bluuebunny/crossref_metadata_2025_split huggingface dataset:
PyPAn: An Automated Graphical User Interface for Protein Sequence and
Structure Analyses
Authors: Mathur Yash , Mohammad Taj , Anjum Farah , Shafie Alaa , Elasbali Abdelbaset M. , Uversky Vladimir N. , Hassan Md. Imtaiyaz 
Published: February 2022

Background:
Protein sequence and structure analyses have been essential components of
bioinformatics and structural biology. They provide a deeper insight into the physicochemical
properties, structure, and subsequent functions of a protein. Advanced computational approaches
and bioinformatics utilities help solve several issues related to protein analysis. Still, beginners and
non-professional may struggle when encountering a wide variety of computational tools and the
sheer number of input parameter variables required by each tool.

Methods:
We introduce a free-to-access graphical user interface (GUI) named PyPAn 'Python-based
Protein Analysis' for varieties of protein sequence/structure analyses. PyPAn serves as a universal
platform to analyze protein sequences, structure, and their properties. PyPAn facilitates onboard
analysis of each task in just a single click. It can be used to calculate the physicochemical properties,
including instability index and molar extinction coefficient, for a protein. PyPAn is one of the few
computational tools that allow users to generate a Ramachandran plot and calculate solvent
accessibility and the radius of gyration (Rg) of proteins at once. In addition, it can refine the protein
model along with computation and minimization of its energy.

Results:
PyPAn can generate a recommendation for an appropriate structure modelling method to
employ for a query protein sequence. PyPAn is one of the few, if not the only, Python-based
computational GUI tools with an array of options for the user to employ as they see fit.

Conclusion:
PyPAn aims to unify many successful academically significant proteomic applications
and is freely available for academic and industrial research uses at https://hassanlab.org/pypan.
Cellular and Molecular Mechanisms of Curcumin in Thyroid Gland
Disorders
Authors: Shakeri Farzaneh , Bibak Bahram , Safdari Mohammad Reza , Keshavarzi Zakieh , Jamialahmadi Tannaz , Sathyapalan Thozhukat , Sahebkar Amirhossein 
Published: February 2022

Abstract:
There is growing literature on the positive therapeutic potentials of curcumin.
Curcumin or diferuloylmethane is a polyphenol obtained from the plant Curcuma longa.
Curcumin is widely used in Ayurvedic and Chinese medicine for various conditions. The
role of curcumin in thyroid gland disorders has been demonstrated by its effects on various
biological pathways, including anti-inflammatory, antioxidant, anti-proliferative,
apoptosis, angiogenesis, cell cycle and metastasis. In this paper, we have reviewed the recent
literature on curcumin applications for thyroid dysfunction, including hyperthyroidism
and hypothyroidism, and discussed the molecular mechanisms of these effects.
This review aims to summarize the wealth of research related to the therapeutic effect of
curcumin on the thyroid gland.
Advances in the Total Synthesis of Gelsemine
Authors: Yang Liyan , Wang Zhonglei 
Published: February 2022

Abstract:
Gelsemine is a remarkable indole alkaloid isolated from the medicinal plant Gelsemium
elegans (Carolina or yellow jasmine) and demonstrates effectiveness in alleviating cognitive
impairment, suggesting it could treat Alzheimer's disease. Gelsemine comprises seven
adjoining chiral carbon centres and hexacyclic cage structures, making it an oddly difficult
synthetic target. The unique structure and potential bio-pharmacological properties of gelsemine
have led to the publication of nine interesting total syntheses of gelsemine (including
three asymmetric syntheses) in the near past three decades by eight distinguished research
groups. Several strategies are brimming with modern concepts of synthesis, such as highly
enantioselective organocatalytic Diels–Alder reaction and the biomimetic enol–oxonium cyclization
reaction. To better explore the therapeutic effects of gelsemine, this review summarizes
the progress in the total synthesis tactics and strategies of the fascinating natural product gelsemine.
miRNA-Based Signature to Predict the Development of Alzheimer’s Disease
Authors: Chen Longfei , Zhan Fangfang , Yang Jinshan , Lin Shifang 
Published: February 2022

Background:
Patients with mild cognitive impairment (MCI) suffer from a high risk of
developing Alzheimer’s disease (AD). Cumulative evidence has demonstrated that the development
of AD is a complex process that could be modulated by miRNAs. Here, we aimed to identify
miRNAs involved in the pathway, and interrogate their ability to predict prognosis in patients with
MCI.

