bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstetrics and gynecology residents’ satisfaction and self-confidence after an anal sphincter injury simulation-based workshop in Indonesia: a pre- and post-intervention comparison study
Authors: Wahyuningtyas Riska , Kurniawati Eighty Mardiyan , Utomo Budi , Hardianto Gatut , Paraton Hari , Hastono Tri , Kuswanto Djoko
Published: February 2022

Purpose: Obstetric anal sphincter injury is one of the most common complications during delivery. Simulation models with manikins can be used as an effective medical learning method to improve students’ abilities before encountering patients. The present study aimed to describe the development of an anal sphincter injury model and to assess residents’ satisfaction and self-confidence after a perineal repair workshop with an anal sphincter injury simulator in Indonesia.Methods: This was a cross-sectional study with evaluation of outcomes before and after the workshop. We created a silicone-latex simulation anal sphincter injury model. Then, we validated this simulation and used it as a simulation model for the workshop. We asked residents about their satisfaction with repairing anal sphincter injuries using a simulation model and residents’ self-confidence when practicing anal sphincter injury repair.Results: All residents felt the simulation-based workshop was valuable (100%). Most of the scores for the similarity of the simulation model were good (about 8 out of maximum 10). The self-assessment of confidence was measured before and after the workshop. Overall self-confidence increased significantly after the workshop in identifying the external sphincter ani (EAS) (P=0.031), suturing the anal mucosa (P=0.001), suturing the internal sphincter ani (P=0.001), suturing the EAS (P<0.001), and evaluating the sphincter ani tone (P=0.016).Conclusion: The anal sphincter injury simulator improved residents’ self-confidence in identifying the EAS, suturing the anal mucosa, suturing the internal sphincter ani, suturing the EAS, and evaluating sphincter ani tone.
DETERMINATION OF ANXIETY STATUS IN WOMEN WITH CHRONIC DISEASE DURING THE COVID-19 PANDEMIC
Authors: BÜYÜKBAYRAM Zeliha , GÜL Sidar , ÖZÜDOĞRU Osman
Published: February 2022

This study was conducted to determine the anxiety status of women with chronic diseases during the coronavirus disease pandemic. This descriptive study was conducted in February-August 2021 within the internal medicine outpatient clinic of a training and research hospital located in the Southeastern Anatolia Region of Turkey. Individual Descriptive Questionnaire and Spielberger State-Trait Anxiety Inventory forms were used to collect data. The mean state anxiety score of the participants was 46.40±10.46, and the mean trait anxiety score was 49.56±9.33. The trait anxiety mean scores of the participants who have a good relationship with the family and whose health status was not affected during the pandemic was found to lower statistically significant (p<0.05). The trait anxiety mean scores of the participants who have poor economic status was found to higher statistically significant (p<0.05). It was determined that women with chronic diseases had moderate anxiety and were negatively affected by the pandemic process. In line with this information, it comes to the fore that women with chronic diseases need more psychosocial support due to their increased anxiety and they are a group that should be handled with care. It is recommended that more descriptive studies be carried out on this subject.
A DIFFERENT ASPECT OF NEGLECT: SMOKING MOTHERS
Authors: POLAT Sevinç , ÇEVİK GÜNER Ümran , GÜNGÖR Sibel
Published: February 2022

Smoking during pregnancy and lactation poses a serious risk in terms of fetus, newborn and child health. Therefore, for mothers all over the world, pregnancy and breastfeeding periods are a good opportunity to end smoking habits. Unfortunately, many mothers ignore this problem and continue to smoke widely. This study was conducted to evaluate the views of mothers with children at 0-2 age group who smoke, about the harms of smoking during pregnancy and breastfeeding, in terms of neglect. This qualitative study was conducted with 19 volunteer mothers who smoke. An introductory information form and a semi-structured questionnaire were used to collect the data. The data were collected through face-to-face interviews, recorded, literally transcribed, and analyzed with content analysis. It was determined that almost half of the mothers continued to smoke during pregnancy although they knew its harmful. Almost none of them had knowledge about the harms of smoking to the baby during breastfeeding period, and only two of the mothers were aware of passive smoking. In this direction, mothers who continue to smoke consciously or unintentionally should be followed more carefully by health professionals to protect children's health and rights.
The Russian Armed Forces “New Look” Reform (2008-2013)
Authors: Anak Agung Banyu Perwit Naufal Ahaddin Caesarialdy
Published: February 2022

Russia-Georgia relations had been declining since Georgia first voiced its intention for NATO membership in 2005 which later escalated into a war in 2008. Despite being victorious in the 2008 Russo-Georgian Five-Day War, the shortcomings of the Russian Armed Forces that were exposed during the war had led the country towards its “New Look” military reform announced months after the war. Many International Relations scholar draw a connection between the reform and Russia’s increasing assertiveness marked by the Crimean annexation and Russia’s involvement in Syria. This piece will then try to understand how Russian military performance in the 2008 war led to Russia’s most rigorous military reform, and more importantly, how did Russia implement its “New Look” reform during 2008 until 2013. Russia had underwent far reaching efforts and goals to transform the armed forces into combat-ready forces but had also faced challenges in modernizing its weaponry system, in increasing the quality and professionalism of its forces
Pentingnya Laboratorium Virtual Bahasa Sebagai Penunjang Proses Pembelajaran Jarak Jauh
Authors: Supratmi Nunung , Pratiwi Brillianing , Izzati Arini Noor
Published: February 2022

