Potential Utility Research Articles

Does Magnetic Resonance Imaging Predict Neurological Deficit in Patients with Traumatic Lower Lumbar Fractures?

A retrospective cohort study. This study aimed to understand the role of magnetic resonance imaging (MRI) in predicting neurological deficits in traumatic lower lumbar fractures (LLFs; L3-L5). Despite studies on the radiological risk factors for neurological deficits in thoracolumbar fractures, very few have focused on LLFs. Moreover, the potential utility of MRI in LLFs has not been evaluated. In total, 108 patients who underwent surgery for traumatic LLFs between January 2010 and January 2020 were reviewed to obtain their demographic details, injury level, and neurology status at the time of presentation (American Spinal Injury Association [ASIA] grade). Preoperative computed tomography scans were used to measure parameters such as anterior vertebral body height, posterior vertebral body height, loss of vertebral body height, local kyphosis, retropulsion of fracture fragment, interpedicular distance, canal compromise, sagittal transverse ratio, and presence of vertical lamina fracture. MRI was used to measure the canal encroachment ratio (CER), cross-sectional area of the thecal sac (CSAT), and presence of an epidural hematoma. Of the 108 patients, 9 (8.3%) had ASIA A, 4 (3.7%) had ASIA B, 17 (15.7%) had ASIA C, 21 (19.4%) had ASIA D, and 57 (52.9%) had ASIA E neurology upon admission. The Thoracolumbar Injury Classification and Severity score (p =0.000), CER (p =0.050), and CSAT (p =0.019) were found to be independently associated with neurological deficits on the multivariate analysis. The receiver operating characteristic curves showed that only CER (area under the curve [AUC], 0.926; 95% confidence interval [CI], 0.860-0.968) and CSAT (AUC, 0.963; 95% CI, 0.908-0.990) had good discriminatory ability, with the optimal cutoff of 50% and 65.3 mm2, respectively. Based on the results, the optimal cutoff values of CER >50% and CSAT >65.3 mm2 can predict the incidence of neurological deficits in LLFs.

An Investigation into the Larvicidal Activity of Biologically Synthesized Silver and Copper Oxide Nanoparticles Against Mosquito Larvae.

This study is primarily focused on the synthesis of silver and copper oxide nanoparticles utilizing the extract of Ipomoea staphylina plant and their larvicidal activity against specific larvae. Notably, Anopheles stephensi and Aedes aegypti are significant disease vectors responsible for transmitting diseases such as malaria, dengue fever, Zika virus, and chikungunya (Anopheles stephensi), and dengue and Zika (Aedes aegypti). These mosquitoes have a substantial impact on urban areas, influencing disease transmission dynamics. In an effort to control these larvae, we have pursued the synthesis of a herbal-based nanomedicine derived from I. staphylina, a valuable herb in traditional medicine. Our successful synthesis of silver and CuO nanoparticles followed environmentally sustainable green chemistry methodologies. The I. staphylina plant extract played a dual role as a reducing agent and dopant, aligning with principles of sustainability. We employed X-ray diffraction (XRD) analysis to validate the nanoparticle structure and size, while field-emission scanning electron microscopy (FE-SEM) revealed well-defined nanostructures. Elemental composition was determined through energy-dispersive X-ray (EDX) analysis, and UV-visible spectroscopy provided insights into the bandgap energy (3.15 eV for silver, 1.2 eV for CuO nanoparticles). These nanoparticles exhibited robust larvicidal activity, with CuO nanoparticles surpassing silver nanoparticles in terms of LC50 and LC90 values. Moreover, the developmental toxicity of CuO and Ag NPs was evaluated in zebrafish embryos as part of non-target eco-toxicological studies conducted in a standard laboratory environment. These findings underscore the potential utility of these nanoparticles as highly effective and environmentally friendly natural pesticides, offering cost-effectiveness and ecological benefits.

Single‐Carbon Atom Doping Reactions Using Atomic Carbon and Its Equivalents

AbstractAtomic carbon, a zerovalent atom with four non‐bonded electrons, has potential utility in organic synthesis as platforms for the formation of four new covalent bonds at the carbon center. Single‐carbon atom doping (SCAD) is the process of inserting an atomic carbon into a reactant molecule with no loss of atoms in the reactant. In this Concept, we overview SCAD reactions, which can be classified by physical or chemical methods.

