bluuebunny/crossref_metadata_2025 huggingface dataset:
PELATIHAN BLOG SEBAGAI SARANA PUBLIKASI PEMBELAJARAN GURU SMA NEGERI 2 KISARAN
Authors: Maha  Putra Guntur , Irawati Novica , Prijuna Adi
Published: February 2021

Abstract: As a formal education institution, acculturation of techniques in Teaching and Learning Activities (KBM) is required by each lesson teacher to be able to transfer knowledge to students maximal and optimally. So far the teaching carried out by the teachers of SMA 2 Kisaran is more dominant in learning done face-to-face in the classroom, so that learning requires the mind and energy that is extra because it is done repeatedly in the classroom and the hours that different. Starting from the above, the dedication team sought solutions so that teaching can be acculturated by online learning using blog media to publish teachers' teaching materials to the internet. It is expected that online-based teaching techniques, one of which is outlined in the making and utilization of blogs can stimulate interest from students to access teaching materials that have been published online, both in the form of text, images, audio and learning videos that have been recorded and uploaded by the teacher into his blog whenever and wherever it is, so that it will create student centered learning and learning objectives can be achieved. Keywords: blogs, teaching materials, online publications, videos, student center learning.  Abstrak: Sebagai institusi pendidikan formal maka diperlukan akulturasi teknik dalam Kegiatan Belajar Mengajar (KBM) yang dilakukan oleh masing-masing guru pelajaran untuk dapat mentransfer ilmu pengetahuan kepada peserta didik secara maksimal dan optimal. Selama ini pengajaran yang dilakukan oleh guru-guru SMA Negeri 2 Kisaran lebih dominan ke-pembelajaran yang dilakukan secara tatap muka di dalam kelas, sehingga pembelajaran membutuhkan pikiran dan tenaga yang ekstra karena dilakukan secara berulang-ulang pada kelas dan jam yang berbeda. Berawal dari hal diatas maka tim pengabdian mencari solusi agar pengajaran dapat diakulturasi dengan pembelajaran secara online menggunakan media blog untuk mempublikasikan bahar ajar para guru ke internet. Diharapkan dengan teknik  pengajaran berbasis online salah satunya yang dituangkan dalam pembuatan dan pemanfaatan blog dapat merangsang minat dari para siswa untuk mengakses bahan ajar yang telah dipublikasikan secara online baik informasi berupa text, gambar, audio maupun video pembelajaran yang telah direkam dan diupload oleh guru ke dalam blognya kapan dan dimanapun berada, sehingga akan tercipta pembelajaran berpusat pada siswa (Student Centred Learning) dan tujuan pembelajaran dapat tercapai. Kata kunci: blog, bahan ajar, publikasi online, video, Student Center Learning.
INTERNET SEHAT DAN AMAN (INSAN)
Authors: Nasution Donni , Rahayu Elly , Rohminatin Rohminatin
Published: February 2021

Abstract: This service activity is carried out in the form of workshop where health and safe Internet became it's theme which was aimed to increasing the knowledge of women, especially the women of Bhayangkari Polsek Porsea in using the internet in a healthy and safe manner. The target audience of this Service Program are 20 women from bhayangkari Polsek Porsea. The method used are the lecture method, direct discussion and also question and answer. The material provided includes such as Women in the Technological Era, Empowering Women through Internet Technology, and also Healthy and Safe Internet. The benefits obtained from this service are the first is to improve current knowledge of technology for the women, the second is to increase the knowledge of the women roles in technology and the third is to educate the internet ethics and its benefits for herself and the family, children especially. Keywords: Insan, health and safe, Women, Internet  Abstrak: Kegiatan pengabdian ini  dilaksanakan dalam bentuk kegiatan Workhshop  yang bertemakan Internet sehat dan aman yang bertujuan meningkatkan pengetahuan perempuan khususnya ibu-ibu Bhayangkari dalam menggunakan internet secara sehat dan aman. Khalayak sasaran dalam kegiatan Pengabdian kepada Masyarakat ini adalah Ibu-Ibu bhayangkari yang berjumlah 20 orang. Metode yang digunakan adalah  metode ceramah, diskusi dan  tanya jawab secara langsung. Materi yang diberikan diantaranya  seperti Perempuan di Era Teknologi, Pemberdayaan Perempuan Melalui Teknologi Internet, serta Internet Sehat dan Aman. Manfaat yang diperoleh dari kegiatan pengabdian ini pertama meningkatkan pengetahuan. Teknologi masa kini kepada perempuan, kedua meningkkat pengetahuan tentang peran perempuan dalam Teknologi  dan ketiga melakukan edukasi etika berinternet serta manfaat  bagi  dirinya dan keluarga, terutama kepada anak-anak. Kata kunci: Insan, Sehat dan Aman, Wanita, Internet
Efeito da frequência de irrigação e fósforo nas características biométricas do milho
Authors: Oliveira Reginaldo Miranda de , Oliveira Rubens Alves de , Oliveira Ednaldo Miranda de , Botelho Margareth Evangelista , Oliveira Job Teixeira de
Published: February 2021

