bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Autosomal Recessive Splice-Altering Variant in PRKD1 Is Associated with Congenital Heart Disease
Authors: Massadeh Salam , Albeladi Maha , Albesher Nour , Alhabshan Fahad , Kampe Kapil Dev , Chaikhouni Farah , Kabbani Mohamed S. , Beetz Christian , Alaamery Manal
Published: April 2021

Congenital heart defects (CHDs) are the most common types of birth defects, and global incidence of CHDs is on the rise. Despite the prevalence of CHDs, the genetic determinants of the defects are still in the process of being identified. Herein, we report a consanguineous Saudi family with three CHD affected daughters. We used whole exome sequencing (WES) to investigate the genetic cause of CHDs in the affected daughters. We found that all affected individuals were homozygous for a novel splice-altering variant (NM_001330069.1: c.265-1G>T) of PRKD1, which encodes a calcium/calmodulin-dependent protein kinase in the heart. The homozygous variant was found in the affected patients with Pulmonary Stenosis (PS), Truncus Arteriosis (TA), and Atrial Septal Defect (ASD). Based on the family’s pedigree, the variant acts in an autosomal recessive manner, which makes it the second autosomal recessive variant of PRKD1 to be identified with a link to CHDs, while all other previously described variants act dominantly. Interestingly, the father of the affected daughters was also homozygous for the variant, though he was asymptomatic of CHDs himself. Since both of his sisters had CHDs as well, this raises the possibility that the novel PRKD1 variant may undergo autosomal recessive inheritance mode with gender limitation. This finding confirms that CHD can be associated with both dominant and recessive mutations of the PRKD1 gene, and it provides a new insight to genotype–phenotype association between PRKD1 and CHDs. To our knowledge, this is the first report of this specific PRKD1 mutation associated with CHDs.
Clinicopathologic Profile of Breast Cancer in Germline ATM and CHEK2 Mutation Carriers
Authors: Toss Angela , Tenedini Elena , Piombino Claudia , Venturelli Marta , Marchi Isabella , Gasparini Elisa , Barbieri Elena , Razzaboni Elisabetta , Domati Federica , Caggia Federica , Grandi Giovanni , Combi Francesca , Tazzioli Giovanni , Dominici Massimo , Tagliafico Enrico , Cortesi Laura
Published: April 2021

The most common breast cancer (BC) susceptibility genes beyond BRCA1/2 are ATM and CHEK2. For the purpose of exploring the clinicopathologic characteristics of BC developed by ATM or CHEK2 mutation carriers, we reviewed the archive of our Family Cancer Clinic. Since 2018, 1185 multi-gene panel tests have been performed. Nineteen ATM and 17 CHEK2 mutation carriers affected by 46 different BCs were identified. A high rate of bilateral tumors was observed in ATM (26.3%) and CHEK2 mutation carriers (41.2%). While 64.3% of CHEK2 tumors were luminal A-like, 56.2% of ATM tumors were luminal B-like/HER2-negative. Moreover, 21.4% of CHEK2-related invasive tumors showed a lobular histotype. About a quarter of all ATM-related BCs and a third of CHEK2 BCs were in situ carcinomas and more than half of ATM and CHEK2-related BCs were diagnosed at stage I-II. Finally, 63.2% of ATM mutation carriers and 64.7% of CHEK2 mutation carriers presented a positive BC family history. The biological and clinical characteristics of ATM and CHEK2-related tumors may help improve diagnosis, prognostication and targeted therapeutic approaches. Contralateral mastectomy should be considered and discussed with ATM and CHEK2 mutation carriers at the first diagnosis of BC.
Transcriptome Analysis Provides Insights into the Mechanism of Astaxanthin Enrichment in a Mutant of the Ridgetail White Prawn Exopalaemon carinicauda
Authors: Jin Yue , Li Shihao , Yu Yang , Zhang Chengsong , Zhang Xiaojun , Li Fuhua
Published: April 2021

A mutant of the ridgetail white prawn, which exhibited rare orange-red body color with a higher level of free astaxanthin (ASTX) concentration than that in the wild-type prawn, was obtained in our lab. In order to understand the underlying mechanism for the existence of a high level of free astaxanthin, transcriptome analysis was performed to identify the differentially expressed genes (DEGs) between the mutant and wild-type prawns. A total of 78,224 unigenes were obtained, and 1863 were identified as DEGs, in which 902 unigenes showed higher expression levels, while 961 unigenes presented lower expression levels in the mutant in comparison with the wild-type prawns. Based on Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis, as well as further investigation of annotated DEGs, we found that the biological processes related to astaxanthin binding, transport, and metabolism presented significant differences between the mutant and the wild-type prawns. Some genes related to these processes, including crustacyanin, apolipoprotein D (ApoD), cathepsin, and cuticle proteins, were identified as DEGs between the two types of prawns. These data may provide important information for us to understand the molecular mechanism of the existence of a high level of free astaxanthin in the prawn.
Hydrogen Conversion in Nanocages
Authors: Ilisca Ernest
Published: April 2021

