Enhanced anticancer efficacy of TRAIL-conjugated and odanacatib-loaded PLGA nanoparticles in TRAIL resistant cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates unique characteristics in anticancer therapies as it selectively induces apoptosis in cancer cells. However, most cancer cells are TRAIL-resistant. Odanacatib (ODN), a cathepsin K inhibitor, is considered a novel sensitizer for cancer treatment. Combination therapy between TRAIL and sensitizers is considered a potent platform that improves TRAIL-based anticancer therapies beyond TRAIL monotherapy. Herein, we developed ODN loaded poly(lactic-co-glycolic) nanoparticles conjugated to GST-TRAIL (TRAIL-ODN-PLGA-NPs) to target and treat TRAIL-resistant cancer. TRAIL-ODN-PLGA-NPs demonstrated a significant increase in cellular uptake via death receptors (DR5 and DR4) on surface of cancer cells. TRAIL-ODN-PLGA-NPs exposure destroyed more TRAIL-resistant cells compared to a single treatment with free drugs. The released ODN decreased the Raptor protein, thereby increasing damage to mitochondria by elevating reactive oxygen species (ROS) generation. Additionally, Bim protein stabilization improved TRAIL-resistant cell sensitization to TRAIL-induced apoptosis. The in vivo biodistribution study revealed that TRAIL-ODN-PLGA-NPs demonstrated high location and retention in tumor sites via the intravenous route. Furthermore, TRAIL-ODN-PLGA-NPs significantly inhibited xenograft tumor models of TRAIL-resistant Caki-1 and TRAIL-sensitive MDA-MB-231 cells.The inhibition was associated with apoptosis activation, Raptor protein stabilizing Bim protein downregulation, Bax accumulation, and mitochondrial ROS generation elevation. Additionally, TRAIL-ODN-PLGA-NPs affected the tumor microenvironment by increasing tumor necrosis factor-α and reducing interleukin-6. In conclusion, we evealed that our formulation demonstrated synergistic effects against TRAIL compared with the combination of free drug in vitro and in vivo models. Therefore, TRAIL-ODN-PLGA-NPs may be a novel candidate for TRAIL-induced apoptosis in cancer treatment.

Design, synthesis, and evaluation of a novel TRAIL-activated HDAC6 inhibitor for the treatment of pulmonary fibrosis.

Pulmonary fibrosis (PF) is a common, severe, chronic, and progressive pulmonary interstitial disease characterized by rapid disease progression and high mortality. Despite the Food and Drug Administration (FDA)'s approval of two antifibrotic drugs, nintedanib and pirfenidone, effectively halting the progression of pulmonary fibrosis remains challenging. Histone deacetylase (HDAC) inhibitors have indeed emerged as an important class of antitumour drugs. However, their application in the treatment of fibrotic diseases is still relatively limited. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has the potential to inhibit fibrotic processes by inducing fibroblast apoptosis. In this study, we designed and synthesized a series of histone deacetylase 6 (HDAC6) inhibitors that activate TRAIL, among which compound 7e exhibited potent inhibitory activity against HDAC6, with an IC50 of 42.90 ± 4.96 nM and superior antiproliferative effects on fibroblasts. Therefore, we further investigated its anti-pulmonary fibrosis effect in mouse models of both idiopathic pulmonary fibrosis (IPF) and silicosis. Our results suggest that compound 7e is a promising candidate for the treatment of pulmonary fibrosis.

Can volumetric magnetic resonance imaging evaluations be helpful in the follow-up of cognitive functions in cognitively normal Parkinson's disease patients?

