bluuebunny/crossref_metadata_2025 huggingface dataset:
Copula‐based predictions in small area estimation
Authors: Grover Kanika , Acar Elif F. , Torabi Mahmoud
Published: July 2020

Unit‐level regression models are commonly used in small area estimation (SAE) to obtain an empirical best linear unbiased prediction of small area characteristics. The underlying assumptions of these models, however, may be unrealistic in some applications. Previous work developed a copula‐based SAE model where the empirical Kendall's tau was used to estimate the dependence between two units from the same area. In this article, we propose a likelihood framework to estimate the intra‐class dependence of the multivariate exchangeable copula for the empirical best unbiased prediction (EBUP) of small area means. One appeal of the proposed approach lies in its accommodation of both parametric and semi‐parametric estimation approaches. Under each estimation method, we further propose a bootstrap approach to obtain a nearly unbiased estimator of the mean squared prediction error of the EBUP of small area means. The performance of the proposed methods is evaluated through simulation studies and also by a real data application.
Estrogen receptor alpha, G‐protein coupled estrogen receptor 1, and aromatase: Developmental, sex, and region‐specific differences across the rat caudate–putamen, nucleus accumbens core and shell
Authors: Krentzel Amanda A. , Willett Jaime A. , Johnson Ashlyn G. , Meitzen John
Published: July 2020

Sex steroid hormones such as 17β‐estradiol (estradiol) regulate neuronal function by binding to estrogen receptors (ERs), including ERα and GPER1, and through differential production via the enzyme aromatase. ERs and aromatase are expressed across the nervous system, including in the striatal brain regions. These regions, comprising the nucleus accumbens core, shell, and caudate–putamen, are instrumental for a wide‐range of functions and disorders that show sex differences in phenotype and/or incidence. Sex‐specific estrogen action is an integral component for generating these sex differences. A distinctive feature of the striatal regions is that in adulthood neurons exclusively express membrane but not nuclear ERs. This long‐standing finding dominates models of estrogen action in striatal regions. However, the developmental etiology of ER and aromatase cellular expression in female and male striatum is unknown. This omission in knowledge is important to address, as developmental stage influences cellular estrogenic mechanisms. Thus, ERα, GPER1, and aromatase cellular immunoreactivity was assessed in perinatal, prepubertal, and adult female and male rats. We tested the hypothesis that ERα, GPER1, and aromatase exhibits sex, region, and age‐specific differences, including nuclear expression. ERα exhibits nuclear expression in all three striatal regions before adulthood and disappears in a region‐ and sex‐specific time‐course. Cellular GPER1 expression decreases during development in a region‐ but not sex‐specific time‐course, resulting in extranuclear expression by adulthood. Somatic aromatase expression presents at prepuberty and increases by adulthood in a region‐ but not sex‐specific time‐course. These data indicate that developmental period exerts critical sex‐specific influences on striatal cellular estrogenic mechanisms.
A new discrete wavelet transform appropriate for hardware implementation
Authors: Meshkat Amin , Dehghani Rasoul
Published: July 2020

A new method for computation of discrete wavelet transform (DWT) is introduced. The impulse response of the FIR filter, as the main block in filter bank (FB) method, is realized such that orthonormal wavelet transform is achieved without using any multiplier as the most challenging part of the FIR filters. The occupied slices and LUTs in the FPGA realization of the proposed wavelet in comparison with those of Daubechies wavelet are decreased by %50 and %56, respectively.
Regeneration and repair in the healing lung
Authors: Lucas Andrew , Yasa Joe , Lucas Michaela
Published: July 2020

The lung achieves an efficient gas exchange between a complex non‐sterile atmosphere and the body via a delicate and extensive epithelial surface, with high efficiency because of elastic deformation allowing for an increase and decrease in volume during the process of breathing and because of an extensive vasculature which aids rapid gas diffusion. The lungs’ large surface area exposes the organ to a continual risk of damage from pathogens, toxins or irritants; however, lung damage can be rapidly healed via regenerative processes that restore its structure and function. In response to sustained and extensive damage, the lung is healed via a non‐regenerative process resulting in scar tissue which locally stiffens its structure, which over time leads to a serious loss of lung function and to increasing morbidities. This review discusses what is known about the factors which influence whether a lung is healed by regeneration or repair and what potential new therapeutic approaches may positively influence lung healing.
A Bethesda‐like system for breast cytopathology: A retrospective assessment two decades on
Authors: Layfield Lester J.
Published: July 2020

Fine‐needle aspiration biopsy (FNAB) has been used for many decades in the investigation of breast lesions. Originally, cases were signed out using the categories benign and malignant. The benign category contained specimens showing fibrocystic change as well as benign neoplasms such as fibroadenoma. The malignant category contained carcinomas, lymphomas, and phyllodes tumors with specific diagnoses often given in place of the term malignant. Categorization was less clear when the cytopathologists could not definitively separate benign from malignant. This led to the use of terms, such as atypical, suspicious for malignancy, and atypical suspicious with variable definitions and utilization among cytopathologists. In 1997, a uniform approach to breast FNAB was proposed with well‐defined diagnostic categories and criteria. This system foreshadowed the recent International Academy of Cytology Standardized Reporting System for Breast Fine‐Needle Aspiration Biopsy. These two systems are compared and contrasted.
Role of nuclear morphometry in diagnosis of salivary gland neoplasms
Authors: Chaurasia Jai Kumar , Gupta Vikas , Mayank Vipul , Tiwari Ishan Raj , Joshi Deepti , Goel Garima , Kapoor Neelkamal
Published: July 2020

Background

Fine needle aspiration cytology is an important diagnostic tool in salivary gland cytopathology. However, cytology of salivary gland neoplasms shows diversity with morphological overlap, heterogeneity and subjective variability, posing diagnostic challenge. Nuclear cytomorphometric image analysis turns the subjective criteria into quantitative parameters, which may aid not only in differentiating between benign and malignant tumours but also can aid in categorising challenging cases with morphological overlap.

