Trial Run Research Articles

12255 Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue And Cognitive Impairment In Mice

Abstract Disclosure: R. Dantzer: None. Brain GFRAL Signaling Mediates Chemotherapy-Induced Fatigue and Cognitive Impairment in Mice Brandon Chelette, PhD, Anand Singh, PhD, Robert Dantzer, DVM, PhDDept. of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA Fatigue and cognitive impairments are commonly reported by cancer patients undergoing chemotherapy. The mechanisms of these neurotoxicities are still obscure. We hypothesize that they are mediated by mitokines that are released by cells undergoing mitochondrial stress in response to chemotherapy. For the present study, we have focused on growth differentiation factor 15 (GDF15) which acts in the brain by activating its receptor, GDNF family receptor alpha-like (GFRAL). Chemotherapy-induced fatigue was assessed by reduced voluntary wheel running. Cognitive impairment was assessed by altered performance in the Puzzle Box Test that measures executive function. We first checked whether commonly used chemotherapeutic drugs can induce GDF15. Mice were injected with cisplatin, paclitaxel, or bortezomib, and their effects on plasma levels of GDF15 were measured 24 h after (ELISA). Cisplatin was used in the following experiments in the form of one or two cycles of daily injections for five days with a rest of five days between cycles. To determine whether GFRAL mediates the effects of cisplatin on wheel running and performance in the puzzle box, mice were injected with a neutralizing antibody targeted to GFRAL (GFRALna) during or after cisplatin treatment. All studies were carried out in male and female C57BL/6 J mice using a 2 (+ chemotherapy) x 2 (+ GFRALna) factorial design with a minimum of 6 mice/group. Mitochondrial dysfunction was measured via Seahorse XF Analyzer Mito Stress Test. To determine whether activation of the GDF15/GFRAL axis recruits a central GDF15 compartment, Gdf15 mRNA was measured by qRT-PCR in the brain parenchyma, meninges, and choroid plexus. All the chemotherapeutic agents we tested induced statistically significant increases in circulating GDF15. GFRALna administered during cisplatin treatment (prevention) or after completion of cisplatin treatment (cure) abrogated cisplatin-induced decrease in wheel running and the deficit displayed by cisplatin-treated mice in the first hard trial run in the puzzle box. GFRALna also blocked the decrease in maximal oxygen consumption rate of mitochondrial in synaptosomes from cisplatin-treated mice. Cisplatin did not induce Gdf15 mRNA in the brain parenchyma but increased its expression in the meninges and choroid plexus. Although the role of this GDF15 brain compartment in the neurotoxicity of cisplatin remains to be determined, the present findings can be interpreted to suggest that GDF15-GFRAL signaling represents a new target for the treatment of chemotherapy-induced fatigue and cognitive impairment. Count: 2,246 characters Presentation: 6/1/2024

Identifying trials run in India that are registered in other clinical trial registries: a cross-sectional study

BackgroundClinical trials play a crucial role in biomedical research, and it is important to register them in public registries to ensure transparency and prevent research waste. In this study, we wished to determine what steps need to be taken to identify every clinical trial run in India that has been registered in any of the (non-Indian) World Health Organization-recognised primary registries. Of the 16 registries, we studied all except that of the European Union, which will be studied separately.MethodsTwo methodologies were employed for each registry, except for four that did not facilitate one or the other method. Methodology A involved downloading all the records in a registry and querying them. Methodology B involved conducting a search via the registry website.ResultsOnly four registries provided consistent results with both methodologies. Seven registries had different results from the two methodologies. Of these, in four cases, in Methodology A one field indicated that the study ran in India, while another indicated otherwise.ConclusionsThe above-mentioned ambiguities should be addressed by the concerned registries. Overall, this study reinforces the need for improved data accuracy and transparency in clinical trial registries and emphasizes the importance of resolving complications faced by users while navigating the registries. Ensuring accurate and comprehensive registration of clinical trials is essential for meta-research and the use of such data by a variety of stakeholders.

