bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Space–Time Analysis of Geodetic and Geological Surveys for Evaluation of the Reliability of the Position of Points in the Geodynamic Network of the City of Zagreb
Authors: Đapo Almin , Pavasović Marko , Pribičević Boško , Prelogović Eduard
Published: December 2020

This paper describes the long-standing interdisciplinary geodynamic research for the wider Zagreb area, the most seismically active area of the continental part of the Republic of Croatia, extending over an area of around 800 km2. As a result of the research, which is based on geodetic and geological field measurements, a unique interdisciplinary movement model of the surface layers of the Earth’s crust for the project area is created. The analysis of survey data has determined the continuous tectonic activity of the wider Zagreb area. In the past 18 years, a total of 10 GPS measurement campaigns have been conducted. For each campaign, the velocities of geodynamic network points were calculated, and the cumulative velocity rate was determined from all measurement campaigns for the entire period of observations using GAMIT/GLOBK software. Displacements at individual measuring points of the network, throughout research, vary widely and depend on its location within the local geologic structural framework and regional tectonic movements. These displacements in detail represent a measurable insight into the tectonic activity of the area of research. Therefore, in this paper, special attention is given to the analysis and explanation of these variations in the displacements of the individual geodynamic points, even indicating the questionable quality of location selection for some points. In this way, we seek to explain the causes and mechanisms of such displacements. The results presented in this paper represent the preseismic area condition and further can be used in coseismic 2020 earthquake displacement analysis.
M-Mode Ultrasound Examination of Soleus Muscle in Healthy Subjects: Intra- and Inter-Rater Reliability Study
Authors: Romero-Morales Carlos , Calvo-Lobo Cesar , Navarro-Flores Emmanuel , Mazoteras-Pardo Victoria , García-Bermejo Paula , López-López Daniel , Martínez-Jiménez Eva María , De-la-Cruz-Torres Blanca
Published: December 2020

Objective: M-mode ultrasound imaging (US) reflects the motion of connective tissue within muscles. The objectives of this study were to evaluate inter-rater and intra-rater reliability of soleus muscle measurements between examiners with different levels of US experience in asymptomatic subjects and to investigate the level of soleus muscle isometric activity in two positions (knee extended and knee flexed at 30°). Methods: Thirty volunteers without a history of ankle pain were evaluated with US examinations of the soleus muscle. Each muscle was scanned independently by two evaluators. Muscle at rest thickness, maximal isometric contraction thickness, time and velocity measures were detailed and blinded to the other examiner. Results: Intra- and inter-rater reliability at rest, in maximal isometric contraction thickness, contraction time and contraction velocity measures for both positions (extended and flexed knee) were reported from good to excellent for all outcome measurements. The position with the knee extended reported a statistically significant increase in thickness after motion showing 1.33 ± 0.27 mm for measurements at rest thickness with knee extended versus 1.50 ± 0.29 mm for measurements at end thickness with the knee in flexed position (p = 0.001), as well as 1.31 ± 0.23 mm for rest thickness with the knee in flexed position measurements with respect to 1.34 ± 0.24 mm for maximal isometric contraction thickness with extended knee measurements (p = 0.058). Conclusions: This study found that intra- and inter-examiner reliability of M-mode ultrasound imaging of the soleus muscle was excellent in asymptomatic subjects and the soleus muscle activity was different between the position with the knee extended and the position with the knee flexed.
The Relationship between Subjective Cognitive Decline and Health Literacy in Healthy Community-Dwelling Older Adults
Authors: Goda Akio , Murata Shin , Nakano Hideki , Nonaka Koji , Iwase Hiroaki , Shiraiwa Kayoko , Abiko Teppei , Anami Kunihiko , Horie Jun
Published: December 2020

Few studies have examined the effects of health literacy on people at risk of developing dementia; its effects on the pathogenesis of subjective cognitive decline (SCD) are particularly unclear. This study aimed to clarify the relationship between health literacy and SCD in a population of healthy community-dwelling older adults. SCD status was assessed using the Cognitive Function domain of the Kihon Checklist (KCL-CF). Health literacy, in turn, was evaluated using the Communicative and Critical Health Literacy (CCHL) scale. Global cognitive function and depressive symptoms were evaluated using the Mini-Mental State Examination (MMSE) and a five-item version of the Geriatric Depression Scale (GDS-5), respectively. Participants who were suspected of having SCD were significantly older than their non-SCD peers, and scored significantly worse on the CCHL, MMSE, and GDS-5. In addition, SCD status was found to be associated with CCHL and GDS-5 scores, as well as age, according to a logistic regression analysis. These findings suggest that low health literacy is linked to SCD morbidity in healthy community-dwelling older adults and should prove useful in the planning of dementia prevention and intervention programs for this population.
Comparing the Scope and Efficacy of COVID-19 Response Strategies in 16 Countries: An Overview
Authors: Rozanova Liudmila , Temerev Alexander , Flahault Antoine
Published: December 2020