Methods

A retrospective analysis of Papanicolaou stained fine needle aspirate smears from 50 patients with salivary gland neoplasms, with available follow‐up histopathology, was performed. The aspirates were categorised in to three neoplastic categories of Milan system for reporting salivary gland cytology (MSRSGC) that is benign neoplasm, salivary gland neoplasm with uncertain malignant potential, and malignant. The smears were subjected to cytomorphometric image analysis using Image Pro Software (version 10). Each nucleus was analysed for 13 parameters including aspect ratio, intensity, diameter, perimeter, roundness, area, Feret diameter, circularity, radii, Fournier description and chromatin texture characteristics such as margination, heterogeneity and clumpiness. The data obtained was compared through relevant statistical methods.

Results

The comparative morphometric data obtained for parameters using ANOVA, for the three categories showed statistically significant P values (<0.001). The post hoc test (Games‐Howel) test also showed significant P values (<.001).

Conclusion

Cytomorphometric image analysis is an important tool in diagnosis of salivary gland neoplasms and can improve the diagnostic accuracy for better treatment and improved prognosis. However, more studies with larger sample size may be needed in future for further affirming its role.
Prevalence and prognostic impact of subclinical pulmonary congestion at discharge in patients with acute heart failure
Authors: Rivas‐Lasarte Mercedes , Maestro Alba , Fernández‐Martínez Juan , López‐López Laura , Solé‐González Eduard , Vives‐Borrás Miquel , Montero Santiago , Mesado Nuria , Pirla Maria J. , Mirabet Sonia , Fluvià Paula , Brossa Vicens , Sionis Alessandro , Roig Eulàlia , Cinca Juan , Álvarez‐García Jesús
Published: July 2020

Aims

Residual pulmonary congestion at hospital discharge can worsen the outcomes in patients with heart failure (HF) and can be detected by lung ultrasound (LUS). The aim of this study was to analyse the prevalence of subclinical pulmonary congestion at discharge and its impact on prognosis in patients admitted for acute HF.

Methods and results

This is a post‐hoc analysis of the LUS‐HF trial. LUS was performed by the investigators in eight chest zones with a pocket device. Physical exam was subsequently performed by the treating physicians. Primary outcome was a combined endpoint of rehospitalization, unexpected visit for HF worsening or death at 6‐ month follow‐up. Subclinical pulmonary congestion at discharge was defined as the presence of ≥5 B‐lines in LUS in absence of rales in the auscultation employing the area under the ROC curve. At discharge, 100 patients (81%) did not show clinical signs of pulmonary congestion. Of these, 41 had ≥5 B‐lines. Independent factors related with the presence of subclinical pulmonary congestion were anaemia, higher New York Heart Association (NYHA) class, and N terminal pro brain natriuretic peptide (NT‐proBNP). After adjusting by propensity score analysis including age, renal insufficiency, atrial fibrillation, NYHA class, NT‐proBNP levels, clinical congestion, and the trial intervention, the presence of subclinical pulmonary congestion at discharge was a risk factor for the occurrence of the primary outcome (hazard ratio 2.63; 95% confidence interval: 1.08–6.41; P = 0.033).

Conclusions

Up to 40% of patients considered ‘dry’ according to pulmonary auscultation presents subclinical congestion at hospital discharge that can be detected by LUS and implies a worse prognosis at 6‐ month follow‐up. Comorbidities, high values of natriuretic peptides, and higher NYHA class are the factors related with its presence.
From Natural Compounds to Bioactive Molecules through NMR and In Silico Methodologies
Authors: De Vita Simona , Terracciano Stefania , Bruno Ines , Chini Maria Giovanna
Published: July 2020

Marine and terrestrial organisms are an unlimited source of active secondary metabolites. They are characterized by high chemical diversity, biochemical specificity, and other molecular features that make them a valid starting point for lead generation in the drug discovery process. Considering the complex structural architecture and the high number of stereogenic centers, compared to the synthetic drugs, the elucidation of the 2D structure and the assessment of the precise 3D arrangements of natural products (NPs) provide essential insights into ligand‐target interaction which can drive a rational lead optimization process. In this regard, the combination of NMR spectroscopy with modern computational techniques represents one of the most effective approaches to achieve this task. The DFT/NMR integrated method, and its application, in combination with the accurate ROE‐distance analysis, have been employed as valid support, both to clarify the configuration and conformational profile of the active secondary metabolites and to shed more light on the molecular basis of their mechanism of action. Indeed, the comprehension at a molecular level of their interactions with specific targets involved in pathologies, like inflammation and cancer, represents a cornerstone for further investigations through computational tools like molecular docking and molecular dynamics. These high‐efficiency in silico techniques play a crucial part in the drug discovery process as well as in lead optimization procedures. Furthermore, this integrated approach provides the identification of novel chemical platforms disclosing new bioactive molecules with enhanced potency and selectivity.
Phylloxanthobilins are Abundant Linear Tetrapyrroles from Chlorophyll Breakdown with Activities Against Cancer Cells
Authors: Karg Cornelia A. , Wang Pengyu , Kluibenschedl Florian , Müller Thomas , Allmendinger Lars , Vollmar Angelika M. , Moser Simone
Published: July 2020

