bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alzheimer disease and the periodontal patient: New insights, connections, and therapies
Authors: Ryder Mark I. , Xenoudi Pinelopi 
Published: August 2021

AbstractLoss of cognitive function in the aging population, particular those with Alzheimer disease, presents unique challenges to health practitioners. For the dental practitioner these include management of periodontal diseases, caries, and other dental conditions in this special population. It is well established in the cognitively impaired patient that a lack of adherence to dental hygiene routines and professional care leads to increases in the prevalence and severity of these dental conditions, leading to increased loss of teeth. More recent evidence has indicated a possible role of the microbiota of dental plaque associated with periodontal diseases in the development and progression of Alzheimer disease, thereby supporting a two‐way interaction of these two diseases. New therapies are needed to address the potential upstream events that may precede overt signs of Alzheimer disease. One of these approaches would be to target these various bacterial, viral, and other microbial pathogens associated with periodontal disease that can translocate into the bloodstream and then to distal sites, such as the brain. Such microbial translocation would lead to local inflammation and buildup of the hallmark signs of Alzheimer disease, including amyloid beta deposits, tau fragmentation and tangles, breakdown of host protective molecules, such as the apolipoproteins, and neuron toxicity. In this review, evidence for the biological basis of the role of the periodontal disease microflora on the initiation and progression of Alzheimer disease will be presented with a focus on the potential role of the keystone pathogen Porphyromonas gingivalis with its family of gingipain enzymes. The various mechanisms for which P. gingivalis gingipains may contribute to the initiation and progression of Alzheimer disease are presented. Small‐molecule inhibitors of these gingipains and their effects on reducing biological markers of Alzheimer disease may have beneficial effects for the initiation and progression of loss of cognitive function in Alzheimer disease. In addition to these targeted therapies for specific periodontal pathogens, considerations for the dental practitioner in applying more general approaches to reducing the periodontal plaque microflora in the management of the cognitively impaired patient are discussed for this special population.
IL‐6 alters migration capacity of CD4+Foxp3+ regulatory T cells in systemic lupus erythematosus
Authors: He SiWei , Xue MingHui , Cai Gang 
Published: August 2021

AbstractRegulatory T cells (Tregs) are impaired in human systemic lupus erythematosus (SLE) and involved in disease pathogenesis. However, the mechanisms responsible for the Treg dysfunction in SLE remain unclear. In this study, we aimed to investigate the chemotaxis of Treg response to inflammatory stimulation. Sixty two patients were enrolled, and chemokine receptors, including CCR4, CCR5, CCR6, CCR8 and CXCR3 on CD4+Foxp3+Tregs and non‐Treg CD4 T cells, were analysed using FACS. The expression of CCR4 and CCR6 on Tregs of SLE patients decreased, while the expression of CCR4 on non‐Treg CD4 T cells increased, as compared with those of age‐ and sex‐matched healthy donors. In parallel, in SLE, the chemotactic capacity of non‐Treg CD4 T cells response to CCR4 and CCR6 ligands dramatically increased, while that of Tregs significantly decreased. Moreover, we found that cytokines IL‐6 and IL‐10 positively and negatively modulate the expression of those receptors respectively. IL‐6, the significantly increased cytokine in active SLE, dramatically elevated CCR4 and CCR6 expression on non‐Treg CD4 T cells. However, as for Tregs, these cells produced more IL‐10 than non‐Treg CD4 T cells upon IL‐6 stimulation, and these IL‐10 led to the inhibition of CCR4 and CCR6. In sum, our data provided new evidence suggesting a functional deficiency of Tregs in SLE. It may suggest that those dysfunctional Tregs have less access to the inflammation locus to exert inhibitory capacity.
Cultural appropriation: What it is and why it matters?
Authors: Arya Rina 
Published: August 2021

AbstractCultural appropriation is a highly contested subject within the media and society more broadly, often provoking moral outrage. It is receiving increasing interest within the academy and the last 20 years have seen the publication of a number of important studies. Cultural appropriation takes many forms, covers a range of types of action, and has many consequences. It is not a uniform practice and needs to be assessed on a case by case basis but there are common themes and issues. What follows is a discussion of the key concepts and literature in the field.
Bayesian Calibration of Multiple Coupled Simulation Models for Metal Additive Manufacturing: A Bayesian Network Approach
Authors: Ye Jiahui , Mahmoudi Mohamad , Karayagiz Kubra , Johnson Luke , Seede Raiyan , Karaman Ibrahim , Arroyave Raymundo , Elwany Alaa 
Published: August 2021

