bluuebunny/crossref_metadata_2025 huggingface dataset:
Peningkatan Kemampuan Internet of Things Bagi Guru TKJ di SMK Walisongo Semarang
Authors: Hirzan Alauddin Maulana , Adhiwibowo Whisnumurti , Daru April Firman
Published: September 2021

Teknologi Internet of Things merupakan sebuah teknologi yang memungkinkan perangkat untuk berkomunikasi satu sama lainnya. Dengan mengimplementasikan teknologi ini, dapat meningkatkan efisiensi serta produktivitas kinerja dunia industri. Karena itulah banyak industri yang menginginkan lulusan yang siap kerja dan memiliki pemahaman mengenai teknologi Internet of Things ini. Untuk mendapatkan lulusan yang sesuai dengan kebutuhan industri ini, para siswa dan guru di SMK Walisongo perlu memiliki pemahaman mengenai teknologi ini. Namun para guru SMK ini belum pernah mendapatkan pelatihan mengenai teknologi ini. Sehingga diperlukanlah pelatihan untuk meningkatkan kemampuan para guru dalam menguasai Internet of Things. Pelatihan ini dilaksanakan selama dua hari dengan durasi yang telah ditentukan. Dari pelatihan yang telah dilakukan, para peserta mengalami peningkatan pemahaman hingga 33,83% dibandingkan sebelum pelatihan diberikan. Oleh karena itu, bisa disimpulkan bahwa pelatihan yang dilakukan ini telah meningkatkan kemampuan para guru sehingga lebih siap untuk menghasilkan lulusan yang sesuai dengan kebutuhan industri.
Sosialisasi Gerakan “Mas AL” dalam Pelayanan Publik Saat Pandemi Covid-19 di Kelurahan Bintoro, Demak
Authors: Marthalina Marthalina , Sulistyaningrum Dwi Ayu
Published: September 2021

Pandemi Covid-19 menarik penulis untuk melakukan kegiatan pengabdian masyarakat berupa sosialisasi gerakan “MAS AL” yang bertujuan untuk mencegah penularan Covid-19 dalam proses pelayanan di Kelurahan Bintoro Kecamatan Demak. Gerakan “MAS AL” merupakan singkatan yang memiliki arti Menerapkan 4M; Aplikasikan hidup sehat; Senantiasa berdoa;Always smile & happy. Gerakan “MAS AL” adalah upaya meningkatkan kesadaran dalam pencegahan Covid-19 yang dikemas oleh penulis dalam bentuk slogan yang menarik dan mudah diingat. Penelitian ini menggunakan metode penelitian deskriptif kualitatif sebagai prosedur pemecahan masalah sedangkan metode pelaksanaan pengabdian masyarakat merupakan langkah atau cara yang dilakukan penulis dalam menemukan solusi dari permasalahan yang ditemui penulis di lingkungan Pemerintah Kelurahan Binotoro dalam menyelenggarakan kegiatan pelayanan kepada warga masyarakat di masa pandemi Covid-19. Kegiatan pengabdian kepada masyarakat yang telah dilaksanakan oleh penulis terdapat simpulan (1) sosialisasi terkait dengan pencegahan Covid-19 telah berjalan dengan tertib dan lancar baik sosialisasi secara langsung maupun sosialisasi melalui media sosial (2) sosialisasi Gerakan “MAS AL” mendapatkan apresiasi yang tinggi dari Camar Demak dan Lurah Bintoro dan seluruh aparatur kelurahan dan masyarakat, (3) para aparatur kelurahan dan warga masyarakat yang sebelumnya belum tertib menjadi mulai tertib dan disiplin dalam mematuhi protokol kesehatan sesuai yang ditetapkan oleh pemerintah, (4) Poster Gerakan “MAS AL” digunakan oleh Lurah Bintoro di lingkungan Kantor Bintoro sebagai media pengingat disiplin protokol kesehatan dan pola hidup bersih dan sehat bagi aparatur kelurahan maupun warga masyarakat (5) disarakan perlu ada penelitian lanjutan tentang perilaku penggunaan media sosial terutama jika dikaitkan dengan kondisi pandemi Covid-19.
Codebook Critique: Teaching Measurement and Operationalization Using Publicly Accessible Data
Authors: Becker Megan
Published: September 2021

Educating 21st century citizens requires lessons in data literacy, allowing learners to better understand and use the large amounts of information available to them. We must encourage our students to go beyond taking data as given, asking them to think critically about where it came from—Who collected it? For what purpose? What did they include/exclude? These questions dovetail with commonly taught topics in research methods courses, such as conceptualization, measurement, and operationalization, that may not be covered in substantive courses. This article describes a course module (of two to four 50-minute sessions) called “Codebook Critique,” where students are asked to review and critically evaluate the codebook from a publicly-accessible dataset. While originally used in an upper-division International Relations course, the exercise is flexible in that the assignment can be split into its component parts as appropriate for course-level and applied in various subfields.
A Novel Splice Variant of Human TGF-β Type II Receptor Encodes a Soluble Protein and Its Fc-Tagged Version Prevents Liver Fibrosis in vivo
Authors: Bertolio Marcela Soledad , La Colla Anabela , Carrea Alejandra , Romo Ana , Canziani Gabriela , Echarte Stella Maris , Campisano Sabrina , Barletta German Patricio , Monzon Alexander Miguel , Rodríguez Tania Melina , Chisari Andrea Nancy , Dewey Ricardo Alfredo
Published: September 2021

