bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Prediabetes and Bone Mass in Adolescents: Analysis of the National Health and Nutrition Examination Survey From 2005 to 2010
Authors: Ma Chun-Ming , Yin Fu-Zai
Published: October 2021

Objective

The purpose of this study was to observe the relationship between impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and bone mineral density (BMD) in different sites in adolescents.

Methods

A retrospective study was conducted on adolescents age 12–19 years of the United States. Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2005–2006, 2007–2008, and 2009–2010 cycles. IFG was defined as fasting plasma glucose (FPG) levels that were ≥5.6 and <7.0 mmol/L. IGT was defined as 2-h plasma glucose levels that were ≥7.8 and <11.1 mmol/L after the oral glucose tolerance test (OGTT).

Results

After controlling for age, gender, race, and body mass index (BMI) Z-score, adolescents in different categories of IGT had significantly different levels of areal BMD (aBMD) and bone mineral apparent density (BMAD) (IGT main effect: P < 0.05 for all, two-way ANOVA). There was no main effect between different categories of IFG with regard to aBMD and BMAD (P > 0.05). There was no interaction between IFG and IGT with regard to aBMD and BMAD (P > 0.05). In multiple regression analysis, the 2-h plasma glucose maintained an independent association with femoral neck aBMD (β = −0.011, 95% CI: −0.017~−0.006, P < 0.001, R2 = 0.012), total femur aBMD (β = −0.015, 95% CI: −0.021~−0.009, P < 0.001, R2 = 0.018), total spine aBMD (β = −0.015, 95% CI: −0.020~−0.010, P < 0.001, R2 = 0.018), and total spine BMAD (β = −0.002, 95% CI: −0.003~0.000, P = 0.006, R2 = 0.003).

Conclusion

The present study demonstrates that BMD was decreased in adolescents with IGT. Two-hour plasma glucose, not FPG, negatively correlated with BMD. The effect of 2-h plasma glucose was consistent across the sites of bone.
The Single-Cell Transcriptomic Analysis of Prefrontal Pyramidal Cells and Interneurons Reveals the Neuronal Expression of Genes Encoding Antimicrobial Peptides and Immune Proteins
Authors: Mittli Dániel , Tukacs Vanda , Micsonai András , Ravasz Lilla , Kardos József , Juhász Gábor , Kékesi Katalin Adrienna
Published: October 2021

The investigation of the molecular background of direct communication of neurons and immune cells in the brain is an important issue for understanding physiological and pathological processes in the nervous system. Direct contacts between brain-infiltrating immune cells and neurons, and the neuromodulatory effect of immune cell-derived regulatory peptides are well established. Several aspects of the role of immune and glial cells in the direct neuro-immune communication are also well known; however, there remain many questions regarding the molecular details of signaling from neurons to immune cells. Thus, we report here on the neuronal expression of genes encoding antimicrobial and immunomodulatory peptides, as well as proteins of immune cell-specific activation and communication mechanisms. In the present study, we analyzed the single-cell sequencing data of our previous transcriptomic work, obtained from electrophysiologically identified pyramidal cells and interneurons of the murine prefrontal cortex. We filtered out the genes that may be associated with the direct communication between immune cells and neurons and examined their expression pattern in the neuronal transcriptome. The expression of some of these genes by cortical neurons has not yet been reported. The vast majority of antimicrobial (~53%) and immune cell protein (~94%) transcripts was identified in the transcriptome of the 84 cells, owing to the high sensitivity of ultra-deep sequencing. Several of the antimicrobial and immune process-related protein transcripts showed cell type-specific or enriched expression. Individual neurons transcribed only a fraction of the investigated genes with low copy numbers probably due to the bursting kinetics of gene expression; however, the comparison of our data with available transcriptomic datasets from immune cells and neurons suggests the functional relevance of the reported findings. Accordingly, we propose further experimental andin silicostudies on the neuronal expression of immune system-related genes and the potential role of the encoded proteins in neuroimmunological processes.
Design of Grating Type GaAs Solar Absorber and Investigation of Its Photoelectric Characteristics
Authors: Huang Meihong , Wei Kaihua , Wu Pinghui , Xu Danyang , Xu Yan
Published: October 2021

In recent years, as a renewable clean energy with many excellent characteristics, solar energy has been widely concerned. In this paper, we propose an ultra-broadband solar absorber based on metal tungsten and semiconductor GaAs structure. A multilayer metal semiconductor composite structure composed of W-Ti-GaAs three-layer films and GaAs gratings is proposed. The finite difference time domain method is used to simulate the performance of the proposed model. High efficiency surface plasmon resonance is excited by adjusting the geometric parameters, and the broadband absorption of up to 2,350 nm in 500–2850 nm is realized. The spectrum of the structure can be changed by adjusting the geometric parameters to meet different needs. The proposed absorber has good oblique incidence characteristics (0–60°) and high short-circuit current characteristics. The geometry of the absorber is clear, easy to manufacture, and has good photoelectric performance. It can realize solar energy collection, light heat conversion, high sensitive sensing and other functions.
Molecular and Clinical Characteristics of Primary Pulmonary Lymphoepithelioma-Like Carcinoma
Authors: Fan Ying , Shan Qianyun , Gong Jiali , Qin Jing , Lu Hongyang
Published: October 2021

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is an extremely rare subtype of non-small cell lung cancer (NSCLC). Currently, there are no established treatment protocols due to rarity of the cancer. Thus, this study aimed to explore the molecular and clinical characteristics of PPLELC.

