bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Solvents and Drying Temperature on the Physicochemical Properties of Darunavir and Darunavir Ethanolate Substances
Authors: Zolotov S. A. , Dain I. A. , Demina N. B. , Zolotova A. S. , Ponomarev E. S. 
Published: February 2021

Introduction. Usage of aggressive conditions (solvents, high temperature, etc.) in a dosage form manufacturing can lead to a change in the properties of a pharmaceutical substance. Darunavir (D) amorphous and darunavir ethanolate (DE) crystalline both have poor solubility, ability to pseudopolymorphism and are sensitive to high temperatures.Aim. Study the effect of solvents and drying temperature on the physicochemical properties of D and DE substancesMaterials and methods. D (Mylan Laboratories Limited), DE (Mylan Laboratories Limited), D (reference standard) 99,9 % (MSN Pharmachem Private Limited). D and DE weighed quantity was suspended in one of the solvents via magnetic stirrer and was dried via universal oven. Powder X-ray diffraction of dried samples was carried out via automatic powder diffractometer. Using DSC thermal properties of the samples were studied. Crystalline samples were examined using IR spectroscopy. Identification of D and DE was performed by HPLC method.Results and discussion. This article summarizes study results of the investigation of various solvents and drying temperature influence on the physicochemical properties of D and DE are presented. The impact of solvent type and drying temperatures in physicochemical properties of the APIs was studied by X-ray powder diffraction, differential scanning calorimetry, IR spectroscopy and HPLC methods. It was shown, that solvent type and drying temperatures can result in the presence of crystalline D solvates or amorphous D.Conclusion. To obtain the final drug containing as an API amorphous D, which perform better dissolution, one of the enlisted solvents can be used: dichloromethane, chloroform and heptane. In such case the intermediate product drying should be performed at not exceeding the solvent boiling point temperatures. In case of ethanol, methanol, acetone and tetrahydrofuran drying phase can be performed at temperatures, that are higher than melting points of obtained pseudopolymorphs. For the utilization of DE as an API only ethanol usage is efficient and drying temperature should not exceed 73.4 °C.
Características físico-químicas e composição centesimal de queijos de coalho comercializados em cidades do Ceará
Authors: Silva Edilene Ferreira da , Silva Priscila Luana da , Barcelos Samuel Carneiro de , Nascimento Vera Lúcia Viana do , Ramos Lidiana de Siqueira Nunes , Cavalcante Antônio Belfort Dantas 
Published: February 2021

Queijo de coalho é um produto popular da cultura nordestina, sendo comum o processo de elaboração com uso de leite cru, o conhecimento prévio da composição físico-química e centesimal do alimento é relevante, tanto por influenciar na escolha saudável, como para obter dados a respeito do que está sendo consumido com qualidade. Objetivou avaliar as características físico-químicas e a composição centesimal do queijo de coalho comercializado em cidades do Ceará. Foram coletadas cinco diferentes marcas de queijos de coalho (A, B, C, D e E) em três repetições, encaminhadas para a Planta Piloto de Leite e Derivados do IFCE – Campus Limoeiro do Norte (CE). As amostras foram homogeneizadas em ralador doméstico, e acondicionadas sob refrigeração (4 ± 2 ºC) até o momento das análises. Análises realizadas: físico-químicas (pH, atividade de água (Aw), acidez titulável e cor), composição centesimal (umidade, proteínas, cinzas, lipídios, carboidratos totais, e valor calórico total). Os dados estatísticos por delineamento inteiramente casualizados, foram submetidos à análise de variância (ANOVA) e teste de Tukey, através do programa R Core Team, 2018, versão 3.5.0, nível de 5% de significância. As análises físico-químicas dos queijos de coalho demonstraram variabilidade entre as amostras, associadas às condições da produção, variação da temperatura de armazenamento e comercialização dos queijos. A composição centesimal e o valor calórico expresso em Kcal variaram entre as amostras estudadas, estando os teores de umidades de acordo com o que a legislação preconiza para queijo de coalho e os valores lipídicos abaixo do mínimo exigido pela legislação.
Characteristics of Multimodal Brain Connectomics in Patients With Schizophrenia and the Unaffected First-Degree Relatives
Authors: Lin Xiao , Li WeiKai , Dong Guangheng , Wang Qiandong , Sun Hongqiang , Shi Jie , Fan Yong , Li Peng , Lu Lin 
Published: February 2021

