Comparison between Woven EndoBridge and coiling with and without stent assistance for intracranial bifurcation and wide-neck aneurysms: a comprehensive systematic review and meta-analysis.

OBJECTIVE: The recent introduction of the Woven EndoBridge (WEB) has presented an alternative treatment modality for intracranial bifurcation and wide-neck aneurysms with a growing body of literature evaluating its efficacy. However, no previous systematic review has focused on comparing WEB with previously using endovascular approaches, specifically primary coiling (PC) and stent-assisted coiling (SAC). Herein, the authors present the first systematic review summarizing available literature to reach a consensus regarding the safety and effectiveness of WEB. METHODS: A systematic review of articles identified through a search of PubMed, Embase, Scopus, and Web of Science was conducted. Studies were included if they compared WEB with PC or SAC from any aspect for intracranial aneurysms. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions tool. Meta-analyses of the outcomes based on stent use and rupture status were performed. RESULTS: A total of 16 studies were included. The three endovascular approaches were comparable in terms of baseline characteristics except for older age and smaller aneurysm neck in the PC group (p < 0.05). Moreover, the follow-up duration was shorter in the WEB group (p < 0.05). Although the WEB group demonstrated lower complete and adequate immediate occlusion rates (p < 0.01), the rates at follow-up evaluations were comparable with SAC and PC (p = 0.61 and p = 0.27, respectively). The WEB group experienced significantly fewer unfavorable neurological outcomes than the SAC group (p = 0.04), while comparable to the PC group (p = 0.36). Retreatment rates were comparable between WEB and coiling (p = 0.92). The WEB group had fewer hemorrhagic and thromboembolic complications (p < 0.01 and p = 0.01, respectively), with similar neurological and procedure-related complications compared with combined PC and SAC groups. Lastly, mortality was comparable among the different endovascular approaches. CONCLUSIONS: This study provides evidence on the noninferiority of WEB compared with PC and SAC in terms of angiographic outcomes. Meanwhile, our findings on lower complication rates, cost, and improved operative aspects associated with WEB establish this novel endovascular treatment as a safe and effective alternative for the treatment of bifurcation and wide-neck aneurysms.

A novel approach for credit card fraud transaction detection using deep reinforcement learning scheme.

Online transactions are still the backbone of the financial industry worldwide today. Millions of consumers use credit cards for their daily transactions, which has led to an exponential rise in credit card fraud. Over time, many variations and schemes of fraudulent transactions have been reported. Nevertheless, it remains a difficult task to detect credit card fraud in real-time. It can be assumed that each person has a unique transaction pattern that may change over time. The work in this article aims to (1) understand how deep reinforcement learning can play an important role in detecting credit card fraud with changing human patterns, and (2) develop a solution architecture for real-time fraud detection. Our proposed model utilizes the Deep Q network for real-time detection. The Kaggle dataset available online was used to train and test the model. As a result, a validation performance of 97.10% was achieved with the proposed deep learning component. In addition, the reinforcement learning component has a learning rate of 80%. The proposed model was able to learn patterns autonomously based on previous events. It adapts to the pattern changes over time and can take them into account without further manual training.

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

OBJECTIVE: This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. METHODS: A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. RESULTS: The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). CONCLUSIONS: The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Integrated Approach to Hydrogeochemical Assessment of Groundwater Quality in Major Industrial Zone of Punjab, Pakistan.

Groundwater contamination with arsenic (As) is a significant concern in Pakistan's Punjab Province. This study analyzed 69 groundwater samples from Faisalabad, Gujranwala, Lahore, and Multan to understand hydrogeochemistry, health impacts, contamination sources, and drinking suitability. Results revealed varying as concentrations across districts, with distinctive cation and anion orders. Faisalabad exhibited Na+ > Mg2+ > Ca2+ > K+ > Fe2+ for cations and SO42- > Cl- > HCO3- > NO3- > F- for anions. Gujranwala showed Na+ > Ca2+ > Mg2+ > K+ for cations and HCO3- > SO42- > Cl- > NO3- > F- for anions. In Lahore, demonstrated: Na+ > Ca2+ > Mg2+ > Fe > K+ for cations and HCO3- > SO42- > Cl- > NO3- > F- for anions. Multan indicated K+ > Ca2+ > Mg2+ > Na+ > Fe for cations and HCO3- > SO42- > Cl- > F- > NO3- ) for anions. Hydrochemical facies were identified as CaHCO3 and CaMgCl types. Principal Component Analysis (PCA), highlighted the influence of natural processes and human activities on groundwater pollution. Water Quality Index (WQI) result reveal that most samples met water quality standards. The carcinogenic risk values for children exceeded permissible limits in all districts, emphasizing a significant cancer risk. The study highlights the need for rigorous monitoring to mitigate (As) contamination and protect public health from associated hazards.

