bluuebunny/crossref_metadata_2025 huggingface dataset:
Salivary Inflammatory Biomarkers and Glycated Haemoglobin among Patients with type 2 Diabetic Mellitus
Authors: Agho Ekhosuehi , Owotade Foluso , Kolawole Babatope , Oyetola Elijah , Adedeji Tewogbade
Published: December 2020

Objectives: This study investigated the association of selected salivary inflammatory biomarkers (Interleukin 6 [IL-6], C-reactive protein [CRP], and Tumour necrosis factor α [TNF-α]) to glycated haemoglobin (HbA1C) in type 2 diabetics.Materials and Methods: Seventy-five participants, 39 type 2 diabetics (52%) and 36 (48%) healthy controls were recruited. Saliva and blood samples were collected for each participant. The levels of selected salivary inflammatory biomarkers (IL-6, CRP and TNF-α) were estimated by Enzyme Linked Immunosorbent Assay (ELISA) method and glycated haemogloin (HbA1C) was estimated using the liquid chromatography method. Periodontal status of the participants were determined using the Basic Periodontal Examination (BPE). Results: The mean salivary levels of CRP was significantly higher in diabetics, 0.05±0.04 µg/ml than in controls, 0.02±0.02 µg/ml (p<0.001). Mean TNF-α was also significantly higher in diabetics, 5.39±12.10 pg/ml than in controls, 1.51± 3.66 pg/ml (p=0.036). Mean salivary IL-6 was also higher in diabetics compared with controls (47.20±18.49 versus 41.94±16.88 pg/ml), but the difference was not statistically significant, p=0.204. In the multivariate analysis adjusting for age and periodontal status, only the mean salivary CRP was significantly higher in diabetics, 0.034 higher than controls (95% CI 0.009, 0.059 and p= 0.01). There was a positive correlation between salivary CRP and HbA1C levels, which was moderate with r-value 0.4929 and p-value <0.0001. Conclusions: Salivary inflammatory biomarkers especially CRP are higher in diabetics compared with controls and CRP is positively correlated with serum HbA1C levels. The biomarkers show potentials as non-invasive alternative method to evaluate glycaemic control in diabetes.
Radical Nephrectomy Provides a Worse Prognosis Than Partial Nephrectomy in T3aN0M0 Renal Cancer of Small (≤4 cm) Size and No Invasion of Perisinus Fat
Authors: Liu Shiliang , Wang Zhixian , Liu Chang
Published: December 2020

Background: Radical nephrectomy (RN) is the recommended treatment for T3aN0M0 renal cell carcinoma (RCC). However, it is not necessarily the best treatment for small T3aN0M0 RCCs. We evaluated the effect of tumor size combined with consideration of anatomic types of extrarenal-fat invasion on the surgical decision-making between partial nephrectomy (PN) vs. RN in T3aN0M0 RCC.Methods: Data were obtained from the Surveillance, Epidemiology, and End Results database (2004 to 2015) with 6125 patients suffering from T3aN0M0 RCC. Cox and Fine and Gray models were used for survival analyses. Propensity-score matching was used for PN vs. RN.Results: A larger T3aN0M0 RCC was associated with higher risk of mortality (hazard ratio (HR)all-cause mortality: 1.07, 95% confidence interval (CI): 1.02–1.13, P = 0.011; HRRCC-cause mortality: 1.13, 95%CI: 1.06–1.21, P < 0.001) compared with a small T3aN0M0 RCC. After propensity-score matching, in T3aN0M0 ≤4 cm, RN compared with PN significantly increased the risk of death (HR: 1.77; 95%CI: 1.14–2.74, P = 0.011) and offered no significant difference in RCC-specific survival (HR: 1.57, 95%CI: 0.74–3.36, P = 0.240). However, RN and PN showed no significant difference in overall survival in T3aN0M0 RCC >4 cm (HR: 0.98; 95%CI: 0.59–1.62, P= 0.929) or in T3aN0M0 RCC with sinus/perisinus-fat invasion (HR: 1.18; 95%CI: 0.61–2.27, P = 0.631).Conclusion: PN provided better overall survival compared with RN for small (≤4 cm) T3aN0M0 RCCs without sinus/perisinus-fat invasion. Focusing only on anatomic-invasion characteristics rather than type and tumor size is not sufficient for treatment decisions in T3aN0M0 RCC.
Naturally occurring phytochemical as inhibitors from Catharanthus roseus: An In-silico approaches for drug development against COVID-19
Authors: Kalaria Rishee K. , Patel Hiren K.
Published: December 2020

The current outbreak of the novel 2019 Coronavirus disease (COVID-19) is caused by SARS-CoV-2, has developed a threat to the world's human population. There are no effective therapies or vaccines yet, urging the serious efforts to tackle this pandemic situation.SARS-CoV-2 spike protein, papain like protease protein (PLPRO), main protease (3CLpro) and RNA dependent DNA polymerase are key factors in the virus infectious process and have been identified as potential targets for therapeutic formulation. Most people in India depend on conventional Indian medicine (phytochemical compounds) to treat diseases due to lower cost, easier accessibility and no adverse effects. A lot of studies have recently shown that phytochemicals contain an effective anti-viral activity. This study aims to investigate phytochemicals metabolites from the IMPPAT database (Indian Medicinal Plants Database) in order to identify potential COVID-19 inhibitors using in silico approaches. Certain phytochemical compounds with structure analogs like hydroxychloroquine and chloroquine from the IMPPAT database were taken for interaction with SARS-CoV-2 proteins. The Apparicine, 12-Chlorotabersonine, AC1NSULH and Vindolininol identified from Catharanthus roseus were further checked the ADMET property as well as ‘Lipinski’s rule and resulted in a strong binding affinity of (-7.6,-7.5) and (-7.6 -7.5) kcal/mol respectively for spikes and papain like protease protein of SARS-CoV-2. Our results indicate that these specific compounds can be used as effective inhibitors and help to pace up the drug development against SARS-CoV-2. Further investigation and testing of these inhibitors against SARS‐CoV‐2 are however required to check their clinical trial candidacy.
Association of Household Socioeconomic Status, Neighborhood Support System and Adherence to Dietary Recommendation among Persons with T2DM, a Facility-based Cross-sectional Study in Ghana
Authors: Doglikuu Be-Ikuu , Abdulai Abubakari , Yaseri Mehdi , Shakibazadeh Elham , Djazayery Abolghassem , Mirzaei Khadijeh
Published: December 2020

