bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemometric tools to investigate complex synchrotron radiation FTIR micro-spectra: focus on historical bowed musical instruments
Authors: Fiocco Giacomo , Grassi Silvia , Invernizzi Claudia , Rovetta Tommaso , Albano Michela , Davit Patrizia , Gulmini Monica , Stani Chiaramaria , Vaccari Lisa , Licchelli Maurizio , Malagodi Marco
Published: April 2021

The investigation of the coating systems used on historical bowed string musical instruments is generally highly complex due to the coatings’ reduced thickness and multi-layered structure. Furthermore, sampling is rarely feasible, and non-invasive approaches do not always allow researchers to undertake a thorough characterisation. Thus, in the rare cases of availability, the opportunity must be taken to investigate the best micro-samples in detail using a suite of analytical spectroscopic techniques that allow for obtaining various informative spectra. Their subsequent interpretation should lead to the characterisation of the finishing layers, the preparation of which involves a careful selection of organic and inorganic compounds.
In the present work, synchrotron radiation and micro-Fourier-transform infrared spectroscopy were combined in terms of reflection geometry and chemometrics to investigate six cross-sectioned micro-samples detached from four bowed string instruments produced by Antonio Stradivari, Francesco Ruggeri, and Lorenzo Storioni. Various chemometric tools enabled us to perform a preliminary exploration of the entire collected infrared dataset, while a classification model based on partial least squares–discriminant analysis was used to discriminate the materials through the characteristic signals. High model specificity (> 0.9) was achieved in the prediction, providing the groundwork for the application of a fast and rigorous methodological approach.
The use of image and laser scanner survey archives for cultural heritage 3D modelling and change analysis
Authors: Martinez Espejo Zaragoza Isabel , Caroti Gabriella , Piemonte Andrea
Published: April 2021

Cultural heritage studies often require the analysis of buildings that have undergone several changes and alterations during their lifetime. This often implies the loss of architectural elements or the construction of new elements, which both change the characteristics of the former buildings. The recovery of lost elements or structures through virtual reconstruction is of paramount importance in both scientific and cultural applications. Novel procedures in surveying and photogrammetric processing including historical photogrammetry and historical terrestrial laser scanning offer powerful tools that enable the extraction of geometric information from historical documentation such as archival images. This paper presents the integration of a metric 3D model with information present in archival surveys of lost architectural volumes. The methodology implies the availability of historical plans representing the survey object at scales consistent with UAV surveys and featuring shared elements. The methodology used to frame these plans in the reference system of the UAV survey for an open source GIS environment is also described as well as the accuracy checks. Finally, the procedure followed for the virtual reconstruction of the Fortezza in a BIM environment, which produced a model derived from the integration of historic and current data, is described.
Metrological characterisation of a textile temperature sensor in archaeological usage
Authors: Zanobini Andrea
Published: April 2021

This paper presents the study of a new generation textile temperature sensor in two different heated ovens. The first chamber was used to evaluate temperature and the second was used to evaluate both temperature and humidity. Data acquisition systems based on LabVIEW and Agilent were developed using thermocouples and Pt100 sensors. The results show many metrological characteristics that prove that the sensor is a resistance temperature detector.
The role of local governments in solving the problems of providing primary health care personnel
Authors:   Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, Son I. M. , Menshikova L. I. ,   Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, Flagler N. A. ,   Federal state budgetary educational institution of higher professional education “Northern state medical University” of the Ministry of health of the Russian Federation,, Senenko A. Sh. ,   Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, Rugles L. V. ,   Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation
Published: April 2021

The problem of staffing in healthcare remains relevant for a long time. The article considers the possibilities of participation of local self-government bodies in attracting and securing medical workers, primarily primary care. The analysis of normative legal acts of the Federal level is presented. Amendments to Federal laws № 131-FZ and № 323-FZ related to specifying the powers of local self-government bodies in terms of health personnel are proposed. The necessity of a comprehensive assessment of the implemented measures of social support for medical workers to identify the most effective measures and select the best practices is justified.
Financing of healthcare in 2021 from the federal budget: priorities within the national project “Healthcare” in the context of the fight against coronavirus infection Covid‑19
Authors:   Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, Kadyrov F. N. , Obukhova O. V. ,   Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, Bazarova I. N. ,   Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation, Endovitskaya Yu. V. ,   Federal Research Institute for Health Organization and Informatics of Ministry of Health of the Russian Federation
Published: April 2021

An analysis of the upcoming financing of healthcare from the Federal budget shows that in 2021–2022, despite the difficult financial situation, the volume of financial support for the industry will continue to grow. These are all the more important parameters because the upcoming budget in the period under review assumed a slight reduction in funding compared to the approved figures of the Federal budget for 2020. This should help to ensure the stable functioning of health care.
Mergulhando no desconhecido: observando controvérsias e estratégias na Fundação Iluminação Silenciosa
Authors: Honorato Bruno Eduardo Freitas , Fernandes de Moura Rodrigo , Rodrigues da Silva Everton
Published: April 2021

