bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pendidikan Karakter
Authors: Wahyuni Akhtim 
Published: January 2022

Puji syukur kepada Allah Swt. atas limpahan rahmat dan kasih sayangNya sehingga penulis bisa menyelesaikan buku ‘Pendidikan Karakter ‘Membentuk Pribadi Positif dan Unggul di Sekolah’ ini dan dapat terbit untuk memperkaya referensi tentang Pendidikan Karakter. Pendidikan karakter menjadi tema penting saat ini untuk mengatasi persoalan-persoalan sosial yang kerap melanda negara ini. Ia menjadi alternatif solusi yang perlu dilestarikan dalam kehidupan sehari-hari. Tidak terkecuali di lembaga pendidikan, yang notabene sebagai wadah penggodokan tiga ranah tingkah laku; kognitif, afektif, dan psikomotorik. Sekolah dipandang sebagai lahan yang efektif untuk membentuk pribadi positif anak, setelah keluarga. Pribadi positif yang terbangun dari proses pembiasaan karakter di sekolah diantaranya: Mampu menilai diri sendiri secara realisitik, Menerima tanggung jawab, kemandirian, dapat mengontrol emosi, berorientasi tujuan, penerimaan sosial, berbahagia, dan lainnya. Ini semua dapat terwujud jika semua stakeholder dilibatkan untuk mengawal dan menjalankan, dan mengevaluasi semua proses ini sehingga menjadi budaya positif di sekolah.Buku Pendidikan Karakter ini melengkapi buku-buku yang telah ada, untuk memperkaya konsep dan wawasan tentang Pendidikan Karakter. Pengalaman penulis di dunia pendidikan dan sebagai tenaga pengajar di Perguruan Tinggi serta peneliti dalam bidang pendidikan dan sosial banyak memberikan kontribusi dalam penulisan, sehingga buku ini terwujud. Penulis menyadari bahwa buku ini masih banyak kekurangan baik dari sisi konseptual maupun aplikasi. Oleh karena itu, kritik dan saran konstruktif selalu penulis harapkan untuk kesempurnaan buku ini. Tidak lupa penulis sampaikan terima kasih kepada semua pihak yang telah membantu dalam berbagai bentuk demi terselesaikannya buku ini. Semoga buku ini bermanfaat bagi para pembaca.
CYP2D6 Genotyping for Personalized Therapy of Tamoxifen in Indonesian Women with ER+ Breast Cancer
Authors: Maggadani Baitha Palanggatan , Junusmin Kathleen Irena , Sani Levana L. , Mahendra Caroline , Amelia Margareta , Gabriella Gabriella , Irwanto Astrid , Chan Alexandre , Harmita Harmita , Harahap Yahdiana , Haryono Samuel J. 
Published: January 2022

Abstract
PurposeTamoxifen, common adjuvant therapy prescribed in estrogen receptor positive (ER+) breast cancer, is metabolized by CYP2D6 enzyme into endoxifen. The phenotypes of CYP2D6, a highly polymorphic gene, vary from ultrarapid (UM), normal (NM), intermediate (IM), and poor metabolizers (PM). Studies showed that reduced CYP2D6 activity in IMs and PMs resulted in lower endoxifen level, thereby reducing therapy efficacy. This study aims to observe the distribution of CYP2D6 profiles and their corresponding endoxifen levels in Indonesian ER+ breast cancer patients.Methods151 patients who have received tamoxifen therapy for ≥8 weeks were recruited prospectively. DNA and blood samples were collected with buccal swab and finger-prick methods, respectively. Genotyping was performed using the qPCR method while metabolites measurement was performed using HPLC-tandem MS. Patients with IM/PM CYP2D6 profile were advised to increase their tamoxifen dose or switch to aromatase inhibitor, while patients with UM or NM CYP2D6 profile remained on 20 mg daily dose. Tamoxifen metabolites levels of those given 40 mg/day of tamoxifen were measured eight weeks post dose adjustment.ResultsWe found that 40.7% of patients recruited were IM. CYP2D6*10 was the most abundant allele (28.8%) and *10/*36 was the most frequently observed diplotype (23.6%). Endoxifen levels between the NM-PM, NM-IM, and IM-PM were statistically significant, and dose increase of tamoxifen successfully increased endoxifen levels in IMs to a similar level with NMs at baseline.ConclusionIndonesian women have a relatively high proportion of IMs. The correlation between CYP2D6 genotype and phenotype was shown in the significant difference in endoxifen levels among NMs, IMs, and PMs. Dose adjustment of tamoxifen to 40 mg daily positively increased endoxifen levels in IMs to a similar level as NMs. Implementing pharmacogenomics testing of CYP2D6 on ER+ breast cancer women taking tamoxifen can potentially increase the likelihood of achieving better treatment efficacy.Trial RegistrationThe trial was retrospectively registered at ClinicalTrials.gov on 18 March 2020 with identifier NCT04312347 (accessible at: https://clinicaltrials.gov/ct2/show/NCT04312347).
Pattern of Nutritional status in Node Negative versus Node Positive Head and Neck Cancer patients undergoing treatment - a prospective cohort study
Authors: Arora Anshika , Saini Sunil , Gupta Meenu 
Published: January 2022