Background: Dietary recommendation help persons with diabetes adopt healthy eating habits to achieve optimal glycemic control. Socioeconomic-status and neighborhood support system could influence adherence to dietary recommendation. The purpose of our study is to assess the association of household-socioeconomic status and neighborhood-support system with adherence to dietary recommendation among persons with type 2 diabetes mellitus (T2DM). Methods: Facility-based cross-sectional-survey was conducted among 530 individuals with T2DM in Brong Ahafo region, Ghana. Six hospitals were randomly selected and persons with T2DM consecutively recruited from the selected hospitals into the study. Structured-questionnaires were used to collect socio-demographic variables. Adherence to dietary recommendation was the outcome -variable, and was assessed using perceived dietary adherence questionnaire. Results: Age (years) (P-value=0.01), place of residence (P-value =0.01), educational level (P-value =0.01) and occupation (P-value =0.01) were significantly correlated with socioeconomic status (P-value 0.01). Age (years) regression coefficient (β) -0.089, 95%CI (-0.12, -0.001), Being married β0.103, 95%CI (0.002, 0.02), moderate and low-social support system β 0.309, 95%CI(0.17, 0.38) and β-0.192, 95%CI(-0.26, -0.06) respectively, and high-socioeconomic status β 0.197, 95%CI(0.06, 0.25) were significantly associated with adherence to dietary recommendation.Conclusion: We found that social-support system and socioeconomic-status could be associated with adherence to dietary recommendation. Therefore, health workers should consider that patients’ social support system and socioeconomic status could be modifiable factors for optimum adherence.
The long shadow of childhood cancer: A qualitative study on insurance hardship among survivors of childhood cancer
Authors: Hendriks Manya J , Harju Erika , Roser Katharina , Ienca Marcello , Michel Gisela
Published: December 2020

Background

The long-term consequences of childhood cancer have received increasing attention due to the growing number of survivors over the past decades. However, insurance hardships of survivors and their families are mostly unknown. This study explored qualitatively, in a sample of childhood cancer survivors (CCS), (i) the experiences and needs of CCS living in Switzerland with a special focus on hardships related to insurance; and (ii) the views of insurance and law experts with experience on childhood cancer.
Methods

Semi-structured interviews were conducted with 28 childhood cancer survivors and 3 experts (one legal expert, two insurance experts). Data was analysed using qualitative content analysis.
Results

Three key themes emerged from the interviews with the CCS: 1) experiences with insurance, 2) perception of discrimination, and 3) needs and barriers for support. The interviewed experts provided further detailed clarification of CCS’ concerns. Our findings indicated that some CCS can move past their cancer history, while others continue to face hardships. CCS reported confusion about the opportunities and services within the social security system and most relied on their personal contacts for guidance. Finally, CCS expressed a strong need for socio-economic and legal support for social insurance questions, especially related to disability insurance.
Conclusions

With the growing population of CCS, it is essential to further assess the interplay between medical and psychosocial health and socio-economic hardship. Supportive psychosocial services should aim to ameliorate insurance hardships. Better understanding of the relationship between childhood cancer and insurance hardships during survivorship will inform efforts to improve long-term financial security and health outcomes for survivors. We call for the public, lawmakers, researchers, insurers, and patient organizations to come together and discuss future perspectives to avoid the risk of discrimination for cancer survivors.
Characteristics and Oncological Outcome of Clinical T3a Prostate Cancer Patients Undergoing Radical Prostatectomy in the Multi-Parametric MRI Era
Authors: Yoshitomi Kasumi , Yamamoto Shinya , Yamamoto Tatsuya , Fukagawa Eri , Hamada Kosuke , Yoneoka Yusuke , Fujiwara Motohiro , Fujiwara Ryo , Oguchi Tomohiko , Komai Yoshinobu , Numao Noboru , Yuasa Takeshi , Fukui Iwao , Yonese Junji
Published: December 2020

We aimed to reveal the association between the method of diagnosis (multi-parametric magnetic resonance imaging [mpMRI] and digital rectal examination [DRE]) and oncological outcomes of patients with clinical T3a (cT3a) prostate cancer after radical prostatectomy (RP) and stratify them according to oncological risk. We included 132 cT3a prostate cancer patients who underwent RP between 2008 and 2018. The biochemical recurrence (BCR)-free survival rate was evaluated according to the method of diagnosis (mpMRI alone; mpMRI group vs. DRE [with or without mpMRI]; DRE group). Several preoperative factors were evaluated in the multivariate analysis. Patients were divided into risk groups by our prediction model. The mpMRI group had significantly longer BCR-free survival than the DRE group (p<0.0001). The method of diagnosis (hazard ratio [HR]=2.69; 95% confidence interval [CI] 1.45-5.06; p=0.0017) and % positive cores (HR=4.36; 95% CI 1.14-16.5; p=0.031) were independent prognostic factors. Patients were divided into three risk groups based on these factors. There was a significant difference in BCR-free survival rate among the groups (p=0.0002).The method of diagnosis of cT3a prostate cancer was associated with BCR-free survival, and we categorized patients into risk groups. These assessments were attributable to the appropriate therapeutic strategy for patients with cT3a prostate cancer.
Experimental Study of Optical Properties of Polymeric Nanowires
Authors: Mbarek Mohamed , Altowyan Abeer , Almaymoni Nawal
Published: December 2020