Pesticide reduction: clustering organic croplands.

Organic and conventional farms often coexist, yet their proximity does not ensure compatibility. Larsen et al. reveal that being surrounded by organic fields reduces pesticide usage in organic fields but increases it in conventional fields. We discuss these findings, emphasizing the need to cluster organic croplands for reduced pesticide use.

Cangrelor for neurointerventional procedures: A systematic review.

Thromboembolism is a complication of neurointerventional procedures that requires patients to be placed under antiplatelet therapy. Current options for antiplatelet therapies have a delayed onset of action that prevents a rapid door to puncture transition for patents presenting in acute settings. Cangrelor (Kengreal, Chiesi, USA) is an intravenous P2Y12 platelet inhibitor approved in percutaneous coronary interventions that has an immediate onset of action and half-life between 2 and 6 min. Thus, the goal of this study is to report on the safety, effectiveness, and indications for using Cangrelor in neurointerventional procedures. A systematic review of studies describing the use of Cangrelor in neurointervention was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search was conducted on PubMed, Ovid Medline, and Embase databases through June 2023. Seventeen studies with 314 patients met inclusion criteria. The most common indication for Cangrelor use was acute ischemic strokes: 70% followed by aneurysms 27.4%. The Infusion protocol varied from 5 to 30 µg/kg bolus and 1 to 4 µg/kg/min infusion with 30 µg/kg bolus and 4 µg/kg/min infusion being reported in 64.7% of studies. Intra-operative platelet reacting unit levels were below 200 in all the studies that reported it, and the percentage of hemorrhagic, thromboembolic, and deaths occurrence in this patient cohort was respectively 11.1%, 4.8%, and 8.6%. Cangrelor appears to be a promising P2Y12 platelet inhibitor for neurointerventional procedures. However, large, randomized trials are needed to determine the full range of its effects in neurointerventional procedures.

Novel Natural Inhibitors for Glioblastoma by Targeting Epidermal Growth Factor Receptor and Phosphoinositide 3-kinase.

BACKGROUND/AIM: Glioblastoma is an extensively malignant neoplasm of the brain that predominantly impacts the human population. To address the challenge of glioblastoma, herein, we have searched for new drug-like candidates by extensive computational and biochemical investigations. METHOD: Approximately 950 compounds were virtually screened against the two most promising targets of glioblastoma, i.e., epidermal growth factor receptor (EGFR) and phosphoinositide 3-kinase (PI3K). Based on highly negative docking scores, excellent binding capabilities and good pharmacokinetic properties, eight and seven compounds were selected for EGFR and PI3K, respectively. RESULTS: Among those hits, four natural products (SBEH-40, QUER, QTME-12, and HCFR) exerted dual inhibitory effects on EGFR and PI3K in our in-silico analysis; therefore, their capacity to suppress the cell proliferation was assessed in U87 cell line (type of glioma cell line). The compounds SBEH-40, QUER, andQTME-12 exhibited significant anti-proliferative capability with IC50 values of 11.97 ± 0.73 µM, 28.27 ± 1.52 µM, and 22.93 ± 1.63 µM respectively, while HCFR displayed weak inhibitory potency (IC50 = 74.97 ± 2.30 µM). CONCLUSION: This study has identified novel natural products that inhibit the progression of glioblastoma; however, further examinations of these molecules are required in animal and tissue models to better understand their downstream targeting mechanisms.

Discovery of Novel Natural Inhibitors Against SARS-CoV-2 Main Protease: A Rational Approach to Antiviral Therapeutics.

