Evaluation of resistance patterns and bioremoval efficiency of hydrocarbons and heavy metals by the mycobiome of petroleum refining wastewater in Jazan with assessment of molecular typing and cytotoxicity of Scedosporium apiospermum JAZ-20.

Jazan Industrial Economic City (JIEC) is located on the Red Sea coast in the province of Jazan, southwest of Saudi Arabia anchors diverse heavy and secondary industries in the energy, water desalination, petroleum, aluminum, copper, refineries, pharmaceuticals and food manufacturing fields. These various industries generate a large quantity of industrial wastewaters containing various toxicants. The present work represents ecologically beneficial alternatives for the advancement of environmental biotechnology, which could help mitigate the adverse impacts of environmental pollution resulting from petroleum refining effluents. The mycobiome (32 fungal strains) isolated from the industrial wastewater of the refinery sector in Jazan were belonged to five fungal genera including Fusarium, Verticillium, Purpureocillium, Clavispora and Scedosporium with a distribution percentage of 31.25, 21.88, 15.63, 12.50 and 18.75 %, respectively. These isolates showed multimetals tolerance and bioremoval efficiency against a large number of heavy metals (Fe2+, Ni2+, Cr6+, Zn2+, As3+, Cu2+, Cd2+, Pb2+, Ag+ and Hg2+) along with potent bioremediation activity toward crude oil and the polycyclic aromatic hydrocarbons. Interestingly, the mycobiome resistance patterns obtained against different classes of fungal antibiotics including azole (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole and ketoconazole), echinocandin (anidulafungin, caspofungin and micafungin) and polyene (amphotericin B) drugs proved the prevalence of antibiotic resistance among the mycobiome of refinery industry in Saudi Arabia is relatively low. The fungal isolate under isolation code JAZ-20 showed the highest bioremoval efficiency against heavy metals (90.8-100.0 %), crude oil (89.50 %), naphthalene (96.7 %), phenanthrene (92.52 %), fluoranthene (100.0 %), anthracene (90.34 %), pyrene (85.60 %) and chrysene (83.4 %). It showed the highest bioremoval capacity ranging from 85.72 % to 100.0 % against numerous pollutants found in a wide array of industrial effluents, including diclofenac, ibuprofen, carbamazepine, acetaminophen, sulfamethoxazole, bisphenol, bleomycin, vincristine, dicofol, methyl parathion, atrazine, diuron, dieldrin, chlorpyrifos, profenofos and phenanthrene. The isolate JAZ-20 was chosen for molecular typing, cytotoxicity assessment, analysis of volatile compounds and optimization investigations. Based on phenotypic, biochemical and phylogenetic analysis, strain JAZ-20 identified as Scedosporium apiospermum JAZ-20. This strain is newly discovered in industrial effluents in Saudi Arabia. Fungal strain JAZ-20 consistently produced various types of saturated and unsaturated fatty acids. the main fatty acids were C14:0 (1.95 %), iso-C14:0 (2.98 %), anteiso-C14:0 (2.13 %), iso-C15:0 (9.16 %), anteiso-C15:0 (11.75 %), C15:0 (7.42 %), C15:1 (2.37 %), anteiso-C16:0 (3.4 %), C16:0 (10.3 %), iso-C16:0 (9.5 %), C17:1 (1.36 %), anteiso-C17:1 (8.64 %), iso-C18:0 (11.0 %), C18:0 (3.63 %), anteiso-C19:0 (3.78 %), anteiso-C20:0 (2.0 %), iso-C21:0 (2.44 %), C23:0 (1.15 %), and C24:0 (2.17 %). These fatty acids serve as natural and eco-friendly antifungal agents, promoting fungal resistance and inhibiting the production of mycotoxins in the environment. Despite being an environmental isolate, its cytotoxicity was assessed against both normal and cancerous human cell lines. The IC50 values of JAZ-20 extract were 8.92, 10.41, 20.0, 16.5, and 40.0 µg/mL against WI38, MRC5, MCF10A, HEK293 and HDFs normal cells and 43.26, 33.75, and 40.0 µg/mL against liver (HepG2), breast (A549) and cervix (HeLa) cancers, respectively. Based on gas chromatography-mass spectrometry (GC-MS), analysis the extract of S. apiospermum JAZ-20 showed 47 known volatile compounds (VOCs) for varied and significant biological activities. Enhancing the bioremoval efficiency of heavy metals from actual refining wastewater involves optimizing process parameters. The parameters optimized were the contact time, the fungal biomass dosage, pH, temperature and agitation rate.

