Efficacy Of Treatment Research Articles

A single-center retrospective chart review of percutaneous PNS for treatment of chronic shoulder pain

ObjectiveThe present IRB-approved retrospective chart review describes the use of a 60-day PNS treatment for shoulder pain at a single center in 60 total consecutive patients. BackgroundChronic shoulder pain affects an increasing number of patients per year and is especially prevalent in elderly populations. Percutaneous peripheral nerve stimulation (PNS) treatment targeting the nerves of the shoulder has been shown to reduce pain in prospective clinical studies and in analysis of real-world data. MethodsData were extracted from the electronic medical records of patients who had previously undergone percutaneous PNS treatment for chronic shoulder pain. Demographic data and treatment characteristics were summarized alongside treatment outcomes. ResultsOverall, 84 % (49/58) of patients reported substantial (≥50 %) pain relief at the end-of-treatment. The records for 2 patients did not include patient-reported percent pain relief. The average indwelling period for leads (i.e., treatment period) was 57 days. Findings on treatment effectiveness were consistent when the patient population was stratified by cause of pain, duration living with pain, and presence of pain-modifying comorbidities. Stimulation paradigms were identified and categorized by the nerve target and stimulation frequency (e.g., motor stimulation, sensory stimulation, or bimodal stimulation). ConclusionsThese results indicate percutaneous PNS is an effective treatment for patients with various shoulder pain histories, and while all stimulation paradigms were effective at reducing pain, patients who received bimodal PNS reported the greatest pain relief. Key limitations of the study included heterogeneous shoulder pain etiologies among patients and sparse availability of long-term follow-up data. These data support existing real-world and prospective clinical evidence on the efficacy of 60-day PNS treatment at treating chronic pain and provide valuable insights into its use in clinical practice.

Colonization of microbiota derived from Macaca fascicularis, Bama miniature pigs, beagle dogs, and C57BL/6J mice alleviates DSS-induced colitis in germ-free mice.

Fecal microbiota transplantation (FMT) is an innovative and promising treatment for inflammatory bowel disease (IBD), which is related to the capability of FMT to supply functional microorganisms to improve recipient gut health. Numerous studies have highlighted considerable variability in the efficacy of FMT interventions for IBD. Several factors, including the composition of the donor microorganisms, significantly affect the efficacy of FMT in the treatment of IBD. Consequently, identifying the functional microorganisms in the donor is crucial for enhancing the efficacy of FMT. To explore potential common anti-inflammatory bacteria with therapeutic implications for IBD, germ-free (GF) BALB/c mice were pre-colonized with fecal microbiota obtained from diverse donors, including Macaca fascicularis (MCC_FMT), Bama miniature pigs (BP_FMT), beagle dogs (BD_FMT), and C57BL/6 J mice (Mice_FMT). Subsequently, mice were treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by MCC_FMT, BP_FMT, BD_FMT, and Mice_FMT, as demonstrated by the prevention of an elevated disease activity index in mice. Additionally, the utilization of distinct donors protected the intestinal barrier and contributed to the regulation of cytokine homeostasis. Metagenomic sequencing data showed that the microbial community structure and dominant species were significantly different among the four groups, which may be linked to variations in the anti-inflammatory efficacy observed in the respective groups. Notably, Lactobacillus reuteri and Flavonifractor plautii were consistently present in all four groups. L. reuteri exhibited a significant negative correlation with IL-1β, and animal studies further confirmed its efficacy in alleviating IBD, suggesting the presence of common functional bacteria across different donors that exert anti-inflammatory effects. This study provides essential foundational data for the potential clinical applications of FMT.IMPORTANCEDespite variations in efficacy observed among donors, numerous studies have underscored the potential of fecal microbiota transplantation (FMT) for managing inflammatory bowel disease (IBD), indicating the presence of shared anti-IBD bacterial species. In the present study, the collective anti-inflammatory efficacy observed across all four donor groups prompted the identification of two common bacterial species using metagenomics. A significant negative correlation between Lactobacillus reuteri and IL-1β was revealed. Furthermore, mice gavaged with L. reuteri successfully managed the colitis challenge induced by dextran sodium sulfate (DSS), suggesting that L. reuteri may act as an efficacious bacterium mediating shared anti-inflammatory effects among variable donors. This finding highlights the utilization of variable donors to screen FMT core bacteria, which may be a novel strategy for developing FMT applications.