Exploring the Potential Role of Metabolomics in COPD: A Concise Review.

Chronic Obstructive Pulmonary Disease (COPD) is a pathological condition of the respiratory system characterized by chronic airflow obstruction, associated with changes in the lung parenchyma (pulmonary emphysema), bronchi (chronic bronchitis) and bronchioles (small airways disease). In the last years, the importance of phenotyping and endotyping COPD patients has strongly emerged. Metabolomics refers to the study of metabolites (both intermediate or final products) and their biological processes in biomatrices. The application of metabolomics to respiratory diseases and, particularly, to COPD started more than one decade ago and since then the number of scientific publications on the topic has constantly grown. In respiratory diseases, metabolomic studies have focused on the detection of metabolites derived from biomatrices such as exhaled breath condensate, bronchoalveolar lavage, and also plasma, serum and urine. Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy are powerful tools in the precise identification of potentially prognostic and treatment response biomarkers. The aim of this article was to comprehensively review the relevant literature regarding the applications of metabolomics in COPD, clarifying the potential clinical utility of the metabolomic profile from several biologic matrices in detecting biomarkers of disease and prognosis for COPD. Meanwhile, a complete description of the technological instruments and techniques currently adopted in the metabolomics research will be described.

A novel type-2 innate lymphoid cell-based immunotherapy for cancer.

Cell-based cancer immunotherapy has achieved significant advancements, providing a source of hope for cancer patients. Notwithstanding the considerable progress in cell-based immunotherapy, the persistently low response rates and the exorbitant costs associated with their implementation still present a formidable challenge in clinical settings. In the landscape of cell-based cancer immunotherapies, an uncharted territory involves Type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) which promotes ILC2 functionality, recognized for their inherent ability to enhance immune responses. Recent discoveries regarding their role in actuating cytolytic T lymphocyte responses, including curbing tumor growth rates and hindering metastasis, have added a new dimension to our understanding of the IL-33/ILC2 axis. These recent insights may hold significant promise for ILC2 cell-based immunotherapy. Nevertheless, the prospect of adoptively transferring ILC2s to confer immune protection against tumors has yet to be investigated. The present study addresses this hypothesis, revealing that ILC2s isolated from the lungs of tumor-bearing mice, and tumor infiltrating ILC2s when adoptively transferred after tumor establishment at a ratio of one ILC2 per sixty tumor cells, leads to an influx of tumor infiltrating CD4+ and CD8+ T lymphocytes as well as tumor infiltrating eosinophils resulting in a remarkable reduction in tumor growth. Moreover, we find that post-adoptive transfer of ILC2s, the number of tumor infiltrating ILC2s is inversely proportional to tumor size. Finally, we find corollaries of the IL-33/ILC2 axis enhancing the infiltration of eosinophils in human prostate carcinomas patients' expressing high levels of IL-33 versus those expressing low levels of IL-33. Our results underscore the heightened efficacy of adoptively transferred ILC2s compared to alternative approaches, revealing an approximately one hundred fifty-fold superiority on a cell-per-cell basis over CAR T-cells in the specific targeting and elimination of tumors within the same experimental model. Overall, this study demonstrates the functional significance of ILC2s in cancer immunosurveillance and provides the proof of concept of the potential utility of ILC2 cell-based cancer immunotherapies.

Syphilis and advancements in its treatment

Syphilis is an infectious disease caused by the bacterium Treponema pallidum. Pallidum and its subspecies is a spirochete microaerophilic virus that sensitive to oxygen and temperature. T. pallidum is responsible for causing syphilis through sexual exposure and vertical transmission from pregnant women to their fetuses. The invasiveness and immunoevasiveness of syphilis is caused by its lack of outer membrane immune targets and with fewer surface transmembrane protein. These features explain why syphilis causes millions of people suffered from this disease and the incidence is still increasing. For the four stages of syphilis, there are different symptoms and courses of treatment approach should be taken. The administration of penicillin has reached a level of maturity and clarity in its therapeutic application. An alternative way of treatment involves the utilization of DNA vaccine. The more refined DNA vaccine technic suggests potential utility of the DNA vaccine in T.pallidum treatment. Furthermore, this review explores the current study on vaccine mRNA which holds substantial promise as a valuable avenue for syphilis treatment. T.pallidum, syphilis, transmission .

