bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Kualitas Pelayanan dan Fasilitas Kantor terhadap Kepuasan Nasabah di Bank Bjb Kantor Cabang Pembantu Cicalengka
Authors: Halim Asep Abdul , Nasution Ade Iskandar , Humairoh Anis Siti
Published: August 2022

Based on the results of interview with the Customer Service at bank BJB Cicalengka Branch Office Assistant, there's fluctuant customer amount during 5 last years period 2016 – 2020. That's suspected of there's some complains from customers about service quality and office facilities like some important machine does'nt work so that's impact to customer satisfaction. This research aims to determine how the influence of service quality on customer satisfaction, the influence of office facilities on customer satisfaction and to determine how the influence of service quality and office facilities on customer satisfaction. The object of research in this report is the customer in bank BJB KCP Cicalengka with the type of research is quantitative associative, in order use primary data wich is taken directly from the place of research. The research sample is taken from 1440 customers at 2020 period in bank BJB Cicalengka Branch Office Assistant. The result of this research show that there is no significance influence between service quality on customer satisfaction, there is significance influence between office facilities on customer satisfaction, And the simultaneosly test show that there is significance influence between service quality and office facilities on customer satisfaction.
Rancang Bangun Sistem Informasi Persediaan Pakan Ternak Berbasis Website di Koperasi Serba Usaha Tandangsari Sumedang
Authors: Nur Sawitri Sarah Ayu , Yusman Nova Indrayana Yusman , Partono Partono
Published: August 2022

Tandangsari Multipurpose Cooperative is a cooperative that develops community businesses in the field of dairy farming, savings and loan cooperatives and animal feed. In the processing of animal feed supplies, this cooperative is still based on semi-computerization. So cooperatives need optimal programs to improve their performance. The design of the inventory information system is a system that will be built to reduce the problems contained in the previous livestock feed inventory information system. Loss and corruption of some data that prevents data from being inputted. The method used in this animal feed inventory information system is object orientation (OOAD) and uses the Rational Unified Process (RUP) model and is supported by the Unified Modeling Language (UML) for software engineering processes with a good structure. The author draws the conclusion that the system in this design can be useful and light in the inventory process and is able to solve problems that occur so that the system that is run can be used anytime and anywhere.
Rancang Bangun Sistem Informasi Penggajian Guru dan Pegawai di MA Al-Hidayah Cikancung
Authors: Robi Ujang , Supriatna Encep , Rachman Tonton Taufik
Published: August 2022

The design of the teacher and employee payroll information system is a system created to facilitate treasurers in managing teacher and employee salary data, for example for attendance which is currently still managed manually and salary calculations are still semi-computerized which are at risk of miscalculation of both the number of days for teachers and employees. incoming employees or the salary itself, reporting takes a lot of time and duplication of data can also occur. This information system uses the SDLC (System Development Life Cycle) for system design methodology, and the writing methodology used is descriptive method, to obtain data using the methods of observation, interviews, and literature study. To design this payroll information system is to use several design tools, including Data Flow Diagrams, Structure Charts, Flowmaps, and ER Diagrams. The development of this information system uses the Microsoft Visual Foxpro 9.0 programming language and is divided into three modules, namely master, transaction, and report. The design of this payroll information system is expected to improve the performance of the treasurer in the management of teacher and employee salaries involving attendance and deductions, and make it easier to make attendance reports, assignments, deductions, and payroll.
Pengaruh Premi, Hasil Underwriting dan RBC terhadap ROA pada Asuransi Syariah yang Terdaftar di OJK Periode 2016-2020
Authors: Tresnawati Tresnawati , Yudhy Yudhy , Nur'aeni Nur'aeni
Published: August 2022

This study aims to determine how the influence of premiums, underwriting results, and RBC (Risk Based Capital) on ROA (Return on Assets) in Sharia General Insurance Registered at OJK (Financial Services Authority) either partially or simultaneously. This research method is associative quantitative with secondary data type in the form of sharia general insurance financial reports published by OJK from 2016 to 2020. The data collection techniques include documentation and literature study. While the data analysis used is multiple correlation analysis, multiple regression analysis, coefficient of determination analysis, t test design, and F test design. The results show that there is no influence between premiums on ROA in sharia general insurance registered with the OJK, there is a positive and negative effect. There is a significant relationship between underwriting results on ROA on sharia general insurance registered with the OJK, and there is no effect between RBC on ROA on sharia general insurance registered with the OJK.
Peran Bank Indonesia dalam Menstabilkan Perekonomian dan Jumlah Uang Beredar Melalui Kebijakan Moneter
Authors: Permana Yunan Hendra , Nur'aeni Nur'aeni , Setiawan Setiawan
Published: August 2022

Based on the observation, that the background in this research is the economic condition and the money supply in Indonesia as seen from the last five years, then what policies have been issued by Bank Indonesia.This study aims to determine the mechanism and role of Bank Indonesia in maintaining economic stability and the money supply through Monetary Policy.The object of research in this is located at the Representative Office of Bank Indonesia, West Java Province. The type of this research is descriptive qualitative with a qualitative approach. The source of the data obtained in the form of primary data with field observations and interviews, namely by direct observation in the field and a question and answer process with resource persons to exchange information and ideas in obtaining information and using secondary data by obtaining information through the official website of Bank Indonesia and the Central Statistics Agency. The results of this study indicate that the mechanisms and roles performed by Bank Indonesia in maintaining economic stability and the Money Supply through Monetary Policy are first, through the BI 7DRR (Bank Indonesia 7 Day Repo Rate) interest rate and Open Market Operations, Second, by using policy instruments. Macroprudential and Discount Policy.
Sistem Informasi UKM Futsal STMIK IKMI Cirebon Berbasis WEB Menggunakan Metode Waterfall
Authors: Baihaqi Achmad , Suarna Nana , Amalia Rizki Dita
Published: August 2022