Abstract
Modeling and simulation for additive manufacturing (AM) are critical enablers for understanding process physics, conducting process planning and optimization, and streamlining qualification and certification. It is often the case that a suite of hierarchically linked (or coupled) simulation models is needed to achieve the above tasks, as the entirety of the complex physical phenomena relevant to the understanding of process-structure-property-performance relationships in the context of AM precludes the use of a single simulation framework. In this study using a Bayesian network approach, we address the important problem of conducting uncertainty quantification (UQ) analysis for multiple hierarchical models to establish process-microstructure relationships in laser powder bed fusion (LPBF) AM. More significantly, we present the framework to calibrate and analyze simulation models that have experimentally unmeasurable variables, which are quantities of interest predicted by an upstream model and deemed necessary for the downstream model in the chain. We validate the framework using a case study on predicting the microstructure of a binary nickel-niobium alloy processed using LPBF as a function of processing parameters. Our framework is shown to be able to predict segregation of niobium with up to 94.3% prediction accuracy on test data.
Effects of Particle Size and Mainstream Inlet Angle on Deposition in a Turbine Cascade
Authors: Wang Jin , Zhao Zhanming , Xie Gongnan , Mikulčić Hrvoje , Vujanović Milan , Sundén Bengt 
Published: August 2021

Abstract
Based on the critical velocity model, impact and capture efficiencies in an AGTB turbine cascade are investigated numerically under various inlet angles of mainstream, blowing ratios, particle sizes, and particle densities. The effect of hole configuration on deposition is analyzed based on comparisons of results from combined hole and cylindrical hole. The impact efficiency increases with the increase of particle size. Impact area on pressure side of blade surface expands with increasing of the mainstream inlet angle from 123 deg to 143 deg. The capture efficiency decreases with the increase of blowing ratio for 10 µm particles. For particles with densities of 1485 kg/m3, 1980 kg/m3, and 2475 kg/m3, the maximum capture efficiency is reached when the particle size is 5 µm. The particle capture efficiency for the combined hole is up to 3.9% lower than that for cylindrical hole when the mainstream inlet angle is 123 deg.
Enhanced Hybrid Model to Predict the Surface Roughness of Honed Cylinder Bore
Authors: Afzal Burhan , Zhang Xueping , Srivastava Anil K. 
Published: August 2021

Abstract
Cylinder bore honing is a finishing process that generates a crosshatch pattern with alternate valleys and plateaus responsible for enhancing lubrication and preventing gas and oil leakage in the engine cylinder bore. The required functional surface in the cylinder bore is generated by a sequential honing process and is characterized by Rk roughness parameters (Rk, Rvk, Rpk, Mr1, Mr2). Predicting the desired surface roughness relies primarily on two techniques: (i) analytical models (AM) and (ii) machine learning (ML) models. Both of these techniques offer certain advantages and limitations. AM's are interpretable as they indicate distinct mapping relation between input variables and honed surface texture. However, AM's are usually based on simplified assumptions to ensure the traceability of multiple variables. Consequently, their prediction accuracy is adversely impacted when these assumptions are not satisfied. However, ML models accurately predict the surface texture but their prediction mechanism is challenging to interpret. Furthermore, the ML models' performance relies heavily on the representativeness of data employed in developing them. Thus, either prediction accuracy or model interpretability suffers when AM and ML models are implemented independently. This study proposes a hybrid model framework to incorporate the benefits of AM and ML simultaneously. In the hybrid model, an artificial neural network (ANN) compensates the AM by correcting its error. This retains the physical understanding built into the model while simultaneously enhancing the prediction accuracy. The proposed approach resulted in a hybrid model that significantly improved the prediction accuracy of the AM and additionally provided superior performance compared to independent ANN.
Flexural–Torsional Free Vibration Analysis of a Double-Cantilever Structure
Authors: Zargarani Anahita , Nima Mahmoodi S. 
Published: August 2021

