Publications by authors named "Song Yao"

272 Publications

Risk of Late-Onset Breast Cancer in Genetically Predisposed Women.

J Clin Oncol 2021 Jul 22:JCO2100531. Epub 2021 Jul 22.

Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose: The prevalence of germline pathogenic variants (PVs) in established breast cancer predisposition genes in women in the general population over age 65 years is not well-defined. However, testing guidelines suggest that women diagnosed with breast cancer over age 65 years might have < 2.5% likelihood of a PV in a high-penetrance gene. This study aimed to establish the frequency of PVs and remaining risks of breast cancer for each gene in women over age 65 years.

Methods: A total of 26,707 women over age 65 years from population-based studies (51.5% with breast cancer and 48.5% unaffected) were tested for PVs in germline predisposition gene. Frequencies of PVs and associations between PVs in each gene and breast cancer were assessed, and remaining lifetime breast cancer risks were estimated for non-Hispanic White women with PVs.

Results: The frequency of PVs in predisposition genes was 3.18% for women with breast cancer and 1.48% for unaffected women over age 65 years. PVs in , , and were found in 3.42% of women diagnosed with estrogen receptor (ER)-negative, 1.0% with ER-positive, and 3.01% with triple-negative breast cancer. Frequencies of PVs were lower among women with no first-degree relatives with breast cancer. PVs in , , , and were associated with increased risks (odds ratio = 2.9-4.0) of breast cancer. Remaining lifetime risks of breast cancer were ≥ 15% for those with PVs in , , and .

Conclusion: This study suggests that all women diagnosed with triple-negative breast cancer or ER-negative breast cancer should receive genetic testing and that women over age 65 years with and PVs and perhaps with and PVs should be considered for magnetic resonance imaging screening.
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http://dx.doi.org/10.1200/JCO.21.00531DOI Listing
July 2021

Genetic Variants in and Genes and Breast Cancer Risk in White and Black Women.

Front Oncol 2021 24;11:679998. Epub 2021 Jun 24.

Department of Cancer Prevention & Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.

and genes are involved in inflammatory processes and that may be related to breast cancer risk differentially between White and Black women. We evaluated distributions of genetic variants involved in and -related pathways and examined their associations with breast cancer risk among 1,275 White and 1,299 Black cases and controls who participated in the Women's Circle of Health Study. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted logistic regression models. Our results showed differential associations of certain genetic variants with breast cancer according to menopausal and ER status in either White or Black women. In White women, an increased risk of breast cancer was observed for -rs689470 (OR: 2.02, = 0.01) in the dominant model, and was strongest among postmenopausal women (OR: 2.72, = 0.02) and for estrogen receptor positive (ER+) breast cancers (OR: 2.60, = 0.001). A reduced risk was observed for -rs7099874 (OR: 0.75, = 0.01) in the dominant model, and was stronger among postmenopausal women (OR: 0.68, = 0.03) and for ER+ cancer (OR: 0.66, = 0.001). Four SNPs (rs3840880, rs1126667, rs434473, rs1042357) in the gene were found in high LD (r >0.98) in White women and were similarly associated with reduced risk of breast cancer, with a stronger association among postmenopausal women and for ER- cancer. Among Black women, increased risk was observed for -rs1369214 (OR: 1.44, = 0.003) in the recessive model and was stronger among premenopausal women (OR: 1.57, = 0.03) and for ER+ cancer (OR: 1.53, = 0.003). Our study suggests that genetic variants of and genes are associated with breast cancer, and that these associations and genotype distributions differ in subgroups defined by menopausal and ER status between White and Black women. Findings may provide insights into the etiology of breast cancer and areas for further research into reasons for breast cancer differences between races.
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http://dx.doi.org/10.3389/fonc.2021.679998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263909PMC
June 2021

Diagnostic accuracy of cardiac magnetic resonance tissue tracking technology for differentiating between acute and chronic myocardial infarction.

Quant Imaging Med Surg 2021 Jul;11(7):3070-3081

Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: This study aimed to explore the diagnostic accuracy of cardiac magnetic resonance tissue tracking (CMR-TT) technology in the quantitative evaluation of left myocardial infarction for differentiating between acute and chronic myocardial infarction.

Methods: A total of 104 human subjects were enrolled in this prospective study. Among them, 64 healthy subjects and 40 patients with left ventricular myocardial infarction and 7 days and 6 months' follow-up CMR studies, including steady-state free precession (SSFP) sequence and late gadolinium enhancement MR imaging, were enrolled. The strain parameters of the infarcted myocardium, its corresponding remote segments, and global right ventricular strain were analyzed using tissue tracking technology, and CMR-TT 3D strain parameters in radial, circumferential, and longitudinal directions were obtained. Receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy of the CMR-TT strain parameters for discriminating between acute and chronic myocardial infarction.

Results: Peak radial strain (RS) of infarcted myocardium increased from 12.99±7.28 to 18.57±6.66 at 6 months (P<0.001), whereas peak circumferential strain (CS) increased from -8.82±4.71 to -12.78±3.55 (P<0.001). CS yielded the best areas under the ROC curve (AUC) of 0.751 in showing differentiation between acute and chronic myocardial infarction of all the strain parameters obtained. The highest significant differences between acute myocardial infarction and normal myocardium, both in the left and right ventricles, were also found in the RS (P<0.001) and CS (P<0.001).

Conclusions: RS and CS obtained by CMR-TT have high sensitivity and specificity in the differential diagnosis of acute versus chronic myocardial infarction, and their use is thus worth popularizing in clinical application.
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http://dx.doi.org/10.21037/qims-20-1109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250004PMC
July 2021

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Nat Commun 2021 07 7;12(1):4198. Epub 2021 Jul 7.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
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http://dx.doi.org/10.1038/s41467-021-24327-xDOI Listing
July 2021

The Expression of Semaphorin 7A in Human Periapical Lesions.

