bluuebunny/crossref_metadata_2025_split huggingface dataset:
PENGEMBANGAN MEDIA MINIATUR BUDAYA PADA PEMBELAJARAN TEMATIK UNTUK MENINGKATKAN HASIL BELAJAR SISWA SEKOLAH DASAR
Authors: Khoir Sifa’ul , Cholifah Tety Nur 
Published: April 2021

Tujuan utama penelitian ini adalah untuk mengetahui: (1) menjelaskan proses pengembangan media miniatur budaya pada pembelajaran tematik subtema keberagaman budaya bangsaku untuk meningkatkan hasil belajar siswa kelas IV, (2) menjelaskan kemenarikan media miniatur budaya dilihat dari fungsinya sebagai media untuk meningkatkan hasil belajar siswa kelas IV SD, (3) menjelaskan keefektifan penggunaan media miniatur budaya digunakan sebagai media meningkatkan hasil belajar subtema keberagaman budaya bangsaku siswa kelas IV SD. Pendekatan penelitian dan pengembangan (R&D) mengikuti prosedur dari Borg and Gall untuk menghasilkan produk tertentu dan menguji keefektifan produk tersebut. Model penelitian dan pengembangan ini terdapat sepuluh langkah pelaksanaan strategi penelitian dan pengembangannya. Instrumen pengumpulan data yang digunakan adalah lembar validasi ahli media dan ahli materi dan tes hasil belajar. Hasil penelitian menunjukkan bahwa, (1) proses pengembangan media miniatur budaya pada pembelajaran tematik subtema keberagaman budaya bangsaku untuk meningkatkan hasil belajar siswa kelas IV ini dilakukan mengikuti teori Borg and Gall, (2) media miniatur budaya terbukti memiliki ketertarikan yang sangat baik bagi siswa (3) hasil belajar siswa mengalami peningkatan setelah menggunakan media miniatur budaya pada proses pembelajaran.
Experimental Aqueous Alteration of Cortical Bone Microarchitecture Analyzed by Quantitative Micro-Computed Tomography
Authors: Kral Anna G. , Ziegler Alexander , Tütken Thomas , Geisler Thorsten 
Published: April 2021

Bones are one of the most common vertebrate fossil remains and are widely used as proxy archives in palaeontology and archaeology. Previous histological analyses have shown that bone microarchitecture is mostly well-preserved in fossil remains, but partially or even entirely lost in most archaeological specimens. As a consequence, processes occurring during early diagenesis are pivotal for the preservation of bones and a better understanding of these processes would be required to assess the significance of information stored in fossilized bones. Although much of the changes occur at the nanometer scale, determining the resistance of bone microarchitecture to diagenetic alteration on a microscopic scale constitutes a prerequisite for more detailed studies. Here, results from the first comparative in vitro taphonomy study of cortical bone simulating conditions potentially encountered in early diagenetic settings are presented. In order to accelerate anticipated early diagenetic changes and to facilitate their study in a practical framework, cortical bone samples were exposed to aqueous solutions with temperature, time, and composition of the experimental solutions as controlled parameters. Before and after the experiments, all samples were characterized quantitatively using micro-computed tomography to document structural changes. The results show that the overall change in cortical porosity predominantly occurred in canals with diameters ≤9 µm (∆Ct.Po = ±30%). Furthermore, the data also show that the solution composition had a stronger impact on changes observed than either temperature or time. It was also found that samples from the two experimental series with a freshwater-like solution composition showed a characteristic reaction rim. However, it remains unclear at present if the observed changes have an impact on reactions occurring at the nanometer scale. Nonetheless, the results clearly demonstrate that on a micrometer scale down to 3 μm, bone microarchitecture is largely resistant to aqueous alteration, even under very different physicochemical conditions. In addition, the data illustrate the complexity of the interaction of different diagenetic factors. The results presented here provide a solid framework for future investigations on reaction and transport mechanisms occurring during the early diagenesis of fossil bones.
A Resource and Policy Driven Assessment of the Geothermal Energy Potential Across the Islands of St. Vincent and the Grenadines
Authors: Koon Koon Randy , Shah Kalim , Ashtine Masaō , Lewis Santana 
Published: April 2021