Linear tetrapyrroles, called phyllobilins, are obtained as major catabolites upon chlorophyll degradation. Primarily, colorless phylloleucobilins featuring four deconjugated pyrrole units were identified. Their yellow counterparts, phylloxanthobilins, were discovered more recently. Although the two catabolites differ only by one double bond, physicochemical properties are very distinct. Moreover, the presence of the double bond seems to enhance physiologically relevant bioactivities: in contrast to phylloleucobilin, we identified a potent anti‐proliferative activity for a phylloxanthobilin, and show that this natural product induces apoptotic cell death and a cell cycle arrest in cancer cells. Interestingly, upon modifying inactive phylloleucobilin by esterification, an anti‐proliferative activity can be observed that increases with the chain lengths of the alkyl esters. We provide first evidence for anti‐cancer activity of phyllobilins, report a novel plant source for a phylloxanthobilin, and by using paper spray MS, show that these bioactive yellow chlorophyll catabolites are more prevalent in Nature than previously assumed.
Rethinking the Importance of the Individual within a Community of Data
Authors: Spector‐Bagdady Kayte , Beever Jonathan
Published: July 2020

The Covid‐19 crisis has underscored the importance of the collection and analysis of clinical and research data and specimens for ongoing work. The federal government recently completed a related revision of the human subjects research regulations, founded in the traditional principles of research ethics, but in this commentary, we argue that the analysis underpinning this revision overemphasized the importance of informed consent, given the low risks of secondary research. Governing the interests of a community is different from governing the interests of individuals, and here we suggest that, moving forward, the analyses of the risks of secondary research protocols be assessed from the perspective of the former.
Functional magnetic resonance imaging multivoxel pattern analysis reveals neuronal substrates for collaboration and competition with myopic and predictive strategic reasoning
Authors: Kim Dong‐Youl , Jung Eun Kyung , Zhang Jun , Lee Soo‐Young , Lee Jong‐Hwan
Published: July 2020

Competition and collaboration are strategies that can be used to optimize the outcomes of social interactions. Research into the neuronal substrates underlying these aspects of social behavior has been limited due to the difficulty in distinguishing complex activation via univariate analysis. Therefore, we employed multivoxel pattern analysis of functional magnetic resonance imaging to reveal the neuronal activations underlying competitive and collaborative processes when the collaborator/opponent used myopic/predictive reasoning. Twenty‐four healthy subjects participated in 2 × 2 matrix‐based sequential‐move games. Searchlight‐based multivoxel patterns were used as input for a support vector machine using nested cross‐validation to distinguish game conditions, and identified voxels were validated via the regression of the behavioral data with bootstrapping. The left anterior insula (accuracy = 78.5%) was associated with competition, and middle frontal gyrus (75.1%) was associated with predictive reasoning. The inferior/superior parietal lobules (84.8%) and middle frontal gyrus (84.7%) were associated with competition, particularly in trials with a predictive opponent. The visual/motor areas were related to response time as a proxy for visual attention and task difficulty. Our results suggest that multivoxel patterns better represent the neuronal substrates underlying the social cognition of collaboration and competition intermixed with myopic and predictive reasoning than do univariate features.
Systematic review and meta‐analysis of racial survival disparities among oropharyngeal cancer cases by HPV status
Authors: Stein Eva , Lenze Nicholas R. , Yarbrough Wendell G. , Hayes D. Neil , Mazul Angela , Sheth Siddharth
Published: July 2020

Background

There is a well documented racial disparity in overall survival for oropharyngeal squamous cell carcinoma (OPSCC); however, it is unknown to what extent this disparity varies by HPV‐status.

Methods

A literature search was conducted through December 2019 using Ovid Medline, Cochrane Library, Embase, Scopus, and Clinicaltrials.gov. PRISMA guidelines were followed. A meta‐analysis was conducted using random effects models to obtain pooled hazard ratios (HRs).

Results

Of 649 studies initially identified, 20 studies met criteria for the narrative review. There were four studies evaluating survival by race in HPV‐positive OPSCC and five studies in HPV‐negative OPSCC suitable for pooling. The pooled HR associated with black race was 1.10 (95% CI 0.96‐1.23) among patients with HPV‐positive (n = 23 608) and 1.50 (95% CI 1.12‐1.88) among patients with HPV‐negative (n = 12 112). There was notable heterogeneity (I2 = 83%) and publication bias among the HPV‐negative OPSCC studies.

Conclusions

The racial disparity in OPSCC survival persists for HPV‐negative disease and is nonsignificant for HPV‐positive disease. Unmeasured differences in socioeconomic status and access to care may contribute to this disparity.
What is the hold up?—Mixed‐methods analysis of postoperative radiotherapy delay in head and neck cancer
Authors: Sykes Kevin J. , Morrow Emily , Smith Joshua B. , Holcomb Andrew J. , TenNapel Mindi , Lominska Christopher E. , Bur Andrés M. , Kakarala Kiran
Published: July 2020

Background

Delays in postoperative radiotherapy (PORT) for head and neck cancer (HNC) increase the risk for recurrence and mortality. The multifactorial nature of delays calls for an in‐depth understanding of potential contributors from the patient's and provider's perspectives. We sought to identify causes of delays in adjuvant radiotherapy initiation for HNC.

Methods

We performed a mixed‐methods study including patients with HNC care team members. Forty in‐depth interviews were performed (26 patients; 14 care team members). Timing and demographic data were collected from medical records.

Results

Median time from surgery to radiotherapy initiation was 45 days; 15 participants began after 42 days. Process delays and failure to communicate the urgency and significance of PORT initiation contributes to delays. Patients with a strong social support system experience less delays.

