bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Stress Responses in a Drosophila Model of Werner Syndrome
Authors: Epiney Derek , Salameh Charlotte , Cassidy Deirdre , Zhou Luhan , Kruithof Joshua , Milutinović Rolan , Andreani Tomas , Schirmer Aaron , Bolterstein Elyse
Published: December 2021

As organisms age, their resistance to stress decreases while their risk of disease increases. This can be shown in patients with Werner syndrome (WS), which is a genetic disease characterized by accelerated aging along with increased risk of cancer and metabolic disease. WS is caused by mutations in WRN, a gene involved in DNA replication and repair. Recent research has shown that WRN mutations contribute to multiple hallmarks of aging including genomic instability, telomere attrition, and mitochondrial dysfunction. However, questions remain regarding the onset and effect of stress on early aging. We used a fly model of WS (WRNexoΔ) to investigate stress response during different life stages and found that stress sensitivity varies according to age and stressor. While larvae and young WRNexoΔ adults are not sensitive to exogenous oxidative stress, high antioxidant activity suggests high levels of endogenous oxidative stress. WRNexoΔ adults are sensitive to stress caused by elevated temperature and starvation suggesting abnormalities in energy storage and a possible link to metabolic dysfunction in WS patients. We also observed higher levels of sleep in aged WRNexoΔ adults suggesting an additional adaptive mechanism to protect against age-related stress. We suggest that stress response in WRNexoΔ is multifaceted and evokes a systemic physiological response to protect against cellular damage. These data further validate WRNexoΔ flies as a WS model with which to study mechanisms of early aging and provide a foundation for development of treatments for WS and similar diseases.
BET Proteins Regulate Expression of Osr1 in Early Kidney Development
Authors: Schreiber Janina , Liaukouskaya Nastassia , Fuhrmann Lars , Hauser Alexander-Thomas , Jung Manfred , Huber Tobias B. , Wanner Nicola
Published: December 2021

In utero renal development is subject to maternal metabolic and environmental influences affecting long-term renal function and the risk of developing chronic kidney failure and cardiovascular disease. Epigenetic processes have been implicated in the orchestration of renal development and prenatal programming of nephron number. However, the role of many epigenetic modifiers for kidney development is still unclear. Bromodomain and extra-terminal domain (BET) proteins act as histone acetylation reader molecules and promote gene transcription. BET family members Brd2, Brd3 and Brd4 are expressed in the nephrogenic zone during kidney development. Here, the effect of the BET inhibitor JQ1 on renal development is evaluated. Inhibition of BET proteins via JQ1 leads to reduced growth of metanephric kidney cultures, loss of the nephron progenitor cell population, and premature and disturbed nephron differentiation. Gene expression of key nephron progenitor transcription factor Osr1 is downregulated after 24 h BET inhibition, while Lhx1 and Pax8 expression is increased. Mining of BRD4 ChIP-seq and gene expression data identify Osr1 as a key factor regulated by BRD4-controlled gene activation. Inhibition of BRD4 by BET inhibitor JQ1 leads to downregulation of Osr1, thereby causing a disturbance in the balance of nephron progenitor cell self-renewal and premature differentiation of the nephron, which ultimately leads to kidney hypoplasia and disturbed nephron development. This raises questions about the potential teratogenic effects of BET inhibitors for embryonic development. In summary, our work highlights the role of BET proteins for prenatal programming of nephrogenesis and identifies Osr1 as a potential target of BET proteins.
Low-Dose Niacin Supplementation Improves Motor Function in US Veterans with Parkinson’s Disease: A Single-Center, Randomized, Placebo-Controlled Trial
Authors: Wakade Chandramohan , Chong Raymond , Seamon Marissa , Purohit Sharad , Giri Banabihari , Morgan John C.
Published: December 2021

A six-month double-blind, placebo-controlled randomized study was conducted to ascertain whether low-dose daily niacin supplementation would improve motor symptoms in Parkinson’s disease (PD) patients. A total of 47 PD patients were assigned to receive low-dose niacin or a placebo. At the end of the double-blind phase, all participants received open-label niacin for the next six months. All patients were evaluated at baseline, after six months, and after one year of treatment. The primary outcome measure was the Unified Parkinson’s Disease Rating Scale III (UPDRS III) scores. Secondary outcome measures were depression, sleep quality, mental flexibility and cognition, and physical fatigue. Niacin treatment was well-tolerated by forty-five subjects. The mean [95% CI] change in UPDRS III scores at six months of placebo was −0.05 [95% CI, −2.4 to 2.32], and niacin was −1.06 [95% CI, −3.68 to 1.57]. From six to twelve months when both groups received open-label niacin supplementation, the average UPDRS III scores significantly decreased for the placebo group by 4.58 [95% CI, −0.85 to 8.30] and the niacin group by 4.63 [95% CI, 1.42 to 7.83] points. Low-dose niacin supplementation is a well-tolerated adjunct therapy and may improve motor function in PD when taken over a longer period.
Small Noncoding RNAs in Reproduction and Infertility
Authors: Zhu Qifan , Kirby Jane Allyn , Chu Chen , Gou Lan-Tao
Published: December 2021

