bluuebunny/crossref_metadata_2025 huggingface dataset:
MEMELIHARA KETENTERAMAN DAN KETERTIBAN UMUM MELALUI LITERASI MEDIA DI KELURAHAN KARIANGAAU KECAMATAN BALIKPAPAN BARAT KOTA BALIKPAPAN
Authors: Rahmadanita Annisa , Nurrahman Agung
Published: January 2022

Informasi Hoax yang dipercayai oleh sebagian masyarakat dapat mengganggu ketenteraman dan ketertiban umum di wilayah Kelurahan Kariangau. Adapun tujuan penelitian ini adalah untuk memperoleh gambaran umum dan mendeskripsikan urgensi dari literasi media dalam memelihara ketenteraman dan ketertiban umum di Kelurahan Kariangau. Penelitian ini merupakan penelitian deskriptif kualitatif. Temuan penelitian menunjukkan bahwa secara teknis, masyarakat Kariangau mampu menggunakan media dengan cukup baik. Namun sebagian masyarakat Kariangau belum mampu memahami apakah informasi tersebut adalah informasi Hoax atau tidak, terutama saat informasi tersebut diperoleh melalui Whatsapp Gorup keluarga. Sehingga sebagian masyarakat mempercayai semua informasi yang diperoleh dari media tersebut. Di sisi lain, sebagian besar masyarakat Kariangau telah berpartisipasi dalam menindaklanjuti informasi yang diperoleh dari suatu media khususnya media sosial, dengan mencari kebenaran informasinya terlebih dahulu atau melakukan penyaringan informasi sebelum informasi tersebut disebarkan kepada orang lain. Kesimpulan penelitian ini adalah bahwa sejauh ini literasi media secara pribadi telah dilakukan oleh masyarakat Kariangau dengan cukup baik, namun pemerintah Kelurahan Kariangau belum memiliki program literasi media secara khusus untuk masyarakat. Sehingga peneliti merekomendasikan bahwa dilihat dari urgensinya, maka program literasi media perlu disusun dan dilaksanakan secara terencana, sistematis dan berkelanjutan oleh Pemerintah Kelurahan Kariangau dan juga dapat membentuk Kelompok Informasi Masyarakat untuk melakukan edukasi kepada masyarakat.

 

Kata Kunci: Literasi Media, Ketenteraman dan Ketertiban Umm, Kelurahan
Anticuerpos monoclonales en la práctica médica
Authors: Carrasco-Yalán Antonio
Published: January 2022

En 1974, Köhler y Milstein(1) publicaron los primeros resultados sobre anticuerpos monoclonales en estudios experimentales; 9 años después son galardonados con el premio Nóbel y el uso clínico se inicia hacia 1986, siendo a la fecha más de 100 anticuerpos monoclonales aprobados.
Anticuerpos Monoclonales: Mecanismos de Acción
Authors: Saldarriaga-Valiente Tatiana
Published: January 2022

Los anticuerpos monoclonales ejercen sus actividades de forma muy diversa y variada en función de las dianas afectadas, ya sean tumorales, citoquinas, virus, factores de crecimiento. Existen diferentes mecanismos de acción por los cuales los anticuerpos monoclonales pueden destruir las células cancerosas: atacando la cascada de supervivencia de las células tumorales, inhibiendo el crecimiento tumoral interfiriendo con la angiogénesis del tumor, eludiendo la muerte celular programada y evadiendo los puntos de control (checkpoints) inmunes. Estos efectos se pueden llevar a cabo mediante diferentes mecanismos: muerte directa de las células tumorales o muerte mediada por mecanismos inmunes.
La prevalencia de anemia infantil no aumentó durante la pandemia de COVID-19
Authors: Vásquez-Velásquez Cinthya , Gonzales Gustavo F.
Published: January 2022

La pandemia por la COVID-19 evidenció un problema sanitario en diversas partes del mundo, las medidas para el freno del avance del virus se basaron en el uso de mascarilla, inmovilización social, aseo preventivo y constante, etc. Así mismo, otros problemas de salud pública como la anemia no pudieron ser abordados como los años pasados. En las encuestas nacionales se refleja que el consumo de hierro, principal medida para el tratamiento preventivo y terapéutico de esta condición hematológica, se redujo significativamente. Por otro lado las cifras de anemia en la región andina no se vieron afectadas, manteniéndose en su valor similar que el año 2019, debido a ello, la hipótesis sustentada es si las políticas han estado basadas en evidencia científica, puesto que a pesar de los grandes esfuerzos por las intervenciones de suplementación con multimicronutrientes, las prevalencias no descendían. El presente análisis está basado en las formulaciones del mal diagnóstico de esta condición, anemia, puesto que se considera como marcador universal y único al valor de hemoglobina. Y el otro punto a sustentar es la multicausalidad de la anemia, debido que la deficiencia de hierro es la única abordada, sin embargo, revisiones recientes muestran que esta etiología no es la única ni la de mayor consideración para el avance progresivo de esta enfermedad.
“Vida y legado de Académicos ilustres”, Tomo I
Authors: Morales-Soto Nelson Raúl
Published: January 2022

Dicen los editores: “Esta publicación es parte de la Edición Conmemorativa del Bicentenario de la Independencia Nacional, preparada por la Academia Nacional de Medicina para rendir homenaje a la patria con motivo de la gesta de la independencia. El propósito es enlazar el pasado institucional con las nuevas generaciones de académicos, reconociendo el legado de quienes hoy ocupan lugar referente en la historia de la medicina peruana. Aunque incorpora apuntes biográficos, este libro centra su interés en la vida acadèmica y el legado intelectual de sus ilustres miembros.
Aplicación de anticuerpos monoclonales en oncología
Authors: Enriquez-Vera Daniel
Published: January 2022

