bluuebunny/crossref_metadata_2025 huggingface dataset:
Welding ANALISA PENGARUH VARIASI ARUS PENGELASAN KOMBINASI SMAW DAN GTAW TERHADAP PENGUJIAN KEKERASAN, KEKUATAN IMPAK SERTA PENGAMATAN STRUKTUR MIKRO PADA BAJA JIS SS400
Authors: Desmon Semuel
Published: August 2022

Sambungan las merupakan bagian sangat penting dalam sebuah kontruksi material yang didalamnya terdapat parameter-parameter penentu kualitas kekuatan dan ketangguhan material dalam menerima pembebanan tertentu, untuk mendapatkan kualitas maksimal penulis mencoba untuk mengangkat tema pengelasan kombinasi Shielded Metal Arc Welding (SMAW) dan Gas Tungsten Arc Welding (GTAW) dengan klasifikasi variasi arus metode pengelasan SMAW 95 A (arus rendah), 110 A (arus sedang), dan 125 A (arus tinggi), sedang pada metode pengelasan GTAW memakai arus 70 A, pada material pelat baja baja JIS SS400 dengan tebal 10 mm. Pada pengamatan struktur mikro dilakukan pada 4 titik bagian HAZ SMAW, HAZ GTAW, weld metal SMAW, dan weld metal GTAW sebagai bagian yang terpengaruh panas terbesar. Hasil uji kekerasan/hardness yang memiliki nilai kekerasan tertinggi pada based metal adalah pelat 1 dengan nilai 78,5 HRB, pada HAZ SMAW kiri adalah pelat 3 dengan nilai 78,66 HRB, pada HAZ GTAW kiri adalah pelat 3 dengan nilai 77,16 HRB, pada weld metal SMAW adalah pelat 1 dengan nilai 82,16 HRB, pada weld metal GTAW adalah pelat 1 dengan nilai 83,66 HRB, pada HAZ SMAW kanan adalah pelat 3 dengan nilai 78,33 HRB, dan pada HAZ GTAW kanan adalah pelat 3 dengan nilai 77,83 HRB. Pada uji impak pelat 1 memiliki nilai kekuatan impak sebesar 130,8 J, pelat 2 sebesar 139,3 J, dan pelat 3 sebesar 103 J.
Pengaruh Profitabilitas, Leverage, Ukuran Perusahaan dan Beban Pajak Tangguhan Terhadap Manajemen Laba (Studi Empiris Pada Perusahaan Perbankan Yang Terdaftar Di Bursa Efek Indonesia)
Authors: Puspita Indah Lia , Lestari Lesti
Published: August 2022

The company was established with the aim of making as much profit as possible, the owner usuallygave up the company's resources to be managed by management. The research objective is to test,prove and know the effect of profitability, leverage, firm size, deferred tax burden on earningsmanagement. this research was conducted at banking companies listed on the Indonesia StockExchange. The number of samples in this study were 20 companies that had met the criteria in thestudy. The results in this study show that, profitability, firm size, deferred tax expense have aninfluence on earnings management while leverage, and tax planning have no influence.Keywords: Profitability, Leverage, Company Size, Deferred Tax Expenses1
Estrategias de enseñanza - aprendizaje en la educación superior: Una experiencia en la ESPOCH
Authors: Toledo Castillo Norma del Rocío , Villacís Venegas Norma Yolanda , Peñafiel Moncayo Isabel Romané
Published: August 2022

Los cambios experimentados en los últimos años en el contexto científico-tecnológico y educativo, han revolucionado las formas de pensar y actuar. Ante esto la comunidad educativa en los diferentes niveles de enseñanza, incluyendo la Educación Superior, se han visto en la necesidad de repensar y adaptar las estrategias de enseñanza-aprendizaje para poder dar respuestas a la diversidad existente en cada grupo escolar y nivel de enseñanza. En el caso de la Educación Superior lo expuesto a presupuesto no sólo, el diseño de nuevos modelos educativos y curriculares, sino también ha implicado un hacer pedagógico y didáctico diferente, frente a un alumnado permeado por los avances tecnológicos, con aspiraciones y necesidades cada vez más creciente. Es por ello que el hecho de enseñar en los tiempos modernos en el contexto de la Educación Superior exige contar con un profesorado altamente calificado, preparado y competente, capaz de hacer frente a un proceso de enseñanza-aprendizaje donde los estudiantes deben ser gestores de su propio aprendizaje y los docentes facilitadores de las estrategias de enseñanza para el logro de un aprendizaje que fomente la formación integral y la preparación para la inserción laboral de forma adecuada.
FINANCIAL RESTATEMENT AFFECTING FACTORS ANALYSIS ON INDONESIA MANUFACTURING COMPANIES
Authors:   Universitas Katolik Widya Mandala Surabaya Indonesia, Marjono Cornelia Clarissa , Lindrawati Lindrawati ,   Universitas Katolik Widya Mandala Surabaya Indonesia
Published: August 2022

Research Purposes. The purpose of this research is to examine and analyze the influence of corporate governance, ownership structure, financial performance, audit quality, related party transaction, and founders on board towards financial restatement of Indonesia manufacturing companies. Research Methods. The design of this research is a quantitative research. The objects of this research are Indonesia Stock Exchange manufacturing companies of 2013-2017. Data analysis technique used in this research is logistic. Research Results and Findings. The result of this research shows that corporate governance represented by board of commissioner positively affect financial restatement, board of director negatively affect financial restatement, while independent commissioner and audit committee have no effect towards financial restatement. Ownership structure has no effect towards financial restatement. Financial performance, audit quality, and related party transaction also have no effect towards financial restatement. While, founders on board positively affect financial restatement.
REMUNERASI DIREKSI, DISPARITAS GAJI ANTAR DIREKSI DAN KINERJA PERUSAHAAN
Authors:   STIE Indonesia Banking School Indonesia, Kirana Candra Anindya , Novita Nova ,   STIE Indonesia Banking School Indonesia
Published: August 2022

