, inhibited GBM cell growth in vitro and in vivo. Diosmin also impeded migration and invasion by GBM8401and LN229 GBM cells by suppressing epithelial-mesenchymal transition, as indicated by increased expression of E-cadherin and decreased expression of Snail and Twist. Diosmin also suppressed autophagic flux, as indicated by increased expression of LC3-II and p62, and induced cell cycle arrest at G1 phase. Importantly, diosmin did not exert serious cytotoxic effects toward control SVG-p12 astrocytes, though it did reduce astrocyte viability at high concentrations. These findings provide potentially helpful support to the development of new therapies for the treatment of GBM.
PDF1.5 Enhances Adaptation to Low Nitrogen Levels and Cadmium Stress
Authors: Wu Zhimin , Liu Dong , Yue Ningyan , Song Haixing , Luo Jinsong , Zhang Zhenhua
Published: September 2021

Environmental acclimation ability plays a key role in plant growth, although the mechanism remains unclear. Here, we determined the involvement of Arabidopsis thaliana PLANT DEFENSIN 1 gene AtPDF1.5 in the adaptation to low nitrogen (LN) levels and cadmium (Cd) stress. Histochemical analysis revealed that AtPDF1.5 was mainly expressed in the nodes and carpopodium and was significantly induced in plants exposed to LN conditions and Cd stress. Subcellular localization analysis revealed that AtPDF1.5 was cell wall- and cytoplasm-localized. AtPDF1.5 overexpression significantly enhanced adaptation to LN and Cd stress and enhanced the distribution of metallic elements. The functional disruption of AtPDF1.5 reduced adaptations to LN and Cd stress and impaired metal distribution. Under LN conditions, the nitrate transporter AtNRT1.5 expression was upregulated. Nitrate transporter AtNRT1.8 expression was downregulated when AtPDF1.5 was overexpressed, resulting in enhanced transport of NO3− to shoots. In response to Cd treatment, AtPDF1.5 regulated the expression of metal transporter genes AtHMP07, AtNRAMP4, AtNRAMP1, and AtHIPP3, resulting in higher Cd accumulation in the shoots. We conclude that AtPDF1.5 is involved in the processing or transmission of signal substances and plays an important role in the remediation of Cd pollution and LN adaptation.
Role of K+ and Ca2+-Permeable Channels in Osteoblast Functions
Authors: Kito Hiroaki , Ohya Susumu
Published: September 2021

Bone-forming cells or osteoblasts play an important role in bone modeling and remodeling processes. Osteoblast differentiation or osteoblastogenesis is orchestrated by multiple intracellular signaling pathways (e.g., bone morphogenetic proteins (BMP) and Wnt signaling pathways) and is modulated by the extracellular environment (e.g., parathyroid hormone (PTH), vitamin D, transforming growth factor β (TGF-β), and integrins). The regulation of bone homeostasis depends on the proper differentiation and function of osteoblast lineage cells from osteogenic precursors to osteocytes. Intracellular Ca2+ signaling relies on the control of numerous processes in osteoblast lineage cells, including cell growth, differentiation, migration, and gene expression. In addition, hyperpolarization via the activation of K+ channels indirectly promotes Ca2+ signaling in osteoblast lineage cells. An improved understanding of the fundamental physiological and pathophysiological processes in bone homeostasis requires detailed investigations of osteoblast lineage cells. This review summarizes the current knowledge on the functional impacts of K+ channels and Ca2+-permeable channels, which critically regulate Ca2+ signaling in osteoblast lineage cells to maintain bone homeostasis.