bluuebunny/crossref_metadata_2025 huggingface dataset:
Perancangan Sistem Informasi Geografis Pemetaan Daerah Bencana Longsor di Kabupaten Garut
Authors:   Sekolah Tinggi Teknologi Garut, Supriatna Asep Deddy , Zulfikar Raihan Sahab
Published: May 2021

Bencana longsor merupakan air yang meresap ke dalam tanah maka akan menambah bobot tanah, jika air tersebut sampai pada tanah kedap air maka tanah menjadi licin dan tanah akan bergerak keluar lereng. Permasalahan pada tingginya kerugian yang dialami masyarakat yang mengakibatkan kehilangan tempat tinggal, bahkan korban jiwa dikarenakan terjadinya longdor disebabkan karena kurangnya informasi yang didapatkan masyarakat akan kemungkinan longsor yang akan terjadi disekitarnya, sehingga kesadaran masyarakat akan tanggap bencana menjadi sangat minim. Pada tujuan penelitian ini menginformasikan mengenai risiko rawan daerah longsor untuk menjadi media informasi yang dapat digunakan sebagai pengetahuan dasar akan bencana longsor bagi masyarakat. Melalui Sistem Informasi Geografis (SIG) diharapkan akan mempermudah penyajian informasi spasial khususnya yang terkait dengan penentuan tingkat bahaya tanah longsor serta dapat menganalisis dan memperoleh informasi baru dalam mengidentifikasi daerah-daerah yang menjadi sasaran tanah longsor. Manfaat dibuatnya aplikasi ini untuk mewujudkan efisiensi dalam proses mengetahui informasi daerah rawan bencana longsor beserta kejadian pertahun, korban jiwa, dan kerusakan, sebelumnya masyarakat harus datang ke kantor BPBD untuk mengetahui informasi daerah rawan bencana longsor, tetapi dengan menggunakan aplikasi ini masyarakat bisa mengetahui informasi daerah rawan bencana longsor secara online. Metodologi yang digunakan untuk merancang aplikasi adalah Rational Unified Process (RUP). Hasil dari penelitian ini di buatlah aplikasi yang berjudul “Perancangan Sistem Informasi Geografis Pemetaan Daerah Bencana Longsor Di Kabupaten Garut”. Berdasarkan hasil dan pembahasan diperoleh struktur menu dan interface yang menggambarkan proses bisnis yang sesungguhnya. Kesimpulan dari penelitian ini adalah perancangan aplikasi ini dapat mengatasi permasalahan yang terjadi karena kurangnya informasi yang didapatkan oleh masyarakat dan meng efisiensi dalam penyajian informasi daerah rawan longsor bagi pemerintahan.
Pengenalan Komponen Komputer Menggunakan Teknologi Augmented Reality
Authors:   Sekolah Tinggi Teknologi Garut, Tresnawati Dewi , Albani Irgi Muhamad
Published: May 2021

Pembelajaran di sekolah mengenai komponen komputer sering kali melalui media ajar buku atau praktik, sehingga terkadang menimbulkan efek bosan terhadap siswa. Pembelajaran membutuhkan suatu inovasi, oleh karena itu diperlukan media yang dapat mengoptimalkan pembelajaran siswa agar memberikan nuansa baru terhadap pembelajaran salah satunya menggunakan teknologi augmented reality. AR merupakan sebuah terobosan dan inovasi bidang multimedia dan image processing yang sedang berkembang. Teknologi ini mampu mengangkat sebuah benda yang sebelumnya datar atau dua dimensi, seolah-olah menjadi nyata dan bersatu dengan lingkungan sekitar. Sehingga dapat diterapkan dalam pembelajaran karena memberikan pengalaman visual yang menarik dan menyenangkan. Penelitian ini bertujuan untuk membuat aplikasi pembelajaran pengenalan komponen komputer menggunakan teknologi augmented reality yang diharapkan dapat membantu guru dalam penyampaian materi pembelajaran sehingga materi mampu tersampaikan terhadap siswa. Pada penelitian ini menggunakan metodologi Research and Development, pengujian aplikasi menggunakan pengujian Alpha. Hasil penelitian ini berupa aplikasi media pembelajaran pengenalan komponen komputer menggunakan teknologi augmented reality yang menarik dan menambah nuansa baru dalam proses belajar mengajar.
Rancang Bangun Aplikasi Game Teka Teki Silang Peribahasa Bahasa Sunda
Authors:   Sekolah Tinggi Teknologi Garut, Tresnawati Dewi , Wardi Dindin Sihabudin Ahmad
Published: May 2021

Dewasa ini kebanyakan anak muda masyarakat Sunda kurang mengenal peribahasa dalam bahasa sunda sendiri yang menjadi kekayaan dari adat dan tradisi, dikarenakan kurangnya minat dalam mempelajari peribahasa dan sulitnya penafsiran membuat peribahasa kian ditinggalkan khususnya oleh kalangan muda. Game merupakan salah satu media yang sangat diminati oleh kalangan anak muda pada saat ini. Selain sebagai media hiburan, game juga dinilai memiliki dampak pada lingkungan beajar yaitu penemuan strategi belajar, kemampuan pemecahan masalah dan kemampuan intelektual, visual serta motorik. Digital Game Based Learning- Instructional Design merupakan metode yang cocok untuk digunakan dalam pembuatan Video dan Game karena karakteristik video dan game harus memberikan suatu pengalaman yang baru bagi penggunanya. Hasil dari penelitian ini yaitu suatu aplikasi untuk menanggulangi kesenjangan pengetahuan tentang paribasa di kalangan masyarakat serta melestarikan budaya lokal khas sunda yang kian hari kian terkikis di kalangan masyarakat sunda sendiri, serta dengan adanya game edukasi ini dapat memberikan pelatihan mengenai daya ingat, daya pikir serta konsentrasi dari pengguna.
Pengaruh Kegiatan Menstempel Dengan Spons Terhadap Kreativitas Pencampuran Warna
Authors: Rahmadani Sani , Pransiska Rismareni , Wirman Asdi
Published: May 2021