Study design and setting: Data from patients with PPLELC who were admitted to Zhejiang Cancer Hospital from August 2009 to September 2020 were retrospectively collected. Next-generation sequencing was performed to obtain a genomic profile and tumor mutation burden (TMB) value of patients with adequate tissue and divided them into two groups according to the expression level of PD-L1. The correlation of PD-L1 expression and the clinicopathological characteristics was evaluated by Pearson Chi-square test. Kaplan-Meier curves was applied to present the probability of survival between PD-L1 expression level and overall survival (OS). Moreover, the literature on the immunotherapy of advanced PPLELC published in PubMed between 2016 and 2020 were reviewed and the efficacy of immunotherapy were analyzed.

Results: A total of 18 patients pathologically diagnosed as PPLELC were included. After a follow-up period of 8.8–138 months, 14 patients survived, three patients died and one patient lost, the median OS was 45.3 months Seven samples (tissue-available) tested by NGS and the median TMB was 2.5 mutations/Mb. 19 somatic mutated genes were recognized and TP53 (43%) and CYLD (43%) were the two most commonly mutated genes. Only seven patients who underwent NGS were tested for PD-L1. Three patients with high PD-L1 expression (PD-L1≥ 50%) and four patients with low PD-L1 expression (PD-L1 <50%) were included. No significant correlation was observed between PD-L1 expression and clinical characteristics (age, gender, smoking status, tumor stage, lymph node metastasis) (p > 0.05) and OS (p = 1). What’s more, 10 PPLELC patients involved in previous studies and one patient received nivolumab in the current study were collected retrospectively. 4/11 (36.4%) patients achieved PR, 6/11 (54.5%) patients achieved SD, and 1/11 (9.1%) patients achieved PD and the disease control rate (DCR) was 90.9%.

Conclusions: The prognosis of PPLELC is better than that of other NSCLC, and immunotherapy may be a promising treatment to prolong the survival of advanced PPLELC patients. Whether the immunotherapy efficacy of PPLELC can be predicted by PD-L1 and TMB needs further clinical investigation. CYLD genetic alterations may participate in Epstein–Barr virus-mediated tumorigenesis in PPLELC, providing a novel therapeutic target.
Arterial Stiffening Moderates the Relationship Between Type-2 Diabetes Mellitus and White Matter Hyperintensity Burden in Older Adults With Mild Cognitive Impairment
Authors: Werhane Madeleine L. , Thomas Kelsey R. , Bangen Katherine J. , Weigand Alexandra J. , Edmonds Emily C. , Nation Daniel A. , Sundermann Erin E. , Bondi Mark W. , Delano-Wood Lisa
Published: October 2021

Background:Cerebrovascular dysfunction has been proposed as a possible mechanism underlying cognitive impairment in the context of type 2 diabetes mellitus (DM). Although magnetic resonance imaging (MRI) evidence of cerebrovascular disease, such as white matter hyperintensities (WMH), is often observed in DM, the vascular dynamics underlying this pathology remain unclear. Thus, we assessed the independent and combined effects of DM status and different vascular hemodynamic measures (i.e., systolic, diastolic, and mean arterial blood pressure and pulse pressure index [PPi]) on WMH burden in cognitively unimpaired (CU) older adults and those with mild cognitive impairment (MCI).

Methods:559 older adults (mean age: 72.4 years) from the Alzheimer’s Disease Neuroimaging Initiative were categorized into those with diabetes (DM+; CU = 43, MCI = 34) or without diabetes (DM-; CU = 279; MCI = 203). Participants underwent BP assessment, from which all vascular hemodynamic measures were derived. T2-FLAIR MRI was used to quantify WMH burden. Hierarchical linear regression, adjusting for age, sex, BMI, intracranial volume, CSF amyloid, and APOE ε4 status, examined the independent and interactive effects of DM status and each vascular hemodynamic measure on total WMH burden.

Results:The presence of DM (p= 0.046), but not PPi values (p= 0.299), was independently associated with greater WMH burden overall after adjusting for covariates. Analyses stratified by cognitive status revealed a significant DM status x PPi interaction within the MCI group (p= 0.001) such that higher PPi values predicted greater WMH burden in the DM + but not DM- group. No significant interactions were observed in the CU group (allps > 0.05).

Discussion:Results indicate that higher PPi values are positively associated with WMH burden in diabetic older adults with MCI, but not their non-diabetic or CU counterparts. Our findings suggest that arterial stiffening and reduced vascular compliance may have a role in development of cerebrovascular pathology within the context of DM in individuals at risk for future cognitive decline. Given the specificity of these findings to MCI, future exploration of the sensitivity of earlier brain markers of vascular insufficiency (i.e., prior to macrostructural white matter changes) to the effects of DM and arterial stiffness/reduced vascular compliance in CU individuals is warranted.
Association Between Plasma Amyloid-β and Neuropsychological Performance in Patients With Cognitive Decline
Authors: Yun Gyihyaon , Kim Hye Jin , Kim Hyug-Gi , Lee Kyung Mi , Hong Il Ki , Kim Sang Hoon , Rhee Hak Young , Jahng Geon-Ho , Yoon Sung Sang , Park Key-Chung , Hwang Kyo Seon , Lee Jin San
Published: October 2021

Objective: To investigate the association between plasma amyloid-β (Aβ) levels and neuropsychological performance in patients with cognitive decline using a highly sensitive nano-biosensing platform.

