bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microfluidic Synthesis of Indomethacin-Loaded PLGA Microparticles Optimized by Machine Learning
Authors: Damiati Safa A. , Damiati Samar 
Published: September 2021

Several attempts have been made to encapsulate indomethacin (IND), to control its sustained release and reduce its side effects. To develop a successful formulation, drug release from a polymeric matrix and subsequent biodegradation need to be achieved. In this study, we focus on combining microfluidic and artificial intelligence (AI) technologies, alongside using biomaterials, to generate drug-loaded polymeric microparticles (MPs). Our strategy is based on using Poly (D,L-lactide-co-glycolide) (PLGA) as a biodegradable polymer for the generation of a controlled drug delivery vehicle, with IND as an example of a poorly soluble drug, a 3D flow focusing microfluidic chip as a simple device synthesis particle, and machine learning using artificial neural networks (ANNs) as an in silico tool to generate and predict size-tunable PLGA MPs. The influence of different polymer concentrations and the flow rates of dispersed and continuous phases on PLGA droplet size prediction in a microfluidic platform were assessed. Subsequently, the developed ANN model was utilized as a quick guide to generate PLGA MPs at a desired size. After conditions optimization, IND-loaded PLGA MPs were produced, and showed larger droplet sizes than blank MPs. Further, the proposed microfluidic system is capable of producing monodisperse particles with a well-controllable shape and size. IND-loaded-PLGA MPs exhibited acceptable drug loading and encapsulation efficiency (7.79 and 62.35%, respectively) and showed sustained release, reaching approximately 80% within 9 days. Hence, combining modern technologies of machine learning and microfluidics with biomaterials can be applied to many pharmaceutical applications, as a quick, low cost, and reproducible strategy.
Microstimulation Is a Promising Approach in Achieving Better Lead Placement in Subthalamic Nucleus Deep Brain Stimulation Surgery
Authors: Shi Lin , Fan Shiying , Yuan Tianshuo , Fang Huaying , Zheng Jie , Xiao Zunyu , Diao Yu , Zhu Guanyu , Zhang Quan , Liu Huanguang , Zhang Hua , Meng Fangang , Zhang Jianguo , Yang Anchao 
Published: September 2021

Background: The successful application of subthalamic nucleus (STN) deep brain stimulation (DBS) surgery relies mostly on optimal lead placement, whereas the major challenge is how to precisely localize STN. Microstimulation, which can induce differentiating inhibitory responses between STN and substantia nigra pars reticulata (SNr) near the ventral border of STN, has indicated a great potential of breaking through this barrier.Objective: This study aims to investigate the feasibility of localizing the boundary between STN and SNr (SSB) using microstimulation and promote better lead placement.Methods: We recorded neurophysiological data from 41 patients undergoing STN-DBS surgery with microstimulation in our hospital. Trajectories with typical STN signal were included. Microstimulation was applied near the bottom of STN to determine SSB, which was validated by the imaging reconstruction of DBS leads.Results: In most trajectories with microstimulation (84.4%), neuronal firing in STN could not be inhibited by microstimulation, whereas in SNr long inhibition was observed following microstimulation. The success rate of localizing SSB was significantly higher in trajectories with microstimulation than those without. Moreover, results from imaging reconstruction and intraoperative neurological assessments demonstrated better lead location and higher therapeutic effectiveness in trajectories with microstimulation and accurately identified SSB.Conclusion: Microstimulation on microelectrode recording is an effective approach to localize the SSB. Our data provide clinical evidence that microstimulation can be routinely employed to achieve better lead placement.
Involvement of Specialist Palliative Care in a Stroke Unit in Austria—Challenges for Families and Stroke Teams
Authors: Riesinger Renate , Altmann Klaus , Lorenzl Stefan 
Published: September 2021

