Multiple Treatment Research Articles

Oxyphenbutazone ameliorates carfilzomib induced cardiotoxicity in rats via inhibition of oxidative free radical burst and NF-κB/IκB-α pathway

Carfilzomib (CFZ), a chemotherapeutic agent used for multiple myeloma treatments reported to cause high incidence of cardiac events either new onset and/or exacerbate formerly diagnosed heart failure with ventricular and myocardial dysfunction.Purpose: Current research designed to explore and examine the preventive effect of oxyphenbutazone in the CFZ -instigated cardiotoxicity. Methodology: Female Wistar Rats weighing 200–250 g selected randomly and grouped as follows: Group 1 designated as the Normal control and receive normal saline only. Group 2 served toxic control and exposed to CFZ (4 mg/kg, intraperitoneally [i.p.]). Group 3 & 4 served as treatment groups and administered with CFZ concomitantly orally fed with oxyphenbutazone at doses of 35 and 70 mg/kg/three times a week, respectively. The total duration of experimental protocol was of 21 days. After completion of the experiments animals subjected to blood collection using light ether anesthesia and serum was separated for biochemical analysis further. The serum levels of Mg+2, Ca+2 and cardiac enzymes (aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB) levels were estimated. Later animals sacrificed and heart tissue isolated for further examinations. Intracellular proteins NFkB and IkBα were estimated by western blot. Results: The serum analysis revealed that CFZ administration significantly elevated the levels of LDH, CK and CKMB in CFZ exposed animals when compared to normal animals while administration of oxyphenbutazone significantly reduced these biochemical changes, Intracellular antioxidant enzymes and NF-kB in treatment groups as compared to disease control animals. Conclusion: Findings of the research protocol suggests significant injuries to cardiac tissues when animals exposed to CFZ and Oxyphenbutazone protected the cardiac tissues.

High-throughput deconvolution of 3D organoid dynamics at cellular resolution for cancer pharmacology with Cellos

Three-dimensional (3D) organoid cultures are flexible systems to interrogate cellular growth, morphology, multicellular spatial architecture, and cellular interactions in response to treatment. However, computational methods for analysis of 3D organoids with sufficiently high-throughput and cellular resolution are needed. Here we report Cellos, an accurate, high-throughput pipeline for 3D organoid segmentation using classical algorithms and nuclear segmentation using a trained Stardist-3D convolutional neural network. To evaluate Cellos, we analyze ~100,000 organoids with ~2.35 million cells from multiple treatment experiments. Cellos segments dye-stained or fluorescently-labeled nuclei and accurately distinguishes distinct labeled cell populations within organoids. Cellos can recapitulate traditional luminescence-based drug response of cells with complex drug sensitivities, while also quantifying changes in organoid and nuclear morphologies caused by treatment as well as cell-cell spatial relationships that reflect ecological affinity. Cellos provides powerful tools to perform high-throughput analysis for pharmacological testing and biological investigation of organoids based on 3D imaging.

Efficiency of Bacillus thuringiensis bioinsecticide in grapevine protection

The problem of contamination of agricultural products with toxic substances is an urgent problem in production. One of the most chemically treated crop is vineyards. Multiple treatments during one growing season have led to the fact that grape plantings have become an accumulator of unsafe chemical plant protection products. Moreover, grapes are consumed fresh. Accordingly, the selection of environmentally friendly pesticides and the replacement of chemicals with biological ones has become a priority for producers of this crop. Our research was devoted to evaluation of bioinsecticide based on entomopathogenic bacteria B. thuringiensis in the system of protecting grapes from pests. Such studies are of great interest and, according to the literature, 90 % of registered insecticides are based on Bacillus thuringiensis . Microorganisms isolated from nature as plant protection agents, when reintroduced into natural conditions, preserve beneficial species in biocenoses. At the same time, they are selective and, while affecting certain harmful objects, do not cause harm to humans and the environment. The purpose of this work was to study the effect of the bioinsecticide Biometch Insecto, WP on grapevine pests: European grape worm ( Lobesia botrana Den. Schiff.) and leafy form of phylloxera ( Viteus vitifolii Fitch.). Biometch Insecto, WP is based on strains of Bacillus thuringiensis var. kurstaki HG207 and Beauveria bassiana HG208. The effect of entomopathogens was compared with the effect of insecticide Bioslip, BW, L, the active ingredient of which is Beauveria bassiana . The results of the research revealed high biological effectiveness (90100 %) of Biometch Insecto, WP in protecting grapevines from pests when applied during the period of mass hatching of European grape worm caterpillars and emergence of phylloxera larvae from galls.

