bluuebunny/crossref_metadata_2025 huggingface dataset:
Wearable Devices for Assessing Function in Alzheimer's Disease: A European Public Involvement Activity About the Features and Preferences of Patients and Caregivers
Authors: Stavropoulos Thanos G. , Lazarou Ioulietta , Diaz Ana , Gove Dianne , Georges Jean , Manyakov Nikolay V. , Pich Emilio Merlo , Hinds Chris , Tsolaki Magda , Nikolopoulos Spiros , Kompatsiaris Ioannis ,   The RADAR-AD Consortium
Published: April 2021

Background: Alzheimer's Disease (AD) impairs the ability to carry out daily activities, reduces independence and quality of life and increases caregiver burden. Our understanding of functional decline has traditionally relied on reports by family and caregivers, which are subjective and vulnerable to recall bias. The Internet of Things (IoT) and wearable sensor technologies promise to provide objective, affordable, and reliable means for monitoring and understanding function. However, human factors for its acceptance are relatively unexplored.

Objective: The Public Involvement (PI) activity presented in this paper aims to capture the preferences, priorities and concerns of people with AD and their caregivers for using monitoring wearables. Their feedback will drive device selection for clinical research, starting with the study of the RADAR-AD project.

Method: The PI activity involved the Patient Advisory Board (PAB) of the RADAR-AD project, comprised of people with dementia across Europe and their caregivers (11 and 10, respectively). A set of four devices that optimally represent various combinations of aspects and features from the variety of currently available wearables (e.g., weight, size, comfort, battery life, screen types, water-resistance, and metrics) was presented and experienced hands-on. Afterwards, sets of cards were used to rate and rank devices and features and freely discuss preferences.

Results: Overall, the PAB was willing to accept and incorporate devices into their daily lives. For the presented devices, the aspects most important to them included comfort, convenience and affordability. For devices in general, the features they prioritized were appearance/style, battery life and water resistance, followed by price, having an emergency button and a screen with metrics. The metrics valuable to them included activity levels and heart rate, followed by respiration rate, sleep quality and distance. Some concerns were the potential complexity, forgetting to charge the device, the potential stigma and data privacy.

Conclusions: The PI activity explored the preferences, priorities and concerns of the PAB, a group of people with dementia and caregivers across Europe, regarding devices for monitoring function and decline, after a hands-on experience and explanation. They highlighted some expected aspects, metrics and features (e.g., comfort and convenience), but also some less expected (e.g., screen with metrics).
Synergistic Antitumor Activity of Gramicidin/Lipophilic Bismuth Nanoparticles (BisBAL NPs) on Human Cervical Tumor Cells
Authors: Cabral-Romero Claudio , García-Cuellar Claudia María , Hernandez-Delgadillo Rene , Sánchez-Pérez Yesennia , Meester Irene , Solís-Soto Juan Manuel , Pineda-Aguilar Nayely , Chellam Shankararaman
Published: April 2021

The objective of this study was to study the synergistic antitumor effect of lipophilic bismuth nanoparticles (BisBAL NPs) with the antibiotic solution Neo-Poly gramicidin on human cervical tumor cells. The effect of BisBAL NPs and Neo-Poly gramicidin solution on cervical cancer cell line (HeLa) was determined by the MTT cell viability assay and fluorescence microscopy. After a 24-h exposure to 0.1× Neo-Poly gramicidin HeLa cell growth decreased 94%. Fluorescence microscopy confirmed the antitumor effect cell death was higher among treated than among non-treated cells cells. Individually, gramicidin (0.04 mg/mL) inhibited HeLa tumor cell growth most (40%), and neomycin (0.04 mg/mL) least (21%). Gramicidin (0.3 mg/mL) in combination with different concentrations (1–150 μM) of BisBAL NPs had a synergistic antitumor effect against HeLa cells, reaching an < 86% tumor growth inhibition. As far as we know, we are the first to describe the antitumor activity of the antibiotic Neo-Poly gramicidin on a human cervical cancer cell line. The action mechanism of gramicidin/BisBAL NP is based on a strong damage on cell membrane and nucleus of tumor cells. A synergistic effect of gramicidin with BisBAL NPs may be useful as an alternative therapy for cervical cancer patients.
The Cellular Prion Protein—ROCK Connection: Contribution to Neuronal Homeostasis and Neurodegenerative Diseases
Authors: Schneider Benoit , Baudry Anne , Pietri Mathéa , Alleaume-Butaux Aurélie , Bizingre Chloé , Nioche Pierre , Kellermann Odile , Launay Jean-Marie
Published: April 2021

Amyloid-based neurodegenerative diseases such as prion, Alzheimer's, and Parkinson's diseases have distinct etiologies and clinical manifestations, but they share common pathological events. These diseases are caused by abnormally folded proteins (pathogenic prions PrPSc in prion diseases, β-amyloids/Aβ and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease) that display β-sheet-enriched structures, propagate and accumulate in the nervous central system, and trigger neuronal death. In prion diseases, PrPSc-induced corruption of the physiological functions exerted by normal cellular prion proteins (PrPC) present at the cell surface of neurons is at the root of neuronal death. For a decade, PrPC emerges as a common cell surface receptor for other amyloids such as Aβ and α-synuclein, which relays, at least in part, their toxicity. In lipid-rafts of the plasma membrane, PrPC exerts a signaling function and controls a set of effectors involved in neuronal homeostasis, among which are the RhoA-associated coiled-coil containing kinases (ROCKs). Here we review (i) how PrPC controls ROCKs, (ii) how PrPC-ROCK coupling contributes to neuronal homeostasis, and (iii) how the deregulation of the PrPC-ROCK connection in amyloid-based neurodegenerative diseases triggers a loss of neuronal polarity, affects neurotransmitter-associated functions, contributes to the endoplasmic reticulum stress cascade, renders diseased neurons highly sensitive to neuroinflammation, and amplifies the production of neurotoxic amyloids.
Effects of Wireless Remote Microphone on Speech Recognition in Noise for Hearing Aid Users in China
Authors: Chen Jing , Wang Zhe , Dong Ruijuan , Fu Xinxing , Wang Yuan , Wang Shuo
Published: April 2021

