Androgen Receptor Inhibitors in Patients With Nonmetastatic Castration-Resistant Prostate Cancer.

Importance: Novel androgen receptor inhibitors (ARIs; darolutamide, enzalutamide, and apalutamide) are standard-of-care treatments for nonmetastatic castration-resistant prostate cancer (nmCRPC). However, there are sparse data comparing their clinical use and tolerability. Objective: To compare clinical use and outcomes for darolutamide, enzalutamide, and apalutamide in patients with nmCRPC. Design, Setting, and Participants: This retrospective cohort study reviewed electronic medical records from the Precision Point Specialty network of US urology practices. Eligible patients had nmCRPC and no prior novel hormonal therapy and initiated novel ARI treatment between August 1, 2019, and March 31, 2022. Data were analyzed from February 1, 2019, to December 31, 2022. Exposures: Patients were prescribed darolutamide, enzalutamide, or apalutamide as their first novel ARI for nmCRPC. Main Outcomes and Measures: The main outcome was a composite of 2 end points, treatment discontinuation and progression to metastatic CRPC (mCRPC), whichever occurred first. Both end points were also assessed separately. Results: All 870 patients meeting eligibility criteria were included (362 receiving darolutamide [41.6%]; 382, enzalutamide [43.9%]; 126, apalutamide [14.5%]); mean (SD) age was 78.8 (8.7) years. Self-reported race was Black or African American in 187 patients (21.5%), White in 585 (67.2%), and other or unknown in 98 (11.3%). The darolutamide cohort had lower proportions of patients with a composite end point event (134 [37.0%] vs 201 [52.6%] for enzalutamide and 66 [52.4%] for apalutamide), discontinuation (110 [30.4%] for darolutamide vs 156 [40.8%] for enzalutamide and 58 [46.0%] for apalutamide), and progression to mCRPC (64 [17.7%] for darolutamide vs 108 [28.3%] for enzalutamide and 35 [27.8%] for apalutamide) during the study period. After adjusting for baseline covariates, patients receiving darolutamide had a lower risk of a composite end point event compared with enzalutamide (risk reduction, 33.8%; hazard ratio [HR], 0.66 [95% CI, 0.53-0.84]) and apalutamide (risk reduction, 35.1%; HR, 0.65 [95% CI, 0.48-0.88]). Similarly, patients receiving darolutamide had a lower risk of discontinuation compared with enzalutamide (risk reduction, 27.4%; HR, 0.73 [95% CI, 0.56-0.94]) and apalutamide (risk reduction, 39.1%; HR, 0.61 [95% CI, 0.44-0.85]) and a lower risk of progression to mCRPC compared with enzalutamide (risk reduction, 40.6%; HR, 0.59 [95% CI, 0.43-0.82]) and apalutamide (risk reduction, 35.3%; HR, 0.65 [95% CI, 0.42-0.99]). There was no difference between enzalutamide and apalutamide treatment across outcomes. Conclusions and Relevance: In this large cohort study of patients with nmCRPC treated with novel ARIs, results suggest better tolerability for darolutamide compared with enzalutamide and apalutamide, which may be associated with a clinical effectiveness advantage. Comparative clinical studies are needed to guide treatment decisions in the absence of head-to-head clinical trials.

Real-world dosing of regorafenib and outcomes among patients with metastatic colorectal cancer: a retrospective analysis using US claims data.