Seperti yang telah diketahui bersama bahwa proses pembelajaran jarak jauh tidak dibatasi oleh ruang dan waktu. Begitu juga untuk proses pembelajaran keterampilan berbahasa Indonesia yang dilaksanakan oleh Program Studi Pendidikan Bahasa dan Sastra Indonesia FKIP UT yang dilaksanakan secara jarak jauh. Untuk menunjang proses pembelajaran keterampilan berbahasa maka laboratorium virtual ini sangat penting untuk dikembangkan. Salah satu tujuannya adalah untuk memberikan pengalaman belajar di laboratorium bahasa walaupun dilaksanakan secara virtual. Artikel ini akan menjelaskan apa saja manfaat dari laboratorium virtual, perangkat apa saja yang sangat dibutuhkan dalam laboratorium virtual bahasa, dan kendala apa saja yang akan dihadapi untuk mengakses laboratorium virtual bahasa
Building a Credential Exchange Infrastructure for Digital Identity: A Sociohistorical Perspective and Policy Guidelines
Authors: Chango Mawaki
Published: February 2022

Credential Exchange Infrastructures based on open standards are emerging with work ongoing across many different jurisdictions, in several global standards bodies and industry associations, as well as at a national level. This article addresses the technology advances on this topic, particularly around identification mechanisms, through the Self-sovereign identity model. It also tackles necessary institutional processes and policy concerns relating to their implementation. Rooted in a sociohistorical culture and practice of inquiry, the goal of the article is to bring emerging digital identity systems within the grasp of a wider public as well as to contribute to mutual understanding across stakeholder groups (technical community, governments, international cooperation entities, civil society and academia) about what is at stake. This is expected to enhance their capacity to better navigate across the pitfalls of this transition period from paper to digital systems and the full adoption of the latter, with each of these stakeholders playing a part in enabling trust around digital identity infrastructure and transactions, both within related ecosystems and in the broader society. This article makes contributions around three axes. First axis is conceptual and analytical. The article outlines three conceptualized phases in the evolution of identity practices in history with the hypothesis that the availability of new record-creation methods invites changes in, and expansion of, the existing identification processes. This helps make a stronger case for why the Internet needs an identity capability. In addition, the article defines or elaborates on key concepts including identity, credential and trust. The second axis of the article is a case study on self-sovereign identity as instantiated by the Sovrin network. The case study presents the technology and its design with a view to enabling a non-technical public to understand what it is and how it works, while highlighting the fact that the technology still needs institutional processes to make it work as intended. The final axis of this article provides guidelines to policy actors potentially facing the need to enable large scale implementations of these emerging technologies, as they mature. Policy-makers approaching this material may want to read this section first and then return to the rest of the paper.
Leaving the Academic Niche–Rhoda Erdmann (1870–1935) and the Democratization of Tissue Culture Research
Authors: Fangerau Heiner
Published: February 2022

In the years after Ross Harrison published his pivotal paper on nerve fiber regeneration in 1907, researchers following his line of research presented tissue culture techniques as an extremely sensitive, difficult, and almost occult methodology. When Philip R. White published a manual on tissue culturing in 1954, he declared that he wanted to disenchant this formerly mystified field of study. With a similar aim Rhoda Erdmann had published a comparable manual more than 30 years before in 1922. Her intention was to offer a book that would make the method “a common property of those who want to do biological research in the future.” When science was about to move from little science to big science, Erdmann tried to democratize tissue culture knowledge. Rhoda Erdmann was in many aspects an extraordinary scholar deviating from the norm. She was one of the few women in the field, working as a low-level assistant at the Robert Koch Institute in Berlin before she took the opportunity to work as a research fellow with Ross Harrison in Yale. She was imprisoned during the First World War on the accusation of being a German spy. After she could return to Germany in 1919, she established a laboratory for experimental cell research in Berlin. In 1929 she was one of the first women to be appointed a professor in Germany. The paper focuses Erdmann’s attempts at distributing practical tissue culturing knowledge. Based on her and other scholars’ research work on nutrient media for cell cultures, and the attempts to optimize these basic tools for different species, this contribution examines the hypothesis that this work constituted an academic niche for underprivileged scientists. The paper analyzes whether Erdmann, due to her extraordinary characteristics, had to use certain niches in the academic world (topics, places, techniques, communities) to pursue her research, and whether her attempts at democratizing her techniques can also be read as an attempt to move out of the niche to gain academic recognition.
Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons
Authors: Sainio Markus T. , Rasila Tiina , Molchanova Svetlana M. , Järvilehto Julius , Torregrosa-Muñumer Rubén , Harjuhaahto Sandra , Pennonen Jana , Huber Nadine , Herukka Sanna-Kaisa , Haapasalo Annakaisa , Zetterberg Henrik , Taira Tomi , Palmio Johanna , Ylikallio Emil , Tyynismaa Henna
Published: February 2022

