bluuebunny/crossref_metadata_2025 huggingface dataset:
PENGARUH PENGELUARAN PEMERINTAH, INDEKS PEMBANGUNAN MANUSIA, DAN INFLASI TERHADAP PERTUMBUHAN EKONOMI NEGARA-NEGARA ASIA TENGGARA: Suatu Pendekatan Panel ARDL
Authors: Awaluddin Awaluddin , Muthalib Abdul Azis , Suriadi La Ode
Published: March 2022

Penelitian ini bertujuan untuk menganalisis pengaruh jangka panjang dan jangka pendek pengeluaran pemerintah, indeks pembangunan manusia, pengangguran, inflasi terhadap pertumbuhan ekonomi negara-negara Asia Tenggara. Jenis data yang digunakan dalam penelitian ini yaitu data sekunder yang diakses melalui website Theworldbank.com,, undp.org  dan ceicdata.com dalam bentuk time series tahunan periode 2000 sampai 2018. Alat analsis yang digunakan yaitu Panel Auto Regressive Distributed Lag (ARDL). Hasil penelitian menunjukkan (1) Dalam jangka panjang pengeluaran pemerintah berpengaruh positif signifikan sedangkan dalam jangka pendek tidak berpengaruh signifikan terhadap pertumbuhan ekonomi negara-negara Asia Tenggara; (2) Dalam jangka panjang indeks pembangunan manusia berpengaruh positif signifikan sedangkan dalam jangka pendek tidak perpengaruh signifikan terhadap pertumbuhan ekonomi negara-negara Asia Tenggara; (3) Dalam jangka panjang inflasi berpengaruh negatif  signifikan sedangkan dalam jangka pendek tidak berpengaruh signifikan terhadap pertumbuhan ekonomi negara-negara Asia Tenggara.
KONTRIBUSI SEKTOR PARIWISATA TERHADAP PENDAPATAN ASLI DAERAH KOTA SURABAYA
Authors: Agustin Dita Nia , Hendrati Ignatia Martha , Asmara Kiky
Published: March 2022

Surabaya mempunyai berbagai potensi dalam banyak bidang, salah satunya adalah pariwisata. Dalam upaya untuk meningkatkan pendapatan daerahnya selain melakukan intensifiksasi pajak, Kota Surabaya juga mengembangkan potensi wisata yang dimilikinya. Pengembangan wisata ini dapat meningkatkan pendapatan sektor pariwisata yang berupa pajak dan retribusi dimana kedua pendapatan ini juga bagian dari Pendapatan Asli Daerah. Penelitian ini bertujuan untuk mengetahui dan menganalisis kontribusi pajak sektor pariwisata dan retribusi sektor pariwisata terhadap PAD Surabaya. Dalam penelitian ini menggunakan variabel pendapatan pajak sektor pariwisata dan retribusi sektor pariwisata Kota Surabaya tahun 2011-2019. Data yang digunakan adalah data sekunder yang diperoleh dari BPKPD Kota Surabaya, BAPPEKO Surabaya, dan Dinas Kebudayaan dan Pariwisata Kota Surabaya. Ruang lingkup penelitian ini adalah seluruh pendapatan sektor pariwisata Kota Surabaya.Menggunakan rasio kontribusi dan trend sebegai metode analisis. Hasil penelitian menunjukkan bahwa pajak sektor pariwisata kurang berkontribusi terhadap PAD dengan nilai rata-rata 14,7% dan retribusi sektor pariwisata sangat kurang berkontribusi terhadap PAD dengan nilai rata-rata 6,75%.Kata Kunci: Pajak Sektor Pariwisata, Retribusi Sektor Pariwisata, Pendapatan Asli Daerah
ANALISIS PENGELOLAAN ASET TETAP PROVINSI SULAWESI TENGGARA
Authors: Asdal Mohamad , Dali Nasrullah , Dali Nasrullah , Saranani Fajar , Saranani Fajar
Published: March 2022

Penelitian ini bertujuan: Pengelolaan Aset Tetap Provinsi Sulawesi Tenggara. Penelitian ini menggunakan pendekatan penelitian kualitatif. informan yang telah dipilih dan dianggap memahami permasalahan penelitian Aset Tetap (Tanah) Milik Pemerintah Daerah Provinsi Sulawesi Tenggara. Analisa data dalam penelitian kualitatif, dilakukan pada saat pengumpulan data berlangsung dan setelah selesai di lapangan. Teknik analisa data yang digunakan dalam penelitian ini adalah dengan menggunakan teknik analisa data kualitatif. Hasil penelitian menunjukkan bahwa; pengelolaan inventarisasi aset  yang meliputi penggunaan; pemanfaatan; pengamanan dan pemeliharaan; penilaian; penatausahaan; serta pembinaan, pengawasan dan pengendalian, dapat dikatakan bahwa kegiatan Inventarisasi dalam pengelolaan aset berupa tanah milik Pemeintah Provinsi Tenggara sudah baik, namun masih terdapat sejumlah aset yang masih dikuasai/diklaim oleh pihak lain, ini terjadi karena kurangnya pemanfaatan, pengawasan dan pengamanan dan barang milik daerah. Kata Kunci: Pengelolaan Aset Tetap
THEORY OF GENERALIZED SEPARATION AXIOMS IN GENERALIZED TOPOLOGICAL SPACES
Authors: KHODABOCUS Mohammad Irshad , SOOKIA Noor-ul-hacq
Published: March 2022

