bluuebunny/crossref_metadata_2025 huggingface dataset:
Alopecia X in dogs: report of seven cases
Authors: Ferreira Marília Aragão de Sousa , Carvalho Victor Machado de , Dutra Marrie da Silva , Rodrigues Fábio Ranyeri Nunes , Viana Daniel de Araújo , Ferreira Tiago Cunha
Published: July 2022

Alopecia X (AX) is a non-inflammatory and non-pruritic skin disease characterized by progressive hair loss. The most commonly affected dogs are male Pomeranian, Chow-Chow and Poodles. Although there is a similarity with endocrinopathies that course with dermatological changes, AX does not bring systemic harm to affected dogs. The diagnosis is based on the exclusion of other diseases that lead to hair loss, in addition to systemic diseases. As it is a disease rarely reported in the literature, the objective of the present work is to make a retrospective study of seven cases of dogs with AX treated in clinical routine, from diagnosis to therapeutic results. At the time, the dogs received a similar therapeutic approach, which consisted of the orchiectomy process, followed by supplementation with omega-3 and vitamin complex. Only one dog was not neutered, due to constant platelet changes. Two dogs underwent the microneedling technique due to partial response to conventional treatment and only one of them showed complete repilation. From the above, it is considered that AX is a disease present in the dermatological routine of dogs and that the recognition of its lesion pattern is important for a better diagnostic and therapeutic direction. In addition, it was observed that, although all the therapies employed resulted in an improvement in hair growth, the therapeutic response was variable, so that some dogs may not show complete repilation. Further researches involving therapy comparison are encouraged in order to provide a better understading of their efficiency.
Diagnóstico de delirium em pacientes admitidos em Unidade de Terapia Intensiva: uma revisão integrativa
Authors: Minella Flávia Cristina Osaku , Mello Neto Salim Abib Attuch de , Osaku Erica Fernanda , Costa Claudia Rejane Lima de Macedo , Giancursi Thiago
Published: July 2022

O delirium em adultos internados em unidade de terapia intensiva pode estar relacionado à ventilação mecânica, ao uso de sedativos e ao tempo prolongado de permanência na UTI, estando associado a piores quadros clínicos e desfechos hospitalares. Objetivos: investigar o diagnóstico de delirium em pacientes internados em UTI e como ele influência no internamento desses pacientes. Metodologia: estudo de revisão integrativa e de caráter exploratório. Foi realizada uma busca por estudos nas bases de dados MEDLINE, PubMed e LILACS, com os seguintes descritores: delirium and ICU and mechanical ventilation and diagnosis. Resultados: foram incluídos 14 pesquisas, sendo: 5 realizados na Europa, 4 na Ásia, 2 na América do Norte e 1 na América do Sul, além de dois estudos bicêntricos. A gravidade da disfunção está relacionada com pacientes com idade mais avançada, com maior tempo de ventilação mecânica, com maior tempo de sedação e dias de internamento. Entre os instrumentos de avaliação diagnostica, o Confusion Assessment Method for Intensive Care Unit (CAM-ICU) obteve resposta satisfatória entre as pesquisas analisadas. Conclusão: a estratégia mais eficaz para redução de delirium é a prevenção primária, como investimento em recursos humanos, uso de medidas não farmacológicas e mudanças no manejo da disfunção. O diagnóstico correto e precoce de delirium pode trazer impacto positivo no prognóstico dos pacientes em UTI, minorando as repercussões orgânicas e a morbimortalidade desses pacientes.
Psicoterapia de orientação analítica e psicoterapia cognitivo-comportamental: integração possível na prática clínica?
Authors: Kronbauer Julya Fernandes , Menezes Marina , Lopes Fernanda Machado
Published: July 2022

A psicoterapia integrativa visa articular conhecimentos teóricos e metodológicos de mais de uma abordagem, aproveitando suas potencialidades de forma complementar para melhor eficácia no tratamento. Esta prática tem sido reconhecida e aplicada em âmbito internacional, mas no Brasil ainda é pouco encorajada. Este relato de experiência tem como objetivo discutir a possibilidade de integração entre a psicoterapia de orientação analítica e a psicoterapia cognitivo-comportamental a partir da análise de um caso clínico. A psicoterapia foi realizada em 2017, totalizando vinte atendimentos. A partir da análise dos atendimentos, observou-se que, apesar de cada escola teórica possuir métodos distintos, ambas têm como objetivo o bem-estar do sujeito através do desenvolvimento de recursos para lidar com as suas dificuldades. Assim, conclui-se que a integração das duas abordagens de forma complementar e não reducionista pode ter boa aplicação clínica. Trabalhos que apresentem procedimentos integrativos e que incentivem a reflexão sobre tal prática psicoterapêutica devem ser encorajados.
Intolerância e alergia alimentar na região metropolitana de Belém - PA
Authors: Moraes Laura Vanessa de Sousa , Matos Jamille de Araujo , Silva Vânia Maria Barboza da , Silva Luísa Margareth Carneiro da , Brasil Alódia
Published: July 2022