J Endod 2021 Jun 11. Epub 2021 Jun 11.

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Department of Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China. Electronic address:

Introduction: Semaphorin 7A (SEMA7A) is a membrane-bound or secretory protein exerting multiple functions in the regulation of inflammation, neural degradation, and cancer progression. Human periapical lesions are chronic and infectious diseases mainly caused by bacteria. However, the involvement of SEMA7A in human periapical lesions is still unclear. This study aimed to explore the expression of SEMA7A in human periapical lesions accompanied by the potential association of SEMA7A with matrix metalloproteinase (MMP)-1 and MMP-3 during the progression of apical periodontitis.

Methods: Samples of periapical lesions and healthy controls were collected. Total RNA and protein were extracted respectively for quantitative real-time polymerase chain reaction and Western blot analysis. Additionally, 6 healthy samples and 27 periapical lesion samples were fixed, dehydrated, and embedded for further histologic and immunochemical analysis. The expression of SEMA7A was quantified by average integrated optical density. Immunofluorescence analysis was conducted to explore the colocalization of SEMA7A/MMP-1 and SEMA7A/MMP-3.

Results: Compared with healthy controls, the messenger RNA and protein expression of SEMA7A was markedly up-regulated in periapical lesions. A stronger expression of MMP-1, MMP-3, and inflammatory cytokines was exhibited in periapical lesions than in healthy groups. An increasing expression of SEMA7A can be observed in both the periapical granuloma group and the radicular cyst group compared with the normal group (P < .01). Immunofluorescence results showed the colocalization of SEMA7A with both MMP-1 and MMP-3 in vascular vessels and extracellular matrix.

Conclusions: SEMA7A was up-regulated in periapical periodontitis and might be involved in the tissue destruction and infiltration of immune cells in periapical lesions.
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http://dx.doi.org/10.1016/j.joen.2021.06.005DOI Listing
June 2021

Risk of Breast Cancer Among Carriers of Pathogenic Variants in Breast Cancer Predisposition Genes Varies by Polygenic Risk Score.

J Clin Oncol 2021 Jun 8:JCO2001992. Epub 2021 Jun 8.

Population Health Sciences Department, Weill Cornell Medicine, New York, NY.

Purpose: This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population.

Methods: A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in , , , , , , , , and . PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor-specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC.

Results: The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of , , and carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of and carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk.

Conclusion: PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of and nearly half of carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.
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http://dx.doi.org/10.1200/JCO.20.01992DOI Listing
June 2021

The Controversy of Pepsinogen A/Pepsin A in Detecting Extra-Gastroesophageal Reflux.

J Voice 2021 Jun 2. Epub 2021 Jun 2.

Department of Oto-Rhino-Laryngology, and West China Biomedical Big Data Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.. Electronic address:

Background: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux.

Methods: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples.

Results: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring.

Conclusions: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.
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http://dx.doi.org/10.1016/j.jvoice.2021.04.009DOI Listing
June 2021

Comparison of the Prevalence of Pathogenic Variants in Cancer Susceptibility Genes in Black Women and Non-Hispanic White Women With Breast Cancer in the United States.

JAMA Oncol 2021 Jul;7(7):1045-1050

Slone Epidemiology Center at Boston University, Boston, Massachusetts.

Importance: The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes in US Black women compared with non-Hispanic White women with breast cancer is poorly described.

Objective: To determine whether US Black and non-Hispanic White women with breast cancer have a different prevalence of PVs in 12 cancer susceptibility genes.

Design, Setting, And Participants: Multicenter, population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Participants were Black and non-Hispanic White women diagnosed with breast cancer, unselected for family history or age at diagnosis. Data were collected from June 1993 to June 2020; data analysis was performed between September 2020 and February 2021.

Main Outcomes And Measures: Prevalence of germline PVs in 12 established breast cancer susceptibility genes.

Results: Among 3946 Black women (mean [SD] age at diagnosis, 56.5 [12.02] y) and 25 287 non-Hispanic White women (mean [SD] age at diagnosis, 62.7 [11.14] y) with breast cancer, there was no statistically significant difference by race in the combined prevalence of PVs in the 12 breast cancer susceptibility genes evaluated (5.65% in Black vs 5.06% in non-Hispanic White women; P = .12). The prevalence of PVs in CHEK2 was higher in non-Hispanic White than Black patients (1.29% vs 0.38%; P < .001), whereas Black patients had a higher prevalence of PVs in BRCA2 (1.80% vs 1.24%; P = .005) and PALB2 (1.01% vs 0.40%; P < .001). For estrogen receptor-negative breast cancer, the prevalence of PVs was not different except for PALB2, which was higher in Black women. In women diagnosed before age 50 years, there was no difference in overall prevalence of PVs in Black vs non-Hispanic White women (8.83% vs 10.04%; P = .25), and among individual genes, only CHEK2 PV prevalence differed by race. After adjustment for age at diagnosis, the standardized prevalence ratio of PVs in non-Hispanic White relative to Black women was 1.08 (95% CI, 1.02-1.14), and there was no longer a statistically significant difference in BRCA2 PV prevalence.

Conclusions And Relevance: This large population-based case-control study revealed no clinically meaningful differences in the prevalence of PVs in 12 breast cancer susceptibility genes between Black and non-Hispanic White women with breast cancer. The findings suggest that there is not sufficient evidence to make policy changes related to genetic testing based on race alone. Instead, all efforts should be made to ensure equal access to and uptake of genetic testing to minimize disparities in care and outcomes.
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http://dx.doi.org/10.1001/jamaoncol.2021.1492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160931PMC
July 2021

Causality Inference of Obesity and Cancer Risk by Mendelian Randomization Analysis: Are We There yet?

