bluuebunny/crossref_metadata_2025 huggingface dataset:
Preserved glycemic control and baroreflex efficacy in young adult hypertensive female obese Zucker rats
Authors: Chaudhary Parul , Das-Earl Paromita , Schreihofer Ann M.
Published: May 2021

Obese Zucker rats (OZRs) develop hypertension and hyperinsulinemia by 3 mo of age. Male OZRs also have diminished baroreflex-mediated activation of nucleus tractus solitarius (NTS) and bradycardia, which are improved by correcting their hyperglycemia. Conversely, 3-mo-old female OZRs and lean Zucker rats (LZRs) have equivalent baroreflex-mediated bradycardia that is impaired in 6-mo-old OZRs. We hypothesized that 3-mo-old female OZRs maintain NTS activation and baroreflexes coincident with glycemic control. We also hypothesized that 6-mo-old female OZRs develop impaired baroreflexes with hyperglycemia and diminished NTS activation. In 12- to 16-wk-old females, sympathetic nerve activity (SNA) and arterial pressure (AP) were higher in OZRs than LZRs. However, baroreflex-mediated inhibition of SNA and bradycardia were equivalent in female OZRs and LZRs. Unlike deficits in male OZRs, female OZRs and LZRs had no differences in phenylephrine-induced c-Fos expression in NTS or decreases in SNA and AP evoked by glutamate into NTS. Compared with hyperglycemia in male OZRs (217.9 ± 34.4 mg/dL), female OZRs had normal fed blood glucose levels (108.2 ± 1.6 mg/dL in LZRs and 113.6 ± 3.5 mg/dL in OZRs) with emerging glucose intolerance. Conscious 24- to 27-wk-old female OZRs had impaired baroreflex-mediated bradycardia, but fed blood glucose was modestly elevated (124.2 ± 5.2 mg/dL) and phenylephrine-induced c-Fos expression in NTS was comparable to LZRs. These data suggest that better glycemic control in 3-mo-old female OZRs prevents diminished NTS activation and baroreflexes, supporting the notion that hyperglycemia impairs these responses in male OZRs. However, 6-mo-old female OZRs had impaired baroreflex efficacy without diminished NTS activation or pronounced hyperglycemia, suggesting baroreflex deficits develop by different mechanisms in female and male OZRs.
MRCP as a biomarker of motor action with varying degree of central and peripheral contribution as defined by ultrasound imaging
Authors: Sosnowska A. , Gollee H. , Vučković A.
Published: May 2021

Ultrasound imaging can detect subtle muscle movements (twitches) that are not detectable with electromyography. Almost a quarter of trials of imagined movements in able-bodied people are accompanied by twitches. Analysis of movement-related cortical potential showed that motor imagination with twitches is a condition distinguishable from motor imagination without twitches and from motor attempts.
The duration of withdrawal affects the muscarinic signaling in the nucleus accumbens after chronic morphine exposure in neonatal rats
Authors: Jiang Xiao , Zhang Jian-Jun , Song Sen , Li Yonghui , Sui Nan
Published: May 2021

We investigated for the first time how the duration of withdrawal affects mAChRs functions in the nucleus accumbens in neonatal rats. Compared with short-term withdrawal time, rats showed downregulation of presynaptic and post/extrasynaptic mAChRs functions during long-term withdrawal time. Our finding introduces a new possible correlation between the mAChRs dysfunction in the nucleus accumbens and the development of withdrawal in neonates.
Correlated structure of neuronal firing in macaque visual cortex limits information for binocular depth discrimination
Authors: Smith Jackson E. T. , Parker Andrew J.
Published: May 2021

Correlated noise reduces the stimulus information in visual cortical neurons during experimental performance of binocular depth discriminations. The temporal scale of these correlations is important. Rapid (20–30 ms) correlations reduce information within and between areas V1 and V4, whereas slow (>100 ms) correlations between areas do not. Separate cortical areas appear to act together to maintain signal fidelity. Rapid correlations reduce the neuronal signal difference between stimuli and adversely affect perceptual discrimination.
Biomechanical Performance of Menisci under Cyclic Loads
Authors: Tseng J.-G. , Huang B.-W. , Chen Y.-T. , Kuo S.-J. , Tseng G.-W.
Published: May 2021

The meniscus, composed of fibrocartilage, is a very important part of the human knee joint that behaves like a buffer. Located in the middle of the femoral condyles and the tibial plateau, it is a necessary structure to maintain normal biomechanical properties of the knee. Whether walking or exercising, the meniscus plays a vital role to protect the articular surface of both the femoral condyles and the tibial plateau by absorbing the conveying shock from body weight. However, modern people often suffer from irreversible degeneration of joint tissue due to exercise-induced harm or aging. Therefore, understanding its dynamic characteristics will help to learn more about the actual state of motion and to avoid unnecessary injury. This study uses reverse engineering equipment, a 3D optical scanner, and a plastic teaching human body model to build the geometry of knee joint meniscus. Then, the finite element method (FEM) is employed to obtain the dynamic characteristics of the meniscus. The results show the natural frequencies, mode shapes, and fatigue life analysis of meniscus, with real human material parameters. The achieved results can be applied to do subsequent knee dynamic simulation analysis, to reduce the knee joint and lower external impacts, and to manufacture artificial meniscus through tissue engineering.
Progress of Interference of Traditional Chinese Medicine on Cirrhosis Treated with Bone Marrow Mesenchymal Stem Cells
Authors: Wang Yaxin , Zhang Huicun , Wang Hongbing
Published: May 2021

