bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDI KEANDALAN TRANSFORMATOR 60 MVA KENDARI NEW
Authors: Mahendra Wahyu , Tachrir Tachrir , Bunyamin Bunyamin
Published: March 2022

Untuk meningkatkan keandalan utilitas, analisis kegagalan dan tingkat, asal kegagalan dan penyebab kerusakan fisik harus dipelajari. Metode yang digunakan adalah distribusi weibull. Statistik Weibull telah banyak digunakan sebagai metode matematika untuk menghitung laju kegagalan, keandalan, dan memprediksi waktu sisa umur peralatan apapun. Tugas Akhir ini membahas analisis keandalan transformator daya (150/20 kV) yang dipasang di Gardu Induk Kendari New. Penyebab PMT 150/20 kV transformator daya 60 MVA trip/lepas yang disebabkan dari gangguan eksternal terjadi 12 kali trip/lepas selama 486 menit, gangguan internal terjadi 7 kali trip/lepas selama 3212 menit dan gangguan yang tidak diketahui penyebabnya terjadi 1 kali trip/lepas selama 83 menit, total gangguan yang terjadi sebanyak 20 kali trip/lepas selama 3781 menit. Berdasarkan hasil pengolahan data, didapatkan nilai MTTF (Mean Time To Failure) adalah 0,8076%/tahun dan nilai dari fungsi laju kegagalan atau % fungsi hazardous didapatkan nilai laju rata-rata kegagalan yaitu 1,2382%/tahun.
ANALISIS PENGARUH INVESTASI DAN TENAGA KERJA TERHADAP PERTUMBUHAN EKONOMI ANTAR PROVINSI DI INDONESIA
Authors: Tasrif Muhamad , Rosnawintang Rosnawintang , Rahim Manat
Published: March 2022

Penelitian ini bertujuan untuk mengetahui dan menganalisis pengaruh investasi dan tenaga kerja terhadap pertumbuhan ekonomi antar Provinsi di Indonesia Periode 2011 sampai 2017. Jenis penelitian ini merupakan penelitian kuantitatif dengan menggunakan data sekunder. Model analisis yang dipakai dalam penelitian adalah analisis regresi data panel dengan menggunakan Random Effect Models (REM), dan diolah menggunakan E-views 10. Penelitian ini dilakukan di 33 Provinsi Indonesia.Hasil penelitian ini menunjukan bahwa, (1) variabel investasi berpengaruh signifikan dan positif terhadap pertumbuhan ekonomi antar Provinsi di Indonesia, artinya peningkatan investasi mampu memberikan dampak terhadap peningkatan pertumbuhan ekonomi, semakin bertambah investasi maka pertumbuhan ekonomi semakin meningkat (2) variabel tenaga kerja berpengaruh signifikan dan positif terhadap pertumbuhan ekonomi antar Provinsi di Indonesia, artinya perkembangan peningkatan tenaga kerja mampu memberikan dampak terhadap peningkatan pertumbuhan ekonomi, semakin bertambah tenaga kerja maka pertumbuhan ekonomi mengalami peningkatan. Kata Kunci: Pertumbuhan Ekonomi, Investasi, Tenaga Kerja
PENGARUH KESADARAN WAJIB PAJAK DAN AKUNTABILITAS PELAYANAN PUBLIK TERHADAP KEPATUHAN WAJIB PAJAK KENDARAAN BERMOTOR PADA KANTOR SAMSAT KOTA KENDARI
Authors: Bulan Nofian Lepong , Husin Husin , Anto La Ode
Published: March 2022

Tujuan penelitian ini adalah sebagai berikut: (1) Untuk mengetahui dan menganalisis pengaruhkesadaran wajib pajak terhadap kepatuhan wajib pajak, (2) Untuk mengetahui dan menganalisis pengaruhpengetahuan pajak kepatuhan wajib pajak, (3) Untuk mengetahui dan menganalisis pengaruh sanksi pajak,terhadap kepatuhan wajib pajak, (4) Untuk mengetahui dan menganalisis pengaruh akuntabilitas pelayananpublik terhadap kepatuhan wajib pajak pada Kantor Samsat Kota KendariJenis penelitian yang dilakukan adalah penelitian dasar (basic research). Populasi sebanyak 115.240wajib pajak, penentuan sampel digunaka rumus Slovin sehingga jumlah sampel dalam penelitian inisebanyak 90 responden. Analisis yang digunakan adalah regresi linear berganda.Berdasarkan hasil analisa dan pembahasan dalam penelitian ini, maka dapat ditarik beberapakesimpulan sebagai berikut: (1) Kesadaran wajib pajak, Akuntabilitas pelayanan publik secara bersama-samaberpengaruh terhadap kepatuhan wajib, (2) Kesadaran wajib pajak secara parsial berpengaruh terhadapkepatuhan wajib pajak. (3) Akuntabilitas pelayanan publik secara parsial berpengaruh terhadap kepatuhanwajib pajak kendaraan bermotor pada kantor samsat Kota Kendari.Kata kunci : Kesadaran wajib pajak, Akuntabilitas pelayanan publik
Pull-Down Into Active Inclusion Bodies and Their Application in the Detection of (Poly)-Phosphates and Metal-Ions
Authors: Hrabarova Eva , Belkova Martina , Koszagova Romana , Nahalka Jozef
Published: March 2022