In this paper, a new class of generalized separation axioms (briefly, g-Tg-separation axioms) whose elements are called g-Tg,K, g-Tg,F, g-Tg,H, g-Tg,R, g-Tg,N-axioms is defined in terms of generalized sets (briefly, g-Tg-sets) in generalized topological spaces (briefly, Tg-spaces) and the properties and characterizations of a Tg-space endowed with each such g-Tg,K, g-Tg,F, g-Tg,H, g-Tg,R, g-Tg,N-axioms are discussed. The study shows that g-Tg,F-axiom implies g-Tg,K-axiom, g-Tg,H-axiom implies g-Tg,F-axiom, g-Tg,R-axiom implies g-Tg,H-axiom, and g-Tg,N-axiom implies g-Tg,R-axiom. Considering the Tg,K, Tg,F, Tg,H, Tg,R, Tg,N-axioms as their analogues but defined in terms of corresponding elements belonging to the class of open, closed, semi-open, semi-closed, preopen, preclosed, semi-preopen, and semi-preclosed sets, the study also shows that the statement Tg,α-axiom implies g-Tg,α-axiom holds for each α ∈ {K, F, H, R, N}. Diagrams expose the various implications amongst the
classes presented here and in the literature, and a nice application supports the overall theory.
PERFECT CODES OVER HURWITZ INTEGERS INDUCED BY CIRCULANT GRAPHS
Authors: GÜZELTEPE Murat , GÜNER Gökhan
Published: March 2022

In this paper, a new family of t−error correcting perfect codes over Hurwitz integers is
presented. To obtain these perfect codes, the perfect t−dominating sets over the circulant
graphs are used. The codewords of such perfect codes are generated by the elements of a
subgroup of the considered group.
Oxygen profile in an experimental cell culture apparatus
Authors: Breward Chris , Parker David
Published: February 2022

Cells can be readily grown outside of the body on the bottom of specialised plastic tissue culture dishes containing a nutrient liquid. The use of culture dishes with an oxygen-permeable base allows oxygen to reach the cells from below. In particular experiments, an impermeable glass slip covered with tumour cells is placed in the centre of a permeable culture dish and endothelial cells are seeded on the base of the dish around the outside of the cover slip. Our aim is to determine whether the tumour cells at the centre become hypoxic. We build and solve mathematical models for the transport of oxygen in this cell culture apparatus. Given the physical parameters, we determine that the original set is likely to be sub-optimal. We propose revised geometries of the apparatus that result in better concentration gradients.
SISTEM PENDUKUNG KEPUTUSAN UNTUK MENENTUKAN TINGKAT KECANDUAN GAME ONLINE MENGGUNAKAN METODE SIMPLE ADDITIVE WEIGHTING (SAW)
Authors: Rizki Ramadhan  , Fitriyani Fitriyani
Published: March 2022

Bermain game online menjadi kegemaran setiap orang dari semua kalangan, baik anak-anak maupun orang dewasa. Game online menjadi idola bagi semua kalangan karena dapat dijadikan alternatif menghilangkan kejenuhan setelah seharian beraktivitas, Sayangnya tidak semua orang dapat mengontrolnya dengan baik hingga menjadi kecanduan terhadap game online. Selain sebagai sarana hiburan game online juga memberikan tantangan yang menarik untuk diselesaikan sehingga seseorang bermain game online tanpa memperhitungkan waktu demi mencapai kepuasan. Seseorang dapat terus menerus bermain game online sampai melupakan waktu bahkan melupakan kondisi lingkungan disekelilingnya. Keseringan dalam bermain game online dapat berdampak pada tingkat kecanduan seseorang terhadap game. Namun, tidak semua orang menyadari bahwa telah memiliki jenis perilaku kecanduan game. Oleh sebab itu, dilakukan penelitian untuk menentukan tingkatkecanduan seseorang terhadap game online. Jenis perilaku tersebut kemudian dibuat ke dalam sebuah sistem pendukung keputusan (SPK) berbasis web. Sistem ini dirancang bangun menggunakan perhitungan metode simple additive weighting (SAW). Dengan dilakukannya penelitian ini, dihasilkan sebuah sistem untuk menentukan tingkat kecanduan game online berdasarkan enam jenis perilaku kecanduan game berdasarkan studi pustaka terdahulu seperti salience, euphoria, conflict, tolerance, withdrawal, relapse and reinstatement. Sistem ini dapat menampilkan hasil perangkingan yang paling banyak memiliki perilaku kecanduan game online berdasarkan hasil peritungan metode simple additive weighting (SAW).
ENKRIPSI SELEKTIF PADA CITRA MEDIS DENGAN MENGGUNAKAN LINEAR CONGRUENTIAL GENERATOR
Authors: Aprianti Nanda  , Trisna Gelar
Published: March 2022

Di bidang rekam medis, citra medis merupakan data yang sensitif. Akan tetapi, masih banyak sistem rekam medis di rumah sakit atau institusi kesehatan yang menyimpan citra medis pasien dalam database tanpa dienkripsi terlebih dahulu. Hal ini memberikan peluang terhadap pihak yang tidak berwenang untuk mengakses citra medis secara ilegal. Pada penelitian ini hanya sebagian bit pada citra medis yang dienkripsi, atau biasa disebut sebagai enkripsi selektif. Sebagian bit pada setiap piksel tersebut dioperasikan dengan bilangan acak yang dibangkitkan dengan menggunakan algoritma Linear Congruential Generator. Dari hasil pengujian, metode yang diajukan memiliki performa yang cukup baik sehingga dapat diaplikasikan pada kasus nyata.
Bioinspired Bare Bones Mayfly Algorithm for Large-Scale Spherical Minimum Spanning Tree
Authors: Zhang Tian , Zhou Yongquan , Zhou Guo , Deng Wu , Luo Qifang
Published: March 2022

