bluuebunny/crossref_metadata_2025_split huggingface dataset:
A di-electrophoretic simulation procedure of iron-oxide micro-particle drug attachment system for leukemia treatment using COMSOL software: a potential treatment reference for LMICs
Authors: Kiwumulo Henry Fenekansi , Muwonge Haruna , Ibingira Charles , Lubwama Michael , Kirabira John Baptist , Ssekitoleko Robert Tamale 
Published: October 2023

BackgroundLeukemia encompasses various subtypes, each with unique characteristics and treatment approaches. The challenge lies in developing targeted therapies that can effectively address the specific genetic mutations or abnormalities associated with each subtype. Some leukemia cases may become resistant to existing treatments over time making them less susceptible to chemotherapy or other standard therapies.ObjectiveDeveloping new treatment strategies to overcome resistance is an ongoing challenge particularly in Low and Middle Income Countries (LMICs). Computational studies using COMSOL software could provide an economical, fast and resourceful approach to the treatment of complicated cancers like leukemia.MethodsUsing COMSOL Multiphysics software, a continuous flow microfluidic device capable of delivering anti-leukemia drugs to early-stage leukemia cells has been computationally modeled using dielectrophoresis (DEP).ResultsThe cell size difference enabled the micro-particle drug attachment to the leukemia cells using hydrodynamic focusing from the dielectrophoretic force. This point of care application produced a low voltage from numerically calculated electrical field and flow speed simulations.ConclusionTherefore, such a dielectrophoretic low voltage application model can be used as a computational treatment reference for early-stage leukemia cells with an approximate size of 5 μm.
Usability and utility of a remote monitoring system to support physiotherapy for people with Parkinson's disease
Authors: van den Bergh Robin , Evers Luc J. W. , de Vries Nienke M. , Silva de Lima Ana L. , Bloem Bastiaan R. , Valenti Giulio , Meinders Marjan J. 
Published: October 2023

BackgroundPhysiotherapy for persons with Parkinson's disease (PwPD) could benefit from objective and continuous tracking of physical activity and falls in daily life.ObjectivesWe designed a remote monitoring system for this purpose and describe the experiences of PwPD and physiotherapists who used the system in daily clinical practice.MethodsTwenty-one PwPD (15 men) wore a sensor necklace to passively record physical activity and falls for 6 weeks. They also used a smartphone app to self-report daily activities, (near-)falls and medication intake. They discussed those data with their PD-specialized physiotherapist (n= 9) during three regular treatment sessions. User experiences and aspects to be improved were gathered through interviews with PwPD and physiotherapists, resulting in system updates. The system was evaluated in a second pilot with 25 new PwPD (17 men) and eight physiotherapists.ResultsWe applied thematic analysis to the interview data resulting in two main themes: usability and utility. First, the usability of the system was rated positively, with the necklace being easy to use. However, some PwPD with limited digital literacy or cognitive impairments found the app unclear. Second, the perceived utility of the system varied among PwPD. While many PwPD were motivated to increase their activity level, others were not additionally motivated because they perceived their activity level as high. Physiotherapists appreciated the objective recording of physical activity at home and used the monitoring of falls to enlarge awareness of the importance of falls for PwPD. Based on the interview data of all participants, we drafted three user profiles for PwPD regarding the benefits of remote monitoring for physiotherapy: for profile 1, a monitoring system could act as a flagging dashboard to signal the need for renewed treatment; for profile 2, a monitoring system could be a motivational tool to maintain physical activity; for profile 3, a monitoring system could passively track physical activity and falls at home. Finally, for a subgroup of PwPD the burdens of monitoring will outweigh the benefits.ConclusionsOverall, both PwPD and physiotherapists underline the potential of a remote monitoring system to support physiotherapy by targeting physical activity and (near-)falls. Our findings emphasize the importance of personalization in remote monitoring technology, as illustrated by our user profiles.
Feasibility of common, enjoyable game play for assessing daily cognitive functioning in older adults
Authors: Schwab Nadine , Wu Chao-Yi , Galler Jake , DeRamus Thomas , Ford Abaigeal , Gerber Jessica , Kitchen Robert , Rashid Barnaly , Riley Misha , Sather Lauren , Wang Xifeng , Young Cathrine , Yang Liuqing , Dodge Hiroko H. , Arnold Steven E. 
Published: October 2023

