Search

Background: Isolated limb infusion (ILI) treats unresectable extremity malignancies with high-dose regional chemotherapy limited to the limb. This study assessed long-term outcomes after ILI for limb-threatening sarcomas. Methods: A retrospective review analyzed patients with an extremity sarcoma who underwent ILI with melphalan and dactinomycin from 2008 to 2023 at a single institution. Results: The study identified 61 patients (52.5% female; median age, 73 years; range, 20–94 years). Of these patients, 68.9% had lower-extremity disease. The median follow-up period was 6.9 years. The overall response rate was 48.3% (complete response [CR], 21.7%; partial response [PR], 26.7%), and the disease control rate (DCR: CR + PR + stable disease [SD]) was 65%. The median progression-free survival (PFS) for the patients with CR/PR/SD/progressive disease (PD) was respectively 16.8/9.6/4.8/2.4 months (P < 0.0001). The responders (CR + PR) had significantly longer PFS than the non-responders (SD + PD) (hazard ratio [HR], 6.3; 95% confidence interval [CI], 3.1–12.9; P < 0.001). The median in-field PFS times for CR/PR/SD/PD were respectively 16.8/12/4.8/2.4 months (P < 0.001). The responders had a significantly longer risk of in-field PFS than the non-responders (HR, 5.9; 95% CI 2.9–12.0; P < 0.001). The median distant relapse PFS for CR/PR/SD/PD was not reached (NR)/NR/44.4/40.8 months (P = 0.02). The responders had a significantly longer distant relapse PFS than the non-responders (HR, 2.7; range, 1.1–6.8; P = 0.04). The median overall survival (OS) was 8.6 years for the responders and 4.1 years for the non-responders (P = 0.02). The disease-specific survival (DSS) rates were 87% at 1 year, 71% at 3 years, and 64% at 5 years. The median DSS was not reached for the responders and was 4.1 years for the non-responders (P = 0.003). The limb salvage rates at 6 months were 85% at 1 year, 80% at 3 years, and 70% at 5 years. The patients with PD had a higher risk of requiring amputation than the patients with CR + PR + SD (HR, 3.0; 95% CI 1.0–8.7; P = 0.04). Conclusions: The 5-year limb salvage rates after ILI are notably high, reaching 70%. After ILI, the responders had significantly better in-field and distant relapse PFS, OS, and DSS. [ABSTRACT FROM AUTHOR]

Purpose: This review article summarizes the pathophysiological aspects of interleukins (ILs) including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, and IL-10 in pancreatic cancer (PC). Methods: Science Direct, PubMed, and Google Scholar were used for the literature review. The search was conducted until August 12, 2024, and particular keywords such as "Pancreatic Cancer," "Interleukins," "Pathophysiological Aspects," "Immunosuppression," "Invasiveness," and "Metastasis" were used. Focusing on interleukins related to pancreatic cancer, 61 original studies were included: 32 studies for human patients, 16 studies for animal models, and 13 studies for both animal models and human patients. All types of PC were considered. The timeframe of 1991 to 2024 was chosen for clinical studies. Results: In epithelial pancreatic tumors, IL-1 is a major inflammation factor. Serum concentrations of soluble interleukin-2-receptor were considerably greater in patients with PC and chronic pancreatitis than in healthy individuals. In comparison to controls, pancreatic cancer patients had considerably greater levels of macrophage colony-stimulating factor and significantly lower levels of stem cell factor and IL-3. The tissues and cells of pancreatic cancer have higher concentrations of IL-4 receptors. IL-5 has a role in the accumulation of pancreatic fibrosis. For individuals with pancreatic ductal adenocarcinoma (PDAC), a high serum level of IL-6 may be a separate risk factor for the development of widespread liver metastases. PDAC patients' peripheral blood mononuclear cells exhibit a substantial upregulation of IL-7 receptor. The role of IL-8 in the growth and spread of PC in humans. The miR-200a/β-catenin axis may be the mechanism by which IL-9 stimulates the proliferation and metastasis of PC cells. Blocking IL-10 in the local microenvironment appears to result in a significant reversal of tumor-induced immunosuppression. Conclusion: The article concludes that interleukins 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 played significant roles in the pathogenesis of PC. [ABSTRACT FROM AUTHOR]

Background: This study compares Selective Amygdalohippocampectomy (SAHE) and Anterior Temporal Lobectomy (ATL) for temporal lobe epilepsy (TLE), focusing on seizure control and visual field deficits (VFD). While previous research suggests potential benefits of SAHE, this meta-analysis aims to clarify the comparative effectiveness of bothprocedures. Methods: This study adhered to PRISMA guidelines, comparing seizure outcomes and VFDs between SAHE and ATL for temporal lobe epilepsy. Comprehensive data extraction and meta-analysis revealed comparable efficacy, with SAHE potentially offering advantages in VFD risk reduction. Quality assessment ensured methodological rigor. Results: 29 studies comparing SAHE and ATL for TLE. Seizure freedom analysis encompassed 23 studies (n = 3238), showing no significant difference between SAHE and ATL (RR = 0.96, 95% CI = 0.89–1.03, P = 0.26). SAHE exhibited significantly lower visual field deficits (RR = 0.87, 95% CI = 0.78–0.97, P = 0.01). Subgroup analyses highlighted differences between transsylvian SAHE and ATL but not transcortical SAHE. No significant difference was found in seizure freedom between SAHE and ATL in patients with hippocampal sclerosis. Conclusions: ATL is more effective than transsylvian SAHE in achieving seizure freedom. However, no significant difference in seizure freedom was observed between transcortical SAHE and ATL. There were no notable differences in seizure outcomes between the two techniques in patients with hippocampal sclerosis. In contrast, SAHE carries a lower risk of postoperative visual field deficits compared to ATL. [ABSTRACT FROM AUTHOR]

Tissue-engineered skin substitutes (TESS) emerged as a new therapeutic option to improve skin transplantation. However, establishing an adequate and rapid vascularization in TESS is a critical factor for their clinical application and successful engraftment in patients. Therefore, several methods have been applied to improve the vascularization of skin substitutes including (i) modifying the structural and physicochemical properties of dermal scaffolds; (ii) activating biological scaffolds with growth factor-releasing systems or gene vectors; and (iii) developing prevascularized skin substitutes by loading scaffolds with capillary-forming cells. This review provides a detailed overview of the most recent and important developments in the vascularization strategies for skin substitutes. On the one hand, we present cell-based approaches using stem cells, microvascular fragments, adipose tissue derived stromal vascular fraction, endothelial cells derived from blood and skin as well as other pro-angiogenic stimulation methods. On the other hand, we discuss how distinct 3D bioprinting techniques and microfluidics, miRNA manipulation, cell sheet engineering and photosynthetic scaffolds like GelMA, can enhance skin vascularization for clinical applications. Finally, we summarize and discuss the challenges and prospects of the currently available vascularization techniques that may serve as a steppingstone to a mainstream application of skin tissue engineering. [ABSTRACT FROM AUTHOR]