New Light on Prions: Putative Role of PrPc in Pathophysiology of Mood Disorders.

Mood disorders are highly prevalent and heterogenous mental illnesses with devastating rates of mortality and treatment resistance. The molecular basis of those conditions involves complex interplay between genetic and environmental factors. Currently, there are no objective procedures for diagnosis, prognosis and personalization of patients' treatment. There is an urgent need to search for novel molecular targets for biomarkers in mood disorders. Cellular prion protein (PrPc) is infamous for its potential to convert its insoluble form, leading to neurodegeneration in Creutzfeldt-Jacob disease. Meanwhile, in its physiological state, PrPc presents neuroprotective features and regulates neurotransmission and synaptic plasticity. The aim of this study is to integrate the available knowledge about molecular mechanisms underlying the impact of PrPc on the pathophysiology of mood disorders. Our review indicates an important role of this protein in regulation of cognitive functions, emotions, sleep and biological rhythms, and its deficiency results in depressive-like behavior and cognitive impairment. PrPc plays a neuroprotective role against excitotoxicity, oxidative stress and inflammation, the main pathophysiological events in the course of mood disorders. Research indicates that PrPc may be a promising biomarker of cognitive decline. There is an urgent need of human studies to elucidate its potential utility in clinical practice.

Comparison of Optical Genome Mapping With Conventional Diagnostic Methods for Structural Variant Detection in Hematologic Malignancies.

Structural variants (SVs) are currently analyzed using a combination of conventional methods; however, this approach has limitations. Optical genome mapping (OGM), an emerging technology for detecting SVs using a single-molecule strategy, has the potential to replace conventional methods. We compared OGM with conventional diagnostic methods for detecting SVs in various hematologic malignancies. Residual bone marrow aspirates from 27 patients with hematologic malignancies in whom SVs were observed using conventional methods (chromosomal banding analysis, FISH, an RNA fusion panel, and reverse transcription PCR) were analyzed using OGM. The concordance between the OGM and conventional method results was evaluated. OGM showed concordance in 63% (17/27) and partial concordance in 37% (10/27) of samples. OGM detected 76% (52/68) of the total SVs correctly (concordance rate for each type of SVs: aneuploidies, 83% [15/18]; balanced translocation, 80% [12/15] unbalanced translocation, 54% [7/13] deletions, 81% [13/16]; duplications, 100% [2/2] inversion 100% [1/1]; insertion, 100% [1/1]; marker chromosome, 0% [0/1]; isochromosome, 100% [1/1]). Sixteen discordant results were attributed to the involvement of centromeric/telomeric regions, detection sensitivity, and a low mapping rate and coverage. OGM identified additional SVs, including submicroscopic SVs and novel fusions, in five cases. OGM shows a high level of concordance with conventional diagnostic methods for the detection of SVs and can identify novel variants, suggesting its potential utility in enabling more comprehensive SV analysis in routine diagnostics of hematologic malignancies, although further studies and improvements are required.

Digital spatial profiling identifies molecular changes involved in development of colitis-associated colorectal cancer.

Chronic colonic inflammation seen in inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC). Colitis-associated cancers (CAC) are molecularly different from sporadic CRC. This study aimed to evaluate spatially defined molecular changes associated with neoplastic progression to identify mechanisms of action and potential biomarkers for prognostication. IBD patients who had undergone colectomy for treatment of their IBD or dysplasia were identified from an institutional database. Formalin-fixed paraffin embedded samples from areas of normal, inflamed, dysplastic and adenocarcinoma tissue were identified for digital spatial profiling using the Nanostring GeoMx™ Cancer Transcriptome Atlas. RNA expression and quantification of 1812 genes was measured and analysed in a spatial context to compare differences in gene expression. Sixteen patients were included, nine patients had CAC, two had dysplasia only and five had colitis only. Significant, step-wise differences in gene expression were seen between tissue types, mainly involving progressive over-expression of collagen genes associated with stromal remodelling. Similarly, MYC over-expression was associated with neoplastic progression. Comparison of normal and inflamed tissue from patients who progressed to those who did not also showed significant differences in immune-related genes, including under-expression of thte chemokines CCL18, CCL25 and IL-R7, as well as CD3, CD6 and lysozyme. The known oncogene CD24 was significantly overexpressed. Both tissue types and patient groups are molecularly distinguishable on the basis of their gene expression patterns. Further prospective work is necessary to confirm these differences and establish their clinical significance and potential utility as biomarkers.