This article synthesizes the results of case studies on the development of the coronavirus disease 2019 (COVID-19) pandemic and control measures by governments in 16 countries. When this work was conducted, only 6 months had passed since the pandemic began, and only 4 months since the first events were recognized outside of China. It was too early to draw firm conclusions about the effectiveness of measures in each of the selected countries; however, the authors present some efforts to identify and classify response and containment measures, country-by-country, for future comparison and analysis. There is a significant variety of policy tools and response measures employed in different countries, and while it is still hard to directly compare the different approaches based on their efficacy, it will definitely provide many inputs for the future data analysis efforts.
Advancing Workaholism Research
Authors: Balducci Cristian , Spagnoli Paola , Clark Malissa
Published: December 2020

Research on workaholism (also called work addiction by some scholars, especially in the clinical psychology field) has increased substantially in the last few years [...]
Effect of Multi-Modal Therapies for Kinesiophobia Caused by Musculoskeletal Disorders: A Systematic Review and Meta-Analysis
Authors: Xu Yining , Song Yang , Sun Dong , Fekete Gusztáv , Gu Yaodong
Published: December 2020

This systematic review and meta-analysis aimed to identify the effect of multi-modal therapies that combined physical and psychological therapies for kinesiophobia caused by musculoskeletal disorders compared with uni-modal therapy of only phycological therapy or psychological therapy. The search terms and their logical connector were as following: (1) “kinesiophobia” at the title or abstract; and (2) “randomized” OR “randomized” at title or abstract; not (3) ”design” OR “protocol” at the title. They were typed into the databases of Medline (EBSCO), PubMed, and Ovid, following the different input rules of these databases. The eligibility criteria were: (1) Adults with musculoskeletal disorders or illness as patients; (2) Multi-modal therapies combined physical and psychological therapy as interventions; (3) Uni-modal therapy of only physical or psychological therapy as a comparison; (4) The scores of the 17-items version of the Tampa Scale of Kinesiophobia as the outcome; (5) Randomized controlled trials as study design. As a result, 12 studies were included with a statistically significant polled effect of 6.99 (95% CI 4.59 to 9.38). Despite a large heterogeneity within studies, multi-modal therapies might be more effective in reducing kinesiophobia than the unimodal of only physical or psychological therapy both in the total and subdivision analysis. The effect might decrease with age. What’s more, this review’s mathematical methods were feasible by taking test-retest reliability of the Tampa Scale of Kinesiophobia into consideration.
Mapping Food and Health Premises in Barcelona. An Approach to Logics of Distribution and Proximity of Essential Urban Services
Authors: Crosas Carles , Gómez-Escoda Eulàlia
Published: December 2020

The research analyzes the image of Barcelona and compares differences in quantity, variety and proximity of some essential services in diverse urban fragments. Focusing on food and health premises as critical universal services, series of maps provide overviews on the intensity of use to which each service is subjected, latent logics of their physical proximity and performance in regular urban fabrics due to the combination of activities and population distribution. The research uses a methodological approach and parameterization of the minimum daily urban mixture to highlight the uniqueness of the case of Barcelona, distinguished by the compactness of the urban fabric and the contiguity of activities, and to describe an extensive characterization of areas that from this perspective can be considered hyper-served or under-served. This investigation aims to contribute to the understanding of the necessity of the urban mixture and to provide clues about the distribution of services and activities.
A BIM Based Hybrid 3D Indoor Map Model for Indoor Positioning and Navigation
Authors: Liu Jianhua , Luo Jingyan , Hou Jiwei , Wen Danqi , Feng Guoqiang , Zhang Xu
Published: December 2020

Accurate and fast indoor Location-Based Services (LBS) is very important for daily life and emergency response. Indoor map is the basis of indoor LBS. The model construction and data organization of indoor map are the key scientific problems that urgently need to be solved in the current indoor LBS application. In recent years, hybrid models have been used widely in the research of indoor map, because they can balance the limitations of single models. However, the current studies about hybrid model pay more attention to the model accuracy and modeling algorithm, while ignoring its relationship between positioning and navigation and its practicality in mobile indoor LBS applications. This paper addresses a new indoor map model, named Building Information Modeling based Positioning and Navigation (BIMPN), which is based on the entity model and the network model. The highlight of BIMPN is that it proposes a concept of Step Node (SN) to assist indoor positioning and navigation function. We developed the Mobile Indoor Positioning and Navigation System (MIPNS) to verify the practicability of BIMPN. Results indicate that the BIMPN can effectively organize the characteristics of indoor spaces and the building features, and assist indoor positioning and navigation. The BIMPN proposed in this paper can be used for the construction of indoor maps and it is suitable for mobile indoor positioning and navigation systems.
In Silico/In Vitro Hit-to-Lead Methodology Yields SMYD3 Inhibitor That Eliminates Unrestrained Proliferation of Breast Carcinoma Cells
Authors: Alshiraihi Ilham M. , Jarrell Dillon K. , Arhouma Zeyad , Hassell Kelly N. , Montgomery Jaelyn , Padilla Alyssa , Ibrahim Hend M. , Crans Debbie C. , Kato Takamitsu A. , Brown Mark A.
Published: December 2020