Real life data: follow-up assessment on Spanish Gaucher disease patients treated with eliglustat. TRAZELGA project

BackgroundThe availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients.AimsTo determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice.MethodsWe designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant.Main ResultsThirty patients were enrolled in the study. The median age was 41.5 years and the male–female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy.ConclusionIn summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy.

Real-world clinical outcomes and treatment patterns in patients with MDD treated with vortioxetine: a retrospective study

BackgroundThis study included evaluation of the effectiveness of vortioxetine, a treatment for adults with major depressive disorder (MDD), using patient-reported outcome measures (PROMs) in a real-world setting.MethodsThis retrospective chart review analyzed the care experiences of adult patients with a diagnosis of MDD from Parkview Physicians Group – Mind-Body Medicine, Midwestern United States. Patients with a prescription for vortioxetine, an initial baseline visit, and ≥ 2 follow-up visits within 16 weeks from September 2014 to December 2018 were included. The primary outcome measure was effectiveness of vortioxetine on depression severity as assessed by change in Patient Health Questionnaire-9 (PHQ-9) scores ~ 12 weeks after initiation of vortioxetine. Secondary outcomes included changes in depression-related symptoms (i.e., sexual dysfunction, sleep disturbance, cognitive function, work/social function), clinical characteristics, response, remission, and medication persistence. Clinical narrative notes were also analyzed to examine sleep disturbance, sexual dysfunction, appetite, absenteeism, and presenteeism. All outcomes were examined at index (start of vortioxetine) and at ~ 12 weeks, and mean differences were analyzed using pairwise t tests.ResultsA total of 1242 patients with MDD met inclusion criteria, and 63.9% of these patients had ≥ 3 psychiatric diagnoses and 65.9% were taking ≥ 3 medications. PHQ-9 mean scores decreased significantly from baseline to week 12 (14.15 ± 5.8 to 9.62 ± 6.03, respectively; p < 0.001). At week 12, the response and remission rates in all patients were 31.0% and 23.1%, respectively, and 67% continued vortioxetine treatment. Overall, results also showed significant improvements by week 12 in anxiety (p < 0.001), sexual dysfunction (p < 0.01), sleep disturbance (p < 0.01), cognitive function (p < 0.001), work/social functioning (p = 0.021), and appetite (p < 0.001). A significant decrease in presenteeism was observed at week 12 (p < 0.001); however, no significant change was observed in absenteeism (p = 0.466).ConclusionsUsing PROMs, our study results suggest that adults with MDD prescribed vortioxetine showed improvement in depressive symptoms in the context of a real-world clinical practice setting. These patients had multiple comorbid psychiatric and physical diagnoses and multiple previous antidepressant treatments had failed.

Efficacy and influential factors of hematoporphyrin monomethyl ether mediated photodynamic therapy in the treatment for port-wine stains