Objective:This study was aimed at evaluating improvements in speech-in-noise recognition ability as measured by signal-to-noise ratio (SNR) with the use of wireless remote microphone technology. These microphones transmit digital signals via radio frequency directly to hearing aids and may be a valuable assistive listening device for the hearing-impaired population of Mandarin speakers in China.

Methods:Twenty-three adults (aged 19–80 years old) and fourteen children (aged 8–17 years old) with bilateral sensorineural hearing loss were recruited. The Mandarin Hearing in Noise Test was used to test speech recognition ability in adult subjects, and the Mandarin Hearing in Noise Test for Children was used for children. The subjects’ perceived SNR was measured using sentence recognition ability at three different listening distances of 1.5, 3, and 6 m. At each distance, SNR was obtained under three device settings: hearing aid microphone alone, wireless remote microphone alone, and hearing aid microphone and wireless remote microphone simultaneously.

Results:At each test distance, for both adult and pediatric groups, speech-in-noise recognition thresholds were significantly lower with the use of the wireless remote microphone in comparison with the hearing aid microphones alone (P< 0.05), indicating better SNR performance with the wireless remote microphone. Moreover, when the wireless remote microphone was used, test distance had no effect on speech-in-noise recognition for either adults or children.

Conclusion:Wireless remote microphone technology can significantly improve speech recognition performance in challenging listening environments for Mandarin speaking hearing aid users in China.
Advances in Carbon-Based Microfiber Electrodes for Neural Interfacing
Authors: Hejazi Maryam , Tong Wei , Ibbotson Michael R. , Prawer Steven , Garrett David J.
Published: April 2021

Neural interfacing devices using penetrating microelectrode arrays have emerged as an important tool in both neuroscience research and medical applications. These implantable microelectrode arrays enable communication between man-made devices and the nervous system by detecting and/or evoking neuronal activities. Recent years have seen rapid development of electrodes fabricated using flexible, ultrathin carbon-based microfibers. Compared to electrodes fabricated using rigid materials and larger cross-sections, these microfiber electrodes have been shown to reduce foreign body responses after implantation, with improved signal-to-noise ratio for neural recording and enhanced resolution for neural stimulation. Here, we review recent progress of carbon-based microfiber electrodes in terms of material composition and fabrication technology. The remaining challenges and future directions for development of these arrays will also be discussed. Overall, these microfiber electrodes are expected to improve the longevity and reliability of neural interfacing devices.
Altered Relationship Between Parvalbumin and Perineuronal Nets in an Autism Model
Authors: Xia Dan , Li Li , Yang Binrang , Zhou Qiang
Published: April 2021

Altered function or presence of inhibitory neurons is documented in autism spectrum disorders (ASD), but the mechanism underlying this alternation is poorly understood. One major subtype of inhibitory neurons altered is the parvalbumin (PV)-containing neurons with reduced density and intensity in ASD patients and model mice. A subpopulation of PV+ neurons expresses perineuronal nets (PNN). To better understand whether the relationship between PV and PNN is altered in ASD, we measured quantitatively the intensities of PV and PNN in single PV+ neurons in the prelimbic prefrontal cortex (PrL-PFC) of a valproic acid (VPA) model of ASD at different ages. We found a decreased PV intensity but increased PNN intensity in VPA mice. The relationship between PV and PNN intensities is altered in VPA mice, likely due to an “abnormal” subpopulation of neurons with an altered PV-PNN relationship. Furthermore, reducing PNN level using in vivo injection of chondroitinase ABC corrects the PV expression in adult VPA mice. We suggest that the interaction between PV and PNN is disrupted in PV+ neurons in VPA mice which may contribute to the pathology in ASD.
Daytime Restricted Feeding Affects Day–Night Variations in Mouse Cerebellar Proteome
Authors: Bertile Fabrice , Plumel Marine , Maes Pauline , Hirschler Aurélie , Challet Etienne
Published: April 2021