Purpose: Severe stroke poses vast challenges. Appropriate goals of care according to individual preferences and values have to be developed under time restrictions—often impeded by limited ability to communicate and the need for decisions by surrogates. The aim of our study was to explore the decision-making process and the involvement of specialist palliative care in the acute phase of severe stroke.Methods: Twenty patients suffering from severe ischemic stroke treated in an Austrian acute inpatient stroke unit were included in a prospective study. Their families were interviewed with a questionnaire (FS-ICU 24), which covered satisfaction with care and decision-making. With a second questionnaire, decision-making processes within the stroke team were investigated.Results: A palliative approach and early integration of specialist palliative care in severe ischemic stroke results in individualized therapeutic goals, including withholding therapeutic or life-sustaining measures, especially in patients with pre-existing illness.Conclusions: Family members benefit from understandable and consistent information, emotional support, and a professional team identifying their needs. Stroke unit professionals need skills as well as knowledge and strategies in order to make decisions and provide treatment at the end-of-life, when there may be ethical or legal issues. Close cooperation with specialist palliative care services supports both treatment teams and families with communication and decision-making for patients with severe ischemic stroke.
Infantile-Onset Charcot–Marie–Tooth Disease With Pyramidal Features and White Matter Abnormalities Due to a De novo MORC2 Gene Variant: A Case Report and Brief Review of the Literature
Authors: Frongia Ivana , Rizzi Susanna , Baga Margherita , Ceteroni Laura Maria , Spagnoli Carlotta , Salerno Grazia Gabriella , Frattini Daniele , Kaare Milja , Pisani Francesco , Fusco Carlo 
Published: September 2021

Background: Charcot–Marie–Tooth (CMT) is the most frequent group of inherited neuropathies and includes several heterogeneous phenotypes. Over 80 causative genes have been described so far. Variants in the microrchidia family CW-type zinc finger 2 (MORC2) gene have been described in several axonal polyneuropathy (CMT2) patients with childhood or adult onset. Occasionally more complex phenotypes with delayed milestones, severe hypotonia, intellectual disability, dystonic postures, pyramidal signs, and neuroimaging abnormalities have been reported.Case Presentation: We report on a patient with a de novo MORC2 gene variant (c.1181A&gt;G p.Tyr394Cys) with a history of developmental delay, axial hypotonia, progressive gait disorder with dystonic features, and intentional tremor. At the age of 8 years, he showed bilateral pyramidal signs (clonus, increased tendon reflexes, and Babinski sign) and bilateral pes cavus. The first neuroimaging performed at the age of 3 years demonstrated white matter abnormalities in the posterior periventricular zone, in the frontal lobes bilaterally and at the midbrain, stable during childhood and adolescence. Nerve conduction studies (NCS) were negative until the age of 15 years, when a sensory axonal neuropathy appeared. The association between pyramidal signs and neuropathy due to the MORC2 gene variant is increasingly being highlighted, although a neuroradiological correlate is evident only in about half of the cases. Longitudinal nerve conduction velocity (NCV) are helpful to identify late-onset features and provide useful information for diagnosis in patients with rare neurogenetic disorders.Conclusions: Characterization of complex neurological disorders is important to delineate the expanding phenotypic spectrum of MORC2-related disease, to confirm if possible the pathogenicity of the variants and to deepen the genotype–phenotype correlation.
Efficacy and Safety of Adherence to dl-3-n-Butylphthalide Treatment in Patients With Non-disabling Minor Stroke and TIA—Analysis From a Nationwide, Multicenter Registry
Authors: Tan Zefeng , Zhao Yin , Yang Wanyong , He Shenwen , Ding Yan , Xu Anding 
Published: September 2021

Background: Dl-3-n-Butylphthalide (NBP) has the potential to improve clinical outcomes in acute ischemic stroke patients by improving collateral circulation. We aimed to evaluate the efficacy and safety of NBP in patients with non-disabling minor ischemic stroke and transient ischemic attack (TIA).Methods: The BRIDGE (the observation study on clinical effectiveness of NBP on patients with non-disabling ischemic cerebrovascular disease) is a prospective registry to monitor the efficacy and safety of NBP therapy in acute non-disabling ischemic stroke or high-risk TIA. Non-disabling minor ischemic stroke patients within 48 h were enrolled across 51 stroke centers in China. We divided patients into NBP compliance or non-compliance groups according to their adherence to NBP. The primary outcome was the favorable functional outcome at 90 days, defined as a modified Rankin scale (mRS) &lt;2.Results: Between 10th October 2016 and 25th June 2019, 3,118 patients were included in this analysis. In multivariable analysis, after adjusting for common risk factors and demographic factors, NBP-compliance group has a higher proportion of favorable functional outcome (92.1 vs. 87.4%, adjusted odds ratio 2.00, 95% confidence interval, 1.50–2.65), and a higher stroke recurrence rate (2.40 vs. 0.31%, adjusted odds ratio 8.86, 95% confidence interval, 3.37–23.30) than the NBP-non-compliance group. There was no significant difference in death and intracranial hemorrhage rate between the two groups. In subgroup analysis, patients with National Institutes of Health Stroke Scale (NIHSS) scores from 3 to 5 who complied to NBP therapy had a higher rate of favorable functional outcomes than the NBP-non-compliance group. [88.82 vs. 76.21%, adjusted odds ratio 2.52 (1.81–3.50), adjusted interaction P = 0.00].Conclusion: In non-disabling minor ischemic stroke or TIA patients, compliance with NBP therapy led to better 90-day functional outcomes despite a higher risk of recurrence, and this effect seems to be stronger in patients with NIHSS scores of 3–5. Further large randomized, double-blind controlled studies to analyse the association between NBP and functional outcome is warranted in the coming future.
Association Between Genetic Risks for Obesity and Working Memory in Children
Authors: Takahashi Nagahide , Nishimura Tomoko , Harada Taeko , Okumura Akemi , Iwabuchi Toshiki , Rahman Md. Shafiur , Kuwabara Hitoshi , Takagai Shu , Nomura Yoko , Takei Nori , Tsuchiya Kenji J. 
Published: September 2021