BackgroundsHematoporphyrin monomethyl ether mediated photodynamic therapy (HMME-PDT) has emerged as an alternative approach for port-wine stain (PWS), which was primarily treated with pulsed dye laser (PDL). This study was aimed to evaluate the efficacy and safety of HMME-PDT for PWS and to explore influential factors on the efficacy. MethodsA total of 254 patients were enrolled. Patients received an intravenous injection of HMME at 5 mg/kg. Lesion areas were irradiated with 532-nm light for 20–25 min. Efficacy was assessed according to fading of lesions and graded as excellent (≥90 %), good (60 %–89 %), fair (20 %–59 %), or poor (<20 %). Adverse events were recorded. Clinical data were analyzed including gender, age, lesion sub-type, lesion location and number of treatments. ResultsOverall, 72.4 % of patients achieved an effective response, with 27.6% showing excellent efficacy, 24.8 % showing good efficacy and 20.1 % showing fair efficacy. Only 27.6 % showed poor efficacy. Patients under the age of 18 obtained a better efficacy than adults. Lesions in face showed a better therapeutic outcome than those in neck or trunk and extremities. A more effective response was seen in pink type compared with nodular thickening type. Multiple HMME-PDT treatments could improve the clinical response. Lesion location, lesion sub-type, number of treatments were independent influential factors on efficacy. Adverse events included edema, blister, crust, hypopigmentation, hyperpigmentation, pain, itch and burning sensation. No severe systemic side events were observed. ConclusionsHMME-PDT was effective for treating PWS and was safe and well-tolerated by patients. It is worth further investigation in efficacy and safety involving more patients from medical institutions in different regions in China. The optimal treatment parameters and treatment protocols are still being explored in the clinical treatment for PWS.

Multi-media interaction improves the efficiency and stability of the bioretention system for stormwater runoff treatment

Bioretention systems are one of the most widely used stormwater control measures for urban runoff treatment. However, stable and effective dissolved nutrient treatment by bioretention systems is often challenged by complicated stormwater conditions. In this study, pyrite-only (PO), pyrite-biochar (PB), pyrite-woodchip (PW), and pyrite-woodchip-biochar mixed (M) bioretention systems were established to study the feasibility of improving both stability and efficiency in bioretention system via multi-media interaction. PB, PW, and M all showed enhanced dissolved nitrogen and/or phosphorus removal compared to PO, with M demonstrating the highest efficiency and stability under different antecedent drying durations (ADD), pollutant levels, and prolonged precipitation depth. The total dissolved nitrogen and dissolved phosphorus removal in M ranged between 64%–86% and 80%–95%, respectively, with limited organic matter and iron leaching. Pore water, microbial community, and material analysis collectively indicate that pyrite, woodchip, and biochar synergistically facilitated multiple nutrient treatment processes and protected each other against by-product leaching. Pyrite-woodchip interaction greatly increased nitrate removal by facilitating mixotrophic denitrification, while biochar further enhanced ammonium adsorption and expanded the denitrification area. The Fe3+ generated by pyrite aerobic oxidation was adsorbed on the biochar surface and potentially formed a Fe-biochar composite layer, which not only reduced Fe3+-induced pyrite excessive oxidation but also potentially increased organic matter adsorption. Fe (oxyhydr)oxides intermediate product formed by pyrite oxidation, in return, controlled the phosphorus and organic matter leaching from biochar and woodchip. Overall, this study demonstrates that multi-media interaction may enable bioretention systems to achieve stable and effective urban runoff treatment.

A Case Report on Prolonged Response with Trastuzumab Emtansine (T-DM1) in Recurrent Advance Breast Cancer Setting

Breast cancer holds the dubious distinction of being the most prevalent malignant tumor among women worldwide the 5 year survival rate for patients with advanced or metastatic forms of the disease is estimated at a mere 23%, with approximately 20% of cases exhibiting an amplification of the human epidermal growth factor receptor 2 (HER2). HER2 overexpression was linked to a dismal prognosis prior to the advent of targeted HER2 therapies. The introduction of ado-trastuzumab emtansine (T-DM1) has emerged as one of the standard treatment options for HER2-positive breast cancer patients who experience a recurrence or progression of the disease. This case concerns a patient with recurrent metastatic breast cancer who achieved an unusually extended period of time without the disease progressing while on T-DM1 treatment. After experiencing disease progression on multiple treatment lines involving trastuzumab, the patient achieved a nearly complete clinical remission (cCR) with T-DM1 therapy. The availability of cost-effective biosimilars has expanded access to advanced biologic therapies, which were previously limited to a small segment of the population due to the cost barrier.