Hydrogen molecules exist in the form of two distinct isomers that can be interconverted by physical catalysis. These ortho and para forms have different thermodynamical properties. Over the last century, the catalysts developed to convert hydrogen from one form to another, in laboratories and industries, were magnetic and the interpretations relied on magnetic dipolar interactions. The variety concentration of a sample and the conversion rates induced by a catalytic action were mostly measured by thermal methods related to the diffusion of the o-p reaction heat. At the turning of the new century, the nature of the studied catalysts and the type of measures and motivations completely changed. Catalysts investigated now are non-magnetic and new spectroscopic measurements have been developed. After a fast survey of the past studies, the review details the spectroscopic methods, emphasizing their originalities, performances and refinements: how Infra-Red measurements characterize the catalytic sites and follow the conversion in real-time, Ultra-Violet irradiations explore the electronic nature of the reaction and hyper-frequencies driving the nuclear spins. The new catalysts, metallic or insulating, are detailed to display the operating electronic structure. New electromagnetic mechanisms, involving energy and momenta transfers, are discovered providing a classification frame for the newly observed reactions.
Where to Look for a Remedy? Burnout Syndrome and its Associations with Coping and Job Satisfaction in Critical Care Nurses—A Cross-Sectional Study
Authors: Friganović Adriano , Selič Polona
Published: April 2021

Background: Burnout is a psychological, work-related syndrome associated with long-term exposure to emotional and interpersonal stressors in the workplace. Burnout syndrome in nurses is often caused by an imbalance between work requirements and preparation and fitness for work, a lack of control, insufficient performance recognition and a prolonged exposure to stress. Aim: The aims of this study were to explore the associations between levels of burnout syndrome, coping mechanisms and job satisfaction in critical care nurses in multivariate modelling process. A specific aim was also to explore whether coping and job satisfaction in critical care nurses are gender related. Methods: A cross-sectional multicentre study was conducted in a convenience sample of 620 critical care nurses from five university hospitals in Croatia in 2017. The data were collected using the Maslach Burnout Inventory and the Ways of Coping and Job Satisfaction Scale together with the nurses’ demographic profiles and were analysed using a multivariable model. Results: The results showed no significant association between gender, coping mechanisms and job satisfaction. However, significant negative associations between burnout and job satisfaction (OR = 0.01, 95%CI = 0.00–0.02, p < 0.001) and positive association between burnout and passive coping (OR = 9.93, 95%CI = 4.01–24.61, p < 0.001) were found. Conclusion: The association between job satisfaction and burnout in nurses urges hospital management teams to consider actions focused on job satisfaction, probably modifications of the work environment. Given that passive coping may increase the incidence of burnout, it is recommendable for active coping to be implemented in nurses’ training programmes as an essential element of capacity building aimed at reducing the incidence of burnout in nurses.
Impact of Pharmacists’ Interventions and Patients’ Decision on Health Outcomes in Terms of Medication Adherence and Quality Use of Medicines among Patients Attending Community Pharmacies: A Systematic Review
Authors: Rajiah Kingston , Sivarasa Shreeta , Maharajan Mari Kannan
Published: April 2021

Community pharmacists are responsible for providing the appropriate information on the use of medications to patients, which may enhance their medication adherence. The extent of control that patients have on their health care preferences creates many challenges for community pharmacists. This study aimed to determine the impact of pharmacist interventions and patient decisions on health outcomes concerning medication adherence and the quality use of medicines among patients attending community pharmacies. Appropriate studies were identified in a systematic search using the databases of Medline, Scopus, Google Scholar, and PubMed. The search included literature published between 2004 and 2019. The database searches yielded 683 titles, of which 19 studies were included after the full-text analysis with a total of 9313 participants. Metaprop command in Stata software version 14 was used for the analysis. This study was undertaken based on the general principles of the Cochrane Handbook for Systematic Reviews of Interventions and subsequently reported according to the Preferred Reporting Items for Systematic Reviews (PRISMA) extension. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was directly used to rate the quality of evidence (high, moderate, low, or very low). The results revealed the effective interaction between patients and community pharmacists, the importance of pharmacist intervention on medication adherence and quality use of medicine, and the role of community pharmacists in counselling patients. Decision/choice of patients in self-care and self-medication is a factor contributing to health outcomes. Effective interaction of community pharmacists with patients in terms of medication adherence and quality use of medicines provided a better health outcome among patients. The community pharmacists influenced the decision/choice of patients in self-care and self-medications.
Towards Solving Health Inequities: A Method to Identify Ideological Operation in Global Health Programs
Authors: Kim Hani , Novakovic Uros
Published: April 2021

