bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resveratrol alleviates the interleukin-1β-induced chondrocytes injury through the NF-κB signaling pathway
Authors: Yi Hong , Zhang Wei , Cui Zhi-Ming , Cui Sheng-Yu , Fan Jian-Bo , Zhu Xin-Hui , Liu Wei 
Published: September 2020

Abstract
Background
Osteoarthritis (OA) is a regular age-related disease that affects millions of people. Resveratrol (RSV) is a flavonoid with a stilbene structure with different pharmacological effects. The purpose of the experiment was to evaluate the protective role of RSV against the human OA chondrocyte injury induced by interleukin-1β (IL-1β).

Methods
Chondrocytes were isolated from OA patients and identified by type II collagen, safranin O staining, and toluidine blue staining. Differentially expressed genes in chondrocytes treated RSV were identified by RNA sequencing. Kyoto encyclopedia of genes and genomes (KEGG) pathway as well as gene ontology (GO) were further conducted through Metascape online tool. A cell counting kit-8 (CCK-8) assay was applied to discover the viability of chondrocytes (6, 12, 24, and 48 μM). Many genes associated with inflammation and matrix degradation are evaluated by real-time PCR (RT-PCR) as well as western blot (WB). The mechanism of RSV for protecting IL-1β induced chondrocytes injury was further measured through immunofluorescence and WB assays.

Results
A total of 845 differentially expressed genes (upregulated = 499, downregulated = 346) were found. These differentially expressed genes mainly enriched into negative regulation of catabolic process, autophagy, and cellular catabolic process, intrinsic apoptotic, apoptotic, and regulation of apoptotic signaling pathway, cellular response to abiotic stimulus, external stimuli, stress, and radiation. These differentially expressed genes were obviously enriched in NF-kB signaling pathway. RSV at the concentration of 48 μM markedly weakened the viability of the cells after 24 h of treatment (87% vs 100%, P < 0.05). No obvious difference was observed between the 6, 12, and 24 μM groups (106% vs 100%, 104% vs 100%, 103% vs 100%, P > 0.05). RSV (24 μM) also markedly depressed the levels of PGE2 and NO induced by IL-1β by 25% and 29% respectively (P < 0.05). Our experiment pointed out that RSV could dramatically inhibit the inflammatory response induced by IL-1β, including the MMP-13, MMP-3, and MMP-1 in human OA chondrocytes by 50%, 35%, and 33% respectively. On the other hand, RSV inhibited cyclooxygenase-2 (COX-2), matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, and inducible nitric oxide synthase (iNOs) expression (P < 0.05), while increased collagen-II and aggrecan levels (P < 0.05). From a mechanistic perspective, RSV inhibited the degradation of IκB-α as well as the activation of nuclear factor-kappa B (NF-κB) induced by IL-1β.

Conclusion
In summary, RSV regulates the signaling pathway of NF-κB, thus inhibiting inflammation and matrix degradation in chondrocytes. More studies should be focused on the treatment efficacy of RSV for OA in vivo.
Neonatal hyperinsulinemic hypoglycemia: case report of kabuki syndrome due to a novel KMT2D splicing-site mutation
Authors: Piro Ettore , Schierz Ingrid Anne Mandy , Antona Vincenzo , Pappalardo Maria Pia , Giuffrè Mario , Serra Gregorio , Corsello Giovanni 
Published: September 2020

Abstract
Background
Persistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia.

Patient presentation
We report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported.

Conclusions
Kabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.
Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study
Authors: Shah Akshay , Donovan Killian , McHugh Anna , Pandey Manish , Aaron Louise , Bradbury Charlotte A. , Stanworth Simon J. , Alikhan Raza , Von Kier Stephen , Maher Keith , Curry Nicola , Shapiro Susan , Rowland Matthew J. , Thomas Matt , Mason Richard , Holland Matthew , Holmes Tom , Ware Michael , Gurney Stefan , McKechnie Stuart R. 
Published: September 2020

Abstract
Background
Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications.

Methods
We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications.

Results
A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49–64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not.

Conclusion
Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.

Graphical abstract
A cohort study among 402 patients with penile cancer in Maranhão, Northeast Brazil with the highest worldwide incidence
Authors: Vieira Ciro Bezerra , Teixeira-Júnior Antonio , Feitoza Laisson , Pinho Jaqueline , Calixto José , do Nascimento Francisco Sérgio Moura Silva , Campos Marcos Adriano Garcia , Lages Joyce , Junior Antonio Machado Alencar , Soares Fernando , Cunha Isabela , Silva Gyl Eanes Barros 
Published: September 2020

Abstract
Objective
Maranhão State—Northeast Brazil–has the world’s highest incidence of penile cancer. This study describes the epidemiological, histopathological and clinical profile of patients stricken across that Brazilian state. The study is aimed at providing new data on neoplasia.

