bluuebunny/crossref_metadata_2025 huggingface dataset:
Preceptoria na formação médica: O conhecimento dos preceptores sobre competências em cenários de prática
Authors: Sequeira Cibele Cristine Remondes , Machado Júnior Celso
Published: June 2022

O objetivo deste estudo foi analisar as competências interpretadas como relevantes pelos preceptores que atua no contexto da Estratégia da Saúde da Família. Desenvolveu-se uma pesquisa utilizando dados quantitativos e qualitativos, coletados junto a profissionais de medicina e de enfermagem que atuam como preceptores de alunos do curso de medicina de uma Instituição de Ensino Superior. As principais competências identificadas como necessárias para a atividade da preceptoria estão relacionadas a integração da teoria e prática, o aprimoramento do raciocínio crítico- reflexivo do aluno, por meio de avaliações, feedbacks construtivos e proficientes. Identificou-se que parcela significativa dos preceptores não realizou formação específica para o desenvolvimento desta atividade. Esta lacuna de formação, se posiciona como um importante elemento a ser superado pelas Instituições de Ensino Superior que encaminham seus alunos para a atividade prática, com a colaboração de um preceptor. A oferta de capacitação para o preceptor, proporcionaria o estabelecimento de padrões de conduta para realizar a atividade de avaliação e de melhoria do sistema de ensino e aprendizagem dos alunos de medicina.
A importância da programação de computadores para compreensão Matemática
Authors: Almeida Juan Rodrigues Teixeira , Colares Fernando , Dias Gustavo Nogueira , Vogado Gilberto Emanoel Reis , Reis Cássio Pinho dos , Lobato Fabricio da Silva , Silva Katiane Pereira da , Beirão Antonio Thiago Madeira , Soares Daniele Cristina de Brito Lima , Barbosa Eldilene da Silva , Santos Ricardo Daniel Soares , Souza Júnior José Carlos Barros de , Ferreira Flávio
Published: June 2022

Esta pesquisa foi desenvolvida para responder perguntas que tomaram forma durante a carreira acadêmica do autor, após o mesmo notar melhora de suas capacidades matemáticas durante sua jornada em um curso superior de ciência da computação, com isto o objetivo geral desta pesquisa foi verificar quais os benefícios que puderam ser notados através da pesquisa bibliográfica levantada. Enquanto os dados foram levantados as perguntas que o autor considerou de fundamental importância para a pesquisa e que nortearam os assuntos aqui tratados foram: Qual a diferença entre a prática atual do ensino de matemática e um ensino baseado na utilização dos recursos de linguagem de programação? Que benefícios a programação pode trazer na vida do estudante dentro e fora de sala de aula? Este trabalho focou principalmente para as aulas de matemática e suas tecnologias, tendo em vista a crescente utilização dos computadores tradicionais e microcomputadores nas mais diversas instâncias da sociedade e as possibilidades que estes aparatos trazem, utilizá-los no ambiente educacional se torna de suma importância na preparação dos alunos. Com este contexto, utilizar os conceitos matemáticos que estão dentro da programação de computadores pode ser de grande ajuda para uma educação mais prática, além de que combinado com a contribuição de o assunto atrair muito interesse dos estudantes, já que o mesmo envolve as novas tecnologias e a possibilidades de criação de jogos e programas de computador, assuntos que hoje estão intrínsecos com o nosso dia a dia.
Análise da prevalência, diagnóstico laboratorial e tratamento da sífilis na gestação: uma revisão de literatura
Authors: Teles Aline dos Santos , Coelho Carla Islene Holanda Moreira
Published: June 2022

A pesquisa objetivou analisar a prevalência, diagnóstico laboratorial e o tratamento da sífilis na gestação. Tratou-se de uma revisão integrativa da literatura, no qual foram utilizadas as bases de dados SciELO, LILACS e o BVS, mediante cruzamento dos descritores: Diagnóstico laboratorial, Gestação, Prevalência, Sífilis e Tratamento. A pesquisa foi norteada pelos seguintes questionamentos: Como ocorre o tratamento, diagnóstico laboratorial e a prevalência da sífilis na gestação atualmente? Quais são as políticas públicas de saúde do Sistema Único de Saúde (SUS) direcionadas a sífilis gestacional. Foram encontradas 5.364 publicações, que após passarem pelos critérios de inclusão e exclusão, foram filtradas e selecionadas 10 publicações, essas compuseram a amostra final do estudo. Os artigos escolhidos estavam entre os anos de 2016 a 2022. Os principais achados do estudo, mostraram que a Sífilis Gestacional e a Sífilis Congênita tem vitimado mães e bebês e desafiado o sistema de saúde no que se refere ao rastreamento, tratamento e erradicação da doença. É evidente a necessidade de ações que objetivem a redução da transmissão vertical da sífilis, ampliação do acesso as metodologias diagnósticas, além de rastreamento sorológico, essas atribuições reforçam a prevenção da doença e a redução de possíveis sequelas. Conclui-se, portanto, que um pré-natal sem qualidade e inadequado contribui para o surgimento de falhas no tratamento de mulheres grávidas, o que possivelmente pode resultar em casos congênitos da Sífilis. Sendo assim, é de fundamental importância a promoção de ações em saúde que almejem eliminar a transmissão vertical da sífilis.
Estudo comparativo no tratamento de Estrias: Peeling de Diamante x Microagulhamento
Authors: Comper Raíne Viana , Pires Thalita Jinny Silva , Moura Juliana Braga Facchinetti
Published: June 2022

