bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing Effects of Superloads on Doweled Jointed Plain Concrete Pavements
Authors: Donnelly Charles , Vandenbossche Julie
Published: April 2022

Superloads are typically defined as vehicles weighing greater than 890 kilonewtons (200,000 pounds), although the geometrics of the vehicle are also a consideration. The damage of these superloads on jointed plain concrete pavements (JPCP) as compared to a standard 80-kN (18-kip) single axle design load are not well defined. The purpose of this study is to identify the effects of these superloads on the performance of JPCP joints in comparison to that of standard traffic loads. One mechanism of failure at the transverse joints in JPCP is the degradation of dowel performance. This can decrease the effectiveness of the joint load transfer efficiency; thereby resulting in large differential deflections and the development of faulting. Therefore, to quantify the damage caused by superloads, typical load configurations were identified using superload permit data obtained from the Pennsylvania Department of Transportation. Using the typical superload profiles established from permit data, the effect on dowel performance is evaluated.
Over-night Renewals of the Concrete Runway at Sabiha Gökcen International Airport Istanbul
Authors: Bäuml Martin , Melchior Jakob , Constandopoulos Felicia
Published: April 2022

Over the last couple of years, new rapid-hardening concretes were developed. They do not only stand out by their high early strength, in excess of 20 MPa already 90 minutes after setting, but are also adjustable to the needs of the construction site in regards to fresh concrete properties and setting behavior. This allows the rapid-hardening concrete to be placed using traditional means and the construction program to be optimized in order to perform the renewals during very short closure windows. After many years of usage, the single runway at Sabiha Gökcen International Airport Istanbul was in need of large-scale renewals due to severe damages in the high wear areas around the centerline. But, with it being the only runway at the airport, closing it for multiple weeks to perform the renewal was not an option. The nightly closure of only 5 hours, due to late-evening and early-morning flights, placed additional demands on the rapid-hardening concrete, the logistics of the construction site and the concrete's long-term durability for a permanent solution. This article presents the step-by-step over-night renewals at Sabiha Gökcen Airport, which is the largest project ever performed involving rapid-hardening concrete. Each night up to 5 slabs (94 m2) of the runway were replaced for a total area of 8700 m2 over 117 nights between March and September 2018. Such large area applications without affecting regular airport operations are possible thanks to the latest generation of rapid-hardening cement and this article shows these possibilities to project owners, design engineers, and contractors.
Fracture Energy of Roller Compacted Concrete Pavements
Authors: Şengün Emin , Alam Burhan , Shabani Reza , Yaman İ. Özgür
Published: April 2022

This study is set out to examine the bending, toughness and fracture energy of RCC pavements produced by double drum vibratory hand roller (DDVHR) to simulate the real performance of RCC in the laboratory environment. To this end, four different binder dosages (200, 300,400, and 600 kg/m3) and two different aggregate gradations (Dmax 12 and 19 mm) were selected to investigate the effect of mixture design on bending, toughness and fracture energy of RCC mixtures. The different mixtures were poured into a large pavement mold (LPM), which was fabricated in laboratory, and compacted by DDVHR. After that, in order to determine the bending, toughness and fracture energy of RCC mixtures, LPM were cut to beam specimens with sizes according to Japan Concrete Institute (JCI). In addition, cores were taken from LPM to compare 28 days' compressive strengths and compaction ratios of the mixtures. At the end of the study, contrary to expectations, the fracture energies for all RCC mixtures except one combination were very close to each other. The increase in cement dosage or the maximum aggregate size did not lead to a significant change in the fracture energy. The mixture that was developed to obtain a high performance RCC appeared to have the lowest fracture energy. Above all, the compaction ratio of the mixtures was effective in the all results.
URGENSI PENEGAKAN HUKUM TATA PEMERINTAHAN
Authors: Jeddawi Murtir
Published: April 2022

Global pandemic, Corona Virus must be prevented, limited and be stopped of spreading to the whole of Indonesian region. As a nation state based on law (regulation) all of government’s activities are limited include of activities which aim to pulfill order and welfare of society There are many instruments could be held it, and one of it, implementation of the governance principle, such as transparancy, efficiency, accountability etc. For supporting it, government law has strong roling to implementing those principles. Besides it, with the government law (bestuursrecht) provided limitation of governemnt authority and protected for the society by the government misused of authority. Therefore, central government issued regulations. Those regulation are government law (bestuursrecht).
STRATEGI PARTAI ACEH DALAM MEMENANGKAN PEMILIHAN UMUM KEPALA DAERAH TAHUN 2017 DI KABUPATEN ACEH BARAT
Authors: Jonsaa Alimas , Sandi Kemal , Sawina Sawina , Salam Rudi , Umar Teuku
Published: April 2022