The function of ideology is to naturalize and maintain unequal relations of power. Making visible how ideology operates is necessary for solving health inequities grounded in inequities of resources and power. However, discerning ideology is difficult because it operates implicitly. It is not necessarily explicit in one’s stated aims or beliefs. Philosopher Slavoj Žižek conceptualizes ideology as a belief in overarching unity or harmony that obfuscates immanent tension within a system. Drawing from Žižek’s conceptualization of ideology, we identify what may be considered as ‘symptoms’ of ideological practice: (1) the recurrent nature of a problem, and (2) the implicit externalization of the cause. Our aim is to illustrate a method to identify ideological operation in health programs on the basis of its symptoms, using three case studies of persistent global health problems: inequitable access to vaccines, antimicrobial resistance, and health inequities across racialized communities. Our proposed approach for identifying ideology allows one to identify ideological practices that could not be identified by particular ideological contents. It also safeguards us from an illusory search for an emancipatory content. Critiquing ideology in general reveals possibilities that are otherwise kept invisible and unimaginable, and may help us solve recalcitrant problems such as health inequities.
The Evolution of Gambling-Related Harm Measurement: Lessons from the Last Decade
Authors: Browne Matthew , Rawat Vijay , Tulloch Catherine , Murray-Boyle Cailem , Rockloff Matthew
Published: April 2021

Jurisdictions around the world have a self-declared mandate to reduce gambling-related harm. However, historically, this concept has suffered from poor conceptualisation and operationalisation. However, recent years have seen swift advances in measuring gambling harm, based on the principle of it being a quantifiable decrement to the health and wellbeing of the gambler and those connected to them. This review takes stock of the background and recent developments in harm assessment and summarises recent research that has validated and applied the Short Gambling Harms Screen and related instruments. We recommend that future work builds upon the considerable psychometric evidence accumulated for the feasibility of direct elicitation of harmful consequences. We also advocate for grounding harms measures with respect to scalar changes to public health utility metrics. Such an approach will avoid misleading pseudo-clinical categorisations, provide accurate population-level summaries of where the burden of harm is carried, and serve to integrate gambling research with the broader field of public health.
Effectiveness of Adherence Therapy in Adults with Type 2 Diabetes: A Systematic Review
Authors: Alenazi Fatimah , Bressington Daniel , Shrestha Monika , Peddle Monica , Gray Richard
Published: April 2021

Adherence therapy has been shown to be an effective adjunct treatment in long-term conditions including hypertension. The purpose of this study is to review and critically appraise evidence on the effectiveness of adherence therapy as an intervention in adults with type 2 diabetes. A systematic search of clinical trials published between 2005 and January 2020 in databases was undertaken in October 2018 and updated in August 2020. Inclusion criteria were any clinical trials where the population under investigation was adults with type 2 diabetes and the experimental intervention was adherence therapy. Version 2 of the Cochrane risk of bias was used to determine the quality of the included studies. No studies met our inclusion criteria. However, four studies that we excluded at full text screening tested some of the components (e.g., problem solving) of adherence therapy. As is recommended when reporting empty reviews, those studies were synthesized to determine if useful information can be extracted. That no trials of adherence therapy have been reported in type 2 diabetes establishes a potentially important gap in knowledge. This review was registered in PROSPERO (registration number: CRD42019115216) after the initial searches were completed.
BlackLivesMatter in Healthcare: Racism and Implications for Health Inequity among Aboriginal and Torres Strait Islander Peoples in Australia
Authors: Gatwiri Kathomi , Rotumah Darlene , Rix Elizabeth
Published: April 2021

Despite decades of evidence showing that institutional and interpersonal racism serve as significant barriers to accessible healthcare for Aboriginal and Torres Strait Islander Peoples, attempts to address this systemic problem still fall short. The social determinants of health are particularly poignant given the socio-political-economic history of invasion, colonisation, and subsequent entrenchment of racialised practices in the Australian healthcare landscape. Embedded within Euro-centric, bio-medical discourses, Western dominated healthcare processes can erase significant cultural and historical contexts and unwittingly reproduce unsafe practices. Put simply, if Black lives matter in healthcare, why do Aboriginal and Torres Strait Islander Peoples die younger and experience ‘epidemic’ levels of chronic diseases as compared to white Australians? To answer this, we utilise critical race perspectives to theorise this gap and to de-center whiteness as the normalised position of ‘doing’ healthcare. We draw on our diverse knowledges through a decolonised approach to promote a theoretical discussion that we contend can inform alternative ways of knowing, being, and doing in healthcare practice in Australia.
Short-Term Effects of Particulate Matter and Its Constituents on Emergency Room Visits for Chronic Obstructive Pulmonary Disease: A Time-Stratified Case-Crossover Study in an Urban Area
Authors: Huang Yii-Ting , Chen Chien-Chih , Ho Yu-Ni , Tsai Ming-Ta , Tsai Chih-Min , Chuang Po-Chun , Cheng Fu-Jen
Published: April 2021