The cerebellum harbors a circadian clock that can be shifted by scheduled mealtime and participates in behavioral anticipation of food access. Large-scale two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry was used to identify day–night variations in the cerebellar proteome of mice fed either during daytime or nighttime. Experimental conditions led to modified expression of 89 cerebellar proteins contained in 63 protein spots. Five and 33 spots were changed respectively by time-of-day or feeding conditions. Strikingly, several proteins of the heat-shock protein family (i.e., Hsp90aa1, 90ab1, 90b1, and Hspa2, 4, 5, 8, 9) were down-regulated in the cerebellum of daytime food-restricted mice. This was also the case for brain fatty acid protein (Fabp7) and enzymes involved in oxidative phosphorylation (Ndufs1) or folate metabolism (Aldh1l1). In contrast, aldolase C (Aldoc or zebrin II) and pyruvate carboxylase (Pc), two enzymes involved in carbohydrate metabolism, and vesicle-fusing ATPase (Nsf) were up-regulated during daytime restricted feeding, possibly reflecting increased neuronal activity. Significant feeding × time-of-day interactions were found for changes in the intensity of 20 spots. Guanine nucleotide-binding protein G(o) subunit alpha (Gnao1) was more expressed in the cerebellum before food access. Neuronal calcium-sensor proteins [i.e., parvalbumin (Pvalb) and visinin-like protein 1 (Vsnl1)] were inversely regulated in daytime food-restricted mice, compared to control mice fed at night. Furthermore, expression of three enzymes modulating the circadian clockwork, namely heterogeneous nuclear ribonucleoprotein K (Hnrnpk), serine/threonine-protein phosphatases 1 (Ppp1cc and Ppp1cb subunits) and 5 (Ppp5), was differentially altered by daytime restricted feeding. Besides cerebellar proteins affected only by feeding conditions or daily cues, specific changes in in protein abundance before food access may be related to behavioral anticipation of food access and/or feeding-induced shift of the cerebellar clockwork.
Low Vitamin D Level in Saudi Women With Polycystic Ovary Syndrome
Authors: Bindayel Iman Abdullah
Published: April 2021

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. In this study, serum 25-hydroxyvitamin D levels were compared between women with and without PCOS and with regard to anthropometric indices and lipid and glucose biomarkers. Thirty-one women with PCOS and 75 controls answered a questionnaire on vitamin D, in addition to general health and lifestyle. The patients with PCOS had lower vitamin D levels (p < 0.05), a significantly higher rate of obesity (p < 0.05), and significantly higher serum triglyceride levels than did controls. The number of patients with PCOS consumed milk and dairy products (p < 0.05) and exposed to sun (p < 0.006) were lower compared to controls. Triglyceride levels were significantly correlated with body mass index (BMI); vitamin D level was not significantly correlated with anthropometrical or biochemical variables. These results affirm that vitamin D levels are lower in women with PCOS; however, despite the significantly higher proportion of obesity among patients with PCOS, hypovitaminosis was not associated with BMI. The relationship between body composition and vitamin D in PCOS and the effect of vitamin D correction on metabolic and hormonal parameters associated with PCOS must be assessed in future trials.
Exploring Dietary Behavior Changes Due to the COVID-19 Confinement in Colombia: A National and Regional Survey Study
Authors: Pertuz-Cruz Sonia L. , Molina-Montes Esther , Rodríguez-Pérez Celia , Guerra-Hernández Eduardo J. , Cobos de Rangel Olga P. , Artacho Reyes , Verardo Vito , Ruiz-Lopez María Dolores , García-Villanova Belén
Published: April 2021

The aim of this study was to evaluate the impact of coronavirus SARS-Cov2 (COVID-19) confinement measures in Colombia on the dietary behaviors of a large population sample, at national and regional levels. A survey was conducted to assess dietary behaviors during the COVID-19 confinement. The survey involved 2,745 participants, aged 18 years or older, from six regions of the country (Atlántica, Bogotá, Central, Oriental, Orinoquía and Amazonía, and Pacífica). Dietary intake of foods and foods groups in grams per day before and during the confinement was estimated by considering standard serving sizes of foods. One-way ANOVA was used to analyze differences between the regions with regard to dietary behavior changes during the confinement. Differences were deemed significant at p-value < 0.05. Dietary patterns (DPs) before and during the confinement were derived from principal component analysis. Certain dietary habits were adopted by the study population during the confinement (e.g., higher frequency of snacking and home cooking), with significant differences by regions with regard to these habits, as well as regarding culinary processes. The levels of consumption of several foods also changed during the confinement, nationally and regionally. We identified three DPs before the confinement (protein-rich, carbohydrate-rich, and sugar foods patterns) and four DPs during the confinement (westernized, carbohydrate-rich, protein-rich, fish and fruits-vegetable patterns), with an explained total variance of 33 and 45%, respectively. The profile of these DPs varied to some extent between the regions; their adherence to each DP also varied (p-value < 0.001). Our results show that there were marked differences by regions in the dietary behaviors of this population during the confinement, with an overall trend toward unhealthier DPs. These results may help to shape public health nutrition interventions in Colombia during the COVID-19 pandemic and in a post-COVID stage.
Identification of Hub Genes Associated With Melanoma Development by Comprehensive Bioinformatics Analysis
Authors: Jiang Jie , Liu Chong , Xu Guoyong , Liang Tuo , Yu Chaojie , Liao Shian , Zhang Zide , Lu Zhaojun , Wang Zequn , Chen Jiarui , Chen Tianyou , Li Hao , Zhan Xinli
Published: April 2021

Introduction

This study aimed to identify important genes associated with melanoma to further develop new target gene therapies and analyze their significance concerning prognosis.

Materials and methods

Gene expression data for melanoma and normal tissue were downloaded from three databases. Differentially co-expressed genes were identified by WGCNA and DEGs analysis. These genes were subjected to GO, and KEGG enrichment analysis and construction of the PPI visualized with Cytoscape and screened for the top 10 Hub genes using CytoHubba. We validated the Hub gene’s protein levels with an immunohistochemical assay to confirm the accuracy of our analysis.

Results

A total of 435 differentially co-expressed genes were obtained. Survival curves showed that high expression of FOXM1,\ EXO1, KIF20A, TPX2, and CDC20 in melanoma patients with 5 of the top 10 hub genes was associated with reduced overall survival (OS). Immunohistochemistry showed that all five genes were expressed at higher protein levels in melanoma than in paracancerous tissues.