Background and purpose: This comparative systematic review and meta-analysis investigated the incidence of ischemic stroke in intermediate-to-high-risk patients undergoing transcatheter aortic valve replacement versus surgical aortic valve replacement. Methods: We conducted a systematic review and meta-analysis following the PRISMA guidelines, searching PubMed, Google Scholar, Embase, Web of Science, and Cochrane CENTRAL databases from their inception to December 2023. The evaluated outcomes were primarily incidence of stroke and transient ischemic attack (TIA), along with other secondary safety end-points at 30 days and 1 year post-procedure. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized for each study, employing a random-effects model for data synthesis irrespective of heterogeneity. Statistical heterogeneity was assessed using I2 statistics. All statistical analyses were conducted using Review Manager. Results: We screened 8028 articles and included 8 studies consisting of 5 randomized controlled trials and 3 observational studies. The studies examining 30-day and 1-year stroke incidence found no significant difference between TAVR and SAVR patients (OR 0.83, 95% CI 0.59 to 1.17, p = 0.30, OR 0.92, 95% CI 0.64 to 1.33, p = 0.67, respectively). Both TAVR and SAVR also had a comparable risk of having a transient ischemic attack within 30 days (OR 0.93, 95% CI 0.24 to 3.63, p = 0.92, I2 52%) and 1 year (OR 1.15, 95% CI 0.72 to 1.82, p = 0.56, I2 0%) following the procedure. Regarding safety endpoints, TAVR had lower rates of all-cause mortality and acute kidney injury at 1 year post-procedure, but a higher incidence of major vascular complications at both 30 days and 1 year compared with SAVR. Conclusion: The results suggest that TAVR and SAVR have comparable outcomes for both TIA and stroke incidence at 30 days and 1 year post-procedure, but display varying safety profiles in intermediate-to-high surgical risk patients. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a malignant neoplasm which is classified into various types defined by underlying molecular factors such as estrogen receptor positive (ER+), progesterone receptor positive (PR+), human epidermal growth factor positive (HER2+) and triple negative (TNBC). Early detection of ER+ and TNBC is crucial in the choice of diagnosis and appropriate treatment strategy. Here we report the key genes associated to ER+ and TNBC using RNA-Seq analysis and machine learning models. Three ER+ and TNBC RNA seq datasets comprising 164 patients in-toto were selected for standard NGS hierarchical data processing and data analyses protocols. Enrichment pathway analysis and network analysis was done and finally top hub genes were identified. To come with a reliable classifier which could distinguish the distinct transcriptome patterns associated to ER+ and TNBC, ML models were built employing Naïve Bayes, SVM and kNN. 1730 common DEG's exhibiting significant logFC values with 0.05 p-value threshold were identified. A list of top ten hub genes were screened on the basis of maximal clique centrality (MCC) which included CDC20, CDK1, BUB1, AURKA, CDCA8, RRM2, TTK, CENPF, CEP55 and NDC80.These genes were found to be involved in crucial cell cycle pathways. k-Nearest Neighbor (kNN) model was observed to be best classifier with accuracy 84%, specificity 66% and sensitivity 95% to differentiate between ER+ and TNBC RNA-Seq transcriptomes. Our screened list of 10 hub genes can thus help unearth novel molecular signatures implicated in ER+ and TNBC onset, prognosis and design of novel protocols for breast cancer diagnostics and therapeutics. [ABSTRACT FROM AUTHOR]

Purpose of Review: This article summarizes the role of coagulation factors in the pathophysiology of heart failure including D-dimer, fibrinogen and fibrin, prothrombin, p-selectin, tissue factor, tissue plasminogen activator, von Willebrand factor, β-thromboglobulin, Factor XI, tissue thromboplastin, plasminogen activator inhibitor-1 (PAI-1), thrombomodulin, soluble urokinase-type plasminogen activator receptor (suPAR) and stuart-prower factor. Recent Findings: The D-dimer, P-selectin, prothrombin, von Willebrand factor, tissue plasminogen activator, fibrinogen, suPAR, tissue factor, thrombomodulin and Factor XI play significant roles the pathophysiology of heart failure. However, no associations were found between β-thromboglobulin, tissue thromboplastin, PAI-1 and stuart-prower factor in the context of heart failure. Summary: Coagulation factors play significant role in the pathophysiology of heart failure. Consequently, the underlying pathophysiological mechanisms that explain changes in the cascade are closely related to the diagnostic, prognostic and therapeutic roles of coagulation cascade factors, which help physicians identify and treat heart failure. [ABSTRACT FROM AUTHOR]

Barshore is a small village in the Pishin District, Balochistan, Pakistan, with dry summers and cold rainy winters. This is an agrarian region, mostly with orchards of various fruit trees. This study investigated the physico-chemical properties and macrofauna of soils under various agricultural management practices of this region. The concentrations of soil organic matter (SOM), soil organic carbon (SOC), nutrients, pH, electrical conductivity, soil texture, and the abundance and number of species of soil macrofauna of the agricultural fields were measured. Fifteen agricultural fields were sampled. Fourteen fields were orchards of apple, apricot or the mixture of apple and apricot trees and one field was a cropland, cultivated with wheat as a monocrop. The orchards were under conservation agricultural practices; whereas, the cropland was under conventional management. These agricultural lands were 2–26 years old. The concentration of soil organic matter (SOM) in the upper 0–10 cm depth of these field sites ranged from 11.6 g kg−1 to 32.8 g kg−1 soil. As compared to cropland, orchards had significantly higher concentration of SOM and SOC. A total of 18 soil macrofauna species were found and the most common and abundant were ants (Monomorium minimum, Camponotus pennsylvanicus, Solenopsis invicta, and Lasius niger) followed by Arion ssp. (Brown Slug) and earthworm Lumbricus terrestris. Regression analysis revealed non-significant relationship of the age and the concentration of SOM with the number of macrofauna species and with the concentrations of total mineral nitrogen, bioavailable phosphorus and clay. The existence of ants had no relationship with the concentration of SOM; whereas, existence of Lumbricus terrestris tended to had a positive relationship with the concentration of SOM. The field of tree-based intercropping system was 2 years of age since the land was converted from rangeland to a cropland, had two ant species coexisting. This indicates the positive influence of crop diversification on soil macrofauna. [ABSTRACT FROM AUTHOR]

Global warming upsets the environmental balance and leads to more frequent and severe climatic events. These extreme events include floods, droughts, and heatwaves. These widespread extreme events disrupt various sectors of ecosystems directly. However, among all these events, drought is one of the most prolonged climatic events that significantly destroys the ecosystem. Therefore, accurate and efficient assessment of droughts is necessary to mitigate their detrimental impacts. In recent years, several drought indices based on global climate models (GCMs) of Coupled Model Intercomparison Project Phase 6 (CMIP6) have been proposed to quantify and monitor droughts. However, each index has its advantages and limitations. As each index ensembles different models by using different statistical approaches, it is well known that the margin of error is always a part of statistics. Therefore, this study proposed a new drought index to reduce the uncertainty involved in the assessment of droughts. The proposed index named the Ridge Ensemble Standardized Drought Index (RESDI) is based on the innovative ensemble approach termed ridge parameters and distance-based weighting (RDW) scheme. And the development of this RDW scheme is based on two types of methods i.e., ridge regression and divergence-based method. In this research, we ensemble 18 different GCMs of CMIP6 using the RDW scheme. A comparative analysis of the RDW scheme is performed against the simple model average (SMA) and Bayesian model averaging (BMA) schemes at 32 locations on the Tibetan plateau. The comparison revealed that RDW has less mean absolute error (MAE) and root-mean-square error (RMSE). Therefore, the developed RESDI based on RDW is used to project drought properties under three distinct shared socioeconomic pathway (SSP) scenarios: SSP1-2.6, SSP2-4.5, and SSP5-8.5, across seven different time scales (1, 3, 7, 9, 12, 24, and 48). The projected data is then standardized by using the K-components Gaussian mixture model (K-CGMM). In addition, the study employs steady-state probabilities (SSPs) to determine the long-term behavior of drought. The outcome of this research shows that "normal drought (ND)" has the highest probability of occurrence under all scenarios and time scales. [ABSTRACT FROM AUTHOR]

