bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Media Digital Interaktif terhadap Keputusan Pembelian
Authors: Putra Hanif Firmansyah , Yandri Pitri
Published: February 2021

The era of digitalization which is an era where everyone uses digital means as a medium of communication and a means of communication. The use of this media is considered very effective and has a tremendous impact on its users, the phenomenon of online shopping is growing rapidly. The current availability of a marketplace is very helpful in finding a product, such as Tokopedia, which is the largest online shopping marketplace in Indonesia. The purpose of this study was to determine the effect of interactive digital media on online product purchasing decisions. The population in this study are active users of the Tokopedia marketplace who have made purchases in the South Tangerang City area. The sampling technique in this study was to use purposive sampling technique. The sample in this study were as many as 64 respondents. The data analysis technique used in this research is Structural Equation Modeling using SmartPLS. The results of the study show that the existence of digital media can influence potential consumers to make purchase transactions, seen through each indicator of the digital media variable, namely the website and social networking Instagram, which shows significant positive results on the decision to purchase fashion products on the Tokopedia marketplace.

Abstrak

Era digitalisasi yang merupakan era di mana setiap orang menggunakan sarana digital sebagai media penghubung dan alat komunikasi. Penggunaan media ini dinilai sangat efektif dan memberikan dampak yang luar biasa kepada penggunanya, fenomena berbelanja secara daring semakin berkembang pesat. Ketersedian marketplace saat ini sangat membantu dalam pencarian suatu produk, seperti Tokopedia yang merupakan marketplace berbelanja daring terbesar di Indonesia. Tujuan penelitian ini adalah untuk mengetahui pengaruh media digital interaktif terhadap keputusan pembelian produk secara online. Populasi dalam penelitian ini adalah pengguna aktif marketplace Tokopedia yang pernah melakukan pembelian yang berada pada wilayah Kota Tangerang Selatan. Teknik pengambilan sampel dalam penelitian ini yaitu dengan menggunakan teknik purposive sampling. Sampel pada penelitian ini adalah sebanyak sebanyak 64 responden. Tekhnik analisis data yang di gunakan dalam penelitian ini adalah dengan Structural Equation Modeling menggunakan SmartPLS. Hasil penelitian dapat diketahui bahwa dengan adanya media digital dapat mempengaruhi calon konsumen untuk melakukan transaksi pembelian, dilihat melalui setiap indikator dari variabel media digital yaitu website dan jejaring sosial instagram menunjukan hasil positif signifikan terhadap keputusan pembelian produk fashion di marketplace Tokopedia.

Kata Kunci : Media Digital, Website, Media Jejaring Sosial Instagram, Keputusan Pembelian Online, Model Persamaan Struktural
Pengaruh Pemahaman Sistem Keuangan dan Pengawasan Kinerja terhadap Fungsi Keuangan
Authors: Praditya Alvin , Wibowo Wahyu Andri , Komala Laura
Published: February 2021

The purpose of this study is to determine the effect of understanding the financial system and monitoring performance on financial functions at the Sasmita Jaya Foundation, Pamulang University. The method used in this research is quantitative descriptive. Analysis, then statistical testing is carried out to measure how much influence the variables under study and the statistical calculation process. While The population in this study was 33 and all members of the population were sampled for respondent determination. The sampling technique used saturated sampling. The simultaneous influence between financial system understanding (X1) and performance monitoring (X2) on financial functions (Y). This is evidenced by the value of R Square =0.249, it can be concluded that, understanding the financial system (X1) and performance supervision (X2) on financial functions (Y) is 24.9% and the remaining 75.1% is influenced by other factors. Hypothesis test shows the value of Fcount 4.982>Ftable 3.32 or probability sig 0.014<0.05 then H01 is rejected and Ha1 is accepted, meaning it is significant, thus the proposed hypothesis determines that there is a simultan influence between the understanding of the financial system (X1) and performance supervision (X2) on financial functions (Y) at the Sasmita Jaya Foundation, Pamulang University.

Abstrak

Tujuan penelitian ini untuk mengetahui pengaruh pemahaman sistem keuangan dan pengawasan kinerja terhadap fungsi keuangan pada Yayasan Sasmita Jaya universitas Pamulang. Metode yang digunakan dalam penelitian ini adalah kuantitatif yang bersifat deskriptif analisis. Makadilakukan pengujian statistic untuk mengukur seberapa besar pengaruh diantara variabel-variabel yang diteliti dan proses perhitungan statistic. Sedangkan populasi dalam penelitian ini sebanyak 33 dan semuaanggota populasi dijadikan sampel untuk penentuan responden, teknik pengambilan sampel menggunakan sampling jenuh.Pengaruh secara simultan antara Pemahaman Sistem Keuangan (X1) dan Pengawasan Kinerja (X2) TerhadapFungsi Keuangan (Y). Hal ini dibuktikan berdasarkan nilai R Square= 0,249 dapat disimpulkan bahwa, Pemahaman SistemKeuangan (X1) dan Pengawasan Kinerja (X2) TerhadapFungsiKeuangan (Y) sebesar 24,9% dan sisanya 75,1% dipengaruhi oleh faktor lain. Uji hipotesis menunjukkan nilai F hitung 4,982> F tabel3,32 atau probabilitas Sig 0,014< 0,05 maka Ho1 di tolak dan Ha1 di terim artinya signifikan dengan demikian hipotesis yang diajukan menetapkan Terdapat pengaruh secara bersama-sama antara Pemahaman Sistem Keuangan (X1) dan Pengawasan Kinerja (X2) Terhadap Fungsi Keuangan (Y) pada Yayasan Sasmita Jaya Pamulang.