BACKGROUND: The randomized, dose-optimization, open-label ReDOS study in US patients with metastatic colorectal cancer (CRC) showed that, compared with a standard dosing approach, initiating regorafenib at 80 mg/day and escalating to 160 mg/day depending on tolerability increased the proportion of patients reaching their third treatment cycle and reduced the incidence of adverse events without compromising efficacy. Subsequently, the ReDOS dose-escalation strategy was included as an alternative regorafenib dosing option in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines. A retrospective analysis was conducted using a US claims database to assess whether inclusion of this dose-escalation strategy in NCCN Guidelines has influenced the use of flexible dosing in routine US clinical practice, and to describe clinical outcomes pre- and post-inclusion in NCCN Guidelines. METHODS: Patients with CRC in the Optum's de-identified Clinformatics® Data Mart database initiating regorafenib for the first time between January 2016 and June 2020 were stratified based on whether they initiated regorafenib pre- or post-inclusion of ReDOS in NCCN Guidelines, and in two groups: flexible dosing (< 160 mg/day; < 84 tablets in the first treatment cycle) and standard dosing (160 mg/day; ≥ 84 tablets in the first treatment cycle). The primary endpoints were the proportion of patients who initiated their third treatment cycle and the mean number of treatment cycles per group. RESULTS: 703 patients initiated regorafenib during the study period, of whom 310 (44%) initiated before and 393 (56%) initiated after inclusion of ReDOS in NCCN Guidelines. After inclusion in the guidelines, the proportion of patients who received flexible dosing increased from 21% (n = 66/310) to 45% (n = 178/393), the proportion who received standard dosing decreased from 79% (n = 244/310) to 55% (n = 215/393), the proportion who initiated their third treatment cycle increased from 36% (n = 113/310) to 46% (n = 179/393), and the mean (standard deviation) number of treatment cycles increased from 2.6 (2.9) to 3.2 (3.1). CONCLUSIONS: Following inclusion of ReDOS in NCCN Guidelines, real-world data suggest that US clinicians have markedly increased use of flexible dosing in clinical practice, potentially maximizing clinical benefits and safety outcomes for patients with metastatic CRC receiving regorafenib.

Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment.

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.

Integration of population genetics with oceanographic models reveals strong connectivity among coral reefs across Seychelles.

Many countries with tropical reef systems face hard choices preserving coral reefs in the face of climate change on limited budgets. One approach to maximising regional reef resilience is targeting management efforts and resources at reefs that export large numbers of larvae to other reefs. However, this requires reef connectivity to be quantified. To map coral connectivity in the Seychelles reef system we carried out a population genomic study of the Porites lutea species complex using 241 sequenced colonies from multiple islands. To identify oceanographic drivers of this connectivity and quantify variability, we further used a 2 km resolution regional ocean simulation coupled with a larval dispersal model to predict the flow of coral larvae between reef sites. Patterns of admixture and gene flow are broadly supported by model predictions, but the realised connectivity is greater than that predicted from model simulations. Both methods detected a biogeographic dispersal barrier between the Inner and Outer Islands of Seychelles. However, this barrier is permeable and substantial larval transport is possible across Seychelles, particularly for one of two putative species found in our genomic study. The broad agreement between predicted connectivity and observed genetic patterns supports the use of such larval dispersal simulations in reef system management in Seychelles and the wider region.

Age-related trends in the incidence of metastatic colorectal cancer from 2010 to 2019 in the USA.

Aim: To evaluate temporal changes in metastatic colorectal cancer (mCRC), incidence, and use of chemotherapy treatment by age group using real-world data (RWD) from the USA. Methods: A retrospective, observational study describing temporal trends in mCRC incidence and FOLFOXIRI treatment by age group using a nationwide database of commercially and Medicare Advantage-insured patients from 2010 to 2019. Results: Incidence of mCRC increased by 22.1 and 14.9% in the 18-49 and 50-64 years cohorts, respectively, and decreased by 21.6% in the ≥65 years cohort. Overall, younger patients were more likely to receive FOLFOXIRI treatment versus older patients. Conclusion: The shifting age distribution of mCRC should be considered when recommending screening and treatment. Further research is needed to inform age-specific treatment guidelines.