Baseado em fatos reais, complementados por dados fictícios, este caso de ensino narra a vivência de Jonas, aluno de Administração Pública da Universidade Federal de Alfenas – Campus Varginha –, na Fundação Iluminação Silenciosa (FIS), uma organização de natureza espiritual, filantrópica e beneficente, que se mantém por meio de doações espontâneas e presta, gratuitamente, vários serviços de amparo e auxílio à humanidade e aos diversos reinos animais e vegetais. Após seis meses de diversas visitas e imersões no local, Jonas conseguiu observar que existem contradições e conflitos na estrutura de gestão da comunidade, materializados na comunicação entre as coordenações e na atribuição de atividades dos indivíduos. Diante do diagnóstico realizado e da análise da situação, Jonas encontra-se confuso e busca soluções criativas para resolver tais dilemas.
3D Printing of True Pore-Scale Berea Sandstone and Digital Rock Verification
Authors: Li Aobo , Zhang Shuo , Xu Chicheng , Zhao Xiaoguang , Zhang Xin
Published: April 2021

In this study, we used two-photon polymerization 3D printing technology to successfully print the first true pore-scale rock proxy of Berea sandstone with a submicrometer resolution. Scanning electron microscope (SEM) and computed tomography (CT) images of the 3D-printed sample were compared with the digital file used for printing to verify the rock’s internal structures. Petrophysical properties were estimated with a digital rock physics (DRP) model based on the 3D-printed sample's initial pore network. The results show that our 3D-printing workflow was able to reproduce true-scale 3D porous media such as Berea sandstone with a submicrometer resolution. With a variety of materials and geometric scaling options, 3D printing of nearly identical rock proxies provides a method to conduct repeatable laboratory experiments without destroying natural rock samples. Rock proxy experiments can potentially validate numerical simulations and complement existing laboratory measurements.
Comprehensive plasma lipidomic profiles reveal a lipid-based signature panel as a diagnostic and predictive biomarker for cerebral aneurysms
Authors: Li Yong-Dong , Zhu Yue-Qi , Zhao Bing , He Yu , Gu Bin-Xian , Lu Hao-Tao , Gu Yi , Wei Li-Ming , Pan Yao-Hua , Chen Zheng-Nong , Sun Yong-Ning , Wang Wu
Published: April 2021

We investigated lipidomic features from healthy controls (HCs), patients with unruptured cerebral aneurysms (UCAs) and ruptured CAs (RCAs) to analyze their lipidomic profiles and identify a lipid signature associated with CAs. Patients (n = 540) were enrolled from two centers. We identified significantly altered plasma lipids in 2 cohort with the total lipid intensity decreasing from HC to UCA to RCA. Triglycerides comprised the distinct profile of lipids in CAs. A four-lipid signatures showed good calibration and diagnostic prediction for CA vs. HC and UCA vs. RCA, but independent discriminate CA from HC, UCA from RCA, and RCA (RI and RII) or UCA (UI and UII) subtypes, in training and validation cohorts. Comprehensive lipidomic profiles identified decreased lipids as a prominent feature of CA development, and a four-lipid signature could not only better diagnose and predict UCAs/RCAs from HCs, but also predicted patients subtypes with severe RCA or high-risk UCA.
Optimizing proliferation and assessment of valak morpho-phenological traits; an endangered nutritious Allium endemic to Iran
Authors: Jafari Sajad , Hassandokht Mohammadreza , Taheri Madi
Published: April 2021

Allium elburzense W. (subg. Melanocrommyum ) is an endangered and endemic species to Iran, which is called “valak” and known as a valuable and pricy vegetable with high nutritional and medicinal properties. This study was carried out in order to domestication, removing barriers of sexual reproduction, micropropagation and investigation of phenological stages and growth cycle of the species. The results indicated that fresh seeds had better germination than one year old seeds and appropriate germination temperature in A. elburzense W. seed was 12 °C. According to ANOVA results, the triple interaction of scarification (Sc), stratification period (StP) and GA 3 had a significant effect on seedling length, seedling fresh and dry weight, bulb height and diameter (p<0.01). Comparison of means showed that the treatments in which the StP (45 days) and scarification was applied had better effects on seed germination (66.5% germination) than other treatments. Murashige and Skoog with 300 mg L -1 KH2PO4 (MSP) medium caused a significant increase in the diameter of the basal plate compared to MS medium. Efficient system for in vitro propagation and conservation of valak genetic resources were the use of MSP culture medium supplemented with 0.6 mg l -1 NAA, 4 mg l -1 BA and 120 g l -1 of sucrose, which resulted in a direct propagation coefficient of 26.83 seedlings and bulblets at 18 weeks. As regards its life cycle, the juvenile phase in a low proportion of individuals (13.33%) lasted 2 years from seeding, while 87.66% of individuals were capable of producing inflorescence in the third year. Results showed that this plant is a metamorphosis and cross pollinator species. Results of present study can be used in domestication, conservation of genetic resources and proper exploitation of valak species.
Factors Influencing Resilience and Burnout Among Resident Physicians - A National Survey
Authors: Nituica Cristina , Bota Oana Alina , Blebea John , Cheng Chin-I , Slotman Gus J.
Published: April 2021

Background

Residency training exposes young physicians to a challenging and high-stress environment, making them vulnerable to burnout. Burnout syndrome not only compromises the health and wellness of resident physicians but has also been linked to prescription errors, reduction in the quality of medical care, and decreased professionalism. This study explored burnout and factors influencing resilience among U.S. resident physicians.
Methods