Synthesis, molecular docking and biological evaluation of 1,2,4-oxadiazole based novel non-steroidal derivatives against prostate cancer

Prostate cancer is one of the most prevalent cancers in men leading to second most death causing cancer in men. Despite the availability of multiple treatment still the prevalence is high for prostate cancer. Steroidal antagonists associated with poor bioavailability, side effects while non-steroidal antagonists show serious side effects like gynecomastia. Therefore, there is a need of potential candidate for the treatment of prostate cancer with better bioavailability, good therapeutic effect and minimal side effects. In the same context, we have designed the series, SP1–SP25 based 3-phenyl-5-styryl-1,2,4-oxadiazole as the core structure. We successfully synthesized all 25 molecules in this series and characterized them using 1H, 13C NMR, and mass spectroscopy. Subsequently, we conducted MTT assays using PC-3 cells and observed that all the compounds exhibited a dose-dependent decrease in cell viability. Notably, compounds SP04, SP16, and SP19 demonstrated a significant decrease in cell viability and exhibited potent activity compared to the other synthesized molecules and standard drug bicalutamide. Among them, SP04 emerged as the one of the most potent compounds with an IC50 value of 238.13 nM and an 89.99 % inhibition of PC-3 cells, compared to synthesized molecules and standard drug bicalutamide.Furthermore, we conducted ROS assays and androgen receptor inhibition assays using the potent compound SP04 and bicalutamide. The results indicated that SP04 increased ROS production and decreased androgen receptor expression dose-dependent manner. Additionally, we conducted a docking study to analyse the interaction patterns within the active site of the androgen receptor. ADMET analysis revealed that all the compounds exhibited favorable physicochemical properties and manageable toxicity profiles.

Factorial survival analysis for treatment effects under dependent censoring.

Factorial analyses offer a powerful nonparametric means to detect main or interaction effects among multiple treatments. For survival outcomes, for example, from clinical trials, such techniques can be adopted for comparing reasonable quantifications of treatment effects. The key difficulty to solve in survival analysis concerns the proper handling of censoring. So far, all existing factorial analyses for survival data have been developed under the independent censoring assumption, which is too strong for many applications. As a solution, the central aim of this article is to develop new methods for factorial survival analyses under quite general dependent censoring regimes. This will be accomplished by combining existing nonparametric methods for factorial survival analyses with techniques developed for survival copula models. As a result, we will present an appealing F-test that exhibits sound performance in our simulation study. The new methods are illustrated in a real data analysis. We implement the proposed method in an R function surv.factorial(.) in the R package compound.Cox.

Dual peptides-modified cationic liposomes for enhanced Lung cancer gene therapy by a gap junction regulating strategy

BackgroundGene therapy for lung cancer has emerged as a novel tumor-combating strategy for its superior tumor specificity, low systematical toxicity and huge clinical translation potential. Especially, the applications of microRNA shed led on effective tumor ablation by directly interfering with the crucial gene expression, making it one of the most promising gene therapy agents. However, for lung cancer therapy, the microRNA treatment confronted three bottlenecks, the poor tumor tissue penetration effect, the insufficient lung drug accumulation and unsatisfied gene transfection efficiency. To address these issues, an inhalable RGD-TAT dual peptides-modified cationic liposomes loaded with microRNA miR-34a and gap junction (GJ) regulation agent all-trans retinoic acid (ATRA) was proposed, which was further engineered into dry powder inhalers (DPIs).ResultsEquipped with a rough particle surface and appropriate aerodynamic size, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs were expected to deposit into the deep lung and reach lung tumor lesions guided by targeting peptide RGD. Assisted by cellular transmembrane peptides TAT, the RGD-TAT-CLPs/ARTA@miR-34a was proven to be effectively internalized by cancer cells, enhancing gene transfection efficiency. Then, the GJ between tumor cells was upregulated by ARTA, facilitating the intercellular transport of miR-34a and boosting the gene expression in the deep tumor.ConclusionOverall, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could enhance tumor tissue penetration, elevate lung drug accumulation and boost gene transfection efficiency, breaking the three bottlenecks to enhancing tumor elimination in vitro and in vivo. We believe that the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could serve as a promising pulmonary gene delivery platform for multiple lung local disease treatments.