What is this article about? This article reports the results of a study that used a US database of commercially and Medicare Advantage-insured adults to evaluate how the number of adults with metastatic colorectal cancer (mCRC) in three age groups (18­49 years, 50­64 years and 65 years and over) changed from 2010 to 2019. The study also looked at the use of an aggressive chemotherapy treatment, known as 5-fluorouracil, oxaliplatin, leucovorin calcium and irinotecan (FOLFOXIRI), by age group. What were the results? Overall, 23,970 adults with mCRC were included in the study. From 2010 to 2019, the number of adults with mCRC increased by 22.1% among those aged 18­49 years, increased by 14.9% among those aged 50­64 years, and decreased by 21.6% among those aged 65 years and over. There were some differences between age groups; a higher percentage of younger patients (18­49 years) were Hispanic or Asian, and from the South compared with the older age groups. In comparison, those aged 65 years and over were more likely to be from the West and Northeast of the USA. The study also found that a higher proportion of those aged 18­49 years received FOLFOXIRI (8.4%) compared with adults aged 50­64 years (4.4%) and 65 years and over (1.9%). What do the results of the study mean? Healthcare providers should be aware that early-onset mCRC is becoming more common and consider this when recommending screening and treatment.

Differing natural killer cell, T cell and antibody profiles in antiretroviral-naive HIV-1 viraemic controllers with and without protective HLA alleles.

Previous work suggests that HIV controllers with protective human leukocyte antigen class I alleles (VC+) possess a high breadth of Gag-specific CD8+ T cell responses, while controllers without protective alleles (VC-) have a different unknown mechanism of control. We aimed to gain further insight into potential mechanisms of control in VC+ and VC-. We studied 15 VC+, 12 VC- and 4 healthy uninfected individuals (UI). CD8+ T cell responses were measured by ELISpot. Flow cytometry was performed to analyse surface markers for activation, maturation, and exhaustion on natural killer (NK) cell and T cells, as well as cytokine secretion from stimulated NK cells. We measured plasma neutralization activity against a panel of 18 Env-pseudotyped viruses using the TZM-bl neutralization assay. We found no significant differences in the magnitude and breadth of CD8+ T cell responses between VC+ and VC-. However, NK cells from VC- had higher levels of activation markers (HLA-DR and CD38) (p = 0.03), and lower cytokine expression (MIP-1ß and TNF-α) (p = 0.05 and p = 0.04, respectively) than NK cells from VC+. T cells from VC- had higher levels of activation (CD38 and HLA-DR co-expression) (p = 0.05), as well as a trend towards higher expression of the terminal differentiation marker CD57 (p = 0.09) when compared to VC+. There was no difference in overall neutralization breadth between VC+ and VC- groups, although there was a trend for higher neutralization potency in the VC- group (p = 0.09). Altogether, these results suggest that VC- have a more activated NK cell profile with lower cytokine expression, and a more terminally differentiated and activated T cell profile than VC+. VC- also showed a trend of more potent neutralizing antibody responses that may enhance viral clearance. Further studies are required to understand how these NK, T cell and antibody profiles may contribute to differing mechanisms of control in VC+ and VC-.

Health-related quality of life and medication use among individuals with Angelman syndrome.

PURPOSE: The primary goal of this analysis is to describe the health-related quality of life (HRQoL), medical history, and medication use among adolescents and adults individuals with Angelman syndrome (AS). METHODS: The analysis uses baseline data collected during the STARS study, a double-blind placebo controlled trial of gaboxadol (OV101) in adolescents and adults with AS. The HRQoL was estimated using EuroQoL 5-Dimension 5-Level (EQ-5D) health questionnaire proxy 1 version, which was completed by the caregivers. EQ-5D consists of two parts, a 5-dimension descriptive and a visual analogue scale (VAS) component. The utility score derived from EQ-5D ranges from 0 to 1 (perfect health) and VAS ranges from 0 to 100 (perfect health). RESULTS: 87 individuals with AS were included in the present analysis. The mean utility score was 0.44 ± 0.20 and VAS score was 84 ± 1.5. The EQ-5D data indicated that the self-care, mobility and daily activities were most impacted. All adolescents (100%) and most adults (93%) had at least moderate problems with self-care activities, such as washing or dressing themselves. More than half (55%) of the adolescents and adults had at least moderate issues with mobility and usual activities. Approximately, 30% of adolescents and adults had moderate to extreme problems with anxiety/depression. High baseline concomitant use of medications was observed across both age groups with an average of 5 medications being used per person. CONCLUSION: This study highlights the impact of AS on HRQoL and medication utilization among adolescents and adults individuals with AS.