We describe, for the first time, a new splice variant of the human TGF-β type II receptor (TβRII). The new transcript lacks 149 nucleotides, resulting in a frameshift and the emergence of an early stop codon, rendering a truncated mature protein of 57 amino acids. The predicted protein, lacking the transmembrane domain and with a distinctive 13-amino-acid stretch at its C-terminus, was named TβRII-Soluble Endogenous (TβRII-SE). Binding predictions indicate that the novel 13-amino-acid stretch interacts with all three TGF-β cognate ligands and generates a more extensive protein–protein interface than TβRII. TβRII-SE and human IgG1 Fc domain were fused in frame in a lentiviral vector (Lv) for further characterization. With this vector, we transduced 293T cells and purified TβRII-SE/Fc by A/G protein chromatography from conditioned medium. Immunoblotting revealed homogeneous bands of approximately 37 kDa (reduced) and 75 kDa (non-reduced), indicating that TβRII-SE/Fc is secreted as a disulfide-linked homodimer. Moreover, high-affinity binding of TβRII-SE to the three TGF-β isoforms was confirmed by surface plasmon resonance (SPR) analysis. Also, intrahepatic delivery of Lv.TβRII-SE/Fc in a carbon tetrachloride-induced liver fibrosis model revealed amelioration of liver injury and fibrosis. Our results indicate that TβRII-SE is a novel member of the TGF-β signaling pathway with distinctive characteristics. This novel protein offers an alternative for the prevention and treatment of pathologies caused by the overproduction of TGF-β ligands.
Sex Differences, Estrogen Metabolism and Signaling in the Development of Pulmonary Arterial Hypertension
Authors: Sun Yanan , Sangam Shreya , Guo Qiang , Wang Jian , Tang Haiyang , Black Stephen M. , Desai Ankit A.
Published: September 2021

Pulmonary arterial hypertension (PAH) is a complex and devastating disease with a poor long-term prognosis. While women are at increased risk for developing PAH, they exhibit superior right heart function and higher survival rates than men. Susceptibility to disease risk in PAH has been attributed, in part, to estrogen signaling. In contrast to potential pathological influences of estrogen in patients, studies of animal models reveal estrogen demonstrates protective effects in PAH. Consistent with this latter observation, an ovariectomy in female rats appears to aggravate the condition. This discrepancy between observations from patients and animal models is often called the “estrogen paradox.” Further, the tissue-specific interactions between estrogen, its metabolites and receptors in PAH and right heart function remain complex; nonetheless, these relationships are essential to characterize to better understand PAH pathophysiology and to potentially develop novel therapeutic and curative targets. In this review, we explore estrogen-mediated mechanisms that may further explain this paradox by summarizing published literature related to: (1) the synthesis and catabolism of estrogen; (2) activity and functions of the various estrogen receptors; (3) the multiple modalities of estrogen signaling in cells; and (4) the role of estrogen and its diverse metabolites on the susceptibility to, and progression of, PAH as well as their impact on right heart function.
Identification of Novel Single-Nucleotide Variants With Potential of Mediating Malfunction of MicroRNA in Congenital Heart Disease
Authors: Liu Wangkai , Cheng Liangping , Chen Ken , Wu Jialing , Peng Rui , Tang Yan-Lai , Chen Jinghai , Yang Yuedong , Li Peiqiang , Huang Zhan-Peng
Published: September 2021

Congenital heart defects (CHDs) represent the most common human birth defects. Our previous study indicates that the malfunction of microRNAs (miRNAs) in cardiac neural crest cells (NCCs), which contribute to the development of the heart and the connected great vessels, is likely linked to the pathogenesis of human CHDs. In this study, we attempt to further search for causative single-nucleotide variants (SNVs) from CHD patients that mediate the mis-regulating of miRNAs on their downstream target genes in the pathogenesis of CHDs. As a result, a total of 2,925 3′UTR SNVs were detected from a CHD cohort. In parallel, we profiled the expression of miRNAs in cardiac NCCs and found 201 expressed miRNAs. A combined analysis with these data further identified three 3′UTR SNVs, including NFATC1 c.*654C>T, FGFRL1 c.*414C>T, and CTNNB1 c.*729_*730insT, which result in the malfunction of miRNA-mediated gene regulation. The dysregulations were further validated experimentally. Therefore, our study indicates that miRNA-mediated gene dysregulation in cardiac NCCs could be an important etiology of congenital heart disease, which could lead to a new direction of diagnostic and therapeutic investigation on congenital heart disease.
Whole Exome Sequencing Analysis in Fetal Skeletal Dysplasia Detected by Ultrasonography: An Analysis of 38 Cases
Authors: Peng Ying , Yang Shuting , Huang Xiaoliang , Pang Jialun , Liu Jing , Hu Jiancheng , Shen Xinzhao , Tang Chengyuan , Wang Hua
Published: September 2021

Background:Skeletal dysplasias (SDs) are a heterogeneous group of genetic disorders that primarily affect bone and cartilage. This study aims to identify the genetic causes for fetal SDs, and evaluates the diagnostic yield of prenatal whole-exome sequencing (WES) for this disorder.

Methods:WES was performed on 38 fetuses with sonographically identified SDs and normal results of karyotype and single nucleotide polymorphism (SNP) analysis. Candidate variants were selected by bioinformatics analysis, and verified by Sanger sequencing.

