bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hsa_circ_0004662 Accelerates the Progression of Osteoarthritis
via the microRNA-424-5p/VEGFA Axis
Authors: Xie Wei , Jiang Luoyong , Huang Xiaoyang , You Wei , Sun Wei 
Published: November 2022

Objective:
Circular RNAs (circRNAs) have been extensively implicated in osteoarthritis (OA) progression. Therefore, this study explores the impact of hsa_circ_00046621 on OA progression and the related molecular mechanism.

Methods:
Human articular chondrocyte injury was induced by IL-1β to construct the OA model in vitro. hsa_circ_0004662 and microRNA (miR)-424-5p expression in chondrocytes was evaluated with qRT-PCR. Vascular endothelial growth factors A (VEGFA) expression was examined with qRT-PCR and western blot after hsa_circ_0004662 knockdown or miR-424-5p overexpression in chondrocytes. Subsequent to loss- and gain-of-function assays in IL-1β-induced chondrocytes, the proliferation and apoptosis of chondrocytes were assessed with CCK-8 assay and flow cytometry, respectively. The expression of MMP13, Aggrecan, and apoptosis-related proteins Bax and Bcl-2 was measured with western blot. The binding of miR-424-5p to hsa_circ_0004662 and VEGFA was assessed with a dual-luciferase reporter gene assay.

Results:
Hsa_circ_0004662 was up-regulated, but miR-424-5p was down-regulated in IL-1β-induced chondrocytes. Mechanistically, both hsa_circ_0004662 and VEGFA bound to miR-424-5p, and hsa_circ_0004662 enhanced VEGFA expression by down-regulating miR-424-5p. Hsa_circ_0004662 knockdown elevated cell proliferation, decreased apoptosis and MMP13 and Bax expression, and increased Aggrecan and Bcl-2 expression in IL-1β-induced chondrocytes, which was counteracted by further miR-424-5p down-regulation or VEGFA overexpression.

method:
Human articular chondrocyte injury was induced by IL-1β to mimic the OA model. hsa_circ_0004662 and microRNA (miR)-424-5p expression in chondrocytes was evaluated using qRT-PCR. Vascular endothelial growth factors A (VEGFA) expression was examined using qRT-PCR and western blot analysis following hsa_circ_0004662 knockdown or miR-424-5p overexpression in chondrocytes. Subsequent to the loss- and gain-of-function assays in IL-1β-induced chondrocytes, proliferation and apoptosis of chondrocytes were assessed using CCK-8 assay and flow cytometry, respectively. The expression of MMP13, Aggrecan, and apoptosis-related proteins Bax and Bcl-2 was measured using western blot analysis. The binding relationship of miR-424-5p to hsa_circ_0004662 and VEGFA was assessed using dual luciferase reporter gene assay.

Conclusion:
Hsa_circ_0004662 facilitates OA progression via the miR-424-5p/VEGFA axis.
Factors Related to Mechanical Thrombectomy Failure in Large Vessel
Occlusion: A Propensity Score Matching Analysis
Authors: Sung Jae Hoon , Yi Ho Jun , Lee Dong Hoon , Shin Dong-Seong , Kim Bum-Tae 
Published: November 2022

Objective:
Mechanical thrombectomy (MT) is an effective treatment for large vessel
occlusion (LVO) with a high successful recanalization (SR) rate. However, MT fails in a proportion
of patients, leading to poor clinical outcomes. We analyzed the factors associated with the failure of
MT.

Methods:
Failed MT was observed in 97 patients (14.3%). Among them, 69 patients (10.2% of the
entire cohort, 71.1% of the failed MT group) were included in the RF group. Propensity matching
analysis with 69 patients in each group showed that the RF group had a higher rate of residual intracranial
atherosclerotic stenosis (ICAS) than the SR group (30.4% vs. 14.5% P = 0.003). The rates of
4 or more passages and no change of method were significantly higher in the RF group than in the
SR group (34.8% vs. 13.0%; P = 0.001 and 28.9% vs. 8.7%; P = 0.001).