Este artigo tem o objetivo de mostrar o dimensionamento quantitativo de pessoas com alergia e intolerância alimentar e os alimentos que frequentemente causam reações alérgicas na região metropolitana de Belém no período de 2020 a 2022. A pesquisa foi feita com base no estudo transversal por formulário eletrônico aplicado pela plataforma G-Suite for Education, e propagado por redes sociais de amplo uso da população. Participaram da pesquisa voluntários maiores de 18 anos que assinaram o Termo de Compromisso Livre e Esclarecido (TCLE). Foram entrevistados 390 moradores da região metropolitana de Belém. A maior parte era do gênero feminino, pardo, solteiro, com ensino superior. Os alimentos mais prevalentes foram relatados por 180 pessoas, sendo eles: lactose, camarão, leite, mariscos, frutos do mar, porco, ovos, corantes artificiais, glúten, abacaxi, peixe, cacau, amendoim, conservantes, caranguejo, coco, laranja, castanhas, chocolate, melão, amêndoas, maracujá, pipoca, pupunha, condimentos artificiais, molho inglês, shoyu, ketchup, maionese, sardinha, outros enlatados, melancia, banana, queijo, polvilho, cupuaçu, goiaba. Conclui-se que o questionário teve um alcance significativo de pessoas, porém é necessário conhecer mais a fundo outros parâmetros que possam propor uma abrangência maior de pessoas e melhor avaliação.
Os jogos digitais nos processos de ensino e aprendizagem de Matemática: Um foco no ensino médio
Authors: Rocha Francisco Bruno Nascimento da , Costa Juliana Evaristo , Maia José Gilvan Rodrigues , Castro Filho José Aires de
Published: July 2022

Os jogos digitais ganham, a cada dia, mais espaço na sociedade contemporânea. Os estabelecimentos de ensino já demonstram essa preocupação em atender a essa nova demanda educacional, procurando inserir os jogos em seus ambientes. Diante dessa realidade, o presente trabalho traz uma Revisão Sistemática de Literatura (RSL) acerca da utilização dos jogos digitais no ensino de matemática com aplicação voltada a estudantes do ensino médio. Foram utilizadas cinco bases de dados para a obtenção dos estudos da RSL, sendo elas: Google Scholar, ERIC, Periódicos CAPES, Gale Academic OneFile  e JSTOR. De acordo com os resultados obtidos, percebe-se que a aplicação de jogos aos alunos do ensino médio, na disciplina de matemática ainda é um campo pouco explorado, há demandas por mais pesquisas e estudos nessa área. Por outro lado, nos artigos analisados nesta RSL, observou-se que todos relatam o grande potencial que os jogos digitais podem acarretar aos estudantes do ensino médio no que se refere à participação, envolvimento e engajamento em seu processo de aprendizagem matemática.
Variable fish habitat function in two open-coast eelgrass species
Authors: Obaza AK , Bird A , Sanders R , Ware R , Ginsburg DW
Published: July 2022

Eelgrasses Zostera are foundation species that perform myriad ecosystem services, yet research into their habitat function is often focused on regions susceptible to intense anthropogenic disturbance. This trend has created a data gap on the role more remote eelgrass beds provide among the mosaic of other temperate marine habitats. In this study, we surveyed 15 Z. marina and Z. pacifica beds along Catalina Island and the Southern California Bight (SCB) mainland coast from 2018 to 2020 for areal coverage, structural components and fish assemblages, from which a relativized index of fish utilization was then created. We then evaluated the landscape and structural components that potentially drive fish utilization in Z. marina using the index as a response variable in a model selection procedure. Zostera beds ranged in size from 0.06 ha to >27.5 ha. Fish assemblages in Z. marina and Z. pacifica beds were significantly different, and in the case of fishes found in both, individuals were often below size at maturity in Z. marina and above size in Z. pacifica. Distance to the nearest reef and bed area, both positively related to the fish assemblage index, were the most important factors. The results suggest Z. marina beds function as a nursery habitat while Z. pacifica are used by mid-level predators for foraging. These data represent the first rigorous study of fish utilization of open-coast Z. marina and Z. pacifica beds, and are invaluable to marine spatial planning efforts that may incorporate a more holistic approach to habitat management in temperate regions.
Investigating the effects of two weaning methods and two genetic hybrids on play behavior in weaner pigs (Sus scrofa)
Authors: Franchi Guilherme A. , Larsen Mona L. V. , Winters Jeanet F. M. , Jensen Margit Bak , Pedersen Lene Juul
Published: July 2022

In conventional pig production, suckling pigs are typically weaned between 3 and 5 weeks of age. This involves separation from the sow, dietary change, and regrouping in a novel environment, which challenge the welfare of pigs. We investigated the effects of two weaning methods [conventional weaning: two litters mixed in a weaner pen of different size and design (MOVE) vs. litter staying in the farrowing pen after removing the sow (STAY)] and two genetic hybrids [DanBred Yorkshire × Landrace (approximately 21 total pigs born/litter; DB) vs. Topigs Norsvin TN70 Yorkshire × Landrace (approximately 16 total pigs born/litter with higher individual birth weight and weaning weight than DB; TN)] on play behavior across weaning. Both genetic hybrids were inseminated with semen of DanBred Duroc boars. Litters were reduced to the number of functional teats at birth. The durations of locomotor-rotational play (LOC) and social play (SOC) of 24 indoor-housed litters [pigs/litter: (average ± SD) 13 ± 2; age at the weaning day: 26 ± 2 days] were video-recorded continuously between 14:00 h and 22:00 h on days −1, 1, and 2 relative to weaning and statistically analyzed with mixed-effects modeling at the individual level. Before weaning, TN pigs performed LOC longer than DB pigs. On day 2 post-weaning, STAY pigs engaged in more SOC than MOVE pigs. Moreover, TN pigs and STAY pigs displayed a steeper increase in LOC from days 1 to 2 than DB pigs and MOVE pigs, respectively. We demonstrated that pigs belonging to the genetic hybrid with higher weight at birth and weaning spent more time playing on the day before weaning. Additionally, weaning pigs in the farrowing pen and, hence, avoiding social mixing and relocation to an unfamiliar environment had a positive effect on social play after weaning. Our study illustrates that weaning stress in pigs may be reduced by using a genetic hybrid featuring higher birth and weaning weight and by keeping litters intact in a familiar environment after weaning. This study also supports the use of play behavior as an animal welfare indicator.
Broadening the spectrum of ivermectin: Its effect on Trypanosoma cruzi and related trypanosomatids
Authors: Fraccaroli Laura , Ruiz María Daniela , Perdomo Virginia Gabriela , Clausi Agustina Nicole , Balcazar Darío Emmanuel , Larocca Luciana , Carrillo Carolina
Published: July 2022