Introdução: Diversas alterações podem afetar a pele, provocando disfunções no tecido, como acontece com as estrias; estas são comumente alterações que ocorrem especificamente na derme, e advém de um estiramento exacerbado da pele. Quando esse processo lesivo acontece, as estrias surgem com uma tonalidade avermelhada ou rosada, gerando as Estrias Rubras (ER) e posteriormente podem se tornar esbranquiçadas, as Estrias Albas (EA). Objetivo: Comparar os efeitos do peeling de diamante e microagulhamento em estrias rubras e/ou albas. Metodologia: A pesquisa é um estudo de caso avaliada como pesquisa-ação, foi realizada por meio da observação direta das práticas aplicadas ao paciente estudado, bem como entrevista, questionários para entender as explicações e interpretações ocorridas na realidade observada. Como as estrias tendem a se apresentar bilateralmente, foram realizadas um total de 04 sessões de microdermoabrasão em um hemicorpo e microagulhamento no outro hemicorpo. Os intervalos entre as sessões foram de 15 dias, sendo realizadas em apenas uma participante. Resultados: Foram obtidos resultados satisfatórios como a redução do tamanho das estrias e da aparência, com respostas positivas também em relação a satisfação pessoal da participante. Conclusão: Ambas as técnicas aplicadas trouxeram resultados positivos no tratamento de estrias atróficas albas, apresentando melhoras nos tamanhos e aspectos delas.
Founder of clinical physiology and functional diagnostics – Alexander Filippovich Samoilov
Authors: Teregulov Y. E. , Podolskaya M. A.
Published: June 2022

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Has Henry Softened the War in A Farewell to Arms? A Translational
Perspective on Hedging
Authors: Ahmad Abualadas Othman
Published: June 2022

This paper provides an empirical investigation of shifts in hedges in an Arabic
translation of A Farewell to Arms (1929). The results reveal a tendency to add rather than
omit hedges. This is associated with several discourse effects, such as a move toward an
increased level of awareness of information quality and relevance, greater
attenuation/mitigation, more politeness, improved interpersonal relations, increased
reinforcement, greater speaker responsibility/commitment, higher cognitive and emotional
involvement, and stronger textual relations in the translated narrative. These effects reflect
a more cooperation/dynamic role on the (literary) translator’s part during his second
verbal materialization and re-narration of the original story. The addition of relevance
hedges points to an explicitation pattern that improves the text’s readability and reflects the
translator’s mediating voice in the translated narrative. The increased attenuation and
reinforcement are indicative of a movement toward standardizing (appropriating) a war
novel that has a less emotive style to an emotionally remote (Arabic) reader, pushing for
more universalized interpretations and more normalized literary translations. Such
movements, which cannot be linked at least in this study to any sociopolitical factors (e.g.,
language status, power relations), are better regarded as visible traces pointing to the
translators’ (conscious or subconscious) orientation toward a greater literary uniformity
and more cross-cultural/universal understanding. .
Studies of the Face(less): Picture Brides and Facial Recognition in
Julie Otsuka’s The Buddha in the Attic
Authors: Alma’aqbeh Hala
Published: June 2022

This paper investigates the ways in which Julie Otsuka’s The Buddha in the Attic
(2011) resists racializing surveillance through making use of what we call unidentifiable
characterization. This technique, we assert, contributes to a complex portrayal of the
internment of Japanese Americans, as it privileges the collective without oversimplifying or
romanticizing that collective and not only avoids but also opposes overemphasizing the role
of the individual, a role that requires intense visualization (that is, surveillance). As a result,
we argue that The Buddha constitutes an anti-surveillance Asian American narrative that
exposes the contradictory (to use Lisa Lowe’s term) realities of the U.S. In analyzing such
a narrative, we develop the term “faceless narrative,” a text that resists surveillance and
rejects visual identification of characters..
Colliding Utopian and Dystopian Worlds:
Revising Ray Bradbury’s Fahrenheit 451 and Ahmed K. Towfik’s
Utopia
Authors: Bohovyk Oksana
Published: June 2022

The article discusses two symptomatic texts that are imbricated within the
utopian/dystopian ambience: Fahrenheit 451 by Ray Bradbury and Utopia by Ahmed
Khaled Towfik. The style and structure of the selected novels are revealed at the level of
the chronotope and aimed at clarifying the correlation of genre-forming components
within the triad of a ‘person – civilisation – society’. This paper tests a hypothesis that
the discursive representation of these components in a narrative structure is realised
through colliding utopian and dystopian worlds. Problematising this idea in fiction
reveals how the tension between the diametrically opposed worlds promotes critical
scrutiny of both to draw attention to the most pressing social problems facing humanity:
the role of ordinary people in society, impact of mass media on public opinion, dissolution
of morals, social disparity, drug addiction, etc. The study primarily follows a
phenomenological-hermeneutic approach to exploring the theoretical and practical
aspects of utopian/dystopian worldviews in the literary dimension. The dichotomy of
utopia/dystopia manifests in the novels through the overt conflict of different patterns of
life, mentalities, and cultures. Analysing the ways of a literary embodiment of this conflict
in Bradbury’s and Towfik’s books explicates how creating a new reality from
utopian/dystopian perspectives alters consciousness and promotes a completely different
paradigm of existence..
The Effect of Work Compensation on Intention to Stay in the Hotel Industry During the COVID 19 Pandemic with Job Embeddedness as Mediation
Authors: Ferdian Feri , Abrian Youmil , Suyuthie Hijriyantomi , Kasmita Kasmita , Sinensis Rizki Amelia
Published: June 2022