Results:
Failed MT was observed in 97 patients (14.3%). Among them, 69 patients (10.2% of the
entire cohort, 71.1% of the failed MT group) were included in the RF group. Propensity matching
analysis with 69 patients in each group showed that the RF group had a higher rate of residual intracranial atherosclerotic stenosis (ICAS) than the SR group (30.4% vs. 14.5% P = 0.003). The rates of
4 or more passages and no change of method were significantly higher in the RF group than in the
SR group (34.8% vs. 13.0%; P = 0.001 and 28.9% vs. 8.7%; P = 0.001).

Conclusion:
The failure rate for all of the MT was approximately 15%, and RF accounted for more
than 70% of the failed MT. RF was associated with residual ICAS. In cases with RF, even in repeated
attempts for recanalization, an alteration of the thrombectomy method should be considered.
Tandem Mass Tag (TMT) Quantitative Proteomic Analysis of Serum Exosomes in Cerebral Small-vessel Disease (CSVD) Patients With Depressive Symptoms
Authors: Zhao Zhong , Zhou Hua , Lu Yanjing , Shen Rong , Zhu Hao , Feng Qian , Li Yifan , Xu Wenxin , Zhang Dayong 
Published: November 2022

Background:Depressive symptoms are one of the main clinical features of the cerebral small-vessel disease (CSVD). However, the pathogenesis of depressive symptoms of CSVD has not been fully studied, and a lack of effective diagnostic methodseffective diagnostic methods exists. Recently, the emerging body of evidence regarding exosomes has rendered them potentially key players in the neuropsychiatric disease theragnostic. This study’s aim was to investigate serumexosome proteomic expression in CSVD patients with depressive symptoms and to screen and analyze potential biomarkers for clinical diagnosis.Methods:Serum samples were collected from 36 CSVD patients, including 18 cerebral small-vessel disease (CSVD+D) patients with depressive clinical manifestations and 18 cerebral small-vessel disease patients that did not present depression-related clinical manifestations (CSVD-D). This investigation employed tandem mass tag (TMT) combined with mass spectrometry for sample detection and quantitative analysis of proteins. The differential proteins with significant dysregulated expression levels in patient plasma exosomes were screened and analyzed through bioinformatics techniques.Results:This investigation focused on a global collection of 659 quantifiable proteins. Compared to the CSVD-D group, 7 up-regulated and 30 down-regulated proteins were identified in the CSVD+D group (P < 0.05). Gene ontology (GO) enrichment analyses revealed proteomic expression profile dysregulations within serum exosomes in patients with depression, such as desmosomes and keratins, rendering them as potential biomarkers. Kyoto encyclopedia of genes and genomes (KEGG) database investigations revealed the differentially expressed proteins to be highly aggregated within the estrogen signaling pathway.Conclusion:This investigation pioneered TMT proteomic evaluation of serum exosomes within CSVD patients suffering from depression and reveals the shifts in proteomic expression profiles by serum exosomes within such patients. This study identified several important molecular / signal pathway abnormalities related to depression. These results provide a possible means to further clarify the pathogenesis of depressive symptoms of cerebrovascular disease and its diagnosis and treatment in the future.
Aromatase Enzyme Activity and Liver Receptor Homolog-1 Levels in
Gestational Diabetes Mellitus
Authors: Bayraktar Nihayet , Tas Hasip , Bayraktar Mehmet , Koyuncu Ismail , Sarı İsmail , Uyanıkoğlu Hacer 
Published: November 2022

Background:
Gestational diabetes mellitus (GDM) is one of the prediabetes conditions in which high blood sugar levels and body weight increase during pregnancy. The underlying molecular and biochemical mechanisms of GDM are poorly defined.

Introduction:
Aromatase enzyme activity is responsible for the conversion of androgens to estrogens and has a share in the regulation of body fat distribution and liver receptor homolog-1 (LRH-1), which plays a critical role in cholesterol transport, acid homeostasis, and steroidogenesis in GDM patients. This study aims to determine the levels of aromatase enzyme and LRH-1 in GDM patients and to investigate the relationship between the levels of aromatase enzyme and LRH-1 and the levels of insulin, HbA 1c and total cholesterol.

