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One approach to refining the taste of Sargassum tea involves subjecting it to fermentation to produce Kombucha tea. This study was designed to assess the impact of fermentation duration and various types of sugars on the sensory attributes of Seaweed Kombucha, alongside the physicochemical properties and flavor profile associated with the optimal sugar type and a fermentation duration. Seaweed Kombucha samples were subjected to treatments involving different sugars (sucrose, sorbitol, and steviol) and fermentation duration of 9 days, with sampling intervals at days 0, 3, 5, 7, and 9. The characteristics of Seaweed Kombucha were evaluated based on parameters such as pH, alcohol content, color, total sugar content, and sensory analysis. Utilizing hedonic sensory assessment, the most favorable Seaweed Kombucha sample was identified as the one treated with steviol sugar and fermented for 3 days. The sensory flavor profile of Seaweed Kombucha was elucidated through Check-All-That-Apply (CATA) and Gas Chromatography-Mass Spectrometry (GC-MS) methodologies. The optimal Seaweed Kombucha sample exhibited a volatile compound profile comprising acids, alcohols, ketones, heterocyclic compounds, and other constituents.

Background: Statistics courses are a necessary component of undergraduate education, but psychology majors often have negative associations with statistics. One way to promote learning within classrooms is to promote classroom connectedness, but few studies have examined classroom connectedness using a social network paradigm. Objective: The purpose of this study was to examine the degree of connectivity within the lab component of a statistics course, and test if the networks were associated with psychological constructs related to academic success, specifically, grit and resilience. Method: Using descriptive network analysis and exponential random graph models (ERGMs), we examined the level of connectedness in statistics labs and whether or not students were likely to connect with each other based on sharing similar levels of grit and resilience. Results: Results suggested an overall low degree of connectivity within each lab. However, in the most well-connected lab, students were more likely to connect with other students who had a dissimilar level of grit, but a similar level of resilience. Conclusion: There is high variability between different student networks, although all networks were sparse. Future research could further examine the connection between student connectedness, grit and/or resilience, and how these could connect to student outcomes.

Focused electron beam-induced deposition (FEBID) is a novel technique for the development of multimaterial nanostructures. More importantly, it is applicable to the fabrication of free-standing nanostructures. Experimenting at the nanoscale requires instruments with sufficient resolution and sensitivity to measure various properties of nanostructures. Such measurements (regardless of the nature of the quantities being measured) are particularly problematic in the case of free-standing nanostructures, whose properties must be separated from the measurement system to avoid possible interference. In this paper, we propose novel devices, namely operational micro-electromechanical system (opMEMS) bridges. These are 3D substrates with nanometer-scale actuation capability and equipped with electrical contacts characterised by leakage resistances above 100 GΩ, which provide a platform for comprehensive measurements of properties (i.e., resistance) of free-standing FEBID structures. We also present a use case scenario in which an opMEMS bridge is used to measure the resistance of a free-standing FEBID nanostructure.

The biggest difference in statistical training from previous decades is the increased use of software. However, little research examines how software impacts learning statistics. Assessing the value of software to statistical learning demands appropriate, valid, and reliable measures. The present study expands the arsenal of tools by reporting on the psychometric properties of the Value of Software to Statistical Learning (VSSL) scale in an undergraduate student sample. We propose a brief measure with strong psychometric support to assess students' perceived value of software in an educational setting. We provide data from a course using SPSS, given its wide use and popularity in the social sciences. However, the VSSL is adaptable to any statistical software, and we provide instructions for customizing it to suit alternative packages. Recommendations for administering, scoring, and interpreting the VSSL are provided to aid statistics instructors and education researchers understand how software influences students' statistical learning.