Results:WES revealed pathogenic or likely pathogenic variants associated with SDs in 65.79% (25/38) of fetuses, variants of uncertain significance (VUS) in SDs-related genes in 10.53% (4/38) cases, and incidental findings in 31.58% (12/38) fetuses. The SDs-associated variants identified in the present study affected 10 genes, and 35.71% (10/28) of the variants were novel.

Conclusion:WES has a high diagnostic rate for prenatal SDs, which improves pregnancy management, prenatal counseling and recurrence risk assessment for future pregnancies. The newly identified variants expanded mutation spectrum of this disorder.
Treatment Options in Congenital Disorders of Glycosylation
Authors: Park Julien H. , Marquardt Thorsten
Published: September 2021

Despite advances in the identification and diagnosis of congenital disorders of glycosylation (CDG), treatment options remain limited and are often constrained to symptomatic management of disease manifestations. However, recent years have seen significant advances in treatment and novel therapies aimed both at the causative defect and secondary disease manifestations have been transferred from bench to bedside. In this review, we aim to give a detailed overview of the available therapies and rising concepts to treat these ultra-rare diseases.
Women and Covid19: How the Italian Government Task Force Fostered Gender Equity
Authors: Camussi E. , Rella R. , Grigis P. , Sassi C. , Annovazzi C.
Published: September 2021

Over the last decades, the social context has been characterized by uncertainty, complexity, and inequalities, with significant impacts on people, groups, and communities. Covid-19 Pandemic has accentuated social discriminations, as inequalities affecting women (World Health Organization, 2018), with repercussions on general income, health, education (Office for National Statistics, 2021) that have been exhausting people, the economic system, and the welfare state (Antonicelli et al., 2020). To cope with these difficulties, on april 10, 2020 the Italian Prime Minister appointed a Task Force of 17 experts with scientific and applicative skills in social and economic fields. Within a short time, the Task Force aimed at identifying practical solutions priming the relaunch of the country. Given the women’s central role in the country’s social and economic development, in the final version of the Task Force plan, Gender Equality was indicated as the third—strategic and innovative—axis, together with Digitization and Green Economy. Its rationale was to promote gender equality in every action, with an allocation of dedicated economic resources. Specifically, the Task Force’s Working Group named “Individuals, Families, and Society” proposed specific initiatives aimed at recognizing and bridging the gender gaps in the various areas, and measures to support vulnerable people. This contribution will focus on the central role that the Task Force has played in encouraging systematic attention to women, considering their needs and the social-economic impacts on their choices and well-being. It will illustrate the Task Force’s internal dynamics (there were four women out of 17 people, then increased), the process of inclusion of different perspectives, both gender and multidisciplinary, and the practices suggested for the post-pandemic rebuilding. The final goal will be to show the inability to promote innovation, resilience and sustainability, without working with and for the community. As shown by the Italian Task Force, an innovative change must consider a multiplicity of perspectives that reflects the complexity of reality, even in the political and decision-making debate. Therefore, it’s central to build multidisciplinary teams that include various professionals from the social sectors, as Social Psychology, Sociology, Pedagogy, Political Philosophy, Demography, and Social Statistics, both women and men.
Serum ANCA and Overall Mortality: A 10-Year Retrospective Cohort Study on 1,024 Italian Subjects
Authors: Brunetta Enrico , Ramponi Giacomo , Folci Marco , De Santis Maria , Morenghi Emanuela , Vanni Elena , Bredi Elena , Furlan Raffaello , Angelini Claudio , Selmi Carlo
Published: September 2021

Background

Antineutrophil cytoplasmic antibodies (ANCA) are primarily involved in the pathogenesis of ANCA-associated vasculitides (AAV). However, ANCA may also be present in healthy subjects and in patients with autoimmune disorders different from AAV. We hypothesized that serum ANCA are associated with a worse prognosis in disorders other than AAV.

Objective

We investigated the association between the overall survival and the presence of serum ANCA in 1,024 Italian subjects with various testing indications in a 10-year interval.

Methods

In this retrospective cohort study, a population of 6,285 patients (many of whom were subsequently excluded due to our criteria) who tested for ANCA at a single center in 10 years was considered, and life status and comorbidities of subjects were collected. We compared the overall survival of ANCA-positive and ANCA-negative patients by means of Kaplan-Meier curves, while a multivariable adjusted Cox regression was used to evaluate the association between the ANCA status and the outcome (death) in terms of hazard ratios (HR) with 95% confidence intervals (CI).

Results

The positivity of perinuclear ANCA (pANCA) increased significantly mortality (HR, 1.60; 95% CI, 1.10–2.32), while cytoplasmic ANCA (cANCA) positivity failed to show a significant association (HR, 1.43; 95% CI, 0.77–2.68). The increased mortality rate was observed for both pANCA and cANCA in patients suffering from rheumatic disorders. No association was found between mortality and anti-MPO (HR, 0.63; 95% CI, 0.20–2.00) or anti-PR3 (HR, 0.98; 95% CI, 0.24–3.96) after adjusting for confounders.