Research on cooperative operation optimization method of internet data center alliance considering diversified flexibility

With the rapid development of large-scale internet data center in China, the goal of carbon peak and carbon neutrality has put forward higher requirements for low-carbon economic operation of internet data center. Considering complementary advantages among internet data centers, this paper proposes a cooperative operation optimization method of internet data center alliance based on diversified flexibility. Firstly, a cooperative operation structure of alliance considering electricity and carbon trading between members was built, as well as the diversified flexibility model considering carbon capture and power to gas device. Then, a cooperative optimization operation model of alliance was constructed based on Nash bargaining theory, and the allocation of cooperation benefit among members can be realized based on electrical carbon contribution rate. In order to improve solution convergence, the alternating direction multiplier method is improved by penalty factor updating and correction factor modeling method. Finally, the proposed method is applied to the demonstration project of “East Data and West Computing” in Qingyang, Gansu, China, and the trial run results are consistent with the theory analysis. On the one hand, the diversified flexibility and the electricity and carbon trading between members can effectively reduce the total cost and carbon emissions of alliance. On the other hand, the cooperation benefits distribution strategy based on the electrical carbon contribution rate can effectively enhance enthusiasm of members to participate in alliance. The improved alternating direction multiplier method can achieve distributed optimization of alliance, protect the privacy of each member, and has good convergence and scalability.

Effect of synthetic CT on dose-derived toxicity predictors for MR-only prostate radiotherapy.

Toxicity-driven adaptive radiotherapy (RT) is enhanced by the superior soft tissue contrast of magnetic resonance (MR) imaging compared with conventional computed tomography (CT). However, in an MR-only RT pathway synthetic CTs (sCT) are required for dose calculation. This study evaluates 3 sCT approaches for accurate rectal toxicity prediction in prostate RT. Thirty-six patients had MR (T2-weighted acquisition optimized for anatomical delineation, and T1-Dixon) with same day standard-of-care planning CT for prostate RT. Multiple sCT were created per patient using bulk density (BD), tissue stratification (TS, from T1-Dixon) and deep-learning (DL) artificial intelligence (AI) (from T2-weighted) approaches for dose distribution calculation and creation of rectal dose volume histograms (DVH) and dose surface maps (DSM) to assess grade-2 (G2) rectal bleeding risk. Maximum absolute errors using sCT for DVH-based G2 rectal bleeding risk (risk range 1.6% to 6.1%) were 0.6% (BD), 0.3% (TS) and 0.1% (DL). DSM-derived risk prediction errors followed a similar pattern. DL sCT has voxel-wise density generated from T2-weighted MR and improved accuracy for both risk-prediction methods. DL improves dosimetric and predicted risk calculation accuracy. Both TS and DL methods are clinically suitable for sCT generation in toxicity-guided RT, however, DL offers increased accuracy and offers efficiencies by removing the need for T1-Dixon MR. This study demonstrates novel insights regarding the effect of sCT on predictive toxicity metrics, demonstrating clear accuracy improvement with increased sCT resolution. Accuracy of toxicity calculation in MR-only RT should be assessed for all treatment sites where dose to critical structures will guide adaptive-RT strategies. Patient data were taken from an ethically approved (UK Health Research Authority) clinical trial run at Guy's and St Thomas' NHS Foundation Trust. Study Name: MR-simulation in Radiotherapy for Prostate Cancer. ClinicalTrials.gov Identifier: NCT03238170.

Comparison of aspiration catheter performance using adaptive pulsatile aspiration in an in vitro thrombectomy model.