Introduction: Obesity is highly heritable, and recent evidence demonstrates that obesity is associated with cognitive deficits, specifically working memory. However, the relationship between genetic risks for obesity and working memory is not clear. In addition, whether the effect of these genetic risks on working memory in children is mediated by increased body mass index (BMI) has not been elucidated.Methods: In order to test whether the polygenic risk score (PRS) for obesity in adulthood (adulthood-BMI-PRS) is associated with working memory at 8 years of age, and whether the effect is mediated by childhood BMI, in children from the general population, participants in the Hamamatsu Birth Cohort for Mothers and Children (HBC) study in Hamamatsu, Japan, underwent testing for association of adulthood-BMI-PRS with working memory. HBC data collection began in December 2007 and is ongoing. Adulthood-BMI-PRS values were generated using summary data from the recent genome-wide association study (GWAS) undertaken in Japan, and the significance of thresholds was calculated for each outcome. Outcomes measured included the working memory index (WMI) of Weschler Intelligence Scale-4 (WISC-IV) scores and the BMI at 8 years of age. Gene-set enrichment analysis was conducted to clarify the molecular basis common to adulthood-BMI and childhood-WMI. Mediation analysis was performed to assess whether childhood-BMI of children mediated the association between adulthood-BMI-PRS and working memory.Results: A total of 734 participants (377 males, 357 females) were analyzed. Adulthood-BMI-PRS was associated with lower childhood-WMI (β[SE], −1.807 [0.668]; p = 0.010, corrected) of WISC-IV. Gene-set enrichment analyses found that regulation of neurotrophin Trk receptor signaling (β[SE], −2.020 [6.39]; p = 0.002, corrected), negative regulation of GTPase activity (β[SE], 2.001 [0.630]; p = 0.002, corrected), and regulation of gene expression epigenetic (β[SE], −2.119 [0.664]; p = 0.002, corrected) were enriched in BMI in adulthood and WMI in childhood. Mediation analysis showed that there is no mediation effect of childhood-BMI between the adulthood-BMI-PRS and working memory deficits in children.Conclusion: Adulthood-BMI-PRS was associated with working memory among children in the general population. These genetic risks were not mediated by the childhood-BMI itself and were directly associated with working memory deficits.
High Expression of SLC16A1 as a Biomarker to Predict Poor Prognosis of Urological Cancers
Authors: Zhang Ling , Song Zheng-Shuai , Wang Zhi-Shun , Guo Yong-Lian , Xu Chang-Geng , Shen Hao 
Published: September 2021