O aproveitamento hídrico pela cultura do milho aparentemente está intimamente relacionada aos níveis de fósforo disponível no solo. O objetivo deste trabalho foi avaliar o efeito da frequência de irrigação combinado a diferentes doses de adubação fosfatada nas características biométricas da cultura do milho sob duas densidades de plantio. O experimento foi instalado num esquema de parcelas sub-subdivididas. Na parcela principal sete frequências de irrigação e duas populações de plantas. Nas sub-subparcelas, cinco doses de fósforo. A população de 80 mil plantas ha-1 apresentou maior altura de plantas e de inserção de espigas, independente do turno de rega adotado e da dose de fósforo aplicada. A população de 60 mil plantas ha-1, apresentou maior comprimento de espigas, número de grãos na fileira e massa de 1000 grãos. Doses crescentes de fósforo, afetaram as alturas de plantas e altura de inserção de espigas na população de 60 mil plantas ha-1. Já a população de 80 mil plantas ha-1, doses crescentes de fósforo afetaram diâmetro de caule. Não foi evidenciado efeito da adubação fosfatada nas características produtivas estudadas: índice de colheita, diâmetro de espigas, comprimento de espigas, número de fileiras de grãos, número de grãos na fileira e massa de 1000 grãos.
Cinética de liofilização e modelagem matemática do leite asinino
Authors: Sousa Francisca Moisés de , Cavalcanti-Mata Mário Eduardo Rangel Moreira , Duarte Maria Elita Martins , Melo Mylena Olga Pessoa , Leite Filho Manoel Tolentino , Santos Rebeca Morais Silva , Almeida Michelly Daiane Araújo de , André Anastácia Maria Mikaella Campos Nóbrega , Lúcio Alexandre da Silva , Santos Kamila de Lima , Martins Jorge Jacó Alves , Rodrigues Larissa Monique de Sousa
Published: February 2021

O interesse no leite de asinino vem destacando-se devido a estudos relacionados às suas características benéficas, apresenta semelhanças na palatabilidade e composição quando comparado ao leite materno. O leite dessa espécie demonstrou ser pobre em proteínas e gorduras, e rico em lactose, além de apresentar propriedades antimicrobianas, tornando-o um alimento ideal para suplemento humano e principalmente como alimento alternativo para crianças com alergia à proteína do leite de vaca. Diante disso, o objetivo deste trabalho foi estudar a cinética de liofilização para o leite asinino submetido a diferentes temperaturas de congelamento (-20, -60, -100 e -140ºC), bem como determinar a difusividade efetiva e as propriedades termodinâmicas. Os dados experimentais foram submetidos a analises dos modelos de secagem teórico, semiteórico, semiempíricos e empírico, e os parâmetros R2, Ra2, P (%), SE e DQM foram determinados. Dentre os modelos de secagem estudados o Modelo de Cavalcanti-Mata modificado, foi o que apresentou melhor ajuste aos dados experimentais. Nos modelos de Fick modificado, Cavalcanti-Mata modificado, Lewis modificado e Page modificado, a difusividade efetiva decresceu com a diminuição da temperatura de congelamento e em consequência disto, constata-se que a entalpia e a entropia diminuiu a medida que a temperatura de congelamento foi baixando e a energia livre de Gibbs demonstrou que o processo não é espontâneo.
Effects of carnosine and hypothermia combination therapy on hypoxic-ischemic brain injury in neonatal rats
Authors: Byun Jun Chul , Lee Seong Ryong , Kim Chun Soo
Published: February 2021

Background: Carnosine has antioxidative and neuroprotective properties against hypoxic-ischemic (HI) brain injury. Hypothermia is used as a therapeutic tool for HI encephalopathy in newborn infants with perinatal asphyxia. However, the combined effects of these therapies are unknown.Purpose: Here we investigated the effects of combined carnosine and hypothermia therapy on HI brain injury in neonatal rats.Methods: Postnatal day 7 (P7) rats were subjected to HI brain injury and randomly assigned to 4 groups: vehicle; carnosine alone; vehicle and hypothermia; and carnosine and hypothermia. Carnosine (250 mg/kg) was intraperitoneally administered at 3 points: immediately following HI injury, 24 hours later, and 48 hours later. Hypothermia was performed by placing the rats in a chamber maintained at 27°C for 3 hours to induce whole-body cooling. Sham-treated rats were also included as a normal control. The rats were euthanized for experiments at P10, P14, and P35. Histological and morphological analyses, in situ zymography, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, and immunofluorescence studies were conducted to investigate the neuroprotective effects of the various interventional treatments.Results: Vehicle-treated P10 rats with HI injury showed an increased infarct volume compared to sham-treated rats during the triphenyltetrazolium chloride staining study. Hematoxylin and eosin staining revealed that vehicle-treated P35 rats with HI injury had decreased brain volume in the affected hemisphere. Compared to the vehicle group, carnosine and hypothermia alone did not result in any protective effects against HI brain injury. However, a combination of carnosine and hypothermia effectively reduced the extent of brain damage. The results of in situ zymography, TUNEL assays, and immunofluorescence studies showed that neuroprotective effects were achieved with combination therapy only.Conclusion: Carnosine and hypothermia may have synergistic neuroprotective effects against brain damage following HI injury.
Interesting Biochemistries in the Structure and Function of Bacterial Effectors
Authors: Mak Hazel , Thurston Teresa L. M.
Published: February 2021

