bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial and Sex Differences in the Response to First-Line Antihypertensive Therapy
Authors: Clemmer John S. , Pruett W. Andrew , Lirette Seth T. 
Published: January 2021

Objective: As compared to whites, the black population develops hypertension (HTN) at an earlier age, has a greater frequency and severity of HTN, and has poorer control of blood pressure (BP). Traditional practices and treatment efforts have had minor impact on these disparities, with over a 2-fold higher death rate currently for blacks as compared to whites. The University of Mississippi Medical Center (UMC) is located in the southeastern US and the Stroke Belt, which has higher rates of HTN and related diseases as compared to the rest of the country.Methods: We retrospectively analyzed the UMC's Research Data Warehouse, containing &gt;30 million electronic health records from &gt;900,000 patients to determine the initial BP response following the first prescribed antihypertensive drug.Results: There were 5,973 white (45% overall HTN prevalence) and 10,731 black (57% overall HTN prevalence) patients who met criteria for the study. After controlling for age, BMI, and drug dosage, black males were overall less likely to have controlled BP (defined as &lt; 140/90 mmHg) and were associated with smaller falls in BP as compared to whites and black females. Blockers of the renin-angiotensin system (RAS) failed to significantly improve odds of HTN control vs. the untreated group in black patients. However, our data suggests that these drugs do provide significant benefit in blacks when combined with THZ, as compared to untreated and as compared to THZ alone.Conclusion: These data support the use of a single-pill formulation with ARB or ACE inhibitor with a thiazide in blacks for initial first-line HTN therapy and suggests that HTN treatment strategies should consider both race and gender. Our study gives a unique insight into initial antihypertensive responses in actual clinical practice and could have an impact in BP control efficiency in a state with prevalent socioeconomic and racial disparities.
Case Report: An EGFR-Targeted 4-1BB-agonistic Trimerbody Does Not Induce Hepatotoxicity in Transgenic Mice With Liver Expression of Human EGFR
Authors: Compte Marta , Harwood Seandean L. , Martínez-Torrecuadrada Jorge , Perez-Chacon Gema , González-García Patricia , Tapia-Galisteo Antonio , Van Bergen en Henegouwen Paul M. P. , Sánchez Aránzazu , Fabregat Isabel , Sanz Laura , Zapata Juan M. , Alvarez-Vallina Luis 
Published: January 2021

Agonistic monoclonal antibodies (mAbs) targeting the co-stimulatory receptor 4-1BB are among the most effective immunotherapeutic agents across pre-clinical cancer models. However, clinical development of full-length 4-1BB agonistic mAbs, has been hampered by dose-limiting liver toxicity. We have previously developed an EGFR-targeted 4-1BB-agonistic trimerbody (1D8N/CEGa1) that induces potent anti-tumor immunity without systemic toxicity, in immunocompetent mice bearing murine colorectal carcinoma cells expressing human EGFR. Here, we study the impact of human EGFR expression on mouse liver in the toxicity profile of 1D8N/CEGa1. Systemic administration of IgG-based anti-4-1BB agonist resulted in nonspecific immune stimulation and hepatotoxicity in a liver-specific human EGFR-transgenic immunocompetent mouse, whereas in 1D8N/CEGa1-treated mice no such immune-related adverse effects were observed. Collectively, these data support the role of FcγR interactions in the major off-tumor toxicities associated with IgG-based 4-1BB agonists and further validate the safety profile of EGFR-targeted Fc-less 4-1BB-agonistic trimerbodies in systemic cancer immunotherapy protocols.
A Fully-Immersive and Automated Virtual Reality System to Assess the Six Domains of Cognition: Protocol for a Feasibility Study
Authors: Lim Jie En , Wong Wei Teen , Teh Tuan Ann , Lim Soon Huat , Allen John Carson , Quah Joanne Hui Min , Malhotra Rahul , Tan Ngiap Chuan 
Published: January 2021