Microplastics pose significant challenges to ecosystems and organisms. They can be ingested by marine and terrestrial species, leading to potential health risks and ecological disruptions. This study aims to address the urgent need for effective remediation strategies by focusing on the biodegradation of microplastics, specifically polyvinyl chloride (PVC) derivatives, using the bacterial strain Bacillus albus. The study provides a comprehensive background on the accumulation of noxious substances in the environment and the importance of harnessing biodegradation as an eco-friendly method for pollutant elimination. The specific objective is to investigate the enzymatic capabilities of Bacillus albus, particularly the alpha/beta hydrolases (ABH), in degrading microplastics. To achieve this, in-silico studies were conducted, including analysis of the ABH protein sequence and its interaction with potential inhibitors targeting PVC derivatives. Docking scores of − 7.2 kcal/mol were obtained to evaluate the efficacy of the interactions. The study demonstrates the promising bioremediation prospects of Bacillus albus for microplastics, highlighting its potential as a key player in addressing microplastic pollution. The findings underscore the urgent need for further experimental validation and practical implementation of Bacillus albus in environmental remediation strategies. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the impact of different irrigation sources on the levels of potentially toxic metals (Cd, Cr, Fe and Mn) in the edibles of citrus fruits (Citrus sinensis and Citrus limetta). The samples of fruit, soil and water were collected from two locations (fresh water irrigated-FW I and sewage water irrigated-SW II) within the city of Sargodha. The samples utilized in the study for metal analysis were prepared utilizing the wet acid digestion method. Metal determination was performed using Atomic Absorption Spectrometry (AAS). The potentially toxic metal values in the citrus samples ranged from 0.010 to 0.063, 0.015 to 0.293, 6.691 to 11.342 and 0.366 to 0.667 mg/kg for Cd, Cr, Fe and Mn, respectively. Analysis of Citrus limetta and Citrus sinensis indicated that the highest concentration of Cr, Fe and Mn is observed at the sewage water irrigation site (SW-II), whilst the minimum levels of Cr, Fe and Mn were observed at the fresh water irrigation site (FW-I). The results show that the levels of these metals in soil and fruit samples meet the acceptable guidelines outlined by USEPA and WHO. It was found that the metal pollution constitutes a potential threat to human health due to the HRI values for Cd, Cr, and Fe being above 1, despite the DIM values being below 1. Regular monitoring of vegetables irrigated with wastewater is highly recommended in order to minimise health risks to individuals. [ABSTRACT FROM AUTHOR]

Accurate ensembles of precipitation data play an important role in precise and efficient drought monitoring systems at the regional level. This article proposes a weighted aggregation scheme – the Divergence and Interdependence-based Hybrid Weighting Scheme (DIHWS) – to ensemble precipitation data for accurate regional drought analysis. The derivation of weights is based on the interdependence among meteorological observatories and the divergence from the mean characteristics of regional data. Here, the interdependence among meteorological observatories is assessed using the Bayesian Network theory. At the same time, the divergence from the mean characteristics of regional data is based on the set of equations used for regional aggregation in (Ali et al., Water Resour Manage 36:4099–4114, 2022). Consequently, the paper introduces a new regional drought index – the Bayesian Network-based Adaptive Regional Drought Index (BNARDI). BNARDI is a standardized regional index and used estimated at multiple time scales. The application of DIHWS and BNARDI is based on five regions of varying observatories. We observed smaller MAE values associated with DIHWS than its Simple Model Average (SMA) and one other of its relevant compitator in all the regions. Therefore, we conclude that the proposed weighting scheme and drought index are more reliable for regional drought monitoring and forecasting. Additionally, the research includes various forecasting models to assess their appropriateness for forecasting the new regional index. The results of this research demonstrate that no single method is suitable for forecasting complex drought data, as generated by BNARDI. Therefore, we suggest using varying methods or a hybrid of various candidate forecasting models for forecasting BNARDI. [ABSTRACT FROM AUTHOR]

Simultaneous wireless information and power transmission (SWIPT) allows the use of RF signals for both information detection and energy harvesting. Integration of cooperation, NOMA and SWIPT can provide energy-efficient, reliable, and spectral-efficient networks. Therefore, this study aims to design energy harvesting-enabled cooperative NOMA (C-NOMA) networks. This work investigates relay selection for multiple relay downlink C-NOMA networks with SWIPT in the presence of interference. The analytical closed-form outage probability expressions for the proposed relay selection are derived. Subsequently, the impact of various parameters, including the number of available relay nodes, energy harvesting parameters, and energy conversion efficiency, is analyzed on the performance of proposed networks. The finding showed that system performance improves with the number of intermediate relaying nodes, transmit power, and energy conversion efficiency. Comparative analysis of NOMA and time division multiple access TDMA proved the superiority of NOMA over traditional OMA schemes. [ABSTRACT FROM AUTHOR]

The emergence of carbapenem-resistant Acinetobacter baumannii, a highly concerning bacterial species designated as a Priority 1: Critical pathogen by the WHO, has become a formidable global threat. In this study, we utilised computational methods to explore the potent molecules capable of inhibiting the IspC enzyme, which plays a crucial role in the methylerythritol 4-phosphate (MEP) biosynthetic pathway. Employing high-throughput virtual screening of small molecules from the Enamine library, we focused on the highly conserved substrate binding site of the DXR target protein, resulting in the identification of 1000 potential compounds. Among these compounds, we selected the top two candidates (Z2615855584 and Z2206320703) based on Lipinski's rule of Five and ADMET filters, along with FR900098, a known IspC inhibitor, and DXP, the substrate of IspC, for molecular dynamics (MD) simulations. The MD simulation trajectories revealed remarkable structural and thermodynamic stability, as well as strong binding affinity, for all the IspC-ligand complexes. Furthermore, binding free energy calculations based on MM/PBSA (Molecular Mechanics/Poisson–Boltzmann Surface Area) methodology demonstrated significant interactions between the selected ligand molecules and IspC. Taking into consideration all the aforementioned criteria, we suggest Z2206320703 as the potent lead candidate against IspC. [ABSTRACT FROM AUTHOR]

Changes in patterns of meteorological parameters, like precipitations, temperature, wind, etc., are causing significant increases in various extreme events. And these extreme events, i.e., floods, heatwaves, hurricanes, droughts, etc., lead to a shortage of water resources, crop failures, wildfires, and economic losses. However, Global Circulation Models (GCMs) are considered the most important tools for quantifying climate change. Therefore, we selected 20 different GCMs of precipitation in our research, as the frequency of extreme events, like drought and flood, is highly related to changes in precipitation patterns. However, this research introduced a new weighting scheme — MCFSAWS-Ensemble: Monte Carlo Feature Selection Adaptive Weighting Scheme to Ensemble multiple GCMs, whereas, Monte Carlo Feature Selection (MCFS) is one of the most popular algorithms for discovering important variables. However, the proposed weighting scheme (MCFSAWS-Ensemble) is mainly based on two sources. Initially, it evaluates the prior performance of each GCM model to define their relative importance using MCFS. Then, it computes value by value difference between the observed and simulated model. In addition, the application of this paper is based on the monthly time series data of precipitation in the Tibet Plateau region of China. In addition, we used twenty GCMs from the Coupled Model Intercomparison Project Phase 6 (CMIP6) to analyze the implications of the MCFSAWS-Ensemble. Further, we compared the performance of the MCFSAWS-Ensemble scheme with Simple Model Averaging (SMA) through Mean Average Error (MAE) and correlation statistics. The results of this research indicate that the proposed weighting scheme (MCFSAWS-Ensemble) is more accurate than the SMA approach. Consequently, we recommend the use of advanced machine learning algorithms such as MCFS for making accurate multi-model ensembles. [ABSTRACT FROM AUTHOR]

To ensure the steady navigation for robot stable controls are one of the basic requirements. Control values selection is highly environment dependent. To ensure reusability of control parameter, system needs to generalize over the environment. Adding adaptability in robots to perform effectively in the environments with no prior knowledge reinforcement leaning is a promising approach. However, tuning hyper parameters and attaining correlation between state space and reward function to train a stable reinforcement learning agent is a challenge. This paper is focused, to design a continuous reward function to minimize the sparsity and stabilizes the policy convergence, to attain control generalization for differential drive robot. To achieve that, Twin Delayed Deep Deterministic Policy Gradient is implemented on PyBullet Racecar model in Open-AIGym environment. System was trained to achieve smart primitive control policy, moving forward in the direction of goal by maintaining an appropriate distance from walls to avoid collision. Resulting policy was tested on unseen environments including dynamic goal environment, boundary free environment and continuous path environment on which it outperformed Deep Deterministic Policy Gradient. [ABSTRACT FROM AUTHOR]

Drought as a natural disaster, can have devastating effects on various sectors. This study proposes a new weighting scheme called weighted aggregation (WA) and introduces the Multi-model weighted drought severity index (MMWDSI) as an improved indicator for drought assessment. The methodology of MMWDSI involves ensemble modeling using the WA scheme, incorporating the K-components Gaussian mixture model (K-CGMM) for appropriate distribution fitting. It employs a multi-stage statistical procedure that considers point-to-point variations and the past performance of climate models through the Taylor Skill Score in the initial stage. Subsequent stages involve linear models and K-CGMM for prediction and standardization. Similar to other standardized drought indices, the proposed index allows for inferring the probabilistic behavior of extreme events, such as extreme drought or extreme wet conditions, and assessing trends using various statistical techniques. For the application of the index, historical precipitation data from 1961 to 2014 was utilized from 32 grid points on the Tibetan Plateau as the reference dataset. Additionally, simulations from 18 models of the Coupled Model Intercomparison Project phase 6, both past and future, were employed for the estimation procedure. The findings demonstrate that the developed weighting scheme surpasses the Equal Weighted Averaging approach. In conclusion, the MMWDSI approach proves to be a flexible and effective method that enhances accuracy in drought monitoring. [ABSTRACT FROM AUTHOR]