Los anticuerpos monoclonales representan una pieza fundamental en el arsenal terapéutico en oncología. Estos compuestos biológicos de alta complejidad han logrado mejorar la supervivencia de los pacientes con cáncer. Entre los clásicos se encuentran: rituximab, bevacizumab, cetuximab, trastuzumab utilizados a diario en nuestro medio. En la última década, la inmunoterapia se ha posicionado como una terapia eficaz para neoplásias de pronóstico adverso como el melanoma, cáncer de pulmón y renal. En el futuro próximo, los nuevos conjugados de anticuerpos y la terapia con células T quiméricas se presentarán como paradigmas de terapias promisorias en el manejo del cáncer.
Anticuerpos monoclonales: uso en reumatología
Authors: Cabello-León Eduardo
Published: January 2022

El avance en el conocimiento de los mecanismos fisiopatológicos de varias enfermedades reumáticas ha permitido indentificar definidos blancos a los cuales dirigir anticuerpos monoclonales con fines terapéuticos, una forma de tratamiento
comúnmente denominado terapia biológica. Un importante número de estos medicamentos biológicos se encuentran aprobados por las agencias reguladoras y están incluidos en las recomendaciones para el manejo de varias enfermedades reumáticas; incluyendo enfermedades reumáticas sistémicas autoinmunes; pero además espondiloartritis y otras enfermedades. Un importante número de anticuerpos monoclonales se encuentran en fases de investigación y se espera que en un futuro cercano se disponga de un mayor número de estos medicamentos. Usados de manera adecuada son terapias seguras y eficaces, pero su uso puede asociarse a efectos colaterales, algunos de los cuales pueden ser serios. En general tienen un costo elevado y pese a la aparición de moléculas biosimilares el costo es aún alto. No suelen ser terapia de primera línea y su uso debe ser racional. Esta revisión ofrece una visión general de los anticuerpos monoclonales aprobados más importantes en las enfermedades reumáticas.
Compressing Aerodynamic Hazard Data
Authors: Zhou Yang , Boullé Nicolas , Barton David , Campillo-Funollet Eduard , Hall Cameron
Published: January 2022

Data compression of three-dimensional computational fluid dynamics (CFD) simulation data is crucial to allow effective data-streaming for drone navigation and control. This problem is computationally challenging due to the complexity of the geometrical features present in the CFD data, and cannot be tackled by standard compression techniques such as sphere-tree. In this report, we present two different methods based on octree and cuboid primitives to compress velocity isosurfaces and volumetric data in three dimensions. Our volume compression method achieves a 1400 compression rate of raw simulation data and allows parallel computing.
Feminism and the Politics of Resilience: Essays on Gender, Media and the End of Welfare
Authors: Burcu Çağatay
Published: January 2022

Encouraging women to work has revealed the relationships between neoliberalism and gender. Neoliberalism, which is based on high performance, has also reflected this feature on the female body. Women, who are constantly asked to be hardworking both at home and at work, have also been exposed to the emphasis on having a fit body seen in women's magazines. This emphasis on success is more for the middle class. While this situation created a competitive environment with women in the lower classes, it negatively affected the psychology of young girls. Therefore, the relationship between neoliberalism and feminism leads to new discussions on the issue of gender equality.
Friluftsliv explored: An environmental and outdoor teaching approach for knowledge, emotions and quality of life
Authors: Brügge Britta , Glantz Matz , Sandell Klas , Lundqvist Jones Therese
Published: January 2022

Friluftsliv explored doesn’t only include nature knowledge, techniques in the outdoors and outdoor pedagogics but also covers ecology, human ecology, geography, environmental and societal questions, history, health, biology, craft and lots of practical activities -both for urban and rural friluftsliv. In this translation to English of the revised fifth edition of the Swedish book there are many activities and the text is suitable for the modern day. Friluftsliv embraces the feeling around the campfire, paddling along winding rivers and walking towards the distant blue mountains. But, it is also to whittle a stick, to remember your waterproofs and to find your way home. Knowledge emerges when you combine imagination with facts and the glint in your eyes, using all our outdoor environments: forests, water, the coast, mountains and the nature close at hand. Emotion is to swim in crystal clear water far out in the archipelago and to see the clouds gliding across the sky. But also, to be able to present other sides of yourself, to be fascinated by your own body, the struggling ant and the sight of frost on trees. Quality of life is to experience friluftsliv – as it happens!
Innovating Traditional Production Systems Through On-Farm Conservation Agriculture and Agroforestry Research
Authors: Fonteyne Simon , Silva Avendaño Columba , Ramos Sanchez Angel , Torres Zambrano Juan Pablo , García Dávila Fernando , Pérez Martínez Zenaida , García Dávila Alejandrina , Castillo Villaseñor Luis , Verhulst Nele
Published: January 2022