This study aimed to analyze the effect of work compensation on intention to stay in the hotel industry during the COVID 19 pandemic with job embeddedness as mediation. This research was conducted with a quantitative approach. The total population was 670 hotel management graduates with the sample's determination based on the type of purposive sampling. The sample size of the study is estimated at 30% of the total population (201 graduates) who are estimated to work in the hotel industry. A total of 145 respondents were successfully collected. The data analysis technique used is Partial Least Square Structural Equation Modelling (PLS-SEM). The results showed that: (1) There is a significant effect of work compensation toward hotel management graduates’ intention to stay in the hotel industry during the COVID 19 pandemic. (2) There is a significant effect of work compensation toward hotel management graduates' job embeddedness in the hotel industry during the COVID 19 pandemic. (3) There is a significant effect of job embeddedness toward hotel management graduates’ intention to stay in the hotel industry during the COVID 19 pandemic and (4) There is a significant mediating effect of job embeddedness toward the relationship between work compensation and hotel management graduates’ intention to stay in the hotel industry during COVID 19 pandemic. What could be said from the result of the study is that the strength of the relationship between work compensation and hotel management graduates' intention to stay in the hotel industry would be increased with the presence of job embeddedness
Changing Seasonality of Lolium rigidum (Annual Ryegrass) in Southeastern Australia
Authors: Thompson Michael , Chauhan Bhagirath Singh
Published: June 2022

Lolium rigidum (annual ryegrass) is the most costly winter weed in Australia and has recently been observed growing in summer. The occurrence of L. rigidum in winter is well documented, but there is no research on populations of this weed that germinate and grow in summer. Herein, we discuss how the potential cause of this seasonal expansion may be related to a change in dormancy duration. Dormancy can affect germination patterns but the growth and reproduction of a plant species depend on other factors, such as temperature and photoperiod. Therefore, dormancy alone cannot be the sole variable responsible for the presence of L. rigidum in summer crops, as typical summer temperature conditions are not favorable for the growth of this weed. Additional changes to the growth and development of summer populations may allow for the adaptation and infestation of L. rigidum in summer conditions.
Scoring Functions for Protein-Ligand Binding Affinity Prediction Using Structure-based Deep Learning: A Review
Authors: Meli Rocco , Morris Garrett M. , Biggin Philip C.
Published: June 2022

The rapid and accurate in silico prediction of protein-ligand binding free energies or binding affinities has the potential to transform drug discovery. In recent years, there has been a rapid growth of interest in deep learning methods for the prediction of protein-ligand binding affinities based on the structural information of protein-ligand complexes. These structure-based scoring functions often obtain better results than classical scoring functions when applied within their applicability domain. Here we review structure-based scoring functions for binding affinity prediction based on deep learning, focussing on different types of architectures, featurization strategies, data sets, methods for training and evaluation, and the role of explainable artificial intelligence in building useful models for real drug-discovery applications.
Liquid Crystal Modified Polylactic Acid Improves Cytocompatibility and M2 Polarization of Macrophages to Promote Osteogenesis
Authors: Zheng Zexiang , Wang Renqin , Lin Jianjun , Tian Jinhuan , Zhou Changren , Li Na , Li Lihua
Published: June 2022

Liquid crystalline phases (LC phases) are widely present in an organism. The well-aligned domain and liquidity of the LC phases are necessary for various biological functions. How to stabilize the floating LC phases and maintain their superior biology is still under study. In addition, it is unclear whether the exogenous LC state can regulate the immune process and improve osteogenesis. In this work, a series of composite films (PLLA/LC) were prepared using cholesteryl oleyl carbonate (COC), cholesteryl pelargonate (CP), and polylactic acid (PLLA) via a controlled facile one-pot approach. The results showed that the thermo-responsive PLLA/LC films exhibited stable LC phases at human body temperature and the cytocompatibility of the composites was improved significantly after modification by the LC. In addition, the M2 polarization of macrophages (RAW264.7) was enhanced in PLLA/LC films, and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was improved as co-cultured with macrophages. The in vivo bone regeneration of the materials was verified by calvarial repair, in which the amount of new bone in the PLLA-30% LC group was greater than that in the PLLA group. This work revealed that the liquid crystal-modified PLLA could promote osteogenesis through immunomodulation.
Hydrogels for Single-Cell Microgel Production: Recent Advances and Applications
Authors: Tiemeijer B. M. , Tel J.
Published: June 2022

Single-cell techniques have become more and more incorporated in cell biological research over the past decades. Various approaches have been proposed to isolate, culture, sort, and analyze individual cells to understand cellular heterogeneity, which is at the foundation of every systematic cellular response in the human body. Microfluidics is undoubtedly the most suitable method of manipulating cells, due to its small scale, high degree of control, and gentle nature toward vulnerable cells. More specifically, the technique of microfluidic droplet production has proven to provide reproducible single-cell encapsulation with high throughput. Various in-droplet applications have been explored, ranging from immunoassays, cytotoxicity assays, and single-cell sequencing. All rely on the theoretically unlimited throughput that can be achieved and the monodispersity of each individual droplet. To make these platforms more suitable for adherent cells or to maintain spatial control after de-emulsification, hydrogels can be included during droplet production to obtain “microgels.” Over the past years, a multitude of research has focused on the possibilities these can provide. Also, as the technique matures, it is becoming clear that it will result in advantages over conventional droplet approaches. In this review, we provide a comprehensive overview on how various types of hydrogels can be incorporated into different droplet-based approaches and provide novel and more robust analytic and screening applications. We will further focus on a wide range of recently published applications for microgels and how these can be applied in cell biological research at the single- to multicell scale.
The Hydration State of Bone Tissue Affects Contrast in Neutron Tomographic Images
Authors: Törnquist Elin , Le Cann Sophie , Tengattini Alessandro , Helfen Lukas , Kok Joeri , Hall Stephen A. , Isaksson Hanna
Published: June 2022