Arsenic speciation, oxidation and immobilization in an unsaturated soil in the presence of green synthesized iron oxide nanoparticles and humic acid.

While the availability of arsenic (As) in soil is well known to be highly correlated with the presence of iron (Fe) oxides and humic acid (HA) in the soil, the relationship between Fe oxides and HA and As species in the soil is less well understood. In this study, As speciation in an unsaturated soil in the presence of external HA and green synthesized Fe oxide nanoparticles (FeNPs) showed that As(V) was mainly distributed to the specifically-bound (F2), amorphous and poorly-crystalline hydrous oxides of Fe, Al (F3) and the well-crystallized hydrous oxides of Fe and Al (F4). While As(III). This was the major component in unsaturated soil, and was mainly distributed to F4 and the residual fraction (F5). As bound to F3 and F5 was most sensitive to the addition of HA and FeNPs, while HA/FeNPs treatment increased the F3-bound As(V); however, it decreased the F5-bound As(III). Nonetheless the effect of HA on As is completely different to the HA/FeNPs treatment. The increase of As(V) in F3 resulted from F5-bound As(III) oxidation when treated by HA/FeNPs. Cyclic voltammetry confirmed that HA and Fe3+/Fe2+ redox enhanced As(III) oxidation, while FTIR revealed that HA-bound As(III) was the least available fraction in the soil. Finally, a mechanism involving a combination of HA and FeNPs was proposed for explaining the redistribution of As species in the soil.

The large key space image encryption algorithm based on modulus synchronization between real and complex fractional-order dynamical systems.

This paper constructs and analyzes the dynamical properties of a new fractional-order real hyper-chaotic system and its corresponding complex variable system. A thorough analysis was done by employing stability of equilibrium points, phase plots, Lyapunov spectrum, and bifurcation analysis for the consequences of varying fractional-order derivative and parameter values on the system. For the first time, a modulus synchronization scheme is proposed to synchronize real and complex fractional-order dynamical systems. Based on Lyapunov stability theory, non-linear controllers are designed to achieve the proposed modulus synchronization scheme. A new modulus synchronization encryption algorithm with a large key space size for digital images is introduced for the application. The experimental results and analysis validate the desired algorithm. Also, we compare our result of the new encryption algorithm with the previously published literature and verify the efficacy of the considered scheme. Numerical simulations are given to validate the theoretical analysis.

Vaginal Lactobacillus fatty acid response mechanisms reveal a novel strategy for bacterial vaginosis treatment.

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related species, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the human vaginal microbiota and sequesters OA in a derivative form that only ohyA-harboring organisms can exploit. Finally, OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro model of BV, suggesting a novel approach for treatment.

Identification of suitable habitat for Taxus wallichiana and Abies pindrow in moist temperate forest using maxent modelling technique.