Maize (Zea mays L.), the staple crop of Mexico, is often produced by smallholder farmers on sloping terrains. Historically, little agronomic research has been performed under the conditions of these farmers to support them in the sustainable intensification of their production systems. We set up trials at two locations in the state of Oaxaca to evaluate conservation agriculture and agroforestry in collaboration with local farmers. Crop diversification through crop rotations, multicropping, relay cropping or agroforestry increased system yields the most, by up to 1.4 t ha−1 in Teopoxco and 1.7 t ha−1 in Tamazulapam. Increased input use through increased fertilization or liming did not increase profitability enough to justify their use. Zero tillage and residue retention increased yields and reduced production costs. Conservation agriculture with agroforestry was a high-yielding, profitable system that also reduced farmers' risk by providing several harvests per year. The most profitable combinations of agroforestry and conservation agriculture could produce up to $4,854 USD ha−1 in Teopoxco and $2,143 USD ha−1 in Tamazulapam, while the control treatments in the same sites and years produced $175 USD ha−1 and $92 USD ha−1 respectively. In several years the main crop failed, while the trees were able to produce due to their different growing season compared to maize. Through adaptive investigation under farmers' conditions, sustainable intensification of traditional production system is possible with low-cost changes that are locally adapted and within farmers' possibilities.
Extending Association Rule Mining to Microbiome Pattern Analysis: Tools and Guidelines to Support Real Applications
Authors: Giulia Agostinetto , Anna Sandionigi , Antonia Bruno , Dario Pescini , Maurizio Casiraghi
Published: January 2022

Boosted by the exponential growth of microbiome-based studies, analyzing microbiome patterns is now a hot-topic, finding different fields of application. In particular, the use of machine learning techniques is increasing in microbiome studies, providing deep insights into microbial community composition. In this context, in order to investigate microbial patterns from 16S rRNA metabarcoding data, we explored the effectiveness of Association Rule Mining (ARM) technique, a supervised-machine learning procedure, to extract patterns (in this work, intended as groups of species or taxa) from microbiome data. ARM can generate huge amounts of data, making spurious information removal and visualizing results challenging. Our work sheds light on the strengths and weaknesses of pattern mining strategy into the study of microbial patterns, in particular from 16S rRNA microbiome datasets, applying ARM on real case studies and providing guidelines for future usage. Our results highlighted issues related to the type of input and the use of metadata in microbial pattern extraction, identifying the key steps that must be considered to apply ARM consciously on 16S rRNA microbiome data. To promote the use of ARM and the visualization of microbiome patterns, specifically, we developed microFIM (microbial Frequent Itemset Mining), a versatile Python tool that facilitates the use of ARM integrating common microbiome outputs, such as taxa tables. microFIM implements interest measures to remove spurious information and merges the results of ARM analysis with the common microbiome outputs, providing similar microbiome strategies that help scientists to integrate ARM in microbiome applications. With this work, we aimed at creating a bridge between microbial ecology researchers and ARM technique, making researchers aware about the strength and weaknesses of association rule mining approach.
Genetic Algorithm-Based Trajectory Optimization for Digital Twin Robots
Authors: Liu Xin , Jiang Du , Tao Bo , Jiang Guozhang , Sun Ying , Kong Jianyi , Tong Xiliang , Zhao Guojun , Chen Baojia
Published: January 2022

Mobile robots have an important role in material handling in manufacturing and can be used for a variety of automated tasks. The accuracy of the robot’s moving trajectory has become a key issue affecting its work efficiency. This paper presents a method for optimizing the trajectory of the mobile robot based on the digital twin of the robot. The digital twin of the mobile robot is created by Unity, and the trajectory of the mobile robot is trained in the virtual environment and applied to the physical space. The simulation training in the virtual environment provides schemes for the actual movement of the robot. Based on the actual movement data returned by the physical robot, the preset trajectory of the virtual robot is dynamically adjusted, which in turn enables the correction of the movement trajectory of the physical robot. The contribution of this work is the use of genetic algorithms for path planning of robots, which enables trajectory optimization of mobile robots by reducing the error in the movement trajectory of physical robots through the interaction of virtual and real data. It provides a method to map learning in the virtual domain to the physical robot.
Synthetic Biology Approaches to Hydrocarbon Biosensors: A Review
Authors: Moratti Claudia F. , Scott Colin , Coleman Nicholas V.
Published: January 2022

Monooxygenases are a class of enzymes that facilitate the bacterial degradation of alkanes and alkenes. The regulatory components associated with monooxygenases are nature’s own hydrocarbon sensors, and once functionally characterised, these components can be used to create rapid, inexpensive and sensitive biosensors for use in applications such as bioremediation and metabolic engineering. Many bacterial monooxygenases have been identified, yet the regulation of only a few of these have been investigated in detail. A wealth of genetic and functional diversity of regulatory enzymes and promoter elements still remains unexplored and unexploited, both in published genome sequences and in yet-to-be-cultured bacteria. In this review we examine in detail the current state of research on monooxygenase gene regulation, and on the development of transcription-factor-based microbial biosensors for detection of alkanes and alkenes. A new framework for the systematic characterisation of the underlying genetic components and for further development of biosensors is presented, and we identify focus areas that should be targeted to enable progression of more biosensor candidates to commercialisation and deployment in industry and in the environment.
Instructional Design Framework for Construction Materials Training
Authors: Jadallah Hazem , Friedland Carol J. , Nahmens Isabelina , Pecquet Charles , Berryman Charles , Zhu Yimin
Published: January 2022

