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Background: When high thromboembolic and bleeding risks coexist, the former tends to influence physicians' decision making for anti-coagulation therapy. However, the ideal is to weigh the risk of major bleeding and stroke together to ensure effective anti-coagulation treatment, which is a limitation of traditional guideline recommended CHA2DS2-VASc and HAS-BLED. This meta-analysis assesses the performance of the two new scores - ABC and GARFIELD-AF compared to CHA2DS2-VASc and HAS-BLED for major bleeding and stroke outcomes in patients with atrial fibrillation (AF) on anticoagulation therapy., Methods: MEDLINE and Cochrane central were searched from 2010 to February 2023 that compared GARFIELD-AF and/or ABC with CHA2DS2-VASc and/or HAS-BLED scores using C-statistics to assess their discriminative ability., Results: 12 studies were included in this meta-analysis. When assessing stroke risk prediction, GARFIELD-AF stroke (C-Statistic: 0.71; 95 % CI: 0.70-0.72; I 2  = 0 %, p < 0.05) was found to be significantly better than ABC-stroke (C-Statistic: 0.67; 95 % CI: 0.65-0.68; I 2  = 0 %, p < 0.05), and CHA2DS2-VASc (C-Statistic: 0.64; 95 % CI: 0.60-0.67; I 2  = 92 %, p < 0.05). Additionally, when assessing bleeding risk prediction, ABC-bleeding (C-Statistic: 0.66; 95 % CI: 0.61-0.70; I 2  = 84 %, p < 0.05), GARFIELD-AF (C-Statistic: 0.64; 95 % CI: 0.60-0.68; I 2  = 95 %, p < 0.05), and HAS-BLED (C-Statistic: 0.64; 95 % CI: 0.62-0.66; I 2  = 85 %, p < 0.05) all showed equivalent performances., Conclusion: The GARFIELD-AF stroke score showed superior performance to the well-established CHA2DS2-VASc score as well as the ABC-stroke score. Therefore, new guidelines should favor GARFIELD-AF use in clinical practice., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Our study produced GO-TiO 2 -chitosan-escin nanocomposites (GTCEnc), characterized them using physical and biological methods, and evaluated their potential as cancer treatment candidates. Standard protocols were used to produce GTCEnc. Nanocomposites are created using XRD, FTIR, UV-Vis, and PL spectroscopy analysis. The morphology and ultrastructure of nanocomposites were investigated using SEM and TEM. Nanocomposites containing TiO 2 , GO, chitosan, and escin nanostructures were characterized using diffraction, microscopy, and spectroscopy; the antimicrobial activity of GTCEnc was investigated. Various methods were used to test the anticancer activity of GTCEnc against COLO 205 cell lines, including MTT, EtBr/AO, DAPI, JC-1, Annexin-V/FITC, cell cycle analysis, and activation of pro-apoptotic markers, such as caspase-3, -8, and -9. The nanocomposites were cytotoxic to COLO 205 cells, with an IC 50 of 22.68 μg/mL, but not to 293T cells. In cells treated with nanomaterials, cytotoxicity, nuclear damage, apoptosis induction, and free radical production were significantly increased. Our finding suggests that GTCEnc has potent anticancer and antibacterial activity in vitro because of its unique nanocomposite properties and antibacterial and anticancer activity in vitro. Additional research is required to understand the clinical efficacy of these nanocomposites., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gold nanoparticles have been broadly investigated as cancer diagnostic and therapeutic agents. Gold nanoparticles are a favorable drug delivery vehicle with their unique subcellular size and good biocompatibility. Chitosan, agarose, fucoidan, porphyran, carrageenan, ulvan and alginate are all examples of biologically active macromolecules. Since they are biocompatible, biodegradable, and irritant-free, they find extensive application in biomedical and macromolecules. The versatility of these compounds is enhanced because they are amenable to modification by functional groups like sulfation, acetylation, and carboxylation. In an eco-friendly preparation process, the biocompatibility and targeting of GNPs can be improved by functionalizing them with polysaccharides. This article provides an update on using carbohydrate-based GNPs in liver cancer treatment, imaging, and drug administration. Selective surface modification of several carbohydrate types and further biological uses of GNPs are focused on., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Carbohydrate polymers-based surface-modified nano-delivery systems have gained significant attention in recent years for enhancing targeted delivery to colon cancer. These systems leverage carbohydrate polymers' unique properties, such as biocompatibility, biodegradability, and controlled