bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy
Authors: Wu Kan Xing , Yeo Natalie Jia Ying , Ng Chun Yi , Chioh Florence Wen Jing , Fan Qiao , Tian Xianfeng , Yang Binxia , Narayanan Gunaseelan , Tay Hui Min , Hou Han Wei , Dunn N. Ray , Su Xinyi , Cheung Chui Ming Gemmy , Cheung Christine 
Published: February 2022

Abstract
Background
Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD), is a global leading cause of vision loss in older populations. Distinct from typical AMD, PCV is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Gold standard anti-vascular endothelial growth factor (anti-VEGF) therapy often fails to regress polypoidal lesions in patients. Current animal models have also been hampered by their inability to recapitulate such vascular lesions. These underscore the need to identify VEGF-independent pathways in PCV pathogenesis.

Results
We cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls to serve as our experimental disease models. When BOECs were exposed to heterogeneous flow, single-cell transcriptomic analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of glycocalyx that interfaces between flow stress and vascular endothelium. Notably, knockdown of hyaluronidase-1 in PCV BOEC improved mechanosensitivity, as demonstrated by a significant 1.5-fold upregulation of Krüppel-like factor 2 (KLF2) expression, a flow-responsive transcription factor. Activation of KLF2 might in turn modulate PCV BOEC migration. Barrier permeability due to glycocalyx impairment in PCV BOECs was also reversed by hyaluronidase-1 knockdown. Correspondingly, hyaluronidase-1 was detected in PCV patient vitreous humor and plasma samples.

Conclusions
Hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.
Obesity, metabolic risk and adherence to healthy lifestyle behaviours: prospective cohort study in the UK Biobank
Authors: Heath Laura , Jebb Susan A. , Aveyard Paul , Piernas Carmen 
Published: February 2022

Abstract
Background
Contested evidence suggests that obesity confers no risk to health in people who have a healthy lifestyle, particularly if there are no metabolic complications of obesity. The aim was to examine the association between adherence to lifestyle recommendations and the absence of metabolic complications on the incident or fatal cardiovascular disease and all-cause mortality across different categories of body mass index (BMI).

Methods
This contemporary prospective cohort study included 339,902 adults without cardiovascular disease at baseline, recruited between 2006 and 2010 from the UK Biobank and followed until 2018–2020. The main exposures were four healthy lifestyle behaviours: never smoker, alcohol intake ≤ 112g/ week, 150 min moderate physical activity or 75 min vigorous activity/week, ≥ 5 servings of fruit or vegetables/day, and we assessed these overall and across the BMI groups. Metabolic complications of excess adiposity were hypertension, diabetes and hyperlipidaemia, and we examined whether obesity was associated with increased risk in the absence of these complications. The outcomes were all-cause mortality, death from, and incident cardiovascular disease (CVD).

Results
Individuals who met four lifestyle recommendations but had excess weight had higher all-cause mortality; for BMI 30–34.9 kg/m2, the hazard ratio (HR) was 1.42 (95% confidence interval 1.20 to 1.68), and for BMI ≥ 35 kg/m2, HR was 2.17 (95% CI 1.71 to 2.76). The risk was lower, but still increased for people with no metabolic complications; for all-cause mortality, BMI 30–34.9 kg/m2 had an HR of 1.09 (95% CI 0.99 to 1.21), and BMI ≥ 35 kg/m2 had an HR of 1.44 (95% CI 1.19 to 1.74) for all-cause mortality. Similar patterns were found for incident and fatal CVD.

Conclusions
Meeting healthy lifestyle recommendations, or the absence of metabolic complications of obesity offsets some, but not all, of the risk of subsequent CVD, and premature mortality in people with overweight or obesity. Offering support to achieve and maintain a healthy weight and to adopt healthy behaviours are likely to be important components in effective preventative healthcare.
Characterization of DNA methylation as well as mico-RNA expression and screening of epigenetic markers in adipogenesis
Authors: Zhang Yong , Chen Fancheng , Zhang Fangxue , Huang Xiaowei 
Published: February 2022