Aspiration with a pump or syringe is a mainstay of mechanical thrombectomy (MT) for acute ischemic stroke (AIS), but this technology has seen minimal evolution. Non-continuous adaptive pulsatile aspiration (APA) has been proposed as a potential alternative to standard continuous aspiration as a means of improving revascularization efficiency. Using a pathophysiological flow bench model with a synthetic clot, we performed in vitro thrombectomies using the ALGO® Von Vascular, Inc. (Sunrise, FL) APA pump. A total of 25 FDA-approved aspiration catheters were tested, representing inner diameters (ID) from 0.035 in. to 0.088 in. The pump was used in 30 trials with each catheter to remove a simulated M1 occlusion. Revascularization, clot ingestion, time to clot removal, and distal embolization were measured. Among catheters tested using APA, first-pass TICI 3 revascularization was achieved in 100% of the 750 thrombectomy trials using 25 different catheters. There were no distal emboli detected in any trial run. Complete clot ingestion into the pump collection chamber was achieved in 87% to 100% of trials (overall 95%) with clot in the remaining trials corking within the catheter and removed from the model. Time from clot contact to clot removal ranged from 11 s to 90 s (mean 22.6 s, SD 16.8 s), which was negatively correlated with catheter ID (p = 0.007). APA via the Von Vascular, Inc. ALGO® pump achieved a high success rate in an in vitro MT model. All catheters tested with the pump achieved complete reperfusion in all trials, and complete clot ingestion into the pump was seen in a majority of trials. The promising in vitro performance of APA using multiple catheters warrants future in vivo investigation.

Calculating Load and Intensity Using Muscle Oxygen Saturation Data.

The study aimed to calculate training intensity and load using muscle oxygen saturation (SmO2) during two differentiated physical tasks. 29 university athletes participated in a 40-m Maximal Shuttle Run Test (MST, 10 × 40-m with 30 s recovery between sprints) and a 3000-m time trial run. Distance and time were used to calculate external load (EL). Internal load indicators were calculated based on percentage of maximum heart rate (%HRMAX) and SmO2 variables: muscle oxygen extraction (∇%SmO2) and the cardio-muscle oxygen index (CMOI) was also provided by relating ∇%SmO2 ÷ %HRMAX, and the training load were calculated as the product of speed (m/min × IL) and the efficiency index [Effindex (m/min ÷ IL)]. A student t test was applied based on Bayesian factor analysis. As expected, EL differed in the 40-m MST (331 ± 22.8) vs. 3000-m trials (222 ± 56.8) [BF10 = 6.25e+6; p = <0.001]. Likewise, IL showed higher values in 40-m MST (39.20 ± 15.44) vs. 3000-m (30.51 ± 8.67) in CMOI: [BF10 = 1.70; p = 0.039]. Training load was greater in 40-m MST (85.77 ± 27.40) vs. 3000-m (15.55 ± 6.77) [(m/min × ∇%SmO2): BF10 = 12.5; p = 0.003] and 40-m MST (129.27 ± 49.44) vs. 3000-m (70.63 ± 32.98) [(m/min × CMOI): BF10 = 169.6; p = <0.001]. Also, the Effindex was higher in 40-m MST (10.19 ± 4.17) vs. 3000-m (6.06 ± 2.21) [(m/min × ∇%SmO2): BF10 = 137.03; p = <0.001] and 40-m MST (9.69 ± 4.11) vs. 3000-m (7.55 ± 1.87) [(m/min × CMOI): BF10 = 1.86; p = 0.035]. This study demonstrates calculations of training intensity and load based on SmO2 as an internal load indicator along with speed as an external load indicator during two differentiated exercises.

Diversifying Quranic revision methods using gamification-based teaching material for tahfiz education

This study discusses the development procedure of the global tahfiz game (GTG) as a teaching aid for the Quranic revision subject for tahfiz students based on the gamification concept. Comprehensive design and development research (DDR) was used as the research method. The analysis includes conceptual and material development, expert evaluation, testing, and the final product. The development of concepts and materials used in this gamification was based on the theoretical framework of mechanics, dynamics, and aesthetics (MDA), with the application of tahfiz education elements. To examine the ability of GTG prototype to tackle the users’ needs, we have conducted the usability analysis. The expert teacher's mean score for the trial run on this gamification was high at 4.85. The trial run score for student participants was also high (4.45). The result demonstrated that most of the constructs are perceived at a high level by respondents. Thus, this indicated the high usability of GTG to be used as a teaching aid for a Quranic revision subject. The gamification of Quranic tahfiz based on board games has been finalized through recommendations and improvements based on the evaluation. The study findings are expected to be useful for educational institutions or researchers in developing teaching materials using the MDA framework for gamification, particularly in the field of Islamic education.