Kata Kunci: Pemahaman Sistem Keuangan, Pengawasan Kinerja, Fungsi Keuangan
Pengaruh Promosi Go-pay Terhadap Keputusan Pengguna Aplikasi Transportasi Online Di Ruang Lingkup Universitas Pamulang
Authors: Febriana Hadijah , Budhiarjo Intan Sari
Published: February 2021

Research purposes This study aims to determine the effect of go-pay promotion on the decisions of users of online transportation applications within the scope of the University of Pamulang. The research method used is quantitative research methods. The population in this study were students of the 7th semester of the Pamulang University management study program. The sample in this study were 200 respondents in the population. The analytical method used is quantitative analysis. Partially Go-pay promotion variable (x) has a tcount of 11.966 > ttable 1.65259 with a significant value of 0.00, it can be concluded that Go-pay promotion has a positive and significant effect on user decisions. Based on the test results the coefficient of determination (R square) shows the number 0.420 which means that the relationship between Go-pay promotion and user decision is 42%, while the remaining 58% is influenced by other variables not examined in this study. Promotion has a positive and significant effect on Go-pay users' decisions to use online transportation at Pamulang University. This means that the higher and more varied the promotions offered by the company, the greater the chance for users to decide to use online transportation services, especially at Pamulang University.

Abstrak

Penelitian ini bertujuan untuk mengetahui pengaruh promosi Go-pay terhadap keputusan pengguna aplikasi transportasi online di ruang lingkup Universitas Pamulang. Metode penelitian yang digunakan adalah metode penelitian kuantitatif. Populasi dalam penelitian ini adalah mahasiswa/mahasiswi semester 7 prodi manajemen Universitas Pamulang. Sampel dalam penelitian ini adalah 200 responden yang terdapat dalam populasi. Metode analisis yang digunakan adalah analisis kuantitatif. Secara parsial promosi Go-pay (x) memiliki thitung sebesar 11,966y > ttabel 1,65259 dengan nilai signifikan 0,00 maka dapat disimpulkan promosi Go-pay berpengaruh positif dan signifikan terhadap keputusan pengguna. Berdasarkan hasil uji koefisien determinasi (R square) menunjukkan angka 0,420 artinya hubungan promosi Go-pay dengan keputusan pengguna sebesar 42%, sedangkan sisanya 58% dipengaruhi oleh variabel lain yang tidak diteliti dalam penelitian ini. Promosi berpengaruh secara positif dan signifikan terhadap keputusan pengguna Go-pay dalam menggunakan trasnportasi online di Universitas Pamulang. Artinya semakin tinggi dan semakin bervariasi promosi yang ditawarkan oleh pihak perusahaan, maka semakin besar peluang pengguna memutuskan untuk menggunakan jasa transportasi online khususnya di Universitas Pamulang.

Kata Kunci : Promosi, Go-Pay, Keputusan Pengguna
LIFE SKILL REMAJA DALAM PENCEGAHAN HIV/AIDS
Authors: Darmawati Irma , Dharmansyah Dhika , Lindayani Linlin , Alfyani Ririn
Published: February 2021

Latar Belakang: Masa remaja merupakan periode terjadinya pertumbuhan dan perkembangan yang pesat baik secara fisik, psikologis, maupun intelektual. Upaya kecakapan remaja dalam pencegahan HIV/AIDS penting untuk diperhatikan sebab ini dapat menekan laju pertumbuhan HIV/AIDS itu sendiri.Â  Tujuan: Penelitian ini bertujuan untuk mengetahui upaya kecakapan hidup (life skill) remaja dalam pencegahan HIV/AIDS. Metode: Penelitian ini merupakan penelitian deskriptif secara kuantitatif menggunakan rancangan cross sectional. Dilakukan dengan subjek penelitian 610 remaja SMK di Bandung yang ditentukan dengan teknik total sampling. Pengumpulan data dengan kuesioner Life Skill Training Questionaire High School dan analisa data dengan distribusi frekuensi. Hasil: Hasil penelitian ini menunjukkan 52% remaja memiliki upaya kecakapan hidup yang baik dengan mean 90.63 Â±10.79. Kesimpulan: Pihak sekolah perlu memberikan pengarahan, informasi, serta edukasi mengenai upaya kecakapan hidup bagi remaja agar memiliki upaya kecakapan hidup yang baik dalam pencegahan HIV/AIDS.
Trainning of Fasilitator Bagi Kader Kesehatan Program Penyakit Tidak Menular dalam Pencegahan dan Pengendalian Potensi Stroke
Authors: Saleh Dunggio Abdul Rivai , Hitijahubessy Christy Natalia Magdalena , Setyowati Sri Eny
Published: February 2021

Di kota Ambon penyakit tidak menular selama 3 tahun terakhir ini terjadi kecenderungan peningkatan kasus penyakit tidak menular terutama penyakit tekanan darah tinggi. RW 08 Desa Batu Merah Kota Ambon belum mempunyai kader penyakit tidak menular sedangkan pada RT 02/RW 08 ditemukan pasien stoke. Tujuan pengabdian masyarakat adalah memberikan pelatihan dengan meningkatkan pengetahuan dan keterampilan kader dalam upaya untuk mengendalikan dan mencegah potensi stroke. Kegiatan ini dilakukan dengan metode ceramah dan pemberian leaflet tentang hipertensi dan simulasi tentang cara mengukur tekanan darah. Karakteristik peserta yang mengikuti kegiatan ini sebanyak 13 orang. Hasil yang diperoleh bahwa peserta terbanyak laki-laki 8 orang (62%) dengan kisaran umur 26-35 sebanyak 7 orang (53%) dan berpendidikan SMA 12 orang (92%). Pengetahuan peserta berada pada tingkat baik 10 orang (77%). Sedangkan kompetensi kader pada tahap pengujian pertama 2 orang (15%) kompeten dan tahap kedua 10 orang (77%) kompeten. Kesimpulannya bahwa terjadi peningkatan pengetahuan dan keterampiran kader setelah dilakukan pelatihan.
Comparative Transcriptome Analysis of Streptomyces nodosus Mutant With a High-Yield Amphotericin B
Authors: Huang Kai , Zhang Bo , Chen Yu , Liu Zhi-Qiang , Zheng Yu-Guo
Published: February 2021