Kegiatan ekstrakurikuler merupakan penunjang dari kegiatan akademik di lembaga PAUD. Hal ini perlu diterapkan diseluruh lembaga ini. Oleh karena itu penelitian ini bertujuan untuk mengetahui pelaksanaan kegiatan ekstrakurikuler tari tradisional di Taman Kanak-kanak Sani Ashila Padang dalam rangka mengetahui penerapannya. Metode penelitian yang digunakan adalah deskriptif dengan pendekatan kualitatif. Hasil penelitian menunjukkan bahwa kegiatan ekstrakurikuler tari tradisional di TK Sani Ashila Padang belum sesuai dengan tahap-tahap pengenalan tari kepada anak. Namun dengan latihan yang rutin dapat mengantarkan TK Sani Ashila Menjuarai beberapa Lomba Tari. Melalui kegiatan ini juga sebagai wahana untuk memperkenalkan kebudayaan pada anak dan juga untuk membantu perkembangan motoriknya. Kendala yang sering terjadi adalah suasana hati anak yang berubah drastis, sehingga guru harus membujuk anak agar bersemangat kembali. Tempat latihan yang digunakan berukuran 4x4 m tidak sebanding dengan jumlah anak yang mengikuti kegiatan. Dari penelitian ini disimpulkan bahwa pelaksanaan kegiatan ekstrakurikuler tari tradisional di Taman Kanak-kanak Sani Ashila Padang belum berjalan dengan baik.
Pensando la inmigración desde las instituciones de la ciudad
Authors: Tshitshi Ndouba Kayamba
Published: May 2021

This paper conducts a bibliographic review of the main theoretical formulations that make migration processes dialogue with urban dynamics. From this, two records of academic literature arise. The first one, from a sociological approach, problematizes not only the modalities of gradual integration of immigrants into urban space but also the challenges resulting from the forms of occupation and transformation of the social, economic, cultural, and symbolic spaces of the city. The second one has a political science approach that explores the new analytical perspectives that reconstruct and reformulates the problems of the urban management of immigration, examining the different scenarios and factors that influence and shape the governance of immigration and cultural diversity in cities. These two approaches are significantly useful and have undeniable heuristic value to construct a modern immigration theory in the urban context.
Self-DNA Sensing by cGAS-STING and TLR9 in Autoimmunity: Is the Cytoskeleton in Control?
Authors: Amadio Roberto , Piperno Giulia Maria , Benvenuti Federica
Published: May 2021

Modified or misplaced DNA can be recognized as a danger signal by mammalian cells. Activation of cellular responses to DNA has evolved as a defense mechanism to microbial infections, cellular stress, and tissue damage, yet failure to control this mechanism can lead to autoimmune diseases. Several monogenic and multifactorial autoimmune diseases have been associated with type-I interferons and interferon-stimulated genes (ISGs) induced by deregulated recognition of self-DNA. Hence, understanding how cellular mechanism controls the pathogenic responses to self-nucleic acid has important clinical implications. Fine-tuned membrane trafficking and cellular compartmentalization are two major factors that balance activation of DNA sensors and availability of self-DNA ligands. Intracellular transport and organelle architecture are in turn regulated by cytoskeletal dynamics, yet the precise impact of actin remodeling on DNA sensing remains elusive. This review proposes a critical analysis of the established and hypothetical connections between self-DNA recognition and actin dynamics. As a paradigm of this concept, we discuss recent evidence of deregulated self-DNA sensing in the prototypical actin-related primary immune deficiency (Wiskott-Aldrich syndrome). We anticipate a broader impact of actin-dependent processes on tolerance to self-DNA in autoimmune disorders.
SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1
Authors: Sui Liyan , Zhao Yinghua , Wang Wenfang , Wu Ping , Wang Zedong , Yu Yang , Hou Zhijun , Tan Guangyun , Liu Quan
Published: May 2021

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of current COVID-19 pandemic, and insufficient production of type I interferon (IFN-I) is associated with the severe forms of the disease. Membrane (M) protein of SARS-CoV-2 has been reported to suppress host IFN-I production, but the underlying mechanism is not completely understood. In this study, SARS-CoV-2 M protein was confirmed to suppress the expression of IFNβ and interferon-stimulated genes induced by RIG-I, MDA5, IKKϵ, and TBK1, and to inhibit IRF3 phosphorylation and dimerization caused by TBK1. SARS-CoV-2 M could interact with MDA5, TRAF3, IKKϵ, and TBK1, and induce TBK1 degradation via K48-linked ubiquitination. The reduced TBK1 further impaired the formation of TRAF3–TANK–TBK1-IKKε complex that leads to inhibition of IFN-I production. Our study revealed a novel mechanism of SARS-CoV-2 M for negative regulation of IFN-I production, which would provide deeper insight into the innate immunosuppression and pathogenicity of SARS-CoV-2.
Decidual NR2F2-Expressing CD4+ T Cells Promote TH2 Transcriptional Program During Early Pregnancy
Authors: Lin Yikong , Zhang Di , Li Yangyang , Li Yunyun , Li Bin , Du Meirong
Published: May 2021