Methods:
We obtained the miRNA-seq profiles and the clinical characteristics of patients with
MCI from the Gene Expression Omnibus (GEO). Cox regression analysis was used to construct a
risk level model. The receiver operating characteristic (ROC) curve was used to assess the performance
of the model for predicting prognosis. Combined with clinical characteristics, factors associated
with prognosis were identified and a predictive prognosis nomogram was developed and
validated. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)
analysis, we evaluated molecular signatures for the candidate miRNAs.

Results:
Our analysis identified 120 DEmiRNAs. The Cox regression analysis showed that two
miRNAs could serve as risk factors for disease development. A risk level model was constructed.
Age, apoe4, and risk level were associated with the prognosis. We developed a nomogram to predict
disease progression. The calibration curve and concordance index (C-index) demonstrated the
reliability of the nomogram. Functional enrichment analysis showed that these miRNAs were involved
in regulating both cGMP-PKG and Sphingolipid signaling pathways.

Conclusion:
We have identified miRNAs associated with the development of MCI. These miRNAs
could be used for early diagnosis and surveillance in patients with MCI, enabling prediction
of the development of AD.
Pharmacophore Modelling and Virtual Screening Studies for the Discovery
of Natural Product-based PDE 3/4 Dual Inhibitors for COPD
Authors: Hui Tan Xuan , Le Lim Jia , Gaurav Anand 
Published: February 2022

Background:
Chronic Obstructive Pulmonary Disorder (COPD) is a chronic and progressive
lung disease with a steady increase in prevalence over the recent years. Current treatment options of
COPD are aimed at symptomatic relief without the ability to cure COPD, and certain corticosteroid treatments
cause patients to be susceptible to infections. Newer studies have hinted that PDE3/4 dual inhibitors
may produce a higher efficacy and better safety profile compared to current alternatives. These novel
inhibitors may potentially improve the control of COPD exacerbation without increasing the risk of infections.
Thus, our study aimed to identify and refine natural compounds with PDE3/4 dual inhibitory activities
through molecular modelling techniques.

Method:
A two-sided approach through ligand-based and structure-based pharmacophore modelling was
employed, followed by virtual screening and molecular docking to identify lead compounds with PDE3/4
dual inhibition activity.

Results:
Pharmacophore-based screening of Universal Natural Products Database (UNPD) resulted in the
identification of one compound for each pharmacophore model, namely UNPD1558 and UNPD139455,
with high binding affinities towards both PDE3B and PDE4B. The two compounds were subsequently
docked with PDE3B and PDE4B to study their interactions with the active site residues. Structural modifications
of the compounds were proposed based on the docking results to optimise their binding affinity
and physicochemical properties.

Conclusion:
Compound 25a4 and compound 28, which were designed based on the structures of
UNPD1558 and UNPD139455, respectively, showed an improved binding affinity for both PDE3B and
PDE4B. These lead compounds showed promising results as drug candidates, and their PDE3/4 dual inhibitory
properties should be further investigated through in vivo and in vivo studies.
Investigating COVID-19 Severity Based on Serum Apelin-17 Levels and Inflammatory Mediators
Authors: Fekri Mitra Samareh , Barfzade Elham , Farokhnia Mehrdad , Bajgani Seyed Mehdi Hashemi , Shafahi Ahmad , Shafiepour Mohsen , Movahedinia Sajjadeh , Dabiri Shariar , Yousefi Meysam 
Published: February 2022

Background:
COVID-19 is an infectious disease caused by SARS-CoV-2 and can lead to acute respiratory distress.

Objective:
We aimed to investigate the association between COVID-19 severity and serum apelin-17 and inflammatory mediator levels.

Method:
This cross-sectional study was conducted on patients with COVID-19. COVID-19 infec-tion was confirmed by the RT-PCR test. The patients' data were extracted from their records. Ve-nous blood samples were obtained from the patients to investigate the serum levels of apelin-17 and inflammatory mediators.

Results:
Eighty-six COVID-19 patients were studied. The mean age of the participants was 55.56±14.88, and 43 (50 %) were male. Clinical symptoms were dyspnea 77.6 %, fever 52.3 %, cough 48.8 %, gastrointestinal symptoms 15.1 %, and chest pain 7 %. The overall mortality rate was 7 %. No significant relationship was found between serum apelin-17 levels and COVID-19 severity (P= 0.48). However, there was a significant and direct relationship between COVID-19 severity and serum levels of CRP (P= 0.038) and D-dimer (P= 0.029).