Methods: We prospectively recruited 44 patients with cognitive decline who underwent plasma Aβ analysis, amyloid positron emission tomography (PET) scanning, and detailed neuropsychological tests. Patients were classified into a normal control (NC, n = 25) or Alzheimer’s disease (AD, n = 19) group based on amyloid PET positivity. Multiple linear regression was performed to determine whether plasma Aβ (Aβ40, Aβ42, and Aβ42/40) levels were associated with neuropsychological test results.

Results: The plasma levels of Aβ42/40 were significantly different between the NC and AD groups and were the best predictor of amyloid PET positivity by receiver operating characteristic curve analysis [area under the curve of 0.952 (95% confidence interval, 0.892–1.000)]. Although there were significant differences in the neuropsychological performance of cognitive domains (language, visuospatial, verbal/visual memory, and frontal/executive functions) between the NC and AD groups, higher levels of plasma Aβ42/40 were negatively correlated only with verbal and visual memory performance.

Conclusion: Our results demonstrated that plasma Aβ analysis using a nano-biosensing platform could be a useful tool for diagnosing AD and assessing memory performance in patients with cognitive decline.
Visual but Not Auditory-Verbal Feedback Induces Aftereffects Following Adaptation to Virtual Prisms
Authors: Bourgeois Alexia , Schmid Audrey , Turri Francesco , Schnider Armin , Ptak Radek
Published: October 2021

Visuo-motor adaptation with optical prisms that displace the visual scene (prism adaptation, PA) has been widely used to study visuo-motor plasticity in healthy individuals and to decrease the lateralized bias of brain-damaged patients suffering from spatial neglect. Several factors may influence PA aftereffects, such as the degree of optical deviation (generally measured in dioptres of wedge prisms) or the direction of the prismatic shift (leftward vs. rightward). However, the mechanisms through which aftereffects of adaptation in healthy individuals and in neglect affect performance in tasks probing spatial cognition remain controversial. For example, some studies have reported positive effects of PA on auditory neglect, while other studies failed to obtain any changes of performance even in the visual modality. We here tested a new adaptation method in virtual reality to evaluate how sensory parameters influence PA aftereffects. Visual vs. auditory-verbal feedback of optical deviations were contrasted to assess whether rightward deviations influence manual and perceptual judgments in healthy individuals. Our results revealed that altered visual, but not altered auditory-verbal feedback induces aftereffects following adaptation to virtual prisms after 30-degrees of deviation. These findings refine current models of the mechanisms underlying the cognitive effects of virtual PA in emphasizing the importance of visual vs. auditory-verbal feedback during the adaptation phase on visuospatial judgments. Our study also specifies parameters which influence virtual PA and its aftereffect, such as the sensory modality used for the feedback.
Kernelized k-Local Hyperplane Distance Nearest-Neighbor Model for Predicting Cerebrovascular Disease in Patients With End-Stage Renal Disease
Authors: Liu Xiaobin , Zhang Xiran , Zhang Yi , Ding Yijie , Shan Weiwei , Huang Yiqing , Wang Liang , Guo Xiaoyi
Published: October 2021

Detecting and treating cerebrovascular diseases are essential for the survival of patients with chronic kidney disease (CKD). Machine learning algorithms can be used to effectively predict stroke risk in patients with end-stage renal disease (ESRD). An imbalance in the amount of collected data associated with different risk levels can influence the classification task. Therefore, we propose the use of a kernelized k-local hyperplane nearest-neighbor model (KHKNN) for the effective prediction of stroke risk in patients with ESRD. We compared our proposed method with other conventional machine learning methods, which revealed that our method could effectively perform the task of classifying stroke risk.
Identification and Validation of an Immune-Related lncRNA Signature to Facilitate Survival Prediction in Gastric Cancer
Authors: Ma Ensi , Hou Sen , Wang Yan , Xu Xiao , Wang Zhengxin , Zhao Jing
Published: October 2021

Background

Long noncoding RNAs (lncRNAs) are versatile in functions and can regulate cancer development, including the modulation of cancer immunity. Immune-related lncRNA signatures predicting prognosis have been reported in multiple cancers, but relevant studies in gastric cancer (GC) are still lacking.

Methods

We performed a comprehensive analysis using TCGA and Immport databases and identified an immune-related lncRNA signature by univariate and multivariate Cox regression analysis. qRT-PCR and immunohistochemistry assays were used for further validation. KEGG and GO analysis and ceRNA network establishment were carried out to explore the regulatory functions.

Results

We first identified an immune-related lncRNA signature, which can stratify gastric cancer patients into high- and low-risk subgroups and the high-risk cases frequently suffered from shorter overall survival time. Next, we validated the reliability of the lncRNA signature in an independent 75 gastric cancer samples and demonstrated that the three-year survival rate in high-risk patients was only 30.8% versus 66.5% in low-risk counterparts. Functional exploration indicated that the lncRNA signature might participate in multiple cancer-associated processes including cell adhesion and migration, cytokine-receptor interaction and immune evasion. Additionally, we observed that high-risk samples tended to form an immunosuppressive microenvironment, which had more M2-polarized macrophages and Tregs, but fewer CD8 effector T cells within tumors. Moreover, we found that PD-1 and PD-L1 were dramatically upregulated in a subset of high-risk patients with abundant M2 and Treg infiltration, implying these patients may benefit from anti-PD-1 and PD-L1 immunotherapy.