Authors:
Song Yao

J Natl Cancer Inst 2021 May 21. Epub 2021 May 21.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

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http://dx.doi.org/10.1093/jnci/djab103DOI Listing
May 2021

Multiplexed digital spatial profiling of invasive breast tumors from Black and White women.

Mol Oncol 2021 May 21. Epub 2021 May 21.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

The NanoString GeoMx digital spatial profiling is a new multiplexed platform that quantifies the abundance of tumor- and immune-related proteins in a spatially resolved manner. We performed DSP for the simultaneous assessment of 52 analytes within spatially resolved tissue compartments defined by pan-cytokeratin expression. We compared protein targets between 94 African American/Black and 65 European American/White cases, tumor and stromal tissue compartments, estrogen receptor alpha (ER)-positive and ER-negative cases, and explored potential biomarkers of survival. Of 33 analytes with robust signal for analysis, results were highly replicable. For a subset of markers, correlative analyses between DSP analytes and traditional immunohistochemistry scores revealed moderate to very strong associations between the two platforms. Similarly, DSP analytes and gene expression scores were concordant for 21 of 25 markers with overlap between the two datasets. Several analytes varied by ER status, and across the 25 immune markers surveyed, 14 had a significant inverse association with ER expression. B7 homolog 3 (B7-H3; encoded by CD276) was the only analyte to show a significant difference by race, being lower in both the tumor and stromal compartments in Black women. DSP markers that were associated with survival included CD8, CD25, CD56, CD127, EpCAM, ER, Ki-67, and STING. We conclude that DSP is an efficient tool for screening tumor- and immune-related markers in a simultaneous fashion and yields results that are concordant with established immune profiling assays. DSP immune analytes were inversely associated with ER expression, in agreement with a substantial body of previous work that documents higher immune infiltration in ER-negative breast cancers. This technology revealed that scores of the B7-H3 protein were significantly lower in breast cancers from Black women compared with White women, an intriguing finding that requires replication in independent and racially diverse female populations.
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http://dx.doi.org/10.1002/1878-0261.13017DOI Listing
May 2021

Effect of ginsenoside-Rg1 on experimental Parkinson's disease: A systematic review and meta-analysis of animal studies.

Exp Ther Med 2021 Jun 25;21(6):552. Epub 2021 Mar 25.

Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.

Previous studies have reported that ginsenoside-Rg1 (G-Rg1) was able to mitigate the loss of dopaminergic neurons in animal models of Parkinson's disease (PD). The present study provided a systematic review and meta-analysis of preclinical studies to pool current evidence on the effect of G-Rg1 on neurogenesis in the treatment of PD. Eligible studies were identified through a search from six databases: PubMed, EMBASE, Web of Science, VIP, Chinese National Knowledge Infrastructure and the Wanfang database. Primary outcomes were tyrosine hydroxylase (TH)-positive cells in the nigra, Nissl staining-positive cells in the nigra, pole test time and dopamine (DA) levels in the striatum. A total of 18 eligible studies were identified, involving 343 animals. Of these, 13 reported a significant relationship between G-Rg1 and improved TH-positive cells in the nigra compared with the control group (P<0.00001). Furthermore, 3 studies reported a significant relationship between G-Rg1 and improved Nissl-positive cells in the nigra compared with the control group (P<0.00001). In addition, 4 studies reported a significant effect of G-Rg1 to reduce the total pole test time compared with that in the control group (P=0.001). A total of 3 studies indicated a significant association between G-Rg1 and improved DA levels in the striatum compared with the control group (P<0.00001). These results suggested that G-Rg1 has positive effects in attenuating damage in models of PD, and thus, it is a potential candidate neuroprotective drug for human PD.
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http://dx.doi.org/10.3892/etm.2021.9984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027743PMC
June 2021

The effect of facial features on facial anthropomorphic trustworthiness in social robots.

Appl Ergon 2021 Jul 3;94:103420. Epub 2021 Apr 3.

School of Design, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China. Electronic address:

As the nature of human-robot relationships have become increasingly bound to shift from supervisor-machine to friend-companion, people have exhibited an increasing interest in making social judgments toward such anthropomorphic objects, such as trustworthiness. However, the facial features of social robots and their potential effect on anthropomorphic trustworthiness are seldom analyzed and discussed comprehensively. This study examined whether the trustworthiness perception toward a social robot shared similarity with baby schema features on the human face. It also explored the effects of different combinations of baby schema facial features, especially the positions and sizes of the eyes and mouth, on facial anthropomorphic trustworthiness. A 5-way mixed experiment (N = 270) was conducted accordingly. The results indicated that people would experience a high level of facial anthropomorphic trustworthiness toward robots with baby schema features (i.e., large eyes, with medium vertical and horizontal positions of the eyes and mouth). This paper contributes to the literature on facial anthropomorphic trustworthiness in human-robot interaction and provides suggestions for social robot design.
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http://dx.doi.org/10.1016/j.apergo.2021.103420DOI Listing
July 2021

Transcriptome Analysis Reveals Downregulation of Urocortin Expression in the Hypothalamo-Neurohypophysial System of Spontaneously Hypertensive Rats.

Front Physiol 2020 17;11:599507. Epub 2021 Mar 17.

Bristol Medical School: Translational Health Sciences, Dorothy Hodgkin Building, University of Bristol, Bristol, United Kingdom.