Infertility has been reported as one of the most common reproductive impairments, affecting nearly one in six couples worldwide. A large proportion of infertility cases are diagnosed as idiopathic, signifying a deficit in information surrounding the pathology of infertility and necessity of medical intervention such as assisted reproductive therapy. Small noncoding RNAs (sncRNAs) are well-established regulators of mammalian reproduction. Advanced technologies have revealed the dynamic expression and diverse functions of sncRNAs during mammalian germ cell development. Mounting evidence indicates sncRNAs in sperm, especially microRNAs (miRNAs) and transfer RNA (tRNA)-derived small RNAs (tsRNAs), are sensitive to environmental changes and mediate the inheritance of paternally acquired metabolic and mental traits. Here, we review the critical roles of sncRNAs in mammalian germ cell development. Furthermore, we highlight the functions of sperm-borne sncRNAs in epigenetic inheritance. We also discuss evidence supporting sncRNAs as promising biomarkers for fertility and embryo quality in addition to the present limitations of using sncRNAs for infertility diagnosis and treatment.
Net-Zero Energy Districts and the Grid: An Energy-Economic Feasibility Case-Study of the National Western Center in Denver, CO, USA
Authors: Saarloos Benjamin A. , Quinn Jason C.
Published: December 2021

Given the enormous impact of buildings on energy consumption, it is important to continue the development of net-zero energy districts. Opportunities exist for energy efficiency and renewable energy on a district level that may not be feasible in individual buildings. Due to the intermittent nature of many renewable energy sources, net-zero energy districts are dependent on the energy grid. The novelty of this work is to quantify and optimize the economic cost and grid independence of a net-zero energy district using the National Western Center (NWC) in Denver, CO, USA as a case study. The NWC is a 100+ ha campus undergoing a major redevelopment process with a planned 170,000 m2 of total building space, an emphasis on sustainability, and a net-zero energy goal. Campus plans, building energy models, and renewable energy performance models of on-site solar, biomass, and thermal renewable energy sources are analyzed in multiple energy scenarios to achieve net-zero energy with and without on-site energy storage. Levelized cost of energy (LCOE) is optimized as a function of variables defining the energy and economic relationship with the grid. Discussion herein addresses trade-offs between net-zero energy scenarios in terms of energy load, LCOE, storage, and grid dependence.
Managing Fast-Track Construction Project in Qatar: Challenges and Opportunities
Authors: Egbelakin Temitope , Ogunmakinde Olabode , Teshich Billie , Omotayo Temitope
Published: December 2021

Fast-track construction projects are becoming increasingly prevalent in the construction industry, particularly where completion time is essential. A high adoption rate in some of the Gulf Cooperation Council (GCC) countries countries and the lack of a conceptual understanding of the challenges inherent in such may jeopardize the future sustainability of the construction sector. To make an informed decision about adopting a fast-track construction method, it is necessary to first identify the opportunities and challenges associated with it. Therefore, this study examines the critical challenges impeding the performance of Qatar’s fast-track construction projects. The research findings were analysed and triangulated using a real-life project as a case study and several data sources. The results of the research identified four critical categories of barriers: design and coordination-related, scope or change orders-related, material and equipment-related, and contractual-related barriers. In addition, strategies such as accurate information, constructability assessment, early involvement of operations and maintenance personnel, and the use of an effective change control system were identified for addressing the identified challenges. The findings are beneficial to professionals who are currently operating or planning to undertake construction projects in Qatar or other Gulf Cooperation Council (GCC) countries countries. This study recommends that project managers be more attentive to key barriers in order to improve the performance of fast-track projects and to meet clients’ objectives.
Optimization of Facile Synthesized ZnO/CuO Nanophotocatalyst for Organic Dye Degradation by Visible Light Irradiation Using Response Surface Methodology
Authors: Siddiqui Vasi , Ansari Afzal , Ansari M. , Akram Md. , Siddiqi Weqar , Alosaimi Abeer , Hussein Mahmoud , Rafatullah Mohd
Published: December 2021

In this study, we aimed to observe how different operating parameters influenced the photocatalytic degradation of rhodamine B (RhB, cationic dye) and bromophenol Blue (BPB, anionic dye) over ZnO/CuO under visible light irradiation. This further corroborated the optimization study employing the response surface methodology (RSM) based on central composite design (CCD). The synthesis of the ZnO/CuO nanocomposite was carried out using the co-precipitation method. The synthesized samples were characterized via the XRD, FT-IR, FE-SEM, Raman, and BET techniques. The characterization revealed that the nanostructured ZnO/CuO formulation showed the highest surface area (83.13 m2·g−1). Its surface area was much higher than that of pure ZnO and CuO, thereby inheriting the highest photocatalytic activity. To substantiate this photocatalytic action, the investigative analysis was carried out at room temperature, associating first-order kinetics at a rate constant of 0.0464 min−1 for BPB and 0.07091 min−1 for RhB. We examined and assessed the binary interactions of the catalyst dosage, concentration of dye, and irradiation time. The suggested equation, with a high regression R2 value of 0.99701 for BPB and 0.9977 for RhB, accurately matched the experimental results. Through ANOVA we found that the most relevant individual parameter was the irradiation time, followed by catalyst dose and dye concentration. In a validation experiment, RSM based on CCD was found to be suitable for the optimization of the photocatalytic degradation of BPB and RhB over ZnO/CuO photocatalysts, with 98% degradation efficiency.
Synthesis, Characterizations and Catalysis of Sulfated Silica and Nickel Modified Silica Catalysts for Diethyl Ether (DEE) Production from Ethanol towards Renewable Energy Applications
Authors: Wijaya Karna , Lammaduma Malau Melynatri Laura , Utami Maisari , Mulijani Sri , Patah Aep , Wibowo Arief Cahyo , Chandrasekaran Murugesan , Rajabathar Jothi Ramalingam , Al-Lohedan Hamad A.
Published: December 2021