Conclusions

These results showed that the immune-related lncRNA signature had a prominent capacity to predict overall survival and the immune status of microenvironment in gastric cancer. Our findings may be useful for the risk-stratification management and provide a valuable clue to identify proper patients potentially benefit from immune checkpoint therapy in gastric cancer.
Alternative Splicing-Based Differences Between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: Genes, Immune Microenvironment, and Survival Prognosis
Authors: Luo Dingan , Zhao Deze , Zhang Mao , Hu Chuan , Li Haoran , Zhang Shun , Chen Xiaowu , Huttad Lakshmi , Li Bailiang , Jin Cheng , Lin Changwei , Han Bing
Published: October 2021

Alternative splicing (AS) event is a novel biomarker of tumor tumorigenesis and progression. However, the comprehensive analysis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is lacking. Differentially expressed analysis was used to identify the differentially expressed alternative splicing (DEAS) events between HCC or ICC tissues and their normal tissues. The correlation between DEAS events and functional analyses or immune features was evaluated. The cluster analysis based on DEAS can accurately reflect the differences in the immune microenvironment between HCC and ICC. Forty-five immune checkpoints and 23 immune features were considered statistically significant in HCC, while only seven immune checkpoints and one immune feature in ICC. Then, the prognostic value of DEAS events was studied, and two transcripts with different basic cell functions (proliferation, cell cycle, invasion, and migration) were produced by ADHFE1 through alternative splicing. Moreover, four nomograms were established in conjunction with relevant clinicopathological factors. Finally, we found two most significant splicing factors and further showed their protein crystal structure. The joint analysis of the AS events in HCC and ICC revealed novel insights into immune features and clinical prognosis, which might provide positive implications in HCC and ICC treatment.
Diagnostic Errors in Wilms' Tumors: Learning From Our Mistakes
Authors: de Carvalho Lucas Garschagen , Kobayashi Thiago , Cypriano Monica dos Santos , Caran Eliana Maria Monteiro , Lederman Henrique Manoel , Alves Maria Teresa de Seixas , Abib Simone de Campos Vieira
Published: October 2021

Aim: This study aimed to analyze clinical characteristics and image findings in patients initially diagnosed with renal masses and treated on the Société Internationale d'Oncologie Pédiatrique (SIOP) 2001 protocol for Wilms tumor (WT) that eventually were diagnosed with different pathologies.

Methods: We reviewed the preoperative symptoms, laboratory tests, and images of patients who were initially treated for WT and proved to have other diagnoses. Data from these patients were compared to those of the last 10 patients with WT and the last 10 patients with neuroblastoma (NBL) treated at a single institution.

Results: From June 2001 to December 2020, we treated 299 patients with NBL and 194 with WT. Five patients treated with preoperative chemotherapy for WT were postoperatively diagnosed with NBL (one patient had bilateral renal masses and one with multifocal xanthogranulomatous pyelonephritis). Three underwent nephrectomy, two biopsies only, and one adrenalectomy due to intraoperative characteristics. Regarding clinical presentation, abdominal mass or swelling was very suggestive of WT (p = 0.011); pain, although very prevalent in the study group (67%), was not statistically significant, as well as intratumoral calcifications on computed tomography (CT) (67%). Urinary catecholamines were elevated in all patients mistreated for WT with the exception of the patient with pyelonephritis in which it was not collected.

Conclusion: Some pathologies can be misdiagnosed as WT, especially when they present unspecified symptoms and dubious images. Diagnostic accuracy was 98.1%, which highlights the quality of the multidisciplinary team. Abdominal mass or swelling is highly suggestive of WT, especially in the absence of intratumoral calcifications on CT. If possible, urinary catecholamines should be collected at presentation as they help in the differential diagnosis of NBL.
Case Report: Deutetrabenazine as an Adjunctive Treatment for Stuttering
Authors: Ha Catherine A. , Maguire Gerald A.
Published: October 2021

Childhood-Onset Fluency Disorder (Stuttering) is a neurodevelopmental disorder in which disturbances occur in the normal fluency and time patterning of speech. While the dopamine system has been well-described in its neurophysiology, there currently is no FDA-approved treatment for stuttering. Second-generation antipsychotics, which have been effective in the treatment of schizophrenia and bipolar disorder, act as dopamine D-2 receptor antagonists at the postsynaptic neuron and have been shown to reduce the symptoms of stuttering. However, the D-2 receptor antagonist and partial agonist agents carry the potential for metabolic side effects and can potentially lead to movement disorders. Deutetrabenazine, a VMAT-2 inhibitor indicated to treat hyperkinetic movement disorders, is a potential candidate in the treatment of stuttering, based on its mechanism of action in decreasing dopamine activity while not carrying the risk of metabolic adverse events.
Influencing Factors Associated With Mental Health Outcomes Among Dental Medical Staff in Emergency Exposed to Coronavirus Disease 2019: A Multicenter Cross-Sectional Study in China
Authors: Chen Yaopian , Li Wei
Published: October 2021

Background: The epidemic infection of coronavirus disease 2019 (COVID-19) may have a profound impact on dentistry, mainly due to the mode of transmission of the pathogen, which poses a risk to almost all dental operations. Therefore, this study aimed to investigate the prevalence and influencing factors of anxiety, depression, perceived stress, and acute stress disorder among dental medical staff in emergency situations during the COVID-19 epidemic.