Information about an Organination or a Student Activity Unit is very important to inform the activities carried out by an organization or Student Activity Unit, such as the Futsal STMIK IKMI Cirebon Student Activity Unit. The process of managing the administration of members who are still manual, providing information that has not been  and the absence of archives of the activities that have been carried out make the Futsal Student Activity Unit at STMIK IKMI Cirebon unable to recap activities. This is a factor in the futsal student activity unit's problems in member data and activity archives. This research will create a system that can accommodate existing problems. This research uses the waterfall method to develop the system. The system created will later use the website as a medium. This research method was chosen because it is a simple process and also easy to apply. The stages in this waterfall method include Needs Analysis, System Design, Workmanship, Verification, and Maintenance. The system created will improve student services and make it easier for futsal student activity unit administrators to convey information and make it easier for members to obtain information.
Pendampingan Belajar Matematika Berbantuan Media Pembelajaran Berbasis Game Counting Bunny untuk Peserta Bimbel di Rumah Belajar Matematika
Authors: Hidayati Arini , Azizah Nur , Maimuna Maimuna , Ulumuddin Deni Ihya , Aisyah Ummi Nur
Published: August 2022

Rumah Belajar Matematika is a tutoring place located in Kebonan Hamlet, Yosowilangun Kidul Village, Yosowilangun District, Lumajang Regency, East Java. The tutoring participants are elementary and junior high school students, totaling 15 people. Based on the results of observations made by the KKN team, so far the tutors at the Mathematics Learning House have never made learning innovations, especially in the use of game-based learning media. This makes us compelled to carry out mentoring activities in learning mathematics by utilizing learning media based on the counting bunny game which can make it easier for students to understand the concepts of addition and multiplication of integers. The expected goals of this service activity include: 1) so that mathematics learning activities in the tutoring can be more attractive, interesting, and fun, so that tutoring participants can be more enthusiastic in learning mathematics; 2) encourage teachers or tutors in tutoring places to be able to innovate more in learning activities, one of which is the use of learning media; 3) the use of learning media is expected to help make it easier for tutors to convey mathematical material or concepts; 4) students find it easier to understand the material or concepts presented; and 5) student learning outcomes are getting better. This learning mentoring activity was carried out for 2 days, where the KKN team acted as tutors. At the end of the activity, a response questionnaire was given to the tutoring participants to find out their response to the learning process using the counting bunny game, including enthusiasm, motivation, and interest. The results of the participants' responses showed positive results, with an average score of 3.35 and included in the high category, which means that the participants felt more enthusiastic, motivated, more interested in learning mathematics after using the counting bunny game learning media.
Measuring The Competence of Human Resources in The Organization
Authors: Garaika Garaika
Published: August 2022

An organization can run effectively if the management functions such as planning, organizing, motivating and controlling in it are functioning properly, and the supporting elements are available and meet the requirements. One of the most important elements that can support the running of the company is human resources (employees). Human resources have an important role in determining the success of the organization. For that we need a tool for measuring employee performance results, so we look for criteria and weights to calculate the results of employee performance achievements, as a measure to calculate achievements using the analytical hierarchy process (AHP) method approach
How Vietnamese healthcare students think of nurses: Students stereotypes about Nursing at University of Medicine and Pharmacy at Ho Chi Minh City
Authors: Nguyen Tuong Thi Kim , Tran Linh Thuy Khanh , Duong Khoa Duy , Tran Tuan Diep
Published: August 2022

Vietnam’s health system increasingly recognizes the importance of interprofessional collaboration and education. Understanding stereotypes and interprofessional attitude could foster successful collaboration. This study aimed to assess stereotypes about nursing amongst healthcare students at University of Medicine and Pharmacy at Ho Chi Minh City.

We invited nursing, medical, pharmacy and rehabilitation therapy students to complete an online survey before an interprofessional education course in September 2020. Student Stereotypes Rating Questionnaire was used to assess student stereotypes about nursing. Univariate regression was used to analyze the association between stereotypes score and other factors including interprofessional attitude as measured by Readiness for Interprofessional Learning Scale.

With 102 students invited, 90 students completed the survey. Students were 20-21 years old, 57% were female, and 9% from minor ethnicity. The total attitude score was 80.2 ± 7.2, which meant favorable interprofessional learning. The total stereotype score was 37.1 ± 4.0, considered as high. Stereotype rated in descending order were: Practical skills (4.4), Interpersonal skills (4.3), Ability to be a team player (4.3), Professional competence (4.2), and Confidence (4.2), Ability to make decisions (3.9), Ability to work independently (3.8) and Leadership skills (3.5). There was an association between stereotype and interprofessional attitude total score (Coefficient 0.25, 95%CI: 0.15; 0.36, p-value < 0.01).