A cross-sectional study was conducted through an online survey, which was distributed to all accredited residency programs by Accreditation Council of Graduate Medical Education (ACGME). The survey included the Connor-Davidson Resilience Scale (CD-RISC 25), Abbreviated Maslach Burnout Inventory, and socio-demographic characteristics questions. The association between burnout, resilience, and socio-demographic characteristics were examined.
Results

The 682 respondents had a mean CD-RISC score of 72.41(12.1), which was equivalent to the bottom 25th percentile of the general population. Males and upper-level trainees were more resilient than females and junior residents. No significant differences in resilience were found associated with age, race, marital status, or training program type. Resilience positively correlated with personal achievement, family, and institutional support (p < 0.001) and negatively associated with emotional exhaustion and depersonalization (p < 0.001).
Conclusions

High resilience, family, and institutional support were associated with a lower risk of burnout, supporting the need for developing a resilience training program to promote a lifetime of mental wellness for future physicians.
Evaluation of Microbial Culture and Antibiogram in Patients With Head and Neck Infections Who Referred to Shahid Rajaee Hospital of Shiraz Between 1392 to 1398
Authors: Ghorbani Farhad , Faryabi Zahra
Published: April 2021

Background: Head and neck infections happen due to different reasons and different microorganisms are responsible for them. These infections can be treated with various antibiotics. The purpose of this study was to specify most frequent etiology of infection, dominant bacterial species and most effective antibiotic in patients with head and neck infections who referred to Shahid Rajaee hospital of Shiraz.Methods: This study has been carried out in cross-sectional pattern from 2019-May to 2020-Oct in Oral & Maxillofacial Ward of Rajaee Hospital of Shiraz. Consent to access data and archive files was taken from the ethics committee of Shiraz University of Medical Sciences. Age, sex, etiology of infection, bacterial species, sensitivity or resistance reaction to Antibiotics and most frequently used antibiotic in patients who referred to this ward between 1392-Apr to 1398-Mar were collected on the basis of laboratory’s results. Data were analyzed with Chi-Square test.Results: statistical analysis showed that, 56 of patients were men (54.9%) and 46 were women (45.1%). The average of age was 38+/−17 and the minimum age was 6 and maximum age was 73. The most frequent etiology was odontogenic infections. Moreover, there was no statistically significant relationship between etiology and bacterial species (p-value=0.38) and Cefazolin had the most frequency in odontogenic infection group. Top three frequent bacterial species were respectively: Staphylococcus DNase & Coagulase Negative, Enterococci Sp., Streptococci Viridians and Klebsiella Sp. . There was no statistically significant relationship between bacterial species and sex (p-value=0.55). 94 (48.7 %) of bacterial species had Sensitive reaction to antibiotics. 21 (10.9 %) of them had Intermediate reactionand 78 (40%) of them had Resistant reaction and Cefazolin had the most frequency in sensitive group.Conclusion: The dominant bacterial species in head and neck infections are Staphylococcus DNase & coagulase negative. And, Cefazolin had the most sensitive reaction in odontogenic infections.
Collaborative care in secondary prevention of cardiovascular disease in India: Findings from a multi-stakeholder, qualitative analysis
Authors: Singh Kavita , Huffman Mark D. , Tandon Nikhil , Devarajan Raji , Prabhakaran Dorairaj , Mendenhall Emily
Published: April 2021

Background. Cardiovascular disease (CVD) is pervasive in India, and little is known about the perception of patients and providers about collaborative care in secondary prevention of CVD. To fill this gap, we performed a needs assessment and investigated the barriers and facilitators of the collaborative quality improvement (C-QIP) strategy for secondary prevention of CVD in India.Methods. Between September 2019 – February 2020, we conducted semi-structured in-depth interviews with providers, health administrators, patients and caregivers to understand the challenges and facilitators of the C-QIP strategy consisting of electronic health records-decision support system (EHR-DSS), non-physician health worker and text messages for healthy lifestyle. Also, data were analyzed from the lens of consolidated framework for implementation research (CFIR) to guide effective implementation of the C-QIP strategy. We used an iterative approach for qualitative data analysis based on the framework method. Results. We interviewed 38 physicians, 14 non-physician health workers (nurses, community health workers, pharmacists), 4 health administrators, 16 patients and their caregivers. Challenges perceived from providers’ and health administrators’ perspectives to implement quality in CVD care were related to CFIR actors and inner and outer settings: high patient volume, too few specialists, time-constraints, physician burnout, lack of robust communication system or referral linkage, paucity of electronic health records, lack of patient counsellors, polypharmacy and lack of sustainable financing schemes for outpatient services. In addition, low health literacy, high cost of treatment, misinformation bias, and difficulty in maintaining lifestyle changes were key barriers from patients’ and caregivers’ perspectives. Potential benefits of the C-QIP strategy emerged, such as standardized treatment protocol to minimize variation in care, reduced medication errors, improved physician-patient relationships, and enhanced self-care management. However, concerns were raised about feasibility, adoption, and implementation of EHR-DSS across heterogenous healthcare settings, including related to interoperability, patient confidentiality and data security, appropriateness across diverse patient groups, and care delivery costs.Conclusions. Our findings reveal context-specific, patient-, provider- and health system factors that will influence C-QIP strategy implementation in India. Strategies to optimize chronic care of CVD need to be low-cost, culturally acceptable, targeted, and integrated into existing systems and care pathways to be successful.
Effect of LINC00320 Regulating the Expression of PLEKHA1 through the Transcription Factor MYC in Glioma Cell Proliferation, Migration, Invasion and Apoptosis In vivo and In vitro
Authors: Ji Jianyong , Xue Pengfei , Zheng Juan , Li Rongrong , Fu Jinyue , Wang Zhaohao , Li Xin
Published: April 2021