BACKGROUND/AIM: The global pandemic caused by the novel SARS-CoV-2 virus underscores the urgent need for therapeutic interventions. Targeting the virus's main protease (Mpro), crucial for viral replication, is a promising strategy. OBJECTIVE: The current study aims to discover novel inhibitors of Mpro. METHODS: The current study identified five natural compounds (myrrhanol B (C1), myrrhanone B (C2), catechin (C3), quercetin (C4), and feralolide (C5) with strong inhibitory potential against Mpro through virtual screening and computational methods, predicting their binding efficiencies and validated it using the in-vitro inhibition activity. The selected compound's toxicity was examined using the MTT assay on a human BJ cell line. RESULTS: Compound C1 exhibited the highest binding affinity, with a docking score of -9.82 kcal/mol and strong hydrogen bond interactions within Mpro's active site. A microscale molecular dynamics simulation confirmed the stability and tight fit of the compounds in the protein's active pocket, showing superior binding interactions. in vitro assays validated their inhibitory effects, with C1 having the most significant potency (IC50 = 2.85 µM). The non-toxic nature of these compounds in human BJ cell lines was also confirmed, advocating their safety profile. CONCLUSION: These findings highlight the effectiveness of combining computational and experimental approaches to identify potential lead compounds for SARS-CoV-2, with C1-C5 emerging as promising candidates for further drug development against this virus.

Greenhouse gas emissions, carbon stocks and wheat productivity following biochar, compost and vermicompost amendments: comparison of non-saline and salt-affected soils.

Understanding the impact of greenhouse gas (GHG) emissions and carbon stock is crucial for effective climate change assessment and agroecosystem management. However, little is known about the effects of organic amendments on GHG emissions and dynamic changes in carbon stocks in salt-affected soils. We conducted a pot experiment with four treatments including control (only fertilizers addition), biochar, vermicompost, and compost on non-saline and salt-affected soils, with the application on a carbon equivalent basis under wheat crop production. Our results revealed that the addition of vermicompost significantly increased soil organic carbon content by 18% in non-saline soil and 52% in salt-affected soil compared to the control leading to improvements in crop productivity i.e., plant dry biomass production by 57% in non-saline soil with vermicompost, while 56% with the same treatment in salt-affected soil. The grain yield was also noted 44 and 50% more with vermicompost treatment in non-saline and salt-affected soil, respectively. Chlorophyll contents were observed maximum with vermicompost in non-saline (24%), and salt-affected soils (22%) with same treatments. Photosynthetic rate (47% and 53%), stomatal conductance (60% and 12%), and relative water contents (38% and 27%) were also noted maximum with the same treatment in non-saline and salt-affected soils, respectively. However, the highest carbon dioxide emissions were observed in vermicompost- and compost-treated soils, leading to an increase in emissions of 46% in non-saline soil and 74% in salt-affected soil compared to the control. The compost treatment resulted in the highest nitrous oxide emissions, with an increase of 57% in non-saline soil and 62% in salt-affected soil compared to the control. In saline and non-saline soils treated with vermicompost, the global warming potential was recorded as 267% and 81% more than the control, respectively. All treatments, except biochar in non-saline soil, showed increased net GHG emissions due to organic amendment application. However, biochar reduced net emissions by 12% in non-saline soil. The application of organic amendments increased soil organic carbon content and crop yield in both non-saline and salt-affected soils. In conclusion, biochar is most effective among all tested organic amendments at increasing soil organic carbon content in both non-saline and salt-affected soils, which could have potential benefits for soil health and crop production.

Evaluation Health Risks and Sorption of Hexavalent Chromium (Cr(VI) by Biochar and Iron Doped Zinc Oxide Modified Biochar (Fe-ZnO@BC) Using Trifolium: A Green Synthesis Technique.