A Novel Technique for Improving Cyclic Behavior of Steel Connections Equipped with Smart Memory Alloys.

Residual drifts are an important measure of post-earthquake functionality in bridges and buildings, and can determine whether the structure remains fit for its intended purpose or not. This study aims at investigating numerically, through finite element (FE) analysis in ABAQUS, the cyclic response of exterior steel I beam-hollow column connection using welded shape memory alloys (SMA) bolts and seat angles. This is followed by validating the numerical model using an accredited experimental data available in the literature through different techniques, (1) SMA bolts, (2) SMA angles, (3) SMA bolts and angles. The parameters investigated included: SMA type, SMA angle thickness, SMA bolt diameter, SMA angle stiffener and SMA angle direction. The cyclic performance of the steel connection was enhanced further by varying the bolt diameter, plate thickness, angle type and direction. The results revealed that the connections equipped with a combination of SMA plates and SMA angles reduced the residual drift by up to 94%, and doubled the self-centering capability compared to conventional steel connections. Moreover, the parametric analysis showed that Fe-based SMA members could be a good alternative to NiTi based SMA members for improving the self-centering capability and reducing the residual drifts of conventional steel connections.

Management of extensive portal vein thrombosis via thrombolysis and thrombectomy without underlying liver disease: A case report.

Portal vein thrombosis (PVT) is a rare condition, particularly in non-cirrhotic patients. Anticoagulation remains the mainstay of the treatment. Extensive PVT can lead to variceal bleeding, ascites, bowel ischemia, and hypersplenism. The role of thrombolysis and thrombectomy in these patients remains unclear. However, there is evidence that local thrombolysis and thrombectomy should be considered in those who remain symptomatic on anticoagulation and are at risk of complications with acute PVT.

Navigating Human Epidermal Growth Factor Receptor 2 (HER2) Conversion: Insights From Recurrent Breast Cancer.

Recurrent breast cancer presents clinical challenges due to its dynamic nature. Turning human epidermal growth factor receptor 2 (HER2) status from negative to positive upon recurrence is a rare but clinically significant phenomenon that can impact treatment decisions. We present the case of a 63-year-old female initially diagnosed with stage IIIA breast cancer, characterized as HER2-negative. However, upon recurrence eight years later, the patient exhibited HER2 conversion, indicating a positive status. Subsequent treatment adjustments were made based on this new HER2-positive status, leading to complete remission. HER2 conversion underscores the dynamic nature of tumor biology in recurrent breast cancer. This case highlights the importance of re-biopsy for accurate biomarker assessment and the necessity of personalized treatment strategies based on current molecular profiles. Understanding and recognizing HER2 conversion in recurrent breast cancer is crucial for optimizing patient outcomes and guiding clinical management decisions. Further research is warranted to elucidate the frequency and clinical implications of HER2 conversion in recurrent breast cancer.

Prevalence and risk factors of osteopenia and osteoporosis among postmenopausal women: A cross-sectional study from Jordan.