Bacterial effector proteins, delivered into host cells by specialized multiprotein secretion systems, are a key mediator of bacterial pathogenesis. Following delivery, they modulate a range of host cellular processes and functions. Strong selective pressures have resulted in bacterial effectors evolving unique structures that can mimic host protein biochemical activity or enable novel and distinct biochemistries. Despite the protein structure-function paradigm, effectors from different bacterial species that share biochemical activities, such as the conjugation of ubiquitin to a substrate, do not necessarily share structural or sequence homology to each other or the eukaryotic proteins that carry out the same function. Furthermore, some bacterial effectors have evolved structural variations to known protein folds which enable different or additional biochemical and physiological functions. Despite the overall low occurrence of intrinsically disordered proteins or regions in prokaryotic proteomes compared to eukaryotes proteomes, bacterial effectors appear to have adopted intrinsically disordered regions that mimic the disordered regions of eukaryotic signaling proteins. In this review, we explore examples of the diverse biochemical properties found in bacterial effectors that enable effector-mediated interference of eukaryotic signaling pathways and ultimately support pathogenesis. Despite challenges in the structural and functional characterisation of effectors, recent progress has been made in understanding the often unusual and fascinating ways in which these virulence factors promote pathogenesis. Nevertheless, continued work is essential to reveal the array of remarkable activities displayed by effectors.
Schistosoma japonicum Cystatin Alleviates Sepsis Through Activating Regulatory Macrophages
Authors: Xie Hong , Wu Lingqin , Chen Xingzhi , Gao Shifang , Li Huihui , Yuan Yuan , Liang Jinbao , Wang Xiaoli , Wang Shuying , Xu Changyan , Chu Liang , Zhan Bin , Zhou Rui , Yang Xiaodi
Published: February 2021

Multi-organ failure caused by the inflammatory cytokine storm induced by severe infection is the major cause of death for sepsis. Sj-Cys is a cysteine protease inhibitor secreted by Schistosoma japonicum with strong immunomodulatory functions on host immune system. Our previous studies have shown that treatment with Sj-Cys recombinant protein (rSj-Cys) attenuated inflammation caused by sepsis. However, the immunological mechanism underlying the immunomodulation of Sj-Cys for regulating inflammatory diseases is not yet known. In this study, we investigated the effect of Sj-Cys on the macrophage M2 polarization and subsequent therapeutic effect on sepsis. The rSj-Cys was expressed in yeast Pichia pastoris. Incubation of mouse bone marrow-derived macrophages (BMDMs) with yeast-expressed rSj-Cys significantly activated the polarization of macrophages to M2 subtype characterized by the expression of F4/80+ CD206+ with the elated secretion of IL-10 and TGF-β. Adoptive transfer of rSj-Cys treated BMDMs to mice with sepsis induced by cecal ligation and puncture (CLP) significantly improved their survival rates and the systemic clinical manifestations of sepsis compared with mice receiving non-treated normal BMDMs. The therapeutic effect of Sj-Cys-induced M2 macrophages on sepsis was also reflected by the reduced pathological damages in organs of heart, lung, liver and kidney and reduced serological levels of tissue damage-related ALT, AST, BUN and Cr, associated with downregulated pro-inflammatory cytokines (IFN-gamma and IL-6) and upregulated regulatory anti-inflammatory cytokines (IL-10 and TGF-β). Our results demonstrated that Sj-Cys is a strong immunomodulatory protein with anti-inflammatory features through activating M2 macrophage polarization. The findings of this study suggested that Sj-Cys itself or Sj-Cys-induced M2 macrophages could be used as therapeutic agents in the treatment of sepsis or other inflammatory diseases.
MicroRNAomes of Cattle Intestinal Tissues Revealed Possible miRNA Regulated Mechanisms Involved in Escherichia coli O157 Fecal Shedding
Authors: Wang Ou , Zhou Mi , Chen Yanhong , McAllister Tim A. , Plastow Graham , Stanford Kim , Selinger Brent , Guan Le Luo
Published: February 2021

Cattle have been suggested as the primary reservoirs of E. coli O157 mainly as a result of colonization of the recto-anal junction (RAJ) and subsequent shedding into the environment. Although a recent study reported different gene expression at RAJ between super-shedders (SS) and non-shedders (NS), the regulatory mechanisms of altered gene expression is unknown. This study aimed to investigate whether bovine non-coding RNAs play a role in regulating the differentially expressed (DE) genes between SS and NS, thus further influencing E. coli O157 shedding behavior in the animals through studying miRNAomes of the whole gastrointestinal tract including duodenum, proximal jejunum, distal jejunum, cecum, spiral colon, descending colon and rectum. The number of miRNAs detected in each intestinal region ranged from 390 ± 13 (duodenum) to 413 ± 49 (descending colon). Comparison between SS and NS revealed the number of differentially expressed (DE) miRNAs ranged from one (in descending colon) to eight (in distal jejunum), and through the whole gut, seven miRNAs were up-regulated and seven were down-regulated in SS. The distal jejunum and rectum were the regions where the most DE miRNAs were identified (eight and seven, respectively). The miRNAs, bta-miR-378b, bta-miR-2284j, and bta-miR-2284d were down-regulated in both distal jejunum and rectum of SS (log2fold-change: −2.7 to −3.8), bta-miR-2887 was down-regulated in the rectum of SS (log2fold-change: −3.2), and bta-miR-211 and bta-miR-29d-3p were up-regulated in the rectum of SS (log2fold-change: 4.5 and 2.2). Functional analysis of these miRNAs indicated their potential regulatory role in host immune functions, including hematological system development and immune cell trafficking. Our findings suggest that altered expression of miRNA in the gut of SS may lead to differential regulation of immune functions involved in E. coli O157 super-shedding in cattle.
Endothelial Cells in Emerging Viral Infections
Authors: Fosse Johanna Hol , Haraldsen Guttorm , Falk Knut , Edelmann Reidunn
Published: February 2021