Aim: This study was carried out to explore the mechanism and function of LINC00320 in the development of glioma by regulating PLEKHA1 expression through transcription factor MYC.Methods: By searching LINCDISEASE database and through difference analysis of glioma chip, glioma related lncRNAs were screened, and lncRNA-transcription factor-mRNA triplet was predicted through lncMAP database. The expressions of LINC00320 and PLEKHA1 were detected in glioma and normal controls, followed by the detection of the proliferation, invasion, migration, and apoptosis of glioma cells by using CCK-8 method, Transwell assay, and flow cytometry, respectively. In addition, the expression patterns of MMP9 and cleaved-Caspase 3 were detected with Western Blot. Furthermore, the possible mechanism of LINC00320 was predicted in gliomas by LncMAP. RIP assay was performed to verify the interaction between LINC00320 and MYC, and ChIP assay was applied to validate the binding of MYC and PLEKHA1 promoter. The existence of binding site between MYC and PLEKHA1 promoter were determined by dual luciferase reporter gene assay. Lastly, in vivo test was conducted by using nude mice as the objects of study for verification of the results obtained by in vitro tests.Results: LINC00320 was found to be significantly down-expressed in glioma, and patients with low expression levels of LINC00320 exhibited an even worse prognostic outcome. Over-expression of LINC00320 in glioma cells brought about a significant reduction in cell proliferation, migration, invasion, and promoted apoptosis. There was a significant decrease in the protein expression of MMP9 but remarkable increase in that of cleaved-Caspase 3 after LINC00320 over-expression. LncRNA-transcription factor-mRNA triplet prediction showed that LINC00320 regulated the expression of PLEKHA1 through MYC. RIP assay demonstrated that MYC could significantly enrich LINC00320, Chip assay showed that MYC bound with the PLEKHA1 promoter, and dual luciferase reporter gene assay further confirmed the presence of binding site between MYC and PLEKHA1 promoter. Cell function experiment verified that PLEKHA1 could reverse the effect of LINC00320 over-expression.Conclusion: Over-expression of LINC00320 can attenuate the binding of MYC with PLEKHA1 by recruiting MYC, and ultimately inhibit the proliferation, migration and invasion, and promote the apoptosis of glioma cells.
Serial Procalcitonin Levels and Bacterial Etiology in Hospitalized Patients with Community-Acquired Pneumonia
Authors: Ankomah Pierre , McCluskey Suzanne M , Abers Michael , Bearnot Benjamin , Schuetz Phillip , Chiappa Victor , Vyas Jatin M , Mansour Michael K.
Published: April 2021

Background: Accurate determination of the microbial etiology of pneumonia has important consequences for appropriate administration of antimicrobials and antimicrobial stewardship. Procalcitonin (PCT) is a biomarker that is finding increasing diagnostic and prognostic utility in lower respiratory infections, however, it remains unclear whether it can be helpful in predicting the bacterial etiology of pneumonia. In this study, we examined the relationship between serial PCT measurements and bacterial etiology in hospitalized patients with community-acquired pneumonia, including those at high risk for infections due to multi-drug resistant organisms (MDRO), to determine whether PCT at admission and its trajectory early in the hospital course of patients provides distinguishing information between different bacterial causes of pneumonia.Methods: We analyzed data collected from a prospective cohort study of 505 patients admitted to a tertiary care center with a clinical syndrome consistent with pneumonia. Bacterial etiology of pneumonia was determined from high quality respiratory samples, blood cultures and other relevant diagnostic tests according to standard protocols in conjunction with clinical review. Daily plasma procalcitonin levels were measured for these patients serially during the first four days of hospitalization. We compared procalcitonin levels associated with different bacterial etiologies of pneumonia over the first four days of admission, using the Mann-Whitney-U test to assess for statistical significance.Results: Out of 505 patients, the diagnosis of pneumonia was adjudicated in 322, and bacterial etiology determined in 64 cases. The predominant pathogens were Staphylococcus aureus (n = 19; 12 Methicillin Resistant (MRSA) and 7 Methicillin Susceptible (MSSA)), Pseudomonas aeruginosa (n = 12), Streptococcus pneumoniae (n = 6), and Haemophilus influenza (n=5). We found higher procalcitonin values for S. pneumoniae relative to other etiologies, a delayed rise for Pseudomonas over time, and consistently low PCT values for infections due to multiple bacteria. In addition, our results also suggest that procalcitonin values on the second day of hospitalization, rather than at admission, may have the most utility in distinguishing between bacterial etiologies.Conclusion: Serial procalcitonin values during the early course of bacterial pneumonia reveal a difference between pneumococcal and other bacterial etiologies, and may have an adjunct role in guiding antibiotic choice and duration.
Design an Optimum Energy Harvesting Model for Bidirectional Cognitive Radio Networks
Authors: Hasan Mohammad Kamrul Kamrul , Chowdhury Md. Monwar Jahan , Ahmed Shakil , Sabuj Saifur Rahman , Nibhen Jamel , Bakar Khairul Azmi Abu
Published: April 2021