The energy security of each Caribbean Community (CARICOM) member state is a key issue specifically addressed based on the energy demands of each nation. St. Vincent and the Grenadines (SVG) has the potential to strengthen its energy sector through the exploitation of immense untapped natural geothermal resources. Currently, SVG is planning to integrate base load power through a 10 Megawatt-electric (MWe) geothermal power plant (GPP1). The paper aims to highlight a detailed resource assessment profile of the renewables across SVG and the projected benefits of the proposed 10 MWe geothermal power potential, such as the positive economic development (displacing 149,000 bbls of crude oil), and the transition to a more climate-sensitive nation (displacing an estimated 0.172 million tCO2e/year). In addition, a volumetric method (Monte Carlo simulations) has been applied to reveal that the geothermal reservoir can sustain a minimum of 31 MWe, 34 MWe and 92 MWe over the lifespan of 25–30 years, for well 1 (SVG01), well 2 (SVG02) and well 3 (SVG03) respectively. Given the findings of the assessment and simulations, several policy approaches are identified as potential means of enhancing geothermal resource development and leveraging the resource for the islands’ sustainable energy demands. These include incentivization for public-private partnerships, information certainty, regulatory processes, and strengthened institutions.
Valproic Acid Protects Chondrocytes from LPS-Stimulated Damage via Regulating miR-302d-3p/ITGB4 Axis and Mediating the PI3K-AKT Signaling Pathway
Authors: Sun Long , Zheng Wei , Liu Qian-Dong , Ge Lei 
Published: April 2021

Background: Osteoarthritis (OA) is one of the most common degenerative joint diseases characterized by increased apoptosis and autophagy deficiency. The investigation was performed to examine the effect of valproic acid (VPA) and molecular mechanism related to miR-302d-3p/ITGB4 axis in OA.Methods: The OA clinical samples were obtained from the GEO database to analyze differentially expressed genes. An in vitro OA model was mimicked by LPS in CHON-001 cells. Autophagy-related genes were downloaded from the HADb website, and potential drugs were mined using the CTD website. The upstream factors of ITGB4 were predicted with bioinformatics analysis, which was validated by luciferase activity assay and RIP assay. Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry. The expression levels, including ITGB4, miR-302d-3p, and autophagy-/PI3K-AKT pathway-related markers, were measured by qRT-PCR or/and western blot.Results: Our results showed that miR-302d-3p inhibited cell viability and promoted apoptosis of LPS-treated CHON-001 cells by targeting ITGB4. VPA treatment remarkably alleviated LPS-stimulated injury in CHON-001 cells. The inhibitory effect of VPA on LPS-stimulated damage in CHON-001 cells was weakened by miR-302d-3p overexpression, while it was intensified because of ITGB4 upregulation. Mechanistically, VPA treatment induced a significant decrease in the levels of p-PI3K and p-AKT in LPS-stimulated CHON-001 cells through regulating miR-302d-3p/ITGB4 axis.Conclusion: Overall, VPA treatment may ameliorate LPS-induced injury on chondrocytes via the regulation of miR-302d-3p/ITGB4 pair and the inactivation of the PI3K-AKT pathway.
Development and Validation of a Nomogram for Preoperative Prediction of Lymph Node Metastasis in Lung Adenocarcinoma Based on Radiomics Signature and Deep Learning Signature
Authors: Ran Jia , Cao Ran , Cai Jiumei , Yu Tao , Zhao Dan , Wang Zhongliang 
Published: April 2021

Background and PurposeThe preoperative LN (lymph node) status of patients with LUAD (lung adenocarcinoma) is a key factor for determining if systemic nodal dissection is required, which is usually confirmed after surgery. This study aimed to develop and validate a nomogram for preoperative prediction of LN metastasis in LUAD based on a radiomics signature and deep learning signature.Materials and MethodsThis retrospective study included a training cohort of 200 patients, an internal validation cohort of 40 patients, and an external validation cohort of 60 patients. Radiomics features were extracted from conventional CT (computed tomography) images. T-test and Extra-trees were performed for feature selection, and the selected features were combined using logistic regression to build the radiomics signature. The features and weights of the last fully connected layer of a CNN (convolutional neural network) were combined to obtain a deep learning signature. By incorporating clinical risk factors, the prediction model was developed using a multivariable logistic regression analysis, based on which the nomogram was developed. The calibration, discrimination and clinical values of the nomogram were evaluated.ResultsMultivariate logistic regression analysis showed that the radiomics signature, deep learning signature, and CT-reported LN status were independent predictors. The prediction model developed by all the independent predictors showed good discrimination (C-index, 0.820; 95% CI, 0.762 to 0.879) and calibration (Hosmer-Lemeshow test, P=0.193) capabilities for the training cohort. Additionally, the model achieved satisfactory discrimination (C-index, 0.861; 95% CI, 0.769 to 0.954) and calibration (Hosmer-Lemeshow test, P=0.775) when applied to the external validation cohort. An analysis of the decision curve showed that the nomogram had potential for clinical application.ConclusionsThis study presents a prediction model based on radiomics signature, deep learning signature, and CT-reported LN status that can be used to predict preoperative LN metastasis in patients with LUAD.
Delirium in Children Undergoing Hematopoietic Cell Transplantation: A Multi-Institutional Point Prevalence Study
Authors: Traube Chani , Gerber Linda M. , Mauer Elizabeth A. , Small Keshia , Broglie Larisa , Chopra Yogi Raj , Duncan Christine N. , Ebens Christen L. , Fitzgerald Julie C. , Freedman Jason L. , Hudspeth Michelle P. , Hurley Caitlin , Mahadeo Kris M. , McArthur Jennifer , Shapiro Miriam C. , Sharron Matthew P. , Wall Donna A. , Zinter Matt S. , Greenwald Bruce M. , Silver Gabrielle , Boulad Farid 
Published: April 2021