BACKGROUND: Tisagenlecleucel was approved by the Food and Drug Administration (FDA) in 2017 for refractory B-cell acute lymphoblastic leukemia (B-ALL) and B-ALL in ≥2nd relapse. Outcomes of patients receiving commercial tisagenlecleucel upon 1st relapse have yet to be established. We aimed to report real-world tisagenlecleucel utilisation patterns and outcomes across indications, specifically including patients treated in 1st relapse, an indication omitted from formal FDA approval. METHODS: We conducted a retrospective analysis of real-world tisagenlecleucel utilisation patterns across 185 children and young adults treated between August 30, 2017 and March 6, 2020 from centres participating in the Pediatric Real-World CAR Consortium (PRWCC), within the United States. We described definitions of refractory B-ALL used in the real-world setting and categorised patients by reported Chimeric Antigen Receptor (CAR) T-cell indication, including refractory, 1st relapse and ≥2nd relapse B-ALL. We analysed baseline patient characteristics and post-tisagenlecleucel outcomes across defined cohorts. FINDINGS: Thirty-six percent (n = 67) of our cohort received tisagenlecleucel following 1st relapse. Of 66 evaluable patients, 56 (85%, 95% CI 74-92%) achieved morphologic complete response. Overall-survival (OS) and event-free survival (EFS) at 1-year were 69%, (95% CI 58-82%) and 49%, (95% CI 37-64%), respectively, with survival outcomes statistically comparable to remaining patients (OS; p = 0.14, EFS; p = 0.39). Notably, toxicity was increased in this cohort, warranting further study. Interestingly, of 30 patients treated for upfront refractory disease, 23 (77%, 95% CI 58-90%) had flow cytometry and/or next-generation sequencing (NGS) minimum residual disease (MRD)-only disease at the end of induction, not meeting the historic morphologic definition of refractory. INTERPRETATION: Our findings suggested that tisagenlecleucel response and survival rates overlap across patients treated with upfront refractory B-ALL, B-ALL ≥2nd relapse and B-ALL in 1st relapse. We additionally highlighted that definitions of refractory B-ALL are evolving beyond morphologic measures of residual disease. FUNDING: St. Baldricks/Stand Up 2 Cancer, Parker Institute for Cancer Immunotherapy, Virginia and D.K. Ludwig Fund for Cancer Research.

Introduction: The evolving role of Artificial Intelligence (AI) in medicine, particularly in radiology and population-based breast cancer screening programs, offers potential accuracy gains and efficiency improvements. However, successful implementation requires understanding of healthcare workers’ views on AI, which this study aims to explore within the Australian BreastScreen program. Methods: An online survey was distributed to clinical staff involved in breast imaging, collecting responses from November 2022 to April 2023. The survey encompassed demographic information, opinions, and experiences with AI in medical imaging, with questions covering various scenarios of AI integration in BreastScreen. Results: Out of an estimated 350 professionals contacted, 95 responded, with 84.2 % (80/95) being radiologists. Less than half of respondents (44.9 %, 40/89) had worked with artificial intelligence for image classification previously. The majority of radiologists 74.2 % (46/62) thought that the use of AI in reading mammograms for BreastScreen would improve workflow. However, radiologists thought they would behave with increasing caution with scenarios where AI was more autonomous, with the majority of radiologists (63.3 %, 38/60) uncomfortable with holding accountability when the AI was used to triage and remove cases from the workflow. Notably, 60 % of radiologists (36/60) expressed concerns about accountability. Discussion: The findings suggest an optimistic attitude towards AI among Australian healthcare workers, although when given hypothetical scenarios for the way AI could be integrated into BreastScreen, there was increasing caution with scenarios where AI was more autonomous. This study highlights understanding and concerns of healthcare professionals working in population screening which are important to address when implementing AI into the healthcare system.

Objective: Over the decade, variety and effectiveness of contraception methods have greatly improved, resulting in increased popularity of oral contraceptive pills (OCPs). However, hormonal contraception carries the risk of multiple side effects. The lack of sufficient knowledge often leads to the development of health concerns, which can affect patient’s adherence. The aim of our research was to describe a side effect profile of OCPs and assess the most frequent concerns and discontinuation reasons in Polish women. The survey included questions regarding OCPs utilization patterns, side effects, health concerns and attitudes of the responders. Materials and methods: This cross-sectional study was based on a survey, which was distributed online and open from 29 April to 15 May 2022. The survey included questions regarding OCPs utilization patterns, side effects, health concerns and attitudes of the responders. Results: Out of 1699 respondents, the current OCPs intake was reported by two thirds of women and 22% had a history of using them in the past. Seventy-nine percent of all OCPs users experienced adverse effects while 9% reported having concerns about safety and potential adverse effects. Decreased libido and weight gain were the most significant reasons for ceasing hormonal contraception. Moreover, the most common concerns and the most unfavorable side effects varied in different age groups. The occurrence of anxiety depended on age and education. Conclusion: Healthcare professionals prescribing OCPs should provide their patients with comprehensive counseling. Understanding and addressing concerns of young women can improve their compliance and reduce the number of unintended pregnancies.

