bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Systemic Endothelial Dysfunction in Patients with Retinal Vein Occlusion
Authors: Bozkurt Erdinc , Cetin Turkhun , Rencuzogulları Ibrahim
Published: April 2021

Purpose: To determine the condition of systemic endothelial function and carotid intima media thickness (CIMT) in patients with retinal vein occlusion (RVO) and to identify the risk factors associated with the disease.Material-Method: Seventy-six patients who presented to the clinic with the diagnosis of RVO and 76 age- and gender-matched healthy individuals without a RVO history were included in the study. The patients' vision levels and central macular thickness were measures, and diabetes, hypertension, hyperlipidemia, carotid artery disease, body mass index and smoking histories were recorded. The endothelial function levels of the patients, pulse wave velocity (PWV), and CIMT were measured. Serum hematological parameters were evaluated.Results: The most important risk factor in patients with RVO was found to be hypertension (OR 1.455, 95% CI 1.981-9.272; p=0.001) compared to the control group, and diabetes (OR 0.460, 95% CI 1.981-9.272; p=0.001) and hyperlipidemia (OR 0.124, 95% CI 0.371-3.456; p=0.828) were significantly more common among the patients.There was a statistically significant difference between the RVO and control groups in terms of flow-mediated dilation (OR 0.050, 95% CI 0.020-0.080; p =0.001), PWV (OR 0.392, 95% CI 0.271-0.513; p<0.001), and the CIMT of both sides (OR 2.434, 95% CI 1.801-3.055 for the right CIMT and OR 2.284, 95% CI 1.646-2.922 for the left CIMT) (p<0.001 for all).Conclusion: Considering that RVO is associated with systemic endothelial dysfunction and may also be accompanied by carotid artery stenosis, we think that additional systemic diseases should be questioned in this patient group.
A clinical study focusing Evaluation and treatment of acute and chronic cartilage injuries of the knee
Authors: Årøen Asbjørn , Kjennvold Stian
Published: April 2021

Treatment of articular cartilage injuries have been a challenge for orthopedic surgeons for decades. The following study protocol add knowledge about ongoing research in the field and outline the ongoing long-term follow-up on the transplantation of bone marrow derived stem cells in a clinical trial with 10 years follow-up. The study protocol describes a method to save chondral fractures, which in the past frequently treated with removal of the detached fragments.
Effects of control measures and their impacts on COVID-19 transmission dynamics
Authors: Supatgiat Chonawee
Published: April 2021

Governments around the world have grappled with the COVID-19 pandemic for more than a year. Control measures such as social distancing, use of face masks in public places, business and school closures, city or transportation lockdowns, mass gathering bans, population education and engagement, contact tracing, and improved mass testing protocols are being used to contain the pandemic. Currently, there are no studies to date that rank the effectiveness of these measures, resulting in government responses that may be uncoordinated and inefficient. In this study, we developed a Discrete Time Markov Chain model that captures the above control measures and ranks them. We found that the importance of the measures changes over time and depends on the stage of transmission dynamics, as well as the ecological environment. For example, contact tracing is a powerful measure to effectively control the pandemic, however, our results show that while it is indeed helpful during the early stages of the pandemic, it is much less important after a vaccination program takes effect. Besides, our model improved the standard SEIR compartmental model by taking into account the dynamic temporal transmission and recovery probabilities along with considering a portion of the population that will not comply with government-mandated control measures. If implemented, our novel and unique model may assist many countries in pandemic control decisions.
Performance Enhancement in Multicore Fiber Using Trench Assisted Technique
Authors: Fatmia Salma , CT Manimegalai , Gauni Sabitha , Kalimuthu K.
Published: April 2021

Analysis of crosstalk in multicore fiber using trench assisted technique. To reduce the crosstalk between the cores in the fiber the coupled mode theory and coupled power theory are adopted for crosstalk estimation and considering different design parameters such as core pitch, bending radius and wavelength to optimize the crosstalk performance. The homogeneous fiber which works under single mode operation has been considered. The study of performance by varying the trench width is also analysed. Crosstalk variation in outer cores and center core of the fiber is studied. And the study of variation of crosstalk with 5 different core radius has been done. The numerical simulation results of crosstalk behavior over bending radius, wavelength and trench width is obtained.
BRAF Mutation Correlates with Worse Local-regional Control Following Radiation Therapy in Patients with Stage III Melanoma
Authors: Wolfe Adam R , Chablani Priyanka , Siedow Michael , Miller Eric D , Walston Steve , Kendra Kari , Wuthrick Evan , Williams Terence M
Published: April 2021

Background

In patients with stage III melanoma, the use of adjuvant radiation therapy (RT) after lymph node dissection (LND) may be currently considered in selected high-risk patients to improve local-regional control. Melanomas harbor BRAF mutations (BRAF+) in 40–50% of cases, the majority of which are on the V600E residue. This study sought to compare the clinical outcomes after RT between patients with BRAF + and BRAF- melanoma.
Methods

This was a retrospective review of 105 Stage III melanoma patients treated at our institution with LND followed by adjuvant RT from 2006–2019. BRAF mutational status was determined on the primary skin or nodal tissue samples from all patients. We compared characteristics of the BRAF + and BRAF- groups using Fisher’s exact test and Wilcoxon rank sum test and performed univariate and multivariate analysis using Kaplan-Meier estimates, log-rank tests, and Cox proportional hazards modeling with the clinical outcomes of local-regional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS).
Results