The authors have requested that this preprint be removed from Research Square.
Insights about the Epidemiology of Salmonella Typhimurium Isolates from different Sources in Brazil using Comparative Genomics
Authors: Seribelli Amanda , Silva Patrick da , Cruz Marcelo da , Almeida Fernanda de , Frazão Miliane , Medeiros Marta , Rodrigues Dália , Kich Jalusa , Benevides Leandro , Soares Siomar , Allard Marc , Falcão Juliana
Published: December 2020

Background: Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) is an important zoonotic agent worldwide. In Brazil, there are few published studies that have characterized the possible differences of S. Typhimurium strains isolated from humans, foods and animal by whole genome sequencing (WGS). The aim of this work was to compare genetically 117 S. Typhimurium isolates from different sources from 30 years (1983 to 2013) in Brazil using different genomics strategies, including: phylogenetic analysis; orthologous protein clusters analysis; Multi-locus sequence typing (MLST); prophages and resistance genes screening related to efflux pumps. Results: The majority of the 117 S. Typhimurium strains studied were grouped into a single cluster (≅90%) by the genome core (cgMLST) and (≅77%) by single copy marker genes (ggTree). The different orthologous protein clusters found for some S. Typhimurium strains isolated from humans and food are involved in metabolic and regulatory processes. For 26 S. Typhimurium isolates from swine the sequence type (ST) 19 was the most common, the ST1921 was the second most prevalent and the STs 14, 64, 516 and 639 were also detected. The main prophages detected were: Gifsy-2 in 79 (67.5%) and Gifsy-1 in 63 (54%) S. Typhimurium isolates. All of the S. Typhimurium isolates contained the acrA, acrB, macA, macB, mdtK, emrA, emrB, emrR and tolC efflux pump genes. Conclusions: Phylogenetic analyses grouped the majority of the S. Typhimurium isolates into a single cluster suggesting that there is one prevalent subtype that has successful contaminated human, food and animal sources for 30 years in Brazil. The orthologous protein clusters analysis revealed unique genes in the S. Typhimurium studied mainly related to bacterial metabolism and that may be important in their pathogenicity. S. Typhimurium isolates from swine showed greater diversity of STs and prophages in comparison to S. Typhimurium strains isolated from humans and foods. The pathogenic potential of S. Typhimurium strains was corroborated by the presence of exclusive prophages of this serovar involved in their virulence. The high number of resistance genes related to efflux pumps is worrying and may lead to therapeutic failures when treatment is needed.
Dental Caries in Pakistan. A Systematic Review and Meta-analysis
Authors: Siddiqui Ammar Ahmed , Alshammary Freah , Mulla Mushir , Al-Zubaidi Saad M. , Afroze Eman , Amin Junaid , Amin Salman , Shaikh Sameer , Madfa Ahmed A. , Alam Mohammad Khursheed
Published: December 2020

BackgroundOptimum oral health is impossible to achieve without managing dental caries. The first step to manage dental caries at community level is to know its prevalence, and trend. Unfortunately, prevalence of dental caries at national/regional level is not known in many developing countries. Pakistan is of no exception. The present meta-analysis was planned to document prevalence of dental caries at national, as well as regional level. This paper will serve as baseline for making future health policies, and health promotion activities in the country.MethodsLiterature was searched through various databases, such as PubMed, SCOPUS, and Web of science using: "Prevalence", "Dental Caries", "Dental Decay" and "Severity" as keywords. Any study that reported prevalence of dental caries, and was conducted in Pakistani population was included. Thirty studies fulfilled the mentioned criteria, and was included. Quality assessment of all the included studies was performed using Joanna Briggs Institute (JBI) critical appraisal checklist for prevalence studies. MedCalc software was used to analyses the data.ResultsIn total 26952 subjects were included in meta-analysis from 30 studies. The prevalence estimate of dental caries at national level was 56.32 % (95% CI: 49.326 to 63.197). The I2 value was 99.07% (95% CI: 98.94 to 99.18), (I2 > 75%) indicating heterogeneity , hence pooled proportion was reported using random effect model. The prevalence estimate of dental caries in Sindh was 58.135% (95% CI: 43.906 to 71.705), and in Punjab it was 53.95% (95% CI: 44.179 to 63.57), whilst in Baluchistan and KPK combined was 51.17% (95% CI: 22.930 to 79.004).ConclusionBased on the existing data nearly 60 % of Pakistani population have dental caries. The proportion is almost same in all provinces. Most of the included studies found to be of high risk.
Research and Evaluation of a Cyberchondria Severity Scale in a Chinese Context
Authors: Hu Yixin , Shao Yunru , Zhang Xiaoyan , Maguire Phil , Wang Dawei
Published: December 2020