Near-Optimal Scheduling for IC Packaging Operations Considering Processing-Time Variations and Factory Practices

Due to the short life cycles of electronic products, trial run lots of new products are crucial in IC packaging for production verification and engineering adjustments. The processing time of trial run lots may differ significantly from production lots due to engineering adjustments and is difficult to predict without sufficient historical data. The purpose of this paper is to develop a framework for near-optimal scheduling of IC packaging considering processing time variations and factory practices. Using an orthogonal greedy algorithm and recurrent neural network, this framework extracts key features and predicts the processing times of trial run lots and production lots for each operation using these algorithms. After formulating the scheduling problem in an integer linear programming form, an ordinal optimization method is embedded within the decomposition and coordination framework to obtain dynamic and near-optimal schedules in a computationally efficient manner. This approach can improve the efficiency of IC packaging and potentially other operations by optimizing lot scheduling, reducing production tardiness, and increasing productivity in the factory, paving the way for self-optimizing factories in the future.

Multimodal bird information retrieval system

Multimodal bird information retrieval system can help people popularize bird knowledge and help bird conservation. In this paper, we use the self-built bird dataset, the ViT-B/32 model in CLIP model as the training model, python as the development language, and PyQT5 to complete the interface development. The system mainly realizes the uploading and displaying of bird pictures, the multimodal retrieval function of bird information, and the introduction of related bird information. The results of the trial run show that the system can accomplish the multimodal retrieval of bird information, retrieve the species of birds and other related information through the pictures uploaded by the user, or retrieve the most similar bird information through the text content described by the user.

Real‐time XFEL data analysis at SLAC and NERSC: A trial run of nascent exascale experimental data analysis

SummaryX‐ray scattering experiments using free electron lasers (XFELs) are a powerful tool to determine the molecular structure and function of unknown samples (such as COVID‐19 viral proteins). XFEL experiments are a challenge to computing in two ways: (i) due to the high cost of running XFELs, a fast turnaround time from data acquisition to data analysis is essential to make informed decisions on experimental protocols; (ii) data‐collection rates are growing exponentially, requiring new scalable algorithms. Here we report our experiences analyzing data from two experiments at the Linac Coherent Light Source (LCLS) during September 2020. Raw data were analyzed on NERSC's Cori XC40 system, using the Superfacility paradigm: our workflow automatically moves raw data between LCLS and NERSC, where it is analyzed using the software package CCTBX. We achieved real time data analysis with a turnaround time from data acquisition to full molecular reconstruction in as little as 10 min—sufficient time for the experiment's operators to make informed decisions. By hosting the data analysis on Cori, and by automating LCLS‐NERSC interoperability, we achieved a data analysis rate which matches the data acquisition rate. Completing data analysis within 10 min is a first for XFEL experiments and an important milestone if we are to keep up with data‐collection trends.