ObjectiveIncreasing pieces of evidence suggest that abnormal brain connectivity plays an important role in the pathophysiology of schizophrenia. As an essential strategy in psychiatric neuroscience, the research of brain connectivity-based neuroimaging biomarkers has gained increasing attention. Most of previous studies focused on a single modality of the brain connectomics. Multimodal evidence will not only depict the full profile of the brain abnormalities of patients but also contribute to our understanding of the neurobiological mechanisms of this disease.MethodsIn the current study, 99 schizophrenia patients, 69 sex- and education-matched healthy controls, and 42 unaffected first-degree relatives of patients were recruited and scanned. The brain was parcellated into 246 regions and multimodal network analyses were used to construct brain connectivity networks for each participant.ResultsUsing the brain connectomics from three modalities as the features, the multi-kernel support vector machine method yielded high discrimination accuracies for schizophrenia patients (94.86%) and for the first-degree relatives (95.33%) from healthy controls. Using an independent sample (49 patients and 122 healthy controls), we tested the model and achieved a classification accuracy of 64.57%. The convergent pattern within the basal ganglia and thalamus–cortex circuit exhibited high discriminative power during classification. Furthermore, substantial overlaps of the brain connectivity abnormality between patients and the unaffected first-degree relatives were observed compared to healthy controls.ConclusionThe current findings demonstrate that decreased functional communications between the basal ganglia, thalamus, and the prefrontal cortex could serve as biomarkers and endophenotypes for schizophrenia.
Functional Mapping of AGO-Associated Zika Virus-Derived Small Interfering RNAs in Neural Stem Cells
Authors: Zeng Jianxiong , Luo Zhifei , Dong Shupeng , Xie Xiaochun , Liang Xinyan , Yan Youzhen , Liang Qiming , Zhao Zhen 
Published: February 2021

Viral interfering RNA (viRNA) has been identified from several viral genomes via directly deep RNA sequencing of the virus-infected cells, including zika virus (ZIKV). Once produced by endoribonuclease Dicer, viRNAs are loaded onto the Argonaute (AGO) family proteins of the RNA-induced silencing complexes (RISCs) to pair with their RNA targets and initiate the cleavage of target genes. However, the identities of functional ZIKV viRNAs and their viral RNA targets remain largely unknown. Our recent study has shown that ZIKV capsid protein interacted with Dicer and antagonized its endoribonuclease activity, which requires its histidine residue at the 41st amino acid. Accordingly, the engineered ZIKV-H41R loss-of-function (LOF) mutant virus no longer suppresses Dicer enzymatic activity nor inhibits miRNA biogenesis in NSCs. By combining AGO-associated RNA sequencing, deep sequencing analysis in ZIKV-infected human neural stem cells (NSCs), and miRanda target scanning, we defined 29 ZIKV derived viRNA profiles in NSCs, and established a complex interaction network between the viRNAs and their viral targets. More importantly, we found that viRNA production from the ZIKV mRNA is dependent on Dicer function and is a limiting factor for ZIKV virulence in NSCs. As a result, much higher levels of viRNAs generated from the ZIKV-H41R virus-infected NSCs. Therefore, our mapping of viRNAs to their RNA targets paves a way to further investigate how viRNAs play the role in anti-viral mechanisms, and perhaps other unknown biological functions.
Tephrostratigraphy and Magma Evolution Based on Combined Zircon Trace Element and U-Pb Age Data: Fingerprinting Miocene Silicic Pyroclastic Rocks in the Pannonian Basin
Authors: Lukács Réka , Guillong Marcel , Bachmann Olivier , Fodor László , Harangi Szabolcs 
Published: February 2021