Degron-Based bioPROTACs for Controlling Signaling in CAR T Cells.

Chimeric antigen receptor (CAR) T cells have made a tremendous impact in the clinic, but potent signaling through the CAR can be detrimental to treatment safety and efficacy. The use of protein degradation to control CAR signaling can address these issues in preclinical models. Existing strategies for regulating CAR stability rely on small molecules to induce systemic degradation. In contrast to small molecule regulation, genetic circuits offer a more precise method to control CAR signaling in an autonomous cell-by-cell fashion. Here, we describe a programmable protein degradation tool that adopts the framework of bioPROTACs, heterobifunctional proteins that are composed of a target recognition domain fused to a domain that recruits the endogenous ubiquitin proteasome system. We develop novel bioPROTACs that utilize a compact four-residue degron and demonstrate degradation of cytosolic and membrane protein targets using either a nanobody or synthetic leucine zipper as a protein binder. Our bioPROTACs exhibit potent degradation of CARs and can inhibit CAR signaling in primary human T cells. We demonstrate the utility of our bioPROTACs by constructing a genetic circuit to degrade the tyrosine kinase ZAP70 in response to recognition of a specific membrane-bound antigen. This circuit can disrupt CAR T cell signaling only in the presence of a specific cell population. These results suggest that bioPROTACs are powerful tools for expanding the CAR T cell engineering toolbox.

Update on antineutrophil cytoplasmic autoantibody vasculitis in children.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is often organ- or life-threatening in children and impacts them during important periods of psychosocial and physical development. This review covers recent advances in the pathophysiology, diagnosis, management, and outcomes of AAV in children and highlights the ongoing need for funding and increased research collaboration. Recent work has improved our understanding of AAV disease pathogenesis, potentially identifying new biomarkers and therapeutic targets. Collaborative clinical studies have also highlighted the variable manifestations in children and identified potential factors associated with poorer outcomes. Consensus-based treatment guidelines are also appearing, but clinical trials are still essential to better understanding treatment efficacy and safety in children affected by AAV. New, validated outcome measures, including those that are patient-reported, will facilitate these much-needed clinical trials in pediatric AAV. There is a continued need for more rigorous study in pediatric AAV, however, there is certainly excitement with the increase in recent research relevant to the pediatric population.

Long-term atrial arrhythmia characterization and treatment efficacy evaluation using noninvasive echocardiography-based electromechanical cycle length mapping: A case series

Long-term atrial arrhythmia characterization and treatment efficacy evaluation using noninvasive echocardiography-based electromechanical cycle length mapping: A case series

Individual Predictors of Language Treatment Response in Children With Developmental Language Disorder: A Systematic Review.