Background: Cyberchondria is the unfounded anxiety that results when people look up their medical conditions online and mistakenly diagnose themselves with serious illnesses. Such internet-derived medical anxiety can manifest itself in different ways across cultures. This study explores the unique nature of cyberchondria in the context of Chinese culture, identifying the risk factors for the condition and the possible negative outcomes.Results: An exploratory factor analysis (EFA) was used to highlight differences in the structure of the scale for Western and Chinese contexts. Through the process of the reliability and validity testing, a Chinese version of the Cyberchondria Severity Scale (C-CSS) was developed. Subsequent regression analysis indicated that three antecedents are effective predictors of cyberchondria, and that C-CSS is related to theoretically relevant outcomes.Conclusions: This study initially demonstrated the applicability of C-CSS to assess the severity of cyberchondria among Chinese undergraduates.
The Interplay Between Information Flux and Temporal Dynamics in Infraslow Frequencies
Authors: Golesorkhi Mehrshad , Tumati Shankar , Gomez-Pilar Javier , Stamatakis Emmanuel , Northoff Georg
Published: December 2020

Unlike the brain’s faster frequencies, the exact role of its more powerful infraslow frequencies (ISF, 0.01 – 0.1Hz) in information processing remains poorly understood. Do and how ISF process information? We investigate information processing and related temporal dynamics of ISF in resting and task state fMRI. To quantify information, we apply the Lempel-Ziv complexity (LZC), a measure of signal compression indexing information. The LZC is combined with direct measurement of the dynamics of ISF themselves, namely their power spectral density by median frequency (MF). We demonstrate the following: (I) topographical differences in resting state between higher- and lower-order networks, showing statistically lower LZC in the former; (II) task-related changes in LZC; (III) modulation of LZC associated with MF changes, with low and high MF resting-state values correlated with different degrees of LZC change. In sum, we provide evidence that ISF carry and process information as mediated through their temporal dynamics.
‘Pediatric Bipolar Disorder’ Rates are Still Lower than Claimed – A Re-examination of Eight Epidemiological Surveys used by an Updated Meta-analysis
Authors: Parry Peter , Allison Stephen , Bastiampillai Tarun
Published: December 2020

Background: ‘Pediatric bipolar disorder’ (PBD) is a controversial diagnosis with varying rates of clinical diagnosis. A highly cited meta-analysis (Van Meter et al. 2011) of a dozen epidemiological surveys suggested a global community prevalence of 1.8%. This was further updated to 3.9% with eight additional surveys (Van Meter et al. 2019a). A narrative analysis (Parry et al. 2018) of the original 12 surveys concluded rates of PBD were substantially lower than 1.8% and led to a nine-article debate on the validity, overdiagnosis and iatrogenic aspects of the PBD diagnosis (e.g. Carlson and Dubicka 2019). This article extends the narrative analysis to include the eight newer community surveys.Methods: In terms of the Cochrane Handbook for Systematic Reviews of Interventions, the heterogenous community surveys were arguably unsuitable for statistical meta-analysis and warranted a narrative analysis.Results: Across all twenty surveys there was significant variation in methodologies and reported prevalence rates. Of the eight newer surveys, five (two Brazilian, one English, one Turkish, one United States) provided information of pre-adolescent rates of bipolar spectrum disorder. These pre-adolescent rates were zero or close to zero. Rates of adolescent hypomania/mania were higher, but follow-up data suggested most hypomania did not progress to adult bipolar disorder.Limitations: Methods in the original surveys vary and criteria used for various bipolar diagnoses were not always fully described. This limitation applies to a narrative analysis but also to a statistical meta-analysis.Conclusion: Bipolar disorder is very rare in childhood and rare in adolescence. PBD as a diagnostic construct fails to correlate with adult bipolar disorder and the term should be abandoned. Hypomanic syndromes in adolescence may not progress to adult bipolar disorder. Early diagnosis of bipolar disorder is important, but over-diagnosis risks adverse iatrogenic consequences.
The therapeutic effects of FGF21 on diabetic nephropathy are realized by augmenting autophagy via AMPK/mTOR signaling pathway
Authors: Meng Rui , Cao Yu , Khoso Mir , Kang Kai , Ren Gui , Xiao Wei , Li Deshan
Published: December 2020

Accumulating evidence demonstrates that FGF21 plays a preventive role in the development of diabetic nephropathy (DN). However, little is known about the therapeutical effects of FGF21 on DN and underlying mechanism. In this study, FGF21 significantly ameliorated blood glucose, HbAlc, insulin resistance, renal function and histopathological change in DN mice (BKS-Leprem2Cd479/Gpt), which develop abnormalities in renal morphology and function. Our results showed that administration of FGF21 upregulated the autophagy related genes LC3Ⅱ and BCL-1 mRNA and protein expression levels. D-glucose was used for high glucose (HG) model in mesangial cells. The results showed that treatment with FGF21 reduced the levels of ROS, AGEs and inflammatory cytokines and significantly downregulated the protein expression of PCNA. Meanwhile, FGF21 significantly enhanced the expression of LC3Ⅱ and BCL-1. Besides, Our studies showed that administration of FGF21 significantly upregulated the phosphorylation of AMPK and downregulated phosphorylation of mTOR. Meanwhile, the effects of FGF21 on autophagy were reversed by siRNA against β-klotho. In conclusion, The therapeutic effects of FGF21 on diabetic nephropathy are realized and FGF21 ameliorates mesangial cell glucotoxicity and abnormal proliferation in vitro by augmenting autophagy via AMPK/mTOR pathway. These results suggest that FGF21 can be a therapeutic target against DN.
Calcium Overload and Ros Accumulation Induced by Selenium Deficiency Promote Autophagy in Swine Intestine
Authors: Zheng Yingying , Guan Haoyue , Yang Jie , Cai Jingzeng , Liu Qi , Ziwei Zhang
Published: December 2020

