bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Kompetensi Sumber Daya Manusia dan Kualitas Pelayanan terhadap Kepuasaan Pasien Umum yang Berdampak Kepada Berkunjung Kembali di Klinik Andilia Kabupaten Bogor
Authors: Honifa Honifa , Derriawan Derriawan , Sampurno Sampurno
Published: May 2022

Klinik harus memiliki sumber daya yang profesional. Klinik juga memiliki tanggung jawab terhadap kualitas pelayanan yang diberikan terhadap pasien. Persaingan yang terjadi tidak hanya dari sisi teknologi pemeriksaan, akan tetapi persaingan yang lebih berat yaitu persaingan dalam pelayanan kesehatan yang berkualitas. adapun tujuan penelitian ini yaitu Untuk menganalisis pengaruh kompetensi sumber daya manusia (SDM) dan kualitas pelayanan terhadap kepuasaan pasien yang berdampak kepada berkunjung kembali di klinik Andilia Kabupaten Bogor. Jenis penelitian ini adalah kuantitatif deskriptif dan survei. Penelitian deskriptif dilakukan untuk mengetahui dan memaparkan karakteristik dari beberapa variabel dalam situasi. Sedangkan penelitian kuantitatif adalah suatu pendekatan penelitian yang bersifat obyektif, mencakup pengumpulan dan analisa data kuantitatif serta menggunakan pengujian statistik. Metode survei merupakan metode dalam penelitian yang informasinya dikumpulkan dari beberapa sampel Penelitian ini menggunakan data primer yang didapat dari kuesioner dan diolah menggunakan metode statistik SEM (Structural Equation Modelling) dengan program lisrel Pengambilan Sampel dalam penelitian dengan teknik probability sampling yaitu pasien umum yang berobat di klinik Andilia Kabupaten Bogor yang telah memenuhi kriteria inklusi, berjumlah dua ratus dua puluh lima responden. Hasil penelitian menunjukkan Kompetensi SDM berpengaruh terhadap kualitas pelayanan pasien t value 14,06 >1,96 Kompetensi SDM berpengaruh terhadap kepuasaan pasien t value 6,54 >1,96 Kualitas pelayanan berpengaruh terhadap kepuasaan pasien t value 6,72 >1,96 Kompetensi SDM berpengaruh terhadap kunjungan kembali t value 4,44 >1,96 Kualitas pelayanan berpengaruh terhadap kunjungan kembali t value 4,47 >1,96 Kepuasaan pasien berpengaruh terhadap kunjungan kembali t value 4,43 >1,96 Hasil dikatakan berpengaruh karena t-value > t-table 1,96 Kesimpulan Kepuasaan pasien menjadi mediator parsial antara dimensi kualitas layanan terhadap minat kunjungan ulang. Pelanggan yang sangat puas akan berminat melakukan kunjungan ulang.
Rancang Bangun Aplikasi Pengelolaan Bug Tracker Berbasis Web pada Pengembangan Software
Authors: Mandala Sendra Ilham , Fitriani Leni , Sutedi Ade
Published: May 2022

Dalam proses pengambangan perangkat lunak, Suatu tim pengembang berkemungkinan besar mendapatkan bug dalam pengembangan perangkat lunak. Untuk mengatasi masalah dibutuhkan suatu alat untuk mengelola bug yang ada pada suatu proyek pengembangan perangkat lunak. Tujuan dibuat rancang bangun suatu aplikasi bug tracker yaitu untuk memudahkan suatu tim proyek software development dalam mengevaluasi, mengoreksi, melacak, dan mengontrol bug dan masalah pada suatu proyek. metode yang digunakan adalah Rational Unified Process yang memiliki empat tahap, yaitu Inception, Elaboration, Construction, dan Transition dan menggunakan framework php yaitu laravel. Hasil penelitian ini berupa aplikasi bug tracker berbasis web untuk mengelola bug pada suatu project secara online yang terdapat fitur seperti Upload gambar untuk menambah informasi berupa file gambar, dan fitur list step to reproduce berupa informasi list berupa text.
Panggilan untuk Merekonstruksi Strategi Pendidikan Agama Kristen yang Kontekstual dan Inovatif
Authors: Hasugian Johanes Waldes , Kakiay Agusthina Christina , Sahertian Novita Loma , Patty Febby Nancy
Published: May 2022

Pendidikan agama Kristen berlangsung secara normatif-ritualistik-konvensional dan cenderung membatasi diri pada perubahan serta menunjukkan praksis di zona nyaman. Praksis semacam itu mengindikasikan bahwa kepedulian dan kepekaan dalam dinamika PAK hanyalah menjadi tugas orang-orang tertentu. Kerapuhan praksis PAK semakin terlihat ketika berjumpa pada masa dimana kecekatan, kapasitas dan kualitas menjadi orientasi dalam sistem sosial. PAK harus mampu menghadapi berbagai isu sosial sekaligus berupaya memperkokoh pondasi serta menjadi jawaban atas kebutuhan dan pergumulan hidup orang-orang. Oleh karena itu, PAK harus direkonstruksi secara kontekstual dan inovatif sehingga PAK benar-benar hadir menjadi wahana dimana orang-orang dapat belajar memaknai hidup dan berdampak bagi banyak orang. Dengan metode penelitian deskriptif-analitis, penelitian ini bertujuan untuk menganalisis berbagai persoalan dalam praktik PAK, baik di sekolah, gereja dan keluarga atau masyarakat, serta menghadirkan rumusan strategi yang kontekstual dan inovatif dalam praksis PAK. Hasil penelitian ini menunjukkan bahwa perhatian PAK tidak hanya sebatas di sekolah, masyarakat atau keluarga dan gereja namun lebih luas menjangkau isu-isu sosial lainnya yang melekat dengan tugas dan panggilan PAK. Berbagai permasalahan atau fenomena yang terjadi dalam kaitannya dengan praksis PAK menegaskan pentingnya upaya rekonstruksi strategi PAK yang kontekstual dan inovatif. Rekonstruksi strategi PAK dimaksudkan agar memperkuat bangunan PAK yang rapuh dan tidak adaptif dengan perkembangan dan kemajuan zaman dewasa ini.
Brain Fluid Channels for Metabolite Removal
Authors: Maloveská M , Humeník F , Vikartovská Z , Hudáková N , Almášiová V , Krešáková L , Čížková D
Published: May 2022