Conclusion

FOXM1, EXO1, KIF20A, TPX2, and CDC20 are prognosis-associated core genes of melanoma, and their high expression correlates with the low prognosis of melanoma patients and can be used as biomarkers for melanoma diagnosis, treatment, and prognosis prediction.
Intravoxel Incoherent Motion Model in Differentiating the Pathological Grades of Esophageal Carcinoma: Comparison of Mono-Exponential and Bi-Exponential Fit Model
Authors: Liu Nian , Yang Xiongxiong , Lei Lixing , Pan Ke , Liu Qianqian , Huang Xiaohua
Published: April 2021

Purpose

To compare the diagnostic efficiency of the mono-exponential model and bi-exponential model deriving from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in differentiating the pathological grade of esophageal squamous cell carcinoma (ESCC).

Methods

Fifty-four patients with ESCC were divided into three groups of poorly-differentiated (PD), moderately-differentiated (MD), and well-differentiated (WD), and underwent the IVIM-DWI scan. Mono-exponential (Dmono, D*mono, and fmono) and bi-exponential fit parameters (Dbi, D*bi, and fbi) were calculated using the IVIM data for the tumors. Mean parameter values of three groups were compared using a one-way ANOVA followed by post hoc tests. The receiver operating characteristic curve was drawn for differentiating pathological grade of ESCC. Correlations between pathological grades and IVIM parameters were analyzed.

Results

There were significant differences in fmono and fbi among the PD, MD and WD ESCC groups (all p<0.05). The fmono were 0.32 ± 0.07, 0.23 ± 0.08, and 0.16 ± 0.05, respectively, and the fbi were 0.35 ± 0.08, 0.26 ± 0.10, and 0.18 ± 0.07, respectively. There was a significant difference in the Dmono between the WD and the PD group (1.48 ± 0.51* 10-3 mm2/s versus 1.05 ± 0.44*10-3 mm2/s, p<0.05), but there was no significant difference between the WD and MD groups, MD and PD groups (all p>0.05). The D*mono, Dbi, and D*bi showed no significant difference among the three groups (all p>0.05). The area under the curve (AUC) of Dmono, fmono and fbi in differentiating WD from PD ESCC were 0.764, 0.961 and 0.932, and the sensitivity and specificity were 92.9% and 60%, 92.9% and 90%, 85.7% and 100%, respectively. The AUC of fmono and fbi in differentiating MD from PD ESCC were 0.839 and 0.757, and the sensitivity and specificity were 78.6% and 80%, 85.7% and 70%, respectively. The AUC of fmono and fbi in differentiating MD from WD ESCC were 0.746 and 0.740, and the sensitivity and specificity were 65% and 85%, 80% and 60%, respectively. The pathologically differentiated grade was correlated with all IVIM parameters (all p<0.05).

Conclusions

The mono-exponential IVIM model is superior to the bi-exponential IVIM model in differentiating pathological grades of ESCC, which may be a promising imaging method to predict pathological grades of ESCC.
Adjuvant EGFR-TKIs for Patients With Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Meta-Analysis of 1,283 Patients
Authors: Chen Rui-Lian , Sun Ling-Ling , Cao Yang , Chen Han-Rui , Zhou Jing-Xu , Gu Chu-Ying , Zhang Ying , Wang Si-Yu , Hou Wei , Lin Li-Zhu
Published: April 2021

Background

Cisplatin-based chemotherapy was previously considered as the standard adjuvant therapy for improved overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. However, the benefit was limited due to high risks of recurrence and adverse events. In the present study, the efficacy of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutant patients after surgery was investigated using the latest updated data.

Methods

This meta-analysis included a comprehensive range of relevant studies identified from database searches. Disease-free survival (DFS) and OS with hazard ratios (HRs) were calculated using random-effect or fixed-effect models. Subgroup analysis was also performed.

Results

A total of seven randomized clinical trials were included in the meta-analysis and involved 1,283 NSCLC patients harboring EGFR mutations. In resected EGFR-mutant NSCLC patients, adjuvant EGFR-TKIs were significantly better than chemotherapy in terms of DFS (HR: 0.41; 95%CI: 0.24–0.70, P = 0.001), without showing any benefit in OS (HR: 0.72; 95%CI: 0.37–1.41, P = 0.336). No significant difference in DFS was observed between patients with EGFR exon 19 deletion and those with L858R mutation. Resected EGFR-mutant NSCLC patients treated with osimertinib experienced improved DFS and a lower risk of brain recurrence than those treated with gefitinib or erlotinib. Adjuvant EGFR-TKIs reduced the risk of bone and lung relapse, without decreasing the risk of local recurrence and liver relapse.

Conclusion

This meta-analysis shows that adjuvant EGFR-TKI therapy could significantly prolong DFS in patients with resected EGFR-mutant NSCLC. Treatment with osimertinib showed improved DFS with a lower risk of brain recurrence than treatment with gefitinib or erlotinib for resected disease.
Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study
Authors: Ko Heejoo , Chang Jee Suk , Moon Jin Young , Lee Won Hee , Shah Chirag , Shim Jin Sup (Andy) , Han Min Cheol , Baek Jong Geol , Park Ryeong Hwang , Kim Yong Bae , Kim Jin Sung
Published: April 2021

Purpose

How modern cardiac sparing techniques and beam delivery systems using advanced x-ray and proton beam therapy (PBT) can reduce incidental radiation exposure doses to cardiac and pulmonary organs individually or in any combination is poorly investigated.