The energy efficiency and spectrum shortage problem of wireless devices has become a concern for researchers worldwide as the number of wireless devices increases at an unparalleled speed. Many new solutions have been proposed to extend mobile devices' battery life, such as wireless energy harvesting from traditional radio frequency signals to design new smart battery chips. This paper considers a cognitive radio network model where primary users have their specific licensed band, and secondary users equipped with necessary hardware required for energy harvesting can use the licensed band of the primary user by smart sensing capability. First, the expression of outage probability is theoretically derived for uplink and downlink scenarios. Moreover, maximum energy efficiency for both uplink and downlink in the cognitive radio network model subject to interference and noise is investigated here. The theoretical analysis is then evaluated. It has been observed that outage probability improves low harvested power in the downlink scenario and high harvested power in the uplink scenario. Finally, the result signifies that energy efficiency is improved using optimum power for uplink and downlink scenarios.
Integrated microRNA and mRNA Gene Expression in Peripheral Blood Mononuclear Cells in Response to Acute Psychosocial Stress: A Repeated-Measures Within-Subject Pilot Study
Authors: Jurkiewicz Magdalena Maria , Müller-Alcazar Anett , Moser Dirk , Jayatilaka Indralatha , Mikhailik Anatoly , Ferri Jamie , Fogelman Nia , Canli Turhan
Published: April 2021

Objective: The impact of psychosocial stress on a variety of negative health outcomes is well documented, with current research efforts directed at possible mechanisms. Here, we focused on a potential mechanism involving differential expression of mRNA and microRNA in response to acute psychosocial stress. We utilized a validated behavioral paradigm, the Trier Social Stress Test (TSST), to induce acute psychosocial stress in a cohort of volunteers. Stress reactivity was assessed repeatedly during the TSST using saliva samples that were analyzed for levels of cortisol. Peripheral blood mononuclear cells were extracted from blood drawn at baseline and at two time points following the stress paradigm. Total RNA was extracted, and mRNA and microRNA microarrays were utilized to assess within-subject changes in gene expression between baseline and the two post-stressor time points. Results: For microarray gene expression analysis, we focused on 12 participants who showed a robust cortisol response to the task, as an indicator of robust HPA-axis activation. We discovered a set of mRNAs and miRNAs that exhibited dynamic expression change in response to the TSST in peripheral blood mononuclear cells, further characterizing the link between psychosocial stress and cellular response mechanisms.
Psychological symptom and its influencing factors among Chinese elementary school students during early COVID-19 outbreak: A cross-section survey
Authors: Li Xiaoshan , Sun Pengyong , Zhou Mingjie , Shen Youtian , Li Li , Huang Lingling , Huang Taohua
Published: April 2021

Background

This study aimed to examine the psychological symptom and its influencing factors among Chinese elementary school students during early COVID-19 outbreak.
Methods

A cross-section survey was used to investigate individual psychological response and its influencing factors among Chinese elementary school students. And the data were analyzed by the statistical software of SPSS 16.0.
Results

The results showed that students who experience large number of COVID-19-related stressors tend to report more depression and anxiety symptoms. Both problem-based coping and online learning satisfaction were protectors in predicting students’ symptoms of depression and anxiety, while emotion-based coping was a vulnerable factor. With regard to demographic variables, students with low family social status reported more symptoms of depression and anxiety than those with high family social status.
Conclusions

These findings present implications for psychological inventions and for education counselling services during the pandemics.
Complement Factor H-Related 3 induces inflammation and complosome activation in human RPE cells
Authors: Schäfer Nicole , Rasras Anas , Ceteras Delia , Amslinger Sabine , Enzmann Volker , Jägle Herbert , Pauly Diana
Published: April 2021