Treatment response is the degree to which an individual benefits from a treatment. This systematic review sought to identify and synthesize research evidence regarding individual characteristics that predict language treatment response among children with developmental language disorder (DLD). To be eligible for inclusion, articles needed to report results of an oral language treatment program in a group of children aged 4-10 years with identified DLD and also include a quantitative analysis of the relation between one or more pretreatment child characteristics and the outcome of language treatment. Seven databases (Cumulated Index to Nursing and Allied Health Literature, Dissertations and Theses Global, Education Resources Information Center, Linguistics and Language Behavior Abstracts, PsycINFO, Medline, and Web of Science) were searched for articles in June and July 2021, with search updates conducted in May 2023. Studies were categorized by the type of treatment provided, and results were synthesized qualitatively. The review included 31 studies, 1,551 participants with DLD, and over 300 statistical tests of a predictor's effect on language treatment response. Most studies (n = 21) included only monolingual speakers of English, with five studies including bilinguals and five including monolingual speakers of non-English languages. Language treatments targeted word learning in controlled or clinical conditions, grammatical learning in controlled or clinical conditions, or multiple language targets in clinical conditions. Predictors of treatment response are summarized across four categories: cognitive, demographic, pretreatment language levels, and other. There were relatively few significant tests of the predictors of language treatment response. A central limitation of the evidence is that most included studies were designed to consider language treatment efficacy, not predictors of treatment response. Increasing research attention to the question of predictors of language treatment response in children with DLD is needed to enhance treatment and optimize outcomes for individual children. https://doi.org/10.23641/asha.26170006.

Efficacy of dexamethasone implant in the management of chronic central serous chorioretinopathy without choroidal neovascularization.

To demonstrate the treatment efficacy of intravitreal dexamethasone (DEX) implant in chronic recurrent/persistent central serous chorioretinopathy (CSC). Prospective, non-randomized, open-label study. In this study, subjects with chronic CSC without signs of choroidal neovascularization (CNV) received intravitreal DEX implant therapy. The primary outcome measure was the change in visual acuity. Changes in central macular thickness (CMT) and change in subfoveal choroidal thickness (SFCT) on optical coherence tomography (OCT), incidence of recurrent fluid, and safety of DEX implant were secondary outcome measures. Subjects were followed up for a minimum of 3 months after DEX implantation. In total, 20 eyes of 20 subjects (mean age: 47 ± 9 years) with a median disease duration of 23.5 months were enrolled. With a single injection of DEX implant, a reduction in CMT was noted in 90% of eyes. Complete resolution of subretinal and intraretinal fluid was noted in 55% of eyes within 3 months of injection. A significant improvement in vision (mean Log MAR visual acuity 0.66 ± 0.49 vs. 0.54 ± 0.45; P = 0.020), mean CMT (338 ± 110 microns to 238 ± 73 microns; P < 0.001) and SFCT (514 ± 95 microns to 445 ± 111 microns; P < 0.001) was noted over 3 months. Recurrent fluid was noted in 50% of eyes after a mean follow-up duration of 7 ± 4 months. Elevated intraocular pressure, managed by topical therapy, was noted in six eyes. The consistent improvement in visual acuity, fluid resolution, and reduction in choroidal thickness suggests a possible role for DEX implants in managing chronic CSC. A larger randomized trial is warranted.

Cerebellitis following COVID-19 infection: A case-based systematic review and pooled analysis

BackgroundThe COVID-19 pandemic has been linked to neurological complications, including Cerebellitis. This study aims to investigate the clinical features, and consequences of Cerebellitis following COVID-19 infection, informing medical management strategies. MethodsA systematic search was conducted through PubMed, Web of Science, Embase, ProQuest, and Cochrane databases from January 2018 to September 12, 2023, on cases post-COVID-19. Demographics, clinical characteristics, and diagnostic techniques were analyzed using descriptive statistics. Chi-Square tests assessed associations between diagnoses and treatments, with visualizations including heatmaps and scatter plots. ResultsAfter the final Screening, the analysis of 18 cases revealed Cerebellitis post-COVID-19 spanned 9 countries, predominantly from the USA (27.8 %), with a mean patient age of 40.1 years (±24.6). Males comprised 94.4 % of cases. Common underlying conditions included hypertension (22.2 %) and diabetes (11.1 %). Neurological symptoms presented on average 15.15 ± 12.7 days post-COVID-19 infection. A moderate negative correlation (r = −0.358) was observed between age and symptom onset. Blood and CSF biomarkers showed weak correlations with symptom onset intervals. Treatment efficacy varied, with most cases achieving symptom-free outcomes. The Chi-Square test for diagnosis-treatment associations yielded a p-value of 0.089, and for follow-up outcomes, a p-value of 0.283, indicating no significant statistical associations. ConclusionThis systematic review highlights increased reports of Cerebellitis in males in their fourth decade of life, with the highest comorbidities being vascular diseases. Marker assessments show a decrease in CSF protein in half of patients, along with complete recovery following combination treatment with antivirals and steroids in acute Cerebellitis.