Vietnamese students highly regarded nursing profession, yet stereotypes about nursing existed and students viewed nurses as a capable team player, almost a follower. We need to study how interprofessional education courses could improve students’ attitude and stereotypes in future research.
Factorials, Integers and Multinomial Coefficients and its Computing Techniques for Machine Learning and Cybersecurity
Authors: Annamalai Chinnaraji
Published: August 2022

Mathematical and combinatorial techniques with nonnegative integers are used as computing algorithms for the programs development to apply in artificial intelligence and cybersecurity. Methodological advances in combinatorics and mathematics play a vital role in artificial intelligence and machine learning for data analysis and artificial intelligence-based cybersecurity for protection of the computing systems, devices, networks, programs and data from cyber-attacks. In connection with these ideas, this article is prepared for applications in computing science and cybersecurity. This paper presents computing and combinatorial formulae such as theorems on factorials, binomial, and multinomial coefficients and probability and binomial distributions.
Carbon dots nanozyme for anti-inflammatory therapy via scavenging intracellular reactive oxygen species
Authors: Dong Chen , Ma Xuehua , Huang Yi , Zhang Yujie , Gao Xiang
Published: August 2022

Developing an efficient antioxidant for anti-inflammatory therapy via scavenging reactive oxygen species (ROS) remains a great challenge owing to the insufficient activity and stability of traditional antioxidants. Herein, we explored and simply synthesized a biocompatible carbon dots (CDs) nanozyme with excellent scavenging activity of ROS for anti-inflammatory therapy. As expected, CDs nanozyme effectively eliminate many kinds of free radicals including •OH, O2•−, and ABTS+•. Benefiting from multienzyme activities against ROS, CDs nanozyme can decrease the levels of pro-inflammatory cytokines, resulting in good anti-inflammatory effect. Taken together, this study not only sheds light on design of bioactive antioxidants but also broadens the biomedical application of CDs in the treatment of inflammation.
BAC cloning and heterologous expression of a giant biosynthetic gene cluster encoding antifungal neotetrafibricin in streptomyces rubrisoli
Authors: Park Heung-Soon , Park Ji-Hee , Kim Hye-Jin , Kang Seung-Hoon , Choi Si-Sun , Kim Eung-Soo
Published: August 2022

Polyene natural products including nystatin A1, amphotericin B, ECO-02301, and mediomycin belong to a large family of valuable antifungal polyketide compounds typically produced by soil actinomycetes. A previous study (Park et al., Front. Bioeng. Biotechnol., 2021, 9, 692340) isolated Streptomyces rubrisoli Inha501 with strong antifungal activity and analyzed a large-sized biosynthetic gene cluster (BGC) of a linear polyene compound named Inha-neotetrafibricin (I-NTF) using whole genome sequencing and bioinformatics. In the present study, an entire I-NTF BGC (∼167 kb) was isolated through construction and screening of Streptomyces BAC library. Overexpression of the cloned I-NTF BGC in the wild-type S. rubrisoli Inha501 and its heterologous expression in S. lividans led to 2.6-fold and 2.8-fold increase in I-NTF yields, respectively. The qRT-PCR confirmed that the transcription levels of I-NTF BGC were significantly increased in both homologous and heterologous hosts containing the BAC integration of I-NTF BGC. In addition, the I-NTF aglycone-producing strains were constructed by a target-specific deletion of glycosyltransferase gene present in I-NTF BGC. A comparison of the in vitro biological activities of I-NTF and I-NTF aglycone confirmed that the rhamnose sugar motif of I-NTF plays a critical role in both antifungal and antibacterial activities. These results suggest that the Streptomyces BAC cloning of a large-sized natural product BGC is a valuable approach for natural product titer improvement and biological activity screening of natural product in actinomycetes.
Integral bridge abutments in response to seasonal temperature changes: State of knowledge and recent advances
Authors: Liu Hao , Han Jie , Parsons Robert L.
Published: August 2022

Expansion and contraction of integral abutment bridges due to temperature changes force integral bridge abutments (IBAs) to move toward and away from the backfill, thus increasing horizontal earth pressures behind the abutments and inducing bending moments on pile foundations. This paper presents the state of knowledge and recent advances in understanding the behavior of IBAs in response to temperature changes including abutment movement, pile response, and horizontal earth pressure behind the abutment, examines the effect of bridge skew on the behavior, and discusses possible measures to mitigate temperature change-induced problems for IBAs. Field data show that both bending moments of piles near the bottom of abutments and axial loads of piles fluctuated with temperature. Redistribution of dead loads among bridge components due to planar temperature gradients and earth pressure changes behind the abutment contributed to axial load fluctuations in piles. Magnitude and distribution of horizontal earth pressures behind the abutment depend on factors such as abutment movement and abutment movement mode. Most of the current design methods overestimated the horizontal earth pressures at the bottom of the abutment during bridge expansion. Compressible inclusions placed behind the abutment, geosynthetic-reinforced backfill, and lightweight backfill in place of typical aggregate backfill are helpful to reduce horizontal earth pressures behind the abutment at high temperatures and temperature change-induced backfill settlements.
Emerging roles of long non-coding RNAs in keloids
Authors: Yu Xin , Zhu Xueqing , Xu Hongjun , Li Linfeng
Published: August 2022