Sulfated silica (SO4/SiO2) and nickel impregnated sulfated silica (Ni-SO4/SiO2) catalysts have been successfully carried out for the conversion of ethanol into diethyl ether (DEE) as a biofuel. The aims of this research were to study the effects of acidity on the SO4/SiO2 and Ni-SO4/SiO2 catalysts in the conversion of ethanol into diethyl ether. This study focuses on the increases in activity and selectivity of SiO2 with the impregnation of sulfate and Ni metal, which had good activity and acidity and were less expensive. The SO4/SiO2 catalysts were prepared using TEOS (Tetraethyl Orthosilicate) as a precursor and sulfuric acid with various concentrations (1, 2, 3, 4 M). The results showed that SO4/SiO2 acid catalyst treated with 2 M H2SO4 and calcined at 400 °C (SS-2-400) was the catalyst with highest total acidity (2.87 g/mmol), while the impregnation of Ni metal showed the highest acidity value at 3%/Ni-SS-2 catalyst (4.89 g/mmol). The SS-2-400 and 3%/Ni-SS-2 catalysts were selected and applied in the ethanol dehydration process into diethyl ether at temperatures 175, 200, and 225 °C. The activity and selectivity of SS-2-400 and 3%/Ni-SS-2 catalysts shown the conversion of ethanol reached up to 9.54% with good selectivity towards diethyl ether liquid product formation.
Gene Expression Profiles Identify Biomarkers of Resistance to Decitabine in Myelodysplastic Syndromes
Authors: Kim Seungyoun , Shin Dong-Yeop , Kim Dayeon , Oh Somi , Hong Junshik , Kim Inho , Kim Eunju
Published: December 2021

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease characterized by inefficient hematopoiesis and the potential development of acute leukemia. Among the most notable advances in the treatment of MDS is the hypomethylating agent, decitabine (5-aza-2′deoxycytidine). Although decitabine is well known as an effective method for treating MDS patients, only a subset of patients respond and a tolerance often develops, leading to treatment failure. Moreover, decitabine treatment is costly and causes unnecessary toxicity. Therefore, clarifying the mechanism of decitabine resistance is important for improving its therapeutic efficacy. To this end, we established a decitabine-resistant F-36P cell line from the parental F-36P leukemia cell line, and applied a genetic approach employing next-generation sequencing, various experimental techniques, and bioinformatics tools to determine differences in gene expression and relationships among genes. Thirty-eight candidate genes encoding proteins involved in decitabine-resistant-related pathways, including immune checkpoints, the regulation of myeloid cell differentiation, and PI3K-Akt signaling, were identified. Interestingly, two of the candidate genes, AKT3 and FOS, were overexpressed in MDS patients with poor prognoses. On the basis of these results, we are pursuing development of a gene chip for diagnosing decitabine resistance in MDS patients, with the goal of ultimately improving the power to predict treatment strategies and the prognosis of MDS patients.
Transcriptomic Profiles Reveal Downregulation of Low-Density Lipoprotein Particle Receptor Pathway Activity in Patients Surviving Severe COVID-19
Authors: Vlasov Ivan , Panteleeva Alexandra , Usenko Tatiana , Nikolaev Mikhael , Izumchenko Artem , Gavrilova Elena , Shlyk Irina , Miroshnikova Valentina , Shadrina Maria , Polushin Yurii , Pchelina Sofya , Slonimsky Petr
Published: December 2021

To assess the biology of the lethal endpoint in patients with SARS-CoV-2 infection, we compared the transcriptional response to the virus in patients who survived or died during severe COVID-19. We applied gene expression profiling to generate transcriptional signatures for peripheral blood mononuclear cells (PBMCs) from patients with SARS-CoV-2 infection at the time when they were placed in the Intensive Care Unit of the Pavlov First State Medical University of St. Petersburg (Russia). Three different bioinformatics approaches to RNA-seq analysis identified a downregulation of three common pathways in survivors compared with nonsurvivors among patients with severe COVID-19, namely, low-density lipoprotein (LDL) particle receptor activity (GO:0005041), important for maintaining cholesterol homeostasis, leukocyte differentiation (GO:0002521), and cargo receptor activity (GO:0038024). Specifically, PBMCs from surviving patients were characterized by reduced expression of PPARG, CD36, STAB1, ITGAV, and ANXA2. Taken together, our findings suggest that LDL particle receptor pathway activity in patients with COVID-19 infection is associated with poor disease prognosis.
Protein Kinase A (PRKA) Activity Is Regulated by the Proteasome at the Onset of Human Sperm Capacitation
Authors: Zapata-Carmona Héctor , Barón Lina , Kong Milene , Morales Patricio
Published: December 2021