Methods

Among 15 patients with left-sided breast cancer, partial wide tangential 3D-conformal radiotherapy (3DCRT) delivered in conventional fractionation (CF) or hypofractionated (HF) schedules; PBT delivered in a CF schedule; and volumetric modulated arc therapy (VMAT) delivered in an HF schedule, each under continuous positive airway pressure (CPAP) and free-breathing (FB) conditions, were examined. Target volume coverage and doses to organs-at-risk (OARs) were calculated for each technique. Outcomes were compared with one-way analysis of variance and the Bonferroni test, with p-values <0.05 considered significant.

Results

Target volume coverage was within acceptable levels in all interventions, except for the internal mammary lymph node D95 (99% in PBT, 90% in VMAT-CPAP, 84% in VMAT-FB, and 74% in 3DCRT). The mean heart dose (MHD) was the lowest in PBT (<1 Gy) and VMAT-CPAP (2.2 Gy) and the highest in 3DCRT with CF/FB (7.8 Gy), respectively. The mean lung dose (MLD) was the highest in 3DCRT-CF-FB (20 Gy) and the lowest in both VMAT-HF-CPAP and PBT (approximately 5–6 Gy). VMAT-HF-CPAP and PBT delivered a comparable maximum dose to the left ascending artery (7.2 and 6.13 Gy, respectively).

Conclusions

Both proton and VMAT in combination with CPAP can minimize the radiation exposure to heart and lung with optimal target coverage in regional RT for left-sided breast cancer. The clinical relevance of these differences is yet to be elucidated. Continued efforts are needed to minimize radiation exposures during RT treatment to maximize its therapeutic index.
The Role of miR-640: A Potential Suppressor in Breast Cancer via Wnt7b/β-catenin Signaling Pathway
Authors: Tang Chun , Wang Xuehui , Ji Changle , Zheng Wenfang , Yu Yunhe , Deng Xiaochong , Zhou Xiqian , Fang Lin
Published: April 2021

In this study, we demonstrated that miR-640 is significantly downregulated in breast cancer (BC) tissues and cell lines. Overexpression of miR-640 inhibited the proliferation and migration of BC in vitro and in vivo, while depletion of miR-640 exhibited the opposite effect. Importantly, miR-640 could directly target Wnt7b, thereby regulating Wnt/β-catenin signaling pathway in BC. In conclusion, miR-640/Wnt7b suppresses BC cells tumorigenesis via Wnt/β-catenin signaling pathway, which might be novel targets for BC targeted therapy.
tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-β1/Smad3 Axis in Breast Cancer
Authors: Mo Dongping , He Fang , Zheng Junyu , Chen Huanhuan , Tang Li , Yan Feng
Published: April 2021

tRNA derivatives have been identified as a new kind of potential biomarker for cancer. Previous studies have identified that there were 30 differentially expressed tRNAs derivatives in breast cancer tissue with the high-throughput sequencing technique. This study aimed to investigate the possible biological function and mechanism of tRNA derivatives in breast cancer cells. One such tRF, a 5’-tRF fragment of tRF-17-79MP9PP (tRF-17) was screened in this study, which is processed from the mature tRNA-Val-AAC and tRNA-Val-CAC. tRF-17 with significantly low expression in breast cancer tissues and serum. The level of tRF-17 differentiated breast cancer from healthy controls with sensitivity of 70.4% and specificity of 68.4%. Overexpression of tRF-17 suppressed cells malignant activity. THBS1 (Thrombospondin-1) as a downstream target of tRF-17, and reduction of THBS1 expression also partially recovered the effects of tRF-17 inhibition on breast cancer cell viability, invasion and migration. Besides, THBS1, TGF-β1, Smad3, p-Smad3 and epithelial-to-mesenchymal transition related genes N-cadherin, MMP3, MMP9 were markedly down-regulated in tRF-17 overexpressing cells. Moreover, tRF-17 attenuated the THBS1-mediated TGF-β1/Smad3 signaling pathway in breast cancer cells. In general, the tRF-17/THBS1/TGF-β1/smad3 axis elucidates the molecular mechanism of breast cancer cells invasion and migration and could lead to a potential therapeutic target for breast cancer.
Study Progression of Apelin/APJ Signaling and Apela in Different Types of Cancer
Authors: Liu Longfei , Yi Xiaoping , Lu Can , Wang Yong , Xiao Qiao , Zhang Liang , Pang Yingxian , Guan Xiao
Published: April 2021

Apelin is an endogenous ligand that binds to the G protein-coupled receptor angiotensin-like-receptor 1 (APJ). Apelin and APJ are widely distributed in organs and tissues and are involved in multiple physiological and pathological processes including cardiovascular regulation, neuroendocrine stress response, energy metabolism, etc. Additionally, apelin/APJ axis was found to play an important role in cancer development and progression. Apela is a newly identified endogenous ligand for APJ. Several studies have revealed the potential role of Apela in cancers. In this article, we review the current studies focusing on the role of apelin/APJ signaling and Apela in different cancers. Potential mechanisms by which apelin/APJ and Apela mediate the regulation of cancer development and progression were also mentioned. The Apelin/APJ signaling and Apela may serve as potential therapeutic candidates for treatment of cancer.
Sensitivity of the Molecular Test in Saliva for Detection of COVID-19 in Pediatric Patients With Concurrent Conditions
Authors: Ana Laura Guzmán-Ortiz , Abraham Josué Nevárez-Ramírez , Briceida López-Martínez , Israel Parra-Ortega , Tania Angeles-Floriano , Nancy Martínez-Rodríguez , Lourdes Jamaica-Balderas , Daniela De la Rosa-Zamboni , Fernando Ortega-Riosvelasco , Carlos Mauricio Jaramillo-Esparza , Sergio René Bonilla-Pellegrini , Irineo Reyna-Trinidad , Horacio Márquez-González , Oscar Medina-Contreras , Héctor Quezada
Published: April 2021