Neurofilament light (NFL) is one of the proteins forming multimeric neuron-specific intermediate filaments, neurofilaments, which fill the axonal cytoplasm, establish caliber growth, and provide structural support. Dominant missense mutations and recessive nonsense mutations in the neurofilament light gene (NEFL) are among the causes of Charcot–Marie–Tooth (CMT) neuropathy, which affects the peripheral nerves with the longest axons. We previously demonstrated that a neuropathy-causing homozygous nonsense mutation inNEFLled to the absence of NFL in patient-specific neurons. To understand the disease-causing mechanisms, we investigate here the functional effects of NFL loss in human motor neurons differentiated from induced pluripotent stem cells (iPSC). We used genome editing to generateNEFLknockouts and compared them to patient-specific nonsense mutants and isogenic controls. iPSC lacking NFL differentiated efficiently into motor neurons with normal axon growth and regrowth after mechanical axotomy and contained neurofilaments. Electrophysiological analysis revealed that motor neurons without NFL fired spontaneous and evoked action potentials with similar characteristics as controls. However, we found that, in the absence of NFL, human motor neurons 1) had reduced axonal caliber, 2) the amplitude of miniature excitatory postsynaptic currents (mEPSC) was decreased, 3) neurofilament heavy (NFH) levels were reduced and no compensatory increases in other filament subunits were observed, and 4) the movement of mitochondria and to a lesser extent lysosomes was increased. Our findings elaborate the functional roles of NFL in human motor neurons. NFL is not only a structural protein forming neurofilaments and filling the axonal cytoplasm, but our study supports the role of NFL in the regulation of synaptic transmission and organelle trafficking. To rescue the NFL deficiency in the patient-specific nonsense mutant motor neurons, we used three drugs, amlexanox, ataluren (PTC-124), and gentamicin to induce translational read-through or inhibit nonsense-mediated decay. However, the drugs failed to increase the amount of NFL protein to detectable levels and were toxic to iPSC-derived motor neurons.
Antioxidant Aryl-Substituted Phthalan Derivatives Produced by Endophytic Fungus Cytospora rhizophorae
Authors: Liu Hongxin , Liu Zhaoming , Zhang Yanjiang , Chen Yuchan , Wang Huan , Tan Haibo , Zhang Weimin
Published: February 2022

Six new phthalan derivatives cytorhizophins D-I (1-6) as well as three known derivatives cytorhizophin C, pestacin and rhizophol B were isolated from Cytospora rhizophorae. Among them, cytorhizophins D-E (1-2) and F-G (3-4) were two pairs of diastereoisomers, all of them featuring a 1-phenyl-1,3-dihydroisobenzofuran scaffold with a highly oxygenated O-linked isopentenyl unit. Besides, cytorhizophins H-I (5-6) represent the first examples of phthalide family with fascinating 6/6/6/5 tetracyclic ring system fusing as unprecedented furo [4,3,2-kl]xanthen-2 (10bH)-one skeleton. The structures of the new phthalan derivatives were extensively confirmed by detail spectroscopic analysis. The partial absolute configurations of compounds 1-6 were established through electronic circular dichroism (ECD) calculations. Moreover, compounds 1-4 showed remarkable antioxidant activities with EC50 values ranging from 5.86 to 26.80 μM, which were better than or comparable to that of ascorbic acid (positive control).
Trace Level Quantification of 4-Methyl-1-nitrosopiperazin in Rifampicin Capsules by LC-MS/MS
Authors: Tao Xiaosha , Tian Ye , Liu Wan-Hui , Yao Shangchen , Yin Lihui
Published: February 2022

Rifampicin is a first-line anti-tuberculosis drug. However, in August 2020, the presence of 1-methyl-4-nitrosopiperazine (MNP), a nitrosamine impurity, was detected by the United Stated Food and Drug Administration (US FDA) in rifampicin capsules. Consequently, the development of efficient methods for the detection of MNP is an important objective. In this study, the MNP present in rifampicin capsules was detected using LC-MS/MS. A total of 27 batches from nine manufacturers in the Chinese market were tested, with MNP (0.33–2.36 ppm) being detected in all samples at levels exceeding the maximum acceptable intake limit of 0.16 ppm initially set by the FDA. However, after considering the associated benefits and risks, the FDA-approved limit was revised to 5 ppm; hence, all the samples examined herein exhibited MNP levels well below the required limit. Furthermore, the results of forced degradation experiments suggest that MNP is formed by the thermal degradation of rifampicin.
Assessment of Serum Macrophage Migration Inhibitory Factor (MIF) as an Early Diagnostic Marker of Leptospirosis
Authors: Sumaiya Krishnamoorthi , Akino Mercy Charles Solomon , Muralitharan Gangatharan , Hajinur Hirad Abdurahman , Alarfaj Abdullah A. , Natarajaseenivasan Kalimuthusamy
Published: February 2022