BackgroundFrequent digital monitoring of cognition is a promising approach for assessing endpoints in prevention and treatment trials of Alzheimer’s disease and related dementias (ADRD). This study evaluated the feasibility of the MIND GamePack© for recurrent semi-passive assessment of cognition across a longitudinal interval.MethodsThe MIND GamePack consists of four iPad-based games selected to be both familiar and enjoyable: Word Scramble, Block Drop, FreeCell, and Memory Match. Participants were asked to play 20 min/day for 5 days (100 min) for 4 months. Feasibility of use by older adults was assessed by measuring gameplay time and game performance. We also evaluated compliance through semi-structured surveys. A linear generalized estimating equation (GEE) model was used to analyze changes in gameplay time, and a regression tree model was employed to estimate the days it took for game performance to plateau. Subjective and environmental factors associated with gameplay time and performance were examined, including daily self-reported questions of memory and thinking ability, mood, sleep, energy, current location, and distractions prior to gameplay.ResultsTwenty-six cognitively-unimpaired older adults participated (mean age ± SD = 71.9 ± 8.6; 73% female). Gameplay time remained stable throughout the 4-months, with an average compliance rate of 91% ± 11% (1946 days of data across all participants) and weekly average playtime of 210 ± 132 min per participant. We observed an initial learning curve of improving game performance which on average, plateaued after 22–39 days, depending on the game. Higher levels of self-reported memory and thinking ability were associated with more gameplay time and sessions.ConclusionMIND GamePack is a feasible and well-designed semi-passive cognitive assessment platform which may provide complementary data to traditional neuropsychological testing in research on aging and dementia.
Greater hemodynamic stresses initiate aneurysms on major cerebral arterial bifurcations
Authors: Guo Hao , Liu Jian-Feng , Li Cong-Hui , Wang Ji-Wei , Li Hui , Gao Bu-Lang 
Published: October 2023

ObjectiveTo retrospectively investigate the hemodynamic stresses in initiating aneurysm formation on major cerebral arterial bifurcations with computational fluid dynamics (CFD) analysis.MethodsThe cerebral 3D angiographic data of major cerebral arterial bifurcations of the internal carotid, middle cerebral, anterior cerebral, and basilar arteries in 80 patients harboring bifurcation aneurysms and 80 control subjects with no aneurysms were retrospectively collected for the CFD analysis of hemodynamic stresses associated with aneurysm formation.ResultsBifurcation angles at major bifurcations in all patients were significantly positively (P &lt; 0.001) correlated with the age. At the center of direct flow impingement (CDFI) on the bifurcation wall, total pressure was the highest but dropped rapidly toward the branches. Wall shear stress, dynamic pressure, strain rate, and vorticity were lowest at the CDFI but they increased quickly toward the branches. The bifurcation angle was significantly (P &lt; 0.001) enlarged in patients with bifurcation aneurysms than those without them, for all major arterial bifurcations. Most aneurysms leaned toward the smaller arterial branch or the arterial branch that formed a smaller angle with the parent artery, where the hemodynamic stresses increased significantly (P &lt; 0.05), compared with those on the contralateral arterial branch forming a larger angle with the parent artery. Following the aneurysm development, all the hemodynamic stresses on the aneurysm dome decreased significantly (P &lt; 0.001) compared with those at the initiation site on the bifurcation wall after virtual aneurysm removal. With the decrease of bifurcation angles, all the hemodynamic stresses decreased.ConclusionThe formation of intracranial aneurysms on major intracranial arterial bifurcations is significantly associated with locally abnormally augmented hemodynamic stresses, which must be reduced.
Bioactive strawberry fruit (Arbutus unedo L.) extract remedies paraquat-induced neurotoxicity in the offspring prenatally exposed rats
Authors: Ait Lhaj Zakaria , Ibork Hind , El Idrissi Sara , Ait Lhaj Farida , Sobeh Mansour , Mohamed Wael M. Y. , Alamy Meryem , Taghzouti Khalid , Abboussi Oualid 
Published: October 2023