release. These properties make them suitable candidates for drug delivery applications. Nano-delivery systems loaded with bioactive compounds are well-studied for targeted colorectal cancer delivery. However, those drugs' target reach is still limited in various nano-delivery systems. To overcome this limitation, surface modification of nanoparticles with carbohydrate polymers like chitosan, pectin, alginate, and guar gum showed enhanced target-reaching capacity along with enhanced anticancer efficacy. Recently, a chitosan-decorated PLGA nanoparticle was constructed with tannic acid and vitamin E and showed long-term release of specific targets along with higher anticancer efficacy. Similarly, Chitosan-conjugated glucuronic acid-coated silica nanoparticles loaded with capecitabine were studied against colon cancer and found to be the pH-responsive controlled release of capecitabine with higher anticancer efficacy. Surface-modified carbohydrate polymers have promising potential for improving colon cancer target delivery. By leveraging the unique properties of these polymers, such as surface modification, pH responsiveness, mucoadhesion, controlled drug release, and combination therapy, researchers are working toward developing more effective and targeted treatment strategies for colon cancer., Competing Interests: Declaration of competing interest Final approval of the manuscript was obtained from all authors. There are no conflicts of interest or personal relationships between the authors that may influence this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Recent studies focusing on the prevalence, characteristics, and outcomes of primary heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) in non-alcoholic fatty liver disease (NAFLD) are sparse. We sought to assess these using a nationally-representative population. We used the 2016-2018 National Inpatient Sample database to study the prevalence, characteristics, clinical risk profiles, morbidity, mortality, cost, and resource utilization among primary HFpEF and HFrEF hospitalizations with and without NAFLD. In the period from January 1, 2016, to December 31, 2018, there were 3,522,459 admissions of patients aged ≥18 years with a diagnosis of primary HF. Of these, 82,585 (2.3%) hospitalizations had secondary diagnosis of NAFLD. Admissions with NAFLD and HFrEF were associated with higher rates of in-hospital mortality (aOR 1.84, CI 1.66-2.04, P < 0.001) compared to admissions of HFrEF without NAFLD. Similarly, hospitalizations with HFpEF-NAFLD were associated with higher rates of in hospital mortality (aOR 1.65 CI 1.43-1.9, P < 0.001) compared to HFpEF admissions without NAFLD. Pressors use, cardiogenic shock, AKI with or without dialysis use, cardiac arrest, LOS and hospitalization cost were higher in admissions of HFrEF and HFpEF with NAFLD compared to those without NAFLD. In-hospital mortality, was higher in primary HFrEF and HFpEF admissions with NAFLD compared to without NAFLD. Physicians must be aware of the worse clinical outcomes of HFrEF and HFpEF in patients with NAFLD. Further clinical research is needed to address the knowledge gap and treatment options available for the patients with HF and NAFLD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sleep-disordered breathing (SDB) is a common comorbidity in patients with heart failure (HF). Prevalence of the most common subtypes of SDB, central sleep apnea (CSA) and obstructive sleep apnea (OSA), is increasing, which is concerning due to the association of SDB with increased mortality in patients with HF. Despite an increasing burden of CSA in HF, it is difficult to detect using current diagnostic tools and the treatment modalities are limited by variable efficacy and patient adherence. Though positive airway pressure therapies remain the cornerstone of OSA treatment, the management of CSA in the setting of HF continues to evolve. The association of the presence of CSA with worse prognosis in HF patients warrants the need for routine screening for signs and symptoms of CSA in this population. In this review, we examine the connection between CSA and HF, and highlight advancements in timely diagnostics, treatment modalities, and strategies to promote facilitation of compliance in this high-risk cohort., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Current kidney death definitions across heart failure (HF) trials are ambiguous and lack standardization. The interlinked shared pathways of HF and kidney failure makes it difficult to adjudicate the cause versus effect relationship of worsening HF and kidney failure