The construction industry is suffering, in part, from a lack of training programs offered to the construction workforce. Unfortunately, most construction training and education research focuses on university student education. Integrating education science theory into construction workforce training has the potential to improve industry training but there is a dearth of studies that present details of this integration process. To address this gap, a training framework was developed to educate material stakeholders on material properties, selection, and installation. This framework is based on andragogical and Universal Design for Learning (UDL) principles. An assessment method evaluates training agendas to improve upon instructional design before training implementation. This method assesses the proposed training framework by enumerating the occurrences of Bloom’s Taxonomy verbs to determine how closely the proposed training’s goals and objectives followed Bloom’s guidelines. This study culminates by establishing linkages from educational theory to proposed training modules. The module template is presented in a goals and objectives format so that organizations can best implement and test this training framework.
Understanding the Impact of Hydrogen Activation by SrCe0.8Zr0.2O3−δ Perovskite Membrane Material on Direct Non-Oxidative Methane Conversion
Authors: Cheng Sichao , Oh Su Cheun , Sakbodin Mann , Qiu Limei , Diao Yuxia , Liu Dongxia
Published: January 2022

Direct non-oxidative methane conversion (DNMC) converts methane (CH4) in one step to olefin and aromatic hydrocarbons and hydrogen (H2) co-product. Membrane reactors comprising methane activation catalysts and H2-permeable membranes can enhance methane conversion by in situ H2 removal via Le Chatelier's principle. Rigorous description of H2 kinetic effects on both membrane and catalyst materials in the membrane reactor, however, has been rarely studied. In this work, we report the impact of hydrogen activation by hydrogen-permeable SrCe0.8Zr0.2O3−δ (SCZO) perovskite oxide material on DNMC over an iron/silica catalyst. The SCZO oxide has mixed ionic and electronic conductivity and is capable of H2 activation into protons and electrons for H2 permeation. In the fixed-bed reactor packed with a mixture of SCZO oxide and iron/silica catalyst, stable and high methane conversion and low coke selectivity in DNMC was achieved by co-feeding of H2 in methane stream. The characterizations show that SCZO activates H2 to favor “soft coke” formation on the catalyst. The SCZO could absorb H2in situ to lower its local concentration to mitigate the reverse reaction of DNMC in the tested conditions. The co-existence of H2 co-feed, SCZO oxide, and DNMC catalyst in the present study mimics the conditions of DNMC in the H2-permeable SCZO membrane reactor. The findings in this work offer the mechanistic understanding of and guidance for the design of H2-permeable membrane reactors for DNMC and other alkane dehydrogenation reactions.
SARS-CoV-2 Spike Antagonizes Innate Antiviral Immunity by Targeting Interferon Regulatory Factor 3
Authors: Freitas Raul S. , Crum Tyler F. , Parvatiyar Kislay
Published: January 2022

Corona virus disease 2019 (COVID-19) pathogenesis is intimately linked to the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and disease severity has been associated with compromised induction of type I interferon (IFN-I) cytokines which coordinate the innate immune response to virus infections. Here we identified the SARS-CoV-2 encoded protein, Spike, as an inhibitor of IFN-I that antagonizes viral RNA pattern recognition receptor RIG-I signaling. Ectopic expression of SARS-CoV-2 Spike blocked RIG-I mediated activation of IFNβ and downstream induction of interferon stimulated genes. Consequently, SARS-CoV-2 Spike expressing cells harbored increased RNA viral burden compared to control cells. Co-immunoprecipitation experiments revealed SARS-CoV-2 Spike associated with interferon regulatory factor 3 (IRF3), a key transcription factor that governs IFN-I activation. Co-expression analysis via immunoassays further indicated Spike specifically suppressed IRF3 expression as NF-κB and STAT1 transcription factor levels remained intact. Further biochemical experiments uncovered SARS-CoV-2 Spike potentiated proteasomal degradation of IRF3, implicating a novel mechanism by which SARS-CoV-2 evades the host innate antiviral immune response to facilitate COVID-19 pathogenesis.
A Novel Nomogram for Predicting the Risk of Premature Delivery Based on the Thyroid Function in Pregnant Women
Authors: Meng Yu , Lin Jing , Fan Jianxia
Published: January 2022

Background

Maternal thyroid dysfunction and autoantibodies were associated with preterm delivery. However, recommendations for cutoff values of thyroperoxidase antibody (TPOAb) positivity and thyroid-stimulating homone (TSH) associated with premature delivery are lacking.

Objective

To identify the pregnancy-specific cutoff values for TPOAb positivity and TSH associated with preterm delivery. To develop a nomogram for the risk prediction of premature delivery based on maternal thyroid function in singleton pregnant women without pre-pregnancy complications.

Methods

This study included data from the International Peace Maternity and Child Care Health Hospital (IPMCH) in Shanghai, China, between January 2013 and December 2016. Added data between September 2019 and November 2019 as the test cohort. Youden’s index calculated the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration. Univariate and multivariable logistic regression analysis were used to screen the risk factors of premature delivery. The nomogram was developed according to the regression coefficient of relevant variables. Discrimination and calibration of the model were assessed using the C-index, Hosmer-Lemeshow test, calibration curve and decision curve analysis.

Results

45,467 pregnant women were divided into the training and validation cohorts according to the ratio of 7: 3. The testing cohort included 727 participants. The pregnancy-specific cutoff values associated with the risk of premature delivery during the first trimester were 5.14 IU/mL for TPOAb positivity and 1.33 mU/L for TSH concentration. Multivariable logistic regression analysis showed that maternal age, history of premature delivery, elevated TSH concentration and TPOAb positivity in the early pregnancy, preeclampsia and gestational diabetes mellitus were risk factors of premature delivery. The C-index was 0.62 of the nomogram. Hosmer-Lemeshow test showed that the Chi-square value was 2.64 (P = 0.955 > 0.05). Decision curve analysis showed a positive net benefit. The calibration curves of three cohorts were shown to be in good agreement.