THE PATTERN AND CLINICAL PROFILE OF ALOPECIA AREATA. PANORAMIC REVIEW: UPDATE AND ADVANCES ON ETIOPATHOGENESIS, ASSOCIATED FACTORS, DIAGNOSIS, COMPLICATIONS, MANAGEMENT AND PROGNOSIS IN TREATMENT 2023

Introduction: Alopecia areata (AA) is a chronic disorder in which the immune system affects the hair follicles, nails, and occasionally, the retinal pigment epithelium. The characteristic manifestation of alopecia areata encompasses isolated, smooth, non-scarring surfaces of hair loss on the scalp or anywhere with hair growth. Objective: to detail the current information related to alopecia areata, etiology, epidemiology, pathophysiology, histopathology, manifestations, diagnosis, treatment and complications of the condition. Methodology: a total of 48 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 32 bibliographies were used because the other articles were not relevant for this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: alopecia areata, hair loss, hair follicles, hair loss, Janus kinase. Results: The lifetime risk of presenting alopecia areata is approximately 2%, it is the second most frequent non-scarring alopecia, after male and female pattern alopecia. So far no study has shown whether the prevalence of alopecia areata is different between ethnic groups. The first appearance of this alteration is more common between the third and fourth decades of life, however it can occur in any age group. Recent evidence suggests that the origin of the condition is autoimmune, with a significant genetic contribution. This alteration is related to medical and psychiatric comorbidities such as depression, anxiety and different autoimmune disorders. Conclusions: Alopecia areata is an autoimmune condition that generates a sudden and uneven hair loss, affecting any area of the body. Recently, alopecia areata has been interpreted as an autoimmune disease with a genetic substrate. The hair follicles do not suffer permanent damage, which is positive because of the possibility of regrowth. It is of vital importance to know the etiology, epidemiology, pathophysiology, histopathology, manifestations, diagnosis and treatment of the condition. At the moment there is no cure for alopecia areata, however the use of some medications has contributed to the improvement of the symptomatology, there are multiple treatment options available. More studies are needed to treat this condition more adequately. KEY WORDS: alopecia areata, hair follicles, hair loss, Janus kinase.

Preparation of CNTs/SCF reinforcement using multiple continuous surface treatments to achieve synergistic improvement of epoxy resin-based composites interfacial properties: Towards industrial production of carbon fiber surface treatment

The silane/maleimide co-modified waterborne polyurethane (WPU-M-S) sizing agent and furan-functionalized carbon nanotubes (CNTs-FA) were prepared through chemical modification method. The continuous grafting of carbon nanotubes (CNTs) was realized on the carbon fiber surface by multiple continuous surface treatments, including electrochemical anodizing (EAO), sizing, and chemical grafting of CNTs. The stable physical and chemical connection between carbon fiber, sizing agent, and resin was constructed through the preparation of CNTs/SCF reinforcement. The results of different surface treatment processes such as ultrasound and CNTs grafting process were contrastively studied in terms of surface morphology, microstructure, and mechanical properties. It is reflected that carbon fiber grafted with CNTs-FA (CNTs/SCF) that were prepared by ultrasound assisted chemical grafting provide optimal wettability and interfacial performance. The interfacial shear strength (IFSS) and interlaminar shear strength (ILSS) of CNTs/SCF reinforced epoxy resin composites are 115.37 % and 93.91 % higher than those of the untreated carbon fiber (UCF), respectively. The synergistic improvement mechanism of reinforcement on carbon fiber reinforced epoxy resin composites interfacial properties was proposed. This research provides a multiple continuous surface treatment technology that matches the industrial production of carbon fiber to prepare CNTs/SCF reinforcement.