A Designing of Wushu Moment Choreography to Three Individual Sparring Events

Background and Aim: Currently, the Taolu movement choreography arrangement has no creativity, which reduces the enjoyment of the competition. Therefore, this research was to design wushu movement choreography for a three-individual sparring event under the competition rules, to get a higher score in the competition. Materials and Methods: The participants in this research were 36 athletes from the top twelve teams in the three-individual boxing of wushu sparring event of the 14th National Games wushu Taolu qualification 2021, 10 wushu Taolu experts and 10 wushu referees. The researcher designed the arrangement of wushu movement choreography for three individual sparring events, through expert interviews and analysis of video competition, and the IOC value was 0.87. To confirm the efficiency of wushu movement choreography, the wushu Taolu three-individual sparring event performance was already conducted by using the designed wushu movement choreography. Then, comparing the result of the scoring of two group referees, by using an independent t-test, to confirm the efficiency of the designed wushu movement choreography. Results: The average scores with the ratings by the two groups of referees were insignificant. The wushu movement choreography in wushu three-individual sparring events designed by the researcher was effective, and it can lead to higher scores in three-individual sparring events competitions. Conclusion: Results of the trial run of the designed wushu movement choreography in three- individual sparring events, by two groups of wushu referees rating score showed that the ratings of the two groups of referees do not differ. The wushu movement choreography designed by the researcher for three individual sparring events is effective.

ANALYSIS OF PIPE NETWORK OPTIMIZATION FOR RAW WATER IN JABUNG SUB-DISTRICT, MALANG DISTRICT

Jabung District is a sub-district located in the Malang Regency area of 135.89 km2 or around 4.56 percent of the total area of Malang Regency. This sub-district consists of 15 villages, including Argosari, Gadingkembar, Gunungjati, Jabung, Kemantren, Kemiri, Kenongo, Ngadirejo, Pandansari Lor, Sidomulyo, Sidorejo, Slamparejo, Sukolilo, Sukopuro, and Taji. With a population of 74,311 people in 2020, with a population density of 592 people/km2. In Jabung District, especially in 4 villages, including Pandansari Lor Village, Gading Kembar Village, Argosari Village, and Kemiri Village, there is currently a water shortage. Siuk Source Potential has water potential large enough to meet the standard needs in these 4 villages by gravity. From the results of instantaneous discharge measurements during the dry season in 2021, it can be seen that the discharge in Sumber Siuk is 65 l/sec, and the planned collection to fulfill these 4 villages is 20 l/sec. Construction of the broncaptering and raw water distribution network was built in 3 stages. Before the physical implementation of the installation of distribution pipes in stage 3, a trial run was carried out from stage 1 and stage 2.

Postural adjustments and perceptual responses of Nordic running: concurrent effects of poles and irregular terrain.

In the natural environment, humans must continuously negotiate irregular and unpredictable terrain. Recently, the poles have been extensively used during trial running events. However, we know little about how humans adjust posture and bilateral coordination to use poles in irregular terrain. Here, we compared kinematics, bilateral coordination and perceptual responses between regular (compact dust) and irregular terrain (medium-length grass) during running at preferred speed with and without poles. In this transversal observational study, thirteen young healthy adults (8 men; mean ± SD; age 29.1 ± 8.0years, body mass 76.8 ± 11.4kg; height 1.75 ± 0.08m) were evaluated during running at a self-selected comfortable speed with and without poles on regular and irregular terrains. Our results show that, despite more flexed pattern on lower-limb joints at irregular terrain, the usage of poles was not enough to re-stabilize the bilateral coordination. Also, the perceived exertion was impaired adding poles to running, probably due to more complex movement pattern using poles in comparison to free running, and the invariance in the bilateral coordination. Besides the invariability of usage poles on bilateral coordination and lower-limb kinematics, the runners seem to prioritize postural stability over lower limb stiffness when running in medium-length grass given the larger range of ankle and knee motion observed in irregular terrain. Further investigations at rougher/hilly terrains will likely provide additional insights into the neuromotor control strategies used to maintain the stability and on perceptual responses using poles during running.