PURPOSE: Nonresponse and relapse after CD19-chimeric antigen receptor (CAR) T-cell therapy continue to challenge survival outcomes. Phase II landmark data from the ELIANA trial demonstrated nonresponse and relapse rates of 14.5% and 28%, respectively, whereas use in the real-world setting showed nonresponse and relapse rates of 15% and 37%. Outcome analyses describing fate after post-CAR nonresponse and relapse remain limited. Here, we aim to establish survival outcomes after nonresponse and both CD19+ and CD19- relapses and explore treatment variables associated with inferior survival. METHODS: We conducted a retrospective multi-institutional study of 80 children and young adults with B-cell acute lymphoblastic leukemia experiencing nonresponse (n = 23) or relapse (n = 57) after tisagenlecleucel. We analyze associations between baseline characteristics and these outcomes and establish survival rates and salvage approaches. RESULTS: The overall survival (OS) at 12 months was 19% across nonresponders (n = 23; 95% CI, 7 to 50). Ninety-five percent of patients with nonresponse had high preinfusion disease burden. Among 156 morphologic responders, the cumulative incidence of relapse was 37% (95% CI, 30 to 47) at 12 months (CD19+; 21% [15 to 29], CD19-; 16% [11 to 24], median follow-up; 380 days). Across 57 patients experiencing relapse, the OS was 52% (95% CI, 38 to 71) at 12 months after time of relapse. Notably, CD19- relapse was associated with significantly decreased OS as compared with patients who relapsed with conserved CD19 expression (CD19- 12-month OS; 30% [14 to 66], CD19+ 12-month OS; 68% [49 to 92], P = .0068). Inotuzumab, CAR reinfusion, and chemotherapy were used as postrelapse salvage therapy with greatest frequency, yet high variability in treatment sequencing and responses limits efficacy analysis across salvage approaches. CONCLUSION: We describe poor survival across patients experiencing nonresponse to tisagenlecleucel. In the post-tisagenlecleucel relapse setting, patients can be salvaged; however, CD19- relapse is distinctly associated with decreased survival outcomes.

Der folgende Artikel ist als eine Marginalie zu der 2022 erschienenen polnischen Übersetzung des Monumentalwerks Thomas Manns Betrachtungen eines Unpolitischen zu lesen. Im Fokus stehen vor allem die Polen-Erwähnungen in dem Werk. Anhand ausgewählter Zitate kann der politische Diskurs und wichtige Akteure der literarisch-politischen Szene der Zeit näher betrachtet werden. Darunter der kulturpolitische Publizist Carl Jentsch und der westpreußische Schriftsteller Bogumil Golz, der in den 1860ern eine ethnographische Studie über die Deutschen verfasste. Es wird auf Meinungen hingewiesen, die Manns Ansichten zu der Zeit beeinflusst haben konnten. Untersucht werden ebenfalls Manns Aussagen über die preußische Wahlreform und Stellen in seinem Werk, die sich für einen polnischen Übersetzer als gewissermaßen problematisch erwiesen haben. Überdies wird kurz die Annahme des Werks in Polen besprochen, sowie die allgemeine Einstellung des Nachbarlandes zu Manns Oeuvre aus der Zeit des Ersten Weltkrieges.

Chimeric antigen receptor (CAR) T cells provide a therapeutic option in hematologic malignancies. However, treatment failure after initial response approaches 50%. In allogeneic hematopoietic cell transplantation, optimal fludarabine exposure improves immune reconstitution, resulting in lower nonrelapse mortality and increased survival. We hypothesized that optimal fludarabine exposure in lymphodepleting chemotherapy before CAR T-cell therapy would improve outcomes. In a retrospective analysis of patients with relapsed/refractory B-cell acute lymphoblastic leukemia undergoing CAR T-cell (tisagenlecleucel) infusion after cyclophosphamide/fludarabine lymphodepleting chemotherapy, we estimated fludarabine exposure as area under the curve (AUC; mg × h/L) using a validated population pharmacokinetic (PK) model. Fludarabine exposure was related to overall survival (OS), cumulative incidence of relapse (CIR), and a composite end point (loss of B-cell aplasia [BCA] or relapse). Eligible patients (n = 152) had a median age of 12.5 years (range,