BackgroundParaquat (1,1′-dimethyl-4-4′-bipyridinium dichloride) exposure is well-established as a neurotoxic agent capable of causing neurological deficits in offspring. This study aimed to investigate therapeutic effects of Arbutus unedo L. aqueous extract (AU) against paraquat (PQ) exposure.MethodsFor that the phytoconstituents of AU was determined by LC/MS, and then its antioxidant potential was assessed by DPPH and ABTS assays. The assessment included its impact on cell viability and mitochondrial metabolism using N27 dopaminergic cells. Additionally, we evaluated the effects of prenatal PQ exposure on motor coordination, dopamine levels, trace element levels, and total antioxidant capacity (TAC) in rat progeny.ResultsThe phytochemical profile of AU extract revealed the presence of 35 compounds, primarily phenolic and organic acids, and flavonoids. This accounted for its strong in vitro antioxidant activities against DPPH and ABTS radicals, surpassing the activities of vitamin C. Our findings demonstrated that AU effectively inhibited PQ-induced loss of N27 rat dopaminergic neural cells and significantly enhanced their mitochondrial respiration. Furthermore, daily post-treatment with AU during the 21 days of the rat's pregnancy alleviated PQ-induced motor deficits and akinesia in rat progeny. These effects inhibited dopamine depletion and reduced iron levels in the striatal tissues. The observed outcomes appeared to be mediated by the robust antioxidant activity of AU, effectively counteracting the PQ-induced decrease in TAC in the blood plasma of rat progeny. These effects could be attributed to the bioactive compounds present in AU, including phenolic acids such as gallic acid and flavonoids such as quercetin, rutin, apigenin, glucuronide, and kaempferol, all known for their potent antioxidant capacity.DiscussionIn conclusion, this preclinical study provided the first evidence of the therapeutic potential of AU extract against PQ-induced neurotoxicity. These findings emphasize the need for further exploration of the clinical applicability of AU in mitigating neurotoxin-induced brain damage.
Effect of neonatal melatonin administration on behavioral and brain electrophysiological and redox imbalance in rats
Authors: Araújo Amanda de Oliveira , Figueira-de-Oliveira Maria Luísa , Noya Arthur Gabriel Alves Furtado de Carvalho , Oliveira e Silva Vitor Palmares , Carvalho Jennyfer Martins de , Vieira Filho Leucio Duarte , Guedes Rubem Carlos Araújo 
Published: October 2023

IntroductionMelatonin (MLT) reportedly has beneficial effects in neurological disorders involving brain excitability (e.g., Epilepsy and Migraine) and behavioral patterns (e.g., Anxiety and Depression). This study was performed to investigate, in the developing rat brain, the effect of early-in-life administration of two different doses of exogenous MLT on behavioral (anxiety and memory) and electrophysiological (CSD analysis) aspects of brain function. Additionally, brain levels of malondialdehyde (MDA) and superoxide dismutase (SOD), both cellular indicators of redox balance status, were evaluated. We hypothesize that MLT differentially affects the behavioral and CSD parameters as a function of the MLT dose.Materials and methodsMale Wistar rats received, from the 7th to the 27th postnatal day (PND), on alternate days, vehicle solution, or 10 mg/kg/or 40 mg/kg MLT (MLT-10 and MLT-40 groups), or no treatment (intact group). To perform behavioral and cognition analysis, from PND30 to PND32, they were tested in the open field apparatus, first for anxiety (PND30) and then for object recognition memory tasks: spatial position recognition (PND31) and shape recognition (PND32). On PND34, they were tested in the elevated plus maze. From PND36 to 42, the excitability-related phenomenon known as cortical spreading depression (CSD) was recorded, and its features were analyzed.ResultsTreatment with MLT did not change the animals’ body weight or blood glucose levels. The MLT-10 treatment, but not the MLT-40 treatment, was associated with behaviors that suggest less anxiety and improved memory. MLT-10 and MLT-40 treatments, respectively, decelerated and accelerated CSD propagation (speed of 2.86 ± 0.14 mm/min and 3.96 ± 0.16 mm/min), compared with the control groups (3.3 ± 0.10 mm/min and 3.25 ± 0.11 mm/min, for the intact and vehicle groups, respectively;p&lt; 0.01). Cerebral cortex levels of malondialdehyde and superoxide dismutase were, respectively, lower and higher in the MLT-10 group but not in the MLT40 group.ConclusionOur findings suggest that MLT intraperitoneal administration during brain development may differentially act as an antioxidant agent when administered at a low dose but not at a high dose, according to behavioral, electrophysiological, and biochemical parameters.
Interplay between noxious heat sensitivity and temporal summation magnitude in patients with fibromyalgia and long-term opioid use
Authors: Bao Jason D. , Rosser Morgan A. , Park Su Hyoun , Baker Anne K. , Martucci Katherine T. 
Published: October 2023