Data description
402 men stricken with penile cancer were studied from January 2004 to December 2018. A retrospective stage was developed with collection of physical and electronic records. A prospective stage was performed with collection of clinical and epidemiological information through a questionnaire. The surgical material was looked into by a uropathologist, and the lesions were evaluated for macroscopic characteristics and various microscopic parameters. Three articles using this data have already been published.
Rapid and economical drug resistance profiling with Nanopore MinION for clinical specimens with low bacillary burden of Mycobacterium tuberculosis
Authors: Chan Wai Sing , Au Chun Hang , Chung Yvonne , Leung Henry Chi Ming , Ho Dona N. , Wong Elaine Yue Ling , Lam Tak Wah , Chan Tsun Leung , Ma Edmond Shiu Kwan , Tang Bone Siu Fai 
Published: September 2020

Abstract
Objective
We designed and tested a Nanopore sequencing panel for direct tuberculosis drug resistance profiling. The panel targeted 10 resistance-associated loci. We assessed the feasibility of amplifying and sequencing these loci from 23 clinical specimens with low bacillary burden.

Results
At least 8 loci were successfully amplified from the majority for predicting first- and second-line drug resistance (14/23, 60.87%), and the 12 specimens yielding all 10 targets were sequenced with Nanopore MinION and Illumina MiSeq. MinION sequencing data was corrected by Nanopolish and recurrent variants were filtered. A total of 67,082 bases across all consensus sequences were analyzed, with 67,019 bases called by both MinION and MiSeq as wildtype. For the 41 single nucleotide variants (SNVs) called by MiSeq with 100% variant allelic frequency (VAF), 39 (95.1%) were called by MinION. For the 22 mixed bases called by MiSeq, a SNV with the highest VAF (70%) was called by MinION. With short assay time, reasonable reagent cost as well as continuously improving sequencing chemistry and signal correction pipelines, this Nanopore method can be a viable option for direct tuberculosis drug resistance profiling in the near future.
A novel target enrichment strategy in next-generation sequencing through 7-deaza-dGTP-resistant enzymatic digestion
Authors: Peng Peng , Xu Yanjuan , Di Bisceglie Adrian M. , Fan Xiaofeng 
Published: September 2020

Abstract
Objective
Owing to the overwhelming dominance of human and commensal microbe sequences, low efficiency is a major concern in clinical viral sequencing using next-generation sequencing. DNA composed of 7-deaza-2′-deoxyguanosine 5′-triphosphate (c7dGTP), an analog of deoxyguanosine triphosphate (dGTP), is resistant to selective restriction enzymes. This characteristic has been utilized to develop a novel strategy for target enrichment in next-generation sequencing.

Results
The new enrichment strategy is named target enrichment via enzymatic digestion in next-generation sequencing (TEEDseq). It combined 7-deaza-2′-deoxyguanosine 5′-triphosphate (c7dGTP)-involved primer extension, splinter-assisted intracellular cyclization, c7dGTP)-resistant enzymatic digestion, and two-phase rolling cycle amplification. We first estimated c7dGTP for its efficiency in PCR amplification and its resistance to three restriction enzymes, AluI, HaeIII, and HpyCH4V. We then evaluated TEEDseq using a serum sample spiked with a 1311-bp hepatitis B virus (HBV) fragment. TEEDseq achieved an HBV on-target rate of 3.31 ± 0.39%, which was equivalent to 454× the enrichment of direct Illumina sequencing. Therefore, the current study has provided a concept proof for TEEDseq as an alternative option for clinical viral sequencing that requires an enrichment in next-generation sequencing.
Assessing the requirements of prenatal UBE3A expression for rescue of behavioral phenotypes in a mouse model for Angelman syndrome
Authors: Sonzogni Monica , Zhai Peipei , Mientjes Edwin J. , van Woerden Geeske M. , Elgersma Ype 
Published: September 2020

Abstract
Background
Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of functional ubiquitin protein ligase E3A (UBE3A). In neurons, UBE3A expression is tightly regulated by a mechanism of imprinting which suppresses the expression of the paternal UBE3A allele. Promising treatment strategies for AS are directed at activating paternal UBE3A gene expression. However, for such strategies to be successful, it is important to know when such a treatment should start, and how much UBE3A expression is needed for normal embryonic brain development.

Methods
Using a conditional mouse model of AS, we further delineated the critical period for UBE3A expression during early brain development. Ube3a gene expression was induced around the second week of gestation and mouse phenotypes were assessed using a behavioral test battery. To investigate the requirements of embryonic UBE3A expression, we made use of mice in which the paternal Ube3a allele was deleted.