Methods: From April 3, 2020, to April 10, 20204, a multicenter cross-sectional study was conducted among 808 first-line dental professionals at an emergency department in mainland China. A self-designed questionnaire was used to collect general demographic information. The 7-item Generalized Anxiety Disorder Scale (GAD-7), 9-item Patient Health Questionnaire (PHQ-9), 10-item Perceived Stress Scale (PSS-10), and Acute Stress Disorder Scale (ASDS) were used to assess the severity of symptoms of anxiety, depression, perceived stress, and acute stress disorder (ASD), respectively.

Results: The prevalence rates of depression, anxiety, perceived pressure, and ASD among the frontline dental medical staff were 46.4, 36.3, 65.2, and 1.1%, respectively. The frontline dental medical staff who were working in the Wuhan area reported experiencing more anxiety (p = 0.038) and perceived stress (p < 0.001) compared with those who were not working in the Wuhan area. The frontline dental medical staff who were working in a general hospital reported experiencing more dissociation symptoms (p = 0.001) compared with those working in a specialized or private hospital. Individuals with a past medical history reported experiencing more anxiety (p = 0.009), depression (p < 0.001), and perceived stress (p = 0.003) than those without, and individuals with lower levels of education showed higher levels of anxiety (p = 0.038). Binary logistic regression analysis results (after controlling for other confounders) suggested that having a past medical history was a risk factor for both anxiety (p = 0.002; OR = 2.441; 95% CI, 1.384–4.306) and perceived stress (p = 0.001; OR = 1.417; 95% CI, 1.145–1.754).

Conclusions: The prevalence of mental symptoms was high among the first-line emergency dental staff. Male sex, working in the Wuhan area, working in a general hospital, a past medical history, and lower levels of education were risk factors. Therefore, we need to pay close attention to the mental health problems of frontline dentists during the COVID-19 outbreak and adopt active preventive strategies to maintain their physical and mental health.
Are in Person and Telephone Interviews Equivalent Modes of Administrating the CAT, the FACIT-FS and the SGRQ in People With COPD?
Authors: Rocha Vânia , Jácome Cristina , Martins Vitória , Marques Alda
Published: October 2021

Background: The COVID-19 pandemic brought numerous challenges, namely in routine assessment of people with chronic obstructive pulmonary disease (COPD). The COPD Assessment Test (CAT), the Functional Assessment of Chronic Illness-Fatigue-Subscale (FACIT-FS) and the St. George's respiratory questionnaire (SGRQ) are important patient-reported outcome measures used to assess people with COPD, but its face-to-face application has been compromised. The telephone interview offers a simple and effective alternative, yet uncertainty regarding its equivalence remains. This study aimed to establish the reliability and validity of the CAT, the FACIT-FS and the SGRQ administered by telephone interview in people with COPD.

Methods: Data from an observational prospective study including people with COPD were analyzed. Participants answered to the CAT, FACIT-FS and SGRQ questionnaires in person and by telephone, with a maximum interval of 48-h. Participants were randomly selected to answer first to the in-person questionnaire followed by telephone or vice versa. Reliability measures included internal consistency with Cronbach's alpha, test-retest reliability with the intraclass correlation coefficient (ICC2,1), test-retest measurement error with the standard error of measurement (SEM) and agreement with the Bland and Altman 95% limits of agreement. Validity was assessed with the Spearman correlation (rho).

Results: Fifty-five people with COPD (44 men; 68.1 ± 7.9 years; FEV1: 59.1 ± 20.3% predicted) were included. Similar internal consistency was observed between in person vs. telephone interview for the CAT (0.82 vs. 0.84), the FACIT-FS (0.83 vs. 0.84) and the SGRQ (0.92 vs. 0.93). Test-retest reliability was excellent, with an ICC2,1 of 0.77 (95% CI: 0.65; 0.86), 0.86 (95% CI: 0.77; 0.92) and 0.94 (95% CI: 0.90; 0.96) for the CAT, FACIT-FS and SGRQ total scores, respectively. The SEM showed a low level of associated measurement error and the Bland and Altman plots illustrated a good level of agreement between both modes of administration, with no evidence of systematic bias. Robust positive correlations (rho 0.87–0.94, p < 0.001) were found for the CAT, FACIT-FS and SGRQ total scores applied by both methods.

Conclusion: The telephonic administration of the CAT, the FACIT-FS and the SGRQ are a valid and reliable alternative approach to in person interviews for monitoring symptoms and health-related quality of life in people with COPD. The telephone might be an important add-on for personalized assessment and management of COPD thru remote monitoring.
Steering Does Affect Biophysical Responses in Asynchronous, but Not Synchronous Submaximal Handcycle Ergometry in Able-Bodied Men
Authors: Kraaijenbrink Cassandra , Vegter Riemer J. K. , Ostertag Nils , Janssens Luc , Vanlandewijck Yves , van der Woude Lucas H. V. , Wagner Heiko
Published: October 2021