IntroductionIn chronic pain conditions such as fibromyalgia (FM), pain amplification within the central nervous system, or “central sensitization,” may contribute to the development and maintenance of chronic pain. Chronic pain treatments include opioid therapy, and opioid therapy may maladaptively increase central sensitization, particularly in patients who take opioids long-term. However, it has remained unknown how central sensitization is impacted in patients who use opioids long-term.MethodsTo investigate how long-term opioid therapy affects central sensitization, we used the validated measure of temporal summation. The temporal summation measurement consists of applying a series of noxious stimuli to a patient’s skin and then calculating changes in the patient’s pain rating to each stimulus. Using this measurement, we evaluated temporal summation in study participants with fibromyalgia who take opioids long-term (i.e., greater than 90 days duration; n = 24, opioid-FM). We compared opioid-FM responses to 2 control groups: participants with fibromyalgia who do not take opioids (n = 33, non-opioid FM), and healthy controls (n = 31). For the temporal summation measurement, we applied a series of 10 noxious heat stimuli (sensitivity-adjusted temperatures) to the ventral forearm (2s duration of each stimulus, applied once every 3 s). Additionally, we collected responses to standard pain and cognitive-affective questionnaires to assess pain severity and other factors.Results and discussionGroup differences in sensitivity-adjusted stimulus temperatures were observed, with only the non-opioid FM group requiring significantly lower stimulus temperatures (The opioid-FM group also required lower temperatures, but not significantly different from the control group). However, all 3 groups exhibited similar magnitudes of temporal summation. Across combined FM groups, temporal summation negatively correlated with pain severity (r = −0.31, p = 0.021). Within the opioid-FM group, higher pain sensitivity to heat (i.e., lower sensitivity-adjusted temperatures) showed a trend relationship with higher opioid dosage (r = −0.45, p = 0.036), potentially reflective of opioid-related hyperalgesia. Our findings also indicated that heightened pain severity may skew sensitivity-adjusted temporal summation, thereby limiting its utility for measuring central sensitization. Overall, in participants taking opioids, temporal summation may be influenced by hypersensitivity to heat pain, which appeared to vary with opioid dosage.
Prednisone-hydrogen sulfide releasing hybrid shows improved therapeutic profile in asthma
Authors: Cerqua Ida , Granato Elisabetta , Corvino Angela , Severino Beatrice , D’Avino Danilo , Simonelli Martina , Perissutti Elisa , Scognamiglio Antonia , Mirra Davida , D’Agostino Bruno , Caliendo Giuseppe , Rossi Antonietta , Cirino Giuseppe , Motta Chiara Maria , Roviezzo Fiorentina 
Published: October 2023

Introduction: Hydrogen sulfide (H2S) is emerging as an important potential therapeutic option for respiratory inflammatory diseases. In this study, we investigated the effectiveness of a novel corticosteroid derivative, that is chemically linked to an H2S donor, in managing asthma features.Methods: The effects of prednisone (PS), H2S donor (4-hydroxybenzamide; TBZ), and their combination (PS-TBZ) have been evaluated in vitro and in vivo. The in vitro experiments were conducted using lipopolysaccharidestimulated J774 macrophages, while the in vivo experiments utilizing an experimental asthma model.Results: In the in vitro study we found that PS-TBZ exhibited an increased effect compared to the individual parent compounds in modulating the production of inflammatory mediators. TBZ also significantly reduced bronchial contractility and enhanced bronchial relaxation. In the in vivo experiments, where we administered PS, TBZ, or PS-TBZ to ovalbumin-sensitized BALB/c mice, we confirmed that PS-TBZ had a significantly better action in controlling airway hyperreactivity as compared to TBZ or PS alone. Moreover, PS-TBZ was more effective in restoring salbutamol-induced relaxation. The immunohistochemistry analysis demonstrated a significant reduction in the production of α-SMA and procollagen III, indicating the efficacy of PS-TBZ in controlling airway remodeling. Moreover, PS-TBZ also promoted epithelial repair, recovery of the bronchial and parenchyma structure and inhibited mucin production.Discussion: In conclusion, PS-TBZ offers an important opportunity to optimize the beneficial impact of corticosteroids on asthma features.
Characteristics and factors influencing soil organic carbon composition by vegetation type in spoil heaps
Authors: Yao Yiwen , Dai Quanhou , Gao Ruxue , Yi Xingsong , Wang Yong , Hu Zeyin 
Published: October 2023