Tujuan dari penelitian ini adalah untuk mengetahui strategi partai aceh dalam memenangkan pemilihan umum kepala daerah tahun di Kabupaten Aceh Barat, serta mengetahui strategi lawan dalam pemilihan kepala daerah di Kabupaten Aceh Barat Tahun 2017.Teori yang dipakai dalam penelitian ini Teori Strategi Politik Sun Tzu. Penelitian ini menggunakan metode penelitian kualitatif dengan pendekatan deskriptif untuk mendeskripsikan dan menjabarkan fenomena yang ada di lokasi penelitian. Teknik pengumpulan data dilaksanakan dengan cara wawancara, dokumentasi, dan observasi. Analisis data dalam penelitian ini menggunakan empat komponen yang terdiri dari pengumpulan data, reduksi data, penyajian data, dan verifikasi data atau penarikan kesimpulan. Hasil penelitian menunjukan bahwa strategi Partai telah menyusun dan menjalankan strategi politik dengan baik dan maksimal di pemilihan kepala daerah tahun 2017 di Kabupaten Aceh Barat sudah berjalan dengan baik dan efektif, karena dari seluruh indikator efektivitas yang dijadikan teori untuk menjawab hasil penelitian di lapangan sudah dilaksanakan dengan baik.
ANALISIS PENGEMBANGAN KOMPETENSI PEGAWAI PADA DINAS PENDIDIKAN DI KOTA MAKASSAR
Authors: Faisal Muhammad
Published: April 2022

This study aims to determine the development of employee competenceincluding the development of skills, knowledge, and attitude of employeesat the Department of Education Makassar. The research used qualitativedecriptive approach with the research informant is Head of Department,Secretary, Head of Division, and Head of Sub Division of General and Personnel as well as employees at Education Department of MakassarCity. Data were collected by interview, observation and documentationtechnique, then the data were analyzed by three stages: data reduction,data display and verification / drawing conclusion. The results of the studyexplain that the development of employee skills in the form of leadership,functional and technical training. The development of employee competencein terms of knowledge development can be seen from formal education, nonformal education, the appropriateness of discipline, and work experience.The development of employee competence in terms of employee attitudedevelopment can be seen from the activities of independence, spirituallecture, direction, sanction, and appreciation.
A Novel Quantification System Combining iTRAQ Technology and Multi-Omics Assessment to Predict Prognosis and Immunotherapy Efficacy in Colon Cancer
Authors: Xia Tianyi , Guo Junnan , Zhang Bomiao , Xue Weinan , Deng Shenhui , Liu Yanlong , Cui Binbin
Published: April 2022

Background: Colon cancer is one of the most common cancer types, although it has certain unique genetic features. This study aimed to develop a unique score for assessing prognosis and immunotherapy efficacy using integrated multi-omics analysis.

Methods: Isobaric tagging for relative and absolute quantification (iTRAQ) based proteomic analysis was used to screen differentially expressed proteins (DEP) between tumor and normal samples. DEP mRNA obtained from TCGA were clustered into different categories to show landscape-related prognosis and function. Following that, DEG was extracted from DEP mRNA, and the DEP-related score (DEPRS) was constructed to investigate the difference in immunotherapy prognosis and sensitivity. Finally, WCGNA, random forest, and artificial neural networks were used to screen for key genes. The prognostic value and protein level of these genes were validated.

Results: A total of 243 DEPs were identified through iTRAQ analysis, and the corresponding DEP mRNA was clustered into three. Following a series of tests, 1,577 DEGs were identified from overlapped DEP mRNA clusters and were classified into three gene clusters. The two types of clusters described above shared comparable characteristics in terms of prognosis and function. Then, it was established that a high DEPRS indicated a poor prognosis and DEPRS had significant associations with TMB, MSI status, and immunotherapeutic response. Finally, the key genes HART3 and FBLN2 were identified and were found to be implicated in immunotherapy and prognosis.

Conclusion: The development of a DEPRS based on multi-omics analysis will aid in improving our understanding of colon cancer and guiding a more effective immunotherapy strategy. DEPRS and key genes are used as biomarkers in the clinical evaluation of patients.
Derivation of Stem Cell-like Cells From Spherical Culture of Astrocytes for Enhanced Neural Repair After Middle Cerebral Artery Occlusion
Authors: Zhu Dan , Cao Zheming , Pang Xiaoyang , Jiang Wei , Li Chihao , Zhang Xing , Tian Xibin , Tu Haijun , Wu Panfeng , Nie Hemin
Published: April 2022

Neural precursor cells (NPCs) tend to aggregate and develop into three-dimensional (3D) spheres, which in turn help maintain the stemness of the cells. This close relationship between spherical environments and cell stemness direct us to assume that 3D spheres of astrocytes (ASTs) may facilitate the acquisition of stem cell-like features and generate sufficient seed cells for the regeneration of neurons. In vitro results confirmed that mouse ASTs cultured on agarose surfaces spontaneously formed cell spheres and exhibited molecular features similar to stem cells, particularly capable of further differentiating into neurons and forming functional synaptic networks with synchronous burst activities. RNA-sequencing results revealed the similarity between AST-derived stem cells (A-iSCs) and NPCs in global gene expression profiles. The potency of A-iSCs in repairing neural injuries was evaluated in a mouse model of middle cerebral artery occlusion. It was observed that the transplanted A-iSCs expressed a series of markers related to neural differentiation, such as NeuN, Tuj1, and Map2, indicating the conversion of the transplanted A-iSCs into neurons in the scenario. We also found that the injured mice injected with A-iSCs exhibited significant improvements in sensorimotor functions after 8 weeks compared with the sham and control mice. Taken together, mouse ASTs form cell spheres on agarose surfaces and acquire stem cell-associated features; meanwhile, the derived A-iSCs possess the capacity to differentiate into neurons and facilitate the regeneration of damaged nerves.
Regulation of T Cell Responses by Nano-Hydroxyapatite to Mediate the Osteogenesis
Authors: Guo Fangze , Yuan Changqing , Huang Hailin , Deng Xuyang , Bian Zirui , Wang Danyang , Dou Keke , Mei Li , Zhou Qihui
Published: April 2022