Conclusions

Serum pANCA and cANCA are independent negative prognostic factors in patients with concurrent autoimmune diseases.
Conserved and Widespread Expression of piRNA-Like Molecules and PIWI-Like Genes Reveal Dual Functions of Transposon Silencing and Gene Regulation in Pinctada fucata (Mollusca)
Authors: Huang Songqian , Ichikawa Yuki , Yoshitake Kazutoshi , Kinoshita Shigeharu , Asaduzzaman Md , Omori Fumito , Maeyama Kaoru , Nagai Kiyohito , Watabe Shugo , Asakawa Shuichi
Published: September 2021

PIWI proteins and PIWI-interacting RNAs (piRNAs) suppress transposon activity in animals, thus safeguarding the genome from detrimental insertion mutagenesis. Recent studies revealed additional targets and functions of piRNAs in various animals. piRNAs are ubiquitously expressed in somatic tissues of the pearl oyster Pinctada fucata, however, the role of somatic piRNAs has not well characterized. This study reports the PIWI/piRNA pathway, including piRNA biogenesis and piRNA-mediated transposon silencing, and gene regulation in P. fucata. The biogenesis factors of PIWI, Zucchini, and HEN1, which are ubiquitous in somatic and gonadal tissues, were first identified in P. fucata using transcriptome analysis. Bioinformatics analyses suggested that different populations of piRNAs participate in the ping-pong amplification loop in a tissue-specific manner. In addition, a total of 69 piRNA clusters were identified in the genome of P. fucata based on the expression of piRNAs, which contained 26% transposons and enhanced for DNA/Crypton, LINE/CR1, SINE/Deu, and DNA/Academ. The expression patterns of the piRNAs and piRNA clusters in somatic tissues were not substantially different, but varied significantly between the somatic and gonadal tissues. Furthermore, locked-nucleic-acid modified oligonucleotide (LNA-antagonist) was used to silence single piRNA (piRNA0001) expression in P. fucata. Hundreds of endogenous genes were differentially expressed after piRNA silencing in P. fucata. Target prediction showed that some endogenous genes were targeted by piRNA0001, including twelve upregulated and nine downregulated genes after piRNA0001 silencing. The results indicated that piRNAs from somatic tissues may be related to gene regulation, whereas piRNAs from gonadal tissues are more closely associated to transposon silencing. This study will enhance our understanding of the role of piRNAs in mollusks, transposon silencing, and the regulatory function of the PIWI/piRNA pathway on protein-coding genes outside of germ line cells in P. fucata.
Different Responses of Soil Bacterial Communities to Nitrogen Addition in Moss Crust
Authors: Huang Tingwen , Liu Weiguo , Long Xi-En , Jia Yangyang , Wang Xiyuan , Chen Yinguang
Published: September 2021

Bacterial communities in soil serve an important role in controlling terrestrial biogeochemical cycles and ecosystem processes. Increased nitrogen (N) deposition in Northwest China is generating quantifiable changes in many elements of the desert environment, but the impacts of N deposition, as well as seasonal variations, on soil bacterial community composition and structure are poorly understood. We used high-throughput sequencing of bacterial 16S rRNA genes from Gurbantünggüt Desert moss crust soils to study the impacts of N addition on soil bacterial communities in March, May, and November. In November, we discovered that the OTU richness and diversity of soil bacterial community dropped linearly with increasing N input. In November and March, the diversity of the soil bacterial community decreased significantly in the medium-N and high-N treatments. In May, N addition caused a substantial change in the makeup of the soil bacterial composition, while the impacts were far less apparent in November and March. Furthermore, the relative abundance of major bacterial phyla reacted non-linearly to N addition, with high-N additions decreasing the relative richness ofProteobacteria,Bacteroidetes, andAcidobacteriawhile increasing the relative abundance ofActinobacteriaandChloroflexi. We also discovered that seasonality, as characterized by changes in soil moisture, pH, SOC, and AK content, had a significant impact on soil bacterial communities. Significant variations in the makeup of the community were discovered at the phylum and genus levels throughout the various months. In May, the variety of soil bacterial community was at its peak. Further investigation showed that the decrease in soil bacterial diversity was mostly attributed to a drop in soil pH. These results indicated that the impact of N deposition on the soil bacterial community was seasonally dependent, suggesting that future research should evaluate more than one sample season at the same time.
Anammox Bacteria Are Potentially Involved in Anaerobic Ammonium Oxidation Coupled to Iron(III) Reduction in the Wastewater Treatment System
Authors: Yang Xiao-Ru , Li Hu , Su Jian-Qiang , Zhou Guo-Wei
Published: September 2021

Anaerobic ammonium oxidation coupled to nitrite reduction (termed as Anammox) was demonstrated as an efficient pathway to remove nitrogen from a wastewater treatment system. Recently, anaerobic ammonium oxidation was also identified to be linked to iron(III) reduction (termed Feammox) with dinitrogen, nitrite, or nitrate as end-product, reporting to enhance nitrogen removal from the wastewater treatment system. However, little is known about the role of Anammox bacteria in the Feammox process. Here, slurry from wastewater reactor amended with ferrihydrite was employed to investigate activity of Anammox bacteria in the Feammox process using the 15N isotopic tracing technique combined with 16S rRNA gene amplicon sequencing. A significantly positive relationship between rates of 15N2 production and iron(III) reduction indicated the occurrence of Feammox during incubation. Relative abundances of Anammox bacteria including Brocadia, Kuenenia, Jettenia, and unclassified Brocadiaceae were detected with low relative abundances, whereas Geobacteraceae dominated in the treatment throughout the incubation. 15N2 production rates significantly positively correlated with relative abundances of Geobacter, unclassified Geobacteraceae, and Anammox bacteria, revealing their contribution to nitrogen generation via Feammox. Overall, these findings suggested Anammox bacteria or cooperation between Anammox bacteria and iron(III) reducers serves a potential role in Feammox process.
Understanding the Pathophysiology of Congenital Vestibular Disorders: Current Challenges and Future Directions
Authors: Peusner Kenna D. , Bell Nina M. , Hirsch June C. , Beraneck Mathieu , Popratiloff Anastas
Published: September 2021