Contamination of aquatic and terrestrial environment with hexavalent chromium Cr(VI) is one of the major hazards worldwide due its carcinogenicity, persistency and immobility. Different research techniques have been adopted for Cr(VI) remediation present in terrestrial and aquatic media, while adsorption being the most advance, low cost, environmentally friendly and common method. The present study discussed the mechanisms of Parthenium hysterophorus derived biochar, iron-doped zinc oxide nanoparticles (nFe-ZnO) and Fe-ZnO modified biochar (Fe-ZnO@BC) involved in Cr(VI) mobility and bioavailability. Pot experiments were conducted to study the effect of Parthenium hysterophorus derived biochar, nFe-ZnO and Fe-ZnO@BC application rates (2%, 2 mg/kg, 10 mg/kg, respectively). The results indicated that the addition of soil amendments reduced Cr(VI) mobility. The findings revealed that the reduction in chromium mobility was observed by P. hysterophorus BC, and Fe-ZnO@BC but nFe-ZnO application significantly (p = 0.05) reduced Cr(VI) and CrT uptake as compared to the control treatments. The results of SEM coupled with EDS showed a high micropores and channel, smooth surface which helped in adsorption, and may enhance soil conditions. The concentration index (CI) by different amendments in trifolium plant was followed the descending order as: nFe-ZnO > Fe-ZnO@BC > P. hysterophorus BC after 30, 60 and 90 days of harvesting, respectively. In addition, human health risk index was found less than one (H1 < 1.0) in amended soils as compared to control treatments.

Untapped potential of food waste derived biochar for the removal of heavy metals from wastewater.

The presence of heavy metals in water pose a serious threat to both public and environmental health. However, the advances in the application of low cost biochar based adsorbent synthesize from various feedstocks plays an effective role in the of removal heavy metals from water. This study implies the introduction of novel method of converting food waste (FW) to biochar through pyrolysis, examine its physiochemical characteristics, and investigate its adsorption potential for the removal of heavy metals from water. The results revealed that biochar yield decreased from 18.4 % to 14.31 % with increase in pyrolysis temperature from 350 to 550 °C. Likewise, increase in the pyrolysis temperature also resulted in the increase in the ash content from 39.87 % to 42.05 % thus transforming the biochar into alkaline nature (pH 10.17). The structural and chemical compositions of biochar produced at various temperatures (350, 450, and 550 °C) showed a wide range of mineralogical composition, and changes in the concentration of surface functional groups. Similarly, the adsorption potential showed that all the produced biochar effectively removed the selected heavy metals from wastewater. However a slightly high removal capacity was observed for biochar produced at 550 °C that was credited to the alkaline nature, negatively charged biochar active sites due to O-containing functional groups and swelling behavior. The results also showed that the maximum adsorption was recorded at pH 8 at adsorbent dose of 2.5 g L-1 with the contact time of 120 min. To express the adsorption equilibrium, the results were subjected to Langmuir and Freundlich isotherms and correlation coefficient implies that the adsorption process follows the Freundlich adsorption isotherm. The findings of this study suggest the suitability of the novel FW derived biochar as an effective and low cost adsorbent for the removal of heavy metals form wastewater.

Improving Access to Anti-HDV Testing: Development and Validation of an Affordable In-House ELISA Assay.

In certain low-income nations, the hepatitis Delta virus and hepatitis B virus (HBV) pose a serious medical burden, where the prevalence of hepatitis B surface antigen (HBsAg) is greater than 8%. Especially in rural places, irregular diagnostic exams are the main restriction and reason for underestimation. Utilizing serum samples from a Pakistani isolate, an internal ELISA for the quick identification of anti-HDV was created, and the effectiveness of the test was compared to a commercial diagnostic kit. HDV-positive serum samples were collected, and a highly antigenic domain of HDAg antigen was derived from them. This antigenic HDAg was expressed in a bacterial expression system, purified by Ni-chromatography, and confirmed by SDS-PAGE and Western blot analysis. The purified antigen was utilized to develop an in-house ELISA assay for anti-HDV antibody detection of the patient's serum samples at very low cost. Purified antigens and positive and negative controls can detect anti-HDV (antibodies) in ELISA plates. The in-house developed kit's efficiency was compared with that of a commercial kit (Witech Inc., USA) by the mean optical density values of both kits. No significant difference was observed (a P value of 0.576) by applying statistical analysis. The newly developed in-house ELISA is equally efficient compared to commercial kits, and these may be useful in regular diagnostic laboratories, especially for analyzing local isolates.

Deciphering the differential expression patterns of yield-related negative regulators in hexaploid wheat cultivars and hybrids at different growth stages.

