bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Inflammatory Markers are Inversely Associated with Heart Rate Variability Measures in type 1 Diabetes
Authors: Wegeberg Anne-Marie Langmach , Okdahl Tina , Fløyel Tina , Brock Christina , Ejskjaer Niels , Riahi Sam , Pociot Flemming , Størling Joachim , Brock Birgitte 
Published: May 2020

Abstract
Background A neuro-immune communication exists, and compiling evidence suggests that diabetic neuropathy and systemic inflammation are linked. Our aims were 1) to investigate biomarkers of the ongoing inflammation processes including cytokines, adhesion molecules and chemokines, and 2) to associate the findings with cardiovascular autonomic neuropathy in type 1 diabetes by measuring heart rate variability and cardiac vagal tone.Methods We included 104 adults with type 1 diabetes. Heart rate variability, time- and frequency domains, were calculated from a 24-hour Holter electrocardiogram, while cardiac vagal tone was determined from a 5-minute electrocardiogram. Cytokines (interleukin (IL)-1α, IL-4, IL-12p70, IL-13, IL-17 and tumor necrosis factor (TNF)-α), adhesion molecules (E-selectin, P-selectin and intercellular adhesion molecule (ICAM)-1) and chemokines (chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4 and C-X-C motif chemokine (CXCL)10) were assessed using a Luminex multiplexing technology. Associations between concentrations of inflammatory biomarkers and continuous variables of heart rate variability and cardiac vagal tone were estimated using multivariable linear regression adjusting for age, sex, disease duration and smoking.Results Participants with the presence of cardiovascular autonomic neuropathy had higher systemic levels of IL-1α, IL-4, CCL2 and E-selectin, than those without cardiovascular autonomic neuropathy. IL-1α, IL-4, IL-12, TNF-α and E-selectin were inversely associated with both sympathetic and parasympathetic heart rate variability measures (p>0.01).Conclusion Our results show that several pro- and anti-inflammatory factors, believed to be involved in the progression of diabetic polyneuropathy are associated with cardiovascular autonomic neuropathy, suggesting that these factors may also contribute to the pathogenesis of cardiovascular autonomic neuropathy. Our findings emphasize the importance of the neuro-immune regulatory system in the pathogenesis of neuropathy in type 1 diabetes.Trial registration: The study was approved by the North Denmark Regional Committee on Health Research Ethics (N2013-0077 and N2017-0045) and registered in public databases (Eudra CT 2013-004375-12 and clinicaltrials.gov NCT02138045.
Altered Metabolism of Mothers of Young Children with Autism Spectrum Disorder: A Case Control Study
Authors: Hollowood-Jones Kathryn , Adams James B. , Coleman Devon M. , Ramamoorthy Sivapriya , Melnyk Stephan , James S. Jill , Woodruff Bryan K. , Pollard Elena L. , Snozek Christine L. , Kruger Uwe , Chuah Joshua , Hahn Juergen 
Published: May 2020

Abstract
Background: Previous research studies have demonstrated abnormalities in the metabolism of mothers of young children with autism. Method: Metabolic analysis was performed on blood samples from 30 mothers of young children with Autism Spectrum Disorder (ASD-M) and from 29 mothers of young typically-developing children (TD-M). Targeted metabolic analysis focusing on the folate one-carbon metabolism (FOCM) and the transsulfuration pathway (TS) as well as broad metabolic analysis were performed. Statistical analysis of the data involved both univariate and multivariate statistical methods. Results: Univariate analysis revealed significant differences in 5 metabolites from the folate one-carbon metabolism and the transsulfuration pathway and differences in an additional 48 metabolites identified by broad metabolic analysis, including lower levels of many carnitine-conjugated molecules. Multivariate analysis with leave one-out cross validation allowed classification of samples as belonging to one of the two groups with 93% sensitivity and 97% specificity with five metabolites. Furthermore, each of these five metabolites correlated with 8-15 other metabolites indicating that there are five clusters of correlated metabolites. In fact, all but 5 of the 50 metabolites with the highest area under the receiver operating characteristic curve were associated with the five identified groups. Many of the abnormalities appear linked to low levels of folate, vitamin B12, and carnitine-conjugated molecules. Conclusions: Mothers of children with ASD have many significantly different metabolite levels compared to mothers of typically developing children at 2-5 years after birth.
Ayurveda botanicals in COVID-19 management: An in silico- multitarget approach
Authors: Borse Swapnil , Joshi Manali , Saggam Akash , Bhat Vedika , Walia Safal , Sagar Sneha , Chavan-Gautam Preeti , Tillu Girish 
Published: May 2020