PurposeTisagenlecleucel is a CD19-specific chimeric antigen receptor T-cell therapy, US Food and Drug Administration-approved for children, adolescents, and young adults (CAYA) with relapsed and/or refractory (RR) B-cell acute lymphoblastic leukemia (B-ALL). The US Food and Drug Administration registration for tisagenlecleucel was based on a complete response (CR) rate of 81%, 12-month overall survival (OS) of 76%, and event-free survival (EFS) of 50%. We report clinical outcomes and analyze covariates of outcomes after commercial tisagenlecleucel.MethodsWe conducted a retrospective, multi-institutional study of CAYA with RR B-ALL across 15 US institutions, who underwent leukapheresis shipment to Novartis for commercial tisagenlecleucel. A total of 200 patients were included in an intent-to-treat response analysis, and 185 infused patients were analyzed for survival and toxicity.ResultsIntent-to-treat analysis demonstrates a 79% morphologic CR rate (95% CI, 72 to 84). The infused cohort had an 85% CR (95% CI, 79 to 89) and 12-month OS of 72% and EFS of 50%, with 335 days of median follow-up. Notably, 48% of patients had low-disease burden (< 5% bone marrow lymphoblasts, no CNS3, or other extramedullary disease), or undetectable disease, pretisagenlecleucel. Univariate and multivariate analyses associate high-disease burden (HB, ≥ 5% bone marrow lymphoblasts, CNS3, or non-CNS extramedullary) with inferior outcomes, with a 12-month OS of 58% and EFS of 31% compared with low-disease burden (OS; 85%, EFS; 70%) and undetectable disease (OS; 95%, EFS; 72%; P < .0001 for OS and EFS). Grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 21% and 7% overall and 35% and 9% in patients with HB, respectively.ConclusionCommercial tisagenlecleucel in CAYA RR B-ALL demonstrates efficacy and tolerability. This first analysis of commercial tisagenlecleucel stratified by disease burden identifies HB preinfusion to associate with inferior OS and EFS and increased toxicity.

The aim of this work was to determine the influence of chosen biostimulants and microbiological preparations on the yield of sweet corn and the occurrence of Ostrinia nubilalis Hbn, and diseases. In both years of the study, the preparations used in this experiment did not have a statistically significant effect on marketable yield; however, in 2017, the highest weight was observed in the cobs of plants treated with Rizocore and Polyversum WP while the lowest in the cobs treated with RhizoVital 42. The biostimulant Asahi SL and the biological fungicide Serenade ASO proved to be the most effective in protecting sweet corn against cob and shoot infections by fungi of the genus Fusarium. All the preparations reduced the development of the common smut in corn, especially on the cobs. There were no statistically significant differences in cob infection by the O. nubilalis in the combinations treated with different preparations, although the lowest number of cobs damaged by pest in both years were observed on plots treated with Serenade ASO and RhizoVital 42, while the highest on plots treated with Goëmar BM.

The adequate technical condition assessment of key apparatuses is a crucial assumption in the delivery of reliable and continuous electric power to customers [...]

An open-field study evaluated the effects of four biostimulants (Asahi, Optysil, Optycal, and Tytanit) on the yield and chemical composition of two white cabbage cultivars (‘Caraflex’ and ‘Alfredo’). Although the biostimulants did not significantly impact the marketable yield, all treatments led to a significant increase in ascorbic acid content. The influence on dry matter, sugars, phenols, and antioxidant activity varied by cultivar but generally did not result in inferior outcomes compared to the control. The effect on nitrate levels also varied, with Optysil and Asahi showing some adverse effects depending on the cultivar.