Abstract A035: Radiation-induced senescence as a driver of glioblastoma recurrence

Abstract Glioblastomas (GBM) are treated with high doses of ionizing radiation (IR), yet these tumors inevitably recur, and the recurrent tumors are highly therapy resistant. An understanding of mechanisms driving GBM recurrence is critical for improving therapy. During GBM therapy, both the tumor and normal brain tissue surrounding the tumor are treated with up to 60 Gy of IR. IR is a potent inducer of senescence, and senescent stromal cells can promote the growth of neighboring tumor cells by secreting matrix metalloproteinases, chemokines, cytokines, and growth factors that create a senescence-associated secretory phenotype (SASP). We have shown previously that IR-induced senescence of astrocytes in the brain leads to the secretion of SASP factors that promote the growth and invasiveness of tumor cells in mouse models of GBM (Fletcher-Sananikone, et al, Cancer Research, 2021). Following up on this study, we irradiated a panel of GBM cell lines and found that a significant fraction of these senesced rapidly in a p21-dependent manner. Senescent glioma cells upregulated SASP genes in a NF-kB-dependent manner, prominently, the interleukin IL6, which is an activator of the JAK-STAT pathway. Conditioned media from senescent GBM cells activated the JAK-STAT pathway in non-senescent GBM cells as well as promoted tumor cell proliferation and radioresistance. Interestingly, conditioned media from senescent GBM cells could also activate the NF-kB pathway and induce SASP in non-senescent cells. These results indicate that senescent GBM cells can activate pro-tumorigenic pathways in their non-senescent counterparts and SASP can spread from senescent to non-senescent cells. Bioinformatic analyses of the transcriptomic profiles of irradiated GBM cells and publicly available data from the TCGA database revealed that the inhibitor of apoptosis protein cIAP2 is a critical survival factor for senescent glioma cells. We find that targeting cIAP2 using Smac mimetics triggers apoptosis of senescent GBM cells with minimal toxicity towards normal brain cells, like astrocytes. Upregulation of cIAP2 in irradiated tumor cells was also observed in PDX models of GBM. Using these PDX models, we are currently validating novel senolytic-based therapeutic approaches to mitigate tumor recurrence after radiotherapy. In sum, our findings illustrate how senescence of both stromal and tumor cells promote GBM recurrence via different mechanisms and underscore the potential utility of adjuvant senolytic therapy for blunting GBM recurrence after radiotherapy. Citation Format: Ben R. Jordan, Nozomi Tomimatsu, Luis Macedo Di Cristofaro, Suman Kanji, Bipasha Mukherjee, Sandeep Burma. Radiation-induced senescence as a driver of glioblastoma recurrence [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A035.

Abstract A020: NAD+ Boosting through NRH supplementation enhances treatment efficacy in EOC