BACKGROUND: Hexaploid bread wheat underwent a series of polyploidization events through interspecific hybridizations that conferred adaptive plasticity and resulted in duplication and neofunctionalization of major agronomic genes. The genetic architecture of polyploid wheat not only confers adaptive plasticity but also offers huge genetic diversity. However, the contribution of different gene copies (homeologs) encoded from different subgenomes (A, B, D) at different growth stages remained unexplored. METHODS: In this study, hybrid of elite cultivars of wheat were developed via reciprocal crosses (cytoplasm swapping) and phenotypically evaluated. We assessed differential expression profiles of yield-related negative regulators in these cultivars and their F1 hybrids and identified various cis-regulatory signatures by employing bioinformatics tools. Furthermore, the preferential expression patterns of the syntenic triads encoded from A, B, and D subgenomes were assessed to decipher their functional redundancy at six different growth stages. RESULTS: Hybrid progenies showed better heterosis such as up to 17% increase in the average number of grains and up to 50% increase in average thousand grains weight as compared to mid-parents. Based on the expression profiling, our results indicated significant dynamic transcriptional expression patterns, portraying the different homeolog-dominance at the same stage in the different cultivars and their hybrids. Albeit belonging to same syntenic triads, a dynamic trend was observed in the regulatory signatures of these genes that might be influencing their expression profiles. CONCLUSION: These findings can substantially contribute and provide insights for the selective introduction of better cultivars into traditional and hybrid breeding programs which can be harnessed for the improvement of future wheat.

A Sensor Placement Approach Using Multi-Objective Hypergraph Particle Swarm Optimization to Improve Effectiveness of Structural Health Monitoring Systems.

In this paper, a novel Multi-Objective Hypergraph Particle Swarm Optimization (MOHGPSO) algorithm for structural health monitoring (SHM) systems is considered. This algorithm autonomously identifies the most relevant sensor placements in a combined fitness function without artificial intervention. The approach utilizes six established Optimal Sensor Placement (OSP) methods to generate a Pareto front, which is systematically analyzed and archived through Grey Relational Analysis (GRA) and Fuzzy Decision Making (FDM). This comprehensive analysis demonstrates the proposed approach's superior performance in determining sensor placements, showcasing its adaptability to structural changes, enhancement of durability, and effective management of the life cycle of structures. Overall, this paper makes a significant contribution to engineering by leveraging advancements in sensor and information technologies to ensure essential infrastructure safety through SHM systems.

Tuning the optoelectronic properties of selenophene-diketopyrrolopyrrole-based non-fullerene acceptor to obtain efficient organic solar cells through end-capped modification.

With the goal of developing a high-performance organic solar cell, nine molecules of A2-D-A1-D-A2 type are originated in the current investigation. The optoelectronic properties of all the proposed compounds are examined by employing the DFT approach and the B3LYP functional with a 6-31G (d, p) basis set. By substituting the terminal moieties of reference molecule with newly proposed acceptor groups, several optoelectronic and photovoltaic characteristics of OSCs have been studied, which are improved to a significant level when compared with reference molecule, i.e., absorption properties, excitation energy, exciton binding energy, band gap, oscillator strength, electrostatic potential, light-harvesting efficiency, transition density matrix, open-circuit voltage, fill factor, density of states and interaction coefficient. All the newly developed molecules (P1-P9) have improved λmax, small band gap, high oscillator strengths, and low excitation energies compared to the reference molecule. Among all the studied compounds, P9 possesses the least binding energy (0.24 eV), P8 has high interaction coefficient (0.70842), P3 has improved electron mobility due to the least electron reorganization energy (λe = 0.009182 eV), and P5 illustrates high light-harvesting efficiency (0.7180). P8 and P9 displayed better Voc results (1.32 eV and 1.33 eV, respectively) and FF (0.9049 and 0.9055, respectively). Likewise, the phenomenon of charge transfer in the PTB7-Th/P1 blend seems to be a marvelous attempt to introduce them in organic photovoltaics. Consequently, the outcomes of these parameters demonstrate that adding new acceptors to reference molecule is substantial for the breakthrough development of organic solar cells (OSCs).

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

The relationship between money supply and inflation in Pakistan.