Introduction: Delirium occurs frequently in adults undergoing hematopoietic cell transplantation, with significant associated morbidity. Little is known about the burden of delirium in children in the peri-transplant period. This study was designed to determine delirium rates, define risk factors (demographic and treatment related), and establish feasibility of multi-institutional bedside screening for delirium in children undergoing hematopoietic cell transplant.Methods: This is a multi-institutional point prevalence study. All subjects were prospectively screened for delirium twice daily using the Cornell Assessment of Pediatric Delirium over a 10-day period. De-identified data, including basic demographics and daily characteristics, were extracted from the electronic medical record.Results: Eleven North American institutions were included, 106 children were enrolled, and 883 hospital days were captured. Delirium screening was successfully completed on more than 98% of the study days. Forty-eight children (45%) developed delirium over the course of the 10-day study. Children were diagnosed with delirium on 161/883 study days, for an overall delirium rate of 18% per day. Higher delirium rates were noted in children &lt;5 years old (aOR 0.41 for children over 5 years), and in association with specific medications (melatonin, steroids, and tacrolimus).Conclusion: Delirium was a frequent occurrence in our study cohort, with identifiable risk factors. Delirium screening is highly feasible in the pediatric hematopoietic cell transplant patient population. A large-scale prospective longitudinal study following children throughout their transplant course is urgently needed to fully describe the epidemiology of pediatric delirium, explore the effects of delirium on patient outcomes, and establish guidelines to prevent and treat delirium in the peri-transplant period.
Case Report: Outcome of Osimertinib Treatment in Lung Adenocarcinoma Patients With Acquired KRAS Mutations
Authors: Xiu Weigang , Zhang Qianqian , Yu Min , Huang Yin , Huang Meijuan 
Published: April 2021

BackgroundOsimertinib belongs to the third-generation epidermal growth factor receptor tyrosine kinase inhibitor that has shown positive effects in treating lung adenocarcinoma cancer. However, the subsequent resistance to Osimertinib has become a clinical challenge.Case PresentationWe present two lung adenocarcinoma cases that developed a resistance to Osimertinib. Among them, one patient attained both KRAS exon 2 and exon 3 mutations and was given paclitaxel (albumin-bound) plus carboplatin. The other patient exhibited a KRAS exon 3 mutation, so the paclitaxel (albumin-bound) plus nivolumab was administered. Eventually, the second patient manifested a better clinical outcome than the first.ConclusionThese results provide supporting evidence that KRAS exon 3 (R68S) mutations may be associated with Osimertinib resistance in lung adenocarcinoma patients. This further reveals the relationship between subtypes of acquired KRAS mutations and the effect of therapeutic approaches. Moreover, the combination of chemotherapy and immune checkpoint inhibitors may generate a satisfying disease control.
Analysis of Adenoviral p53 Gene Therapy Clinical Trials in Recurrent Head and Neck Squamous Cell Carcinoma
Authors: Sobol Robert E. , Menander Kerstin B. , Chada Sunil , Wiederhold Dora , Sellman Beatha , Talbott Max , Nemunaitis John J. 
Published: April 2021