events and raises concerns whether 'kidney death' is an affirmative or exclusionary diagnosis. Universally standardized definition of kidney death is therefore of utmost importance to accurately ascertain if kidney death is due to kidney failure itself or due to complications associated with it. Conceptually comprehensive and applicable definition(s) would be beneficial for clinicians and investigators in comparing data across trials and for shared decision making. Herein, we review the current definitions of kidney death, the frequency of reporting it across HF trials and the limitations associated with it. Additionally, we propose clinically relevant and comprehensive definitions pertaining kidney organ death which may aid clinicians and researchers alike in accurately distinguishing kidney death from a non-kidney death event., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is the most prevalent arrhythmia in the United States. However, studies evaluating the impact of iron deficiency anemia on AF outcomes are limited. Therefore, we aimed to evaluate the association of iron deficiency anemia (IDA) on clinical outcomes in patients hospitalized with AF. A retrospective analysis of adult hospital discharges from the National Inpatient Sample (NIS) between 2004 and 2018 was conducted. Multivariable logistic regression was used to assess the association of IDA and other clinical outcomes ie inpatient mortality, acute myocardial infarction, cardiogenic shock, acute kidney injury, vasopressors use, length of stay, and other resource utilization. These models were adjusted for patient and hospital-level characteristics. A total of 5,975,241 weighted primary AF hospitalizations were identified. Out of these, 152,059 (2.5%) had diagnosis of IDA. After adjustment of variables, admissions with IDA were associated with higher rates of acute myocardial infarction (adjusted odds ratio [aOR] = 1.10, 95% CI 1.01-1.19 P = 0.026), use of vasopressors (aOR = 1.30, CI 1.27-1.32, P <0.001), invasive mechanical ventilation (aOR = 1.26, CI 1.14-1.40 P <0.001) and acute kidney injury (aOR = 1.72, CI 1.66-1.79 P <0.001). There was no significant difference in all-cause mortality (aOR = 0.97, CI 0.87-1.07, P = 0.513), cardiogenic shock, in-hospital cardiac arrest or use of mechanical circulatory support. Adjusted mortality in patients with AF and IDA decreased from 1.09% to 0.54% from 2004 to2018 (P -trend < 0.001). Among hospitalized patients with AF, our study did not show any difference in all-cause mortality between those with and without IDA., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Rapid industrialization is causing a serious threat for the environment. Therefore, this research was aimed in developing ceramic cobalt ferrite (CoFe 2 O 4 ) nanocomposite photocatalyst coated with coal fly ash (CFA-CoFe 2 O 4 ) using facile hydrothermal synthesis route and their applications against methylene blue. The pristine cobalt ferrite photocatalyst was also prepared, characterized, and applied for efficiency comparison. Prepared photocatalyst were characterized by X-ray diffraction (XRD), fourier transformed infrared (FTIR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy with energy dispersive spectroscopy (SEM/EDS). Optical response of catalysts was check using photoluminescence spectroscopy (PL). pH drift method was used for the surface charge characteristics of the material under acidic and basic conditions of solution pH. The photocatalytic degradation potential of all the materials were determined under ultra-violet irradiations. The influencing reaction parameters like pH, catalyst dose, oxidant dose, dye concentration, and irradiation time, were sequentially optimized to obtain best suited conditions. The 99% degradation of 10 ppm methylene blue was achieved within 60 min of reaction time under pH = 5 and 7, catalyst dose = 10 and 12 mg/100 mL, oxidant = 12 mM and 5 mM for cobalt ferrite and CFA-CoFe 2 O 4 photocatalysts, respectively. Afterwards, the radical scavenging experiments were conducted to find out the effective radical scavengers (˙OH, h + , and e - ) in photocatalytic degradation process. The kinetic study of the process was done by applying 1st order, 2nd order, and BMG models. Statistical assessment of interaction effect among experimental variables was achieved using response surface methodology (RSM)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The efficacy of antidiabetic agents for the treatment of non-alcoholic fatty liver disease (NAFLD) remains unclear., Aim: To conduct a meta-analysis to study the efficacy of