The chronically increased blood pressure characteristic of essential hypertension represents an insidious and cumulative risk for cardiovascular disease. Essential hypertension is a multifactorial condition, with no known specific aetiology but a strong genetic component. The Spontaneously Hypertensive rat (SHR) shares many characteristics of human essential hypertension, and as such is a commonly used experimental model. The mammalian hypothalamo-neurohypophyseal system (HNS) plays a pivotal role in the regulation of blood pressure, volume and osmolality. In order to better understand the possible role of the HNS in hypertension, we have used microarray analysis to reveal differential regulation of genes in the HNS of the SHR compared to a control normotensive strain, the Wistar Kyoto rat (WKY). These results were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). One of the genes identified and validated as being downregulated in SHR compared to WKY was that encoding the neuropeptide urocortin (Ucn). Immunohistochemical analyses revealed Ucn to be highly expressed within magnocellular neurons of the PVN and SON, with pronounced localisation in dendritic projections containing oxytocin and vasopressin. When Ucn was overexpressed in the PVN of the SHR by lentiviral mediated gene transfer, blood pressure was unaffected but there were significant, transient reductions in the VLF spectra of systolic blood pressure consistent with an action on autonomic balance. We suggest that Ucn may act, possibly via dendritic release, to subtly regulate neurohumoral aspects of arterial pressure control.
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http://dx.doi.org/10.3389/fphys.2020.599507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011454PMC
March 2021

Transport of coupled particles in rough ratchet driven by Lévy noise.

Chaos 2021 Mar;31(3):033104

School of Mathematics and Information Science, Shaanxi Normal University, Xi'an 710119, People's Republic of China.

This paper studies the transport of coupled particles in a tilted rough ratchet potential. The relationship between particles transport and roughness, noise intensity, external force, coupling strength, and free length is explored numerically by calculating the average velocity of coupled particles. Related investigations have found that rough potential can accelerate the process of crossing the barrier by increasing the particles velocity compared with smooth potential. It is based on the fact that the roughness on the potential surface is like a "ladder," which helps particles climb up and blocks them from sliding down. Moreover, superimposing an appropriate external force on the coupled particles or strengthening the Lévy noise leads to the particles velocity to increase. It is worth emphasizing that when the external force is selected properly, an optimal roughness can be found to maximize the particles velocity. For a given roughness, an optimal coupling coefficient is discovered to match the maximum velocity. And once the coupling coefficient is greater than the optimal value, the particles velocity drops sharply to zero. Furthermore, our results also indicate that choosing an appropriate free length between particles can also speed up transport.
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http://dx.doi.org/10.1063/5.0027116DOI Listing
March 2021

Enterolignan Production in a Flaxseed Intervention Study in Postmenopausal US Women of African Ancestry and European Ancestry.

Nutrients 2021 Mar 12;13(3). Epub 2021 Mar 12.

Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Lignans are phytochemicals studied extensively as dietary factors in chronic disease etiology. Our goal was to examine associations between the gut microbiota and lignan metabolism and whether these associations differ by ethnicity. We conducted a flaxseed (FS) dietary intervention in 252 healthy, postmenopausal women of African ancestry (AA) and European ancestry (EA). Participants consumed ~10 g/d ground flaxseed for 6 weeks and provided overnight urine collections and fecal samples before and after intervention. The gut microbiota was characterized using 16S rRNA gene sequencing and differences in microbial community composition compared by ethnicity and intervention status. We observed a significant difference in the composition of the microbiota measured as beta diversity ( < 0.05) between AA and EA at baseline that was attenuated with FS consumption. Genera that were significantly associated with ENL production (e.g., , , , ) were unique to each group. Bacteria (e.g., , and ) previously associated with colorectal cancer and cardiovascular disease, both diet-related chronic diseases, were unique to either AA or EA and were significantly reduced in the FS intervention. This study suggests that ethnic variation in ENL metabolism may be linked to gut microbiota composition, and its impact on disease risk deserves future investigation.
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http://dx.doi.org/10.3390/nu13030919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001909PMC
March 2021

What Influences the Perceived Trust of a Voice-Enabled Smart Home System: An Empirical Study.

Sensors (Basel) 2021 Mar 13;21(6). Epub 2021 Mar 13.

Department of Industrial Design, Faculty of Design and Architecture, Universiti Putra Malaysia, Selangor 43400, Malaysia.

Contemporarily, almost all the global IT giants have aimed at the smart home industry and made an active strategic business layout. As the early-stage and entry-level product of the voice-enabled smart home industry, the smart speakers have been going through rapid development and rising fierce market competition globally in recent years. China, one of the most populous and largest markets in the world, has tremendous business potential in the smart home industry. The market sales of smart speakers in China have gone through rapid growth in the past three years. However, the market penetration rate of related smart home devices and equipment still stays extremely low and far from mass adoption. Moreover, the market sales of smart speakers have also entered a significant slowdown and adjustment period since 2020. Chinese consumers have moved from early impulsive consumption to a rational consumption phase about this early-stage smart home product. Trust in the marketing field is considered an indispensable component of all business transactions, which plays a crucial role in adopting new technologies. This study explores the influencing factors of Chinese users' perceived trust in the voice-enabled smart home systems, uses structural equation modeling (SEM) to analyze the interaction mechanism between different variables, and establishes a perceived trust model through 475 valid samples. The model includes six variables: system quality, familiarity, subjective norm, technology optimism, perceived enjoyment, and perceived trust. The result shows that system quality is the essential influence factor that impacts all other variables and could significantly affect the perceived trust. Perceived enjoyment is the most direct influence variable affected by system quality, subjective norm, and technology optimism, and it positively affects the perceived trust in the end. The subjective norm is one of the most distinguishing variables for Chinese users, since China has a collectivist consumption culture. People always expect their behavior to meet social expectations and standards to avoid criticism and acquire social integration. Therefore, policy guidance, authoritative opinions, and people with important reference roles will significantly affect consumers' perceived trust and purchase intention. Familiarity and technology optimism are important influential factors that will have an indirect impact on the perceived trust. The related results of this study can help designers, practitioners, and researchers of the smart home industry produce products and services with higher perceived trust to improve consumers' adoption and acceptance so that the market penetration rate of related products and enterprises could be increased, and the maturity and development of the voice-enabled smart home industry could be promoted.
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http://dx.doi.org/10.3390/s21062037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998654PMC
March 2021

Evaluating Polygenic Risk Scores for Breast Cancer in Women of African Ancestry.