Pond aquaculture has been developed to increase the production of the Pangasius hypothalamus, an important aquatic species; it plays a pivotal role in providing food, fish, nutrition, income, and livelihoods for various value-chain actors in Pakistan. However, this method is mainly used in intensive monoculture, and little knowledge is available on polyculture approaches in Pakistan. Therefore, this study was conducted to evaluate the growth and production of fish at the different species composition in polyculture. The experiment was conducted for 90 days at the Department of Fisheries and Aquaculture UVAS, Lahore, Pakistan. There were three treatment groups, each with three replications. In all treatments, the stocking density of pangas was similar at different species compositions. All the ponds were subjected to the same regime of feeding and fertilization. Fortnightly random sampling was done to adjust the feeding rate. In this study, the Pangasius hypothalamus, showed significant variations with a final weight of 385.34 g, in T3, and 318.50 g, in T1 compared to others. %Weight gain and % SGR of Pangasius were comparatively higher among other fishes in T1 and T3. The FCR of pangas was recorded as 1.9 in T1 and 1.30 in T3, which shows a better result than the control and other groups. In addition, the polyculture of the pangas influenced the nitrate level, which was increased in the high-density group compared to low density and control. At the end of the trial, we observed non-significant variations in cortisol and glucose levels among all treatments, which indicates that there was no stress on Pangasius in the polyculture system. Due to positive effects on growth parameters, it is concluded that the polyculture of pangas with only Indian and mixed (Indian and Chinese carp) could be tried to enhance the economic benefits in Pakistan. [ABSTRACT FROM AUTHOR]

Staphylococcus sciuri (also currently Mammaliicoccus sciuri) are anaerobic facultative and non-motile bacteria that cause significant human pathogenesis such as endocarditis, wound infections, peritonitis, UTI, and septic shock. Methicillin-resistant S. sciuri (MRSS) strains also infects animals that include healthy broilers, cattle, dogs, and pigs. The emergence of MRSS strains thereby poses a serious health threat and thrives the scientific community towards novel treatment options. Herein, we investigated the druggable genome of S. sciuri by employing subtractive genomics that resulted in seven genes/proteins where only three of them were predicted as final targets. Further mining the literature showed that the ArgS (WP_058610923), SecY (WP_058611897), and MurA (WP_058612677) are involved in the multi-drug resistance phenomenon. After constructing and verifying the 3D protein homology models, a screening process was carried out using a library of Traditional Chinese Medicine compounds (consisting of 36,043 compounds). The molecular docking and simulation studies revealed the physicochemical stability parameters of the docked TCM inhibitors in the druggable cavities of each protein target by identifying their druggability potential and maximum hydrogen bonding interactions. The simulated receptor-ligand complexes showed the conformational changes and stability index of the secondary structure elements. The root mean square deviation (RMSD) graph showed fluctuations due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points where the pattern of the RMSD and root mean square fluctuation (RMSF) (< 1.0 Å) support any major domain shifts within the structural framework of the protein–ligand complex and placement of ligand was well complemented within the binding site. The β-factor values demonstrated instability at few points while the radius of gyration for structural compactness as a time function for the 100-ns simulation of protein–ligand complexes showed favorable average values and denoted the stability of all complexes. It is assumed that such findings might facilitate researchers to robustly discover and develop effective therapeutics against S. sciuri alongside other enteric infections. [ABSTRACT FROM AUTHOR]

The annual growth rate of pharmaceutical industry in Pakistan is 10% and is continuously expanding to fulfill the increasing demand of the rapidly growing population. But inability of the pharmaceutical sector to comply with the environmental standards leads to the introduction of large quantities of various pollutants in the natural environment which presents serious ecological challenges. In this study, effluent wastewater samples from 14 manufacturing units of the pharmaceutical industries of the National Industrial Zone, Rawat, Pakistan, were collected and characterized for physicochemical parameters including color, odor, pH, electric conductivity, temperature, total dissolved solids, total suspended solids, salinity, dissolved oxygen (DO), chemical oxygen demand (COD), nitrates, sulfates and phosphates according to the standard methods. The detection and quantification of diclofenac (DCF)—one of the commonly prescribed drugs in Pakistan—were carried out in the pharmaceutical wastewater samples (PWWSs) using HPLC-PAD. Exceptionally high concentration of the diclofenac was detected in the industrial disposal of MB-12 (311,495 µg L−1). PWWSs were analyzed using chemometric techniques including principal factor analysis (PFA) and cluster analysis (CA). PFA explained almost 81.48% of the total variance by the newly extracted four components and complemented the strong Pearson's correlation coefficient (r) of DCF concentrations to that of the levels of COD, r = 0.752, and DO, r = − 0.609, in PWWSs. Six clusters were generated during similar wastewater characteristics-based CA dendrogram, in which reverse osmosis-treated PWWSs were observed to cluster with the untreated PWWSs, suggesting the need to adopt an advance and better wastewater treatment methods by the pharmaceutical industries. [ABSTRACT FROM AUTHOR]

The diagnostic accuracy of a screening tool is often characterized by its sensitivity and specificity. An analysis of these measures must consider their intrinsic correlation. In the context of an individual participant data meta-analysis, heterogeneity is one of the main components of the analysis. When using a random-effects meta-analytic model, prediction regions provide deeper insight into the effect of heterogeneity on the variability of estimated accuracy measures across the entire studied population, not just the average. This study aimed to investigate heterogeneity via prediction regions in an individual participant data meta-analysis of the sensitivity and specificity of the Patient Health Questionnaire-9 for screening to detect major depression. From the total number of studies in the pool, four dates were selected containing roughly 25%, 50%, 75% and 100% of the total number of participants. A bivariate random-effects model was fitted to studies up to and including each of these dates to jointly estimate sensitivity and specificity. Two-dimensional prediction regions were plotted in ROC-space. Subgroup analyses were carried out on sex and age, regardless of the date of the study. The dataset comprised 17,436 participants from 58 primary studies of which 2322 (13.3%) presented cases of major depression. Point estimates of sensitivity and specificity did not differ importantly as more studies were added to the model. However, correlation of the measures increased. As expected, standard errors of the logit pooled TPR and FPR consistently decreased as more studies were used, while standard deviations of the random-effects did not decrease monotonically. Subgroup analysis by sex did not reveal important contributions for observed heterogeneity; however, the shape of the prediction regions differed. Subgroup analysis by age did not reveal meaningful contributions to the heterogeneity and the prediction regions were similar in shape. Prediction intervals and regions reveal previously unseen trends in a dataset. In the context of a meta-analysis of diagnostic test accuracy, prediction regions can display the range of accuracy measures in different populations and settings. [ABSTRACT FROM AUTHOR]