pioglitazone and three novel anti-diabetic agents: glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors in treating NAFLD., Methods: Online databases were searched in May 2020 for randomized clinical trials. Results from random-effects meta-analysis are presented as weighted mean differences (WMDs) or standard mean differences (SMDs) and corresponding 95% confidence intervals (CIs)., Results: Twenty-six studies (n=946 NAFLD patients) were included. Reductions in ALT were seen with all four drugs: pioglitazone (MD -38.41, p<0.001), SGLT2 inhibitors (MD -16.17, p<0.001), GLP-1 agonists (MD -27.98, p=0.04) and DPP-4 inhibitors (MD -7.41, p<0.001). Pioglitazone (SMD -1.01; p<0.001) and GLP-1 agonists (SMD -2.53, p=0.03) also demonstrated significant improvements in liver steatosis. SGLT2 inhibitors (SMD -4.64, p=0.06) and DPP-4 (SMD -2.49, p=0.06) inhibitors trended towards reduced steatosis; however, these results were non-significant., Conclusion: Pioglitazone demonstrates significant improvements in transaminases and liver histology in both diabetic and non-diabetic NAFLD patients. Early evidence from diabetic NAFLD patients suggests that novel antidiabetics may lead to improvements in liver enzymes and hepatic steatosis, and this should encourage further research into possible utility of these drugs in treating NAFLD., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The objective of this paper is to assess the clinical outcomes between non-traumatic intracerebral hemorrhage(ICH) in patients using direct oral anticoagulants(DOAC) versus vitamin K antagonists(VKA) for non-valvular atrial fibrillation. We also evaluated the predictors of the poor post-ICH outcomes., Methods: We have performed pooled meta-analysis to assess long-term clinical outcomes in patients with DOAC-ICH as compared to those with VKA-ICH. A systematic literature search was conducted by searching the full-text English literature in PubMed, EMBASE, and Cochrane databases for observational studies reporting outcomes on interest. MOOSE guidelines were used to collect data till December 31, 2019 and random effects analysis was carried out to account for heterogeneity. For outcomes, risk ratios(RR) and the mean differences were pooled using a random-effects model and weighted mean differences (WMDs), respectively., Results: Seventeen studies met the inclusion criteria (n = 25,354 patients; DOAC-ICH arms = 5,631; VKA-ICH arm = 19,273). Patients with DOAC-ICH had smaller hematoma volumes (WMD=-9.59; 95%CI=-15.33--3.85; I2 = 68.6%) and reduced mortality rate at discharge (RR = 0.82; 95%CI = 0.71-0.96; I2 = 9.4%). There was no significant difference between the two groups in rate of hematoma expansion (RR = 0.79; 95%CI = 0.56-1.11; I2 = 50.9%), unfavorable functional outcome(Modified Rankin Scale) at discharge (RR = 0.82; 95%CI = 0.56-1.18; I2 = 80.2%), unfavorable outcome at 3-months (RR = 0.77; 95%CI = 0.56-1.06; I2 = 63.9), and mortality at 3-months (RR = 0.90; 95%CI = 0.73-1.10; I2 = 35∙8%). Multivariate meta-regression revealed that the average age of patient population had a significantly negative correlation with(RR=-0.202; p = 0.017) hematoma expansion., Conclusion: We conclude that use of DOAC is associated with reduced hematoma volume and mortality rate at discharge. Age is a predictor of the poor outcome of hematoma expansion., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Publications are considered a major factor for advancement in academia. An effort has been made to study authorship trends in neurosurgery publications. The objective of this study was to investigate authorship trends in the neurosurgery literature for the last 20 years (1998-2018)., Methods: Articles for the years 1998, 2008, and 2018 were extracted from Neurosurgery, Journal of Neurosurgery, and World Neurosurgery for this retrospective study. Only original articles, case reports, and review articles were included. The gender of the first, senior, and corresponding author was determined. Subspecialty topic, type of paper, geographic origin of articles, and the number of citations for each article were also collected., Results: A total of 3912 articles were included. The number of articles, the total number of authors, and nonexperimental studies increased in the successive decades. A total of 744 women (19.0%) were first authors and 520 (13.3%) were senior authors of their respective publications. A decreasing trend (P < 0.05) was noted between female first authors and male senior authors over time. All 3 journals showed an increasing pattern of female authorships across the 2 decades., Conclusions: A rapid rise in female authorship positions in particular and authorship positions in general demonstrates the diversity that is slowly burgeoning to cater to perspectives and issues that require a multidimensional approach in neurosurgery. Increasing linkages among researchers in neurosurgery on a global scale are evident by the increase in multinational collaborations. Expansive efforts are needed at institutional and individual levels to eradicate sex-based pitfalls that hinder excellence in neurosurgery research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Chemically cross-linked cellulose nanocrystal (CNC) aerogels possess many properties beneficial for bone tissue scaffolding applications. CNCs were extracted using sulfuric acid or phosphoric acid, to produce CNCs with sulfate and phosphate half-ester surface groups, respectively. Hydrazone cross-linked aerogels fabricated from the two types of CNCs were investigated using scanning electron microscopy, X-ray micro-computed tomography, X-ray photoelectron spectroscopy, nitrogen sorption isotherms, and compression testing. CNC aerogels were evaluatedin vitrowith osteoblast-like Saos-2 cells and showed an increase in cell metabolism up to 7 days while alkaline phosphatase assays revealed that cells maintained their phenotype. All aerogels demonstrated hydroxyapatite growth over 14 days while submerged in simulated body fluid solution with a 0.1 M CaCl 2 pre-treatment. Sulfated CNC aerogels slightly outperformed phosphated CNC aerogels in terms of compressive strength and long-term stability in liquid environments, and were implanted into the calvarian bone of adult male Long Evans rats. Compared to controls at 3 and 12 week time points, sulfated CNC aerogels showed increased bone volume fraction of 33% and 50%, respectively, compared to controls, and evidence of osteoconductivity. These results demonstrate that cross-linked CNC aerogels are flexible, porous and effectively facilitate bone growth after they are implanted in bone defects. STATEMENT OF SIGNIFICANCE: Due to the potential complications associated with autografts, there is a need for synthetic bone tissue scaffolds. Here, we report a new naturally-based aerogel material for bone regeneration made solely from chemically cross-linked cellulose nanocrystals (CNC). These highly porous CNC aerogels were shown to promote the proliferation of bone-like cells and support the growth of hydroxyapatite on their surface in vitro. The first in vivo study on these materials was conducted in rats and showed their osteconductive properties and an increase in bone volume up to 50% compared to sham sites. This study demonstrates the potential of using functionalized cellulose nanocrystals as the basis for aerogel scaffolds for bone tissue engineering., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Purpose: Chronic hepatitis C has infected approximately 170 million people worldwide. The novel direct-acting antivirals have proven their clinical efficacy to treat hepatitis C infection but still very expensive and beyond the financial range of most infected patients in low income and even resource replete nations. This study was conducted to establish an in vitro stable human hepatoma 7 (Huh-7) cell culture system with consistent expression of the non-structural 5B (NS5B) protein of hepatitis C virus (HCV) 1a genotype and to explore inhibitory effects of sequence-specific short interference RNA (siRNA) targeting NS5B in stable cell clones, and against viral replication in serum-inoculated Huh-7 cells., Materials and Methods: In vitro stable Huh-7 cells with persistent expression of NS5B protein was produced under gentamycin (G418) selection. siRNAs inhibitory effects were determined by analysing NS5B expression at mRNA and protein level through reverse transcription-polymerase chain reaction (PCR), quantitative real-time PCR, and Western blot, respectively. Statistical significance of data (NS5B gene suppression) was performed using SPSS software (version 16.0, SPSS Inc.)., Results: siRNAs directed against NS5B gene significantly decreased NS5B expression at mRNA and protein levels in stable Huh-7 cells, and a vivid decrease in viral replication was also exhibited in serum-infected Huh-7 cells., Conclusions: Stable Huh-7 cells persistently expressing NS5B protein should be helpful for molecular pathogenesis of HCV infection and development of anti-HCV drug screening assays. The siRNA was effective against NS5B and could be considered as an adjuvant therapy along with other promising anti-HCV regimens., Competing Interests: None