Abstract
Purpose

The aim of this study was to study the nutritional profile of node negative and node positive patients undergoing treatment for head and neck squamous cell cancer (HNSCC).
Methods

This prospective cohort study was conducted between 2018 and 2020. Patients diagnosed with HNSCC, planned for treatment were enrolled after written informed consent. In Node negative(N0) and Node positive(N+) cohorts of patients, nutritional status was determined using- anthropometric measures and Subjective Global Assessment (SGA) scale pre-treatment, during and after treatment. Statistical analysis was performed using SPSS version 22. Data was analyzed using parametric and non-parametric tests, p value of 0.05 was considered significant.
Results

161 patients were analyses, 73 N0 and 88 N+ cohorts. Pre-treatment, 9.6 to 20.4% patients in N0 and 23.9 to 32.8% patients in N+ cohorts were malnourished. Incidence of malnutrition at completion of treatment was 40.8–52.5% overall, 20.5–41.1% N0, 39.5–62.8% N+. Mean reduction in weight (11.1% ±7.82 v/s 6.26% ±8.3, p=0.000), mean reduction in BMI (2.57 ±1.87 v/s 1.29 ±1.62, p=0.000), median reduction in MUAC (2cm v/s 1cm, p=0.000) and median increase in SGA score were higher (13 v/s 6, p=0.000) in multi-modality as compared to single modality treatment. Similar findings were noted in N0 and N+ cohorts.
Conclusion

As compared to N0, N+ patients had higher burden of malnutrition at diagnosis, more worsening of nutritional parameters during treatment. More decline in Nutritional status was seen in patients receiving multi-modality as compared to single modality treatment.
Trigonometric Fmn-Transform of Multi-Variable Functions and Its Application to the Partial Differential Equations and Image Processing
Authors: Alikhani Robab , Perfilieva Irina , Ganjeh-Alamdari M. 
Published: January 2022

Abstract
In this study, we focus on the extension of the trigonometric F m-transform technique for functions with one-variable in order to improve its approximation properties at the end points of [a,b] and then generalize the extended trigonometric Fm -transform technique to functions with more variables. The approximation and convergence properties of the direct and inverse multi-variable extended trigonometric Fm -transforms are discussed. The applicability of multi-variable trigonometric F m -transforms to approximate multi-variable functions are illustrated by some examples. Moreover, some direct formulas for the multi-variable extended trigonometric Fm -transforms of partial derivatives of multi-variable functions are obtained and they are applied to solving the Cauchy problem of the transport equation. Also, the application of multi-variable extended trigonometric Fm -transforms for image compression is described. Some examples for the validity of the obtained results about the partial differential equations and image compression are given. The results are compared with some existence ones in the literature.
Bioavailability Enhancement of Vitamin E TPGS Coated Liposomes of Nintedanib Esylate Formulation Developed Using Quality by Design Approach
Authors: Kala Shabari Girinath , Chinni Santhivardhan 
Published: January 2022

