bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat and mass transfer analysis of MWCNT‐kerosene nanofluid flow over a wedge with thermal radiation
Authors: Sreedevi Paluru , Sudarsana Reddy Patakota
Published: August 2020

A comparison between the unsteady and steady magnetohydrodynamics Tiwari‐Das model Williamson nanofluid flow through a wedge occupied by carbon nanotubes of multiwalled type nanoparticles and kerosene as base fluid is presented in this analysis. A suitable similarity variable technique is adopted to transmute the governing partial differential equations into a set of nonlinear ordinary differential equations (ODEs). To solve these ODEs together along with boundary conditions, we have utilized finite element analysis. The behavior of concentration, temperature, and velocity sketches for diverse values of the pertinent parameters is plotted through graphs. The impact on the above parameters on the rates of velocity, heat, and concentration is also evaluated and depicted through tables. It is noted that as the values of nanoparticle volume fraction parameter rises, the rates of temperature increase in both the unsteady and steady cases.
Heat transport and stagnation‐point flow of magnetized nanoliquid with variable thermal conductivity, Brownian moment, and thermophoresis aspects
Authors: Swain Kharabela , Mahanthesh Basavarajappa , Mebarek‐Oudina Fateh
Published: August 2020

The improvement of heat transport is a very important phenomenon in nuclear reactors, solar collectors, heat exchangers, and coolers, which can be achieved by choosing the nanofluid as the functional fluid. Nanofluids improve thermophysical properties; as a result, they have made great progress in engineering, biomedical, and industrial applications. Therefore, a numerical study has been proposed to analyze the flow and heat transport of nanoliquids over an extendable surface near a stagnation point with variable thermal conductivity under the influence of the magnetic field, due to their importance in the engineering field. Nanoliquid attributes explain the Brownian motion and the diffusion of thermophoresis. The effects of the chemical reaction and the uniform internal heat source/heat sink are also considered. The Nachtsheim‐Swigert shooting procedure based on the Runge‐Kutta scheme is used for numerical calculation. The impact of effective parameters on velocity, temperature, and volume fraction of the nanoparticles is shown in the graphs and reported in detail. The surface criteria are also estimated with respect to the shear stress and the rate of heat and mass transfer. The aspects of the Brownian moment and Lorentz force are positively correlated to the thermal field of the nanoliquid. Also, the variable thermal conductivity aspect favors the growth of the thermal boundary layer.
Does foreign capital go where the returns are? Financial integration and capital allocation efficiency1
Authors: Mann Katja
Published: August 2020

This paper asks whether financial integration leads to a more efficient allocation of capital within economies. I build a model of a small economy with an investment and a consumption goods sector. Financial frictions impede capital from allocating optimally between the two sectors. Capital account opening has positive allocation effects if the economy is financially less developed than the rest of the world, but negative effects otherwise. I test the model predictions on a sample of 113 countries, using the relative price of consumption and investment goods as a measure of allocation efficiency. I find that international capital flows indeed have adverse effects in highly developed countries, whereas there is less evidence of positive effects in low‐development countries. Overall, financial integration leads to more similar capital allocations across countries.
Biomaterial strategies for improved intra‐articular drug delivery
Authors: Mancipe Castro Lina M. , García Andrés J. , Guldberg Robert E.
Published: August 2020

Osteoarthritis (OA) is a joint degenerative disease that has become one of the leading causes of disability in the world. It is estimated that OA affects 50 million adults in the United States. Currently, there are no FDA‐approved treatments that slow OA progression and its treatment is limited to pain management strategies and life style changes. Despite the discovery of several disease‐modifying OA drugs (DMOADs) and promising results in preclinical studies, their clinical translation has been significantly limited because of poor intra‐articular (IA) bioavailability and challenges in delivering these compounds to tissues of interest within the joint. Here, we review current OA treatments and their effectiveness at reducing joint pain, as well as novel targets for OA treatment and the challenges related to their clinical translation. Moreover, we discuss intra‐articular (IA) drug delivery as a promising route of administration, describe its inherent challenges, and review recent advances in biomaterial‐based IA drug delivery for OA treatment. Finally, we highlight the potential of tissue targeting in the development of effective IA drug delivery systems.
Molecular diagnostic in fetuses with isolated congenital anomalies of the kidney and urinary tract by whole‐exome sequencing
Authors: Zhou Xiaoyan , Wang Yan , Shao Binbin , Wang Chen , Hu Ping , Qiao Fengchang , Xu Zhengfeng
Published: August 2020