Keloids are pathologic wound healing conditions caused by fibroblast hyperproliferation and excess collagen deposition following skin injury or irritation, which significantly impact patients by causing psychosocial and functional distress. Extracellular matrix (ECM) deposition and human fibroblast proliferation represents the main pathophysiology of keloid. Long non-coding RNAs (LncRNAs) play important roles in many biological and pathological processes, including development, differentiation and carcinogenesis. Recently, accumulating evidences have demonstrated that deregulated lncRNAs contribute to keloids formation. The present review summarizes the researches of deregulated lncRNAs in keloid. Exploring lncRNA-based methods hold promise as new effective therapies against keloid.
Emerging trends and focus for the link between the gastrointestinal microbiome and kidney disease
Authors: Tan Jiaxing , Chen Ming , Wang Yutong , Tang Yi , Qin Wei
Published: August 2022

The clinical value of the relationship between gastrointestinal microbiome imbalance and its corresponding interventions with kidney disease is emerging. This study describes the hotspots and evolution of gastrointestinal microbiome and kidney disease research over the past three decades by scientific collaboration networks and finally predicts future trends in the field through bibliometric analysis and visualization studies. CiteSpace was used to explore the original articles from January 1990 to August 2021 to visualize the knowledge network of journals, countries, institutions, authors, references, and keywords in this field. Publications were extracted from Web of Science Core Collection database using the terms “gastrointestinal microbiome” and “kidney disease” (and their synonyms in MeSH). A total of 2145 publications with 93880 references in 102 journals were included in the analyses. The number of studies combining gastrointestinal microbiomes with kidney diseases has increased significantly over the past two decades. The United States is the leading country in the number of documents, and the leading institution is the Cleveland Clinic. The most landmark articles in the field are on chronic renal failure, L-Carnitin, and cardiovascular disease. The pathogenesis of uremia toxin is an emerging trend in gastrointestinal microbiomes and kidney diseases. In addition, probiotic or synbiotic supplements have strong clinical value in adjusting abnormal intestinal symbiotic environments. This study demonstrates a growing understanding of the interaction between gut microbiota and kidney disease over time. Using microbial supplements to improve the living conditions of kidney disease patients is a promising and hot research focus. Based on publications extracted from the database, this study may provide clinicians and researchers with valuable information to identify potential collaborators and partner institutions and better predict their dynamic progression.
Potential value of pre- and post-therapy [68Ga]Ga-DOTA-TATE PET/CT in the prognosis of response to PRRT in disseminated neuroendocrine tumors
Authors: Opalińska Marta , Morawiec-Sławek Karolina , Kania-Kuc Adrian , Al Maraih Ibraheem , Sowa-Staszczak Anna , Hubalewska-Dydejczyk Alicja
Published: August 2022

Background

Peptide receptor radionuclide therapy (PRRT) is one of the most effective therapeutic options for the treatment of metastatic, well-differentiated neuroendocrine tumors (NETs). It improves progressive disease-free survival and enables the control of hormone secretion in functioning tumors.

Currently, there are no clearly established predictors of response to PRRT. The main factors hindering such a prediction are the heterogeneity of somatostatin receptor expression within and between lesions, lack of standardized parameters for functional imaging, and the use of different PRRT protocols.

The main goal of our study was to quantify SUVmax changes in [68Ga]Ga-DOTA-TATE PET/CT scans as a potential predictor of long-term response to PRRT.

Material and methods

Out of 20 patients treated with PRRT using [177Lu]Lu and/or [177Lu]Lu/[90Y]Y-DOTA-TATE in 2017–2019 due to dissemination of neuroendocrine neoplasm, 12 patients underwent [68Ga]Ga-DOTA-TATE PET/CT on average 3.1 months before and 4.5 months after PRRT and were eligible for the analysis.

In total, 76 NET lesions were evaluated. We measured SUVmax for every lesion in both PET/CT scans (before and after PRRT). Those values were corrected by liver SUVmax and liver SUVmean measured in volumetric analysis and specified as SUVlmax and SUVlmean. As a next step, changes in SUVlmax and SUVlmean were assessed based on both PET/CT scans. Finally, results were correlated with the clinical outcome assessed as progressive disease, disease stabilization, or partial response.

Results

The mean follow-up period was 19.9 months. Progressive disease, partial response, and disease stabilization were found in five, two, and five patients, respectively. Among patients with a partial response, the decrease in mean SUVlmax was 66.3% when compared to baseline. In patients with stable disease, the decrease in SUVlmax was 30.3% when compared to baseline. In patients with progressive disease, the mean increase in SUVlmax was 9.1% when compared to baseline. The changes in SUVlmean were -69,8%, -30.8%, and -3.7%, respectively.