Neutron tomography has emerged as a promising imaging technique for specific applications in bone research. Neutrons have a strong interaction with hydrogen, which is abundant in biological tissues, and they can penetrate through dense materials such as metallic implants. However, in addition to long imaging times, two factors have led to challenges in running in situ mechanical characterization experiments on bone tissue using neutron tomography: 1) the high water content in specimens reduces the visibility of internal trabecular structures; 2) the mechanical properties of bone are dependent on the hydration state of the tissue, with drying being reported to cause increased stiffness and brittleness. This study investigates the possibility of improving image quality in terms of neutron transmission and contrast between material phases by drying and rehydrating in heavy water. Rat tibiae and trabecular bovine bone plugs were imaged with neutron tomography at different hydration states and mechanical testing of the bone plugs was carried out to assess effects of drying and rehydration on the mechanical properties of bone. From analysis of image histograms, it was found that drying reduced the contrast between bone and soft tissue, but the contrast was restored with rehydration. Contrast-to-noise ratios and line profiles revealed that the contrast between bone tissue and background was reduced with increasing rehydration duration but remained sufficient for identifying internal structures as long as no free liquid was present inside the specimen. The mechanical analysis indicated that the proposed fluid exchange protocol had no adverse effects on the mechanical properties.
Reforming the Chimeric Antigen Receptor by Peptide Towards Optimized CAR T Cells With Enhanced Anti-Cancer Potency and Safety
Authors: Liu Cuijuan , Li Lin , Gao Fan , Zhou Jundong , Qin Yingzhou , Yuan Xin , Yang Guang , Zhu Yimin
Published: June 2022

The emerging chimeric antigen receptor (CAR) T cell revolutionized the clinic treatment of hematological cancers, but meet its Waterloo in solid tumor therapy. Although there exist many reasons for this limitation, one of the largest challenges is the scarcity of recognition for tumor cells, resulting in the undesirable side effects and the subsequent ineffectiveness. To overcome it, a lung-cancer-cell-targeting peptide termed A1 was used in this work to reform the scFv domain of CAR by genetic manipulation. As a result, this modified A1CAR T exhibited the optimized cancer-cell targeting and cytotoxicity in vitro and in vivo. More importantly, by tuning the sensitivity of CAR to antigen, peptide-based A1CAR T cells could distinguish tumors from normal tissue, thereby eliminating the off-tumor toxicity in healthy organs. Collectively, we herein constructed a genetic peptide-engineered CAR T cells by inserting A1 peptide into the scFv domain. Profitted from the optimized recognition pattern and sensitivity, A1CAR T cells showed the ascendancy in solid tumor treatment. Our findings demonstrate that peptide-based CAR T holds great potential in solid tumor therapy due to an excellent targeting ability towards tumor cells.
Limb Mesoderm and Head Ectomesenchyme Both Express a Core Transcriptional Program During Chondrocyte Differentiation
Authors: Gomez-Picos Patsy , Ovens Katie , Eames B. Frank
Published: June 2022

To explain how cartilage appeared in different parts of the vertebrate body at discrete times during evolution, we hypothesize that different embryonic populations co-opted expression of a core gene regulatory network (GRN) driving chondrocyte differentiation. To test this hypothesis, laser-capture microdissection coupled with RNA-seq was used to reveal chondrocyte transcriptomes in the developing chick humerus and ceratobranchial, which are mesoderm- and neural crest-derived, respectively. During endochondral ossification, two general types of chondrocytes differentiate. Immature chondrocytes (IMM) represent the early stages of cartilage differentiation, while mature chondrocytes (MAT) undergo additional stages of differentiation, including hypertrophy and stimulating matrix mineralization and degradation. Venn diagram analyses generally revealed a high degree of conservation between chondrocyte transcriptomes of the limb and head, includingSOX9,COL2A1, andACANexpression. Typical maturation genes, such asCOL10A1,IBSP, andSPP1, were upregulated in MAT compared to IMM in both limb and head chondrocytes. Gene co-expression network (GCN) analyses of limb and head chondrocyte transcriptomes estimated the core GRN governing cartilage differentiation. Two discrete portions of the GCN contained genes that were differentially expressed in limb or head chondrocytes, but these genes were enriched for biological processes related to limb/forelimb morphogenesis or neural crest-dependent processes, respectively, perhaps simply reflecting the embryonic origin of the cells. A core GRN driving cartilage differentiation in limb and head was revealed that included typical chondrocyte differentiation and maturation markers, as well as putative novel “chondrocyte” genes. Conservation of a core transcriptional program during chondrocyte differentiation in both the limb and head suggest that the same core GRN was co-opted when cartilage appeared in different regions of the skeleton during vertebrate evolution.
Investigating the Perovskite Ag1-3xLaxNbO3 as a High-Rate Negative Electrode for Li-Ion Batteries
Authors: Le Calvez Etienne , Espinosa-Angeles Julio César , Whang Grace J. , Dupré Nicolas , Dunn Bruce S. , Crosnier Olivier , Brousse Thierry
Published: June 2022

