bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell non-autonomy amplifies disruption of neurulation by mosaic Vangl2 deletion
Authors: Galea Gabriel , Maniou Eirini , Marshall Abigail R , DE Greene Nicholas , Copp Andrew J 
Published: September 2020

Abstract
Post-zygotic mutations that generate tissue mosaicism are increasingly associated with severe congenital defects, including those arising from failed neural tube closure. We observed that elevation of the neural folds during mouse spinal neurulation is vulnerable to deletion of the planar cell polarity core component Van Gogh-like (Vangl)2 in as few as 16% of neuroepithelial cells. Vangl2-deleted cells are typically dispersed throughout the neuroepithelium, and each non-autonomously prevents apical constriction by an average of five Vangl2-replete neighbours. This inhibition of apical constriction involves reduced myosin-II recruitment to neighbour cell borders and shortening of basally-extending microtubule tails, which are known to facilitate apical constriction. Vangl2-deleted cells themselves continue to apically constrict and preferentially recruit myosin-II to their apical cell cortex rather than to apical cap sarcomere-like organisations. Such non-autonomous effects can explain how post-zygotic mutations affecting a minority of cells can cause catastrophic failure of morphogenesis leading to clinically important birth defects.
Screening, Identification and Interaction Analysis of Key MicroRNAs and Genes in Asthenozoospermia
Authors: Li Li-Man , Chen Song 
Published: September 2020

Abstract
Background: Asthenozoospermia, one of the most common causes of male infertility, is a complicate multifactorial pathological condition that genetic factors are involved in. However, the epigenetic signature and mechanism of asthenozoospermia still remain limited. Our study aimed to confirm the key microRNAs (miRNAs) and genes in asthenozoospermia and demonstrate the underlying epigenetic regulatory mechanisms. Methods: We screened out and pooled previous studies to extracted potential differentially expressed miRNAs (DEMs). GSE22331 and a published profile dataset were integrated to identify differentially expressed genes (DEGs). Pathway and gene ontology analysis were performed using DAVID. A protein-protein network (PPI) was constructed using STRING. The target genes of DEMs were predicted using TargetScan and then built the miRNA-mRNA network.Results: We reported 3 DEMs and 423 DEGs by pooling included dataset and published studies. Pathway analysis showed that these DEGs might participate in signaling pathways regulating pluripotency of stem cells, wnt signaling pathway and notch signaling pathway. 25 hub genes were identified, and the most significant gene was BDNF. We screened out the overlapped DEGs between the predicted target genes of 3 DEMs and the 423 DEGs. Then we constructed miRNA-mRNA network. Conclusion: This study firstly pooled several published studies and a GEO dataset to determine the significance of potential miRNAs and genes, such as miR-374b, miR-193a, miR-34b, BDNF, NTRK2, HNRNPD and EFTUD2 in regulating asthenozoospermia and underscore their interactions in the pathophysiological mechanism. Our results provided theoretical basis and new clues for potential therapeutic treatment in asthenozoospermia. Validations in vivo and in vitro are required in future studies.
A comparison between remaining and resecting the posterior longitudinal ligament in percutaneous endoscopic transforaminal discectomy for disc herniation: A retrospective cohort study
Authors: Hu Wenhao , Hu Fanqi , Liu Chao , Liu Weibo , Jiang Yi , Li Jing , Wang Yan , Li Teng , Li Li , Zhang Xuesong 
Published: September 2020

Abstract
Background

Nowadays, percutaneous endoscopic lumbar discectomy (PELD) has become a popular surgical option for the management of LDH, On the basis of the approach to the herniation disc materials, PELD could be classified into percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID). During PETD procedure, especially in in-and-out approach, accurate determination of whether the posterior longitudinal ligament is needed resection seems particularly important.In the study, we tried assessing comparative clinical outcome, surgical duration and complications between the two different surgical methods of LDH treated by PETD via inside-and-out approach.
Methods

A total of 135 symptomatic LDH patients who were treated by PETD resecting the posterior longitudinal ligament (68 patients) or remaining the posterior longitudinal ligament (67 patients) during the surgery were included in the study. Visual analog scale (VAS) score, Oswestry disability index (ODI) and modified MacNab criteria were used to evaluate clinical outcomes. Operation time, blood loss, recurrence of LDH and other complication such as dural tear, nerve injury, intervertebral infection, etc. of these two groups were recorded. Clinical evaluation was performed preoperatively, immediately postoperatively, and at each follow-up visit (1 month, 3 months, and final follow-up).
Results