Conclusions

A decrease in the SUVmax value in NET lesions, corrected by normal liver tissue uptake assessed in [68Ga]Ga-DOTA-TATE PET/CT scans, indicates a lower risk for NET progressive disease within 20 months after PRRT and may constitute an additional and independent parameter for the estimation of overall risk for disease progression.
Pharmacological activation of PPARβ/δ preserves mitochondrial respiratory function in ischemia/reperfusion via stimulation of fatty acid oxidation-linked respiration and PGC-1α/NRF-1 signaling
Authors: Papatheodorou Ioanna , Makrecka-Kuka Marina , Kuka Janis , Liepinsh Edgars , Dambrova Maija , Lazou Antigone
Published: August 2022

Myocardial ischemia/reperfusion (I/R) injury leads to significant impairment of cardiac function and remains the leading cause of morbidity and mortality worldwide. Activation of peroxisome proliferator-activated receptor β/δ (PPARβ/δ) confers cardioprotection via pleiotropic effects including antioxidant and anti-inflammatory actions; however, the underlying mechanisms are not yet fully elucidated. The aim of this study was to investigate the effect of PPARβ/δ activation on myocardial mitochondrial respiratory function and link this effect with cardioprotection after ischemia/reperfusion (I/R). For this purpose, rats were treated with the PPARβ/δ agonist GW0742 and/or antagonist GSK0660 in vivo. Mitochondrial respiration and ROS production rates were determined using high-resolution fluororespirometry. Activation of PPARβ/δ did not alter mitochondrial respiratory function in the healthy heart, however, inhibition of PPARβ/δ reduced fatty acid oxidation (FAO) and complex II-linked mitochondrial respiration and shifted the substrate dependence away from succinate-related energy production and towards NADH. Activation of PPARβ/δ reduced mitochondrial stress during in vitro anoxia/reoxygenation. Furthermore, it preserved FAO-dependent mitochondrial respiration and lowered ROS production at oxidative phosphorylation (OXPHOS)-dependent state during ex vivo I/R. PPARβ/δ activation was also followed by increased mRNA expression of components of FAO -linked respiration and of transcription factors governing mitochondrial homeostasis (carnitine palmitoyl transferase 1b and 2-CPT-1b and CPT-2, electron transfer flavoprotein dehydrogenase -ETFDH, peroxisome proliferator-activated receptor gamma co-activator 1 alpha- PGC-1α and nuclear respiratory factor 1-NRF-1). In conclusion, activation of PPARβ/δ stimulated both FAO-linked respiration and PGC-1α/NRF -1 signaling and preserved mitochondrial respiratory function during I/R. These effects are associated with reduced infarct size.
Peafowl optimization algorithm based PV cell models parameter identification
Authors: Zheng You , Zhang Enyou , An Peng
Published: August 2022

Photovoltaic (PV) power generation can considerably reduce the consumption of traditional fossil energy and improve environmental problems. Reliable photovoltaic (PV) cell modelling owns great significance to the following output characteristics analysis and optimal operation of the whole PV system, while there are several unknown physical parameters within different PV cell models. Thus, the identification of the internal parameters of the PV cell model is the first and foremost step for PV cell modelling, nevertheless, the intrinsic highly complex and non-linear and multi-modal features make traditional approaches, such as analytical methods hard to achieve satisfactory performance in solving this problem. Hence, this work aims to employ a powerful tool to effectively and efficiently overcome this thorny problem based on the most advanced optimization method. A recently developed meta-heuristic algorithm called peafowl optimization algorithm (POA) is employed in this work for PV cell modelling parameter identification. For comprehensive validation, two different PV cell models, i.e., double diode model (DDM) and triple diode model (TDM) are utilized. Simulation results demonstrate that POA can more accurately identify the unknown parameters of PV cell models in a higher convergence speed compared against other algorithms.
Spatiotemporal impacts of the Anthropocene on small mammal communities, and the role of small biological preserves in maintaining biodiversity
Authors: Viteri Maria C. , Hadly Elizabeth A.
Published: August 2022

The multi-faceted impacts of the Anthropocene are increasingly modifying natural ecosystems and threatening biodiversity. Can small protected spaces conserve small mammal diversity across spatial and temporal scales of human impact? We identified small mammal remains from modern raptor pellets and Holocene archeological sites along a human modification gradient in the San Francisco Bay Area, CA and evaluated alpha and beta diversity across sites and time periods. We found that Shannon diversity, standardized species richness, and evenness decrease across modern sites based on level of human modification, with no corresponding change between Holocene sites. Additionally, the alpha diversity of modern sites with moderate and high levels of human modification was significantly lower than the diversity of modern sites with low levels of human modification as well as all Holocene sites. On the other hand, the small mammal communities from Jasper Ridge Biological Preserve, a small protected area, retain Holocene levels of alpha diversity. Jasper Ridge has also changed less over time in terms of overall community composition (beta diversity) than more modified sites. Despite this, Holocene and Anthropocene communities are distinct regardless of study area. Our results suggest that small mammal communities today are fundamentally different from even a few centuries ago, but that even relatively small protected spaces can partially conserve native faunal communities, highlighting their important role in urban conservation.
A novel defined cuproptosis-related gene signature for predicting the prognosis of lung adenocarcinoma
Authors: Zhang Huizhe , Shi Yanchen , Yi Qing , Wang Cong , Xia Qingqing , Zhang Yufeng , Jiang Weilong , Qi Jia
Published: August 2022