Background: PM2.5 exposure is associated with pulmonary and airway inflammation, and the health impact might vary by PM2.5 constitutes. This study evaluated the effects of increased short-term exposure to PM2.5 constituents on chronic obstructive pulmonary disease (COPD)-related emergency department (ED) visits and determined the susceptible groups. Methods: This retrospective observational study performed in a medical center from 2007 to 2010, and enrolled non-trauma patients aged >20 years who visited the emergency department (ED) and were diagnosed as COPD. Concentrations of PM2.5, PM10, and the four PM2.5 components, including organic carbon (OC), elemental carbon (EC), nitrate (NO3−), and sulfate (SO42−), were collected by three PM supersites in Kaohsiung City. We used an alternative design of the Poisson time series regression models called a time-stratified and case-crossover design to analyze the data. Results: Per interquartile range (IQR) increment in PM2.5 level on lag 2 were associated with increments of 6.6% (95% confidence interval (CI), 0.5–13.0%) in risk of COPD exacerbation. An IQR increase in elemental carbon (EC) was significantly associated with an increment of 3.0% (95% CI, 0.1–5.9%) in risk of COPD exacerbation on lag 0. Meanwhile, an IQR increase in sulfate, nitrate, and OC levels was not significantly associated with COPD. Patients were more sensitive to the harmful effects of EC on COPD during the warm season (interaction p = 0.019). The risk of COPD exacerbation after exposure to PM2.5 was higher in individuals who are currently smoking, with malignancy, or during cold season, but the differences did not achieve statistical significance. Conclusion: PM2.5 and EC may play an important role in COPD events in Kaohsiung, Taiwan. Patients were more susceptible to the adverse effects of EC on COPD on warm days.
Phase Angle Is Related to 10 m and 30 m Sprint Time and Repeated-Sprint Ability in Young Male Soccer Players
Authors: Martins Priscila Custódio , Teixeira Anderson Santiago , Guglielmo Luiz Guilherme ANTONACCI , Francisco Juliana Sabino , Silva Diego Augusto Santos , Nakamura Fábio Yuzo , Lima Luiz Rodrigo Augustemak de
Published: April 2021

Objective: To examine the association between phase angle (PhA) and bioelectrical impedance vector analysis (BIVA) and components of physical performance in male youth soccer players. Design: Cross-sectional. Methods: Sixty-two players from two professional soccer academies were recruited. Electrical bioimpedance was used to obtain the PhA and BIVA. Body fat (BF) and lean soft tissue mass (LSTM) were measured by dual-energy X-ray absorptiometry. All players completed physical tests including the standing long jump (SLJ), Carminatti’s test (peak speed at the end of the test, PST-CAR), 10 m and 30 m straight-line sprints, and repeated-sprint ability (RSA) test (RSAbest and RSAmean times). Results: Adjusting for chronological age, BF, and LSTM, multiple regression analysis outputs showed that PhA remained inversely related to RSAmean (β = −0.362; p < 0.001), RSAbest (β = −0.239; p = 0.020), 10 m (β = −0.379; p = 0.012), and 30 m (β = −0.438; p < 0.001) sprint times, while the association with PST-CAR and SLJ performance were statistically non-significant. In addition, BIVA showed that differences in confidence ellipses were found between athletes in the reference population and the study sample (p < 0.05). The tolerance ellipses indicated that the athletes in the present study had more total body water (TCW) and lower proportions of intracellular water (ICW) to extracellular water (ECW). The reference population had more TCW and ICW/ECW. Conclusions: Our results suggest that young soccer players with higher PhA values, indicating better cell integrity and functionality, have better performance in typical anaerobic running activities, such as sprinting speed and RSA performance, adjusted to age and body composition characteristics.
Importance of Geospatial Heterogeneity in Chronic Disease Burden for Policy Planning in an Urban Setting Using a Case Study of Singapore
Authors: Tan Ken Wei , Koo Joel R. , Lim Jue Tao , Cook Alex R. , Dickens Borame L.
Published: April 2021

Chronic disease burdens continue to rise in highly dense urban environments where clustering of type II diabetes mellitus, acute myocardial infarction, stroke, or any combination of these three conditions is occurring. Many individuals suffering from these conditions will require longer-term care and access to clinics which specialize in managing their illness. With Singapore as a case study, we utilized census data in an agent-modeling approach at an individual level to estimate prevalence in 2020 and found high-risk clusters with >14,000 type II diabetes mellitus cases and 2000–2500 estimated stroke cases. For comorbidities, 10% of those with type II diabetes mellitus had a past acute myocardial infarction episode, while 6% had a past stroke. The western region of Singapore had the highest number of high-risk individuals at 173,000 with at least one chronic condition, followed by the east at 169,000 and the north with the least at 137,000. Such estimates can assist in healthcare resource planning, which requires these spatial distributions for evidence-based policymaking and to investigate why such heterogeneities exist. The methodologies presented can be utilized within any urban setting where census data exists.
Determinants Affecting Purchase Willingness of Contractors towards Construction and Demolition Waste Recycling Products: An Empirical Study in Shenzhen, China
Authors: Yu Bo , Wang Jiayuan , Liao Ying , Wu Huanyu , Wong Aslan B.
Published: April 2021