Conservation of any species necessitates knowledge of its biology and natural history, as well as prospective locations or newer adaptive landscapes where the species can survive and thrive. This study presents habitat suitability and local conservation status of Taxus wallichiana and Abies pindrow in moist temperate forest of Hazara division, Pakistan. Data was collected through field surveys based on 363 samples from field, topographical and bioclimatic variables. In the present study, we employed the MaxEnt model exclusively for each tree species along with 23 independent or environment variables (19 bioclimatic and 4 topographic). The jackknife test was used to demonstrate the significance of variables with the highest gain, and it was found that overall tree cover, annual temperature range was the factors with the highest gain, while slope was amongst the least important. The MaxEnt model produced high accuracy for each tree species, with receiver operating characteristic (ROC), area under the curve (AUC), training mean testing values for Taxus wallichiana was 0.966 followed by 0.944 for Abies pindrow. Local conservation status of Taxus wallichiana and Abies pindrow was evaluated using IUCN criteria 2001. Taxus wallichiana was declared critically endangered locally as the population size reduced by 87%. In contrast, Abies pindrow was declared as endangered as population size reduced by 69% falling under endangered criteria A of IUCN. The decline in population size of Taxus wallichiana and Abies pindrow species were due to human cause anthropogenic activities such as exploitation and loss of habitat, the extent of occurrence, and slow regeneration of tree species. Results and field-based observation revealed that suitable habitat modeling showed unsuitable (0.0-0.2), less suitable (0.2-0.4), moderately (0.4-0.6), highly (0.6-0.7), and very highly (0.7-1.0) suitable habitat for Taxus wallichiana and Abies pindrow. Results also revealed that both species were distributed irregularly in the moist temperate forest of Hazara division. Habitat suitability of Taxus wallichiana and Abies pindrow can be considered one of most significant points toward conserving these tree species. Habitat loss is a major threat to their occurrence, which should be overcome by ensuring the protection of suitable habitat and conservation approaches. Considering the species ecological and economic value, it is essential to understand how the species distribution may vary as a result of climate change to establish effective conservation policies. This study also includes significant environmental elements that influence species distribution, which could help locate regions where the species could be planted. Forest tree species require effective, scientific, and long-term management and conservation techniques in the study area. Furthermore, the formulation and implementation of protective laws and policies are required to conserve and protect both the conifer species.

Life cycle environmental sustainability and cumulative energy assessment of biomass pellets biofuel derived from agroforest residues.

This study was carried out to produce low-emitting biomass pellets biofuel from selected forest trees such as (Cedrus deodara and Pinus wallichiana) and agricultural crop residues such as (Zea mays and Triticum aestivum) in Gilgit-Baltistan, Pakistan using indigenously developed technology called pelletizer machine. Characterization, environmental life cycle impact assessment, and cumulative energy demand of biomass pellets biofuel produced from selected agriculture crops and forest tree residues were conducted. The primary data for biomass pellets production was collected by visiting various wood processing factories, sawmills, and agricultural crop fields in the study area. Biomass pellets are a type of biofuel that is often made by compressing sawdust and crushing biomass material into a powdery form. The particles are agglomerated as the raw material is extensively compressed and pelletized. Biomass pellets have lower moisture content, often less than 12%. Physically, the produced pellets were characterized to determine moisture content, pellet dimensions, bulk density, higher heating value, ash content, lower heating value, and element analysis. A functional unit of one kilogram (kg) biomass pellets production was followed in this study.The life cycle impact assessment of one kg biomass pellets biofuel produced from selected agro-forest species revealed environmental impact categories such as acidification (0.006 kg SO2 eq/kg pellets), abiotic depletion (0.018 kg Sb eq/kg pellets), marine aquatic ecotoxicity (417.803 kg 1,4-DB eq/kg pellets), human toxicity (1.107 kg 1,4-DB eq/kg pellets), freshwater aquatic ecotoxicity (0.191 kg 1,4-DB eq/kg pellets), eutrophication (0.001 kg PO4 eq/kg pellets), global warming (0.802 kg CO2 eq/kg pellets), and terrestrial ecotoxicity (0.008 kg 1,4-DB eq/kg pellets). Fossil fuel consumption was the hotspot source to all environmental impacts investigated. To measure the cumulative energy demand of biomass pellets made from different agroforestry species leftovers showed that the maximum cumulative energy was from wheat straw pellets (13.737 MJ), followed by corncob pellets (11.754 MJ), deodar sawdust pellets (10.905 MJ) and blue pine sawdust pellets (10.877 MJ). Among the various production activities, collection and transportation of primary raw material, crushing, screening, adding adhesives, pelletizing, cooling, final screening, and packing have the maximum contribution to the water scarcity index, followed by lubricating oil (0.00147m3). In contrast, the minimum contribution to water footprint was from electricity (0.00008m3) and wheat starch (0.00005m3). The highest contribution to the ecological footprint impact categories such as carbon dioxide, nuclear, and land occupation was lubricating oil and less contribution of wheat starch and electricity for manufacturing one kg pellets biofuel. It is concluded that physico-mechanical and combustion properties of the biomass pellets biofuel developed in the present study were following the Italian recommended standards. Therefore, it is strongly recommended that the Government of Pakistan should introduce the renewable biomass pellets industry in the country to reduce dependency on fossil fuels for cooking and heating purposes.