Lung adenocarcinoma (LUAD) has become the most prevalent histologic subset of primary lung cancer, and effective innovative prognostic models are needed to enhance the feasibility of targeted therapies for the disease. Programmed cell death (PCD) performs an integral function in the origin and treatment of cancer. Some PCD-related effective signatures for predicting prognosis in LUAD patients could provide potential therapeutic options in LUAD. A copper-dependent cell death referred to as cuproptosis is distinct from known PCD. However, whether cuproptosis is associated with LUAD patients' prognoses and the potential roles of cuproptosis-related genes involved is still unknown. For the prediction of LUAD prognosis, we developed a unique cuproptosis-associated gene signature. In The Cancer Genome Atlas (TCGA) cohort, the score derived from the risk signature on the basis of six cuproptosis-related genes was found to independently serve as a risk factor for anticipating lung cancer-related death. The differentially expressed genes between the high- and low-risk groups were linked to the cilium-related function. LUAD patients’ prognoses may now be predicted by a unique gene signature identified in this work. This discovery also provides a substantial foundation for future research into the links between cuproptosis-associated genes and cilium-related function in LUAD patients.
B7H3-dependent myeloid-derived suppressor cell recruitment and activation in pulmonary fibrosis
Authors: Liu Tianju , Gonzalez De Los Santos Francina , Rinke Andrew E. , Fang Chuling , Flaherty Kevin R. , Phan Sem H.
Published: August 2022

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease without effective curative therapy. Recent evidence shows increased circulating myeloid-derived suppressor cells (MDSCs) in cancer, inflammation, and fibrosis, with some of these cells expressing B7H3. We sought to investigate the role of MDSCs in IPF and its potential mediation via B7H3. Here we prospectively collected peripheral blood samples from IPF patients to analyze for circulating MDSCs and B7H3 expression to assess their clinical significance and potential impact on co-cultured lung fibroblasts and T-cell activation. In parallel, we assess MDSC recruitment and potential B7H3 dependence in a mouse model of pulmonary fibrosis. Expansion of MDSCs in IPF patients correlated with disease severity. Co-culture of soluble B7H3 (sB7H3)-treated mouse monocytic MDSCs (M-MDSCs), but not granulocytic MDSCs (G-MDSCs), activated lung fibroblasts and myofibroblast differentiation. Additionally, sB7H3 significantly enhanced MDSC suppression of T-cell proliferation. Activated M-MDSCs displayed elevated TGFβ and Arg1 expression relative to that in G-MDSCs. Treatment with anti-B7H3 antibodies inhibited bone marrow-derived MDSC recruitment into the bleomycin-injured lung, accompanied by reduced expression of inflammation and fibrosis markers. Selective telomerase reverse transcriptase (TERT) deficiency in myeloid cells also diminished MDSC recruitment associated with the reduced plasma level of sB7H3, lung recruitment of c-Kit+ hematopoietic progenitors, myofibroblast differentiation, and fibrosis. Lung single-cell RNA sequencing (scRNA-seq) revealed fibroblasts as a predominant potential source of sB7H3, and indeed the conditioned medium from activated mouse lung fibroblasts had a chemotactic effect on bone marrow (BM)-MDSC, which was abolished by B7H3 blocking antibody. Thus, in addition to their immunosuppressive activity, TERT and B7H3-dependent MDSC expansion/recruitment from BM could play a paracrine role to activate myofibroblast differentiation during pulmonary fibrosis with potential significance for disease progression mediated by sB7H3.
Prognostic impacts of soluble immune checkpoint regulators and cytokines in patients with SARS-CoV-2 infection
Authors: Lee Nuri , Jeong Seri , Jeon Kibum , Park Min-Jeong , Song Wonkeun
Published: August 2022