The adult human brain represents only 2 % of the body's total weight, however it is one of the most metabolically active organs in the mammalian body. Its high metabolic activity necessitates an efficacious waste clearance system. Besides the blood, there are two fluids closely linked to the brain and spinal cord drainage system: interstitial fluid (ISF) and cerebrospinal fluid (CSF). The aim of this review is to summarize the latest research clarifying the channels of metabolite removal by fluids from brain tissue, subarachnoid space (SAS) and brain dura (BD). Special attention is focused on lymphatic vascular structures in the brain dura, their localizations within the meninges, morphological properties and topographic anatomy. The review ends with an account of the consequences of brain lymphatic drainage failure. Knowledge of the physiological state of the clearance system is crucial in order to understand the changes related to impaired brain drainage.
Progesterone Inhibitory Role on Gastrointestinal Motility
Authors: Alqudah M , Al-Shboul O , Al-Dwairi A , Al-U´Dat D G , Alqudah A
Published: May 2022

Progesterone is a steroidal hormone that is produced from the corpus luteum of the ovaries and from the placenta. The main function of progesterone is to promote the secretory differentiation in the endometrium of the uterus and to maintain pregnancy by inhibiting uterine contractions throughout pregnancy. Progesterone performs its actions by activating the classical progesterone nuclear receptors that affect gene transcription and by the non-classical activation of cell surface membrane receptors that accounts for the rapid actions of progesterone. Besides the reproductive roles of progesterone, it exerts functions in many tissues and systems such as the nervous system, the bone, the vascular system, and the gastrointestinal (GI) tract. This review will summarize the recent literature that investigated the role of progesterone in GI tract motility. Most literature indicates that progesterone exerts an inhibitory role on gut smooth muscle cells in part by elevating nitric oxide synthesis, which induces relaxation in smooth muscle. Moreover, progesterone inhibits the signaling pathways that lead to contraction such as Rho kinase inhibition. These data serve as a quick resource for the future directions of progesterone research that could lead to better understanding and more effective treatment of gender-related GI tract motility disorders.
General Anesthesia and Electrocardiographic Parameters in in vivo Experiments Involving Rats
Authors: Švorc P , Švorc P
Published: May 2022

In in vivo cardiovascular or toxicological studies involving rat models, changes in selected electrocardiographic (ECG) parameters are monitored after various interventions to assess the origin and development of heart rhythm disorders. Each ECG parameter has diagnostic significance; as such, commonly evaluated ECG parameters, including heart rate, PR interval, P wave duration, P wave amplitude, QRS complex, QT and QTc interval duration, R wave and T wave amplitude, of rats under various types of general anesthesia were the focus of this study. Studies that performed in vivo cardiovascular or toxicological experiments in rats were retrieved from a search of the Web of Science database for articles published mainly between 2000 and 2021. In total, the search retrieved 123 articles. ECG parameters that were reported as baseline or control values were summarized and averages with ranges were calculated. It is important to be cautious when interpreting results and, in discussions addressing the mechanisms underlying a given type of arrhythmia, acknowledge that initial ECG parameters may already be affected to some extent by the general anesthesia as well as by sex and the time of day the experiments were performed.
Türkiye’de Sosyolojinin İnşasında Siyasetin Belirleyiciliği: Kuruluş Dönemi Üzerine Bir Değerlendirme
Authors: TURĞUT Faruk
Published: May 2022

Bu çalışmada, Türkiye’de sosyolojinin bir bilim olarak kuruluşunun ilk dönemine odaklanılmıştır. Batı Avrupa’da modern bir bilimsel disiplin olarak on dokuzuncu yüzyılda ortaya çıkan sosyolojinin Osmanlı Devleti’ne intikal ettirilmesi sürecindeki sosyal arka plan üzerinde durulmuştur. Özellikle devletin/toplumun içerisinde bulunduğu iç ve dış siyasal ortamın sosyolojinin biçimlenişi, gelişimi ve kurumsallaşması üzerindeki belirleyiciliği tespit edilmeye çalışılmıştır. Aynı bağlamda, siyasetin etkisinden bağımsız olarak değerlendirilemeyecek olan Batılılaşma ve pozitivizmin etkisi de tartışmaya açılmıştır. Dönemin hem iktidarının hem de aydınlarının benimsediği Batılılaşma reformların yönünü ve amacını belirlemiştir. Pozitivizm ise programın bilimsel zemini ve yöntemini belirlemiştir. Toplumsal alanın hemen her boyutunda hâkim olan bu iki paradigma sosyolojinin inşasında da temel karakteristik olmuştur. Bu çalışmada, Osmanlı’nın son döneminden başlayarak 1940 yılına kadar devam eden süreç değerlendirilmiştir. Siyasetin, sosyolojinin kuruluşundaki belirleyiciliği dönem içerisinde gerçekleştirilen sosyolojik çalışmalar üzerinden analiz edilmiştir. Özellikle iki kurucu isim olan Prens Sabahattin ve Ziya Gökalp’in çalışmaları üzerine odaklanılmıştır. Yukarıda odağa alınan konuların neticesinde, Türkiye’de sosyoloji yeni bir bilim olarak inşa edilirken siyasete koşullu bir şekilde varlık kazandığı tespit edilmiştir.
Approxism or Socio-Existential Realism: Investigation on Contemporary Revolutionary Aesthetics in the African Novel: A Critical Reading of Seydou Badian’s in “Storm
Authors: ETEKA James , DOUGLAS Josiah Gogo-ogute
Published: May 2022