OBJECTIVES: Our aim was to predict the prevalence of osteopenia and osteoporosis and their associated risk factors among postmenopausal women from Jordan. METHODOLOGY: In this cross-sectional study, a total of 368 postmenopausal women were recruited from King Abdullah University Hospital (KAUH) in the North of Jordan between September 2022 and April 2023. Bone mineral density (BMD) was measured using a dual-energy X-ray absorptiometry scan. T-score was used for osteoporosis diagnosis in accordance with the International Society for Clinical Densitometry (ISCD) guidelines. Data about sociodemographic and lifestyle variables were collected using face-to-face interviews. Medical records were used to retrieve participants' BMD information. Predictors of osteoporosis were identified using logistic regression. RESULTS: Prevalence of osteoporosis was 40.5%, while 44.6% of participants were diagnosed with osteopenia. The lumbar spine had the highest frequency of osteoporosis (30.4%), while the left femoral neck had the highest prevalence of osteopenia (46.3%). Postmenopausal women's age (p-value = .024), and history of chronic diseases (p-value = .038) were significant factors associated with increased osteoporosis risk. CONCLUSIONS: Postmenopausal women from Jordan had high prevalence of osteoporosis and osteopenia. It is therefore necessary to target risk factors leading to osteoporosis and to improve patients' lifestyles through patient education. Healthcare systems should consider early screening approaches for osteoporosis at the age of menopause and thereafter. Supplements of calcium and vitamin D may be routinely considered for this age group depending on their serum levels.

The impact of the COVID-19 pandemic on the performance of the Rapid Access Lung Cancer Clinic.

BACKGROUND: The Rapid Access Lung Cancer Clinic (RALC) experienced fewer referrals during the COVID-19 pandemic in Ireland. AIMS: Our aim was to determine the impact of the pandemic on the key performance indicators (KPIs) of the Cork University Hospital (CUH) RALC, using a retrospective chart review of the referrals and attendances. METHODS: The medical charts of patients referred to CUH-RALC from 03/2019 to 02/2020 (period I), and from 03/2020 to 02/2021 (period II) were reviewed. Performance of the RALC was determined based on average wait time from referral to 1] acquisition of the first CT scan, 2] consultation, and 3] receiving a cancer diagnosis, and compared between periods I and II. RESULTS: Average monthly referrals (57.3 vs 42.1, p = 0.0078) and RALC reviews (24.3 vs 22, p = 0.0310) were lower in period II compared to period I. However, no difference was seen in the length of time from referral to review at RALC or time to receive cancer diagnosis. There were shorter wait times from referral to CT scan (11.2 vs. 8.7 days, p = 0.0011) and to surgery (109.0 vs 79.3 days, p = 0.0236) in period II. CONCLUSIONS: The COVID-19 pandemic had minimal impact on the performance of RALC at our institution. Fewer referrals to RALC in period II may relate to hesitancy in attending general practitioner (GP) and/or GPs raising the thresholds for referrals to RALC during the early lockdown period of the pandemic. A national evaluation will be required to fully determine the impact of this pandemic on lung cancer in Ireland.

Are maximum magnitudes of induced earthquakes controlled by pressure diffusion?

There is an ongoing discussion about how to forecast the maximum magnitudes of induced earthquakes based on operational parameters, subsurface conditions and physical process understanding. Although the occurrence of damage caused by induced earthquakes is rare, some cases have caused significant economic loss, injuries and even loss of life. We analysed a global compilation of earthquakes induced by hydraulic fracturing, geothermal reservoir stimulation, water disposal, gas storage and reservoir impoundment. Our analysis showed that maximum magnitudes scale with the characteristic length of pressure diffusion in the brittle Earth's crust. We observed an increase in the nucleation potential of larger-magnitude earthquakes with time and explained it by diffusion-controlled growth of the pressure-perturbed part of faults. Numerical and analytical fault size modelling supported our findings. Finally, we derived magnitude scaling laws to manage induced seismic hazard of upcoming energy projects prior to operation. This article is part of the theme issue 'Induced seismicity in coupled subsurface systems'.

Vaccinium myrtillus L. Leaf Waste as a Source of Biologically Potent Compounds: Optimization of Polyphenol Extractions, Chemical Profile, and Biological Properties of the Extracts.