The diagnostic accuracy of a screening tool is often characterized by its sensitivity and specificity. An analysis of these measures must consider their intrinsic correlation. In the context of an individual participant data meta-analysis, heterogeneity is one of the main components of the analysis. When using a random-effects meta-analytic model, prediction regions provide deeper insight into the effect of heterogeneity on the variability of estimated accuracy measures across the entire studied population, not just the average. This study aimed to investigate heterogeneity via prediction regions in an individual participant data meta-analysis of the sensitivity and specificity of the Patient Health Questionnaire-9 for screening to detect major depression. From the total number of studies in the pool, four dates were selected containing roughly 25%, 50%, 75% and 100% of the total number of participants. A bivariate random-effects model was fitted to studies up to and including each of these dates to jointly estimate sensitivity and specificity. Two-dimensional prediction regions were plotted in ROC-space. Subgroup analyses were carried out on sex and age, regardless of the date of the study. The dataset comprised 17,436 participants from 58 primary studies of which 2322 (13.3%) presented cases of major depression. Point estimates of sensitivity and specificity did not differ importantly as more studies were added to the model. However, correlation of the measures increased. As expected, standard errors of the logit pooled TPR and FPR consistently decreased as more studies were used, while standard deviations of the random-effects did not decrease monotonically. Subgroup analysis by sex did not reveal important contributions for observed heterogeneity; however, the shape of the prediction regions differed. Subgroup analysis by age did not reveal meaningful contributions to the heterogeneity and the prediction regions were similar in shape. Prediction intervals and regions reveal previously unseen trends in a dataset. In the context of a meta-analysis of diagnostic test accuracy, prediction regions can display the range of accuracy measures in different populations and settings. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CP) and profenofos (PF) are organophosphate pesticides (OPs) widely used in agriculture and are noxious to both fauna and flora. The presented work was designed to attenuate the toxicity of both pesticides in the growth parameters of a cotton crop by applying plant growth–promoting rhizobacteria (PGPR), namely Pseudomonas aeruginosa PM36 and Bacillus sp. PM37. The multifarious biological activities of both strains include plant growth–promoting traits, including phosphate solubilization; indole-3-acetic acid (IAA), siderophore, and HCN production; nitrogen fixation; and enzymatic activity such as cellulase, protease, amylase, and catalase. Furthermore, the molecular profiling of multi-stress-responsive genes, including acdS, ituC, czcD, nifH, and sfp, also confirmed the plant growth regulation and abiotic stress tolerance potential of PM36 and PM37. Both strains (PM36 and PM37) revealed 92% and 89% of CP degradation at 50 ppm and 87% and 81% at 150 ppm within 7 days. Simultaneously 94% and 98% PF degradation was observed at 50 ppm and 90% and 92% at 150 ppm within 7 days at 35 °C and pH 7. Biodegradation was analyzed using HPLC and FTIR. The strains exhibited first-order reaction kinetics, indicating their reliance on CP and PF as energy and carbon sources. The presence of opd, mpd, and opdA genes in both strains also supported the CP and PF degradation potential of both strains. Inoculation of strains under normal and OP stress conditions resulted in a significant increase in seed germination, plant biomass, and chlorophyll contents of the cotton seedling. Our findings indicate that the strains PM36 and PM37 have abilities as biodegraders and plant growth promoters, with potential applications in crop sciences and bioremediation studies. These strains could serve as an environmentally friendly, sustainable, and socially acceptable solution to manage OP-contaminated sites. [ABSTRACT FROM AUTHOR]

This critique discusses neuroprotective strategies for aneurysmal subarachnoid hemorrhage (SAH), excluding Nimodipine, emphasizing alternatives like verapamil, albumin, and cilostazol. While these options show potential, their efficacy lacks robust confirmation from randomized controlled trials (RCTs), relying mainly on observational studies and small trials. The letter underscores the need for comprehensive safety assessments and long-term outcome studies to enhance practical application. Highlighting ongoing trials and emerging therapies like clazosentan and TAK-044, it advocates for future research directions focused on large-scale RCTs and combination therapies, such as cilostazol and Nimodipine, which have demonstrated synergistic benefits in reducing delayed cerebral ischemia (DCI) and improving patient outcomes. [ABSTRACT FROM AUTHOR]

This letter evaluates the recent study on the management of cystic vestibular schwannomas (VS) compared to solid VS, focusing on the clinical outcomes of surgery (SURGERY) and radiosurgery (SRS). The study offers significant insights into the differences between these tumor types, emphasizing the challenges posed by cystic VS, including rapid growth, enhanced peritumoral adhesion, and worse post-operative facial nerve outcomes. Notably, cystic VS are associated with higher recurrence rates and poorer preoperative status. The study also highlights lower gross total resection (GTR) rates and poorer long-term tumor control in cystic VS. While SRS shows high rates of functional preservation, it is less effective in ensuring recurrence-free survival in cystic VS compared to solid VS, suggesting surgery may be preferable for achieving the best long-term outcomes, particularly when safe maximal resection is possible. However, the study's retrospective design and limited sample size, along with the lack of standardized follow-up protocols, may impact the generalizability of the findings. Future research should focus on prospective, multicenter studies with standardized protocols to develop evidence-based guidelines for managing cystic VS. Innovative techniques, such as advanced imaging and minimally invasive surgical approaches, may further improve diagnostic accuracy and treatment efficacy. This study underscores the complexities of managing cystic VS and the need for tailored treatment strategies. [ABSTRACT FROM AUTHOR]

Item 10 of the Edinburgh Postnatal Depression Scale (EPDS) is intended to assess thoughts of intentional self-harm but may also elicit concerns about accidental self-harm. It does not specifically address suicide ideation but, nonetheless, is sometimes used as an indicator of suicidality. The 9-item version of the EPDS (EPDS-9), which omits item 10, is sometimes used in research due to concern about positive endorsements of item 10 and necessary follow-up. We assessed the equivalence of total score correlations and screening accuracy to detect major depression using the EPDS-9 versus full EPDS among pregnant and postpartum women. We searched Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science from database inception to October 3, 2018 for studies that administered the EPDS and conducted diagnostic classification for major depression based on a validated semi-structured or fully structured interview among women aged 18 or older during pregnancy or within 12 months of giving birth. We conducted an individual participant data meta-analysis. We calculated Pearson correlations with 95% prediction interval (PI) between EPDS-9 and full EPDS total scores using a random effects model. Bivariate random-effects models were fitted to assess screening accuracy. Equivalence tests were done by comparing the confidence intervals (CIs) around the pooled sensitivity and specificity differences to the equivalence margin of δ = 0.05. Individual participant data were obtained from 41 eligible studies (10,906 participants, 1407 major depression cases). The correlation between EPDS-9 and full EPDS scores was 0.998 (95% PI 0.991, 0.999). For sensitivity, the EPDS-9 and full EPDS were equivalent for cut-offs 7–12 (difference range − 0.02, 0.01) and the equivalence was indeterminate for cut-offs 13–15 (all differences − 0.04). For specificity, the EPDS-9 and full EPDS were equivalent for all cut-offs (difference range 0.00, 0.01). The EPDS-9 performs similarly to the full EPDS and can be used when there are concerns about the implications of administering EPDS item 10. Trial registration: The original IPDMA was registered in PROSPERO (CRD42015024785). [ABSTRACT FROM AUTHOR]

Background: The “heterotaxy syndrome” also called “situs ambiguus” is a rare condition in which the internal organs of the chest and abdomen are abnormally arranged. This syndrome is usually associated with a spectrum of health-related conditions involving birth defects in organs like the heart, spleen, liver, lungs and others. Case presentation: We present a case of a 29-year-old male who came with an episode of massive upper gastrointestinal bleeding. On arrival he was vitally unstable and after resuscitation underwent a contrast-enhanced CT scan examination. The CT scan identified the features of heterotaxy syndrome with left isomerism and an abnormal blush from the branch of splenic artery supplying the greater curvature of the stomach. Embolization of the splenic artery branches was performed with the help of gel foam. No abnormal blush was identified post-embolization. Later on, in his hospital stay the patient went into pulse less electrical activity and died. Conclusion: Upper gastrointestinal bleed in the patients with heterotaxy syndrome is a rare presentation of a rare condition. Our case highlights the importance of diagnostic and interventional radiology in diagnosing such patients and identifying the site of bleed especially where endoscopic visualization is not possible and managing the bleeding efficiently. [ABSTRACT FROM AUTHOR]