Mayfly algorithm (MA) is a bioinspired algorithm based on population proposed in recent years and has been applied to many engineering problems successfully. However, it has too many parameters, which makes it difficult to set and adjust a set of appropriate parameters for different problems. In order to avoid adjusting parameters, a bioinspired bare bones mayfly algorithm (BBMA) is proposed. The BBMA adopts Gaussian distribution and Lévy flight, which improves the convergence speed and accuracy of the algorithm and makes better exploration and exploitation of the search region. The minimum spanning tree (MST) problem is a classic combinatorial optimization problem. This study provides a mathematical model for solving a variant of the MST problem, in which all points and solutions are on a sphere. Finally, the BBMA is used to solve the large-scale spherical MST problems. By comparing and analyzing the results of BBMA and other swarm intelligence algorithms in sixteen scales, the experimental results illustrate that the proposed algorithm is superior to other algorithms for the MST problems on a sphere.
Pathways and Mechanisms of Cellular Cholesterol Efflux—Insight From Imaging
Authors: Juhl Alice Dupont , Wüstner Daniel
Published: March 2022

Cholesterol is an essential molecule in cellular membranes, but too much cholesterol can be toxic. Therefore, mammalian cells have developed complex mechanisms to remove excess cholesterol. In this review article, we discuss what is known about such efflux pathways including a discussion of reverse cholesterol transport and formation of high-density lipoprotein, the function of ABC transporters and other sterol efflux proteins, and we highlight their role in human diseases. Attention is paid to the biophysical principles governing efflux of sterols from cells. We also discuss recent evidence for cholesterol efflux by the release of exosomes, microvesicles, and migrasomes. The role of the endo-lysosomal network, lipophagy, and selected lysosomal transporters, such as Niemann Pick type C proteins in cholesterol export from cells is elucidated. Since oxysterols are important regulators of cellular cholesterol efflux, their formation, trafficking, and secretion are described briefly. In addition to discussing results obtained with traditional biochemical methods, focus is on studies that use established and novel bioimaging approaches to obtain insight into cholesterol efflux pathways, including fluorescence and electron microscopy, atomic force microscopy, X-ray tomography as well as mass spectrometry imaging.
Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System
Authors: Su Xin-Jin , Shen Bei-Duo , Wang Kun , Song Qing-Xin , Yang Xue , Wu De-Sheng , Shen Hong-Xing , Zhu Chao
Published: March 2022

The neuron-restrictive silencer factor (NRSF), also known as repressor element 1 (RE-1) silencing transcription factor (REST) or X2 box repressor (XBR), is a zinc finger transcription factor that is widely expressed in neuronal and non-neuronal cells. It is a master regulator of the nervous system, and the function of NRSF is the basis of neuronal differentiation, diversity, plasticity, and survival. NRSF can bind to the neuron-restrictive silencer element (NRSE), recruit some co-repressors, and then inhibit transcription of NRSE downstream genes through epigenetic mechanisms. In neurogenesis, NRSF functions not only as a transcriptional silencer that can mediate the transcriptional inhibition of neuron-specific genes in non-neuronal cells and thus give neuron cells specificity, but also as a transcriptional activator to induce neuronal differentiation. Many studies have confirmed the association between NRSF and brain disorders, such as brain injury and neurodegenerative diseases. Overexpression, underexpression, or mutation may lead to neurological disorders. In tumorigenesis, NRSF functions as an oncogene in neuronal tumors, such as neuroblastomas, medulloblastomas, and pheochromocytomas, stimulating their proliferation, which results in poor prognosis. Additionally, NRSF-mediated selective targets gene repression plays an important role in the development and maintenance of neuropathic pain caused by nerve injury, cancer, and diabetes. At present, several compounds that target NRSF or its co-repressors, such as REST-VP16 and X5050, have been shown to be clinically effective against many brain diseases, such as seizures, implying that NRSF and its co-repressors may be potential and promising therapeutic targets for neural disorders. In the present review, we introduced the biological characteristics of NRSF; reviewed the progress to date in understanding the roles of NRSF in the pathophysiological processes of the nervous system, such as neurogenesis, brain disorders, neural tumorigenesis, and neuropathic pain; and suggested new therapeutic approaches to such brain diseases.
Exosomal miR-483-5p in Bone Marrow Mesenchymal Stem Cells Promotes Malignant Progression of Multiple Myeloma by Targeting TIMP2
Authors: Gu Jianmei , Wang Maoye , Wang Xinfeng , Li Jiao , Liu Haiyan , Lin Zenghua , Yang Xi , Zhang Xu , Liu Hong
Published: March 2022