Inclusion bodies are typically ignored as they are considered unwanted protein waste generated by prokaryotic host cells during recombinant protein production or harmful protein inclusions in human cell biology. However, these protein particles may have applications for in vivo immobilization in industrial biocatalysis or as cell-tolerable protein materials for the pharmaceuticals industry and clinical development. Thus, there is a need to in vivo “pull-down” (insolubilize) soluble enzymes and proteins into inclusion bodies. Accordingly, in this study, sequences from the short-chain polyphosphatase ygiF were used to design pull-down tags capable of detecting (poly)-phosphates and metal ions. These tags were compared with the entire CHAD domain from Escherichia coli ygiF and SACS2 CHAD from Saccharolobus solfataricus. The results demonstrated that highly soluble green fluorescent protein variants could be pulled down into the inclusion bodies and could have modified sensitivity to metals and di-/tri-inorganic phosphates.
A Tale of Two Loads: Modulation of IL-1 Induced Inflammatory Responses of Meniscal Cells in Two Models of Dynamic Physiologic Loading
Authors: Andress Benjamin D. , Irwin Rebecca M. , Puranam Ishaan , Hoffman Brenton D. , McNulty Amy L.
Published: March 2022

Meniscus injuries are highly prevalent, and both meniscus injury and subsequent surgery are linked to the development of post-traumatic osteoarthritis (PTOA). Although the pathogenesis of PTOA remains poorly understood, the inflammatory cytokine IL-1 is elevated in synovial fluid following acute knee injuries and causes degradation of meniscus tissue and inhibits meniscus repair. Dynamic mechanical compression of meniscus tissue improves integrative meniscus repair in the presence of IL-1 and dynamic tensile strain modulates the response of meniscus cells to IL-1. Despite the promising observed effects of physiologic mechanical loading on suppressing inflammatory responses of meniscus cells, there is a lack of knowledge on the global effects of loading on meniscus transcriptomic profiles. In this study, we compared two established models of physiologic mechanical stimulation, dynamic compression of tissue explants and cyclic tensile stretch of isolated meniscus cells, to identify conserved responses to mechanical loading. RNA sequencing was performed on loaded and unloaded meniscus tissue or isolated cells from inner and outer zones, with and without IL-1. Overall, results from both models showed significant modulation of inflammation-related pathways with mechanical stimulation. Anti-inflammatory effects of loading were well-conserved between the tissue compression and cell stretch models for inner zone; however, the cell stretch model resulted in a larger number of differentially regulated genes. Our findings on the global transcriptomic profiles of two models of mechanical stimulation lay the groundwork for future mechanistic studies of meniscus mechanotransduction, which may lead to the discovery of novel therapeutic targets for the treatment of meniscus injuries.
Contribution of Minimally Invasive Bone Augmentation With PMMA Cement in Primary Fixation of Schatzker Type II Tibial Plateau Fractures
Authors: Vendeuvre T. , Koneazny C. , Brèque C. , Rigoard P. , Severyns M. , Germaneau A.
Published: March 2022

Background: The most common type of fracture of the lateral tibial plateau is the Schatzker type II split-depressed fracture. Minimally invasive surgery using balloon reduction appears to be very promising compared to the gold standard using a bone tamp. This surgery aims to have the best reduction and stabilization to benefit from an early passive and active rehabilitation to avoid stiffening and muscle wasting. Using a balloon for fracture reduction has allowed the use of semi-liquid Injectable Bone Cement (IBC) fillers. These fillers can be phosphocalcic or polymethyl methacrylate (PMMA). The latest recommendations on these IBCs in spinal surgery increasingly rule out phosphocalcic fillers because of their low mechanical strength.

Questions/purposes: 1) What is the mechanical influence of IBC filling (PMMA) regarding the split and depression components of a Schatzker type II fracture? 2) What is the mechanical influence of osteosynthesis regarding the split and depression components of a Schatzker type II fracture with or without PMMA filing in three different kinds of percutaneous fixations?

Methods: This biomechanical study was performed on 36 fresh frozen tibia/fibula specimens. Six groups were formed according to the type of percutaneous osteosynthesis or possible PMMA filling. Mechanical strength tests were carried out using a Unicompartmental Knee prosthesis and displacement components were measured on either side of the separation on the anterolateral facet by optical method.

Results: We found a significant difference between cementless and cemented osteosynthesis for depression fracture stabilization (difference −507.56N with 95% confidence interval [−904.17; −110.94] (p-value = 0.026)). The differences between the different types of osteosynthesis were not significant (p-value = 0.58). There was a significant difference between osteosynthesis without cement and osteosynthesis with cement on separation (difference −477.72N [−878.52; −76.93] (p-value = 0.03)). The differences between the different types of fixations were not significant regarding separation (p-value = 0.99).

Conclusion: PMMA cement significantly improves primary stability, regardless of the type of osteosynthesis for a Schatzker type II plateau fracture. Filling with PMMA cement during tuberoplasty seems to be a very promising strategy in association with percutaneous osteosynthesis to allow rapid recovery after surgery.
Advanced Surface Modification for 3D-Printed Titanium Alloy Implant Interface Functionalization
Authors: Sheng Xiao , Wang Ao , Wang Zhonghan , Liu He , Wang Jincheng , Li Chen
Published: March 2022

With the development of three-dimensional (3D) printed technology, 3D printed alloy implants, especially titanium alloy, play a critical role in biomedical fields such as orthopedics and dentistry. However, untreated titanium alloy implants always possess a bioinert surface that prevents the interface osseointegration, which is necessary to perform surface modification to enhance its biological functions. In this article, we discuss the principles and processes of chemical, physical, and biological surface modification technologies on 3D printed titanium alloy implants in detail. Furthermore, the challenges on antibacterial, osteogenesis, and mechanical properties of 3D-printed titanium alloy implants by surface modification are summarized. Future research studies, including the combination of multiple modification technologies or the coordination of the structure and composition of the composite coating are also present. This review provides leading-edge functionalization strategies of the 3D printed titanium alloy implants.
Intensity-Based Sentiment and Topic Analysis. The Case of the 2020 Aegean Earthquake
Authors: Contreras Diana , Wilkinson Sean , Aktas Yasemin Didem , Fallou Laure , Bossu Rémy , Landès Matthieu
Published: March 2022