Leather industry is the second largest export-earning sector of Pakistan. However, because of poor waste management, this industry has been continuously polluting the environment. In this paper, the impact of tanneries on the groundwater quality of Kasur city (i.e., the second largest leather producing city) is examined. The study is conducted in the following three phases: (I) water samples collection, (II) determination of physio-chemical properties, and (III) application of data mining techniques. In phase I, groundwater samples were collected from various sources such as hand pumps, motor pumps, and tube wells. In phase II, several physio-chemical properties such as (i) total dissolved solids (TDS), (ii) pH, (iii) turbidity, (iv) electrical conductivity (EC), (v) total hardness (TH), (vi) total alkalinity (TA), (vii) nitrates, (viii) chromium, (ix) fluoride, and (x) chloride were estimated. The estimated values of all these foregoing parameters are then compared with the Punjab Environmental Quality Standards for Drinking Water (PEQSDW). In phase III, principle component analysis and cluster analysis of the estimated parameters were performed to elucidate the relation between various parameters and to highlight the highly vulnerable sites, respectively. The results exhibit that most of the sampling collections sites are at the threshold of losing quality water. Moreover, it is also found that Mangal Mandi carries the worst groundwater quality among all sampling locations. Overall, it is concluded that serious attention is due from the water and wastewater authorities to further investigate and monitor the groundwater quality of Kasur before the country strikes with another pandemic after COVID-19. [ABSTRACT FROM AUTHOR]

A recent study published in the Annals of Hematology examined the effectiveness of the apoptosis inhibitor Asunercept in treating patients with lower-risk Myelodysplastic Neoplasms (MDS). The study used deep whole exome sequencing to analyze the impact of Asunercept on clonal bone marrow composition and found that it reduced clone sizes in patients. This suggests that Asunercept may have potential as a targeted therapy for MDS. However, the study's small sample size and lack of long-term follow-up data limit the generalizability and understanding of Asunercept's effects. Further research with larger cohorts and extended follow-up periods is needed to validate these findings and assess the clinical significance of Asunercept in MDS treatment. [Extracted from the article]

This critique examines a 12-year retrospective study on serum magnesium concentration-guided administration of magnesium sulfate in 548 patients with aneurysmal subarachnoid hemorrhage (aSAH). The study reported that maintaining serum magnesium levels between 2 and 2.5 mmol/L reduced rates of delayed cerebral infarction and improved clinical outcomes. However, limitations due to its retrospective nature, single-center design, and unequal treatment group sizes may affect generalizability. Future multicentric randomized controlled trials are recommended to validate these findings and refine magnesium dosing strategies for aSAH treatment. [ABSTRACT FROM AUTHOR]

Purpose: Recurrent Miscarriages (RM) commonly complicates the reproductive outcome where prominently chromosomal aberrations and molecular factors lead to recurrent miscarriages. We investigated couples with RM for cytogenetic abnormalities and Y chromosome microdeletions in males along with detection of aneuploidies de novo in the product of conception from a highly ethnic consanguineous population (Kashmir, North India). Study design: Chromosomal analysis was done by Karyotyping on peripheral blood lymphocyte cultures and analyzed by Cytovision software Version 3.9. Microdeletion in Y chromosome was performed by STS-PCR and QF-PCR was used to detect aneuploidy in the product of conception. Results: Of the 380 samples (190 couples) screened for cytogenetic analysis, 50 (13.1%) chromosomal aberrations were detected in both couples. Numerical aberrations were detected in 16.0%, inversions 22%, duplications 16.0% and translocations were found in 26.0% with three unique reciprocal translocations in males. The couples bonded consanguineously had 32% chromosomal changes with a significant difference in chromosomal inversions (37.5% vs. 14.7%) and translocations (37.5% vs. 20.6%) for consanguineous and non-consanguineous group, respectively (p < 0.05). Further, translocations and inversions (44.5% and 33.3%) were significantly implicated in couples with a positive family history of RM (p < 0.05). Y chromosome deletions were found in 2.1% cases of males. Conclusion: We conclude 15.2% couples affected either by chromosomal or Y chromosome deletions contribute hugely in the diagnosis and management of repeated pregnancy losses. It is recommended that couples that belong to consanguineous and multigenerational group of RM should be considered for cytogenetic and molecular testing after two abortions for successful pregnancy outcomes and management of RM. [ABSTRACT FROM AUTHOR]

Human falls seldom occur; however, predicting falls is critical in health and safety. When aged people are alone at home, the chances of a dangerous fall are high. There is no one to help them instantly; therefore, timely notifying the concerned caregivers is crucial. Our approach has created a low computational cost algorithm, which depends on the head joint extracted using Kinect. The standard deviation formula is used to check variation in the Y-axis of head joints in every frame. The rate of change is then compared to the value of standard deviation generated from experimental results. After calculating the head trajectory's standard deviation, the next step is to classify every event into a separate fall and non-fall using the k-NN model. For assessing the k-NN model, we captured around 120 video samples of different activities tested by performance metrics to achieve an accuracy of 0.95. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a polygenic, and highly prevalent disorder affecting 322 million people globally. It results in several psychological changes which adversely affect different dimensions of life and may lead to suicide. Methods: Whole exome sequencing of 15 MDD patients, enrolled at the Dr. A. Q. Khan Institute of Behavioral Sciences, Karachi, was performed using NextSeq500. Different bioinformatics tools and databases like ANNOVAR, ALoFT, and GWAS were used to identify both common and rare variants associated with the pathogenesis of MDD. Results: A total of 1985 variations were identified in 479 MDD-related genes. Several SNPs including rs1079610, rs11750538, rs1799913, rs1801131, rs2230267, rs2231187, rs3819976, rs4314963, rs56265970, rs587780434, rs6330, rs75111588, rs7596487, and rs9624909 were prioritized due to their deleteriousness and frequency difference between the patients and the South Asian population. A non-synonymous variation rs56265970 (BCR) had 26% frequency in patients and was not found in the South Asian population; a multiallelic UTR-5′ insertion rs587780434 (RELN) was present with an allelic frequency of 70% in patients whereas 22% in the SAS population. Genetic alterations in PABPC1 genes, a stress-associated gene also had higher allele frequency in the cases than in the normal population. Conclusion: This present study identifies both common and rare variants in the genes associated with the pathogenesis of MDD in Pakistani patients. Genetic variations in BCR, RELN, and stress-associated PABPC1 suggest potential roles in the pathogenesis of MDD. [ABSTRACT FROM AUTHOR]

Background: Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma. Methods: An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed. Results: Of 112 patients, median age at T-VEC initiation was 69 years (range 21–93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE). Conclusions: T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response. [ABSTRACT FROM AUTHOR]

This letter to the editor critiques a recent study evaluating the role of biologically effective dose (BED) in stereotactic radiosurgical thalamotomy for essential tremor (ET). The study, conducted retrospectively on 78 ET patients, demonstrates a significant correlation between BED and tremor improvement post-SRS. Moreover, the study suggests adjusting the prescribed dose rather than changing cobalt-60 sources to maintain treatment efficacy while minimizing toxicity. This suggestion aligns with previous research indicating an annual decrease in BED due to cobalt-60 decay. The letter emphasizes the importance of considering BED and cobalt-60 decay in optimizing treatment outcomes for ET patients undergoing stereotactic radiosurgery. Further research is recommended to explore innovative techniques for dose modulation in response to cobalt-60 decay and validate findings in larger cohorts. [ABSTRACT FROM AUTHOR]

This study presents a critical analysis of complications following cranioplasty (CP) after decompressive hemicraniectomy, focusing on autologous, polymethylmethacrylate (PMMA), and computer-aided design (CAD) implants. The analysis encompasses a retrospective bicenter assessment, evaluating factors influencing surgical outcomes and emphasizing the significance of material selection in minimizing postoperative complications. The study's comprehensive examination of complication rates associated with various implant materials contributes significantly to understanding CP outcomes. While polymethylmethacrylate (PMMA) and autologous bone flaps (ABFs) exhibited higher rates of surgical site infection (SSI) and explantation, a meta-analysis revealed a contrasting lower infection rate for polyether ether ketone (PEEK) implants. The study underscores the critical role of material selection in mitigating postoperative complications. Despite its strengths, the study's retrospective design, reliance on data from two centers, and limited sample size pose limitations. Future research should prioritize prospective, multicenter studies with standardized protocols to enhance diagnostic accuracy and treatment efficacy in CP procedures. [ABSTRACT FROM AUTHOR]