Method:
This prospective cross-sectional study was conducted over eleven months (September 2020 to July 2021). The study population was selected at Harran University Teaching and Research Hospital. The study included 32 GDM patients and 32 healthy pregnants. The automated assay measured serum fasting blood glucose, HbA1c, and insulin levels (AVIDA 1800 Chemistry System; Siemens). Aromatase enzyme activity and LRH-1 levels were determined by using a commercial enzyme-linked immunosorbent assay (ELISA) kit.

Result:
Aromatase activity decreased in GDM patients while LRH1 increased. Significant differences in means levels of fasting blood glucose (p=0.11), insulin (p= 0.001) and HbA1c (p= 0.001) between the patients and control groups. There was a significant negative correlation between the levels of aromatase and insulin (r=-370, p =0.037). In addition, a positive significant correlation coefficient (r=0.645, p=0.001) was found between HbA1c and total cholesterol among the patients' group.

Conclusion:
Our findings indicate that there is a negative relationship between aromatase activity and insulin levels. Aromatase and LRH 1 may play a role in the pathogenesis of GDM, and the use of LRH-1 agonists in treating the disease may be considered an alternative treatment in the future. However, additional studies are required to reveal the possible functions of these two proteins in GDM with their mechanisms.
CLABSI in Hemodialysis– New Face to an Old Foe; A Look at Current Trends and a Review of Literature
Authors: Jose Nisha , S. Manikantan , John Kevin , Prasad Ram , Jayakumar M. 
Published: November 2022

Background:
Bloodstream infections are a potentially devastating complication of hemodialysis. This study aimed to elucidate the rates of CLABSI (Central Line Associated Blood Stream Infections)in a south Indian dialysis cohort and determine the catheter care and hygiene practices in the dialysis unit which might contribute to CLABSI

Methods:
A prospective observational study involving in-center dialysis patients with temporary access was conducted from June 2019 to December 2019. The catheter insertion and line handling techniques were monitored using a proforma adapted from the CDC (Center for Disease Control) guidelines. Adherence to infection control practices, rates of CLABSI identified using CDC surveillance definitions, and organisms identified were reported.

Results and Discussion:
The median rate of CLABSI in this dialysis unit was 1.68 per 1000 catheter days. Gram-positive organisms were the majority – 69.2% and 72.27% were drug-resistant pathogens. The adherence to infection control practices in hand sterility, use of barriers, and sterile insertion technique were 100% with respect to existing CDC guidelines. The use of sterile semi-transparent dressings, however, was 98.2%. 65% of all patients had soiled dressings on arrival to the hospital. Line handling protocols were followed in accordance with CDC guidelines in 97.1% of cases

Conclusion:
CLABSI rates in this institute are in keeping with those around the world. There is a predominance of gram-positive organisms causing CLABSI. Drug-resistant organisms represent an alarming 72.27%of all infections. Soiled dressing and home care of the dialysis catheters represent a neglected aspect of catheter care and should be addressed.
What's the Relation between Iron Deficiency (ID) and Febrile Seizure (FS)? A Case Control Study in Tehran, Iran
Authors: Ehsanipour Fahimeh , Noorbakhsh Samileh , Tavasooli Azita , Tahernia Leila 
Published: November 2022

Objective:
To evaluate the role of ID in the pathogenesis of FS.

Methods:
In this case-control study (2014-2016), 70 children were studied, 35 children with FS and 35 (controls)children with febrile diseases without convulsion (The mean age of cases was 2.191 ± 0946 vs. 1.93 ± 1.433 years in controls). Serum ferritin was estimated by the EIAS test. Data were compared between 2 groups, The ROC (receiver-operating-characteristic) curve was illustrated. The sensitivity, specificity, PPV, and NPV of the test, were calculated.

Results:
Serum ferritin levels had no significant difference between the 2 groups. The ferritin level (36ng/ml) had 74.3% sensitivity, 20% specificity, 56% PPV, and 52% NPV, with a Positive likelihood Ratio being 1.3 and a Negative likelihood Ratio: 0.93 to discriminate the 2 groups.