Chagas disease is an endemic American parasitosis, caused byTrypanosoma cruzi. The current therapies, benznidazole (BZN) and nifurtimox (NFX), show limited efficacy and multiple side effects. Thus, there is a need to develop new trypanocidal strategies. Ivermectin (IVM) is a broad-spectrum antiparasitic drug with low human and veterinary toxicity with effects againstT. bruceiandLeishmaniaspp. Considering this and its relatively low cost, we evaluate IVM as a potential repurposed trypanocidal drug onT. cruziand other trypanosomatids. We found that IVM affected, in a dose-dependent manner, the proliferation ofT. cruziepimastigotes as well as the amastigotes and trypomastigotes survival. The Selectivity Index for the amastigote stage with respect to Vero cells was 12. The IVM effect was also observed inPhytomonas jma 066andLeishmania mexicanaproliferation but not inCrithidia fasciculata. On the epimastigote stage, the IVM effect was trypanostatic at 50 μM but trypanocidal at 100 μM. The assays of the drug combinations of IVM with BNZ or NFX showed mainly additive effects among combinations.In silicostudies showed that classical structures belonging to glutamate-gated Cl channels, the most common IVM target, are absent in kinetoplastids. However, we found in the studied trypanosomatid genomes one copy for putative IMPα and IMPβ, potential targets for IVM. The putative IMPα genes (with 76% similarity) showed conserved Armadillo domains but lacked the canonical IMPβ binding sequence. These results allowed us to propose a novel molecular target inT. cruziand suggest IVM as a good candidate for drug repurposing in the Chagas disease context.
Pathological and protective roles of dendritic cells in Mycobacterium tuberculosis infection: Interaction between host immune responses and pathogen evasion
Authors: Kim Hongmin , Shin Sung Jae
Published: July 2022

Dendritic cells (DCs) are principal defense components that play multifactorial roles in translating innate immune responses to adaptive immunity inMycobacterium tuberculosis(Mtb) infections. The heterogeneous nature of DC subsets follows their altered functions by interacting with other immune cells, Mtb, and its products, enhancing host defense mechanisms or facilitating pathogen evasion. Thus, a better understanding of the immune responses initiated, promoted, and amplified or inhibited by DCs in Mtb infection is an essential step in developing anti-tuberculosis (TB) control measures, such as host-directed adjunctive therapy and anti-TB vaccines. This review summarizes the recent advances in salient DC subsets, including their phenotypic classification, cytokine profiles, functional alterations according to disease stages and environments, and consequent TB outcomes. A comprehensive overview of the role of DCs from various perspectives enables a deeper understanding of TB pathogenesis and could be useful in developing DC-based vaccines and immunotherapies.
Clinical characteristics and risk factors associated with ICU-acquired infections in sepsis: A retrospective cohort study
Authors: He Yajun , Xu Jiqian , Shang Xiaopu , Fang Xiangzhi , Gao Chenggang , Sun Deyi , Yao Lu , Zhou Ting , Pan Shangwen , Zou Xiaojing , Shu Huaqing , Yang Xiaobo , Shang You
Published: July 2022

Intensive care unit (ICU)-acquired infection is a common cause of poor prognosis of sepsis in the ICU. However, sepsis-associated ICU-acquired infections have not been fully characterized. The study aims to assess the risk factors and develop a model that predicts the risk of ICU-acquired infections in patients with sepsis.

Methods

We retrieved data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients were randomly divided into training and validation cohorts at a 7:3 ratio. A multivariable logistic regression model was used to identify independent risk factors that could predict ICU-acquired infection. We also assessed its discrimination and calibration abilities and compared them with classical score systems.

Results

Of 16,808 included septic patients, 2,871 (17.1%) developed ICU-acquired infection. These patients with ICU-acquired infection had a 17.7% ICU mortality and 31.8% in-hospital mortality and showed a continued rise in mortality from 28 to 100 days after ICU admission. The classical Systemic Inflammatory Response Syndrome Score (SIRS), Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS), Simplified Acute Physiology Score II (SAPS II), Logistic Organ Dysfunction Score (LODS), Charlson Comorbidity Index (CCI), and Acute Physiology Score III (APS III) scores were associated with ICU-acquired infection, and cerebrovascular insufficiency, Gram-negative bacteria, surgical ICU, tracheostomy, central venous catheter, urinary catheter, mechanical ventilation, red blood cell (RBC) transfusion, LODS score and anticoagulant therapy were independent predictors of developing ICU-acquired infection in septic patients. The nomogram on the basis of these independent predictors showed good calibration and discrimination in both the derivation (AUROC = 0.737; 95% CI, 0.725–0.749) and validation (AUROC = 0.751; 95% CI, 0.734–0.769) populations and was superior to that of SIRS, SOFA, OASIS, SAPS II, LODS, CCI, and APS III models.