SMYD3 is a lysine methyltransferase that regulates the expression of over 80 genes and is required for the uncontrolled proliferation of most breast, colorectal, and hepatocellular carcinomas. The elimination of SMYD3 restores normal expression patterns of these genes and halts aberrant cell proliferation, making it a promising target for small molecule inhibition. In this study, we sought to establish a proof of concept for our in silico/in vitro hit-to-lead enzyme inhibitor development platform and to identify a lead small molecule candidate for SMYD3 inhibition. We used Schrodinger® software to screen libraries of small molecules in silico and the five compounds with the greatest predicted binding affinity within the SMYD3 binding pocket were purchased and assessed in vitro in direct binding assays and in breast cancer cell lines. We have confirmed the ability of one of these inhibitors, Inhibitor-4, to restore normal rates of cell proliferation, arrest the cell cycle, and induce apoptosis in breast cancer cells without affecting wildtype cell behavior. Our results provide a proof of concept for this fast and affordable small molecule hit-to-lead methodology as well as a promising candidate small molecule SMYD3 inhibitor for the treatment of human cancer.
Pluripotent Stem Cell-Derived Hepatocytes Phenotypic Screening Reveals Small Molecules Targeting the CDK2/4-C/EBPα/DGAT2 Pathway Preventing ER-Stress Induced Lipid Accumulation
Authors: Parafati Maddalena , Bae Sang Hyo , Kirby R. Jason , Fitzek Martina , Iyer Preeti , Engkvist Ola , Smith David M. , Malany Siobhan
Published: December 2020

Non-alcoholic fatty liver disease (NAFLD) has a large impact on global health. At the onset of disease, NAFLD is characterized by hepatic steatosis defined by the accumulation of triglycerides stored as lipid droplets. Developing therapeutics against NAFLD and progression to non-alcoholic steatohepatitis (NASH) remains a high priority in the medical and scientific community. Drug discovery programs to identify potential therapeutic compounds have supported high throughput/high-content screening of in vitro human-relevant models of NAFLD to accelerate development of efficacious anti-steatotic medicines. Human induced pluripotent stem cell (hiPSC) technology is a powerful platform for disease modeling and therapeutic assessment for cell-based therapy and personalized medicine. In this study, we applied AstraZeneca’s chemogenomic library, hiPSC technology and multiplexed high content screening to identify compounds that significantly reduced intracellular neutral lipid content. Among 13,000 compounds screened, we identified hits that protect against hiPSC-derived hepatic endoplasmic reticulum stress-induced steatosis by a mechanism of action including inhibition of the cyclin D3-cyclin-dependent kinase 2-4 (CDK2-4)/CCAAT-enhancer-binding proteins (C/EBPα)/diacylglycerol acyltransferase 2 (DGAT2) pathway, followed by alteration of the expression of downstream genes related to NAFLD. These findings demonstrate that our phenotypic platform provides a reliable approach in drug discovery, to identify novel drugs for treatment of fatty liver disease as well as to elucidate their underlying mechanisms.
Adipokine-Modulated Immunological Homeostasis Shapes the Pathophysiology of Inflammatory Bowel Disease
Authors: Tsai Yi-Wen , Fu Shin-Huei , Dong Jia-Ling , Chien Ming-Wei , Liu Yu-Wen , Hsu Chao-Yuan , Sytwu Huey-Kang
Published: December 2020

Inflammatory colon diseases, which are a global health concern, include a variety of gastrointestinal tract disorders, such as inflammatory bowel disease and colon cancer. The pathogenesis of these colon disorders involves immune alterations with the pronounced infiltration of innate and adaptive immune cells into the intestines and the augmented expression of mucosal pro-inflammatory cytokines stimulated by commensal microbiota. Epidemiological studies during the past half century have shown that the proportion of obese people in a population is associated with the incidence and pathogenesis of gastrointestinal tract disorders. The advancement of understanding of the immunological basis of colon disease has shown that adipocyte-derived biologically active substances (adipokines) modulate the role of innate and adaptive immune cells in the progress of intestinal inflammation. The biomedical significance in immunological homeostasis of adipokines, including adiponectin, leptin, apelin and resistin, is clear. In this review, we highlight the existing literature on the effect and contribution of adipokines to the regulation of immunological homeostasis in inflammatory colon diseases and discuss their crucial roles in disease etiology and pathogenesis, as well as the implications of these results for new therapies in these disorders.
Anti-Proliferative Effects of Standardized Cornus officinalis on Benign Prostatic Epithelial Cells via the PCNA/E2F1-Dependent Cell Cycle Pathway
Authors: Jin Bo-Ram , Cheon Se-Yun , Kim Hyo-Jung , Kim Myoung-Seok , Lee Kwang-Ho , An Hyo-Jin
Published: December 2020

Cornus officinalis, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells. We standardized C. officinalis 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment.
High-Density Mapping and Candidate Gene Analysis of Pl18 and Pl20 in Sunflower by Whole-Genome Resequencing
Authors: Ma Guojia , Song Qijian , Li Xuehui , Qi Lili
Published: December 2020