The aims of the present research include (1) optimization of extraction from Vaccinium myrtillus leaf waste via investigation of plant material:medium ratio, extraction medium, and extraction period, employing extractions at room and high temperatures, or using ultrasound and microwaves (M, HAE, UAE, and MAE, respectively), (2) physicochemical characterization, and (3) investigation of extract biological potential. The statistical analysis revealed that optimal levels of parameters for the greatest polyphenolic yield were a proportion of 1:30 g/mL, ethyl alcohol 50% (v/v) during 2 min of microwave irradiation. By LC-MS analysis, 29 phenolic components were detected; HAE showed the highest richness of almost all determined polyphenols, while chlorogenic acid and quercetin 3-O-glucuronide were dominant. All extracts showed a high inhibition of Staphylococcus aureus growth. The effect of different parameters on extracts' antioxidant capacity depended on the used tests. The extracts also showed a stimulative influence on keratinocyte viability and anti-inflammatory activity (proven in cell-based ELISA and erythrocyte stabilization assays). The extraction procedure significantly affected the extraction yield (MAE ≥ maceration ≥ UAE ≥ HAE), whereas conductivity, density, surface tension, and viscosity varied in a narrow range. The presented research provides evidence on the optimal extraction conditions and technique, chemical composition, and antioxidant, antimicrobial, anti-inflammatory, and keratinocyte viability properties of bilberry extracts for potential applications in pharmacy and cosmetics.

Tannery effluent treatments with mangrove fungi, grass root biomass, and biochar.

Tannery effluents contain high amounts of polluting chemicals, such as salts and heavy metals released often to surface waters. New economic and eco-friendly purification methods are needed. Two adsorbing materials and five salt-tolerant fungal isolates from mangrove habitat were studied. Purification experiments were carried out using the pollutant adsorbents biochar and the biomass of vetiver grass (Chrysopogon zizanioides) roots and the fungi Cladosporium cladosporioides, Phomopsis glabrae, Aspergillus niger, Emericellopsis sp., and Scopulariopsis sp., which were isolated from mangrove sediment. They efficacy to reduce pollutants was studied in different combinations. Salinity, turbidity, total dissolved solids, total suspended solids, phenols, nitrogen, ammonia. Biological and chemical oxygen demand (BOD, COD) and several heavy metals were measured. The adsorbents were efficient reducing the pollutants to 15-50% of the original. The efficiency of the combination of biochar and roots was generally at the same level as the adsorbents alone. Some pollutants such as turbidity, COD and ammonium were reduced slightly more by the combination than the adsorbents alone. From all 14 treatments, Emericellopsis sp. with biochar and roots appeared to be the most efficient reducing pollutants to < 10-30%. BOD and COD were reduced to ca 5% of the original. The treatment was efficient in reducing also heavy metals (As, Cd, Cr, Mn Pb, Zn). The fungal species originating from the environment instead of the strains present in the tannery effluent reduced pollutants remarkably and the adsorbents improved the reduction efficiency. However, the method needs development for effluents with high pollutant concentrations to fulfil the environmental regulations.

Novel report on soil infection with Metarhizium rileyi against soil-dwelling life stages of insect pests.

Entomopathogenic fungi are the most effective control remedy against a wide range of medical and agricultural important pests. The present study aimed to isolate, identify, and assess the virulence of Metarhizium rileyi against Spodoptera litura and Spodoptera frugiperda pupae under soil conditions. The biotechnological methods were used to identify the isolate as M. rileyi. The fungal conidial pathogenicity (2.0 × 107, 2.0 × 108, 2.0 × 109, 2.0 × 1010, and 2.0 × 1011 conidia/mL-1) was tested against prepupae of S. litura and S. frugiperda at 3, 6, 9, and 12 days after treatments. Additionally, the artificial soil-conidial assay was performed on a nontarget species earthworm Eudrilus eugeniae, using M. rileyi conidia. The present results showed that the M. rileyi caused significant mortality rates in S. litura pupae (61-90%), and S. litura pupae were more susceptible than S. frugiperda pupae (46%-73%) at 12 day posttreatment. The LC50 and LC90 of M. rileyi against S. litura, were 3.4 × 1014-9.9 × 1017 conidia/mL-1 and 6.6 × 105-4.6 × 1014 conidia/mL-1 in S. frugiperda, respectively. The conidia of M. rileyi did not exhibit any sublethal effect on the adult stage of E. eugeniae, and Artemia salina following a 12-day treatment period. Moreover, in the histopathological evaluation no discernible harm was observed in the gut tissues of E. eugeniae, including the lumen and epithelial cells, as well as the muscles, setae, nucleus, mitochondria, and coelom. The present findings provide clear evidence that M. rileyi fungal conidia can be used as the foundation for the development of effective bio-insecticides to combat the pupae of S. litura and S. frugiperda agricultural pests.