Background Complement Factor H-Related 3 (FHR-3) is a major regulator of the complement system, which is associated with different diseases, such as age-related macular degeneration. The non-canonical local, cellular functions of FHR-3 remained poorly understood.Methods Human retinal pigment epithelium (RPE) cells (ARPE-19 cells and primary human RPE cells (hpRPE)), cultivated in Transwell® inserts, were apically treated with either FHR‑3 alone or with the chimerized monoclonal anti‑FHR-3 antibody RETC-2-ximab, or with FHR-1, FH, Properdin or not treated for 5 – 24 h, respectively. Interaction of FHR-3 with oxidative stress epitopes was determined by ELISA. Internalization studies of FHR-3 or FH by ARPE‑19 cells was determined by immunofluorescence live cell imaging. Impact of FHR-3 on RPE cell-specific complement components and inflammation markers were analyzed on mRNA (RT-qPCR) and on protein level (Western Blot, ELISA, protein secretion assays, immunofluorescence). Results Here, we report that FHR-3 bound to oxidative stress epitopes and competed with FH for interaction. Furthermore, FHR-3 was internalized by senescent viable RPE cells and modulated time-dependently complement component (C3, CFB) and receptor (C3aR, CR3) expression of human RPE cells. Independently of any external blood-derived proteins, complement activation products were detected. Anaphylatoxin C3a was visualized in treated cells and showed a translocation from the cytoplasm to the cell membrane after FHR-3 exposure. Subsequently, FHR-3 induced a RPE cell dependent pro-inflammatory micro-environment. Inflammasome NLRP3 activation and pro-inflammatory cytokine secretion of IL-1ß, IL-18, IL-6 and TNF-α were induced after FHR-3-RPE interaction. Additionally, important pattern recognition molecules of the innate immune system, Toll-like receptors 1 and 3, as well as proteasome subunits were impaired in RPE cells after FHR-3 incubation. A chimerized monoclonal anti-FHR-3 antibody, RETC‑2‑ximab, ameliorated the effect of FHR-3 on ARPE-19 cells.Conclusion Our studies suggest FHR-3 as an exogenous trigger molecule for the RPE cell complosome and as a productive target for a new therapeutic approach using RETC‑2‑ximab for associated degenerative diseases.
Identification and functional significance of MicroRNAs in esophageal squamous cell carcinoma
Authors: Yu Jiarui , Wang Wei , Zeng Chao , Li Jianing , Zheng Qiangxin , Sun Guogui
Published: April 2021

Background: Oesophageal carcinoma is one of the most frequently seen malignancies, and its incidence ranks third among men and fifth among women in China. Among all the histological categories, oesophageal squamous cell carcinoma (ESCC) accounted for the most of the cases. At present, there are few therapeutic methods applied in clinical practice for ESCC due to the limited evidence with respect to the underlying signaling pathways and the miRNAs related to the ESCC. Methods: To identify the differentially-expressed miRNAs (DE-miRNAs) in different stages of ESCC, we performed a microarray on 92 ESCC and 3 normal tissues. At the mean time, the potentially targeted genes as well as the highly-enriched signaling pathways and the relevant protein–protein interaction (PPI) network were analyzed and constructed by using a series of bioinformatic methods. Moreover, the identified DE-miRNAs in different stages of the ESCC were verified by using the TCGA dataset. Results: According to our analysis, overall 37 DE-miRNAs were identified, including 6 up-regulated miRNAs and 31 down-regulated miRNAs. 1884 genes were selected as the potentially targeted genes for the above miRNAs, most of which were found to be enriched in the PI3K-Akt signaling pathway and the Hippo signaling pathway. Based on the PPI network we constructed, PIK3R1 and NOTCH1 were considered as the potential hub genes. Conclusion: Our study provided additional explanations regarding the molecular mechanisms and prognosis of ESCC through the identification of a number of potential targeted genes of the DE-miRNAs in different stages of ESCC as well as the mostly enriched signaling pathways of the above genes, which could promote the development of the targeted treatment and improve the prognosis evaluation of ESCC.
Joint modelling of multivariate longitudinal clinical laboratory safety outcomes, concomitant medication and clinical adverse events: Application to artemisinin-based treatment during pregnancy clinical trial
Authors: Patson Noel , Mukaka Mavuto , D’Alessandro Umberto , Chapotera Gertrude , Mwapasa Victor , Mathanga Don , Kazembe Lawrence , Laufer Miriam K , Chirwa Tobias
Published: April 2021

Background In drug trials, clinical adverse events (AEs), concomitant medication and laboratory safety outcomes are repeatedly collected to support drug safety evidence. Despite the potential correlation of these outcomes, they are typically analysed separately, potentially leading to misinformation and inefficient estimates due to partial assessment of safety data. Using joint modelling, we investigated whether clinical AEs vary by treatment and how laboratory outcomes (alanine amino-transferase, total bilirubin) and concomitant medication are associated with clinical AEs over time following artemisinin-based antimalarial therapy. Methods We used data from a trial of artemisinin-based treatments for malaria during pregnancy that randomized 870 women to receive artemether–lumefantrine (AL), amodiaquine–artesunate (ASAQ) and dihydroartemisinin–piperaquine (DHAPQ). We fitted a joint model containing four sub-models from four outcomes: longitudinal sub-model for alanine aminotransferase, longitudinal sub-model for total bilirubin, Poisson sub-model for concomitant medication and Poisson sub-model for clinical AEs. Since the clinical AEs was our primary outcome, the longitudinal sub-models and concomitant medication sub-model were linked to the clinical AEs sub-model via current value and random effects association structures respectively. We fitted a conventional Poisson model for clinical AEs to assess if the effect of treatment on clinical AEs (i.e. incidence rate ratio (IRR)) estimates differed between the conventional Poisson and the joint models, where AL was reference treatment.Results Out of the 870 women, 564 (65%) experienced at least one AE. Using joint model, AEs were associated with the concomitant medication (log IRR 1.7487; 95% CI: 1.5471, 1.9503; p<0.001) but not the total bilirubin (log IRR: -0.0288; 95% CI: -0.5045, 0.4469; p=0.906) and alanine aminotransferase (log IRR: 0.1153; 95% CI: -0.0889, 0.3194; p=0.269). The Poisson model underestimated the effects of treatment on AE incidence such that log IRR for ASAQ was 0.2118 (95% CI: 0.0082, 0.4154; p=0.041) for joint model compared to 0.1838 (95% CI: 0.0574, 0.3102; p=0.004) for Poisson model.Conclusion We demonstrated that although the AEs did not vary across the treatments, the joint model yielded efficient AE incidence estimates compared to the Poisson model. The joint model showed a positive relationship between the AEs and concomitant medication but not with laboratory outcomes. Trial registration ClinicalTrials.gov: NCT00852423.
The regulation of miR-320a/XBP1 axis through LINC00963 for endoplasmic reticulum stress and autophagy in diffuse large B-cell lymphoma
Authors: Cui Yuying , Xu Hui , Yang Yu , Zhao Dongmei , Wen Yu , Lv Chao , Qiu Hongbin , Wang Chennan
Published: April 2021