Conclusion:
Serum apelin-17 levels were higher in recovered patients than those who died (4.90 vs. 3.19). Moreover, serum apelin-17 levels were higher in the patients admitted to the general ward than those admitted to the ICU (5.15 vs. 3.98). The difference was not statistically significant. How-ever, there was a significant and direct relationship between serum apelin-17 levels and lymphocyte count (P= 0.022). Moreover, there was a significant and inverse relationship between lymphocyte count and COVID-19 severity (P= 0.004). Therefore, it can be interpreted that COVID-19 severity may decrease with an increase in serum apelin-17 levels. Therefore, to prove this hypothesis, a study with larger sample size is recommended.
Portal Venous and Mesenteric Wall Calcifications along with
Intra-splenic Vascular Calcification: A Rare Case Report and Literature
Review
Authors: Wettasinghe Mihiri Chami , Rodrigo Ganganath , Wickramasinghe Nuwan Darshana 
Published: February 2022

Background:
Cross-sectional imaging findings of portal vein calcification were found to be
an indicator of portal vein thrombosis. Calcification of the portal vein and its tributaries in portal hypertension
is an uncommon finding and the mechanical stress due to long-standing portal hypertension
on the vessel wall is considered leading to sclerosis and calcification in the intima and media of the
vessel wall. Intra-splenic vascular calcification is a rare occurrence and has been seen in patients with
portal hypertension.

Case Presentation:
A 60-year-old male was referred for an ultrasound scan of the abdomen, as he was
found to have mild elevation of liver enzymes during a routine medical investigation. His ultrasound
scan showed features of cirrhosis and portal hypertension. Furthermore, there were intra-splenic calcifications
with branching pattern. Subsequent CT confirmed intra-splenic vascular calcification and
calcifications in the wall of the thrombosed portal vein and its tributaries.

Conclusion:
Pre-operative identification of portal venous calcification is important, as this might adversely
affect surgical interventions for cirrhosis and portal hypertension. Furthermore, to our best
knowledge, there have not been any cases reported with concurrent calcification of the portal venous
system and intra-splenic vascular calcification in association with portal hypertension in literature.
A Case of Intestinal Perforation Associated with Mesenteric Thrombosis
Due to Post-COVID-19 Syndrome
Authors: Gündoğdu Elif , Cihan Çağatay , Aydın Nevin , Demirayak Dilay , Özakyol Ayşegül , Kebapçı Mahmut 
Published: February 2022

Purpose:
We aimed to present a case who developed intestinal ischemia and associated
perforation and abscess due to superior mesenteric vein (SMV) thrombosis caused by post-COVID-19
syndrome and discuss the preoperative computed tomography (CT) imaging findings used in diagnosis.

Case Report:
A 58-year-old patient presented to our clinic with a complaint of acute abdominal pain.
His CT examination revealed thrombosis in SMV, congestion in the mesenteric venous structures,
contamination in the mesentery, and thickening and dilatation of the jejunal loops due to ischemia. The
patient had a history of acute COVID-19 infection. He had typical COVID-19 pneumonia findings
(peripheral ground-glass opacities in both lung parenchyma predominantly in the lower lobe) on the
thorax CT at that time. He was followed up with anticoagulant therapy. During his follow-up, a thoracic
and abdominal CT was performed due to recurrent acute abdominal findings. On thorax CT, there
was a web-like filling defect consistent with pulmonary embolism, traction bronchiectasis consistent
with late findings of COVID-19 pneumonia, and poorly circumscribed subpleural ground glass opacities.
On abdominal CT, in addition to mesenteric ischemia findings, loss of wall integrity was observed
in the jejunal loops due to perforation and collection areas containing air consistent with an abscess. He
was treated with small bowel resection and abscess drainage.