Introduction: Dementia is increasing in prevalence in aging populations. Current questionnaire-based cognitive assessments may not comprehensively assess cognitive function and real-time task-performance. Virtual reality (VR) technology has been used in cognitive assessments but existing systems have limited scope in evaluating all cognitive domains. We have developed a novel, fully-immersive VR system (CAVIRE: Cognitive Assessment by VIrtual REality), which incorporates automated audio-visual instructions. An automated scoring matrix to assess the six cognitive domains—perceptual-motor function, executive function, complex attention, social cognition, learning and memory, and language—is embedded in the CAVIRE system.Aims: The primary aim is to evaluate the feasibility of using the CAVIRE system to assess cognitive function of participants across different age groups from 35 to 84 years old. The secondary aims are to determine the CAVIRE performance-indices (completion time and scores) of the participants and to assess their acceptability toward the use of CAVIRE as a modality for cognitive assessment.Methods: One hundred and seventy-five participants will be assessed by CAVIRE at a primary care clinic in Singapore. They will be first assessed using questionnaires: Montreal Cognitive Assessment (MoCA), Abbreviated Mental Test (AMT), Mini-Mental State Examination (MMSE), Basic Activities of Daily Living (BADLs), Instrumental Activities of Daily Living (IADLs). Those aged 65–84 years will be grouped into cognitively intact (n = 50, MoCA score ≥ 26) and cognitively impaired (n = 50, MoCA &lt; 26). The CAVIRE performance-indices of cognitively healthy younger participants aged 35–64 years (n = 75) will serve as benchmark references. CAVIRE auto-computes the participant's performance-indices in 13 different segments. The tasks include domestic chores, memory, shopping, and social interactions. The proportion of participants who complete the entire VR assessment in each age group will be evaluated as feasibility indicators. The CAVIRE performance-indices will be compared across the different age groups. Feedback on the acceptability of the CAVIRE system will be collated and compared among the participants across the age groups.Significance: CAVIRE is designed to assess the six domains of cognitive function using VR. The results of this feasibility study will provide insights for the implementation of the CAVIRE system as an alternative modality of cognitive assessment in the community.
Quantitative Comparison of Knowledge-Based and Manual Intensity Modulated Radiation Therapy Planning for Nasopharyngeal Carcinoma
Authors: Hu Jiang , Liu Boji , Xie Weihao , Zhu Jinhan , Yu Xiaoli , Gu Huikuan , Wang Mingli , Wang Yixuan , Qi ZhenYu 
Published: January 2021

Background and purposeTo validate the feasibility and efficiency of a fully automatic knowledge-based planning (KBP) method for nasopharyngeal carcinoma (NPC) cases, with special attention to the possible way that the success rate of auto-planning can be improved.Methods and materialsA knowledge-based dose volume histogram (DVH) prediction model was developed based on 99 formerly treated NPC patients, by means of which the optimization objectives and the corresponding priorities for intensity modulation radiation therapy (IMRT) planning were automatically generated for each head and neck organ at risk (OAR). The automatic KBP method was thus evaluated in 17 new NPC cases with comparison to manual plans (MP) and expert plans (EXP) in terms of target dose coverage, conformity index (CI), homogeneity index (HI), and normal tissue protection. To quantify the plan quality, a metric was applied for plan evaluation. The variation in the plan quality and time consumption among planners was also investigated.ResultsWith comparable target dose distributions, the KBP method achieved a significant dose reduction in critical organs such as the optic chiasm (p&lt;0.001), optic nerve (p=0.021), and temporal lobe (p&lt;0.001), but failed to spare the spinal cord (p&lt;0.001) compared with MPs and EXPs. The overall plan quality evaluation gave mean scores of 144.59±11.48, 142.71±15.18, and 144.82±15.17, respectively, for KBPs, MPs, and EXPs (p=0.259). A total of 15 out of 17 KBPs (i.e., 88.24%) were approved by our physician as clinically acceptable.ConclusionThe automatic KBP method using the DVH prediction model provided a possible way to generate clinically acceptable plans in a short time for NPC patients.
Contrast-Enhanced Ultrasound in the Differential Diagnosis of Primary Thyroid Lymphoma and Nodular Hashimoto’s Thyroiditis in a Background of Heterogeneous Parenchyma
Authors: Yang Lulu , Zhao Haina , He Yushuang , Zhu Xianglan , Yue Can , Luo Yan , Ma Buyun 
Published: January 2021