Downy mildew (DM) is one of the severe biotic threats to sunflower production worldwide. The inciting pathogen, Plasmopara halstedii, could overwinter in the field for years, creating a persistent threat to sunflower. The dominant genes Pl18 and Pl20 conferring resistance to known DM races have been previously mapped to 1.5 and 1.8 cM intervals on sunflower chromosomes 2 and 8, respectively. Utilizing a whole-genome resequencing strategy combined with reference sequence-based chromosome walking and high-density mapping in the present study, Pl18 was placed in a 0.7 cM interval on chromosome 2. A candidate gene HanXRQChr02g0048181 for Pl18 was identified from the XRQ reference genome and predicted to encode a protein with typical NLR domains for disease resistance. The Pl20 gene was placed in a 0.2 cM interval on chromosome 8. The putative gene with the NLR domain for Pl20, HanXRQChr08g0210051, was identified within the Pl20 interval. SNP markers closely linked to Pl18 and Pl20 were evaluated with 96 diverse sunflower lines, and a total of 13 diagnostic markers for Pl18 and four for Pl20 were identified. These markers will facilitate to transfer these new genes to elite sunflower lines and to pyramid these genes with broad-spectrum DM resistance in sunflower breeding.
Lipopolysaccharide Enhances Tanshinone Biosynthesis via a Ca2+-Dependent Manner in Salvia miltiorrhiza Hairy Roots
Authors: Zhang Bin , Li Xueying , Li Xiuhong , Lu Zhigang , Cai Xiaona , Ou Yang Qing , Ma Pengda , Dong Juane
Published: December 2020

Tanshinones, the major bioactive components in Salvia miltiorrhiza Bunge (Danshen), are synthesized via the mevalonic acid (MVA) pathway or the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway and the downstream biosynthesis pathway. In this study, the bacterial component lipopolysaccharide (LPS) was utilized as a novel elicitor to induce the wild type hairy roots of S. miltiorrhiza. HPLC analysis revealed that LPS treatment resulted in a significant accumulation of cryptotanshinone (CT) and dihydrotanshinone I (DTI). qRT-PCR analysis confirmed that biosynthesis genes such as SmAACT and SmHMGS from the MVA pathway, SmDXS and SmHDR from the MEP pathway, and SmCPS, SmKSL and SmCYP76AH1 from the downstream pathway were markedly upregulated by LPS in a time-dependent manner. Furthermore, transcription factors SmWRKY1 and SmWRKY2, which can activate the expression of SmDXR, SmDXS and SmCPS, were also increased by LPS. Since Ca2+ signaling is essential for the LPS-triggered immune response, Ca2+ channel blocker LaCl3 and CaM antagonist W-7 were used to investigate the role of Ca2+ signaling in tanshinone biosynthesis. HPLC analysis demonstrated that both LaCl3 and W-7 diminished LPS-induced tanshinone accumulation. The downstream biosynthesis genes including SmCPS and SmCYP76AH1 were especially regulated by Ca2+ signaling. To summarize, LPS enhances tanshinone biosynthesis through SmWRKY1- and SmWRKY2-regulated pathways relying on Ca2+ signaling. Ca2+ signal transduction plays a key role in regulating tanshinone biosynthesis in S. miltiorrhiza.
Zika M Oligopeptide ZAMP Confers Cell Death-Promoting Capability to a Soluble Tumor-Associated Antigen through Caspase-3/7 Activation
Authors: Vanwalscappel Bénédicte , Haddad Juliano G. , Almokdad Roba , Decotter Jason , Gadea Gilles , Desprès Philippe
Published: December 2020

Mosquito-borne Zika virus (ZIKV) is an emerging flavivirus of medical concern associated with neurological disorders. ZIKV utilizes apoptosis as a mechanism of cell killing. The structural M protein may play a role in flavivirus-induced apoptosis. The death-promoting capability of M has been restricted to an oligopeptide representing the residues M-32/40. Here, we evaluated the apoptosis inducing ability of the residues M-31/41 of ZIKV. The ZIKV M oligopeptide was associated to a soluble form of GFP (sGFP) and the resulting sGFP-M31/41 construct was assessed in Huh7 cells. Expression of sGFP-M31/41 can trigger apoptosis in Huh7 cells through caspase-3/7 activation. The translocation of sGFP-M31/41 in the endoplasmic reticulum was a prerequisite for apoptosis induction. The residues M-33/35/38 may play a critical role in the death-promoting activity of sGFP-M31/41. The effect of ZIKV M oligopeptide defined as ZAMP (for Zika Apoptosis M Peptide) on expression of a tumor-associated antigen was assayed on megakaryocyte-potentiating factor (MPF). Expression of MPF-ZAMP construct resulted in caspase-associated apoptosis activation in A549 and Huh7 cells. ZIKV has been proposed as an oncolytic virus for cancer therapy. The ability of the Zika M oligopeptide to confer death-promoting capability to MPF opens up attractive perspectives for ZAMP as an innovative anticancer agent.
Melanoma Biomarkers and Their Potential Application for In Vivo Diagnostic Imaging Modalities
Authors: Hessler Monica , Jalilian Elmira , Xu Qiuyun , Reddy Shriya , Horton Luke , Elkin Kenneth , Manwar Rayyan , Tsoukas Maria , Mehregan Darius , Avanaki Kamran
Published: December 2020