We present a novel approach to use zircon as a correlation tool as well as a monitor for magma reservoir processes in silicic volcanic systems. Fingerprinting eruption products based on trace element content and U-Pb dates of zircon offers a promising, previously underestimated tephra correlation perspective, particularly in cases where the main minerals and glass are altered. Using LA-ICP-MS analyses, a rapid and cost-effective method, this study presents U-Pb dates and trace element concentration data of more than 950 zircon crystals from scattered occurrences of early to mid-Miocene silicic ignimbrites in the northern Pannonian Basin, eastern-central Europe. This magmatic phase produced &gt;4000 km3of erupted material, which provide unique stratigraphic marker horizons in central and southern Europe. The newly determined zircon U-Pb eruption ages for the distal pyroclastic deposits are between 17.5 and 14.3 Ma, comparable with the previously published ages of the main eruptive events. Multivariate discriminant analysis of selected trace element concentrations in zircon proved to be useful to distinguish the main volcanic units and to correlate the previously ambiguously categorized pyroclastic deposits with them. Using the zircon trace element content together with published glass data from crystal-poor ignimbrites, we determined the zircon/melt partition coefficients. The obtained values of the distinct eruption units are very similar and comparable to published data for silicic volcanic systems. This suggests that zircon/melt partition coefficients in calc-alkaline dacitic to rhyolitic systems are not significantly influenced by the melt composition at &gt;70 wt% SiO2at near solidus temperature. The partition coefficients and zircon trace element data were used to calculate the equilibrium melt composition, which characterizes the eruption products even where glass is thoroughly altered or missing. Hence, our results provide important proxies for tephrostratigraphy in addition to yielding insights into the complex processes of silicic magma reservoirs.
Impact of COVID-19 on Educational Services in Canadian Children With Attention-Deficit/Hyperactivity Disorder
Authors: Hai Tasmia , Swansburg Rose , MacMaster Frank P. , Lemay Jean-François 
Published: February 2021

The COVID-19 pandemic led to school closures and a rapid transition to online classes. However, little is known about the impact of online learning in Canadian children with Attention-Deficit/Hyperactivity Disorder (ADHD). An online survey created on Qualtrics was distributed to families across Canada. Data collection was conducted over a total of five weeks in May and June 2020. We reviewed 587 surveys (4% margin of error using a 95% confidence interval) completed by caregivers/parents of children with ADHD (mean child age 10.14 years, SD = 3.06). Survey questions focused on hours of schoolwork completed and whether the learning needs of children with ADHD were met during school closures. Results indicated 90% of children with ADHD received web-based learning during the pandemic. Parents (41%) reported &lt; 5 h of schoolwork per week, and 35% indicated between 5 to 10 h. Of the parents who said their child with ADHD had a modified curriculum (68%), 40% reported receiving educational materials that met their learning expectations during online classes. Parents (59%) reported that their child found it “very challenging” adjusting to online classes. The results indicated that children with ADHD faced significant challenges in adapting to online learning during the pandemic. Binary logistic regression indicated significant associations between depression severity, difficulties with starting and managing tasks and challenges adjusting to online learning. Long-term consequences of these challenges will need to be determined to ensure children with ADHD are able to meet their academic expectations.
Long-Term Outcomes and Prognoses of Elderly Patients (≥65-Years-Old) With Distant Metastases From Well-Differentiated Thyroid Cancer During Radioiodine Therapy and Follow-Up
Authors: Qiu Zhong-Ling , Shen Chen-Tian , Sun Zhen-Kui , Song Hong-Jun , Xi Chuang , Zhang Guo-Qiang , Wang Yang , Luo Quan-Yong 
Published: February 2021

ObjectiveThe objective of this study was to investigate the clinicopathological characteristics, long-term outcomes, and prognostic factors of elderly patients with distant metastases at initial diagnosis from well-differentiated thyroid cancer (WDTC) during radioactive iodine (131I) treatment and follow-up.MethodsA retrospective review of medical records identified 183 elderly patients with DTC who underwent 131I treatment at our institution between 2006 and 2019.ResultsIn total, 57 elderly WDTC patients with distant metastases were enrolled in this study. After 131I treatment, 32 (56.14%) patients had 131I avidity and 25 (43.86%) had non-131I avidity; 35 (61.40%) cases were classified as radioiodine refractory (RR)-WDTC and 22 (38.60%) as non-RR-WDTC. At the end of follow-up, 25 (43.86%) patients had died and 32 (56.14%) were alive. The 5- and 10-year overall survival (OS) rates were 71.50% and 30.49%, respectively, while the 5- and 10-year disease-specific survival (DSS) rates were 76.89% and 48.71%, respectively. Multivariate analyses showed that gross extrathyroidal extension and RR-DTC were independent prognostic factors for poor OS (P=0.04 and P=0.03, respectively), while gross extrathyroidal extension, extrapulmonary distant metastases, and RR-WDTC were independent prognostic factors for poor DSS at the end of follow-up (P=0.02, P=0.03, and P=0.02, respectively).ConclusionsWDTC with distant metastases at initial diagnosis accounted for 31.15% of all elderly patients with DTC. Gross extrathyroidal extension and RR-DTC were the major factors associated with poor OS; gross extrathyroidal extension, extrapulmonary distant metastases, and RR-DTC were independent prognostic factors for poor DSS in elderly DTC patients with distant metastases.
Iron Deficiency, a Risk Factor of Thyroid Disorders in Reproductive-Age and Pregnant Women: A Systematic Review and Meta-Analysis
Authors: Luo Jingyi , Wang Xiaoxia , Yuan Li , Guo Lixin 
Published: February 2021