There are several reasons to consider the role of endothelial cells in COVID-19 and other emerging viral infections. First, severe cases of COVID-19 show a common breakdown of central vascular functions. Second, SARS-CoV-2 replicates in endothelial cells. Third, prior deterioration of vascular function exacerbates disease, as the most common comorbidities of COVID-19 (obesity, hypertension, and diabetes) are all associated with endothelial dysfunction. Importantly, SARS-CoV-2's ability to infect endothelium is shared by many emerging viruses, including henipaviruses, hantavirus, and highly pathogenic avian influenza virus, all specifically targeting endothelial cells. The ability to infect endothelium appears to support generalised dissemination of infection and facilitate the access to certain tissues. The disturbed vascular function observed in severe COVID-19 is also a prominent feature of many other life-threatening viral diseases, underscoring the need to understand how viruses modulate endothelial function. We here review the role of vascular endothelial cells in emerging viral infections, starting with a summary of endothelial cells as key mediators and regulators of vascular and immune responses in health and infection. Next, we discuss endotheliotropism as a possible virulence factor and detail features that regulate viruses' ability to attach to and enter endothelial cells. We move on to review how endothelial cells detect invading viruses and respond to infection, with particular focus on pathways that may influence vascular function and the host immune system. Finally, we discuss how endothelial cell function can be dysregulated in viral disease, either by viral components or as bystander victims of overshooting or detrimental inflammatory and immune responses. Many aspects of how viruses interact with the endothelium remain poorly understood. Considering the diversity of such mechanisms among different emerging viruses allows us to highlight common features that may be of general validity and point out important challenges.
Association of Trimethylamine N-Oxide Levels and Calcification in Culprit Lesion Segments in Patients With ST-Segment–Elevation Myocardial Infarction Evaluated by Optical Coherence Tomography
Authors: Li Jiannan , Tan Yu , Zhou Peng , Liu Chen , Zhao Hanjun , Song Li , Zhou Jinying , Chen Runzhen , Wang Ying , Zhao Xiaoxiao , Chen Yi , Yan Hongbing
Published: February 2021

The presence of calcified plaques is one of the pathological phenotypes of acute coronary syndrome (ACS) and can be frequently found in culprit lesion segments. Trimethylamine N-oxide (TMAO) is reported to be involved in vascular calcification and plaque instability. This study investigated the relationship between plasma TMAO levels and calcified lesions in culprit lesion segments in STEMI patients. A prospective series of 179 patients with STEMI were enrolled, and calcified lesions from 127 patients were analyzed by OCT. The plasma TMAO levels were measured by using stable isotope dilution liquid chromatography tandem mass spectrometry. Patients were divided into two groups according to the median plasma TMAO level. The prevalence of intimal calcified lesions in the high TMAO group was significantly higher than that in the low TMAO group (90.6 vs. 57.1%, p < 0.001; 84.4 vs. 44.4%, p < 0.001). After adjustment of traditional risk factors and medication history, patients with calcification in their culprit lesion segments had higher plasma TMAO levels than those without calcification. Moreover, plasma TMAO levels were significantly positively associated with the parameters of calcium burden, including maximal calcification arc (r = 0.392, p < 0.001), maximal calcification thickness (r = 0.443, p < 0.001), and calcified length (r = 0.466, p < 0.001). These results suggested that the level of TMAO is significantly correlated with the incidence of calcification in the culprit lesion segment, and the measurement of TMAO levels might improve clinical management in patients with heavy calcification.

Clinical Trial Registration: This study is registered at ClinicalTrials.gov as NCT03593928.
Gray Matter and Regional Brain Activity Abnormalities in Subclinical Hypothyroidism
Authors: Zhang Yang , Yang Yaqiong , Tao Bo , Lv Qingguo , Lui Su , He Li
Published: February 2021

Background

Subclinical hypothyroidism (SCH) brain structure and resting state of functional activity have remained unexplored.

Purpose

To investigate gray matter volume (GMV) and regional brain activity with the fractional amplitude of low-frequency fluctuations (fALFF) in subclinical hypothyroidism (SCH) patients before and after treatment.

Material and Methods

We enrolled 54 SCH and 41 age-, sex-, and education-matched controls. GMV and fALFF of SCH were compared with controls and between pre- and post-treatment within SCH group. Correlations of GMV and fALFF in SCH with thyroid function status and mood scales were assessed by multiple linear regression analysis.

Results

Compared to controls, GMV in SCH was significantly decreased in Orbital part of inferior frontal, superior frontal, pre-/postcentral, inferior occipital, and temporal pole gyrus. FALFF values in SCH were significantly increased in right angular, left middle frontal, and left superior frontal gyrus. After treatment, there were no significant changes in GMV and the local brain function compared to pre-treatment, however the GMV and fALFF of the defective brain areas were improved. Additionally, decreased values of fALFF in left middle frontal gyrus were correlated with increased mood scales.