Conclusions

We identified the pregnancy-specific cutoff values for TPOAb positivity and TSH concentration associated with preterm delivery in singleton pregnant women without pre-pregnancy complications. We developed a nomogram to predict the occurrence of premature delivery based on thyroid function and other risk factors as a clinical decision-making tool.
Does the Carbon Emissions Trading Policy Increase Corporate Tax Avoidance? Evidence from China
Authors: Feng Chen , Zhu Xingshu , Gu Yu , Liu Yuecheng
Published: January 2022

Based on the natural experiment of carbon emissions trading pilots in China, this paper investigates the effect of environmental regulation on corporate tax avoidance. The results show that: 1) Market-incentivized environmental regulation significantly increase the level of corporate tax avoidance. 2) Heterogeneity analysis shows that the effect is more obvious on the non-state-owned firms, firms with severe financing constraints, and firms in highly competitive industries. 3) We find that the reduction of cash flow is the channel for environmental regulation to affect corporate tax avoidance. 4) Further analysis shows that government subsidies can alleviate the enhancement of tax avoidance by environmental regulation. The more government subsidies a company receives, the less tax avoidance it has.
Sequence Divergence and Functional Specializations of the Ancient Spliceosomal SF3b: Implications in Flexibility and Adaptations of the Multi-Protein Complex
Authors: Yazhini Arangasamy , Srinivasan Narayanaswamy , Sandhya Sankaran
Published: January 2022

Multi-protein assemblies are complex molecular systems that perform highly sophisticated biochemical functions in an orchestrated manner. They are subject to changes that are governed by the evolution of individual components. We performed a comparative analysis of the ancient and functionally conserved spliceosomal SF3b complex, to recognize molecular signatures that contribute to sequence divergence and functional specializations. For this, we recognized homologous sequences of individual SF3b proteins distributed across 10 supergroups of eukaryotes and identified all seven protein components of the complex in 578 eukaryotic species. Using sequence and structural analysis, we establish that proteins occurring on the surface of the SF3b complex harbor more sequence variation than the proteins that lie in the core. Further, we show through protein interface conservation patterns that the extent of conservation varies considerably between interacting partners. When we analyze phylogenetic distributions of individual components of the complex, we find that protein partners that are known to form independent subcomplexes are observed to share similar profiles, reaffirming the link between differential conservation of interface regions and their inter-dependence. When we extend our analysis to individual protein components of the complex, we find taxa-specific variability in molecular signatures of the proteins. These trends are discussed in the context of proline-rich motifs of SF3b4, functional and drug binding sites of SF3b1. Further, we report key protein-protein interactions between SF3b1 and SF3b6 whose presence is observed to be lineage-specific across eukaryotes. Together, our studies show the association of protein location within the complex and subcomplex formation patterns with the sequence conservation of SF3b proteins. In addition, our study underscores evolutionarily flexible elements that appear to confer adaptive features in individual components of the multi-protein SF3b complexes and may contribute to its functional adaptability.
Elevated Expression of Gamma-Glutamyl Hydrolase Is Associated With Poor Prognosis and Altered Immune Signature in Uterine Corpus Endometrial Carcinoma
Authors: Yu Cong , Qi Haining , Zhang Yanhui , Zhao Wen , Wu Guoying
Published: January 2022

Uterine corpus endometrial carcinoma (UCEC) is a common malignant tumor of the female reproductive system with poor prognosis in advanced, recurrent, and metastatic cases. Identification of reliable molecular markers will help in the development of clinical strategies for early detection, diagnosis, and intervention. Gamma-glutamyl hydrolase (GGH) is a key enzyme in folate metabolism pathway. High expression of GGH is associated with severe clinicopathological features and poor prognosis of several cancers. High GGH expression is also related to cell resistance to antifolate drugs such as methotrexate. In this study we focused on the prognostic value of immunohistochemical GGH expression level in UCEC tissue and RNA-seq data from The Cancer Genome Atlas to establish associations with clinical features and outcomes. Further, we conducted comprehensive bioinformatics analyses to identify and functionally annotate differentially expressed genes (DEGs) associated with UCEC upregulation and assessed the effects of upregulation on immune infiltration. Both GGH mRNA and protein expression levels were elevated in tumor tissues, and higher expression was significantly associated with advanced clinicopathological features and poor prognosis by univariate analysis. Further multivariate analysis identified elevated GGH expression as an independent risk factor for poor outcome. Nomograms including GGH expression yielded a c-index for disease-specific survival prediction of 0.884 (95% confidence interval: 0.861–0.907). A total of 520 DEGs (111 upregulated and 409 downregulated) were identified between high and low GGH expression groups. Analysis using Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Gene set enrichment analysis, and protein‒protein interaction indicated significant associations of altered GGH expression with cell proliferation, immune response, and the occurrence and development of UCEC tumors. Finally, GGH expression level was associated with high Th2 cell and low natural killer CD56bright cell infiltration. Collectively, these findings indicate that GGH drives UCEC progression and could be a useful biomarker for survival prediction as well as a therapeutic target.
Bacterial Response to Oxidative Stress and RNA Oxidation
Authors: Seixas André F. , Quendera Ana P. , Sousa João P. , Silva Alda F. Q. , Arraiano Cecília M. , Andrade José M.
Published: January 2022