Fifty-three (50%) patients harbored a BRAF mutation (92%, pV600E). BRAF + patients were younger and had primary tumors more commonly found in the trunk vs head and neck compared to BRAF- patients (p < 0.05). The 5 year local-regional control in the BRAF + patients was 60% compared to 81% in the BRAF- patients (HR 4.5, 95% CI 1.3–15.5, p = 0.02). There were no significant differences in 5-year DMFS, DFS, and OS rates between the two BRAF patient groups. The presence of 4 or more positive LNs remained a significant prognostic factor for LRC, DFS, and OS in multivariate analysis.
Conclusions

Stage III melanoma patients with BRAF mutation treated with adjuvant RT had > 4 times increased risk of loco-regional recurrence. These results could be useful for adjuvant RT consideration in lymph node positive melanoma patients and supports other data that BRAF mutation confers radiation resistance.
Long-term SST Prediction Based on RSST-ARGM
Authors: Zhu Linqian , Liu Qi , Liu Xiaodong , Zhang Yonghong
Published: April 2021

For the purpose of exploring the long-term variation of regional SST, this paper studies the historical SST in local sea areas and the emission pattern of greenhouse gases and proposes a gray model of regional SST based on atmospheric reflection which can be used to predict SST variation in a long time span. By studying the grey systematic relationship between historical SST data, the model obtains the development law of temperature change, and furtherintroduces different future greenhouse gas emission scenarios as the index coefficient to determine the corresponding changing results of seawater temperature in the next 50 years. Taking the North Atlantic Ocean as an example, the cosine similarity test method is used to verify the model proposed in this paper, and its accuracy is as high as 0.99984. The model predicts that the local SST could reach a maximum of 15.3°C by 2070. This model is easy to calculate, with advantages of the high accuracy and good robustness.
Elucidation of the inhibitory activity of plant-derived SARS-CoV inhibitors and their potential as SARS-CoV-2 inhibitors
Authors: Bello Martiniano , Hasan Md. Kamrul
Published: April 2021

Due to the necessity of treating the SARS-CoV-2 infection, several drugs are now being tested as possible therapies. Although approved vaccines bring much hope, a vaccination program covering the entire global population will take a very long period, which makes the development of effective antiviral drugs an effective solution for the immediate treatment of this dangerous infection. Previous studies found that three natural compounds: tannic acid, 3-isotheaflavin-3-gallate and theaflavin-3,3-digallate are effective proteinase (3CLpro) inhibitors of SARS-CoV (IC50 < 10 µM). Based on this information, and due to the high percentage of sequence identity of SARS-CoV and SARS-CoV-2 3CLpro, these three compounds could be candidate inhibitors of SARS-CoV-2 3CLpro. In this paper, we explore the structural and energetic features that guided the molecular recognition of these three compounds for dimeric SARS-CoV2 and SARS-CoV 3CLpro, the functional state of this enzyme, by using docking and MD simulations with the molecular mechanics-generalized-born surface area (MMGBSA) approach. Energetic analysis demonstrated that the three compounds reached favorable affinities in both systems in the following order: tannic acid > 3-isotheaflavin-3-gallate > theaflavin-3,3-digallate, a tendency that is in line with that which was experimentally reported between these ligands and SARS-CoV 3CLpro. Therefore, tannic acid may have clinical usefulness against COVID-19 by acting as a potent inhibitor of SARS-CoV-2 3CLpro.
Expanded and Filtered Features based ELM Model for Thyroid Disease Classification
Authors: Juneja Kapil
Published: April 2021

Thyroid disorder affects the regulation of various metabolic processes throughout the human body. The structural and functional disorders can affect the body as well as the brain. The computer-aided diagnosis system can identify the kind of Thyroid disease. One such machine learning framework is presented in this paper to recognize disease existence and type. In this paper, a fuzzy adaptive feature filtration, expansion, and again filtration based model is presented for generating the most relevant and contributing features. This two-level filtration model is processed in a controlled fuzzy-based multi-measure evaluation. At the first level, the composite-fuzzy measures are combined with expert’s recommendations for identifying the ranked and relevant features. At the second level, the statistical computation based distance measure is applied for expanding the featureset. The fuzzification is applied to expanded featureset for transiting the continuous values to fuzzy-values. At this level, the fuzzy-based composite-measure is applied for selecting the most contributing and relevant features over the expanded dataset. This processing featureset is processed by the ELM classifier to predict the disease existence and class. Five experiments are conducted on two datasets for validating the performance and reliability of the proposed framework. The comparative analysis is conducted against the NaiveBayes, Decision Tree, Decision Forest, Random Tree, Multilevel Perceptron, and RBF Networks. The analysis outcome is taken in terms of accuracy, error, and relevancy based parameters. The proposed framework clams the significant gain in accuracy, relevancy, and reduction in the error rate.
Chemoinformatic analysis of alkaloids isolated from Peganum genus
Authors: Bayazeid Omer , Nasibova Tohfa
Published: April 2021

Peganum genus is rich with its high phytochemical and botanical variability. Peganum species have been used as sedative, antitumor, analgesics, antidepressant, and other medicinal purposes. The aim of this research is to study the molecular diversity of Peganum genus to shed more lights on the structure-activity relationship of the alkaloids isolated from Peganum genus. All Peganum alkaloids were grouped according to their structure properties. A chemoinformatic approach (Swiss Model) was used to determine the molecular targets of these alkaloids. To visualize the results, R programming language was used to generate hierarchical clustering heatmaps. The results of this study helps researcher to better understanding of the structural-activity relationship of Peganum alkaloids.
Development of the CFQ-R-8D: Estimating Utilities From the Cystic Fibrosis Questionnaire-Revised
Authors: Acaster Sarah , Mukuria Clara , Rowen Donna , Brazier John E , Wainwright Claire E , Quon Bradley S , Duckers Jamie , Quittner Alexandra L , Lou Yiyue , Sosnay Patrick , McGarry Lisa J
Published: April 2021