AbstractThis study aimed to use bioinformatics methods to characterize epigenetic changes in terms of micro-RNA(miRNA) expression and DNA methylation during adipogenesis. The mRNA and miRNA expression microarray and DNA methylation dataset were obtained from the GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylated probes (DMPs) were filtered using the limma package. The R language cluster profile package was used for functional and enrichment analysis. A protein–protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape. The Connection map (CMap) website tool was used to screen potential therapeutic drugs for adipogenesis. When comparing the early and late stages of adipogenesis, 111 low miRNA targeted upregulated genes and 64 high miRNA targeted downregulated genes were obtained, as well as 663 low-methylated high-expressed genes and 237 high-methylated low-expressed genes. In addition, 41 genes (24 upregulated and 17 downregulated) were simultaneously regulated by abnormal miRNA changes and DNA methylation. Ten chemicals were identified as putative therapeutics for adipogenesis. In addition, among the dual-regulated genes identified, CANX, HNRNPA1, MCL1, and PPIF may play key roles in the epigenetic regulation of adipogenesis and may serve as aberrant methylation or miRNA targeting biomarkers.
The prevalence and pattern of cannabis use among patients attending a methadone treatment clinic in Nairobi, Kenya
Authors: Ngarachu Elizabeth Wambui , Kiburi Sarah Kanana , Owiti Frederick R. , Kangethe Rachel 
Published: February 2022

Abstract
Background
Cannabis use during methadone treatment may negatively impact treatment outcomes. The aim of this study was to determine the prevalence and pattern of cannabis use among patients attending a methadone treatment clinic in Nairobi, Kenya.

Methods
This was a retrospective study of 874 patients on methadone therapy at a methadone maintenance treatment clinic in Nairobi, Kenya from December 2014 to November 2018. Data on sociodemographic characteristics and drug use patterns based on urine drug screens was collected from patient files. Data was analyzed using Statistical Package for the Social Sciences (SPSS) for windows version 23.0.

Results
Point prevalence of cannabis use was 85.8% (95% CI, 83.3 – 88.0) at baseline and 62.7% (95% CI, 59.5 – 65.8) during follow-up. A pattern of polysubstance use was observed where opioids, cannabis and benzodiazepines were the most commonly used drugs. The mean age of the patients was 35.3 (SD 9.0) years with the majority being male, unemployed (76%), (51.4%) had reached primary level of education, and (48.5%) were divorced or separated. University education was associated with reduced risk for cannabis use OR = 0.1 (95% CI, 0.02-0.8, p = 0.031).

Conclusion
Cannabis use is prevalent among patients attending a methadone treatment clinic in Kenya, suggesting need for targeted interventions to address the problem of cannabis use during methadone treatment.
Efficiently sparse listing of classes of optimal cophylogeny reconciliations
Authors: Wang Yishu , Mary Arnaud , Sagot Marie-France , Sinaimeri Blerina 
Published: February 2022

Abstract
Background
Cophylogeny reconciliation is a powerful method for analyzing host-parasite (or host-symbiont) co-evolution. It models co-evolution as an optimization problem where the set of all optimal solutions may represent different biological scenarios which thus need to be analyzed separately. Despite the significant research done in the area, few approaches have addressed the problem of helping the biologist deal with the often huge space of optimal solutions.

Results
In this paper, we propose a new approach to tackle this problem. We introduce three different criteria under which two solutions may be considered biologically equivalent, and then we propose polynomial-delay algorithms that enumerate only one representative per equivalence class (without listing all the solutions).

Conclusions
Our results are of both theoretical and practical importance. Indeed, as shown by the experiments, we are able to significantly reduce the space of optimal solutions while still maintaining important biological information about the whole space.
In vitro effect of triamcinolone and platelet-rich plasma on cytokine levels of elbow lateral epicondylitis-derived cells
Authors: de Melo Viveiros Márcio Eduardo , Viveiros Magda Massae Hata , da Silva Márcia Guimarães , Rainho Cláudia Aparecida , Schellini Silvana Artioli 
Published: February 2022