There were 38 males and 30 females in the group A that resecting the posterior longitudinal ligament (mean age = 52.40 ± 8.73 years) and 35 males and 32 females in the group B that remaining the posterior longitudinal ligament (mean age = 53.50 ± 9.24 years). The mean operation time of the group A and the group B respectively, were 82.7 ± 18.5 min and 115.6 ± 24.6 min (P < 0.01). The postoperative VAS scores and ODI were significantly higher than those before surgery in two groups (P < 0.01). The differences in the results were not significant between the two groups (P > 0.05). There was no significant difference in the complication rate, the excellent/good ratio and the recurrence rate between the two groups (P > 0.05).
Conclusion

Whether the posterior longitudinal ligament is resected do not make any difference on curative effect in PETD via inside-and-out approach, and remaining the ligament when it’s intact is preferred because of its shorter operation time.
Validation of IMU-Based Gait Event Detection During Curved Walking and Turning in Older Adults and Parkinson's Disease Patients
Authors: Romijnders Robbin , Warmerdam Elke , Hansen Clint , Welzel Julius , Schmidt Gerhard , Maetzler Walter 
Published: September 2020

Abstract
Background: Identication of individual gait events is essential for clinical gait analysis, because it can beused for diagnostic purposes or tracking disease progression in neurological diseases such as Parkinson'sdisease. Previous research has shown that gait events can be detected from a shank-mounted inertialmeasurement unit (IMU), however detection performance was often evaluated only from straight-line walking.For use in daily life, the detection performance needs to be evaluated in curved walking and turning as well asin single-task and dual-task conditions.Methods: Participants (older adults, people with Parkinson's disease, or people who had suered from astroke) performed three dierent walking trials: 1) straight-line walking, 2) slalom walking, 3) Stroop-and-walktrial. An optical motion capture system was used a reference system. Markers were attached to the heel andtoe regions of the shoe, and participants wore IMUs on the lateral sides of both shanks. The angular velocity ofthe shank IMUs was used to detect instances of initial foot contact (IC) and nal foot contact (FC), whichwere compared to reference values obtained from the marker trajectories.Results: The detection method showed high recall, precision and F1 scores in dierent populations for bothinitial contacts and nal contacts during straight-line walking (IC: recall = 100%, precision = 100%, F1 score= 100%; FC: recall = 100%, precision = 100%, F1 score = 100%), slalom walking (IC: recall = 100%,precision 99%, F1 score =100%; FC: recall = 100%, precision 99%, F1 score =100%), and turning (IC:recall 85%, precision 95%, F1 score 91%; FC: recall 84%, precision 95%, F1 score 89%).Conclusions: Shank-mounted IMUs can be used to detect gait events during straight-line walking, slalomwalking and turning. However, more false events were observed during turning and more events were missedduring turning. For use in daily life we recommend identifying turning before extracting temporal gaitparameters from identied gait events.
CYP19A1 rs10046 Pharmacogenetics in Postmenopausal Breast Cancer Patients Treated with Aromatase Inhibitors: One-year Follow-up
Authors: Baatjes Karin , Peeters Armand , McCaul Micheal , Conradie Maria M. , Apffelstaedt Justus , Conradie Magda , Kotze Maritha J. 
Published: September 2020

Background:
Significant individual variation in bone loss associated with aromatase inhibitors (AIs)
emphasizes the importance of identifying postmenopausal breast cancer patients at high risk for this adverse effect.
The study explores the clinical relevance of genetic variation in the Cytochrome P450 19A1 (CYP19A1)
gene in a subset of South African patients during the first year of taking AIs for estrogen receptor (ER)-positive
breast cancer.

Methods:
The study population consisted of ER-positive breast cancer patients on AIs, followed in real-life clinical
practice. Body mass index was measured and bone mineral density (BMD) was determined at baseline and at
month 12. CYP19A1 genotyping was performed using real-time polymerase chain reaction analysis of rs10046,
extended to Sanger sequencing and whole exome sequencing in 10 patients with more than 5% bone loss at
month 12 at the lumbar spine.

Results:
After 12 months of AI treatment, 72 patients had completed BMD and were successfully genotyped. Ten
patients (14%) experienced more than 5% bone loss at the lumbar spine over the study period. Genotyping for
CYP19A1 rs10046 revealed that patients with two copies of the A-allele were 10.79 times more likely to have an
ordinal category change of having an increased percentage of bone loss or no increase at the lumbar spine, compared
to patients with the GA or GG genotypes (CI of 1.771- 65.830, p=0.01). None of the 34 patients without
lumbar spine bone loss at month 12 were homozygous for the functional CYP19A1 polymorphism. At the total
hip region, patients with the AA genotype were 7. 37 times more likely to have an ordinal category change of
having an increased percentage of bone loss or no increase (CI of 1.101- 49.336, p=0.04).