Background: The reference standard for the molecular diagnostic testing for COVID-19 is the use of nasopharyngeal or combined nasopharyngeal and oropharyngeal (NP/OP) swabs. Saliva has been proposed as a minimally invasive specimen whose collection reduces the risks for health care personnel.

Objective: To assess the suitability of saliva for COVID-19 diagnosis as a replacement of the reference standard NP/OP swab in the setting of a tertiary care pediatric unit.

Study design: A paired study based in the prospective cohort design in patients suspected of having COVID-19.

Methods: RT-PCR was used to detect SARS-CoV-2 in paired samples of saliva and NP/OP swab collected from May through August 2020 from 156 pediatric participants, of whom 128 has at least one comorbidity and 91 showed clinical symptoms related to SARS-CoV-2 infection. Additionally, we studied a group of 326 members of the hospital staff, of whom 271 had symptoms related to SARS-CoV-2 infection.

Results: In the group of pediatric participants the sensitivity of the diagnostic test in saliva was 82.3% (95% CI 56.6–96.2) and the specificity 95.6% (95% CI 90.8–98.4). The prevalence of COVID-19 was 10.9% (17/156). In 6 of the 23 participants who tested positive for SARS-CoV-2 in at least one specimen type, the virus was detected in saliva but not in NP/OP swab, while in 3 participants the NP/OP swab was positive and saliva negative. In the group of adults, the sensitivity of the test in saliva was 77.8% (95% CI 67.2–86.3) and prevalence 24.8% (81/326). Discordant results between the two types of specimens showed a significant association with low viral load in the pharynx of adults but not of pediatric participants.

Interpretation: In the context of a pediatric tertiary care hospital, the sensibility of the test in saliva is not high enough to replace the use of NP/OP swab for COVID-19 diagnosis. Neither NP/OP swab nor saliva could detect all the participants infected with SARS-CoV-2.
The Direct and Indirect Relationships Within the Extended Trans-contextual Model for Moderate-to-vigorous Physical Activity
Authors: Mieziene Brigita , Emeljanovas Arunas , Putriute Vitalija , Novak Dario
Published: April 2021

Given the low levels of physical activity (PA) in adolescence, there are challenges to increasing students' PA outside of the school setting. Thus, researchers emphasize the supportive role that physical education (PE) teachers can play in PA motivation both in and out of school. The aim of the present study was to examine an expanded trans-contextual model (TCM) model for the transit of teachers' perceived support of students' autonomy in terms of contextual and situational motivation in PE to objectively measured moderate-to-vigorous physical activity (MVPA) in PE across different PE contents as well as to the motivational sequence for, and participation in, subjective MVPA during leisure time. This cross-sectional study involved 283 high school students, of whom 43.9% were boys. The autonomous support students received and other motivational factors and objective measures of MVPA in PE and subjective MVPA in leisure time were measured. The results indicate that support for autonomy was significantly and directly related to needs satisfaction (β = 0.61, p < 0.001) and indirectly to autonomous motivation in PE (β = 0.19, p < 0.001) and leisure time (β = 0.16, p < 0.001), intention in PE (β = 0.03, p < 0.05) and leisure time (β = 0.07, p < 0.001), and leisure time MVPA (β = 0.04, p < 0.001), although not MVPA in PE. Gender was a significant covariate for both MVPA in PE (β = −0.62, p < 0.001) and MVPA in leisure time (β = −0.37, p < 0.001), with higher MVPA in boys than girls. This study filled a gap in the scientific literature by demonstrating the full motivational sequence resulting in actual MVPA in PE classes. It also demonstrated that the main goal of PE of enhancing PA not only in school but also outside of school is working. The main motivator is needs satisfaction based on PE teachers' support.
Filtering Inequality: Screening and Knowledge in Senegal’s Topography of Hepatitis B Care
Authors: Tousignant Noemi
Published: April 2021