Realism, in the romantic universe, can be compared to a drama of marveled theater pushing the spectator outside of his being by transforming him into a creature full of unexpected gestures. This realism which reflects in the mirror the existence of man in society never ceases to launch universal calls by informing sapiens-beings to analyze, criticize and, if necessary, to rebuild their society, even the values and the cosmic practices immanent in their landscape over time and history. Realism, which henceforth, in this company, can also be designated as “Approxism” is “a force that goes”, if you will, a force in movement. It is an aquilon that awakens man in the midst of his deep sleep, warning him to react against all the negations in the itinerary of his existence in the society in which he is an integral part. In this case, the man who exists must face upsetting novelties in the society where he exists. It is such a position that characterizes “socio-existential approxism” in African literature. This work allows us to make a critical and revolutionary investigation in the contemporary African novel.
Paper-Based Portable Sensor and Nanosensor For Sulfur Dioxide Detection
Authors: Le Thuy , Macchi Samantha , Jalihal Amanda , Szwedo Sylvia , Siraj Noureen
Published: May 2022

Sulfur dioxide (SO2) pollution has become an increasing issue world-wide as it is produced both naturally and as industrial waste. Thus, it is critical to develop a sensor and detection methods to analyze SO2 in the atmosphere. In order to design and generate an effective sensor that detects low levels of SO2, fuchsine dyes have been used as a potential sensor material. New hydrophobic derivatives of Pararosaniline hydrochloride (pR-HCl) is developed to further improve the sensitivity of fuchsine dyes towards SO2 gas. It has been shown that these dyes can provide an economic and efficient colorimetric detection of SO2. In this work, (pR-HCl) is converted into an ionic material (IM) via a facile ion exchange reaction with bis (trifluoromethane) sulfonamide (NTF2) counterion. The new, hydrophobic derivative, pararosaniline bis (trifluoromethane) sulfonamide (pR-NTF2) IM was converted into stable aqueous ionic nanomaterials (INMs) by a reprecipitation method. Examination of absorption spectra results revealed that pR-NTF2 IM exhibits enhanced molar absorptivity in comparison to the parent dye (pR-HCl). The improved photophysical properties allowed a framework for a highly sensitive nanosensor for detection of SO2. A paper based portable SO2 sensor was also developed and tested for its ability to colorimetric detection of SO2. The cost effective and stable paper-based sensor exhibited the rapid response to decolorize the fuchsine dyes in few seconds as compared to their parent compound.

Keywords: SO2 Detection, Portable and Low-cost Sensor, Nanosensor.
DivCom: A Tool for Systematic Partition of Groups of Microbial Profiles Into Intrinsic Subclusters and Distance-Based Subgroup Comparisons
Authors: Intze Evangelia , Lagkouvardos Ilias
Published: May 2022

When analyzing microbiome data, one of the main objectives is to effectively compare the microbial profiles of samples belonging to different groups. Beta diversity measures the level of similarity among samples, usually in the form of dissimilarity matrices. The use of suitable statistical tests in conjunction with those matrices typically provides us with all the necessary information to evaluate the overall similarity of groups of microbial communities. However, in some cases, this approach can lead us to deceptive conclusions, mainly due to the uneven dispersions of the groups and the existence of unique or unexpected substructures in the dataset. To address these issues, we developed divide and compare (DivCom), an automated tool for advanced beta diversity analysis. DivCom reveals the inner structure of groups by dividing their samples into the appropriate number of clusters and then compares the distances of every profile to the centers of these clusters. This information can be used for determining the existing interrelation of the groups. The proposed methodology and the developed tool were assessed by comparing the response of anemic patients with or without inflammatory bowel disease to different iron replacement therapies. DivCom generated results that revealed the inner structure of the dataset, evaluated the relationship among the clusters, and assessed the effect of the treatments. The DivCom tool is freely available at: https://github.com/Lagkouvardos/DivCom.
Thermotropic Liquid Crystals for Temperature Mapping
Authors: Miskovic Vanja , Malafronte Elena , Minetti Christophe , Machrafi Hatim , Varon Carolina , Iorio Carlo Saverio
Published: May 2022

Wound management in Space is an important factor to be considered in future Human Space Exploration. It demands the development of reliable wound monitoring systems that will facilitate the assessment and proper care of wounds in isolated environments, such as Space. One possible system could be developed using liquid crystal films, which have been a promising solution for real-time in-situ temperature monitoring in healthcare, but they are not yet implemented in clinical practice. To progress in the latter, the goal of this study is twofold. First, it provides a full characterization of a sensing element composed of thermotropic liquid crystals arrays embedded between two elastomer layers, and second, it discusses how such a system compares against non-local infrared measurements. The sensing element evaluated here has an operating temperature range of 34–38°C, and a quick response time of approximately 0.25 s. The temperature distribution of surfaces obtained using this system was compared to the one obtained using the infrared thermography, a technique commonly used to measure temperature distributions at the wound site. This comparison was done on a mimicked wound, and results indicate that the proposed sensing element can reproduce the temperature distributions, similar to the ones obtained using infrared imaging. Although there is a long way to go before implementing the liquid crystal sensing element into clinical practice, the results of this work demonstrate that such sensors can be suitable for future wound monitoring systems.
Asiaticoside Combined With Carbon Ion Implantation to Improve the Biocompatibility of Silicone Rubber and to Reduce the Risk of Capsule Contracture
Authors: Liu Xing , Song Ya-Jun , Chen Xing , Huang Meng-Ya , Zhao Chen-Xi , Zhou Xun , Zhou Xin
Published: May 2022