Transplantation of bone marrow mesenchymal stem cells has attracted more and more attention as a regenerative therapy for the treatment of liver diseases. A large number of studies have shown that this kind of cells can inhibit the activation of hepatic stellate cells and regulate tissue homeostasis and immune system via a variety of ways. Meanwhile, bone marrow mesenchymal stem cells can inhibit apoptosis of hepatocyte, improve liver function, and reduce inflammation through multiple pathways. These cells have a broad prospect in the treatment of liver cirrhosis. At present, there are many studies on the specific mechanism of bone marrow mesenchymal stem cells transplantation in the treatment of liver cirrhosis. This paper reviews the pathogenesis of liver cirrhosis and the mechanism of bone marrow mesenchymal stem cells transplantation in the treatment of liver cirrhosis, discusses the effectiveness of traditional Chinese medicine method in enhancing the efficacy of bone marrow mesenchymal stem cells transplantation, and looks forward to its application prospect in the future.
The
G
-Asymptotic Tracking Property and
G
-Asymptotic Average Tracking Property in the Inverse Limit Spaces under Group Action
Authors: Ji Zhanjiang
Published: May 2021

Firstly, we introduce the definitions of

G

-asymptotic tracking property,

G

-asymptotic average tracking property, and

G

-quasi-weak almost-periodic point. Secondly, we study their dynamical properties and characteristics. The results obtained improve the conclusions of asymptotic tracking property, asymptotic average tracking property, and quasi-weak almost-periodic point in the inverse limit space and provide the theoretical basis and scientific foundation for the application of tracking property in computational mathematics, biological mathematics, and computer science.
Estimating the Possibility of Lead Contamination in Soil Surface due to Lead Deposition in Atmosphere
Authors: Binh Nguyen Thi Lan , Hoang Nguyen Trung , Truc Nguyen Thi Thanh , Khang Vu Dinh , Le Hung Anh
Published: May 2021

An increase in heavy metal soil contamination, especially lead, in the industrial area or near industrial areas has become a serious environmental problem. An industrial zone including paints, electrical plants, metal works, machining, and smelting factories, in the suburban of Ho Chi Minh City, was chosen as the study area. Soil samples were collected from the industrial area and in the residential area next to the industrial area for three experiments, namely, lead content in the surface soils, lead leachate into the water, and movement of lead in soil. Then, the results were compared to the values in the Soil Contamination Countermeasures Law of the Japan Ministry of Environment to assess the possibility of soil contamination which may cause health risks to a human living in that area. The results of the analysis show that the soil has been contaminated by lead. In particular, the lead concentrations of the surface soil samples are 23–35 mg kg-1, while the lead elution of soil samples is quite high, about 0.6 mg L-1. With these results, the soil can harm people by direct ingestion. More importantly, this work proves that lead species have been going down gradually. To assess the possibility of lead approaching groundwater, more further studies need to be achieved.
Study on the Mechanism of Stabilizing Loess with Lime: Analysis of Mineral and Microstructure Evolution
Authors: Ma Yawei , Chen Wenwu
Published: May 2021

X‐ray diffraction (XRD) technique was adopted to test the mineral composition of quicklime‐solidified loess with different lime‐adding rates at different curing periods. Scanning electron microscopy (SEM) and nitrogen adsorption were used to analyze the microporous structure of the solidified loess. The unconfined compressive strength and limit moisture content of solidified loess were combined to analyze the evolution mechanism of mineral composition and microstructure of solidified loess with the change of curing period and clarify the mechanism of quicklime‐solidified loess. The results showed reduced content of clay minerals and decrease in the number of large pores due to increase of hydrates and pozzolanic products during extended curing period. The solidified soil fabric transformed from a compact structure into a mesh structure composing of acicular crystal and cementation. The main reasons for strength increase and change of liquid and plastic limits with the lime‐solidified loess after extended curing are the change of the substance and the microstructure.
Research on the Development Path and Growth Mechanism of Unicorn Enterprises
Authors: Guo Kai , Zhang Tiantian
Published: May 2021

Combining with the growth environment of Unicorns, from the aspects of emerging industries, business environment, platform support, and financial support, we propose an overall analysis framework for the existence or absence of Unicorns, use the fuzzy set qualitative comparative analysis (fsQCA) method to carry out configuration analysis on the status quo of Unicorns in 40 cities in China, and analyze the cultivation path of Unicorns. The research results indicate that the synergy of emerging industries, business environment, platform support, and financial support can foster Unicorns. According to the differences in the core conditions in the configuration and the characteristics of the cases contained, it is divided into two cultivation paths, which are driven by emerging industries and supported by the business environment; combining with the status quo and characteristics of the cities where Unicorns are missing, it provides suggestions for the selection of the cultivation path of Unicorns in different regions.
Software-Defined Networking: An Evolving Network Architecture—Programmability and Security Perspective
Authors: Kaliyamurthy Nitheesh Murugan , Taterh Swapnesh , Shanmugasundaram Suresh , Saxena Ankit , Cheikhrouhou Omar , Ben Elhadj Hadda
Published: May 2021