Abstract
This paper aims to investigate the free coupled flexural–torsional vibrations of a double-cantilever structure. The structure consists of two identical Euler–Bernoulli cantilever beams with a piezoelectric layer on top. The beams are connected by a rigid tip connection at their free ends. The double-cantilever structure in this study vibrates in two distinct modes: flexural mode or coupled flexural–torsional mode. The flexural mode refers to the in-phase flexural vibrations of the two cantilever beams resulting in translation of the tip connection, while the coupled flexural–torsional mode refers to the coupled flexural–torsional vibrations of the cantilever beams resulting in rotation of the tip connection. The latter is the main interest of this research. The governing equations of motion and boundary conditions are developed using Hamilton’s principle. Two uncoupled equations are realized for each beam: one corresponding to the flexural vibrations and the other one corresponding to the torsional vibrations. The characteristic equations for both the flexural and the coupled flexural–torsional vibration modes are derived and solved to find the natural frequencies corresponding to each mode of vibration. The orthogonality condition among the mode shapes is derived and utilized to determine the modal coefficients corresponding to each mode of vibration. Moreover, the analytical and experimental investigations show that the coupled flexural–torsional fundamental frequency of the structure is dependent on dimensional parameters including the length of the cantilever beams and the length of the tip connection.
Surveillance of Physical Activity and Sedentary Behavior Among Youth and Adults in the United States: History and Opportunities
Authors: Omura John D. , Whitfield Geoffrey P. , Chen Tiffany J. , Hyde Eric T. , Ussery Emily N. , Watson Kathleen B. , Carlson Susan A. 
Published: August 2021

Background: Surveillance is a core function of public health, and approaches to national surveillance of physical activity and sedentary behavior have evolved over the past 2 decades. The purpose of this paper is to provide an overview of surveillance of physical activity and sedentary behavior in the United States over the past 2 decades, along with related challenges and emerging opportunities. Methods: The authors reviewed key national surveillance systems for the assessment of physical activity and sedentary behavior among youth and adults in the United States between 2000 and 2019. Results: Over the past 20 years, 8 surveillance systems have assessed physical activity, and 5 of those have assessed sedentary behavior. Three of the 8 originated in nonpublic health agencies. Most systems have assessed physical activity and sedentary behavior via surveys. However, survey questions varied over time within and also across systems, resulting in a wide array of available data. Conclusion: The evolving nature of physical activity surveillance in the United States has resulted in both broad challenges (eg, balancing content with survey space; providing data at the national, state, and local level; adapting traditional physical activity measures and survey designs; and addressing variation across surveillance systems) and related opportunities.
Trends in Aerobic and Muscle-Strengthening Physical Activity by Race/Ethnicity Across Income Levels Among US Adults, 1998–2018
Authors: Watson Kathleen B. , Whitfield Geoffrey , Chen Tiffany J. , Hyde Eric T. , Omura John D. 
Published: August 2021

Background: Although disparities in leisure-time physical activity (LTPA) participation by race/ethnicity and income are known, the combined association of these characteristics with LTPA participation is less understood. This study aims to describe trends and determine whether racial/ethnic differences in adult physical activity by income level have changed over the past 2 decades. Methods: The authors estimated LTPA participation (outcomes: any aerobic activity, meeting the aerobic activity guideline, meeting the muscle-strengthening guideline, and meeting the combined aerobic and muscle-strengthening guidelines) among adults ≥18 years by race/ethnicity across income levels using 1998–2018 National Health Interview Survey data in 3-year aggregates. They also tested for trends, prevalence differences, and difference in differences using logistic regression. Results: LTPA participation increased from 1998–2000 to 2016–2018 for all outcomes for non-Hispanic white, non-Hispanic black, and Hispanic adults at all income levels. Disparities narrowed for some groups but persisted between white and racial/ethnic minority groups across income levels for engaging in any aerobic activity and meeting the aerobic guideline (0.2–8.8 percentage point difference in differences). Disparities in meeting the muscle-strengthening and combined guidelines were less common. Conclusions: Opportunities exist to ensure that adults, particularly members of lower income racial/ethnic minority groups, have support to help them participate in LTPA.
Impact of Polycystic Ovary Syndrome Phenotypes on in Vitro Fertilization Outcomes in Vietnamese Women: A Secondary Analysis of a Randomized Controlled Trial
Authors: Ho Vu N.A. , Pham Toan D. , Hoang Hieu L.T. , Vuong Lan N. 
Published: August 2021