Bone marrow-derived mesenchymal stem cell (BMSC) is one crucial component of the multiple myeloma (MM) microenvironment and supports the malignant progression of MM. Whether BMSCs act on MM cells via exosomes has not been well characterized. Herein, we used microarrays to screen out differentially expressed miRNAs in BMSCs from patients with MM (MM-MSCs) or benign diseases (BD-MSCs). We found that miR-483-5p was highly expressed in MM-MSCs, which may be transported through exosomes from MM-MSCs to MM cells to increase miR-483-5p expression in them. We then investigated the role and mechanism of miR-483-5p in the aggressive progression of MM in vitro. We verified that miR-483-5p promoted MM cell proliferation and reduced apoptosis. Then we predicted and validated that TIMP2, a tumor suppressor gene, is the downstream target of miR-483-5p in MM. In summary, our study indicated that MM-MSCs promote MM malignant progression via the release of exosomes and regulation of miR-483-5p/TIMP2 axis, suggesting an essential role of BMSCs derived exosomal miRNA in MM and a potential marker for MM diagnosis and therapy.
The Centriole’s Role in Miscarriages
Authors: Avidor-Reiss Tomer , Achinger Luke , Uzbekov Rustem
Published: March 2022

Centrioles are subcellular organelles essential for normal cell function and development; they form the cell’s centrosome (a major cytoplasmic microtubule organization center) and cilium (a sensory and motile hair-like cellular extension). Centrioles with evolutionarily conserved characteristics are found in most animal cell types but are absent in egg cells and exhibit unexpectedly high structural, compositional, and functional diversity in sperm cells. As a result, the centriole’s precise role in fertility and early embryo development is unclear. The centrioles are found in the spermatozoan neck, a strategic location connecting two central functional units: the tail, which propels the sperm to the egg and the head, which holds the paternal genetic material. The spermatozoan neck is an ideal site for evolutionary innovation as it can control tail movement pre-fertilization and the male pronucleus’ behavior post-fertilization. We propose that human, bovine, and most other mammals–which exhibit ancestral centriole-dependent reproduction and two spermatozoan centrioles, where one canonical centriole is maintained, and one atypical centriole is formed–adapted extensive species-specific centriolar features. As a result, these centrioles have a high post-fertilization malfunction rate, resulting in aneuploidy, and miscarriages. In contrast, house mice evolved centriole-independent reproduction, losing the spermatozoan centrioles and overcoming a mechanism that causes miscarriages.
On the Bias and Stability of the Results of Comparative Judgment
Authors: Crompvoets Elise A. V. , Béguin Anton A. , Sijtsma Klaas
Published: March 2022

Comparative judgment is a method that allows measurement of a competence by comparison of items with other items. In educational measurement, where comparative judgment is becoming an increasingly popular assessment method, items are mostly students’ responses to an assignment or an examination. For assessments using comparative judgment, the Scale Separation Reliability (SSR) is used to estimate the reliability of the measurement. Previous research has shown that the SSR may overestimate reliability when the pairs to be compared are selected with certain adaptive algorithms, when raters use different underlying models/truths, or when the true variance of the item parameters is below one. This research investigated bias and stability of the components of the SSR in relation to the number of comparisons per item to increase understanding of the SSR. We showed that many comparisons are required to obtain an accurate estimate of the item variance, but that the SSR can be useful even when the variance of the items is overestimated. Lastly, we recommend adjusting the general guideline for the required number of comparisons per item to 41 comparisons per item. This recommendation partly depends on the number of items and the true variance in our simulation study and needs further investigation.
Abnormal Glucose Metabolism Parameters and the Aggressiveness of Differentiated Thyroid Carcinoma: A Hospital-Based Cross-Section Study in China
Authors: Zhao Junyu , Tian Yutian , Jia Zhen , Yao Jinming , Liao Lin , Dong Jianjun
Published: March 2022

Purpose

The correlation of abnormal glucose metabolism and thyroid carcinoma, especially the aggressiveness of thyroid cancer, still remains controversial. We conducted this study to investigate the relationship between abnormal glucose metabolism parameters and differentiated thyroid carcinoma (DTC) in the Chinese population.

Materials and Methods

The study was designed as a hospital-based case–control study and was approved by the Ethics Committee of our hospital and registered in the Clinical Trial Protocol Registration and Results System (Registration code: NCT 03006289). From January 1, 2018 to June 30, 2021, a total of 377 DTC patients were enrolled in the study. Demographic and general characteristics, details of thyroid surgery and histopathological results, hematological test indicators were collected. Glucose metabolism parameters were calculated. Variables were analyzed by t-test, ANOVA, chi-squared analysis and Fisher’s exact test. Pearson bi-variate correlation and Spearman’s correlation analysis were used for bi-variate analysis.

Results

More than 40% of patients with DTC were multifocality, more than half were extra-glandular invasion, and nearly 85% complied by lymph node metastasis. The prevalence of diabetes mellitus (DM) was about 10.08% in DTC patients. It was found that the proportion of postprandial 2 h blood glucose ≥11.1mmol/L and HbA1c ≥6.5% was significantly higher than the known proportion of DM (17.8%, 16.7% vs. 10.08%). Additionally, 87.3% of the DTC patients in this study had varying degrees of insulin resistance. Further analysis found that higher T staging was associated with higher levels of area under curve of C-peptide (P = 0.029), insulin sensitivity index (P = 0.012) and C-peptide sensitivity index (P = 0.016). A delayed peak of insulin secretion was found to be positive related with capsule invasion (r = 0.206, P = 0.004). In patients without a DM history, homeostasis model assessment of insulin resistance (P = 0.017), insulin sensitivity index (P = 0.019) and C-peptide sensitivity index (P = 0.020) were statistic associated with T staging. Also, the glucose metabolism parameter at 3-hour after a meal was related to a larger number of metastatic lymph nodes.