Software-defined networking is an evolving network architecture beheading the traditional network architecture focusing its disadvantages in a limited perspective. A couple of decades before, programming and networking were viewed as different domains which today with the lights of SDN bridging themselves together. This is to overcome the existing challenges faced by the networking domain and an attempt to propose cost-efficient effective and feasible solutions. Changes to the existing network architecture are inevitable considering the volume of connected devices and the data being held together. SDN introduces a decoupled architecture and brings customization within the network making it easy to configure, manage, and troubleshoot. This paper focuses on the evolving network architecture, the software-defined networking. Unlike a generic view on the evolving network, which makes work as a review, this work addresses various perspectives of the architecture leaving it an intermediate work in between the review of the literature and implementation, contributing towards factors like the design, programmability, security, security behaviors, and security lapses. This paper also analyses various weak points of the architecture and evolves the attack vectors in each plane leaving a conclusion to further progress towards identifying the impacts of the attacks and proposing mitigation strategies.
Notas sobre o fazer de uma psicóloga escolar na pandemia
Authors: Souza Carolina Apolinário de
Published: May 2021

Sabemos que o ato de educar é uma prática social discursiva, imergindo a criança na linguagem e a tornando capaz de fazer laço social. Entretanto, o ensino a  distância (EAD) impôs-se como realidade atual. Como consequência, as restrições sociais e esse novo modo de estar na escola impactaram a saúde mental de alunos, de pais e de professores, e o psicólogo escolar foi convidado a ajudar na construção de formas possíveis de atravessamento do mal-estar. Este artigo, portanto, propõe reflexões acerca do meu trabalho como psicóloga escolar de orientação psicanalítica. Atuando em uma escola particular, durante uma pandemia que afastou os alunos da escola, defendo que a escola seja um “lugar de vida” (Kupfer, 2010), constituindo-se como palco de construção de sentidos para experiências prazerosas e desafiadoras.
Custos assimétricos e regulação em operadoras de planos de saúde
Authors: Avelar Ewerton Alex , Santos Wesley Cirino dos , Souza Antônio Artur de , Cailleau Romain
Published: May 2021

Este artigo apresenta os resultados de uma pesquisa que visou analisar efeitos da regulação da Agência Nacional de Saúde Suplementar (ANS) sobre o comportamento assimétrico dos custos em operadoras de planos de saúde (OPS) brasileiras. Especificamente, enfocaram-se as operadoras classificadas como cooperativas médicas e medicina de grupo entre os anos de 2010 e 2018. Os dados financeiros e operacionais empregados para o seu desenvolvimento foram secundários e coletados junto à ANS. A análise dos dados foi realizada por meio de regressão com dados em painel. Os modelos estimados consideraram diferentes proxies de custos (variável dependente) e variáveis explicativas. Verificou-se que duas proxies de custos tiveram relações significantes em todos os modelos estimados: despesas com vendas, gerais e administrativas, e custo total. No que se refere às variáveis de regulação, observou-se que uma delas foi considerada significante em ambas as modalidades: a razão de dependência das OPS. Esta pesquisa apresenta diversas contribuições aos diferentes stakeholders das OPS, tais como: a ANS, seus gestores e a sociedade. Podem ser citadas como inovações da pesquisa desenvolvida em relação aos estudos predecessores: (a) verificou-se a importância de se considerar a natureza jurídica das organizações, mesmo que pertencentes a um mesmo setor (proxy de estrutura de custos), para se analisar o fenômeno da assimetria de custos; (b) foram propostas diferentes variáveis regulatórias para compreender esse fenômeno, demonstrando sua relevância em setores bastante regulados; e (c) destacou-se a importância do uso de distintas proxies para se mensurar a assimetria de custos.
Impacto do COAP sobre o acesso à atenção básica no Ceará e Mato Grosso do Sul por meio da análise de séries temporais interrompidas
Authors: Pires Débora Castanheira , Campos Mônica Rodrigues , Emmerrick Isabel Martins
Published: May 2021

OBJETIVO: Analisar o impacto da implementação do Contrato Organizativo de Ação Pública (COAP) sobre a ampliação do acesso à atenção básica nos estados do Ceará e Mato Grosso do Sul. MÉTODOS: Utilizou-se o método de séries temporais interrompidas para analisar o efeito do COAP sobre a cobertura da atenção básica (CobAB) e sobre as taxas de internação evitáveis. Para analisar os efeitos do aumento da CobAB sobre as internações evitáveis ao longo do tempo, foram utilizados modelos de séries temporais não segmentadas. RESULTADOS: Os resultados mostraram que a implementação do COAP teve impacto positivo sobre o aumento da cobertura nos dois casos, o que não aconteceu nos controles. Contudo, esse impacto não se refletiu na diminuição das taxas de internação por condições sensíveis à atenção básica (ICSAB) ou por causas evitáveis agudas. Quando analisamos os efeitos do aumento da CobAB sobre as internações evitáveis entre 2009 e 2016, observamos que a cobertura teve impacto positivo na diminuição da taxa de ICSAB apenas no Ceará, apesar de as internações terem tendência significativa de queda no tempo tanto neste estado quanto no Mato Grosso do Sul, exceto por infecções respiratórias agudas. CONCLUSÕES: O COAP continua sendo o instrumento regulador da regionalização vigente, contudo, os resultados obtidos pela adesão a ele na expansão da atenção básica no Ceará e no Mato Grosso do Sul fazem questionar se o modelo contratual, tal como previsto, é o melhor instrumento para o avanço da regionalização do Sistema Único de Saúde.
Clinical Impact of eCASH Combined with Nano-Silver Dressings for the Treatment of II Burn Wounds
Authors: Yang Minlie , Zhou Xiaojin , Ding Xian , Zhu Yugang , Jiang Donglin , Ding Lingtao , Chu Guoping , Cheng Jia , Lv Guozhong
Published: May 2021