Nano-hydroxyapatite (nHA) has been widely applied as a tissue-engineering biomaterial and interacted with osteoblasts/stem cells to repair bone defects. In addition, T cells that coexist with osteoblasts/stem cells in the bone modulate the regulation of osteoimmunology by cytokine formation. However, the effects of nHA on T cells and the following regulatory interplay on osteogenic differentiation have been rarely examined. In this work, the physicochemical properties of needle-like nHA are characterized by field emission scanning electron microscopy, zeta potential, Fourier transform-infrared and X-ray diffraction. It is found that as the concentration of nHA increases, the proliferation of T cells gradually increases, and the proportion of apoptotic T cells decreases. The percentage of CD4+ T cells is higher than that of CD8+ T cells under the regulation of needle-like nHA. Furthermore, the supernatant of T cells co-cultured with nHA significantly inhibits the osteogenic differentiation of MC3T3-E1 by downregulating the formation of alkaline phosphatase and calcium nodule compared with the supernatant of nHA. Thus, our findings provide new insight into the nHA-mediated T cell and osteoblast interactions.
Histone Chaperones as Cardinal Players in Development
Authors: Rajam Sruthy Manuraj , Varghese Pallavi Chinnu , Dutta Debasree
Published: April 2022

Dynamicity and flexibility of the chromatin landscape are critical for most of the DNA-dependent processes to occur. This higher-order packaging of the eukaryotic genome into the chromatin is mediated by histones and associated non-histone proteins that determine the states of chromatin. Histone chaperones- “the guardian of genome stability and epigenetic information” controls the chromatin accessibility by escorting the nucleosomal and non-nucleosomal histones as well as their variants. This distinct group of molecules is involved in all facets of histone metabolism. The selectivity and specificity of histone chaperones to the histones determine the maintenance of the chromatin in an open or closed state. This review highlights the functional implication of the network of histone chaperones in shaping the chromatin function in the development of an organism. Seminal studies have reported embryonic lethality at different stages of embryogenesis upon perturbation of some of the chaperones, suggesting their essentiality in development. We hereby epitomize facts and functions that emphasize the relevance of histone chaperones in orchestrating different embryonic developmental stages starting from gametogenesis to organogenesis in multicellular organisms.
Infusion of Non-HLA-Matched Off-the-Shelf Ex Vivo Expanded Cord Blood Progenitors in Patients Undergoing Cord Blood Transplantation: Result of a Phase II Clinical Trial
Authors: Milano F. , Thur L.A. , Blake J. , Delaney C.
Published: April 2022

Recipients of myeloablative cord blood transplants (CBT) are known to experience delayed hematopoietic recovery and an increased risk of transplant related mortality (TRM). We developed methods for ex vivo expansion and cryopreservation of CB stem and progenitor cells. 15 patients with hematologic malignancies were enrolled in this single center phase II trial between September 2010 and August 2012 to assess the safety of infusing a non-HLA-matched expanded CB product to bolster a conventional CBT. On the day of transplant, an infusion of the expanded CB product followed the primary graft (1 or 2 unmanipulated CB units). All patients engrafted. Median time to neutrophil and platelet recovery was 19 and 35 days, respectively. Early myelomonocytic recovery was almost entirely due to cells arising from the non-HLA-matched expansion product and were no longer detected at day 14 in all but 2 patients. The probability of 3-years disease free survival was 86%. No TRM was observed throughout the study period, and only 2 patients relapsed. All patients presented with grade II acute graft-versus-host disease (aGVHD) at a median time of 32 days, with no grade III-IV aGVHD observed. At 2 years only 2 patients remain on immunosuppressive therapy for mild chronic GVHD. This phase II safety study demonstrate that infusion of an off-the-shelf non-HLA-matched expanded CB product in addition to a conventional CB graft was safe and led to sustained myeloid recovery. Based on these encouraging results, a prospective multicenter randomized trial utilizing this product has been conducted and results will be soon released. ClinicalTrials.gov Identifier: NCT01175785.
Analysis of the Vulvar Skin Microbiota in Asymptomatic Women and Patients With Vulvar Lichen Sclerosus Based on 16S rRNA Sequencing
Authors: Liu Xiaoxiao , Zhuo Yingying , Zhou Yunlu , Hu Jun , Wen Hongwu , Xiao Changji
Published: April 2022

Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disease that brings life-long and psychological distress to patients. It remains unclear whether this condition is related to changes in the skin microbial community. The aim of this study was to evaluate the compositional characteristics of the vulvar skin microbiota between VLS patients and asymptomatic postmenopausal women. We included 60 cases of postmenopausal patients in the outpatient vulvar clinic of Peking University First Hospital from August 2020 to October 2020. Thirty-one patients were diagnosed with VLS by vulvar skin biopsy (VLS group), while 29 women were asymptomatic volunteers (control group). DNA was extracted from vulvar skin swabs of the VLS and control groups. The V3-V4 fragments of 16S rRNA were targeted for high-throughput sequencing and gene sequence analysis. The sequencing results were analysed byαdiversity,βdiversity, species composition, LEfSe analysis to compare the compositional differences of the vulvar skin microbiota between the two groups. Our study revealed that at the phylum level, patients with VLS had a lower relative abundance of Firmicutes (p< 0.0001) and a higher relative abundance of Proteobacteria than the control group (p< 0.0001). At the genus level,Lactobacillusspp. accounted for the largest proportion of the microflora in the asymptomatic controls, while the proportion ofPrevotellaspp. in the VLS group was the highest. In the VLS group, the relative abundance ofFinegoldiaspp.,Ralstoniaspp.,Peptoniphilusspp.,Anaerococcusspp.,Campylobacterspp.,Providenciaspp.Kelbsiellaspp.,Ezakiellaspp., andEscherichia-Shigellaspp. was significantly increased compared with the control group. Although there was no significant difference in theαdiversity of the vulvar skin microbiota, theβdiversity differed significantly between the two groups.
Cathelicidin Mediates an Anti-Inflammatory Role of Active Vitamin D (Calcitriol) During M. paratuberculosis Infection
Authors: Vaccaro Joseph A. , Qasem Ahmad , Naser Saleh A.
Published: April 2022