Background/aim: In this study, besides the evaluation of gray and white matter changes in cognitively normal Parkinson's disease (PD-CN) patients with volumetric magnetic resonance imaging (MRI) parameters, it was tried to show that some neuropsychological tests may be impaired in PD-CN patients. Materials and methods: Twenty-six PD-CN patients and 26 healthy elderly (HC) participants were included in the current study. Global cognitive status was assessed using the mini-mental state examination (MMSE), and the Montreal cognitive assessment scale (MoCA). Attention and executive functions were evaluated using the Wechsler memory scale-revised (WMS-R) digit span test and trail making test (TMT) part A and part B, the Stroop test, semantic and phonemic fluency tests, and clock drawing test. Magnetic resonance imaging (MRI) was acquired according to the Alzheimer's disease neuroimaging initiative (ADNI) protocol. Results: There were no significant differences among groups regarding age, sex, handedness, and years of education. In the comparison of the PD-CN group and the HC group, there was a statistical decrease in the total animal scores, lexical fluency, TMT part A and TMT part B scores in the PD-CN group. Subcortical gray matter volumes (GMV) were significantly lower in PD-CN patients. The PD-CN group had a significantly reduced total volume of right putamen and left angular gyrus compared to that in the HC group. We observed that putamen and angular gyrus volumes were lower in PD-CN patients. On the other hand, TMT part B may be a useful pretest in detecting the conversion of mild cognitive impairment in PD. Conclusion: Significant MRI volumetric measurements and neuropsychological test batteries can be helpful in the clinical follow-up in PD-CN patients.

Attention and processing speed tests: Normative data for Spanish-speaking adults in the United States.

BACKGROUND: Hispanics/Latinos are the largest racial/ethnic group among underrepresented populations in the U.S. and multiple sociodemographic, cultural, and linguistic factors have been found to impact their performances on cognitive testing. Despite this, few normative data are available for the heterogeneous Spanish-speaking population in the U.S. OBJECTIVE: To generate normative data on the Trail-Making Test (TMT), Bells Test, Symbol-Digit Modalities Test (SDMT), and the Brief Test of Attention (BTA) for Spanish speakers residing in the U.S. METHODS: The sample included 245 Spanish-speaking individuals aged 18- 80 from eight states across the U.S. (California, Connecticut, Florida, Indiana, New Jersey, Oregon, Virginia, and Wisconsin). Participants were administered attention and processing speed measures as part of a comprehensive neuropsychological battery. We used a Bayesian regression approach to estimate normative data, including covariates found to be important for predicting performances on measures of attention and processing speed. RESULTS: Sociodemographic factors including education, time in the U.S., acculturation, age, and/or sex had differential effects on the TMT-A, TMT-B, SDMT, and the BTA whereas the Bells Test was not influenced by any of these sociodemographic factors. CONCLUSION: Our findings indicate that while sex, age, and educational attainment are important factors to consider, language and acculturation can also influence attention and processing speed performances among Spanish speakers in the U.S.

Walk this way: modeling foraging ant dynamics in multiple food source environments.

Foraging for resources is an essential process for the daily life of an ant colony. What makes this process so fascinating is the self-organization of ants into trails using chemical pheromone in the absence of direct communication. Here we present a stochastic lattice model that captures essential features of foraging ant dynamics inspired by recent agent-based models while forgoing more detailed interactions that may not be essential to trail formation. Nevertheless, our model's results coincide with those presented in more sophisticated theoretical models and experiments. Furthermore, it captures the phenomenon of multiple trail formation in environments with multiple food sources. This latter phenomenon is not described well by other more detailed models. We complement the stochastic lattice model by describing a macroscopic PDE which captures the basic structure of lattice model. The PDE provides a continuum framework for the first-principle interactions described in the stochastic lattice model and is amenable to analysis. Linear stability analysis of this PDE facilitates a computational study of the impact various parameters impart on trail formation. We also highlight universal features of the modeling framework that may allow this simple formation to be used to study complex systems beyond ants.

TRAIL C1595T Variant Critically Alters the Level of sTRAIL in Terms of Histopathological Parameters in Colorectal Cancer.