After an earthquake, it is necessary to understand its impact to provide relief and plan recovery. Social media (SM) and crowdsourcing platforms have recently become valuable tools for quickly collecting large amounts of first-hand data after a disaster. Earthquake-related studies propose using data mining and natural language processing (NLP) for damage detection and emergency response assessment. Using tex-data provided by the Euro-Mediterranean Seismological Centre (EMSC) collected through the LastQuake app for the Aegean Earthquake, we undertake a sentiment and topic analysis according to the intensities reported by their users in the Modified Mercalli Intensity (MMI) scale. There were collected 2,518 comments, reporting intensities from I to X being the most frequent intensity reported III. We use supervised classification according to a rule-set defined by authors and a two-tailed Pearson correlation to find statistical relationships between intensities reported in the MMI by LastQuake app users, polarities, and topics addressed in their comments. The most frequent word among comments was: “Felt.” The sentiment analysis (SA) indicates that the positive polarity prevails in the comments associated with the lowest intensities reported: (I-II), while the negative polarity in the comments is associated with higher intensities (III–VIII and X). The correlation analysis identifies a negative correlation between the increase in the reported MMI intensity and the comments with positive polarity. The most addressed topic in the comments from LastQuake app users was intensity, followed by seismic information, solidarity messages, emergency response, unrelated topics, building damages, tsunami effects, preparedness, and geotechnical effects. Intensities reported in the MMI are significantly and negatively correlated with the number of topics addressed in comments. Positive polarity decreases with the soar in the reported intensity in MMI demonstrated the validity of our first hypothesis, despite not finding a correlation with negative polarity. Instead, we could not prove that building damage, geotechnical effects, lifelines affected, and tsunami effects were topis addressed only in comments reporting the highest intensities in the MMI.
An Aging-Related Gene Signature-Based Model for Risk Stratification and Prognosis Prediction in Lung Squamous Carcinoma
Authors: Zhai Wen-Yu , Duan Fang-Fang , Chen Si , Wang Jun-Ye , Zhao Ze-Rui , Wang Yi-Zhi , Rao Bing-Yu , Lin Yao-Bin , Long Hao
Published: March 2022

Aging is an inevitable process characterized by a decline in many physiological activities, and has been known as a significant risk factor for many kinds of malignancies, but there are few studies about aging-related genes (ARGs) in lung squamous carcinoma (LUSC). We designed this study to explore the prognostic value of ARGs and establish an ARG-based prognosis signature for LUSC patients. RNA-sequencing and corresponding clinicopathological data of patients with LUSC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The ARG risk signature was developed on the basis of results of LASSO and multivariate Cox analysis in the TCGA training dataset (n = 492). Furthermore, the GSE73403 dataset (n = 69) validated the prognostic performance of this ARG signature. Immunohistochemistry (IHC) staining was used to verify the expression of the ARGs in the signature. A five ARG-based signature, including A2M, CHEK2, ELN, FOS, and PLAU, was constructed in the TCGA dataset, and stratified patients into low- and high-risk groups with significantly different overall survival (OS) rates. The ARG risk score remained to be considered as an independent indicator of OS in the multivariate Cox regression model for LUSC patients. Then, a prognostic nomogram incorporating the ARG risk score with T-, N-, and M-classification was established. It achieved a good discriminative ability with a C-index of 0.628 (95% confidence interval [CI]: 0.586–0.671) in the TCGA cohort and 0.648 (95% CI: 0.535–0.762) in the GSE73403 dataset. Calibration curves displayed excellent agreement between the actual observations and the nomogram-predicted survival. The IHC staining discovered that these five ARGs were overexpression in LUSC tissues. Besides, the immune infiltration analysis in the TCGA cohort represented a distinctly differentiated infiltration of anti-tumor immune cells between the low- and high-risk groups. We identified a novel ARG-related prognostic signature, which may serve as a potential biomarker for individualized survival predictions and personalized therapeutic recommendation of anti-tumor immunity for patients with LUSC.
Applying Sodium Carbonate Extraction Mass Spectrometry to Investigate Defects in the Mitochondrial Respiratory Chain
Authors: Robinson David R. L. , Hock Daniella H. , Muellner-Wong Linden , Kugapreethan Roopasingam , Reljic Boris , Surgenor Elliot E. , Rodrigues Carlos H. M. , Caruana Nikeisha J. , Stroud David A.
Published: March 2022

Mitochondria are complex organelles containing 13 proteins encoded by mitochondrial DNA and over 1,000 proteins encoded on nuclear DNA. Many mitochondrial proteins are associated with the inner or outer mitochondrial membranes, either peripherally or as integral membrane proteins, while others reside in either of the two soluble mitochondrial compartments, the mitochondrial matrix and the intermembrane space. The biogenesis of the five complexes of the oxidative phosphorylation system are exemplars of this complexity. These large multi-subunit complexes are comprised of more than 80 proteins with both membrane integral and peripheral associations and require soluble, membrane integral and peripherally associated assembly factor proteins for their biogenesis. Mutations causing human mitochondrial disease can lead to defective complex assembly due to the loss or altered function of the affected protein and subsequent destabilization of its interactors. Here we couple sodium carbonate extraction with quantitative mass spectrometry (SCE-MS) to track changes in the membrane association of the mitochondrial proteome across multiple human knockout cell lines. In addition to identifying the membrane association status of over 840 human mitochondrial proteins, we show how SCE-MS can be used to understand the impacts of defective complex assembly on protein solubility, giving insights into how specific subunits and sub-complexes become destabilized.
Origin of Cancer: Cell work is the Key to Understanding Cancer Initiation and Progression
Authors: Hanselmann Rainer G. , Welter Cornelius
Published: March 2022