Combination analysis of genome-wide association and transcriptome sequencing identifies tuberous root development-related homeobox transcription factors and functional analysis of IbHB040 in sweetpotato

Homeobox (HB) transcription factors are a large gene family and function as critical regulators in plant growth and development. Here, 134 sweetpotato HBs (IbHBs) were systematically identified from the sweetpotato genome and designated as IbHB001-IbHB134. These IbHBs were unevenly distributed on 15 chromosomes, and multiple segmental duplications were identified between them. Collinearity analysis between IbHBs and HBs from other species revealed the evolution of the HB gene family. The 134 IbHB proteins were categorized into 13 classes based on phylogenetic analysis and conserved motifs, while no members were found in the LD class. Additionally, transcriptome data showed 77 differentially expressed IbHBs, and six IbHBs (IbHB003, IbHB040, IbHB064, IbHB071, IbHB080 and IbHB117) were selected for further analysis. The qRT‒PCR results suggested that the selected IbHBs were variably expressed in different sweetpotato tissues and varied in response to multiple hormone treatments (IAA, indoleacetic acid; ZT, zeatin and ABA, abscisic acid). Moreover, multiple hormone-related and light-responsive cis-elements were detected in IbHB promoters. In addition, multiple complexes between IbHB proteins were predicted and IbHB064, IbHB071, and IbHB080 exhibited transactivation activity in yeasts. The function of IbHB040 in sweetpotato roots was investigated using the sweetpotato root transgenic system, and the results indicated that IbHB040 might regulate tuberous root development by impacting auxin biosynthesis, cell division and SRD1. These findings provide valuable information for further functional investigation of HBs in tuberous root development.

The effect of a mobile education application (MobilMS) developed for multiple sclerosis patients in Turkey on symptom management and quality of life: A randomized controlled study

BackgroundMultiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system (CNS) and is caused by immune dysfunction. MS results in a variety of symptoms that affect physical, emotional, social, and cognitive functioning. Effective symptom management is a critical factor in improving the quality of life (QoL) of patients with MS. PurposeTo determine the effects of a comprehensive mobile education application developed for Turkish patients with MS on symptom management and QoL. MethodsThe study was conducted as a randomized controlled trial and included 63 patients with MS older than 18 years who had an Expanded Disability Status Scale score of ≤6 and were actively using smart phones (intervention group, n = 31; control group, n = 32). Data were collected using a patient information form, the Multiple Sclerosis-Related Symptom (MS-RS) checklist, the Multiple Sclerosis Quality of Life Scale (MSQoL-54), and the Multiple Sclerosis Treatment Adherence Questionnaire (MS-TAQ). The scales were administered three times: at baseline, first month, and third month. Patients with MS in the intervention group were followed up for three months using MobilMS. ResultsIn the intervention group, the mean rating of MobilMS was 8.74±1.29. Most patients indicated that MobilMS was an “informative and useful application”. None of the patients in the study reported any side effects or difficulties when using MobilMS application. The mean MSQL-54 score of the intervention group was significantly higher compared to that of the control group at the first and third months (p = 0.001). The mean scores on the MS-RS checklist (p = 0.985), MS-TAQ subscale, Disease modifying therapies (DMT) barriers (p = 0.237), DMT side effects (p = 0.994), DMT coping strategies (p = 0.469), and Missing Doze Rate (MDR) (p = 0.765) were lower in the intervention group than in the control group, but these results were not statistically significant. ConclusionThe results of the study showed that MobilMS was highly appreciated, accepted, and used by patients with MS. MobilMS has the potential to meet the requirements for a free and accessible symptom management tool for patients with MS. The innovative MobilMS-based education intervention for support and symptom management is recommended as part of supportive care for this patient population. It is hoped that this study will pave the way for future studies on the utility of mobile applications for symptom management in patients with MS.

Reusable Wrinkled Nanoporous Silver Film Fabricated by Plasma Treatment for Surface-Enhanced Raman Scattering Applications.