The broader development of the electric car for tomorrow’s mobility requires the emergence of new fast-charging negative electrode materials to replace graphite in Li-ion batteries. In this area, the design of new compounds using innovative approaches could be the key to discovering new negative electrode materials that allow for faster charging and discharging processes. Here, we present a partially substituted AgNbO3 perovskite material by introducing lanthanum in the A-site. By creating two vacancies for every lanthanum introduced in the structure, the resulting general formula becomes Ag1-3xLax□2xNbO3 (with x ≤ 0.20 and where □ is a A-site vacancy), allowing the insertion of lithium ions. The highly substituted Ag0.40La0.20□0.40NbO3 oxide shows a specific capacity of 40 mAh.g−1 at a low sweep rate (0.1 mV s−1). Interestingly, Ag0.70La0.10□0.20NbO3 retains 64% of its capacity at a very high sweep rate (50 mV s−1) and about 95% after 800 cycles. Ex situ7Li MAS NMR experiments confirmed the insertion of lithium ions in these materials. A kinetic analysis of Ag1-3xLax□2xNbO3 underlines the ability to store charge without solid-state ion-diffusion limitations. Furthermore, in situ XRD indicates no structural modification of the compound when accommodating lithium ions, which can be considered as zero-strain material. This finding explains the interesting capacity retention observed after 800 cycles. This paper thus demonstrates an alternative approach to traditional insertion materials and identifies a different way to explore not-so common electrode materials for fast energy storage application.
Unsupported MoS2-Based Catalysts for Bio-Oil Hydrodeoxygenation: Recent Advances and Future Perspectives
Authors: Cao Jing , Zhang Youming , Wang Li , Zhang Cen , Zhou Congshan
Published: June 2022

In recent years, unsupported MoS2-based catalysts have been reported as promising candidates in the hydrodeoxygenation (HDO) of bio-oil. However, preparing MoS2-based catalysts with both high activity and good stability for HDO reaction is still challenging and of great importance. Hence, this mini-review is focused on the recent development of unsupported MoS2-based HDO catalysts from the understanding of catalyst design. The three aspects including morphology and defect engineering, metal doping, and deactivation mechanism are highlighted in adjusting the HDO performance of MoS2-based catalysts. Finally, the key challenges and future perspectives about how to design efficient catalysts are also summarized in the conclusions.
How the Way a Naphthalimide Unit is Implemented Affects the Photophysical and -catalytic Properties of Cu(I) Photosensitizers
Authors: Yang Yingya , Doettinger Florian , Kleeberg Christian , Frey Wolfgang , Karnahl Michael , Tschierlei Stefanie
Published: June 2022

Driven by the great potential of solar energy conversion this study comprises the evaluation and comparison of two different design approaches for the improvement of copper based photosensitizers. In particular, the distinction between the effects of a covalently linked and a directly fused naphthalimide unit was assessed. For this purpose, the two heteroleptic Cu(I) complexes CuNIphen (NIphen = 5-(1,8-naphthalimide)-1,10-phenanthroline) and Cubiipo (biipo = 16H-benzo-[4′,5′]-isoquinolino-[2′,1′,:1,2]-imidazo-[4,5-f]-[1,10]-phenanthroline-16-one) were prepared and compared with the novel unsubstituted reference compound Cuphen (phen = 1,10-phenanthroline). Beside a comprehensive structural characterization, including two-dimensional nuclear magnetic resonance spectroscopy and X-ray analysis, a combination of electrochemistry, steady-state and time-resolved spectroscopy was used to determine the electrochemical and photophysical properties in detail. The nature of the excited states was further examined by (time-dependent) density functional theory (TD-DFT) calculations. It was found that CuNIphen exhibits a greatly enhanced absorption in the visible and a strong dependency of the excited state lifetimes on the chosen solvent. For example, the lifetime of CuNIphen extends from 0.37 µs in CH2Cl2 to 19.24 µs in MeCN, while it decreases from 128.39 to 2.6 µs in Cubiipo. Furthermore, CuNIphen has an exceptional photostability, allowing for an efficient and repetitive production of singlet oxygen with quantum yields of about 32%.
Streptococcus oralis Employs Multiple Mechanisms of Salivary Mucin Binding That Differ Between Strains
Authors: Chahal Gurdeep , Quintana-Hayashi Macarena P. , Gaytán Meztlli O. , Benktander John , Padra Medea , King Samantha J. , Linden Sara K.
Published: June 2022

Streptococcus oralis is an oral commensal and opportunistic pathogen that can enter the bloodstream and cause bacteremia and infective endocarditis. Here, we investigated the mechanisms of S. oralis binding to oral mucins using clinical isolates, isogenic mutants and glycoconjugates. S. oralis bound to both MUC5B and MUC7, with a higher level of binding to MUC7. Mass spectrometry identified 128 glycans on MUC5B, MUC7 and the salivary agglutinin (SAG). MUC7/SAG contained a higher relative abundance of Lewis type structures, including Lewis b/y, sialyl-Lewis a/x and α2,3-linked sialic acid, compared to MUC5B. S. oralis subsp. oralis binding to MUC5B and MUC7/SAG was inhibited by Lewis b and Lacto-N-tetraose glycoconjugates. In addition, S. oralis binding to MUC7/SAG was inhibited by sialyl Lewis x. Binding was not inhibited by Lacto-N-fucopentaose, H type 2 and Lewis x conjugates. These data suggest that three distinct carbohydrate binding specificities are involved in S. oralis subsp. oralis binding to oral mucins and that the mechanisms of binding MUC5B and MUC7 differ. Efficient binding of S. oralis subsp. oralis to MUC5B and MUC7 required the gene encoding sortase A, suggesting that the adhesin(s) are LPXTG-containing surface protein(s). Further investigation demonstrated that one of these adhesins is the sialic acid binding protein AsaA.
Bacteriophage Therapy for Staphylococcus Aureus Infections: A Review of Animal Models, Treatments, and Clinical Trials
Authors: Plumet Lucile , Ahmad-Mansour Nour , Dunyach-Remy Catherine , Kissa Karima , Sotto Albert , Lavigne Jean-Philippe , Costechareyre Denis , Molle Virginie
Published: June 2022