The authors have requested that this preprint be removed from Research Square.
Deciphering the role of fungal calmodulin gene using Host-mediated gene silencing approach in apple
Authors: Verma Shalini , Modgil Manju , Chauhan Arjun
Published: April 2021

Premature leaf fall caused by Marssonina coronaria is one of the most destructive diseases of apple in India. In this study, host induced gene silencing approach was exploited to develop resistance to this disease in an apple cultivar ‘Red Chief’. Calmodulin gene (CaM) having its role in fungal differentiation, development and pathogenicity was selected as target. hpRNAi construct was prepared from the conserved off target free partial gene sequence of CaM and used for transformation trials. Upto 6% kanamycin resistant shoots were obtained on selective medium having 5–6 mg/l kan after 7 weeks of coculture. In PCR analysis of 13 RNAi putative transformants, 10 lines were found positive with CaM and nptII gene specific primers and six lines showed hybridization signal. Semi qRT-PCR revealed variable levels of transgene expression among RNAi lines which seems to be related to copy number of integrated gene. In vitro detached leaf assay revealed lesion development and disease progression in wild type after 5 dpi but not visible in five CaM RNAi lines. Microscopic examination of infected control leaves showed fully developed, septate mycelium, and conidia along with necrosis of whole tissue while three transformants showed reduced growth and differentiation of fungus and in rest three, hyphal development and necrosis were strongly restricted. We conclude that trafficking of dsRNA/ siRNA from apple plants to pathogen might have triggered the down regulation of fungal CaM gene which confirms that deciphering the role of CaM through HIGS lead to resistance to Marssonina blotch in apple.
Postoperatively Determined High-Risk Histopathologic Features in Papillary Thyroid Carcinoma Initially Eligible for Thyroid Lobectomy: A Game Changer
Authors: Bakkar Sohail , Al-Omar Khaled , Donatini Gianluca , Aljarrah Qusai , Papavramidis Theodosios S , Materazzi Gabriele , Miccoli Paolo
Published: April 2021

Purpose.

Recent clinical practice guidelines consider thyroid lobectomy a viable alternative for low-risk papillary thyroid carcinoma PTC measuring 1–4 cm in size. We aimed to assess the likelihood of finding postoperatively determined high-risk histopathologic features that would lead to the recommendation of completion thyroidectomy.
Methods.

A retrospective review of patients who underwent total thyroidectomy for PTC measuring 1–4 cm in size between Jan 2012-Jan 2018 was conducted. Patients with pre-operative high-risk characteristics were excluded; history of radiation exposure, positive family history, clinically suspicious cervical lymphadenopathy, and gross extrathyroidal extension (ETE). A hypothetical group of 245 patients remained eligible for lobectomy. The pathology specimens from the cancer-containing lobes were evaluated for high-risk features: aggressive histology, capsular and/or vascular invasion, microscopic ETE, and multifocality. A subgroup analysis was performed with 2 cm being the cut-off size.
Results.

The average age was 39 years with 73% being females. Mean cancer size was 16 mm. Evaluation of the cancer-containing lobe for high-risk features revealed: aggressive histology (33%), ETE (12%), capsular invasion (33%), vascular invasion (17%), and ipsilateral multifocality (30%). The cumulative risk of having ≥ 1 high-risk feature mandating completion thyroidectomy was 59%. The risk was considerably higher for lesions ≤ 2 cm compared to larger lesions (64% vs.48%; p = 0.049; RR = 1.3).
Conclusion.

A considerable proportion of patients initially eligible for lobectomy have high-risk features that only become evident at pathology. Therefore, a comprehensive approach is advocated to determine the extent of surgery for PTC incorporating patient preferences regarding risks and benefits.
Modeling and analysis of the friction in a nonlinear sliding-mode triboelectric energy harvester
Authors: Tan Dongguo , Zhou Jiaxi , Wang Kai , Cai Changqi , Xu Daolin
Published: April 2021

Friction plays a pivotal role in the sliding-mode triboelectric energy harvester (TEH), which not only enables the charge transfer between two dielectrics, but also influences the energy harvesting performance by affecting the dynamic response of the TEH. How to evaluate the effects of the friction on TEHs is important for optimizing TEHs in engineering practices. In order to analyze the effects of the friction on the dynamic response and evaluate the energy harvesting performance of TEHs, the paper models the friction of a devised nonlinear TEH based on the Coulomb friction model and the Macro-slip friction theory. The TEH equips a pair of magnets, rendering a switching between the bistability and the monostability by tuning the distance between two magnets. The dynamic model of the nonlinear TEH is established by the extended Hamilton principle. The effects of the friction in sliding-mode TEH are dissected in detail. The influences of parameters on both the mechanical and electrical responses are also systemically studied, to explore an optimal energy harvesting performance in the low-frequency range. This work provides a guideline for designing and accurately analyzing a sliding-mode TEH.
Professional Love in Early Childhood Education: the experience of Aotearoa New Zealand
Authors: Stewart-MacKenzie Helen Lorraine Grace
Published: April 2021