IntroductionThe variation of organic carbon content in spoil heaps is closely related to improving soil structure, maintaining soil fertility, and regulating soil carbon cycling balance. Analyzing the soil organic carbon content and related driving factors during the natural vegetation restoration process of spoil heaps is of great significance for promoting the accumulation of soil organic carbon in the spoil heaps.Methodswe selected spoil heaps with the same number of years of restoration to research the variations in soil organic carbon components under different vegetation types (grassland: GL, shrubland: SL, secondary forest: SF) and compared the results with those on bare land (BL).ResultsOur results showed that vegetation type and soil depth significantly affect the content of soil organic carbon components. There was no difference in soil organic carbon components between SF and SL, but both were considerably superior to GL and BL (p&lt;0.05), and the particulate organic carbon (POC) and light fraction organic carbon (LFOC) contents of SL were the highest. A significant positive linear correlation existed between SOC and active organic carbon components. Pearson’s correlation and redundancy analysis showed that the available potassium (AK) and total nitrogen (TN) contents and gravel content (GC) in the BL soil significantly impacted soil organic carbon. When vegetation is present, TN, total phosphorus (TP), and Fine root biomass (FRB) significantly affect soil organic carbon. Structural equation modelling (SEM) shows that AK and soil moisture content (SMC) directly affect the organic carbon composition content of BL, When there is vegetation cover, fine root biomass (FRB) had the largest total effect in the SEM. Soil bulk density (BD) has a negative impact on soil organic carbon, especially in the presence of vegetation.ConclusionThese findings suggest that vegetation restoration can significantly increase soil organic carbon content, FRB, AK, and TN play important roles in enhancing soil organic carbon. Supplementation with nitrogen and potassium should be considered in the bare land stage, and shrubs nitrogen-fixing functions and well-developed roots are more beneficial for the accumulation of soil organic carbon.
Revealing the impact of psychiatric comorbidities on treatment outcome in early psychosis using counterfactual model explanation
Authors: van Dee Violet , Kia Seyed Mostafa , Winter-van Rossum Inge , Kahn René S. , Cahn Wiepke , Schnack Hugo G. 
Published: October 2023

IntroductionPsychiatric comorbidities have a significant impact on the course of illness in patients with schizophrenia spectrum disorders. To accurately predict outcomes for individual patients using computerized prognostic models, it is essential to consider these comorbidities and their influence.MethodsIn our study, we utilized a multi-modal deep learning architecture to forecast symptomatic remission, focusing on a multicenter sample of patients with first-episode psychosis from the OPTiMiSE study. Additionally, we introduced a counterfactual model explanation technique to examine how scores on the Mini International Neuropsychiatric Interview (MINI) affected the likelihood of remission, both at the group level and for individual patients.ResultsOur findings at the group level revealed that most comorbidities had a negative association with remission. Among them, current and recurrent depressive disorders consistently exerted the greatest negative impact on the probability of remission across patients. However, we made an interesting observation: current suicidality within the past month and substance abuse within the past 12 months were associated with an increased chance of remission in patients. We found a high degree of variability among patients at the individual level. Through hierarchical clustering analysis, we identified two subgroups: one in which comorbidities had a relatively limited effect on remission (approximately 45% of patients), and another in which comorbidities more strongly influenced remission. By incorporating comorbidities into individualized prognostic prediction models, we determined which specific comorbidities had the greatest impact on remission at both the group level and for individual patients.DiscussionThese results highlight the importance of identifying and including relevant comorbidities in prediction models, providing valuable insights for improving the treatment and prognosis of patients with psychotic disorders. Furthermore, they open avenues for further research into the efficacy of treating these comorbidities to enhance overall patient outcomes.