Melanoma is the deadliest form of skin cancer and remains a diagnostic challenge in the dermatology clinic. Several non-invasive imaging techniques have been developed to identify melanoma. The signal source in each of these modalities is based on the alteration of physical characteristics of the tissue from healthy/benign to melanoma. However, as these characteristics are not always sufficiently specific, the current imaging techniques are not adequate for use in the clinical setting. A more robust way of melanoma diagnosis is to “stain” or selectively target the suspect tissue with a melanoma biomarker attached to a contrast enhancer of one imaging modality. Here, we categorize and review known melanoma diagnostic biomarkers with the goal of guiding skin imaging experts to design an appropriate diagnostic tool for differentiating between melanoma and benign lesions with a high specificity and sensitivity.
The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines
Authors: Vieira Filipa Quintela , Marques-Magalhães Ângela , Miranda-Gonçalves Vera , Ferraz Ricardo , Vieira Mónica , Prudêncio Cristina , Jerónimo Carmen , Silva Regina Augusta
Published: December 2020

Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side effects. Therefore, there is an urgent need for more effective antineoplastic agents. Herein, BrCa, PCa, and benign cell lines were treated with two ionic liquids and two quinoxalines and functional experiments were performed—namely cell viability, apoptosis, cytotoxicity, and colony formation assays. At the molecular level, an array of gene expressions encompassing several molecular pathways were used to explore the impact of treatment on gene expression. Although both quinoxalines and the ionic liquid [C2OHMIM][Amp] did not show any effect on the BrCa and PCa cell lines, [C16Pyr][Amp] significantly decreased cell viability and colony formation ability, while it increased the apoptosis levels of all cell lines. Importantly, [C16Pyr][Amp] was found to be more selective for cancer cells and less toxic than cisplatin. At the molecular level, this ionic liquid was also associated with reduced expression levels of CPT2, LDHA, MCM2, and SKP2, in both BrCa and PCa cell lines. Hence, [C16Pyr][Amp] was shown to be a promising anticancer therapeutic agent for BrCa and PCa cell lines.
Philippine Performance Evaluation and Assessment Scheme (PPEAS): Experiences in Newborn Screening System Quality Improvement
Authors: Padilla Carmencita D. , Therrell Bradford L. , Panol Karen Asuncion R. , Suarez Riza Concordia N. , Reyes Ma. Elouisa L. , Jomento Charity M. , Maceda Ebner Bon G. , Lising Jovy Ann C. , Beltran Frederick David E. , Orbillo Lita L.
Published: December 2020

Newborn Bloodspot Screening (NBS) has existed for over 60 years, having been initiated by Guthrie in the U.S. In the Philippines, NBS was introduced in 1996 and later was supported by legislation. The NBS program now includes 29 conditions, covering 91.6% of the newborn population in 2019. Program growth and expansion necessitated development of a formal performance evaluation and assessment scheme (PEAS) for monitoring performance and for continuously improving quality. This study’s objective was to present the development, implementation, and results to date of the Philippine Performance PEAS (PPEAS). Using the comprehensive listing of laboratory and non-laboratory elements in the model PEAS system in the U.S., PPEAS tools were developed for critical Philippine NBS system components: regional Department of Health (national health agency, Philippines) (DOH) offices (CHDs), NBS laboratories (NSCs), NBS specimen submitters (NSFs), and long-term case management centers (NBSCCs). Data generated from the various PPEAS have been periodically reviewed and analyzed for NBS system impact. PPEAS were developed to facilitate quality improvement at various levels of the Philippine NBS system. PPEAS identified successes, gaps, and challenges to be addressed by NSCs, NSFs, CHDs, and NBSCCs with the assistance of the Newborn Screening Reference Center and the Department of Health.
Tissue Engineering and Three-Dimensional Printing in Periodontal Regeneration: A Literature Review
Authors: Raveau Simon , Jordana Fabienne
Published: December 2020

The three-dimensional printing of scaffolds is an interesting alternative to the traditional techniques of periodontal regeneration. This technique uses computer assisted design and manufacturing after CT scan. After 3D modelling, individualized scaffolds are printed by extrusion, selective laser sintering, stereolithography, or powder bed inkjet printing. These scaffolds can be made of one or several materials such as natural polymers, synthetic polymers, or bioceramics. They can be monophasic or multiphasic and tend to recreate the architectural structure of the periodontal tissue. In order to enhance the bioactivity and have a higher regeneration, the scaffolds can be embedded with stem cells and/or growth factors. This new technique could enhance a complete periodontal regeneration. This review summarizes the application of 3D printed scaffolds in periodontal regeneration. The process, the materials and designs, the key advantages and prospects of 3D bioprinting are highlighted, providing new ideas for tissue regeneration.
Asthma-Like Features and Anti-Asthmatic Drug Prescription in Children with Non-CF Bronchiectasis
Authors: Douros Konstantinos , Sardeli Olympia , Prountzos Spyridon , Galani Angeliki , Moriki Dafni , Alexopoulou Efthymia , Priftis Kostas N.
Published: December 2020