Real-life daily handcycling requires combined propulsion and steering to control the front wheel. Today, the handcycle cranks are mostly mounted synchronously unlike the early handcycle generations. Alternatively, arm cycle ergometers do not require steering and the cranks are mostly positioned asynchronously. The current study aims to evaluate the effects of combining propulsion and steering requirements on synchronous and asynchronous submaximal handcycle ergometry. We hypothesize that asynchronous handcycling with steering results in the mechanically least efficient condition, due to compensation for unwanted rotations that are not seen in synchronous handcycling, regardless of steering. Sixteen able-bodied male novices volunteered in this lab-based experiment. The set-up consisted of a handcycle ergometer with 3D force sensors at each crank that also allows “natural” steering. Four submaximal steady-state (60 rpm, ~35 W) exercise conditions were presented in a counterbalanced order: synchronous with a fixed steering axis, synchronous with steering, asynchronous with a fixed axis and asynchronous with steering. All participants practiced 3 × 4 mins with 30 mins rest in between every condition. Finally, they did handcycle for 4 mins in each of the four conditions, interspaced with 10 mins rest, while metabolic outcomes, kinetics and kinematics of the ergometer were recorded. The additional steering component did not influence velocity, torque and power production during synchronous handcycling and therefore resulted in an equal metabolically efficient handcycling configuration compared to the fixed condition. Contrarily, asynchronous handcycling with steering requirements showed a reduced mechanical efficiency, as velocity around the steering axis increased and torque and power production were less effective. Based on the torque production around the crank and steering axes, neuromuscular compensation strategies seem necessary to prevent steering movements in the asynchronous mode. To practice or test real-life daily synchronous handcycling, a synchronous crank set-up of the ergometer is advised, as exercise performance in terms of mechanical efficiency, metabolic strain, and torque production is independent of steering requirements in that mode. Asynchronous handcycling or arm ergometry demands a different handcycle technique in terms of torque production and results in higher metabolic responses than synchronous handcycling, making it unsuitable for testing.
Performance of Computed Tomography Angiography Before Revascularization Is Associated With Higher Amputation-Free Survival in Rutherford IIb Acute Lower Limb Ischaemia
Authors: Saphir Ebba , Svensson-Björk Robert , Acosta Stefan
Published: October 2021

Background: Acute lower limb ischemia with a motor deficit (Rutherford IIb) needs urgent revascularization to avoid major amputation and mortality. It is unclear whether immediate revascularization without performing CT angiography (CTA) prior to revascularization in Rutherford IIb acute lower limb ischemia (ALI) is associated with better outcomes.

Methods: Retrospective observational study of Rutherford IIb ALI patients treated between 2006 and 2018. A propensity score adjusted analysis was performed to compare outcomes after the performance of CTA examination or not.

Results: Among 681 patients, 260 had Rutherford IIb ALI. CTA prior to revascularization was performed in 131 (50.4%) and increased (p < 0.001) throughout the study period. Open vascular and endovascular surgery was first performed in 147 (56.5%) and 113 (43.5%) patients, respectively. The proportion of endovascular treatment increased while the open vascular surgery decreased during the study period (p = 0.031). In the propensity score adjusted analysis, the performance of CTA was associated with decreased risk of combined major amputation /mortality (odds ratio 0.52, 95% confidence interval 0.27–0.99; p = 0.046) at 1 year.

Conclusion: Performance of CTA was associated with a higher amputation-free survival in revascularized patients with Rutherford IIb ALI. CTA seem to provide guidance in selecting the most appropriate candidates for revascularization and choice of technique.
Do Pet Cats Deserve the Disproportionate Blame for Wildlife Predation Compared to Pet Dogs?
Authors: Franklin Michael , Rand Jacquie , Marston Linda , Morton John
Published: October 2021

Concerns about the impact of pet dogs and cats on native wildlife populations have shaped pet control legislation, despite there being scant research of their impact in urban areas. Using an online questionnaire, we obtained data from 662 Australian dog and cat owners who had observed their pets capture prey in the previous 6 months. Of the pets observed to catch prey, dogs caught a median of 2 mammals, 2 birds, 2 reptiles, and 3 amphibians, whereas cats caught a median of 3 mammals, 2 birds, 4 reptiles, and 2 amphibians. Of mammals caught by dogs and cats, 88 and 93%, respectively, were identifiable as introduced mice, rats, and rabbits. Of pets that caught prey, a substantial proportion caught native animals (62% of dogs and 47% of cats). However, median numbers of native animals caught per dog (2) or cat (3) over 6 months were low. Small skinks and lizards comprised the greatest proportion for dogs and cats, but dogs also caught larger native prey (e.g., possums, kangaroos, and wallabies). Most birds caught by dogs and cats were common or introduced (dogs: crested pigeons and lorikeets; cats: noisy miners and rosellas). To design measures that will effectively protect Australia's native wildlife, thorough understanding of the role dogs and cats play in Australian urban ecosystems is required. These findings can inform that understanding, and assist with development of management strategies for urban dogs and cats, and as well as directing resources to efforts that will most protect urban wildlife.
Psicoterapia cognitivo-narrativa: la construcción hermenéutica de los significados alternativos.
Authors: Gonçalves Oscar
Published: October 2021

Las psicoterapias cognitivas están experimentando grandes cambios conceptuales. En los más recientes desarrollos de la teoría cognitiva han aparecido una creciente orientación constructivista junto con un modelo narrativo de los procesos de conocimiento. Estos cambios prueban la necesidad de desarrollar nuevas metodologías terapéuticas que sean capaces de efectuar grandes cambios en los procesos de conocimiento. Este artículo intenta tratar estas cuestiones presentando una ilustración de una nueva metodología terapéutica a la cual nos referiremos como psicoterapia cognitivo-narrativa.
The GM-BP Neural Network Prediction Model for International Competitiveness of Computer Information Service Industry
Authors: Xu Xianhang , Arshad Mohd Anuar , Ali Ubaid , Mahmood Arshad
Published: October 2021