Conclusion

Abnormal glucose metabolism, namely, DM, hyperinsulinemia and insulin resistance, were significantly associated with the carcinogensis and aggressiveness of DTC.
Multiple Fungi May Connect the Roots of an Orchid (Cypripedium reginae) and Ash (Fraxinus nigra) in Western Newfoundland
Authors: Weerasuriya Nimalka M. , Kukolj Katarina , Spencer Rebecca , Sveshnikov Dmitry , Thorn R. Greg
Published: March 2022

Showy lady's slipper (Cypripedium reginae Walter, Orchidaceae) and black ash (Fraxinus nigra Marshall, Oleaceae) often co-occur in close proximity in fens in western Newfoundland, Canada. Metabarcoding of DNA extracted from root samples of both species following surface sterilization, and others without surface sterilization was used to determine if there were shared fungal endophytes in the roots of both species that could form a common mycorrhizal network between them. A wide variety of fungi were recovered from primers amplifying the nuclear ribosomal internal transcribed spacer region (ITS2). Sixty-six fungal sequences were shared by surface-sterilized roots of both orchid and ash, among them arbuscular mycorrhizal fungi (Claroideoglomus, Dominikia, Glomus and Rhizophagus), ectomycorrhizal fungi (Inocybe and Tomentella), the broad-host root endophyte Cadophora orchidicola, along with root pathogens (Dactylonectria, Ilyonectria, Pyricularia, and Xylomyces) and fungi of unknown function. There appear to be multiple fungi that could form a common mycorrhizal network between C. reginae and F. nigra, which might explain their frequent co-occurrence. Transfer of nutrients or carbon between the orchid and ash via one or more of the shared fungal endophytes remains to be demonstrated.
Viscera Characteristics of MSTN-Edited Heterozygous Pigs
Authors: Pei Yangli , Fan Ziyao , Song Yuxin , Chen Chujie , Mu Yulian , Li Bugao , Feng Zheng , Li Hua , Li Kui
Published: March 2022

Myostatin (MSTN) is a protein that negatively regulates growth of skeletal muscle, and inactivation of MSTN improves the mass of skeletal muscle. Our previous work found that MSTN+/− pigs have higher muscle depth and lower fat depth compared to wild type without any developmental problems. Therefore, MSTN-edited pigs are most likely to appear as heterozygotes in the potential future market, but the characteristics of organs in digestive and reproductive system of pigs with MSTN gene editing remains unclear. Here, we investigated the histological of the organs in the digestive system and reproductive system in MSTN gene heterozygotes at adult stages. The length of intestine was further compared between adult heterozygous and wild type pigs. We found no significant differences in histomorphology of organs, including heart, duodenum, jejunum, ileum, cecum, colon, testis, epididymis, ovaries, oviducts and uterus, between individuals from two genotypes. Moreover, there was no significant difference in the average length of intestine in adult pigs. Our data provide a reference for further clarifying the applications of MSTN gene edited pigs.
Human ILC3 Exert TRAIL-Mediated Cytotoxicity Towards Cancer Cells
Authors: Siegler Jana-Julia , Correia Margareta P. , Hofman Tomáš , Prager Isabel , Birgin Emrullah , Rahbari Nuh N. , Watzl Carsten , Stojanovic Ana , Cerwenka Adelheid
Published: March 2022

Group 3 helper Innate Lymphoid Cells (ILC3s) are cytokine-producing lymphocytes that respond to stress signals released during disturbed tissue homeostasis and infection. Upon activation, ILC3s secrete IL-22 and IL-17, and orchestrate immune responses against extracellular pathogens. Their role in cancer remains poorly explored. To determine their anti-cancer effector potential, we co-cultured cytokine-activated human ILC3s with cancer cells of different origins. ILC3s were able to directly respond to tumor cells, resulting in enhanced IFN-γ production. Upon tumor cell encounter, ILC3s maintained expression of the transcription factor RORγt, indicating that ILC3s preserved their identity. ILC3s were able to directly kill both hepatocellular carcinoma and melanoma tumor cells expressing cell-death receptor TRAILR2, through the activation of Caspase-8 in target cells. Moreover, liver-derived cytokine-activated ILC3s also expressed TRAIL and were able to eliminate hepatoblastoma cells. Together, our data reveal that ILC3s can participate in anti-tumor immune response through direct recognition of tumor cells resulting in IFN-γ release and TRAIL-dependent cytotoxicity. Thus, ILC3s might be ancillary players of anti-tumor immunity in tissues, acting as primary responders against transformed or metastasizing cells, which might be further exploited for therapies against cancer.
Case Report: Immune Checkpoint Inhibitors Successfully Controlled Asymptomatic Brain Metastasis in Esophageal Squamous Cell Carcinoma
Authors: Xiao Linlin , Lin Chi , Liu Yueping , Wu Yajing , Wang Jun
Published: March 2022

Background

Brain metastases are the most common cause of intracranial malignancy, often resulting in significant morbidity and mortality. Brain metastases from esophageal squamous cell carcinoma (ESCC) are relatively rare, with a rate of generally less than 2%.

Case Report

In this article, we report a rare case of ESCC with asymptomatic brain metastasis. The combined positive score (CPS) of programmed cell death-ligand 1 (PD-L1) from the primary tumor was 2 by DAKO 22C3 and 3 by VENTANA SP263. The proportion of tumor infiltrating lymphocytes (TILs) was 1%. After receiving 15 cycles of immune checkpoint inhibitors (ICIs), the patient’s brain metastatic lesion had disappeared and was replaced by a local necrotic area. He retains good cognitive function with a stable disease at the primary site.