Research Purposes. This research investigates the effect of directors' remuneration and pays dispersion among directors on firm performance. The study used a sample of non-financial services and insurance State-Owned Enterprises listed on the Indonesia Stock Exchange in 2015-2019. Research Methods. Data analysis technique used in this research is multiple regression. The firm performance is measured using the financial aspect health score, as stated in the Decree of the Minister of State-Owned Enterprises No. KEP-100 / MBU / 2002. The remuneration variable is measured using total remuneration. The pays dispersion between directors is measured using the average difference between the president director and other directors in the form of a percentage. Research Results and Findings. The test results show that directors' remuneration positively affects performance, while the pays dispersion between directors does not affect performance. These results indicate that the current regulations regarding the arrangements for BUMN directors' remuneration can reduce conflicts of interest of directors and prevent the negative impact of pays dispersion between directors.
Analisis Pendekatan Arsitektur Atmosfer Pada Karya Anthony Liu, Studi Kasus: Poliklinik Griya Anugerah
Authors: Hariyanto Moses Luca , Khamdevi Muhammar
Published: August 2022

Atmospheric approach in a building provides an architectural experience to its users. One of the architects who applied this approach was Anthony Liu. This study tries to explore one of his works, namely the Griya Anugerah Polyclinic. How is the atmospheric approach applied to the building? The qualitative method will analyze the application of this approach to the building. The results of this study indicate the application of the atmosphere by the architect to each element, especially dominantly in space exploration. It prioritizes function, comfort, and experience. The use of white and the play of light is the character of Anthony Liu's design.
Fenomena Alih Kode dan Campur Kode pada Tindak Tutur Anak Muda Indonesia: Studi Kasus Wawancara Anindita Hidayat di Kanal Youtube TruezID Indonesia
Authors: Suwarna Dadan
Published: August 2022

Globalisasi dan perkembangan teknologi informasi dan komunikasi mengubah perilaku manusia, khususnya dalam tindak tutur. Penggunaan bahasa asing adalah hal yang lazim dilakukan. Di Indonesia, terdapat fenomen alih kode dan campur kode dalam tindak tutur anak muda Indonesia. Penelitian ini membahas alih kode dan campur kode dalam tindak tutur anak muda Indonesia. Penelitian ini menggunakan metode deskriptif kualitatif. Subjek penelitian ini adalah Anindita Hidayat (selebgram). Penelitian ini mengamati wawancara Aninditas Hidayat di kanal YouTube TrueID Indonesia  pada episode “Check In with Onad feat. Anindita Hidayat - TrueID Original Series”. Wawancara itu diunggah pada 11 Februari 2022. Hasil penelitian ini menunjukkan bahwa terdapat campur kode dan alih kode pada tindak tutur Anindita Hidayat. pada situasi tertentu, penutur seharusnya dapat menggunakan bahasa Indonesia, tetapi penutur menggunakan bahasa Inggris. Sementara itu, fenomena alih kode ditunjukkan pada peralihan kalimat. Misalnya, pada saat tertentu, penutur menggunakan kalimat dalam bahasa Indonesia, tetapi pada kalimat berikutnya penutur menggunakan bahasa Inggris.
Odor-induced modification of oscillations and related theta-higher gamma coupling in olfactory bulb neurons of awake and anesthetized rats
Authors: Zhu Ping , Liu Shuge , Tian Yulan , Chen Yating , Chen Wei , Wang Ping , Du Liping , Wu Chunsheng
Published: August 2022

Olfactory gamma oscillations (40–100 Hz) are generated spontaneously in animals and represent the activity of local olfactory bulb (OB) networks, which play important roles in cognitive mechanisms. In addition, high-frequency oscillations (HFO, 130–180 Hz) have attracted widespread attention and are novel neuronal oscillations with a frequency range closer to high gamma oscillations (60–100 Hz, HGOs). Both HGOs and HFOs are distinctly regulated by θ rhythm in the hippocampus. To understand their mediation mechanisms in the OB, we investigated whether local field potential (LFP) oscillations including HGOs and HFOs and even their coupling with theta rhythm are modified by odor stimulation in both freely moving and anesthetized rats. Therefore, we combined electrophysiological technology and cross-frequency coupling analysis approaches to determine the difference in the odor-modulated LFP oscillations between awake and anesthetized rats. The obtained results indicate that LFP oscillations including HGOs and HFOs were differently modified by odor stimulation in animals of both states. However, θ-HGO and θ-HFO coupling were modified in only awake animals. It is suggested that these oscillations and their interactions with theta oscillations may play crucial roles in olfactory network activity. This could pave the way for further understanding the underlying mechanisms of oscillations in OB neurons towards odor sensation.
Metagenomic next-generation sequencing for the diagnosis of pulmonary aspergillosis in non-neutropenic patients: a retrospective study
Authors: Bao Shujun , Song Huihui , Chen Yang , Zhong Caiming , Tang Hao
Published: August 2022