The cell is the smallest unit of life. It is a structure that maintains order through self-organization, characterized by a high level of dynamism, which in turn is characterized by work. For this work to take place, a continuous high flow of energy is necessary. However, a focused view of the physical relationship between energy and work is inadequate for describing complex biological/medical mechanisms or systems. In this review, we try to make a connection between the fundamental laws of physics and the mechanisms and functions of biology, which are characterized by self-organization. Many different physical work processes (work) in human cells are called cell work and can be grouped into five forms: synthetic, mechanical, electrical, concentration, and heat generation cell work. In addition to the flow of energy, these cell functions are based on fundamental processes of self-organization that we summarize with the term Entirety of molecular interaction (EoMI). This illustrates that cell work is caused by numerous molecular reactions, flow equilibrium, and mechanisms. Their number and interactions are so complex that they elude our perception in their entirety. To be able to describe cell functions in a biological/medical context, the parameters influencing cell work should be summarized in overarching influencing variables. These are “biological” energy, information, matter, and cell mechanics (EMIM). This makes it possible to describe and characterize the cell work involved in cell systems (e.g., respiratory chain, signal transmission, cell structure, or inheritance processes) and to demonstrate changes. If cell work and the different influencing parameters (EMIM influencing variables) are taken as the central property of the cell, specific gene mutations cannot be regarded as the sole cause for the initiation and progression of cancer. This reductionistic monocausal view does not do justice to the dynamic and highly complex system of a cell. Therefore, we postulate that each of the EMIM influencing variables described above is capable of changing the cell work and thus the order of a cell in such a way that it can develop into a cancer cell.
Single-Cell Atlas of the Chinese Tongue Sole (Cynoglossus semilaevis) Ovary Reveals Transcriptional Programs of Oogenesis in Fish
Authors: Liu Xiang , Huang Yingyi , Tan Fujian , Wang Hong-Yan , Chen Jian-Yang , Zhang Xianghui , Zhao Xiaona , Liu Kaiqiang , Wang Qian , Liu Shanshan , Piferrer Francesc , Fan Guangyi , Shao Changwei
Published: March 2022

Oogenesis is a highly orchestrated process that depends on regulation by autocrine/paracrine hormones and growth factors. However, many details of the molecular mechanisms that regulate fish oogenesis remain elusive. Here, we performed a single-cell RNA sequencing (scRNA-seq) analysis of the molecular signatures of distinct ovarian cell categories in adult Chinese tongue sole (Cynoglossus semilaevis). We characterized the successive stepwise development of three germ cell subtypes. Notably, we identified the cellular composition of fish follicle walls, including four granulosa cell types and one theca cell type, and we proposed important transcription factors (TFs) showing high activity in the regulation of cell identity. Moreover, we found that the extensive niche–germline bidirectional communications regulate fish oogenesis, whereas ovulation in fish is accompanied by the coordination of simultaneous and tightly sequential processes across different granulosa cells. Additionally, a systems biology analysis of the homologous genes shared by Chinese tongue sole and macaques revealed remarkably conserved biological processes in germ cells and granulosa cells across vertebrates. Our results provide key insights into the cell-type-specific mechanisms underlying fish oogenesis at a single-cell resolution, which offers important clues for exploring fish breeding mechanisms and the evolution of vertebrate reproductive systems.
Integrins and Epithelial-Mesenchymal Cooperation in the Tumor Microenvironment of Muscle-Invasive Lethal Cancers
Authors: Harryman William L. , Marr Kendra D. , Nagle Ray B. , Cress Anne E.
Published: March 2022

Muscle-invasive lethal carcinomas traverse into and through this specialized biophysical and growth factor enriched microenvironment. We will highlight cancers that originate in organs surrounded by smooth muscle, which presents a barrier to dissemination, including prostate, bladder, esophageal, gastric, and colorectal cancers. We propose that the heterogeneity of cell-cell and cell-ECM adhesion receptors is an important driver of aggressive tumor networks with functional consequences for progression. Phenotype heterogeneity of the tumor provides a biophysical advantage for tumor network invasion through the tensile muscle and survival of the tumor network. We hypothesize that a functional epithelial-mesenchymal cooperation (EMC)exists within the tumor invasive network to facilitate tumor escape from the primary organ, invasion and traversing of muscle, and navigation to metastatic sites. Cooperation between specific epithelial cells within the tumor and stromal (mesenchymal) cells interacting with the tumor is illustrated using the examples of laminin-binding adhesion molecules—especially integrins—and their response to growth and inflammatory factors in the tumor microenvironment. The cooperation between cell-cell (E-cadherin, CDH1) and cell-ECM (α6 integrin, CD49f) expression and growth factor receptors is highlighted within poorly differentiated human tumors associated with aggressive disease. Cancer-associated fibroblasts are examined for their role in the tumor microenvironment in generating and organizing various growth factors. Cellular structural proteins are potential utility markers for future spatial profiling studies. We also examine the special characteristics of the smooth muscle microenvironment and how invasion by a primary tumor can alter this environment and contribute to tumor escape via cooperation between epithelial and stromal cells. This cooperative state allows the heterogenous tumor clusters to be shaped by various growth factors, co-opt or evade immune system response, adapt from hypoxic to normoxic conditions, adjust to varying energy sources, and survive radiation and chemotherapeutic interventions. Understanding the epithelial-mesenchymal cooperation in early tumor invasive networks holds potential for both identifying early biomarkers of the aggressive transition and identification of novel agents to prevent the epithelial-mesenchymal cooperation phenotype. Epithelial-mesenchymal cooperation is likely to unveil new tumor subtypes to aid in selection of appropriate therapeutic strategies.
Lactobacillus Suppresses Tumorigenesis of Oropharyngeal Cancer via Enhancing Anti-Tumor Immune Response
Authors: Wang Ke-Ke , He Kai-Yue , Yang Jing-Yu , Liu Meng-Jie , Guo Jin-Rong , Liang Ji-Yong , Wang Jin-Hua , Xu Zhi-Xiang , Jian Yong-Ping
Published: March 2022