Waste recycling is a critical method to effectively address environmental issues raised by construction and demolition waste (C&DW). As highlighted in previous studies, the contractor is considered the primary purchaser for recycled C&DW products. However, there is a limited understanding of the factors affecting the contractor’s purchase willingness towards C&DW recycling products. This study investigated these key drivers using the Exploratory Sequential Mixed Approach. Firstly, a hypothetical model was developed based on the theory of planned behavior (TPB). Secondly, a questionnaire survey was then employed in data collection. Thirdly, structural equation modeling (SEM) was adopted for data analysis. It is revealed that multiple factors directly affect the contractor’s purchase willingness towards C&DW recycling products. These factors include government measures, the contractor’s attitude, perceived behavioral control, perceived consumer effectiveness, and subjective norms. Besides, recycling product information indirectly affects the contractor’s purchase willingness. Based on the findings, the study provides strategies for the government, contractors, recycling enterprises, and public buyers to increase C&DW recycling products’ purchase willingness. Findings derived from the empirical study can be used as a theoretical reference for government departments to develop related promotion policies. Moreover, the suggestions provided are helpful to guide recycling enterprises to promote their products.
Changes in Multimorbidity and Polypharmacy Patterns in Young and Adult Population over a 4-Year Period: A 2011–2015 Comparison Using Real-World Data
Authors: Mucherino Sara , Gimeno-Miguel Antonio , Carmona-Pirez Jonas , Gonzalez-Rubio Francisca , Ioakeim-Skoufa Ignatios , Moreno-Juste Aida , Orlando Valentina , Aza-Pascual-Salcedo Mercedes , Poblador-Plou Beatriz , Menditto Enrica , Prados-Torres Alexandra
Published: April 2021

The pressing problem of multimorbidity and polypharmacy is aggravated by the lack of specific care models for this population. We aimed to investigate the evolution of multimorbidity and polypharmacy patterns in a given population over a 4-year period (2011–2015). A cross-sectional, observational study among the EpiChron Cohort, including anonymized demographic, clinical and drug dispensation information of all users of the public health system ≥65 years in Aragon (Spain), was performed. An exploratory factor analysis, stratified by age and sex, using an open cohort was carried out based on the tetra-choric correlations among chronic diseases and dispensed drugs during 2011 and compared with 2015. Seven baseline patterns were identified during 2011 named as: mental health, respiratory, allergic, mechanical pain, cardiometabolic, osteometabolic, and allergic/derma. Of the epidemiological patterns identified in 2015, six were already present in 2011 but a new allergic/derma one appeared. Patterns identified in 2011 were more complex in terms of both disease and drugs. Results confirmed the existing association between age and clinical complexity. The systematic associations between diseases and drugs remain similar regarding their clinical nature over time, helping in early identification of potential interactions in multimorbid patients with a high risk of negative health outcomes due to polypharmacy.
The Effectiveness of Massage Therapy for Improving Sequelae in Post-Stroke Survivors. A Systematic Review and Meta-Analysis
Authors: Cabanas-Valdés Rosa , Calvo-Sanz Jordi , Serra-Llobet Pol , Alcoba-Kait Joana , González-Rueda Vanessa , Rodríguez-Rubio Pere Ramón
Published: April 2021

Objective: To assess the effect of therapeutic massage for improving sequelae in stroke survivors. Methods: A systematic review of the nine medical databases from January 1961 to December 2020 was carried out. The bibliography was screened to identify randomized controlled clinical trials (RCTs). Two reviewers independently screened references, selected relevant studies, extracted data and assessed the risk of bias using the PEDro scale. The primary outcome was upper and lower limb motor function and spasticity. Results: A total of 3196 studies were identified and 18 RCT were finally included (1989 individuals). A meta-analysis of RCTs in the comparison of Chinese massage (Tuina) plus conventional physiotherapy versus conventional physiotherapy was performed. The mean difference (MD) in the subacute stage on upper limb motor-function using the Fugl Meyer Assessment was 2.75; (95% confidence interval (CI) from 0.97 to 4.53, p = 0.002, I2 = 36%). The MD on upper limb spasticity using modified Ashworth scale was −0.15; (95% CI from −0.24 to −0.06, p < 0.02, I2 = 0%).The MD on lower limb spasticity was −0.59; (95% CI from −0.78 to −0.40, p < 0.001, I2 = 0%) in the endpoint. Conclusions: Therapeutic massage, especially Tuina, in addition to conventional therapy is effective for improving motor function and for reducing spasticity in stroke survivors.
Roles of the Functional Interaction between Brain Cholinergic and Dopaminergic Systems in the Pathogenesis and Treatment of Schizophrenia and Parkinson’s Disease
Authors: Acharya Srijan , Kim Kyeong-Man
Published: April 2021