This study aimed to obtain further in-depth information on the value of metagenomic next-generation sequencing (mNGS) for diagnosing pulmonary aspergillosis in non-neutropenic patients. We did a retrospective study, in which 33 non-neutropenic patients were included, of which 12 were patients with pulmonary aspergillosis and 21 were diagnosed with non-pulmonary aspergillosis. Fungi and all other co-pathogens in bronchoalveolar lavage fluid (BALF) (27 cases), blood (6 cases), and/or pleural fluid (1 case) samples were analyzed using mNGS. One of the patients submitted both BALF and blood samples. We analyzed the clinical characteristics, laboratory tests, and radiologic features of pulmonary aspergillosis patients and compared the diagnostic accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value of mNGS with conventional etiological methods and serum (1,3)-β-D-glucan. We also explored the efficacy of mNGS in detecting mixed infections and co-pathogens. We further reviewed modifications of antimicrobial therapy for patients with pulmonary aspergillosis according to the mNGS results. Finally, we compared the detection of Aspergillus in BALF and blood samples from three patients using mNGS. In non-neutropenic patients, immunocompromised conditions of non-pulmonary aspergillosis were far less prevalent than in patients with pulmonary aspergillosis. More patients with pulmonary aspergillosis received long-term systemic corticosteroids (50% vs. 14.3%, p < 0.05). Additionally, mNGS managed to reach a sensitivity of 91.7% for diagnosing pulmonary aspergillosis, which was significantly higher than that of conventional etiological methods (33.3%) and serum (1,3)-β-D-glucan (33.3%). In addition, mNGS showed superior performance in discovering co-pathogens (84.6%) of pulmonary aspergillosis; bacteria, bacteria-fungi, and bacteria-PJP-virus were most commonly observed in non-neutropenic patients. Moreover, mNGS results can help guide effective treatments. According to the mNGS results, antimicrobial therapy was altered in 91.7% of patients with pulmonary aspergillosis. The diagnosis of Aspergillus detected in blood samples, which can be used as a supplement to BALF samples, seemed to show a higher specificity than that in BALF samples. mNGS is a useful and effective method for the diagnosis of pulmonary aspergillosis in non-neutropenic patients, detection of co-pathogens, and adjustment of antimicrobial treatment.
Prevalence, awareness, treatment, and control rates of hypertension in patients hospitalized with atrial fibrillation in China: Findings from the CCC-AF project
Authors: Sun Zhaoqing , Hao Yongchen , Liu Jun , Yang Na , Qi Yue , Hu Danqing , Yang Yiqian , Wang Haimei , Zhao Dong , Sang Caihua , Liu Jing
Published: August 2022

Background

The status of hypertension in patients with atrial fibrillation (AF) remains unknown in China.

Methods

This study used data from patients hospitalized with AF recruited by the Improving Care for Cardiovascular Disease in China-AF (CCC-AF) project from 236 hospitals enrolled by geographic-economic level in China from 2015 to 2019. The prevalence, awareness, treatment, and control rates of hypertension in patients hospitalized with AF were estimated. Multivariable logistic regression was used to analyze the factors associated with uncontrolled hypertension.

Results

Among 60,390 patients hospitalized with AF, the prevalence of hypertension according to the 2018 Chinese hypertension guidelines was 66.1%. The awareness, treatment, and control rates of hypertension were 80.3, 55.8, and 39.9%, respectively. Among patients treated for hypertension, the treatment control rate was 46.2%. These rates varied according to patient clinical characteristics and geographic regions. The young (18–44 and 45–54 years old), rural insurance, alcohol drinking, history of heart failure, valvular AF, first diagnosed AF, and permanent AF, were associated with uncontrolled hypertension. Under the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines, the prevalence of hypertension was 79.3%, and the control and treatment control rates dropped to 16.7 and 21.2%, respectively.

Conclusion

Hypertension is common in patients hospitalized with AF in China. Although most patients were aware of their hypertensive status, the treatment and control rates of hypertension were still low. The management of hypertension in patients with AF needs to be further improved.
Isolation and in vitro characterization of murine young-adult long bone skeletal progenitors
Authors: Loopmans Shauni , Stockmans Ingrid , Carmeliet Geert , Stegen Steve
Published: August 2022

Skeletal stem and progenitor cells (SSPCs) constitute a reservoir of bone-forming cells necessary for bone development, modeling and remodeling, as well as for fracture healing. Recent advances in tools to identify and isolate SSPCs have revealed that cells with multipotent properties are present not only in neonatal bone, but also in adult bone marrow and periosteum. The long bone metaphysis and endosteum have been proposed as an additional SSPC niche, although in vitro approaches to study their cellular and molecular characteristics are still limited. Here, we describe a comprehensive procedure to isolate and culture SSPCs derived from the metaphysis and endosteum of young-adult mice. Based on flow cytometry analysis of known SSPC markers, we found the presence of putative multipotent SSPCs, similar to neonatal bone tissue. In vitro, metaphyseal/endosteal SSPCs possess self-renewing capacity, and their multipotency is underscored by the ability to differentiate into the osteogenic and adipogenic lineage, while chondrogenic potential is limited. Expansion of metaphyseal/endosteal SSPCs under low oxygen conditions increases their proliferation capacity, while progenitor properties are maintained, likely reflecting their hypoxic niche in vivo. Collectively, we propose a validated isolation and culture protocol to study metaphyseal/endosteal SSPC biology in vitro.
Treatment gaps in epilepsy
Authors: Pellinen Jacob
Published: August 2022

Over 50 million people around the world have epilepsy, and yet, epilepsy recognition and access to care are ongoing issues. Nearly 80% of people with epilepsy live in low-and middle-income countries and face the greatest barriers to quality care. However, there are substantial disparities in care within different communities in high-income countries as well. Across the world, under-recognition of seizures continues to be an issue, leading to diagnostic and treatment delays. This stems from issues surrounding stigma, public education, basic access to care, as well as healthcare worker education. In different regions, people may face language barriers, economic barriers, and technological barriers to timely diagnosis and treatment. Even once diagnosed, people with epilepsy often face gaps in optimal seizure control with the use of antiseizure medications. Additionally, nearly one-third of people with epilepsy may be candidates for epilepsy surgery, and many either do not have access to surgical centers or are not referred for surgical evaluation. Even those who do often experience delays in care. The purpose of this review is to highlight barriers to care for people with epilepsy, including issues surrounding seizure recognition, diagnosis of epilepsy, and the initiation and optimization of treatment.
YAP1 alleviates sepsis-induced acute lung injury via inhibiting ferritinophagy-mediated ferroptosis
Authors: Zhang Jing , Zheng Yongping , Wang Yun , Wang Jin , Sang Aming , Song Xuemin , Li Xinyi
Published: August 2022