Love is essential for human psycho-social development, in particular in the early years. Just as the love of parents/care-givers and others in the home setting is vital, there is increasing recognition that love is important for infants, toddlers and young children in early childhood education settings (ECES). However, love demonstrated by teaching professionals continues to be under-researched (Dalli 2005; Page 2017a). As a result, educational policy and practice guidelines are still embryonic, or may not yet exist (Dalli et al 2011; Hughs 2013). This article presents findings from a nation-wide survey of early childhood professionals in Aotearoa New Zealand (NZ) undertaken in 2020 which explored early childhood teachers’ understandings of professional love in ECES in NZ; the first such survey undertaken. Respondents emphasised that a professional approach to love is important despite many responses indicating love is still viewed as unprofessional by early childhood education (ECE) teachers and managers. A key finding of this research is that understanding the nature of love in ECES is required in order to legitimise professional love and thereby inform policy and practice. Findings from the research suggest a way forward.
Methods for improving the accuracy of frequency shift estimation in 5G NR
Authors: Milyutin Vladimir Sergeevich , Rogozhnikov Eugeniy Vasilevich , Petrovskiy Kirill , Pokamestov Dmitriy , Dmitriyev Edgar , Novichkov Serafim
Published: April 2021

Frequency synchronization is a necessary operation for all wireless communication systems. Due to the wide frequency range defined for 5G NR systems, this procedure becomes critical. To ensure high transmission rates and the use of high-order modulation, up to 256 QAM for 5G communication systems, it is necessary to ensure high frequency synchronization accuracy. In this article, we have reviewed various approaches to implementing frequency synchronization and proposed, in our opinion, the most effective method for correcting the frequency shift of the signal.
A Simple Nomogram Developed for Predicting HCC Metastasis Based on Micrornas 
Authors: Zhu Yong , Jie Yusheng , Wu Yuankai , Tang Wenting , Cao Jing , Su Zhongzhen , Zhuo ZhenJian , Gong Jiao , Chong Yutian
Published: April 2021

BackgroundOwing to lack of predictive models for HCC metastasis based on the expression of miRNAs, we aimed to develop a simple model for identification of HCC patients at high risk of metastasis. MethodsHCC datasets with metastasis information were acquired from the Gene Expression Omnibus (GEO), and samples were randomly divided into training group (n=169) and testing group (n=72). Based on expression of miRNAs in the training group, we developed a predictive nomogram for HCC metastasis and evaluated its performance using area under the receiver operating characteristic curve (AUC), calibration curve, decision curve and clinical impact curve analysis.ResultsWe found that the expression of miR-30c, miR-185 and miR-323 in HCC correlated with metastasis by the least absolute shrinkage and selection operator regression (LASSO) method and multivariate logistic regression. Based on these three miRNAs, we generated the nomogram for predicting metastasis in the training group (AUC 0.869 [95% CI .813-0.925], sensitivity 80.5%, specificity 78.9%); in testing group (0.821 [0.770-0.872], 48.5%, 92.3%). The calibration curve showed a good agreement between actual observation and prediction by nomogram. The nomogram represented high clinical net benefits using decision curve and clinical impact curve analysis. Moreover, total scores calculated by nomogram were higher in dead patients than that in alive patients. In addition, the predicted target genes of these 3 miRNAs correlated with tumor metastasis by functional enrichment analysis, such as filopodium. Our easy-to-use nomogram could assist in identifying HCC patients at high risk of metastasis, which offer valuable information for clinical treatment.
Aphid Species Specializing on Milkweed Have Distinct Bacterial Symbiont Communities
Authors: Enders Laramy , Hansen Thorsten , Brichler Kirsten , Couture John , French Elizabeth
Published: April 2021

Host plant range is arguably one of the most important factors shaping microbial communities associated with insect herbivores. However, it is unclear whether host plant specialization limits microbial community diversity or to what extent herbivores sharing a common host plant evolve distinct microbiomes. To investigate whether variation in host plant specialization influences the composition of herbivore symbiont populations we compared bacterial diversity across three milkweed aphid species (Aphis nerii, Aphis asclepiadis, Myzocallis asclepiadis) feeding on a common host plant (Asclepias syriaca) using 16S rRNA metabarcoding. Overall, bacterial species richness did not vary with degree of host plant specialization. However, aphid species harbored distinct bacterial communities that varied in composition and relative abundance of key symbionts. Differences in aphid microbiomes were primarily due to strain variation in the obligate symbiont Buchnera and facultative symbiont Arsenophonus, as most of the low-abundant taxa were found in all three species. Interestingly, A. asclepiadis harbored a greater diversity of unique strains of Buchnera and significantly higher Arsenophonus relative abundances compared to the other two aphid species. Although many low abundance microbes were shared across all milkweed aphids, key differences exist in symbiotic partnerships that could influence additional ecological variation, including variation in ant tending observed across milkweed aphid species via microbial induced changes to honeydew or defensive chemical profiles. This study suggests generalist and specialist herbivore microbiomes are similar when feeding on a common host plant and highlights an intriguing potential role for strain level variation of key aphid symbionts in host-plant interactions.
Urinary Level of Dimethoate, Bisphenol a and Benzo[a]pyrene in the First-year Students of Hohai University From Different Geographical Regions
Authors: Xu Yu-Juan , Gao Hong-Liang , Liu He , Zhao Ning-Wei , Cheng Qi , Zhang Fu-Rong , Ye Juan , Wang Ai-Qing , Dou Yan-Jun , Ma Bei , Zhu Feng , Xu Xian-Lin , Li Chao-Jun , Wu Jing , Shen Ning , Xue Bin
Published: April 2021