The search for valuable early diagnostic markers for leptospirosis is ongoing. The aim of the present study was to evaluate the diagnostic value of macrophage migration inhibitory factor (MIF) for leptospirosis. MIF is an immunoregulatory cytokine secreted by a variety of cell types involved in immune response and the pathogenesis of various diseases. It was previously described as a severity predictor of diseases. Samples of 142 leptospirosis cases, 101 other febrile cases, and 57 healthy controls were studied. The prevalence of leptospirosis was 47.3%. Autumnalis, Australis, and Canicola were the highly prevalent leptospiral serovars with a microscopic agglutination test (MAT) titer in the range 1:80–1:2,560. Enzyme-linked immunosorbent assay (ELISA) of MIF was carried out to measure the serum MIF levels. We found that the serum MIF levels [median, (interquartile range)] were significantly (p < 0.001) elevated in different clinical forms of leptospirosis, such as febrile illness [7.5 ng/ml (5.32–8.97)], pulmonary hemorrhage [13.2 ng/ml (11.77–16.72)], Weil’s syndrome [8.8 ng/ml (7.25–9.95)], and renal failure [8.6 ng/ml (7.18–10.5)], than in healthy controls [0.65n g/ml (0.5–1.1)]. Serum MIF had sensitivity, specificity, positive predictive value, and negative predictive value of 100%, >90%, >90%, and 100%, respectively. Receiver operating characteristic (ROC) analysis revealed that the serum MIF levels between leptospirosis cases and control subjects had an area under the curve (AUC) value of >0.9 (p < 0.0001). In leptospirosis patients, elevation of serum MIF was significantly (p < 0.001) higher in severe cases with organ dysfunction [10 ng/ml (7.8–14.5)] than that in mild febrile cases [7.5 ng/ml (5.32–8.97)], with the difference of 2.5 indicating that serum MIF acts as a predictor of leptospirosis severity. Pearson’s correlation test demonstrated that the serum MIF level was strongly correlated (r = 0.75, p < 0.0001) with disease progression. The median lethal dose (LD50) of leptospiral lipopolysaccharide (LPS) in BALB/c mice was determined to be 20 mg/kg, which gave rise to endotoxemia. Leptospiral LPS triggered the upregulation of MIF expression at 24 h post-infection, which reached the peak level at 24 h post-treatment in THP-1 cells and showed elevated MIF expressions in different tissues of BALB/c mice at the early stage of infection. Taken together, MIF is an early-phase cytokine that could serve as a rapid diagnostic marker for leptospirosis.
The Crosstalk Between Saliva Bacteria and Fungi in Early Childhood Caries
Authors: Tu Ye , Zhou Zhiyan , Shu Chang , Zhou Yuan , Zhou Xuedong
Published: February 2022

Early childhood caries (ECC) is the most prevalent oral disease in children, which greatly affects the quality of life and health condition of the patients. Although co-infection of oral streptococci and fungi has been well recognized in the development of ECC, the correlation between other core members of oral mycobiome and ECC progression remains unclear. In the current study, saliva samples obtained from severe ECC (SECC), ECC, and caries-free children were collected, and both V3–V4 16S rRNA and ITS1 rRNA gene amplicon sequencing were performed to investigate the salivary bacterial and fungal profiles. Significant alteration of salivary fungal community in SECC/ECC children was observed compared with the caries-free control. The typing analysis determined the fungal community into five fungal types, which influenced the structure of salivary bacteria. By performing Spearman correlation analysis, carious phenotypes were positively related to Fusobacterium but negatively linked to Neocosmospora, and a significant correlation of cross-kingdom taxonomic pairs was identified. Our work demonstrated the interactions between oral bacteria and fungi at the community level, which may advance our knowledge on the etiological role of bacteria/fungi in the development of ECC and promote better management of this disease.
Caregiver-Reported Changes in the Socioemotional Wellbeing and Daily Habits of Children With Special Educational Needs During the First COVID-19 National Lockdown in the United Kingdom
Authors: Morgül Evren , Kallitsoglou Angeliki , Essau Cecilia A. , Castro-Kemp Susana
Published: February 2022

The implementation of social distancing measures (e.g., school closures) by governments worldwide to prevent the spread of COVID-19 has affected millions of children and their families. However, the consequences of such measures on the wellbeing of children with special educational needs (SEN) and their caregivers are not fully understood. The present study examined the socioemotional wellbeing and daily habits of children between 5 and 12 years old with SEN during the first national COVID-19 lockdown in the United Kingdom. Participants were 995 caregivers between 18 and 61 years old living in the United Kingdom who completed a 20 -min electronic survey on child and family wellbeing distributed via social networks between July and August 2020. The findings showed that children with SEN were more likely to experience more emotional and behavioral difficulties during the lockdown than children without SEN. Children with SEN but without mental health difficulties did not have more behavior difficulties during the lockdown than children without SEN. There was a significant increase in screen time and decrease in sleep time for children with and without SEN during the lockdown, but children with SEN were using screens more often than children without SEN both before and during the lockdown. Finally, caregivers with children with SEN reported more difficulty with the confinement than caregivers with children without SEN, but caregiver and child poor mental health were likely to explain the difference. The findings show that the wellbeing of children with SEN was more likely to be negatively affected by the lockdown than the wellbeing of children without SEN. Caregiver and child mental health were likely to explain the differences.
Outcomes After a Single Ovarian Stimulation Cycle in Women of Advanced Reproductive Age: A Retrospective Analysis
Authors: Liu Mengdi , Zhao Xusheng , Peng Yuanyuan , Zheng Jiahua , Guo Kaixuan , Fan Yanli , Jiang Lei , Yang Aimin , Cui Na , Hao Guimin , Wang Wei
Published: February 2022

Objectives

Previous studies showed that age is the most important factor that determines the outcome after embryo transfer (ET), with either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), regardless whether fresh or frozen cycles. The average cumulative live birth rate (CLBR) following a single ovarian stimulation cycle in women of advanced reproductive age (≥38 years of age) has been reported to be 22.6–34.1%. The purpose of this study is to compare the CLBR after a single ovarian stimulation cycle in women of different advanced reproductive age bracket (38/39, 40/41, 42/43 years of age or older), and to explore the factors (e.g., age, type of infertility, body mass index (BMI), ovarian stimulation protocols) associated with CLBR.

Methods

This retrospective analysis included all women of advanced reproductive age (38 years or older) undergoing IVF or ICSI at authors’ institute during a period from January 1, 2016 to December 31, 2018. The study protocol was approved by the Ethics Committee of the Second Hospital of Hebei Medical University (No. 2021-P045). Subjects with underlying diseases were excluded from analysis. The last follow-up was conducted in December 2020, with minimal 2-year follow-up.