Deficiency in T cell-mediated adaptive immunity, such as low CD8+ T cell infiltration, inhibits the immune surveillance, promotes malignant transformation, and facilitates tumor growth. Microbiota dysbiosis diminishes the immune system and contributes to the occurrence of cancer. However, the impact of oral dysbiosis on the occurrence and molecular mechanisms of oropharyngeal cancer (OPC) remains largely unknown. In the current study, we used 4-nitroquinoline-1-oxide (4NQO) to mimic tobacco-related carcinogenesis to generate a murine OPC model and determine the role of microbiota changes in OPC tumorigenesis. Our results showed that the oral flora composition of mice was deregulated during the tumorigenesis of OPC. The abundance of Streptococcus, Veillonella, Muribacter, Rodentibacter, and Gemella was increased, whereas the dominant genus Lactobacillus was gradually decreased with disease progression. We further demonstrated that infiltration of CD8+ T lymphocytes was markedly reduced due to the reduction of Lactobacillus. Supplementation of Lactobacillus increased the infiltration of CD8+ T cells, promoted the expression of IFN-γ and granzyme B, and lessened the OPC progression. Analyzing the metabolites of the Lactobacillus, we demonstrated that Lactobacillus enhanced the anti-tumor immune response by producing acetate in OPC development. Administration of acetate to mice could increase the expression of IFN-γ and IFN-γ-inducible chemokines in tumor tissues by activating GPR43 to promote the infiltration of CD8+ T lymphocytes and substantially delay the development of OPC. Together, our data suggest that dysbiosis of oral microbiota promotes the tumorigenesis of OPC through downregulation of cytotoxic T lymphocytes. Lactobacillus and its metabolite acetate improve the tumor microenvironment, which could be applied in the treatment of OPC.
Extracellular Vesicles: The Landscape in the Progression, Diagnosis, and Treatment of Triple-Negative Breast Cancer
Authors: Dong Menglu , Liu Quan , Xu Yi , Zhang Qi
Published: March 2022

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) with diverse biological behavior, high aggressiveness, and poor prognosis. Extracellular vesicles (EVs) are nano-sized membrane-bound vesicles secreted by nearly all cells, and are involved in physiological and pathological processes. EVs deliver multiple functional cargos into the extracellular space, including proteins, lipids, mRNAs, non-coding RNAs (ncRNAs), and DNA fragments. Emerging evidence confirms that EVs enable pro-oncogenic secretome delivering and trafficking for long-distance cell-to-cell communication in shaping the tumor microenvironment (TME). The transferred tumor-derived EVs modify the capability of invasive behavior and organ-specific metastasis in recipient cells. In addition, TNBC cell-derived EVs have been extensively investigated due to their promising potential as valuable biomarkers for diagnosis, monitoring, and treatment evaluation. Here, the present review will discuss the recent progress of EVs in TNBC growth, metastasis, immune regulation, as well as the potential in TNBC diagnosis and treatment application, hoping to decipher the advantages and challenges of EVs for combating TNBC.
Extracellular Matrix Stiffness and TGFβ2 Regulate YAP/TAZ Activity in Human Trabecular Meshwork Cells
Authors: Li Haiyan , Raghunathan VijayKrishna , Stamer W. Daniel , Ganapathy Preethi S. , Herberg Samuel
Published: March 2022

Primary open-angle glaucoma progression is associated with increased human trabecular meshwork (HTM) stiffness and elevated transforming growth factor beta 2 (TGFβ2) levels in the aqueous humor. Increased transcriptional activity of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), central players in mechanotransduction, are implicated in glaucomatous HTM cell dysfunction. Yet, the detailed mechanisms underlying YAP/TAZ modulation in HTM cells in response to alterations in extracellular matrix (ECM) stiffness and TGFβ2 levels are not well understood. Using biomimetic ECM hydrogels with tunable stiffness, here we show that increased ECM stiffness elevates YAP/TAZ nuclear localization potentially through modulating focal adhesions and cytoskeletal rearrangement. Furthermore, TGFβ2 increased nuclear YAP/TAZ in both normal and glaucomatous HTM cells, which was prevented by inhibiting extracellular-signal-regulated kinase and Rho-associated kinase signaling pathways. Filamentous (F)-actin depolymerization reversed TGFβ2-induced YAP/TAZ nuclear localization. YAP/TAZ depletion using siRNA or verteporfin decreased focal adhesions, ECM remodeling and cell contractile properties. Similarly, YAP/TAZ inactivation with verteporfin partially blocked TGFβ2-induced hydrogel contraction and stiffening. Collectively, our data provide evidence for a pathologic role of aberrant YAP/TAZ signaling in glaucomatous HTM cell dysfunction, and may help inform strategies for the development of novel multifactorial approaches to prevent progressive ocular hypertension in glaucoma.
The Chlamydia trachomatis Early Effector Tarp Outcompetes Fascin in Forming F-Actin Bundles In Vivo
Authors: Aranjuez George F. , Kim Jongeon , Jewett Travis J.
Published: March 2022