Abstract
PurposeNintedanib esylate (NE) is a kinase inhibitor designated for the cure of non-small cell lung cancer suffers from first-pass metabolism which resulted in low oral bioavailability (~4.7%). The intent of this exploration was to increase the oral bioavailability of NE by means of TPGS coated liposomes. MethodsThe NE-loaded TPGS coated liposomes were formulated by high-speed homogenization by optimizing process parameters like phospholipids: cholesterol molar ratio, drug loading and sonication time through the design of experiments. The drug's behaviour was studied using a variety of techniques, including physicochemical characterization, in-vitro and in-vivo studies. ResultsThe NE-liposomes had a particle size of 125±6.68 nm, entrapment efficiency of 88.64±4.12% and zeta potential of +46±2.75 mV. X-ray diffraction analysis revealed that NE had been converted to an amorphous state, while transmission electron microscope images showed spherical shape and smooth coating of TPGS on surface of liposomes. The formulation showed Higuchi kinetics with sustained drug release of 88.72 ± 3.40% in 24 hours. Cellular uptake of C-6 labelled liposomes was observed in A-549 cells and cytotoxicity testing revealed that NE-liposomes were more effective than marketed formulation Ofev®. Formulation remained in simulated fluids and for three months in stability chamber and. Liposomal oral bioavailability was ~6.23 times greater in sprague dawley male rats compared to marketed formulation Ofev®, according to in-vivo pharmacokinetic data. ConclusionNE-Liposomal formulations are better for oral administration compared to the marketed capsules because of the prolonged drug release and increased oral bioavailability as a result, the developed formulation can become a successful strategy in cancer chemotherapy.
Novel Splice-Site and Missense Variant of PNPLA6 in an Austrian Family Causing Spastic Paraplegia-39 with Cerebellar Oculomotor Disorder
Authors: Viertauer Sebastian , Kurth Ingo , Eggermann Katja , Eggers Christian 
Published: January 2022

Abstract
Background The term hereditary spastic paraplegia comprises an ever-expanding array of neurological disorders with distinct aetiologies. Spastic paraplegia 39 is one of the many variants with additional features of other organs and neurological systems. We describe a large kindred with two hitherto undescribed mutations of PNPLA6 and a novel clinical phenotype as, in addition to spastic paraplegia, affected subjects suffered from a prominent cerebellar oculomotor dysfunction. Methods Three of five genetically tested family members of a large kindred were affected by spastic gait and cerebellar oculomotor dysfunction. Clinical, imaging, laboratory and electrophysiological data were analyzed. Genetic analysis was done using next-generation sequencing. Segregation analyses were performed by Sanger sequencing. To assess the pathogenicity of genetic variants on the encoded protein, in silico assessments were carried out. Results Two hitherto unknown sequence variants in the PNPLA6 gene, a splice-site variant c.1635+3G>T and a missense variant c.3401A>T, p.(Asp1134Val), were detected. Compound-heterozygous siblings presented with lower limb spasticity and a marked cerebellar oculomotor disorder accompanied by moderate hypogonadotropic hypogonadism in the female. A paternal uncle being homozygous for the splice-site variant of PNPLA6 presented with increased lower limb reflexes, an unstable gait and cerebellar oculomotor dysfunction. Treatment with 4-aminopyridin, a potassium channel blocker, lead to meaningful improvement of clinical symptoms. Conclusion PNPLA6 gene variants are associated with a broad phenotypic spectrum to which we add cerebellar oculomotor dysfunction. In our kindred, the full clinical manifestation only occurred in compound-heterozygous subjects indicating that biallelic pathogenic variants lead to more serious and earlier onset of symptoms. Our findings emphasize the role of PNPLA6 in different neurodegenerative disorders.
Prognostic Value of Exercise Capacity In Incidence Diabetes: A Country With High Prevalence of Diabetes
Authors: Jamiel Abdelrahman A. , Ardah Husam , Ahmed Amjad M. , Al-Mallah Mouaz H. 
Published: January 2022