TRAIL, a member of the TNF family, is expressed in tumor and tumor surrounding tissue in many solid organ cancers. While the induction of tumor-specific apoptosis in correlation with cytokine stimulation may cause anti-tumoral effects, the pro-tumorigenic effects of its expression by tumor surrounding tissue members have been reported in the literature. In our study, it was aimed to evaluate the effect of the gene variant of TRAIL on soluble levels in patients with colorectal cancer (CRC) on the molecular pathological axis. TRAIL C1595 gene variant PCR-RFLP and sTRAIL levels were determined by ELISA in age and sex adjusted CRC and control groups. It was determined that CT carriage was high in patients without perineural invasion and sTRAIL levels were approximately 2.72 times lower than CC in patients with CT in this group (p < 0.05). Similarly, sTRAIL level was found to be high in patients with CC genotype in CRC without lymph node metastas. It was determined that CT carriage was high in patients without perineural invasion and sTRAIL levels were approximately 2.49 times lower than CC in patients with CT in this group.is (p < 0.05). We think that TRAIL C1595T in CRC can change sTRAIL levels in the clinicopathological axis in advanced stages such as metastasis and invasion, but both are not independent risk factors.

Effectiveness of Technological Interventions for Older Adults With Parkinson Disease: Systematic Review.

BACKGROUND: Among the older population, Parkinson disease (PD) stands out as a leading contributor to disability. Clinically, the foremost objectives in managing PD involve proactively delaying and preventing disability. Understanding the pivotal role of gait and balance in daily functionality holds substantial clinical significance, signaling imminent disability and prompting a reevaluation of management approaches. A key priority lies in identifying novel and effective interventions for symptoms that substantially contribute to disability. OBJECTIVE: This paper presents a systematic review that critically examines the existing body of literature on the use of technology in the rehabilitation of older patients with PD. By synthesizing current evidence, we aim to provide insights into the state of the field, identify gaps in knowledge, and offer recommendations for future research and clinical practice. METHODS: A systematic review of the literature was conducted in September 2023 analyzing manuscripts and papers of the last 5 years from the PubMed, Scopus, Embase, Web of Science, and CINAHL databases following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 14 papers were included. The inclusion criteria are as follows: (1) randomized controlled trial, (2) PD in people aged 65 years and older, and (3) use of technology in the rehabilitation training in the older population. RESULTS: A large portion of effective interventions relies on the incorporation of technology, particularly through virtual reality exergames. This technology appears to have effects not only on the cognitive aspect but also on the physical domain. The analysis of the results clearly indicates that, in terms of gait and balance performance, the technological intervention outperforms the traditional approach, irrespective of the specific technology employed. CONCLUSIONS: This systematic review seeks to shed light on the evolving landscape of technology-assisted rehabilitation for older individuals with PD. As we delve into the available evidence, we will assess the extent to which technology can serve as a valuable adjunct to conventional therapy, offering new avenues for optimized care and improved outcomes in this growing patient demographic. As we sift through the existing evidence, our goal is to evaluate the potential of technology as a valuable supplement to traditional therapy, presenting fresh opportunities for enhanced care and better outcomes in this expanding patient demographic.

Assessment of MeMed BV assays for differentiating between bacterial and viral respiratory infections.

INTRODUCTION: Distinguishing bacterial from viral infections remains a challenge due to clinically indistinguishable presentations. Non-infectious conditions such as malignancy, pulmonary emboli and rheumatological conditions may also present with fever. Consequently, patients are often over-treated with antimicrobial agents or may not receive adequate therapy. AREAS COVERED: This article provides a comprehensive review of a novel protein host-signature assay, the MeMed BV assay, that distinguishes bacterial from viral infections. The focus is on the use of the test in respiratory tract infections including assay performance characteristics, clinical profiles and data on cost-effectiveness. The changing landscape from the use of single inflammatory biomarkers, such as C-reactive protein, to alternative and diverse host signature biomarkers, is also discussed. EXPERT OPINION: The MeMed BV assay is one of several novel host biomarkers that provide rapid results and demonstrate enhanced performance compared to single test biomarkers. This assay has been validated by a large number of carefully controlled clinical trials that demonstrate improved performance characteristics for distinguishing bacterial infections or combined bacterial/viral infections from viral or noninfectious causes of fever compared to C-reactive protein and procalcitonin. However, these trials may over-state assay performance as samples with equivocal band results are often not included in the statistical analysis. More real-world studies addressing clinical implementation of the MeMed BV assay or other biomarkers into ambulatory settings are needed.