Bacteria have to cope with oxidative stress caused by distinct Reactive Oxygen Species (ROS), derived not only from normal aerobic metabolism but also from oxidants present in their environments. The major ROS include superoxide O2−, hydrogen peroxide H2O2 and radical hydroxide HO•. To protect cells under oxidative stress, bacteria induce the expression of several genes, namely the SoxRS, OxyR and PerR regulons. Cells are able to tolerate a certain number of free radicals, but high levels of ROS result in the oxidation of several biomolecules. Strikingly, RNA is particularly susceptible to this common chemical damage. Oxidation of RNA causes the formation of strand breaks, elimination of bases or insertion of mutagenic lesions in the nucleobases. The most common modification is 8-hydroxyguanosine (8-oxo-G), an oxidized form of guanosine. The structure and function of virtually all RNA species (mRNA, rRNA, tRNA, sRNA) can be affected by RNA oxidation, leading to translational defects with harmful consequences for cell survival. However, bacteria have evolved RNA quality control pathways to eliminate oxidized RNA, involving RNA-binding proteins like the members of the MutT/Nudix family and the ribonuclease PNPase. Here we summarize the current knowledge on the bacterial stress response to RNA oxidation, namely we present the different ROS responsible for this chemical damage and describe the main strategies employed by bacteria to fight oxidative stress and control RNA damage.
Promising Immunotherapy in Metastatic Testicular Sex Cord Stromal Tumours After First-Line Chemotherapy
Authors: Shang Bingqing , Cao Chuanzhen , Jiang Weixing , Shi Hongzhe , Bi Xingang , Cui Chengxu , Shou Jianzhong , Zheng Shan , Zhang Jin , Zhou Aiping , Li Changling , Ma Jianhui
Published: January 2022

Background

Testicular sex cord stromal tumours (TSCSTs) are rare, with few studies focusing on the metastatic TSCST prognosis. The value of treatments, including radical orchiectomy (RO) and retroperitoneal lymph node dissection (RPLND), in preventing metastasis is controversial. Additionally, metastatic TSCSTs are resistant to chemotherapy. We aimed to assess the effectiveness and safety of immunotherapy in metastatic TSCSTs after first-line chemotherapy.

Methods

We retrospectively screened patients with testicular tumours undergoing testis surgery between January 2005 and January 2019. Patients with TSCSTs who had undergone testis-sparing surgery (TSS) or RO were identified. The malignant type was defined as metastasis confirmed by pathology. Treatment responses, progression-free survival (PFS), overall survival (OS) and safety were analysed.

Results

Among the 494 testicular tumour patients who received TSS or RO, 11 (2.2%) patients with histologically proven TSCSTs were identified. At the last follow-up, 7 patients survived without tumours, and 4 patients developed metastasis and received first-line cisplatin-based chemotherapy, with 1 of them achieving an objective response. Their PFS times were 1.5, 2.2, 9.0, and 17.0 months, respectively. Two patients received immune checkpoint inhibitors (ICIs) after developing chemotherapy resistance and achieved a partial response up to the last follow-up; one of them experienced Grade 1 adverse events, and the other experienced Grade 2 adverse events during immunotherapy. The median OS time of the 4 patients with metastatic TSCSTs was 32 months.

Conclusions

TSCSTs are rare, and most are benign with a good prognosis. ICIs represent a promising option for improving clinical outcomes in metastatic TSCSTs.
Myeloid-Derived Suppressor Cells Are Increased in Lung Transplant Recipients and Regulated by Immunosuppressive Therapy
Authors: Iglesias-Escudero María , Segundo David San , Merino-Fernandez David , Mora-Cuesta Victor M. , Lamadrid Patricia , Alonso-Peña Marta , Raso Sandra , Iturbe David , Fernandez-Rozas Sonia , Cifrian Jose , López-Hoyos Marcos
Published: January 2022

Lung transplantation remains as a primary treatment for end-stage lung diseases. Although remarkable improvement has been achieved due to the immunosuppressive protocols, long-term survival for lung transplant recipients (LTR) is still limited. In the last few decades, an increasing interest has grown in the study of dysregulation of immune mechanisms underlying allograft failure. In this regard, myeloid-derived suppressor cells (MDSCs) could play an important role in the promotion of graft tolerance due to their immune regulatory function. Here, we describe for the first time circulating subsets MDSCs from LTR at several time points and we evaluate the relationship of MDSCs with sort-term lung transplant outcomes. Although no effect of MDSCs subsets on short-term clinical events was observed, our results determine that Mo-MDSCs frequencies are increased after acute cellular rejection (ACR), suggesting a possible role for Mo-MDSCs in the development of chronic lung allograft dysfunction (CLAD). Therefore, whether MDSCs subsets play a role as biomarkers of chronic rejection remains unknown and requires further investigations. Also, the effects of the different immunosuppressive treatments on these subpopulations remain under research and further studies are needed to establish to what extend MDSCs immune modulation could be responsible for allograft acceptance.
Evaluation of Nonviral piggyBac and lentiviral Vector in Functions of CD19chimeric Antigen Receptor T Cells and Their Antitumor Activity for CD19+ Tumor Cells
Authors: Lin Zhicai , Liu Xiangzhen , Liu Tao , Gao Haixia , Wang Sitong , Zhu Xingli , Rong Lijie , Cheng Jingbo , Cai Zhigang , Xu Fu , Tan Xue , Lv Linjie , Li Zhong , Sun Yan , Qian Qijun
Published: January 2022