ObjectiveTo investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the differentiation of primary thyroid lymphoma (PTL) and nodular Hashimoto’s thyroiditis (NHT) in patients with background of heterogeneous diffuse Hashimoto’s thyroiditis (HT).MethodsSixty HT patients with 64 thyroid nodules (31 PTL and 33 NHT) who had undergone CEUS examination were included in this study. With histopathological results as the reference, we evaluated the imaging features of each nodule on both conventional ultrasonography (US) and CEUS. Quantitative CEUS parameters including peak intensity (PI), time to peak (TTP), and area under the time–intensity curve (AUC) were gathered in the nodule and background parenchyma. The ratio indexes of theses parameters were calculated by the ratio of the lesion and the corresponding thyroid parenchyma. Logistic regression and receiver operating characteristic (ROC) curves analyses of valuable US indicators were further preformed to evaluate the diagnostic capability of CEUS in discrimination of PTL and NHT.ResultsAmong all the observed US imaging features and CEUS parameters, 10 indicators showed significant differences between PTL and NHT (all P &lt; 0.05). All the significant indicators were ranked according to the odds ratios (ORs). Eight of them were CEUS associated including imaging features of enhancement pattern, degree, homogeneity, and quantification parameters of PI, AUC, ratios of PI, AUC, and TTP, while indicators on conventional US, including vascularity and size ranked the last two with ORs less than 3. The five single CEUS parameters showed good diagnostic performance in diagnosis of PTL with areas under ROC curves of 0.72–0.83 and accuracies of 70.3–75.0%. The combination of CEUS imaging features and the ratios of PI, AUC, and TTP demonstrated excellent diagnostic efficiency and achieved area under ROC curve of 0.92, which was significantly higher than any of the five single parameters (all P &lt; 0.05), with a sensitivity of 83.9%, specificity of 87.9%, and accuracy of 85.9%.ConclusionsCEUS is an efficient diagnostic tool in the differential diagnosis of PTL and NHT for patients with diffuse HT. Conjoint analysis of CEUS imaging features and quantification parameters could improve the diagnostic values.
Proprotein Convertase Subtilisin/Kexin Type 9 Promotes Gastric Cancer Metastasis and Suppresses Apoptosis by Facilitating MAPK Signaling Pathway Through HSP70 Up-Regulation
Authors: Xu Beili , Li Shuyu , Fang Yong , Zou Yanting , Song Dongqiang , Zhang Shuncai , Cai Yu 
Published: January 2021

ObjectiveTo examine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on gastric cancer (GC) progression and prognosis, and to explore the underlying mechanism.MethodsPCSK9 expression levels in human GC tissues were determined by quantitative real-time PCR, western blotting, and immunohistochemical assay. PCSK9 serum levels were detected by enzyme-linked immunosorbent assay. The relationships of PCSK9 and GC progression and survival were analyzed using the Chi-square test, Kaplan-Meier analysis, and Cox proportional hazards model. The effect of PCSK9 on cell invasion, migration, and apoptosis were determined in human GC cell lines and mouse xenograft model separately using PCSK9 knockdown and overexpression strategies. The PCSK9 interacting molecules, screened by co-immunoprecipitation combined with LC-MS/MS, were identified by immunofluorescence localization and western blotting. Additionally, the mitogen-activated protein kinase (MAPK) pathway was assessed by western blotting.ResultsPCSK9 mRNA and protein levels were significantly elevated in GC tissues compared with the paired normal tissues at our medical center (P &lt; 0.001). Notably, the up-regulation of PCSK9 expression in GC tissues was related to tumor progression and poor survival. GC patients had higher serum levels of PCSK9 than the age-matched healthy controls (P &lt; 0.001); PCSK9 promoted invasive and migratory ability and inhibited apoptosis in GC cells with no apparent affection in cell proliferation. The silencing of PCSK9 reversed these effects, suppressing tumor metastasis in vitro and in vivo. Furthermore, PCSK9 maintained these functions through up-regulating heat shock protein 70 (HSP70), ultimately facilitating the mitogen-activated protein kinase (MAPK) pathway.ConclusionCollectively, our data revealed that high PCSK9 expression levels in GC tissue were correlated with GC progression and poor prognosis and that PCSK9 could promote GC metastasis and suppress apoptosis by facilitating MAPK signaling pathway through HSP70 up-regulation. PCSK9 may represent a novel potential therapeutic target in GC.
Respiratory Symptoms in Post-infancy Children. A Dutch Pediatric Cohort Study
Authors: de Vries Esther , van Hout Roeland W. N. M. 
Published: January 2021