Background: The objective of this study was to detect the urinary level of dimethoate, benzo(a)pyrene (BaP), and bisphenol A (BPA) in the first-year Hohai University students of different geographic origins.Methods: First-morning urine samples were collected from 540 healthy freshmen aged 17 to 19. Toxin levels were measured using β-glucuronidase hydrolysis followed by a high-performance liquid chromatography-tandem mass spectrometry-based method. Geometric means (GM) are presented by BMI (Body Mass Index) and different locations for these three toxins in a volume-based and creatinine-standardized way.Results: GM concentration of dimethoate, BPA and BaP were 9.47 µg/L (10.80 µg/g creatinine), 3.54 µg/L (4.04 µg/g creatinine) and 0.34 ng/L (0.39 ng/g creatinine), respectively. The GM concentration of dimethoate in males was significantly higher than that in females. The BMI higher than 23.9 had a higher GM concentration of dimethoate, BPA, and BaP. The inhabitant in the Southwest of China had a significantly lower GM concentration of dimethoate, BPA, and BaP than those who live in other locations of China.Conclusion: The average level of environmental toxins accumulation in freshmen is relatively high and differs in the youth who live in different regions. Besides, obesity is correlated to higher toxins levels in youth.
Gestational Period-Specific Renal Functions: Evidence From a Large, Community-Based, Prospective Cohort in Rural Sri Lanka
Authors: Agampodi Suneth Buddhika , Agampodi Thilini Chanchala , Amarasinghe Gayani Shashikala , Warnasekara Janith Niwanthaka , Hettiarachchi Ayesh Umeshana , Jayasinghe Imasha Upulini , Koralegedara Iresha Sandamali , Abeyrathna Parami , Sriman Shalka Madushan , de Silva Farika Nirmani , Gunaratne Sajaan Praveen , Wickramasinghe Nuwan Dharshana
Published: April 2021

Renal functions in pregnancy undergo rapid changes, and the thresholds for normal values is a major research gap and are still debatable. We used a prospective cohort design with 2,259 first trimester pregnant women from Anuradhapura, Sri Lanka to estimate the gestational age-specific serum creatinine levels and compared with 2.012 nonpregnant women from the same geographical area. The mean (SD) sCr of the 2,012 nonpregnant women was 62.8(12.4) μmol/L, with a 97.5th percentile of 89.0 μmol/L. The mean (SD) sCr was 55.1, 52.7, 51.0, 47.2, and 49.3, while the 97.5th percentile for sCr was 72.4, 69.2, 69.3, 63.9, and 66.0 μmol/L, respectively, in the sample of pregnant women. In the first and second trimesters, the average sCr value was 84.7% and 76.4% of that of the nonpregnant group, respectively. The mean eGFR increased up to 129.4 mL/min/1.73 m2 in the 24th week of gestation. The analysis of cohort data clearly confirmed a significant reduction in sCr with advancing pregnancy (p<0 .001). This study confirms the previously reported secondary-data-based thresholds, and the clinical validation of the upper limits proposed needs to be evaluated with pregnancy and new-born outcomes.
Evaluation of Thiamine as Adjunctive Therapy in COVID-19 Critically Ill Patients: A Multicenter Propensity Score Matched Study
Authors: Sulaiman Khalid Al , Aljuhani Ohoud , Dossari Maram Al , Alshahrani Asma , Alharbi Aisha , Algarni Rahmah , Jeraisy Majed Al , Harbi Shmeylan Al , Katheri Abdulmalik Al , Eidan Fahad Al , Bekairy Abdulkareem M. Al , Qahtani Nouf Al , Muqrin Mashael Al , Vishwakarma Ramesh , Ghamdi Ghassan Al
Published: April 2021

Background: Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate (TPP) required for glucose metabolism; it improves the immune system function and has been shown to reduce the risk of several diseases. The role of thiamine in COVID-19 critically ill patients is still unclear, however, its role in the critically ill septic patient has been addressed in multiple studies. The objective of this study was to evaluate the use of thiamine as adjunctive therapy on the mortality in COVID 19 critically ill patients. Methods: This is a multicenter, non-interventional, retrospective cohort study for all critically ill patients admitted to intensive care units (ICUs) with a confirmed diagnosis of COVID19. All patients aged 18 years or older who were admitted to ICUs between March 1st to December 31st, 2020 with positive PCR COVID-19 were included in the study. We investigated the association between thiamine use as an adjunctive therapy and clinical outcomes in COVID -19 after propensity score matching using baseline severity scores, systemic use of corticosteroids and study centers. Results: A total of 738 critically ill patients with COVID-19 who had been admitted in ICUs at the two governmental hospitals included in the study. Among 166 patients matched using propensity score, 83 had received thiamine as adjunctive therapy. There was significant association between thiamine use with in-hospital mortality (OR=0.49; 95% CI = 0.25- 0.97; P=0.04) as well with 30-day ICU mortality (OR=0.45; 95% CI = 0.215- 0.935; P=0.03). Moreover, patients who received thiamine as an adjunctive therapy were less likely to have thrombosis during ICU stay by 81 % (OR (95%CI): 0.19 (0.040,0.884), p-value=0.034).Conclusion: Thiamine use as an adjunctive therapy may have potential survival benefits in critically ill patients with COVID-19.
Network Pharmacology to Explore Active Components and Pharmacological Mechanism of Action of Compound Longmaining for the Treatment of Myocardial Infarction
Authors: Li Jia , Wang Wenfei , Bu Diaodiao , Zou Junbo , Wang Yao , Jia Yanzhuo , Yu Shangshang , Zheng Jiahui , Zhang Xiaofei , Wang Changli
Published: April 2021