The intracellular pathogen Chlamydia trachomatis secretes multiple early effectors into the host cell to promote invasion. A key early effector during host cell entry, Tarp (translocated actin-recruiting phosphoprotein) is comprised of multiple protein domains known to have roles in cell signaling, G-actin nucleation and F-actin bundle formation. In vitro, the actin bundles generated by Tarp are uncharacteristically flexible, however, in vivo, the biological significance of Tarp-mediated actin bundles remains unknown. We hypothesize that Tarp’s ability to generate unique actin bundles, in part, facilitates chlamydial entry into epithelial cells. To study the in vivo interaction between Tarp and F-actin, we transgenically expressed Tarp in Drosophila melanogaster tissues. Tarp expressed in Drosophila is phosphorylated and forms F-actin-enriched aggregates in tissues. To gain insight into the significance of Tarp actin bundles in vivo, we utilized the well-characterized model system of mechanosensory bristle development in Drosophila melanogaster. Tarp expression in wild type flies produced curved bristles, indicating a perturbation in F-actin dynamics during bristle development. Two F-actin bundlers, Singed/Fascin and Forked/Espin, are important for normal bristle shape. Surprisingly, Tarp expression in the bristles displaced Singed/Fascin away from F-actin bundles. Tarp’s competitive behavior against Fascin during F-actin bundling was confirmed in vitro. Loss of either singed or forked in flies leads to highly deformed bristles. Strikingly, Tarp partially rescued the loss of singed, reducing the severity of the bristle morphology defect. This work provides in vivo confirmation of Tarp’s F-actin bundling activity and further uncovers a competitive behavior against the host bundler Singed/Fascin during bundle assembly. Also, we demonstrate the utility of Drosophila melanogaster as an in vivo cell biological platform to study bacterial effector function.
Satellite-Based Data Assimilation System for the Initialization of Arctic Sea Ice Concentration and Thickness Using CICE5
Authors: Lee Jeong-Gil , Ham Yoo-Geun
Published: March 2022

The satellite-derived sea ice concentration (SIC) and thickness (SIT) observation over the Arctic region are assimilated by implementing the Ensemble Optimal Interpolation (EnOI) into the Community Ice CodE version 5.1.2 (CICE5) model. The assimilated observations are derived from Special Sensor Microwave Imager/Sounder (SSMIS) for the SIC, European Space Agency's (ESA) Soil Moisture and Ocean Salinity mission (SMOS) for the SIT of the thin ice, and ESA's CryoSat-2 satellite for the SIT of the thick ice. The SIC, and SIT observations are assimilated during 2000–2019, and 2011–2019, respectively. The quality of the reanalysis is evaluated by comparing with observation and modeled data. Three data assimilation experiments are conducted: noDA without data assimilation, Ver1 with SIC assimilation, and Ver2 with SIC and SIT assimilation. The climatological bias of the SIC in noDA was reduced in Ver1 by 29% in marginal ice zones during boreal winter, and 82% in pan-Arctic ocean during boreal summer. The quality of simulating the interannual variation of sea ice extent (SIE) is improved in all months particularly during boreal summer. The root-mean-square errors (RMSEs) of SIE anomaly in August are significantly reduced compared to noDA. However, the interannual variations of SIT is unrealistic in Ver1 which requires the additional assimilation of the SIT observation. The climatological bias of SIT over the Arctic was further reduced in Ver2 by 28% during boreal winter compared to that in Ver1. The interannual variability of SIT anomalies is realistically simulated in Ver2 by reducing the RMSEs of SIT anomalies by 33% in February, and 28% in August by compared to that in Ver1. The dominant interannual variation extracted by empirical orthogonal function (EOF) of SIT anomalies in Ver2 is better simulated than Ver1. The additional assimilation of SIT improves not only SIT, but also SIC. The climatological bias of SIE and the errors in leading EOF of SIC anomalies in Ver2 is further reduced compared to those in Ver1 during boreal winter. However, improvements led by assimilating additional SIT observation is not clear during boreal summer, possible due to the lack of available SIT observation during this season.
N-Terminal Pro-B-Type Natriuretic Peptide in Risk Stratification of Heart Failure Patients With Implantable Cardioverter-Defibrillator
Authors: Deng Yu , Cheng Si-Jing , Hua Wei , Cai Min-Si , Zhang Ni-Xiao , Niu Hong-Xia , Chen Xu-Hua , Gu Min , Cai Chi , Liu Xi , Huang Hao , Zhang Shu
Published: March 2022

Background

The prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) is well-established. However, whether it could facilitate the risk stratification of HF patients with implantable cardioverter-defibrillator (ICD) is still unclear.

Objective

To determine the associations between baseline NT-proBNP and outcomes of all-cause mortality and first appropriate shock due to sustained ventricular tachycardia/ventricular fibrillation (VT/VF) in ICD recipients.

Methods and results

N-terminal pro-B-type natriuretic peptide was measured before ICD implant in 500 patients (mean age 60.2 ± 12.0 years; 415 (83.0%) men; 231 (46.2%) Non-ischemic dilated cardiomyopathy (DCM); 136 (27.2%) primary prevention). The median NT-proBNP was 854.3 pg/ml (interquartile range [IQR]: 402.0 to 1,817.8 pg/ml). We categorized NT-proBNP levels into quartiles and used a restricted cubic spline to evaluate its nonlinear association with outcomes. The incidence rates of mortality and first appropriate shock were 5.6 and 9.1%, respectively. After adjusting for confounding factors, multivariable Cox regression showed a rise in NT-proBNP was associated with an increased risk of all-cause mortality. Compared with the lowest quartile, the hazard ratios (HRs) with 95% CI across increasing quartiles were 1.77 (0.71, 4.43), 3.98 (1.71, 9.25), and 5.90 (2.43, 14.30) for NT-proBNP (p for trend < 0.001). A restricted cubic spline demonstrated a similar pattern with an inflection point found at 3,231.4 pg/ml, beyond which the increase in NT-proBNP was not associated with increased mortality (p for nonlinearity < 0.001). Fine-Gray regression was used to evaluate the association between NT-proBNP and first appropriate shock accounting for the competing risk of death. In the unadjusted, partial, and fully adjusted analysis, however, no significant association could be found regardless of NT-proBNP as a categorical variable or log-transformed continuous variable (all p > 0.05). No nonlinearity was found, either (p = 0.666). Interactions between NT-proBNP and predefined factors were not found (all p > 0.1).