Background:Selenium deficiency can seriously affect the intestinal status of swine, and cause diarrhea in swine. However, the specific mechanism of selenium intestinal injury caused by selenium deficiency is rarely reported.Methods:Here, to explore the damage of selenium deficiency on the calcium homeostasis and autophagy mechanism of swine, in vivo and in vitro models of swine intestinal selenium deficiency were established. The intestinal model of swine intestine was established by feeding different selenium concentrations. Besides, selenium-deficient medium and normal medium were used to culture IPEC-J2 cells to establish in vitro models. Morphological observation and cell staining were used to determine the way of intestinal injury, and gene expression was quantitatively detected by qPCR and WB.Results:Morphological observations showed that compared with the control group, intestinal cells in the Se-deficiency group were significantly damaged, and autophagosomes increased. MDC staining and cytoplasmic calcium staining results showed that in the Se-deficiency group, autophagy increased and calcium homeostasis was destroyed. Also, according to the ROS test results, the percentage of ROS in the Se-deficiency group is higher than the control group in the in vitro model. Compared with the control group, the protein and mRNA expressions of autophagy and calcium-related genes (Beclin1, LC3-1, LC3-2, ATG5, ATG12, ATG16, mTOR, CAMKK-β, AMPK, SERCA, calpain) in the Se-deficiency group were significantly increased which was consistent in vivo and in vitro. Under the influence of selenium deficiency, the mRNA expression level of selenoproteins decreased significantly, and the steady-state content of some elements was also destroyed. Conclusion:Altogether, our results indicated that selenium deficiency could destroy the calcium homeostasis and antioxidant homeostasis of swine intestine to trigger cell autophagy. Moreover, selenium deficiency reduces the overall expression of selenoproteins and affects the content of elements in the intestine.
Analysis of trace element levels in the nails in patients with colorectal cancer: Consider to the effects of chemotherapy or radiotherapy
Authors: Phuong Huynh Truc , Binh Dinh Thanh , Linh Nguyen Thi Truc , Loan Truong Thi Hong , Hanh Nguyen Van , Dung Ho Manh , Dong Nguyen Van , Anh Tran Tuan
Published: December 2020

Nails are considered as suitable biological materials for the diagnosis of diseases by measuring trace element levels. This study aimed to evaluate the role of trace elements in detecting the risk of colorectal cancer. Evaluating the effects of cancer treatment with chemotherapy or radiotherapy was also the aim of this study. The levels of trace elements in the nails of 104 patients with colorectal cancer and 112 healthy subjects were analyzed using the k0-standardization method of neutron activation analysis. The results showed that there were significant differences of the following elements, As, Fe, Hg, Sc, Se, and Zn between the control and the patient groups, while it was not the case for the elements Br, Co, and Cr. Furthermore, this study showed that there was no significant difference in the levels of the obtained trace elements in both colon and rectal cancer patient groups between untreated and treated subjects. We conclude that the levels of As, Hg, Fe, Se, and Zn in integrated samples of the fingernail and toenails may be used to evaluate the colorectal cancer risk, and they were not affected by chemotherapy or radiotherapy.
Facilitation of Reparative Dentin Using a Drug Repositioning Approach With 4-Phenylbutric Acid
Authors: Lee Eui-Seon , Aryal Yam , Kim Tae-Young , Kim Ji-Youn , Yamamoto Hitoshi , An Chang-Hyeon , An Seo-Young , Lee Youngkyun , Sohn Wern-Joo , Jung Jae-Kwang , Ha Jung-Hong , Kim Jae-Young
Published: December 2020

For hard tissue formation, cellular mechanisms, involved in protein folding, processing, and secretion play important roles in the endoplasmic reticulum (ER). In pathological and regeneration conditions, ER stress hinders proper formation and secretion of proteins, and tissue regeneration by unfolded protein synthesis. 4-Phenylbutyric acid (4PBA) is a chemical chaperone that alleviates ER stress through modulation in proteins folding and protein trafficking. However, previous studies about 4PBA only focused on the metabolic diseases rather than on hard tissue formation and regeneration. Herein, we evaluated the function of 4PBA in dentin regeneration using an exposed pulp animal model system via a local delivery method as a drug repositioning strategy. Altered morphological changes and cellular physiology were examined with histology and immunohistochemistry. The 4PBA treatment modulated the inflammation reaction and resolved ER stress in the early stage of pulp exposure. In addition, 4PBA treatment activated blood vessel formation and TGF-𝛽1 expression in the dentin-pulp complex. Micro-computed tomography and histological examinations confirmed the facilitated formation of the dentin bridge in the 4PBA-treated specimens. These results suggest that proper modulation of ER stress would be an important factor for secretion and patterned formation in dentin regeneration.
Factors Influencing the Reference Interval of Thyroid Stimulating Hormone in Healthy Adults: A Systematic Review and Meta-analysis
Authors: xing dongyang , Li Ri , Zhou Qi , Liu Delong , xu jiancheng
Published: December 2020