Nonviral transposon piggyBac (PB) and lentiviral (LV) vectors have been used to deliver chimeric antigen receptor (CAR) to T cells. To understand the differences in the effects of PB and LV on CAR T-cell functions, a CAR targeting CD19 was cloned into PB and LV vectors, and the resulting pbCAR and lvCAR were delivered to T cells to generate CD19pbCAR and CD19lvCAR T cells. Both CD19CAR T-cell types were strongly cytotoxic and secreted high IFN-γ levels when incubated with Raji cells. TNF-α increased in CD19pbCAR T cells, whereas IL-10 increased in CD19lvCAR T cells. CD19pbCAR and CD19lvCAR T cells showed similar strong anti-tumor activity in Raji cell-induced mouse models, slightly reducing mouse weight while enhancing mouse survival. High, but not low or moderate, concentrations of CD19pbCAR T cells significantly inhibited Raji cell-induced tumor growth in vivo. These CD19pbCAR T cells were distributed mostly in mesenteric lymph nodes, bone marrow of the femur, spleen, kidneys, and lungs, specifically accumulating at CD19-rich sites and CD19-positive tumors, with CAR copy number being increased on day 7. These results indicate that pbCAR has its specific activities and functions in pbCAR T cells, making it a valuable tool for CAR T-cell immunotherapy.
COVID-19 Changed Prevalence, Disease Spectrum and Management Strategies of Ocular Trauma
Authors: Yu Haozhe , Xu Minhui , Zhao Yue , Li Jingyi , Wu Wenyu , Feng Yun
Published: January 2022

The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the health of people around the world and has reshaped social behaviors and clinical practice. The purpose of this perspective is to provide epidemiologists and clinicians with information about how the spectrum of ocular trauma diseases changed, as well as to optimize management for improving patient prognosis during this crisis. Analysis of current studies revealed that the prevalence of eye trauma decreased overall, with a trend of delayed medical treatment during the COVID-19 era. Irregular epidemic prevention and control measures, unprotected home activities, and unusual mental states are the main causes of ocular trauma. Strategies for reducing morbidity are also discussed, including popularizing the use norms of prevention and control supplies, taking heed to the safety of family activities, highlighting the special status of child protection, and paying attention to previous case data to implement region-specific precautions. The procedure of ophthalmological emergency and outpatient management should also be optimized, and mental health should be emphasized during this pandemic.
Repurposing of Medicines in the EU: Launch of a Pilot Framework
Authors: Asker-Hagelberg Charlotte , Boran Tomas , Bouygues Christelle , Eskola Sini Marika , Helmle Laszlo , Hernández César , Houýez François , Lee Helen , Lingri Dimitra D. , Louette Laurent , Meheus Lydie , Penninckx Wim , Stepniewska Beata
Published: January 2022

Repurposing of authorised medicines has been under discussion for a long time. Drug repurposing is the process of identifying a new use for an existing medicine in an indication outside the scope of the original approved indication. Indeed, the COVID-19 health crisis has brought the concept to the frontline by proving the usefulness of this practise in favour of patients for an early access to treatment. Under the umbrella of the Pharmaceutical Committee and as a result of the discussions at the European Commission Expert Group on Safe and Timely Access to Medicines for Patients (STAMP) a virtual Repurposing Observatory Group (RepOG) was set up in 2019 to define and test the practical aspects of a pilot project thought to provide support to “not-for-profit” stakeholders generating or gathering data for a new therapeutic use for an authorised medicine. The group's initial plan was impacted by the outbreak of the SARS-CoV-2 pandemic and the launch of the pilot needed to be postponed. This article describes the progress and the activities conducted by the group during this past and yet extraordinary 2020–2021 to keep the project alive and explores on the background of this topic together with the obvious opportunities this health crisis has brought up in terms of repurposing of medicines.
Hsp90 Inhibitors Inhibit the Entry of Herpes Simplex Virus 1 Into Neuron Cells by Regulating Cofilin-Mediated F-Actin Reorganization
Authors: Song Xiaowei , Wang Yiliang , Li Feng , Cao Wenyan , Zeng Qiongzhen , Qin Shurong , Wang Zhaoyang , Jia Jiaoyan , Xiao Ji , Hu Xiao , Liu Kaisheng , Wang Yifei , Ren Zhe
Published: January 2022

Herpes simplex virus 1 (HSV-1) is a common neurotropic virus, the herpes simplex encephalitis (HSE) caused by which is considered to be the most common sporadic but fatal encephalitis. Traditional antiviral drugs against HSV-1 are limited to nucleoside analogs targeting viral factors. Inhibition of heat shock protein 90 (Hsp90) has potent anti-HSV-1 activities via numerous mechanisms, but the effects of Hsp90 inhibitors on HSV-1 infection in neuronal cells, especially in the phase of virus entry, are still unknown. In this study, we aimed to investigate the effects of the Hsp90 inhibitors on HSV-1 infection of neuronal cells. Interestingly, we found that Hsp90 inhibitors promoted viral adsorption but inhibited subsequent penetration in neuronal cell lines and primary neurons, which jointly confers the antiviral activity of the Hsp90 inhibitors. Mechanically, Hsp90 inhibitors mainly impaired the interaction between Hsp90 and cofilin, resulting in reduced cofilin membrane distribution, which led to F-actin polymerization to promote viral attachment. However, excessive polymerization of F-actin inhibited subsequent viral penetration. Consequently, unidirectional F-actin polymerization limits the entry of HSV-1 virions into neuron cells. Our research extended the molecular mechanism of Hsp90 in HSV-1 infection in neuron cells and provided a theoretical basis for developing antiviral drugs targeting Hsp90.
Phosphoinositide-Dependent Protein Kinases Regulate Cell Cycle Progression Through the SAD Kinase Cdr2 in Fission Yeast
Authors: Liu Kun , Liu Qiannan , Sun Yanli , Fan Jinwei , Zhang Yu , Sakamoto Norihiro , Kuno Takayoshi , Fang Yue
Published: January 2022