Conclusion

In HF patients with ICD, the rise in NT-proBNP is independently associated with increased mortality until it reaches the inflection point. However, its association with the first appropriate shock was not found. Patients with higher NT-proBNP levels might derive less benefit from ICD implant.
Remote Cardiac Rhythm Monitoring in the Era of Smart Wearables: Present Assets and Future Perspectives
Authors: Xintarakou Anastasia , Sousonis Vasileios , Asvestas Dimitrios , Vardas Panos E. , Tzeis Stylianos
Published: March 2022

Remote monitoring and control of heart function are of primary importance for patient evaluation and management, especially in the modern era of precision medicine and personalized approach. Breaking technological developments have brought to the frontline a variety of smart wearable devices, such as smartwatches, chest patches/straps, or sensors integrated into clothing and footwear, which allow continuous and real-time recording of heart rate, facilitating the detection of cardiac arrhythmias. However, there is great diversity and significant differences in the type and quality of the information they provide, thus impairing their integration into daily clinical practice and the relevant familiarization of practicing physicians. This review will summarize the different types and dominant functions of cardiac smart wearables available in the market. Furthermore, we report the devices certified by official American and/or European authorities and the respective sources of evidence. Finally, we comment pertinent limitations and caveats as well as the potential answers that flow from the latest technological achievements and future perspectives.
The Heat Source Origin of Geothermal Resources in Xiong’an New Area, North China, in View of the Influence of Igneous Rocks
Authors: Cui Yue , Zhu Chuanqing , Qiu Nansheng , Tang Boning , Guo Sasa , Lu Zhiwei
Published: March 2022

The Xiong’an new area has abundant geothermal resources, and heat source research plays an important role in the geothermal system. Using the logging curve, we calculated the radioactive heat production of sedimentary layers and igneous rocks in non-sample wells; analyzed the influence of igneous rock distribution, residual heat, and its thermal increment on crust; and clarified the heat source origin of hydrothermal geothermal resources in Xiong’an new area. Sedimentary layers data (5,504) of 20 wells were converted to determine the applicable GR-A empirical relationship, and the radioactive heat production of igneous rocks with different lithologies was estimated. Finite element simulations show that igneous rock intrusions in the study area reach thermal equilibrium with the surrounding rock after 0.5 Ma at most. Upon cooling, the difference in thermal physical properties to the surrounding rock only leads to a higher heat flow of about 3.55 mW/m2 in the partial of the Niutuozhen salient. It is known that the development of igneous facies impacts the heat source. Under the geothermal background of “cold crust-hot mantle,” the mantel heat was the primary source, which the Yanshanian intrusions injected into the central salient, increasing the crustal heat by about 12% and the heat source by about 6%. The measured heat flow becomes higher in the salient (raised about 12.04 mW/m2–29.25 mW/m2) where the deep faults developed due to the groundwater convection. Heat conduction from crust-mantle heat flow and heat convection caused by deep faults are responsible for the current geothermal state in Xiong’an new area.
Simulation of Glacial Lake Outburst Flood in Southeastern Qinghai-Tibet Plateau—A Case Study of JiwenCo Glacial Lake
Authors: Zhang Yuan , Yao Xiaojun , Duan Hongyu , Wang Qi
Published: March 2022

Glacial lake outburst floods (GLOFs) is one of the main natural disasters in alpine areas, which can cause extreme destruction to downstream settlements and infrastructures. A moraine-dammed lake named JiwenCo glacial lake (JGL) in the southeastern Qinghai-Tibetan Plateau failed on 26 June 2020, destroying many buildings, roads, bridges, and farmlands along the flow path. We reconstructed the process of this GLOF event by the Hydrological Engineering Center’s River Analysis System (HEC-RAS) and examined the JGL’s evolution (area, length, and volume) before its outburst, based on the measured cross sections and hydrological data, videos, and pictures taken by inhabitants, DEM data, and Landsat Thematic Mapper (TM)/Enhanced Thematic Mapper (ETM+)/Operational Land Imager (OLI) images. The result showed that area, length, and volume of the JGL increased by 0.20 ± 0.07 km2, 0.66 ± 0.03 km, and 0.03 ± 0.001 km3 from 1988 to 2020 (before the outburst), respectively. Approximately 0.05 km3 of water volume was discharged with the dropped water level of 15.63 m after the outburst. The peak flow was 534.4 m3/s at breach and increased to 1,408.11 m3/s at Zhongyu town. The difference between the simulated and measured peak flows in Zhongyu town was 41.88 m3/s (3.53%), showing the high accuracy of the modeling results. For villages along the river-channel, the highest velocity was found in Yiga village (14.23 m/s) and the lowest was in Gongwa village (1.22 m/s). The maximum depth was gradually increased as the river reached downstream, 8.03 m in Yiga village and 50.96 m in Duiba village. The combination of landslide, high temperature, and extremely heavy precipitation resulted in this GLOF disaster. An integrated disaster prevention and mitigation plan needs to be developed for susceptible areas such as Niduzangbo basin that experienced two GLOFs in recent 10 years.
Childhood ADHD, Going Beyond the Brain: A Meta-Analysis on Peripheral Physiological Markers of the Heart and the Gut
Authors: Payen Ameanté , Chen Michelle J. , Carter T. Grace , Kilmer Ryan P. , Bennett Jeanette M.
Published: March 2022

Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common neurodevelopmental disorder diagnosed in children. Questions regarding its increased diagnostic rates and pharmacological treatments in developing children have led to a more holistic review of the multi-system pathophysiology observed in ADHD. The dopaminergic neurotransmitter system, known for its influence on reward-motivated behaviors and motor control, and the frontostriatal systems, that mediate motor, cognition, and behavior, are associated with ADHD’s development. However, studies have shown that these neural systems do not wholly account for ADHD’s multilayered and heterogeneous symptom presentation. For instance, the literature suggests that emotional dysregulation, the inability to regulate one’s emotional responses to provoking stimuli, is associated with increased risk for social impairment in ADHD. A broader examination of physiological systems in children with ADHD has found potential markers in the heart-brain and gut-brain axes that correspond with certain behaviors associated with emotional dysregulation in recent studies. Hence, the purpose of this meta-analysis is to aggregate ten applicable published case studies and analyze task-related heart rate reactivity (HRR; n = 5 studies) and gut microbiota (n = 5 studies) data in children with and without ADHD. Data from a total of 531 youth with ADHD and 603 youth without ADHD revealed significant small and medium effect sizes for higher Chao1 levels and Actinobacteria levels in the ADHD group, respectively, but no evidence of altered task-related HRR. Thus, further research into multi-system psychophysiological measures of emotional dysregulation and ADHD is warranted. The clinical, empirical, and educational implications of these findings are discussed.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021236819).
Risk Factors and Prognosis for Metastatic Follicular Thyroid Cancer
Authors: Wu Ming-Hsien , Lee Yi-Yin , Lu Yu-Ling , Lin Shu-Fu
Published: March 2022

Background

Follicular thyroid cancer (FTC) is the second most common malignancy of thyroid. About 7%–23% of patients with FTC have distant metastasis. The aim of this study was to investigate the risk factors associated with distant metastasis and the impact of distant metastasis on survival in FTC patients.

Methods

Patients with FTC were analyzed using a prospectively maintained dataset of thyroid cancer registered at a tertiary hospital in Taiwan between December 1976 and May 2020.

Results

A total of 190 patients with a mean follow-up of 7.7 years were included in this study, including 29 with distant metastasis at diagnosis, 14 who developed metastasis during follow-up, and 147 without metastasis. Multivariate analysis adjusted for age, gender, tumor stage, and extrathyroidal invasion revealed old age (≥ 55 years) (adjusted odds ratio, 27.6; 95% confidence interval [CI], 8.75–86.8; P < 0.001) and extrathyroidal invasion (odds ratio, 24.1; 95% CI, 3.50–166.5; P = 0.001) were significantly associated with an increased risk of distant metastasis. Metastasis was correlated with higher cancer-specific mortality (adjusted hazard ratio, 35.5; 95% CI, 6.1–206.1; P < 0.001). In addition, patients with metastatic FTC diagnosed on initial presentation had the lowest 10-year cancer-specific survival rate (26.0%), followed by those who developed metastatic disease after initial treatment (76.6%), while patients without metastasis were all alive (100%) (P ≤ 0.002 for all comparisons).

Conclusions

Age and extrathyroidal invasion are significant risk factors for distant metastasis of FTC. Patients with metastatic FTC, especially when diagnosed on initial presentation, have dismal survival outcomes.
MiR-200c-3p Regulates DUSP1/MAPK Pathway in the Nonalcoholic Fatty Liver After Laparoscopic Sleeve Gastrectomy
Authors: Zhang Tao-tao , Wang Yong , Zhang Xiang-wen , Yang Ke-yu , Miao Xiu-qin , Zhao Guo-hua
Published: March 2022

Aim

Non-alcoholic fatty liver disease (NAFLD) is a health burden worldwide, which is closely related to obesity. The effect of sleeve gastrectomy (SG) on NAFLD is efficient, and the underlying mechanism remains unknown. Our study sought to investigate the mechanism of dual-specificity protein phosphatase 1 (DUSP1) expression regulation following the SG procedure in NAFLD patients and C57BL/6J mice via miR-200c-3p.

Methods

The serum was extracted from NAFLD patients who underwent laparoscopic sleeve gastrectomy (LSG) and volunteers. Next, the correlation between miR-200c-3p and DUSP1 was identified in vitro. NAFLD mice were modelled by high-fat diets (HFD). The hepatic tissue expression levels of miR-200c-3p, DUSP1, phospho-extracellular regulated protein kinases1/2 (p-ERK1/2), phospho -p38 mitogen-activated protein kinases (p-p38), and phospho-c-Jun N-terminal kinases (p-JNK) induced by SG procedure were evaluated.

Results

The SG procedure contributed to significant weight loss, reduced lipids in NAFLD patients and mice. The increased expression level of miR-200c-3p and reduced expression of DUSP1 were observed in NAFLD patients and mice (p<0.05). The reduced expression levels of miR-200c-3p and increased expression of DUSP1 were observed in patients and mice with NAFLD who underwent SG procedure. DUSP1 is a potential target of miR-200c-3p.

Conclusions

A novel mechanism was identified in which miR-200c-3p regulates the MAPK-dependent signals that are linked to the promotion of hepatosteatosis via DUSP1 after sleeve gastrectomy. The findings suggested that miR-200c-3p should be further explored as a potential target for the treatments of NAFLD.