Introduction: Huge amounts of gene-sequencing data have been used to guide fundamental researches. The study combined bioinformatics tools with basic study to analyze the pathological mechanisms of diffuse large B-cell lymphoma. Methods: A LncRNA-miRNA-mRNA ceRNA network of diffuse large B cell lymphoma was constructed by GTEx combined with TCGA database analysis. qPCR was used to detect the expression of LINC00963 and miR-320a in DLBCL cell lines. The proteins levels of UPR sensors, GRP78, p-IRE1α, IRE1α, active ATF6, ATF4 and XBP1, were assessed through Western blot, along with apoptosis markers (Bcl-2, Bax, caspase 3) and autophagy indicators (Beclin1, LC3II, LC3I and p62) after LINC00963 overexpression or miR-320a overexpression in vitro. Additionally, the expression of LC3 was analyzed through immunofluorescence (IF) assay. Results: Evaluation of SUDHL4 cell showed marked up-regulation of key elements of the UPR (GRP78, p-IRE1α, spliced XBP-1(XBP-1(s))), apoptosis (Bax, cleaved caspase 3) and autophagy (Beclin1, LC3II) after LINC00963 overexpression in vitro, whereas miR-320a mimic reversed the effects. Besides, LINC00963 targeted miR-320a while miR-320a bound to the 3’UTR of XBP1. The work also found that LINC00963 overexpression resulted in significant tumor growth delay in a xenograft model of DLBCL. Conclusion: Mechanistically, LINC00963 / miR-320a regulated XBP1-apoptosis pathway and autophagy, making this pathway an attractive therapeutic target for selective targeting. The data presented here are the first to comprehensively survey the mechanism of LINC00963 / miR-320a/XBP1 in DLBCL.
Translation, Adaptation and Validation of an Arabic Version of Human Resource Practices Scale among Nurses
Authors: El-Gazar Heba , Zoromba Mohamed , El-Gilany Abdel-Hady
Published: April 2021

Background: Human resource practices (HRP) have a unique role in healthcare organizations, especially among nurses. Therefore, a valid and reliable tool to measure HRP is crucial. The present study aimed to translate, culturally adapt, and validate the Human resource practices (HRP) scale into Arabic language among nurses. Methods: A methodological study was applied in a sample of 328 nurses from 16 hospitals in Port-Said, Egypt. Face, content, construct and concurrent validity were assessed. Cronbach’s alpha coefficients and intra-class correlation coefficient (ICC) to test reliability were evaluated. Results: The Arabic version of HRP scale had good content validity with I-CVI ranged from 0.727 to 1 and S-CVI with the average approach 0.961. Confirmatory factor analysis showed a better fit for the second-order model consisting of performance enhancement and employee support factors (CFI, NFI and RMSEA= 0.932, 0.926, and 0.064; respectively). The Arabic version of HRP scale correlated significantly with performance excellence and nurses' performance (r= 0.701, and 0.565; respectively), indicating good concurrent validity. Internal consistency with Cronbach's alpha was 0.95 and the intra-class correlation coefficient was 0.91 for the total scale showed good reliability. Conclusion: The Arabic version of HRP scale showed evidence of validity and reliability, and it could be recommended for use in clinical and research settings to assess HRP among Arabic nurses.
Refractive lens exchange surgery in early-onset high myopia patients with partial cataract: a pilot study
Authors: Zhang Xifang , Qiao Liya , Li Xiaoxia , Kline Brad , Kang Mengtian , Li Meng , Ying Han , Wang Ningli
Published: April 2021

Background

By reporting clinical characteristics and retinal image quality before and after refractive lens replacement surgery in early-onset high myopia (eoHM) patients presenting with partial cataract, we emphasized the need for an objective way to grade the severity of partial cataracts.
Methods

This retrospective, consecutive case series included six Chinese patients (nine eyes). Analysis of previous medical records, visual acuity, optometry, and axial length (AXL) before surgery and 2–4 years after surgery was performed. Retinal image quality was measured by the Optical Quality Analysis System and recorded as modulation transfer function cutoff frequency (MTFcutoff) and objective scatter index (OSI) at the same time point.
Results