Coronavirus disease 2019 (COVID-19) has been a pandemic for the past two years. Predicting patient prognosis is critical. Although immune checkpoints (ICs) were shown to be involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, quantitative studies of ICs in clinical practice are limited. In this study, various soluble ICs (sICs) and cytokine levels in patients with SARS-CoV-2 infection at different time points were compared between survivors and deaths; we also examined whether sICs are useful for predicting prognosis. sICs and cytokines were measured in serum samples from 38 patients diagnosed with COVID-19 in the first and second week post-diagnosis. All assays were performed by bead-based multiplexed immunoassay system using Luminex Bio-Plex 200 system. The correlation of sICs and cytokines with laboratory markers was evaluated, and the levels of sICs in survivors were compared with those in deaths. Among the sICs, the second-week levels of soluble cluster of differentiation (sCD27, p = 0.012), sCD40 (p< 0.001), cytotoxic T-lymphocyte-associated protein 4 (sCTLA-4, p< 0.001), herpes virus entry mediator (sHVEM, p = 0.026), and T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3, p = 0.002) were significantly higher in deaths than in survivors. The levels of nine cytokines assessed in the second week of deaths were significantly higher than those in survivors. The sICs sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines chemokine CC motif ligand 2 (CCL2), GM-CSF, IL-10, and IL-8 showed significant positive correlations with the levels of C-reactive protein (CRP) and procalcitonin and were negatively correlated with the absolute lymphocyte count and platelet values. Increased levels of sICs including sCD27, sCD40, sCTLA-4, and sTIM-3 and cytokines were significant factors for poor prognosis. sICs, together with cytokines and inflammatory markers, may be useful as prognostic stratification markers in SARS-CoV-2-infected patients.
Antibodies against the SARS-CoV-2 S1-RBD cross-react with dengue virus and hinder dengue pathogenesis
Authors: Cheng Yi-Ling , Chao Chiao-Hsuan , Lai Yen-Chung , Hsieh Kun-Han , Wang Jen-Ren , Wan Shu-Wen , Huang Hong-Jyun , Chuang Yung-Chun , Chuang Woei-Jer , Yeh Trai-Ming
Published: August 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally since December 2019. Several studies reported that SARS-CoV-2 infections may produce false-positive reactions in dengue virus (DENV) serology tests and vice versa. However, it remains unclear whether SARS-CoV-2 and DENV cross-reactive antibodies provide cross-protection against each disease or promote disease severity. In this study, we confirmed that antibodies against the SARS-CoV-2 spike protein and its receptor-binding domain (S1-RBD) were significantly increased in dengue patients compared to normal controls. In addition, anti-S1-RBD IgG purified from S1-RBD hyperimmune rabbit sera could cross-react with both DENV envelope protein (E) and nonstructural protein 1 (NS1). The potential epitopes of DENV E and NS1 recognized by these antibodies were identified by a phage-displayed random peptide library. In addition, DENV infection and DENV NS1-induced endothelial hyperpermeability in vitro were inhibited in the presence of anti-S1-RBD IgG. Passive transfer anti-S1-RBD IgG into mice also reduced prolonged bleeding time and decreased NS1 seral level in DENV-infected mice. Lastly, COVID-19 patients’ sera showed neutralizing ability against dengue infection in vitro. Thus, our results suggest that the antigenic cross-reactivity between the SARS-CoV-2 S1-RBD and DENV can induce the production of anti-SARS-CoV-2 S1-RBD antibodies that cross-react with DENV which may hinder dengue pathogenesis.
Passive immunization with equine RBD-specific Fab protects K18-hACE2-mice against Alpha or Beta variants of SARS-CoV-2
Authors: Barbier Mariette , Lee Katherine S. , Vikharankar Mayur S. , Rajpathak Shriram N. , Kadam Nandkumar , Wong Ting Y. , Russ Brynnan P. , Cyphert Holly A. , Miller Olivia A. , Rader Nathaniel A. , Cooper Melissa , Kang Jason , Sen-Kilic Emel , Wong Zeriel Y. , Winters Michael T. , Bevere Justin R. , Martinez Ivan , Devarumath Rachayya , Shaligram Umesh S. , Damron F. Heath
Published: August 2022

Emergence of variants of concern (VOC) during the COVID-19 pandemic has contributed to the decreased efficacy of therapeutic monoclonal antibody treatments for severe cases of SARS-CoV-2 infection. In addition, the cost of creating these therapeutic treatments is high, making their implementation in low- to middle-income countries devastated by the pandemic very difficult. Here, we explored the use of polyclonal EpF(ab’)2 antibodies generated through the immunization of horses with SARS-CoV-2 WA-1 RBD conjugated to HBsAg nanoparticles as a low-cost therapeutic treatment for severe cases of disease. We determined that the equine EpF(ab’)2 bind RBD and neutralize ACE2 receptor binding by virus for all VOC strains tested except Omicron. Despite its relatively quick clearance from peripheral circulation, a 100μg dose of EpF(ab’)2 was able to fully protect mice against severe disease phenotypes following intranasal SARS-CoV-2 challenge with Alpha and Beta variants. EpF(ab’)2 administration increased survival while subsequently lowering disease scores and viral RNA burden in disease-relevant tissues. No significant improvement in survival outcomes or disease scores was observed in EpF(ab’)2-treated mice challenged using the Delta variant at 10μg or 100µg doses. Overall, the data presented here provide a proof of concept for the use of EpF(ab’)2 in the prevention of severe SARS-CoV-2 infections and underscore the need for either variant-specific treatments or variant-independent therapeutics for COVID-19.
Human metapneumovirus M2-2 protein inhibits RIG-I signaling by preventing TRIM25-mediated RIG-I ubiquitination
Authors: Tanaka Yukie , Morita Naoko , Kitagawa Yoshinori , Gotoh Bin , Komatsu Takayuki
Published: August 2022

Retinoic acid-inducible gene I (RIG-I) is a receptor that senses viral RNA and interacts with mitochondrial antiviral signaling (MAVS) protein, leading to the production of type I interferons and inflammatory cytokines to establish an antiviral state. This signaling axis is initiated by the K63-linked RIG-I ubiquitination, mediated by E3 ubiquitin ligases such as TRIM25. However, many viruses, including several members of the family Paramyxoviridae and human respiratory syncytial virus (HRSV), a member of the family Pneumoviridae, escape the immune system by targeting RIG-I/TRIM25 signaling. In this study, we screened human metapneumovirus (HMPV) open reading frames (ORFs) for their ability to block RIG-I signaling reconstituted in HEK293T cells by transfection with TRIM25 and RIG-I CARD (an N-terminal CARD domain that is constitutively active in RIG-I signaling). HMPV M2-2 was the most potent inhibitor of RIG-I/TRIM25-mediated interferon (IFN)-β activation. M2-2 silencing induced the activation of transcription factors (IRF and NF-kB) downstream of RIG-I signaling in A549 cells. Moreover, M2-2 inhibited RIG-I ubiquitination and CARD-dependent interactions with MAVS. Immunoprecipitation revealed that M2-2 forms a stable complex with RIG-I CARD/TRIM25 via direct interaction with the SPRY domain of TRIM25. Similarly, HRSV NS1 also formed a stable complex with RIG-I CARD/TRIM25 and inhibited RIG-I ubiquitination. Notably, the inhibitory actions of HMPV M2-2 and HRSV NS1 are similar to those of V proteins of several members of the Paramyxoviridae family. In this study, we have identified a novel mechanism of immune escape by HMPV, similar to that of Pneumoviridae and Paramyxoviridae family members.
The gut microbiome molecular mimicry piece in the multiple sclerosis puzzle
Authors: Elsayed Noha S. , Aston Paula , Bayanagari Vishnu R. , Shukla Sanjay K.
Published: August 2022