Drug eluting protein and polysaccharides-based biofunctionalized fabric textiles- pioneering a new frontier in tissue engineering: An extensive review.

In the ever-evolving landscape of tissue engineering, medicated biotextiles have emerged as a game-changer. These remarkable textiles have garnered significant attention for their ability to craft tissue scaffolds that closely mimic the properties of natural tissues. This comprehensive review delves into the realm of medicated protein and polysaccharide-based biotextiles, exploring a diverse array of fabric materials. We unravel the intricate web of fabrication methods, ranging from weft/warp knitting to plain/stain weaving and braiding, each lending its unique touch to the world of biotextiles creation. Fibre production techniques, such as melt spinning, wet/gel spinning, and multicomponent spinning, are demystified to shed light on the magic behind these ground-breaking textiles. The biotextiles thus crafted exhibit exceptional physical and chemical properties that hold immense promise in the field of tissue engineering (TE). Our review underscores the myriad applications of drug-eluting protein and polysaccharide-based textiles, including TE, tissue repair, regeneration, and wound healing. Additionally, we delve into commercially available products that harness the potential of medicated biotextiles, paving the way for a brighter future in healthcare and regenerative medicine. Step into the world of innovation with medicated biotextiles-where science meets the art of healing.

4D Printing for Biomedical Applications.

4D (bio-)printing endows 3D printed (bio-)materials with multiple functionalities and dynamic properties. 4D printed materials have been recently used in biomedical engineering for the design and fabrication of biomedical devices, such as stents, occluders, microneedles, smart 3D-cell engineered microenvironments, drug delivery systems, wound closures, and implantable medical devices. However, the success of 4D printing relies on the rational design of 4D printed objects, the selection of smart materials, and the availability of appropriate types of external (multi-)stimuli. Here, this work first highlights the different types of smart materials, external stimuli, and design strategies used in 4D (bio-)printing. Then, it presents a critical review of the biomedical applications of 4D printing and discusses the future directions of biomedical research in this exciting area, including in vivo tissue regeneration studies, the implementation of multiple materials with reversible shape memory behaviors, the creation of fast shape-transformation responses, the ability to operate at the microscale, untethered activation and control, and the application of (machine learning-based) modeling approaches to predict the structure-property and design-shape transformation relationships of 4D (bio)printed constructs.

Preclinical development of novel PD-L1 tracers and first-in-human study of [68Ga]Ga-NOTA-RW102 in patients with lung cancers.