Capsular contracture caused by silicone rubber is a critical issue in plastic surgery that urgently needs to be solved. Studies have shown that carbon ion implant in silicone rubber (carbon silicone rubber, C-SR) can significantly improve the capsular structure, but the effect of this improvement only appear 2months or later. In this study, asiaticoside combined with carbon silicone rubber was used to explore the changes in the capsule to provide a reference for the treatment of capsule contracture. Human fibroblasts (HFF-1) were used for in vitro experiments. The combined effect of asiaticoside and carbon silicone rubber on cell proliferation was determined by the CCK8 method, cell migration changes were measured by Transwell assays, cell cycle changes were measured by flow cytometry, and the expression levels of fibroblast transformation markers (vimentin and α-SMA), collagen (Col-1A1) and TGF-β/Smad signaling pathway-related proteins (TGF-β1, TβRI, TβRII and Smad2/3) were detected by immunofluorescence. In vivo experiments were carried out by subcutaneous implantation of the material in SD rats, and asiaticoside was oral administered simultaneously. WB and ELISA were used to detect changes in the expression of TGF-β/Smad signaling pathway-related proteins. TGF-β/Smad signaling pathway proteins were then detected and confirmed by HE, Masson and immunohistochemical staining. The results shown that asiaticoside combined with carbon ion implantation inhibited the viability, proliferation and migration of fibroblasts on silicone rubber. In vitro immunofluorescence showed that the secretion levels of α-SMA and Col-1A1 were significantly decreased, the transformation of fibroblasts into myofibroblasts was weakened, and the TGF-β/Smad signaling pathway was inhibited. In vivo experimental results showed that asiaticoside combined with carbon silicone rubber inhibited TGF-β1 secretion and inhibited the TGF-β/Smad signaling pathway, reducing the thickness of the capsule and collagen deposition. These results imply that carbon silicone rubber combined with asiaticoside can regulate the viability, proliferation and migration of fibroblasts by inhibiting the TGF-β/Smad signaling pathway and reduce capsule thickness and collagen deposition, which greatly reduces the incidence of capsule contracture.
Comparative Proteomics Reveals Evidence of Enhanced EPA Trafficking in a Mutant Strain of Nannochloropsis oculata
Authors: Wan Razali Wan Aizuddin , Evans Caroline A. , Pandhal Jagroop
Published: May 2022

The marine microalga Nannochloropsis oculata is a bioproducer of eicosapentaenoic acid (EPA), a fatty acid. EPA is incorporated into monogalactosyldiacylglycerol within N. oculata thylakoid membranes, and there is a biotechnological need to remodel EPA synthesis to maximize production and simplify downstream processing. In this study, random mutagenesis and chemical inhibitor-based selection method were devised to increase EPA production and accessibility for improved extraction. Ethyl methanesulfonate was used as the mutagen with selective pressure achieved by using two enzyme inhibitors of lipid metabolism: cerulenin and galvestine-1. Fatty acid methyl ester analysis of a selected fast-growing mutant strain had a higher percentage of EPA (37.5% of total fatty acids) than the wild-type strain (22.2% total fatty acids), with the highest EPA quantity recorded at 68.5 mg/g dry cell weight, while wild-type cells had 48.6 mg/g dry cell weight. Label-free quantitative proteomics for differential protein expression analysis revealed that the wild-type and mutant strains might have alternative channeling pathways for EPA synthesis. The mutant strain showed potentially improved photosynthetic efficiency, thus synthesizing a higher quantity of membrane lipids and EPA. The EPA synthesis pathways could also have deviated in the mutant, where fatty acid desaturase type 2 (13.7-fold upregulated) and lipid droplet surface protein (LDSP) (34.8-fold upregulated) were expressed significantly higher than in the wild-type strain. This study increases the understanding of EPA trafficking in N. oculata, leading to further strategies that can be implemented to enhance EPA synthesis in marine microalgae.
Identification of a Pyroptosis-Related Gene Signature for Predicting the Immune Status and Prognosis in Lung Adenocarcinoma
Authors: Gong Zetian , Li Qifan , Yang Jian , Zhang Pengpeng , Sun Wei , Ren Qianhe , Tang Junjie , Wang Wei , Gong Hui , Li Jun
Published: May 2022

Background: Pyroptosis is a form of programmed cell death triggered by the rupture of cell membranes and the release of inflammatory substances; it is essential in the occurrence and development of cancer. A considerable number of studies have revealed that pyroptosis is closely associated to the biological process of several cancers. However, the role of pyroptosis in lung adenocarcinoma (LUAD) remains elusive. The purpose of this study was to explore the prognostic role of pyroptosis-related genes (PRGs) and their relationship with the tumor immune microenvironment (TIME) in LUAD.