The proteasome increases its activity at the onset of sperm capacitation due to the action of the SACY/PRKACA pathway; this increase is required for capacitation to progress. PRKA activity also increases and remains high during capacitation. However, intracellular levels of cAMP decrease in this process. Our goal was to evaluate the role of the proteasome in regulating PRKA activity once capacitation has started. Viable human sperm were incubated in the presence and absence of epoxomicin or with 0.1% DMSO. The activity of PRKA; the phosphorylation pattern of PRKA substrates (pPRKAs); and the expression of PRKAR1, PRKAR2, and AKAP3 were evaluated by Western blot. The localization of pPRKAs, PRKAR1, PRKAR2, and AKAP3 was evaluated by immunofluorescence. Treatment with epoxomicin changed the localization and phosphorylation pattern and decreased the percentage of pPRKAs-positive sperm. PRKA activity significantly increased at 1 min of capacitation and remained high throughout the incubation. However, epoxomicin treatment significantly decreased PRKA activity after 30 min. In addition, PRKAR1 and AKAP3 were degraded by the proteasome but with a different temporal kinetic. Our results suggest that PRKAR1 is the target of PRKA regulation by the proteasome.
Vardenafil Activity in Lung Fibrosis and In Vitro Synergy with Nintedanib
Authors: Bourne Michael H. , Kottom Theodore J. , Hebrink Deanne M. , Choudhury Malay , Leof Edward B. , Limper Andrew H.
Published: December 2021

Idiopathic pulmonary fibrosis (IPF) remains an intractably fatal disorder, despite the recent advent of anti-fibrotic medication. Successful treatment of IPF, like many chronic diseases, may benefit from the concurrent use of multiple agents that exhibit synergistic benefit. In this light, phosphodiesterase type 5 inhibitors (PDE5-Is), have been studied in IPF primarily for their established pulmonary vascular effects. However, recent data suggest certain PDE5-Is, particularly vardenafil, may also reduce transforming growth factor beta 1 (TGF-β1) activation and extracellular matrix (ECM) accumulation, making them a potential target for therapy for IPF. We evaluated fibroblast TGF-β1-driven extracellular matrix (ECM) generation and signaling as well as epithelial mesenchymal transformation (EMT) with pretreatment using the PDE5-I vardenafil. In addition, combinations of vardenafil and nintedanib were evaluated for synergistic suppression of EMC using a fibronectin enzyme-linked immunosorbent assay (ELISA). Finally, the effects of vardenafil on fibrosis were investigated in a bleomycin mouse model. Our findings demonstrate that vardenafil suppresses ECM generation alone and also exhibits significant synergistic suppression of ECM in combination with nintedanib in vitro. Interestingly, vardenafil was shown to improve fibrosis markers and increase survival in bleomycin-treated mice. Vardenafil may represent a potential treatment for IPF alone or in combination with nintedanib. However, additional studies will be required.
The Stiffness of Cardiac Fibroblast Substrates Exerts a Regulatory Influence on Collagen Metabolism via α2β1 Integrin, FAK and Src Kinases
Authors: Gałdyszyńska Małgorzata , Radwańska Paulina , Szymański Jacek , Drobnik Jacek
Published: December 2021

Information about mechanical strain in the extracellular space is conducted along collagen fibers connected with integrins and then transmitted within cells. An aim of the study is to verify the hypothesis that the stiffness of cardiac human fibroblast substrates exerts a regulatory effect on collagen metabolism via integrin α2β1 and downstream signaling. The experiments were performed on human cardiac fibroblasts cultured on stiff or soft polyacrylamide gels. Extracellular and intracellular collagen content, metalloproteinase-1 (MMP-1), metalloproteinase-9 (MMP-9) and expression of the α1 chain of the procollagen type I gene (Col1A1) were elevated in cultures settled on soft substrate. The substrate stiffness did not modify tissue inhibitors of matrix metalloproteinase capacity (TIMPs 1–4). Integrin α2β1 inhibition (TC-I 15) or α2 subunit silencing resulted in augmentation of collagen content within the culture. Expression of Col1A1 and Col3A1 genes was increased in TC-I 15-treated fibroblasts. Total and phosphorylated levels of both FAK and Src kinases were elevated in fibroblasts cultured on stiff substrate. Inhibition of FAK (FAK kinase inhibitor 14) or Src kinase (AZM 47527) increased collagen content within the culture. The substrate stiffness exerted a regulatory influence on collagen metabolism via integrin α2β1 and its downstream signaling (FAK and Src kinases) in cardiac fibroblasts.
Functional Roles for CD26/DPP4 in Mediating Inflammatory Responses of Pulmonary Vascular Endothelial Cells
Authors: Takahashi Yukiko , Kawasaki Takeshi , Sato Hironori , Hasegawa Yoshinori , Dudek Steven M. , Ohara Osamu , Tatsumi Koichiro , Suzuki Takuji
Published: December 2021