Targeting Death Receptor 5 (DR5) for imaging and treatment of primary bone and soft tissue tumors: an update of the literature.

Background: Death Receptor 5 (DR5) is expressed on the surface of primary bone and soft tissue sarcoma cells, and its activation induces cell death primarily through apoptosis. The combination of DR5 agonists and commonly used chemotherapeutic agents, such as doxorubicin, can promote cell death. Currently, clinical trials are investigating the effectiveness of DR5 activation using new biological agents, such as bi-specific or tetravalent antibodies, in improving the survival of patients with relapsed or refractory cancers. Furthermore, investigations continue into the use of novel combination therapies to enhance DR5 response, for example, with inhibitor of apoptosis protein (IAP) antagonist agents [such as the second mitochondria-derived activator of caspase (SMAC) mimetics] and with immune checkpoint inhibitor anti-programmed death-ligand 1 (anti-PD-L1) or anti-programmed cell death-1 (anti-PD-1) antibodies. Other therapies include nanoparticle-mediated delivery of TRAIL plasmid DNA or TRAIL mRNA and stem cells as a vehicle for the targeted delivery of anti-cancer agents, such as TRAIL, to the tumor. Methods: scoping review of the literature from November 2017 to March 2024, utilizing PubMed and Google Scholar. Results: New agents under investigation include nanoTRAIL, anti-Kv10.1, multimeric IgM, and humanized tetravalent antibodies. Developments have been made to test novel agents, and imaging has been used to detect DR5 in preclinical models and patients. The models include 3D spheroids, genetically modified mouse models, a novel jaw osteosarcoma model, and patient-derived xenograft (PDX) animal models. There are currently two ongoing clinical trials focusing on the activation of DR5, namely, IGM-8444 and INBRX-109, which have progressed to phase 2. Further modifications of TRAIL delivery with fusion to single-chain variable fragments (scFv-TRAIL), directed against tumor-associated antigens (TAAs), and in the use of stem cells focus on targeted TRAIL delivery to cancer cells using bi-functional strategies. Conclusion: In vitro, in vivo, and clinical trials, as well as advances in imaging and theranostics, indicate that targeting DR5 remains a valid strategy in the treatment of some relapsed and refractory cancers.

Essential updates 2022/2023: A review of current topics in robotic hepatectomy.

The liver requires careful handling intra-operatively owing to its vital functions and complexity. Traditional open hepatectomy, while standard, is invasive and requires long recovery periods. Laparoscopic hepatectomy is a less invasive option, with its own challenges. The rise of robotic surgery, such as the da Vinci® system, improves precision and control, addressing the limitations of conventional methods, but brings new concerns, such as costs and training. This review focuses on the latest advancements in robotic hepatectomy from 2022/23 articles, delving into topics like "robotic surgery in liver transplantation," "robotic hepatectomy for hilar cholangiocarcinoma," "robotic vascular reconstruction following hepatectomy," "robotic repeat hepatectomy," and "prospective trials in robotic hepatectomy." To retrieve articles, a focused literature search was conducted using PubMed for articles from 2022/23 with a 5-year filter, excluding reviews. Initially, abstracts were screened, and relevant articles on robotic surgery were examined in full for inclusion in this review. Although all the above items are cutting-edge, and many of the references are necessarily at the level of case reports, recent articles are still accompanied by surgical videos, which are useful to readers, especially surgeons who are considering imitating the procedures. In summary, we examined the recent advancements in robotic liver resection. The inclusion of videos that present new techniques aids in knowledge transfer. We anticipate the continued growth of this field of research.

Microglia either promote or restrain TRAIL-mediated excitotoxicity caused by Aß1-42 oligomers.