Conclusions:
Homozygosity for the CYP19A1 rs10046 A-allele may provide information, in addition to clinical
and biochemical factors that may be considered in risk stratification to optimize bone health in postmenopausal
breast cancer women on AIs. Further investigation is required to place the clinical effect observed for a single
CYP19A1 gene variant in a genomic context.
Fusion Protein Targeted Antiviral Peptides: Fragment-Based Drug Design (FBDD) Guided Rational Design of Dipeptides Against SARS-CoV-2
Authors: Manna Sounik , Chowdhury Trinath , Baindara Piyush , Mandal Santi M. 
Published: September 2020

:
Infectious diseases caused by viruses have become a serious public health issue in the recent
past, including the current pandemic situation of COVID-19. Enveloped viruses are most commonly
known to cause emerging and recurring infectious diseases. Viral and cell membrane fusion is the major
key event in the case of enveloped viruses that is required for their entry into the cell. Viral fusion
proteins play an important role in the fusion process and in infection establishment. Because of this,
the fusion process targeting antivirals become an interest to fight against viral diseases caused by the
enveloped virus. Lower respiratory tract infections casing viruses like influenza, respiratory syncytial
virus (RSV), and severe acute respiratory syndrome coronavirus (SARS-CoV) are examples of such
enveloped viruses that are at the top in public health issues. Here, we summarized the viral fusion protein
targeted antiviral peptides along with their mechanism and specific design to combat the viral
fusion process. The pandemic COVID-19, severe respiratory syndrome disease is an outbreak worldwide.
There are no definitive drugs yet, but few are in on-going trials. Here, an approach of fragmentbased
drug design (FBDD) methodology is used to identify the broad spectrum agent target to the conserved
region of fusion protein of SARS CoV-2. Three dipeptides (DL, LQ and ID) were chosen from
the library and designed by the systematic combination along with their possible modifications of
amino acids to the target sites. Designed peptides were docked with targeted fusion protein after energy
minimization. Results show strong and significant binding affinity (DL = -60.1 kcal/mol; LQ = -
62.8 kcal/mol; ID= -71.5 kcal/mol) during interaction. Anyone of the active peptides from the developed
libraries may help to block the target sites competitively to successfully control COVID-19.
Novel 4-Oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylic Acid Derivatives as HIV-1 Integrase Inhibitors: Synthesis, Docking Studies, Molecular Dynamics Simulation and Biological Activities
Authors: Zadeh Elnaz Ebrahim , Vahabpour Rouhollah , Beirami Amirreza Dowlati , Hajimahdi Zahra , Zarghi Afshin 
Published: September 2020

Background:
HIV-1 integrase (IN) has been considered as an important target for the development
of novel anti-HIV-1 drugs.

Objective:
The aim of this study was to design novel groups of HIV IN inhibitors.

Method:
In this study, we presented a novel series of 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-
a]pyrimidine-3-carboxylic acid derivatives by structural modification of N-arylindole β-diketoacids
as a well-known group of IN inhibitors.

Results:
Based on in-vitro anti-HIV-1 activity in a cell-based assay, compounds 5, 6a and 6k displayed
moderate to good inhibitory activity with EC50 values of 4.14, 1.68 and 0.8 μM, respectively.
However, integrase inhibition assay showed that most of the analogues did not have significant effects
against integrase enzyme except compound 5 with an IC50 value of 45 μM. Our results indicated
that compound 6k was the best one among synthesized compounds with an EC50 of 0.8 μM and SI of
175. Docking and molecular dynamics simulation studies were also performed to provide some insights
into the probable mechanism of tested compounds.

Conclusion:
These findings suggest that 4-oxo-4,10-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-
carboxylic acid derivatives may consider as promising lead compounds for the development of new
anti-HIV-1 drugs.
Design, Synthesis, and Anti-Neuroinflammatory Activity of Amide- Containing Dithiolethiones
Authors: Craig Karrington , Avila Paula , Brown Dennis A. 
Published: September 2020

Background:
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central
nervous system characterized by demyelination of neurons and neurodegeneration. Current MS therapies
ameliorate inflammatory damage but are unable to address the degenerative aspects of the disease.