Conclusions

This is the first to be reported in an ESCC patient whose brain metastatic lesion had a complete response to ICIs, which may provide supporting data for using ICIs as an option of treatment for ESCC patients with brain metastases.
Safety and Feasibility of Esophagectomy Following Combined Immunotherapy and Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score Matching Analysis
Authors: Hong Zhi-Nuan , Gao Lei , Weng Kai , Huang Zhixin , Han Wu , Kang Mingqiang
Published: March 2022

Objectives

The combination of neoadjuvant chemotherapy and immunotherapy (nICT) is a novel treatment for locally advanced esophageal cancer. There is concern that nICT may increase operation difficulty, postoperative morbidity, and mortality. This study aimed to compare short-term outcomes among esophagectomy after neoadjuvant chemoradiotherapy (nCRT) and nICT and for locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

A retrospective analysis of a prospectively maintained database was performed to identify patients (from January 2017 through July 2021) who underwent surgery for ESCC following neoadjuvant therapy. A 1:1 propensity score matching (PSM) with a caliper 0.05 was conducted to balance potential bias.

Results

A 1:1 PSM was conducted based on clinical stage, age, body mass index (BMI), and tumor location, and then 32 comparable pairs were matched. After PSM, age, gender, BMI, American Society of Anesthesiologists (ASA) status, smoking history, clinical stage, tumor location, lymphadenectomy field, pathological stage, anastomotic position, route of gastric conduit, procedure type, and operative approach were comparable between groups. Compared with the nICT group (median, 300 min), the operation time was significantly longer in the nCRT group (median, 376 min). However, both groups were comparable in intraoperative blood loss, thoracic drainage volume, intensive care unit (ICU) stay, postoperative hospital stays, and hospital cost. Further, 30-day mortality, 30-day readmission, ICU readmission, and major complications were similar in both groups. The nCRT group had an advantage in pathological response. The pathological complete response (pCR) was 18.8% (6/32) in the nICT group and 43.8% (14/32) in the nCRT group (p = 0.03). The major pathological response (MPR) was 71.9% (23/32) in the nCRT group and 34.4% (11/32) in the nICT group (p = 0.03).

Conclusions

Based on our preliminary experience, esophagectomy appears to be safe and feasible following combined neoadjuvant immunotherapy with chemotherapy for locally advanced esophageal cancer.
Identification of Down-Regulated ADH1C is Associated With Poor Prognosis in Colorectal Cancer Using Bioinformatics Analysis
Authors: Li Ming , Liu Ziming , Song Jia , Wang Tian , Wang Hongjie , Wang Yanan , Guo Jiguang
Published: March 2022

Colorectal cancer (CRC) is the second most deadly cancer in the whole world, with the underlying mechanisms largely indistinct. Therefore, we aimed to identify significant pathways and genes involved in the initiation, formation and poor prognosis of CRC using bioinformatics methods. In this study, we compared gene expression profiles of CRC cases with those from normal colorectal tissues from three chip datasets (GSE33113, GSE23878 and GSE41328) to identify 105 differentially expressed genes (DEGs) that were common to the three datasets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the highest proportion of up-regulated DEGs was involved in extracellular region and cytokine-cytokine receptor interaction pathways. Integral components of membrane and bile secretion pathways were identified as containing down-regulated DEGs. 13 hub DEGs were chosen and their expression were further validated by GEPIA. Only four DEGs (ADH1C, CLCA4, CXCL8 and GUCA2A) were associated with a significantly lower overall survival after the prognosis analysis. Lower ADH1C protein level and higher CXCL8 protein level were verified by immunohistochemical staining and western blot in clinical CRC and normal colorectal tissues. In conclusion, our study indicated that the extracellular tumor microenvironment and bile metabolism pathways play critical roles in the formation and progression of CRC. Furthermore, we confirmed ADH1C being down-regulated in CRC and reported ADH1C as a prognostic predictor for the first time.
Routing Brain Traffic Through the Von Neumann Bottleneck: Parallel Sorting and Refactoring
Authors: Pronold Jari , Jordan Jakob , Wylie Brian J. N. , Kitayama Itaru , Diesmann Markus , Kunkel Susanne
Published: March 2022

Generic simulation code for spiking neuronal networks spends the major part of the time in the phase where spikes have arrived at a compute node and need to be delivered to their target neurons. These spikes were emitted over the last interval between communication steps by source neurons distributed across many compute nodes and are inherently irregular and unsorted with respect to their targets. For finding those targets, the spikes need to be dispatched to a three-dimensional data structure with decisions on target thread and synapse type to be made on the way. With growing network size, a compute node receives spikes from an increasing number of different source neurons until in the limit each synapse on the compute node has a unique source. Here, we show analytically how this sparsity emerges over the practically relevant range of network sizes from a hundred thousand to a billion neurons. By profiling a production code we investigate opportunities for algorithmic changes to avoid indirections and branching. Every thread hosts an equal share of the neurons on a compute node. In the original algorithm, all threads search through all spikes to pick out the relevant ones. With increasing network size, the fraction of hits remains invariant but the absolute number of rejections grows. Our new alternative algorithm equally divides the spikes among the threads and immediately sorts them in parallel according to target thread and synapse type. After this, every thread completes delivery solely of the section of spikes for its own neurons. Independent of the number of threads, all spikes are looked at only two times. The new algorithm halves the number of instructions in spike delivery which leads to a reduction of simulation time of up to 40 %. Thus, spike delivery is a fully parallelizable process with a single synchronization point and thereby well suited for many-core systems. Our analysis indicates that further progress requires a reduction of the latency that the instructions experience in accessing memory. The study provides the foundation for the exploration of methods of latency hiding like software pipelining and software-induced prefetching.
The Plasma Distribution of Non-cholesterol Sterol Precursors and Products of Cholesterol Synthesis and Phytosterols Depend on HDL Concentration
Authors: Nunes Valéria Sutti , da Silva Eliton Juniro , Ferreira Guilherme da Silva , Assis Sayonara Ivana Santos de , Cazita Patrícia Miralda , Nakandakare Edna Regina , Zago Vanessa Helena de Souza , de Faria Eliana Cotta , Quintão Eder Carlos Rocha
Published: March 2022