Staphylococcus aureus (S. aureus) is a common and virulent human pathogen causing several serious illnesses including skin abscesses, wound infections, endocarditis, osteomyelitis, pneumonia, and toxic shock syndrome. Antibiotics were first introduced in the 1940s, leading to the belief that bacterial illnesses would be eradicated. However, microorganisms, including S. aureus, began to develop antibiotic resistance from the increased use and abuse of antibiotics. Antibiotic resistance is now one of the most serious threats to global public health. Bacteria like methicillin-resistant Staphylococcus aureus (MRSA) remain a major problem despite several efforts to find new antibiotics. New treatment approaches are required, with bacteriophage treatment, a non-antibiotic strategy to treat bacterial infections, showing particular promise. The ability of S. aureus to resist a wide range of antibiotics makes it an ideal candidate for phage therapy studies. Bacteriophages have a relatively restricted range of action, enabling them to target pathogenic bacteria. Their usage, usually in the form of a cocktail of bacteriophages, allows for more focused treatment while also overcoming the emergence of resistance. However, many obstacles remain, particularly in terms of their effects in vivo, necessitating the development of animal models to assess the bacteriophage efficiency. Here, we provide a review of the animal models, the various clinical case treatments, and clinical trials for S. aureus phage therapy.
Long Chain Fatty Acids and Virulence Repression in Intestinal Bacterial Pathogens
Authors: Mitchell Mary K. , Ellermann Melissa
Published: June 2022

When bacterial pathogens enter the gut, they encounter a complex milieu of signaling molecules and metabolites produced by host and microbial cells or derived from external sources such as the diet. This metabolomic landscape varies throughout the gut, thus establishing a biogeographical gradient of signals that may be sensed by pathogens and resident bacteria alike. Enteric bacterial pathogens have evolved elaborate mechanisms to appropriately regulate their virulence programs, which involves sensing and responding to many of these gut metabolites to facilitate successful gut colonization. Long chain fatty acids (LCFAs) represent major constituents of the gut metabolome that can impact bacterial functions. LCFAs serve as important nutrient sources for all cellular organisms and can function as signaling molecules that regulate bacterial metabolism, physiology, and behaviors. Moreover, in several enteric pathogens, including Salmonella enterica, Listeria monocytogenes, Vibrio cholerae, and enterohemorrhagic Escherichia coli, LCFA sensing results in the transcriptional repression of virulence through two general mechanisms. First, some LCFAs function as allosteric inhibitors that decrease the DNA binding affinities of transcriptional activators of virulence genes. Second, some LCFAs also modulate the activation of histidine kinase receptors, which alters downstream intracellular signaling networks to repress virulence. This mini-review will summarize recent studies that have investigated the molecular mechanisms by which different LCFA derivatives modulate the virulence of enteric pathogens, while also highlighting important gaps in the field regarding the roles of LCFAs as determinants of infection and disease.
H2-Driven Reduction of Flavin by Hydrogenase Enables Cleaner Operation of Nitroreductases for Nitro-Group to Amine Reductions
Authors: Ramirez Miguel A. , Joseph Srinivasan Shiny , Cleary Sarah E. , Todd Peter M. T. , Reeve Holly A. , Vincent Kylie A.
Published: June 2022

Hydrogenase-mediated reduction of flavin mononucleotide by H2 is exploited to enable cleaner application of nitroreductase enzymes for reduction of aromatic nitro functional groups. This turns the overall reaction into a biocatalytic hydrogenation. Use of flavin-containing nitroreductases in industrial biotechnology typically relies upon NADH or NADPH as reductant, together with glucose dehydrogenase and glucose as a regeneration system for the reduced nicotinamide cofactor, with 3 equivalents of the carbon-intensive glucose required for a single 6-electron nitro to amine conversion. We show here that reduced flavin mononucleotide is an alternative reductant for nitroreductases, and by combining this with H2-driven recycling of reduced flavin, we avoid glucose, thereby enabling atom-efficient biocatalytic nitro reductions. We compare this biocatalytic system, via green chemistry metrics, to existing strategies for biocatalytic nitro-group reductions, particularly with respect to replacing glucose with H2 gas. We take steps towards demonstrating industrial viability: we report an overexpression system for E. coli hydrogenase 1, giving a 12-fold improvement in enzyme yield; we show a reaction in which the hydrogenase exhibits > 26,000 enzyme turnovers; and we demonstrate reasonable solvent tolerance of the hydrogenase and flavin reduction system which would enable reaction intensification.
A Cardiovascular Disease Prediction Model Based on Routine Physical Examination Indicators Using Machine Learning Methods: A Cohort Study
Authors: Qian Xin , Li Yu , Zhang Xianghui , Guo Heng , He Jia , Wang Xinping , Yan Yizhong , Ma Jiaolong , Ma Rulin , Guo Shuxia
Published: June 2022

Background

Cardiovascular diseases (CVD) are currently the leading cause of premature death worldwide. Model-based early detection of high-risk populations for CVD is the key to CVD prevention. Thus, this research aimed to use machine learning (ML) algorithms to establish a CVD prediction model based on routine physical examination indicators suitable for the Xinjiang rural population.