J Natl Cancer Inst 2021 Mar 26. Epub 2021 Mar 26.

Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.

Background: Polygenic risk scores (PRS) have been demonstrated to identify women of European, Asian and Latino ancestry at elevated risk of developing breast cancer (BC). We evaluated the performance of existing PRSs trained in European ancestry populations among women of African ancestry.

Methods: We assembled genotype data for women of African ancestry, including 9,241 cases and 10,193 controls. We evaluated associations of 179- and 313-variant PRSs with overall and subtype-specific BC risk. PRS discriminatory accuracy was assessed using area under the receiver operating characteristic curve (AUC). We also evaluated a recalibrated PRS, replacing the index variant with variants in each region that better captured risk in women of African ancestry, and estimated lifetime absolute risk of BC in African Americans by PRS category.

Results: For overall BC, the odds ratios per standard deviation of PRS313 was 1.27 (95%CI = 1.23 to 1.31), with an AUC of 0.571 (95%CI = 0.562 to 0.579). Compared to women with average risk (40th-60th PRS percentile), women in the top decile of PRS313 had a 1.54-fold increased risk (95% CI = 1.38 to 1.72). By age 85 years, the absolute risk of overall BC was 19.6% for African American women in the top 1% of PRS313 and 6.7% for those in the lowest 1%. The recalibrated PRS did not improve BC risk prediction.

Conclusion: The PRSs stratify BC risk in women of African ancestry, with attenuated performance compared to that reported in European, Asian and Latina populations. Future work is needed to improve BC risk stratification for women of African ancestry.
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http://dx.doi.org/10.1093/jnci/djab050DOI Listing
March 2021

Resilience, vulnerability and adaptability: A qualitative study of COVID-19 lockdown experiences in two Henan villages, China.

PLoS One 2021 25;16(2):e0247383. Epub 2021 Feb 25.

School of Political Science and Public Administration, Wuhan University, Wuhan, Hubei, China.

Background: The Chinese government's early handling of COVID-19 has been perceived as aggressive and oppressive. Many of the most radical measures were adopted in Henan province, immediately north of Hubei, the pandemic's epicentre in China. However, little is known about how rural residents-a group systematically disadvantaged in Chinese society-responded to authorities' draconian restrictions.

Methods: To understand the lockdown measures and rural community responses at the grassroots level, face-to-face interviewers were conducted with both village cadres and villagers from two Henan villages in May and June 2020. The interviews were analysed with qualitative content analysis methods, with the coding process guided by the concepts of resilience, vulnerability and adaptability from the literature on disaster risk reduction.

Results: We found that the lockdown measures were indeed radical and disproportionate relative to the level of risk presented; however, they were largely accepted by villagers. This contradiction can be explained by two key contributing factors: (i) shared interests of individual villagers and the converged goal of government and civil society, and (ii) tacit flexibility in COVID-19 adaption strategies to tackle conflict resulting from goal diversion between citizens and local governments.

Conclusions: These findings highlight the nuances of ground-level politics. Despite their 'radical' nature, the lockdown measures were not implemented as simple top-down coercion. Instead, they involved, importantly, the bottom-up, localised response of villagers, and they were negotiated and adapted according to local circumstances.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247383PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906399PMC
March 2021

The involvement of semaphorin 7A in tumorigenic and immunoinflammatory regulation.

J Cell Physiol 2021 Sep 21;236(9):6235-6248. Epub 2021 Feb 21.

State Key Laboratory of Oral Diseases and National Clinical Research Center of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Semaphorins, a large group of highly conserved proteins, consist of eight subfamilies that are widely expressed in vertebrates, invertebrates, and viruses and exist in membrane-bound or secreted forms. First described as axon guidance cues during neurogenesis, semaphorins also perform physiological functions in other organ systems, such as bone homeostasis, immune response, and tumor progression. Semaphorin 7A (SEMA7A), also known as CDw108, is an immune semaphorin that modulates diverse immunoinflammatory processes, including immune cell interactions, inflammatory infiltration, and cytokine production. In addition, SEMA7A regulates the proliferation, migration, invasion, lymph formation, and angiogenesis of multiple types of tumor cells, and these effects are mediated by the interaction of SEMA7A with two specific receptors, PLXNC1 and integrins. Thus, SEMA7A is intimately related to the pathogenesis of multiple autoimmune and inflammation-related diseases and tumors. This review focuses on the role of SEMA7A in the pathogenesis of autoimmune disorders, inflammatory diseases, and tumors, as well as the underlying mechanisms. Furthermore, strategies targeting SEMA7A as a potential predictive, diagnostic, and therapeutic agent for these diseases are also addressed.
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http://dx.doi.org/10.1002/jcp.30340DOI Listing
September 2021

A prospective study of lifestyle factors and bone health in breast cancer patients who received aromatase inhibitors in an integrated healthcare setting.

J Cancer Surviv 2021 Feb 9. Epub 2021 Feb 9.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Purpose: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown.

Methods: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture.