This paper investigates the long-run and short-run relationship between money supply and inflation in Pakistan, utilizing annual data spanning from 1981 to 2021. The key objective is to assess the impact of monetary policy, specifically money supply, on inflation dynamics in the country. To achieve this, the Autoregressive Distributed Lag (ARDL) bounds testing approach is employed, which is suitable for analyzing cointegration among variables with mixed integration orders. The results reveal both short and long-run cointegration between inflation, money supply, unemployment, and interest rates. Notably, unemployment demonstrates a negative correlation with inflation, while money supply and interest rates exhibit a positive relationship. These findings underscore the importance of dedicated policy measures to manage inflation effectively. The paper concludes by recommending the establishment of a policy implementation body and collaboration between the government and the central bank to ensure financial stability and control inflation through well-calibrated monetary and fiscal policies.

Exploring the determinants of methane emissions from a worldwide perspective using panel data and machine learning analyses.

This article contributes to the scant literature exploring the determinants of methane emissions. A lot is explored considering CO2 emissions, but fewer studies concentrate on the other most long-lived greenhouse gas (GHG), methane which contributes largely to climate change. For the empirical analysis, a large dataset is used considering 192 countries with data ranging from 1960 up to 2022 and considering a wide set of determinants (total central government debt, domestic credit to the private sector, exports of goods and services, GDP per capita, total unemployment, renewable energy consumption, urban population, Gini Index, and Voice and Accountability). Panel Quantile Regression (PQR) estimates show a non-negligible statistical effect of all the selected variables (except for the Gini Index) over the distribution's quantiles. Moreover, the Simple Regression Tree (SRT) model allows us to observe that the losing countries, located in the poorest world regions, abundant in natural resources, are those expected to curb methane emissions. For that, public interventions like digitalization, green education, green financing, ensuring the increase in Voice and Accountability, and green jobs, would lead losers to be positioned in the winner's rankings and would ensure an effective fight against climate change.

Regulatory pathways and therapeutic potential of PDE4 in liver pathophysiology.

Phosphodiesterase 4 (PDE4), crucial in regulating the cyclic adenosine monophosphate (cAMP) signaling pathway, significantly impacts liver pathophysiology. This article highlights the comprehensive effects of PDE4 on liver health and disease, and its potential as a therapeutic agent. PDE4's role in degrading cAMP disrupts intracellular signaling, increasing pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). This contributes to liver inflammation in conditions such as hepatitis and non-alcoholic steatohepatitis (NASH). Additionally, PDE4 is a key factor in liver fibrosis, characterized by excessive extracellular matrix deposition. Inhibiting PDE4 shows promise in reducing liver fibrosis by decreasing the activation of hepatic stellate cells, which is pivotal in fibrogenesis. PDE4 also influences hepatocyte apoptosis a common feature of liver diseases. PDE4 inhibitors protect against hepatocyte apoptosis by raising intracellular cAMP levels, thus activating anti-apoptotic pathways. This suggests potential in targeting PDE4 to prevent hepatocyte loss. Moreover, PDE4 regulates hepatic glucose production and lipid metabolism, essential for liver function. Altering cAMP levels through PDE4 affects enzymes in these metabolic pathways, making PDE4 a target for metabolic disorders like type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Since PDE4 plays a multifaceted role in liver pathophysiology, influencing PDE4's mechanisms in liver diseases could lead to novel therapeutic strategies. Still, extensive research is required to explore the molecular mechanisms and clinical potential of targeting PDE4 in liver pathologies.

Phytochemicals for Cancer Treatment: An Update on Plant-Derived Anti-Cancer Compounds and their Mechanisms of Action.

Cancer remains one of the major causes of morbidity and mortality worldwide. Scientists from different fields are working to devise an efficient treatment strategy in order to reduce the global burden of cancer. Commonly used treatment approaches for cancer treatment include chemotherapy, immunotherapy, photodynamic therapy, radiation, surgery, etc. These treatment procedures have several pitfalls, such as toxicity, limited bioavailability, rapid elimination, poor specificity, and high cost. On the other side, plant-derived anticancer compounds exhibit several advantages and can overcome these shortcomings. Plant-based anticancer compounds are safer, potent, easily available, and comparatively cost-effective. The current review discusses pure plant- based compounds that are used as a therapeutic remedy for anticancer application. The proposed mechanisms of action, through which these compounds inhibit cancer cell growth, tumor growth, angiogenesis, instigate apoptosis, cytotoxicity, mitochondrial membrane degradation, and reduce cell viability as well as cell cycle progression, are also reviewed. These naturally occurring compounds exhibit great therapeutic potential and could be used as candidate drugs in clinical applications.