Abstract Background: Dihydronicotinamide riboside (NRH), the reduced form of nicotinamide riboside (NR), is a recently identified, naturally occurring precursor of arguably the most crucial cofactor for cellular function, Nicotinamide Adenine Dinucleotide (NAD+). Recent investigation suggests that NRH is more adept at increasing NAD+ stores than traditional NAD precursors, and such extreme NAD+ boosting via NRH supplementation induces cytotoxicity in certain cellular contexts. It has also been shown that the lack of functional BRCA protein in epithelial ovarian cancer (EOC) directly impacts intracellular NAD+ levels. Given that altered cellular metabolism and DNA repair mechanisms are central alterations in EOC, and these processes are functionally dependent on NAD+, we sought to assess whether NRH supplementation in EOC cell lines enhanced cellular cytotoxicity alone and in combination with standard therapeutic agents. Methods: We supplemented 3 ovarian cancer cell lines (SKOV3, OVCAR8 and ES2) with NRH and traditional NAD precursor, NA (nicotinic acid) alone and in combination with carboplatin, paclitaxel, combination, and olaparib. Cytotoxicity was measured via CellTiter-Glo. RNA sequencing of EOC cell lines was performed to determine the differential expression of NAD+ anabolic and catabolic enzymes. Of note, all three cell lines are known to be BRCA1 &2 wildtype while OVCAR8 cells are hypermethylated and harbor loss of heterozygosity (LOH high) at the BRCA1 loci. Results: Significant cytotoxicity was noted in NRH treated cells (~40 %) with minimal cell death in the NA treated lines. Strikingly, NRH supplementation enhanced carboplatin cytotoxicity by 25-50 % depending on cell line, paclitaxel cytotoxicity by 10-25 %, and the combination by 10-35 % whereas NA supplementation had no effect on the baseline treatment induced cytotoxicity. Interestingly, the effect of NRH supplementation with olaparib differed between the ES2 and OVCAR8 cell lines, with a significant 20 % increase in cell death in ES2 vs OVCAR8 cells with a negligible increase in cell death. PARP inhibition by olaparib requires NAD+. RNA sequencing revealed an increased expression in NAMPT, an enzyme involved in the NAD+ salvage pathway in the ES2 cell line relative to the OVCAR8, suggesting that the ES2 cells harbor a baseline NAD+ deficit rendering them more vulnerable to PARP inhibition following NAD+ boosting. This is also consistent with the OVCAR8 data suggesting that hypermethylated BRCA1 results in a relative increase in NAD+ to the extent that NRH supplementation does not enhance the efficacy of PARP inhibition. Conclusions: Here we show that in the context of EOC, exploitation of the NAD+ bioenergetic phenotype through NRH supplementation is a biologically feasible strategy to enhance the response of traditional therapy with potentially minimal toxicity. This data suggests several potential mechanisms by which cellular NAD+ availability belies treatment efficacy and resistance and highlights the potential utility of NAD+ metabolomics as a biomarker to guide treatment decisions. Citation Format: Kevin Lee, Tanvi Joshi, Catherine Lyons, Mary Howard Singleton, Elizabeth Catranis, Sagar Chokshi, Luciana Madiera da Silva, Marie Migaud, Jennifer Scalici. NAD+ Boosting through NRH supplementation enhances treatment efficacy in EOC [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A020.

Heavy Metal Bioaccumulation in Rabbit Organs and Chrysomya albiceps (Wiedemann, 1819) Larvae: Implications for Forensic Entomology

Background: A closer relationship has been established between entomology and toxicology, giving rise to a new field known as entomotoxicology, which focuses on the bioaccumulation of toxic substances in scavenging insects and other arthropods. Methods: This study investigates the impact of lethal doses of Mercury Chloride (HgCl2) and Cadmium Chloride (CdCl2) administered to male rabbits (Oryctolagus cuniculus Linnaeus) on the distribution of Mercury and Cadmium in rabbit organs and their subsequent accumulation in Chrysomya albiceps larvae. The experimental groups were subjected to oral administration of specific concentrations of HgCl2 and CdCl2, while a control group received distilled water. Organ dissection and subsequent larval feeding were followed by acid digestion for sample preparation and inductively coupled plasma torch spectrometry coupled with a mass spectrometer (ICP-MS) was employed for analysis. Result: Results indicate a significant increase in Mercury concentrations in treated rabbit organs, with the liver exhibiting the highest concentration. Cadmium showed diverse distribution among rabbit organs, with the highest concentrations in the kidneys. Ch. albiceps larvae, reared on rabbit organs, exhibited varied concentrations of both Mercury and Cadmium, with significantly higher levels in the treated group. These findings underscore the ecological implications of heavy metal exposure and the potential utility of insect larvae in forensic investigations as bioindicators of environmental contamination.