BACKGROUND: Alzheimer's disease (AD) features progressive neurodegeneration and microglial activation that results in dementia and cognitive decline. The release of soluble amyloid (Aß) oligomers into the extracellular space is an early feature of AD pathology. This can promote excitotoxicity and microglial activation. Microglia can adopt several activation states with various functional outcomes. Protective microglial activation states have been identified in response to Aß plaque pathology in vivo. However, the role of microglia and immune mediators in neurotoxicity induced by soluble Aß oligomers is unclear. Further, there remains a need to identify druggable molecular targets that promote protective microglial states to slow or prevent the progression of AD. METHODS: Hippocampal entorhinal brain slice culture (HEBSC) was employed to study mechanisms of Aß1-42 oligomer-induced neurotoxicity as well as the role of microglia. The roles of glutamate hyperexcitation and immune signaling in Aß-induced neurotoxicity were assessed using MK801 and neutralizing antibodies to the TNF-related apoptosis-inducing ligand (TRAIL) respectively. Microglial activation state was manipulated using Gi-hM4di designer receptor exclusively activated by designer drugs (DREADDs), microglial depletion with the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX3397, and microglial repopulation (PLX3397 withdrawal). Proteomic changes were assessed by LC-MS/MS in microglia isolated from control, repopulated, or Aß-treated HEBSCs. RESULTS: Neurotoxicity induced by soluble Aß1-42 oligomers involves glutamatergic hyperexcitation caused by the proinflammatory mediator and death receptor ligand TRAIL. Microglia were found to have the ability to both promote and restrain Aß-induced toxicity. Induction of microglial Gi-signaling with hM4di to prevent pro-inflammatory activation blunted Aß neurotoxicity, while microglial depletion with CSF1R antagonism worsened neurotoxicity caused by Aß as well as TRAIL. HEBSCs with repopulated microglia, however, showed a near complete resistance to Aß-induced neurotoxicity. Comparison of microglial proteomes revealed that repopulated microglia have a baseline anti-inflammatory and trophic phenotype with a predicted pathway activation that is nearly opposite that of Aß-exposed microglia. mTORC2 and IRF7 were identified as potential targets for intervention. CONCLUSION: Microglia are key mediators of both protection and neurodegeneration in response to Aß. Polarizing microglia toward a protective state could be used as a preventative strategy against Aß-induced neurotoxicity.

Unusual Developmental Vascular Anomalies: Insights From a Chest Physician's Perspective.

This case report discusses three developmental vascular anomalies (DVAs) observed in adults and highlights the challenges related to the diagnosis and management. Even though detected at early ages, diagnostic difficulties are observed in the adult age due to the scarcity and diverse clinical features. These cases illustrate the necessity of a multidisciplinary approach involving clinicians and radiologists for precise and prompt diagnosis in adults, where misdiagnosis and delays in intervention are frequent. The cases comprised a 17-year-old female with an absent right pulmonary artery and mitral stenosis, a 46-year-old female with chronic obstructive pulmonary disease (COPD), with an absent left pulmonary artery, and a 60-year-old female with bronchial asthma and tuberculosis exhibiting a rare DVA. This discussion highlights the importance of intensified clinical suspicion and thorough evaluation for the cases of unexplained respiratory symptoms and abnormal image findings in patients, which can further provide the medical community with valuable insights.

Spatial memory and learning: investigating the role of dynamic visual acuity.