Aberration in the control of cell cycle contributes to the development and progression of many diseases including cancers. Ksg1 is a Schizosaccharomyces pombe fission yeast homolog of mammalian phosphoinositide-dependent protein kinase 1 (PDK1) which is regarded as a signaling hub for human tumorigenesis. A previous study reported that Ksg1 plays an important role in cell cycle progression, however, the underlying mechanism remains elusive. Our genomic library screen for novel elements involved in Ksg1 function identified two serine/threonine kinases, namely SAD family kinase Cdr2 and another PDK1 homolog Ppk21, as multicopy suppressors of the thermosensitive phenotype of ksg1-208 mutant. We found that overexpression of Ppk21 or Cdr2 recovered the defective cell cycle transition of ksg1-208 mutant. In addition, ksg1-208 Δppk21 cells showed more marked defects in cell cycle transition than each single mutant. Moreover, overexpression of Ppk21 failed to recover the thermosensitive phenotype of the ksg1-208 mutant when Cdr2 was lacking. Notably, the ksg1-208 mutation resulted in abnormal subcellular localization and decreased abundance of Cdr2, and Ppk21 deletion exacerbated the decreased abundance of Cdr2 in the ksg1-208 mutant. Intriguingly, expression of a mitotic inducer Cdc25 was significantly decreased in ksg1-208, Δppk21, or Δcdr2 cells, and overexpression of Ppk21 or Cdr2 partially recovered the decreased protein level of Cdc25 in the ksg1-208 mutant. Altogether, our findings indicated that Cdr2 is a novel downstream effector of PDK1 homologs Ksg1 and Ppk21, both of which cooperatively participate in regulating cell cycle progression, and Cdc25 is involved in this process in fission yeast.
Association of Circulating Magnesium Levels in Patients With Alzheimer's Disease From 1991 to 2021: A Systematic Review and Meta-Analysis
Authors: Du Ke , Zheng Xi , Ma Zi-Tai , Lv Jun-Ya , Jiang Wen-Juan , Liu Ming-Yan
Published: January 2022

Alzheimer's disease (AD) remains a medical and social challenge worldwide. Magnesium (Mg) is one of the most frequently evaluated essential minerals with diverse biological functions in human body. However, the association between circulating Mg levels and AD remains controversial. We conducted a meta-analysis of 21 studies published between 1991 and 2021 to determine whether the Mg levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data without language limitations. A pooled subject sample including 1,112 AD patients and 1,001 healthy controls (HCs) was available to assess Mg levels in serum and plasma; 284 AD patients and 117 HCs were included for Mg levels in CSF. It was found that serum and plasma levels of Mg were significantly reduced in AD patients compared with HCs (standardized mean difference [SMD] = −0.89; 95% confidence interval [CI] [−1.36, −0.43];P= 0.000). There was statistically non-significant for Mg level in CSF between AD and HCs, whereas a decreased tendency were detected (SMD = −0.16; 95% CI [−0.50, 0.18];P= 0.364). .In addition, when we analyzed the Mg levels of serum, plasma and CSF together, the circulating Mg levels in AD patients was significantly lower (SMD = −0.74, 95% CI [−1.13; −0.35];P= 0.000). These results indicate that Mg deficiency may be a risk factor of AD and Mg supplementation may be a potentially valuable adjunctive treatment for AD.

Systematic Review Registration:www.crd.york.ac.uk/PROSPERO/, registration number CRD42021254557.
The Pressor Response to the Drinking of Cold Water and Cold Carbonated Water in Healthy Younger and Older Adults
Authors: Kubota Satoshi , Endo Yutaka , Kubota Mitsue , Miyazaki Hiroko , Shigemasa Tomohiko
Published: January 2022

Purpose: Water drinking has been proposed for the treatment of orthostatic hypotension because it can increase blood pressure in patients. This study aimed to investigate whether drinking water with a cold or carbonation stimulus would cause a more effective pressor response, and whether it would be greater in older than in younger adults.

Methods: We assessed blood pressure and heart rate from non-invasive arterial pressure (a volume-clamp method) and type II electrocardiography in 13 healthy young adults (6 females, 7 males; mean age, 19.9 ± 1.1 years) and nine healthy older adults (all females; mean age, 71.4 ± 4.2 years) who drank 200 mL of cold, cold carbonated, and room temperature water.

Results: The pressor response to the drinking of cold and cold carbonated water was greater than that to room temperature water in both younger and older participants (p < 0.05; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in young: 15.31 ± 9.66, 22.56 ± 11.51 and 32.6 ± 17.98 mmHg, respectively; changes in systolic blood pressure of room temperature water, cold water and cold carbonated water in elderly: 21.84 ± 14.31, 41.53 ± 19.82 and 48.16 ± 16.77 mmHg, respectively). In addition, the pressor response to cold and cold carbonated water was persistent during the recovery period by about 5–10 mmHg (p < 0.05). Furthermore, the pressor response during the drinking and recovery periods was greater in the older than in the younger participants (p < 0.05).

Conclusion: Our data suggest that even smaller amounts of water are able to elicit a sustained pressor response, in particular if the water is cold and carbonated. We speculate that the pressor effect may render cold and carbonated water an appropriate first aid method against certain forms of acute hypotension.