Excessive inflammation in the lung is a primary cause of acute respiratory distress syndrome (ARDS). CD26/dipeptidyl peptidase-4 (DPP4) is a transmembrane protein that is expressed in various cell types and exerts multiple pleiotropic effects. We recently reported that pharmacological CD26/DPP4 inhibition ameliorated lipopolysaccharide (LPS)-induced lung injury in mice and exerted anti-inflammatory effects on human lung microvascular endothelial cells (HLMVECs), in vitro. However, the mechanistic roles of CD26/DPP4 in lung injury and its effects on HLMVECs remain unclear. In this study, transcriptome analysis, followed by various confirmation experiments using siRNA in cultured HLMVECs, are performed to evaluate the role of CD26/DPP4 in response to the pro-inflammatory involved in inflammation, barrier function, and regenerative processes in HLMVECs after pro-inflammatory stimulation. These are all functions that are closely related to the pathophysiology and repair process of lung injury. Confirmatory experiments using flow cytometry; enzyme-linked immunosorbent assay; quantitative polymerase chain reaction; dextran permeability assay; WST-8 assay; wound healing assay; and tube formation assay, reveal that the reduction of CD26/DPP4 via siRNA is associated with altered parameters of inflammation, barrier function, and the regenerative processes in HLMVECs. Thus, CD26/DPP4 can play a pathological role in mediating injury in pulmonary endothelial cells. CD26/DPP4 inhibition can be a new therapeutic strategy for inflammatory lung diseases, involving pulmonary vascular damage.
Advanced Management Protocol of Transanal Irrigation in Order to Improve the Outcome of Pediatric Patients with Fecal Incontinence
Authors: Caruso Anna Maria , Milazzo Mario Pietro Marcello , Bommarito Denisia , Girgenti Vincenza , Amato Glenda , Paviglianiti Giuseppe , Casuccio Alessandra , Catalano Pieralba , Cimador Marcello , Di Pace Maria Rita
Published: December 2021

Background: Transanal irrigation (TAI) is employed for children with fecal incontinence, but it can present several problems which require a study of their outcomes among different pathologies and without a tailored work up. The aim of our study was to evaluate the effectiveness of an advanced protocol in order to tailor TAI, prevent complications, and evaluate outcomes. Methods: We included 70 patients (14 anorectal malformation, 12 Hirschsprung’s disease, 24 neurological impairment, 20 functional incontinence) submitted to a comprehensive protocol with Peristeen®: fecal score, volumetric enema, rectal ultrasound, anorectal 3D manometry, and diary for testing and parameter adjustment. Results: Among the patients, 62.9% needed adaptations to the parameters, mainly volume of irrigated water and number of puffs of balloon. These adaptations were positively correlated with pre-treatment manometric and enema data. In each group, the improvement of score was statistically significant in all cases (p 0.000); the main factor influencing the efficacy was the rate of sphincter anomalies. The ARM group had slower improvement than other groups, whereas functional patients had the best response. Conclusions: Our results showed that TAI should not be standardized for all patients, because each one has different peculiarities; evaluation of patients before TAI with rectal ultrasound, enema, and manometry allowed us to tailor the treatment, highlighting different outcomes among various pathologies, thus improving the efficacy.
Role of Single Nucleotide Variants in FSHR, GNRHR, ESR2 and LHCGR Genes in Adolescents with Polycystic Ovary Syndrome
Authors: Lidaka Lasma , Bekere Laine , Rota Adele , Isakova Jekaterina , Lazdane Gunta , Kivite-Urtane Anda , Dzivite-Krisane Iveta , Kempa Inga , Dobele Zane , Gailite Linda
Published: December 2021

Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women, affecting up to 16.6% of reproductive-age women. PCOS symptoms in adolescents comprise oligomenorrhoea/amenorrhoea and biochemical and/or clinical hyperandrogenism. Long-term health risks of PCOS patients include infertility, metabolic syndrome, type 2 diabetes and cardiovascular disease. Genetic factors have been proven to play a role in development of the syndrome and its symptoms. Objective: To investigate single nucleotide variants (SNVs) in the GNRHR, ESR2, LHCGR and FSHR genes in adolescent patients with PCOS and their association with PCOS symptoms. Methods: We conducted a cross-sectional study comprising of 152 adolescents: 63 patients with PCOS, 22 patients at risk of developing PCOS and 67 healthy controls. Participants were recruited from out-patients attending a gynaecologist at the Children’s Clinical University Hospital, Riga, Latvia, between January 2017 and December 2020. Genomic DNA was extracted from whole blood, and SNVs in the GNRHR, ESR2, LHCGR and FSHR genes were genotyped. The distributions of SNV genotypes were compared among the three groups and genotype-phenotype associations within the PCOS group were evaluated. Results: No statistically significant differences were found in the distributions of genotypes for GNRHR (rs104893837), ESR2 (rs4986938), LHCGR (rs2293275) and FSHR (rs6166, rs6165, rs2349415) among PCOS patients, risk patients and healthy controls. Within the PCOS group, ESR2 rs4986938 minor allele homozygous patients had a significantly higher level of total testosterone than major allele homozygous patients and heterozygous patients. A significantly higher total testosterone level was also observed in PCOS patients carrying the LHCGR rs2293275 minor allele compared with major allele homozygous patients. Conclusions: The SNVs ESR2 rs4986938 and LHCGR rs2293275 play a role in the phenotypic characteristics of PCOS. To fully uncover their influence on the development of PCOS and its symptoms, further studies of larger cohorts and a follow up of this study sample through to adulthood are required. Furthermore, studies of adolescent PCOS patients conducted prior to the latest European Society of Human Reproduction and Embryology (ESHRE) criteria (2018) should be re-evaluated as the study groups might include risk patients according to these updated criteria, thereby potentially significantly impacting the published results.
In Vitro Fertilization Using Preimplantation Genetic Testing in a Romanian Couple Carrier of Mutations in the TTN Gene: A Case Report and Literature Review
Authors: Doroftei Bogdan , Maftei Radu , Ilie Ovidiu-Dumitru , Armeanu Theodora , Puiu Maria , Ivanov Iuliu , Nemtanu Loredana
Published: December 2021