92 cases of second degree burn wounds treated in our hospital from January 2019 to December 2019 were selected as the research objects, and the clinical effect of eCASH concept treatment combined with nano silver dressing on the second degree burn wounds was studied. The patients were
randomly divided into control group (n = 46) and observation group (n = 46). The control group was treated with conventional treatment combined with eCASH concept nursing, and the observation group was treated with eCASH concept combined with nano silver dressing. We found that
the effective rate of the observation group was 95.65% higher than that of the control group (76.09%); the wound healing time of the observation group was significantly lower than that of the control group; the average VAS pain score of the observation group during wound treatment was significantly
lower than that of the control group The total positive rate of bacterial detection in the observation group was 8.70%, which was lower than 28.26% in the control group; the incidence of complications in the observation group was 2.17% lower than that in the control group (17.39%); the differences
were statistically significant (all P < 0.05). These results indicate that eCASH concept combined with nano silver dressing in the treatment of second degree burn wounds has a significant effect, which can accelerate the recovery, reduce the pain, and effectively reduce the total
positive rate of bacterial detection and the incidence of complications.
Collagen Type I α-1 Promotes Malignant Glioma Cell Proliferation and Is Associated with Glioma Prognosis
Authors: Chunsik Im Bruce , Li Junjun , Kessete Afewerky Henok , Jiang Xiaobing
Published: May 2021

Collagen type I α-1 chain (COL1A1) is closely involved in the advancement of various tumors, yet the role of COL1A1 in the progression of glioma is not clear. Herein, we evaluated the effect of COL1A1 on glioma cell proliferation. The effect of COL1A1 on glioma cell proliferation
was assessed through overexpression or knockdown of COL1A1. The CCK-8 and colony formation assays, as well as immunohistochemistry (IHC) were used to detect COL1A1 expression in different glioma grades. U-87MG as well as U-251MG cells were stably-inserted with lentivirus containing COL1A1
through transfection, we additionally used qRT-PCR as well as Western blot assay to validate their overexpression efficiencies. COL1A1 mRNA and protein levels were upregulated in the high-grade glioma (HGG) compared to the low-grade glioma (LGG). COL1A1 IHC score was remarkably higher in HGG
than LGG. The staining index (SI) further showed that COL1A1 protein levels were higher in HGG than LGG. The Kaplan–Meier analysis showed that elevated COL1A1 mRNA levels were obviously correlated with lower overall survival (OS) and disease-free survival (DFS) for brain glioma patients.
COL1A1 mRNA and protein levels were markedly upregulated in human glioma cell lines when compared with brain astrocyte cell lines. The high expression level of COL1A1 facilitated glioma cell proliferation. COL1A1 knockdown remarkably inhibited glioma cell proliferation. Thus, this research
shows that COL1A1 promotes glioma cell proliferation and is closely related to glioma prognosis.
Intervention and state strength: Association of Southeast Asian Nations and Economic Community of West African States compared
Authors: Suzuki Sanae
Published: May 2021

How can we explain variations in the approaches of regional organizations (ROs) to cross-border security threats, especially those derived from internal conflicts such as civil wars and unconstitutional changes of government? On the one hand, regional security threats appear regularly throughout the world. Pulling in the opposite direction, governments steadfastly insist on their sovereign right to conduct business within their borders as they see fit. In practice, some ROs have intervened more than others in the internal conflicts of their member states. How can we explain the difference? This article argues that ROs are intrusive when their member states share a belief that a state is too fragile to survive without intervention. Such a shared belief about state strength is fostered by historical developments, notably national economic development that strengthens state resources available to a regime, and past willingness of a regime to accept intervention. The argument is developed through a comparative analysis of the Association of Southeast Asian Nations and the Economic Community of West African States, respectively the world’s least and most intrusive ROs.
Subarachnoid hemorrhage in the emergency department
Authors: Patel Sima , Parikh Amay , Okorie Okorie Nduka
Published: May 2021

Background

Subarachnoid hemorrhage accounts for more than 30,000 cases of stroke annually in North America and encompasses a 4.4% mortality rate. Since a vast number of subarachnoid hemorrhage cases present in a younger population and can range from benign to severe, an accurate diagnosis is imperative to avoid premature morbidity and mortality. Here, we present a straightforward approach to evaluating, risk stratifying, and managing subarachnoid hemorrhages in the emergency department for the emergency medicine physician.

Discussion

The diversities of symptom presentation should be considered before proceeding with diagnostic modalities for subarachnoid hemorrhage. Once a subarachnoid hemorrhage is suspected, a computed tomography of the head with the assistance of the Ottawa subarachnoid hemorrhage rule should be utilized as an initial diagnostic measure. If further investigation is needed, a CT angiography of the head or a lumbar puncture can be considered keeping risks and limitations in mind. Initiating timely treatment is essential following diagnosis to help mitigate future complications. Risk tools can be used to assess the complications for which the patient is at greatest.