Introduction: The vestibular system's contribution to spatial learning and memory abilities may be clarified using the virtual Morris Water Maze Task (vMWMT). This is important because of the connections between the vestibular system and the hippocampus area. However, there is ongoing debate over the role of the vestibular system in developing spatial abilities. This study aimed to evaluate the relationship between Dynamic Visual Acuity (DVA) across three planes and spatial abilities. Methods: This cross-sectional study was conducted with 50 healthy adults aged 18 to 55 with normal stress levels and mental health and no neurological, audiological, or vestibular complaints. The Trail-Making Test (TMT) Forms A and B for the assessment of executive functions, the DVA test battery for the evaluation of visual motor functions, and the Virtual Morris Water Maze Test (vMWMT) for the assessment of spatial learning and spatial memory were performed. All participants also underwent the Benton Face Recognition Test (BFRT) and Digit Symbol Substitution Tests (DSST) to assess their relation with spatial memory. Results: DVA values in horizontal (H-DVA), vertical (V-DVA), and sagittal (S-DVA) planes ranged from (-0.26) to 0.36 logMAR, (-0.20) to 0.36 logMAR, and (-0.28) to 0.33 logMAR, respectively. The latency of three planes of DVA was affected by vMWMT (Horizontal, Vertical, and Sagittal; Estimate: 22.733, 18.787, 13.341, respectively p < 0.001). Moreover, a moderately significant correlation was also found, with a value of 0.571 between the Virtual MWM test and BFRT and a value of 0.539 between the DSST (p < 0.001). Conclusion: Spatial abilities in healthy adults were significantly influenced by dynamic visual functions across horizontal, vertical, and sagittal planes. These findings are expected to trigger essential discussions about the mechanisms that connect the vestibular-visual system to the hippocampus. The original vMWMT protocol is likely to serve as a model for future studies utilizing this technology.

IL-8 and PI3K pathway influence the susceptibility of TRAIL-sensitive colorectal cancer cells to TRAIL-induced cell death.

BACKGROUND: Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an apoptosis inducer that exhibits an ideal therapeutic safety profile with less adverse effects than conventional chemotherapy. However, the occurrence of TRAIL resistance has been reported in various cancers including colorectal cancer (CRC). Substantial efforts have been channelled towards managing TRAIL resistance including identifying molecular targets. Interleukins (ILs) have been recently shown to play critical roles in modulating TRAIL sensitivity in cancer cells. METHODS AND RESULTS: This study investigated the roles of two ILs, IL-8 and IL⍺, in TRAIL resistance in CRC. TRAIL-resistant HT-29 and TRAIL-sensitive HCT 116 cells, were treated with human recombinant IL-8 and IL-1⍺. The results indicated that treatment with IL-8 (2.5 ng/mL) significantly protected TRAIL-sensitive HCT 116 cells from TRAIL-induced cell death (p < 0.05). However, IL-1⍺ did not play a role in modulating CRC cells' responses to TRAIL. Data from RT-qPCR and Western blotting revealed the molecular regulations of IL-8 on TRAIL decoy receptor genes (OPG) and autophagy-related genes (BECN1 and LC3B) expression. The activation of the phosphoinositide 3-kinase (PI3K) pathway was shown to counteract TRAIL-induced cell death. By inhibiting its activation with wortmannin, the protective role of IL-8 against TRAIL treatment was reversed, suggesting the involvement of the PI3K pathway. CONCLUSION: Collectively, findings from this study identified the role of IL-8 and PI3K in modulating CRC cells' sensitivity to TRAIL. Further validation of these two potential molecular targets is warranted to overcome TRAIL resistance in CRC.

Evaluating TRAIL and IP-10 alterations in vaccinated pregnant women after COVID-19 diagnosis and their correlation with neutralizing antibodies.

Background: This study evaluates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-γ-induced protein-10 (IP-10) in pregnant women with COVID-19 and their newborns, exploring the effects of antiviral treatments and vaccine-induced neutralizing antibody (Nab) inhibition on these key viral infection biomarkers. Methods: We studied 61 pregnant women with past COVID-19 and either three (n=56) or four (n=5) doses of vaccination, and 46 without COVID-19 but vaccinated. We analyzed them and their newborns' blood for TRAIL, IP-10, and Nab levels using enzyme-linked immunosorbent assays (ELISA), correlating these with other clinical factors. Results: Our study found lower TRAIL but higher IP-10 levels in maternal blood than neonatal cord blood, irrespective of past COVID-19 diagnosis. Cases diagnosed with COVID-19 < 4 weeks previously had higher maternal blood TRAIL levels (16.49 vs. 40.81 pg/mL, p=0.0064) and IP-10 (154.68 vs. 225.81 pg/mL, p=0.0170) than those never diagnosed. Antiviral medication lowered TRAIL and IP-10 in maternal blood without affecting Nab inhibition (TRAIL: 19.24 vs. 54.53 pg/mL, p=0.028; IP-10: 158.36 vs. 255.47 pg/mL, p=0.0089). TRAIL and IP-10 levels were similar with three or four vaccine doses, but four doses increased Nab inhibition (p=0.0363). Previously COVID-19 exposed pregnant women had higher Nab inhibition (p < 0.0001). No obvious correlation was found among TRAIL, IP-10, and Nab inhibition level. Conclusions: Our study suggests that lower maternal TRAIL and higher IP-10 levels compared to neonatal cord blood coupled with a rise in both markers following COVID-19 diagnosis that could be reduced by antivirals indicates a correlation to infection severity. Higher vaccine doses enhance Nab inhibition, irrespective of antiviral medication use and independent of TRAIL or IP-10 levels, highlighting the significance and safety of adequate vaccination and antiviral use post-diagnosis in pregnant women.