Conclusions

ICU-acquired infections increase the likelihood of septic mortality. The individualized prognostic model on the basis of the nomogram could accurately predict ICU-acquired infection and optimize management or tailored therapy.
Meal Replacements for Weight-Related Complications in Type 2 Diabetes: What Is the State of the Evidence?
Authors: Noronha Jarvis C. , Kendall Cyril WC. , Sievenpiper John L.
Published: July 2022

Comprehensive lifestyle management is a fundamental aspect of diabetes care. Clinical practice guidelines for the nutritional management of diabetes have evolved considerably over the last 25 years shifting from a focus on single nutrients to food- and dietary pattern-based recommendations. Use of meal replacements as a temporary short-term strategy to induce weight loss and then transitioning to a healthier dietary pattern (e.g., Mediterranean or Portfolio) for weight loss maintenance fits well with this new shift in focus of clinical practice guidelines. As adherence is the most important determinant for attaining the benefits of any diet, health professionals should recommend evidence-based dietary patterns (including meal replacements) that align best with the patient’s values, preferences, and treatment goals.
Role of nuclear pregnane X receptor in Cu-induced lipid metabolism and xenobiotic responses in largemouth bass (Micropterus salmoides)
Authors: Li Hongyan , Gong Wangbao , Wang Guangjun , Yu Ermeng , Tian Jingjing , Xia Yun , Li Zhifei , Zhang Kai , Xie Jun
Published: July 2022

The pregnane X receptor (PXR) is a master xenobiotic-sensing receptor in response to toxic byproducts, as well as a key regulator in intermediary lipid metabolism. Therefore, the present study was conducted to investigate the potential role of PXR in mediating the lipid dysregulation and xenobiotic responses under Cu-induced stress in largemouth bass (Micropterus salmoides). Four groups of largemouth bass (52.66 ± 0.03 g) were treated with control, Cu waterborne (9.44 μmol/L), Cu+RIF (Rifampicin, 100 mg/kg, PXR activator), and Cu+KET (Ketoconazole, 20 mg/kg, PXR inhibitor) for 48 h. Results showed that Cu exposure significantly elevated the plasma stress indicators and triggered antioxidant systems to counteract Cu-induced oxidative stress. Acute Cu exposure caused liver steatosis, as indicated by the significantly higher levels of plasma triglycerides (TG), lipid droplets, and mRNA levels of lipogenesis genes in the liver. Liver injuries were detected, as shown by hepatocyte vacuolization and severe apoptotic signals after Cu exposure. Importantly, Cu exposure significantly stimulated mRNA levels of PXR, suggesting the response of this regulator in the xenobiotic response. The pharmacological intervention of PXR by the agonist and antagonist significantly altered hepatic mRNA levels of PXR, implying that RIF and KET were effective agents of PXR in largemouth bass. Administration of RIF significantly exacerbated liver steatosis, and such alterations were dependent on the regulations on pparγ and cd36 rather than srebp1 signaling, which suggested that PXR-PPARγ might be another pathway for Cu-induced lipid deposition in fish. Whereas, KET administration showed reverse effects on lipid metabolism as indicated by the lower hepatic TG levels, suppressed mRNA levels of pparγ and cd36. Activation of PXR stimulated autophagy and inhibited apoptosis, leading to lower hepatic vacuolization; while inhibition of PXR showed higher apoptotic signals, inhibition of autophagic genes and stimulation of apoptotic genes. Taken together, PXR played a cytoprotective role in Cu-induced hepatotoxicity through regulations on autophagy and apoptosis. Overall, our data has demonstrated for the first time on the dual roles of PXR as a co-regulator in mediating xenobiotic responses and lipid metabolism in fish, which implying the potential of PXR as a therapy target for xenobiotics-induced lipid dysregulation and hepatotoxicity.
An overview of the efficacy and signaling pathways activated by stem cell-derived extracellular vesicles in diabetic kidney disease
Authors: Lin Yongda , Yang Qian , Wang Jiali , Chen Xiutian , Liu Yiping , Zhou Tianbiao
Published: July 2022

Diabetic kidney disease (DKD) is one of complications of diabetes mellitus with severe microvascular lesion and the most common cause of end-stage chronic kidney disease (ESRD). Controlling serum glucose remains the primary approach to preventing and slowing the progression of DKD. Despite considerable efforts to control diabetes, people with diabetes develop not only DKD but also ESRD. The pathogenesis of DKD is very complex, and current studies indicate that mesenchymal stromal cells (MSCs) regulate complex disease processes by promoting pro-regenerative mechanisms and inhibiting multiple pathogenic pathways. Extracellular vesicles (EVs) are products of MSCs. Current data indicate that MSC-EVs-based interventions not only protect renal cells, including renal tubular epithelial cells, podocytes and mesangial cells, but also improve renal function and reduce damage in diabetic animals. As an increasing number of clinical studies have confirmed, MSC-EVs may be an effective way to treat DKD. This review explores the potential efficacy and signaling pathways of MSC-EVs in the treatment of DKD.
Parent-offspring turn-taking dynamics influence parents’ song structure and elaboration in a singing primate
Authors: De Gregorio Chiara , Zanoli Anna , Carugati Filippo , Raimondi Teresa , Valente Daria , Torti Valeria , Miaretsoa Longondraza , Rajaonson Andry , Gamba Marco , Giacoma Cristina
Published: July 2022