Conclusion

Subarachnoid hemorrhages are frequently misdiagnosed; therefore, we believe it is imperative to address the diagnosis and initiation of early management in the emergency medicine department to minimize poor outcomes in the future.
DSCMF: prediction of LncRNA-disease associations based on dual sparse collaborative matrix factorization
Authors: Liu Jin-Xing , Gao Ming-Ming , Cui Zhen , Gao Ying-Lian , Li Feng
Published: May 2021

Background

In the development of science and technology, there are increasing evidences that there are some associations between lncRNAs and human diseases. Therefore, finding these associations between them will have a huge impact on our treatment and prevention of some diseases. However, the process of finding the associations between them is very difficult and requires a lot of time and effort. Therefore, it is particularly important to find some good methods for predicting lncRNA-disease associations (LDAs).

Results

In this paper, we propose a method based on dual sparse collaborative matrix factorization (DSCMF) to predict LDAs. The DSCMF method is improved on the traditional collaborative matrix factorization method. To increase the sparsity, the L2,1-norm is added in our method. At the same time, Gaussian interaction profile kernel is added to our method, which increase the network similarity between lncRNA and disease. Finally, the AUC value obtained by the experiment is used to evaluate the quality of our method, and the AUC value is obtained by the ten-fold cross-validation method.

Conclusions

The AUC value obtained by the DSCMF method is 0.8523. At the end of the paper, simulation experiment is carried out, and the experimental results of prostate cancer, breast cancer, ovarian cancer and colorectal cancer are analyzed in detail. The DSCMF method is expected to bring some help to lncRNA-disease associations research. The code can access thehttps://github.com/Ming-0113/DSCMFwebsite.
IIMLP: integrated information-entropy-based method for LncRNA prediction
Authors: Li Junyi , Li Huinian , Ye Xiao , Zhang Li , Xu Qingzhe , Ping Yuan , Jing Xiaozhu , Jiang Wei , Liao Qing , Liu Bo , Wang Yadong
Published: May 2021

Background

The prediction of long non-coding RNA (lncRNA) has attracted great attention from researchers, as more and more evidence indicate that various complex human diseases are closely related to lncRNAs. In the era of bio-med big data, in addition to the prediction of lncRNAs by biological experimental methods, many computational methods based on machine learning have been proposed to make better use of the sequence resources of lncRNAs.

Results

We developed the lncRNA prediction method by integrating information-entropy-based features and machine learning algorithms. We calculate generalized topological entropy and generate 6 novel features for lncRNA sequences. By employing these 6 features and other features such as open reading frame, we apply supporting vector machine, XGBoost and random forest algorithms to distinguish human lncRNAs. We compare our method with the one which has more K-mer features and results show that our method has higher area under the curve up to 99.7905%.

Conclusions

We develop an accurate and efficient method which has novel information entropy features to analyze and classify lncRNAs. Our method is also extendable for research on the other functional elements in DNA sequences.
TREM2 promotes natural killer cell development in CD3−CD122+NK1.1+ pNK cells
Authors: Lee Hwa-Youn , Lee Eun-Hee , Yi Jawoon , Ji Kon-Young , Kim Su-Man , Choi Ha-Rim , Yee Su-Min , Kang Hyung-Sik , Kim Eun-Mi
Published: May 2021

Background

Triggering receptor expressed on myeloid cells 2 (TREM2) signaling is considered to regulate anti-inflammatory responses in macrophages, dendritic cell maturation, osteoclast development, induction of obesity, and Alzheimer’s disease pathogenesis. However, little is known regarding the effect of TREM2 on natural killer (NK) cells.

Results

Here, we demonstrated for the first time that CD3−CD122+NK1.1+precursor NK (pNK) cells expressed TREM2 and their population increased in TREM2-overexpressing transgenic (TREM2-TG) mice compared with that in female C57BL/6 J wild type (WT) mice. Both NK cell-activating receptors and NK cell-associated genes were expressed at higher levels in various tissues of TREM2-TG mice than in WT mice. In addition, bone marrow-derived hematopoietic stem cells (HSCs) of TREM2-TG mice (TG-HSCs) successfully differentiated into NK cells in vitro, with a higher yield from TG-HSCs than from WT-HSCs. In contrast, TREM2 signaling inhibition by TREM2-Ig or a phosphatidylinositol 3-kinase (PI3K) inhibitor affected the expression of the NK cell receptor repertoire and decreased the expression levels of NK cell-associated genes, resulting in significant impairment of NK cell differentiation. Moreover, in melanoma-bearing WT mice, injection of bone marrow cells from TREM2-TG mice exerted greater antitumor effects than that with cells from WT control mice.

Conclusions

Collectively, our data clearly showed that TREM2 promoted NK cell development and tumor regression, suggesting TREM2 as a new candidate for cancer immunotherapy.
Cancer-associated mutations reveal a novel role for EpCAM as an inhibitor of cathepsin-L and tumor cell invasion
Authors: Sankpal Narendra V. , Brown Taylor C. , Fleming Timothy P. , Herndon John M. , Amaravati Anusha A. , Loynd Allison N. , Gillanders William E.
Published: May 2021

Background

EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors.