A nanoporous silver film (npAgF), a promising structure for surface-enhanced Raman spectroscopy (SERS), can be fabricated by using successive O2 and Ar plasma treatments on a planar silver film. The common dealloying method for producing an npAgF involves annealing at high temperatures to produce an alloy film, as well as harsh etching using corrosive chemicals. By contrast, the plasma-based method can be applied directly to various functional substrates to produce more sophisticated npAgF structures. Herein, we report a facile fabrication method for a wrinkled npAgF (w-npAgF) for SERS applications using a thermally contractible polystyrene substrate. The w-npAgF had 3D wrinkles of the nanoporous structure and showed approximately 8 times higher SERS enhancement than did the flat npAgF. Moreover, the w-npAgF could be reused for multiple SERS measurements of different molecules by mild O2 and Ar plasma treatments after each use, in which the O2 plasma effectively removed the adsorbed organic molecules and the Ar plasma reduced silver oxide to pristine silver for subsequent SERS measurements. The wrinkled nanoporous structure was maintained after multiple mild plasma treatments for reuse. The simplicity of plasma-based fabrication and high sensitivity of w-npAgFs are promising features for the green production of low-cost and reusable 3D SERS substrates.

SiRNA-Mediated B7H7 Knockdown in Gastric Cancer Lysate-Loaded Dendritic Cells Amplifies Expansion and Cytokine Secretion of Autologous T Cells.

Gastric cancer, ranked as the fifth most common cancer worldwide, presents multiple treatment challenges. These obstacles often arise due to cancer stem cells, which are associated with recurrence, metastasis, and drug resistance. While dendritic cell (DC)-based immunotherapy has shown promise as a therapeutic strategy, its efficacy can be limited by the tumor microenvironment and certain inhibitory immune checkpoint molecules, such as B7H7. SiRNA-medicated knockdown of B7H7 in tumor cell lysate-pulsed DCs can increase cytokine secretion and autologous T lymphocyte expansion. This study aimed to evaluate the impact of B7H7 suppression in gastric cancer cell lysate-pulsed DCs on the stimulatory potential of autologous CD3+ T lymphocytes. Peripheral blood mononuclear cells (PBMCs) were isolated and monocytes were obtained; then, they were differentiated to immature DCs (iDCs) by GM-CSF and IL-4. Tumor cell lysates from human gastric cancer cell lines were harvested, and iDCs were transformed into mature DCs (mDCs) by stimulating iDCs with tumor cell lysate and lipopolysaccharide. B7H7-siRNA was delivered into mDCs using electroporation, and gene silencing efficiency was assessed. The phenotypic characteristics of iDCs, mDCs, and B7H7-silenced mDCs were evaluated using specific surface markers, an inverted light microscope, and flow cytometry. CD3+ T cells were isolated via magnetically activated cell sorting. They were labeled with CFSE dye and co-cultured with mDCs and B7H7-silenced mDCs to evaluate their ability to induce T-cell proliferation. T-cell proliferation was assessed using flow cytometry. The concentration of TGF-β, IL-4, and IFN-γ secreted from CD3+ T cells in the co-cultured supernatant was evaluated to investigate the cytokine secretory activity of the cells. Transfection of B7H7 siRNA into mDCs was performed in optimal conditions, and the siRNA transfection effectively reduced B7H7 mRNA expression in a dose-dependent manner. SiRNA-mediated B7H7 knockdown in mDCs enhanced maturation and activation of the DCs, as demonstrated by an increased surface expression of CD11c, CD86, and CD40. Co-culture experiments revealed that B7H7-silenced mDCs had more capacity to induce T cell proliferation compared to non-transfected mDCs. The cytokine production patterns of T cells were also altered. Upon examining the levels of TGF-β, IL-4, and IFN-γ released by CD3+ T cells in the co-culture supernatant, we found that silencing B7H7 in mDCs resulted in a rise in IL-4 secretion and a reduction in TGF-β levels compared to mDCs that were not transfected. The study found that suppressing B7H7 expression in DCs significantly enhances their maturation and stimulatory activity when exposed to gastric cancer cell lysate. These B7H7-silenced DCs can substantially increase cytokine production and promote co-cultured T-cell expansion. Consequently, inhibiting B7H7 in DCs may offer a practical strategy to enhance the ability of DCs to initiate T lymphocyte responses and improve the effectiveness of DC-based cell therapy for cancer patients.

Extended peptide receptor radionuclide therapy: evaluating nephrotoxicity and therapeutic effectiveness in neuroendocrine tumor patients receiving more than four treatment cycles.