Examining the interplay of dust and defects: A comprehensive experimental analysis on the performance of photovoltaic modules.

The performance of photovoltaic (PV) modules is greatly impacted by dust accumulation and defects appearing in photovoltaic (PV) modules. Existing studies primarily focus on the effect of dust on general photovoltaic performance, neglecting the interactions with pre-existing defects such as snail trails. These defects are known to degrade the efficiency of PV modules. However, their interaction with environmental factors like dust accumulation has not been extensively analyzed. This research comprehensively analyzes the impact of dust accumulation on the performance of PV modules affected by snail trails. Using an experimental setup under outdoor conditions, the study incorporates thermal imaging, current-voltage characteristic curve tracing (IV curve tracing), electroluminescence (EL) imaging, and chemical analysis of the accumulated dust, to evaluate the electrical and thermal parameters affecting PV module performance. The study focuses on three types of modules, clean serves as a reference module (PV-R), normal unclean (PV-N), and snail trail-affected unclean PV module (PV-S). Compared to the PV-R module, the study meticulously quantifies the effect of accumulated dust on key performance indicators such as output power, V, and I. The PV-N module exhibits reductions of 17.7 % in current, 3.91 % in voltage, and 18.15 % in power output. The PV-S module experienced a decrease of 7.4 % in current, 7.55 % in voltage, and 14.87 % in power output under the dust deposition density of 6.984 g/m^2 having a mean particle size of 2.2279 µm. The dust deposition reduced the transmittance of glass, which indicates a potentially adverse impact on the PV module's efficiency. The findings highlighted in the current work provide a significant understanding of the detrimental impacts of dust accumulation on defected photo voltaic modules, highlighting the need for regular maintenance and cleaning to ensure optimal performance.

Advancements in monitoring: a comparison of traditional and application-based tools for measuring outdoor recreation.

Outdoor recreation has experienced a boom in recent years and continues to grow. While outdoor recreation provides wide-ranging benefits to human well-being, there are growing concerns about the sustainability of recreation with the increased pressures placed on ecological systems and visitor experiences. These concerns emphasize the need for managers to access accurate and timely recreation data at scales that match the growing extent of the recreation footprint. Here, we compare spatial and temporal patterns of winter and summer recreation using traditional (trail cameras, infrared counters, aerial surveys, participatory mapping) and application-based tools (Strava Metro, Strava Global Heatmap, Wikiloc) across the Columbia and Canadian Rocky Mountains of western Canada. We demonstrate how recreation use can be estimated using traditional and application-based tools, although their accuracy and utility varies across space, season and activity type. We found that trail cameras and infrared counters captured similar broad-scale patterns in count estimates of pedestrians and all recreation activities. Aerial surveys captured areas with low recreation intensity and participatory mapping captured coarser information on the intensity and extent of recreation across large spatial and temporal scales. Application-based data provided detailed spatiotemporal information on recreation use, but datasets were biased towards specific activities. Strava Metro data was more suited for capturing broad-scale spatial patterns in biking than pedestrian recreation. Application-based data should be supplemented with data from traditional tools to identify biases in data and fill in data gaps. We provide a comparison of each tool for measuring recreation use, highlight each tools' strengths and limitations and applications to address real-world monitoring and management scenarios. Our research contributes towards a better understanding of which tool, or combinations of tools, to use that can expand the rigor and scope of recreation research. These findings support decision-making to mitigate pressures on wildlife and their habitats while allowing for high-quality recreation experiences.