Methods

The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of cancer associated EpCAM mutations. To determine how EpCAM mutations affect cancer biology we studied C66Y, a damaging TY-1 domain mutation identified in liver cancer, as well as 13 other cancer-associated EpCAM mutations. In vitro and in vivo models were used to determine the effect of wild type (WT) and mutant EpCAM on CTSL activity and invasion. Immunoprecipitation and localization studies tested EpCAM and CTSL protein binding and determined compartmental expression patterns of EpCAM mutants.

Results

We demonstrate that WT EpCAM, but not C66Y EpCAM, inhibits CTSL activity in vitro, and the TY-1 domain of EpCAM is responsible for this inhibition. WT EpCAM, but not C66Y EpCAM, inhibits tumor cell invasion in vitro and lung metastases in vivo. In an extended panel of human cancer cell lines, EpCAM expression is inversely correlated with CTSL activity. Previous studies have demonstrated that EpCAM germline mutations can prevent EpCAM from being expressed at the cell surface. We demonstrate that C66Y and multiple other EpCAM cancer-associated mutations prevent surface expression of EpCAM. Cancer-associated mutations that prevent EpCAM cell surface expression abrogate the ability of EpCAM to inhibit CTSL activity and tumor cell invasion.

Conclusions

These studies reveal a novel role for EpCAM as a CTSL inhibitor, confirm the functional relevance of multiple cancer-associated EpCAM mutations, and suggest a therapeutic vulnerability in cancers harboring EpCAM mutations.
The changes in socioeconomic inequalities and inequities in health services utilization among patients with hypertension in Pearl River Delta of China, 2015 and 2019
Authors: Liu Yan , Liu Nan , Cheng Mengjiao , Peng Xin , Huang Junxuan , Ma Jinxiang , Wang Peixi
Published: May 2021

Background

Assessing inequities in health services utilization contributes to build effective strategies for health equity promotion. This study aimed to evaluate the socioeconomic inequalities and inequities in health services utilization among hypertensive patients and explore the changes between 2015 and 2019 in Pearl River Delta of China.

Methods

The cross-sectional surveys were conducted using the questionnaire. Eight hundred thirty and one thousand one hundred sixty-six hypertensive patients in 2015 and 2019 were interviewed, respectively. The concentration index (CI) and the horizontal inequity index (HI) were used to access the socioeconomic inequalities and horizontal inequities in outpatient and inpatient health services use. The contribution of influential factors to the overall inequalities was estimated via the concentration index decomposition. Oaxaca-type decomposition technique was utilized to measure the changes in socioeconomic inequalities between the observation periods.

Results

In 2015 and 2019, the CIs for outpatient and inpatient utilization decreased from 0.1498 to 0.1198, 0.1982 to 0.1648, respectively, and the HIs for outpatient and inpatient utilization decreased from 0.1478 to 0.1078, 0.1956 to 0.1390, respectively. Economic status contributed the maximum ratio of the socioeconomic inequalities in the use of outpatient service (81.05% in 2015, 112.89% in 2019) and inpatient service (82.46% in 2015, 114.68% in 2019) in these 2 years. Oaxaca decomposition revealed that educational level (78.30% in outpatient, 53.79% in inpatient) and time to the nearest health facilities (66.78% in outpatient, 31.06% in inpatient) made the main positive contributions to decline the inequalities. While the main factor pushing the equalities toward deterioration was economic status (− 46.11% in outpatient, −76.56% in inpatient).

Conclusion

There were certain declines in the socioeconomic inequalities and inequities in health services utilization by hypertensive patients in Pearl River Delta of China over time. The widening economic gap was the largest contribution to the observed inequalities. Interventions to protect the vulnerable group deserve further concern from policy makers.
Stress- and smoke free pregnancy study protocol: a randomized controlled trial of a personalized eHealth intervention including heart rate variability-biofeedback to support pregnant women quit smoking via stress reduction
Authors: van Dijk Willeke , Oosterman Mirjam , Jansen Imke , de Vente Wieke , Huizink Anja
Published: May 2021

Background

Maternal smoking and stress during pregnancy are associated with adverse health effects for women themselves and are risk factors for adverse developmental outcomes of the unborn child. Smoking and stress seem to be intertwined in various ways. First, the majority of smoking pregnant women is of lower socio-economic status, which is associated with higher levels of perceived stress. Second, smoking women often report to smoke because they feel stressed. Third, quitting smoking often increases perceived stress levels initially. Therefore, effective interventions are needed to support women with smoking cessation by reducing stress. The aim of this study is to test the effectiveness of an eHealth intervention on stress reduction and smoking cessation.