Vitamin D is a key regulator in calcium and phosphorus metabolism which are essential for maintaining bone health. Recent reports also showed a role for vitamin D in immune regulation which may be linked to vitamin D deficiency in autoimmune disorders including inflammatory diseases and Crohn’s disease (CD). This study examines the role of vitamin D deficiency in the regulation of Cathelicidin Antimicrobial Peptide (CAMP) in CD-like macrophages. The latter includes macrophages infected with Mycobacterium avium subsp. paratuberculosis (MAP) isolated from CD patient. Initially, we measured cathelicidin and calcitriol in ex vivo plasma samples from CD patients with or without MAP infection (N=40 per group). We also measured the expression and production of CAMP/LL-37, TNF-α, IL-1β, IL-10, cellular oxidative stress markers, and bacterial viability following treatment of MAP-infected macrophages with four different forms of vitamin D (D2, D3, calcifediol, and calcitriol). From these studies, we determined that LL-37 and calcitriol were significantly lower in CD samples from MAP-positive patients [155.55 ± 49.77 ng/mL and 51.48 ± 31.04 pg/mL, respectively] compared to MAP-negative patients [193.01 ± 78.95 ng/mL and 272.36 ± 94.77 pg/mL, respectively]. Moreover, calcitriol and calcifediol upregulated CAMP expression by nearly 5-fold and 3-fold, respectively. However, following MAP infection, only calcitriol increased CAMP by 3-folds. Both calcitriol and LL-37 reduced intracellular MAP viability by ~3 folds and inhibited TNF-α and IL-1β expression and production in these cells. Treating co-culture of Caco-2 monolayers and MAP-infected macrophages with LL-37 or calcitriol have shown a reduction in NOX-1 expression and DHE signal, in addition to a higher NADPH/NADPt ratio. Notably, calcitriol’s anti-inflammatory effects were lost upon CAMP knockdown by CAMP-siRNA transfection. Altogether, the data indicate that MAP infection and burden is significant in CD by disrupting the conversion of calcifediol to calcitriol and downregulation of CAMP expression leading to vitamin D deficiency.
Infective Endocarditis: Clinical Characteristics and Echocardiographic Findings
Authors: Poorzand Hoorak , Hamidi Fatemeh , Sheybani Fereshte , Ghaderi Fereshteh , Fazlinezhad Afsoon , Alimi Hedieh , Bigdelu Leila , Khosravi Bizhaem Saeede
Published: April 2022

Purpose

Infective endocarditis (IE) remains a disease with high morbidity and mortality. The aim of this study was to determine the clinical characteristics and echocardiographic features of patients with IE.

Methods

We analyzed patients with either definitive or probable diagnosis of IE who were hospitalized in a teaching hospital in Mashhad, Iran between June 2011 and January 2020. Patients who survived were followed up by echocardiography for at least 6-month after hospital discharge.

Results

A total of 82 cases with IE were included of which 62 (75.6%) received definitive diagnosis. The mean age was 39.7 ± 18.7 years and 52 (63.4%) were male. The most common preexisting structural cardiac abnormality that predispose patients to IE were congenital heart diseases (28 %) of which bicuspid aortic valve was more common (n = 12, 14.6%), followed by ventricular septal defect (n = 9, 11%) and Tetralogy of Fallot (TOF) (n = 2, 2.4%). Three (3.6 %) cases had rheumatic heart disease and 12 (14.6 %) were injecting drug users. The most common causative pathogen was Staphylococcus aureus, detected in 7 (19.4%) cases. Follow-up echocardiography revealed right or left ventricular failure in 10 (12.1%) cases. Cardiac complications occurred in 41 (50%) cases and systemic complications in 63 (76.8%). All-cause mortality was 41.5% (n = 34) and 6 (18.1%) patients died due to cardiovascular complications.

Conclusions

The short- and long-term prognosis in IE was poor and the predictors for in-hospital and 1-year mortality were defined as heart failure and septic shock. Congenital heart disease and intravenous illicit drug using (IVDU) were the most common predisposing condition which may necessitate a revision in the IE prophylaxis recommendations.
Impact of Ticagrelor vs. Clopidogrel in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention After Risk Stratification With the CHA2DS2-VASc Score
Authors: Na Kun , Qiu Miaohan , Ma Sicong , Li Yi , Li Jing , Liu Rong , Zhang Jiaoyang , Han Yaling
Published: April 2022

Backgrounds

The clinical benefit of ticagrelor vs. clopidogrel in unselected patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) remains controversial in the real world. This study was aimed to investigate the impact of ticagrelor vs. clopidogrel in subjects with ACS without atrial fibrillation or flutter (AF) after PCI based on risk stratification using the CHA2DS2-VASc score.