The computer information service industry is closely related to the fourth industrial revolution and stands at the core of the global value chain. It has become an essential engine for developing industries in various countries, and its scale is constantly expanding. In the critical period of global economic transformation and development, the use of mathematical models to predict its international competitiveness will help scientifically evaluate the development level of the industry and accelerate the adaptation to the needs of the fourth industrial revolution. In this article, a prediction model is proposed for the international competitiveness of the computer information service industry. First, we used the Revealed Comparative Advantage (RCA) index to measure the international competitiveness of the computer information service industry. Furthermore, based on the characteristics of the industry and high-quality development theory, we constructed the evaluation indicator system of influencing factors and used the grey relational analysis method to screen key indicators. Then, we combined the Grey model and BP neural network algorithm to construct the GM-BP prediction model. Finally, China is used as an example to predict the international competitiveness of its computer information service industry, and suggestions are made for industrial development. The results show that the grey relational analysis method can genuinely reflect the impact of different aspects on the international competitiveness of China’s computer information service industry and better determine the key indicators of influencing factors. The GM-BP model has minor errors and excellent simulation results and can accurately predict the future status of international competitiveness. The applicability and reliability of the model are reasonable.
Artificial Neural Network-Derived Cerebral Metabolic Rate of Oxygen for Differentiating Glioblastoma and Brain Metastasis in MRI: A Feasibility Study
Authors: Baazaoui Hakim , Hubertus Simon , Maros Máté E. , Mohamed Sherif A. , Förster Alex , Schad Lothar R. , Wenz Holger
Published: October 2021

Glioblastoma may appear similar to cerebral metastasis on conventional MRI in some cases, but their therapies differ significantly. This prospective feasibility study was aimed at differentiating them by applying the quantitative susceptibility mapping and quantitative blood-oxygen-level-dependent (QSM + qBOLD) model to these entities for the first time. We prospectively included 15 untreated patients with glioblastoma (n = 7, median age: 68 years, range: 54–84 years) or brain metastasis (n = 8, median age 66 years, range: 50–78 years) who underwent preoperative MRI including multi-gradient echo and arterial spin labeling sequences. Oxygen extraction fraction (OEF), cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were calculated in the contrast-enhancing tumor (CET) and peritumoral non-enhancing T2 hyperintense region (NET2), using an artificial neural network. We demonstrated that OEF in CET was significantly lower (p = 0.03) for glioblastomas than metastases, all features were significantly higher (p = 0.01) in CET than in NET2 for metastasis patients only, and the ratios of CET/NET2 for CBF (p = 0.04) and CMRO2 (p = 0.01) were significantly higher in metastasis patients than in glioblastoma patients. Discriminative power of a support-vector machine classifier was highest with a combination of two features, yielding an area under the receiver operating characteristic curve of 0.94 with 93% diagnostic accuracy. QSM + qBOLD allows for robust differentiation of glioblastoma and cerebral metastasis while yielding insights into tumor oxygenation.
Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells
Authors: Gao Jing-Yan , Chang Chih-Shiang , Lien Jin-Cherng , Chen Ting-Wei , Hu Jing-Lan , Weng Jing-Ru
Published: October 2021

Trytanthrin, found in Ban-Lan-Gen, is a natural product containing an indoloquinazoline moiety and has been shown to possess anti-inflammatory and anti-viral activities. Chronic inflammation and hepatitis B are known to be associated with the progression of hepatocellular carcinoma (HCC). In this study, a series of tryptanthrin derivatives were synthesized to generate potent anti-tumor agents against HCC. This effort yielded two compounds, A1 and A6, that exhibited multi-fold higher cytotoxicity in HCC cells than the parent compound. Flow cytometric analysis demonstrated that A1 and A6 caused S-phase arrest and downregulated the expression of cyclin A1, B1, CDK2, and p-CDC2. In addition to inducing caspase-dependent apoptosis, A1 and A6 exhibited similar regulation of the phosphorylation or expression of multiple signaling targets, including Akt, NF-κB, and mitogen-activated protein kinases. The anti-tumor activities of A1 and A6 were also attributable to the generation of reactive oxygen species, accompanied by an increase in p-p53 levels. Therefore, A1 and A6 have potential clinical applications since they target diverse aspects of cancer cell growth in HCC.
Delivery Capacity and Anticancer Ability of the Berberine-Loaded Gold Nanoparticles to Promote the Apoptosis Effect in Breast Cancer
Authors: Chiu Chen-Feng , Fu Ru-Huei , Hsu Shan-hui , Yu Yang-Hao (Alex) , Yang Shun-Fa , Tsao Thomas Chang-Yao , Chang Kai-Bo , Yeh Chun-An , Tang Cheng-Ming , Huang Sheng-Chu , Hung Huey-Shan
Published: October 2021