Conclusions

Achieving reductions in PORT initiation requires efficient care coordination, improved communication between interdisciplinary teams, and strengthening social support systems for patients with HNC.
Transoral robotic selective neck dissection for papillary thyroid carcinoma: Dissection of Levels III and IV
Authors: Tae Kyung , Kim Keon‐Ho
Published: July 2020

We present the operative procedure of transoral robotic selective neck dissection for papillary thyroid carcinoma. A 28‐year‐old woman, diagnosed with papillary thyroid carcinoma and lymph node metastasis at right level IV, underwent total thyroidectomy, central neck dissection, and selective neck dissection involving levels III and IV via the transoral robotic approach. A 1.5‐2‐cm central incision was made near the base of the lower lip frenulum, and two lateral incisions were made close to the oral commissure. An additional right axillary port was made to place a third robotic instrument for counter‐traction. The operation was completed successfully without conversion to the conventional transcervical approach. The working space and surgical view were enough to perform selective neck dissection of levels III and IV. There were no major postoperative complications. Transoral robotic selective neck dissection of levels III and IV is feasible and safe in selected patients.
Long‐term in vivo integrity and safety of 3D‐bioprinted cartilaginous constructs
Authors: Apelgren Peter , Amoroso Matteo , Säljö Karin , Lindahl Anders , Brantsing Camilla , Stridh Orrhult Linnéa , Markstedt Kajsa , Gatenholm Paul , Kölby Lars
Published: July 2020

Long‐term stability and biological safety are crucial for translation of 3D‐bioprinting technology into clinical applications. Here, we addressed the long‐term safety and stability issues associated with 3D‐bioprinted constructs comprising a cellulose scaffold and human cells (chondrocytes and stem cells) over a period of 10 months in nude mice. Our findings showed that increasing unconfined compression strength over time significantly improved the mechanical stability of the cell‐containing constructs relative to cell‐free scaffolds. Additionally, the cell‐free constructs exhibited a mean compressive stress and stiffness (compressive modulus) of 0.04 ± 0.05 MPa and 0.14 ± 0.18 MPa, respectively, whereas these values for the cell‐containing constructs were 0.11 ± 0.08 MPa (p = .019) and 0.53 ± 0.59 MPa (p = .012), respectively. Moreover, histomorphologic analysis revealed that cartilage formed from the cell‐containing constructs harbored an abundance of proliferating chondrocytes in clusters, and after 10 months, resembled native cartilage. Furthermore, extension of the experiment over the complete lifecycle of the animal model revealed no signs of ossification, fibrosis, necrosis, or implant‐related tumor development in the 3D‐bioprinted constructs. These findings confirm the in vivo biological safety and mechanical stability of 3D‐bioprinted cartilaginous tissues and support their potential translation into clinical applications.
CCN1/Cyr61 Is Required in Osteoblasts for Responsiveness to the Anabolic Activity of PTH
Authors: Zhao Gexin , Kim Elliot W , Jiang Jie , Bhoot Chimay , Charles Kemberly R , Baek Jongseung , Mohan Subburaman , Adams John S , Tetradis Sotirios , Lyons Karen M
Published: July 2020

CCN1/Cyr61 is a dynamically expressed matricellular protein that serves regulatory functions in multiple tissues. Previous studies from our laboratory demonstrated that CCN1 regulates bone maintenance. Using an osteoblast and osteocyte conditional knockout mouse model (Ccn1OCN), we found a significant decrease in trabecular and cortical bone mass in vivo, in part through suppression of Wnt signaling since the expression of the Wnt antagonist sclerostin (SOST) is increased in osteoblasts lacking CCN1. It has been established that parathyroid hormone (PTH) signaling also suppresses SOST expression in bone. We therefore investigated the interaction between CCN1 and PTH-mediated responses in this study. We find that loss of Ccn1 in osteoblasts leads to impaired responsiveness to anabolic intermittent PTH treatment in Ccn1OCN mice in vivo and in osteoblasts from these mice in vitro. Analysis of Ccn1OCN mice demonstrated a significant decrease in parathyroid hormone receptor-1 (PTH1R) expression in osteoblasts in vivo and in vitro. We investigated the regulatory role of a non-canonical integrin-binding domain of CCN1 because several studies indicate that specific integrins are critical to mechanotransduction, a PTH-dependent response, in bone. These data suggest that CCN1 regulates the expression of PTH1R through interaction with the αvβ3 and/or αvβ5 integrin complexes. Osteoblasts that express a mutant form of CCN1 that cannot interact with αvβ3/β5 integrin demonstrate a significant decrease in mRNA and protein expression of both PTH1R and αv integrin. Overall, these data suggest that the αvβ3/β5-binding domain of CCN1 is required to endow PTH signaling with anabolic activity in bone cells. © 2020 American Society for Bone and Mineral Research (ASBMR).
Association between mitochondrial DNA content and opium exposure
Authors: Ebrahimi Elmira , Akhavan Mohammad H. , Akrami Rahim , Mahmoodi Majid , Hesami Sara , Hashemi Mehrdad , Razavi Seyed M. , Hadji Maryam , Zendehdel Kazem
Published: July 2020