Ferroptosis is a phospholipid peroxidation-mediated and iron-dependent cell death form, involved in sepsis-induced organ injury and other lung diseases. Yes-associated protein 1 (YAP1), a key regulator of the Hippo signaling pathway, could target multiple ferroptosis regulators. Herein, this study aimed to explore the involvement of ferroptosis in the etiopathogenesis of sepsis-induced acute lung injury (ALI) and demonstrate that YAP1 could disrupt ferritinophagy and moderate sepsis-induced ALI. Cecal ligation and puncture (CLP) models were constructed in wild-type (WT) and pulmonary epithelium-conditional knockout (YAP1f/f) mice to induce ALI, while MLE-12 cells with or without YAP1 overexpression were stimulated by lipopolysaccharide (LPS) in vitro. In-vivo modes showed that YAP1 knockout aggravated CLP-induced ALI and also accelerated pulmonary ferroptosis, as presented by the downregulated expression of GPX4, FTH1, and SLC7A11, along with the upregulated expression of SFXN1 and NCOA4. Transcriptome research identified these key genes and ferroptosis pathways involved in sepsis-induced ALI. In-vitro modes consistently verified that YAP1 deficiency boosted the ferrous iron accumulation and mitochondrial dysfunction in response to LPS. Furthermore, the co-IP assay revealed that YAP1 overexpression could prevent the degradation of ferritin to a mass of Fe2+ (ferritinophagy) via disrupting the NCOA4–FTH1 interaction, which blocked the transport of cytoplasmic Fe2+ into the mitochondria via the mitochondrial membrane protein (SFXN1), further reducing the generation of mitochondrial ROS. Therefore, these findings revealed that YAP1 could inhibit ferroptosis in a ferritinophagy-mediated manner, thus alleviating sepsis-induced ALI, which may provide a new approach to the therapeutic orientation for sepsis-induced ALI.
Curcumin and Curcuma longa Extract in the Treatment of 10 Types of Autoimmune Diseases: A Systematic Review and Meta-Analysis of 31 Randomized Controlled Trials
Authors: Zeng Liuting , Yang Tiejun , Yang Kailin , Yu Ganpeng , Li Jun , Xiang Wang , Chen Hua
Published: August 2022

Objective

To evaluate the randomized controlled trials (RCTs) of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases.

Methods

Databases such as Embase, Web of Science, PubMed and The Cochrane Library were searched from the database establishment to February 2022 to collect RCTs of Curcumin and Curcuma longa Extract in the treatment of autoimmune diseases. Then the literature was screened and the data were extracted. Meta-analysis was performed using RevMan 5.3 software.

Results

A total of 34 records were included, involving 31 RCTs and 10 types of autoimmune disease. Among them, ankylosing spondylitis (AS) involves one RCT, Behcet ‘s disease (BD) involves one RCT, Crohn ‘s disease involves two RCTs, multiple sclerosis (MS) involves two RCTs, oral lichen planus involves six RCTs, psoriasis involves two RCTs, rheumatoid arthritis (RA) involves five RCTs, systemic lupus erythematosus (SLE) involves two RCTs, arteritis involves one RCT, ulcerative colitis (UC) involves nine RCTs. Among them, most of the RCTs of ulcerative colitis (UC), oral lichen planus, RA showed that curcumin and curcumin extracts improved clinical or laboratory results. Crohn ‘ s disease, MS, SLE, psoriasis included two RCTs; they all showed improvements (at least one RCT reported improvements in clinical outcomes). AS, BD and arteritis included only one RCT, and the clinical results showed improvement. However, due to the small number of RCTs and the small number of patients involved in each disease, there is still a need for more high-quality RCTs.

Conclusion

Curcumin and Curcuma longa Extract had good clinical efficacy in the treatment of Psoriasis, UC and RA, so Curcumin and Curcuma longa Extract could be used in the treatment of the above diseases in the future. The results of Meta-analysis showed that Curcumin and Curcuma longa Extract did not show efficacy in the treatment of oral lichen planus, while Takayasu arteritis, SLE, MS, AS, BD and CD did not report sufficient clinical data for meta-analysis. Therefore, large-sample, multi-center clinical trials are still needed for revision or validation.
Robust humoral and cellular immune responses in long-term convalescent COVID-19 individuals following one-dose SARS-CoV-2 inactivated vaccination
Authors: Liang Boyun , Xiang Tiandan , Wang Hua , Li Ziwei , Quan Xufeng , Feng Xuemei , Li Sumeng , Lu Sihong , Fan Lei , Xu Ling , Wang Tong , Wang Xiaoyan , Zhu Bin , Wang Junzhong , Yang Dongliang , Liu Jia , Zheng Xin
Published: August 2022