Methods/design

The Stress- and Smoke Free Start of Life (SSFSL) study is a randomized controlled trial (RCT) comparing a personalized eHealth intervention with a control condition. Inclusion criteria for the women are: (1) > 18 years of age, (2) < 28 weeks pregnant at recruitment, (3) currently smoking. Consenting participants will be randomly assigned to the intervention or control group. Participants allocated to the intervention group will receive an 8-week intervention delivered on their smartphone. The application includes psycho-education on pregnancy, stress, and smoking (cessation); stress-management training consisting of Heart Rate Variability-biofeedback; and a personalized stop-smoking-plan. Participants in the control condition will be invited to visit a webpage with information on pregnancy, stress, and smoking (cessation). Study outcomes will be collected via online questionnaires, at four timepoints: pre-intervention (baseline; t0), post-intervention (8 weeks + 1 day after t0; t1), follow up at two weeks after birth (t2), and follow up at three months after birth (t3). The primary outcome measure is self-reported smoking cessation. Secondary outcomes include daily self-reported number of cigarettes smoked, perceived stress, pregnancy experience, birth outcomes, and negative affectivity scores of the baby. Moreover, the mediating effect of stress reduction on smoking cessation will be examined, and possible moderators will be tested.

Discussion

If the eHealth intervention is effective in smoking cessation among pregnant smoking women, it can be implemented as a tool into the health care in the Netherlands.

Trial registration

Netherlands Trial Register, ID: NL8156. Registered on 11 November 2019.
Protocol for the Mason: Health Starts Here prospective cohort study of young adult college students
Authors: Cuellar Alison E. , Adams Leah M. , de Jonge Lilian , Espina Virginia , Espinoza Laurette , Fischer Sarah F. , Frankenfeld Cara L. , Hines Denise A. , Kornienko Olga , Lawrence Heidi Y. , Rana Ziaul H. , Ramezani Niloofar , Rossheim Matthew E. , Short Jerome L. , Waithaka Eric N. , Wilson Alyssa N. , Cheskin Lawrence J.
Published: May 2021

Background

Young adulthood is a period of increasing independence for the 40% of young adults enrolled in U.S. colleges. Previous research indicates differences in how students’ health behaviors develop and vary by gender, race, ethnicity, and socioeconomic status. George Mason University is a state institution that enrolls a highly diverse student population, making it an ideal setting to launch a longitudinal cohort study using multiple research methods to evaluate the effects of health behaviors on physical and psychological functioning, especially during the COVID-19 pandemic.

Results

Mason: Health Starts Here was developed as a longitudinal cohort study of successive waves of first year students that aims to improve understanding of the natural history and determinants of young adults’ physical health, mental health, and their role in college completion. The study recruits first year students who are 18 to 24 years old and able to read and understand English. All incoming first year students are recruited through various methods to participate in a longitudinal cohort for 4 years. Data collection occurs in fall and spring semesters, with online surveys conducted in both semesters and in-person clinic visits conducted in the fall. Students receive physical examinations during clinic visits and provide biospecimens (blood and saliva).

Conclusions

The study will produce new knowledge to help understand the development of health-related behaviors during young adulthood. A long-term goal of the cohort study is to support the design of effective, low-cost interventions to encourage young adults’ consistent performance of healthful behaviors, improve their mental health, and improve academic performance.
Production of IgY polyclonal antibody against diphtheria toxin and evaluation of its neutralization effect by Vero cell assay
Authors: Rezaeifard Morteza , Solhi Roya , Mohammadi Mohammad , Abbasi Ebrahim , Aminian Mahdi
Published: May 2021

Background

Diphtheria is a bacterial disease which is caused byCorynebacterium diphtheriae. The symptoms are due to the diphtheria toxin produced by the bacteria. Antibiotic therapy and the use of diphtheria antitoxin is a recommended strategy to control diphtheria. Although mammalian antibodies are used to treat patients, IgY antibody has advantages over mammalian ones, including cost-effectiveness and production through non-invasive means. Moreover, in contrast to mammalian antibodies, IgY does not bind to the rheumatoid factor and does not activate the complement system. The objective of this study was to evaluate the in vitro neutralizing effect of IgY against diphtheria toxin.

Results

Anti-DT IgY was produced by immunization of the laying white leghorn chickens. Indirect enzyme-linked immunosorbent assay revealed successful immunization of the animals, and the IgY was purified with a purity of 93% via polyethylene glycol precipitation method. The neutralizing activity of the purified IgY was evaluated by Vero cell viability assay. This assay confirmed that 1.95 μg (8.6 μg/ml of culture medium) of anti-DT IgY would neutralize 10 fold of cytotoxic dose 99% of DT, which was 0.3 ng (1.33 ng/ml of culture medium).

Conclusion

This anti-DT IgY may be applicable for diphtheria treatment and quality controls in vaccine production.
Psychosocial, emotional and professional challenges faced by female healthcare professionals during the COVID-19 outbreak in Lahore, Pakistan: a qualitative study
Authors: Shahbaz Sumbal , Ashraf Muhammad Zeshan , Zakar Rubeena , Fischer Florian
Published: May 2021

Background

The novel coronavirus disease (COVID-19) is spreading rapidly, increasing the stress and challenges for healthcare professionals around the world. This study aims to discover the psychosocial, emotional and professional challenges faced by female healthcare professionals (HCPs) treating COVID-19 patients in Pakistan.

Methods

Using an empirical phenomenological methodology, semi-structured telephone-based qualitative interviews were conducted with 22 female HCPs who were providing their expertise for COVID-19 patients in tertiary-level hospitals in Lahore, Pakistan. Purposive sampling was used for recruitment. The interviews were conducted between 20 July and 20 August 2020. The interviews were analysed using thematic analysis.