ObjectiveTumor metabolism has always been the focus of cancer research. SLC16A1, as a key factor in catalysis of monocarboxylate transport across the plasma membrane, has been found to be associated with the occurrence and metastasis of a variety of cancers, but its prognostic significance and mechanism in different tumors are still unclear.MethodsBased on the gene expression matrix and clinical information of human cancer tissues acquired from TCGA and GTEX databases, the differential expression of SLC16A1 in different tumors and normal tissues was analyzed. To confirm the association between its expression, the mutation of MMRS gene, and the expression level of DNMTs. Univariate Cox regression was applied to analyze the association between SLC16A1 expression and patient prognosis. The effect of SLC16A1 expression on patient survival was examined by Kaplan Meier analysis. GSEA was used to identify related signaling pathways.ResultsThe expression of SLC16A1 was differentially expressed in most tumors, especially in the urinary tract where it is commonly highly expressed, and differential expression of SLC16A1 in different clinical stages. SLC16A1 expression was significantly positively correlated with MMRS gene mutation and DNMTS expression. Moreover, high SLC16A1 expression was associated with poorer overall survival (OS) and progression-free survival (PFS) in urological cancers. In particular, the results of the enrichment analysis showed that SLC16A1 was associated with processes such as cell adhesion and many signaling pathways affecting cell cycle were significantly enriched in the group with high-expressed SLC16A1.ConclusionSLC16A1 expression was upregulated in urological cancer. SLC16A1 may promote tumor development by regulating the epigenetic process of urological cancer and demonstrated a great potential as a prognostic biomarker of urological cancer patients.
Inflow Occlusion Combined With Bleomycin Sclerotherapy for Management of Macro/Mixed Cystic Lymphatic Malformation in Children
Authors: Han Tao , Ji Yi , Cui Jie , Shen Weimin 
Published: September 2021

Background: The link between cystic lymphatic malformation (cLM) and normal lymphatic system has become the focus of research. This study aimed to assess the outcomes of indocyanine green (ICG) lymphography-guided inflow occlusion combined with bleomycin sclerotherapy for the management of macro or mixed cLM in children.Methods: Between June 2018 and October 2020, inflow occlusion combined with bleomycin sclerotherapy was performed in 81 cLM patients (age range from 6 months to 8 years). All cases were evaluated by the following parameters: cLM location, histological typing, number of afferent lymph vessels, dermal backflow, curative effects, treatment frequency, and postoperative complications. The duration of postoperative follow-up was from 10 to 16 months.Results: All cLM cases could be found with at least one lymphatic inflow. Excellent outcomes were observed in 68 cases (84.0%), 11 cases (13.6%) experienced good outcomes, and two (2.5%) cases had fair outcome. No case experienced repeated treatment for more than three times. Wound infection, fever, and scar hyperplasia were the independent adverse events, which were managed by symptomatic treatment.Conclusion: Inflow occlusion combined with bleomycin sclerotherapy renders a safe and efficient approach for the management of macro or mixed cLM.
Effect of Training and Detraining in the Components of Physical Fitness in People Living With HIV/AIDS
Authors: Araujo Juliany de Souza , Medeiros Rafaela Catherine da Silva Cunha de , Silva Tatiane Andreza Lima da , Medeiros Danielle Coutinho de , Medeiros Jason Azevedo de , Santos Isis Kelly dos , Wilde Phelipe , Cabral Breno Guilherme de Araújo Tinoco , Medeiros Radamés Maciel Vitor , Dantas Paulo Moreira Silva 
Published: September 2021

The aim of the study was to evaluate the effect of training and detraining on the physical fitness components of people living with HIV/AIDS (PLHA). The study was characterized as experimental with a sample composed of 21 people divided into two groups: 11 volunteers (PLHA, 46.9 ± 8.0 years, 63.8 ± 12.7 kg, 161.7 ± 8.7 cm, 7 men, and 4 women), using antiretroviral therapy (ART) and 10 people without HIV/AIDS in the control group (CG, 43.8 ± 13.8 years, 75.2 ± 11.2 kg, 163.3 ± 7.8 cm, 3 men, and 7 women), with the same average age and level of physical activity. The intervention, applied to both groups, consisted of combined training for 15 weeks, followed by detraining for 5 weeks. Before and after the training and detraining period the following parameters were evaluated: body composition by dual energy radiological absorptiometry (DXA), cardiorespiratory fitness by ergospirometer, and strength of upper and lower limbs by isometric dynamometer. The results show the effect of the intervention moments on the strength and oxygen consumption variables (time factor), considering the two study groups. Regarding the analysis of the interaction (group vs. time), there was a significant effect on the isometric extension strength of the left (p = 0.019) and right (p = 0.030) knees, with training (left: 10.4%; right: 12.4%) and detraining (left: −10.8%; right: −12.1%) effect in PLHA, when compared with the control group (left: 8.1 and 3.9%, respectively; right: 11.5 and −0.2%, respectively). In addition, there was a significant interaction on ventilatory threshold 1 (p = 0.002), indicating a significantly greater increase with training (27.3%) and decrease with detraining (−22.7%) in the PLHA group compared with the Control group (19.9 and −6.7%, respectively). In conclusion, combined training and the subsequent period of detraining caused similar responses in body composition, isometric strength, and cardiorespiratory fitness of PLHA and CG, except for the extensor strength of the lower limbs and ventilatory threshold 1, which presented positive effects on training and negative effects on detraining for PLHA.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03075332.
What Drives Outpatient Care Costs in Kenya? An Analysis With Generalized Estimating Equations
Authors: Mwenda Ngugi , Nduati Ruth , Kosgei Mathew , Kerich Gregory 
Published: September 2021