Methods

In 2016–2019, patients who underwent PCI with at least one stent implanted in the General Hospital of Northern Theater Command were classified as low- or high-risk groups according to the CHA2DS2-VASc score. Incidences of 12-month ischemia [cardiac death, myocardial infarction (MI), or stroke], all-cause death, Bleeding Academic Research Consortium (BARC) 2,3,5 bleeding, BARC 3,5 bleeding, and net adverse clinical events (NACEs) (all-cause death, MI, stroke, or BARC 3, 5 bleeding) with aspirin plus different P2Y12 inhibitors (clopidogrel or ticagrelor) were appraised among different risk groups. Propensity score matching (PSM) and Cox multivariate analysis were used to balance the groups.

Results

A total of consecutive 17,037 patients with ACS were enrolled. The optimal cut-off value of the CHA2DS2-VASc score for ischemic events by the Youden test was 3 points. Among patients with high risk (CHA2DS2-VASc ≥ 3, n = 6,151), ticagrelor was associated with slightly lower risks of ischemic events (2.29% vs. 3.54%, P = 0.02) and stroke (0.39% vs. 1.08%, P = 0.01) without excessive risk of BARC 3, 5 bleeding events (2.16% vs. 2.11%, P = 0.92) compared to clopidogrel within 12 months after PCI. For patients with low risk (CHA2DS2-VASc < 3, n = 10,886), a statistically significant difference was seen in the incidence of overall 12-month BARC 2, 3, 5 bleeding events by P2Y12 receptor inhibitor (4.00% vs. 3.26%) with a similar incidence of the ischemic events (1.40% vs. 1.52%). Results in the PSM cohort and the adjustment with Cox multivariate analysis were consistent with the main outcomes.

Conclusion

Higher CHA2DS2-VASc scores were associated with a higher incidence of 1-year ischemic events for the patients with ACS after PCI. Compared with clopidogrel, ticagrelor was associated with lower ischemic events within 12 months after PCI without excessive risk of bleeding in high-risk patients but shows poor safety with excess bleeding in low-risk patients.
Case Report: Systemic Amyloidosis Involving the Heart and Skeletal Muscle
Authors: Lv Pinchao , Li Yuxi , Wu Lin , Shi Qiuping , Meng Lingchao , Yu Xiaojuan , Nong Lin , Li Jianping
Published: April 2022

Background

Amyloidosis refers to an etiologically heterogeneous group of protein misfolding diseases characterized by extracellular deposition in organs and tissues of amyloid fibers, leading to severe organ dysfunction and death. Systemic amyloidosis often involves multiple organs. Heart and kidney are the most commonly affected organs, whereas skeletal muscle involvement is rare and often accompanied by other organs’ involvement.

Case Summary

We reported a 70-year-old man manifested with myopathy followed by heart failure who was suspected of transthyretin amyloidosis clinically, after the pathological results and the 99mTc-pyrophosphate (99mTc-PYP) scintigraphy, light-chain (AL) amyloidosis involving the heart and skeletal muscle was confirmed.

Conclusion

The patient’s unique presentation gives insight into a rare but debilitating disorder and the potential link between various types of amyloidosis. In addition, myopathy in amyloidosis should be recognized.
Differences in Teacher Burnout Between Schools: Exploring the Effect of Proactive Strategies on Burnout Trajectories
Authors: Tikkanen Lotta , Haverinen Kaisa , Pyhältö Kirsi , Pietarinen Janne , Soini Tiina
Published: April 2022

Differences in teacher burnout between schools are likely to occur due to differences in the quantity and quality of interaction within the schools. Multilevel latent growth curve analyses of burnout symptoms were performed on three-wave longitudinal data collected from 2,619 teachers in 75 schools in Finland. The results showed that differences in teacher burnout between schools were pronounced in cynicism, followed by emotional exhaustion. Organizational factors were not strong predictors of differences in teacher burnout. Proactive co-regulation strategies were related to lower levels of teachers’ cynicism about the professional community, implying that they might be useful in preventing the teachers’ cynicism at the school level.
Suitability and Eligibility of Phyllostachys pubescens (Moso Bamboo) Afforestation for GHG (Greenhouse Gases) Projects: Case Study in Central Italy
Authors: Vadalà Rossella , Cicero Nicola , Dugo Giacomo , Costa Rosaria
Published: April 2022

A case study concerning an experimental moso bamboo plantation (5 ha), located in central Italy, is presented. In order to evaluate CO2 capturing potential, a computational study was developed and applied to the bamboo field to predict and quantify the tons of CO2 equivalent annually sequestered, during a project range of 15 years. The computational model, based on allometric parameters and field density, was integrated with an accurate analysis of the geological, pedological and climatic scenario, and of the socio-economic context. The study aimed to correlate the growth and thickening trend of moso bamboo field, namely its CO2 capturing potential, with the geopedoclimatic context. This allowed to evaluate if the bamboo afforestation projects are capable to offset carbon dioxide emissions in the Italian context. The highest segregation power of the bamboo plantation equated 3,651.32 tCO2e ⋅ yr−1, segregated by the whole field in the 12th year (out of a total timeframe of 15 years). The study demonstrated the eligibility requirements for a GHG project and the suitability of moso bamboo farming finalized to carbon trading. Our findings represent a valid model to encourage the voluntary carbon market in Italy from afforestation with bamboo species.
The Natural Suitability of Human Settlements and Their Spatial Differentiation in the Nenjiang River Basin, China
Authors: Zhao Yang , Zhang Junling
Published: April 2022