Abstract
Background: Diabetes Mellitus (DM) is a fast-growing health problem that imposes an enormous economic burden. Several studies demonstrated the association between physical inactivity and predicting the incidence of diabetes. However, these prediction models have limited validation locally. Therefore, we aim to explore the predictive value of exercise capacity in the incidence of diabetes within a high diabetes prevalence population.Methodology: A retrospective cohort study including consecutive patients free of diabetes who underwent clinically indicated treadmill stress testing. Diabetic patients at baseline or patients younger than 18 years of age were excluded. Incident diabetes was defined as an established clinical diagnosis post-exercise testing date. The predictive value of exercise capacity was examined using Harrell’s c-index, net reclassification index (NRI), and integrated discrimination index (IDI).Results: A total of 8,722 participants (mean age 46±12 years, 66.3% were men) were free of diabetes at baseline. Over a median follow-up period of 5.24 (2.17-8.78) years, there were 2,280 (≈26%) new cases of diabetes. In a multivariate model adjusted for conventional risk factors, we found a 12% reduction in the risk of incident diabetes for each one greater MET achieved (HR, 0.9; 95% CI, 0.88–0.92; P<0.001). Using Cox regression, exercise capacity improved the prediction ability beyond the conventional risk factors (AUC=0.62 to 0.66 and c-index= 0.62 to 0.68).Conclusion: Exercise capacity improved the overall predictability of incidence diabetes. Patients with reduced exercise capacity are at high risk for developing incidence diabetes. Improvement of both physical activity and functional capacity represents a preventive measure for the general population.
Identification of a Prognostic Six-Immune-Gene Signature and a Nomogram Model for Uveal Melanoma
Authors: Yang Binghua , Fan Yuxia , Liang Renlong , Wu Yi , Gu Aiping 
Published: January 2022

Abstract
Background: To identify an immune-related prognostic signature and find potential therapeutic targets for uveal melanoma. Methods: The RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The prognostic six-immune-gene signature was constructed through least absolute shrinkage and selection operator and multi-variate Cox regression analyses. Functional enrichment analysis and single sample GSEA were carried out. In addition, a nomogram model established by integrating clinical variables and this signature risk score was also constructed and evaluated.Results: We obtained 130 prognostic immune genes, and six of them were selected to construct a prognostic signature in the TCGA uveal melanoma dataset. Patients were classified into high-risk and low-risk groups according to a median risk score of this signature. High-risk group patients had poorer overall survival in comparison to the patients in the low-risk group (p < 0.001). These findings were further validated in two external GEO datasets. A nomogram model proved to be a good classifier for uveal melanoma by combining this signature. Both functional enrichment analysis and single sample GSEA analysis verified that this signature was truly correlated with immune system. In addition, in vitro cell experiments results demonstrated the consistent trend of our computational findings.Conclusion: Our newly identified six-immune-gene signature and a nomogram model could be used as meaningful prognostic biomarkers, which might provide uveal melanoma patients with individualized clinical prognosis prediction and potential novel treatment targets.
Association between Time of Residence and OQ-45.2 and Self-Perception of Distress, Interpersonal Relationships, and Social Role in Venezuelan Immigrants in Lima, Peru 2018-19: Mixed-methods Study.
Authors: Delgado-Cáceres Frank Milton , Silva-Parra Kevin Angel , Torres-Slimming Paola A. 
Published: January 2022

Abstract
BackgroundImmigrants arriving in a new country face changes that affect their social, employment, and migratory status. We carried out a mixed methods study in the rapidly growing Venezuelan immigrant population in Lima, Peru. The objective was to determine whether there was an association between time in Peru and self-perception of symptom distress (SD), interpersonal relationships (IR), and social role (SR). MethodsThe quantitative central component consisted of a cross-sectional study, surveying 152 participants using the Outcome Questionnaire 45.2 (OQ-45.2). The qualitative component, based on phenomenology, explored experiences and challenges during the migration process. Semi-structured in-depth interviews were done in 16 informants.ResultsAn association that was observed was the increase in the risk of clinically significant SR score with additional years of age. All informants mentioned having witnessed or experienced xenophobia in Peru. Every informant stated that significant labor differences existed between the countries. The most reported somatic symptoms were symptoms of anxiety and alterations of sleep. Additionally, no informant expressed a desire to remain in Peru long term. ConclusionsA minority of participants registered a clinically significant total and domain score. No association between months in Lima and the self-perception of distress was found. However, this could be due to the short amount of time spent in Peru and any change in self-perception might only be perceived after years or decades spent in Peru. This study is one of the first to use mixed methods to explore the mental health of the immigrant Venezuelan population.
Spline-based specimen shape optimization for robust material model calibration
Authors: Chapelier Morgane , Bouclier Robin , Passieux Jean-Charles 
Published: January 2022