AbstractBackgroundThe pathogenesis and treatment of lateral elbow epicondylitis (LEE) are still controversial. The purpose of the current study was to evaluate the production of inflammatory cytokines by LEE-derived cells and to compare the anti-inflammatory effect of triamcinolone acetonide with platelet-rich plasma (PRP) on cytokines production in primary culture of these cells.MethodsThird passage cells from primary cultures of LEE were assessed for the production of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α by immune-enzymatic assay (ELISA), after the treatment with 1, 10 and 100 μM triamcinolone compared to no treated controls at the time points 6, 12, 18, 24, 48, 72 and 96 h, and to PRP at 48, 72 and 96 h.ResultsThe cytokines IL-6 and IL-8 were produced in high concentrations by LEE cells. One, 10 and 100 μM triamcinolone induced significant decrease in the production of IL-6 and IL-8 at 48, 72 and 96 h, adding the time point 12 h for IL-8. Compared to controls, PRP caused a significant increase in the production of IL-6 and IL-8 and there was a significant increase in IL-10 production with the use of 100 μM triamcinolone at 48 h. The production of IL1-β and TNF-α was very low and did not change when the cultures were treated with triamcinolone or PRP.ConclusionLEE-derived cells produce IL-6 and IL-8, confirming the inflammatory nature of this condition. While triamcinolone inhibited the production of IL-6 and IL-8 by LEE cells, PRP induced an increase in these cytokines compared with controls.
Global prevalence of Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis
Authors: Salari Nader , Fatahi Behnaz , Valipour Elahe , Kazeminia Mohsen , Fatahian Reza , Kiaei Aliakbar , Shohaimi Shamarina , Mohammadi Masoud 
Published: February 2022

Abstract
Background
A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker (BMD) muscular dystrophies are located at the severe end of the spectrum that primarily affects skeletal muscle. Progressive muscle weakness in these purely genetic disorders encourages families with a positive history for genetic counseling to prevent a recurrence, which requires an accurate prevalence of the disorder. Here, we provide a systematic review and meta-analysis to determine the prevalence of DMD and BMD worldwide.

Method
The current systematic review and meta-analysis was carried out using Cochrane seven-step procedure. After determining the research question and inclusion and exclusion criteria, the MagIran, SID, ScienceDirect, WoS, ProQuest, Medline (PubMed), Embase, Cochrane, Scopus, and Google Scholar databases were searched to find relevant studies using defined keywords and all possible keyword combinations using the AND and OR, with no time limit until 2021. The heterogeneity of studies was calculated using the I2 test, and the publication bias was investigated using the Begg and Mazumdar rank correlation test. Statistical analysis of data was performed using Comprehensive Meta-Analysis software (version 2).

Results
A total of 25 articles involving 901,598,055 people were included. The global prevalence of muscular dystrophy was estimated at 3.6 per 100,000 people (95 CI 2.8–4.5 per 100,000 people), the largest prevalence in the Americans at 5.1 per 100,000 people (95 CI 3.4–7.8 per 100,000 people). According to the subgroup analysis, the prevalence of DMD and BMD was estimated at 4.8 per 100,000 people (95 CI 3.6–6.3 per 100,000 people) and 1.6 per 100,000 people (95 CI 1.1–2.4 per 100,000 people), respectively.

Conclusion
Knowing the precise prevalence of a genetic disorder helps to more accurately predict the likelihood of preventing its occurrence in families. The global prevalence of DMD and BMD was very high, indicating the urgent need for more attention to prenatal screening and genetic counseling for families with a positive history.
α-Tocopherol phosphate as a photosensitizer in the reaction of nucleosides with UV light: formation of 5,6-dihydrothymidine
Authors: Suzuki Toshinori , Ono Chiaki 
Published: February 2022

Abstract
Introduction
α-Tocopherol phosphate, a natural water-soluble α-tocopherol analog, exists in biological tissues and fluids. Synthesized α-tocopherol phosphate is used as an ingredient of cosmetics.

Findings
When a neutral mixed solution of 2′-deoxycytidine, 2′-deoxyguanosine, thymidine, and 2′-deoxyadenosine was irradiated with UV light at wavelengths longer than 300 nm in the presence of α-tocopherol phosphate, thymidine was markedly consumed in an α-tocopherol phosphate dose-dependent manner, whereas other nucleosides only slightly decreased. Two major product peaks were detected in an HPLC chromatogram. The products were identified as diastereomers of 5,6-dihydrothymidine. The addition of radical scavengers had almost no effects on the generation of 5,6-dihydrothymidine, whereas the reactions of nucleosides other than thymidine were suppressed. Trolox, another water-soluble α-tocopherol analog, did not generate 5,6-dihydrothymidine, although all nucleosides were slightly consumed. When UV irradiation of thymidine with α-tocopherol phosphate was conducted in D2O, two deuterium atoms were added to 5 and 6 positions of thymidine with both syn and anti configurations. The ratio of syn and anti configurations alternated depending on pD of the solution.