Transparent and hard TiO2/Au electromagnetic shielding antireflection coatings on aircraft canopy PMMA organic glass

This research addresses the critical need for a highly stable and transparent electromagnetic shielding coating for aircraft PMMA windows and canopies, crucial for safeguarding against electromagnetic interference and enhancing aircraft stealth capabilities. The study presents the novel design, deposition and investigation of transparent coatings, specifically TiO2/Au, on PMMA organic glass cockpit canopies. Optimization of TiO2 and Au film thicknesses is achieved through simulation using TFcalc software, incorporating polarization and optical constants data obtained in this study. The experiments reveal that the deposition of TiO2/Au/TiO2 on PMMA results in fogging, reducing transparency, while novel TiO2/Au coating does not exhibit this issue. The TiO2/Au configuration, featuring a TiO2 layer approximately 30 nm thick and an Au film ranging from 11 to 15 nm in thickness, demonstrates outstanding attributes, including a remarkable transparency level of approximately 70–80% and robust electromagnetic interference shielding efficiency within the range of 19–29 dB across S, C, X, and Ku bands of electromagnetic waves. These exceptional performance characteristics position it as an ideal choice for aviation applications. The synergy of the stable Au and durable TiO2 components, with their high hardness and self-cleaning properties, extends its potential utility to a diverse array of applications.

Genome-Wide Identification and Characterization of the Sweet Orange (Citrus sinensis) GATA Family Reveals a Role for CsGATA12 as a Regulator of Citrus Bacterial Canker Resistance.

Citrus bacterial canker (CBC) is a severe bacterial infection caused by Xanthomonas citri subsp. citri (Xcc), which continues to adversely impact citrus production worldwide. Members of the GATA family are important regulators of plant development and regulate plant responses to particular stressors. This report aimed to systematically elucidate the Citrus sinensis genome to identify and annotate genes that encode GATAs and evaluate the functional importance of these CsGATAs as regulators of CBC resistance. In total, 24 CsGATAs were identified and classified into four subfamilies. Furthermore, the phylogenetic relationships, chromosomal locations, collinear relationships, gene structures, and conserved domains for each of these GATA family members were also evaluated. It was observed that Xcc infection induced some CsGATAs, among which CsGATA12 was chosen for further functional validation. CsGATA12 was found to be localized in the nucleus and was differentially upregulated in the CBC-resistant and CBC-sensitive Kumquat and Wanjincheng citrus varieties. When transiently overexpressed, CsGATA12 significantly reduced CBC resistance with a corresponding increase in abscisic acid, jasmonic acid, and antioxidant enzyme levels. These alterations were consistent with lower levels of salicylic acid, ethylene, and reactive oxygen species. Moreover, the bacteria-induced CsGATA12 gene silencing yielded the opposite phenotypic outcomes. This investigation highlights the important role of CsGATA12 in regulating CBC resistance, underscoring its potential utility as a target for breeding citrus varieties with superior phytopathogen resistance.

Preparation and characterization of Sorafenib nano-emulsion: impact on pharmacokinetics and toxicity; an in vitro and in vivo study.

Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths worldwide. Current treatment strategies include surgical resection, liver transplantation, liver-directed therapy, and systemic therapy. Sorafenib (Sor) is the first systemic drug authorized by the US Food and Drug Administration (FDA) for HCC treatment. Nevertheless, the conventional oral administration of Sor presents several limitations: poor solubility, low bioavailability, drug resistance development, and off-target tissue accumulation, leading to numerous adverse effects. Nano-emulsion, a nano-delivery system, is a viable carrier for poorly water-soluble drugs. It aims to enhance drug bioavailability, target organ accumulation, and reduce off-target tissue exposure, thus improving therapeutic outcomes while minimizing side effects. This study formulated Sor nano-emulsion (Sor NanoEm) using the homogenization technique. The resultant nano-emulsion was characterized by particle size (121.75 ± 12 nm), polydispersity index (PDI; 0.310), zeta potential (-12.33 ± 1.34 mV), viscosity (34,776 ± 3276 CPs), and pH (4.38 ± 0.3). Transmission Electron Microscopy exhibited spherical nano-droplets with no aggregation signs indicating stability. Furthermore, the encapsulation of Sor within the nano-emulsion sustained its release, potentially reducing the frequency of therapeutic doses. Cytotoxicity assessments on the HepG2 cell line revealed that Sor NanoEm had a significantly (P < 0.05) more potent cytotoxic effect compared to Sor suspension. Subsequent tests highlighted superior pharmacokinetic parameters and reduced dosage requirements of Sor NanoEm in mice. It exhibited an enhanced safety profile, particularly in behavior, brain, and liver, compared to its suspended form. These findings underscore the enhanced pharmacological and toxicological attributes of Sor Nano-emulsion, suggesting its potential utility in HCC treatment.