In congenital vestibular disorders (CVDs), children develop an abnormal inner ear before birth and face postnatal challenges to maintain posture, balance, walking, eye-hand coordination, eye tracking, or reading. Only limited information on inner ear pathology is acquired from clinical imaging of the temporal bone or studying histological slides of the temporal bone. A more comprehensive and precise assessment and determination of the underlying mechanisms necessitate analyses of the disorders at the cellular level, which can be achieved using animal models. Two main criteria for a suitable animal model are first, a pathology that mirrors the human disorder, and second, a reproducible experimental outcome leading to statistical power. With over 40 genes that affect inner ear development, the phenotypic abnormalities resulting from congenital vestibular disorders (CVDs) are highly variable. Nonetheless, there is a large subset of CVDs that form a common phenotype of a sac-like inner ear with the semicircular canals missing or dysplastic, and discrete abnormalities in the vestibular sensory organs. We have focused the review on this subset, but to advance research on CVDs we have added other CVDs not forming a sac-like inner ear. We have included examples of animal models used to study these CVDs. Presently, little is known about the central pathology resulting from CVDs at the cellular level in the central vestibular neural network, except for preliminary studies on a chick model that show significant loss of second-order, vestibular reflex projection neurons.
Treatment of Tinnitus in Children—A Systematic Review
Authors: Dullaart Max J. , Kip Marijn , Smit Adriana L. , Stegeman Inge
Published: September 2021

Objectives: To systematically review studies on the effect of treatment of subjective tinnitus in children.

Data Sources: We searched for studies in MEDLINE and EMBASE databases, after which additional studies were hand searched using Scopus databases. The methods are described in the study protocol, which has been registered in the PROSPERO register. PRISMA guidelines were followed in the reporting of this study.

Eligibility Criteria: We considered for inclusion randomized controlled trials (RCTs), observational studies, case reports, and case series, with tinnitus as primary outcome in children (0–18 years old) with acute or chronic subjective tinnitus. We excluded studies in which both children and adults participated but outcomes were not specifically reported for children, as well as animal studies, studies with a non-original study design and studies about children with pulsatile or objective tinnitus.

Data Selection: Two reviewers independently assessed studies for eligibility and quality, collected and extracted data. Statistical analyses were performed in case of homogeneous outcomes.

Results: The search yielded a total of 4,447 studies. Of these, 147 eligible studies were selected. One case report and five observational studies met the eligibility criteria. Three studies applied counseling and (simplified-)TRT and reported improvement in tinnitus outcome in 68 out of 82 children after 3–6 months of treatment. Two studies used pharmacological treatments and reported improvement in 74 out of 86 patients after 10 days to 3 months of treatment. One study reported the outcome of biofeedback therapy, describing an improvement in tinnitus loudness and annoyance after 2 months of treatment.

Conclusion: Due to the high risk of bias of the included studies, we cannot determine the effectiveness of the treatment of subjective tinnitus in children. Also, owing to brief follow-up periods, it is not possible to draw conclusions regarding long-term effects. Randomized controlled trials with longer follow-up periods are necessary to provide substantial evidence of the effects of therapies for children affected by tinnitus. https://www.crd.york.ac.uk/prospero/

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier [CRD42020178134].
Azoximer Bromide: Mystery, Serendipity, and Promise
Authors: Grivtsova Lyudmila Yuryevna , Falaleeva Natalia Alexandrovna , Tupitsyn Nikolay Nikolaevich
Published: September 2021

Azoximer bromide (AZB) was identified as an immunomodulator, and was initially developed and currently successfully indicated as one of several natural polyelectrolytes, a vaccine adjuvant, and an effective agent for the treatment of infectious and inflammatory diseases of viral, bacterial, and fungal origin. AZB has the potential to increase an individual’s resistance to local and general infection and is indicated for the treatment of viral infections, and has also demonstrated clinical efficacy in the treatment of a variety of secondary immunodeficiencies. However, AZB may offer long-term promise beyond use against infection. Multiple clinical trials and research studies in cancer patients have reported favourable outcomes with AZB as well as an optimal safety and tolerability profile. The findings raise the possibility of direct antitumor properties. This literature review analyses the novel mechanisms that mediate the AZB direct anticancer effects. Overall, the evidence suggests that AZB has the hallmark of an agent that could be used to support existing cancer treatments at different stages of disease.
Radiomic Evaluations of the Diagnostic Performance of DM, DBT, DCE MRI, DWI, and Their Combination for the Diagnosisof Breast Cancer
Authors: Niu Shuxian , Wang Xiaoyu , Zhao Nannan , Liu Guanyu , Kan Yangyang , Dong Yue , Cui E-Nuo , Luo Yahong , Yu Tao , Jiang Xiran
Published: September 2021

Objectives

This study aims to evaluate digital mammography (DM), digital breast tomosynthesis (DBT), dynamic contrast-enhanced (DCE), and diffusion-weighted (DW) MRI, individually and combined, for the values in the diagnosis of breast cancer, and propose a visualized clinical-radiomics nomogram for potential clinical uses.