Background and objective: Myocardial Infarction (MI) is a cardiovascular disease with a high morbidity and mortality rate. While MI is currently treated with pharmaceuticals, there is a need for new treatment options: compound Chinese medicines may have unique advantages for the treatment of MI. In this study, we used network pharmacology to explore the molecular mechanisms of action of Compound Longmaining (CLMN) decoction as a potential treatment approach.Methods: Chip data related to Myocardial Infarction were downloaded from the GEO database and genes from GSE48060 and GSE66360 chips were obtained by R language. The targets of active components of CLMN and myocardial infarction disease were predicted by network pharmacology. After intersection analysis, the core targets were obtained and functional enrichment analysis was carried out. CLMN biological activity was verified by molecular docking prior to establishing a mouse MI model to verify efficacy using hematoxylin-eosin (HE) staining and immunohistochemistry.Results: KEGG pathway analysis showed that TNF, IL1B, PTGS2, VCAM1, and NFKBIA which mainly act on NF-kappa B pathway contribute to the anti-inflammatory effects of CLMN. Immunohistochemical analysis showed that TNF-α and TRAF-2 expression levels in MI of CLMN-treated mice were decreased, while IkBα was increased (P < 0.05). HE staining showed CLMN reduced inflammation in mouse cardiomyocytes and decreased fibrosis.Conclusion: CLMN regulates the NF-kappa B signaling pathway and the expression of TNF, IL1B, PTGS2, VCAM1 and NFKBIA. Chemical analysis showed that CLMN active components such as Daidzein-4,7-diglucoside, rutin and puerarin may be responsible for the therapeutic effect of the decoction.
A DFT Study of the Impact of Doping on the Electronic and Optical Properties of Indium Nitride Nanocage
Authors: Das Amarjyoti , Yadav Rajesh Kumar
Published: April 2021

Density functional theory (DFT) calculations are used to investigate the structural, electronic, and optical properties of the significant fullerene-like cage of In12N12 nanoclusters with Zn (group II) and Si (group IV) dopants. In terms of formation energies and binding energies, the structural stability of the nanocages were studied. It has been seen that stability of the structure is slightly increases with the inclusion of doping. The study found that both the dopants significantly reduce the energy gap of the In12N12 nanocluster. The electronic properties of the In12N12 nanocluster seems to be sensitive to dopants, and it could be altered by a specific impurity. Moreover, electronic properties such as density of states (DOS) analysis, dipole moment, HOMO energies, LUMO energies, energy gaps, chemical potential, electron affinity, ionization potential, hardness, and electrophilicity index are also discussed. The optical absorption spectra of pure and doped nanocages were computed using TDDFT formalism. The maximum wavelength of the pure In12N12 nanocage is moved towards higher wavelength region within the infrared region after doping with Zn and Si, indicating a redshift.
Identification of Oncosuppressing Effects of Seven Selenoproteins in Thyroid Cancer: Implications for Distinct Roles of Selenoproteins in Tumorigenesis
Authors: Zhao Yang , Chen Pu , Lv Hong-jun , Wu Yuan , Liu Shu , Deng Xueyang , Fu Jiao
Published: April 2021

Background: Low selenium levels are associated with increased incidence and advanced stage of thyroid cancers. In response to changes in selenium levels, a hierarchy of selenoprotein biosynthesis allows tissue-specific fine-tuning of the 25 selenoproteins. To determine the role of individual selenoproteins on thyroid carcinogenesis, we carried out a multiomic data mining study.Methods: The expressions of individual selenoproteins and their correlation with prognosis in thyroid cancers were analyzed using Oncomine, GEPIA and Kaplan–Meier plotter platforms. Co-expression analysis using cBioportal database was carried out to identify genes that are correlated with selenoproteins. GO and KEGG enrichment were further performed for genes correlated with selenoproteins that are clinically significant.Results: DIO1, GPX3, SELENOP, SELENOM SELENOS, SELENOO and SELENOV were significantly downregulated and with a poor prognosis in thyroid cancers. 35 biological processes including GO: 0045926 (negative regulation of growth) and 23 biological processes including GO:0001525 (angiogenesis) and GO:0007155 (cell adhesion) were enriched in DIO1-positively and DIO1-negatively correlated genes, respectively. 41 biological processes including GO: 0045926 (negative regulation of growth) and 23 biological processes including GO:0007165 (signal transduction) and GO: 0000165 (MAPK cascade) were enriched in GPX3-positively and GPX3-negatively correlated genes, respectively. The antitumor effects of SELENOM and SELENOS might be attributed to their protection against endoplasmic reticulum (ER) stress. SELENOO was revealed to be correlated with ER stress, mitochondria translation and telomere maintenance. Biological processes of SELENOV-correlated genes were enriched in oxidation-reduction process and ER calcium ion homeostasis. Moreover, cell adhesion and angiogenesis were also shown to be negatively regulated by SELENOV, providing an anti-metastatic effect similar as DIO1.Conclusion: This study confirms the distinct roles of the 25 selenoproteins in thyroid cancer pathogenesis, providing useful information to uncover the currently unknown functions of selenoproteins and open up the possibility for targeted regulation of individual selenoproteins for treatment of thyroid cancer.
Immunoinformatic Responses of Host MHC I/II and CD4+ Cells Against Conserved Spike Fragments of SARS CoV-2 of 186 Countries With In-Silico Mutations: Implications in Universal Vaccination
Authors: Maiti Smarajit , Banerjee Amrita , Kanwar Mehak , Santra Dipannita
Published: April 2021