Non-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity.
N6-Methyladenosine Regulators Promote Malignant Progression of Gastric Adenocarcinoma
Authors: Zhao Yibin , Yan Xiao , Wang Yu , Zhou Juan , Yu Yang
Published: March 2022

N6-methyladenosine (m6A) RNA methylation is dynamically and reversibly regulated by methyltransferases, binding proteins, and demethylases. The restoration of m6A to adenosine could result in demethylation modifications. Abnormalities in m6A epigenetic modifications in cancer are of increasing interest in recent years. According to the progression and prognostic performance of m6A epigenetic modifications in gastric adenocarcinoma (STAD), this study comprehensively analyzed the m6A modification patterns of gastric adenocarcinoma specimens in The Cancer Genome Atlas (TCGA) database based on 20 m6A regulators. Here, we found that 20 m6A RNA methylation regulators were high-expressed in gastric adenocarcinoma. m6A RNA methylation regulators were closely associated with pT staging of gastric cancer. Based on such findings, we developed a prognostic model using four m6A RNA methylation regulators (IGF2BP1, RBM15, FTO, ALKBH5), and the FTO was confirmed as an independent prognostic marker.
Identification of a Novel Tumor Microenvironment Prognostic Signature for Bladder Urothelial Carcinoma
Authors: Xu Chaojie , Pei Dongchen , Liu Yi , Yu Yang , Guo Jinhua , Liu Nan , Kang Zhengjun
Published: March 2022

Background

The tumor microenvironment (TME) regulates the proliferation and metastasis of solid tumors and the effectiveness of immunotherapy against them. We investigated the prognostic role of TME-related genes based on transcriptomic data of bladder urothelial carcinoma (BLCA) and formulated a prediction model of TME-related signatures.

Methods

Molecular subtypes were identified using the non-negative matrix factorization (NMF) algorithm based on TME-related genes from the TCGA database. TME-related genes with prognostic significance were screened with univariate Cox regression analysis and lasso regression. Nomogram was developed based on risk genes. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used for inner and outer validation of the model. Risk scores (RS) of patients were calculated and divided into high-risk group (HRG) and low-risk group (LRG) to compare the differences in clinical characteristics and PD-L1 treatment responsiveness between HRG and LRG.

Results

We identified two molecular subtypes (C1 and C2) according to the NMF algorithm. There were significant differences in overall survival (OS) (p<0.05), progression-free survival (PFS) (p<0.05), and immune cell infiltration between the two subtypes. A total of eight TME-associated genes (CABP4, ZNF432, BLOC1S3, CXCL11, ANO9, OAS1, FBN2, CEMIP) with independent prognostic significance were screened to build prognostic risk models. Age (p<0.001), grade (p<0.001), and RS (p<0.001) were independent predictors of survival in BLCA patients. The developed RS nomogram was able to predict the prognosis of BLCA patients at 1, 3, and 5 years more potentially than the models of other investigators according to ROC and DCA. RS showed significantly higher values (p = 0.047) in patients with stable disease (SD)/progressive disease (PD) compared to patients with complete response (CR)/partial response (PR).

Conclusions

We successfully clustered and constructed predictive models for TME-associated genes and helped guide immunotherapy strategies.
Sulforaphane Modulates the Inflammation and Delays Neurodegeneration on a Retinitis Pigmentosa Mice Model
Authors: Canto Antolín , Martínez-González Javier , Miranda María , Olivar Teresa , Almansa Inma , Hernández-Rabaza Vicente
Published: March 2022

The term retinitis pigmentosa (RP) describes a large group of hereditary retinopathies. From a cellular view, retinal degeneration is prompted by an initial death of rods, followed later by cone degeneration. This cellular progressive degeneration is translated clinically in tunnel vision, which evolves to complete blindness. The mechanism underlying the photoreceptor degeneration is unknown, but several mechanisms have been pointed out as main co-stars, inflammation being one of the most relevant. Retinal inflammation is characterized by proliferation, migration, and morphological changes in glial cells, in both microglia and Müller cells, as well as the increase in the expression of inflammatory mediators. Retinal inflammation has been reported in several animal models and clinical cases of RP, but the specific role that inflammation plays in the pathology evolution remains uncertain. Sulforaphane (SFN) is an antioxidant natural compound that has shown anti-inflammatory properties, including the modulation of glial cells activation. The present work explores the effects of SFN on retinal degeneration and inflammation, analyzing the modulation of glial cells in the RP rd10 mice model. A daily dose of 20 mg/kg of sulforaphane was administered intraperitoneally to control (C57BL/6J wild type) and rd10 (Pde6brd10) mice, from postnatal day 14 to day 20. On postnatal day 21, euthanasia was performed. Histological retina samples were used to assess cellular degeneration, Müller cells, and microglia activation. SFN administration delayed the loss of photoreceptors. It also ameliorated the characteristic reactive gliosis, assessed by retinal GFAP expression. Moreover, sulforaphane treatment regulated the microglia activation state, inducing changes in the microglia morphology, migration, and expression through the retina. In addition, SFN modulated the expression of the interleukins 1β, 4, Ym1, and arginase inflammatory mediators. Surprisingly, M2 polarization marker expression was increased at P21 and was reduced by SFN treatment. To summarize, SFN administration reduced retinal neurodegeneration and modified the inflammatory profile of RP, which may contribute to the SFN neuroprotective effect.
Decline in Liver Mitochondria Metabolic Function Is Restored by Hochuekkito Through Sirtuin 1 in Aged Mice With Malnutrition
Authors: Nahata Miwa , Fujitsuka Naoki , Sekine Hitomi , Shimobori Chika , Ohbuchi Katsuya , Iizuka Seiichi , Mogami Sachiko , Ohnishi Shunsuke , Takeda Hiroshi
Published: March 2022