The natural suitability of human settlements (NSHS) of the Nenjiang River Basin was carried out by evaluation indices such as terrain characteristics, vegetation, hydrology, and climate of the region. The NSHS model is built using a GIS spatial analysis platform to reveal the suitability zoning and spatial differentiation (SD) characteristics of human settlements in the study area. The results show that the NSHS index of the study area ranges from 0.31 to 0.92, with an average of 0.54, indicating that the values show a gradual increase from northwest to southeast and from mountainous and hilly areas to plains. The most suitable and generally suitable areas constitute nearly 41.81% of the basin, and the population of these terrain accounts for about 84.25% of the total population of the basin. The suitable area category covers the largest area among all other categories accounting for about 25.16%, and the population of these regions accounts for about 12.46%. The critical suitable area category accounts for 21.70% of the basin, whereas unsuitable areas account for 11.32%, constituting the smallest areas compared to other categories. It is also evident that diverse limiting factors of NSHS characterize distinct areas in the study area. For example, high NSHS index, the normalized difference vegetation index (NDVI), and water resource index (WRI) are the main limiting factors in plane areas, low NSHS index, the relief degree of land surface (RDLS) index, and temperature-humidity index (THI) are the major limiting factors in the mountainous, hilly and plateau areas.
Genetic Modeling and Genomic Analyses of Yearling Temperament in American Angus Cattle and Its Relationship With Productive Efficiency and Resilience Traits
Authors: Alvarenga Amanda B. , Oliveira Hinayah R. , Miller Stephen P. , Silva Fabyano F. , Brito Luiz F.
Published: April 2022

Cattle temperament has been considered by farmers as a key breeding goal due to its relevance for cattlemen’s safety, animal welfare, resilience, and longevity and its association with many economically important traits (e.g., production and meat quality). The definition of proper statistical models, accurate variance component estimates, and knowledge on the genetic background of the indicator trait evaluated are of great importance for accurately predicting the genetic merit of breeding animals. Therefore, 266,029 American Angus cattle with yearling temperament records (1–6 score) were used to evaluate statistical models and estimate variance components; investigate the association of sex and farm management with temperament; assess the weighted correlation of estimated breeding values for temperament and productive, reproductive efficiency and resilience traits; and perform a weighted single-step genome-wide association analysis using 69,559 animals genotyped for 54,609 single-nucleotide polymorphisms. Sex and extrinsic factors were significantly associated with temperament, including conception type, age of dam, birth season, and additional animal–human interactions. Similar results were observed among models including only the direct additive genetic effect and when adding other maternal effects. Estimated heritability of temperament was equal to 0.39 on the liability scale. Favorable genetic correlations were observed between temperament and other relevant traits, including growth, feed efficiency, meat quality, and reproductive traits. The highest approximated genetic correlations were observed between temperament and growth traits (weaning weight, 0.28; yearling weight, 0.28). Altogether, we identified 11 genomic regions, located across nine chromosomes including BTAX, explaining 3.33% of the total additive genetic variance. The candidate genes identified were enriched in pathways related to vision, which could be associated with reception of stimulus and/or cognitive abilities. This study encompasses large and diverse phenotypic, genomic, and pedigree datasets of US Angus cattle. Yearling temperament is a highly heritable and polygenic trait that can be improved through genetic selection. Direct selection for temperament is not expected to result in unfavorable responses on other relevant traits due to the favorable or low genetic correlations observed. In summary, this study contributes to a better understanding of the impact of maternal effects, extrinsic factors, and various genomic regions associated with yearling temperament in North American Angus cattle.
The Prognostic Significance of RIMKLB and Related Immune Infiltrates in Colorectal Cancers
Authors: Cao Yinghao , Deng Shenghe , Yan Lizhao , Gu Junnan , Mao Fuwei , Xue Yifan , Qin Le , Jiang Zhengxing , Cai Wentai , Zheng Changmin , Nie Xiu , Liu Hongli , Sun Zhuolun , Shang Fumei , Tao Kaixiong , Wang Jiliang , Wu Ke , Zhu Bin , Cai Kailin
Published: April 2022