Five females and one male (nine eyes) with a mean (± SD) age of 11.6 ± 7.9 years were included in this study. The preoperative spherical power ranged from − 7.5 D to -42 D. The mean follow-up time was 36 (36–36) months (range: 24–48 months). Phacoemulsification was followed by in-the-bag implantation of intraocular lens. For younger patients who could not cooperate with postoperative laser capsulotomy, posterior capsulotomy + anterior vitrectomy were performed simultaneously. All surgeries were uneventful and no postoperative complications occurred during the entire follow-up period. Four eyes underwent YAG-laser capsulotomies at 12–18 months postoperatively. Initial spherical correction (treatment achieved) averaged 18.25 ± 11.15 D (range: 7.75-44 D). All patients’ uncorrected visual acuity improved by ≥ 2 lines postoperatively. LogMAR BCVA was significantly improved at 24-month (95%CI: 0.015–0.878, p = 0.042) and endpoint (95%CI: 0.008–0.909, p = 0.046) follow-ups. MTFcutoff and OSI was significantly improved at 12-month (p = 0.025, p = 0.038), 24-month (p = 0.005, p = 0.007) and endpoint (p = 0.005, p = 0.008) follow-ups. Postoperative AXL remained stable during 2–4 year follow-ups compared to the pre-operative value (p༞0.05). Eight eyes (0.89%) exhibited myopia shift (~-0.5 D/year except for case 3), whereas case 5 (age 25) showed hyperopic change.
Conclusion

Refractive lens replacement surgery is safe and effective for improving functional vision in eoHM patients presenting with partial cataract. Retinal image quality could provide a useful and objective way to facilitate partial cataract severity evaluation and surgery decision making.
Hypothyroidism symptoms in LT4-euthyroid thyroidectomized patients reflect an alteration of the serum proteome
Authors: Landi Claudia , Cantara Silvia , Shaba Enxhi , Marzocchi Carlotta , Vantaggiato Lorenza , Maino Fabio , Carleo Alfonso , Giuseppe Fabrizio Di , Angelucci Stefania , Bini Luca , Castagna Maria Grazia
Published: April 2021

In patients undergoing thyroidectomy one of the goals of post-surgical follow-up is the correct maintenance of thyroid hormone (TH) levels by replacement therapy with levo-thyroxine (LT4). Nevertheless, some patients complain of symptoms of hypothyroidism (memory loss, weight gain, fatigue, depression, and reduced quality of life) despite values of thyroid hormones get the physiological range. Since this recurrent issue, we aim to compare serum proteomic profiles of LT4-euthyroid thyroidectomized patients with good or reduced post-operative quality of life. Proteomic analysis highlights a different protein profile in the serum of patients with reduced quality of life compared to the other although both resulted euthyroid. Differential proteins are involved in coagulation processes, complement system activation and in lipoprotein particles remodeling, that together lead to a pro-inflammatory response. Moreover, a particular degradome of apolipoprotein A1, thrombin heavy chain and alpha 1 antitrypsin, was also detected. This study suggests that LT4 replacement therapy might restore euthyroid conditions in thyroidectomized patients but in some cases without re-establish body tissues euthyroidism and serum protein profiles strongly suggest a behavior similar to overt hypothyroidism.
Omega-3 Polyunsaturated Fatty Acid Biomarkers and Risk of Type 2 Diabetes, Cardiovascular Disease, Cancer, and Mortality: A Systematic Review and Meta-analysis
Authors: Jiang Hong , Wang Lina , Wang Duolao , Yan Ni , Li Chao , Wu Min , Lin Jing , Jia Wanru , Liu Xi , Lv Jiaxin , Liu Yan , ma le
Published: April 2021

Background: Considerable attention has focused on omega-3 polyunsaturated fatty acids (PUFA) role in protect against the development of cardiometabolic diseases, which has led to dietary recommendations to increase omega-3 fatty acid intake.Methods: MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and reference lists were searched for articles from inception to May 2020. Random-effects model was used to estimate the pooled relative risk (RR) and 95% confidence intervals (CIs) for the association of omega-3 PUFAs, including α-linoleic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with risk of developing type 2 diabetes (T2D), cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, cancer, and mortality.Results: 66 prospective studies comprised of 211,600 participants were identified. Individual omega-3 PUFAs showed divergent associations with the study outcomes of interest. An inverse association with risk of T2D was observed comparing extreme categories of ALA concentration (RR,0.91;95%CI,0.83-0.99), but not for the marine-origin omega-3 fatty acids biomarkers. The marine-origin omega-3 fatty acids biomarkers, but not ALA, were significantly associated with lower risks of total CVD, CHD, and overall mortality, with RRs ranging from 0.70 for DHA-CHD association to 0.85 for EPA-CHD association. Lower risk of colorectal cancer was observed at higher levels of DPA (RR,0.76;95%CI:0.59-0.98) and DHA (RR,0.80;95%CI:0.65-0.99). In dose-response analyses, inverse linear associations were observed between EPA, DPA, and DHA biomarkers and CVD or CHD risk, except for DHA-CVD association which showed a nonlinearity association.Conclusion: Higher concentrations of marine-derived omega-3 PUFA biomarkers were associated with a significantly reduced risk of total CVD, CHD, certain types of cancer, and total mortality. Levels of ALA were inversely with a lower risk of T2D but not CVD-related outcomes. These data support the dietary recommendations advocating the role of omega-3 PUFAs in maintaining an overall lower risk of developing cardiovascular disease and premature deaths.