Background: Polycystic ovary syndrome (PCOS) is diagnosed when [Formula: see text]2 of the following symptoms are present: ovulation disorder (OD), hyperandrogenism (HA), and polycystic ovary morphology (PCO). Clinical features of PCOS are heterogeneous and there are four clinical phenotypes: A (OD + HA + PCO); B (HA + OD); C (HA + PCO); and D (OD + PCO). Women with a PCOS phenotype that includes severe HA are at increased risk for pregnancy complications. There are currently no data on impact of PCOS phenotypes on in vitro fertilization (IVF) outcomes in Vietnamese women. This study investigated the association between PCOS phenotypes and IVF outcomes. Methods: This is a secondary analysis of a randomized controlled trial conducted in patients with PCOS undergoing IVF at IVFMD, My Duc Hospital, Ho Chi Minh City, Vietnam between January 2018 and April 2019. The primary outcome was live birth rate. Results: A total of 192 patients were included, of whom 33 patients had phenotype A (17.2%) and 159 had phenotype D (82.8%); no patients had phenotype B or C. Body mass index was significantly higher in patients with phenotype A than D (25.36 ± 4.78 versus 22.08 ± 3.21, [Formula: see text] = 0.001). There were no differences in laboratory and pregnancy outcomes between patients with phenotypes A and D. The live birth rate was lower in patients with phenotype A versus D, but the between-group difference did not reach statistical significance (33.3% vs. 42.8%, [Formula: see text] = 0.419). Conclusions: The common PCOS phenotypes in Vietnamese women with infertility were A and D. No impact of PCOS phenotypes on IVF treatment outcomes was detected in this secondary analysis; larger studies are needed
The Indication of Poor Prognosis by High Expression of ENO1 in Squamous Cell Carcinoma of the Lung
Authors: Huang Wan-Ying , Chen Gang , Chen Shang-Wei , Dang Yi-Wu , Deng Yun , Zhou Hua-Fu , Kong Jin-Liang , Zhang Yu , Mo Jun-Xian , Li Chang-Bo , He Juan 
Published: August 2021

The purpose of this study is to investigate the significance of alpha-enolase (ENO1) expression in squamous cell carcinoma of the lung (LUSC), its prognostic value, and prospective molecular mechanism. Using multiplatforms data, including in-house immunohistochemistry, in-house real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), in-house microarray, and public high-throughput data, the expression significance and prognostic role of ENO1 in LUSC tissues were analyzed comprehensively. With the combination of all eligible cases, compared with 941 non-LUSC lung tissues, ENO1 was significantly overexpressed in 1163 cases of LUSC (standardized mean difference (SMD) = 1.23, 95% confidence interval (CI) = 0.76–1.70,

P

< 0.001). ENO1 also displayed a great ability to differentiate LUSC tissues from non-LUSC lung tissues (AUC = 0.8705) with the comprehensive sensitivity being 0.88 [0.83–0.92], and comprehensive specificity being 0.89 [0.84–0.94]). Moreover, in 1860 cases of LUSC with survival information, patients with higher expression of ENO1 had poorer prognosis (hazard ratio (HR) = 1.20, 95% CI = 1.01–1.43,

P

= 0.043). ENO1 and its related genes mainly participated in the pathways of cell division and proliferation. In conclusion, the upregulation of ENO1 could affect the carcinogenesis and unfavorable outcome of LUSC.
Safety and Antitumor Activity of α-PD-L1 Antibody as Monotherapy or in Combination with α-TIM-3 Antibody in Patients with Microsatellite Instability–High/Mismatch Repair–Deficient Tumors
Authors: Hollebecque Antoine , Chung Hyun C. , de Miguel Maria J. , Italiano Antoine , Machiels Jean-Pascal , Lin Chia-Chi , Dhani Neesha C. , Peeters Marc , Moreno Victor , Su Wu-Chou , Chow Kay Hoong , Galvao Violeta R. , Carlsen Michelle , Yu Danni , Szpurka Anna M. , Zhao Yumin , Schmidt Shelly L. , Gandhi Leena , Xu Xiaojian , Bang Yung-Jue 
Published: August 2021

Abstract

Purpose:
Immune checkpoint inhibitors show high response rates and durable clinical benefit in microsatellite instability–high/mismatch repair–deficient (MSI-H/dMMR) tumors. However, 50%–60% do not respond to single-agent anti–programmed death-1/programmed death ligand 1 (PD-1/PD-L1) antibodies, and approximately 50% of responders relapse within 6–12 months. This phase Ib trial evaluated safety and antitumor activity of anti–PD-L1 antibody LY3300054 monotherapy or in combination with anti–TIM-3 antibody LY3321367 in patients with MSI-H/dMMR advanced solid tumors.