Antibiotics play an important role in human health. Most antibiotics are derived from microbial secondary metabolites. Amphotericin is a polyene macrolide antibiotic synthesized byStreptomyces nodosus.S. nodosusZJB2016050 with high-yield amphotericin B (AmB) was obtained by traditional mutagenesis usingS. nodosusATCC14899 as the original strain. The differences in the characterization of the two strains were found in color, mycelium morphology, and AmB yield. Subsequent comparative transcriptome explained the yield differences between the two strains. Pathways including the carbohydrate metabolic pathway and the secondary product synthesis pathway were targeted. The upregulation of glucokinase, phosphoglycerate mutase, and pyruvate dehydrogenase accelerates the consumption of glucose and has great effects on the accumulation of precursors. One of the competitive secondary metabolites of the polyketone synthetase (PKS) II type sapromomycin analog synthesis gene cluster was downregulated, which competes for malonyl-CoA. Five PKS modules (except for the first module amphA) of the amphotericin synthetic gene cluster in the high-yielding strain were downregulated, which resulted in the total amphotericin A (AmA) and AmB ofS. nodosusZJB2016050 being less than that of the wild-typeS. nodosusATCC14899. Combined with gene differential expression in the pentose phosphate pathway and the reaction mechanism of the ER5 domain, the reason thatS. nodosusZJB2016050 preferred to synthesize AmB was probably related to intracellular reduction.
A Simple in vivo Assay Using Amphipods for the Evaluation of Potential Biocompatible Metal-Organic Frameworks
Authors: Sifaoui Ines , Pacheco-Fernández Idaira , Piñero José E. , Pino Verónica , Lorenzo-Morales Jacob
Published: February 2021

In this study, the application of amphipods in vivo assays was evaluated. The main aim of this work was to check the potential use of this model in biocompatibility assessments of metal-organic frameworks (MOFs). Hence, six different MOFs were synthesized and the in vitro and ex vivo cytotoxicity was first assessed using a colorimetric assay and a macrophage cell line. Obtained results were compared to validate the in vivo toxicity tests carried out using amphipods and increasing concentrations of the different MOFs. Amphipods do not require the need of ethics approval and also are less expensive to keep than conventional in vivo models, showing its potential as a fast and reliable platform in toxicity studies. The obtained results showed that the amphipods based-assay was simple, easy to replicate and yielded toxicity data corresponding to the type of MOFs tested. In addition, it was observed that only CIM-80(Al) and CIM-84(Zr) did not show any toxicity to the animals at the different tested concentrations. Therefore, the developed in vivo model could be applied as a high-throughput toxicity screening method to evaluate the toxicity of numerous materials, chemicals and therapeutic agents among others.
The Fate of Speckled Protein 100 (Sp100) During Herpesviruses Infection
Authors: Collados Rodríguez Mila
Published: February 2021

The constitutive expression ofSpeckled-100(Sp100) is known to restrict the replication of many clinically important DNA viruses. This pre-existing (intrinsic) immune defense to virus infection can be further upregulated uponinterferon(IFN) stimulation as a component of the innate immune response. In humans, Sp100 is encoded by a single gene locus, which can produce alternatively spliced isoforms. The widely studied Sp100A, Sp100B, Sp100C and Sp100HMG have functions associated with the transcriptional regulation of viral and cellular chromatin, either directly through their characteristic DNA-binding domains, or indirectly through post-translational modification (PTM) and associated protein interaction networks. Sp100 isoforms are resident component proteins ofpromyelocyticleukemia-nuclearbodies (PML-NBs), dynamic nuclear sub-structures which regulate host immune defenses against many pathogens. In the case of human herpesviruses, multiple protein antagonists are expressed to relieve viral DNA genome transcriptional silencing imposed by PML-NB and Sp100-derived proteinaceous structures, thereby stimulating viral propagation, pathogenesis, and transmission to new hosts. This review details how different Sp100 isoforms are manipulated during herpesviruses HSV1, VZV, HCMV, EBV, and KSHV infection, identifying gaps in our current knowledge, and highlighting future areas of research.
Reverse Transcription Recombinase-Aided Amplification Assay With Lateral Flow Dipstick Assay for Rapid Detection of 2019 Novel Coronavirus
Authors: Zheng Yu-Zhong , Chen Jiang-Tao , Li Jian , Wu Xian-Jing , Wen Jin-Zhou , Liu Xiang-Zhi , Lin Li-Yun , Liang Xue-Yan , Huang Hui-Ying , Zha Guang-Cai , Yang Pei-Kui , Li Lie-Jun , Zhong Tian-Yu , Liu Long , Cheng Wei-Jia , Song Xiao-Nan , Lin Min
Published: February 2021

Background

The emerging Coronavirus Disease-2019 (COVID-19) has challenged the public health globally. With the increasing requirement of detection for SARS-CoV-2 outside of the laboratory setting, a rapid and precise Point of Care Test (POCT) is urgently needed.