Bronchiectasis and asthma may share some characteristics and some patients may have both conditions. The present study aimed to examine the rationale of prophylactic inhaled corticosteroids (ICS) prescription in children with bronchiectasis. Data of children with radiologically established bronchiectasis were retrospectively reviewed. Episodes of dyspnea and wheezing, spirometric indices, total serum IgE, blood eosinophil counts, sensitization to aeroallergens, and air-trapping on expiratory CT scans, were recorded. The study included 65 children 1.5–16 years old, with non-CF bronchiectasis. Episodes of dyspnea or wheezing were reported by 22 (33.8%) and 23 (35.4%), respectively. Skin prick tests to aeroallergens (SPTs) were positive in 15 (23.0%) patients. Mosaic pattern on CT scans was observed in 37 (56.9%) patients. Dyspnea, presence of mosaic pattern, positive reversibility test, and positive SPTs were significantly correlated with the prescription of ICS. The prescription of ICS in children with bronchiectasis is more likely when there are certain asthma-like characteristics. The difficulty to set the diagnosis of real asthma in cases of bronchiectasis may justify the decision of clinicians to start an empirical trial with ICS in certain cases.
A Systematic Review on the Association of Acquired Human Cytomegalovirus Infection with Hearing Loss
Authors: Martinez-Gomez Estrella , Perez-Carpena Patricia , Flook Marisa , Lopez-Escamez José
Published: December 2020

Congenital cytomegalovirus (CMV) infection induces a clinical syndrome usually associated with hearing loss. However, the effect of acquired CVM infection in adults and children has not been clearly defined. The objective of this review is to critically appraise scientific evidence regarding the association of acquired CMV infection with postnatal hearing loss or tinnitus. A systematic review of records reporting sensorineural hearing loss (SNHL) or tinnitus and acquired CMV infection including articles published in English was performed. Search strategy was limited to human studies with acquired CMV infection. After screening and quality assessment, nine studies involving 1528 individuals fulfilled the inclusion criteria. A total of 14% of patients with SNHL showed evidence of previous exposure to CMV, while in individuals without SNHL (controls) the percentage rose up to 19.3%. SNHL was reported as unilateral or bilateral in 15.3%, and not specified in 84.7% of cases. The degree of SNHL ranged from mild to profound for both children and adults. None of the records reported tinnitus. The prevalence of children or adults with acquired SNHL with a confirmed acquired CMV infection by Polymerase Chain Reaction (PCR) or IgM anti-CMV antibodies is low. Phenotyping of patients with acquired CMV infection was limited to hearing loss by pure tone audiometry and no additional audiological testing was performed in most of the studies. Additional symptoms deserve more attention, including episodic vertigo or tinnitus, since some patients with the clinical spectrum of Meniere Disease could result from a CMV latent infection.
Deep Convolutional Neural Network-Assisted Feature Extraction for Diagnostic Discrimination and Feature Visualization in Pancreatic Ductal Adenocarcinoma (PDAC) versus Autoimmune Pancreatitis (AIP)
Authors: Ziegelmayer Sebastian , Kaissis Georgios , Harder Felix , Jungmann Friederike , Müller Tamara , Makowski Marcus , Braren Rickmer
Published: December 2020

The differentiation of autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC) poses a relevant diagnostic challenge and can lead to misdiagnosis and consequently poor patient outcome. Recent studies have shown that radiomics-based models can achieve high sensitivity and specificity in predicting both entities. However, radiomic features can only capture low level representations of the input image. In contrast, convolutional neural networks (CNNs) can learn and extract more complex representations which have been used for image classification to great success. In our retrospective observational study, we performed a deep learning-based feature extraction using CT-scans of both entities and compared the predictive value against traditional radiomic features. In total, 86 patients, 44 with AIP and 42 with PDACs, were analyzed. Whole pancreas segmentation was automatically performed on CT-scans during the portal venous phase. The segmentation masks were manually checked and corrected if necessary. In total, 1411 radiomic features were extracted using PyRadiomics and 256 features (deep features) were extracted using an intermediate layer of a convolutional neural network (CNN). After feature selection and normalization, an extremely randomized trees algorithm was trained and tested using a two-fold shuffle-split cross-validation with a test sample of 20% (n = 18) to discriminate between AIP or PDAC. Feature maps were plotted and visual difference was noted. The machine learning (ML) model achieved a sensitivity, specificity, and ROC-AUC of 0.89 ± 0.11, 0.83 ± 0.06, and 0.90 ± 0.02 for the deep features and 0.72 ± 0.11, 0.78 ± 0.06, and 0.80 ± 0.01 for the radiomic features. Visualization of feature maps indicated different activation patterns for AIP and PDAC. We successfully trained a machine learning model using deep feature extraction from CT-images to differentiate between AIP and PDAC. In comparison to traditional radiomic features, deep features achieved a higher sensitivity, specificity, and ROC-AUC. Visualization of deep features could further improve the diagnostic accuracy of non-invasive differentiation of AIP and PDAC.
Resveratrol-Based Multivitamin Supplement Increases Sperm Concentration and Motility in Idiopathic Male Infertility: A Pilot Clinical Study
Authors: Illiano Ester , Trama Francesco , Zucchi Alessandro , Iannitti Rossana Giulietta , Fioretti Bernard , Costantini Elisabetta
Published: December 2020