Methods: Gene expression profiles and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A prognostic PRG signature was established in the training set and verified in the validation sets. Functional enrichment and immune microenvironment analyses related to PRGs were performed and a nomogram based on the risk score and clinical characteristics was established. What is more, quantitative real-time PCR (qRT-PCR) analysis was applied in order to verify the potential biomarkers for LUAD.

Results: A prognostic signature based on five PRGs was constructed to separate LUAD patients into two risk groups. Patients in the high-risk group had worse prognoses than those in the low-risk group. The signature was identified as independent via Cox regression analyses and obtained the largest area under the curve (AUC = 0.677) in the receiver operating characteristic (ROC). Functional enrichment and immune microenvironment analyses demonstrated that the immune status was significantly different in the two subgroups and that immunotherapy may be effective for the high-risk group. Furthermore, qRT-PCR analysis verified that serum PRKACA and GPX4 could serve as diagnostic biomarkers for LUAD.

Conclusion: Overall, a risk signature based on five PRGs was generated, providing a novel perspective on the determinants of prognosis and survival in LUAD, as well as a basis for the development of individualized regimes.
Humic Substances Derived From Biomass Waste During Aerobic Composting and Hydrothermal Treatment: A Review
Authors: Hu Zhong-Ting , Huo Weizhong , Chen Yue , Zhang Qiang , Hu Mian , Zheng Weicheng , Shao Yuchao , Pan Zhiyan , Li Xiaonian , Zhao Jun
Published: May 2022

Humic substances (HSs) occupy 80% of organic matter in soil and have been widely applied for soil remediation agents, potential battery materials, and adsorbents. Since the HS extraction rate is very low by microbial degradation in nature, artificial humification processes such as aerobic composting (AC) and hydrothermal treatment (HT) have attracted a great deal of attention as the most important strategies in HS production. This article aims to provide a state-of-the-art review on the development of conversion of biomass waste into HSs based on AC and HT for the first time in terms of mechanisms, characteristics of HSs’ molecular structure, and influencing factors. In addition, some differences based on the aforementioned information between AC and HT are reviewed and discussed in the conversion of biomass waste into HSs in a pioneering way. For biomass waste conversion, a feasible strategy on effective humification processes by combining AC with HT is proposed.
Application of Microfluidics in Detection of Circulating Tumor Cells
Authors: Li Can , He Wei , Wang Nan , Xi Zhipeng , Deng Rongrong , Liu Xiyu , Kang Ran , Xie Lin , Liu Xin
Published: May 2022

Tumor metastasis is one of the main causes of cancer incidence and death worldwide. In the process of tumor metastasis, the isolation and analysis of circulating tumor cells (CTCs) plays a crucial role in the early diagnosis and prognosis of cancer patients. Due to the rarity and inherent heterogeneity of CTCs, there is an urgent need for reliable CTCs separation and detection methods in order to obtain valuable information on tumor metastasis and progression from CTCs. Microfluidic technology is increasingly used in various studies of CTCs separation, identification and characterization because of its unique advantages, such as low cost, simple operation, less reagent consumption, miniaturization of the system, rapid detection and accurate control. This paper reviews the research progress of microfluidic technology in CTCs separation and detection in recent years, as well as the potential clinical application of CTCs, looks forward to the application prospect of microfluidic technology in the treatment of tumor metastasis, and briefly discusses the development prospect of microfluidic biosensor.
Altered mRNAs Profiles in the Testis of Patients With “Secondary Idiopathic Non-Obstructive Azoospermia”
Authors: Tang Dongdong , Li Kuokuo , Lv Mingrong , Xu Chuan , Geng Hao , Wang Chao , Cheng Huiru , He Xiaojin , Zhang Yan , Cao Yunxia
Published: May 2022

Background: Non-obstructive azoospermia (NOA) is the most severe form of male infertility. Currently, known causative factors, including congenital and several acquired causes only account for approximately 30% of NOA cases. The causes for NOA remain unclear for most patients, which is known as idiopathic (iNOA). However, whether iNOA is due to congenital defects or acquired abnormalities is a confusing problem due to the delayed diagnosis of this frustrating condition until the childbearing age. Therefore, we collected several cases with “secondary idiopathic NOA” and detected the altered mRNAs profiles in the testicular tissues to explore the possible molecular basis.

Materials and Methods: In this study, several patients with a previous history of natural pregnancy with their partners before, who were diagnosed as iNOA based on the outcomes of routine semen analysis and multiple testis biopsies now, were enrolled. Some known risk factors and genetic factors were excluded. Therefore, we defined this phenotype as “secondary idiopathic NOA.” To explore the possible molecular basis of this disease, we performed mRNA expression analysis through next-generation sequencing on three cases and other three patients with obstructive azoospermia as controls. Bioinformatics analyses were conducted to assess differentially expressed genes and possible biological mechanisms involved in the disease. Quantitative real-time reverse transcription polymerase chain reaction assays were applied to confirm the results in several selected mRNAs involved in stages and metabolism of Sertoli cells.

Results: A series of mRNAs were found to be altered in testicular tissues between patients with “secondary idiopathic NOA” and controls, including 6,028 downregulated and 3,402 upregulated mRNAs. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses revealed a range of GO and KEGG terms, such as cellular process involved in reproduction, protein degradation, and absorption.