Enhanced oxidation and stabilization of arsenic in a soil-rice system by phytosynthesized iron oxide nanomaterials: Mechanistic differences under flooding and draining conditions.

Despite arsenic (As) bioavailability being highly correlated with water status and the presence of iron (Fe) minerals, limited information is currently available on how externally applied Fe nanomaterials in soil-rice systems affect As oxidation and stabilization during flooding and draining events. Herein, the stabilization of As in a paddy soil by a phytosynthesized iron oxide nanomaterials (PION) and the related mechanism was investigated using a combination of chemical extraction and functional microbe analysis in soil at both flooding (60 d) and draining (120 d) stages. The application of PION decreased both specifically bound and non-specifically bound As. The As content in rice root, stem, husk and grain was reduced by 78.5, 17.3, 8.4 and 34.4%, respectively, whereas As(III) and As(V) in root declined by 96.9 and 33.3% for the 1% PION treatment after 120 d. Furthermore, the 1% PION treatment decreased the ratio of As(III)/As(V) in the rhizosphere soil, root and stem. Although PION had no significant effect on the overall Shannon index, the distribution of some specific functional microbes changed dramatically. While no As(III) oxidation bacteria were found at 60 d in any treatments, PION treatment increased As(III) oxidation bacteria by 3-9 fold after 120 d cultivation. Structural equation model analysis revealed that the ratio of Fe(III)/Fe(II) affected As stabilization directly at the flooding stage, whereas nitrate reduction and As(III) oxidation microbial groups played a significant role in the stabilization of As at the draining stage. These results highlight that PION exhibits a robust ability to reduce As availability to rice, with chemical oxidation, reduction inhibition and adsorption dominating at the flooding stage, while microbial oxidation, adsorption and coprecipitation dominant during draining.

Bimetallic Fe/Ni nanoparticles derived from green synthesis for the removal of arsenic (V) in mine wastewater.

Since the incidences of arsenicosis have significantly increased worldwide in the last decade, remediation of arsenic (As) pollution is now imperative. In this study, calcined green synthesized Fe/Ni nanoparticles (C-Fe/Ni NPs) were evaluated for their efficacy for As (V) removal from aqueous solution. Under optimal experimental conditions As (V) removal efficiency reached 87.3%. Analysis of changes in the surface properties of C-Fe/Ni NPs before and after interaction with As (Ⅴ) using a range of advanced characterization techniques including IC-AFS, SEM-EDS, XPS and XRD revealed that the As removal mechanism involved only adsorption. Adsorption kinetics followed a pseudo-second order rate model (R2 > 0.986) and adsorption best fit the Langmuir isotherm model (R2 > 0.958). Thermodynamic studies indicated that adsorption was a spontaneous endothermic process. On the basis of these results, a removal mechanism of As (Ⅴ) by C-Fe/Ni NPs was proposed. Finally, the efficacy of the material for practical remediation of As from aqueous solution was assessed, including the influence of coexisting anions. While Cl-, NO3- and SO42- had little influence on As (V) removal, both H2PO4- and HCO3- significantly negatively affected removal.