Only a fraction of the estimated tenth or so of Senegalese who are chronically infected with hepatitis B virus (HBV) have been diagnosed. Of these, few have been assessed for their risk of progressing to potentially fatal liver disease (indicating need for treatment), and fewer still are taking antiviral drugs. A massive gap between those needing and getting treatment is widely acknowledged among experts. But given that HBV and its biomedical treatment options are largely invisible in bodies, health data, care practices, public messaging, or mass media, how can we observe, ethnographically, the effects of constraints on and inequalities in treatment? What are the stakes of access to drugs, when this access is not being sought out, claimed, or enacted? This article tackles these questions by examining how HBV is being enacted in Senegal, but not necessarily in relation to antiviral treatment. I first describe the emergence, over the past decade and a half, of an exclusionary topography of HBV diagnosis and treatment. I introduce the notion of “filtration” to describe the effects of this topography on the formation of potential “subjects of access.” The diagnostic therapies and expertise required to determine need for treatment are expensive, urban, and largely privatized. Moreover, knowledge about HBV and its possibilities of care circulates in narrow and sparsely distributed channels. Only a tiny minority of persons are effectively “filtered into” care, while issues of access remain largely outside of public debate. I then move onto small-scale efforts, led by rural primary health workers and community associations, to raise awareness of and expand screening for HBV. Those driving information and screening either do not reveal that effective drugs exist or locate these beyond the reach of most of their audiences or patients. Why then do they do it? I examine the logics and effects of their work to identify the forms of inclusion, care, efficacy, and explanation these open up. At the same time, I seek to discern the indirect effects of unequal access to knowledge and resources in the ambivalence, uncertainties, and contradictions that pervade these efforts to inform, diagnose, and advise.
The Production of Testosterone and Gene Expression in Neonatal Testes of Rats Exposed to Diisoheptyl Phthalate During Pregnancy is Inhibited
Authors: Ji Bin , Wen Zina , Ni Chaobo , Zhu Qiqi , Wang Yiyan , Li Xiaoheng , Zhong Ying , Ge Ren-Shan
Published: April 2021

Background: Diisoheptyl phthalate (DIHP) is a phthalate plasticizer, which is a branched phthalate. Here, we reported the effects of gestational exposure to DIHP on testis development in male rats.

Methods: Pregnant Sprague-Dawley rats were orally fed with vehicle (corn oil, control) or DIHP (10, 100, 500, and 1,000 mg/kg) from gestational day (GD) 12–21. At GD21, serum testosterone levels, the number and distribution of fetal Leydig cells, and testicular mRNA and protein levels, the incidence of multinucleated gonocytes, and focal testicular hypoplasia in the neonatal testis were measured.

Results: DIHP increased the fetal Leydig cell cluster size and decreased the fetal Leydig cell size with LOAEL of 10 mg/kg. DIHP did not affect the fetal Leydig cell number. DIHP significantly lowered serum testosterone levels, down-regulated the expression of steroidogenesis-related genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3) and testis descent-related gene (Insl3) as well as protein levels of cholesterol side-chain cleavage enzyme (CYP11A1) and insulin-like 3 (INSL3). DIHP dose-dependently increased the percentage of multinucleated gonocytes with the low observed adverse-effect level (LOAEL) of 100 mg/kg. DIHP induced focal testicular hypoplasia.

Conclusion: Gestational exposure to DIHP causes testis dysgenesis in rats.
Repurposing Chloroquine Against Multiple Diseases With Special Attention to SARS-CoV-2 and Associated Toxicity
Authors: Kamat Siya , Kumari Madhuree
Published: April 2021

Chloroquine and its derivatives have been used since ages to treat malaria and have also been approved by the FDA to treat autoimmune diseases. The drug employs pH-dependent inhibition of functioning and signalling of the endosome, lysosome and trans-Golgi network, immunomodulatory actions, inhibition of autophagy and interference with receptor binding to treat cancer and many viral diseases. The ongoing pandemic of COVID-19 has brought the whole world on the knees, seeking an urgent hunt for an anti-SARS-CoV-2 drug. Chloroquine has shown to inhibit receptor binding of the viral particles, interferes with their replication and inhibits “cytokine storm”. Though multiple modes of actions have been employed by chloroquine against multiple diseases, viral diseases can provide an added advantage to establish the anti–SARS-CoV-2 mechanism, thein vitroandin vivotrials against SARS-CoV-2 have yielded mixed results. The toxicological effects and dosage optimization of chloroquine have been studied for many diseases, though it needs a proper evaluation again as chloroquine is also associated with several toxicities. Moreover, the drug is inexpensive and is readily available in many countries. Though much of the hope has been created by chloroquine and its derivatives against multiple diseases, repurposing it against SARS-CoV-2 requires large scale, collaborative, randomized and unbiased clinical trials to avoid false promises. This review summarizes the use and the mechanism of chloroquine against multiple diseases, its side-effects, mechanisms and the different clinical trials ongoing against “COVID-19”.
Computational and In Vitro Analysis of Plumbagin’s Molecular Mechanism for the Treatment of Hepatocellular Carcinoma
Authors: Wei Yanfei , Lin Yuning , Chen Wanjun , Liu Shasha , Jin Lijie , Huang Delun
Published: April 2021

Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and the second leading cause of cancer-related death in the world. Plumbagin (PL) is a small molecule naphthoquinone compound isolated from Plumbago zeylanica L. that has important anticancer properties, but its mechanism requires further investigation. In this study, we used a comprehensive network pharmacology approach to study the mechanism of action of PL for the treatment of HCC. The method includes the construction of multiple networks; moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify biological processes and signaling pathways. Subsequently, in vitro experiments were performed to verify the predicted molecular mechanisms obtained from the network pharmacology-based analysis. Network pharmacological analysis showed that PL may exert anti-HCC effects by enhancing reactive oxygen species (ROS) production to generate oxidative stress and by regulating the PI3K/Akt and MAPK signaling pathways. In vitro experiments confirmed that PL mainly mediates the production of ROS, regulates the PI3K/Akt and MAPK signaling pathways to promote apoptosis and autophagy, and shows significant therapeutic effects on HCC. In conclusion, our work proposes a comprehensive systems pharmacology approach to explore the potential mechanism of PL for the treatment of HCC.
Dezocine, An Opioid Analgesic, Exerts Antitumor Effects in Triple-Negative Breast Cancer by Targeting Nicotinamide Phosphoribosyltransferase
Authors: Xue Chenyang , Chen Wei , Yuan Aiwu , Chen Cheng , Li Shuaihu , Chen Kai , Zhao Yang , Xiao Tian , Shao Genze , Zou Yongdong , Zheng Duo
Published: April 2021