Background. It is known that a multitude of factors may lead to male factor infertility, but still, in the majority of cases, the cause remains largely idiopathic, reflecting poor understanding of the basic process of spermatogenesis and the mechanisms involved. Resveratrol is a polyphenol compound that displays several cellular aspects mainly associated with SIRT1-pathway activation and promotion of mitochondrial enhancer activities. In several animal models, resveratrol has shown positive effects on mitochondria and membrane potential. This could explain effects on sperm concentration and motility. The aim of this study is to evaluate the effects on the semen parameters of GENANTE®, a multivitamin supplement containing 150 mg of resveratrol/day, in patients with idiopathic infertility. Methods. This was a prospective single center clinical study. Twenty patients took a multivitamin supplement based on 150 mg of resveratrol (GENANTE®), in the form of an oral tablet every 12 h, and were followed up at 1, 3, and 6 months after treatment. Pre- and post-treatment evaluation included history, clinical examination, semen analysis, hormonal determinations, and scrotal and prostatic ultrasound. Results. Our preliminary pilot study demonstrated that the multivitamin supplement based on resveratrol improves sperm motility (48.3% ± 13.8 vs. 59.0% ± 12.8, p = 0.0001) and concentration (22.6 × 106/mL ± 9.5 vs. 25.7 × 106/mL ± 8.1, p = 0.0001) after 3 and 6 months of treatment in men with idiopathic infertility. Conclusion. Our data suggest that targeting the metabolic and energetic pathways involved in spermatogenesis and mitochondrial activity could lead to potential effects and counteract subfertility/infertility in men through a mitochondria dynamics mechanism. Trial registration number: ClinicalTrials.gov registration identifier: NCT03864198, registered on 1 January 2019.
Physical Activity and Mental Health of Patients with Pulmonary Hypertension during the COVID-19 Pandemic
Authors: Dobler Carolin Leoni , Krüger Britta , Strahler Jana , Weyh Christopher , Gebhardt Kristina , Tello Khodr , Ghofrani Hossein Ardeschir , Sommer Natascha , Gall Henning , Richter Manuel Jonas , Krüger Karsten
Published: December 2020

The aim of the study was to analyze the effect of personal restrictions on physical activity, mental health, stress experience, resilience, and sleep quality in patients with pulmonary hypertension (PH) during the “lockdown” period of the COVID-19 pandemic. In total, 112 PH patients and 52 age-matched healthy control subjects completed a questionnaire on the topics of physical activity, mental health, resilience, and sleep quality. PH patients had significantly lower physical activity, mental health, and sleep quality compared to age-matched healthy controls. Physical activity positively correlated with mental health and sleep quality in the PH group. Mental wellbeing and life satisfaction could be predicted by total physical activity, sleep, stress level, and resilience. PH patients appeared as an especially vulnerable group, demanding interventions to promote an active lifestyle and protect mental health in these patients. This could be helpful in counseling on how to carry out physical activity while maintaining infection control.
Simplified Diagnosis of Critical Illness Polyneuropathy in Patients with Prolonged Mechanical Ventilation: A Prospective Observational Cohort Study
Authors: Jung Chul , Choi Nak-Jun , Kim Won Jun , Chun Yoon Mok , Lee Hak-Jae , Kim Tae Hyun , Pak Sae Rom , Lee Jung Hoon , Hong Suk-Kyung , Kim Won
Published: December 2020

Background: Although early identification of critical illness polyneuropathy (CIP) is necessary, the established diagnostic criteria have several limitations in the intensive care unit (ICU) setting. The purpose of this study was to define simplified diagnostic criteria of CIP that best predict clinical outcomes. Methods: This prospective, single-center study included 41 ICU patients with prolonged mechanical ventilation (≥21 days). We applied three different sets of diagnostic criteria (combining the results of the Medical Research Council (MRC) sum score and nerve conduction studies (NCS)) for CIP in order to identify the criteria with the best predictive power for clinical outcomes. Results: The simplified diagnosis of CIP meeting the criteria, i.e., that the MRC sum score < 48 and amplitudes of the tibial and sural nerve < 80% of the lower limit of normal, showed the strongest association with 0 ventilator-free days at day 60 (odds ratio, 6.222; p = 0.029). Conclusions: The diagnostic criteria combining the MRC sum score and the tibial and the sural NCS were identified as the simplified criteria of CIP that best predicted the clinical outcomes. The implementation of these simplified criteria may allow for early identification of CIP in the ICU, thereby contributing to prompt interventions for patients with a poor prognosis.
Helicobacter pylori Infection and the Patterns of Gastric Mucin Expression in Children
Authors: Domșa Ana-Maria Teodora , Lupușoru Raluca , Gheban Dan , Buruiană-Simic Alexandra , Gheban Bogdan Alexandru , Lazăr Camelia , Borzan Cristina Maria
Published: December 2020

Background: The updated model for the mechanism of gastric carcinogenesis demonstrates that Helicobacter pylori (H. pylori) is a risk factor in every step of the process. The expression of certain gastric mucins is altered by H. pylori infection in adult patients. The aim of our research was to assess the impact of H. pylori infection on the expression of secretory mucins in the pediatric antral mucosa. Methods: Slides were stained with monoclonal antibodies for MUC5AC, MUC6 and MUC2, digitalized and scored using both a semiquantitative and a quantitative approach. Results: The expression of MUC5AC was significantly lower in infected children. Also, MUC2 expression was more pronounced in infected children. MUC6 expression did not differentiate between infected and noninfected children. Additionally, the presence of chronic inflammation significantly altered the expression of MUC6 and MUC2. The expression of MUC6 was significantly higher in patients with gastric atrophy. Conclusion: The minor differences in mucin expression at distinct ages might stem from different H. pylori exposure periods. Further research is needed to determine the particular patterns of expression according to age and to evaluate the effects of the interaction between H. pylori and mucins in the progression of the gastric carcinogenesis cascade.
Handling of Doubtful WBC Scintigraphies in Patients with Suspected Prosthetic Joint Infections
Authors: Lauri Chiara , Lauretti Giancarlo , Galli Filippo , Campagna Giuseppe , Tetti Simone , Riolo Donatella , Signore Alberto
Published: December 2020