Results

The final analysis included 826 women (40.00 ± 2.10 years of age at the time of ovarian stimulation; n = 633 and 193 for IVF-ET and ICSI-ET, respectively). The number of women in each age bracket was: 424 for 38/39 y, 226 for 40/41 y, 118 for 42/43 y, and 58 for ≥44 y. The number of transferable embryos was 2 (interquartile range: 2,4) for 38/39 y, 2 (2,3) for 40/41 y, 2 (2,3) for 42/43 y, and 2 (1.75,3) for ≥44 y. The rate of fresh embryo transfer was comparable (62.03–72.58%) among the 4 age brackets. The average CLBR following a single cycle was 26.27% in the overall study population, 32.31% for 38/39 y, 26.99% for 40/41 y, 14.4% for 42/43 y, and 3.44% for ≥44 y (P <0.001). In multivariate regression, CLBR was independently associated with younger age (OR for each year: 1.538, 95%CI: 1.193, 1.984) and higher number of transferable embryos (OR for each embryo: 1.495, 95%CI: 1.297, 1.722). CLBR differed significantly in the 38/39 group (P = 0.014), with higher rate in women receiving the Gonadotropin-releasing hormone agonist (GnRH-a) long or GnRH-a ultra-long protocols.

Conclusions

Forty-two years of age seemed to be a critical cutoff to achieve reasonable level of CLBR after a single ovarian stimulation cycle in women of advanced reproductive age.
Can Environmental Governance and Corporate Performance be Balanced in the Context of Carbon Neutrality? — A Quasi-Natural Experiment of Central Environmental Inspections
Authors: Deng Xiang , Huang Benxin , Zheng Qiuyan , Ren Xiaohang
Published: February 2022

This paper creatively studies the impact of the environmental governance on corporate performance in the context of China. We take the first round of central environmental inspections as the quasi-natural experiment shocks, and then test its effects on Chinese listed companies’ performance using the propensity score matching method and the difference-in-differences with multiple periods method. Furthermore, we discuss the transmission mechanism between central environmental inspections and corporate performance. The results indicate that central environmental inspections have significantly improved the corporate performance of listed companies in polluting industries in the inspected provinces. The central environmental inspections reduce agency costs and enhance corporate performance by improving the internal agency problems of listed companies. In addition, state-owned and large-scale companies are more sensitive to the central environmental inspections, and the effect of corporate performance improvement is more obvious. However, in regions with different levels of environmental regulations, there is no significant difference in the effects of central environmental inspections on the improvement of corporate performance.
Research on Emission Reduction Strategies of Building Materials Manufacturers and Real Estate Developers in the Context of Carbon Trading
Authors: Yao Qingzhen , Shao Liangshan
Published: February 2022

External carbon trading, free transfer between enterprises and, internal carbon trading are the primary forms of carbon trading between real estate enterprises and building materials enterprises. This paper establishes the Stackelberg game model under three conditions of carbon trading and analyzes the emission reduction strategies of real estate developers and building materials manufacturers. The results show that the low carbon degree of building materials is proportional to that of residential buildings and is affected by the external carbon trading price; The order quantity of building materials is directly proportional to the low carbon degree of building materials and housing and has nothing to do with the form of carbon trading; When only external carbon trading is carried out, the maximum profit of real estate developers is positively correlated with carbon quota and external carbon trading price, and the maximum profit of building materials manufacturers is positively correlated with carbon quota and negatively correlated with external carbon trading price. When internal carbon trading and external carbon trading coexist, the maximum profit of real estate developers increases with the rise of carbon quota, and the maximum profit of building materials manufacturers does not change significantly with the rise of carbon quota; Internal carbon trading can increase the profits of building materials manufacturers and reduce the selling prices of building materials, thereby increasing their enthusiasm for carbon emission reduction. An example is given to verify the effectiveness of the above conclusions.
A New Prognostic Risk Score: Based on the Analysis of Autophagy-Related Genes and Renal Cell Carcinoma
Authors: He Minxin , Li Mingrui , Guan Yibing , Wan Ziyan , Tian Juanhua , Xu Fangshi , Zhou Haibin , Gao Mei , Bi Hang , Chong Tie
Published: February 2022

Introduction: Clear cell renal cell carcinoma (ccRCC) patients suffer from its high recurrence and metastasis rate, and a new prognostic risk score to predict individuals with high possibility of recurrence or metastasis is in urgent need. Autophagy has been found to have a dual influence on tumorigenesis. In this study we aim to analyze autophagy related genes (ATGs) and ccRCC patients and find a new prognostic risk score. Method: Analyzing differential expression genes (DEGs) in TCGA-KIRC dataset, and took intersection with ATGs. Through lasso, univariate, and multivariate cox regression, DEGs were chosen, and the coefficients and expression levels of them were components constructing the formula of risk score. We analyzed mRNA expression of DEGs in tumor and normal tissue in ONCOMINE database and TCGA-KIRC dataset. The Human Protein Atlas (HPA) was used to analyze protein levels of DEGs. The protein-protein interaction (PPI) network was examined in STRING and visualized in cytoscape. Functional enrichment analysis was performed in RStudio. To prove the ability and practicibility of risk score, we analyzed univariate and multivariate cox regression, Kaplan-Meier curve (K-M curve), risk factor association diagram, receiver operating characteristic curve (ROC curve) of survival and nomogram, and the performance of nomogram was evaluated by calibration curve. Then we further explored functional enrichment related to risk groups through Gene Set Enrichment Analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and Metascape database. At last, we investigated immune cell infiltration of DEGs and two risk groups through TIMER database and “Cibersort” algorithm.