Copper oxide thin films were deposited by using pulsed DC magnetron sputtering system on glass substrates for various powers. The X-ray diffraction, optical spectroscopy, and SEM were used to characterize the physical and optical properties of films. Sputtered copper oxide films showed Cu2O and CuO phases. Copper oxide films deposited at 90 W were implanted with silver ions, which is one of the interesting methods to tune the electrical and optical properties of metal oxides. The optical and electrical properties of the films were also studied after ion implantation. The band gap, refractive index, and resistivity were found to be decreased after silver ion implantation. Furthermore, the influence of the silver (Ag) ion implantation on the optical properties of CuO and Cu2O was calculated using the density functional theory, with CASTEP code, which is complying with experimental trend. This study has revealed on the basis of the physical characteristics that CuO and Cu2O can be used as a suitable absorbent material in solar cells. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis lead to durable clinical responses in subsets of cancer patients across multiple indications, including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC) and renal cell carcinoma (RCC). Herein, we complement PD-L1 immunohistochemistry (IHC) and tumor mutation burden (TMB) with RNA-seq in 366 patients to identify unifying and indication-specific molecular profiles that can predict response to checkpoint blockade across these tumor types. Multiple machine learning approaches failed to identify a baseline transcriptional signature highly predictive of response across these indications. Signatures described previously for immune checkpoint inhibitors also failed to validate. At the pathway level, significant heterogeneity is observed between indications, in particular within the PD-L1+ tumors. mUC and NSCLC are molecularly aligned, with cell cycle and DNA damage repair genes associated with response in PD-L1- tumors. At the gene level, the CDK4/6 inhibitor CDKN2A is identified as a significant transcriptional correlate of response, highlighting the association of non-immune pathways to the outcome of checkpoint blockade. This cross-indication analysis reveals molecular heterogeneity between mUC, NSCLC and RCC tumors, suggesting that indication-specific molecular approaches should be prioritized to formulate treatment strategies. PD-L1 immune checkpoint inhibition has been used for several tumour types. Here, the authors use immunohistochemistry, tumour mutation burden and RNA-seq data from 366 patients with different indications to identify molecular signatures of response to atezolizumab and reveal pathway heterogeneity and the involvement of non-immune pathways. [ABSTRACT FROM AUTHOR]

Chronic wounds may lead to the development of various pathological conditions such as diabetic foot ulcers and pressure sores. The current study evaluated wound healing and anti-inflammatory potentials of methanolic extract of Ephedra ciliata using series of in vivo models. Methanolic extract of Ephedra ciliata was prepared by maceration (Ec.Me). Qualitative and quantitative (HPLC) phytochemical and metal analyses were conducted to explore the chemical and metal profiles of Ec.Me. Safety profile (behavioural) and, antimicrobial, antioxidant, wound healing, anti-inflammatory and anti-angiogenic potentials of Ec.Me were evaluated using well-established in vitro and in vivo models. ELISA assay was performed to estimate the effects of Ec.Me treatment on serum levels of TNF-α. HPLC analysis identified quercetin as one of the major compounds in Ec.Me. Safety study data showed that Ec.Me was safe up to the dose of 2000 mg/kg. Antimicrobial assay data showed that Ec.Me was active against bacterial (Staphylococcus aureus) as well as fungal (Candida albicans and Aspergillus niger) strains. Ec.Me showed modertate antioxidant potential in in vitro and in vivo models. Data of excision and burn wound healing models showed that Ec.Me, promoted wound closure in a dose and time-dependent manner. Treatment with 20% Ec.Me cream and heparin showed almost the same effects with no statistical differences (p > 0.05). Ec.Me also showed time-dependent anti-inflammatory activities in both acute and chronic models. In carrageenan model, treatment with 200 mg/kg of Ec.Me showed comparable anti-inflammatory effects (p > 0.05) with quercetin and indomethacin throughout the study. In cotton pellet granuloma model treatment with 200 mg/kg of Ec.Me and indomethacin inhibited granuloma formation significantly better (p < 0.05) as compared with the rest of the treatment groups. Histopathological examination of skin samples showed marked improvement in architecture with minimal infiltration of inflammatory cells. Data of in vivo angiogenesis assay showed marked improvement in vessels length, density, branching points, total segments and total nets after treatment with Ec.Me, indicating no toxic effects towards vasculature development. Significant (p < 0.05) downregulation of TNF-α was observed in serum samples of animals treated with Ec.Me. Based on data of the current study, it is concluded that quercetin-rich extract of Ephedra ciliata has wound healing and anti-inflammatory potentials via downregulation of TNF-α. Moreover, it is suggested that the antimicrobial activity of Ec.Me prevented microbial invasion, thus promoted natural wound healing mechanisms as well. [ABSTRACT FROM AUTHOR]

Background: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose chemotherapy to extremities affected by locally advanced or in-transit melanoma. This study compared the outcomes of melanoma patients treated with ILI in the United States of America (USA) and Australia (AUS). Methods: Patients with locally recurrent in-transit melanoma treated with ILI at USA or AUS centers between 1992 and 2018 were identified. Demographic and clinicopathologic characteristics were collected. Primary outcomes of treatment response, in-field progression-free survival (IPFS), distant progression-free survival (DPFS), and overall survival (OS) were evaluated by the Kaplan-Meier method. Multivariable analysis evaluated whether availability of new systemic therapies affected outcomes. Results: More ILIs were performed in AUS (n = 411, 60 %) than in the USA (n = 276, 40 %). In AUS, more ILIs were performed for stage 3B disease than in the USA (62 % vs 46 %; p < 0.001). The reported complete response rates were similar (AUS 30 % vs USA 29 %). Among the stage 3B patients, AUS patients had better IPFS (p = 0.001), whereas DPFS and OS were similar between the two countries. Among the stage 3C patients, the USA patients had better OS (p < 0.001), whereas IPFS and DPFS were similar. Availability of new systemic therapies did not affect IPFS or DPFS in either country. However, the USA patients who received ILI after ipilimumab approval in 2011 had significantly improved OS (hazard ratio, 0.62; p = 0.013). Conclusions: AUS patients were treated at an earlier disease stage than the USA patients with better IPFS for stage 3B disease. The USA patients treated after the availability of new systemic therapies had a better OS. [ABSTRACT FROM AUTHOR]

Conjunction of 1D as well as 2D carbonaceous materials (CMs) is of great importance because of the significant improvement in the optoelectronic properties. Through extensive optimization, a rapid, facile and heat-treatment free route is progressed which ensues 88.4 and 92.3% degradation of congo-red dye for CNTs/ZnO and g-C3N4/ZnO, respectively. g-C3N4/ZnO shows the highest value of correlation co-efficient (R2) (0.9927) and rate constant (KC) (0.0390 min−1) among all others. g-C3N4/ZnO-HPs4 displays the highest potential of 1.54 V and over potential of 310 mV for current density value of 10 mA/cm2 compared to others composite while CNTs/ZnO-HPs4 Tafel slope has a value of 42 mV/dec. Scanning and transmission electron microscopy, X-ray diffractometry and energy dispersive spectrometry were carried out to confirm the efficacy of nano-composites while electron LSV, Tafel slopes and Nyquist plots were plotted to reveal the consequent efficient electro-catalytic behavior. The modified recipe for the development of nanocomposites having CMs exhibited its potential for use in multiple engineering applications, including but not limited to photocatalysis and oxygen evolution reaction. [ABSTRACT FROM AUTHOR]

Knee issues are very frequent among people of all ages, and osteoarthritis is one of the most common reasons behind them. The primary feature in observing extremity and advancement of osteoarthritis is joint space narrowing (cartilage loss) which is manually computed on knee x-rays by a radiologist. Such manual inspections require an expert radiologist to analyze the x-ray image; moreover, it is a tedious and time-consuming task. In this paper, we present a computer-vision-based system that can assist the radiologists by analyzing the radiological symptoms in knee x-rays for osteoarthritis. Different image processing techniques have been applied on knee radiographs to enhance their quality. The knee region is extracted automatically using template matching. The knee joint space width is calculated, and the radiographs are classified based on the comparison with the standard normal knee joint space width. The experimental evaluation performed on a large knee x-ray dataset shows that our method is able to efficiently detect osteoarthritis, achieving more than 97% detection accuracy. [ABSTRACT FROM AUTHOR]