Despite the application of EANM recommendations for radiolabelled white-blood-cells (WBC) scintigraphy, some cases still remain doubtful based only on visual analysis. The aim of this study was to investigate the role of semi-quantitative analysis and bone marrow scan (BMS) in solving doubtful cases. We retrospectively evaluated all [99mTc]HMPAO-WBC scintigraphies performed, in the last 7 years, for a suspected monolateral prosthetic joint infection (PJI). In doubtful cases, we used five different thresholds of increase of target-to-background (T/B) ratio, between delayed and late images, as criteria of positivity (5%, 10%, 15%, 20% and 30%). BMS were also analysed and sensitivity, specificity and accuracy of different methods were calculated according to final diagnosis. The sensitivity, specificity and accuracy were, respectively, 77.8%, 43.8% and 53.0% for the cut-off at 5%; 72.2%, 66.7% and 68.2% for the cut-off at 10%; 66.7%, 75.0% and 72.7% for the cut-off at 15%; 66.7%, 85.4% and 80.3% for the cut-off at 20%; 33.3%, 93.8% and 77.3% for the cut-off at 30%. BMS provided a significantly higher diagnostic performance than 5%, 10% and 15% thresholds. Conversely, we did not observe any statistically significant difference between BMS and the cut-off of more than 20%. Therefore, doubtful cases should be analysed semi-quantitatively. An increase in T/B ratio of more than 20% between delayed and late images, should be considered as a criterion of positivity, thus avoiding BMS.
Cellular Proliferation, Dermal Repair, and Microbiological Effectiveness of Ultrasound-Assisted Wound Debridement (UAW) Versus Standard Wound Treatment in Complicated Diabetic Foot Ulcers (DFU): An Open-Label Randomized Controlled Trial
Authors: Lázaro-Martínez José Luis , Álvaro-Afonso Francisco Javier , Sevillano-Fernández David , García-Álvarez Yolanda , Sanz-Corbalan Irene , García-Morales Esther
Published: December 2020

We aimed to evaluate the effects of ultrasound-assisted wound (UAW) debridement on cellular proliferation and dermal repair in complicated diabetic foot ulcers as compared to diabetic foot ulcers receiving surgical/sharp wound debridement. A randomized controlled trial was performed involving 51 outpatients with complicated diabetic foot ulcers that either received surgical debridement (n = 24) or UAW debridement (n = 27) every week during a six-week treatment period. Compared to patients receiving surgical debridement, patients treated with UAW debridement exhibited significantly improved cellular proliferation, as determined by CD31 staining, Masson’s trichrome staining, and actin staining. Bacterial loads were significantly reduced in the UAW debridement group compared to the surgical group (UAW group 4.27 ± 0.37 day 0 to 2.11 ± 0.8 versus surgical group 4.66 ± 1.21 day 0 to 4.39 ± 1.24 day 42; p = 0.01). Time to healing was also significantly lower (p = 0.04) in the UAW group (9.7 ± 3.8 weeks) compared to the surgical group (14.8 ± 12.3 weeks), but both groups had similar rates of patients that were healed after six months of follow-up (23 patients (85.1%) in the UAW group vs. 20 patients (83.3%) in the surgical group; p = 0.856). We propose that UAW debridement could be an effective alternative when surgical debridement is not available or is contraindicated for use on patients with complicated diabetic foot ulcers.
Characterization and Numerical Modelling of Through-Thickness Metallic-Pin-Reinforced Fibre/Thermoplastic Composites under Bending Loading
Authors: Böhm Holger , Zhang Hailun , Gröger Benjamin , Hornig Andreas , Gude Maik
Published: December 2020

Through-Thickness Reinforcement (TTR) technologies are well suited to improving the mechanical properties in the out-of-plane direction of fibre-reinforced composites. However, besides the enhancement of delamination resistance and thus the prevention of overall catastrophic failure, the presence of additional reinforcement elements in the composite structure affects also the mechanical properties in in-plane direction. In this work, the flexural behaviour of a glass-polypropylene (GF/PP) hybrid yarn-based composite with TTR in form of metallic pins has been investigated experimentally and numerically. The insertion of the metallic pins is realized via thermoactivated pinning technology (TAP). In four-point-bending tests, it is shown that the flexural stiffness and strength decreases with an increase of the overall pin density. Hereby, it is observed that the pins act as crack initiators. For numerical modelling on specimen level, a continuum damage mechanic (CDM) model is used to predict the nonlinear deformation response of the composite, as well as fibre fracture and matrix cracking. A debonding and slipping phenomena of the pin in the composite is modelled by a cohesive zone modelling approach for the interface between pin and composite.