A unique immunotolerant microenvironment with Th2 bias in the decidua provides an essential security for successful pregnancy. The disorganized maternal-fetal immune tolerance contributes to more than 50% of unexplained recurrent spontaneous abortion (RSA). How the Th2 bias is developed at the maternal-fetal interface remains undefined. NR2F2, a member of steroid/thyroid nuclear receptor superfamily, is endowed with diverse importance in cell-fate specification, organogenesis, angiogenesis, and metabolism. Here, we showed that NR2F2 was absolutely highly expressed in decidual CD4+T(dCD4+T) cells, but not in peripheral circulating CD4+T cells during early pregnancy. Decidual NR2F2-expressing CD4+T cells dominantly produced Th2 cytokines. In unexplained RSA patients, NR2F2 expression in dCD4+T cells was significantly decreased, accompanied with disordered phenotype of dCD4+T cells. Furthermore, overexpression of NR2F2 promoted the Th2 differentiation of naive CD4+T cells. Immunoprecipitation experiment confirmed the binding relationship between GATA-3 and NR2F2, which implied GATA-3 may be an important interactive element involved in the immunoregulatory process of NR2F2. This study is the first to reveal a previously unappreciated role for NR2F2-mediated dCD4+T cells in maternal-fetal immune tolerance and maintenance of normal pregnancy, in the hope of providing a potential biomarker for prediction and prevention of clinical unexplained RSA.
Enhanced mPGES-1 Contributes to PD-Related Peritoneal Fibrosis via Activation of the NLRP3 Inflammasome
Authors: Luo Qimei , Hu Qinghua , Zheng Qingkun , Gong Lewei , Su Lijuan , Ren Baojun , Ju Yongle , Jia Zhanjun , Dou Xianrui
Published: May 2021

Background: Microsomal prostaglandin E synthase-1 (mPGES-1)-derived prostaglandin E2 (PGE2) is a chief mediator of inflammation. However, the role and mechanism of mPGES-1 in peritoneal dialysis (PD)-associated peritoneal fibrosis have not been investigated.

Material and Methods: In PD patients, mPGES-1 expression in peritoneum tissues and the levels of PGE2, IL-1β, and IL-18 in the dialysate were examined. In rat peritoneal mesothelial cells (RPMCs), the regulation and function of mPGES-1 and NLRP3 inflammasome were investigated. The expression of extracellular matrix proteins and the components of NLRP3 inflammasome were detected by Western blotting or real-time quantitative PCR.

Results: In PD patients with ultrafiltration failure (UFF), mPGES-1 was enhanced in the peritoneum, which was associated with the degree of peritoneal fibrosis. Accordingly, the intraperitoneal PGE2 levels were also positively related to the PD duration, serum C-reactive protein levels, and serum creatinine levels in incident PD patients. In RPMCs, high-glucose treatment significantly induced mPGES-1 expression and PGE2 secretion without affecting the expressions of mPGES-2 and cPGES. Inhibition of mPGES-1 via short hairpin RNA significantly ameliorated the expression of extracellular matrix proteins of RPMCs induced by high glucose. Additionally, high glucose markedly activated NLRP3 inflammasome in RPMCs that was blunted by mPGES-1 inhibition. Furthermore, silencing NLRP3 with siRNA significantly abrogated the expression of extracellular matrix proteins in RPMCs treated with high glucose. Finally, we observed increased IL-1β and IL-18 levels in the dialysate of incident PD patients, showing a positive correlation with PGE2.

Conclusion: These data demonstrate that mPGES-1-derived PGE2 plays a critical role in PD-associated peritoneal fibrosis through activation of the NLRP3 inflammasome. Targeting mPGES-1 may offer a novel strategy to treat peritoneal fibrosis during PD.
Probiotics Bacillus licheniformis Improves Intestinal Health of Subclinical Necrotic Enteritis-Challenged Broilers
Authors: Kan Liugang , Guo Fangshen , Liu Yan , Pham Van Hieu , Guo Yuming , Wang Zhong
Published: May 2021

Necrotic enteritis infection poses a serious threat to poultry production, and there is an urgent need for searching effective antibiotic alternatives to control it with the global ban on in-feed antibiotics. This study was conducted to investigate the effects of dietary Bacillus licheniformis replacing enramycin on the growth performance and intestinal health of subclinical necrotic enteritis (SNE)-challenged broilers. In total, 504 1-day-old Arbor Acres male chickens were selected and subsequently assigned into three treatments, including PC (basal diet + SNE challenge), PA (basal diet extra 10 mg/kg enramycin + SNE challenge), and PG (basal diet extra 3.20 × 109 and 1.60 × 109 CFU B. licheniformis per kg diet during 1–21 days and 22–42 days, respectively + SNE challenge). Results showed that B. licheniformis significantly decreased the intestinal lesion scores and down-regulated the Claudin-3 mRNA levels in jejunum of SNE-infected broilers on day 25, but increased the mucin-2 gene expression in broilers on day 42. In addition, B. licheniformis significantly up-regulated the mRNA levels of TRIF and NF-κB of SNE-challenged broilers compared with the control group on day 25 and TLR-4, TRIF compared with the control and the antibiotic group on day 42. The mRNA expression of growth factors (GLP-2 and TGF-β2) and HSPs (HSP60, HSP70, and HSP90) were up-regulated in B. licheniformis supplementary group on days 25 and 42 compared with group PC. LEfSe analysis showed that the relative abundance of Lachnospiraceae_UCG_010 was enriched in the PG group; nevertheless, Clostridiales_vadinBB60 and Rnminococcaceae_NK4A214 were in PA. PICRUSt analysis found that the metabolism of cofactors and vitamins, amino acid metabolism, and carbohydrate metabolism pathways were enriched, whereas energy metabolism, membrane transport, cell motility, and lipid metabolism were suppressed in B. licheniformis-supplemented groups as compared with the PC control. In conclusion, dietary supplementation of B. licheniformis alleviated the intestinal damage caused by SNE challenge that coincided with modulating intestinal microflora structure and barrier function as well as regulating intestinal mucosal immune responses.
Salt-Tolerant Synechococcus elongatus UTEX 2973 Obtained via Engineering of Heterologous Synthesis of Compatible Solute Glucosylglycerol
Authors: Cui Jinyu , Sun Tao , Chen Lei , Zhang Weiwen
Published: May 2021