Malnutrition impairs basic daily activities and leads to physical frailty, which is aggravated in the elderly compared with young adults. It is also well-known that the elderly are more vulnerable to metabolic stress. Therefore, in this study, using a food restricted (FR) mouse, we aimed to evaluate the effect of aging on locomotor activity and liver metabolic function. Further, we also investigated the involvement of hepatic mitochondria in liver metabolic function during aging, as well as the therapeutic benefit of the traditional Japanese medicine, hochuekkito (HET). Our findings indicated that following food restriction provided as 30% of ad libitum intake for 5 days, the locomotor activity was lower in 23–26-month-old (aged) mice than in 9-week-old (young) mice. Further, compared with young mice, aged mice exhibited significant decreases in the levels of metabolites related to the urea cycle, mitochondrial function, and anti-oxidative stress. The livers of the aged mice also showed a greater decrease in mitochondrial DNA copy number than young mice. Furthermore, the gene expression levels of sirtuin 1 (SIRT1) and mitochondrial biogenesis-related regulators were attenuated in aged mice. However, these changes were partially restored by HET treatment, which also improved locomotor activity, and combined treatment with alanine resulted in more significant effects in this regard. Therefore, our findings suggested that the decrease in locomotor activity in aged FR mice was associated with a decline in the metabolic function of hepatic mitochondria via decreased SIRT1 expression, which was restored by HET treatment. This implies that enhancing the metabolic function of liver mitochondria can contribute to alleviating energy deficiency in the elderly.
Storage Temperature or Thermal Treatments During Long Egg Storage Duration Influences Hatching Performance and Chick Quality
Authors: Guinebretière Maryse , Puterflam Julie , Keïta Alassane , Réhault-Godbert Sophie , Thomas Rodolphe , Chartrin Pascal , Cailleau-Audouin Estelle , Coudert Edouard , Collin Anne
Published: March 2022

This study was designed to improve the hatching performance, chick robustness and poultry health in the event of long-term egg storage and suboptimal age of the reproductive flock. A total of 9,600 eggs from one young breeder flock (28 weeks of age, batch B) and 9,600 eggs from an older breeder flock (59 weeks of age, batch E) were used (ROSS 308). Each batch was separated into three sub-groups and stored for 14 days. The first sub-group of eggs (Cool, group C) was stored at 11.6°C. The second sub-group of eggs (Warm, group W) was stored at 18.3°C with two pre-incubation on days 6 and 10 of the storage period. The final sub-group of eggs (Control, group Ct) was stored at 18.3°C throughout the storage period. Eggs were similarly incubated and hatched birds were raised on the same experimental farm. In both batches, embryonic development was significantly more advanced in W eggs than in C and Ct eggs ( p < 0.01). In both batches, C and W treatments decreased early embryonic mortality by more than 10% compared with Ct, decreased the proportion of late-hatched chicks and improved the percentage of first grade chicks: in batch E, 42% of Ct eggs were first grade chicks vs. 57% in group W and 59% in group C. Benefits were even higher in batch B, where only 60% of Ct eggs gave first grade chicks vs. 83% in others groups. The hatching rate was thus higher in groups C and W regardless of flock age: for batch B eggs, 85% hatched in W and 84% in C vs. 62% in Ct, while for batch E eggs, 59% hatched in W and 61% in C vs. 45% in Ct. Day-old Ct chicks from batch E were heavier than W and C ones, and heavier than W chicks from batch B ( p < 0.05). Long-term parameters on farm were not significantly different between groups. Thermal treatments during the storage of eggs from both young and old breeder flocks counterbalance the negative effects of prolonged egg storage on hatching rate, without altering chicken performance during rearing.
A Review of the Relationship Between EFL Teachers’ Academic Buoyancy, Ambiguity Tolerance, and Hopelessness
Authors: Huang Shuyun
Published: March 2022

Second/foreign language education has been approved emotionally tense due to its inherent challenges, adversities, complications, and ambiguities. These factors can affect various language teaching and learning domains. Hence, it is critical for EFL teachers to be buoyant and tolerant of ambiguity so that they can teach efficiently and prevent a sense of hopelessness that can damage everything. Although there are investigations on these variables in L2 contexts, their main focus has been on EFL students and teachers’ perspectives have been largely ignored. Against this shortcoming, this study aimed to review the definitions, conceptualizations, and research findings related to teachers’ academic buoyancy, ambiguity tolerance, and hopelessness. Moreover, practical implications for EFL teachers and teacher trainers are presented to increase their awareness of language teaching challenges and ways to overcome them. Finally, the study provides directions for future research.