BackgroundWe conducted an analysis of previous adenoviral p53 (Ad-p53) treatment data in recurrent head and neck squamous cell carcinoma (HNSCC) patients to identify optimal Ad-p53 treatment methods for future clinical trials.MethodsThe analysis involved recurrent HNSCC patients treated with Ad-p53 for whom p53 genotyping and immunohistochemistry tumor biomarker studies had been performed (n = 70). Ad-p53 tumor treatment responses defined by RECIST 1.1 criteria were correlated with Ad-p53 dose and tumor p53 biomarkers. Gene expression profiles induced by Ad-p53 treatment were evaluated using the Nanostring IO 360 panel.ResultsAd-p53 dose based upon the injected tumor volume had a critical effect on tumor responses. All responders had received Ad-p53 doses greater than 7 × 1010 viral particles/cm3 of tumor volume. There was a statistically significant difference in tumor responses between patients treated with greater than 7 × 1010 viral particles/cm3 compared to patients treated at lower Ad-p53 doses (Tumor Response 31% (9/29) for Ad-p53 &gt; 7 × 1010 viral particles/cm3 versus 0% (0/25) for Ad-p53 &lt; 7 × 1010 viral particles/cm3; p = 0.0023). All responders were found to have favorable p53 biomarker profiles defined by less than 20% p53 positive tumor cells by immunohistochemistry (IHC), wild type p53 gene sequence or p53 deletions, truncations, or frame-shift mutations without functional p53 tetramerization domains. Preliminary gene expression profiling results revealed that Ad-p53 treatment increased interferon signaling, decreased TGF-beta and beta-catenin signaling resulting in an increased CD8+ T cell signature which are associated with increased responses to immune checkpoint blockade.ConclusionsOur findings have important implications for future p53 targeted cancer treatments and identify fundamental principles to guide Ad-p53 gene therapy. We discovered that previous Ad-p53 clinical trials were negatively impacted by the inclusion of patients with unfavorable p53 biomarker profiles and by under dosing of Ad-p53 treatment. Future Ad-p53 clinical trials should have favorable p53 biomarker profiles inclusion criteria and Ad-p53 dosing above 7 × 1010 viral particles/cm3 of injected tumor volume. Preliminary gene expression profiling identified p53 mechanisms of action associated with responses to immune checkpoint blockade supporting evaluation of Ad-p53 in combination with immune checkpoint inhibitors.
p53 Expression, Programmed Death Ligand 1, and Risk Factors in Urinary Tract Small Cell Carcinoma
Authors: Golijanin Borivoj , Gershman Boris , De Souza Andre , Kott Ohad , Carneiro Benedito A. , Mega Anthony , Golijanin Dragan J. , Amin Ali 
Published: April 2021

Introduction: Small cell carcinoma of the urinary tract (SCCUT) is a rare finding with poor clinical course. This study sheds light on the molecular subtype and identifies risk factors in patients diagnosed with SCCUT.Methods: Immunohistochemical expression of immunotherapy target programmed death ligand 1 (PD-L1) and luminal (GATA3), basal (p63), and p53 markers are assessed in patients diagnosed with SCCUT. Univariate analysis identified risk factors. Overall survival (OS) is computed using the Kaplan–Meier method.Results: Tissue was available for 70.2% (33/47). All showed a high PD-L1 expression phenotype. p53 is seen in 93.9% (31/33), mostly as overexpression, GATA3 in 45.5% (15/33), and p63 in 57.6% (19/33). For the entire cohort (n = 47), 1-year survival was 59.6%, and the median OS was 17 months. Univariate analysis shows that chemotherapy [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.14–0.61, p = 0.001], radical surgery (HR = 0.37, 95% CI = 0.18–0.76, p = 0.007), and diagnosis of non-pure SCCUT (HR = 0.44, 95% CI = 0.22–0.86, p = 0.02) are favorable prognostic features. Metastasis had negative associations with survival (HR = 2.1, 95% CI = 1.1–4.2, p = 0.03).Conclusions: In this series, pure and mixed SCCUT are characterized by p53 overexpression and a high PD-L1 phenotype. Histology of non-pure SCCUT is a positive prognosticator, and radical cystectomy or chemotherapy can improve OS. These findings demonstrate that SCCUT may be eligible for PD-L1 immunotherapy.
β3 Adrenergic Receptor Stimulation Promotes Reperfusion in Ischemic Limbs in a Murine Diabetic Model
Authors: Bubb Kristen J. , Ravindran Dhanya , Cartland Siân P. , Finemore Meghan , Clayton Zoe E. , Tsang Michael , Tang Owen , Kavurma Mary M. , Patel Sanjay , Figtree Gemma A. 
Published: April 2021