Conclusion

In this study we found that patients with SCH, the gray matter volume in some brain areas were significantly reduced, and regional brain activity was significantly increased. After treatment, the corresponding structural and functional deficiencies had a tendency for improvement. These changes may reveal the neurological mechanisms of mood disorder in SCH patients.
Review and Survey of Methods for Analysis of Impurities in Hydrogen for Fuel Cell Vehicles According to ISO 14687:2019
Authors: Beurey Claire , Gozlan Bruno , Carré Martine , Bacquart Thomas , Morris Abigail , Moore Niamh , Arrhenius Karine , Meuzelaar Heleen , Persijn Stefan , Rojo Andrés , Murugan Arul
Published: February 2021

Gaseous hydrogen for fuel cell electric vehicles must meet quality standards such as ISO 14687:2019 which contains maximal control thresholds for several impurities which could damage the fuel cells or the infrastructure. A review of analytical techniques for impurities analysis has already been carried out by Murugan et al. in 2014. Similarly, this document intends to review the sampling of hydrogen and the available analytical methods, together with a survey of laboratories performing the analysis of hydrogen about the techniques being used. Most impurities are addressed, however some of them are challenging, especially the halogenated compounds since only some halogenated compounds are covered, not all of them. The analysis of impurities following ISO 14687:2019 remains expensive and complex, enhancing the need for further research in this area. Novel and promising analyzers have been developed which need to be validated according to ISO 21087:2019 requirements.
Gene Set Enrichment Analysis of Interaction Networks Weighted by Node Centrality
Authors: Zito Alessandra , Lualdi Marta , Granata Paola , Cocciadiferro Dario , Novelli Antonio , Alberio Tiziana , Casalone Rosario , Fasano Mauro
Published: February 2021

Gene set enrichment analysis (GSEA) is a powerful tool to associate a disease phenotype to a group of genes/proteins. GSEA attributes a specific weight to each gene/protein in the input list that depends on a metric of choice, which is usually represented by quantitative expression data. However, expression data are not always available. Here, GSEA based on betweenness centrality of a protein–protein interaction (PPI) network is described and applied to two cases, where an expression metric is missing. First, personalized PPI networks were generated from genes displaying alterations (assessed by array comparative genomic hybridization and whole exome sequencing) in four probands bearing a 16p13.11 microdeletion in common and several other point variants. Patients showed disease phenotypes linked to neurodevelopment. All networks were assembled around a cluster of first interactors of altered genes with high betweenness centrality. All four clusters included genes known to be involved in neurodevelopmental disorders with different centrality. Moreover, the GSEA results pointed out to the evidence of “cell cycle” among enriched pathways. Second, a large interaction network obtained by merging proteomics studies on three neurodegenerative disorders was analyzed from the topological point of view. We observed that most central proteins are often linked to Parkinson’s disease. The selection of these proteins improved the specificity of GSEA, with “Metabolism of amino acids and derivatives” and “Cellular response to stress or external stimuli” as top-ranked enriched pathways. In conclusion, betweenness centrality revealed to be a suitable metric for GSEA. Thus, centrality-based GSEA represents an opportunity for precision medicine and network medicine.
Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis
Authors: Wang Xue-quan , Xu Shi-wen , Wang Wei , Piao Song-zhe , Mao Xin-li , Zhou Xian-bin , Wang Yi , Wu Wei-dan , Ye Li-ping , Li Shao-wei
Published: February 2021

Backgrounds:Colorectal cancer (CRC) with high incidence, has the third highest mortality of tumors. DNA damage and repair influence a variety of tumors. However, the role of these genes in colon cancer prognosis has been less systematically investigated. Here, we aim to establish a corresponding prognostic signature providing new therapeutic opportunities for CRC.

Method:After related genes were collected from GSEA, univariate Cox regression was performed to evaluate each gene’s prognostic relevance through the TCGA-COAD dataset. Stepwise COX regression was used to establish a risk prediction model through the training sets randomly separated from the TCGA cohort and validated in the remaining testing sets and two GEO datasets (GSE17538 and GSE38832). A 12-DNA-damage-and-repair-related gene-based signature able to classify COAD patients into high and low-risk groups was developed. The predictive ability of the risk model or nomogram were evaluated by different bioinformatics‐ methods. Gene functional enrichment analysis was performed to analyze the co-expressed genes of the risk-based genes.

Result:A 12-gene based prognostic signature established within 160 significant survival-related genes from DNA damage and repair related gene sets performed well with an AUC of ROC 0.80 for 5 years in the TCGA-CODA dataset. The signature includes CCNB3, ISY1, CDC25C, SMC1B, MC1R, LSP1P4, RIN2, TPM1, ELL3, POLG, CD36, and NEK4. Kaplan-Meier survival curves showed that the prognosis of the risk status owns more significant differences than T, M, N, and stage prognostic parameters. A nomogram was constructed by LASSO regression analysis with T, M, N, age, and risk as prognostic parameters. ROC curve, C-index, Calibration analysis, and Decision Curve Analysis showed the risk module and nomogram performed best in years 1, 3, and 5. KEGG, GO, and GSEA enrichment analyses suggest the risk involved in a variety of important biological processes and well-known cancer-related pathways. These differences may be the key factors affecting the final prognosis.