Conclusion:
Patients with acute COVID-19 infection should be followed up for the early diagnosis of
serious symptoms that may develop due to post-COVID-19 syndrome, and contrast-enhanced CT
should be the imaging method of choice to detect possible mesenteric vascular thrombosis in patients
with acute abdominal symptoms.
Berberine Ameliorates Cognitive Impairment by Regulating Microglial Polarization
and Increasing Expression of Anti-inflammatory Factors following
Permanent Bilateral Common Carotid Artery Occlusion in Rats
Authors: Tian Yue , Zheng Yangmin , Wang Qi , Yan Feng , Tao Zhen , Zhao Fangfang , Wang Yuqing , Huang Yuyou , Li Fengjuan , Du Yitong , Wang Ningqun , Luo Yumin 
Published: February 2022

Background:
Chronic cerebral hypoperfusion is associated with vascular cognitive impairment,
and there are no specific therapeutic agents for use in clinical practice. Berberine has demonstrated
good neuroprotective effects in models of acute cerebral ischemia; however, whether it
can alleviate cognitive impairment caused by chronic cerebral hypoperfusion has rarely been investigated.

Objective:
The present study aimed to explore the mechanism by which berberine alleviates cognitive
impairment resulting from chronic cerebral hypoperfusion.

Methods:
Forty-two male Sprague-Dawley rats were randomly divided into three groups: sham,
model, and berberine. The models of chronic cerebral hypoperfusion were established via permanent
bilateral common carotid artery occlusion (BCCAO). Cognitive function was evaluated using
the Morris water maze, while neuronal damage and microglial activation and polarization were
evaluated using western blotting and immunofluorescence, respectively. Enzyme-linked immunosorbent
assays were used to detect the expression of anti-inflammatory factors including interleukin-
4 (IL-4) and interleukin-10 (IL-10).

Results:
Rats exhibited cognitive dysfunction after BCCAO, which was significantly attenuated following
the berberine intervention. Levels of synaptophysin and NeuN were decreased in states of
chronic cerebral hypoperfusion, during which microglial activation and a transition from the M2 to
M1 phenotype were observed. Berberine treatment also significantly reversed these features. Moreover,
levels of IL-4 and IL-10 expression increased significantly after berberine treatment.

Conclusion:
Berberine may mitigate vascular cognitive dysfunction by promoting neuronal plasticity,
inhibiting microglial activation, promoting transformation from an M1 to an M2 phenotype,
and increasing levels of IL-4 and IL-10 expression.
Active Control Algorithm of Hybrid Vibroacoustic for Vehicle Interior
Sound Quality
Authors: Shen Weitao , Wang Xiaolan , Wang Tongzhou , Wang Yansong , Liu Ningning 
Published: February 2022

Background:
In some applications, retaining the residual noise at a specified frequency
can provide a better vehicle interior sound quality for occupant’s driving experience. The hybrid
vibro-acoustic adaptive noise equalizer (HVA-ANE) algorithm introduces a sound retention factor
on the basis of the hybrid vibro-acoustic filter-u, and filter-x least mean square (HVA-FUXLMS)
algorithm to achieve control of the sound quality, but it is not possible to retain varying degrees of
different frequency bands. The hybrid vibro-acoustic empirical-mode-decomposition frequencydomain
block adaptive noise equalizer (HVA-EBANE) algorithm introduces Empirical-Mode-
Decomposition (EMD) and frequency domain block methods to achieve different degrees of retention
of noise in different frequency bands but cannot deal with the irrelevant frequency components
in the error signal.

Objective:
This paper proposes an improved active control algorithm for vehicle interior sound quality,
the so-called hybrid vibro-acoustic EMD frequency-domain block FELMS (HVA-EBFELMS)
algorithm.

Methods:
Based on the filtered error, the least mean square algorithm and the residual filter of the
specific frequency band are designed according to the psychoacoustic parameters of each component.
The filter filters the irrelevant frequency components in the residual signal, and only retains
the frequency components that have a great influence on the sound quality so as to achieve the regulation
of the desired sound quality.

Results:
In order to verify the effectiveness of our algorithm, we used the noise and vibration in the
vehicle at idle speed as the object and compared the noise control effect with HVA-ANE and HVAEBANE
algorithms considering the sound quality. The simulation experiment shows that our algorithm
reduces the loudness of the ear-side noise by more than 40% while taking into account the
noise and vibration control.