BackgroundIron deficiency (ID) is concerned as the most common nutritional deficiency worldwide. The effects of ID on thyroid function and autoimmunity in pregnant women and reproductive-age women are controversial. The aim of the current study was to summarize the evidences and evaluate the relationship between ID and thyroid disorders.MethodsIn this systematic review and meta-analysis, studies published on the Cochrane, Embase, Medline, and PubMed databases by October 2020 were searched. A total of 636 studies which discussed the correlation between ID and thyroid disorders were eligible in the initial search. Pooled mean differences (MD) and 95% confidence intervals (CI) were calculated for the assessment of thyrotropin (TSH) and free thyroxine (FT4) levels. Combined odd ratios (OR) and 95% CI were calculated for the assessment of the prevalence of overt and subclinical hypothyroidism, positive thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb).ResultsFor women of reproductive age, ID could significantly increase the risk of positive TPOAb (OR: 1.89; 95% CI: 1.17, 3.06:P= 0.01) and both positive TPOAb and TgAb (OR: 1.48; 95% CI: 1.03, 2.11:P= 0.03). The meta-analysis of pregnant women showed that pregnant women with ID had increased serum TSH levels (MD: 0.12; 95% CI: 0.07, 0.17; P &lt; 0.00001) and decreased FT4 levels (MD: −0.73; 95% CI: −1.04, −0.41; P &lt; 0.00001). Meanwhile, the prevalence of overt (OR: 1.60; 95% CI: 1.17, 2.19; P = 0.004) and subclinical (OR: 1.37; 95% CI: 1.13, 1.66; P = 0.001) hypothyroidism in pregnant women with ID was significantly increased.ConclusionsID may adversely affect thyroid function and autoimmunity of pregnant and reproductive-age women and it is very necessary for monitoring iron nutritional status and early treatment of ID for them.
Six Metabolism Related mRNAs Predict the Prognosis of Patients With Hepatocellular Carcinoma
Authors: Wu Xiwen , Lan Tian , Li Muqi , Liu Junfeng , Wu Xukun , Shen Shunli , Chen Wei , Peng Baogang 
Published: February 2021

Background: Hepatocellular carcinoma (HCC) is one of the most common aggressive solid malignant tumors and current research regards HCC as a type of metabolic disease. This study aims to establish a metabolism-related mRNA signature model for risk assessment and prognosis prediction in HCC patients.Methods: HCC data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) was used to screen out the candidate mRNAs and calculate the risk coefficient to establish the prognosis model. A high-risk group and low-risk group were separated for further study depending on their median risk score. The reliability of the prediction was evaluated in the validation cohort and the whole cohort.Results: A total of 548 differential mRNAs were identified from HCC samples (n = 374) and normal controls (n = 50), 45 of which were correlated with prognosis. A total of 373 samples met the screening criteria and there were randomly divided into the training cohort (n = 186) and the validation cohort (n = 187). In the training cohort, six metabolism-related mRNAs were used to construct a prognostic model with a LASSO regression model. Based on the risk model, the overall survival rate of the high-risk cohort was significantly lower than that of the low-risk cohort. The results of a time-ROC curve proved that the risk score (AUC = 0.849) had a higher prognostic value than the pathological grade, clinical stage, age or gender.Conclusion: The model constructed by the six metabolism-related mRNAs has a significant value for survival prediction and can be applied to guide the evaluation of HCC and the designation of clinical therapy.
Examining Different Motor Learning Paradigms for Improving Balance Recovery Abilities Among Older Adults, Random vs. Block Training—Study Protocol of a Randomized Non-inferiority Controlled Trial
Authors: Nachmani Hadas , Paran Inbal , Salti Moti , Shelef Ilan , Melzer Itshak 
Published: February 2021