The recently isolated cyanobacteriumSynechococcus elongatusUTEX 2973 (Syn2973) is characterized by a faster growth rate and greater tolerance to high temperature and high light, making it a good candidate chassis for autotrophic photosynthetic microbial cell factories. However, Syn2973 is sensitive to salt stress, making it urgently important to improve the salt tolerance of Syn2973 for future biotechnological applications. Glucosylglycerol, a compatible solute, plays an important role in resisting salt stress in moderate and marine halotolerant cyanobacteria. In this study, the salt tolerance of Syn2973 was successfully improved by introducing the glucosylglycerol (GG) biosynthetic pathway (OD750improved by 24% at 60 h). In addition, the salt tolerance of Syn2973 was further enhanced by overexpressing the rate-limiting step of glycerol-3-phosphate dehydrogenase and downregulating the generfbA, which encodes UDP glucose pyrophosphorylase. Taken together, these results indicate that the growth of the end-point strain M-2522-GgpPS-drfbA was improved by 62% compared with the control strain M-pSI-pSII at 60 h under treatment with 0.5 M NaCl. Finally, a comparative metabolomic analysis between strains M-pSI-pSII and M-2522-GgpPS-drfbA was performed to characterize the carbon flux in the engineered M-2522-GgpPS-drfbA strain, and the results showed that more carbon flux was redirected from ADP-GLC to GG synthesis. This study provides important engineering strategies to improve salt tolerance and GG production in Syn2973 in the future.
Multiple Omics Integration Reveals Key Circular RNAs in Hepatocellular Carcinoma
Authors: Huang Zi-Li , Huang Xiu-Yan , Huang Jin , Huang Xin-Yu , Xu Yong-Hua , Zhou Jian , Tang Zhao-You
Published: May 2021

Background

HCC is one of the most common malignancies with an increasing incidence worldwide, especially in Asian countries. However, even though targeted cancer therapy drugs such as sorafenib and regorafenib are available, the overall outcome of HCC remains unsatisfactory. Thus, it is urgent to investigate the molecular mechanisms of HCC progression, so as to provide accurate diagnostic criteria and therapeutic targets.

Methods

RNA-seq data was used to identify and quantify circular RNAs (circRNAs). DESeq2 was used to identify the differentially expressed circRNAs. miRNA binding sites within circRNAs were identified by miRanda. Gene set enrichment analysis (GSEA) was conducted to predict the biological function of circRNAs.

Results

The differential expression analysis identified 107 upregulated and 95 downregulated circRNAs in HCC tissues. We observed that a differentially expressed circRNA (DE-circRNA), hsa_circ_0141900 was highly negatively correlated with its parental gene RAB1A (PCC < -0.6), which was also closely associated with mTOR signaling pathway. Moreover, we also constructed competing endogenous RNA (ceRNA) network to identify key circRNAs involved in HCC. Notably, hsa_circ_0002130 and hsa_circ_0008774 were highly correlated with the genes involved in gluconeogenesis and HNF3A pathway via the target genes, GOT2 and AR, suggesting that the two circRNAs might regulate these pathways, respectively. Survival analysis revealed that GOT2 was associated with favorable prognosis. Furthermore, high expression of hsa_circ_0002130 was found to inhibit tumor cell growth and promotes GOT2 expression.

Conclusion

In summary, the circRNAs highlighted by the integrative analysis greatly improved our understanding of the underlying mechanism of circRNAs in HCC.
Prognostic Significance of SUVmax Combined With Lactate Dehydrogenase in Advanced Lung Cancer Patients Treated With Immune Checkpoint Inhibitor Plus Chemotherapy: A Retrospective Study
Authors: Ke Linping , Wang Lu , Yu Jinming , Meng Xue
Published: May 2021

Purpose

This research aims to investigate the predictive capacity of PET/CT quantitative parameters combined with haematological parameters in advanced lung cancer patients treated with immune checkpoint inhibitor (ICI) plus chemotherapy.

Methods

A total of 120 patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were enrolled before therapy. The following parameters were calculated: the maximum, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); total tumour volume (MTV) and total lesion glycolysis (TLG); and whole-body metabolic values (MTVwb, TLGwb, SUVmeanwb, and SUVmaxwb). Lactate dehydrogenase (LDH) levels, absolute neutrophil count, absolute platelet count, albumin levels and derived neutrophil to lymphocyte ratio (dNLR) were also computed. The associations between the variables and therapy outcome (evaluated by iRECIST) were analyzed.

Results

Based on iRECIST, 32 of 120 patients showed iPD, 43 iSD, 36 iPR and 9 iCR. Multivariate analysis found that SUVmax, MTVwb, LDH and absolute platelet count were associated with treatment response (P =0.015, P =0.005, P <0.001 and P =0.015, respectively). Kaplan-Meier survival analyses showed that SUVmax ≥11.42 and LDH ≥245 U/L were associated with shorter OS (P = 0.001 and P = 0.004, respectively). Multivariate Cox regression revealed that SUVmax and LDH alone were not correlated with survival prognosis (p>0.05), but the combination of SUVmax and LDH was independently associated with OS (P=0.015, P=0.001, respectively). The median survival time (MST) for the low (LDH<245 and SUVmax<11.42), intermediate(LDH<245 or SUVmax<11.42), and high(SUVmax≥11.42 and LDH≥245) groups was 24.10 months (95% CI: 19.43 to 28.77), 17.41 months (95% CI: 15.83 to 18.99), and 13.76 months (95% CI: 12.51 to 15.02), respectively.