Abstract
Identification from field measurements allows several parameters to be identified from a single test, provided that the measurements are sensitive enough to the parameters to be identified. To do this, authors use empirically defined geometries (with holes, notches...). The first attempts to optimize the specimen to maximize the sensitivity of the measurement are linked to a design space that is either very small (parametric optimization), which does not allow the exploration of very different designs, or, conversely, very large (topology optimization), which sometimes leads to designs that are not regular and cannot be manufactured. In this paper, we propose an intermediate approach based on a non-invasive CAD-inspired optimization strategy which relies on the definition of univariate spline Free-Form Deformation boxes to reduce the design space and thus regularize the problem. Then, from the modeling point of view, we propose a new objective function that takes into account the experimental setup and we add constraint functions that ensure that the gain is real and the shape physically sound. Several examples show that with this method and at low cost, one can significantly improve the identification of constitutive parameters without changing the experimental setup.
A comprehensive single-cell map of T cell exhaustion-associated immune environments in human breast cancer
Authors: Tietscher Sandra , Wagner Johanna , Anzeneder Tobias , Langwieder Claus , Rees Martin , Sobottka Bettina , de Souza Natalie , Bodenmiller Bernd 
Published: January 2022

Abstract
Immune checkpoint therapy in breast cancer remains restricted to triple negative patients, and long-term clinical benefit is rare. The primary aim of immune checkpoint blockade is to prevent or reverse exhausted T cell states, but the causes and implications of T cell exhaustion in breast tumors are not well understood. Here, we used single-cell transcriptomics combined with imaging mass cytometry to comprehensively study exhausted and non-exhausted immune environments in human breast tumors, with a focus on Luminal subtypes. We found that the presence of a PD-1high exhaustion-like T cell phenotype was indicative of an inflammatory immune environment with a characteristic cytotoxic profile and spatial features. Accumulation of natural killer T cells and increased myeloid cell activation in exhausted immune environments provide further support for tissue inflammation in these environments. Consistent with this, our comprehensive map of cellular interactions within the breast tumor microenvironment revealed elevated immunomodulatory, chemotactic, and cytokine signaling in exhausted environments. These data reveal fundamental differences between exhausted and non-exhausted immune environments within Luminal breast cancer, and show that expression of PD-1 and CXCL13 on T cells, and MHC-I – but not PD-L1 – on tumor cells are strong distinguishing features between these environments; these factors are potential new biomarkers for patient stratification.
Spatio-temporal Evaluation of Gridded Precipitation and Evapotranspiration Products Over Balochistan Province in Pakistan
Authors: Jan Aman , Baez-Villanueva Oscar Manuel , Ribbe Lars 
Published: January 2022

Abstract
This study evaluated the performance of four state-of-the-art precipitation (P; CHIRPSv2, MSWEPv2.2, PERSIANN-CDR, and ERA5) and three state-of-the-art evaporation (Ea; GLEAMv3.3a, SSEBopv4.0, and ERA5) products in the data-scarce province of Balochistan, Pakistan. The P products were evaluated through a point-to-pixel comparison at the monthly, annual, and seasonal temporal scales using data from 17 gauges. The modified Kling-Gupta efficiency (KGE’) and the root mean square error (RMSE) were used as statistical indices to evaluate the performance of the P products. We used the Budyko framework to evaluate the Ea component due to unavailability of ground-based Ea data. For this purpose, we calculated the multi-annual mean Ea — defined as Ea_WB — for 12 defined catchments for a period of 16 years (2003–2018). Subsequently, the estimated Ea_WB was used as the reference to evaluate the performance of the Ea products. The results of the study revealed that among the P products generally MSWEPv2.2 closely followed by ERA5 presented the best spatio-temporal KGE’ performance over most of the stations and across the province. CHIRPSv2 and PERSIANN-CDR relatively showed poor KGE’ performance. Whereas, for the Ea component, ERA5 generally outperformed the other two products — i.e., GLEAMv3.3a and SSEBopv4.0 — in most of the evaluated catchments except for those located over the north-eastern region where GLEAMv3.3a performed the best. The results of this study can be beneficial to shift towards a proactive water management approach that can serve as a basis to improve the decision-making process in the region.