Parent-offspring interactions are essential to interpret animal social evolution and behavior, but their role in mediating acoustic communication in animals that interact vocally is still unclear. Increasing evidence shows that primate vocal communication is way more flexible than previously assumed, and research on this topic can provide further information on how the social environment shaped vocal plasticity during the evolution of the Primate order. Indris communicate through elaborated vocal emissions, usually termed songs. Songs are interactive vocal displays in which all members of the family group alternate their emissions, taking turns during chorusing events. We aimed to understand whether specific rules regulate the turn-taking of different group members and investigate the flexibility of indris’ vocal behavior when co-singing with their offspring. We found that social factors can influence the turn-taking organization in a chorus, as offspring were more likely to drop out from the parents’ duet than join in, and we speculate that overlap might signal competition by members of the same-sex. The duet between the reproductive pair was the most common type of singing organization, followed by a duet between mothers and sons and the triadic interaction between mother, father, and son. Interestingly, parents’ solo singing seems to stimulate offspring to vocalize, and we also found that mothers and fathers simplify, at least in part, song elaboration when chorusing with offspring. Our results indicate that indris can perform short-time adjustments to the number of co-emitters and their identity: our approach is advantageous in highlighting the multilevel influences on primate vocal flexibility. Moreover, it provides evidence that some aspects of our vocal plasticity were already present in the lemur lineage.
Transcriptomic and gene-family dynamic analyses reveal gene expression pattern and evolution in toxin-producing tissues of Asiatic toad (Bufo gargarizans)
Authors: Lv Yunyun , Li Yanping , Wen Zhengyong , Shi Qiong
Published: July 2022

Comprising a major clade of Anura, toads produce and secrete numerous toxins from both the parotoid glands behind their eyes and their dorsal skin. These toxins, made of various proteins and compounds, possess pharmacological potential to be repurposed to benefit human health. However, the detailed genetic regulation of toad toxin production is still poorly understood. A recent publication uncovering the genome of the representative Asiatic toad (Bufo gargarizans) provides a good reference to resolve this issue. In the present study, we sequenced the transcriptomes of parotoid gland, dorsal skin and liver from the Asiatic toad. Combining our data with 35 previously published transcriptomes across eight different tissues from the same species but from different locations, we constructed a comprehensive gene co-expression network of the Asiatic toad with the assistance of the reference genome assembly. We identified 2,701 co-expressed genes in the toxin-producing tissues (including parotoid gland and dorsal skin). By comparative genomic analysis, we identified 599 expanded gene families with 2,720 genes. Through overlapping these co-expressed genes in the toad toxin-producing tissues, we observed that three cytochrome P450 (Cyp) family members (Cyp27a1, Cyp2c29, and Cyp2c39) were significantly enriched in pathways related to cholesterol metabolism. Cholesterol is a critical precursor to steroids, and the known main steroidal toxins of bufadienolides are considered as the major bioactive components in the parotoid glands of Asiatic toad. We found 3-hydroxy-methylglutaryl CoA reductase (hmgcr), encoding the major rate-limiting enzyme for cholesterol biosynthesis, appears with multiple copies in both Asiatic toad and common toad, possibly originating from a tandem duplication event. The five copies of hmgcr genes consistently displayed higher transcription levels in the parotoid gland when compared with the abdominal skin, suggesting it as a vital candidate gene in the involvement of toad toxin production. Taken together, our current study uncovers transcriptomic and gene-family dynamic evidence to reveal the vital role of both expanded gene copies and gene expression changes for production of toad toxins.
Study on the synergistic effect of foreign trade, technological progress, and carbon emissions
Authors: Zhang Guohua , Wang Hao , Hua Xin , Liao Yiyi , Peng Lin
Published: July 2022

A primary development plan for a country is to attain carbon neutrality and high-quality international commerce development. This study uses panel data from 30 provinces in mainland China to analyze the dynamic interplay between international trade, technological innovation, and carbon emissions. The findings show that foreign trade, technological progress, and carbon emissions all have their own “economic inertia” that can be self-motivated and self-reinforcing. Foreign commerce and carbon emissions are mutually inhibiting, but technical progress and carbon emissions are mutually reinforcing. This illustrates that achieving a positive cycle of international trade, technological improvement, and carbon emissions necessitates a significant baseline need. Overcoming carbon trade barriers is currently the most difficult challenge for Chinese enterprises involved in foreign commerce. Low-carbon technology advancements are a critical part in this process. Our research strengthens the positive connections between international trade and carbon emissions as a result of technological improvement and proposes a feasible plan for international trade to achieve carbon peaking and carbon neutrality.
Transcriptomic Response of Fusarium verticillioides to Variably Inhibitory Environmental Isolates of Streptomyces
Authors: Satterlee Timothy R. , Williams Felicia N. , Nadal Marina , Glenn Anthony E. , Lofton Lily W. , Duke Mary V. , Scheffler Brian E. , Gold Scott E.
Published: July 2022

Fusarium verticillioides is a mycotoxigenic fungus that is a threat to food and feed safety due to its common infection of maize, a global staple crop. A proposed strategy to combat this threat is the use of biological control bacteria that can inhibit the fungus and reduce mycotoxin contamination. In this study, the effect of multiple environmental isolates of Streptomyces on F. verticillioides was examined via transcriptome analysis. The Streptomyces strains ranged from inducing no visible response to dramatic growth inhibition. Transcriptionally, F. verticillioides responded proportionally to strain inhibition with either little to no transcript changes to thousands of genes being differentially expressed. Expression changes in multiple F. verticillioides putative secondary metabolite gene clusters was observed. Interestingly, genes involved in the fusaric acid gene cluster were suppressed by inhibitory strains of Streptomyces. A F. verticillioides beta-lactamase encoding gene (FVEG_13172) was found to be highly induced by specific inhibitory Streptomyces strains and its deletion increased visible response to those strains. This study demonstrates that F. verticillioides does not have an all or nothing response to bacteria it encounters but rather a measured response that is strain specific and proportional to the strength of inhibition.
Determinants of fluconazole resistance and the efficacy of fluconazole and milbemycin oxim combination against Candida parapsilosis clinical isolates from Brazil and Turkey
Authors: Daneshnia Farnaz , Hilmioğlu Polat Süleyha , Ilkit Macit , Shor Erika , de Almeida Júnior João Nobrega , Favarello Larissa M. , Colombo Arnaldo Lopes , Arastehfar Amir , Perlin David S.
Published: July 2022