BACKGROUND: The programmed cell death protein-1 (PD-1)/programmed death receptor ligand 1 (PD-L1) axis critically facilitates cancer cells' immune evasion. Antibody therapeutics targeting the PD-1/PD-L1 axis have shown remarkable efficacy in various tumors. Immuno-positron emission tomography (ImmunoPET) imaging of PD-L1 expression may help reshape solid tumors' immunotherapy landscape. METHODS: By immunizing an alpaca with recombinant human PD-L1, three clones of the variable domain of the heavy chain of heavy-chain only antibody (VHH) were screened, and RW102 with high binding affinity was selected for further studies. ABDRW102, a VHH derivative, was further engineered by fusing RW102 with the albumin binder ABD035. Based on the two targeting vectors, four PD-L1-specific tracers ([68Ga]Ga-NOTA-RW102, [68Ga]Ga-NOTA-ABDRW102, [64Cu]Cu-NOTA-ABDRW102, and [89Zr]Zr-DFO-ABDRW102) with different circulation times were developed. The diagnostic efficacies were thoroughly evaluated in preclinical solid tumor models, followed by a first-in-human translational investigation of [68Ga]Ga-NOTA-RW102 in patients with non-small cell lung cancer (NSCLC). RESULTS: While RW102 has a high binding affinity to PD-L1 with an excellent KD value of 15.29 pM, ABDRW102 simultaneously binds to human PD-L1 and human serum albumin with an excellent KD value of 3.71 pM and 3.38 pM, respectively. Radiotracers derived from RW102 and ABDRW102 have different in vivo circulation times. In preclinical studies, [68Ga]Ga-NOTA-RW102 immunoPET imaging allowed same-day annotation of differential PD-L1 expression with specificity, while [64Cu]Cu-NOTA-ABDRW102 and [89Zr]Zr-DFO-ABDRW102 enabled longitudinal visualization of PD-L1. More importantly, a pilot clinical trial shows the safety and diagnostic value of [68Ga]Ga-NOTA-RW102 immunoPET imaging in patients with NSCLCs and its potential to predict immune-related adverse effects following PD-L1-targeted immunotherapies. CONCLUSIONS: We developed and validated a series of PD-L1-targeted tracers. Initial preclinical and clinical evidence indicates that immunoPET imaging with [68Ga]Ga-NOTA-RW102 holds promise in visualizing differential PD-L1 expression, selecting patients for PD-L1-targeted immunotherapies, and monitoring immune-related adverse effects in patients receiving PD-L1-targeted treatments. TRIAL REGISTRATION NUMBER: NCT06165874.

Comparative analysis of basal and etoposide-induced alterations in gene expression by DNA-PKcs kinase activity.

Background: Maintenance of the genome is essential for cell survival, and impairment of the DNA damage response is associated with multiple pathologies including cancer and neurological abnormalities. DNA-PKcs is a DNA repair protein and a core component of the classical nonhomologous end-joining pathway, but it also has roles in modulating gene expression and thus, the overall cellular response to DNA damage. Methods: Using cells producing either wild-type (WT) or kinase-inactive (KR) DNA-PKcs, we assessed global alterations in gene expression in the absence or presence of DNA damage. We evaluated differential gene expression in untreated cells and observed differences in genes associated with cellular adhesion, cell cycle regulation, and inflammation-related pathways. Following exposure to etoposide, we compared how KR versus WT cells responded transcriptionally to DNA damage. Results: Downregulated genes were mostly involved in protein, sugar, and nucleic acid biosynthesis pathways in both genotypes, but enriched biological pathways were divergent, again with KR cells manifesting a more robust inflammatory response compared to WT cells. To determine what major transcriptional regulators are controlling the differences in gene expression noted, we used pathway analysis and found that many master regulators of histone modifications, proinflammatory pathways, cell cycle regulation, Wnt/ß-catenin signaling, and cellular development and differentiation were impacted by DNA-PKcs status. Finally, we have used qPCR to validate selected genes among the differentially regulated pathways to validate RNA sequence data. Conclusion: Overall, our results indicate that DNA-PKcs, in a kinase-dependent fashion, decreases proinflammatory signaling following genotoxic insult. As multiple DNA-PK kinase inhibitors are in clinical trials as cancer therapeutics utilized in combination with DNA damaging agents, understanding the transcriptional response when DNA-PKcs cannot phosphorylate downstream targets will inform the overall patient response to combined treatment.