Results: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37).

Conclusions: Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy.

Implications For Cancer Survivors: Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies.
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http://dx.doi.org/10.1007/s11764-021-00993-0DOI Listing
February 2021

Genetic ancestry and skeletal toxicities among childhood acute lymphoblastic leukemia patients in the DFCI 05-001 cohort.

Blood Adv 2021 01;5(2):451-458

Jacob School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY.

Hispanic children have a higher incidence of acute lymphoblastic leukemia (ALL) and inferior treatment outcomes relative to non-Hispanic White children. We previously reported that Hispanic children with ALL had lower risk of fracture and osteonecrosis. To unravel the genetic root of such ethnic differences, we genotyped 449 patients from the DFCI 05-001 cohort and analyzed their ancestry. Patients with discordant clinical and genetic ancestral groups were reclassified, and those with unknown ancestry were reassigned on the basis of genetic estimates. Both clinical and genetic ancestries were analyzed in relation to risk of bone toxicities and survival outcomes. Consistent with clinically reported race/ethnicity, genetically defined Hispanic and Black patients had significantly lower risk of fracture (Hispanic: subdistribution hazard ratio [SHR], 0.42; 95% confidence interval [CI], 0.22-0.81; P = .01; Black: SHR, 0.28; 95% CI, 0.10-0.75; P = .01), and osteonecrosis (Hispanic: SHR, 0.12; 95% CI, 0.02-0.93; P = .04; Black: SHR, 0.24; 95% CI, 0.08-0.78; P = .02). The lower risk was driven by African but not Native American or Asian ancestry. In addition, patients with a higher percentage of Native American ancestry had significantly poorer overall survival and event-free survival. Our study revealed that the lower risk of bone toxicities among Black and Hispanic children treated for ALL was attributed, in part, to the percentage of African ancestry in their genetic admixture. The findings provide suggestive evidence for the protective effects of genetic factors associated with African decent against bone damage caused by ALL treatment and clues for future studies to identify underlying biological mechanisms.
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http://dx.doi.org/10.1182/bloodadvances.2020003060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839368PMC
January 2021

A Population-Based Study of Genes Previously Implicated in Breast Cancer.

N Engl J Med 2021 02 20;384(5):440-451. Epub 2021 Jan 20.

From Mayo Clinic, Rochester, MN (C. Hu, S.N.H., R.G., K.Y.L., J.N., J.L., S. Yadav, N.J.B., T.L., J.E.O., C.S., C.M.V., E.C.P., F.J.C.); Harvard University T.H. Chan School of Public Health (H.H., C.G., D.J.H., P.K.), Slone Epidemiology Center at Boston University (K.A.B., J.R.P., L.R.), and Brigham and Women's Hospital (H.E.) - all in Boston; Qiagen, Hilden, Germany (R.S., J.K.); Roswell Park Comprehensive Cancer Center, Buffalo (C.B.A., S. Yao), and Weill Cornell Medicine, New York (R.T.) - both in New York; the University of California, Irvine (H.A.-C., A.Z.), Beckman Research Institute of City of Hope, Duarte (L.B., H.M., S.N., J.N.W.), Keck School of Medicine, University of Southern California, Los Angeles (C. Haiman), and Stanford University School of Medicine, Stanford (E.M.J., A.W.K.) - all in California; the University of Wisconsin-Milwaukee Joseph J. Zilber School of Public Health, Milwaukee (P.A.), and the University of Wisconsin-Madison, Madison (E.S.B., I.M.O., A.T.-D.); the Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, State University of New Jersey, New Brunswick (E.V.B.); the Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta (B.D.C., S.M.G., M.G., J.M.H., E.J.J., A.V.P.); the University of Oxford, Oxford, United Kingdom (D.J.H.); the Fred Hutchinson Cancer Research Center (C.K., P.A.N.) and the Department of Epidemiology, University of Washington (S.L.) - both in Seattle; the Epidemiology Program, University of Hawaii Cancer Center, Honolulu (L.L.M.); the National Institute of Environmental Health Sciences, Durham, NC (K.M.O., D.P.S., J.A.T., C.W.); Vanderbilt University, Nashville (T.P., S.R.); the University of Utah, Salt Lake City (D.E.G.); and the Department of Medicine and the Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (S.M.D., K.L.N.).

Background: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants.

Methods: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed.

Results: Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in and were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in , , and were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in , , and were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in , were not associated with an increased risk of breast cancer.

Conclusions: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.).
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http://dx.doi.org/10.1056/NEJMoa2005936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127622PMC
February 2021

Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy.

Cancers (Basel) 2021 Jan 8;13(2). Epub 2021 Jan 8.

Department of Radiation Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

Background: The benefit of aspirin in rectal cancer during chemoradiation therapy (CRT) and the factors affecting its efficacy are not well characterized. We compared the outcomes of rectal patients undergoing neoadjuvant CRT based on aspirin use.

Methods: Patients undergoing CRT for rectal cancer from 2010 to 2018 were evaluated. Aspirin use was determined by medication list prior to treatment. RNA sequencing and subsequent gene set enrichment analysis was performed on surgically resected specimens.

Results: 147 patients underwent neoadjuvant CRT with a median follow-up of 38.2 months. Forty-two patients were taking aspirin prior to CRT. Aspirin users had significantly less local and distant progression, and improved progression-free and overall survival. On RNA-sequencing, neither nor mutational status were associated with the benefit of aspirin use or tumor downstaging. PTGS2/COX2 expression trended lower in aspirin users, but not with tumor response. Aspirin use was associated with increases of M1 macrophages, plasma cells, CD8+ T cells, and reduction of M2 macrophages in the resected tumor.