Results
We observed a full behavioral rescue of the AS mouse model phenotypes when Ube3a gene reactivation was induced around the start of the last week of mouse embryonic development. We found that full silencing of the paternal Ube3a allele was not completed till the first week after birth but that deletion of the paternal Ube3a allele had no significant effect on the assessed phenotypes.

Limitations
Direct translation to human is limited, as we do not precisely know how human and mouse brain development aligns over gestational time. Moreover, many of the assessed phenotypes have limited translational value, as the underlying brain regions involved in these tasks are largely unknown.

Conclusions
Our findings provide further important insights in the requirement of UBE3A expression during brain development. We found that loss of up to 50% of UBE3A protein during prenatal mouse brain development does not significantly impact the assessed mouse behavioral phenotypes. Together with previous findings, our results indicate that the most critical function for mouse UBE3A lies in the early postnatal period between birth and P21.
Facilitating islet transplantation using a three-step approach with mesenchymal stem cells, encapsulation, and pulsed focused ultrasound
Authors: Razavi Mehdi , Ren Tanchen , Zheng Fengyang , Telichko Arsenii , Wang Jing , Dahl Jeremy J. , Demirci Utkan , Thakor Avnesh S. 
Published: September 2020

Abstract
Background
The aim of this study was to examine the effect of a three-step approach that utilizes the application of adipose tissue-derived mesenchymal stem cells (AD-MSCs), encapsulation, and pulsed focused ultrasound (pFUS) to help the engraftment and function of transplanted islets.

Methods
In step 1, islets were co-cultured with AD-MSCs to form a coating of AD-MSCs on islets: here, AD-MSCs had a cytoprotective effect on islets; in step 2, islets coated with AD-MSCs were conformally encapsulated in a thin layer of alginate using a co-axial air-flow method: here, the capsule enabled AD-MSCs to be in close proximity to islets; in step 3, encapsulated islets coated with AD-MSCs were treated with pFUS: here, pFUS enhanced the secretion of insulin from islets as well as stimulated the cytoprotective effect of AD-MSCs.

Results
Our approach was shown to prevent islet death and preserve islet functionality in vitro. When 175 syngeneic encapsulated islets coated with AD-MSCs were transplanted beneath the kidney capsule of diabetic mice, and then followed every 3 days with pFUS treatment until day 12 post-transplantation, we saw a significant improvement in islet function with diabetic animals re-establishing glycemic control over the course of our study (i.e., 30 days). In addition, our approach was able to enhance islet engraftment by facilitating their revascularization and reducing inflammation.

Conclusions
This study demonstrates that our clinically translatable three-step approach is able to improve the function and viability of transplanted islets.
A non-integer sliding mode controller to stabilize fractional-order nonlinear systems
Authors: Haghighi Ahmadreza , Ziaratban Roveida 
Published: September 2020

AbstractIn this study, we examine the stabilization of fractional-order chaotic nonlinear dynamical systems with model uncertainties and external disturbances. We used the sliding mode controller by a new approach for controlling and stabilization of these systems. In this research, we replaced a continuous function with the sign function in the controller design and the sliding surface to suppress chattering and undesirable vibration effects. The advantages of the proposed control method are rapid convergence to the equilibrium point, the absence of chattering and unwanted oscillations, high resistance to uncertainties, and the possibility of applying this method to most fractional order chaotic systems. We applied the direct method of Lyapunov stability theory and the frequency distributed model to prove the stability of the slip surface and closed loop system. Finally, we simulated this method on two commonly used and practical chaotic systems and presented the results.
The lower bathyal and abyssal seafloor fauna of eastern Australia
Authors: O’Hara T. D. , Williams A. , Ahyong S. T. , Alderslade P. , Alvestad T. , Bray D. , Burghardt I. , Budaeva N. , Criscione F. , Crowther A. L. , Ekins M. , Eléaume M. , Farrelly C. A. , Finn J. K. , Georgieva M. N. , Graham A. , Gomon M. , Gowlett-Holmes K. , Gunton L. M. , Hallan A. , Hosie A. M. , Hutchings P. , Kise H. , Köhler F. , Konsgrud J. A. , Kupriyanova E. , Lu C. C. , Mackenzie M. , Mah C. , MacIntosh H. , Merrin K. L. , Miskelly A. , Mitchell M. L. , Moore K. , Murray A. , O’Loughlin P. M. , Paxton H. , Pogonoski J. J. , Staples D. , Watson J. E. , Wilson R. S. , Zhang J. , Bax N. J. 
Published: September 2020

Abstract
Background
Our knowledge of the benthic fauna at lower bathyal to abyssal (LBA, > 2000 m) depths off Eastern Australia was very limited with only a few samples having been collected from these habitats over the last 150 years. In May–June 2017, the IN2017_V03 expedition of the RV Investigator sampled LBA benthic communities along the lower slope and abyss of Australia’s eastern margin from off mid-Tasmania (42°S) to the Coral Sea (23°S), with particular emphasis on describing and analysing patterns of biodiversity that occur within a newly declared network of offshore marine parks.