Methods

Targeting the nucleocapsid (N) gene of SARS-CoV-2, specific primers, and probes for reverse transcription recombinase-aided amplification coupled with lateral flow dipstick (RT-RAA/LFD) platform were designed. For specificity evaluation, it was tested with human coronaviruses, human influenza A virus, influenza B viruses, respiratory syncytial virus, and hepatitis B virus, respectively. For sensitivity assay, it was estimated by templates of recombinant plasmid and pseudovirus of SARS-CoV-2 RNA. For clinical assessment, 100 clinical samples (13 positive and 87 negatives for SARS-CoV-2) were tested via quantitative reverse transcription PCR (RT-qPCR) and RT-RAA/LFD, respectively.

Results

The limit of detection was 1 copies/μl in RT-RAA/LFD assay, which could be conducted within 30 min at 39°C, without any cross-reaction with other human coronaviruses and clinical respiratory pathogens. Compared with RT-qPCR, the established POCT assay offered 100% specificity and 100% sensitivity in the detection of clinical samples.

Conclusion

This work provides a convenient POCT tool for rapid screening, diagnosis, and monitoring of suspected patients in SARS-CoV-2 endemic areas.
Orders of Social Science: Understanding Social-Scientific Controversies and Confluence on What “High-Quality” Knowledge and “Good” Adaptation Is
Authors: Skelton Maurice
Published: February 2021

Various scholars have noted—and experienced—tribal tendencies between social-scientific “schools of thought” or “paradigms.” The intensity and fervor of such controversies has led some scientists to compare them with frictions between religiousorders. In the research domain focused on the use of climate science for climate adaptation, such disputes revolve around the what “high-quality” climate knowledge and “good” adaptation is or should be. Emphasizing this diversity oforders of social science and the humanities, this article describes five distinct ways social scientists and humanities scholars have thought and written about climate adaptation:descriptivistsaim to empirically portray climate adaptation as objectively as possible from an assumed subject-independent perspective;pragmatists'research wants to increase climate resilience through usable climate information;argumentivistsstrive for assessing the justification of climate scientific findings, as well as adaptation decision-making that is based on these findings;interpretivistsseek to empirically redescribe how the use of climate science for adaptation is shaped by, and shapes, various other social processes and political actors; andcriticalscholars work toward revealing how pervasive powerful interests and marginalizing discourses shape adaptation projects negatively. By comparing these five orders' respective scientific, environmental and social aims and concerns, this article pinpoints to how epistemological, ontological and methodological priorities not only drive scientific controversies on issues such as what “high-quality knowledge” is, but also how interdependent orders' methodological choices are with their epistemological and ontological positions. However, this analysis also reveals that while some scholars implicitly stick to their order, others are comfortable to collaborate across such borders. Overall, the diverging aims, priorities, and methods are unlikely to be ever fully reconciled. A better understanding of why academics from different orders differ in the approaches they take and the issues they care about will likely lead to a larger appreciation of the differences of other orders' research and broaden our understanding of key dynamics in studying “good” climate adaptation and “high-quality” climate knowledge.
Identification of Potential Biomarkers and Immune Infiltration Characteristics in Idiopathic Pulmonary Arterial Hypertension Using Bioinformatics Analysis
Authors: Zeng Haowei , Liu Xiaoqin , Zhang Yushun
Published: February 2021

Objectives: Idiopathic pulmonary arterial hypertension (IPAH) is a rare but severe lung disorder, which may lead to heart failure and early mortality. However, little is known about the etiology of IPAH. Thus, the present study aimed to establish the differentially expressed genes (DEGs) between IPAH and normal tissues, which may serve as potential prognostic markers in IPAH. Furthermore, we utilized a versatile computational method, CIBERSORT to identify immune cell infiltration characteristics in IPAH.

Materials and Methods: The GSE117261 and GSE48149 datasets were obtained from the Gene Expression Omnibus database. The GSE117261 dataset was adopted to screen DEGs between IPAH and the control groups with the criterion of |log2 fold change| ≥ 1, adjusted P < 0.05, and to further explore their potential biological functions via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes Pathway analysis, and Gene Set Enrichment Analysis. Moreover, the support vector machine (SVM)-recursive feature elimination and the least absolute shrinkage and selection operator regression model were performed jointly to identify the best potential biomarkers. Then we built a regression model based on these selected variables. The GSE48149 dataset was used as a validation cohort to appraise the diagnostic efficacy of the SVM classifier by receiver operating characteristic (ROC) analysis. Finally, immune infiltration was explored by CIBERSORT in IPAH. We further analyzed the correlation between potential biomarkers and immune cells.

Results: In total, 75 DEGs were identified; 40 were downregulated, and 35 genes were upregulated. Functional enrichment analysis found a significantly enrichment in heme binding, inflammation, chemokines, cytokine activity, and abnormal glycometabolism. HBB, RNASE2, S100A9, and IL1R2 were identified as the best potential biomarkers with an area under the ROC curve (AUC) of 1 (95%CI = 0.937–1.000, specificity = 100%, sensitivity = 100%) in the discovery cohort and 1(95%CI = 0.805–1.000, specificity = 100%, sensitivity = 100%) in the validation cohort. Moreover, immune infiltration analysis by CIBERSORT showed a higher level of CD8+ T cells, resting memory CD4+ T cells, gamma delta T cells, M1 macrophages, resting mast cells, as well as a lower level of naïve CD4+ T cells, monocytes, M0 macrophages, activated mast cells, and neutrophils in IPAH compared with the control group. In addition, HBB, RNASE2, S100A9, and IL1R2 were correlated with immune cells.