Different types of quickly-developed vaccines have been introduced against Covid-19 with largely inconclusive results. On the course of time, somewhere Covid-19 declines its infection/mortality rate and in some countries it revived with some new mutant-variants. Considering the large number of global variants, in the current study several conserved (186 countries) sequences (checked by ClustalX2) epitopic regions (by SVMTriP and IEDB) and in-silico mutants of SARS CoV-2 spike protein fragments (Cut 1-4) were screened for their stability against proteases, antigenicity (VaxiJen V2.0 and for glycosylation effects NetOGlyc-NetNGlyc), MHCI/II reactivity (IEDB TOOLS) and CD4+ cellular responses utilizing Haddock 2.4 and PatchDock programme. The cut4 mutant and its peptide SRLFRKSNLKPFERD showed highest combined-score 48.23548 and Immunogenicity-Score of 92.0887. The core-sequence SRLFRKSNL showed highest Median Percentile Rank (7 HLA-allele) of 19. CD4+ immunogenicity also confirms representation of CUT4TM2 epitope SRLFRKSNL by MHC Class II. The epitope YNYKYRLFR from CUT4 showed IC50 value of ~30 nM with allele HLA-DRB1*11:01 and HLA-DRB5*01:01. Binding affinity and RMSD score suggest that different epitopic regions of Cut4 mutants interacted MHC II with large number of H-bonds. Cut4 double mutants strongly interacted with exposed T-cell surface and facilitated by its receptors. According to the antigenicity analysis, epitopes 3, 4, and 5 were the potent antigens with antigenicity values of 0.6268, 1.2404, and 0.4639, respectively. Screening of conserved SARS CoV-2 spike fragments globally may help to find most stable antigenic determinant and further their mutation-engendered counterparts have better immunogenic responses. Further studies are necessary to develop global vaccination strategies against Covid-19.
Engineered Endolysin-based "Artilysins" for Controlling the Gram-negative Pathogen Helicobacter Pylori
Authors: Xu Dengyuan , Zhao Shanshan , Dou Jun , Xu Xiaofeng , Zhi Yanyan , Wen Liangzhu
Published: April 2021

Helicobacter pylori infection can cause a variety of gastrointestinal diseases. In severe cases, there is a risk of gastric cancer. Antibiotics are often used for clinical treatment of H. pylori infections. However, because of antibiotic overuse in recent years and the emergence of multidrug-resistant bacteria, there is an urgent need to develop new treatment methods and drugs to achieve complete eradication of H. pylori. Endolysins and holins encoded by bacterial viruses (i.e., phages) represent a promising avenue of investigation. These lyase-based antibacterial drugs act on the bacterial cell wall to destroy the bacteria. Currently, a type of endolysin that has been studied more frequently acts on the amide bond between peptidoglycans, and holin is a transmembrane protein that can punch holes in the cell membrane. However, as a Gram-negative bacterium, H. pylori possesses a layer of impermeable lipopolysaccharides on the cell wall, which prevents endolysin interaction with the cell wall. Therefore, we designed a genetic linkage between an endolysin enzyme and a holin enzyme with a section of polypeptides (e.g., polycations and hydrophobic peptides) that enable penetration of the outer membrane. These complexes were designated “artilysins” and were efficiently expressed in Escherichia coli. In vitro bacteriostasis experiments showed that the purified artilysins had strong bacteriostatic effects on H. pylori. In addition, the surface of H. pylori was perforated and destroyed, as confirmed by electron microscopy, which was proved that artilysins had bacteriolytic effect on H. pylori.
Mental Health Contact Episodes in the Year Prior to First Adult Imprisonment Among Men Who Inject Drugs in Victoria, Australia
Authors: Stewart Ashleigh Cara , Cossar Reece , Wilkinson Anna Lee , Quinn Brendan , Dietze Paul , Walker Shelley , Winter Rebecca , Curtis Michael , Stoové Mark
Published: April 2021

Background: People in prison experience higher rates of mental illness than the general community, and commonly have cooccurring histories of drug dependence. While patterns of mental health service contacts following prison release have been extensively described, limited research has explored histories of service contacts prior to adult imprisonment. We describe public mental health contacts in the 12 months prior to first adult imprisonment among a cohort of men recruited in prison in Victoria, Australia, with recent histories of injecting drug use (IDU).Methods: Retrospective data from two administrative databases — public mental health service contacts from the Victorian state-wide public mental health database and imprisonment episodes from Corrections Victoria — were linked to primary data from the Prison and Transition Health (PATH) cohort study. We describe patterns of mental health contact episodes (contact days) and contact types, including continuing community care (categorised as non-urgent care) and crisis/emergency contacts (categorised as urgent) in the 12 months prior to participants’ first adult imprisonment.Results: Among 400 participants, 60 (15%) had contact with a mental health service in the year prior to their first adult imprisonment, accounting for 861 contact episodes [median 5; interquartile range (IQR) 2–11]. The median days between last contact and imprisonment was 52 (IQR 7–116) and the median days between contacts was three (IQR 1–7). Of the total contacts, 52% (n=450/861) were for continuing community care and 27% (n=234/861) involved crisis assessment treatment; 42 (70%) participants with mental health service contacts had at least one crisis/emergency contact within one year of their first adult imprisonment. ­Conclusion: We found that 15% of a cohort of men with histories of IDU had mental health service contacts in the 12 months prior to their first adult imprisonment. These contacts were typically frequent and more than one in four involved crisis/emergency care. These findings highlight significant vulnerabilities and potential missed opportunities for intervention early in offending trajectories. Further research is required to understand how these vulnerabilities can be better identified and more appropriately addressed in-community to reduce pathways into prison.
Prevalence of maternal Group B Streptococcus rectovaginal colonization among pregnant women in Ethiopia: protocol for a systematic review and meta-analysis
Authors: Bekele Delayehu , Assefa Dawit Getachew , Gudu Wondimu , Wondafrash Mekitie , Tolu Lemi Belay
Published: April 2021