RimK-like family member B (RIMKLB) is an enzyme that post-translationally modulates ribosomal protein S6, which can affect the development of immune cells. Some studies have suggested its role in tumor progression. However, the relationships among RIMKLB expression, survival outcomes, and tumor-infiltrating immune cells (TIICs) in colorectal cancer (CRC) are still unknown. Therefore, we analyzed RIMKLB expression levels in CRC and normal tissues and investigated the correlations between RIMKLB and TIICs as well as the impact of RIMKLB expression on clinical prognosis in CRC using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), PrognoScan, and UALCAN databases. Enrichment analysis was conducted with the cluster Profiler package in R software to explore the RIMKLB-related biological processes involved in CRC. The RIMKLB expression was significantly decreased in CRC compared to normal tissues, and correlated with histology, stage, lymphatic metastasis, and tumor status (p < 0.05). Patients with CRC with high expression of RIMKLB showed poorer overall survival (OS) (HR = 2.5,p = 0.00,042), and inferior disease-free survival (DFS) (HR = 1.9,p = 0.19) than those with low expression of RIMKLB. TIMER analysis indicated that RIMKLB transcription was closely related with several TIICs, including CD4+ and CD8+ T cells, B cells, tumor-associated macrophages (TAMs), monocytes, neutrophils, natural killer cells, dendritic cells, and subsets of T cells. Moreover, the expression of RIMKLB showed significant positive correlations with infiltrating levels of PD1 (r = 0.223, p = 1.31e-06; r = 0.249, p = 1.25e-03), PDL1 (r = 0.223, p = 6.03e-07; r = 0.41, p = 5.45e-08), and CTLA4 (r = 0.325, p = 9.68e-13; r = 0.41, p = 5.45e-08) in colon and rectum cancer, respectively. Enrichment analysis showed that the RIMKLB expression was positively related to extracellular matrix and immune inflammation-related pathways. In conclusion, RIMKLB expression is associated with survival outcomes and TIICs levels in patients with CRC, and therefore, might be a potential novel prognostic biomarker that reflects the immune infiltration status.
PPA-GCN: A Efficient GCN Framework for Prokaryotic Pathways Assignment
Authors: Lu Yuntao , Li Qi , Li Tao
Published: April 2022

With the rapid development of sequencing technology, completed genomes of microbes have explosively emerged. For a newly sequenced prokaryotic genome, gene functional annotation and metabolism pathway assignment are important foundations for all subsequent research work. However, the assignment rate for gene metabolism pathways is lower than 48% on the whole. It is even lower for newly sequenced prokaryotic genomes, which has become a bottleneck for subsequent research. Thus, the development of a high-precision metabolic pathway assignment framework is urgently needed. Here, we developed PPA-GCN, a prokaryotic pathways assignment framework based on graph convolutional network, to assist functional pathway assignments using KEGG information and genomic characteristics. In the framework, genomic gene synteny information was used to construct a network, and ideas of self-supervised learning were inspired to enhance the framework’s learning ability. Our framework is applicable to the genera of microbe with sufficient whole genome sequences. To evaluate the assignment rate, genomes from three different genera (Flavobacterium (65 genomes) and Pseudomonas (100 genomes), Staphylococcus (500 genomes)) were used. The initial functional pathway assignment rate of the three test genera were 27.7% (Flavobacterium), 49.5% (Pseudomonas) and 30.1% (Staphylococcus). PPA-GCN achieved excellence performance of 84.8% (Flavobacterium), 77.0% (Pseudomonas) and 71.0% (Staphylococcus) for assignment rate. At the same time, PPA-GCN was proved to have strong fault tolerance. The framework provides novel insights into assignment for metabolism pathways and is likely to inform future deep learning applications for interpreting functional annotations and extends to all prokaryotic genera with sufficient genomes.
Nanodiamond-Induced Thrombocytopenia in Mice Involve P-Selectin-Dependent Nlrp3 Inflammasome-Mediated Platelet Aggregation, Pyroptosis and Apoptosis
Authors: Hung Shih-Che , Ke Lu-Chu , Lien Te-Sheng , Huang Hsuan-Shun , Sun Der-Shan , Cheng Chia-Liang , Chang Hsin-Hou
Published: April 2022

Nanodiamond (ND) has been developed as a carrier to conduct various in vivo diagnostic and therapeutic uses. Safety is one of the major considerations, while the hemocompatibility of ND is not clearly addressed. Here we found that, compared to the other sizes of ND with relatively inert properties, treatments of 50 nm ND induced stronger platelet aggregation, platelet pyroptosis, apoptosis and thrombocytopenia in mice. Blockage treatments of soluble P-selectin, reactive oxygen species (ROS), and Nlrp3 inflammasome inhibitors markedly suppressed such adverse effects, suggesting ND-induced platelet activation and pyroptosis involves surface P-selectin-mediated enhancement of mitochondrial superoxide levels and Nlrp3 inflammasome activation. In addition, challenges of NDs induced less platelet pyroptosis and displayed less thrombocytopenia in P-selectin (Selp-/-), Nlrp3 (Nlrp3-/-) and caspase-1 (Casp1-/-) mutants, as compared to the wild type mice. Blockers of P-selectin, ROS, and Nlrp3 inflammasome pathways could be considered as antidotes for ND induced platelet activation and thrombocytopenia.
Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects
Authors: Jiang Hongxia , Zhao Hanqiu , Zhang Mengzhe , He Yuanzhou , Li Xiaochen , Xu Yongjian , Liu Xiansheng
Published: April 2022