Conclusions: Concurrent aspirin use during neoadjuvant CRT was associated with improved local and distant tumor control leading to significantly improved survival. Neither mutations in or , nor the levels of COX-2 expression at the time of resection of the residual tumor were predictive of these aspirin benefits.
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http://dx.doi.org/10.3390/cancers13020205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826684PMC
January 2021

Breast Tumor Microenvironment in Black Women: A Distinct Signature of CD8+ T Cell Exhaustion.

J Natl Cancer Inst 2021 Jan 5. Epub 2021 Jan 5.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Background: Blacks tend to have a stronger inflammatory immune response than Whites. We hypothesized that racial differences in host immunity also manifest in the tumor microenvironment (TME), constituting part of a distinct aggressive tumor biology underlying higher mortality in Black women.

Methods: Pathological and gene expression profiling approaches were used for characterizing infiltrating immune cells in breast TME from 1,315 patients from the Women's Circle of Health Study. Racial differences in tumor immune phenotypes were compared, with results validated in a publicly accessible dataset. Prognostic associations of immune phenotypes were assessed in three independent cohorts.

Results: We found marked and consistent differences in tumor immune responses between Black and White patients. Not only did tumors from Blacks display a stronger overall immune presence, but the composition and quality of immune infiltrates differed, regardless of tumor subtypes. Black patients had a stronger CD4+/B cell response, and further, a more exhausted CD8+ T cell profile. A signature indicating a higher ratio of exhausted CD8+ T cells to total CD8+ T cells (ExCD8-r) was consistently associated with poorer survival, particularly among hormone receptor (HR)-positive patients. Among HR-negative patients, combinations of the absolute fraction of CD8+ T cells and ExCD8-r signature identified the CD8lowExCD8-rhigh subgroup, the most prevalent among Blacks, with the worst survival.

Conclusions: Our findings of a distinct exhausted CD8+ T cell signature in Black breast cancer patients indicates an immunobiological basis for their more aggressive disease, and also a rationale for the use of immune checkpoint inhibitors targeting the exhaustion phenotype.
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http://dx.doi.org/10.1093/jnci/djaa215DOI Listing
January 2021

Sinonasal teratocarcinosarcoma: a case report and literature review.

J Int Med Res 2020 Dec;48(12):300060520971488

Department of Oto-Rhino-Laryngology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.

Background: Sinonasal teratocarcinosarcoma (SNTCS) is a highly invasive malignant tumor most frequently found in the nasal cavity and paranasal sinuses. As a result, it can be confused with other sinonasal tumors. In addition, SNTCS progresses rapidly and often infiltrates other tissues or organs in the early phase, resulting in poor patient prognosis. The objective of this article was to report the case of a patient with SNTCS and discuss the management strategy. Furthermore, we conducted a literature review for SNTCS and summarized the findings from 107 cases. Here, we report a 47-year-old man diagnosed with SNTCS and treated with radiochemotherapy after an initial operation. After follow-up for 5 years, no tumor recurrence was observed.

Conclusions: As SNTCS progresses rapidly, early diagnosis and surgical treatment combined with radiochemotherapy can improve patient survival.
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http://dx.doi.org/10.1177/0300060520971488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754799PMC
December 2020

The emerging roles of semaphorin4D/CD100 in immunological diseases.

Biochem Soc Trans 2020 12;48(6):2875-2890

State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

In vertebrates, the semaphorin family of proteins is composed of 21 members that are divided into five subfamilies, i.e. classes 3 to 7. Semaphorins play crucial roles in regulating multiple biological processes, such as neural remodeling, tissue regeneration, cancer progression, and, especially, in immunological regulation. Semaphorin 4D (SEMA4D), also known as CD100, is an important member of the semaphorin family and was first characterized as a lymphocyte-specific marker. SEMA4D has diverse effects on immunologic processes, including immune cell proliferation, differentiation, activation, and migration, through binding to its specific membrane receptors CD72, PLXNB1, and PLXNB2. Furthermore, SEMA4D and its underlying signaling have been increasingly linked with several immunological diseases. This review focuses on the significant immunoregulatory role of SEMA4D and the associated underlying mechanisms, as well as the potential application of SEMA4D as a diagnostic marker and therapeutic target for the treatment of immunological diseases.
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http://dx.doi.org/10.1042/BST20200821DOI Listing
December 2020

Hedonic and Utilitarian Motivations of Home Motion-Sensing Game Play Behavior in China: An Empirical Study.

Int J Environ Res Public Health 2020 11 26;17(23). Epub 2020 Nov 26.

School of Design, Kyushu University, Fukuoka 8158540, Japan.

As an important branch of video games and the integration of emerging motion-sensing technology, home motion-sensing games cannot only bring hedonic entertainment but also promote utilitarian benefits including exercise and social interaction for people to improve their physical and psychological health. As one of the most populous countries in the world, China has the largest number of households in the world but quite a low home game penetration rate due to the 13 year game industry winter for international enterprises. Whether Chinese customers have the intention of using motion-sensing games to improve their health status in the home environment will directly determine the commercial potential of the relevant industry in the Chinese market. In order to understand the motives of users and explore the market possibility and prospects of the game industry, this study adopts empirical research and structural equation modeling to construct a motivation model of Chinese consumers toward motion-sensing gameplay behavior in the household environment. We distributed 515 questionnaires to conduct a survey; 427 valid responses have been received, and 203 data, which meet the inclusion criteria of the required game experience, have been analyzed by SPSS25.0 and AMOS25.0. A structural equation model for the gameplay motivation has been constructed. The result shows that the three functional motivators, exercise (Path efficient = 0.40, < 0.01), entertainment (Path efficient = 0.27, < 0.01), and social interaction (Path efficient = 0.36, < 0.01) of home motion-sensing games have a significantly positive impact on the user's intention to play. Furthermore, the diversity and the time-and-place flexibility variables exert an important positive influence on the users' gameplay behavior through their effects on the three main functional motive variables. To sum up, (1) exercise, (2) entertainment, and (3) social interaction are the main functional motivations of the Chinese consumers' gameplay behaviors; (4) diversity and (5) time-and-place flexibility are the two main attribute motivators. The acceptance of Chinese users for home motion-sensing games remains positive and high. The motion-sensing game industry has broad market prospects in China through its potential in promoting consumer's wellness and health in the home environment.
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http://dx.doi.org/10.3390/ijerph17238794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730092PMC
November 2020

Forecasting the spread of COVID-19 under different reopening strategies.