Background

In prenatal care, accumulating evidences has demonstrated that whole‐exome sequencing (WES) expedites the genetic diagnosis of fetal structural anomalies. However, the clinical value of WES in the diagnosis of prenatal isolated congenital anomalies of the kidney and urinary tract (CAKUT) is unknown.

Methods

Forty‐one fetuses with unexplained isolated CAKUT, normal karyotype and negative chromosomal microarray analysis (CMA) results, underwent WES and were accordingly grouped as (a) Group 1: complex cases with bilateral renal abnormalities (N = 19); and (b) Group 2: cases with isolated unilateral fetal renal abnormalities (N = 22).

Results

The detection rate of WES for pathogenic variants and incidental variants was 7.32% (3/41) and 2.4% (1/41), respectively. The three pathogenic variants were identified in the genes ACTA2 (multisystem smooth muscle dysfunction syndrome), PKHD1 (autosomal recessive form of polycystic kidney disease), and PKD1 (autosomal dominant polycystic kidney disease type 1). The incidental variants were detected in genes PPM1D (syndromic neurodevelopmental disorders). Furthermore, all above fetuses carrying pathogenic variants came from bilateral kidney anomalies. Thus, the detection rate was 0 for fetuses with unilateral fetal renal abnormalities and 15.7% (3/19) for bilateral renal abnormalities.

Conclusion

This cohort shows that prenatal WES is a supplementary approach for the etiologic diagnosis of unexplained isolated CAKUT with negative CMA, especially for fetuses with bilateral renal abnormality.
Long noncoding RNA NEAT 1 and its target microRNA‐125a in sepsis: Correlation with acute respiratory distress syndrome risk, biochemical indexes, disease severity, and 28‐day mortality
Authors: Yang Yongkai , Yang Liu , Liu Zhenqing , Wang Yujun , Yang Junhui
Published: August 2020

Background

Sepsis is one of the main contributors to in‐hospital deaths. This study aimed to evaluate the clinical roles of long noncoding RNA (lncRNA) nuclear‐enriched abundant transcript 1 (NEAT1) and microRNA (miR)‐125a in sepsis.

Methods

LncRNA NEAT1 and miR‐125a in plasma samples from 102 sepsis patients and 100 healthy controls (HCs) were detected by reverse transcription‐quantitative polymerase chain reaction. In sepsis patients, general disease severity was assessed by acute physiology and chronic health evaluation (APACHE) II score and sequential organ failure assessment (SOFA) score. Meanwhile, acute respiratory distress syndrome (ARDS) occurrence and mortality during 28 days were recorded.

Results

LncRNA NEAT1 was increased, but miR‐125a was decreased in sepsis patients compared to HCs, and in ARDS sepsis patients compared to non‐ARDS sepsis patients. The receiver's operative characteristic (ROC) curves revealed that higher lncRNA NEAT1 or lower miR‐125a had certain predictive value for ARDS risk. Further multivariate logistic regression revealed miR‐125a but not lncRNA NEAT1 was correlated with ARDS risk independently in sepsis patients. Additionally, lncRNA NEAT1 was positively, but miR‐125a was negatively correlated with APACHE II score and SOFA score in sepsis patients. Moreover, higher lncRNA NEAT1 and lower miR‐125a were observed in 28‐day deaths compared to 28‐day survivors and were correlated with increased accumulating mortality in sepsis patients.