Severe congenital myopathy with fatal cardiomyopathy (EOMFC) is a rare genetic neuromuscular disorder inherited in an autosomal recessive manner. Here we presented a successful pregnancy obtained by in vitro fertilization (IVF) using preimplantation genetic testing (PGT) in one young Romanian carrier couple that already lost mutation(s) within the TNN gene and whose first baby passed away due to multiple complications. It was delivered via emergency C-section at 36 weeks and fully dependent on artificial ventilation for a couple of months, weighing 2200 g and an APGAR score of 3. The aCGH + SNP analysis revealed an abnormal profile of the first newborn; three areas associated with loss of heterozygosity on chromosome 1 (q25.1–q25.3) of 6115 kb, 5 (p15.2–p15.1) of 2589 kb and 8 (q11.21–q11.23) of 4830 kb, a duplication of 1104 kb on chromosome 10 in the position q11.22, and duplication of 1193 kb on chromosome 16 in the position p11.2p11.1. Subsequently, we proceeded to test the parents and showed that both parents are carriers; confirmed by Sanger and NGS sequencing—father—on Chr2(GRCh37):g.179396832_179396833del—TTN variant c.104509_104510del p.(Leu34837Glufs*12)—exon 358 and mother—on Chr2(GRCh37):g.179479653G>C—TTN variant c.48681C>G p.(Tyr16227*)—exon 260. Their first child died shortly after birth due to multiple organ failures, possessing both parent’s mutations; weighing 2200 g at birth and received an APGAR score of 3 following premature delivery via emergency C-section at 36 weeks. Two embryos were obtained following the IVF protocol; one possessed the mother’s mutation, and the other had no mutations and was normal (WT). In contrast with the first birth, the second one was uneventful. A healthy female baby weighing 2990 g was delivered by C-section at 38 weeks, receiving an APGAR score of 9.
A Rare Case of Allantoic Cyst with Patent Urachus in Fetus with a Microdeletion in 1q21.1q21.2 Region
Authors: Bouariu Alexandra , Scutelnicu Ana Maria , Ciobanu Anca Marina , Cimpoca Raptis Brîndușa Ana , Dumitru Andreea Elena , Nedelea Florina , Gică Nicolae , Panaitescu Anca Maria
Published: December 2021

An allantoic cyst is a rare malformation with a frequency of 3 in 1,000,000 that may be seen antenatally by ultrasound assessment when the connection between the cloaca (future bladder) and the allantois fails to regress. A patent urachus that presents as a cyst (allantoic) is usually considered not to be associated with chromosomal abnormalities, but if it is not repaired after birth this leads to complications such as urinary tract infections and stone formation. We present a case of a fetus diagnosed with allantoic cyst at the first trimester ultrasound assessment at 12 weeks gestation. The follow up scans showed a decrease in size of the allantoic cyst with no other obvious major defects and, when invasive testing (amniocentesis with microarray analysis) was performed, a rare microdeletion, 1q21.1q21.2 was identified (1.82 Mb deletion).
The Role of Echocardiography in the Management of Heart Transplant Recipients
Authors: Masarone Daniele , Kittleson Michelle , Gravino Rita , Valente Fabio , Petraio Andrea , Pacileo Giuseppe
Published: December 2021

Transthoracic echocardiography is the primary non-invasive modality for the investigation of heart transplant recipients. It is a versatile tool that provides comprehensive information on cardiac structure and function. Echocardiography is also helpful in diagnosing primary graft dysfunction and evaluating the effectiveness of therapeutic approaches for this condition. In acute rejection, echocardiography is useful with suspected cellular or antibody-mediated rejection, with findings confirmed and quantified by endomyocardial biopsy. For identifying chronic rejection, ultrasound has a more significant role and, in some specific patients (e.g., patients with renal failure), it may offer a role comparable to coronary angiography to identify cardiac allograft vasculopathy. This review highlights the usefulness of echocardiography in evaluating normal graft function and its role in the management of heart transplant recipients.
Neurogranin as a Reliable Biomarker for Synaptic Dysfunction in Alzheimer’s Disease
Authors: Agnello Luisa , Lo Sasso Bruna , Vidali Matteo , Scazzone Concetta , Piccoli Tommaso , Gambino Caterina Maria , Bivona Giulia , Giglio Rosaria Vincenza , Ciaccio Anna Maria , La Bella Vincenzo , Ciaccio Marcello
Published: December 2021

(1) Background: Neurogranin is a post-synaptic protein expressed in the neurons of the hippocampus and cerebral cortex. It has been recently proposed as a promising biomarker of synaptic dysfunction, especially in Alzheimer’s disease (AD). However, more efforts are needed before introducing it in clinical practice, including the definition of its reference interval (RI). The aim of the study was to establish the RI of cerebrospinal fluid (CSF) neurogranin levels in controls and individuals with non-neurodegenerative neurological diseases; (2) We included a total of 136 individuals that were sub-grouped as follows: AD patients (n = 33), patients with non-neurodegenerative neurological diseases (n = 70) and controls (33). We measured CSF neurogranin levels by a commercial ELISA kit. CSF RI of neurogranin was calculated by a robust method; (3) Results: AD patients showed increased levels of neurogranin. We also found that neurogranin was significantly correlated with T-tau, P-tau and mini mental state examination in AD patients. The lower and upper reference limits of the RI were 2.9 (90%CI 0.1–10.8) and 679 (90%CI 595–779), respectively; (4) Conclusion: This is the first study establishing the RI of CSF neurogranin.
Translation and Validation of Italian Version of Index of Dental Anxiety and Fear (IDAF-4C+): A Cross-Sectional Study
Authors: Salgarello Stefano , Garo Maria Luisa , Paganelli Corrado , Vita Antonio , Salvadori Matteo , Audino Elisabetta
Published: December 2021