Result: We identified 7 DEGs (BIRC5, CAPS, CLDN7, CLVS1, GMIP, IFI16, and TCIRG1) as components of construction of risk score. All 7 DEGs were differently expressed in ccRCC and normal tissue according to ONCOMINE database and TCGA-KIRC dataset. Functional enrichment analysis indicated DEGs, and their most associated genes were shown to be abundant in autophagy-related pathways and played roles in tumorigenesis and progression processes. A serious analysis proved that this risk score is independent from the risk signature of ccRCC patients.

Conclusion: The risk score constructed by 7 DEGs had the ability of predicting prognosis of ccRCC patients and was conducive to the identification of novel prognostic molecular markers. However, further experiment is still needed to verify its ability and practicability.
Identifying Key Genes and Functionally Enriched Pathways of Diverse Adipose Tissue Types in Cattle
Authors: Pan Cuili , Yang Chaoyun , Wang Shuzhe , Ma Yun
Published: February 2022

Background: Fat is a tissue that not just stores energy and plays a protective role; it is also a vital endocrine organ that generates and integrates signals to influence metabolism. Meanwhile, the excessive accumulation of lipids in adipose tissue can lead to metabolic disturbance and diseases. To date, the complicated molecular mechanisms of bovine adipose tissue are still unknown. This study aimed to identify key genes and functionally enriched pathways in various adipose tissue types.

Results: The RNAseq data of 264 samples were downloaded from Gene Expression Omnibus (GEO) and analyzed by weighted gene co-expression network analysis (WGCNA). We identified 19 modules that significantly associated with at least one adipose tissue type. The brown module from GSE39618 was most closely associated with intramuscular fat tissue, which contained 550 genes. These genes were significantly enriched in pathways that related to inflammation and disease, such as TNF signaling pathway, IL-17 signaling pathway, and NF-kappa B signaling pathway. The pink module (GSE39618) that contained 58 genes was most closely associated with omental fat tissue. The turquoise (GSE39618), blue (GSE116775), and yellow (GSE65125) module were most closely associated with subcutaneous fat tissue. Genes in these modules were significantly enriched in pathways related to fat metabolism, such as the PPAR signaling pathway, fatty acid metabolism and PI3K-Akt signaling pathway. At last, key genes for intramuscular fat (PTGS2 and IL6), omental fat (ARHGEF5 and WT1), and subcutaneous fat (KIT, QR6Q1, PKD2L1, etc.) were obtained and verified. In addition, it was found that IL10 and VCAM1 might be potential genes to distinguish adipose and muscle.

Conclusion: The study applied WGCNA to generate a landscape of adipose tissue and provide a basis for identifying potential pathways and hub genes of different adipose tissue types.
Immune Epigenetic Crosstalk Between Malignant B Cells and the Tumor Microenvironment in B Cell Lymphoma
Authors: Mondello Patrizia , Ansell Stephen M. , Nowakowski Grzegorz S.
Published: February 2022

Epigenetic reprogramming is a hallmark of lymphomagenesis, however its role in reshaping the tumor microenvironment is still not well understood. Here we review the most common chromatin modifier mutations in B cell lymphoma and their effect on B cells as well as on T cell landscape. We will also discuss precision therapy strategies to reverse their aberrant signaling by targeting mutated proteins or counterbalance epigenetic mechanisms.
Implications of Gut Microbiota in Neurodegenerative Diseases
Authors: Zhang Haoming , Chen Yijia , Wang Zifan , Xie Gaijie , Liu Mingming , Yuan Boyu , Chai Hongxia , Wang Wei , Cheng Ping
Published: February 2022

The morbidity associated with neurodegenerative diseases (NDs) is increasing, posing a threat to the mental and physical quality of life of humans. The crucial effect of microbiota on brain physiological processes is mediated through a bidirectional interaction, termed as the gut–brain axis (GBA), which is being investigated in studies. Many clinical and laboratory trials have indicated the importance of microbiota in the development of NDs via various microbial molecules that transmit from the gut to the brain across the GBA or nervous system. In this review, we summarize the implications of gut microbiota in ND, which will be beneficial for understanding the etiology and progression of NDs that may in turn help in developing ND interventions and clinical treatments for these diseases.
Role of HLA-G in Viral Infections
Authors: Jasinski-Bergner Simon , Schmiedel Dominik , Mandelboim Ofer , Seliger Barbara
Published: February 2022

The human leukocyte antigen (HLA)-G is a non-classical HLA class I molecule, which has distinct features to classical HLA-A, -B, -C antigens, such as a low polymorphism, different splice variants, highly restricted, tightly regulated expression and immune modulatory properties. HLA-G expression in tumor cells and virus-infected cells, as well as the release of soluble HLA-G leads to escape from host immune surveillance. Increased knowledge of the link between HLA-G expression, viral infection and disease progression is urgently required, which highlights the possible use of HLA-G as novel diagnostic and prognostic biomarker for viral infections, but also as therapeutic target. Therefore, this review aims to summarize the expression, regulation, function and impact of HLA-G in the context of different viral infections including virus-associated cancers. The characterization of HLA-G-driven immune escape mechanisms involved in the interactions between host cells and viruses might result in the design of novel immunotherapeutic strategies targeting HLA-G and/or its interaction with its receptors on immune effector cells.
Antigen-Specific CD4+ T-Cell Activation in Primary Antibody Deficiency After BNT162b2 mRNA COVID-19 Vaccination
Authors: Sauerwein Kai M. T. , Geier Christoph B. , Stemberger Roman F. , Akyaman Hüseyin , Illes Peter , Fischer Michael B. , Eibl Martha M. , Walter Jolan E. , Wolf Hermann M.
Published: February 2022