Conclusion

LncRNA NEAT1 high expression and miR‐125a low expression correlate with increased ARDS risk, enhanced disease severity, higher 28‐day mortality, and negatively associate with each other in sepsis patients.
Childhood trauma, parental bonding, and social cognition in patients with schizophrenia and healthy adults
Authors: Rokita Karolina I. , Dauvermann Maria R. , Mothersill David , Holleran Laurena , Holland Jessica , Costello Laura , Cullen Caroline , Kane Ruán , McKernan Declan , Morris Derek W. , Kelly John , Gill Michael , Corvin Aiden , Hallahan Brian , McDonald Colm , Donohoe Gary
Published: August 2020

Objective

This study investigated associations between childhood trauma, parental bonding, and social cognition (i.e., Theory of Mind and emotion recognition) in patients with schizophrenia and healthy adults.

Methods

Using cross‐sectional data, we examined the recollections of childhood trauma experiences and social cognitive abilities in 74 patients with schizophrenia and 116 healthy adults.

Results

Patients had significantly higher scores compared with healthy participants on childhood trauma, and lower scores on parental bonding and social cognitive measures. Physical neglect was found to be the strongest predictor of emotion recognition impairments in both groups. Optimal parental bonding attenuated the impact of childhood trauma on emotion recognition.

Conclusion

The present study provides evidence of an association between physical neglect and emotion recognition in patients with schizophrenia and healthy individuals and shows that both childhood trauma and parental bonding may influence social cognitive development. Psychosocial interventions should be developed to prevent and mitigate the long‐term effects of childhood adversities.
Beyond perfect? A case illustration of working with perfectionism using cognitive behavior therapy
Authors: Rozental Alexander
Published: August 2020

Perfectionism can result in negative consequences for those who set unattainable goals and repeatedly strive to achieve high standards. Relying on inflexible behaviors and building one's self‐worth around success can become problematic and affect performance, interpersonal relationships, and cause mental distress. In the current case illustration, perfectionism's negative implications are depicted through a client named Sara, a stressed‐out junior physician who just graduated from medical school. Struggling with issues related to self‐worth, depression, worry, independence, and interpersonal difficulties, Sara underwent cognitive behavior therapy during 15 sessions. The case illustration shows how an individualized conceptualization of perfectionism can be made and what is important to target in treatment, such as preventing the need for repeated checking, conducting surveys to refute dysfunctional beliefs, and introducing activities that are unrelated to accomplishments. Current research on the efficacy of treating perfectionism is also summarized and interventions particularly relevant for clinical practice are presented.
Joint action as a practice of memory transmission in a poor urban neighborhood of Santiago, Chile
Authors: Jeanneret Brith Francisco J. , Reyes Andreani María J. , Cruz Contreras María A. , Castillo Vega César M. , Jeanneret Brith Juan E. , Pavez Pérez Juan F. , Badilla Rajevic Manuela
Published: August 2020

In Latin America, one of the key tasks of Community and Liberation Psychology has been to recover the memories of marginalized and excluded communities that have experienced multiple pasts marked by political violence. In Chile, researchers have focused on poor urban neighborhoods, where the question of how memories are transmitted in areas where conflicts and violence are still present has been overlooked. In this context, the following article aims to analyze the ways in which memories are transmitted in a neighborhood that has a long organizational history in the struggle against social inequalities; while at the same time being classified as a critical area by the state due to its current levels of violence and social conflict. The researchers led a 3‐year case study from an ethnographic perspective, and applied a collaborative methodology that brought together the research team and the members of a territorial organization. The analysis is based on 72 interviews, 5 conversation groups and ethnographic observation. The data was analyzed using discourse analysis. The results revealed that the main form of memory transmission is not based on intergenerational narratives of the past, but rather on joint action; namely, dialogical practices among neighborhood residents that generate an ethos; a common way of life.
Finding home: Community integration experiences of formerly homeless women with problematic substance use in Housing First
Authors: Bassi Amandeep , Sylvestre John , Kerman Nick
Published: August 2020

Aims

This study explored community integration among women participating in a Housing First program. Physical, social, and psychological dimensions of community integration were examined.