Conclusion: The present study introduces a novel classification called “secondary idiopathic NOA.” We provide a global view of the altered mRNAs involved in spermatogenetic failure in these cases. Regarding the limited samples, further studies should be taken to understand this new classification.
Thyroid Hormones Deficiency Impairs Male Germ Cell Development: A Cross Talk Between Hypothalamic-Pituitary-Thyroid, and—Gonadal Axes in Zebrafish
Authors: Rodrigues Maira S. , Tovo-Neto Aldo , Rosa Ivana F. , Doretto Lucas B. , Fallah Hamideh P. , Habibi Hamid R. , Nóbrega Rafael H.
Published: May 2022

In vertebrates, thyroid hormones are critical players in controlling different physiological processes such as development, growth, metabolism among others. There is evidence in mammals that thyroid hormones are also an important component of the hormonal system that controls reproduction, although studies in fish remain poorly investigated. Here, we tested this hypothesis by investigating the effects of methimazole-induced hypothyroidism on the testicular function in adult zebrafish. Treatment of fish with methimazole, in vivo, significantly altered zebrafish spermatogenesis by inhibiting cell differentiation and meiosis, as well as decreasing the relative number of spermatozoa. The observed impairment of spermatogenesis by methimazole was correlated with significant changes in transcript levels for several genes implicated in the control of reproduction. Using an in vitro approach, we also demonstrated that in addition to affecting the components of the brain-pituitary-peripheral axis, T3 (triiodothyronine) also exerts direct action on the testis. These results reinforce the hypothesis that thyroid hormones are an essential element of multifactorial control of reproduction and testicular function in zebrafish and possibly other vertebrate species.
A Novel SNP in the Promoter Region of IGF1 Associated With Yunshang Black Goat Kidding Number via Promoting Transcription Activity by SP1
Authors: Li Kunyu , Liu Yufang , He Xiaoyun , Tao Lin , Jiang Yanting , Lan Rong , Hong Qionghua , Chu Mingxing
Published: May 2022

IGF1, a member of the insulin-like growth factor (IGF) superfamily, is also known as the growth-promoting factor (somatomedin C).IGF1is involved in vertebrate growth and development, immunity, cell metabolism, reproduction, and breeding. However, there are relatively few studies on the relationship betweenIGF1and goat reproduction. In this study, a new transcription factorSP1bound to theIGF1g. 64943050T>C promoted granulosa cell (GC) proliferation. A mutation g.64943050T>C located in the promoter region ofIGF1was identified. Association analysis revealed that the kidding number in the first and second litters and the average number of first three litters of the CC genotype (2.206 ± 0.044, 2.254 ± 0.056, and 2.251 ± 0.031) were significantly higher than those in the TC genotype (1.832 ± 0.049, 1.982 ± 0.06, and 1.921 ± 0.034) and TT genotype (1.860 ± 0.090, 1.968 ± 0.117, and 1.924 ± 0.062) (p< 0.05). The kidding number in the third litter of the CC genotype (2.355 ± 0.057) was significantly higher than that in the TT genotype (2.000 ± 0.107) (p< 0.05). Then, the function of this mutation was validated by the dual-luciferase reporter assay and EMSA. The results showed that the luciferase activity of IGF1-mutant-C was significantly higher than that of IGF1-Wild-T (p< 0.05). The EMSA also showed that the binding ability of IGF1-mutant-C was higher than that of IGF1-Wild-T (p< 0.05). Subsequently, the transcription factorSP1was predicted to bind to the mutation ofIGF1(g.64943050T>C). Overexpression of SP1 promotes the expression ofIGF1in the primary granulosa cells (GCs). The results of the CCK-8 assay and the expression of GC proliferation factors (CDK4,cyclin D1, andcyclin D2) demonstrated thatSP1promoted GC proliferation by regulatingIGF1expression. Our results suggested that theIGF1g.64943050T>C was significantly associated with the kidding number of Yunshang black goats, andSP1as a transcription factor ofIGF1binding to the mutation T>C regulated the expression ofIGF1. Furthermore,SP1promoted goat GC proliferation by regulating the expression ofIGF1, which provides a new insight for the goat fertility trait.
Emerging Role of Ubiquitin-Specific Protease 19 in Oncogenesis and Cancer Development
Authors: Rossi Fabiana Alejandra , Rossi Mario
Published: May 2022

Ubiquitination and ubiquitin-like post-translational modifications control the activity and stability of different tumor suppressors and oncoproteins. Hence, regulation of this enzymatic cascade offers an appealing scenario for novel antineoplastic targets discovery. Among the different families of enzymes that participate in the conjugation of Ubiquitin, deubiquitinating enzymes (DUBs), responsible for removing ubiquitin or ubiquitin-like peptides from substrate proteins, have attracted increasing attention. In this regard, increasing evidence is accumulating suggesting that the modulation of the catalytic activity of DUBs represents an attractive point of therapeutic intervention in cancer treatment. In particular, different lines of research indicate that USP19, a member of the DUBs, plays a role in the control of tumorigenesis and cancer dissemination. This review aims at summarizing the current knowledge of USP19 wide association with the control of several cellular processes in different neoplasms, which highlights the emerging role of USP19 as a previously unrecognized prognosis factor that possesses both positive and negative regulation activities in tumor biology. These observations indicate that USP19 might represent a novel putative pharmacologic target in oncology and underscores the potential of identifying specific modulators to test in clinical settings.
Valproic Acid Reduces Neuroinflammation to Provide Retinal Ganglion Cell Neuroprotection in the Retina Axotomy Model
Authors: Tribble James R. , Kastanaki Elizabeth , Uslular A. Berşan , Rutigliani Carola , Enz Tim J. , Williams Pete A.
Published: May 2022