To date, not much study has been done to investigate the mitochondrial DNA (mtDNA) copy number as the potential biomarker for opium exposure. Here, we conducted a cross‐sectional study to determine the relative mtDNA content as the potential biomarker for opium exposure. Quantitative real‐time PCR was performed to investigate the mtDNA copy number variation across 205 individuals, including blood samples of 45 opium users, 41 cigarette users, 47 dual users, and 72 never users of any product. We found a significantly higher mtDNA content among the opium‐only users (adjusted OR: 3.21; 95% CI: [1.34, 7.66]; P = .009) and dual users (adjusted OR: 2.64; 95% CI: [1.15, 6.1]; P = .02) compared to that in never users even after adjustment for confounding factors, age, and sex. Discordantly, analysis of mitochondrial DNA in cigarette smokers revealed an indirect association between cigarette smoking and mtDNA content although it was not statistically significant. The reason behind the increased mitochondrial DNA is unclear. The possible hypothesis is that there might be a way to compensate for the oxidative damage induced by opium consumption. Taken together, our findings indicated that the mtDNA copy number may alter during opium exposure. Since changes in the mitochondrial DNA copy number was associated with the etiology of many diseases including cancer, further investigations on the mtDNA copy number may shed light on the carcinogenicity of opium consumption and means for early detection among the populations who have been exposed to opium and its products.
Angiogenic factor with G patch and FHA domains 1 protects retinal vascular endothelial cells under hyperoxia by inhibiting autophagy
Authors: Yao Guomin , Li Rong , Du Junhui , Yao Yang
Published: July 2020

Angiogenic factor with G patch and FHA domains 1 (AGGF1) has strong proangiogenic effects on embryonic vascular development and angiogenesis in disease; however, its role in retinopathy has not been elucidated. Retinopathy of prematurity is a serious retinal disorder of premature infants, which is caused by the arrest of immature retinal vascular growth under hyperoxia. This study aims to investigate the effects of AGGF1 on retinal vascular endothelial cells under hyperoxia and the association with autophagy by using rhesus macaque choroid‐retinal endothelial (RF/6A) cells. Western blot analysis and immunofluorescence staining were used to detect the expression of AGGF1 in RF/6A cells. Cell Counting Kit‐8, flow cytometry, and transwell and matrigel assays were applied to detect the vitality, apoptosis, migration, and tube formation of RF/6A cells, respectively. Western blot analysis was then used to detect the expression of autophagy markers LC3 and Beclin‐1, and mCherry‐GFP‐LC3 adenovirus was used to detect autophagy flux in RF/6A cells. Under hyperoxia, the expression of AGGF1 in RF/6A cells decreased compared with the control. Cell vitality, migration, and tube formation decreased, and apoptosis of RF/6A cells increased under hyperoxia, and these effects of hyperoxia were attenuated by AGGF1. The protein expressions of LC3 and Beclin‐1 increased in RF/6A cells and autophagy flux enhanced under hyperoxia. AGGF1 reduced the expression of LC3 and Beclin‐1 as well as the autophagy flux stimulated by hyperoxia. The results clearly showed that exogenous AGGF1 can protect retinal vascular endothelial cells and promote angiogenesis under hyperoxia, in which the expression of AGGF1 was inhibited. Inhibition of autophagy by AGGF1 may be one of the mechanisms involved.
The role of acceptance in mood improvement during Mindfulness‐Based Stress Reduction
Authors: Arlt Mutch Virginia K. , Evans Susan , Wyka Katarzyna
Published: July 2020

Objective

This study elucidates the association between acceptance, mindfulness, and psychological well‐being in a community‐based sample participating in a Mindfulness‐Based Stress Reduction (MBSR) program.

Method

Participants (n = 52) completed an 8‐week MBSR program at an academic medical center. Participants completed the Profile of Mood States (POMS), Mindfulness Attention Awareness Scale (MAAS), and Acceptance and Action Questionnaire (AAQ‐II) at pre‐ and post‐MSBR programs.

Results

Serial mediation analysis suggested that changes in mindfulness preceded changes in acceptance, which improved well‐being (indirect effect = −6.57, 95% confidence interval [CI; −13.38, −1.57]). Participants with low pre‐MSBR acceptance significantly increased acceptance and well‐being (p < .001). Moderated mediation models suggested that the pre‐MBSR acceptance level moderated the mindfulness‐acceptance and the acceptance‐well‐being link.

Conclusions

Acceptance may be related to mindfulness and pre‐MSBR acceptance may differentially affect outcomes. Limitations include a nonclinical sample and a lack of a control group. Future research may examine mindfulness “dose” and other mechanisms that facilitate improvements in outcomes.
Peer delivery of a brief cognitive‐behavioral treatment for posttraumatic stress disorder: A hybrid effectiveness‐implementation pilot study
Authors: Smith Ashley M. , Stewart Kaylee , Baul Tithi , Valentine Sarah E.
Published: July 2020

Objective

Posttraumatic stress disorder (PTSD) treatment delivery by peer specialist providers could increase access to and engagement with PTSD treatment in low resource settings. The current pilot study tested the feasibility, acceptability, and initial effectiveness of a peer‐delivered, brief cognitive‐behavioral therapy for PTSD.

Method

Four certified peer specialists delivered the intervention to 18 participants with probable PTSD. We assessed PTSD symptoms weekly and administered surveys and interviews at baseline and posttreatment.

Results

Our mixed‐methods approach suggests that the intervention was feasible and acceptable, demonstrating high client satisfaction. We also found significant improvements in PTSD, depressive, anxiety, and general stress symptoms.