Conclusion:
Here the ferritin level (cut-off=36ng/ml) has an acceptable sensitivity (74.3%) but poor specificity (20%) and just 56% PPV and 52% NPV to differentiate the FS cases from non-convulsive febrile children. Although a different cut-off value 21.50 ng/ml provides 91% sensitivity and very low specificity . This lower threshold cut-off might have clinically relevant outcomes in FS children if considering the other comorbidities. In our opinion, ID could not lead to FS in all children, but in some cases, with a genetic basis; ID raises the threshold for seizures. The ferritin levels as an acute phase reactant are acceptable in every febrile case. The ferritin base level in each child (case /control) before infection was unknown, but in the present study, both groups were febrile in contrast to previous studies in which ferritin levels were compared with afebrile children. Due to the high prevalence of ID (26%), especially in the young Iranian population, adding iron to the diet might help decrease FS in susceptible cases. We recommend in the future study the FS cases selected with known iron levels before convulsion.
The Role of the World Health Organization in Increasing the Capacity of COVID-19 Laboratories in Indonesia
Authors: Candrawati Tanti Belinda , Mustikawati Inggrid Galuh , Wulandari Endah 
Published: November 2022

Objective:
The aim of this research to explore the role of WHO in increasing the capacity of the COVID-19 laboratories in Indonesia.

Methods:
Explorative research, assesses deeply about issues or social phenomena that is not widely understood, new cases that have not been handled optimally. This study explores various data and information regarding the development of Corona cases and WHO program to solve the health crisis through data, literature review, and interview.

Results:
The role of WHO in increasing the capacity of COVID-19 laboratories in Indonesia can be seen in two sectors, namely surveillance activation and improvement of national laboratory diagnostics. To activate and strengthen the surveillance, several actions were taken by WHO, such as introducing the COVID-19 surveillance system to the Indonesian Government, supporting surveillance activities on various platforms, utilizing the Influenza Surveillance System to track COVID-19 cases, anticipating the increase of COVID-19 cases due to religious event, broadening the contact tracing network, developing an application to track close contact, and facilitating regular training for contact tracing officer. In the second sector, improvement of national laboratory diagnostic, WHO is actively supplying COVID-19 testing kits to Indonesia, conducting capacity building for laboratory staff, creating guidelines for COVID-19 testing, activating the existing Influenza Laboratory as COVID-19 Laboratory, and monitoring the quality of COVID-19 diagnostic.

Conclusion:
In order to increase the capacity of COVID-19 Laboartory in Indonesia, WHO actively contributes in strengthening the surveillance system and improving national laboratories' diagnostic.
Current Remedial Strategies for the Treatment of Rheumatoid Arthritis
through the Oral Route with Janus Kinase Inhibitors
Authors: Mathur Pooja , Verma Ravinder , Kumar Manish , Jhawat Vikas , Dutt Rohit , Bhatt Shailendra 
Published: November 2022

Abstract:
Rheumatoid arthritis (RA) is a well-known chronic inflammatory disease that results in
articular degradation, comorbidities, and body part functional loss. In the last two decades, the development of effective biologics and small compounds, such as Janus kinase inhibitors (Jakinibs),
has significantly improved clinical outcomes. Low-molecular-weight chemicals known as jakinibs
are currently used for effective treatment of RA. Jakinibs are a new class of drugs being developed
to treat RA, and several of them are now in different phases of clinical trials to establish their safety
and efficacy in humans. Jakinibs can be very different in their selectivity against JAK inhibitors.
For an efficient therapy of RA, it is critical to fully comprehend the properties of JAK inhibitors as
well as their mechanism of action. Tofacitinib, Baricitinib, Upadacitinib, Peficitinib, Filgotinib, Decernotinib, Itacitinib, Ruxolitinib, and PF-06651600 are a few selective orally active Jakinibs that
have entered clinical trials to treat RA. This review aims to elaborate on Jakinibs for the treatment
of Rheumatoid Arthritis (RH), including their mechanism of action (MOA), efficacy and safety profiles, clinical trials of adverse effects (AEs) associated with Jakinibs and combination therapy with
other DMARDs.
Optimization and Fabrication of Curcumin Loaded Solid Lipid Nanoparticles
Using Box-Behnken Design for Nasal Delivery
Authors: Bhatt Shailendra , Sharma Sherry , Sharma Jai Bharti , Kumar Manish 
Published: November 2022

Aims:
To prepare curcumin loaded solid lipid nanoparticles for nasal administration using
Box-Behnken design.