Method

The research cohort data collection was divided into two stages. The first stage involved a baseline survey from 2010 to 2012, with follow-up ending in December 2017. The second-phase baseline survey was conducted from September to December 2016, and follow-up ended in August 2021. A total of 12,692 participants (10,407 Uyghur and 2,285 Kazak) were included in the study. Screening predictors and establishing variable subsets were based on least absolute shrinkage and selection operator (Lasso) regression, logistic regression forward partial likelihood estimation (FLR), random forest (RF) feature importance, and RF variable importance. The selected subset of variables was compared with L1 regularized logistic regression (L1-LR), RF, support vector machine (SVM), and AdaBoost algorithm to establish a CVD prediction model suitable for this population. The incidence of CVD in this population was then analyzed.

Result

After 4.94 years of follow-up, a total of 1,176 people were diagnosed with CVD (cumulative incidence: 9.27%). In the comparison of discrimination and calibration, the prediction performance of the subset of variables selected based on FLR was better than that of other models. Combining the results of discrimination, calibration, and clinical validity, the prediction model based on L1-LR had the best prediction performance. Age, systolic blood pressure, low-density lipoprotein-L/high-density lipoproteins-C, triglyceride blood glucose index, body mass index, and body adiposity index were all important predictors of the onset of CVD in the Xinjiang rural population.

Conclusion

In the Xinjiang rural population, the prediction model based on L1-LR had the best prediction performance.
The Association Between Congestive Heart Failure and One-Year Mortality After Surgery in Singaporean Adults: A Secondary Retrospective Cohort Study Using Propensity-Score Matching, Propensity Adjustment, and Propensity-Based Weighting
Authors: Han Yong , Hu Haofei , Liu Yufei , Li Qiming , Huang Zhiqiang , Wang Zhibin , Liu Dehong , Wei Longning
Published: June 2022

Background

Although congestive heart failure (CHF) is considered a risk factor for postoperative mortality, reliable quantification of the relationship between CHF and postoperative mortality risk is limited. We aimed to investigate the association between CHF and 1-year mortality after surgery in a large cohort of the Singaporean population.

Methods

In this retrospective cohort study, the study population included 69,032 adult patients who underwent surgery at Singapore General Hospital between 1 January 2012 and 31 October 2016. The target independent and dependent variables were CHF and 1-year mortality after surgery, respectively. Propensity score was estimated using a non-parsimonious multivariable logistic regression model. Multivariable adjustment, propensity score matching, propensity score adjustment, and propensity score-based weighting Cox proportional-hazards regression were performed to investigate the association between CHF and 1-year mortality after surgery.

Results

The multivariate-adjusted hazard ratio (HR) in the original cohort was 1.39 (95% confidence interval (CI): 1.20–1.61, P < 0.001). In additional propensity score adjustment, the HR between CHF and 1-year mortality after surgery was 1.34 (95% CI: 1.15–1.56, P < 0.001). In the propensity score-matched cohort, the multivariate-adjusted Cox proportional hazard regression model analysis showed participants with CHF had a 54% increased risk of 1-year mortality after surgery (HR 1.54, 95% CI: 1.19–1.98, P < 0.001). The multivariate-adjusted HR of the inverse probability of treatment-weighted and standardised mortality ratio-weighted cohorts was 1.34 (95% CI: 1.10–1.62, P = 0.004) and 1.24 (95% CI: 1.17–1.32, P < 0.001), respectively.

Conclusion

CHF is an independent risk factor for 1-year mortality after surgery in patients undergoing surgery. Depending on the statistical method, patients with CHF had a 24–54% increased risk of 1-year all-cause mortality after surgery. This provides a reference for optimising clinical decision-making, improving preoperative consultation, and promoting clinical communication.
Diffuse Myocardial Fibrosis and Cardiomyocyte Diameter Are Associated With Heart Failure Symptoms in Chagas Cardiomyopathy
Authors: Nardi Gemme Cristiane , Silva Thiago Quinaglia A. C. , Martins Luiz C. , da Silva Luis Miguel , Paim Layde Rosane , Sposito Andrei , Nadruz Wilson , Fernandes Fabio , San Juan Dertkigil Sergio , da Silva Wanderley Jamiro , de Almeida Eros A. , Metze Konradin , Neilan Tomas G. , Jerosch-Herold Michael , Coelho-Filho Otávio R.
Published: June 2022

Background

Chronic Chagas cardiomyopathy (CCC) constitutes the most life-threatening consequence of the Trypanosoma cruzi infection. Our goal was to test in CCC the associations of the myocardial tissue phenotype with cardiac dysfunction, and heart failure (HF) severity, using cardiac magnetic resonance (CMR).

Methods

We performed a prospective observational cohort of patients with consecutive CCC with a CMR protocol, including ventricular function, myocardial T1, and late gadolinium enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τic, a measure of cardiomyocyte diameter, were compared to CCC disease progression, including Rassi score and New York Heart Association (NYHA) class. An exploratory prognostic analysis was performed to investigate the association of both ECV and τic with CV death.