Fluconazole-resistant Candida parapsilosis (FLZR-CP) outbreaks are a growing public health concern and have been reported in numerous countries. Patients infected with FLZR-CP isolates show fluconazole therapeutic failure and have a significantly increased mortality rate. Because fluconazole is the most widely used antifungal agent in most regions with outbreaks, it is paramount to restore its antifungal activity. Milbemycin oxim (MOX), a well-known canine endectocide, is a potent efflux pump inhibitor that significantly potentiates the activity of fluconazole against FLZR C. glabrata and C. albicans. However, the FLZ-MOX combination has not been tested against FLZR-CP isolates, nor is it known whether MOX may also potentiate the activity of echinocandins, a different class of antifungal drugs. Furthermore, the extent of involvement of efflux pumps CDR1 and MDR1 and ergosterol biosynthesis enzyme ERG11 and their link with gain-of-function (GOF) mutations in their transcription regulators (TAC1, MRR1, and UPC2) are poorly characterized among FLZR-CP isolates. We analyzed 25 C. parapsilosis isolates collected from outbreaks in Turkey and Brazil by determining the expression levels of CDR1, MDR1, and ERG11, examining the presence of potential GOF mutations in their transcriptional regulators, and assessing the antifungal activity of FLZ-MOX and micafungin-MOX against FLZR and multidrug-resistant (MDR) C. parapsilosis isolates. ERG11 was found to be universally induced by fluconazole in all isolates, while expression of MDR1 was unchanged. Whereas mutations in MRR1 and UPC2 were not detected, CDR1 was overexpressed in three Brazilian FLZR-CP isolates, which also carried a novel TAC1L518F mutation. Of these three isolates, one showed increased basal expression of CDR1, while the other two overexpressed CDR1 only in the presence of fluconazole. Interestingly, MOX showed promising antifungal activity against FLZR isolates, reducing the FLZ MIC 8- to 32-fold. However, the MOX and micafungin combination did not exert activity against an MDR C. parapsilosis isolate. Collectively, our study documents that the mechanisms underpinning FLZR are region specific, where ERG11 mutations were the sole mechanism of FLZR in Turkish FLZR-CP isolates, while simultaneous overexpression of CDR1 was observed in some Brazilian counterparts. Moreover, MOX and fluconazole showed potent synergistic activity, while the MOX-micafungin combination showed no synergy.
Efficient derivation of chimeric-antigen receptor-modified TSCM cells
Authors: Kranz Emiko , Kuhlmann Charles J. , Chan Joshua , Kim Patrick Y. , Chen Irvin S. Y. , Kamata Masakazu
Published: July 2022

Chimeric-antigen receptor (CAR) T-cell immunotherapy employs autologous-T cells modified with an antigen-specific CAR. Current CAR-T manufacturing processes tend to yield products dominated by effector T cells and relatively small proportions of long-lived memory T cells. Those few cells are a so-called stem cell memory T (TSCM) subset, which express naïve T-cell markers and are capable of self-renewal and oligopotent differentiation into effector phenotypes. Increasing the proportion of this subset may lead to more effective therapies by improving CAR-T persistence; however, there is currently no standardized protocol for the effective generation of CAR-TSCM cells. Here we present a simplified protocol enabling efficient derivation of gene-modified TSCM cells: Stimulation of naïve CD8+ T cells with only soluble anti-CD3 antibody and culture with IL-7 and IL-15 was sufficient for derivation of CD8+ T cells harboring TSCM phenotypes and oligopotent capabilities. These in-vitro expanded TSCM cells were engineered with CARs targeting the HIV-1 envelope protein as well as the CD19 molecule and demonstrated effector activity both in vitro and in a xenograft mouse model. This simple protocol for the derivation of CAR-TSCM cells may facilitate improved adoptive immunotherapy.
An update on Ym1 and its immunoregulatory role in diseases
Authors: Kang Qi , Li Luyao , Pang Yucheng , Zhu Wenhua , Meng Liesu
Published: July 2022

Ym1 is a rodent-specific chitinase-like protein (CLP) lacking catalytic activity, whose cellular origins are mainly macrophages, neutrophils and other cells. Although the detailed function of Ym1 remains poorly understood, Ym1 has been generally recognized as a fundamental feature of alternative activation of macrophages in mice and hence one of the prevalent detecting targets in macrophage phenotype distinguishment. Studies have pointed out that Ym1 may have regulatory effects, which are multifaceted and even contradictory, far more than just a mere marker. Allergic lung inflammation, parasite infection, autoimmune diseases, and central nervous system diseases have been found associations with Ym1 to varying degrees. Thus, insights into Ym1’s role in diseases would help us understand the pathogenesis of different diseases and clarify the genuine roles of CLPs in mammals. This review summarizes the information on Ym1 from the gene to its expression and regulation and focuses on the association between Ym1 and diseases.
Comprehensive analysis of mycobacterium tuberculosis antigen-specific CD4+ T cell responses restricted by single HLA class II allotype in an individual
Authors: Lee Yong-Hun , Hyun You-Seok , Jo Hyeong-A , Baek In-Cheol , Kim Sun-Mi , Sohn Hyun-Jung , Kim Tai-Gyu
Published: July 2022