Opioids are a potential adjuvant treatment for certain cancers; while they are primarily used to relieve chronic pain, these drugs may also affect cancer progression and recurrence. Dezocine is one opioid commonly used in China, but its effects on cancer cells are unknown. Here, we demonstrated the inhibitory effect of dezocine on triple-negative breast cancer (TNBC) cells, and determined the underlying molecular mechanism. We found that dezocine suppressed cell proliferation, migration and invasion, and induced apoptosis in TNBC cells. Xenograft models demonstrated the inhibitory effects of dezocine treatment on TNBC tumor growth in vivo. The anticancer effects of dezocine were independent of opioid receptors, which are not highly expressed by normal breast or breast cancer tissues. A pull-down assay and LC-MS/MS analysis indicated that dezocine directly targets NAMPT: computer modeling verified that the free energy of dezocine kinetically bound into the pocket of NAMPT was −17.4 kcal/mol. Consequently, dezocine treatment inhibited NAMPT enzyme activity, resulting in cellular NAD abolishment. We confirmed the dezocine-induced inhibition of cell proliferation by both NAMPT knockdown and upon treatment with the inhibitor FK866. Our results suggest that both dezocine and NAMPT might represent novel therapeutic targets for TNBC.
Phytoconstituents, In Vitro Anti-Infective Activity of Buddleja indica Lam., and In Silico Evaluation of its SARS-CoV-2 Inhibitory Potential
Authors: Youssef Fadia S. , Altyar Ahmed E. , Omar Abdelsattar M. , Ashour Mohamed L.
Published: April 2021

Phytochemical investigation of Buddleja indica Lam. leaves methanol extract (BIT) resulted in the isolation of six known compounds for the first time from the plant, namely, p-hydroxybenzoic acid 1), caffeic acid 2), quercetin 3-O-β-D glucoside-7-O-α-L-rhamnoside 3), kaempferol 3-O-β-D glucoside-7-O-α-L-rhamnoside 4), quercetin 7-O-β-D glucoside 5) and kaempferol 6). BIT extract showed potent antibacterial activity with MIC values ranging between 0.48 and 1.95 μg/ml with Bacillus subtilis was the most susceptible to the BIT effect. It showed a notable antimycobacterial and anti-Helicobacter pylori activity with MIC values of 100 and 80 μg/ml, respectively. Vesicular stomatitis virus (VSV) was more sensitive to the antiviral activity of BIT comparable to herpes simplex virus type 1 (HSV-1), showing 48.38 and 41.85% inhibition of the viral replication at a dose of 50 μg/ml for VSV and HSV-1, respectively. In silico molecular docking of the isolated compounds revealed that caffeic acid 2) showed the highest fitting within the active sites of DNA-gyrase, topoisomerase IV, and SARS-CoV-2 MPro. Quercetin 7-O-β-D glucoside 5) revealed the best fitting in dihydrofolate reductase active site with ∆ G value equals −36.53 Kcal/mol. Kaempferol 6) exhibited the highest fitting towards β-lactamase, SARS-CoV-2PLpro, and SARS-CoV-2 3CLpro active sites. Thus, B. indica Lam. can be considered as a future source of cheap, substantially safe, and credible antibacterial, antifungal, and antiviral candidate of natural origin that could effectively participate in solving the problem of COVID-19 pandemic. These findings provide a scientific consolidation for the ethnomedicinal uses of Buddleja indica Lam. as a topical antiseptic.
Cocaine Reduces the Neuronal Population While Upregulating Dopamine D2-Receptor-Expressing Neurons in Brain Reward Regions: Sex-Effects
Authors: Clare Kevin , Pan Chelsea , Kim Gloria , Park Kicheon , Zhao Juan , Volkow Nora D. , Lin Zhicheng , Du Congwu
Published: April 2021

Addiction to cocaine is associated with dysfunction of the dopamine mesocortical system including impaired dopamine-2 receptor (D2r) signaling. However, the effects of chronic cocaine on neuronal adaptations in this system have not been systematically examined and data available is mostly from males. Here, we investigated changes in the total neuronal density and relative concentration of D2r-expressing neurons in the medial prefrontal cortex (mPFC), dorsal striatum (Dstr), nucleus accumbens (NAc), and ventral tegmental area (VTA) in both male and female mice passively exposed to cocaine for two weeks. In parallel experiments, we measured mRNA levels for Drd2 and for opioid peptides (mPenk and mPdyn). Through a combination of large field of view fluorescent imaging with BAC transgenic D2r-eGFP mice and immunostaining, we observed that cocaine exposed mice had a higher density of D2r-positive cells that was most prominent in mPFC and VTA and larger for females than for males. This occurred amidst an overall significant decrease in neuronal density (measured with NeuN) in both sexes. However, increases in Drd2 mRNA levels with cocaine were only observed in mPFC and Dstr in females, which might reflect the limited sensitivity of the method. Our findings, which contrast with previous findings of cocaine-induced downregulation of D2r binding availability, could reflect a phenotypic shift in neurons that did not previously express Drd2 and merits further investigation. Additionally, the neuronal loss particularly in mPFC with chronic cocaine might contribute to the cognitive impairments observed with cocaine use disorder.