Aims/Hypothesis: Peripheral arterial disease (PAD) is a major burden, resulting in limb claudication, repeated surgical interventions and amputation. There is an unmet need for improved medical management of PAD that improves quality of life, maintains activities of daily life and reduces complications. Nitric oxide (NO)/redox balance is a key regulator of angiogenesis. We have previously shown beneficial effects of a β3 adrenergic receptor (β3AR) agonist on NO/redox balance. We hypothesized that β3AR stimulation would have therapeutic potential in PAD by promoting limb angiogenesis.Methods: The effect of the β3AR agonist CL 316,243 (1–1,000 nmol/L in vitro, 1 mg/kg/day s. c) was tested in established angiogenesis assays with human endothelial cells and patient-derived endothelial colony forming cells. Post-ischemia reperfusion was determined in streptozotocin and/or high fat diet-induced diabetic and non-diabetic mice in vivo using the hind limb ischemia model.Results: CL 316,243 caused accelerated recovery from hind limb ischemia in non-diabetic and type 1 and 2 diabetic mice. Increased eNOS activity and decreased superoxide generation were detected in hind limb ischemia calf muscle from CL 316, 243 treated mice vs. controls. The protective effect of CL 316,243 in diabetic mice was associated with &gt;50% decreases in eNOS glutathionylation and nitrotyrosine levels. The β3AR agonist directly promoted angiogenesis in endothelial cells in vitro. These pro-angiogenic effects were β3AR and NOS-dependent.Conclusion/Interpretation:β3AR stimulation increased angiogenesis in diabetic ischemic limbs, with demonstrable improvements in NO/redox balance and angiogenesis elicited by a selective agonist. The orally available β3AR agonist, Mirabegron, used for overactive bladder syndrome, makes translation to a clinical trial by repurposing of a β3AR agonist to target PAD immediately feasible.
Longitudinal-Survival Models for Case-Based Tuberculosis Progression
Authors: Kiplimo Richard , Kosgei Mathew , Mwangi Ann , Onyango Elizabeth , Ogero Morris , Koske Joseph 
Published: April 2021

Introduction: Tuberculosis (TB) disease continues to be responsible for a high global burden with an estimated 10 million people falling ill each year and an estimated 1.45 million deaths. Widely carried out analyses to utilize routine data coming from this disease, and well-established in literature, have paid attention to time-to-event with sputum smear results being considered only at baseline or even ignored. Also, logistic regression models have been used to demonstrate importance of sputum smear results in patient outcomes. A feature presented by this disease, however, is that each individual patient is usually followed over a period of time with sputum smear results being documented at different points of the treatment curve. This provides both repeated measures and survival times, which may require a joint modeling approach. This study aimed to investigate the association between sputum smear results and the risk of experiencing unfavorable outcome among TB patients and dynamically predict survival probabilities.Method: A joint model for longitudinal and time-to-event data was used to analyze longitudinally measured smear test results with time to experiencing unfavorable outcome for TB patients. A generalized linear mixed-effects model was specified for the longitudinal submodel and cox proportional hazards model for the time-to-event submodel with baseline hazard approximated using penalized B-splines. The two submodels were then assumed to be related via the current value association structure. Bayesian approach was used to approximate parameter estimates using Markov Chain Monte Carlo (MCMC) algorithm. The obtained joint model was used to predict the subject's future risk of survival based on sputum smear results trajectories. Data were sourced from routinely collected TB data stored at National TB Program database.Results: The average baseline age was 35 (SD: 15). Female TB patients constituted 36.42%. Patients with previous history of TB treatment constituted 6.38% (event: 15.25%; no event: 5.29%). TB/HIV co-infection was at 31.23% (event: 47.87%; no event: 29.20%). The association parameter 1.03 (CI[1.03,1.04]) was found to be positive and significantly different from zero, interpreted as follows: The estimate of the association parameter α = 1.033 denoted the log hazard ratio for a unit increase in the log odds of having smear positive results. HIV status (negative) 0.47 (CI [0.46,49]) and history of TB treatment (previously treated) (2.52 CI [2.41,2.63]), sex (female) (0.82 CI [0.78,0.84]), and body mass index (BMI) categories (severe malnutrition being reference) were shown to be statistically significant.Conclusion: Sputum smear result is important in estimating the risk to unfavorable outcome among TB patients. Men, previously treated, TB/HIV co-infected and severely malnourished TB patients are at higher risk of unfavorable outcomes.