Approbation of the test stand for piston hydraulic cylinders

Test of the end production in the mechanic engineering requires extensive energy consumption which is often lost irrevocably during testing processes and inflict damage on environment. Thus, issues of energy conservation during testing processes become actual. The most productive way of energy conservation during the process of machine testing is recuperation of energy. The objective of the present article is to confirm of the proposed theory about the possibility of recuperating part of the energy while testing piston hydraulic cylinders. Piston hydraulic cylinders are actively used in machines’ hydraulic drive and various stationary production equipment. Operating time to failure of the hydraulic cylinder is usually regulated by a manufacturing plant and commonly includes number of working cycles or general piston’s motion distance. To achieve the stated objective, the structure of the test stand for a trial run of piston hydraulic cylinders. The principal diagram is also developed. On the basis of the theory of volume stiffness, the simulation of test stand’s operation is made. The software program is developed using the software package SimInTech. The preliminary calculations of test stand’s functioning are made. Its operating factors are obtained.

Jungle Math: An Educational Mobile Games for Preschoolers Learning Mathematics

This project is about developing an educational game for kindergarten children. Educational games for kids are designed to teach important concepts such as numbers, letters, colours, shapes, and more in a fun and engaging way. They can also help develop important skills such as problem-solving, critical thinking, and creativity. Mathematics is a challenging subject for most children at an early age, especially preschoolers. This is due to the lack of understanding, interest, and successful ways to help them learn. Typically, mathematical games are presented with an emphasis on entertainment or education. Games can be an effective way to teach children mathematics. They can also help foster a positive attitude towards the subject, which can lead to better learning outcomes. Thus, creating an educational mobile game would be an excellent solution to this problem. This project aims to create a mobile game that can be installed on mobile phones or tablets to teach children mathematics. The RAD (Rapid Application Development) model will be used as the project methodology to conduct this project. First, the functional requirements were determined. Then, the prototype was developed and named Jungle Math. A field usability test was conducted with the targeted users to evaluate the application's ease of use. The findingssuggest that the application is ready to be used in a learning and fun environment for kindergarten children upon the success of the trial run, as the targeted users found the application easy to use and enjoyed playing and learning with the application.

Similar effectiveness with primary HPV and cytology screening - Long-term follow-up of randomized cervical cancer screening trial

BackgroundLong-term effects of primary human papillomavirus (HPV) screening on cervical cancer incidence and mortality are still missing. We conducted a long-term follow-up of the Finnish randomized HPV screening trial, the first HPV screening trial run within the routine screening program, to assess these measures. MethodsDuring 2003–2008, over 236,000 individuals were randomized (1:1) to HPV and cytology screening arms in Southern Finland. To compare the study arms, we calculated the cervical cancer incidence and mortality rate ratios using Poisson regression. ResultsDuring a total of 3.5 million person-years of follow-up, we observed 129 cervical cancers and 32 cervical cancer deaths in the cytology arm, 139 cervical cancers and 32 cervical cancer deaths in the HPV arm. Compared to the cytology arm, in the HPV arm, the incidence rate ratio was 1.08 (95% CI 0.85–1.37), and the mortality rate ratio was 1.01 (95% CI 0.61–1.64). ConclusionsWe studied the effects of HPV screening on both cervical cancer incidence and mortality for the first time in a setting with an already well-established, high-quality cytology screening program. In this kind of setting with a low incidence of cervical cancer, HPV and cytology screening showed similar effectiveness. HPV screening provides, however, an objective, validated test system and enables self-sampling which can improve screening coverage. More attention is needed yet to ensure the balance between the harms and benefits of HPV screening.

Failure analysis on premature perforation of multiple effect evaporators in vacuum salt making system

Multiple effect evaporators (MEEs) are extensively utilized across diverse industries, such as pulp and paper, sugar, and desalination, for the purpose of concentration and purification. Nevertheless, MEEs often bring forth the issue of corrosion because of severe service conditions, thereby leading to equipment damage and decrease in efficiency. This study scrutinizes the premature perforation and corrosion of some multiple effect evaporators encountered soon after their commencement in a salt processing plant. The failed MEEs, designed to serve for 15 years, underwent severe corrosion and the emergence of multiple leakage points during a trial run of 40 days, with only 18 days of actual operation. To unearth the reasons for this failure, various macroscopic and microscopic analyses were carried out. The studies demonstrated that welding defects not found in time during the fabrication of evaporators reduced the corrosion resistance of the composite plate. Additionally, improper welding during the maintenance made the repair ineffective. Once the stainless-steel cladding layer was damaged, the carbon steel backing layer corroded and perforated rapidly under galvanic corrosion. Based on these findings, effective countermeasures were suggested to evade any future failures of the same kind. The outcomes of this analysis are likely to aid in enhancing the operational safety and reliability of multiple effect evaporators in vacuum salt-making systems.