Conclusion:HBB, RNASE2, S100A9, and IL1R2 were identified as potential biomarkers to discriminate IPAH from the control. There was an obvious difference in immune infiltration between patient with IPAH and normal groups.
Kallmann Syndrome Due to Heterozygous Mutation in SOX10 Coexisting With Waardenburg Syndrome Type II: Case Report and Review of Literature
Authors: Chen Kan , Wang Haoyu , Lai Yaxin
Published: February 2021

Introduction

Kallmann syndrome (KS) is idiopathic hypogonadotropic hypogonadism with olfactory loss or decline. Waardenburg syndrome type II (WS2) is a clinically and genetically heterogeneous disease, characterized by congenital sensorineural deafness and abnormal pigmentation of the iris, hair, and skin. Recently, mutations in the well-known WS pathogenic gene SOX10 have been found in some KS patients with deafness, but whether SOX10 is a co-pathogenic gene of KS and WS remains uncertain. Here, we report a rare case of KS and WS2 co-occurrence due to SOX10 mutations.

Methods

Detailed histories were collected through questionnaires and physical examination. Blood samples of the patient and his family members were collected after obtaining informed consents. Suspected mutations were amplified and verified by Sanger sequencing after the next generation sequencing of related genes. The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039).

Results

A 28-year-old male patient sought treatment for hypogonadism and the absence of secondary sexual characteristics. In addition, he showed signs of obesity, hyposmia, sensorineural hearing loss, and blue iris. Magnetic resonance imaging (MRI) of the olfactory bulb showed small bilateral olfactory bulbs and tracts and diaphragma cerebri. MRI of the pituitary gland revealed a flat pituitary gland in the sella. Laboratory examination demonstrated hypogonadotropic hypogonadism, pituitary hypothyroidism, subclinical hypothyroidism, and the presence of insulin resistance with normal blood glucose levels. Sequencing of the SOX10 gene showed a 20 bp insertion in between coding bases 1,179 and 1,180 (c.1179_1180insACTATGGCTCAGCCTTCCCC). This results in a frame-shifting mutation of the 394th amino acid serine in exon4 with the resulting the amino acid sequence of the protein predicted to be TMAQPSP PSPAPSLTTL TISPQDPIMA TRARPLASTR PSPIWGPRSG PSTRPSLTPA PQGPSPTAPH TGSSQYIRHC PGPKGGPVAT TPRPAPAPSL CALFLAHLRP GGGSGGG*.

Conclusion

SOX10 plays an important role in some critical stages of neural crest cell development and SOX10 mutation may be a common pathogenic factor for both KS and WS. Therefore, SOX10 mutation analysis should be considered for KS patients with combined WS clinical manifestations, especially deafness.
Machine Learning Approaches Identify Genes Containing Spatial Information From Single-Cell Transcriptomics Data
Authors: Loher Phillipe , Karathanasis Nestoras
Published: February 2021

The development of single-cell sequencing technologies has allowed researchers to gain important new knowledge about the expression profile of genes in thousands of individual cells of a model organism or tissue. A common disadvantage of this technology is the loss of the three-dimensional (3-D) structure of the cells. Consequently, the Dialogue on Reverse Engineering Assessment and Methods (DREAM) organized the Single-Cell Transcriptomics Challenge, in which we participated, with the aim to address the following two problems: (a) to identify the top 60, 40, and 20 genes of theDrosophila melanogasterembryo that contain the most spatial information and (b) to reconstruct the 3-D arrangement of the embryo using information from those genes. We developed two independent techniques, leveraging machine learning models from least absolute shrinkage and selection operator (Lasso) and deep neural networks (NNs), which are applied to high-dimensional single-cell sequencing data in order to accurately identify genes that contain spatial information. Our first technique, Lasso.TopX, utilizes the Lasso and ranking statistics and allows a user to define a specific number of features they are interested in. The NN approach utilizes weak supervision for linear regression to accommodate for uncertain or probabilistic training labels. We show, individually for both techniques, that we are able to identify important, stable, and a user-defined number of genes containing the most spatial information. The results from both techniques achieve high performance when reconstructing spatial information inD. melanogasterand also generalize to zebrafish (Danio rerio). Furthermore, we identified novelD. melanogastergenes that carry important positional information and were not previously suspected. We also show how the indirect use of the full datasets’ information can lead to data leakage and generate bias in overestimating the model’s performance. Lastly, we discuss the applicability of our approaches to other feature selection problems outside the realm of single-cell sequencing and the importance of being able to handle probabilistic training labels. Our source code and detailed documentation are available athttps://github.com/TJU-CMC-Org/SingleCell-DREAM/.
Exploring the Differential Expression and Prognostic Significance of the COL11A1 Gene in Human Colorectal Carcinoma: An Integrated Bioinformatics Approach
Authors: Patra Ritwik , Das Nabarun Chandra , Mukherjee Suprabhat
Published: February 2021