Dose-response and temporal ergogenic effects of ginseng supplementation in athletes and active participants: A systematic review and meta-analysis.

This review sought to assess the dose-response, i.e., low (<300 mg/day) and high (>300 mg/day), and temporal effects of ginseng, i.e., immediate, short-term (up to 4 weeks) and long-term (>4 weeks) in comparison to placebo on physical performance [visual analogue scale (VAS) level, vertical jump(VJ), rating of perceived exertion (RPE), peak power output (PPO)] and physiological measures [VO2 max, creatine kinase(CK), heart rate(HR)], in athletes and active participants. Search in four databases with English language constraints yielded 492 studies. Fourteen studies were shortlisted through PEDro scale by methodological quality evaluation. Ginseng exhibited significant short-term effect at high dosage for VJ improvement (SMD: -8.17, 95% CI: -16.28 to -0.06, p= 0.05). Ginseng had no effect on VAS (SMD: -0.65, 95% CI: -1.35 to 0.06, p= 0.07), RPE (SMD: -1.11, 95% CI: -2.57 to 0.35, p= 0.14), PPO (SMD: -0.70, 95% CI: -1.78 to 0.38, p= 0.20), HR (SMD: -0.54, 95% CI: -2.05 to 0.96, p= 0.48), CK (SMD: 0.33, 95% CI: -0.18 to 0.84, p= 0.21) and VO2 max (SMD: 0.08, 95% CI: -0.69 to 0.85, p= 0.08).The ginseng supplementation was found to have significant short-term effect at high dose only for VJ in athletic and active participants. Methodologically strong research is warranted to further consolidate these findings.

A systematic literature review on cybercrime legislation.

Background: Cybercrime is a fast-growing digital crime and legislation falling behind with the fast-moving advancement of technology. One important factor projected by literature in combating cybercrime is legislation. In order to combat cybercrime, the role of cybercrime legislation is a challenge that has not been clearly studied before. This paper thus aims to recapitulate the literature on cybercrime legislation in combating cybercrime. The literature in this context emphasises on existing studies relating to cybercrime legislation and addressing the importance of adequate and efficient responses in place in order to combat cybercrime efficiently. Methods: This paper finds an extensive literature review using the "Preferred Reporting Items for Systematic Review and Meta-Analysis" method based on legislation to combat cybercrime and explains a systematic analysis of the legislation in most advanced countries in both technology and legal framework. The study was done by selecting keywords, validated by the experts to discover research trends of cybercrime legislation. A search was then run across seven academic databases, including the ACM Digital Library, Emerald, Hein Online, ProQuest, ScienceDirect, Scopus, and Westlaw Asia. Initially, five hundred and forty-eight articles were retrieved and out of which seventy-two studies met the inclusion criteria and were fully reviewed. Results: The findings of the study revealed that comprehensive cybercrime legislation plays a vital role in combating cybercrime and cybercrime legislation should be strengthened, enhanced, and made up to date with the rapid advancement of technology in order to address the rising number of cybercrime. Discussion: This systematic review is timely and highlights future research directions to improve a comprehensive legal framework to combat the rising of cybercrime effectively. To fill the research gap, the findings also have fundamental practical implications for the policy makers, in enacting an up to date cybercrime legislation by highlighting the role of legislation in combating cybercrime.

Removal mechanism of Sb(III) by a hybrid rGO-Fe/Ni composite prepared by green synthesis via a one-step method.