Pediatric Patients with High-Risk B-Cell ALL in First Complete Remission May Benefit from Less Toxic Immunotherapy with Blinatumomab - Results from Randomized Controlled Phase 3 Trial AIEOP-BFM ALL 2017

Background: One of the key questions in trial AIEOP-BFM ALL 2017 focused on the reduction of treatment-related complications by replacing parts of the highly intensive consolidation phase by two courses of Blinatumomab (Blina) in a prospective randomized trial. Herein, we report the toxicity profile of B-cell acute lymphoblastic leukemia (B-ALL) patients (pts) with high-risk (HR) characteristics pending final outcome data. Patients and Methods: 728 pts with HR B-ALL were enrolled from July 15, 2018 to October 31, 2022 in this multicenter trial run in 8 different countries. Patients were included in the HR group in view of the presence of at least one of the following criteria: induction failure; high levels of minimal residual disease (MRD) at day 15 of induction, or at the end of induction (EOI), or at the end of consolidation (EOC); presence of KMT2A::AFF1, of IKZF1+ and positive MRD at EOI (Stanulla et al, JCO 2018), TCF3::HLF, or hypodiploidy. B-ALL pts with one or several of these characteristics represented 20.8% of all pts aged 0-18 years of age with B-ALL. After a 4-drug induction phase, and two weeks of consolidation treatment, patients were randomized to receive Bortezomib in addition to standard consolidation (not part of this report). Before treatment continued with intensive consolidation block HR-1', MRD was analyzed in order to identify patients eligible for subsequent hematopoietic stem cell transplantation (HSCT) based on MRD results. After block HR-1', all B-ALL HR pts were randomized to receive either two courses of consolidation (blocks HR-2', and HR-3'), or two 28-day courses of Blina at 15µg/m 2/d administered by continuous IV infusion (with a 2-week treatment-free interval). Two intrathecal injections of methotrexate (MTX) for CNS prophylaxis were given on days 1 and 29 of each Blina course, respectively. Out of 728 HR B-ALL pts, 619 pts were eligible for randomization [reasons for non-eligibility were: Event (death or relapse) before randomization was due (26), Down syndrome (25; scheduled for a non-randomized intervention with Blina), presence of TCF3::HLF (3; could receive any alternative therapy including Blina), discontinuation/substantial change of preceding therapy (23) or other protocol exclusion criteria (32)]. 572 pts were randomized (92.4% of those eligible). One pt assigned to the experimental arm (EA) and 4 pts assigned to the control arm (CA) received the other arms, respectively. Results: Toxicity was evaluated in randomized pts according to treatment administered during the randomized phase, respectively, until next element started: 268 pts were treated in the control and 281 in the EA (see Table). 16 of them switched in/after the first Blina cycle to the HR blocks due to toxicity or poor response to Blina (due to increasing MRD, &amp;gt;=1x10 -4). Medically relevant adverse reactions of special interest (ARSI) according to MedDRA (specified in the protocol) were evaluated in the randomized treatment phases (CA: HR-2‘/HR-3‘ block, EA: 2 Blina cycles). ARSI were recorded in 61 of 268 pts in the CA (22.8%, 71 ARSI) and in 29 of 281 pts in the EA (10.3% [p&amp;lt;0.001], 33 ARSI); 3 of the 33 ARSI in the EA were related to HR blocks and were observed in 3 of the 16 pts that switched to HR blocks. Life-threatening SAR were seen in 14 pts of the control group (5.2%) and in no patient in the EA (p&amp;lt;0.001). Conclusions: Taken together, these results show for the first time in newly diagnosed pts with HR B ALL, the favorable toxicity profile previously reported with Blinatumomab in pediatric relapsed ALL (Locatelli F et al, JAMA 2021; Brown P et al, JAMA 2021). We have demonstrated that the toxicity profile of Blinatumomab is much more favorable as compared to the intensive chemotherapy approach using HR-blocks. If upcoming analyses of outcome data will show no inferiority of the EA, blinatumomab replacement of some of the intensive chemotherapy blocks will become the new standard of care for treatment if newly diagnosed patients with HR B-ALL.