Conclusions

Peer‐delivered interventions may be a good fit for addressing posttraumatic stress symptoms for people accessing care in low resource settings. Future research should evaluate peer‐delivered PTSD treatment as a strategy for both reducing symptoms and improving access and engagement in professional care.
A Slug‐dependent mechanism is responsible for tumor suppression of p53‐stabilizing compound CP‐31398 in p53‐mutated endometrial carcinoma
Authors: Liu Ling , Yu Zhi‐Ying , Yu Tan‐Tan , Cui Shi‐Hong , Yang Li , Chang Hui , Qu Yan‐Hong , Lv Xiao‐Feng , Zhang Xiao‐An , Ren Chen‐Chen
Published: July 2020

Mutation in the tumor suppressor gene p53 is the most frequent molecular defect in endometrial carcinoma (EC). Recently, CP‐31398, a p53‐stabilizing compound, has been indicated to possess the ability to alter the expression of non‐p53 target genes in addition to p53 downstream genes in tumor cells. Herein, we explore the alternative mechanisms underlying the restoration of EC tumor suppressor function in mutant p53 by CP‐31398. A p53‐mutated EC cell was constructed in AN3CA cells with restored or partial loss of Slug using lentiviral vectors, followed by treatment with 25 μM CP‐31398. A p53‐independent mechanism of CP‐31398 was confirmed by the interaction between mouse double minute 2 homolog (MDM2) and Slug AN3CA cells treated with IWR‐1 (inhibitor of Wnt response 1). Furthermore, the AN3CA cells were treated with short hairpin RNA against Slug, Wnt‐specific activators (LiCl) or inhibitors (XAV‐939) followed by CP‐31398 treatment. Moreover, AN3CA cell proliferation and apoptosis were examined. A tumorigenicity assay was conducted in nude mice. CP‐31398 could promote the apoptosis of p53‐mutated EC cells, while Slug reversed this effect. Slug ubiquitination was found to occur via binding of Slug to MDM2 in AN3CA cells. We found that CP‐31398 increased the GSK‐3ß, p‐Slug, Puma, Wtp53, and Bax expressions whereas Wnt, Mtp‐53, Slug, Bcl‐2, and Ki‐67 expressions were decreased. However, these findings were reversed following the activation of the Wnt pathway and overexpression of Slug. Finally, the in vivo experimental evidence confirmed that CP‐31398 with depleted Slug suppressed tumor growth by downregulating the Slug. Collectively, CP‐31398‐regulated Slug downregulation represses the p53‐mutated EC via the p53/Wnt/Puma pathway.
Long intergenic noncoding RNA 00908 promotes proliferation and inhibits apoptosis of colorectal cancer cells by regulating KLF5 expression
Authors: Shan Ti‐Dong , Tian Zi‐Bin , Li Qian , Jiang Yue‐ Ping , Liu Fu‐Guo , Sun Xue‐Guo , Han Yue , Sun Li‐Juan , Chen Li
Published: July 2020

Long intergenic noncoding RNAs (lincRNAs) play a vital role in the occurrence and progression of cancer. The mechanism of lincRNAs in colorectal cancer (CRC) has not been fully elucidated. In this context, an integrated comparative long noncoding RNA (lncRNA) microarray technology was used to determine the expression profile of lncRNAs in CRC. The roles of LINC00908 are unclear. We found that LINC00908 was significantly upregulated in CRC. Inhibition of LINC00908 resulted in reduced cell proliferation and G1 cell cycle arrest, which was mediated by cyclin D1, cyclin‐dependent kinase 4, and phosphorylated retinoblastoma. Moreover, inhibition of LINC00908‐induced apoptosis through the intrinsic apoptosis signaling pathway, as shown by the activation of caspase‐9 and caspase‐3. Mechanistically, miR‐143‐3p directly bound to LINC00908. miR‐143‐3p expression was negatively correlated with LINC00908 expression in CRC tissue. Functional experiments revealed opposing roles for miR‐143‐3p and LINC00908, suggesting that LINC00908 negatively regulates miR‐143‐3p. Mechanistically, miR‐143‐3p directly targets LINC00908. The KLF5 inhibitor ML264 affected proliferation and apoptosis, indicating that LINC00908 may act as a competing endogenous RNA to facilitate the expression of the miR‐143‐3p target gene KLF5. Thus, LINC00908 has an important proliferative and antiapoptotic role in CRC by regulating the cell cycle and intrinsic apoptosis. LINC00908 could be a potential biomarker and a new therapeutic target for CRC.
Carnitine palmitoyltransferase 1C reverses cellular senescence of MRC‐5 fibroblasts via regulating lipid accumulation and mitochondrial function
Authors: Chen Panpan , Zhang Qianbin , Zhang Huizhen , Gao Yue , Zhou Yanying , Chen Yixin , Guan Lihuan , Jiao Tingying , Zhao Yingyuan , Huang Min , Bi Huichang
Published: July 2020

Cellular senescence, a state of growth arrest, is involved in various age‐related diseases. We previously found that carnitine palmitoyltransferase 1C (CPT1C) is a key regulator of cancer cell proliferation and senescence, but it is unclear whether CPT1C plays a similar role in normal cells. Therefore, this study aimed to investigate the role of CPT1C in cellular proliferation and senescence of human embryonic lung MRC‐5 fibroblasts and the involved mechanisms. The results showed that CPT1C could reverse the cellular senescence of MRC‐5 fibroblasts, as evidenced by reduced senescence‐associated β‐galactosidase activity, downregulated messenger RNA (mRNA) expression of senescence‐associated secretory phenotype factors, and enhanced bromodeoxyuridine incorporation. Lipidomics analysis further revealed that CPT1C gain‐of‐function reduced lipid accumulation and reversed abnormal metabolic reprogramming of lipids in late MRC‐5 cells. Oil Red O staining and Nile red fluorescence also indicated significant reduction of lipid accumulation after CPT1C gain‐of‐function. Consequently, CPT1C gain‐of‐function significantly reversed mitochondrial dysfunction, as evaluated by increased adenosine triphosphate synthesis and mitochondrial transmembrane potential, decreased radical oxygen species, upregulated respiratory capacity and mRNA expression of genes related to mitochondrial function. In summary, CPT1C plays a vital role in MRC‐5 cellular proliferation and can reverse MRC‐5 cellular senescence through the regulation of lipid metabolism and mitochondrial function, which supports the role of CPT1C as a novel target for intervention into cellular proliferation and senescence and suggests CPT1C as a new strategy for antiaging.
The interaction between microbes and electrodes decorated with bio‐reduced graphene oxide— from an electrochemical point of view
Authors: Zhu Weihuang , Gao Haoxiang , li Peng , Li Yaqi , Zhang Jianfeng , Bai Huiling
Published: July 2020