Sci Rep 2020 11 23;10(1):20367. Epub 2020 Nov 23.

Olin Business School, Washington University in St. Louis, Missouri, 63130, USA.

We combine COVID-19 case data with mobility data to estimate a modified susceptible-infected-recovered (SIR) model in the United States. In contrast to a standard SIR model, we find that the incidence of COVID-19 spread is concave in the number of infectious individuals, as would be expected if people have inter-related social networks. This concave shape has a significant impact on forecasted COVID-19 cases. In particular, our model forecasts that the number of COVID-19 cases would only have an exponential growth for a brief period at the beginning of the contagion event or right after a reopening, but would quickly settle into a prolonged period of time with stable, slightly declining levels of disease spread. This pattern is consistent with observed levels of COVID-19 cases in the US, but inconsistent with standard SIR modeling. We forecast rates of new cases for COVID-19 under different social distancing norms and find that if social distancing is eliminated there will be a massive increase in the cases of COVID-19.
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http://dx.doi.org/10.1038/s41598-020-77292-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683602PMC
November 2020

Selective optogenetic stimulation of efferent fibers in the vagus nerve of a large mammal.

Brain Stimul 2021 Jan-Feb;14(1):88-96. Epub 2020 Nov 17.

Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK. Electronic address:

Background: Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used to treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes to the disease progression and electrical stimulation of the vagus nerve has been pursued as a treatment for the purpose of restoring the autonomic balance. However, this approach lacks selectivity in activating function- and organ-specific vagal fibers and, despite promising results of many preclinical studies, has so far failed to translate into a clinical treatment of cardiovascular disease.

Objective: Here we report a successful application of optogenetics for selective stimulation of vagal efferent activity in a large animal model (sheep).

Methods And Results: Twelve weeks after viral transduction of a subset of vagal motoneurons, strong axonal membrane expression of the excitatory light-sensitive ion channel ChIEF was achieved in the efferent projections innervating thoracic organs and reaching beyond the level of the diaphragm. Blue laser or LED light (>10 mW mm; 1 ms pulses) applied to the cervical vagus triggered precisely timed, strong bursts of efferent activity with evoked action potentials propagating at speeds of ∼6 m s.

Conclusions: These findings demonstrate that in species with a large, multi-fascicled vagus nerve, it is possible to stimulate a specific sub-population of efferent fibers using light at a site remote from the vector delivery, marking an important step towards eventual clinical use of optogenetic technology for autonomic neuromodulation.
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http://dx.doi.org/10.1016/j.brs.2020.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836098PMC
November 2020

Gene expression of adipokines and adipokine receptors in the tumor microenvironment: associations of lower expression with more aggressive breast tumor features.

Breast Cancer Res Treat 2021 Feb 16;185(3):785-798. Epub 2020 Oct 16.

Department of Epidemiology and Biostatistics, SUNY Downstate Health Sciences University School of Public Health, Brooklyn, NY, USA.

Purpose: Limited epidemiologic data are available on the expression of adipokines leptin (LEP) and adiponectin (ADIPOQ) and adipokine receptors (LEPR, ADIPOR1, ADIPOR2) in the breast tumor microenvironment (TME). The associations of gene expression of these biomarkers with tumor clinicopathology are not well understood.

Methods: NanoString multiplexed assays were used to assess the gene expression levels of LEP, LEPR, ADIPOQ, ADIPOR1, and ADIPOR2 within tumor tissues among 162 Black and 55 White women with newly diagnosed breast cancer. Multivariate mixed effects models were used to estimate associations of gene expression with breast tumor clinicopathology (overall and separately among Blacks).

Results: Black race was associated with lower gene expression of LEPR (P = 0.002) and ADIPOR1 (P = 0.01). Lower LEP, LEPR, and ADIPOQ gene expression were associated with higher tumor grade (P = 0.0007, P < 0.0001, and P < 0.0001, respectively) and larger tumor size (P < 0.0001, P = 0.0005, and P < 0.0001, respectively). Lower ADIPOQ expression was associated with ER- status (P = 0.0005), and HER2-enriched (HER2-E; P = 0.0003) and triple-negative (TN; P = 0.002) subtypes. Lower ADIPOR2 expression was associated with Ki67+ status (P = 0.0002), ER- status (P < 0.0001), PR- status (P < 0.0001), and TN subtype (P = 0.0002). Associations of lower adipokine and adipokine receptor gene expression with ER-, HER2-E, and TN subtypes were confirmed using data from The Cancer Genome Atlas (P-values < 0.005).

Conclusion: These findings suggest that lower expression of ADIPOQ, ADIPOR2, LEP, and LEPR in the breast TME might be indicators of more aggressive breast cancer phenotypes. Validation of these findings are warranted to elucidate the role of the adipokines and adipokine receptors in long-term breast cancer prognosis.
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http://dx.doi.org/10.1007/s10549-020-05972-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925351PMC
February 2021