Conclusion:The established gene signature for CRC prognosis provides a new molecular tool for clinical evaluation of prognosis, individualized diagnosis, and treatment. Therapies based on targeted DNA damage and repair mechanisms may formulate more sensitive and potential chemotherapy regimens, thereby expanding treatment options and potentially improving the clinical outcome of CRC patients.
Children's Vulnerability to Sexual Violence During COVID-19 in Kenya: Recommendations for the Future
Authors: Stevens Laura M. , Rockey James C. , Rockowitz Sarah R. , Kanja Wangu , Colloff Melissa F. , Flowe Heather D.
Published: February 2021

This article discusses the latest research that reveals that children seem to be facing new risks of sexual violence in Kenya during the COVID-19 pandemic. The evidence suggests there have been changes in patterns of sexual offenses against children coincident with lockdowns, curfews, and school closures. In particular, emerging evidence from Kenya suggests that child victims are younger, more likely to be victimized by a neighbor in a private residence, and in the daytime, compared to pre-pandemic. We conclude that situational crime prevention strategies that focus on providing alternative safe venues to reduce offending opportunities must be a central part of a public health approach to reduce children's vulnerability during crises such as COVID-19.
A Novel Method for Polyacrylamide Gel Preparation Using N-hydroxysuccinimide-acrylamide Ester to Study Cell-Extracellular Matrix Mechanical Interactions
Authors: Kumai Jun , Sasagawa Satoru , Horie Masanobu , Yui Yoshihiro
Published: February 2021

Mechanical stimulation by the extracellular matrix (ECM) controls physiological and pathological cellular responses, such as stem cell differentiation, organogenesis, and tumor progression. Polyacrylamide (PA) gels have been widely used to study cell-ECM mechanical interactions. Typically, sulfosuccinimidyl 6-(4′-azido-2′-nitrophenylamino)hexanoate (sulfo-SANPAH) is used as a protein crosslinker in these gels. However, its low solubility, unstable binding with proteins, and high cost are barriers to its application. The objective of this study was to improve and simplify the preparation of PA gels using an economical crosslinker, N-hydroxysuccinimide-acrylamide (NHS-AA) ester, to enable increased stability in protein coating. By exposing excess NHS to the gel surface, we found an optimal ratio of NHS-AA ester:AA to obtain NHS-AA ester-containing PA gels with a uniform ECM protein coating and stiffness similar to that of sulfo-SANPAH-containing PA gels. The biological behavior of MCF7 and MCF10A cells were similar on NHS-AA ester and sulfo-SANPAH gels. Acini formation in Matrigel overlay culture were also consistent on NHS-AA ester and sulfo-SANPAH gels. This novel PA gel preparation method using NHS-AA ester can effectively replace the sulfo-SANPAH method and will be immensely useful in the evaluation of cell-ECM mechanical interactions.
Case Report: Proven Diagnosis of Culture-Negative Chronic Disseminated Candidiasis in a Patient Suffering From Hematological Malignancy: Combined Application of mNGS and CFW Staining
Authors: Jin Yanqi , Wang Zhouhan , Zhu Chunxia , Yang Qing , Lu Yingfeng , Yu Xiaopeng , Hong Bao , Wang Xiaojing , Zhang Yimin
Published: February 2021

Chronic disseminated candidiasis (CDC) is a severe complication with high morbidity and mortality in patients with hematological malignancies who have undergone chemotherapy. Blood or sterile liver biopsy cultures are negative due to recurrent empirical antifungal therapy. With the escalating resistance to azole-based antifungal drugs in infection by Candida species, pathogen identification is becoming increasingly important for determining definitive diagnosis and treatment strategy. In this case report, we present, for the first time, diagnostic confirmation of a culture-negative CDC case with Candida tropicalis infection using a combination of metagenomics next-generation sequencing and calcofluor white staining.
Eosinophilic Granulomatosis With Polyangiitis: Dissecting the Pathophysiology
Authors: Fagni Filippo , Bello Federica , Emmi Giacomo
Published: February 2021

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystemic disease classified both amongst hypereosinophilic disorders and ANCA-associated vasculitis. Vessel inflammation and eosinophilic proliferation are the hallmarks of the disease and main effectors of organ damage. Two distinct disease phenotypes have classically been described according to ANCA-status: the ANCA-negative subset with eosinophil-driven manifestation and the ANCA-positive one with vasculitic manifestations. An analogous dichotomization has also been backed by histological findings and a distinct genetic background. EGPA is typically consider a Th2-mediated disease and blood and tissue eosinophilia represent the cornerstone of diagnosis. Besides, ANCA are known for inducing endothelial injury and vascular inflammation by activating the circulating neutrophils. Thus, the pathogenesis of EGPA seems to be mediated by two coexisting mechanisms. However, the verbatim application of this strict dualism cannot always be translated into routine clinical practice. In the present review we describe the current knowledge on the eosinophilic and ANCA-mediated aspects of EGPA pathogenesis. Finally, we review the rationale of the currently proposed EGPA dichotomy and future research perspectives.
Systemic Management of Pandemic Risks in Dental Practice: A Consolidated Framework for COVID-19 Control in Dentistry
Authors: Benzian Habib , Beltrán-Aguilar Eugenio , Niederman Richard
Published: February 2021