BACKGROUND

The extracellular electron transfer (EET) between microbes and electrodes modified by graphene‐based functional material has attracted increasing attention. EET is an important process through which the anode can act as the acceptor for the electrons produced via microbial respiration, and it also plays a key role in organic matter degradation and nutrient cycling in the environment.

RESULTS

Our results showed that the interaction between microbes and carbon felt (CF) electrodes decorated with bio‐reduced graphene oxide (GO‐br) was significantly enhanced compared to that between the unmodified CF electrode and microbes. The promoted biological current production and cyclic voltammetric (CV) current response indicated the considerable electro‐activity of the GO‐br‐CF electrode. diffusion resistance (Rdif) of the GO‐br‐CF electrode decreased significantly by 97.3% from 2.76 × 105 ± 7644 Ω at the initial incubation stage to 7341 ± 1322 Ω after 58 h of incubation time for GO‐br decoration. We also noticed that the GO‐br‐CF electrode intermittently poised at +0.1 V (vs Ag/AgCl/KCl sat.) was favorable for EET. The GO‐br‐CF electrode, which enhanced MFC performance significantly, was further used as the anode in a microbial fuel cell (MFC).

CONCLUSION

Overall, the results of this study indicated the decoration of CF electrode with GO‐br could regulate the electrochemical activity of the electrode and the EET process between the microbes and electrode. The elevated electrochemical activity and EET were attributed to the rapid decrease in the diffusion resistance (Rdif) of the GO‐br‐CF electrode.
Can phosphorus adsorption clog an alum sludge‐based biofiltration system? Evidence and insight
Authors: Yang Yan , Wang Jiefu , Zhao Yaqian , Tang Cheng , Liu Ranbin , Shen Cheng
Published: July 2020

BACKGROUND

Aluminium‐based drinking water treatment residual (Al‐DWTR) has been used as an emergent substrate in laboratory‐scale and pilot‐scale biofiltration systems (biofilters and constructed wetlands) for its good affinity for phosphorus (P) adsorption. However, there is a concern about whether the P adsorption process will contribute to substrate clogging. Two laboratory‐scale up‐flow biofiltration systems were set up to identify the contribution of the P adsorption process to clogging under various operation conditions.

RESULTS

Contributions of individual processes to clogging from biosolids production (SBS), inert matter generated from the conversion of residual biomass (SIS), P adsorption (SP) and inert matter production from influent total suspended solids (SSS) during operation of the two systems were assessed. After 262 days of operation, results indicated that SBS contributed most (53.16 ± 7.73%) to the clogging, followed by SSS (41.48 ± 8.02%), SP (3.14 ± 0.06%) and SIS (2.20 ± 0.27%) when treating the influent with concentrations of 284–558 mg L−1 for COD, 54–197 mg L−1 for SS and 5–13 mg L−1 for P.

CONCLUSIONS

The minor contribution of the P adsorption process to substrate clogging further suggests that dewatered Al‐DWTR with a high P removal capacity is a promising substrate for use in biofiltration systems. © 2020 Society of Chemical Industry (SCI)
High‐cell‐density fermentation of Escherichia coli for expression of a recombinant phenylalanine dehydrogenase mutant and its purification
Authors: Zhao Chen , Wang Lu , Li Duanhua , Li Jinjun , Ge Yan , Liang Tao , Zhu Yu , Yu Rong
Published: July 2020

BACKGROUND

Phenylalanine dehydrogenase (PheDH; l‐phenylalanine: NAD+ oxidoreductase, deaminating (EC 1.4.1.20)) is widely used in the pharmaceutical industry. It is the main biocatalyst in the enantioselective synthesis of l‐phenylalanine, related l‐amino acids as well as some non‐natural amino acids which are important pharmaceutical intermediates. However, growing demands for PheDH and its limited production result in the shortage of the enzyme's supply so that it is necessary to explore and establish an industrial production process for PheDH.

RESULTS

In this study, the high‐cell‐density fermentation of recombinant Escherichia coli for expression of an engineered mutant R272M/E331Q/E196N of PheDH was investigated, which is a key catalyst with improved catalytic capability during the important intermediate production of saxagliptin. Cultivation media and induction conditions of recombinant E. coli were tested in shake flask experiments. A fed‐batch fermentation strategy using MR2 as cultivation medium and lactose as inducer was developed in a 30 L fermenter. After 24 h of cultivation, the dry cell weight reached 52.32 g L–1 (based on OD600), and the specific activity of crude extracts was 0.49 U mg–1. By applying the aqueous two‐phase system strategy, a purified PheDH productivity of 191.96 mg·L−1·h−1 was obtained. The specific activity, recovery, yield and purification fold of PheDH were 3.21 U mg–1, 104.19%, 84.53% and 6.55, respectively.