Neuroinflammation is a critical and targetable pathogenic component of neurodegenerative diseases, including glaucoma, the leading cause of irreversible blindness. Valproic acid has previously been demonstrated to reduce neuroinflammation and is neuroprotective in a number of experimental settings. To determine whether valproic acid can limit retinal neuroinflammation and protect retinal neurons we used an ex vivo retina explant (axotomy) model to isolate resident glial responses from blood-derived monocytes. Neuroinflammatory status was defined using high resolution confocal imaging with 3D morphological reconstruction and cytokine protein arrays. Valproic acid significantly reduced microglia and astrocyte morphological changes, consistent with a reduction in pro-inflammatory phenotypes. Cytokine profiling demonstrated that valproic acid significantly attenuated or prevented expression of pro-inflammatory cytokines in injured retina. This identifies that the retinal explant model as a useful tool to explore resident neuroinflammation in a rapid timescale whilst maintaining a complex system of cell interactions and valproic acid as a useful drug to further explore anti-neuroinflammatory strategies in retinal disease.
Environmental Isolation of Sporothrix brasiliensis in an Area With Recurrent Feline Sporotrichosis Cases
Authors: Rabello Vanessa Brito Souza , Almeida-Silva Fernando , Scramignon-Costa Bruno de Souza , Motta Beatriz da Silva , de Macedo Priscila Marques , Teixeira Marcus de Melo , Almeida-Paes Rodrigo , Irinyi Laszlo , Meyer Wieland , Zancopé-Oliveira Rosely Maria
Published: May 2022

Sporotrichosis has been expanding throughout the Brazilian territory in recent years. New outbreaks have emerged, and consequently, the sporotrichosis agents, mainly Sporothrix brasiliensis, should remain in the environment somehow. Therefore, the aim of this study was to investigate the presence of Sporothrix spp. in the environment from an area of ​​the Rio de Janeiro state, Brazil, with recurrent cases of human and animal sporotrichosis. Abandoned demolition timber wood samples were collected in the garden of a house where the cases of human and feline sporotrichosis have occurred in the last 10 years. The environmental survey revealed a Sporothrix spp. colony from the serial dilution cultures of one abandoned demolition wood sample. In addition, a fungal strain isolated from a cat with skin lesions that lived in the house was also included in the study. The species-specific PCR, and calmodulin partial sequencing identified the environmental and cat isolates as S. brasiliensis. Furthermore, the phylogenetic analysis performed with the partial sequences of internal transcribed spacer region and constitutive genes (calmodulin, β-tubulin, and chitin synthase) showed high similarity between environmental and cat isolates from the same geographic region. Moreover, the antifungal susceptibility test revealed that the minimal inhibitory concentration of itraconazole from the environment isolate was lower than the cat isolate, while amphotericin B and terbinafine were similar. Our results show that S. brasiliensis is able to maintain itself in the environmental material for years. With this, we corroborate that the eco-epidemiology of sporotrichosis is not well understood, and despite the major occurrence of S. brasiliensis in Brazil, it is rarely isolated from the environment.
Evaluation of Spatial Directional Guidance Using Cheek Haptic Stimulation in a Virtual Environment
Authors: Nakamura Fumihiko , Verhulst Adrien , Sakurada Kuniharu , Fukuoka Masaaki , Sugimoto Maki
Published: May 2022

Spatial cues play an important role in navigating people in both physical and virtual spaces. In spatial navigation, visual information with additional cues, such as haptic cues, enables effective guidance. Most haptic devices are applied to various body parts to make mechanical stimuli, while few devices stimulate a head despite the excellent sensitivity. This article presents Virtual Whiskers, a spatial directional guidance technique by cheek haptic stimulation using tiny robot arms attached to a Head-Mounted Display (HMD). The tip of the robotic arm has photo reflective sensors to detect the distance between the tip and the cheek surface. Using the robot arms, we stimulate a point on the cheek obtained by calculating an intersection between the cheek surface and the target direction. In the directional guidance experiment, we investigated how accurately participants identify the target direction provided by our guidance method. We evaluated an error between the actual target direction and the participant's pointed direction. The experimental result shows that our method achieves the average absolute directional error of 2.54° in the azimuthal plane and 6.54° in the elevation plane. We also conducted a spatial guidance experiment to evaluate task performance in a target search task. We compared the condition of visual information, visual and audio information, and visual information and cheek haptics for task completion time, System Usability Scale (SUS) score, NASA-TLX score. The averages of task completion time were M = 6.39 s, SD = 3.34 s, and M = 5.62 s, SD = 3.12 s, and M = 4.35 s, SD = 2.26 s, in visual-only condition, visual+audio condition, and visual+haptic condition, respectively. In terms of the SUS score, visual condition, visual+audio condition, and visual+haptic condition achieved M = 55.83, SD = 20.40, and M = 47.78, SD = 20.09, and M = 80.42, SD = 10.99, respectively. As for NASA-TLX score, visual condition, visual+audio condition, and visual+haptic condition resulted in M = 75.81, SD = 16.89, and M = 67.57, SD = 14.96, and M = 38.83, SD = 18.52, respectively. Statistical tests revealed significant differences in task completion time, SUS score, and NASA-TLX score between the visual and the visual+haptic condition and the visual+audio and the visual+haptic condition.
Polar Bear Harvest Patterns Across the Circumpolar Arctic
Authors: Vongraven Dag , Derocher Andrew E. , Pilfold Nicholas W. , Yoccoz Nigel G.
Published: May 2022