Dental teams and their workplaces are among the most exposed to airborne and bloodborne infectious agents, and therefore at the forefront of pandemic-related changes to how dental care is organized and provided to patients. The increasing complexity of guidelines makes is challenging for clinicians to navigate the multitude of COVID-19 guidelines issued by different agencies. A comparative analysis of guidance issued for managing COVID-19 in dental settings leading U.S. agencies was conducted, including documents of the Occupational Safety and Health Administration (OSHA), an agency of the U.S. Secretary of Labor, and of the U.S. Centers for Disease Prevention and Control (CDC), an agency of the U.S. Secretary of Health and Human Services. Details of infection control and other risk mitigation measures were reviewed for consistency, overlaps and similarities, then clustered according to thematic areas covering all domains of managing a dental healthcare setting. The analysis revealed five distinct areas of pandemic control, comprising (1) planning and protocols, (2) patient screening, (3) preparation of facilities, (4) PPE and infection control, and (5) procedures and aerosol control; thereby covering systematically all aspects requiring adaptation in a pandemic context. The “Pandemic-5 Framework for COVID-19 Control in Dentistry” provides an opportunity to simplify comprehensive decision-making from a clinical practitioner perspective. The framework supports a comprehensive systems-driven approach by using dental clinics as a setting to integrate pandemic clinical responses with the implementation of appropriate infection control protocols. Traditionally these two aspects are addressed independently from each other in separate concepts.
Extracellular Vesicle-Associated miRNAs as a Biomarker for Lung Cancer in Liquid Biopsy
Authors: He Xue , Park Sujeong , Chen Yan , Lee Heedoo
Published: February 2021

Extracellular vesicles are cell-derived membranous vesicles that are secreted into biofluids. Emerging evidence suggests that EVs play an essential role in the pathogenesis of many diseases by transferring proteins, genetic material, and small signaling molecules between cells. Among these molecules, microRNAs (miRNAs), a type of small noncoding RNA, are one of the most important signals and are involved in various biological processes. Lung cancer is one of the leading causes of cancer-related deaths worldwide. Early diagnosis of lung cancer may help to reduce mortality and increase the 5 years survival rate and thereby reduce the associated socioeconomic burden. In the past, EV-miRNAs have been recognized as biomarkers of several cancers to assist in diagnosis or prognosis. In this review, we discuss recent findings and clinical practice for EV-miRNAs of lung cancer in several biofluids, including blood, bronchoalveolar lavage fluid (BALF), and pleural lavage.
Failure of Glial Cell-Line Derived Neurotrophic Factor (GDNF) in Clinical Trials Orchestrated By Reduced NR4A2 (NURR1) Transcription Factor in Parkinson’s Disease. A Systematic Review
Authors: Kambey Piniel Alphayo , Kanwore Kouminin , Ayanlaja Abiola Abdulrahman , Nadeem Iqra , Du YinZhen , Buberwa Wokuheleza , Liu WenYa , Gao Dianshuai
Published: February 2021

Parkinson’s disease (PD) is one of the most common neurodegenerative maladies with unforeseen complex pathologies. While this neurodegenerative disorder’s neuropathology is reasonably well known, its etiology remains a mystery, making it challenging to aim therapy. Glial cell-line derived neurotrophic factor (GDNF) remains an auspicious therapeutic molecule for treating PD. Neurotrophic factor derived from glial cell lines is effective in rodents and nonhuman primates, but clinical findings have been equivocal. Laborious exertions have been made over the past few decades to improve and assess GDNF in treating PD (clinical studies). Definitive clinical trials have, however, failed to demonstrate a survival advantage. Consequently, there seemed to be a doubt as to whether GDNF has merit in the potential treatment of PD. The purpose of this cutting edge review is to speculate as to why the clinical trials have failed to meet the primary endpoint. We introduce a hypothesis, “Failure of GDNF in clinical trials succumbed by nuclear receptor-related factor 1 (Nurr1) shortfall.” We demonstrate how Nurr1 binds to GDNF to induce dopaminergic neuron synthesis. Due to its undisputable neuro-protection aptitude, we display Nurr1 (also called Nr4a2) as a promising therapeutic target for PD.
The Paraventricular Nucleus of the Thalamus as an Integrating and Relay Node in the Brain Anxiety Network
Authors: Kirouac Gilbert J.
Published: February 2021

The brain anxiety network is composed of a number of interconnected cortical regions that detect threats and execute appropriate defensive responses via projections to the shell of the nucleus accumbens (NAcSh), dorsolateral region of the bed nucleus of the stria terminalis (BSTDL) and lateral region of the central nucleus of the amygdala (CeL). The paraventricular nucleus of the thalamus (PVT) is anatomically positioned to integrate threat- and arousal-related signals from cortex and hypothalamus and then relay these signals to neural circuits in the NAcSh, BSTDL, and CeL that mediate defensive responses. This review describes the anatomical connections of the PVT that support the view that the PVT may be a critical node in the brain anxiety network. Experimental findings are reviewed showing that the arousal peptides orexins (hypocretins) act at the PVT to promote avoidance of potential threats especially following exposure of rats to a single episode of footshocks. Recent anatomical and experimental findings are discussed which show that neurons in the PVT provide divergent projections to subcortical regions that mediate defensive behaviors and that the projection to the NAcSh is critical for the enhanced social avoidance displayed in rats exposed to footshocks. A theoretical model is proposed for how the PVT integrates cortical and hypothalamic signals to modulate the behavioral responses associated with anxiety and other challenging situations.
Activation of Basolateral Amygdala to Nucleus Accumbens Projection Neurons Attenuates Chronic Corticosterone-Induced Behavioral Deficits in Male Mice
Authors: Dieterich Andrew , Floeder Joseph , Stech Karina , Lee Jay , Srivastava Prachi , Barker David J. , Samuels Benjamin A.
Published: February 2021