Most physiologic processes in the brain and related diseases involve more than one neurotransmitter system. Thus, elucidation of the interaction between different neurotransmitter systems could allow for better therapeutic approaches to the treatments of related diseases. Dopaminergic (DAergic) and cholinergic neurotransmitter system regulate various brain functions that include cognition, movement, emotion, etc. This review focuses on the interaction between the brain DAergic and cholinergic systems with respect to the pathogenesis and treatment of schizophrenia and Parkinson’s disease (PD). We first discussed the selection of motor plans at the level of basal ganglia, the major DAergic and cholinergic pathways in the brain, and the receptor subtypes involved in the interaction between the two signaling systems. Next, the roles of each signaling system were discussed in the context of the negative symptoms of schizophrenia, with a focus on the α7 nicotinic cholinergic receptor and the dopamine D1 receptor in the prefrontal cortex. In addition, the roles of the nicotinic and dopamine receptors were discussed in the context of regulation of striatal cholinergic interneurons, which play crucial roles in the degeneration of nigrostriatal DAergic neurons and the development of L-DOPA-induced dyskinesia in PD patients. Finally, we discussed the general mechanisms of nicotine-induced protection of DAergic neurons.
The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction
Authors: Khalyfa Abdelnaby , Sanz-Rubio David
Published: April 2021

Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).
Hypoxia-Induced FAM13A Regulates the Proliferation and Metastasis of Non-Small Cell Lung Cancer Cells
Authors: Ziółkowska-Suchanek Iwona , Podralska Marta , Żurawek Magdalena , Łaczmańska Joanna , Iżykowska Katarzyna , Dzikiewicz-Krawczyk Agnieszka , Rozwadowska Natalia
Published: April 2021

Hypoxia in non-small cell lung cancer (NSCLC) affects cancer progression, metastasis and metabolism. We previously showed that FAM13A was induced by hypoxia in NSCLC but the biological function of this gene has not been fully elucidated. This study aimed to investigate the role of hypoxia-induced FAM13A in NSCLC progression and metastasis. Lentiviral shRNAs were used for FAM13A gene silencing in NSCLC cell lines (A549, CORL-105). MTS assay, cell tracking VPD540 dye, wound healing assay, invasion assay, BrdU assay and APC Annexin V staining assays were performed to examine cell proliferation ability, migration, invasion and apoptosis rate in NSCLC cells. The results of VPD540 dye and MTS assays showed a significant reduction in cell proliferation after FAM13A knockdown in A549 cells cultured under normal and hypoxia (1% O2) conditions (p < 0.05), while the effect of FAM13A downregulation on CORL-105 cells was observed after 96 h exposition to hypoxia. Moreover, FAM13A inhibition induced S phase cell cycle arrest in A549 cells under hypoxia conditions. Silencing of FAM13A significantly suppressed migration of A549 and CORL-105 cells in both oxygen conditions, especially after 72 and 96 h (p < 0.001 in normoxia, p < 0.01 after hypoxia). It was showed that FAM13A reduction resulted in disruption of the F-actin cytoskeleton altering A549 cell migration. Cell invasion rates were significantly decreased in A549 FAM13A depleted cells compared to controls (p < 0.05), mostly under hypoxia. FAM13A silencing had no effect on apoptosis induction in NSCLC cells. In the present study, we found that FAM13A silencing has a negative effect on proliferation, migration and invasion activity in NSCLC cells in normal and hypoxic conditions. Our data demonstrated that FAM13A depleted post-hypoxic cells have a decreased cell proliferation ability and metastatic potential, which indicates FAM13A as a potential therapeutic target in lung cancer.
Hypophosphatasia: A Unique Disorder of Bone Mineralization
Authors: Villa-Suárez Juan Miguel , García-Fontana Cristina , Andújar-Vera Francisco , González-Salvatierra Sheila , de Haro-Muñoz Tomás , Contreras-Bolívar Victoria , García-Fontana Beatriz , Muñoz-Torres Manuel
Published: April 2021