Background:
The effectiveness of curcumin in neurological disorders is widely studied by various researchers,
but its use is limited due to its poor bioavailability. The brain-targeting efficiency of curcumin
can be improved using solid lipid nanoparticles via nasal administration.

Objective:
In the present work, Curcumin loaded solid lipid nanoparticles (CUR-SLN) were formulated
and optimized for nasal administration.

Methods:
Based on solubility studies, cetostearyl alcohol and poloxamer 407 were selected as lipid and
surfactant, respectively. Box-Behnken design (BBD) was used to analyze the effects of drug-to-lipid ratio
(X1), surfactant concentration (X2) and homogenization time (X3) on particle size (Y1) and % entrapment
efficiency (Y2). The CUR-SLN were formulated by the high shear homogenization method. The
optimized formulation was evaluated for DSC, TEM, drug release and ex-vivo studies.

Results:
Good results were obtained for the particle size and entrapment efficiency analyzed using BBD.
The optimized formulation of CUR-SLN obtained using BBD was observed with a particle size of 96.09
nm and % EE of 78.23. In-vitro release of the drug was found to be 82.93± 0.15% after 8 hours. DSC
studies revealed that crystalline form of curcumin changed to an amorphous form in SLN. TEM results of
optimized CUR-SLN were in correlation with the results obtained using a zeta sizer. No harmful effects
were observed on nasal mucosa in the histopathology study.

Conclusion:
The SLN can be safely utilized for the intranasal administration of curcumin.
Effect of the Surfactant Charge on the Characteristics and Anticancer
Effects of Docetaxel-loaded Poloxamer Polymeric Micelles
Authors: Harry Nugraha Dwianto , Anggadiredja Kusnandar , Rachmawati Heni 
Published: November 2022

Background:
The main problem in the use of docetaxel as a potent chemotherapeutic agent is its solubility. Practically insoluble docetaxel requires a harsh formulation with high surfactant and alcohol concentrations to comply with the product quality. However, this formulation is inconvenient for patients. Polymeric micelles using a biocompatible polymer, poloxamer, seem to be a promising approach to increase the solubility of docetaxel, avoiding the high polysorbate and alcohol contents in the commercial product and yielding similar or better anticancer effects.

Objective:
This study aims to investigate the effects of surfactant with three different charges on the particle size, chemical stability, in vitro drug release and anticancer efficacy of the docetaxel-loaded poloxamer-based polymeric micelle formulation.

Methods:
The freeze drying method was used to prepare polymeric micelles of docetaxel. Dynamic light scattering was used to determine particle size. The morphology of particles was investigated using a transmission electron microscope. High Pressure Liquid Chromatography was used to measure encapsulation efficiency, drug loading, and percentage of drug released. MTT assay was used to assess the anticancer effect.

Result:
Nonionic and anionic surfactants tended to increase the particle size, while cationic surfactants
had no effect. Furthermore, the addition of cationic surfactant increased the chemical stability
of docetaxel. Poloxamer polymeric micelles have sustained drug release, and the addition of
a surfactant can increase polymeric micelle drug release. All surfactant charges increased the anticancer
efficacy of docetaxel compared to the commercial formulation Taxotere, except for the
formulation prepared with an anionic surfactant.

Conclusion:
The charge of the surfactant affects the particle size, chemical stability, drug release and anticancer properties of docetaxel-loaded poloxamer polymeric micelles. Cationic surfactant formulations have shown to be promising, resulting in the most stable and highest anticancer effect.