Methods

A total of 120 patients were enrolled between September 2017 and July 2018, all underwent preoperative DM, DBT, DCE, and DWI scans. Radiomics features were extracted and selected using the least absolute shrinkage and selection operator (LASSO) regression. A radiomics nomogram was constructed integrating the radiomics signature and important clinical predictors, and assessed with the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).

Results

The radiomics signature derived from DBT plus DM generated a lower area under the ROC curve (AUC) and sensitivity, but a higher specificity compared with that from DCE plus DWI. The nomogram integrating the combined radiomics signature, age, and menstruation status achieved the best diagnostic performance in the training (AUCs, nomogram vs. combined radiomics signature vs. clinical model, 0.975 vs. 0.964 vs. 0.782) and validation (AUCs, nomogram vs. combined radiomics signature vs. clinical model, 0.983 vs. 0.978 vs. 0.680) cohorts. DCA confirmed the potential clinical usefulness of the nomogram.

Conclusions

The DBT plus DM provided a lower AUC and sensitivity, but a higher specificity than DCE plus DWI for detecting breast cancer. The proposed clinical-radiomics nomogram has diagnostic advantages over each modality, and can be considered as an efficient tool for breast cancer screening.
The Stromal and Immune Landscape of Nasopharyngeal Carcinoma and Its Implications for Precision Medicine Targeting the Tumor Microenvironment
Authors: Gong Lanqi , Kwong Dora Lai-Wan , Dai Wei , Wu Pingan , Wang Yan , Lee Anne Wing-Mui , Guan Xin-Yuan
Published: September 2021

The evolution of the tumor microenvironment (TME) is a cancer-dependent and dynamic process. The TME is often a complex ecosystem with immunosuppressive and tumor-promoting functions. Conventional chemotherapy and radiotherapy, primarily focus on inducing tumor apoptosis and hijacking tumor growth, whereas the tumor-protective microenvironment cannot be altered or destructed. Thus, tumor cells can quickly escape from extraneous attack and develop therapeutic resistance, eventually leading to treatment failure. As an Epstein Barr virus (EBV)-associated malignancy, nasopharyngeal carcinoma (NPC) is frequently infiltrated with varied stromal cells, making its microenvironment a highly heterogeneous and suppressive harbor protecting tumor cells from drug penetration, immune attack, and facilitating tumor development. In the last decade, targeted therapy and immunotherapy have emerged as promising options to treat advanced, metastatic, recurrent, and resistant NPC, but lack of understanding of the TME had hindered the therapeutic development and optimization. Single-cell sequencing of NPC-infiltrating cells has recently deciphered stromal composition and functional dynamics in the TME and non-malignant counterpart. In this review, we aim to depict the stromal landscape of NPC in detail based on recent advances, and propose various microenvironment-based approaches for precision therapy.
Metabolomics Analysis Reveals Interaction of Base-Line Chemotherapy and Shiyiwei Shenqi Tablets in Breast Cancer Treatment
Authors: Wan Hong , Xu Xiaojun , Yang Xiaowei , Li Angqing , Ma Xiaopeng , Xu Aman , Yuan Xiao , Wang Wenbin , Guo Tao , Luo Guangtao , He Xiaobo , Li Wang , Wang Zhaorui , Sun Qiang , Pei Jing , Guo Yongzhen , Zhu Yong
Published: September 2021

Shiyiwei Shenqi Tablet (SSTs) has been widely used for treatment of different types of cancer including breast cancer. SST has drawn more and more interest due to the low rate of side effects. The aim of this study was to investigate the metabolites in serums of breast cancer patients who received base-line chemotherapy only or combination treatment with SST. An untargeted metabolomics method was developed to investigate the alteration of metabolism in patients’ serums using ultra-high-performance liquid chromatography/Q-exactive Orbitrap mass spectrometry. The patients were separated based on the metabolomics data, and further analyses showed that SST treatment can affect the metabolism of glucose, fatty acid, bile acid and amino acid. In particular, SST treatment significantly reduced some short peptides which are potential tumor neoantigens. This study may provide novel insights into the mechanism underlying interaction between SST and base-line chemotherapy in terms of affecting metabolic pathways and thereby changing metabolic products, which might shed new light for clinical medication.
Effects of Trandolapril on Structural, Contractile and Electrophysiological Remodeling in Experimental Volume Overload Heart Failure
Authors: Jarkovská Dagmar , Miklovič Matúš , Švíglerová Jitka , Červenka Luděk , Škaroupková Petra , Melenovský Vojtěch , Štengl Milan
Published: September 2021

Chronic volume overload induces multiple cardiac remodeling processes that finally result in eccentric cardiac hypertrophy and heart failure. We have hypothesized that chronic angiotensin-converting enzyme (ACE) inhibition by trandolapril might affect various remodeling processes differentially, thus allowing their dissociation. Cardiac remodeling due to chronic volume overload and the effects of trandolapril were investigated in rats with an aortocaval fistula (ACF rats). The aortocaval shunt was created using a needle technique and progression of cardiac remodeling to heart failure was followed for 24 weeks. In ACF rats, pronounced eccentric cardiac hypertrophy and contractile and proarrhythmic electrical remodeling were associated with increased mortality. Trandolapril substantially reduced the electrical proarrhythmic remodeling and mortality, whereas the effect on cardiac hypertrophy was less pronounced and significant eccentric hypertrophy was preserved. Effective suppression of electrical proarrhythmic remodeling and mortality but not hypertrophy indicates that the beneficial therapeutic effects of ACE inhibitor trandolapril in volume overload heart failure might be dissociated from pure antihypertrophic effects.
The Contribution of Phospholipase C in Vomiting in the Least Shrew (Cryptotis Parva) Model of Emesis
Authors: Zhong Weixia , Darmani Nissar A.
Published: September 2021