Nanoparticle-mediated gene delivery of TRAIL to resistant cancer cells: A review.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), also known as APO2L, has emerged as a highly potential anticancer agent because of its capacity to effectively trigger apoptosis in tumor cells by specifically binding to either of its death receptors (DR4 or DR5) while having no adverse effects on normal cells. Nevertheless, its practical use has been hindered by its inefficient pharmacokinetics characteristics, the challenges involved in its administration and delivery to targeted cells, and the resistance exhibited by most cancer cells towards TRAIL. Gene therapy, as a promising approach would be able to potentially circumvent TRAIL-based cancer therapy challenges mainly through localized TRAIL expression and generating a bystander impact. Among different strategies, using nanoparticles in TRAIL gene delivery allows for precise targeting, and overcoming TRAIL resistance by combination therapy. In this review, we go over potential mechanisms by which cancer cells achieve resistance to TRAIL and provide an overview of different carriers for delivering of the TRAIL gene to resistant cancer cells, focusing on different types of nanoparticles utilized in this context. We will also explore the challenges, and investigate future perspectives of this nanomedicine approach for cancer therapy.

Blockchain-enabled EHR access auditing: Enhancing healthcare data security.

In the realm of modern healthcare, Electronic Health Records EHR serve as invaluable assets, yet they also pose significant security challenges. The absence of EHR access auditing mechanisms, which includes the EHR audit trails, results in accountability gaps and magnifies security vulnerabilities. This situation effectively paves the way for unauthorized data alterations to occur without detection or consequences. Inadequate EHR compliance auditing procedures, particularly in verifying and validating access control policies, expose healthcare organizations to risks such as data breaches, and unauthorized data usage. These vulnerabilities result from unchecked unauthorized access activities. Additionally, the absence of EHR audit logs complicates investigations, weakens proactive security measures, and raises concerns to put healthcare institutions at risk. This study addresses the pressing need for robust EHR auditing systems designed to scrutinize access to EHR data, encompassing who accesses it, when, and for what purpose. Our research delves into the complex field of EHR auditing, which includes establishing an immutable audit trail to enhance data security through blockchain technology. We also integrate Purpose-Based Access Control (PBAC) alongside smart contracts to strengthen compliance auditing by validating access legitimacy and reducing unauthorized entries. Our contributions encompass the creation of audit trail of EHR access, compliance auditing via PBAC policy verification, the generation of audit logs, and the derivation of data-driven insights, fortifying EHR access security.

Effects of Foot-Strike Pattern on Neuromuscular Function During a Prolonged Graded Run.

PURPOSE: To study whether, during typical-level running, non-rear-foot strikers (non-RFS) or rear-foot strikers (RFS) presented a similar or different extent of neuromuscular fatigue after a prolonged graded run. METHODS: Sixteen experienced male trail runners (8 non-RFS and 8 RFS) performed a 2.5-hour treadmill graded running exercise. Before and after exercise, neuromuscular tests were performed to assess neuromuscular fatigue of the plantar flexors. Biomechanical gait parameters were acquired with an instrumented treadmill, and electromyographic activity of the lower-limb muscles was collected as an index of muscle activation. RESULTS: There were no significant time × foot strike interactions for neuromuscular (all P ≥ .742), muscle activation (all P ≥ .157), or biomechanical (all P ≥ .096) variables. CONCLUSIONS: A dominant level running foot-strike pattern did not directly affect the extent of neuromuscular fatigue during a prolonged graded run. This suggests that no ideal running foot-strike pattern exists to minimize neuromuscular fatigue during prolonged-duration races wherein cumulative uphill and downhill segments are high, such as in trail running.