Hypophosphatasia (HPP) is a rare genetic disease characterized by a decrease in the activity of tissue non-specific alkaline phosphatase (TNSALP). TNSALP is encoded by the ALPL gene, which is abundantly expressed in the skeleton, liver, kidney, and developing teeth. HPP exhibits high clinical variability largely due to the high allelic heterogeneity of the ALPL gene. HPP is characterized by multisystemic complications, although the most common clinical manifestations are those that occur in the skeleton, muscles, and teeth. These complications are mainly due to the accumulation of inorganic pyrophosphate (PPi) and pyridoxal-5′-phosphate (PLP). It has been observed that the prevalence of mild forms of the disease is more than 40 times the prevalence of severe forms. Patients with HPP present at least one mutation in the ALPL gene. However, it is known that there are other causes that lead to decreased alkaline phosphatase (ALP) levels without mutations in the ALPL gene. Although the phenotype can be correlated with the genotype in HPP, the prediction of the phenotype from the genotype cannot be made with complete certainty. The availability of a specific enzyme replacement therapy for HPP undoubtedly represents an advance in therapeutic strategy, especially in severe forms of the disease in pediatric patients.
Mesenchymal Stromal Cell Therapy in Novel Porcine Model of Diffuse Liver Damage Induced by Repeated Biliary Obstruction
Authors: Vištejnová Lucie , Liška Václav , Kumar Arvind , Křečková Jana , Vyčítal Ondřej , Brůha Jan , Beneš Jan , Kolinko Yaroslav , Blassová Tereza , Tonar Zbyněk , Brychtová Michaela , Karlíková Marie , Racek Jaroslav , Mírka Hynek , Hošek Petr , Lysák Daniel , Králíčková Milena
Published: April 2021

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p < 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-β, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine.
RETRACTED: Formation of Proto-Kranz in C3 Rice Induced by Spike-Stalk Injection Method
Authors: Jiang Dexing , Wang Feng , Zhang Haizi , Gao Wenwen , Tong Xi , Lv Chuangen , Chen Guoxiang
Published: April 2021

Introduction of C4 photosynthetic traits into C3 crops is an important strategy for improving photosynthetic capacity and productivity. Here, we report the research results of a variant line of sorghum–rice (SR) plant with big panicle and high spikelet density by introducing sorghum genome DNA into rice by spike-stalk injection. The whole-genome resequencing showed that a few sorghum genes could be integrated into the rice genome. Gene expression was confirmed for two C4 photosynthetic enzymes containing pyruvate, orthophosphate dikinase and phosphoenolpyruvate carboxykinase. Exogenous sorghum DNA integration induced a series of key traits associated with the C4 pathway called “proto-Kranz” anatomy, including leaf thickness, bundle sheath number and size, and chloroplast size in bundle sheath cells. Significantly, transgenic plants exhibited enhanced photosynthetic capacity resulting from both photosynthetic CO2-concentrating effect and improved energy balance, which led to an increase in carbohydrate levels and productivity. Furthermore, such rice plant exhibited delayed leaf senescence. In summary, this study provides a proof for the feasibility of inducing the transition from C3 leaf anatomy to proto-Kranz by spike-stalk injection to achieve efficient photosynthesis and increase productivity.
Insight on Solution Plasma in Aqueous Solution and Their Application in Modification of Chitin and Chitosan
Authors: Chokradjaroen Chayanaphat , Niu Jiangqi , Panomsuwan Gasidit , Saito Nagahiro
Published: April 2021

Sustainability and environmental concerns have persuaded researchers to explore renewable materials, such as nature-derived polysaccharides, and add value by changing chemical structures with the aim to possess specific properties, like biological properties. Meanwhile, finding methods and strategies that can lower hazardous chemicals, simplify production steps, reduce time consumption, and acquire high-purified products is an important task that requires attention. To break through these issues, electrical discharging in aqueous solutions at atmospheric pressure and room temperature, referred to as the “solution plasma process”, has been introduced as a novel process for modification of nature-derived polysaccharides like chitin and chitosan. This review reveals insight into the electrical discharge in aqueous solutions and scientific progress on their application in a modification of chitin and chitosan, including degradation and deacetylation. The influencing parameters in the plasma process are intensively explained in order to provide a guideline for the modification of not only chitin and chitosan but also other nature-derived polysaccharides, aiming to address economic aspects and environmental concerns.
Metallothionein 3 Promotes Osteoblast Differentiation in C2C12 Cells via Reduction of Oxidative Stress
Authors: Li Santie , Kim Myeong-Ji , Lee Sung-Ho , Jin Litai , Cong Weitao , Jeong Hye-Gwang , Lee Kwang-Youl
Published: April 2021