Chimeric antigen receptor (CAR) T cells have transformed the therapeutic options for relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia. Data for CAR therapy in extramedullary (EM) involvement are limited. Retrospective data were abstracted from the Pediatric Real World CAR Consortium (PRWCC) of 184 infused patients from 15 US institutions. Response (complete response) rate, overall survival (OS), relapse-free survival (RFS), and duration of B-cell aplasia (BCA) in patients referred for tisagenlecleucel with EM disease (both central nervous system (CNS)3 and non-CNS EM) were compared with bone marrow (BM) only. Patients with CNS disease were further stratified for comparison. Outcomes are reported on 55 patients with EM disease before CAR therapy (CNS3, n = 40; non-CNS EM, n = 15). The median age at infusion in the CNS cohort was 10 years (range,

Abstract Background Endometriosis is a condition that significantly affects the quality of life of about 10 % of reproductive-aged women. It is characterized by the presence of tissue similar to the uterine lining (endometrium) outside the uterus, which can lead lead scarring, adhesions, pain, and fertility issues. While numerous factors associated with endometriosis are documented, a wide range of symptoms may still be undiscovered. Methods In this study, we employed machine learning algorithms to predict endometriosis based on the patient symptoms extracted from 13,933 questionnaires. We compared the results of feature selection obtained from various algorithms (i.e., Boruta algorithm, Recursive Feature Selection) with experts’ decisions. As a benchmark model architecture, we utilized a LightGBM algorithm, along with Multivariate Imputation by Chained Equations (MICE) and k-nearest neighbors (KNN), for missing data imputation. Our primary objective was to assess the model’s performance and feature importance compared to existing studies. Results We identified the top 20 predictors of endometriosis, uncovering previously overlooked features such as Cesarean section, ovarian cysts, and hernia. Notably, the model’s performance metrics were maximized when utilizing a combination of multiple feature selection methods. Specifically, the final model achieved an area under the receiver operator characteristic curve (AUC) of 0.85 on the training dataset and an AUC of 0.82 on the testing dataset. Conclusions The application of machine learning in diagnosing endometriosis has the potential to significantly impact clinical practice, streamlining the diagnostic process and enhancing efficiency. Our questionnaire-based prediction approach empowers individuals with endometriosis to proactively identify potential symptoms, facilitating informed discussions with healthcare professionals about diagnosis and treatment options.

IntroductionCorticotroph pituitary neuroendocrine tumors (PitNETs) develop from ACTH-producing cells. They commonly cause Cushing’s disease (CD), however, some remain clinically silent. Recurrent USP8, USP48, BRAF and TP53 mutations occur in corticotroph PitNETs. The aim of our study was to determine frequency and relevance of these mutations in a possibly large series of corticotroph PitNETs.MethodsStudy included 147 patients (100 CD and 47 silent tumors) that were screened for hot-spot mutations in USP8, USP48 and BRAF with Sanger sequencing, while 128 of these patients were screened for TP53 mutations with next generation sequencing and immunohistochemistry.ResultsUSP8 mutations were found in 41% CD and 8,5% silent tumors, while USP48 mutations were found in 6% CD patients only. Both were more prevalent in women. They were related to higher rate of biochemical remission, non-invasive tumor growth, its smaller size and densely granulated histology, suggesting that these mutation may be favorable clinical features. Multivariate survival analyses did not confirm possible prognostic value of mutation in protein deubiquitinases. No BRAF mutations were found. Four TP53 mutations were identified (2 in CD, 2 in silent tumors) in tumors with size >10mm including 3 invasive ones. They were found in Crooke’s cell and sparsely granulated tumors. Tumors with missense TP53 mutations had higher TP53 immunoreactivity score than wild-type tumors. Tumor with frameshift TP53 variant had low protein expression. TP53 mutation was a poor prognostic factor in CD according to uni- and multivariate survival analyses in spite of low mutations frequency.ConclusionsWe confirmed high prevalence of USP8 mutations and low incidence of USP48 and TP53 mutations. Changes in protein deubiquitinases genes appear to be favorable prognostic factors in CD. TP53 mutations are rare, occur in both functioning and silent tumors and are related to poor clinical outcome in CD.

In vivo recordings in freely behaving animals are crucial to understand the neuronal circuit basis of behavior. Although current multi-channel silicon probes provide unparalleled sampling density, the study of interacting neuronal populations requires the implantation of multiple probes across different regions of the brain. Ideally, these probes should be independently adjustable, to maximize the yield, and recoverable, to mitigate costs. In this work, we describe the implementation of a miniaturized 3D-printed headgear system for chronic in vivo recordings in mice using independently movable silicon probes targeting multiple brain regions. We successfully demonstrated the performance of the headgear by simultaneously recording the neuronal activity in the prelimbic cortex and dorsal hippocampus. The system proved to be sturdy, ensuring high-quality stable recordings and permitted reuse of the silicon probes, with no observable interference in mouse innate behaviors.