COVID-19, caused by SARS-CoV-2, has resulted in hundreds of millions of infections and millions of deaths worldwide. Preliminary results exhibited excellent efficacy of SARS-CoV-2 vaccine in preventing hospitalization and severe disease. However, data on inactivated vaccine-induced immune responses of naturally infected patients are limited. Here, we characterized SARS-CoV-2 RBD-specific IgG (anti-S-RBD IgG) and neutralizing antibodies (NAbs) against SARS-CoV-2 wild type and variants of concerns (VOCs), as well as RBD-specific IgG-secreting B cells and antigen-specific T cells respectively in 51 SARS-CoV-2 recovered subjects and 63 healthy individuals. In SARS-CoV-2 recovered patients, a single dose vaccine is sufficient to reactivate robust anti-S-RBD IgG and NAbs. The neutralizing capacity against VOCs increased significantly post-vaccination no matter healthy individuals or SARS-CoV-2 recovered patients. In addition, RBD-specific IgG-secreting B cells in SARS-CoV-2 recovered patients were significantly higher than that in healthy vaccine recipients. After the vaccine booster, the frequencies of specific IFN-γ+ CD4+ T cell, IL-2+ CD4+ T cell, and TNF-α+ CD4+ T cell responses were significantly increased in SARS-CoV-2 recovered patients. Our data highlighted the safety and utility of SARS-CoV-2 inactivated vaccine and demonstrated that robust humoral and cellular immune response can be reactivated by one-dose inactivated vaccine in SARS-CoV-2 recovered patients.
Lightella neohaematopini: A new lineage of highly reduced endosymbionts coevolving with chipmunk lice of the genus Neohaematopinus
Authors: Říhová Jana , Bell Kayce C. , Nováková Eva , Hypša Václav
Published: August 2022

Sucking lice (Anoplura) are known to have established symbiotic associations multiple times with different groups of bacteria as diverse as Enterobacteriales, Legionellales, and Neisseriales. This diversity, together with absence of a common coevolving symbiont (such as Buchnera, in aphids), indicates that sucking lice underwent a series of symbiont acquisitions, losses, and replacements. To better understand evolution and significance of louse symbionts, genomic and phylogenetic data are needed from a broader taxonomic diversity of lice and their symbiotic bacteria. In this study, we extend the known spectrum of the louse symbionts with a new lineage associated with Neohaematopinus pacificus, a louse species that commonly parasitizes North American chipmunks. The recent coevolutionary analysis showed that rather than a single species, these lice form a cluster of unique phylogenetic lineages specific to separate chipmunk species (or group of closely related species). Using metagenomic assemblies, we show that the lice harbor a bacterium which mirrors their phylogeny and displays traits typical for obligate mutualists. Phylogenetic analyses place this bacterium within Enterobacteriaceae on a long branch related to another louse symbiont, “Candidatus Puchtella pedicinophila.” We propose for this symbiotic lineage the name “Candidatus Lightella neohaematopini.” Based on the reconstruction of metabolic pathways, we suggest that like other louse symbionts, L. neohaematopini provides its host with at least some B vitamins. In addition, several samples harbored another symbiotic bacterium phylogenetically affiliated with the Neisseriales-related symbionts described previously from the lice Polyplax serrata and Hoplopleura acanthopus. Characterizing these bacteria further extend the known diversity of the symbiotic associations in lice and show unique complexity and dynamics of the system.
Spontaneous Resistance of Erwinia amylovora Against Bacteriophage Y2 Affects Infectivity of Multiple Phages
Authors: Knecht Leandra E. , Born Yannick , Pelludat Cosima , Pothier Joël F. , Smits Theo H. M. , Loessner Martin J. , Fieseler Lars
Published: August 2022

Broad application of antibiotics gave rise to increasing numbers of antibiotic resistant bacteria. Therefore, effective alternatives are currently investigated. Bacteriophages, natural predators of bacteria, could work as such an alternative. Although phages can be highly effective at eliminating specific bacteria, phage resistance can be observed after application. The nature of this resistance, however, can differ depending on the phage. Exposing Erwinia amylovora CFBP 1430, the causative agent of fire blight, to the different phages Bue1, L1, S2, S6, or M7 led to transient resistance. The bacteria reversed to a phage sensitive state after the phage was eliminated. When wild type bacteria were incubated with Y2, permanently resistant colonies (1430Y2R) formed spontaneously. In addition, 1430Y2R revealed cross-resistance against other phages (Bue1) or lowered the efficiency of plating (L1, S2, and S6). Pull down experiments revealed that Y2 is no longer able to bind to the mutant suggesting mutation or masking of the Y2 receptor. Other phages tested were still able to bind to 1430Y2R. Bue1 was observed to still adsorb to the mutant, but no host lysis was found. These findings indicated that, in addition to the alterations of the Y2 receptor, the 1430Y2R mutant might block phage attack at different stage of infection. Whole genome sequencing of 1430Y2R revealed a deletion in the gene with the locus tag EAMY_2231. The gene, which encodes a putative galactosyltransferase, was truncated due to the resulting frameshift. The mutant 1430Y2R was monitored for potential defects or fitness loss. Weaker growth was observed in LB medium compared to the wild type but not in minimal medium. Strain 1430Y2R was still highly virulent in blossoms even though amylovoran production was observed to be reduced. Additionally, LPS structures were analyzed and were clearly shown to be altered in the mutant. Complementation of the truncated EAMY_2231 in trans restored the wild type phenotype. The truncation of EAMY_2231 can therefore be associated with manifold modifications in 1430Y2R, which can affect different phages simultaneously.
Mycoplasma bovis is associated with Mannheimia haemolytica during acute bovine respiratory disease in feedlot cattle
Authors: Valeris-Chacin Robert , Powledge Sherri , McAtee Taylor , Morley Paul S. , Richeson John
Published: August 2022