The Interaction Between Nutraceuticals and Gut Microbiota: a Novel Therapeutic Approach to Prevent and Treatment Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, leading to motor and non-motor symptoms. Emerging research has shed light on the role of gut microbiota in the pathogenesis and progression of PD. Nutraceuticals such as curcumin, berberine, phytoestrogens, polyphenols (e.g., resveratrol, EGCG, and fisetin), dietary fibers have been shown to influence gut microbiota composition and function, restoring microbial balance and enhancing the gut-brain axis. The mechanisms underlying these benefits involve microbial metabolite production, restoration of gut barrier integrity, and modulation of neuroinflammatory pathways. Additionally, probiotics and prebiotics have shown potential in promoting gut health, influencing the gut microbiome, and alleviating PD symptoms. They can enhance the gut's antioxidant capacity of the gut, reduce inflammation, and maintain immune homeostasis, contributing to a neuroprotective environment. This paper provides an overview of the current state of knowledge regarding the potential of nutraceuticals and gut microbiota modulation in the prevention and management of Parkinson's disease, emphasizing the need for further research and clinical trials to validate their effectiveness and safety. The findings suggest that a multifaceted approach involving nutraceuticals and gut microbiota may open new avenues for addressing the challenges of PD and improving the quality of life for affected individuals.

Mapping sustainable supply chain innovation: A comprehensive bibliometric analysis.

This comprehensive bibliometric study investigates Sustainable Supply Chain Innovation (SSCI) research, examining its evolution, identifying key contributors, and unveiling emerging trends. Analyzing 1158 English-language SSCI articles using the robust Scopus dataset exposes noteworthy journals, authors, institutions, and global contributions. The findings suggest a consistent increase in research output since 1999, with a notable surge in the past decade. Network analysis and density-based spatial clustering identified six SSCI research clusters: Sustainability and Responsibility in Business, Navigating Innovation and Disruption, Sustainable Business Strategies, Environmental Sustainability and Innovation, Sustainable Food Systems and Environmental Impact, and Sustainable Business Dynamics. These clusters highlight the diverse nature of the evolving Sustainability and Supply Chain Management (SCM) field, contributing to a thorough understanding of the SSCI research landscape and emphasizing interconnections between sustainability and SCM themes, potentially leading to more comprehensive theoretical models. Furthermore, this understanding aids businesses in anticipating emerging trends and implementing optimal practices in SSCI. Moreover, recognizing active institutions and global contributors provides practical insights for fostering strategic collaborations.

Virtual Reality and Mixed Reality-Assisted Endoscopic DCR in Extremely Complex Lacrimal Obstructions.

OBJECTIVE: To report the techniques and outcomes of virtual reality (VR) and mixed reality (MR)-assisted powered endoscopic dacryocystorhinostomy (DCR) in extremely complex lacrimal drainage obstructions. METHODS: A prospective, non-randomized clinical study was performed in complex syndromic congenital nasolacrimal duct obstruction (CNLDO) and post-traumatic secondary acquired lacrimal duct obstruction (SALDO) in the setting of Le Fort fractures. All patients underwent preoperative planning in VR and intraoperative planning with a step ahead with MR assistance during the surgery. Surgery was supported by mixed reality intraoperative guidance with the use of the prearranged 3D models and real-time-rendered digital models. Parameters assessed include demographics, clinical presentation, complexities of the nasolacrimal duct obstruction, preoperative and intraoperative utility of VR and MR models, surgical techniques, complications, and outcomes. RESULTS: The technique is described as a proof of concept in challenging situations with Apert syndrome and traumatic SALDOs with gross malposition of the sac, and gross nasal and lacrimal anatomical deformities. The VR models helped the surgeon to assess the details of the altered anatomy preoperatively to plan an appropriate approach. Intraoperatively, MR models were present in the surgeon's view without disturbing the endoscopic procedure. Intermittently, the surgeon could pull any of the models virtually present in the operating room, slice them, rotate them, and intricately study the alterations in a stepwise manner, as the surgery proceeds. CONCLUSION: Virtual reality and mixed reality-assisted powered endoscopic DCR can be an alternate approach reserved for extremely challenging cases of complex syndromic CNLDOs and post-traumatic SALDOs. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3508-3515, 2024.