Colorectal cancer is one of the most common cancers of humans and the second highest in cancer-related death. Genes used as prognostic biomarkers play an imperative role in cancer detection and may direct the development of appropriate therapeutic strategies. Collagen type XI alpha 1 (COL11A1) is a minor fibrillary collagen that has an essential role in the regulation of cell division, differentiation, proliferation, migration, growth, and apoptosis of intestinal and colon cells. The present study seeks to evaluate the significance of the COL11A1 gene in the progression of colorectal cancer in humans across the various parameters using advanced bioinformatics approaches. The application of various databases and servers like ONCOMINE, UALCAN, and GEPIA were accessed for analyzing the differential expression of the COLL11A1 gene and its relative influence over the survival of the transformed subjects. In addition, oncogenomics of COL11A1 gene, mutations associated with this gene and interacting partners of the gene in the context of oncogenesis were studied using COSMIC, cBioPortal, GeneMANIA, and NetworkAnalyst. Our experimental data indicate that the COL11A1 gene is overexpressed in the transformed tissues across the various clinicopathological parameters reduces the probability of survival in both overall and disease-specific survival cases. Mutational studies imply that it can induce perturbations in various signaling pathways viz. RTK-RAS-PI3K, Wnt, TGF-β, and TP53 pathways influencing cancer development. Also, a positive association and correlation amongst the THBS2, COL10A1, COL5A2, and COL1A2 genes were observed, which most likely to contribute to the upregulation of carcinogenesis. Conclusively, this comprehensive study indicates the COL11A1 gene to be a significant contributor in the etiology of colorectal cancer, henceforth this gene can be considered as a prognostic biomarker for the conception of diagnostic and therapeutic strategies against colorectal cancer in the near future.
Allelic Dropout Is a Common Phenomenon That Reduces the Diagnostic Yield of PCR-Based Sequencing of Targeted Gene Panels
Authors: Shestak Anna G. , Bukaeva Anna A. , Saber Siamak , Zaklyazminskaya Elena V.
Published: February 2021

Primary cardiomyopathies (CMPs) are monogenic but multi-allelic disorders with dozens of genes involved in pathogenesis. The implementation of next-generation sequencing (NGS) approaches has resulted in more time- and cost-efficient DNA diagnostics of cardiomyopathies. However, the diagnostic yield of genetic testing for each subtype of CMP fails to exceed 60%. The aim of this study was to demonstrate that allelic dropout (ADO) is a common phenomenon that reduces the diagnostic yield in primary cardiomyopathy genetic testing based on targeted gene panels assayed on the Ion Torrent platform. We performed mutational screening with three custom targeted gene panels based on sets of oligoprimers designed automatically using AmpliSeq Designer® containing 1049 primer pairs for 37 genes with a total length of 153 kb. DNA samples from 232 patients were screened with at least one of these targeted gene panels. We detected six ADO events in both IonTorrent PGM (three cases) and capillary Sanger sequencing (three cases) data, identifying ADO-causing variants in all cases. All ADO events occurred due to common or rare single nucleotide variants (SNVs) in the oligoprimer binding sites and were detected because of the presence of “marker” SNVs in the target DNA fragment. We ultimately identified that PCR-based NGS involves a risk of ADO that necessitates the use of Sanger sequencing to validate NGS results. We assume that oligoprimer design without ADO data affects the amplification efficiency of up to 0.77% of amplicons.
Mitochondrial Genome Structures and Phylogenetic Analyses of Two Tropical Characidae Fishes
Authors: Sun Cheng-He , Liu Hong-Yi , Xu Nan , Zhang Xiao-Li , Zhang Qun , Han Bo-Ping
Published: February 2021

The Characidae family contains the largest number of tropical fish species. Morphological similarities make species identification difficult within this family. Here, the complete mitogenomes of two Characidae fish were determined and comparatively analyzed with those of nine other Characidae fish species. The two newly sequenced complete mitogenomes are circular DNA molecules with sizes of 16,701 bp (Hyphessobrycon amandae; MT484069) and 16,710 bp (Hemigrammus erythrozonus; MT484070); both have a highly conserved structure typical of Characidae, with the start codon ATN (ATG/ATT) and stop codon TAR (TAA/TAG) or an incomplete T−−/TA−. Most protein-coding genes of the 11 Characidae mitogenomes showed significant codon usage bias, and the protein-coding gene cox1 was found to be a comparatively slow-evolving gene. Phylogenetic analyses via the maximum likelihood and Bayesian inference methods confirmed that H. amandae and H. erythrozonus belong to the family Characidae. In all Characidae species studied, one genus was well supported; whereas other two genera showed marked differentiation. These findings provide a phylogenetic basis for improved classification of the family Characidae. Determining the mitogenomes of H. erythrozonus and H. amandae improves our understanding of the phylogeny and evolution of fish species.
Potentiating the Antitumor Activity of Cytotoxic T Cells via the Transmembrane Domain of IGSF4 That Increases TCR Avidity
Authors: Kim Hye-Ran , Park Jeong-Su , Fatima Yasmin , Kausar Maiza , Park Jin-Hwa , Jun Chang-Duk
Published: February 2021

A robust T-cell response is an important component of sustained antitumor immunity. In this respect, the avidity of TCR in the antigen-targeting of tumors is crucial for the quality of the T-cell response. This study reports that the transmembrane (TM) domain of immunoglobulin superfamily member 4 (IGSF4) binds to the TM of the CD3 ζ-chain through an interaction between His177 and Asp36, which results in IGSF4-CD3 ζ dimers. IGSF4 also forms homo-dimers through the GxxVA motif in the TM domain, thereby constituting large TCR clusters. Overexpression of IGSF4 lacking the extracellular (IG4ΔEXT) domain potentiates theOTICD8+T cells to release IFN-γ and TNF-α and to kill OVA+-B16F10 melanoma cells. In animal models, IG4ΔEXT significantly reduces B16F10 tumor metastasis as well as tumor growth. Collectively, the results indicate that the TM domain of IGSF4 can regulate TCR avidity, and they further demonstrate that TCR avidity regulation is critical for improving the antitumor activity of cytotoxic T cells.
A Selective α7 Nicotinic Acetylcholine Receptor Agonist, PNU-282987, Attenuates ILC2s Activation and Alternaria-Induced Airway Inflammation
Authors: Yuan Fang , Jiang Lili , Li Qianyang , Sokulsky Leon , Wanyan Yuanyuan , Wang Lingli , Liu Xiaojie , Zhou Lujia , Tay Hock L. , Zhang Guojun , Yang Ming , Li Fuguang
Published: February 2021

Background

The anti-inflammatory effect of an α7nAChR agonist, PNU-282987, has previously been explored in the context of inflammatory disease. However, the effects of PNU-282987 on type 2 innate lymphoid cells (ILC2s)-mediated allergic airway inflammation has not yet been established.