Gold nanoparticles (AuNPs) were fabricated with biocompatible collagen (Col) and then conjugated with berberine (BB), denoted as Au-Col-BB, to investigate the endocytic mechanisms in Her-2 breast cancer cell line and in bovine aortic endothelial cells (BAEC). Owing to the superior biocompatibility, tunable physicochemical properties, and potential functionalization with biomolecules, AuNPs have been well studied as carriers of biomolecules for diseases and cancer therapeutics. Composites of AuNPs with biopolymer, such as fibronectin or Col, have been revealed to increase cell proliferation, migration, and differentiation. BB is a natural compound with impressive health benefits, such as lowering blood sugar and reducing weight. In addition, BB can inhibit cell proliferation by modulating cell cycle progress and autophagy, and induce cell apoptosis in vivo and in vitro. In the current research, BB was conjugated on the Col-AuNP composite (“Au-Col”). The UV-Visible spectroscopy and infrared spectroscopy confirmed the conjugation of BB on Au-Col. The particle size of the Au-Col-BB conjugate was about 227 nm, determined by dynamic light scattering. Furthermore, Au-Col-BB was less cytotoxic to BAEC vs. Her-2 cell line in terms of MTT assay and cell cycle behavior. Au-Col-BB, compared to Au-Col, showed greater cell uptake capacity and potential cellular transportation by BAEC and Her-2 using the fluorescence-conjugated Au-Col-BB. In addition, the clathrin-mediated endocytosis and cell autophagy seemed to be the favorite endocytic mechanism for the internalization of Au-Col-BB by BAEC and Her-2. Au-Col-BB significantly inhibited cell migration in Her-2, but not in BAEC. Moreover, apoptotic cascade proteins, such as Bax and p21, were expressed in Her-2 after the treatment of Au-Col-BB. The tumor suppression was examined in a model of xenograft mice treated with Au-Col-BB nanovehicles. Results demonstrated that the tumor weight was remarkably reduced by the treatment of Au-Col-BB. Altogether, the promising findings of Au-Col-BB nanocarrier on Her-2 breast cancer cell line suggest that Au-Col-BB may be a good candidate of anticancer drug for the treatment of human breast cancer.
Polycaprolactone Electrospun Scaffolds Produce an Enrichment of Lung Cancer Stem Cells in Sensitive and Resistant EGFRm Lung Adenocarcinoma
Authors: Polonio-Alcalá Emma , Rabionet Marc , Ruiz-Martínez Santiago , Palomeras Sònia , Porta Rut , Vásquez-Dongo Carmen , Bosch-Barrera Joaquim , Puig Teresa , Ciurana Joaquim
Published: October 2021

The establishment of a three-dimensional (3D) cell culture model for lung cancer stem cells (LCSCs) is needed because the study of these stem cells is unable to be done using flat surfaces. The study of LCSCs is fundamental due to their key role in drug resistance, tumor recurrence, and metastasis. Hence, the purpose of this work is the evaluation of polycaprolactone electrospun (PCL-ES) scaffolds for culturing LCSCs in sensitive and resistant EGFR-mutated (EGFRm) lung adenocarcinoma cell models. We performed a thermal, physical, and biological characterization of 10% and 15%-PCL-ES structures. Several genes and proteins associated with LCSC features were analyzed by RT-qPCR and Western blot. Vimentin and CD133 tumor expression were evaluated in samples from 36 patients with EGFRm non-small cell lung cancer through immunohistochemistry. Our findings revealed that PC9 and PC9-GR3 models cultured on PCL-ES scaffolds showed higher resistance to osimertinib, upregulation of ABCB1, Vimentin, Snail, Twist, Sox2, Oct-4, and CD166, downregulation of E-cadherin and CD133, and the activation of Hedgehog pathway. Additionally, we determined that the non-expression of CD133 was significantly associated with a low degree of histological differentiation, disease progression, and distant metastasis. To sum up, we confirmed PCL-ES scaffolds as a suitable 3D cell culture model for the study of the LCSC niche.
A DOCK1 Gene-Derived Circular RNA Is Highly Expressed in Luminal Mammary Tumours and Is Involved in the Epithelial Differentiation, Growth, and Motility of Breast Cancer Cells
Authors: Kurosaki Mami , Terao Mineko , Liu Dawei , Zanetti Adriana , Guarrera Luca , Bolis Marco , Gianni’ Maurizio , Paroni Gabriela , Goodall Gregory J. , Garattini Enrico
Published: October 2021

Circular RNAs are regulatory molecules involved in numerous cellular processes and may be involved in tumour growth and diffusion. Here, we define the expression of 15 selected circular RNAs, which may control the process of epithelial-to-mesenchymal transition, using a panel of 18 breast cancer cell lines recapitulating the heterogeneity of these tumours and consisting of three groups according to the mesenchymal/epithelial phenotype. A circular RNA from the DOCK1 gene (hsa_circ_0020397) shows low/undetectable levels in triple-negative mesenchymal cell lines, while its content is high in epithelial cell lines, independent of estrogen receptor or HER2 positivity. RNA-sequencing experiments performed on the triple-negative/mesenchymal MDA-MB-231 and MDA-MB-157 cell lines engineered to overexpress hsa_circ_0020397 demonstrate that the circRNA influences the expression of 110 common genes. Pathway analysis of these genes indicates that overexpression of the circular RNA differentiates the two mesenchymal cell lines along the epithelial pathway and increases cell-to-cell adhesion. This is accompanied by growth inhibition and a reduction in the random/directional motility of the cell lines. The upregulated AGR2, ENPP1, and PPP1R9A genes as well as the downregulated APOE, AQP3, CD99L2, and IGFBP4 genes show an opposite regulation by hsa_circ_0020397 silencing in luminal CAMA1 cells. The results provide novel insights into the role played by specific circular RNAs in the generation/progression of breast cancer.
How Does Obesity Cause Cancer?
Authors: Hoehn Kyle Lee
Published: October 2021

This series comprises 14 articles (5 original articles and 9 reviews) that investigate connections between excess body mass and cancer risk or cancer treatment response [...]