Conclusion

This study identified that SUVmax plus LDH correlated with the survival outcome in patients with advanced lung cancer receiving PD-1/PD-L1 blockade plus chemotherapy.
Acute Radiation Syndrome and the Microbiome: Impact and Review
Authors: Hollingsworth Brynn A. , Cassatt David R. , DiCarlo Andrea L. , Rios Carmen I. , Satyamitra Merriline M. , Winters Thomas A. , Taliaferro Lanyn P.
Published: May 2021

Study of the human microbiota has been a centuries-long endeavor, but since the inception of the National Institutes of Health (NIH) Human Microbiome Project in 2007, research has greatly expanded, including the space involving radiation injury. As acute radiation syndrome (ARS) is multisystemic, the microbiome niches across all areas of the body may be affected. This review highlights advances in radiation research examining the effect of irradiation on the microbiome and its potential use as a target for medical countermeasures or biodosimetry approaches, or as a medical countermeasure itself. The authors also address animal model considerations for designing studies, and the potential to use the microbiome as a biomarker to assess radiation exposure and predict outcome. Recent research has shown that the microbiome holds enormous potential for mitigation of radiation injury, in the context of both radiotherapy and radiological/nuclear public health emergencies. Gaps still exist, but the field is moving forward with much promise.
A Biosimilarity Study Between QX001S and Ustekinumab in Healthy Chinese Male Subjects
Authors: Gao Lei , Li Qingmei , Zhang Hong , Wu Min , Fang Min , Yang Lizhi , Li Xiaojiao , Liu Jingrui , Li Cuiyun , Chen Hong , Zhu Xiaoxue , Ding Yanhua , Zhou Mingwei
Published: May 2021

Objective: To evaluate the tolerance, variability, and pharmacokinetics (PK) of QX001S, a biosimilar for ustekinumab, in healthy Chinese men.

Methods: One hundred and seventy-eight healthy men were recruited in this randomized, double-blind, single-dose, two-arm, parallel study, and received 45 mg of QX001S or ustekinumab in a single subcutaneous injection. PK, immunogenicity, and tolerance were evaluated in all participants for a period of 113°days.

Results: The similarity between the two drugs was determined by comparing the baseline characteristics for each drug. The PK parameters were similar in the two groups: QX001S (n = 89) and ustekinumab (n = 88). The 90% confidence intervals (CIs) for the geometric mean ratio (GMR) of QX001S to the reference (ustekinumab) for the maximum observable serum concentration (Cmax), area under the curve (AUC) from zero to the final quantifiable concentration (AUC0–t), and AUC from zero to infinity (AUC0–∞) were 100.90–118.68%, 98.71–115.26%, and 98.49–115.81%, respectively, which were within the predefined bioequivalence limit of 80.00–125.00%. High inter-subject variability (ranging from 32.0 to 33.5%) was observed. A total of 17 participants (19.1%) in the QX001S group and 36 (40.9%) in the ustekinumab group developed anti-drug antibodies (ADA) after administration. Nevertheless, the ADA did not affect the outcomes of the bioequivalence tests. Adverse reactions were recorded in 38 individuals injected with QX001S and 37 injected with ustekinumab. The most common adverse reactions were upper respiratory infection and elevated alanine aminotransferase.

Conclusions: Our study ratified pharmacokinetic biosimilarity between QX001 S and ustekinumab, with high variability between subjects.
Double-Stranded RNA Targeting Dicer-Like Genes Compromises the Pathogenicity of Plasmopara viticola on Grapevine
Authors: Haile Zeraye Mehari , Gebremichael Daniel Endale , Capriotti Luca , Molesini Barbara , Negrini Francesca , Collina Marina , Sabbadini Silvia , Mezzetti Bruno , Baraldi Elena
Published: May 2021

Downy mildew caused by Plasmopara viticola is one of the most devastating diseases of grapevine, attacking all green parts of the plant. The damage is severe when the infection at flowering stage is left uncontrolled. P. viticola management consumes a significant amount of classical pesticides applied in vineyards, requiring efficient and environmentally safe disease management options. Spray-induced gene silencing (SIGS), through the application of exogenous double-stranded RNA (dsRNA), has shown promising results for the management of diseases in crops. Here, we developed and tested the potential of dsRNA targeting P. viticola Dicer-like (DCL) genes for SIGS-based crop protection strategy. The exogenous application of PvDCL1/2 dsRNA, a chimera of PvDCL1 and PvDCL2, highly affected the virulence of P. viticola. The reduced expression level of PvDCL1 and PvDCL2 transcripts in infected leaves, treated with PvDCL1/2 dsRNA, was an indication of an active RNA interference mechanism inside the pathogen to compromise its virulence. Besides the protective property, the PvDCL1/2 dsRNA also exhibited a curative role by reducing the disease progress rate of already established infection. Our data provide a promising future for PvDCL1/2 dsRNA as a new generation of RNA-based resistant plants or RNA-based agrochemical for the management of downy mildew disease in grapevine.
Effect of Blood Transfusion on Short- and Long-Term Outcomes in Oral Squamous Cell Carcinoma Patients Undergoing Free Flap Reconstruction
Authors: Feng Aimin , Zhang Jiaqiang , Lu Xihua , Fang Qigen
Published: May 2021

Purpose: To analyze the short- and long-term effect of perioperative blood transfusion (PBT) in patients undergoing surgical treatment for oral squamous cell carcinoma (SCC).