Abstract
The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagiousdisease. Presently, existing anti-virals and disease-modifying agents are being repurposed to manage COVID-19. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific anti-viralsand immunomodulators.The objective of this study is to explore the immunomodulatory and anti-SARS-CoV-2 potential of key phytoconstituents from Ayurveda based Rasayana drugs, Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi) and Asparagus racemosus (Shatavari) using in silico approaches like network pharmacology, and molecular docking. The SWISS-ADME tool was used to predict the pharmacokinetic and pharmacodynamic (PK-PD) interactions and drug likeliness potential. Using these approaches we propose a library of phytomolecules with potential to be developed as phytopharmaceuticals for COVID 19 management.The plant extracts were prepared as per Ayurvedic procedures and a total of 31 phytoconstituents were identified using HPLC and MS studies. The network pharmacology model shows that these phytoconstituents possess the potential to modulate several immune pathways. Amongst the three botanicalsWithania somnifera was found to be the most potent immunomodulator through its potential to modulate T cell differentiation, NK cell cytotoxicity as well as T cell, B cell and NOD-like receptor signalling pathways.Molecular docking studies showed thatseveral phytoconstituents possess good affinity for the Spike protein, Main Protease and RNA dependent RNA polymerase of SARS-CoV-2 suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would beneficial herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of these Rasayana botanicals in the management of COVID-19 following rigorous experimental validation.
Transmissibility of SARS-CoV-2 during incubation period: Epidemiologic evidence from 178 confirmed clusters in China
Authors: Wu Yuyan , Liu Shelan , Sun Jimin , Gong Zhenyu , Ling Feng , Chen Zhiping , Chan Ta-Chien , Lin Junfen , Pan Jinren , Chen Enfu 
Published: May 2020

Abstract
An outbreak of novel coronavirus (SARS-CoV-2) was identified in China in December 2019, and has spread rapidly to more than 200 countries and areas in four months. A few studies have reported that transmissibility exists during the late incubation period based on one single infection cluster caused by SARS-CoV-2. Here based on 178 SARS-CoV-2 clusters confirmed in Zhejiang Province, we analyzed the epidemic link between all 212 secondary cases with their previous cases, and found 49 secondary cases (from 26 clusters), which were 23.11% (49/212) of the total secondary cases infected from previous cases during the latter’s incubation period. The median days from the last exposure of secondary cases to the onset of previous cases was 2.0 days (IQR: 1.00~5.00 days, 90th percentile: 9.00 days) .This study has shown transmission of the SARS-CoV-2 during the incubation period and indicated that some cases might be infectious soon after they were exposed to a prior transmitter. The results highlight the importance of extending the contact group for medical observation and isolation to those in contact with the index case nine (90th percentile) or more days before the latter’s illness onset, when medical resources were sufficient.
Comparative Proteomics of Commensal and Pathogenic Strains of Escherichia coli
Authors: Singhal Neelja , Sharma Divakar , Kumar Manish , Bisht Deepa , Virdi Jugsharan Singh 
Published: May 2020

Background:
Most of the proteomic studies in Escherichia coli have focussed on pathogenic
strains, while very few studies have studied the commensal strains. It is important to study
the commensal strains because under the selective pressure of their habitat, commensal strains
might serve as reservoirs of virulent and pathogenic strains.

Objective:
In this study, we have performed a comparative proteomic analysis of commensal and
pathogenic strains of E. coli isolated from a major river flowing through northern India.

Methods:
Proteins were resolved by two dimensional gel electrophoresis and the differentially expressed
proteins were identified using matrix-assisted laser desorption ionization-time of flight
mass-spectrometry (MALDI-TOF MS).