Dupilumab in Adults With Moderate to Severe Atopic Dermatitis

Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important. To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD. The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023. At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals. The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline. A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study. In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

Combining app-based behavioral therapy with electronic cigarettes for smoking cessation: a study protocol for a single-arm mixed-methods pilot trial

BackgroundCigarette smoking remains a leading cause of preventable illness and death, underscoring the need for effective evidence-based smoking cessation interventions. Nuumi, a novel smoking cessation program integrating a digital behavioral therapy and an electronic cigarette, may provide a solution.ObjectiveTo investigate the initial efficacy, acceptability and psychological outcomes of an evidence-based smoking cessation intervention comprised of a mobile phone app and an electronic cigarette among adults who smoke and who are motivated to quit.MethodsA prospective 6-month single-arm mixed-methods pilot study will be conducted. Seventy adults who smoke and who are motivated to quit will be recruited via web-based advertisements and flyers. Participants receive access to an app and an electronic cigarette with pods containing nicotine for temporary use of at least 3 months. The electronic cigarette is coupled with the app via Bluetooth, allowing for tracking of patterns of use. The behavioral therapy leverages evidence-based content informed by cognitive behavioral therapy and mindfulness-informed principles. Web-based self-report surveys will be conducted at baseline, at 4 weeks, at 8 weeks, at 12 weeks, and at 24 weeks post-baseline. Semi-structured interviews will be conducted at baseline and at 12 weeks post-baseline. Primary outcomes will be self-reported 7-day point prevalence abstinence from smoking at 12 weeks and 24 weeks. Secondary outcomes will include other smoking cessation-related outcomes, psychological outcomes, and acceptability of the nuumi intervention. Descriptive analyses and within-group comparisons will be performed on the quantitative data, and content analyses will be performed on the qualitative data. Recruitment for this study started in October 2023.DiscussionAs tobacco smoking is a leading cause of preventable morbidity and mortality, this research addresses one of the largest health burdens of our time. The results will provide insights into the initial efficacy, acceptability, and psychological outcomes of a novel mobile health intervention for smoking cessation. If successful, this pilot may generate an effective intervention supporting adults who smoke to quit smoking. The results will inform feasibility of a future randomized controlled trial.Trial Registration German Clinical Trials Register DRKS00032652, registered 09/15/2023, https://drks.de/search/de/trial/DRKS00032652.

Combining app-based behavioral therapy with electronic cigarettes for smoking cessation: a study protocol for a single-arm mixed-methods pilot trial