Patients and Methods:
Eligible patients ≥18 years without prior anti–PD-1/PD-L1 therapy received LY3300054 monotherapy (N = 40) or combination (N = 20); patients with PD-1/PD-L1 inhibitor–resistant/refractory tumors received the combination (N = 22). LY3300054 (700 mg) and anti–TIM-3 antibody (cycles 1–2: 1,200 mg, cycle 3 onward: 600 mg) were administered intravenously every 2 weeks. Primary endpoints were safety and tolerability.

Results:
Eighty-two patients were enrolled. Most had colorectal (n = 39, 47.6%) or endometrial (n = 14, 17.1%) tumors. More than 70% of patients in the PD-1/PD-L1 inhibitor–resistant/refractory combination cohort had received ≥3 treatment lines. Treatment-related adverse events (TRAE) occurred in 22 patients (55.0%) receiving monotherapy, 13 (65.0%) in the PD-1/PD-L1 inhibitor–naïve combination cohort, and 6 (27.3%) in the PD-1/PD-L1 inhibitor–resistant/refractory combination cohort. A total of 2 patients (5.0%) receiving monotherapy and 3 (7.1%) receiving the combination experienced grade ≥3 TRAEs. Objective responses occurred in 13 patients (32.5%) with monotherapy, 9 (45.0%) in the PD-1/PD-L1 inhibitor–naïve combination cohort, and 1 patient (4.5%) in the PD-1/PD-L1 inhibitor–resistant/refractory combination cohort.

Conclusions:
LY3300054 monotherapy and combined LY3300054/anti–TIM-3 had manageable safety profiles. Both regimens showed promising clinical activity against PD-1/PD-L1 inhibitor–naïve MSI-H/dMMR tumors. The combination had limited clinical benefit in patients with PD-1/PD-L1 inhibitor–resistant/refractory MSI-H/dMMR tumors.
Alpha-smooth Muscle Actin Expression in the Stroma Predicts Resistance to Trastuzumab in Patients with Early-stage HER2-positive Breast Cancer
Authors: Vathiotis Ioannis A. , Moutafi Myrto K. , Divakar Prajan , Aung Thazin Nwe , Qing Tao , Fernandez Aileen , Yaghoobi Vesal , El-Abed Sarra , Wang Yingbo , Guillaume Sebastien , Nuciforo Paolo , Huober Jens , Di Cosimo Serena , Kim Sung-Bae , Harbeck Nadia , Gomez Henry , Shafi Saba , Syrigos Konstantinos N. , Fountzilas George , Sotiriou Christos , Pusztai Lajos , Warren Sarah , Rimm David L. 
Published: August 2021

Abstract

Purpose:
The companion diagnostic test for trastuzumab has not changed much in the last 25 years. We used high-plex digital spatial profiling to identify biomarkers besides HER2 that can help predict response to trastuzumab in HER2-positive breast cancer.

Experimental Design:
Fifty-eight protein targets were measured in three different molecularly defined compartments by the NanoString GeoMx Digital Spatial Profiler (DSP) in a tissue microarray containing 151 patients with breast cancer that received adjuvant trastuzumab as part of the Hellenic Cooperative Oncology Group 10/05 clinical trial. Promising candidate biomarkers were orthogonally validated with quantitative immunofluorescence (QIF). RNA-sequencing data from the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation Study (NeoALTTO) were accessed to provide independent cohort validation. Disease-free survival (DFS) was the main outcome assessed. Statistical analyses were performed using a two-sided test (α = 0.05) and multiple testing correction (Benjamini–Hochberg method, FDR &lt; 0.1).

Results:
By DSP, high expression of alpha-smooth muscle actin (α-SMA), both in the leukocyte and stromal compartments, was associated with shorter DFS in univariate analysis (P = 0.002 and P = 0.023, respectively). High α-SMA expression in the stroma was validated by QIF after controlling for estrogen receptor and progesterone receptor status [HR, 3.12; 95% confidence interval (CI), 1.12–8.68; P = 0.029] showing recurrence on trastuzumab in the same cohort. In the NeoALTTO cohort, elevated levels of ACTA2 were predictive for shorter DFS in the multivariate analysis (HR, 3.21; 95% CI, 1.14–9.05; P = 0.027).

Conclusions:
This work identifies α-SMA as a novel, easy-to-implement biomarker of resistance to trastuzumab that may be valuable in settings where trastuzumab is combined with other therapies.