Methods: Patients undergoing free flap reconstruction were retrospectively enrolled and divided into two groups based on the implementation of PBT. Flap revision, surgical site infection (SSI), flap failure, overall survival (OS), and disease-specific survival (DSS) were compared between the two groups.

Results: In 170 patients with PBT, 10 (5.9%) flaps required exploration revision, SSI occurred in 18 (10.6%) patients, and flap necrosis was noted in 6 (3.5%) patients. These rates were comparable to those in patients without PBT. The two groups had similar DSS rates, but the 5-year OS rates were 49 and 59% in patients with PBT and without PBT, respectively. This difference was significant. Patients with 4 units of PBT had OS rates comparable to those of patients with >4 units of PBT. A Cox model confirmed the fact that the decrease in OS was independent of PBT.

Conclusion: In patients with free flap reconstruction for oral SCC, PBT did not increase the short-term complication rate or cancer-linked mortality. However, it was related to an elevated overall risk of death.
Understanding Vaccine Hesitancy in the Context of COVID-19: The Role of Trust and Confidence in a Seventeen-Country Survey
Authors: Rozek Laura S. , Jones Pauline , Menon Anil , Hicken Allen , Apsley Samantha , King Elizabeth J.
Published: May 2021

Objectives: An effective vaccine to SARS-CoV-2 cannot be successfully deployed if a significant number of people worldwide are unwilling to accept it. We investigated the relationship between trust in scientists and medical professionals and perceptions of vaccine safety and effectiveness. We also build on past studies by exploring the relationship between confidence in global health organizations and vaccine hesitancy.

Methods: We conducted an online survey in seventeen countries/territories across five world regions between May -June 2020. We assessed the relationship between COVID19 vaccine hesitancy, confidence in public health organizations, and trust in key experts and leaders.

Results: Our findings strongly suggest that confidence in the World Health Organization combined with trust in domestic scientists and healthcare professionals is a strong driver of vaccine acceptance across multiple countries/territories.

Conclusion: We find that hesitancy is widespread, and uptake would be insufficient to achieve herd immunity. There is widespread confidence in how public health organizations have responded to the current pandemic and this is related to vaccine acceptance. Our results also highlight the important role of trust in health care providers and scientists in reducing COVID19 vaccine hesitancy.
Retrospective Evaluation of Septic Subtendinous Calcaneal Bursitis in 29 Cattle
Authors: Kofler Johann , Sullmann Florian
Published: May 2021

Septic subtendinous calcaneal bursitis in cattle commonly results from hock lesions, and less commonly from penetrating wounds. The goal of this retrospective study was to describe clinical and diagnostic imaging findings, outcomes, postoperative complications and postoperative survival times (SURV-T) in cattle with this condition. Clinical data from 29 cattle with a mean age of 4.1 years were included. Twelve (41.4%) cattle were assigned to group 1 (septic bursitis only) and 17 (58.6%) to group 2 (septic bursitis, concurrent bone infection at the calcaneal tuber (CT) and lesions of the superficial digital flexor tendon. Eleven cattle (37.9%) with comorbidities were euthanized after diagnosis due to poor prognosis. Surgical treatment was performed in 18 (62.1%) patients of which 15 showed full recovery and a median cumulative SURV-T of 23.0 months. The success rate of surgically treated patients was 100% (8/8) in group 1 and 70% (7/10) in group 2. There was no statistically significant association (p > 0.05) between the duration of septic bursitis and concurrent bone infection at the CT with occurrence of postoperative complications and SURV-T. However, there was a clear trend favoring more postoperative complications and shorter SURV-T in cattle with concurrent CT bone infection. In conclusion, cattle with septic subtendinous calcaneal bursitis exclusively have a good prognosis, provided adequate surgical treatment is performed.
Differential Modulation of Dorsal Horn Neurons by Various Spinal Cord Stimulation Strategies
Authors: Lee Kwan Yeop , Lee Dongchul , Kagan Zachary B. , Wang Dong , Bradley Kerry
Published: May 2021

New strategies for spinal cord stimulation (SCS) for chronic pain have emerged in recent years, which may work better via different analgesic mechanisms than traditional low-frequency (e.g., 50 Hz) paresthesia-based SCS. To determine if 10 kHz and burst SCS waveforms might have a similar mechanistic basis, we examined whether these SCS strategies at intensities ostensibly below sensory thresholds would modulate spinal dorsal horn (DH) neuronal function in a neuron type-dependent manner. By using an in vivo electrophysiological approach in rodents, we found that low-intensity 10 kHz SCS, but not burst SCS, selectively activates inhibitory interneurons in the spinal DH. This study suggests that low-intensity 10 kHz SCS may inhibit pain-sensory processing in the spinal DH by activating inhibitory interneurons without activating DC fibers, resulting in paresthesia-free pain relief, whereas burst SCS likely operates via other mechanisms.
KRAS Mutation Dictates the Cancer Immune Environment in Pancreatic Ductal Adenocarcinoma and Other Adenocarcinomas
Authors: Gu Meichen , Gao Yanli , Chang Pengyu
Published: May 2021