The annual influx of antimony (Sb) into the environment due to the widespread use of Sb compounds in industry and agriculture has become of global concern. Herein, a functional nanomaterial composite based on loading bimetallic iron/nickel nanoparticles on reduced graphene oxide (rGO-Fe/Ni) was initially prepared in a one-step phytogenic synthesis using a green tea extract. Subsequently, when applied for Sb(III) removal, the removal efficiency of rGO-Fe/Ni reached 69.7% within 3 h at an initial Sb concentration of 1.0 mg·L-1. Advanced materials characterization via scanning electron microscopy-energy dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy revealed that Sb(III) was initially adsorbed onto the surface of rGO and then oxidized to Sb(V). This result was also supported by adsorption isotherm, kinetics, and thermodynamic analysis. These studies revealed that the adsorption was spontaneous and endothermic, following a Langmuir adsorption model with pseudo-second-order kinetics and allowed a Sb(III) removal mechanism based on adsorption and catalytic oxidation to be proposed. Furthermore, when rGO-Fe/Ni was practically used to remove Sb(III) in groundwater a 95.7% removal efficiency was obtained at 1 mg·L-1 Sb(III), thus successfully demonstrating that rGO-Fe/Ni has significant potential for the practical remediation of Sb contaminated groundwater.

Removal of low Sb(V) concentrations from mining wastewater using zeolitic imidazolate framework-8.

Wastewater generated during mining remains a significant source of antimony pollution, because techniques to quickly and efficiently remove antimony from wastewater do not exist. In this study, zeolitic imidazolate framework-8 (ZIF-8), a specific type of Metal Organic Frameworks (MOFs), was successfully used to remove trace levels (1 mg L-1) of Sb(V) with a high removal efficiency when the ZIF-8 dose was 0.5 g L-1. Scanning electron microscopy-X-ray energy dispersive spectrometry (SEM-EDS) indicated that Sb(V) was adsorbed onto the ZIF-8surface. The powder X-ray diffraction (XRD) pattern of ZIF-8 before and after adsorption of Sb(V) indicated that ZIF-8 was successfully synthesized, and remained structurally stable after Sb(V) was adsorbed. Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) both suggested complexation of zinc on ZIF-8 with Sb(V), where removal of Sb(V) by ZIF-8 followed the Langmuir adsorption isotherm with pseudo second-order kinetics. Thus, a possible removal mechanism was proposed which involved Sb(V) complexing with the zinc hydroxyl groups on ZIF-8 (Zn-OH-Sb). Practically, ZIF-8, could remove 78.6% of Sb(V) from a mining wastewater containing 20 µg L-1 Sb(V). Furthermore, ZIF-8 could be remain active after repeated uses and could still remove and 42.3% of Sb(V) from wastewater containing 1 mg L-1) Sb(V) even when the ZIF-8 was reused five time. This indicated that ZIF-8 had potential for practical removal of Sb(V) from mining wastewaters.

Removal of As(V) by iron-based nanoparticles synthesized via the complexation of biomolecules in green tea extracts and an iron salt.

While iron-based nanoparticles (nFe) prepared using green tea extracts have been successfully used to degrade many organic contaminants, their application to remove As(V) remains limited. Thus, in this work, nFe (GT-1) prepared using a green tea extract was used to removal As(V). The maximum adsorption capacity of GT-1 for As(V) was 19.9 mg g-1 at 298 K. The formation of GT-1 and the removal mechanism of As(V) by GT-1, was examined using XRD, TEM and SEM, which showed that GT-1 was composed of amorphous particulates sized between 50 and 100 nm. GC-MS and LC-MS analysis also showed that biomolecules presented in the green tea extract, including polyphenols and L-theanine, participated in the formation of GT-1. Mössbauer spectral analysis confirmed that an organo-Fe(III) complex was formed due to the reaction between biomolecules and Fe(III). FTIR and XPS showed that the adsorption of As(V) by GT-1 occurred both via complexation with Fe(III) in GT-1 and via coordination of As(V) with free hydroxyl groups on the surface of GT-1. Batch experiments showed that adsorption was spontaneous and conformed to the pseudo-second order kinetic model. Finally, mechanisms for the formation of GT-1 and the removal of As (V) by GT-1 were proposed.