Previous studies on immune responses following COVID-19 vaccination in patients with common variable immunodeficiency (CVID) were inconclusive with respect to the ability of the patients to produce vaccine-specific IgG antibodies, while patients with milder forms of primary antibody deficiency such as immunoglobulin isotype deficiency or selective antibody deficiency have not been studied at all. In this study we examined antigen-specific activation of CXCR5-positive and CXCR5-negative CD4+memory cells and also isotype-specific and functional antibody responses in patients with CVID as compared to other milder forms of primary antibody deficiency and healthy controls six weeks after the second dose of BNT162b2 vaccine against SARS-CoV-2. Expression of the activation markers CD25 and CD134 was examined by multi-color flow cytometry on CD4+T cell subsets stimulated with SARS-CoV-2 spike peptides, while in parallel IgG and IgA antibodies and surrogate virus neutralization antibodies against SARS-CoV-2 spike protein were measured by ELISA. The results show that in CVID and patients with other milder forms of antibody deficiency normal IgG responses (titers of spike protein-specific IgG three times the detection limit or more) were associated with intact vaccine-specific activation of CXCR5-negative CD4+memory T cells, despite defective activation of circulating T follicular helper cells. In contrast, CVID IgG nonresponders showed defective vaccine-specific and superantigen-induced activation of both CD4+T cell subsets. In conclusion, impaired TCR-mediated activation of CXCR5-negative CD4+memory T cells following stimulation with vaccine antigen or superantigen identifies patients with primary antibody deficiency and impaired IgG responses after BNT162b2 vaccination.
Activation of RARα Receptor Attenuates Neuroinflammation After SAH via Promoting M1-to-M2 Phenotypic Polarization of Microglia and Regulating Mafb/Msr1/PI3K-Akt/NF-κB Pathway
Authors: Tian Yang , Liu Binbing , Li Yuchen , Zhang Yongzhi , Shao Jiang , Wu Pei , Xu Chao , Chen Guangduo , Shi Huaizhang
Published: February 2022

Background and Purpose

Subarachnoid hemorrhage (SAH) is a life-threatening subtype of stroke with high rates of mortality. In the early stages of SAH, neuroinflammation is one of the important mechanisms leading to brain injury after SAH. In various central nervous system diseases, activation of RARα receptor has been proven to demonstrate neuroprotective effects. This study aimed to investigate the anti-inflammatory effects of RARα receptor activation after SAH.

Methods

Internal carotid artery puncture method used to established SAH model in Sprague-Dawley rats. The RARα specific agonist Am80 was injected intraperitoneally 1 hour after SAH. AGN196996 (specific RARα inhibitor), Msr1 siRNA and LY294002 (PI3K-Akt inhibitor) were administered via the lateral ventricle before SAH. Evaluation SAH grade, neurological function score, blood-brain barrier permeability. BV2 cells and SH-SY5Y cells were co-cultured and stimulated by oxyhemoglobin to establish an in vitro model of SAH. RT-PCR, Western blotting, and immunofluorescence staining were used to investigate pathway-related proteins, microglia activation and inflammatory response. Results: The expression of RARα, Mafb, and Msr1 increased in rat brain tissue after SAH. Activation of the RARα receptor with Am80 improved neurological deficits and attenuated brain edema, blood brain barrier permeability. Am80 increased the expression of Mafb and Msr1, and reduced neuroinflammation by enhancing the phosphorylation of Akt and by inhibiting the phosphorylation of NF-κB. AGN196996, Msr1 siRNA, and LY294002 reversed the therapeutic effects of Am80 by reducing the expression of Msr1 and the phosphorylation of Akt. In vitro model of SAH, Am80 promoted M1-to-M2 phenotypic polarization in microglia and suppressed the nuclear transcription of NF-κB.

Conclusion

Activation of the RARα receptor attenuated neuroinflammation by promoting M1-to-M2 phenotypic polarization in microglia and regulating the Mafb/Msr1/PI3K-Akt/NF-κB pathway. RARα might serve as a potential target for SAH therapy.
Gout Arthritis During Admission for Decompensated Heart Failure—A Descriptive Analysis of Risk Factors, Treatment and Prognosis
Authors: Ritter Fabian , Franzeck Fabian , Geisshardt Julian , Walker Ulrich A. , Osthoff Michael
Published: February 2022

Background

Chronic heart failure and hospital admissions are well-known risk factors for acute gouty arthritis. However, in-depth analyses of patients admitted for decompensated heart failure (DHF) who subsequently developed a gout attack are sparse. This study aims to characterize DHF patients who developed a gout attack during their inpatient treatment and describe potential risk factors, its consequences, and its management in the setting of heart failure exacerbation.

Methods

Retrospective chart review of 50 patients with an admission diagnosis of DHF who subsequently experienced a gout attack during admission at a Swiss tertiary care hospital between 2018 and 2020. Patients with a refusal of the general research consent were excluded (n = 10).