Results:
Many proteins of the commensal strain showed an increased expression compared to the
pathogenic strain, of which seventeen proteins were identified by MALDI-TOF MS. Functional
classification of these proteins revealed that they belonged to different functional pathways like energy
metabolism, nucleotide and nucleoside conversions, translation, biosynthesis of amino acids
and motility and energytaxis/chemotaxis.

Conclusion:
As per the best of our knowledge, this is the first report on comparative proteomic
analysis of E. coli commensal and pathogenic strains of aquatic origin. Our results suggest that the
increased production of these proteins might play an important role in adaptation of E. coli to a
commensal/pathogenic lifestyle. However, further experiments are required to understand the precise
role of these proteins in regulating the pathogenicity/commensalism of E. coli.
Transcription/Expression of KLRB1 Gene as A Prognostic Indicator in Human Esophageal Squamous Cell Carcinoma
Authors: Zhang Guangwei , Liu Ying , Dong Fajin , Liu Xianming 
Published: May 2020

Aim and Objective:
Esophageal squamous cell carcinoma (ESCC) is the most prevalent
type of cancer with worldwide distribution and dismal prognosis despite ongoing efforts to
improve treatment options. Therefore, it is essential to determine the prognostic factors for ESCC.

Methods and Results:
We determined KLRB1 to be a prognostic indicator of human ESCC.
KLRB1 was expressed at low levels in ESCC patients. Based on the risk score, patients were
divided into high and low-risk groups. High-risk patients showed a poor survival rate. The
prediction model based on the N stage, sex, and KLRB1 was significantly better than that based on
the N stage and sex. The modified prediction model showed a robust ROC curve with an AUC
value of 0.973. The knockdown of KLRB1 inhibited the growth of human ESCC cells. KLRB1
regulated Akt, mTOR, p27, p38, NF-κB, Cyclin D1, and JNK signaling, which was consistent with
the result of GSEA.

Conclusion:
KLRB1 is a potential prognostic marker for human ESCC patients.
Combined Analysis of Clinical Data on HGF Gene Therapy to Treat Critical Limb Ischemia in Japan
Authors: Morishita Ryuichi , Shimamura Munehisa , Takeya Yasushi , Nakagami Hironori , Chujo Mitsuaki , Ishihama Tetsuya , Yamada Ei , Rakugi Hiromi 
Published: May 2020

Objectives:
The objective of this combined analysis of data from clinical trials in Japan, using
naked plasmid DNA encoding hepatocyte growth factor (HGF), was to document the safety and
efficacy of intramuscular HGF gene therapy in patients with critical limb ischemia (CLI).

Methods:
HGF gene transfer was performed in 22 patients with CLI in a single-center open trial at
Osaka University; 39 patients in a randomized, placebo-controlled, multi-center phase III trial, 10 patients
with Buerger’s disease in a multi-center open trial; and 6 patients with CLI in a multi-center
open trial using 2 or 3 intramuscular injections of naked HGF plasmid at 2 or 4 mg. Resting pain on a
visual analogue scale (VAS) and wound healing as primary endpoints were evaluated at 12 weeks after
the initial injection. Serious adverse events caused by gene transfer were detected in 7 out of 77 patients
(9.09%). Only one patient experienced peripheral edema (1.30%), in contrast to those who had
undergone treatment with VEGF. At 12 weeks after gene transfer, combined evaluation of VAS and
ischemic ulcer size demonstrated a significant improvement in HGF gene therapy group as compared
to the placebo group (P=0.020).

Results:
The long-term analysis revealed a sustained decrease in the size of ischemic ulcer in HGF
gene therapy group. In addition, VAS score over 50 mm at baseline (total 27 patients) demonstrated a
tendency (P=0.059), but not significant enough, to improve VAS score in HGF gene therapy as compared
to the placebo group.