Results

A total of 37 patients with intermediate-to-high-risk CCC were enrolled (Chagas Rassi score ≥7, mean left ventricle (LV) ejection fraction (EF) 32 ± 16%). Myocardial ECV (0.40 ± 0.07) was correlated with Rassi score (r = 0.43; P = 0.009), higher NYHA class, and LV EF (r = −0.51; P = 0.0015). τic decreased linearly with NYHA class (P = 0.007 for non-parametric test of linear trend) and showed a positive association with LV EF (r = 0.47; P = 0.004). Over a median follow-up of 734 days (range: 6–2,943 days), CV death or cardiac transplantation occurred in 10 patients. The Rassi score (heart rate [HR] = 1.3; 95% CI = [1.0, 1.8]; P = 0.028) and ECV (HR = 3.4 for 0.1 change, 95% CI = [1.1, 11.0], P = 0.039) were simultaneously associated with CV death.

Conclusion

In patients with intermediate-to-high-risk CCC, an expanded ECV and regression of cardiomyocyte diameter were associated with worsening systolic function and HF severity, respectively. The exploratory analysis indicates that ECV may have a prognostic value to identify patients with CCC at a higher risk for cardiovascular events.
Adenosine Concentration in Patients With Neurally Mediated Syncope
Authors: Groppelli Antonella , Brignole Michele , Chefrour Mohamed , Gastaldi Marguerite , El Oufir Farid , Deharo Jean Claude , Parati Gianfranco , Guieu Régis
Published: June 2022

Background

Either high or low values of adenosine blood level (ABL) can differentiate some forms of neurally mediated syncope (NMS). A rapid method of measurement has recently been developed. The aim of the present study was: (1) to compare ABLs in an unselected population of consecutive patients referred for evaluation of suspected NMS syncope and in healthy controls; and (2) to assess the relative prevalence of low and high adenosine forms among an unselected syncope population.

Method

Whole blood was collected after finger puncture, blood being deposit on a blot paper and adenosine concentration was measured by liquid chromatography/mass spectrometry (LC-MS/MS).

Results

Among 89 control subjects, the median ABL value was 0.54 μM (IQR, 0.46–0.65). The lowest 5% and the upper 95% percentile were 0.40 and 0.80 μM, respectively. Compared with healthy subjects, the 146 patients with syncope showed, on average, a higher median ABL value [0.63 (IQR 0.45–0.73, p = 0.04)] and a larger distribution of values. Low ABL values below the 5th percentile were observed in 28 (19%) patients, and, in five controls, p = 0.003 and high ABL values were observed in 26 (18%) patients and five controls, p = 0.009.

Conclusions

ABL is different in patients with suspected NMS than in healthy subjects. Patients with low and high adenosine values account for 19% and 18% of the general population. Thus, low and high ABL limits, as defined in this study, may help to define the purinergic profile of unselected subjects with a clinical diagnosis of suspected NMS.
Maximum Likelihood Reconstruction of Water Cherenkov Events With Deep Generative Neural Networks
Authors: Jia Mo , Kumar Karan , Mackey Liam S. , Putra Alexander , Vilela Cristovao , Wilking Michael J. , Xia Junjie , Yanagisawa Chiaki , Yang Karan
Published: June 2022

Large water Cherenkov detectors have shaped our current knowledge of neutrino physics and nucleon decay, and will continue to do so in the foreseeable future. These highly capable detectors allow for directional and topological, as well as calorimetric information to be extracted from signals on their photosensors. The current state-of-the-art approach to water Cherenkov reconstruction relies on maximum-likelihood estimation, with several simplifying assumptions employed to make the problem tractable. In this paper, we describe neural networks that produce probability density functions for the signals at each photosensor, given a set of inputs that characterizes a particle in the detector. The neural networks we propose allow for likelihood-based approaches to event reconstruction with significantly fewer assumptions compared to traditional methods, and are thus expected to improve on the current performance of water Cherenkov detectors.
The Cenozoic Multiple-Stage Uplift of the Qiangtang Terrane, Tibetan Plateau
Authors: Zhao Zhongbao , Lu Haijian , Wang Shiguang , Li Haibing , Li Chao , Liu Dongliang , Pan Jiawei , Zheng Yong , Bai Minkun
Published: June 2022

Cenozoic collision between the Indian and Asian continents is generally considered as the main driver forming the high Tibetan Plateau (TP). However, it remains hotly debated when and how the relatively flat and highly elevated TP was formed. Here, we present combined analyses of the apatite fission track (AFT) and apatite (U-Th)/He (AHe) of 18 granite samples along three steep topographic transects in the central part of the Qiangtang Terrane (QT), TP. The results indicate that the AFT ages of all samples are mostly between 130 Ma and 80 Ma, while the AHe ages range from 80 Ma to 40 Ma. Further thermal history modeling indicates that no significant cooling occurred after 40 Ma for most samples, except those lying close to the Reganpei Co extensional fault in the QT. The results are generally consistent with other low-temperature thermochronological data, as well as structural and sedimentologic data from the QT, suggesting that low relief and the relatively flat topography of the QT were almost completely formed before ∼40 Ma. As both megafossils and pollen had undergone a sharp change from subtropical- to psychro-species, indicating a relatively low elevation (∼2 km) at ∼40 Ma and >2 km uplift during the Oligocene. We use simple one-dimensional isostatic modeling to assess the contribution of convective removal of the lithospheric mantle to the present elevation of the QT. The results suggest that a combined effect of isostatic rebound (≥2 km) and thermal expansion related to asthenosphere upwelling and subsequent crustal base heating (∼0.4 km) led to the final uplift of the QT. Therefore, the QT experienced multiple-stage uplift processes which were controlled by crustal thickening before ∼40 Ma and lithospheric mantle delamination during the Oligocene, respectively.