BackgroundCigarette smoking remains a leading cause of preventable illness and death, underscoring the need for effective evidence-based smoking cessation interventions. Nuumi, a novel smoking cessation program integrating a digital behavioral therapy and an electronic cigarette, may provide a solution.ObjectiveTo investigate the initial efficacy, acceptability and psychological outcomes of an evidence-based smoking cessation intervention comprised of a mobile phone app and an electronic cigarette among adults who smoke and who are motivated to quit.MethodsA prospective 6-month single-arm mixed-methods pilot study will be conducted. Seventy adults who smoke and who are motivated to quit will be recruited via web-based advertisements and flyers. Participants receive access to an app and an electronic cigarette with pods containing nicotine for temporary use of at least 3 months. The electronic cigarette is coupled with the app via Bluetooth, allowing for tracking of patterns of use. The behavioral therapy leverages evidence-based content informed by cognitive behavioral therapy and mindfulness-informed principles. Web-based self-report surveys will be conducted at baseline, at 4 weeks, at 8 weeks, at 12 weeks, and at 24 weeks post-baseline. Semi-structured interviews will be conducted at baseline and at 12 weeks post-baseline. Primary outcomes will be self-reported 7-day point prevalence abstinence from smoking at 12 weeks and 24 weeks. Secondary outcomes will include other smoking cessation-related outcomes, psychological outcomes, and acceptability of the nuumi intervention. Descriptive analyses and within-group comparisons will be performed on the quantitative data, and content analyses will be performed on the qualitative data. Recruitment for this study started in October 2023.DiscussionAs tobacco smoking is a leading cause of preventable morbidity and mortality, this research addresses one of the largest health burdens of our time. The results will provide insights into the initial efficacy, acceptability, and psychological outcomes of a novel mobile health intervention for smoking cessation. If successful, this pilot may generate an effective intervention supporting adults who smoke to quit smoking. The results will inform feasibility of a future randomized controlled trial.Trial Registration German Clinical Trials Register DRKS00032652, registered 09/15/2023, https://drks.de/search/de/trial/DRKS00032652.

A Single Large Center Experience of Medically Treating Impending Compartment Syndrome of Tibia with Deflazacort

Abstract Background: Acute compartment syndrome (ACS) is a rare condition characterized by increased pressure in the closed compartments of the limbs resulting in ischemic tissue necrosis. Most of the patients present following limb fractures. Apart from surgical options such as fasciotomy, which has inherent complication of myonecrosis and severe infection, conservative management with corticosteroids hasshown to be useful. We conducted this study to understand the changes in intra-compartment pressures in ACS after regular monitoring following corticosteroids treatment. Materials and Methods: Consecutive patients of ACS following closed fractures lower limb fractures of tibia or fibula from June 2021 to February 2022 were included. The intra-compartment pressure was measured using a manometer at the time of presentation and after 3, 6, 12, 24, 48, 72, and 96 h of treatment with tab Deflazacort 6 mg × 1 Tablet × Tds. The efficacy of treatment was assessed on the basis of changes in intra-compartmental pressure and improvement in the clinical signs and symptoms of ACS. Results: The study included 60 patients, most (63.3%) suffering from fracture of proximal tibia or fibula (36.7%), presenting with ACS. The mean age was 32.4 ± 8.6 years and most (53%) were males. We observed a statistically significant change (P &lt; 0.05) in the intra-compartment pressures from the baseline to 3 h, 24 h, 48 h, 72 h, and 96 h after corticosteroid treatment. None of these patients suffered from ischemic necrosis or any other complication of ACS. Conclusion: Our results suggest that the timely diagnosis of ACS in patients with lower limb fractures and early initiation of conservative management with corticosteroids can be a mainstay of treatment in these patients. This conservative approach can avoid surgical intervention and reduce the cost of management.

Per- and Polyfluorinated Substances (PFAS); a Literature Review

This literature review aims to assess contemporary research on human exposure to Per- and Polyfluorinated Substances (PFAS) using the PubMed database. A series of research papers were acquired and examined, revealing novel exposure routes (firefighting, blood transfusions), associations with renal cell carcinoma, impact on DNA methylation, and links to pregnancy and early infant health. PFAS is also associated with adiposity, heart disease, and impaired immune response post-vaccination. The literature suggests potential interventions through blood and plasma donations. Limitations in the scope and scale of research, along with gaps in the understanding of the carcinogenic potential of PFAS and the efficacy of interventions in reducing PFAS exposure, were identified. Further public health research should address these gaps and limitations to enhance our understanding and address the negative health outcomes associated with PFAS exposure.

Dysregulation of hepatic one-carbon metabolism in classical homocystinuria: Implications of redox-sensitive DHFR repression and tetrahydrofolate depletion for pathogenesis and treatment.