Pre-job loss grief reactions and work attachment among sick-listed employees: Introduction of the imminent Job Loss Scale

BackgroundWith this study, we aimed to explore the emotional experiences of sick-listed employees facing imminent job loss, as this emotional distress may hinder successful job search outcomes. The study had two objectives: (1) to develop and validate the Imminent Job Loss Scale (IJLS) for assessing pre-job loss grief reactions and (2) to examine its relationship to work attachment.MethodsDevelopment of the 9-item IJLS was carried out using feedback from an expert panel, consisting of five academic experts in grief and labour, five re-integration specialists, and five sick-listed employees facing imminent job loss. The psychometric properties of the IJLS were evaluated, and its association with work attachment was examined using data from 200 sick-listed employees facing imminent job loss.ResultsThe IJLS demonstrated strong internal consistency and temporal stability, distinctiveness from depression and anxiety symptoms, and solid convergent validity. Work-centrality and organizational commitment were positively related to pre-job loss grief reactions, while work engagement and calling showed no significant associations.ConclusionThis study provides valuable insights into pre-job loss grief reactions and shows the potential utility of the IJLS for screening and monitoring purposes. Understanding pre-job loss grief reactions can improve the re-integration and job prospects of sick-listed employees. In future research, explorations of these dynamics should continue to provide better support to sick-listed employees during this challenging period.

Second-line immunotherapy in new onset refractory status epilepticus.

Several pieces of evidence suggest immune dysregulation could trigger the onset and modulate sequelae of new onset refractory status epilepticus (NORSE), including its subtype with prior fever known as febrile infection-related epilepsy syndrome (FIRES). Consensus-driven recommendations have been established to guide the initiation of first- and second-line immunotherapies in these patients. Here, we review the literature to date on second-line immunotherapy for NORSE/FIRES, presenting results from 28 case reports and series describing the use of anakinra, tocilizumab, or intrathecal dexamethasone in 75 patients with NORSE. Among them, 52 patients were managed with anakinra, 21 with tocilizumab, and eight with intrathecal dexamethasone. Most had elevated serum or cerebrospinal fluid cytokine levels at treatment initiation. Treatments were predominantly initiated during the acute phase of the disease (92%) and resulted, within the first 2 weeks, in seizure control for up to 73% of patients with anakinra, 70% with tocilizumab, and 50% with intrathecal dexamethasone. Cytokine levels decreased after treatment for most patients. Anakinra and intrathecal dexamethasone were mainly initiated in children with FIRES, whereas tocilizumab was more frequently prescribed for adults, with or without a prior febrile infection. There was no clear correlation between the response to treatment and the time to initiate the treatment. Most patients experienced long-term disability and drug-resistant post-NORSE epilepsy. Initiation of second-line immunotherapies during status epilepticus (SE) had no clear effect on the emergence of post-NORSE epilepsy or long-term functional outcomes. In a small number of cases, the initiation of anakinra or tocilizumab several years after SE onset resulted in a reduction of seizure frequency for 67% of patients. These data highlight the potential utility of anakinra, tocilizumab, and intrathecal dexamethasone in patients with NORSE. There continues to be interest in the utilization of early cytokine measurements to guide treatment selection and response. Prospective studies are necessary to understand the role of early immunomodulation and its associations with epilepsy and functional outcomes.

Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma

BackgroundSelective biomarkers may improve outcomes in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitor therapy. We investigated three independent biomarkers for association with efficacy in the randomized, phase III KESTREL study (NCT02551159) of first-line durvalumab monotherapy or durvalumab plus tremelimumab versus the EXTREME regimen: programmed cell death ligand-1 (PD-L1) immunohistochemistry, blood tumor mutational burden (bTMB) via circulating tumor DNA, and neutrophil-to-lymphocyte ratio (NLR).MethodsTumor or blood samples from patients enrolled in the KESTREL study were analyzed for PD-L1, bTMB, and NLR. Associations with overall survival (OS) or objective response rates (ORRs) were evaluated based on prespecified cut-offs for PD-L1 (tumor cell [TC] ≥ 50%/immune cell ≥ 25% or TC ≥ 25%), bTMB (≥ 16 mutations [mut] per megabase [Mb]), and NLR (≤ 7). Ad hoc analyses of exploratory cut-offs were performed.ResultsPrespecified or exploratory cut-offs for PD-L1 did not enrich for ORR or OS for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME. In the bTMB ≥ 16 mut/Mb subgroup, OS hazard ratios (95% confidence interval) for durvalumab monotherapy and durvalumab plus tremelimumab versus EXTREME were 0.90 (0.48–1.72) and 0.69 (0.39–1.25), respectively. Complete response rates were 8.6% with durvalumab plus tremelimumab and 4.3% with EXTREME (≥ 16 mut/Mb subgroup). No improvement in OS was observed for durvalumab monotherapy or durvalumab plus tremelimumab versus EXTREME at prespecified or exploratory NLR cut-offs.ConclusionsbTMB demonstrated potential utility for selecting patients with R/M HNSCC who benefited from durvalumab with or without tremelimumab versus EXTREME.Trial registration ClinicalTrials.gov identifier NCT02551159.

The Hirshfeld topological surfaces, volumes, and their voids charge density interplay on radiation shielding properties: A case study of carbide-based ceramics

Transition metal carbides (TMCs) are explored for their potential as radiation shielding materials, with a focus on their γ-ray attenuation properties. These high-density materials, including WC, TaC, HfC, NbC, and VC, are evaluated across an energy range of 0.015–15.0 MeV. Notably, at low incoming photon energy (0.0150 MeV), these TMCs exhibit mass attenuation coefficients (MAC) (TMC, MAC (g/cm2)): (WC, 130.417), (TaC, 125.730), (HfC, 120.873), (NbC, 23.751), and (VC, 32.377) and effective atomic numbers (Zeff) from 22.69 to 73.68. These values surpass those of silicon dioxide (SiO2), highlighting the superior γ-ray attenuation capabilities of TMCs. TMCs exhibit a distinct trend in MAC values, with tungsten carbide (WC) consistently demonstrating the highest MAC values, making it the most efficient γ-ray attenuator. Hafnium carbide (HfC) closely follows, with tantalum carbide (TaC) exhibiting lower MAC values, while niobium carbide (NbC) and vanadium carbide (VC) display the lowest values. These differences can be attributed to variations in material composition and structure. Furthermore, the study delves into the impact of charge density within Hirshfeld voids on LAC values, revealing that as X⁴⁺ … C interactions increase due to higher charge density, LAC values rise. This fine-tuning of topological and charge density distributions within the crystal's voids offers a promising avenue to optimize these materials for enhanced radiation shielding effectiveness. Overall, this research contributes to the understanding of the potential utility of TMCs in radiation shielding applications, showcasing the interplay between crystal structure, composition, and charge distribution as key factors in determining their radiation attenuation capabilities.

Reliability and Agreement of Free Web-Based 3D Software for Computing Facial Area and Volume Measurements

Background: Facial surgeries require meticulous planning and outcome assessments, where facial analysis plays a critical role. This study introduces a new approach by utilizing three-dimensional (3D) imaging techniques, which are known for their ability to measure facial areas and volumes accurately. The purpose of this study is to introduce and evaluate a free web-based software application designed to take area and volume measurements on 3D models of patient faces. Methods: This study employed the online facial analysis software to conduct ten measurements on 3D models of subjects, including five measurements of area and five measurements of volume. These measurements were then compared with those obtained from the established 3D modeling software called Blender (version 3.2) using the Bland–Altman plot. To ensure accuracy, the intra-rater and inter-rater reliabilities of the web-based software were evaluated using the Intraclass Correlation Coefficient (ICC) method. Additionally, statistical assumptions such as normality and homoscedasticity were rigorously verified before analysis. Results: This study found that the web-based facial analysis software showed high agreement with the 3D software Blender within 95% confidence limits. Moreover, the online application demonstrated excellent intra-rater and inter-rater reliability in most analyses, as indicated by the ICC test. Conclusion: The findings suggest that the free online 3D software is reliable for facial analysis, particularly in measuring areas and volumes. This indicates its potential utility in enhancing surgical planning and evaluation in facial surgeries. This study underscores the software’s capability to improve surgical outcomes by integrating precise area and volume measurements into facial surgery planning and assessment processes.