Conclusions
The results indicate that α-tocopherol phosphate is a photosensitizer of nucleosides, especially thymidine, and that it introduces two hydrogen atoms to thymidine from H2O, generating 5,6-dihydrothymidine.
Effect of cationic monomer structure on the aggregation behavior of amphoteric acrylic polymer around isoelectric point
Authors: Li Qijun , Yi Yudan , Wang Ya-nan , Li Jing , Shi Bi 
Published: February 2022

AbstractAmphoteric polymer can be used as retanning agent in leather manufacture. It is particularly useful in chrome-free tanning systems since it can regulate the charge properties of chrome-free leather and enhance the fixation of anionic post-tanning chemicals in leather. However, the aggregation and precipitation of amphoteric polymer retanning agents around the isoelectric point (pI) hinder their wide application. Herein, we synthesized five amphoteric acrylic polymers (AAPs) by free radical copolymerization with acrylic acid and five different cationic acrylic monomers. The effect of cationic monomer structure on the aggregation behavior of AAPs was investigated. The aggregation of AAPs in aqueous solution showed pH and concentration dependence. Light scattering analysis showed that Poly (AA-co-MAPTAC) and Poly (AA-co-DMAPMA) were in the shape of coiled linear flexible chains with small particle size (Rg 7.6 nm and 14.8 nm, respectively) near the pI. However, Poly (AA-co-DAC), Poly (AA-co-DMC) and Poly (AA-co-DMAEMA) were in the shape of hollow spheres and exhibited serious aggregation. Quantum chemical calculations suggested that the amide groups in the cationic monomers MAPTAC and DMAPMA enhanced the nucleophilicity of AAPs. Thus the corresponding AAPs could carry a large number of cationic charges to slow their aggregation when the pH just climbed over the pI. The results are expected to provide theoretical reference for the synthesis and widespread application of AAPs.
Bletilla striata polysaccharide modified collagen fiber composite sponge with rapid hemostasis function
Authors: Yan Xingyu , Chen Yining , Dan Weihua , Dan Nianhua , Li Zhengjun 
Published: February 2022

AbstractEmergencies often result in uncontrollable bleeding, which is thought to be the leading cause of death at the scene of the injured. Among various hemostasis scenarios, collagen fiber (CF) is gradually replacing traditional hemostatic materials due to its superior properties and ease of sourcing from animals. Herein, we use CF and the natural herbaceous Bletilla striata as raw materials to prepare a collagen fiber-oxidized Bletilla striata composite hemostatic sponge (CFOB). During the cross-linking process, the triple helix structure of collagen stays intact, and its porous three-dimensional network structure brings excellent bulkiness and water absorption properties. Experiments show that the optimal amount of sponge CFOB-10, namely oxidized Bletilla striata polysaccharide 0.5 mg/mL and CF 5 mg/mL, only needed 25 ± 4.06 s for hemostasis time in the rat liver hemorrhage model. In addition, CFOB meets the safety performance requirements of cytotoxicity classification standard 0. Therefore, the optimal amount of CFOB is an excellent new hemostatic material with application potential.
Graphical Abstract
Emerging complications of COVID-19 in a subset of Indian population: a pathological review with clinico-radiological case scenarios
Authors: Agarwal Aniket , Prachi  , Haider Andaleeb , Lalit Ekansh , Agarwal Ajay Kumar , Agarwal Seema 
Published: February 2022

Abstract
Background
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was declared a pandemic by the World Health Organization on 11 March 2020 has been reported in most countries around the world since its origins in Wuhan, China. As of September 2021, there have been over 229 million cases of COVID-19 reported worldwide, with over 4.7 million COVID-19–associated deaths.

Body
The devastating second wave of the COVID-19 pandemic in India has seen a rise in various extrapulmonary manifestations. One of key components in the pathogenesis of COVID-19 is downregulation of ACE-2, which is expressed on many organs and counterbalances the pro-inflammatory effects of ACE/angiotensin-II axis. This leads to influx of inflammatory cells into alveoli, increased vascular permeability and activation of prothrombotic mediators. Imaging findings such as ground glass opacities, interlobular septal thickening, vascular dilatation and pulmonary thrombosis correlate well with the pathogenesis.