Gq and Gβγ protein-dependent phospholipase C (PLC) activation is extensively involved in G protein-coupled receptor (GPCR)-mediated signaling pathways which are implicated in a wide range of physiological and pathological events. Stimulation of several GPCRs, such as substance P neurokinin 1-, dopamine D2/3-, histamine H1- and mu-opioid receptors, can lead to vomiting. The aim of this study was to investigate the role of PLC in vomiting through assessment of the emetic potential of a PLC activator (m-3M3FBS), and the antiemetic efficacy of a PLC inhibitor (U73122), in the least shrew model of vomiting. We find that a 50 mg/kg (i.p.) dose of m-3M3FBS induces vomiting in ∼90% of tested least shrews, which was accompanied by significant increases in c-Fos expression and ERK1/2 phosphorylation in the shrew brainstem dorsal vagal complex, indicating activation of brainstem emetic nuclei in m-3M3FBS-evoked emesis. The m-3M3FBS-evoked vomiting was reduced by pretreatment with diverse antiemetics including the antagonists/inhibitors of: PLC (U73122), L-type Ca2+ channel (nifedipine), IP3R (2-APB), RyR receptor (dantrolene), ERK1/2 (U0126), PKC (GF109203X), the serotoninergic type 3 receptor (palonosetron), and neurokinin 1 receptor (netupitant). In addition, the PLC inhibitor U73122 displayed broad-spectrum antiemetic effects against diverse emetogens, including the selective agonists of serotonin type 3 (2-Methyl-5-HT)-, neurokinin 1 receptor (GR73632), dopamine D2/3 (quinpirole)-, and muscarinic M1 (McN-A-343) receptors, the L-type Ca2+ channel (FPL64176), and the sarco/endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin. In sum, PLC activation contributes to emesis, whereas PLC inhibition suppresses vomiting evoked by diverse emetogens.
Can We Harness “Enviromics” to Accelerate Crop Improvement by Integrating Breeding and Agronomy?
Authors: Cooper Mark , Messina Carlos D.
Published: September 2021

The diverse consequences of genotype-by-environment (GxE) interactions determine trait phenotypes across levels of biological organization for crops, challenging our ambition to predict trait phenotypes from genomic information alone. GxE interactions have many implications for optimizing both genetic gain through plant breeding and crop productivity through on-farm agronomic management. Advances in genomics technologies have provided many suitable predictors for the genotype dimension of GxE interactions. Emerging advances in high-throughput proximal and remote sensor technologies have stimulated the development of “enviromics” as a community of practice, which has the potential to provide suitable predictors for the environment dimension of GxE interactions. Recently, several bespoke examples have emerged demonstrating the nascent potential for enhancing the prediction of yield and other complex trait phenotypes of crop plants through including effects of GxE interactions within prediction models. These encouraging results motivate the development of new prediction methods to accelerate crop improvement. If we can automate methods to identify and harness suitable sets of coordinated genotypic and environmental predictors, this will open new opportunities to upscale and operationalize prediction of the consequences of GxE interactions. This would provide a foundation for accelerating crop improvement through integrating the contributions of both breeding and agronomy. Here we draw on our experience from improvement of maize productivity for the range of water-driven environments across the US corn-belt. We provide perspectives from the maize case study to prioritize promising opportunities to further develop and automate “enviromics” methodologies to accelerate crop improvement through integrated breeding and agronomic approaches for a wider range of crops and environmental targets.
Parent Gender Affects the Influence of Parent Emotional Eating and Feeding Practices on Child Emotional Eating
Authors: Trevino Shaina D. , Kelly Nichole R. , Budd Elizabeth L. , Giuliani Nicole R.
Published: September 2021

Extant research supports a direct association between parent’s own emotional eating and their child’s emotional eating, and demonstrates correlations among parent emotional eating, feeding practices, and child emotional eating. However, the majority of this work focuses on the separate influences of these factors. The current study aims to add to the literature by simultaneously examining the indirect effects of three major parental feeding practices (i.e., emotion regulation, instrumental, and restrictive feeding) in the association between parent emotional eating and child emotional eating, and exploring how these indirect effects vary based on parent gender. Parents (86 fathers, 324 mothers) of an elementary school-age child (M= 8.35,SD= 2.29, range = 5–13) completed an online survey through Qualtrics Panels. Results suggested that restrictive feeding partially accounted for the association between parent and child emotional eating in the combined sample of mothers and fathers. Exploratory analyses revealed that the indirect effects of parental feeding practices in the association between parent emotional eating and child emotional eating varied based on parent gender. Among mothers, restrictive feeding was the only feeding practice that partially accounted for the association between maternal and child emotional eating, whereas all three feeding practices fully accounted for the association between father and child emotional eating. As the bulk of the literature on parent emotional eating and feeding has solely focused on mothers, these findings offer insight into how feeding practices may differentially function in the relation between parent emotional eating and child emotional eating for mothers versus fathers.
Temperamental and Personality Traits as Factors Related to Changes in Health Behaviors and Quality of Life in Patients With Metabolic Syndrome in Poland
Authors: Burnos Agnieszka , Skrobowski Andrzej
Published: September 2021