Generally, patients with pancreatic ductal adenocarcinoma, especially those with wide metastatic lesions, have a poor prognosis. Recently, a breakthrough in improving their survival has been achieved by using first-line chemotherapy, such as gemcitabine plus nab-paclitaxel or oxaliplatin plus irinotecan plus 5-fluorouracil plus calcium folinate. Unfortunately, regimens with high effectiveness are still absent in second- or later-line settings. In addition, although immunotherapy using checkpoint inhibitors definitively represents a novel method for metastatic cancers, monotherapy using checkpoint inhibitors is almost completely ineffective for pancreatic ductal adenocarcinomas largely due to the suppressive immune milieu in such tumors. Critically, the genomic alteration pattern is believed to impact cancer immune environment. Surprisingly, KRAS gene mutation is found in almost all pancreatic ductal adenocarcinomas. Moreover, KRAS mutation is indispensable for pancreatic carcinogenesis. On these bases, a relationship likely exists between this oncogene and immunosuppression in this cancer. During pancreatic carcinogenesis, KRAS mutation-driven events, such as metabolic reprogramming, cell autophagy, and persistent activation of the yes-associated protein pathway, converge to cause immune evasion. However, intriguingly, KRAS mutation can dictate a different immune environment in other types of adenocarcinoma, such as colorectal adenocarcinoma and lung adenocarcinoma. Overall, the KRAS mutation can drive an immunosuppression in pancreatic ductal adenocarcinomas or in colorectal carcinomas, but this mechanism is not true in KRAS-mutant lung adenocarcinomas, especially in the presence of TP53 inactivation. As a result, the response of these adenocarcinomas to checkpoint inhibitors will vary.
Predictive and Prognostic Value of Microsatellite Instability in Gynecologic Cancer (Endometrial and Ovarian)
Authors: Evrard Camille , Alexandre Jérôme
Published: May 2021

For endometrial cancer, a new classification is now available from ESMO, ESGO, and ESTRO based on clinical and molecular characteristics to determine adjuvant therapy. The contribution of molecular biology is major for this pathology mainly by the intermediary of deficient mismatch repair/microsatellite instability. Detection techniques for this phenotype have many peculiarities in gynecologic cancers (endometrial and ovarian) because it has been initially validated in colorectal cancer only. Endometrial cancer is the most common tumor with deficient mismatch repair, which is an important prognostic factor and a predictor of the benefit of adjuvant treatments. Concerning advanced stages, this phenotype is a theragnostic marker for using immunotherapy. Among ovarian cancer, microsatellite instability is less described in literature but exists, particularly in endometrioid type ovarian cancer. This review aims to provide an overview of the publications concerning deficient mismatch repair/microsatellite instability in endometrial and ovarian cancers, detection techniques, and clinical implications of these molecular characteristics.
Differential Effect of Non-Thermal Plasma RONS on Two Human Leukemic Cell Populations
Authors: Mohamed Hager , Gebski Eric , Reyes Rufranshell , Beane Samuel , Wigdahl Brian , Krebs Fred C. , Stapelmann Katharina , Miller Vandana
Published: May 2021

Non-thermal plasma application to cancer cells is known to induce oxidative stress, cytotoxicity and indirect immunostimulatory effects on antigen presenting cells (APCs). The purpose of this study was to evaluate the responses of two leukemic cell lines—Jurkat T lymphocytes and THP-1 monocytes—to NTP-generated reactive oxygen and nitrogen species (RONS). Both cell types depleted hydrogen peroxide, but THP-1 cells neutralized it almost immediately. Jurkat cells transiently blunted the frequency-dependent increase in nitrite concentrations in contrast to THP-1 cells, which exhibited no immediate effect. A direct relationship between frequency-dependent cytotoxicity and mitochondrial superoxide was observed only in Jurkat cells. Jurkat cells were very responsive to NTP in their display of calreticulin and heat shock proteins 70 and 90. In contrast, THP-1 cells were minimally responsive or unresponsive. Despite no NTP-dependent decrease in cell surface display of CD47 in either cell line, both cell types induced migration of and phagocytosis by APCs. Our results demonstrate that cells modulate the RONS-mediated changes in liquid chemistry, and, importantly, the resultant immunomodulatory effects of NTP can be independent of NTP-induced cytotoxicity.
Digestive Well-Differentiated Grade 3 Neuroendocrine Tumors: Current Management and Future Directions
Authors: Pellat Anna , Cottereau Anne Ségolène , Palmieri Lola-Jade , Soyer Philippe , Marchese Ugo , Brezault Catherine , Coriat Romain
Published: May 2021

Digestive well-differentiated grade 3 neuroendocrine tumors (NET G-3) have been clearly defined since the 2017 World Health Organization classification. They are still a rare category lacking specific data and standardized management. Their distinction from other types of neuroendocrine neoplasms (NEN) not only lies in morphology but also in genotype, aggressiveness, functional imaging uptake, and treatment response. Most of the available data comes from pancreatic series, which is the most frequent tumor site for this entity. In the non-metastatic setting, surgical resection is recommended, irrespective of grade and tumor site. For metastatic NET G-3, chemotherapy is the main first-line treatment with temozolomide-based regimen showing more efficacy than platinum-based regimen, especially when Ki-67 index <55%. Targeted therapies, such as sunitinib and everolimus, have also shown some positive therapeutic efficacy in small samples of patients. Functional imaging plays a key role for detection but also treatment selection. In the second or further-line setting, peptide receptor radionuclide therapy has shown promising response rates in high-grade NEN. Finally, immunotherapy is currently investigated as a new therapeutic approach with trials still ongoing. More data will come with future work now focusing on this specific subgroup. The aim of this review is to summarize the current data on digestive NET G-3 and explore future directions for their management.
Local Immune Changes in Early Stages of Inflammation and Carcinogenesis Correlate with the Collagen Scaffold Changes of the Colon Mucosa
Authors: Čaja Fabián , Stakheev Dmitry , Chernyavskiy Oleksandr , Kubinová Lucie , Křížan Jiří , Dvořák Jiří , Rossmann Pavel , Štěpánková Renata , Makovický Peter , Makovický Pavol , Vymetalková Veronika , Souček Pavel , Vodička Pavel , Vodičková L’udmila , Levý Miroslav , Vannucci Luca E.
Published: May 2021