Launaea spinosa is used as an anti-inflammatory agent traditionally. This study was conducted to evaluate anti-inflammatory and anti-angiogenic activities of methanol extract of Launaea spinosa. Extraction was performed by maceration and the resultant green coloured extract was labelled as Ls.Me. Solubility analysis showed that Ls.Me was miscible with distilled water, normal saline, ethanol and methanol. Metal analysis following acid digestion method exhibited the presence of copper, magnesium, manganese, iron, zinc and calcium. Phytochemical analysis confirmed the presence of different classes of secondary metabolites in Ls.Me. HPLC analysis showed the presence of quercetin, gallic acid, caffeic acid, benzoic acid and sinapic acid in Ls.Me. Data of in vitro antioxidant assays showed moderate antioxidant potential of Ls.Me which was also confirmed by data of in vivo enzymes (SOD, CAT, and TSP) assays. Antimicrobial assays data showed that Ls.Me was active against S.aureus and S.epidermidis (bacterial) as well as C.albicans and A.niger (fungal) strains. Data of acute physio-pathological studies showed no abnormalities in Albino rats up to the dose of 2000 mg/kg of Ls.Me. Acute and chronic inflammatory models were used to evaluate anti-inflammatory effects of Ls.Me. Data of acute studies showed that Ls.Me has the potential to arrest inflammation produced by different mediators in a dose-dependent manner. 200 mg/kg of Ls.Me was found to produce significantly (p < 0.05) better anti-inflammatory effects than 100 mg/kg of Ls.Me. Ls.Me also significantly (p < 0.05) inhibited ear edema induced by xylene. Ls.Me showed profound anti-inflammatory responses in paw edema induced by formalin and also inhibited granuloma development in cotton pellet-induced granuloma model. Histopathological and biochemical investigations showed marked reduction in the number of inflammatory cells. TNF-α and IL-6 ELSIA kits were used to study effects of Ls.Me treatment on serum levels of TNF-α and IL-6. Data obtained showed significant (p < 0.05) reduction in TNF-α and IL-6 levels in serum of animals treated with Ls.Me. Data of in vivo angiogenesis assay showed that 200 µg/ml of Ls.Me significantly halted vasculature development indicating its potent anti-angiogenic potential. On the basis of findings of the current study, it is concluded that multiple phytochemicals present in Ls.Me act synergistically to produce anti-inflammatory and anti-angiogenic effects. Further studies are required to standardize the plant extract and explore its safety profile. [ABSTRACT FROM AUTHOR]

In this paper we consider a single-cell massive multiple-input-multiple-output scenario, where the number of base station (BS) antennas is larger than the number of single antenna user terminals (UTs). We study and investigate common impairment named as channel aging caused by the relative movement between BS antenna and UTs. To acquire channel state information we apply minimum-mean-square-error detector. After that we study some commonly used channel predictors. Then we apply Wiener predictor and ARMA predictor to mitigate the effects of channel aging. We provide signal-to-interference-plus-noise ratios for each channel predictor and demonstrate their overall performance. We apply matched filtering for precoding. We perform thorough analysis with both predictors and observe that Wiener predictor performs better than ARMA predictor in all aspects such as achievable rates, cumulative distribution function and with higher Doppler spreads. The calculated results are deterministic and simulations show that they are even more accurate for system dimensions practically. [ABSTRACT FROM AUTHOR]

Anthracyclines used in the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase II (topo II) isoforms, topo II α and topo IIβ. In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determined expression of topo IIα and topo IIβ by RT-PCR and its relationship to immunophenotype (IP) and outcomes. Treatment outcomes were analyzed by logistic or Cox regression. In 211 patients, available for analysis, topo IIα expression was significantly lower than topo IIβ (P < 0.0001). In contrast to topo IIα, topo IIβ was significantly associated with blast percentage in marrow or blood (P = 0.0001), CD7 (P = 0.01), CD14 (P < 0.0001) and CD54 (P < 0.0001). Event free survival was worse for CD56-negative compared to CD56-high (HR = 1.9, 95% CI [1.0–3.5], p = 0.04), and overall survival was worse for CD-15 low as compared to CD15-high (HR = 2.2, 95% CI [1.1–4.2], p = 0.02). Ingenuity pathway analysis indicated topo IIβ and immunophenotype markers in a network associated with cell-to-cell signaling, hematological system development/function and inflammatory response. Topo IIβ expression reflects disease biology of highly proliferative disease and distinct IP but does not appear to be an independent variable influencing outcome in adult AML patients treated with anthracycline-based therapy. [ABSTRACT FROM AUTHOR]

Non-orthogonal multiple access (NOMA) scheme is emerging as a favourable multiple access scheme for future 5G networks. Compared to orthogonal multiple access techniques, NOMA provides spectral efficiency, user fairness, better connectivity, enhanced data rate and reduced latency. Thus, NOMA can be a suitable multiple access technique for 5G networks. On the other hand, in wireless networks, cooperation is a well-recognized proven technique for performance enhancement. Cooperative networks offer multiple desirable advantages, including high performance, reliability and greater coverage area. It is believed that in future 5G systems, many existing wireless technologies will be combined with new technologies. Power domain-NOMA (PD-NOMA) has features that can provide opportunities of improved performance and better spectral utilization for downlink cooperative networks. Recently, research works of incorporating PD-NOMA in cooperative networks have gained attention of researchers around the globe. This article surveys the recent research trends in PD-NOMA based cooperative network by reviewing related recent research on performance analysis of cooperative PD-NOMA systems, resources allocation, and impact of relay selection. Additionally, this review article discusses the performance of cooperative PD-NOMA networks when they are integrated with other 5G technologies including cognitive radio, full duplex radio and wireless energy harvesting. Furthermore, some unaddressed issues are highlighted for future research in this area. [ABSTRACT FROM AUTHOR]

The prevalence of insect resistance against Bt toxins has led to the idea of enhancing demethylation from cell wall pectin by pectin methylesterase enzyme for overproduction of methanol which is toxic to insects pests. The AtPME and AnPME fragments ligated into pCAMBIA1301 vector were confirmed through restriction digestion with EcoR1 and BamH1. Excision of 3363 bp fragment from 11,850 bp vector confirmed the ligation of both fragments into pCAMBIA1301 vector. Transformation of pectin methylesterase-producing genes, i.e., AtPME and AnPME from Arabidopsis thaliana and Aspergillus niger cloned in plant expression vector pCAMBIA1301 under 35S promoter into cotton variety CEMB-33 harboring two Bt genes Cry1Ac and Cry2A, respectively, was done by using shoot apex-cut Agrobacterium-mediated transformation method. The plantlets were screened on MS medium supplemented with hygromycin on initial basis. Amplification of 412 and 543 bp, respectively, through gene-specific primer has been obtained which confirmed the successful introduction of pCAMBIA AtPME and AnPME genes into cotton variety CEMB 33. Relative expression of AtPME and AnPME genes through real-time PCR determined the expression level of both gene ranges between 3- and 3.5-fold in different transgenic cotton lines along with quantity of methanol ranging from 0.8 to 0.9% of maximum while 0.5% to 0.6% of minimum but no expression was obtained in negative non-transgenic control cotton plant with least quantity of methanol, i.e., 0.1%. Almost 100% mortality was observed in insect bioassay for Helicoverpa armigera on detached leaves bioassay and 63% for Pink Bollworm (Pectinophora gossypiella) on growing transgenic cotton bolls as compared to positive control transgenic cotton with double Bt genes where mortality was found to be 82% for H. armigera and 50% for P. gossypiella while 0% in negative control non-transgenic plants. [ABSTRACT FROM AUTHOR]

An amplify-and-forward-based relay network is considered in which an energy-constrained relay is capable of harvesting energy from radio frequency (RF) signal. The source transmits the RF signal that contains both energy and information. The relay first scavenges the RF energy using the time switching (TS) or power-splitting (PS) protocols and then utilizes this energy to forward the signal to the destination. In this paper, new analytical framework has been presented for the outage and ergodic throughputs of the TS and PS protocols considering the Nakagami-m fading channels. Specifically, an exact closed-form expression for the outage throughput has been derived assuming an integer fading parameter. Furthermore, as the exact closed-form expressions for the outage throughput (for arbitrary fading parameters) and ergodic throughput (for both integer and arbitrary fading parameters) are mathematically intractable, new closed-form approximations and bounds have been derived. Finally all the derived expressions have been validated by the Monte Carlo simulations. [ABSTRACT FROM AUTHOR]