Bovine Respiratory Disease (BRD) represents a significant burden to the health of feedlot cattle and the profitability of the beef industry in the US.Mannheimia haemolyticais widely regarded as the primary bacterial pathogen driving acute BRD. WhileMycoplasma bovisis most commonly implicated in chronic cases of BRD, this agent's potential role in acute stages of BRD is unclear. Therefore, this study aimed to evaluate potential associations betweenM. bovisandM. haemolyticaduring acute BRD in feedlot cattle. Nasal swabs (n= 1,044) were collected over time from feedlot cattle (n= 270) enrolled in an experiment assessing the effect of vaccination for Bovine Respiratory Syncytial Virus (BRSV). Swabs were analyzed for detection ofM. bovis, M. haemolytica, Pasteurella multocida, Histophilus somni, and BRSVviamultiplex qPCR assays. Data were analyzed using inverse conditional probability weighted (ICPW) logistic regression models to investigate potential effects ofM. bovispresence on arrival (d0), day seven (d7) and day 14 (d14) post-arrival onM. haemolyticaprevalence on day 28 (d28) post-arrival, adjusting for the previous history ofP. multocida, H. somni, BRSV, BRD morbidity, and body weight. The potential association between time-to-BRD detection andM. bovispresence on d0, d7, and d14 post-arrival, was inferredviaan ICPW time-to-event model. The presence ofM. bovisin nasal swabs collected on d7 post-arrival was significantly associated with an increase in the prevalence ofM. haemolyticaon d28 (prevalence difference: 45%; 95% Confidence Interval: 31%, 60%;P-value < 0.001). Significant time-varying coefficients forM. bovispresence were detected at d0, d7, and d14 post-arrival in the ICPW time-to-event model (P-value < 0.001). The shortest median time-to-BRD detection was 29 days in cattle that wereM. bovispositive on d0, d7, and d14 post-arrival and in those that were positive on d0 and d14 post-arrival. Under the conditions of this study, our findings suggest thatM. bovismay be influencing the respiratory environment during the acute phase of BRD, increasing the abundance ofM. haemolytica, which could have important impacts on the occurrence of BRD.
Construction of gene modification system with highly efficient and markerless for Monascus ruber M7
Authors: Xu Na , Li Li , Chen Fusheng
Published: August 2022

Monascus spp. are traditional medicinal and edible filamentous fungi in China, and can produce various secondary metabolites, such as Monascus pigments (MPs) and citrinin (CIT). Genetic modification methods, such as gene knock-out, complementation, and overexpression, have been used extensively to investigate the function of related genes in Monascus spp.. However, the resistance selection genes that can have been used for genetic modification in Monascus spp. are limited, and the gene replacement frequency (GRF) is usually <5%. Therefore, we are committed to construct a highly efficient gene editing system without resistance selection marker gene. In this study, using M. ruber M7 as the starting strain, we successfully constructed a so-called markerlessly and highly genetic modification system including the mutants ΔmrpyrGΔmrlig4 and ΔmrpyrGΔmrlig4::mrpyrG, in which we used the endogenous gene mrpyrG from M. ruber M7 instead of the resistance marker gene as the screening marker, and simultaneously deleted mrlig4 related to non-homologous end joining in M. ruber M7. Then, the morphology, the growth rate, the production of MPs and CIT of the mutants were analyzed. And the results show that the mutant strains have normal mycelia, cleistothecia and conidia on PDA+Uridine(U) plate, the biomass of each mutant is also no different from M. ruber M7. However, the U addition also has a certain effect on the orange and red pigments yield of M. ruber M7, which needs our further study. Finally, we applied the system to delete multiple genes from M. ruber M7 separately or continuously without any resistance marker gene, and found that the average GRF of ΔmrpyrGΔmrlig4 was about 18 times of that of M. ruber M7. The markerlessly and highly genetic modification system constructed in current study not only will be used for multi-gene simultaneous modification in Monascus spp., and also lays a foundation for investigating the effects of multi-genes modification on Monascus spp..
Modulation of extracellular Penicillium expansum-driven acidification by Papiliotrema terrestris affects biosynthesis of patulin and has a possible role in biocontrol activity
Authors: Palmieri Davide , Miccoli Cecilia , Notardonato Ivan , Avino Pasquale , Lima Giuseppe , De Curtis Filippo , Ianiri Giuseppe , Castoria Raffaello
Published: August 2022

The active regulation of extracellular pH is critical for the virulence of fungal pathogens. Penicillium expansum is the causal agent of green-blue mold on stored pome fruits and during its infection process acidifies the host tissues by secreting organic acids. P. expansum is also the main producer of patulin (PAT), a mycotoxin found in pome fruit-based products and that represents a serious health hazard for its potential carcinogenicity. While it is known that PAT biosynthesis in P. expansum is regulated by nutritional factors such as carbon and nitrogen and by the pH, the mechanistic effects of biocontrol on PAT production by P. expansum are not known. In this work, we assessed how optimal and suboptimal concentrations of the biocontrol agent (BCA) Papiliotrema terrestris LS28 affect both extracellular pH and PAT biosynthesis in P. expansum. In wounded apples, the optimal and suboptimal concentrations of the BCA provided almost complete and partial protection from P. expansum infection, respectively, and reduced PAT contamination in both cases. However, the suboptimal concentration of the BCA increased the specific mycotoxigenic activity by P. expansum. In vitro, the rate of PAT biosynthesis was strictly related to the extracellular pH, with the highest amount of PAT detected in the pH range 4–7, whereas only traces were detectable at pH 3. Moreover, both in vitro and in apple wounds the BCA counteracted the extracellular P. expansum-driven acidification maintaining extracellular pH around 4, which is within the pH range that is optimal for PAT biosynthesis. Conversely, in the absence of LS28 the pathogen-driven acidification led to rapidly achieving acidic pH values (<3) that lie outside of the optimal pH range for PAT biosynthesis. Taken together, these results suggest that pH modulation by LS28 is important to counteract the host tissue acidification and, therefore, the virulence of P. expansum. On the other hand, the buffering of P. expansum-driven acidification provided by the BCA increases the specific rate of PAT biosynthesis through the extension of the time interval at which the pH value lies within the optimal range for PAT biosynthesis. Nevertheless, the antagonistic effect provided by the BCA greatly reduced the total amount of PAT.
Intraneuronal sortilin aggregation relative to granulovacuolar degeneration, tau pathogenesis and sorfra plaque formation in human hippocampal formation
Authors: Jiang Juan , Yang Chen , Ai Jia-Qi , Zhang Qi-Lei , Cai Xiao-Lu , Tu Tian , Wan Lily , Wang Xiao-Sheng , Wang Hui , Pan Aihua , Manavis Jim , Gai Wei-Ping , Che Chong , Tu Ewen , Wang Xiao-Ping , Li Zhen-Yan , Yan Xiao-Xin
Published: August 2022