Background: Thyroid stimulating hormone (TSH) is an important indicator for evaluating thyroid function. Many studies have reported that the TSH reference interval is susceptible to external factors. This paper summarizes the related studies published in recent years and comprehensively analyzes the effects of these factors on the TSH reference interval in healthy people.Methods: Articles published from January 1980 to January 2020 were searched in PubMed, EMBASE, Cochrane, Scopus, Medline English databases and CNKI, WanFang and CQVIP Chinese databases. In total, 21 studies were ultimately included. All data were analyzed using Review Manager 5.3 software and STATA 16.0 software. Microsoft Excel 2010 was used to draw the TSH concentration curve changing with age, and GraphPad 6.0 was used to draw the TSH concentration curve with sex.Results: The TSH reference interval was significantly influenced by sex and age. The overall trend of TSH concentration reveals that males are lower than females. The TSH reference interval is divided into 20~59-year-old, 60~69-year-old and over 70-year-old age groups for males and 20~39-year-old, 40~49-year-old, 50~69-year-old and over 70-year-old age groups for females. Regardless of sex, TSH concentrations all increase with age. In iodine-deficient areas, TSH reference intervals are generally lower than those in iodine-sufficient or iodine-excessive areas. The TSH reference interval in Asia and North American countries is generally higher than that in most European countries. Even the detection methods are consistent, different detection instruments can affect the TSH reference interval. Sample size and race are also important factors.Conclusion: The TSH reference interval was significantly influenced by sex and age, race, region, iodine intake, sample size, detection instruments and methods, but other factors should not be ignored. Therefore, it is necessary for each laboratory to validate an appropriate TSH reference interval based on local conditions.
The Role of Entrainment in Human Walking: Energy Minimization in Oscillating Environments
Authors: Schroeder Ryan , Croft James , Bertram John
Published: December 2020

During locomotion, humans often entrain (i.e. synchronize) their steps to external oscillations: e.g. swaying bridges, tandem walking, bouncy harnesses, vibrating treadmills, exoskeletons. Previous studies have discussed the role of nonlinear oscillators (e.g. central pattern generators) in facilitating entrainment. However, the underlying benefits of entrainment are unknown. Given substantial evidence that humans prioritize economy during locomotion, we tested whether reduced metabolic expenditure accompanies human entrainment to vertical force oscillations, where frequency and amplitude were prescribed via a custom mechatronics system during walking. Although metabolic cost was not significantly reduced during entrainment, individuals who experienced negative work from oscillations had a higher cost than those who experienced positive work, and subjects generally selected phase relationships indicating the latter. It is possible that individuals use mechanical cues to infer energy cost and inform effective gait strategies. If so, an accurate prediction may rely on the relative stability of interactions with the environment. Our results suggest that entrainment is preferred over a wide range of oscillation parameters, though not as a direct priority for minimizing metabolic cost. Instead, entrainment may act to stabilize interactions with the environment, thus increasing predictability for the effective implementation of internal models that guide energy minimization.
Phylogenetic Relationships of Sucrose Transporters (SUTs) in Plants and Genome-wide Characterization of SUT Genes in Orchidaceae
Authors: Wang Yunzhu , Chen Yue , Wei Qingzhen , Wan Hongjian , Sun Chongbo
Published: December 2020

BackgroundSucrose is the primary form of photosynthetically produced carbohydrates transported long distance in many plant species, which significantly affects plant growth, development and physiology. Sucrose transporters (SUTs or SUCs) are a group of membrane proteins that play vital roles in mediating sucrose allocation within cells and at the whole plant level.ResultsIn this study, we investigated the relationship of SUTs in 24 representative plant species and performed a comprehensive analysis of SUT genes in three sequenced Orchidaceae species, Dendrobium officinale, Phalaenopsis equestris, and Apostasia shenzhenica. All the SUTs from 24 plants were classified into three groups and five subgroups: subgroups A, B1, B2.1, B2.2, and C, based on the evolutionary relationships. A total of 22 SUT genes were identified in Orchidaceae species, among which D. officinale had 8 genes (DenSUT01-08), P. equestris had 8 genes (PeqSUT01-08) and A. shenzhenica had 6 genes (PeqSUT01-06). For the 22 Orchidaceae SUTs, each of the subgroups A, B2.2 and C contains three genes, whereas the SUT genes were significantly expanded in the monocot-specific subgroup B2.1 which contained 12 genes. To shed light into sucrose partitioning and functions of sucrose transporters in Orchidacea species, we analysed water-soluble sugar content and performed RNA sequencing of different tissues of D. officinale, including leaves, stems, flowers and roots. The results showed that although total content of water-soluble polysaccharides was highest in the stems of D. officinale, the sucrose content was highest in flowers. Moreover, gene expression analysis showed that most of the DenSUTs were expressed in flowers, among which DenSUT01, DenSUT07 and DenSUT06 had significantly high expression levels.ConclusionsThese results indicated that stems are used as main storage sinks for photosynthetically produced sugar in D. officinale, and that the DenSUTs mainly take functions in the cellular machinery and development of floral organs. Our findings provide valuable information on sucrose partitioning and the evolution and functions of SUT genes in Orchidaceae and other species.
Diet-induced prediabetes: Effects on the systemic and renal renin-angiotensin-aldosterone system
Authors: Mkhize Bongeka , Mosili Palesa , Ngubane Phikelelani , Sibiya Ntethelelo , Khathi Andile
Published: December 2020