Aims

To determine the effects of PNU-282987 on the function of ILC2s in the context of IL-33– or Alternaria Alternata (AA)– induced airway inflammation.

Methods

PNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published α7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-κB were also determined.

Results

PNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-κB phosphorylation in the PNU-282987–treated group when compared to the GTS-21–treated ILC2s.

Conclusion

PNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.
Chicken cGAS Senses Fowlpox Virus Infection and Regulates Macrophage Effector Functions
Authors: Oliveira Marisa , Rodrigues Damaris Ribeiro , Guillory Vanaique , Kut Emmanuel , Giotis Efstathios S. , Skinner Michael A. , Guabiraba Rodrigo , Bryant Clare E. , Ferguson Brian J.
Published: February 2021

The anti-viral immune response is dependent on the ability of infected cells to sense foreign nucleic acids. In multiple species, the pattern recognition receptor (PRR) cyclic GMP-AMP synthase (cGAS) senses viral DNA as an essential component of the innate response. cGAS initiates a range of signaling outputs that are dependent on generation of the second messenger cGAMP that binds to the adaptor protein stimulator of interferon genes (STING). Here we show that in chicken macrophages, the cGAS/STING pathway is essential not only for the production of type-I interferons in response to intracellular DNA stimulation, but also for regulation of macrophage effector functions including the expression of MHC-II and co-stimulatory molecules. In the context of fowlpox, an avian DNA virus infection, the cGAS/STING pathway was found to be responsible for type-I interferon production and MHC-II transcription. The sensing of fowlpox virus DNA is therefore essential for mounting an anti-viral response in chicken cells and for regulation of a specific set of macrophage effector functions.
A Phenomic Perspective on Factors Influencing Breast Cancer Treatment: Integrating Aging and Lifestyle in Blood and Tissue Biomarker Profiling
Authors: Arana Echarri Ainhoa , Beresford Mark , Campbell John P. , Jones Robert H. , Butler Rachel , Gollob Kenneth J. , Brum Patricia C. , Thompson Dylan , Turner James E.
Published: February 2021

Breast cancer is the most common malignancy among women worldwide. Over the last four decades, diagnostic and therapeutic procedures have improved substantially, giving patients with localized disease a better chance of cure, and those with more advanced cancer, longer periods of disease control and survival. However, understanding and managing heterogeneity in the clinical response exhibited by patients remains a challenge. For some treatments, biomarkers are available to inform therapeutic options, assess pathological response and predict clinical outcomes. Nevertheless, some measurements are not employed universally and lack sensitivity and specificity, which might be influenced by tissue-specific alterations associated with aging and lifestyle. The first part of this article summarizes available and emerging biomarkers for clinical use, such as measurements that can be made in tumor biopsies or blood samples, including so-called liquid biopsies. The second part of this article outlines underappreciated factors that could influence the interpretation of these clinical measurements and affect treatment outcomes. For example, it has been shown that both adiposity and physical activity can modify the characteristics of tumors and surrounding tissues. In addition, evidence shows that inflammaging and immunosenescence interact with treatment and clinical outcomes and could be considered prognostic and predictive factors independently. In summary, changes to blood and tissues that reflect aging and patient characteristics, including lifestyle, are not commonly considered clinically or in research, either for practical reasons or because the supporting evidence base is developing. Thus, an aim of this article is to encourage an integrative phenomic approach in oncology research and clinical management.
Diverse Functions of γδ T Cells in the Progression of Hepatitis B Virus and Hepatitis C Virus Infection
Authors: Hou Wen , Wu Xiaoli
Published: February 2021

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are primary risk factors for a wide spectrum of liver diseases that severely affect human health. The liver is an immunological organ that has an abundance of immune cells. Thus, various innate or adaptive immune cells are involved in the progression of HBV or HCV infection. Among those cells, a unique kind of immune cell, the γδ T cell, contributes to promoting or inhibiting the progression of liver diseases. To reveal the diverse roles of γδ T cells in HBV or HCV infection, the properties and functions of these cells in human and mouse models are analyzed. Here, we briefly describe the characteristics and functions of γδ T cells subsets in liver diseases. Then, we fully discuss the diverse roles of γδ T cells in the progression of HBV or HCV infection, including stages of acute infection, chronic infection, liver cirrhosis, and hepatocellular carcinoma. Finally, the functions and existing problems of γδ T cells in HBV or HCV infection are summarized. A better understanding of the function of γδ T cells during the progression of HBV and HCV infection will be helpful for the treatment of virus infection.
Prognostic Accuracy of Early Warning Scores for Clinical Deterioration in Patients With COVID-19
Authors: Su Ying , Ju Min-jie , Xie Rong-cheng , Yu Shen-ji , Zheng Ji-li , Ma Guo-guang , Liu Kai , Ma Jie-fei , Yu Kai-huan , Tu Guo-wei , Luo Zhe
Published: February 2021

Background: Early Warning Scores (EWS), including the National Early Warning Score 2 (NEWS2) and Modified NEWS (NEWS-C), have been recommended for triage decision in patients with COVID-19. However, the effectiveness of these EWS in COVID-19 has not been fully validated. The study aimed to investigate the predictive value of EWS to detect clinical deterioration in patients with COVID-19.