Extracellular β-amyloid (Aβ) deposition and intraneuronal phosphorylated-tau (pTau) accumulation are the hallmark lesions of Alzheimer’s disease (AD). Recently, “sorfra” plaques, named for the extracellular deposition of sortilin c-terminal fragments, are reported as a new AD-related proteopathy, which develop in the human cerebrum resembling the spatiotemporal trajectory of tauopathy. Here, we identified intraneuronal sortilin aggregation as a change related to the development of granulovacuolar degeneration (GVD), tauopathy, and sorfra plaques in the human hippocampal formation. Intraneuronal sortilin aggregation occurred as cytoplasmic inclusions among the pyramidal neurons, co-labeled by antibodies to the extracellular domain and intracellular C-terminal of sortilin. They existed infrequently in the brains of adults, while their density as quantified in the subiculum/CA1 areas increased in the brains from elderly lacking Aβ/pTau, with pTau (i.e., primary age-related tauopathy, PART cases), and with Aβ/pTau (probably/definitive AD, pAD/AD cases) pathologies. In PART and pAD/AD cases, the intraneuronal sortilin aggregates colocalized partially with various GVD markers including casein kinase 1 delta (Ck1δ) and charged multivesicular body protein 2B (CHMP2B). Single-cell densitometry established an inverse correlation between sortilin immunoreactivity and that of Ck1δ, CHMP2B, p62, and pTau among pyramidal neurons. In pAD/AD cases, the sortilin aggregates were reduced in density as moving from the subiculum to CA subregions, wherein sorfra plaques became fewer and absent. Taken together, we consider intraneuronal sortilin aggregation an aging/stress-related change implicating protein sorting deficit, which can activate protein clearance responses including via enhanced phosphorylation and hydrolysis, thereby promoting GVD, sorfra, and Tau pathogenesis, and ultimately, neuronal destruction and death.
Effectiveness of aerobic and resistance training on the motor symptoms in Parkinson's disease: Systematic review and network meta-analysis
Authors: Zhou Xiao , Zhao Peng , Guo Xuanhui , Wang Jialin , Wang Ruirui
Published: August 2022

Background/objectives

Aerobic and resistance training are common complementary therapies to improve motor symptoms in people with Parkinson's disease (PD), and there is still a lack of advice on which intensity and period of aerobic or resistance training is more appropriate for people with PD. Therefore, a network meta-analysis was conducted to assess the comparative efficacy of aerobic and resistance training of different intensities and cycles on motor symptoms in patients with Parkinson's disease.

Methods

Based on several biomedical databases, a search strategy system was conducted to retrieve randomized controlled trials (RCTs) without language restrictions. A network meta-analysis with a frequentist approach was conducted to estimate the efficacy and probability rankings of aerobic and resistance training on Parkinson's patients. What's more, a range of analyses and assessments, such as routine meta-analyses and risk of bias, were performed as well.

Results

Twenty trials with 719 patients evaluating 18 different therapies were identified. Through the Unified Parkinson's Disease Motor Rating Scale, (UPDRS III); 6-minute walk test, (6MWT); 10-meter walk test, (TWM); and time up and go (TUG) and Quality of Life Scale-39 (PDQ-39), to explore the effects of different intensity resistance and aerobic exercise on PD. As a result, short period high intensity resistance movement (standard mean difference (SMD) = −0.95, 95% confidence interval (CI) −1.68 to −0.22) had significantly decreased the Unified Parkinson's Disease Motor Rating Scale (UPDRS III). Short period high intensity resistance exercise showed similar superiority in other indices; also, aerobic and resistance training of different cycle intensities produced some efficacy in PD patients, both in direct and indirect comparisons.

Conclusion

For patients with moderate to mild Parkinson's symptoms, short periods high intensity resistance training may provide complementary therapy for PD, and aerobic or resistance training of varying intensity and periodicity may be recommended as exercise prescription for PD patients. However, more large scale and high quality clinical trials are needed to confirm the effectiveness of this exercise therapy in the future.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022324824.
Is It Me or the Robot? A Critical Evaluation of Human Affective State Recognition in a Cognitive Task
Authors: Jirak Doreen , Aoki Motonobu , Yanagi Takura , Takamatsu Atsushi , Bouet Stephane , Yamamura Tomohiro , Sandini Giulio , Rea Francesco
Published: August 2022