Conclusion:
The loudness control effect of hybrid vibro-acoustic EMD frequency-domain block
FELMS (HVA-EBFELMS) algorithm is better than HVA-ANE and HVA-EBANE algorithms; it
has a better effect of improving loudness as well.
The Effectiveness of Virtual Reality Exposure–Based Cognitive Behavioral Therapy for Severe Anxiety Disorders, Obsessive-Compulsive Disorder, and Posttraumatic Stress Disorder: Meta-analysis
Authors: van Loenen Inge , Scholten Willemijn , Muntingh Anna , Smit Johannes , Batelaan Neeltje 
Published: February 2022

Background
In recent years, virtual reality exposure–based cognitive behavioral therapy (VRE-CBT) has shown good treatment results in (subclinical) anxiety disorders and seems to be a good alternative to exposure in vivo in regular cognitive behavioral therapy (CBT). However, previous meta-analyses on the efficacy of VRE-CBT on anxiety disorders have included studies on specific phobias and subthreshold anxiety; therefore, these results may not be generalizable to patients with more severe and disabling anxiety disorders.

Objective
The objective of our study is to determine the efficacy of VRE-CBT on more severe anxiety disorders, excluding specific phobias and subthreshold anxiety disorders. Meta-analyses will be conducted to examine the efficacy of VRE-CBT versus waitlist and regular CBT. Our secondary objectives are to examine whether the efficacy differs according to the type of anxiety disorder, type of recruitment, and type of VRE-CBT (virtual reality exposure either with or without regular CBT). Furthermore, attrition in VRE-CBT and CBT will be compared.

Methods
Studies published until August 20, 2020, were retrieved through systematic literature searches in PubMed, PsycINFO, and Embase. We calculated the effect sizes (Hedges g) for the difference between the conditions and their 95% CIs for posttest and follow-up measurements in a random effects model. A separate meta-analysis was performed to compare attrition between the VRE-CBT and CBT conditions.

Results
A total of 16 trials with 817 participants were included. We identified 10 comparisons between VRE-CBT and a waitlist condition and 13 comparisons between VRE-CBT and a CBT condition. With regard to risk of bias, information on random sequence generation, allocation concealment, and risk of bias for selective outcome reporting was often absent or unclear. The mean effect size of VRE-CBT compared with waitlist (nco=10) was medium and significant, favoring VRE-CBT (Hedges g=−0.490, 95% CI −0.82 to −0.16; P=.003). The mean effect size of VRE-CBT compared with CBT (nco=13) was small and nonsignificant, favoring CBT (Hedges g=0.083, 95% CI −0.13 to 0.30; P=.45). The dropout rates between VRE-CBT and CBT (nco=10) showed no significant difference (odds ratio 0.79, 95% CI 0.49-1.27; P=.32). There were no indications of small study effects or publication bias.

Conclusions
The results of our study show that VRE-CBT is more effective than waitlist and as effective as CBT in the treatment of more severe anxiety disorders. Therefore, VRE-CBT may be considered a promising alternative to CBT for patients with more severe anxiety disorders. Higher-quality randomized controlled trials are needed to verify the robustness of these findings.
An Imported Measles Outbreak in Al Buraimi Governorate, Oman, in April 2020
Authors: Al-Marbouai Hanan 
Published: February 2022

Background
On April 16, 2020, the communicable disease department of Al Buraimi Governorate, Oman, was notified about 3 cases of measles. On laboratory confirmation of measles on April 19, 2020, further field investigation was conducted. Oman has had few cases of measles since 1995; however, Al Buraimi Governorate has had imported cases of measles in recent years.

Objective
We conducted this study to investigate the epidemiology of imported cases of measles in Al Buraimi, Oman, in April 2020.

Methods
This case series retrospectively reported measles cases. Epidemiological investigation began by meeting the families of the affected children. The data obtained included clinical symptoms, exposure information, travel history, immunization, and history of contact with others.

Results
Among the positive cases of measles, 75% were in girls and 25% were in boys. In addition, 6 patients were Afghani nationals and 2 were Pakistani nationals. A detailed investigation that included virus isolation and genotyping identified the B3 genotype in all measles cases and traced the virus to Pakistan as the country of origin. Despite Pakistan being the place of origin of the virus, most cases of measles (75%) were reported in Afghani nationals because of low vaccination coverage. We also found that most of the children affected were 10 to 19 years old (75%). All children who did not have vaccination records or were unvaccinated, regardless of whether they had contracted the virus, were given the measles-mumps-rubella vaccine. This was done to prevent future outbreaks and to increase measles vaccination coverage.

Conclusions
This study demonstrated that the greatest challenge in eliminating measles in Oman is imported cases among non-Omani expatriates and unvaccinated children. It should therefore be a priority to vaccinate all expatriate children. Only when everyone is vaccinated in Oman can the goal of creating a measles-free country be realized.