Aim:To study the pattern of respiratory symptoms in children in the general population.Method:We followed a cohort of children for up to 2 years through parents completing weekly online questionnaires in the Child-Is-Ill study (“Kind-en-Ziekmeting” in Dutch); the study was running 2012–2015. Inclusion criteria were “an ordinary child” (according to the parents) and &lt;18 years old at inclusion. We especially encouraged participation of post-infancy children. Age at inclusion, sex, smoking exposure, allergy in the family, and frequent infections in the family were noted. Pearson's correlation, principal component analysis, latent class analysis, latent profile analysis, linear regression, and linear mixed effects regression were used in the statistical analyses.Results:Data were collected on 55,524 childweeks in 755 children (50% girls; median age, 7 years; interquartile range, 4–11 years, 97% ≥2 years at inclusion), with reported symptom(s) in 8,425 childweeks (15%), leading to school absenteeism in 25%, doctor's visits in 12%, and parental sick leave in 8%; symptoms lasting ≥3 weeks were rare (2% of episodes). Linear mixed effects regression showed significant, but only limited, effects of season on the proportion of “symptom(s) reported” per individual child. Only runny nose showed a significant, but very small, age effect. However, the variability between the children was considerable. There were no obvious subgroups of children with specific symptom combinations.Conclusion:In any randomly chosen week, the vast majority of children (85%) in our—mainly—post-infancy cohort derived from the general population did not have any symptom, even in the younger age group, even in winter. The children showed considerable variability; no clear subgroups of symptom patterns could be identified, underlining the difficult position of healthcare providers. These results support our opinion that post-infancy children in the general population should not be evaluated as if they are infants when they have recurrent respiratory symptoms. If they clearly deviate from the above-described most common pattern, it is wise to keep an eye on potential, maybe even rare, serious underlying causes.
Case Report: Primary Ewing Sarcoma of the Penis With Multiple Metastases
Authors: Zheng Chuanxi , Zhou Yong , Luo Yi , Zhang Hongying , Tu Chongqi , Min Li 
Published: January 2021

Background: Ewing sarcoma is the second most common malignant bone tumor in children, but it rarely originates from extra-skeletal sites. The commonly involved sites of soft tissue include paravertebral spaces, lower extremities, the pelvis, head, and neck, while primary extra-skeletal Ewing sarcoma (EES) located in the genitals is extremely rare.Case Presentation: We report a young patient who presented to our hospital with a painful erection of the penis and limited motion of the left hip. Magnetic resonance imaging showed a hyperintense mass with invasion of adjacent tissue in the penis and a heterogeneously high signal lesion in the left proximal femur. 18F-fluorodeoxyglucose positron-emission tomography detected widespread metastatic lesions in the bilateral lung and multiple skeletons. An incisional biopsy of the penis was performed; the histopathological findings and EWS gene translocation identified by molecular analysis confirmed the diagnosis of Ewing sarcoma. Subsequently, the punch-biopsy specimen from the left femur showed undifferentiated small round cells, a finding consistent with the microscopic presence of Ewing sarcoma metastasis. However, after the first course of multiagent chemotherapy, the penile mass did not obtain stabilization but instead grew progressively with surface ulceration and multidrug resistant bacteria infection. Despite receiving antibiotics and maximal supportive therapy, the patient died from sepsis and lung metastasis complications in the intensive care unit 2 months later.Conclusion: This case indicates that although EES as a subtype of Ewing sarcoma is rare, it can occur virtually in any soft tissue site, even in the genitals. Therefore, clinicians need to distinguish this entity from other soft tissue sarcomas with rapid progression since early diagnosis and timely treatment of EES are pivotal for a favorable prognosis.
The Prevalence and Independent Risk Factors of Significant Tricuspid Regurgitation Jets in Maintenance Hemodialysis Patients With ESRD
Authors: Zhang Ying , Ding Xiao-Han , Pang Fang , Zhang Laiping , Wang Yiqin , Wang Weili , Rao Rongsheng , Bian Shi-Zhu 
Published: January 2021