A key goal in human-robot interaction (HRI) is to design scenarios between humanoid robots and humans such that the interaction is perceived as collaborative and natural, yet safe and comfortable for the human. Human skills like verbal and non-verbal communication are essential elements as humans tend to attribute social behaviors to robots. However, aspects like the uncanny valley and different technical affinity levels can impede the success of HRI scenarios, which has consequences on the establishment of long-term interaction qualities like trust and rapport. In the present study, we investigate the impact of a humanoid robot on human emotional responses during the performance of a cognitively demanding task. We set up three different conditions for the robot with increasing levels of social cue expressions in a between-group study design. For the analysis of emotions, we consider the eye gaze behavior, arousal-valence for affective states, and the detection of action units. Our analysis reveals that the participants display a high tendency toward positive emotions in presence of a robot with clear social skills compared to other conditions, where we show how emotions occur only at task onset. Our study also shows how different expression levels influence the analysis of the robots' role in HRI. Finally, we critically discuss the current trend of automatized emotion or affective state recognition in HRI and demonstrate issues that have direct consequences on the interpretation and, therefore, claims about human emotions in HRI studies.
The gene diagnosis of neurofibromatosis type I with headache as the main symptom: A case report and review of the literature
Authors: Gao Ming , Liu Haokun , Sun Qiying , Yang Guang
Published: August 2022

Neurofibromatosis type I (NF1) is an autosomal dominant disease. Some NF1 patients experience atypical clinical manifestations, genetic testing is not widely available, and the types of mutations vary; thus, they are prone to misdiagnosis and missed diagnosis. Although headache is not included in the diagnostic criteria for NF1, the incidence of headache in NF1 patients is not low. We report an NF1 family in which the proband presented with prominent headache and atypical clinical presentation, with limited skin pigmentation. We identified a frameshift mutation (c.1541_1542del, p. Q514Rfs*) in the NF1 gene by whole-exome sequencing of this family, and the patients were diagnosed with NF1. We hope to attract the attention of clinicians to these patients and improve genetic testing as soon as possible to increase the diagnosis rate.
An updated network meta-analysis of EGFR-TKIs and combination therapy in the first-line treatment of advanced EGFR mutation positive non-small cell lung cancer
Authors: Qi Yuexiao , Xia Xiaojun , Shao Lihua , Guo Liyun , Dong Yumei , Tian Jinhui , Xu Lijun , Niu Ruijun , Wei Shihong
Published: August 2022

Objectives

Tyrosine kinase inhibitors (TKIs) are a standard care option in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation. TKI-based combination treatment modes show encouraging outcomes. However, it remains unknown which is the optimal treatment as the first-line regimen for these patients on overall survival (OS).

Materials and methods

Randomized controlled trials and meeting abstracts that investigated EGFR-TKIs alone or in combination as front-line care for patients with NSCLC were systematically searched in relevant databases and reviewed. Fixed and random effects network meta-analysis models were used to estimate progression-free survival (PFS), OS, overall response rate, and grade three and higher adverse events (AEs). Surface under the cumulative ranking curves (SUCRAs) were used to rank treatment effects.

Results

Eighteen studies covering six treatments and involving a total of 4389 patients were included in this network meta-analysis. On OS, the top three treatment were first-generation EGFR-TKIs (1G EGFR-TKIs) plus chemotherapy (SUCRA, 88.1%), osimertinib (SUCRA, 65.8%) and second-generation EGFR-TKIs (2GEGFR-TKIs) (SUCRA, 63.3%). On PFS, the top three treatments were osimertinib (SUCRA, 96.0%), 1G EGFR-TKIs plus chemotherapy (SUCRA, 67.1%), and 1G EGFR-TKIs plus antiangiogenesis (SUCRA, 48.2%). Two types of TKI-based combination therapy have significantly higher risk of grade three and higher AEs than TKI alone.

Conclusion

1G EGFR-TKIs plus chemotherapy and osimertinib seem to be the two better options as first-line care in advanced NSCLC patients with EGFR-mutation. Osimertinib caused the lowest incidence of AEs. However, TKIs-based combination therapy significantly increased AEs.
EGFR amplification is a putative resistance mechanism for NSCLC–LM patients with TKI therapy and is associated with poor outcome
Authors: Yang Hainan , Wen Lei , Zhao Chao , Li Xuefei , Shan Changguo , Liu Da , Hong Weiping , Zhou Zhaoming , Zhou Cheng , Cai Linbo , Zhou Caicun
Published: August 2022

Background

Leptomeningeal metastases (LM) have become increasingly common in non-small cell lung cancer (NSCLC) patients who harbor epidermal growth factor receptor (EGFR) mutation treated with EGFR-TKI and are correlated with inferior prognosis. Evidence in prior research demonstrated that EGFR amplification was more likely presented in advanced clinical stages and was associated with worse survival. However, whether EGFR amplification is a prognostic marker in NSCLC–LM is still inconclusive.

Methods

This study enrolled patients diagnosed with NSCLC–LM from June 2019 to September 2021 and who had received previous EGFR-TKI at Guangdong Sanjiu Brain Hospital. Cerebrospinal fluid (CSF) samples were collected and subjected to targeted next-generation sequencing of 168 cancer-related genes. Clinical characteristics and overall survival (OS) were compared in patients with and without EGFR amplification.

Results

This study enrolled 53 NSCLC–LM patients, all of whom had EGFR mutations. TP53 and EGFR amplifications are the two most frequent mutations in the study cohort, presenting at 72% (38 of 53) and 40% (21 of 53), respectively. The rate of EGFR amplification was much higher at the time of leptomeningeal progression than at initial diagnosis (p < 0.01). Karnoskfy performance status was poorer (p = 0.021), and CSF pressure was higher (p = 0.0067) in patients with EGFR amplification than those without. A multivariable Cox proportional hazard regression model showed that EGFR amplification was an independent prognostic factor for poorer OS (8.3 vs. 15 months; p = 0.017). The median OS was shorter in NSCLC–LM patients with mutated TP53 than those with wild-type TP53, but the difference was not statistically significant (10 vs. 17.3 months, p = 0.184).

Conclusions

EGFR gene amplification could be a potential resistance mechanism to EGFR-TKI failure in NSCLC–LM and is associated with inferior clinical outcomes.