Dental anxiety (DA) is defined as unreasonable apprehension toward dental procedures. About 4–20% of the worldwide adult population presents DA, with peaks of 30% in the younger population. Managing patients with dental anxiety and fear with a reliable and valid instrument is necessary to understand the multidimensional dimensions of dental fear. This work aimed to validate the Index of Dental Anxiety and Fear (IDAF-4C+) into Italian. Two hundred and eighty dental students attending an Italian university were enrolled. The IDAF-4C+ was translated by experts and a native English translator, blinded to the original version. The Modified Dental Anxiety Scale (MDAS) was used to assess the validity of IDAF-4C+. Spearman correlation coefficients and Exploratory Factorial Analysis (EFA) were used. Reliability was evaluated by Cronbach’s alpha. The reliability of the Italian version of IDAF-4C+ was good (Cronbach’s alpha = 0.88). Correlation between IDAF-4C+ and MDAS ranged between 0.42 to 0.68. From EFA, one factor explained 58.76% of the common variance. Women showed a higher level of dental fear. The Italian IDAF-4C+ is a valid and reliable tool to assess DA in any clinical context. This instrument allows for a proper understanding and management of DA, and therefore a better patient oral health-related quality of life and compliance with the dentist’s instructions.
Quantifying the Endogeneity in Online Donations
Authors: Wang Peng , Li Jinyi , Ma Yinjie , Jiang Zhiqiang
Published: December 2021

Charitable crowdfunding provides a new channel for people and families suffering from unforeseen events, such as accidents, severe illness, and so on, to seek help from the public. Thus, finding the key determinants which drive the fundraising process of crowdfunding campaigns is of great importance, especially for those suffering. With a unique data set containing 210,907 crowdfunding projects covering a period from October 2015 to June 2020, from a famous charitable crowdfunding platform, specifically Qingsong Chou, we will reveal how many online donations are due to endogeneity, referring to the positive feedback process of attracting more people to donate through broadcasting campaigns in social networks by donors. For this aim, we calibrate three different Hawkes processes to the event data of online donations for each crowdfunding campaign on each day, which allows us to estimate the branching ratio, a measure of endogeneity. It is found that the online fundraising process works in a sub-critical state and nearly 70–90% of the online donations are endogenous. Furthermore, even though the fundraising amount, number of donations, and number of donors decrease rapidly after the crowdfunding project is created, the measure of endogeneity remains stable during the entire lifetime of crowdfunding projects. Our results not only deepen our understanding of online fundraising dynamics but also provide a quantitative framework to disentangle the endogenous and exogenous dynamics in complex systems.
Ground State, Magnetization Process and Bipartite Quantum Entanglement of a Spin-1/2 Ising–Heisenberg Model on Planar Lattices of Interconnected Trigonal Bipyramids
Authors: Gálisová Lucia , Kaczor Michał
Published: December 2021

The ground state, magnetization scenario and the local bipartite quantum entanglement of a mixed spin-1/2 Ising–Heisenberg model in a magnetic field on planar lattices formed by identical corner-sharing bipyramidal plaquettes is examined by combining the exact analytical concept of generalized decoration-iteration mapping transformations with Monte Carlo simulations utilizing the Metropolis algorithm. The ground-state phase diagram of the model involves six different phases, namely, the standard ferrimagnetic phase, fully saturated phase, two unique quantum ferrimagnetic phases, and two macroscopically degenerate quantum ferrimagnetic phases with two chiral degrees of freedom of the Heisenberg triangular clusters. The diversity of ground-state spin arrangement is manifested themselves in seven different magnetization scenarios with one, two or three fractional plateaus whose values are determined by the number of corner-sharing plaquettes. The low-temperature values of the concurrence demonstrate that the bipartite quantum entanglement of the Heisenberg spins in quantum ferrimagnetic phases is field independent, but twice as strong if the Heisenberg spin arrangement is unique as it is two-fold degenerate.
QoS-Ledger: Smart Contracts and Metaheuristic for Secure Quality-of-Service and Cost-Efficient Scheduling of Medical-Data Processing
Authors: Khan Abdullah Ayub , Shaikh Zaffar Ahmed , Baitenova Laura , Mutaliyeva Lyailya , Moiseev Nikita , Mikhaylov Alexey , Laghari Asif Ali , Idris Sahar Ahmed , Alshazly Hammam
Published: December 2021