The activity of the renin-angiotensin-aldosterone system (RAAS) in type2 diabetes (T2D) has been characterized. However, the effects of high-fat high carbohydrate diet-induced prediabetes on the RAAS has not been elucidated. Hence, male Sprague Dawley rats were randomly assigned to a normal diet (NPD) group and (HFHC) group (n=6) for 20 weeks to allow for the induction of prediabetes. Blood glucose concentration, mean arterial pressure (MAP), kidney renin, angiotensinogen, angiotensin-converting enzyme (ACE), angiotensin II type 1a receptor (Agtr1a) in addition to kidney and plasma angiotensin II (Ang II), aldosterone were analyzed at week 20 to investigate the RAAS activity. In addition to kidney injury marker (Kim1) and urinary protein, concentrations were analyzed at week 20.
The results demonstrated an increase in blood glucose, MAP, relative expression of kidney RAAS components in the HFHC group by comparison to the NPD. Furthermore, an increase in plasma Ang II and aldosterone was accompanied by elevated Kim-1 and albumin excretion in the HFHC diet group by comparison to the NPD group. Thus, we suggest that the RAAS is activated in diet-induced prediabetes and may induce early kidney damage.
Cell-free DNA Comparative Analysis of Genomic Landscape of First-line Hormone-receptor Positive Metastatic Breast Cancer From US and China
Authors: Liu Xiao-Ran , Davis Andrew A. , Xie Feng , Gui Xinyu , Chen Yifei , Zhang Qiang , Gerratana Lorenzo , Zhang Youbin , Shah Ami N , Behdad Amir , Wehbe Firas , Huang Yong , Yu Jianjun , Du Pan , Jia Shidong , Li Huiping , Cristofanilli Massimo
Published: December 2020

Background: The differential mutation landscape between ethnics is more comparable when using the identical detecting platform.We explored the differences in genomic landscape of patients with hormone-receptor positive (HR+), HER2-negative MBC of first recurrence or Stage IV at diagnosis from the United States (US) and China (CN).Methods: Twenty-seven US patients and 65 CN patients had circulating tumor DNA (ctDNA) sequencing from plasma using the harmonized CLIA-certified, 152-gene PredicineCareTM liquid biopsy assay. Clinical outcomes were correlated with ctDNA variants. Progression-free survival (PFS) and overall survival analysis was performed for patients and compared using log-rank test. Results: Mutations were detected in 23 of 27 (85%) US patients and 54 of 65 (83%) CN patients. The most common mutations detected included TP53, PIK3CA, CDH1, AKT1, ESR1, and BRCA2 in both US and CN patients. AKT1(18.5% vs. 3.1%, P = 0.008) and CDH1 mutations were more frequent in the US population (18.5% vs. 1.5%, P = 0.021), and gain of FGFR1 was more common in the CN cohort (7.4% vs. 24.6%, P = 0.048). PTEN deletion (5.7 months vs. 13.2 months, P = 0.03) and ESR1 alterations (9.0 months vs. 13.2 months, P = 0.02) were associated with significantly shorter PFS in CN cohort. Conclusions: To our knowledge, this is the first real world study using a single harmonized ctDNA assay to profile plasma samples of patients from the US and CN. Differential prevalence of the mutations with therapeutic potential were found between US and CN.
Clinical Analysis and Long-term Treatment Monitoring of 3 Patients with Glycogen Storage Disease Type Ib
Authors: Du Caiqi , Li Zhuoguang , Wei Hong , Zhang Min , Hu Minghui , Zhang Cai , Luo Xiaoping , Liang Yan
Published: December 2020

Background To investigate the clinical and genetic characteristics of patients with glycogen storage disease type Ib (GSD Ib).Methods Retrospectively analyzed the clinical data of 3 patients with GSD Ib admitted into our hospital, and summarized their onset characteristics, clinical manifestations, related examinations and treatment as well as mutational spectrum.Results After gene sequencing, the diagnosis of GSD Ib was confirmed in all 3 patients. Five variants of SLC37A4 gene were detected, of which c. 572C>T was the common variant and c. 680G>A was a novel variant. The 3 cases of GSD Ib were mainly affected by liver enlargement, growth retardation, etc., and all had a history of repeated infections. At the onset, patients mainly manifested as mildly elevated alanine-aminotransferase (ALT), accompanied by decreased absolute neutrophil count (ANC), hypertriglyceridemia, and metabolic disorders (hypoglycemia, hyperlactic acidemia, metabolic acidosis, etc.). After long-term treatment by oral uncooked cornstarch, the abnormal liver enzymes gradually returned to normal, and metabolic abnormalities were basically controlled most of the time. With increasing age, ANC of the 3 patients decreased progressively, whereas the times of infections was reduced.Conclusions The possibility of GSD type Ib should be kept on alert when a patient suffers recurrent infections, accompanied by hepatomegaly, elevated liver enzymes，hypoglycemia, dyslipidemia, and metabolic disorders. At present, the treatment of GSD Ib is mainly a comprehensive intervention based on diet therapy, and it is necessary to be alert to the occurrence of infectious immune diseases such as inflammatory bowel disease during follow-up.
Plasmonics-Nanofluidics Metamaterial: An Ultrasensitive Platform for Terahertz biosensing and Quantitative Measurement of Molecules
Authors: Xie Mingzhen , He Jinchun , Liu Yu , Tian Huiyan , Zhan Xinyu , Xia Ke , Li Mengya , Marc Lamy de la Chapelle , Fu Weiling , Zhang Yang
Published: December 2020