Cystathionine beta-synthase-deficient homocystinuria (HCU) is a life-threatening disorder of sulfur metabolism. HCU can be treated by using betaine to lower tissue and plasma levels of homocysteine (Hcy). Here, we show that mice with severely elevated Hcy and potentially deficient in the folate species tetrahydrofolate (THF) exhibit a very limited response to betaine indicating that THF plays a critical role in treatment efficacy. Analysis of a mouse model of HCU revealed a 10-fold increase in hepatic levels of 5-methyl -THF and a 30-fold accumulation of formiminoglutamic acid, consistent with a paucity of THF. Neither of these metabolite accumulations were reversed or ameliorated by betaine treatment. Hepatic expression of the THF-generating enzyme dihydrofolate reductase (DHFR) was significantly repressed in HCU mice and expression was not increased by betaine treatment but appears to be sensitive to cellular redox status. Expression of the DHFR reaction partner thymidylate synthase was also repressed and metabolomic analysis detected widespread alteration of hepatic histidine and glutamine metabolism. Many individuals with HCU exhibit endothelial dysfunction. DHFR plays a key role in nitric oxide (NO) generation due to its role in regenerating oxidized tetrahydrobiopterin, and we observed a significant decrease in plasma NOx (NO2 + NO3) levels in HCU mice. Additional impairment of NO generation may also come from the HCU-mediated induction of the 20-hydroxyeicosatetraenoic acid generating cytochrome CYP4A. Collectively, our data shows that HCU induces dysfunctional one-carbon metabolism with the potential to both impair betaine treatment and contribute to multiple aspects of pathogenesis in this disease.

Cellular adaptation to cancer therapy along a resistance continuum.

Advancements in precision oncology over the past decades have led to new therapeutic interventions, but the efficacy of such treatments is generally limited by an adaptive process that fosters drug resistance1. In addition to genetic mutations2, recent research has identified a role for non-genetic plasticity in transient drug tolerance3 and the acquisition of stable resistance4,5. However, the dynamics of cell-state transitions that occur in the adaptation to cancer therapies remain unknown and require a systems-level longitudinal framework. Here we demonstrate that resistance develops through trajectories of cell-state transitions accompanied by a progressive increase in cell fitness, which we denoteas the 'resistance continuum'. This cellular adaptation involves a stepwise assembly of gene expression programmes and epigenetically reinforced cell states underpinned by phenotypic plasticity, adaptation to stress and metabolic reprogramming. Our results support the notion that epithelial-to-mesenchymal transition or stemness programmes-often considered a proxy for phenotypic plasticity-enable adaptation, rather than a full resistance mechanism. Through systematic genetic perturbations, we identify the acquisition of metabolic dependencies, exposing vulnerabilities that can potentially be exploited therapeutically. The concept of the resistance continuum highlights the dynamic nature of cellular adaptation and calls for complementary therapies directed at the mechanisms underlying adaptive cell-state transitions.

Efficacy and safety of direct oral anticoagulants versus warfarin in the treatment of cerebral venous sinus thrombosis.

Given the evolving application and promising outcomes of direct oral anticoagulants (DOACs) in various thromboembolic conditions, we aimed to compare the efficacy and safety of DOACs with warfarin in the post-acute treatment of cerebral venous sinus thrombosis (CVST) using clinical and radiological parameters. A total of 140 CVST patients were enrolled, with 95 receiving warfarin and 45 receiving DOACs as post-acute treatment. Clinical and imaging parameters of the patients in follow-up visits were investigated, including the last modified Rankin Scale (mRS), venousthromboembolic events, CVST recurrence, mortality rate, recanalization status, and hemorrhagic events, to compare the efficacy and safety of treatment between the two groups. At baseline, patients' assessments using two prognostic scores, ISCVT-RS and IN-REvASC, revealed that there was no statistically significant difference in the distribution of prognostic risk categories between the warfarin and DOACs groups. Following acute therapy, patients in the warfarin and DOACs groups were followedup forthemedian of359 and325days, respectively. Analysis to compare the efficacy of warfarin and DOACs revealed no significant difference in last mRS scores, CVST recurrencerate, venousthromboembolic events, and recanalizationstatus between the two groups. Additionally, there was no statistically significant difference in the risk of hemorrhagic events between warfarin and DOACsgroups. Our findings show that DOACs have comparable safety and efficacy in the post-acute treatment of CVST patients; however, large-scalerandomized controlled trials are required to validate our findings.