CONCLUSIONS

This study shows that the application of high‐cell‐density fermentation in conjunction with aqueous two‐phase system strategy provides vital support for large‐scale production of recombinant PheDH. © 2020 Society of Chemical Industry (SCI)
Crown preparations by undergraduate dental students: A comparison of conventional versus digital assessment via an intraoral scanner
Authors: Seet Ren Hao , Soo Peng Ru , Leong Karen Jia Mian , Pang Joyce Jia Hui , Lee Frank Kong Fei , Tan Ming Yi
Published: July 2020

Purpose

This study aims to assess the effectiveness of the 3Shape TRIOS intraoral scanner (IOS) in student crown preparation evaluation.

Design

Students were tasked to perform a full metal crown preparation on the upper left first molar on a patient simulator within 45 minutes. Marginal Width, Occlusal Reduction, Presence of Undercuts, Taper, Planes of Reduction, Line Angles, Conformity to Gingival Contour, and Smoothness were evaluated via 3 assessment modes: (a) Conventional assessment by 2 supervisors; (b) Conventional assessment by students; (c) Digital assessment by students. Agreement between assessment modes was investigated using Kappa (κ), with a threshold set at κ > 0.4. Effectiveness of IOS for objective parameters was determined via physical verification, while that for subjective parameters was defined by agreement with the stricter supervisor grade.

Results

Substantial agreement (κ = 0.631) was found between IOS measurement of Marginal Width and physical verification. Two of 5 subjective parameters met κ > 0.4 for agreement between IOS and the stricter supervisor grade. Agreement between supervisors ranged from slight (κ = 0.103) for Occlusal Reduction to Fair (κ = 0.399) for Marginal Width. Agreement between conventional assessments of supervisors and students ranged from less than chance (κ = −0.142) for Occlusal Reduction to moderate (κ = 0.577) for Line Angles. Agreement between conventional assessments of supervisors and digital assessments of students ranged from slight (κ = 0.130) for Planes of Reduction to moderate (κ = 0.538) for Line Angles.

Conclusions

IOS may be used to overcome limitations in conventional assessment of objective parameters and some subjective parameters. Digital assessment of crown preparations cannot completely replace conventional assessment.
Experiences and attitudes of dental hygiene faculty regarding the mentorship of undergraduate student research
Authors: Partido Brian B. , Chartier Elizabeth A. , Heminger Brittini
Published: July 2020

Purpose

Research remains a strong emphasis in entry‐level dental hygiene programs as mandated by the Commission on Dental Accreditation. However, more exploration is needed to understand the faculty mentor and student research mentee relationship specific to undergraduate dental hygiene students. The purpose of the study was to identify factors and attitudes of undergraduate faculty influencing their level of interest in mentoring undergraduate student research.

Methods

Using a cross‐sectional survey research design, a non‐probability sample of dental hygiene faculty from U.S. dental hygiene programs were asked questions about their experiences and attitudes about mentoring undergraduate student research.

Results

From the 248 survey invitations sent to dental hygiene program directors, 68 of the 75 responses received were analyzed. Fifty‐six percent (n = 38) of respondents mentored undergraduate research and 77% (n = 52) of respondents expressed interest in mentoring undergraduate research. Full‐time faculty (>75% FTE), mid‐career faculty (7–20 years) and late‐career faculty (>20 years) were more likely to have mentored undergraduate research. Mentors of undergraduate research were more likely to enjoy teaching students about research more than faculty without mentorship experience. Faculty members with interest in research mentorship were more likely to enjoy teaching students about research and help students become better prepared for graduate studies than faculty not interested in research mentorship. Experience with mentoring student research, early‐career status (<7 years), and mid‐career status (7–20 years) were significant predictors of interest in mentoring student research.

Conclusion

Efforts should be directed to identifying and providing support for faculty mentors of undergraduate student research.
An update on the origin of SARS‐CoV‐2: Despite closest identity, bat (RaTG13) and pangolin derived coronaviruses varied in the critical binding site and O‐linked glycan residues
Authors: Malaiyan Jeevan , Arumugam Suresh , Mohan Kamalraj , Gomathi Radhakrishnan Gokul
Published: July 2020

The initial cases of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) occurred in Wuhan, China, in December 2019 and swept the world by 23 June 2020 with 8 993 659 active cases, 469 587 deaths across 216 countries, areas or territories. This strongly implies global transmission occurred before the lockdown of China. However, the initial source's transmission routes of SARS‐CoV‐2 remain obscure and controversial. Research data suggest bat (RaTG13) and pangolin carried CoV were the proximal source of SARS‐CoV‐2. In this study, we used systematic phylogenetic analysis of Coronavirinae subfamily along with wild type human SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 strains. The key residues of the receptor‐binding domain (RBD) and O‐linked glycan were compared. SARS‐CoV‐2 strains were clustered with RaTG13 (97.41% identity), Pangolin‐CoV (92.22% identity) and Bat‐SL‐CoV (80.36% identity), forms a new clade‐2 in lineage B of beta‐CoV. The alignments of RBD contact residues to ACE2 justified? Those SARS‐CoV‐2 strains sequences were 100% identical by each other, significantly varied in RaTG13 and pangolin‐CoV. SARS‐CoV‐2 has a polybasic cleavage site with an inserted sequence of PRRA compared to RaTG13 and only PRR to pangolin. Only serine (Ser) in pangolin and both threonine (Thr) and serine (Ser) O‐linked glycans were seen in RaTG13, suggesting that a detailed study needed in pangolin (Manis javanica) and bat (Rhinolophus affinis) related CoV.