Conclusion
We hypothesize that the systemic complications of COVID-19 are caused by either direct viral invasion or effect of cytokine storm leading to inflammation and thrombosis or a combination of both. Gaining insights into pathobiology of SARS-CoV-2 will help understanding the various multisystemic manifestations of COVID-19. To date, only a few articles have been published that comprehensively describe the pathophysiology of COVID-19 along with its various multisystemic imaging manifestations.
Autism and autistic traits in those who died by suicide in England
Authors: Cassidy Sarah , Au-Yeung Sheena , Robertson Ashley , Cogger-Ward Heather , Richards Gareth , Allison Carrie , Bradley Louise , Kenny Rebecca , O'Connor Rory , Mosse David , Rodgers Jacqui , Baron-Cohen Simon 
Published: February 2022

BackgroundAutism and autistic traits are risk factors for suicidal behaviour.AimsTo explore the prevalence of autism (diagnosed and undiagnosed) in those who died by suicide, and identify risk factors for suicide in this group.MethodStage 1: 372 coroners’ inquest records, covering the period 1 January 2014 to 31 December 2017 from two regions of England, were analysed for evidence that the person who died had diagnosed autism or undiagnosed possible autism (elevated autistic traits), and identified risk markers. Stage 2: 29 follow-up interviews with the next of kin of those who died gathered further evidence of autism and autistic traits using validated autism screening and diagnostic tools.ResultsStage 1: evidence of autism (10.8%) was significantly higher in those who died by suicide than the 1.1% prevalence expected in the UK general alive population (odds ratio (OR) = 11.08, 95% CI 3.92–31.31). Stage 2: 5 (17.2%) of the follow-up sample had evidence of autism identified from the coroners’ records in stage 1. We identified evidence of undiagnosed possible autism in an additional 7 (24.1%) individuals, giving a total of 12 (41.4%); significantly higher than expected in the general alive population (1.1%) (OR = 19.76, 95% CI 2.36–165.84). Characteristics of those who died were largely similar regardless of evidence of autism, with groups experiencing a comparably high number of multiple risk markers before they died.ConclusionsElevated autistic traits are significantly over-represented in those who die by suicide.
First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1)
Authors: Ou Sai-Hong Ignatius , Jänne Pasi A. , Leal Ticiana A. , Rybkin Igor I. , Sabari Joshua K. , Barve Minal A. , Bazhenova Lyudmila , Johnson Melissa L. , Velastegui Karen L. , Cilliers Cornelius , Christensen James G. , Yan Xiaohong , Chao Richard C. , Papadopoulos Kyriakos P. 
Published: February 2022

PURPOSE Adagrasib (MRTX849) is an oral, highly selective, small-molecule, covalent inhibitor of KRASG12C. We report results from a phase I/IB study of adagrasib in non–small-cell lung cancer, colorectal cancer, and other solid tumors harboring the KRAS G12C mutation. MATERIALS AND METHODS Patients with advanced KRAS G12C-mutant solid tumors were treated with adagrasib 150 mg orally once daily, 300 mg once daily, 600 mg once daily, 1,200 mg once daily, or 600 mg orally twice a day using an accelerated titration design, which transitioned to a modified toxicity probability interval design when a predefined degree of toxicity was observed or target adagrasib exposure was achieved. Safety, pharmacokinetics, and clinical activity were evaluated. RESULTS Twenty-five patients were enrolled and received at least one dose of adagrasib. The recommended phase II dose (RP2D) was 600 mg twice a day on the basis of safety, tolerability, and observed pharmacokinetics properties. No maximum tolerated dose was formally defined. After a median follow-up of 19.6 months, eight of 15 patients (53.3%; 95% CI, 26.6 to 78.7) with RECIST-evaluable KRAS G12C-mutant non–small-cell lung cancer treated at 600 mg twice a day achieved a confirmed partial response. The median duration of response was 16.4 months (95% CI, 3.1 to not estimable). The median progression-free survival was 11.1 months (95% CI, 2.6 to not estimable). One of two patients with KRAS G12C-mutant colorectal cancer treated at 600 mg twice a day achieved a partial response (duration of response, 4.2 months). At the RP2D, the most common treatment-related adverse events (any grade) were nausea (80.0%), diarrhea (70.0%), vomiting (50.0%), and fatigue (45.0%). The most common grade 3-4 treatment-related adverse event was fatigue (15.0%). CONCLUSION Adagrasib 600 mg twice a day was well tolerated and exhibited antitumor activity in patients with advanced solid tumors harboring the KRAS G12C mutation.