Methods: Between February 7, 2020 and February 17, 2020, patients confirmed with COVID-19 were screened for this study. The outcomes were early deterioration of respiratory function (EDRF) and need for intensive respiratory support (IRS) during the treatment process. The EDRF was defined as changes in the respiratory component of the sequential organ failure assessment (SOFA) score at day 3 (ΔSOFAresp = SOFA resp at day 3–SOFAresp on admission), in which the positive value reflects clinical deterioration. The IRS was defined as the use of high flow nasal cannula oxygen therapy, noninvasive or invasive mechanical ventilation. The performances of EWS including NEWS, NEWS 2, NEWS-C, Modified Early Warning Scores (MEWS), Hamilton Early Warning Scores (HEWS), and quick sepsis-related organ failure assessment (qSOFA) for predicting EDRF and IRS were compared using the area under the receiver operating characteristic curve (AUROC).

Results: A total of 116 patients were included in this study. Of them, 27 patients (23.3%) developed EDRF and 24 patients (20.7%) required IRS. Among these EWS, NEWS-C was the most accurate scoring system for predicting EDRF [AUROC 0.79 (95% CI, 0.69–0.89)] and IRS [AUROC 0.89 (95% CI, 0.82–0.96)], while NEWS 2 had the lowest accuracy in predicting EDRF [AUROC 0.59 (95% CI, 0.46–0.720)] and IRS [AUROC 0.69 (95% CI, 0.57–0.81)]. A NEWS-C ≥ 9 had a sensitivity of 59.3% and a specificity of 85.4% for predicting EDRF. For predicting IRS, a NEWS-C ≥ 9 had a sensitivity of 75% and a specificity of 88%.

Conclusions: The NEWS-C was the most accurate scoring system among common EWS to identify patients with COVID-19 at risk for EDRF and need for IRS. The NEWS-C could be recommended as an early triage tool for patients with COVID-19.
Lung Cancer Adverse Events Reports for Angiotensin-Converting Enzyme Inhibitors: Data Mining of the FDA Adverse Event Reporting System Database
Authors: Meng Long , Yang Bing , Qiu Feng , Jia Yuntao , Sun Shusen , Yang JunQing , Huang Jing
Published: February 2021

Because of contradictory evidence from clinical trials, the association between angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer needs further evaluation. As such, the current study is to assess disproportionate reporting of primary malignant lung cancer among reports for ACEIs submitted to the FDA adverse event reporting system utilizing a pharmacovigilance approach. We conducted a disproportionality analysis of primary malignant lung cancer adverse events associated with 10 ACEIs by calculating the reported odds ratios (ROR) and information component (IC) with 95% confidence intervals (CI). ROR was adjusted for sex, age, and reporting year by logistic regression analyses. From January 2004 to March 2020, a total of 622 cases of lung cancer adverse event reports were identified for ACEIs users. Significant disproportionate association was found for ACEIs as a drug class (ROR: 1.22, 95% CI: 1.13–1.32; IC: 0.28, 95% CI: 0.17–0.39. adjusted ROR: 1.23, 95% CI: 1.02–1.49). After stratification based on gender, a subset analysis suggested that female patients exhibited a significant disproportionate association, while male patients did not. Sensitivity analyses that limited the data by reporting region, comorbidity, and reporting year also showed similar trends. Statistical significant lung cancer signals were detected among patients who received ACEI, especially female patients. The disproportionality analysis of the FAERS database suggests mildly increased reporting of lung cancer among ACEI users. Further robust epidemiological studies are necessary to confirm this relationship.
Integrative Metagenomics–Metabolomics for Analyzing the Relationship Between Microorganisms and Non-volatile Profiles of Traditional Xiaoqu
Authors: Zhao Chi , Su Wei , Mu Yu , Mu Yingchun , Jiang Li
Published: February 2021

Xiaoqu, one of three traditional jiuqu in China, is a saccharifying and fermenting agent used in Xiaoqu jiu brewing, with different ingredient compositions and preparation techniques used in various regions. The yield and quality of Xiaoqu jiu are significantly affected by the metabolites and microbiota of Xiaoqu; however, the associated relationship remains poorly understood. This study aimed to analyze this relationship in three typical traditional Xiaoqu from the Guizhou province in China. The non-volatile metabolites of Xiaoqu were detected using gas chromatography time-of-flight mass spectrometry, whereas the classification and metabolic potential of the microbiota were investigated using metagenomic sequencing. Results show that Firmicutes, Proteobacteria, and Actinobacteria represent the dominant bacterial phyla, with Lactobacillus, Bacillus, Acinetobacter, Leuconostoc, and Weissella found to be the dominant bacterial genera. Meanwhile, Ascomycota, Mucoromycota, and Basidiomycota are the dominant fungal phyla with Aspergillus, Saccharomyces, Pichia, Rhizopus, and Phycomyces being the predominant fungal genera. Functional annotation of the microbiota revealed a major association with metabolism of carbohydrates, cofactors, and vitamins, as well as amino acids. A total of 39 significantly different metabolites (SDMs) were identified that are involved in 47 metabolic pathways, primarily that of starch and sucrose; glycine, serine, and threonine; glyoxylate and dicarboxylate; pyruvate; as well as biosynthesis of pantothenate and CoA. Further, based on Spearman's correlation analysis, Aspergillus, Saccharomyces, Lactobacillus, Acetobacter, Weissella, Pantoea, Desmospora, and Bacillus are closely correlated with production of physicochemical indexes and SDMs. Moreover, the metabolic network generated for the breakdown of substrates and formation of SDMs in Xiaoqu was found to primarily center on the metabolism of carbohydrates and the tricarboxylic acid cycle. These results provide insights into the functional microorganisms and metabolic patterns present in traditional Guizhou Xiaoqu and might guide researchers in the production of stable and efficient Xiaoqu in the future.