Objective: This study aimed to identify the factors associated with outpatient expenses incurred by households in Kenya.Background: The problem of outpatient healthcare expenses incurred by citizens in countries with limited resources has received little attention. Thus, this study aimed to determine the predictors of household spending on outpatient expenses in Kenya.Method: We conducted a cross-sectional analysis on households in Kenya using data from the 2018 Kenya Household Health Expenditure and Utilization Survey. We applied the generalized estimating equations method to determine the best subset of predictors of outpatient care cost.Findings: The best predictors of outpatient care expenses in Kenya are age, wealth index, and education level of the household head.Conclusions: There were no differences regarding age in the mean spending on outpatient care. Moreover, we found that the cost of outpatient care changes with age in a sinusoidal manner. We observed that rich households spent more on outpatient care, mostly owing to their financial ability. Households whose heads reported primary or secondary school education level spent less on outpatient costs than households headed by those who never went to school.
5G New Radio Requires the Best Possible Risk Assessment Studies: Perspective and Recommended Guidelines
Authors: Mattsson Mats-Olof , Simkó Myrtill , Foster Kenneth R. 
Published: September 2021

The development and establishment of mobile communication technologies has necessitated assessments of possible risks to human health from exposures to radio-frequency electromagnetic fields (RF EMF). A number of expert committees have concluded that there is no evidence for such risks as long as exposures are at or below levels that do not allow tissue heating. These assessments have been based primarily on studies investigating frequencies up to 6 GHz including frequencies similar to those used by two of three major bands of fifth generation (more accurately 5G New Radio or 5G NR) of mobile communication. Bioeffects studies in so-called high-band at 25–39 GHz are particularly sparse. Future assessments relevant for these frequencies will need to rely on still unperformed studies. Due to few available studies at 5G NR “high band” frequencies, and questions raised by some existing studies, a recent review recommended a wide range of RF biostudies be done at 5G NR “high band” frequencies. It is of importance that such studies be done using the best possible science. Here we suggest factors to consider when performing future studies in this area. The present focus is on laboratory studies to clarify biological effects of radiofrequency (RF) energy at 5G “high band” frequencies and, more generally at millimeter wave (mm-wave) frequencies (30-300 GHz) which will be increasingly used by communications technologies in the future. Similar comments would apply to epidemiology and exposure assessment studies, but those are not the focus of the present Perspective.
Incremento del rendimiento y calidad de grano en germoplasma mejorado de trigo (Triticum aestivum L.) del INIAP, en el año 2020
Authors: Garófalo Sosa Javier Alberto , Ponce Molina Luis Jonatan , Noroña Zapata Patricio Javier 
Published: September 2021

El trigo (Triticum aestivum L.) es uno de los cereales más utilizados por las familias ecuatorianas, con una producción nacional del 1% de la demanda. El Instituto Nacional de Investigaciones Agropecuarias – INIAP, tiene como objetivo generar germoplasma de alto rendimiento y calidad industrial. En el año 2020 en la Estación Experimental Santa Catalina, en parcelas de 3.6 m2 se evaluaron en campo 580 líneas de trigo seleccionadas durante el 2019 de introducciones provenientes del CIMMYT y de cruzas locales. Los resultados obtenidos muestran que las líneas introducidas alcanzaron un incremento en el rendimiento del 6% en comparación a los testigos mejorados (7,14 t ha-1), entre tanto que, las líneas de cruzas nacionales obtuvieron un incremento del 13,3%. Para la calidad de grano, peso hectolítrico, se observó que las líneas introducidas presentan menores valores de calidad (71,05 kg hl-1) en comparación con los testigos (71,87 kg hl-1); mientras que las líneas de cruzas nacionales presentaron un incremento del 2,4%. Denotando, que los programas de mejoramiento pueden obtener germoplasma con mejores características al realizar sus propios cruzamientos empleando materiales locales y mejor adaptados.