Mycobacterium tuberculosis infection is generally asymptomatic as latent tuberculosis, but it is still known as the world’s leading bacterial cause of death. The diagnosis of latent tuberculosis infection relies on the evidence of cellular immunity to mycobacterial antigens. Since the association between HLA class II and tuberculosis infection has been reported in several population groups, a detailed study on the CD4+ T cell response to major tuberculosis antigens is needed. To elucidate which HLA class II allotypes in an individual are preferentially used in tuberculosis, CD4+ T cells specific to TB10.4, Ag85b, ESAT-6, and CFP-10 of Mycobacterium tuberculosis antigens were analyzed comprehensively. A total of 33 healthy donors were analyzed by ex vivo and cultured ELISPOT using panels of artificial antigen-presenting cells expressing a single HLA class II allotype. The CD4+ T cell responses were increased by an average of 39-fold in cultured ELISPOT compared with ex vivo ELISPOT. In ex vivo and cultured ELISPOT, CD4+ T cell responses showed significantly higher by HLA-DR than those of HLA-DQ and HLA-DP locus. In cultured ELISPOT, 9 HLA-DR allotypes, 4 HLA-DQ allotypes, and 3 HLA-DP allotypes showed positive CD4+ T cell responses. Among ten donors with positive CD4+ T cell responses when tested for mixed Mycobacterium tuberculosis antigens, seven donors were positive for only a single allotype, and three were positive for two allotypes in an individual. However, only one allotype was used for a single antigen-specific response when a single tuberculosis antigen was used individually. These results on the distribution of HLA class II allotypes showing high CD4+ T-cell responses to Mycobacterium tuberculosis antigens and the intra-individual allotype dominance will provide valuable information for understanding the immunobiology and immunogenetics of tuberculosis, which can contribute to the development of more effective vaccines.
Design and implementation of a mobile app for the pharmacotherapeutic follow-up of patients diagnosed with immune-mediated inflammatory diseases: eMidCare
Authors: Romero-Jimenez Rosa , Escudero-Vilaplana Vicente , Chamorro-de-Vega Esther , Ais-Larisgoitia Arantza , Lobato-Matilla Elena , Somoza-Fernández Beatriz , Ruiz-Briones Paula , González Carlos , Baniandrés Ofelia , Menchén Luis , Lobo-Rodríguez Carmen , Herranz Ana , Sanjurjo María
Published: July 2022

Background

Pharmacotherapeutic management of immune-mediated inflammatory diseases (IMID) has become more complex due to the development of new treatments, such as biological therapies. Mobile health, especially apps, can provide IMID patients with greater autonomy and facilitate communication with healthcare professionals. Our objective was to design and implement an app for remote monitoring and communication with IMID patients.

Methods

A multidisciplinary group was created to design and develop an app for IMID patients in a tertiary hospital. The app functionalities were identified through a focus group with IMID patients and through an observational, descriptive study of available apps for IMID patients at App Store and Play Store platforms. Once the app was designed and developed, we offered the app to IMID patients who initiated a new biological therapy. The inclusion period was from December 2020 to August 2021. We performed an observational, longitudinal study to assess the app’s impact on medication safety, communication, satisfaction, and usability.

Results

We designed an app (eMidCare®) with the following modules: My Medication, My Questionnaires, Adverse Events, Useful Information, Messages, and Patient Profile. A total of 85 patients were installed with the app. The median (range) follow-up time for app use was 123 (5-270) days. In the My Medication module, 100% of patients registered their biological therapy and 25.9% also used this module to record each dose of medication administered. A total of 82 adverse events (AEs) were registered. Thirty-two percent of the patients registered at least 1 AE. The most frequent AEs were fatigue, injection site reaction, headache, and nausea. Fifty-two percent of patients used the Messages module to communicate with healthcare professionals. The most frequent messages concerned doubts about managing AEs (26.2%) and drug interactions (18.9%). The satisfaction survey yielded a median (range) score of 9.1 (7-10) out of 10.

Conclusions

We developed an app, eMidCare®, which reminds patients to take their medication, enables them to record AEs, and helps them communicate with healthcare professionals. Approximately one-third of the patients registered the administration of the biological therapies and registered at least 1 AE. The most used and most satisfactory functionality was communication with health professionals.
Effects of helicobacter pylori on tumor microenvironment and immunotherapy responses
Authors: Deng Ruiyi , Zheng Huiling , Cai Hongzhen , Li Man , Shi Yanyan , Ding Shigang
Published: July 2022

Helicobacter pylori is closely associated with gastric cancer. During persistent infection, Helicobacter pylori can form a microenvironment in gastric mucosa which facilitates the survival and colony formation of Helicobacter pylori. Tumor stromal cells are involved in this process, including tumor-associated macrophages, mesenchymal stem cells, cancer-associated fibroblasts, and myeloid-derived suppressor cells, and so on. The immune checkpoints are also regulated by Helicobacter pylori infection. Helicobacter pylori virulence factors can also act as immunogens or adjuvants to elicit or enhance immune responses, indicating their potential applications in vaccine development and tumor immunotherapy. This review highlights the effects of Helicobacter pylori on the immune microenvironment and its potential roles in tumor immunotherapy responses.
Lentinan -triggered butyrate-producing bacteria drive the expulsion of the intestinal helminth Trichinella spiralis in mice
Authors: Jin Xuemin , Liu Yi , Vallee Isabelle , Karadjian Gregory , Liu Mingyuan , Liu Xiaolei
Published: July 2022