Quality-of-service (QoS) is the term used to evaluate the overall performance of a service. In healthcare applications, efficient computation of QoS is one of the mandatory requirements during the processing of medical records through smart measurement methods. Medical services often involve the transmission of demanding information. Thus, there are stringent requirements for secure, intelligent, public-network quality-of-service. This paper contributes to three different aspects. First, we propose a novel metaheuristic approach for medical cost-efficient task schedules, where an intelligent scheduler manages the tasks, such as the rate of service schedule, and lists items utilized by users during the data processing and computation through the fog node. Second, the QoS efficient-computation algorithm, which effectively monitors performance according to the indicator (parameter) with the analysis mechanism of quality-of-experience (QoE), has been developed. Third, a framework of blockchain-distributed technology-enabled QoS (QoS-ledger) computation in healthcare applications is proposed in a permissionless public peer-to-peer (P2P) network, which stores medical processed information in a distributed ledger. We have designed and deployed smart contracts for secure medical-data transmission and processing in serverless peering networks and handled overall node-protected interactions and preserved logs in a blockchain distributed ledger. The simulation result shows that QoS is computed on the blockchain public network with transmission power = average of −10 to −17 dBm, jitter = 34 ms, delay = average of 87 to 95 ms, throughput = 185 bytes, duty cycle = 8%, route of delivery and response back variable. Thus, the proposed QoS-ledger is a potential candidate for the computation of quality-of-service that is not limited to e-healthcare distributed applications.
LAN Traffic Capture Applications Using the Libtins Library
Authors: Costin Adrian-Tiberiu , Zinca Daniel , Dobrota Virgil
Published: December 2021

Capturing traffic and processing its contents is a valuable skill that when put in the right hands makes diagnosing and troubleshooting network issues an approachable task. Apart from aiding in fixing common problems, packet capture can also be used for any application that requires getting a deeper understanding of how things work under the hood. Many tools have been developed in order to allow the user to study the flow of data inside of a network. This paper focuses on documenting the process of creating such tools and showcasing their use in different contexts. This is achieved by leveraging the power of the C++ programming language and of the libtins library in order to create custom extensible sniffing tools, which are then used in VoIP (Voice over IP) and IDS (Intrusion Detection System) applications.
FP-Growth Algorithm for Discovering Region-Based Association Rule in the IoT Environment
Authors: Jang Hong-Jun , Yang Yeongwook , Park Ji Su , Kim Byoungwook
Published: December 2021

With the development of the Internet of things (IoT), both types and amounts of spatial data collected from heterogeneous IoT devices are increasing. The increased spatial data are being actively utilized in the data mining field. The existing association rule mining algorithms find all items with high correlation in the entire data. Association rules that may appear differently for each region, however, may not be found when the association rules are searched for all data. In this paper, we propose region-based frequent pattern growth (RFP-Growth) to search for association rules by dense regions. First, RFP-Growth divides item transaction included position data into regions by a density-based clustering algorithm. Second, frequent pattern growth (FP-Growth) is performed for each transaction divided by region. The experimental results show that RFP-Growth discovers new association rules that the original FP-Growth cannot find in the whole data.
Comparative Assessment of the Impact of Electricity Consumption in Different Economic Sectors on the Economic Development of the EU Member States
Authors: Ginevičius Romualdas , Noga Gracjana , Žemaitis Eigirdas , Piontek Barbara , Šuhajda Karel
Published: December 2021

Recently, the Member States of the European Union (EU) have found themselves in a controversial situation. On the one hand, national economic development is barely possible without increasing electricity consumption, whereas on the other we are facing increased use of natural resources (coal, oil, gas, wood), thermal effects, pollution and risks to human health. The European Green Deal is a response to the currently observed negative trends. The strategy aims to accelerate the economic development of the EU Member States, thus reducing electricity consumption. Objectives may include both the national economy and the electricity generation sector by applying advanced technologies and introducing innovations that increase output efficiency while reducing electricity costs. Assessing the current situation is vital for the successful implementation of the European Green Deal, i.e., by comparing the impact of electricity consumption on the economic development of the Member States. Thus, combining indicators for national economic development and the extent of electricity consumption into a single aggregate is necessary because electricity greatly affects economic development. The proposed methodology allows dividing the analysed EU Member States into three groups, in line with the degree of national economic development and the scope of electricity consumption in their economy sectors.
PV-Supercapacitor Cascaded Topology for Primary Frequency Responses and Dynamic Inertia Emulation
Authors: Karpana Sivakrishna , Batzelis Efstratios , Maiti Suman , Chakraborty Chandan
Published: December 2021

Owing to rapid increase in PV penetration without inherent inertia, there has been an unremitting deterioration of the effective inertia of the existing power systems. This may pose a serious threat to the stability of power systems during disturbances if not taken care of. Hence, the problem of how to emulate Synthetic Inertia (SI) in PV Systems (PVS) to retain their frequency stability demands attention. Super Capacitor (SC)-based storage become an attractive option over the other energy storage types because of its high-power density, burst power handling capability, faster response and longer life cycle. Considering this, the authors here propose a novel PV-SC Cascaded Topology (PSCT) as a cost-effective approach to emulate SI by integrating a low voltage SC to a high voltage grid-connected PVS. The proposed PSCT helps in operating the SC as a voltage source rather than a current source. Thus, it eliminates the high gain requirements of the SC interfacing converters. The aim is to target two main frequency response services, i.e., Primary Frequency Response (PFR) and Synthetic Inertial Response (SIR), using a novel common control scheme, but without affecting any other energy intensive services. The authors introduced a Droop-Inspired (DI) method with an adjustable inertia constant to emulate dynamic inertia so that a wider range of Rate of Change of Frequency (RoCoF) values can be serviced with a limited storage. A very streamlined analysis was also carried out for sizing of the SC stage based on a simple Three-Point Linearization (TPL) technique and DI technique with a limited knowledge of the disturbance parameters. The whole system was initially validated in a MATLAB Simulink environment and later confirmed with the OPAL-RT Real-Time Simulator. The investigated response was subject to variation in terms of control parameters, changes in solar irradiance, grid frequency variation, etc.