Results

This study explored the psychosocial, emotional and professional challenges faced by female HCPs serving COVID-19 patients. Five themes were observed in the interviews: apprehension while treating COVID-19 patients; feelings towards COVID-19 patients; challenges as female HCPs and coping strategies; confidence in government, administration and self-reflection; and finally, future concerns and recommendations. Many of these themes have also been linked with cultural issues, making the results specific to Pakistan.

Conclusions

During the COVID-19 pandemic, female frontline HCPs have faced immense psychosocial pressure, ranging from unsupportive family norms to an unwelcoming working environment and insensitive hospital administrations. Moreover, rumours among the general public, lack of proper training, missing incentives and improper system surveillance have increased the anxiety and stress among HCPs. Hence, legislators are advised to take appropriate actions countrywide in order to alleviate the still ongoing challenges and support female HCPs in their working environment.
Implementing a digital health model of care in Australian youth mental health services: protocol for impact evaluation
Authors: Piper Sarah , Davenport Tracey A. , LaMonica Haley , Ottavio Antonia , Iorfino Frank , Cheng Vanessa Wan Sze , Cross Shane , Lee Grace Yeeun , Scott Elizabeth , Hickie Ian B.
Published: May 2021

Background

The World Economic Forum has recently highlighted substantial problems in mental health service provision and called for the rapid deployment of smarter, digitally-enhanced health services as a means to facilitate effective care coordination and address issues of demand. In mental health, the biggest enabler of digital solutions is the implementation of an effective model of care that is facilitated by integrated health information technologies (HITs); the latter ensuring the solution is easily accessible, scalable and sustainable. The University of Sydney’s Brain and Mind Centre (BMC) has developed an innovative digital health solution – delivered through the Youth Mental Health and Technology Program – which incorporates two components: 1) a highly personalised and measurement-based (data-driven) model of youth mental health care; and 2) an industrial grade HIT registered on the Australian Register of Therapeutic Goods. This paper describes a research protocol to evaluate the impact of implementing the BMC’s digital health solution into youth mental health services (i.e. headspace - a highly accessible, youth-friendly integrated service that responds to the mental health, physical health, alcohol or other substance use, and vocational concerns of young people aged 12 to 25 years) within urban and regional areas of Australia.

Methods

The digital health solution will be implemented into participating headspace centres using a naturalistic research design. Quantitative and qualitative data will be collected from headspace health professionals, service managers and administrators, as well as from lead agency and local Primary Health Network (PHN) staff, via service audits, Implementation Officer logs, online surveys, and semi-structured interviews, at baseline and then three-monthly intervals over the course of 12 months.

Discussion

At the time of publication, six headspace centres had been recruited to this study and had commenced implementation and impact evaluation. The first results are expected to be submitted for publication in 2021. This study will focus on the impact of implementing a digital health solution at both a service and staff level, and will evaluate digital readiness of service and staff adoption; quality, usability and acceptability of the solution by staff; staff self-reported clinical competency; overall impact on headspace centres as well as their lead agencies and local PHNs; and social return on investment.
Apoptosis is not conserved in plants as revealed by critical examination of a model for plant apoptosis-like cell death
Authors: Minina Elena A. , Dauphinee Adrian N. , Ballhaus Florentine , Gogvadze Vladimir , Smertenko Andrei P. , Bozhkov Peter V.
Published: May 2021

Background

Animals and plants diverged over one billion years ago and evolved unique mechanisms for many cellular processes, including cell death. One of the most well-studied cell death programmes in animals, apoptosis, involves gradual cell dismantling and engulfment of cellular fragments, apoptotic bodies, through phagocytosis. However, rigid cell walls prevent plant cell fragmentation and thus apoptosis is not applicable for executing cell death in plants. Furthermore, plants are devoid of the key components of apoptotic machinery, including phagocytosis as well as caspases and Bcl-2 family proteins. Nevertheless, the concept of plant “apoptosis-like programmed cell death” (AL-PCD) is widespread. This is largely due to superficial morphological resemblances between plant cell death and apoptosis, and in particular between protoplast shrinkage in plant cells killed by various stimuli and animal cell volume decrease preceding fragmentation into apoptotic bodies.

Results

Here, we provide a comprehensive spatio-temporal analysis of cytological and biochemical events occurring in plant cells subjected to heat shock at 40–55 °C and 85 °C, the experimental conditions typically used to trigger AL-PCD and necrotic cell death, respectively. We show that cell death under both conditions was not accompanied by membrane blebbing or formation of apoptotic bodies, as would be expected during apoptosis. Instead, we observed instant and irreversible permeabilization of the plasma membrane and ATP depletion. These processes did not depend on mitochondrial functionality or the presence of Ca2+and could not be prevented by an inhibitor of ferroptosis. We further reveal that the lack of protoplast shrinkage at 85 °C, the only striking morphological difference between cell deaths induced by 40–55 °C or 85 °C heat shock, is a consequence of the fixative effect of the high temperature on intracellular contents.

Conclusions

We conclude that heat shock-induced cell death is an energy-independent process best matching definition of necrosis. Although the initial steps of this necrotic cell death could be genetically regulated, classifying it as apoptosis or AL-PCD is a terminological misnomer. Our work supports the viewpoint that apoptosis is not conserved across animal and plant kingdoms and demonstrates the importance of focusing on plant-specific aspects of cell death pathways.