Conclusions:
The findings indicated that intramuscular injection of naked HGF plasmid tended to improve
the resting pain and significantly decreased the size of the ischemic ulcer in the patients with
CLI who did not have any alternative therapy, such as endovascular treatment (EVT) or bypass graft
surgery. An HGF gene therapy product, CollategeneTM, was recently launched with conditional and
time-limited approval in Japan to treat ischemic ulcer in patients with CLI. Further clinical trials
would provide new therapeutic options for patients with CLI.
A Polyphenolic Complex Attenuates Inflammatory Response and Blood- Brain Barrier Disruption
Authors: Bian Yuting , Yamashita Toru , Taira Yuki , Shang Jingwei , Tsunoda Keiichiro , Feng Tian , Sasaki Ryo , Liu Xia , Shi Xiaowen , Tadokoro Koh , Nomura Emi , Matsumoto Namiko , Osakada Yusuke , Omote Yoshio , Takemoto Mami , Hishikawa Nozomi , Ohta Yasuyuki , Abe Koji 
Published: May 2020

Background:
Cerebral ischemia causes a strong inflammatory response. Neumentix is a
dietary supplement containing 14.9% rosmarinic acid and 29.9% total phenolic content, which has
been proved to be beneficial against inflammatory response. Therefore, Neumentix’s effect on
anti-inflammatory and blood brain barrier (BBB) disruption in transient middle cerebral artery occlusion
(tMCAO) model mice is investigated in this study.

Methods:
After the pretreatment of vehicle or Neumentix 134 mg/kg/d, intraperitoneal injection
(i.p.) (containing rosmarinic acid 20 mg/kg/d) for 14 days, mice were subjected to tMCAO for
60 min and kept receiving vehicle or Neumentix daily 5 days afterward.

Results:
Neumentix treatment ameliorated neurobehavioral impairment in the corner test (5d after
tMCAO, **P<0.01), reduced infarct volume (#P<0.05), suppressed expression of ionized calciumbinding
adapter molecule-1 (Iba-1), tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant
protein-1 (MCP-1) (###P<0.001), and improved the integrity of BBB (§P<0.05) at 5 days
after tMCAO.

Conclusios:
The present study provided an evidence of Neumentix’s anti-inflammatory and neuroprotection
effect against BBB disruption on experimental tMCAO model mice, suggesting that
Neumentix could be a potential therapeutic agent for stroke.
Immunomodulatory Effects of Medicinal Plants used for Vitiligo in Traditional Persian Medicine
Authors: Ebrahimabadi Mohsen Haghir , Lamardi Seyede Nargess Sadati , Shirbeigi Laila 
Published: May 2020

Background:
Vitiligo is a hypopigmentation disorder that affects 1% of the world's
population. Vitiligo causes white spots on the skin, mucous membranes, or white hair by destroying
skin melanocytes. The pathogenesis of vitiligo is unknown but autoimmune, autocytotoxic, and
neural mechanisms are suggested. According to the autoimmune theory, in people with vitiligo,
immune cells invade and damage melanocytes. T cells are more commonly present in vitiligo patients'
skin and remain in the lesion site, which is composed of CD8 and CD4 T cells. Many studies
have been conducted on the presence and role of cytokines such as interleukins and interferongamma
(IFN-γ) in the vitiligo process.

Aim:
This study aimed to introduce herbs effective against vitiligo from the perspective of Persian
medicine and to investigate their possible therapeutic mechanisms with the possible effects of
herbs on autoimmune mechanisms.

Methods:
For this purpose, keywords were used to extract data from Persian medicine textbooks,
and then relevant scientific databases, including Google Scholar, PubMed, Web of Science, and
Scopus were examined.

Results:
It was found that Persian medicine scholars used 50 different medicinal plants to treat and
reduce the complications of vitiligo, and recent scientific studies have proven immune-regulating
properties and reducing the effect of many of them on cytokines.

Conclusion:
According to scientific evidence on immunomodulatory effects, new research into the
effects of these plants on vitiligo can lead to the discovery of new drugs and approaches for treating
this disease.
Optimized Radial Basis Neural Network for Classification of Breast Cancer Images
Authors: Rajathi G. M. 
Published: May 2020

Background:
Breast cancer is a curable disease if diagnosed at an early stage. The
chances of having breast cancer are the lowest in married women after the breast-feeding phase because
the cancer is formed from the blocked milk ducts.