Evaluating the impact of an information-based education and training platform on the incidence, severity, and coping resources status of workplace violence among nurses: a quasi-experimental study

BackgroundWorkplace violence among nurses has emerged as a critical issue, posing a significant threat to their occupational safety. Education and training are the primary measures employed to prevent and respond to workplace violence. However, the current approaches have proven ineffective, possibly due to a lack of consideration for the specific needs of clinical nurses. Therefore, it is essential to explore the effectiveness of an informational education and training platform tailored to nurses' requirements. This study aimed to investigate the impact of such a platform on the incidence, severity, and coping resources of WPV in nurses.MethodsThis research was a quasi-experimental study. An information-based education and training platform focused on nurse workplace violence was developed through literature reviews, expert meetings, consultations with software development companies, and a trial run. A tertiary general hospital in Suzhou was selected, in which hospital district A was the intervention group and hospital district B was the control group. A total of 276 nurses were recruited, 140 in the intervention group and 136 in the control group. The nurses' incidence, severity, coping resources status, and evaluation of the application were measured before the intervention and at 1, 3, and 6 months after the intervention.ResultsThe overall incidence of workplace violence, verbal aggression, and verbal threat among nurses showed statistically significant differences (P < 0.05) for the time effect, while the incidence of physical aggression demonstrated statistically significant differences (P < 0.05) for the between-group effect and the time effect. The severity of physical violence among nurses exhibited statistically significant differences (P < 0.05) for the between-group effect and time effect, and the severity of psychological violence showed statistically significant differences (P < 0.05) for the time effect. Nurses' total coping resources score and dimensions also showed statistically significant differences in terms of group, time, and interaction effects (P < 0.001). The evaluation questionnaire for the mobile application indicated usefulness scores of 2 (1, 2); ease of learning scores of 2 (1, 2); ease of use scores of 2 (1, 2); trust scores of 2 (1, 2.75); acceptance score of 1 (1, 2); and satisfaction scores of 2 (1, 2).ConclusionsImplementing the nurse workplace violence information-based education and training platform proved beneficial in reducing the incidence and severity of workplace violence among nurses and enhancing their coping resources. This outcome suggested the platform's potential for further application and promotion in clinical settings.

Blending Coursera in CEU Courses: A Study on the Quality and Educational Impact

Enrolling in Massive Open Online Courses (MOOCs) has become a global phenomenon, with millions of students from around the world signing up for courses offered by prestigious universities such as Harvard, MIT, and the University of London. Among the many platforms like edX, Udacity, and FutureLearn, Coursera was chosen to provide courses to blend in with Centro Escolar University (CEU) for its trial run. An evaluation was conducted across CEU's three campuses using data from 198 students among the 459 enrollees in courses where Coursera was blended. This inferential study determined the quality and educational impact of blending Coursera into their CEU courses. The findings include the results on the effectiveness of course materials in meeting the learning needs of students, their engagement and involvement, the course structure, and the quality and educational impact on students. The results of this study can help educators better understand how to design effective learning experiences that promote student engagement, improve learning outcomes, and optimize the use of technology and resources in an online and offline setting. Keywords: MOOCs, courses, educational impact, Coursera, course materials