Lifestyle changes in diet and physical activity are necessary for managing metabolic syndrome. The aim of this longitudinal study was to examine temperamental and personality traits as moderators of lifestyle changes prompted by motivational intervention. The sample consisted of 50 patients aged 22–65years (M=45.26; SD=9.79) who fulfilled the diagnostic criteria for metabolic syndrome and were undergoing treatment at the Military Institute of Medicine in Warsaw. There were two measurements: an initial measurement and a second 15months after motivational counseling. Each patient completed the questionnaires: Formal Characteristics of Behavior – Temperament Inventory, NEO Five Factor Inventory, Inventory of Health Behavior, and Short Form Survey SF-36. Body Mass Index (BMI), Fat Mass, Fat-free Mass, Intracellular Water, and Basal Metabolic Rate (BMR) were also measured. Data were analyzed using dependent samples t-tests to detect the changes in consecutive measurements, the hierarchical regression analysis was used to investigate temperamental and personality traits as predictors of change, the cluster analysis was used to extract the subgroups of patients with distinct profiles of temperamental and personality traits, and the analysis of variance was used to analyze extracted profiles as potential moderators of change. Three subgroups were extracted using k-means clustering: patients with higher Neuroticism, Perseveration, and Emotional Reactivity; patients higher Extraversion, Briskness, Sensory Sensitivity, Endurance, Activity, and Conscientiousness; and patients with lower Perseveration. All patients improved significantly in terms of physical quality of life (QoL), health behaviors, BMI, BMR, and Fat-free Mass (p<0.05). Regression analysis found that higher Sensory Sensitivity, lower Perseveration, and higher Agreeableness fostered positive change (p<0.05). Patients with higher Neuroticism, Perseveration, and Emotional Reactivity also improved in terms of their Emotional Quality of Life and Health Practices, reaching parity with other patients, which was verified on the basis of statistically significant interaction (p<0.05). The temperamental and personality trait profiles moderated the changes in health practices and emotional QoL. Motivational counseling was effective for patients diagnosed with metabolic syndrome in general, but patients with higher Neuroticism, Perseveration, and Emotional Reactivity benefited even more, as they were in poorer psychological condition before the motivational intervention.
Predictors of Parental Coping During the Covid-19 Pandemic: A Survey in Germany
Authors: Clemens Vera , Köhler-Dauner Franziska , Ziegenhain Ute , Fegert Jörg M.
Published: September 2021

The Covid-19 pandemic has been profoundly affecting nearly everybody, but families with minors have been hit particularly. Closure of schools and kindergartens, home schooling, and working from home have led to a profound upheaval in family life. Parental adverse childhood experiences (ACEs) are an important determinant for parenting behavior. Importantly, ACEs can increase the vulnerability to stress and impair coping strategies. The current pandemic leads to increased parental stress, a risk factor for harsh parenting behavior, Therefore, we aimed to assess the role of ACEs and sociodemographic factors associated to parental coping during the current pandemic. In a cross-sectional online survey, 687 parents of minors in Germany were included. Demographic and psychosocial factors associated to parental coping during the first lockdown due to the Covid-19 pandemic were assessed. Results show that younger age of the respective child, income loss, dissatisfaction with the sharing of childcare duties, and ACEs were significantly associated with an increase of potential harmful parenting behavior during the Covid-19 pandemic. An increase of dissatisfaction with the sharing of childcare duties during the pandemic was predicted by working from home and taking care of the children mainly by oneself, while sharing childcare duties with the partner equally resulted even in an increase of satisfaction with sharing of childcare duties during the pandemic. These findings demonstrate that a history of childhood adversity in a parent is a risk factor for harmful parenting during the pandemic. Parental satisfaction with sharing of caregiving is an important factor for parental coping during the pandemic. Sharing of caregiving between partners should be encouraged.
Deep Learning of Histopathology Images at the Single Cell Level
Authors: Lee Kyubum , Lockhart John H. , Xie Mengyu , Chaudhary Ritu , Slebos Robbert J. C. , Flores Elsa R. , Chung Christine H. , Tan Aik Choon
Published: September 2021

The tumor immune microenvironment (TIME) encompasses many heterogeneous cell types that engage in extensive crosstalk among the cancer, immune, and stromal components. The spatial organization of these different cell types in TIME could be used as biomarkers for predicting drug responses, prognosis and metastasis. Recently, deep learning approaches have been widely used for digital histopathology images for cancer diagnoses and prognoses. Furthermore, some recent approaches have attempted to integrate spatial and molecular omics data to better characterize the TIME. In this review we focus on machine learning-based digital histopathology image analysis methods for characterizing tumor ecosystem. In this review, we will consider three different scales of histopathological analyses that machine learning can operate within: whole slide image (WSI)-level, region of interest (ROI)-level, and cell-level. We will systematically review the various machine learning methods in these three scales with a focus on cell-level analysis. We will provide a perspective of workflow on generating cell-level training data sets using immunohistochemistry markers to “weakly-label” the cell types. We will describe some common steps in the workflow of preparing the data, as well as some limitations of this approach. Finally, we will discuss future opportunities of integrating molecular omics data with digital histopathology images for characterizing tumor ecosystem.