The basolateral amygdala (BLA) is critical for reward behaviors via a projection to the nucleus accumbens (NAc). Specifically, BLA-NAc projections are involved in reinforcement learning, reward-seeking, sustained instrumental responding, and risk behaviors. However, it remains unclear whether chronic stress interacts with BLA-NAc projection neurons to result in maladaptive behaviors. Here we take a chemogenetic, projection-specific approach to clarify how NAc-projecting BLA neurons affect avoidance, reward, and feeding behaviors in male mice. Then, we examine whether chemogenetic activation of NAc-projecting BLA neurons attenuates the maladaptive effects of chronic corticosterone (CORT) administration on these behaviors. CORT mimics the behavioral and neural effects of chronic stress exposure. We found a nuanced role of BLA-NAc neurons in mediating reward behaviors. Surprisingly, activation of BLA-NAc projections rescues CORT-induced deficits in the novelty suppressed feeding, a behavior typically associated with avoidance. Activation of BLA-NAc neurons also increases instrumental reward-seeking without affecting free-feeding in chronic CORT mice. Taken together, these data suggest that NAc-projecting BLA neurons are involved in chronic CORT-induced maladaptive reward and motivation behaviors.
Real Time Generation of Three Dimensional Patterns for Multiphoton Stimulation
Authors: Pozzi Paolo , Mapelli Jonathan
Published: February 2021

The advent of optogenetics has revolutionized experimental research in the field of Neuroscience and the possibility to selectively stimulate neurons in 3D volumes has opened new routes in the understanding of brain dynamics and functions. The combination of multiphoton excitation and optogenetic methods allows to identify and excite specific neuronal targets by means of the generation of cloud of excitation points. The most widely employed approach to produce the points cloud is through a spatial light modulation (SLM) which works with a refresh rate of tens of Hz. However, the computational time requested to calculate 3D patterns ranges between a few seconds and a few minutes, strongly limiting the overall performance of the system. The maximum speed of SLM can in fact be employed either with high quality patterns embedded into pre-calculated sequences or with low quality patterns for real time update. Here, we propose the implementation of a recently developed compressed sensing Gerchberg-Saxton algorithm on a consumer graphical processor unit allowing the generation of high quality patterns at video rate. This, would in turn dramatically reduce dead times in the experimental sessions, and could enable applications previously impossible, such as the control of neuronal network activity driven by the feedback from single neurons functional signals detected through calcium or voltage imaging or the real time compensation of motion artifacts.
Changes in Patients’ Desired Control of Their Deep Brain Stimulation and Subjective Global Control Over the Course of Deep Brain Stimulation
Authors: Merner Amanda R. , Frazier Thomas , Ford Paul J. , Cooper Scott E. , Machado Andre , Lapin Brittany , Vitek Jerrold , Kubu Cynthia S.
Published: February 2021

Objective: To examine changes in patients’ desired control of the deep brain stimulator (DBS) and perception of global life control throughout DBS.

Methods: A consecutive cohort of 52 patients with Parkinson’s disease (PD) was recruited to participate in a prospective longitudinal study over three assessment points (pre-surgery, post-surgery months 3 and 6). Semi-structured interviews assessing participants’ desire for stimulation control and perception of global control were conducted at all three points. Qualitative data were coded using content analysis. Visual analog scales were embedded in the interviews to quantify participants’ perceptions of control over time.

Results: Participants reported significant increases in their perception of global control over time and significant declines in their desired control of the stimulation. These changes were unrelated to improvements in motor symptoms. Improvements in global control were negatively correlated with a decline in desired stimulation control. Qualitative data indicate that participants have changed, nuanced levels of desired control over their stimulators. Increased global life control following DBS may be attributed to increased control over PD symptoms, increased ability to engage in valued activities, and increased overall self-regulation, while other domains related to global control remained unaffected by DBS.

Conclusions: There are few empirical data documenting patients’ desire for stimulation control throughout neuromodulation and how stimulation control is related to other aspects of control despite the growing application of neuromodulation devices to treat a variety of disorders. Our data highlight distinctions in different types of control and have implications for the development of patient-controlled neurostimulation devices.
(Dys)regulation of Synaptic Activity and Neurotransmitter Release by β-Amyloid: A Look Beyond Alzheimer's Disease Pathogenesis
Authors: Fagiani Francesca , Lanni Cristina , Racchi Marco , Govoni Stefano
Published: February 2021

Beside its widely studied role in the pathogenesis of Alzheimer's disease (AD), β-amyloid (Aβ) is a normal and soluble product of neuronal metabolism that regulates several key physiological functions, exerting neuromodulatory effects on synaptic plasticity, memory, and neurotransmitter release. Such effects have been observed to occur in a hormetic fashion, with Aβ exhibiting a dual role influenced by its concentration, the different isoforms, or aggregation forms of the peptide. However, to date, our knowledge about the physiological functions of Aβ and, in particular, its modulatory role on synaptic activity and neurotransmission in the normal brain is fragmentary, thus hindering a clear comprehension of the biological mechanisms underlying the derangement from function to dysfunction. In particular, according to the amyloid cascade hypothesis, the switch from physiology to pathology is linked to the abnormal increase in Aβ levels, due to an imbalance in Aβ production and clearance. In this regard, increased Aβ levels have been hypothesized to induce early defects in synaptic function and such alterations have been suggested to account, at least in part, for the onset of neuropsychiatric symptoms (e.g., apathy, anxiety, changes in mood, depression, and agitation/aggression), frequently observed in the prodromal stage of AD. Therefore, understanding the biological mechanisms underlying early synaptic alterations in AD is a key starting point to frame the relevant time windows for AD treatment and to gain insight into AD etiopathogenesis.