Impact of proton pump inhibitors on the efficacy of androgen receptor signaling inhibitors in metastatic castration-resistant prostate cancer patients.

Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

Potentiometric ion-selective membrane sensing of microbially induced calcite precipitation

Microbially induced calcite precipitation (MICP) is an emerging biogeotechnical technique that facilitates a bio-cementation process through biomineralisation and which can bond otherwise loose soil particles, thereby increasing the shear strength and stiffness of the soil while decreasing its permeability and compressibility. However, the uniformity of calcite (calcium carbonate) precipitation may have a relatively low ‘certainty of execution’ in situ due to strict environmental conditions required for the reaction, highlighting a strong need for in situ monitoring of the subsurface during and following the treatment. This research explored an electrochemical approach to monitoring MICP treatment through the development and use of potentiometric ion-selective sensors to measure ammonium and calcium ions continuously in both aqueous batch reactors and small laboratory-scale soil test cells. Sensor calibrations indicate a strong and reliable correlation between the electrochemical potential and target ion concentration, which shows promise in sensor technology for monitoring MICP and other similar processes. Improvements to the current design are, however, needed, as fouling due to calcite precipitation, and to some extent biofouling of the sensor, was observed in the highly dynamic, biomineralisation environment, which caused data drift/interference. These effects should be considered in data analysis and eliminated/minimised for eventual adoption towards monitoring the efficacy of MICP treatment in situ.

Knockdown of DJ-1 Resulted in a Coordinated Activation of the Innate Immune Antiviral Response in HEK293 Cell Line

PARK7, also known as DJ-1, plays a critical role in protecting cells by functioning as a sensitive oxidation sensor and modulator of antioxidants. DJ-1 acts to maintain mitochondrial function and regulate transcription in response to different stressors. In this study, we showed that cell lines vary based on their antioxidation potential under basal conditions. The transcriptome of HEK293 cells was tested following knockdown (KD) of DJ-1 using siRNAs, which reduced the DJ-1 transcripts to only 12% of the original level. We compared the expression levels of 14k protein-coding transcripts and 4.2k non-coding RNAs relative to cells treated with non-specific siRNAs. Among the coding genes, approximately 200 upregulated differentially expressed genes (DEGs) signified a coordinated antiviral innate immune response. Most genes were associated with the regulation of type 1 interferons (IFN) and the induction of inflammatory cytokines. About a quarter of these genes were also induced in cells treated with non-specific siRNAs that were used as a negative control. Beyond the antiviral-like response, 114 genes were specific to the KD of DJ-1 with enrichment in RNA metabolism and mitochondrial functions. A smaller set of downregulated genes (58 genes) was associated with dysregulation in membrane structure, cell viability, and mitophagy. We propose that the KD DJ-1 perturbation diminishes the protective potency against oxidative stress. Thus, it renders the cells labile and responsive to the dsRNA signal by activating a large number of genes, many of which drive apoptosis, cell death, and inflammatory signatures. The KD of DJ-1 highlights its potency in regulating genes associated with antiviral responses, RNA metabolism, and mitochondrial functions, apparently through alteration in STAT activity and downstream signaling. Given that DJ-1 also acts as an oncogene in metastatic cancers, targeting DJ-1 could be a promising therapeutic strategy where manipulation of the DJ-1 level may reduce cancer cell viability and enhance the efficacy of cancer treatments.

Factors Associated with Postoperative Recurrence in Stage I to IIIA Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: Analysis of Korean National Population Data.

Recent development in perioperative treatment of resectable non-small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.