Continuous activation of the immune system inside a tissue can lead to remodelling of the tissue structure and creation of a specific microenvironment, such as during the tumour development. Chronic inflammation is a central player in stimulating changes that alter the tissue stroma and can lead to fibrotic evolution. In the colon mucosa, regulatory mechanisms, including TGF-β1, avoid damaging inflammation in front of the continuous challenge by the intestinal microbiome. Inducing either DSS colitis or AOM colorectal carcinogenesis in AVN-Wistar rats, we evaluated at one month after the end of each treatment whether immunological changes and remodelling of the collagen scaffold were already in development. At this time point, we found in both models a general downregulation of pro-inflammatory cytokines and even of TGF-β1, but not of IL-6. Moreover, we demonstrated by multi-photon microscopy the simultaneously presence of pro-fibrotic remodelling of the collagen scaffold, with measurable changes in comparison to the control mucosa. The scaffold was significantly modified depending on the type of induced stimulation. These results suggest that at one month after the end of the DSS or AOM inductions, a smouldering inflammation is present in both induced conditions, since the pro-inflammatory cytokines still exceed, in proportion, the local homeostatic regulation of which TGF-β1 is a part (inflammatory threshold). Such an inflammation appears sufficient to sustain remodelling of the collagen scaffold that may be taken as a possible pathological marker for revealing pre-neoplastic inflammation.
Milled Surface Integrity: Application to Fixed Dental Prosthesis
Authors: Lebon Nicolas , Tapie Laurent
Published: May 2021

Surface integrity is a multiphysics (biological, mechanical, optical, chemical, esthetic, etc.) and multiscale (from nm to mm) concept. It is defined as the residual signature left on the surface by the manufacturing or post-treatment process and permits correlating the process with the expected surface functionalities. Thanks to the advances made in mechanical engineering, the concept of surface integrity has been transposed to dentistry and oral science. The surface integrity concept transposed to fixed dental prostheses is presented in this article. The main components of surface integrity and their correlations within the triptych of surface integrity–process–clinical functionalities are presented.
Outcomes of Older Patients with Resectable Colorectal Liver Metastases Cancer (CRLM): Single Center Experience
Authors: Nassabein Rami , Mansour Laura , Richard Corentin , Vandenbroucke-Menu Franck , Aubin Francine , Ayoub Jean-Pierre , Dagenais Michel , Lapointe Real , Letourneau Richard , Plasse Marylène , Roy André , Turcotte Simon , Tehfe Mustapha
Published: May 2021

Surgery is the only potential curative option of CRLM if resectable. The curative approach in patients over 70 years old is challenging mainly because of comorbidities and other geriatric syndromes. Herein, we report outcomes of older patients with resectable CRLM in our center. We retrospectively analyzed characteristics and outcomes of older patients with CRLM operated at “Centre Hospitalier de l’Université de Montréal” (CHUM) between 2010 and 2019. We identified 210 patients aged ≥70 years with a median age of 76 (range: 70–85). CRLM were synchronous in 56% of patients. Median disease-free survival (DFS) was 41.3 months. Median overall survival (OS) was 62.2 months and estimated 5-year survival rate was 51.5% similar to those of younger counterparts. Patients with metachronous CRLM had a trend to a higher OS compared to those with synchronous disease (67.2 vs. 58.7 months; p = 0.42). Factors associated with lower survival in the multivariate analysis were right-sided tumors and increased Charlson Comorbidity index (CCI). Survival outcomes of patients aged ≥70 years were comparable to those of younger patients and those reported in the literature. Age should not be a limiting factor in the curative management of older patients with resectable CRLM.
Revisited Molecular Phylogeny of the Genus Sphaerotheca (Anura: Dicroglossidae): The Biogeographic Status of Northernmost Populations and Further Taxonomic Changes
Authors: Jablonski Daniel , Masroor Rafaqat , Hofmann Sylvia
Published: May 2021

Heretofore, the populations of the genus Sphaerotheca Günther, 1859 (Dicroglossidae) in their northern and western borders laying in Pakistan have been assigned to two species, S. breviceps (Schneider, 1799) and S. strachani (Murray, 1884). The genus originated in the Oriental zoogeographic region and comes to close geographic proximity with the Palearctic region in Pakistan. The recent molecular studies have on one hand restricted the distribution range of S. breviceps to the eastern coastal plains of India and, on the other hand, revealed the northern- and westernmost population in India as a separate species, S. pashchima Padhye et al., 2017. This species has recently been synonymized with S. maskeyi (Schleich and Anders, 1998). These taxonomic changes, however, warranted the need for validation of Pakistani Sphaerotheca based on genetic data. We sequenced and analyzed 16S rRNA mitochondrial gene from specimens originating from the Himalayan foothills of Pakistan and compared these with all available GenBank sequences of the genus. Based on this data, we conclude that the Himalayan foothills of Pakistan are occupied by S. maskeyi. Simultaneously, we bring the first record of this species for the Palearctic region. We further suggest that more genetic material from across Pakistan is required to ascertain the validity of S. strachani and for the phylogeographic evaluation of western and northern border populations of the genus. Our geographically wide and revisited molecular phylogeny shows that the genus exhibits genetic diversity suggesting further taxonomic changes. The low level of genetic divergences between S. breviceps and S. magadha Prasad et al., 2019 compared to other species of the genus, indicates that the taxonomic status of S. magadha is questionable. Moreover, we found that S. magadha and S. swani (Mayers and Leviton, 1956) are genetically conspecific with S. breviceps and both should be thus considered its junior synonyms. On the other hand, S. dobsonii and populations from Myanmar need further detailed investigations.