Trichinellosis caused by Trichinella spiralis is a serious zoonosis with a worldwide distribution. Lentinan (LNT) is known to modulate the intestinal environment with noted health benefits, yet the effect of LNT against intestinal helminth is unknown. In our study, we first observed that LNT could trigger worm expulsion by promoting mucus layer functions through alteration of gut microbiota. LNT restored the abundance of Bacteroidetes and Proteobacteria altered by T. spiralis infection to the control group level. Interestingly, LNT triggered the production of butyrate. Then, we determined the deworming capacity of probiotics (butyrate-producing bacteria) in mice. Collectively, these findings indicated that LNT could modulate intestinal dysbiosis by T. spiralis, drive the expulsion of intestinal helminth and provided an easily implementable strategy to improve the host defence against T. spiralis infection.
Aedes aegypti CLIPB9 activates prophenoloxidase-3 in the presence of CLIPA14 after fungal infection
Authors: Ji Yannan , Lu Tengfei , Zou Zhen , Wang Yanhong
Published: July 2022

Melanization is an integral part of the insect defense system and is often induced by pathogen invasion. Phenoloxidases (POs) are critical enzymes that catalyze melanin formation. PO3 is associated with the antifungal response of the mosquito, Aedes aegypti, but the molecular mechanism of the prophenoloxidase-3 (PPO3) activation is unclear. Here we report that PPO3 cleavage activation is mediated by a clip-domain serine protease, CLIPB9. We purified recombinant CLIPB9 and found that it cleaved PPO3 and increased PO activity in the hemolymph. We then identified CLIPA14 (a serine protease homolog) by co-immunoprecipitation using anti-CLIPB9 antibody. After being cleaved by CLIPB9, Ae. aegypti CLIPA14 acted as a cofactor for PPO3 activation. In addition, dsRNA co-silencing of CLIPB9 and CLIPA14 genes reduced melanization after infection with the entomopathogen, Beauveria bassiana, making the adult mosquitoes more sensitive to fungal infection. These results illustrate the roles of CLIPB9 and CLIPA14 in the PPO activation pathway and revealed the complexity of the upstream serine protease network controlling melanization.
Viral immunogenic footprints conferring T cell cross-protection to SARS-CoV-2 and its variants
Authors: Antonio Eduardo Cheuiche , Meireles Mariana Rost , Bragatte Marcelo Alves de Souza , Vieira Gustavo Fioravanti
Published: July 2022

COVID-19 brought scenes from sci-fi movies into real life. Infected individuals include asymptomatic cases to severe disease leading to death, suggesting the involvement of the genetic constitution of populations and pathogens contributing to differential individuals’ outcomes. To investigate shared immunogenic features between SARS-CoV-2 targets and other coronaviruses, we modeled their peptides in 3D structures of HLA-A*02:01 (pMHC), comparing their molecular surfaces These structures were also compared with a panel of epitopes from unrelated viruses, looking for potential triggers conferring cross-protection in uninfected individuals. As expected, SARS-CoV 1 and 2 peptides share molecular and physicochemical features, providing an explanation for the verified experimental immunogenicity among them. Surprisingly, even discordant sequences from human coronaviruses 229E, OC43 and epitopes from unrelated viruses involved in endemic human infections exhibit similar fingerprints of immunogenicity with SARS-CoV-2 peptides. The same approach indicates a conserved CD8+ T cell recognition between Wuhan SARS-CoV-2 sequences and altered peptides from Variants of Concern. Examination of structural data over epitope sequence analysis here could explain how previous infections may produce a heterologous immunity response in a global scale against emergent diseases such as Covid-19, mitigating its full lethal potential, and paves the way for the development of wide spectrum vaccine development.
From IL-17 to IFN-γ in inflammatory skin disorders: Is transdifferentiation a potential treatment target?
Authors: Belpaire Arno , van Geel Nanja , Speeckaert Reinhart
Published: July 2022

The targeted inhibition of effector cytokines such as interleukin 17 (IL-17) in psoriasis and IL-13 in atopic dermatitis offers impressive efficacy with a favorable side effect profile. In contrast, the downregulation of interferon gamma (IFN-γ) in T helper (Th) 1-dominant skin disorders may lead to more adverse events, given the crucial role of IFN-γ in antiviral and antitumoral immunity. Modulating Th17 and Th2 cell differentiation is performed by blocking IL-23 and IL-4, respectively, whereas anti-IL-12 antibodies are only moderately effective in downregulating Th1 lymphocyte differentiation. Therefore, a targeted approach of IFN-γ-driven disorders remains challenging. Recent literature suggests that certain pathogenic Th17 cell subsets with Th1 characteristics, such as CD4+CD161+CCR6+CXCR3+IL-17+IFN-y+ (Th17.1) and CD4+CD161+CCR6+CXCR3+IL-17-IFN-y+ (exTh17), are important contributors in Th1-mediated autoimmunity. Differentiation to a Th17.1 or exTh17 profile results in the upregulation of IFN-y. Remarkably, these pathogenic Th17 cell subsets are resistant to glucocorticoid therapy and the dampening effect of regulatory T cells (Treg). The identification of Th17.1/exTh17 cells in auto-immune disorders may explain the frequent treatment failure of conventional immunosuppressants. In this review, we summarize the current evidence regarding the cellular plasticity of Th17 cells in inflammatory skin disorders. A deeper understanding of this phenomenon may lead to better insights into the pathogenesis of various skin diseases and the discovery of a potential new treatment target.