Results

A gout attack developed in 66/1,832 (3.6%) DHF admissions of whom 50 individual patients were analyzed. Patients were predominately male (76%), of advanced age (median 80.5 years), with several comorbidities including chronic kidney disease (74%), comorbid gout (70%, only 43% on urate lowering therapy) and hyperuricemia (median 547 μmol/l, IQR 434–667 μmol/l). Diuretics were intensified in all patients. Acute gout presented as polyarticular arthritis (62%) and was often accompanied by fever (30%). Joint aspiration was performed in 32%, and intra-articular steroid injections administered in 20% of patients. Median length of stay and 6-month mortality were 16 days (IQR 12–25) and 32%, respectively, compared to 9 days (IQR 6–14) and 16% for DHF patients without a gout attack.

Conclusion

Our study highlights features of gout attacks in the context of DHF including the absence of comorbid gout in a significant proportion of patients, the presence of polyarticular disease during the flare, and a poor prognosis. The present study identifies the necessity to better address gout as a comorbidity in DHF patients and may assist clinicians in identifying DHF patients at risk for a gout attack.
Bacteriophage Lytic Enzyme P9ly as an Alternative Antibacterial Agent Against Antibiotic-Resistant Shigella dysenteriae and Staphylococcus aureus
Authors: Wang Feng , Xiao Yao , Lu Yao , Deng Zheng-Yu , Deng Xian-Yu , Lin Lian-Bing
Published: February 2022

Developing new strategies to replace or supplement antibiotics to combat bacterial infection is a pressing task in the field of microbiological research. In this study, we report a lytic enzyme named P9ly deriving from the bacteriophage PSD9 that could infect multidrug-resistant Shigella. This enzyme was identified through whole-genome sequencing of PSD9. The results show that P9ly contains a conserved T4-like_lys domain and belongs to the phage lysozyme family. Recombinant P9ly obtained from protein purification presented biological activity and could digest bacterial cell walls (CW), resulting in the destruction of cell structure and leakage of intracellular components. Furthermore, P9ly exhibited bacteriolytic and bactericidal activity on different strains, especially multidrug-resistant Gram-negative Shigella dysenteriae and Gram-positive Staphylococcus aureus. Additionally, combined use of P9ly with ceftriaxone sodium (CRO) could decrease necessary dose of the antibiotic used and improve the antibacterial effect. In summary, under the current backdrop of extensive antibiotic usage and the continuous emergence of bacterial resistance, this study provides an insight into developing bacteriophage-based antibacterial agents against both Gram-negative and Gram-positive pathogens.
Biofilms in Water Hoses of a Meat Processing Environment Harbor Complex Microbial Communities
Authors: Voglauer Eva M. , Zwirzitz Benjamin , Thalguter Sarah , Selberherr Evelyne , Wagner Martin , Rychli Kathrin
Published: February 2022

Safe and hygienic water distribution is essential for maintaining product quality and safety. It is known that biofilms alter the appearance and microbial quality of water along the distribution chain. Yet, biofilms in water hoses throughout the food processing environment have not been investigated in detail. Here, microbial communities from water hoses and other environmental sites in contact with water, in addition to the source water itself, were studied in the meat processing environment. Biofilms were present in all water hoses as determined by the presence of bacterial DNA and biofilm matrix components (carbohydrates, extracellular DNA, and proteins). The microbial community of the biofilms was dominated by Proteobacteria, represented mainly by Comamonadaceae and Pseudoxanthomonas. Moreover, genera that are associated with an intracellular lifestyle (e.g., Neochlamydia and Legionella) were present. Overall, the microbial community of biofilms was less diverse than the water microbial community, while those from the different sample sites were distinct from each other. Indeed, only a few phyla were shared between the water hose biofilm and the source water or associated environmental samples. This study provides first insights towards understanding the microbiota of water hose biofilms in the food processing environment.
Emerging Role of Translational Digital Biomarkers Within Home Cage Monitoring Technologies in Preclinical Drug Discovery and Development
Authors: Baran Szczepan W. , Bratcher Natalie , Dennis John , Gaburro Stefano , Karlsson Eleanor M. , Maguire Sean , Makidon Paul , Noldus Lucas P. J. J. , Potier Yohann , Rosati Giorgio , Ruiter Matt , Schaevitz Laura , Sweeney Patrick , LaFollette Megan R.
Published: February 2022

In drug discovery and development, traditional assessment of human patients and preclinical subjects occurs at limited time points in potentially stressful surroundings (i.e., the clinic or a test arena), which can impact data quality and welfare. However, recent advances in remote digital monitoring technologies enable the assessment of human patients and preclinical subjects across multiple time points in familiar surroundings. The ability to monitor a patient throughout disease progression provides an opportunity for more relevant and efficient diagnosis as well as improved assessment of drug efficacy and safety. In preclinical in vivo animal models, these digital technologies allow for continuous, longitudinal, and non-invasive monitoring in the home environment. This manuscript provides an overview of digital monitoring technologies for use in preclinical studies including their history and evolution, current engagement through use cases, and impact of digital biomarkers (DBs) on drug discovery and the 3Rs. We also discuss barriers to implementation and strategies to overcome them. Finally, we address data consistency and technology standards from the perspective of technology providers, end-users, and subject matter experts. Overall, this review establishes an improved understanding of the value and implementation of digital biomarker (DB) technologies in preclinical research.