Background: The terahertz spectroscopy has attracted enormous attention for label free chemical and biological sensing, due to the presence of molecular fingerprints and remote sensing capabilities. However, because of the strong absorption of THz waves in aqueous solutions, detecting liquid-phase biological samples by THz spectroscopy has encountered strong constraints. Results: Here, we demonstrate for the first time a rapid and label-free sensing for liquid-phase biological samples using THz spectroscopy based on microfluidic metasensors. The metasensors were integrated with microfluidic chip to precisely control the liquid sample thickness within 220 nanometer (MMS-N) and 50 micrometer (MMS-U). The metasensors include a periodic split ring resonator (SRR) with two resonant peaks in the THz range. The sensitivity(S) and corresponding figure of merit (FOM) of the two resonance peaks of MMS-N and MMS-U are analyzed with respect to different refractive index matching solution. Both the two resonance peaks of the metasensors are sensitive to the varies refractive index environment and high-frequency resonant of MMS-N shows the best sensitivity(~136GHz/RIU). In addition, the label-free biological sensing capability was conducted through qualitative and quantitative LDL and ox-LDL, where a shift of resonance frequency was observed as the LDL and ox-LDL concentration increased. Conclusions: The results indicated nanofluidic metasensor presented excellent sensing capability for liquid-phase molecular analysis by THz spectroscopy, and the proposed sensing system has the potentials to be developed as a rapid, label-free and highly sensitive detection tool for molecular analysis by THz sensing.
Lead Isotopic Constraints on the Provenance of Antarctic Dust and Relevant Atmospheric Circulation Patterns Prior to the Mid-Brunhes Event (~430 Kyr Ago)
Authors: Han Changhee , Burn Laurie , Vallelonga Paul , Hur Soon Do , Boutron Claude , Lee Sanghee , Hong Sungmin
Published: December 2020

A lead (Pb) isotopic record, covering the two oldest glacial-interglacial cycles (~572 to 801 kyr ago), from the European Project for Ice Coring in Antarctica Dome C ice core provides isotopic evidence for the provenance of dust in deep Antarctic ice prior to the Mid-Brunhes Event (MBE), ~430 kyr ago, characterized by less warm interglacials. The isotopic signatures suggest Patagonia and central-western Argentina (CWA) as the primary sources of dust in central East Antarctica during both pre-MBE glacials and interglacials, in concert with an equatorward shift of the southern westerly winds (SWW). The contribution from extra-Antarctic volcanic emissions appears to be important for non-dust Pb in the pre-MBE interglacial and intermediate climates, most likely due to the reduction of wet removal efficiency with a weakening of the hydrologic cycle. Our results show a close coupling of the Southern Hemisphere atmospheric circulation patterns to climatic conditions prior to the MBE.
An Initial Investigation of Accuracy Required for the Identification of Small Molecules in Complex Samples Using Quantum Chemical Calculated NMR Chemical Shifts
Authors: Yesiltepe Yasemin , Govind Niri , Metz Thomas O. , Renslow Ryan
Published: December 2020

The majority of primary and secondary metabolites in nature have yet to be identified, representing a major challenge for metabolomics studies that currently require reference libraries from analyses of authentic compounds. Using currently available analytical methods, complete chemical characterization of metabolomes is infeasible for both technical and economic reasons. For example, unambiguous identification of metabolites is limited by the availability of authentic chemical standards, which, for the majority of molecules, do not exist. Computationally predicted or calculated data are a viable solution to expand the currently limited metabolite reference libraries, if such methods are shown to be sufficiently accurate. For example, determining nuclear magnetic resonance (NMR) spectroscopy spectra in silico has shown promise in the identification and delineation of metabolite structures. Many researchers have been taking advantage of density functional theory (DFT), a computationally inexpensive yet reputable method for the prediction of carbon and proton NMR spectra of metabolites. However, such methods are expected to have some error in predicted 13C and 1H NMR spectra with respect to experimentally measured values. This leads us to the question–what accuracy is required in predicted 13C and 1H NMR chemical shifts for confident metabolite identification? Using the set of 11,716 small molecules found in the Human Metabolome Database (HMDB), we simulated both experimental and theoretical NMR chemical shift databases. We investigated the level of accuracy required for identification of metabolites in simulated pure and impure samples by matching predicted chemical shifts to experimental data. We found 90% or more of molecules in simulated pure samples can be successfully identified when errors of 1H and 13C chemical shifts in water are below 0.6 ppm and 7.1 ppm, respectively, and below 0.5 ppm and 4.6 ppm in chloroform solvation, respectively. In simulated complex mixtures, as the complexity of the mixture increased, greater accuracy of the calculated chemical shifts was required, as expected. However, if the number of molecules in the mixture is known, e.g., when NMR is combined with MS and sample complexity is low, the likelihood of confident molecular identification increased by 90%.
Childhood Onset Exercise Addiction or Atypical Anorexia Nervosa During Covid-19: Case Report
Authors: McNicholas Fiona
Published: December 2020

Background: Childhood-onset Anorexia Nervosa is recognised to be atypical in presentation, both in terms of degree and type of eating pathology, exercise and compensatory behaviours, with many falling short of full diagnostic criteria. Failure to consider an eating disorder diagnosis in youth who present with extreme weight loss may have serious immediate and long term impacts. However, failure to consider other non-organic causes of weight loss may be equally detrimental to the child’s health. Case Presentation: This case reports on the acute presentation of a 12-year old boy with no prior eating concerns, who presented to hospital in a severely malnourished state 8 weeks into lockdown. To compensate for Covid-19 induced restrictions on sporting activity, this boy had followed a self-imposed daily schedule of arduous exercise, without increasing his nutritional intake. The case report examines the clinical features suggestive of Anorexia Nervosa along with a discussion on the diagnostic differential of exercise addiction, and the treatment implications. The case report highlights the unintended consequences of the pandemic restrictions. Conclusion:Accepting that pre-pubertal onset of Anorexia Nervosa, may be atypical, it is important to maintain an open mind in cases without goal directed weight loss. Although weight loss was indeed significant in this case, its occurrence was due to an excessive exercise regime, originating perhaps as a coping strategy in response to Covid-19 restrictions, but becoming addictive and impairing in nature. Worldwide responses in an effort to halt the spread of Covid-19 pandemic have been far reaching, impacting children and families in ways hitherto never imagined. Clinicians need to be alert to potentially maladaptive coping strategies and atypical and altered pathways of presentations, especially in younger children. This case illustrates some of these features.