The etiological complexity of multiple sclerosis, an immune-mediated, neurodegenerative disease with multifactorial etiology is still elusive because of an incomplete understanding of the complex synergy between contributing factors such as genetic susceptibility and aberrant immune response. Recently, the disease phenotypes have also been shown to be associated with dysbiosis of the gut microbiome, a dynamic reservoir of billions of microbes, their proteins and metabolites capable of mimicring the autoantigens. Microbial factors could potentially trigger the neuroinflammation and symptoms of MS. In this perspective article, we discussed how microbial molecules resulting from a leaky gut might mimic a host’s autoantigen, potentially contributing to the disease disequilibrium. It further highlights the importance of targeting the gut microbiome for alternate therapeutic options for the treatment of MS.
Putative role of corazonin in the ovarian development of the swimming crab Portunus trituberculatus
Authors: Tu Shisheng , Ge Fuqiang , Han Yaoyao , Wang Mengen , Xie Xi , Zhu Dongfa
Published: August 2022

Corazonin (Crz) is a neuropeptide that widely distributed in insects and crustaceans. The Crz is proposed to have pleiotropic functions in insects, but its physiological roles in crustaceans are poorly understood. In the present study, Crz and its putative receptor (CrzR) were identified from the swimming crab, Portunus trituberculatus, and their interaction was validated using the Dual-Luciferase reporter assay system. Tissue distribution analysis showed the PtCrz was mainly derived from center nerve system, while its receptor was highly expressed in Y-organ, the main site for ecdysteroids synthesis. Exposure of YO to synthetic Crz and CrzR dsRNA respectively led to the transcriptional changes of two ecdysteroidogenesis genes, further indicating a putative role of Crz signaling on ecdysteroids synthesis. During the ovarian development, the mRNA levels of PtCrz and PtCrzR increased significantly in vitellogenic stages, suggesting a potential role of Crz signaling in vitellogenesis. The hypothesis was further strengthened by in vitro experiments that the expression of vitellogenin (Vg), Vg receptor (VgR), cyclinB, and Cdc2 in ovary explants could be induced by synthetic Crz, whereas reduced by CrzR dsRNA. In addition, since 20-hydroxyecdysone also showed a stimulating effect on Vg expression, an indirect regulation of Crz signaling on ovarian development via ecdysteroids might also exist.
Orlistat and ezetimibe could differently alleviate the high-fat diet-induced obesity phenotype by modulating the gut microbiota
Authors: Jin Jin , Wang Jiani , Cheng Ruyue , Ren Yan , Miao Zhonghua , Luo Yating , Zhou Qingqing , Xue Yigui , Shen Xi , He Fang , Tian Haoming
Published: August 2022

This study aimed to evaluate the possible anti-obesity effects of orlistat and ezetimibe and determine the mechanism by which they alter the composition of gut microbiota and short-chain fatty acids (SCFAs) in mice with a high-fat diet (HFD)-induced obesity. Eighty male, specific pathogen-free C57BL/6J mice aged 3 weeks were divided into four groups (n = 20). The NCD group was fed with a normal diet, and the HFD, HFD+ORL, and HFD+EZE groups were fed with HFD for 20 weeks. From the 13th week onward, the HFD+ORL and HFD+EZE groups were administered with orlistat and ezetimibe, respectively. The glucose and lipid metabolism of the tested mice were evaluated by analyzing blood biochemical indicators during the intervention. Furthermore, the changes in the structure of the fecal microbiota and the fecal SCFA content were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry, respectively. HFD induced the obesity phenotype in mice. Compared to the HFD group, the body weight, visceral fat-to-body weight ratio, serum total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and oral glucose tolerance test (OGTT) of the HFD+ORL group significantly decreased, whereas fecal butyric acid levels significantly increased. Ezetimibe intervention significantly reduced the OGTT, serum TC, and HDL-C levels only. The α-diversity of the gut microbiota significantly decreased after intervention with orlistat and ezetimibe. Orlistat altered the relative abundance of some bacteria in the fecal microbiota. The populations of Firmicutes, Alistipes, and Desulfovibrio decreased, whereas those of Verrucomicrobia and Akkermansia significantly increased. Ezetimibe caused changes only in some low-abundance bacteria, as manifested by a decrease in Proteobacteria and Desulfovibrio, and an increase in Bacteroides. The administration of orlistat and ezetimibe can characteristically influence the body weight and serum lipid metabolism, and glucolipid levels in diet-induced obese mice and is accompanied by significant changes in the gut microbiota and SCFAs. These results suggest that the two drugs might exert their own specific anti-obesity effects by modulating the gut microbiota in a different manner. The enhanced health-promoting effect of orlistat might result from its stronger ability to alter the gut microbiota and SCFAs, at least partly.