Metallothioneins (MTs) are intracellular cysteine-rich proteins, and their expressions are enhanced under stress conditions. MTs are recognized as having the ability to regulate redox balance in living organisms; however, their role in regulating osteoblast differentiation is still unclear. In this research, we found that the expression of MT3, one member of the MT protein family, was specifically upregulated in the differentiation process of C2C12 myoblasts treated with bone morphogenetic protein 4 (BMP4). Transfection with MT3-overexpressing plasmids in C2C12 cells enhanced their differentiation to osteoblasts, together with upregulating the protein expression of bone specific transcription factors runt-related gene 2 (Runx2), Osterix, and distal-less homeobox 5 (Dlx5). Additionally, MT3 knockdown performed the opposite. Further studies revealed that overexpression of MT3 decreased reactive oxygen species (ROS) production in C2C12 cells treated with BMP4, and MT3 silencing enhanced ROS production. Treating C2C12 cells with antioxidant N-acetylcysteine also promoted osteoblast differentiation, and upregulated Runx2/Osterix/Dlx5, while ROS generator antimycin A treatment performed the opposite. Finally, antimycin A treatment inhibited osteoblast differentiation and Runx2/Osterix/Dlx5 expression in MT3-overexpressing C2C12 cells. These findings identify the role of MT3 in osteoblast differentiation and indicate that MT3 may have interesting potential in the field of osteogenesis research.
Barley Seeds miRNome Stability during Long-Term Storage and Aging
Authors: Puchta Marta , Groszyk Jolanta , Małecka Magdalena , Koter Marek D. , Niedzielski Maciej , Rakoczy-Trojanowska Monika , Boczkowska Maja
Published: April 2021

Seed aging is a complex biological process that has been attracting scientists’ attention for many years. High-throughput small RNA sequencing was applied to examine microRNAs contribution in barley seeds senescence. Unique samples of seeds that, despite having the same genetic makeup, differed in viability after over 45 years of storage in a dry state were investigated. In total, 61 known and 81 novel miRNA were identified in dry seeds. The highest level of expression was found in four conserved miRNA families, i.e., miR159, miR156, miR166, and miR168. However, the most astonishing result was the lack of significant differences in the level of almost all miRNAs in seed samples with significantly different viability. This result reveals that miRNAs in dry seeds are extremely stable. This is also the first identified RNA fraction that is not deteriorating along with the loss of seed viability. Moreover, the novel miRNA hvu-new41, with higher expression in seeds with the lowest viability as detected by RT-qPCR, has the potential to become an indicator of the decreasing viability of seeds during storage in a dry state.
Analysis of Astroglial Secretomic Profile in the Mecp2-Deficient Male Mouse Model of Rett Syndrome
Authors: Ehinger Yann , Matagne Valerie , Cunin Valérie , Borloz Emilie , Seve Michel , Bourgoin-Voillard Sandrine , Borges-Correia Ana , Villard Laurent , Roux Jean-Christophe
Published: April 2021

Mutations in the X-linked MECP2 gene are responsible for Rett syndrome (RTT), a severe neurological disorder. MECP2 is a transcriptional modulator that finely regulates the expression of many genes, specifically in the central nervous system. Several studies have functionally linked the loss of MECP2 in astrocytes to the appearance and progression of the RTT phenotype in a non-cell autonomous manner and mechanisms are still unknown. Here, we used primary astroglial cells from Mecp2-deficient (KO) pups to identify deregulated secreted proteins. Using a differential quantitative proteomic analysis, twenty-nine proteins have been identified and four were confirmed by Western blotting with new samples as significantly deregulated. To further verify the functional relevance of these proteins in RTT, we tested their effects on the dendritic morphology of primary cortical neurons from Mecp2 KO mice that are known to display shorter dendritic processes. Using Sholl analysis, we found that incubation with Lcn2 or Lgals3 for 48 h was able to significantly increase the dendritic arborization of Mecp2 KO neurons. To our knowledge, this study, through secretomic analysis, is the first to identify astroglial secreted proteins involved in the neuronal RTT phenotype in vitro, which could open new therapeutic avenues for the treatment of Rett syndrome.
Genome-Wide Identification, Comparison, and Expression Analysis of Transcription Factors in Ascidian Styela clava
Authors: Zhang Jin , Wei Jiankai , Yu Haiyan , Dong Bo
Published: April 2021

Tunicates include diverse species, as they are model animals for evolutionary developmental biology study. The embryonic development of tunicates is known to be extensively regulated by transcription factors (TFs). Styela clava, the globally distributed invasive tunicate, exhibits a strong capacity for environmental adaptation. However, the TFs were not systematically identified and analyzed. In this study, we reported 553 TFs categorized into 60 families from S. clava, based on the whole genome data. Comparison of TFs analysis among the tunicate species revealed that the gene number in the zinc finger superfamily displayed the most significant discrepancy, indicating this family was under the highly evolutionary selection and might be related to species differentiation and environmental adaptation. The greatest number of TFs was discovered in the Cys2His2-type zinc finger protein (zf-C2H2) family in S. clava. From the point of temporal view, more than half the TFs were expressed at the early embryonic stage. The expression correlation analysis revealed the existence of a transition for TFs expression from early embryogenesis to the later larval development in S. clava. Eight Hox genes were identified to be located on one chromosome, exhibiting different arrangement and expression patterns, compared to Ciona robusta (C. intestinalis type A). In addition, a total of 23 forkhead box (fox) genes were identified in S. clava, and their expression profiles referred to their potential roles in neurodevelopment and sensory organ development. Our data, thus, provides crucial clues to the potential functions of TFs in development and environmental adaptation in the leathery sea squirt.