Wildlife harvest remains a conservation concern for many species and assessing patterns of harvest can provide insights on sustainability and inform management. Polar bears (Ursus maritimus) are harvested over a large part of their range by local people. The species has a history of unsustainable harvest that was largely rectified by an international agreement that required science-based management. The objective of our study was to examine the temporal patterns in the number of polar bears harvested, harvest sex ratios, and harvest rates from 1970 to 2018. We analyzed data from 39,049 harvested polar bears (annual mean 797 bears) collected from 1970 to 2018. Harvest varied across populations and times that reflect varying management objectives, episodic events, and changes based on new population estimates. More males than females were harvested with an overall M:F sex ratio of 1.84. Harvest varied by jurisdiction with 68.0% of bears harvested in Canada, 18.0% in Greenland, 11.8% in the USA, and 2.2% in Norway. Harvest rate was often near the 4.5% target rate. Where data allowed harvest rate estimation, the target rate was exceeded in 11 of 13 populations with 1–5 populations per year above the target since 1978. Harvest rates at times were up to 15.9% of the estimated population size suggesting rare episodes of severe over-harvest. Harvest rate was unrelated to a proxy for ecosystem productivity (area of continental shelf within each population) but was correlated with prey diversity. In the last 5–10 years, monitored populations all had harvest rates near sustainable limits, suggesting improvements in management. Polar bear harvest management has reduced the threat it once posed to the species. However, infrequent estimates of abundance, new management objectives, and climate change have raised new concerns about the effects of harvest.
Barriers to Management of a Foreign Animal Disease at the Wildlife-Domestic Animal Interface: The Case of Rabbit Hemorrhagic Disease in the United States
Authors: Shapiro Hannah G. , Pienaar Elizabeth F. , Kohl Michel T.
Published: May 2022

The increasing global emergence of pathogens transmitted between wildlife and domestic animals are critically important conservation and economic concerns. International organizations, such as the World Organization for Animal Health (OIE), have called for cross-jurisdictional government investment in defensible, reliable surveillance systems and biosecurity measures to prevent pathogen transmission at the wildlife-domestic animal interface. A classic example of a pathogen that transmits across the wildlife-domestic animal interface is rabbit hemorrhagic disease virus 2 (RHDV2), which has spread to five continents in the 11 years since its discovery. RHDV2 is a highly contagious virus that infects wild and domestic rabbits and hares (lagomorphs). Globally, RHDV2 has resulted in population declines of wild lagomorphs, with associated biodiversity and hunting impacts, as well as economic losses for commercial rabbit industries. To assess the degree to which government agencies are positioned to engage in cross-jurisdictional approaches to mitigate pathogen spillover, we conducted the first study of how agricultural and wildlife agencies in the United States of America (U.S.) have responded to RHDV2 since it was detected in wild and domestic lagomorphs in March 2020. We surveyed and interviewed animal health personnel at 95 state wildlife and agricultural agencies, thereby accounting for all 50 states. Agencies have primarily responded to RHDV2 through disease investigations of potential RHDV2 cases, vaccinations, and education and outreach with the public and stakeholder groups. However, agencies' inconsistent jurisdiction within and across states over lagomorph populations and industries, limited knowledge of wild lagomorph populations and the composition of the domestic rabbit industry, and resource constraints have hindered management efforts. Improved understanding of the domestic lagomorph trade and transport routes is urgently needed to mitigate the risks associated with human-mediated movement of rabbits and RHDV2 across the U.S. Greater flexibility in agency funding and increased allocation of discretionary funds to agencies for management of animal diseases would allow agencies to respond more rapidly and effectively to emerging pathogens such as RHDV2. Federal leadership is needed to engage state agencies in collaborative, proactive interagency disease management across the U.S.
The Core Role of Neutrophil–Lymphocyte Ratio to Predict All-Cause and Cardiovascular Mortality: A Research of the 2005–2014 National Health and Nutrition Examination Survey
Authors: Gu Linguo , Xia Zhenkun , Qing Bei , Chen Hongzuo , Wang Wei , Chen Ying , Yuan Yunchang
Published: May 2022

Objective

To further supplement the previous research on the relationship between neutrophil–lymphocyte ratio (NLR) and all-cause and cardiovascular mortality, and construct clinical models to predict mortality.

Methods

A total number of 2,827 observers were included from the National Health and Nutrition Examination Survey (NHANES) database in our research. NLR was calculated from complete blood count. According to the quartile of baseline NLR, those observers were divided into four groups. A multivariate weighted Cox regression model was used to analyze the association of NLR with mortality. We constructed simple clinical prognosis models by nomograms. Kaplan–Meier survival curves were used to depict cause-specific mortality. Restricted cubic spline regression was used to make explicit relationships between NLR and mortality.

Results

This study recruited 2,827 subjects aged ≥ 18 years from 2005 to 2014. The average age of these observers was 51.55 ± 17.62, and 57.69% were male. NLR is still an independent predictor, adjusted for age, gender, race, drinking, smoking, dyslipidemia, and other laboratory covariates. The area under the receiver operating characteristic curves (AUCs) of NLR for predicting all-cause mortality and cardiovascular mortality were 0.632(95% CI [0599, 0.664]) and 0.653(95% CI [0.581, 0.725]), respectively, which were superior to C-reactive protein (AUCs: 0.609 and 0.533) and WBC (AUCs: 0.522 and 0.513). The calibration and discrimination of the nomograms were validated by calibration plots and concordance index (C-index), and the C-indexes (95% CIs) of nomograms for all-cause and cardiovascular mortality were 0.839[0.819,0.859] and 0.877[0.844,0.910], respectively. The restricted cubic spline showed a non-linear relationship between NLR and mortality. NLR > 2.053 might be a risk factor for mortality.

Conclusion

There is a non-linear relationship between NLR and mortality. NLR is an independent factor related to mortality, and NLR > 2.053 will be a risk factor for prognosis. NLR and nomogram should be promoted to medical use for practicality and convenience.