Introduction:
Nowadays, cancer is considered the leading cause of death globally. Breast cancer is
the most common cancer among females. It is possible to develop breast cancer while breast-feeding
a baby, but it is rare. Mammography is one of the most effective methods used in hospitals and
clinics for early detection of breast cancer. Various researchers are used in artificial intelligence-
based mammogram techniques. This process of mammography will reduce the death rate of
the patients affected by breast cancer. This process is improved by the image analysing, detection,
screening, diagnosing, and other performance measures.

Methods:
The radial basis neural network will be used for classification purposes. The radial basis
neural network is designed with the help of the optimization algorithm. The optimization is to tune
the classifier to reduce the error rate with the minimum time for the training process. The cuckoo
search algorithm will be used for this purpose.

Results:
Thus, the proposed optimum RBNN is determined to classify breast cancer images. In
this, the three sets of properties were classified by performing the feature extraction and feature reduction.
In this breast cancer MRI image, the normal, benign, and malignant is taken to perform
the classification. The minimum fitness value is determined to evaluate the optimum value of possible
locations. The radial basis function is evaluated with the cuckoo search algorithm to optimize
the feature reduction process. The proposed methodology is compared with the traditional radial basis
neural network using the evaluation parameter like accuracy, precision, recall and f1-score. The
whole system model is done by using Matrix Laboratory (MATLAB) with the adaptation of 2018a
since the proposed system is most efficient than most recent related literature.

Conclusion:
Thus, it concluded with the efficient classification process of RBNN using a cuckoo
search algorithm for breast cancer images. The mammogram images are taken into recent research
because breast cancer is a major issue for women. This process is carried to classify the various features
for three sets of properties. The optimized classifier improves performance and provides a better
result. In this proposed research work, the input image is filtered using a wiener filter, and the
classifier extracts the feature based on the breast image.
The Effect of Alkaloid Extracted from Huperzia Phlegmaria on Cognitive Deficits Scopolamine-Induced in Mice
Authors: Thu Dang K. , Vui Dao T. , Huyen Nguyen T.N. , Binh Nguyen T.T. , Huyen Nguyen T. , Yen Nguyen T.H. , Tung Bui T. 
Published: May 2020

Background:
Huperzia phlegmaria has been used for the treatment of neurological disorder. Alkaloids are main bioactive
compounds found in Huperzia phlegmaria. We aimed to investigate the acetylcholinesterase (AChE) inhibitory activity in vitro of
Huperzia phlegmaria alkaloid extract (HpAE) and protective effects on mice which were induced cognitive deficits by scopolamine.

Methods:
AChE inhibitory activity and kinetic inhibition mechanism was investigated by Ellman's assay. Mice were administrated
orally HpAE (30 mg/kg and 60 mg/kg) for fourteen days, and injected scopolamine at a dose of 1 mg/kg intraperitoneally for four
days to induce cognitive impairment. The Y-maze and the Morris water maze were used for evaluating the memory behaviors. Acetylcholine (ACh) levels and AChE activity were measured in brain tissue. Glutathione peroxidase (GPx), superoxide dismutase (SOD)
activities, and malondialdehyde (MDA) groups were also evaluated in the mouse brain tissues.

Results:
Our data showed that HpAE had a strong AChE inhibitory activity with an IC50 value of
5.12 ± 0.48 μg/mL in a concentration-dependent manner. Kinetic inhibition analysis demonstrated
that HpAE inhibited AChE followed the mixed inhibition type with Ki (representing the affinity of
the enzyme and inhibitor) was 4.37 ± 0.35 μg/mL. Scopolamine induced the cognitive impairment
in the Morris Water Maze and Y-maze test along with reduced brain levels of ACh and antioxidant
enzyme and increased AChE activity in mouse brain tissues. Treatment with HpAE at both doses
(30 mg/kg and 60 mg/kg) decreased the SCP-induced cognitive impairment in both behavioral tests
along with decreased acetylcholinesterase activity and MDA level, and increased ACh level and antioxidant
enzyme in mouse brain tissues.

Conclusion:
Our results suggested that the HpAE at both dose (30 mg/kg and 60 mg/kg) may be used for prevent and treatment of
Alzheimer’s disease.