Objective:
In this report, we evaluate the ability of amide-based dithiolethiones (DTTs) to suppress
neuroinflammation in microglia and increase anti-oxidant capacity in neuron-like cells.

Methods:
A series of amide-containing DTTs were designed, synthesized, and assayed for the ability
to suppress pro-neuroinflammatory cytokines IL-12p40 and IL-23p19 induced by LPS in the BV2
microglial cell line. Lead analog 2c was identified and further characterized.

Results:
Structure-activity data revealed tolerance towards a variety of amides. Morpholine analog 2c
dose-dependently reduced various other inflammatory cytokines and mediators, including TNF, IL-6,
IL-1β, NOS2, and COX2. Additionally, 2c elevated cellular levels of glutathione in SH-SH5Y neuronal
cell line. Furthermore, mechanistic studies showed that 2c increased the expression of antiinflammatory
Nrf2 and HMOX proteins.

Conclusion:
The combination of anti-neuroinflammatory and anti-oxidant activities of amide-based
DTTs suggests that they are promising agents for the treatment of both demyelination and neurodegeneration
in MS.
RNA Splicing: Basic Aspects Underlie Antitumor Targeting
Authors: Fergany Alzahraa A.M. , Tatarskiy Victor V. 
Published: September 2020

Background:
RNA splicing, a fundamental step in gene expression, is aimed at intron removal
and ordering of exons to form the protein’s reading frame.

Objective:
This review is focused on the role of RNA splicing in cancer biology; the splicing abnormalities
that lead to tumor progression emerge as targets for therapeutic intervention.

Methods:
We discuss the role of aberrant mRNA splicing in carcinogenesis and drug response.

Results and Conclusion:
Pharmacological modulation of RNA splicing sets the stage for treatment
approaches in situations where mRNA splicing is a clinically meaningful mechanism of the disease.
Transcriptionomic Study on Apoptosis of SKOV-3 Cells Induced by Phycoerythrin from Gracilaria lemaneiformis
Authors: Ying Jun , Tang Zhouhao , Zhao Guanan , Li Xia , Pan Ruowang , Lin Shuangxiang , Lou Yang , Wang Wanping , Li Peizhen , Bao Qiyu , Yan Chunxia 
Published: September 2020

Objective:
To investigate the effects of phycoerythrin (PE) on the human ovarian cancer cell line SKOV-3 and
its antitumor mechanisms from a transcriptional point of view.

Methods:
SKOV-3 cells were exposed to different concentrations of phycoerythrin. The efficiency of this treatment was
evaluated through cell growth inhibition, changes in cell morphology, apoptosis and intracellular ROS levels. High
throughput sequencing (RNA-seq) was performed to screen differentially expressed genes (DEGs), which was verified
using RT-PCR and Western blotting.

Results:
PE showed a significant inhibitory effect on the growth of SKOV-3 cells in a time- and dose-dependent manner.
H&E staining, electron microscopy and flow cytometry revealed that PE induced apoptosis in SKOV-3 cells.
Transcriptome analysis showed that 2963 genes were differentially expressed between untreated or PE-treated cells. GO
and KEGG pathway analyses identified 16 classical pathways that were enriched. We verified 8 DEGs including, JNK,
GADD45A, EDEM2, RAD23, UBQLN, CAPN1, XBP1, and OS9. These results were consistent with results from
transcriptional sequences.

Conclusion:
The inhibitory effect of PE on SKOV-3 cells was a result of interaction with multiple pathways and signaling
molecules. Among these, the ROS/JNK/Bcl-2 signaling pathway, upregulation of JNK, GADD45A and RAD23 as well as
downregulation of XBP1 and OS9 played a critical role in the PE -induced apoptosis in human ovarian cancer cells.
Fabrication, In vitro and In vivo Characterization of Solid Dispersion- Microsphere Controlled Release System for Lornoxicam
Authors: Nupane Suraj , Srivastava Dipti , Chaurasia Mohini , Awasthi Himani 
Published: September 2020

Background:
Lornoxicam is widely used for its anti-inflammatory, analgesic and antipyretic
properties. However, it suffers from the limitations of possessing a relatively short elimination half-life
ranging from 3 to 5 h, thereby; leading to repeated dosing which in turn may cause local irritation and
ulceration. In addition, LXM also exhibits pH-dependent solubility. Effective management of inflammation
in diseases such as arthritis requires the formulation of delivery systems that may be able to
provide immediate release of drug for instant relief which shall be maintained for a prolonged period.