Currently, the most used peptide receptor radionuclide therapy (PRRT) regimen for neuroendocrine tumors comprises 4 treatment cycles, and there is not enough large-scale data to support the safety of more individualized extended PRRT. This study aims to evaluate the therapeutic effectiveness and potential nephrotoxicity related to PRRT using more than four treatment cycles. In this retrospective analysis, we included patients who had received at least four PRRT cycles and had available follow-up data. We analyzed renal function indicators before and after multiple treatments, comparing nephrotoxicity in patients receiving four cycles ("standard") with those receiving more than four ("extended treatment"). Nephrotoxicity was assessed via creatinine levels and CTCAE creatinine grades. Treatment effectiveness was gauged using Kaplan-Meier survival analysis, focusing on overall survival and disease-specific survival (DSS). Statistical analyses were performed using SPSS version 26 (IBM), R 4.2.3, and GraphPad Prism 9.0.0. Statistical significance was defined as a P-value of less than 0.05. Our study cohort consisted of 281 patients in the standard group and 356 in the extended treatment group. No significant differences in baseline characteristics or renal function were noted between the two groups pre-treatment. Mean post-treatment creatinine levels did not significantly differ between the standard (89.30 ± 51.19μmol/L) and extended treatment groups (93.20 ± 55.98μmol/L; P = 0.364). Similarly, there was no statistical significance between the CTCAE creatinine grades of the two groups (P = 0.448). Adverse renal events were observed in 0.4% of patients in the standard group and 1.1% in the extended treatment group. After a median follow-up time of 88.3months, we found that median overall survival was significantly higher in the extended treatment group (72.8months) compared to the standard treatment group (52.8months). A Cox regression analysis further supported these findings, indicating a better prognosis for the extended treatment group in terms of overall survival (HR: 0.580, P < 0.001) and DSS (HR: 0.599, P < 0.001). Our findings suggest that extending PRRT treatment beyond the standard four cycles may be a safe and effective therapeutic strategy for NET patients. This approach could be particularly beneficial for patients experiencing disease recurrence or progression following standard treatment.

The ‚Target Trial Emulation‘ for CAR-T in the AMNOG

The concept of ‚target trial emulation‘ and propensity score-based adjustment procedures are recommended methods for minimising systematic bias in indirect comparisons without a bridging comparator. Based on the comparison of the single-arm evidence for the CAR-T Ciltacel with data from the LocoMMotion study, which was recognised in the medical community as the best prospective study on the standard of care for multiple myeloma with multiple prior treatments, the application of the concept in the AMNOG is presented. The comparison and the dramatic survival benefit shown with Ciltacel, the validity and clinical significance of which is confirmed by medical experts, contrasts with the complete rejection by the G-BA. This discrepancy is worth looking back on.

Photodynamic Therapy in Treating a Subset of Basal Cell Carcinoma: Strengths, Shortcomings, Comparisons with Surgical Modalities, and Potential Role as Adjunctive Therapy.

Basal cell carcinoma (BCC) is the most common skin cancer, for which there are multiple treatment options, including the gold standard Mohs micrographic surgery (MMS), surgical excision, electrodesiccation and curettage, radiation therapy, cryosurgery, and photodynamic therapy (PDT). While PDT is currently approved for treating actinic keratosis, it has been used off-label to treat BCC patients who may not tolerate surgery or other treatment modalities. We present a review of the efficacy of these modalities and describe important considerations that affect the usage of PDT and MMS. ALA-PDT and MAL-PDT are both efficacious treatment options for lower-risk BCC that can serve as non-invasive alternatives to surgical excision with favorable cosmetic outcomes in patients unsuitable to undergo surgery. In particular, PDT may be considered an adjuvant for the prevention and treatment of BCC lesions in patients with some genetic syndromes such as Gorlin syndrome, and in combination with surgical excision in lesions presenting in certain locations. Limitations to PDT include lack of margin control to prevent recurrence, pain, and cost of certain photosensitizers. Future studies should investigate the role of PDT as adjunctive therapy, standardization of protocols, and causes and ways to address recurrence following PDT treatment.