Introduction: Falls are the leading cause of fatal and nonfatal injuries among older adults. Studies showed that older adults can reduce the risk of falls after participation in an unexpected perturbation-based balance training (PBBT), a relatively novel approach that challenged reactive balance control. This study aims to investigate the effect of the practice schedule (i.e., contextual interference) on reactive balance function and its transfer to proactive balance function (i.e., voluntary step execution test and Berg balance test). Our primary hypothesis is that improvements in reactive balance control following block PBBT will be not inferior to the improvements following random PBBT.Methods and Analysis: This is a double-blind randomized controlled trial. Fifty community-dwelling older adults (over 70 years) will be recruited and randomly allocated to a random PBBT group (n = 25) or a block PBBT group (n = 25). The random PBBT group will receive eight training sessions over 4 weeks that include unexpected machine-induced perturbations of balance during hands-free treadmill walking. The block PBBT group will be trained by the same perturbation treadmill system, but only one direction will be trained in each training session, and the direction of the external perturbations will be announced. Both PBBT groups (random PBBT and block PBBT) will receive a similar perturbation intensity during training (which will be customized to participant’s abilities), the same training period, and the same concurrent cognitive tasks during training. The generalization and transfer of learning effects will be measured by assessing the reactive and proactive balance control during standing and walking before and after 1 month of PBBT, for example, step and multiple steps and fall thresholds, Berg balance test, and fear of falls. The dependent variable will be rank transformed prior to conducting the analysis of covariance (ANCOVA) to allow for nonparametric analysis.Discussion: This research will explore which of the balance retraining paradigms is more effective to improve reactive balance and proactive balance control in older adults (random PBBT vs. block PBBT) over 1 month. The research will address key issues concerning balance retraining: older adults’ neuromotor capacities to optimize training responses and their applicability to real-life challenges.Clinical Trial Registration: Helsinki research ethics approval has been received (Soroka Medical Center approval #0396-16-SOR; MOH_2018-07-22_003536; www.ClinicalTrials.gov, NCT04455607).
A Prognostic Model for Glioblastoma Patients Treated With Standard Therapy Based on a Prospective Cohort of Consecutive Non-Selected Patients From a Single Institution
Authors: Abedi Armita Armina , Grunnet Kirsten , Christensen Ib Jarle , Michaelsen Signe Regner , Muhic Aida , Møller Søren , Hasselbalch Benedikte , Poulsen Hans Skovgaard , Urup Thomas 
Published: February 2021

BackgroundGlioblastoma patients administered standard therapies, comprising maximal surgical resection, radiation therapy with concomitant and adjuvant temozolomide, have a variable prognosis with a median overall survival of 15–16 months and a 2-year overall survival of 30%. The aim of this study was to develop a prognostic nomogram for overall survival for glioblastoma patients treated with standard therapy outside clinical trials.MethodsThe study included 680 consecutive, non-selected glioblastoma patients administered standard therapy as primary treatment between the years 2005 and 2016 at Rigshospitalet, Copenhagen, Denmark. The prognostic model was generated employing multivariate Cox regression analysis modeling overall survival.ResultsThe following poor prognostic factors were included in the final prognostic model for overall survival: Age (10-year increase: HR = 1.18, 95% CI: 1.08–1.28, p &lt; 0.001), ECOG performance status (PS) 1 vs. 0 (HR = 1.30, 95% CI: 1.07–1.57, p = 0.007), PS 2 vs. 0 (HR = 2.99, 95% CI: 1.99–4.50, p &lt; 0.001), corticosteroid use (HR = 1.42, 95% CI: 1.18–1.70, p &lt; 0.001), multifocal disease (HR = 1.63, 95% CI: 1.25–2.13, p &lt; 0.001), biopsy vs. resection (HR = 1.35, 95% CI: 1.04–1.72, p = 0.02), un-methylated promoter of the MGMT (O6-methylguanine-DNA methyltransferase) gene (HR = 1.71, 95% CI: 1.42–2.04, p &lt; 0.001). The model was validated internally and had a concordance index of 0.65.ConclusionA nomogram for overall survival was established. This model can be used for risk stratification and treatment planning, as well as improve enrollment criteria for clinical trials.