Background: Rectovaginal colonization with Group B streptococcus (GBS) during pregnancy is an important risk factor for serious infections including neonatal sepsis, pneumonia, and meningitis. It is also associated with stillbirth and preterm birth. Since globally rates of GBS colonization, as well as rates of vertical transmission to the newborn, differ broadly, having national data is important for implementing strategies to reduce neonatal morbidity and mortality as a result of GBS infection. We propose this systematic review and meta-analysis to describe the prevalence of rectovaginal GBS colonization, rate of vertical transmission, and the antibiotic resistance pattern among third trimester pregnant women in Ethiopia.Methods: A systematic search will be done of PubMed (MEDLINE), EMBASE, CINHAL, and Cochrane Library. In addition, google scholar will be searched, and a reference list of the already identified articles will be checked to find additional eligible articles that were missed during the initial search. Two reviewers will screen all retrieved articles and assess the methodological quality of included studies using the Newcastle-Ottawa Scale (NOS) checklist. Any disagreement between two reviewers will be resolved by a third reviewer. We will extract data using the JBI data extraction tool for the systematic review of prevalence studies. The data analysis will be conducted using Stata Statistical Software: Release 15. We will present pooled estimates of the prevalence of GBS colonization and rates of vertical transmission with a 95% confidence interval.Discussion: This will be the first synthesis of data on GBS during pregnancy at a national level. It will inform decision-makers in determining whether a universal or a risk-based screening strategy is most appropriate, as well as guiding them in adopting an intrapartum antibiotic protocol.Registration: Submitted to PROSPERO on 18/03/2021
Malignant Phyllodes Tumor With Metastases to the Femur the Lung and Bilateral Axillas: A Case Report and Review of Literature
Authors: Zhou Jie-Yu , Fu Wei-Da , Gu Jun-Wei , Lu Kang-Kang , Guo Gui-Long
Published: April 2021

Background: Phyllodes tumor is rare accounting for <1% of all breast tumors. It is classified as benign, borderline, or malignant.The lymph node is involved rarely, and the most common metastasis path is through hematogenous channels mainly to the lung the pleura and the bone. Case presentation: This case report presents a 34-year-old woman suffered from metastases to the femur the lung and bilateral axillas from a malignant phyllodes tumor in 9 years. The most recent recurrence was discovered on bilateral axillas. The patient accepted adjuvant chemotherapy. However, because no obvious benefit of chemotherapy was found, the patient received bilateral axillary lymph node dissection finally. Genetic testing after surgery showed tumor-specific mutations and mutations about thepolymorphism of drug metabolism-related enzymes. Conclusions: The primary treatment modality for phyllodes tumor is surgery. For metastases, adjuvant chemotherapy may be efficient. However, when the effect of chemotherapy is not obvious, aggressive surgical therapies should be performed. Besides, genetic testing can provide advices on effective treatments.
Supplier's cooperation strategy with two competing manufacturers under wholesale price discount contract considering technology investment
Authors: Yang Shanxue , Liu Hongwei , Wang Guoli , Hao Yifei
Published: April 2021

Cooperation between upstream suppliers and downstream manufacturers in technology investment is a popular way to improve production technology for reducing suppliers' production costs of key components. Technology investments undertaken by manufacturers and wholesale price discount contract provided by suppliers have an important impact on their cooperation. This paper explores whether a supplier should cooperate with two downstream competing manufacturers to accept their technology investments to reduce the supplier's production cost of a key component. Specifically, we consider the following three cooperation strategies: the supplier does not accept manufacturers' technology investments, only accepts one manufacturer's technology investment and accepts both manufacturers' technology investments. Our results demonstrate that the wholesale price discount contract and the technology investment can enhance the profits of the supplier and two manufacturers when the discount degree is low. Further, we conclude that when the discount degree is relatively low or when the discount degree and the technology investment efficiency are relatively high, the supplier's optimal cooperation strategy with two manufacturers is to accept both manufacturers' technology investments for reducing the supplier's production cost of the key component and both manufacturers are also willing to invest simultaneously. At last, we extend the model to the asymmetric potential market size and show that our theoretical results are robust.
Total Synthesis of (±)-Decursivine via BINOL-Phosphoric Acid Catalyzed Tandem Oxidative Cyclization
Authors: Parvatkar Prakash T. , Smotkin Eugene S. , Manetsch Roman
Published: April 2021

Synthesis of tetracyclic indole alkaloid (±)-decursivine was accomplished through BINOL-phosphoric acid catalyzed tandem oxidative cyclization as a key step with hypervalent bis(trifluoroacetoxy)iodo)benzene (PIFA) as an oxidizing agent. This represents one of the shortest and highest yielding route for the synthesis of (±)-decursivine from readily available starting materials.