Methods
The study design was to deploy a 4 m (metal) beam trawl and Brenke sled to collect samples on soft sediment substrata at the target seafloor depths of 2500 and 4000 m at every 1.5 degrees of latitude along the western boundary of the Tasman Sea from 42° to 23°S, traversing seven Australian Marine Parks.

Results
The biological sampling included 35 beam trawls, 28 Brenke sleds, 8 box cores, 20 surface meso-zooplankton tows, and 7 Deep Towed Camera transects. In total, 25,710 specimens were identified to 1084 taxonomic entities, including 847 species-level, 144 genus-level and 69 family-level and 24 higher-level taxa. Of the species-level taxa, only 457 were assigned species-level taxonomic names, which implies that up to 58% of the collected fauna is undescribed. In addition, the ranges of numerous species have been extended to include the western Tasman Sea.

Conclusions
The lower bathyal and abyssal fauna of soft sediment seafloors off eastern Australia has been systematically surveyed for the first time. The resultant collections will provide the foundation for much future ecological, biogeographical, phylogenetic and taxonomic research.
Evaluation of cerebrospinal fluid flow dynamic changes in patients with idiopathic intracranial hypertension using phase contrast cine MR imaging
Authors: Belal Tamer , Al Tantawy Abd-Elhalim , Sherif Fatema Mohamed , Ramadan Alshaimaa 
Published: September 2020

Abstract
Background
Idiopathic intracranial hypertension (IIH) mainly affects overweight women in the middle age period. The pathophysiology of IIH stays unclear, but suggested mechanisms include excess CSF production, reduced CSF absorption, increased brain water content, and increased cerebral venous pressure

Objectives
To assess the cerebrospinal fluid (CSF) flow dynamic changes in aqueduct of Sylvius in patients of idiopathic intracranial hypertension (IIH) with new MRI technique: phase contrast cine MRI (PCC-MRI).

Methods
Thirty patients diagnosed with idiopathic intracranial hypertension were divided into 3 groups according to treatment options (no treatment, medical treatment, and medical treatment with repeated lumbar tapping). CSF flow data were evaluated by phase contrast cine MRI.

Results
PCC-MRI parameters were significantly higher in group who was on medical treatment (group II) than other groups. The sensitivity of PCC MRI parameters ranged from 56.7 (stroke volume (SV) and mean flow (MF)) to 83.3% (peak systolic velocity (PSV)). A statistically significant difference was found for the mean flow value (p 0.039) between the control group and IIH patients.

Conclusion
The most specific CSF flowmetry parameter detected to help diagnosis of IIH is mean flow especially among early discovered patients. PCC MRI can be used as non-invasive technique for diagnosis of IIH and treatment follow-up.
Comparative study of African catfish parasites from cultured and natural habitats
Authors: Afolabi Olajide Joseph , Olususi Fayokemi Christianah , Odeyemi Olusola Olasumbo 
Published: September 2020

AbstractBackgroundThe study was conducted to compare parasitic loads ofClarias gariepinusfrom cultured and natural habitats. A total number of 80 live adults (200–799 g)C. gariepinuscomprising of 20 each were randomly obtained from two cultured habitats (ponds) and two natural habitats (rivers). In the laboratory, these fish were all examined for the presence of parasites. Their sexes were identified while the lengths and weights were measured and recorded prior to dissection. The parasites observed were also identified using morphological characteristics.ResultsOut of the 80C. gariepinussampled, 43 (53.75%) were infected and a total of 409 parasites comprising of 141 (34.47%) ectoparasites and 268 (65.53%) endoparasites were observed from the infected fish. The prevalence of parasitic infection in cultured and natural habitats was 20% and 33.75%, respectively. The results showed that there was a significant difference (P< 0.05) in parasitic infection ofC. gariepinusobtained from cultured and natural habitats. Parasitic loads were observed to be significantly higher in natural habitat (33.74% and 26.16% for river A and river B, respectively) compared to cultured habitat (20.54% and 19.55% for pond A and pond B, respectively). The prevalence of parasites in relation to sexes ofC. gariepinuswas not significantly different (P> 0.05) for both habitats. It was also noted that catfishes with body weight 500–599 g had the highest prevalence (100%) both in cultured and natural habitats.ConclusionsThe study showed that the parasite loads were more inC. gariepinusobtained from natural habitat compared to those obtained from cultured habitat. It is therefore recommended that the sanitary conditions under which fishes are reared in fish pond should be improved and fish stocked from natural habitats or unscreened ponds should be quarantined to eliminate and treat possible parasitic infection before introducing them into other fish ponds.