Objective:
The present research work was aimed to modify the release pattern of poorly water-soluble
drug Lornoxicam by designing a biphasic tablet comprising of solid dispersion (immediate release
form) and microspheres (controlled release form) for the effective management of inflammation.

Methods:
The solid dispersion (SD) was prepared by melting method using PEG 4000 and tween 80
and formation was confirmed by Differential Scanning Calorimetry (DSC) and Powder X-ray Diffraction
(PXRD) studies. Polymeric microspheres loaded with Lornoxicam were prepared by ‘Emulsion
Solvent-Evaporation’ method using Eudragit S-100 and Eudragit L-100. Microspheres (MS) were evaluated
for drug entrapment efficiency, drug loading, drug content, particle size and in vitro release
behaviour. Optimized microspheres (polymer concentration 0.5% w/v and drug concentration
0.1% w/v and solid dispersion (drug: PEG 4000: 4:6) were compressed in the ratio of 1:3 to produce
biphasic tablet. The prepared tablets were evaluated for various pre-compression and post-compression
parameters. Anti-inflammatory activity of the F4, M6 and the combination of SD and Microspheres in a
ratio of 1:3 was carried out by Carrageenan induced paw edema method in Wistar rats.

Results:
The solid dispersions prepared by melting technique showed an enhanced dissolution rate as
compared to the pure drug. LXM microspheres exhibited a sustained drug release. In vitro release of
lornoxicam from biphasic tablets showed that 20% of the drug released at the end of first one hour, followed
by 33% release at the end of 4th h and maximum release of 94.1% at the end of 10 h. The prolonged
effect continued till the end of 12 h. Results showed that the mixture of MS + SD exhibited 48%
inhibition in 30 min which is increased to 88.63% at the end of 4 h which can be explained by initial
burst release from the soluble layer of SD (which gave initial required effective concentration of Lornoxicam)
followed by sustained release from matrix of microspheres (which maintained required level
of Lornoxicam in blood).

Conclusion:
A successful modification of the release pattern of LXM was achieved by designing a biphasic
tablet comprising of solid dispersion for the effective management of inflammation.
Applications of Selectfluor for the Oxidation of Sulfides, Urazoles and Alcohols Under the Solvent-free Conditions
Authors: Chehardoli Gholamabbas , Zolfigol Mohammad A. , Mallakpour Shadpour 
Published: September 2020

Aims:
Using Selectorfluor® for the oxidation of urazoles and sulfides as well as the oxidation
of alcohols under mild conditions.

Background:
[1-Chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane-bis(tetrafluoroborate)]
so-called Selectorfluor®, is a reagent/catalyst that is donor of the electrophilic fluorine atom. Selectorfluor
® is a colorless salt which was first introduced in 1992. This year, Banks et al. prepared a
salt from the reaction of dichloromethane with dabco and sodium tetrafluoroborate, and then reacted
it with fluorine gas to prepare the Selectorfluor®.

Objective:
Unlike the highly hazardous F2, the Selectorfluor® is a stable, non-hygroscopic, easy to
handle and commercially available reagent that has many applications in organic reactions.

Methods:
Substrate [alcohols, urazoles or sulfides (1 mmol)] was added to the mixture of Selectorfluor
® (0.708 g, 2 mmol), KBr (0.236 g, 2 mmol), and 0.2 g wet SiO2 (50%). The mixture was
ground with a mortar and pestle for 10-15 minutes. Then, the product was extracted with CH2Cl2
(2×10 mL). The solution was dried with anhydrous sodium sulfate and filtered again. Simple distillation
of the CH2Cl2 gave the crude product. Aldehyde/ketones and sulfoxides were purified by
short column chromatography on silica gel with EtOAc/n-hexane (1:3 to 1:5). Urazoles were purified
by the sublimation method.

Results:
Some advantages of these oxidation reactions using the Selectorfluor®/KBr system are: a)
both reagent and catalyst are safe and easy to handle; b) the procedure is solvent-free; c) the reaction
is carried out at room temperature; d) yields are good to excellent; e) work-up is convenient
since the reagent/catalyst residue is ionic and insoluble in the organic solvents.

Conclusion:
Selectorfluor® is a safe and stable reagent that is easy to work with, although it is slow
and lazy in reaction, and it cannot react well at room temperature. The literature survey shows that
the best conditions for a reaction are acetonitrile reflux and that the solvent-free is not very desirable
conditions.