Exosomes are small extracellular vesicles that are secreted by almost all types of cells and exist in almost all extracellular spaces. As an important mediator of intercellular communication, exosomes encapsulate the miRNA, lncRNA, cirRNA, mRNA, cytokine, enzyme, lipid, and other components from the cytoplasm into its closed single membrane structure and transfer them to recipient units in an autocrine, paracrine, or endocrine manner. Hypoxia is a state of low oxygen tension and is involved in many pathological processes. Hypoxia influences the size, quantity, and expression of exosome cargos. Exosomes derived from hypoxic tumor cells transfer genetics, proteins, and lipids to the recipient units to exert pleiotropic effects. Different donor cells produce different cargo contents, target different recipient units and lead to different biological effects. Hypoxic exosomes derived from tumor cells uptaken by normoxic tumor cells lead to promoted proliferation, migration, and invasion; uptaken by extracellular space or liver lead to promoted metastasis; uptaken by endothelial cells lead to promoted angiogenesis; uptaken by immune cells lead to promoted macrophage polarization and changed tumor immune microenvironment. In addition to various types of tumors, hypoxic exosomes also participate in the development of diseases in the cardiovascular system, neuron system, respiratory system, hematology system, endocrine system, urinary system, reproduction system, and skeletomuscular system. Understanding the special characteristics of hypoxic exosomes provide new insight into elaborating the pathogenesis of hypoxia related disease. This review summarizes hypoxia induced cargo changes and the biological effects of hypoxic exosomes in tumors and non-malignant diseases in different systems.
Discovery of Anti-PD-L1 Human Domain Antibodies for Cancer Immunotherapy
Authors: Liu Hao , Liu Yanli , Zhao Zhen , Li Yuanke , Mustafa Bahaa , Chen Zhijin , Barve Ashutosh , Jain Akshay , Yao Xiaolan , Li Guangfu , Cheng Kun
Published: April 2022

Immunotherapy using monoclonal antibodies targeting the PD-1/PD-L1 interaction has shown enormous success for various cancers. Despite their encouraging results in clinics, antibody-based checkpoint inhibitors have several limitations, such as poor tumor penetration. To address these limitations of monoclonal antibodies, there is a growing interest in developing low-molecular-weight checkpoint inhibitors, such as antibody fragments. Several antibody fragments targeting PD-1/PD-L1 were recently discovered using phage libraries from camel or alpaca. However, animal-derived antibody fragments may elicit unwanted immune responses, which limit their therapeutic applications. For the first time, we used a human domain antibody phage library and discovered anti-human PD-L1 human single-domain antibodies (dAbs) that block the PD-1/PD-L1 interaction. Among them, the CLV3 dAb shows the highest affinity to PD-L1. The CLV3 dAb also exhibits the highest blocking efficacy of the PD-1/PD-L1 interaction. Moreover, the CLV3 dAb significantly inhibits tumor growth in mice implanted with CT26 colon carcinoma cells. These results suggest that CLV3 dAb can be potentially used as an anti-PD-L1 inhibitor for cancer immunotherapy.
Identification and Contribution of Inflammation-Induced Novel MicroRNA in the Pathogenesis of Systemic Lupus Erythematosus
Authors: Singh Ram P. , Hahn Bevra H. , Bischoff David S.
Published: April 2022

Recently microRNAs (miRNAs) have been recognized as powerful regulators of many genes and pathways involved in the pathogenesis of inflammatory diseases including Systemic Lupus Erythematosus (SLE). SLE is an autoimmune disease characterized by production of various autoantibodies, inflammatory immune cells, and dysregulation of epigenetic changes. Several candidate miRNAs regulating inflammation and autoimmunity in SLE are described. In this study, we found significant increases in the expression of miR21, miR25, and miR186 in peripheral blood mononuclear cells (PBMCs) of SLE patients compared to healthy controls. However, miR146a was significantly decreased in SLE patients compared to healthy controls and was negatively correlated with plasma estradiol levels and with SLE disease activity scores (SLEDAI). We also found that protein levels of IL-12 and IL-21 were significantly increased in SLE patients as compared to healthy controls. Further, our data shows that protein levels of IL-12 were positively correlated with miR21 expression and protein levels of IL-21 positively correlated with miR25 and miR186 expression in SLE patients. In addition, we found that levels of miR21, miR25, and miR186 positively correlated with SLEDAI and miR146a was negatively correlated in SLE patients. Thus, our data shows a dynamic interplay between disease pathogenesis and miRNA expression. This study has translational potential and may identify novel therapeutic targets in patients with SLE.
Molnupiravir and Its Antiviral Activity Against COVID-19
Authors: Tian Lili , Pang Zehan , Li Maochen , Lou Fuxing , An Xiaoping , Zhu Shaozhou , Song Lihua , Tong Yigang , Fan Huahao , Fan Junfen
Published: April 2022

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a major worldwide public health threat and economic burden. The pandemic is still ongoing and the SARS-CoV-2 variants are still emerging constantly, resulting in an urgent demand for new drugs to treat this disease. Molnupiravir, a biological prodrug of NHC (β-D-N(4)-hydroxycytidine), is a novel nucleoside analogue with a broad-spectrum antiviral activity against SARS-CoV, SARS-CoV-2, Middle East respiratory syndrome coronavirus (MERS-CoV), influenza virus, respiratory syncytial virus (RSV), bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV) and Ebola virus (EBOV). Molnupiravir showed potent therapeutic and prophylactic activity against multiple coronaviruses including SARS-CoV-2, SARS-CoV, and MERS-CoV in animal models. In clinical trials, molnupiravir showed beneficial effects for mild to moderate COVID-19 patients with a favorable safety profile. The oral bioavailability and potent antiviral activity of molnupiravir highlight its potential utility as a therapeutic candidate against COVID-19. This review presents the research progress of molnupiravir starting with its discovery and synthesis, broad-spectrum antiviral effects, and antiviral mechanism. In addition, the preclinical studies, antiviral resistance, clinical trials, safety, and drug tolerability of molnupiravir are also summarized and discussed, aiming to expand our knowledge on molnupiravir and better deal with the COVID-19 epidemic.