An efficient and cost-effective method for disrupting genes in RAW264.7 macrophages using CRISPR-Cas9.

The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) are widely used for genome editing in cultured cell lines. However, the implementation of genome editing is still challenging due to the complex and often costly multi-step process associated with this technique. Moreover, the efficiency of genome editing varies across cell types, often limiting utility. Herein, we describe pCRISPR-EASY, a vector for simplified cloning of single guide RNAs (sgRNAs) and its simultaneous introduction with CRISPR-Cas9 into cultured cells using a non-viral delivery system. We outline a comprehensive, step-by-step protocol for genome editing in RAW264.7 macrophages, a mouse macrophage cell line widely used in biomedical research for which genome editing using CRISPR-Cas9 has been restricted to lentiviral or expensive commercial reagents. This provides an economical, highly efficient and reliable method for genome editing that can easily be adapted for use in other systems.

Deep learning-enhanced characterization of bubble dynamics in proton exchange membrane water electrolyzers.

The ever-increasing utility of imaging technology in proton exchange membrane water electrolyzer research raises the demand for rapid and precise image analysis. In particular, for optical video recordings, the challenge primarily lies in the large number of frames that impede the delineation of bubble dynamics with standard methods. In order to address this problem, the present study supports the automation of data analysis to facilitate swift, comprehensive, and measurable insights from captured imagery. We present a deep learning-based framework to perform high-throughput analyses of bubble dynamics using optical images of proton exchange membrane water electrolyzers. Leveraging a relatively small annotated imaging dataset of just 35 images, various configurations of the U-Net architecture were trained to perform bubble segmentation tasks. The best model achieved a precision of 95%, a recall of 78%, and an F1-score of 86% on the validation set. Subsequent to segmentation, the methodology enabled the rapid extraction of parameters such as time-resolved bubble area, size distributions, bubble position probability density, and individual bubble shape analytics. The findings underscore the potential of deep learning to enhance the analysis of polymer electrolyte membrane water electrolyzer imaging, offering a path toward more efficient and informative evaluations in electrochemical research.

Noninvasive PET imaging of tumor PD-L1 expression with 64Cu-labeled Durvalumab.

Breast cancer (BrCa) ranks as the most prevalent malignant neoplasm affecting women worldwide. The expression of programmed death-ligand 1 (PD-L1) in BrCa has recently emerged as a biomarker for immunotherapy response, but traditional immunohistochemistry (IHC)-based methods are hindered by spatial and temporal heterogeneity. Noninvasive and quantitative PD-L1 imaging using appropriate radiotracers can serve to determine PD-L1 expression in tumors. This study aims to demonstrate the viability of PET imaging with 64Cu-labeled Durvalumab (abbreviated as Durva) to assess PD-L1 expression using a murine xenograft model of breast cancer. Durvalumab, a human IgG1 monoclonal antibody against PD-L1, was assessed for specificity in vitro in two cancer cell lines (MDA-MB-231 triple-negative breast cancer cell line and AsPC-1 pancreatic cancer cell line) with positive and negative PD-L1 expression by flow cytometry. Next, we performed the in vivo evaluation of 64Cu-NOTA-Durva in murine models of human breast cancer by PET imaging and ex vivo biodistribution. Additionally, mice bearing AsPC-1 tumors were employed as a negative control. Tumor uptake was quantified based on a 3D region-of-interest (ROI) analysis of the PET images and ex vivo biodistribution measurements, and the results were compared against conventional IHC testing. The radiotracer uptake was evident in MDA-MB-231 tumors and showed minimal nonspecific binding, corroborating IHC-derived results. The results of the biodistribution showed that the MDA-MB-231 tumor uptake of 64Cu-NOTA-Durva was much higher than 64Cu-NOTA-IgG (a nonspecific radiolabeled IgG). In Conclusion, 64Cu-labeled Durvalumab PET/CT imaging offers a promising, noninvasive approach to evaluate tumor PD-L1 expression.