Background and AimTricuspid regurgitation (TR) is a frequent complication in various cardiovascular diseases. However, few studies have reported the prevalence of TR especially the moderate to severe or significant TR (ms-TR) maintenance dialysis patients. Thus, we aimed to identify the prevalence of ms-TR and its associated factors.MethodsA total of 491 maintenance dialysis patients underwent echocardiographic examinations, while a subgroup (n = 283) also received routine blood tests, renal function examinations, and electrolyte analysis. We first compared the differences in abovementioned parameters among groups with various TR areas (TRAs). Finally, univariate and adjusted regression were also used to identify factors that were independently associated with ms-TR.ResultsThe incidence of TR jets was 62.6%, which included a mildly increased TRA (47.8%), moderately increased TRA (10.4%), and severely increased TRA (3.5%). Most of the cardiac structures and functional parameters, such as the end-diastolic internal diameters of the left atrium (LA), left ventricle (LVDD), right atrium (RA), right ventricle (RV), left ventricular ejection fraction (LVEF), and fractional shortening (FS), were significantly associated with ms-TR. Among serum ions, only total CO2 (TCO2; r = −0.141, p = 0.047) was negatively correlated with TRA. After adjusted, only Na+ [odds ratio (OR): 0.871 0.888, p = 0.048], RA (OR: 1.370, p &lt; 0.001), and FS (OR: 0.887, p &lt; 0.001) were independently associated with ms-TR.ConclusionTricuspid regurgitation occurs in maintenance hemodialysis patients with ESRD. Na+ FS and RA were independently associated with ms-TR, and these parameters may be potential risk factors/predictors for ms-TR.
EEG Functional Connectivity and Cognitive Variables in Premanifest and Manifest Huntington’s Disease: EEG Low-Resolution Brain Electromagnetic Tomography (LORETA) Study
Authors: Delussi Marianna , Nazzaro Virgilio , Ricci Katia , de Tommaso Marina 
Published: January 2021

BackgroundScientific literature does not offer sufficient data on electroencephalography (EEG) functional connectivity and its correlations with clinical and cognitive features in premanifest and manifest HD.AimThis study tries to identify abnormal EEG patterns of functional connectivity, in conditions of “brain resting state” and correlations with motor decline and cognitive variable in Huntington’s disease (HD), in premanifest and manifest phase, looking for a reliable marker measuring disease progression.MethodThis was an observational cross-sectional study; 105 subjects with age ≥18 years submitted to HD genetic test. Each subject underwent a neurological, psychiatric, and cognitive assessment, EEG recording and genetic investigation for detecting the expansion of the CAG trait. EEG connectivity analysis was performed by means of exact Low Resolution Electric Tomography (eLORETA) in 18 premanifest HD (pHD), 49 manifest HD (mHD), and 38 control (C) subjects.ResultsHD patients showed a Power Spectral Density reduced in the alpha range and increased in delta band compared to controls; no difference was detectable between pHD and mHD; the Global Connectivity in pHD revealed no significant differences if compared to mHD. The Current Source Density was similar among groups. No statistically significant results when comparing pHD with C group, even in comparison of mHD with Controls, and pHD with mHD. mHD compared to Controls showed a significant increase in delta, alpha1, alpha2, beta2, and beta3. Lagged Phase Synchronization in delta, alpha1, alpha2, beta2, and beta3 bands was increased in HD compared to controls (t = −3.921, p &lt; 0.05). A significant correlation was found in Regression Analysis: statistically significant results in pHD for the “Symbol Digit Modality Test and lagged phase synchronization” in the Beta1 (r = −0.806, p &lt; 0.05) in the prefrontal regions. The same correlation was found in mHD for the Stroop Word Reading Test (SWRT) in the Alpha2 band (r = −0.759, p &lt; 0.05).ConclusionIncreased phase synchronization in main bands characterized EEG in HD patients, as compared to controls. pHD were not dissimilar from mHD as regard to this EEG pattern. Increased phase synchronization correlated to cognitive decline in HD patients, with a similar trend in pHD, suggesting that it would be a potential biomarker of early phenotypical expression.