Methods

This study used neighborhood walk‐along and photo‐elicitation interviews to explore 16 formerly homeless women's experiences of community integration.

Results

Participants described limited community integration. Health, poverty, service inaccessibility, and safety concerns shaped how they took part in activities in their neighborhoods. Participants primarily socialized with people in their buildings, though some preferred to keep to themselves. There was minimal sense of neighborhood belonging, with participants not interested in belonging to a community and being judged by others.

Conclusion

Housing First promoted housing stability but did not contribute to community integration. Participants did not express a strong desire to integrate in their communities. Future research should consider the extent to which community integration remains a priority for marginalized populations, such as formerly homeless women.
The tumour microenvironment and metabolism in renal cell carcinoma targeted or immune therapy
Authors: Lai Yongchang , Tang Fucai , Huang Yapeng , He Chengwu , Chen Chiheng , Zhao Jiquan , Wu Wenqi , He Zhaohui
Published: August 2020

Renal cell carcinoma (RCC) is one of the most common tumours of the urinary system, and is insidious and not susceptible to chemoradiotherapy. As the most common subtype of RCC (70–80% of cases), clear cell renal cell carcinoma (ccRCC) is characterized by the loss of von Hippel–Lindau and the accumulation of robust lipid and glycogen. For advanced RCC, molecular‐targeted drugs, tyrosine kinase inhibitors (TKIs) and the immune checkpoint inhibitors (ICIs) have been increasingly recommended and investigated. Due to the existence of a highly dynamic, adaptive and heterogeneous tumour microenvironment (TME), and due to the glucose and lipid metabolism in RCC, this cancer may be accompanied by various types of resistance to TKIs and ICIs. With the increased production of lactate, nitric oxide, and other new by‐products of metabolism, novel findings of the TME and key metabolic enzymes drived by HIF and other factors have been increasingly clarified in RCC carcinogenesis and therapy. However, there are few summaries of the TME and tumour metabolism for RCC progression and therapy. Here, we summarize and discuss the relationship of the important implicated characteristics of the TME as well as metabolic molecules and RCC carcinogenesis to provide prospects for future treatment strategies to overcome TME‐related resistance in RCC.
SPARC is a key mediator of TGF‐β‐induced renal cancer metastasis
Authors: Bao Ji‐Ming , Dang Qiang , Lin Chun‐Jung , Lo U‐Ging , Feldkoren Boris , Dang Andrew , Hernandez Elizabeth , Li Fei , Panwar Vandana , Lee Cheng‐Fan , Cen Jun‐Jie , Guan Bing , Margulis Vitaly , Kapur Payal , Brekken Rolf A. , Luo Jun‐Hang , Hsieh Jer‐Tsong , Tan Wan‐Long
Published: August 2020

Aberrant expression of transforming growth factor‐β1 (TGF‐β1) is associated with renal cell carcinoma (RCC) progression by inducing cancer metastasis. However, the downstream effector(s) in TGF‐β signaling pathway is not fully characterized. In the present study, the elevation of secreted protein acidic and rich in cysteine (SPARC) as a TGF‐β regulated gene in RCC was identified by applying differentially expressed gene analysis and microarray analysis, we further confirmed this result in several RCC cell lines. Clinically, the expression of these two genes is positively correlated in RCC patient specimens. Furthermore, elevated SPARC expression is found in all the subtypes of RCC and positively correlated with the RCC stage and grade. In contrast, SPARC expression is inversely correlated with overall and disease‐free survival of patients with RCC, suggesting SPARC as a potent prognostic marker of RCC patient survival. Knocking down SPARC significantly inhibits RCC cell invasion and metastasis both in vitro and in vivo. Similarly, in vitro cell invasion can be diminished by using a specific monoclonal antibody. Mechanistically, SPARC activates protein kinase B (AKT) pathway leading to elevated expression of matrix metalloproteinase‐2 that can facilitate RCC invasion. Altogether, our data support that SPARC is a critical role of TGF‐β signaling network underlying RCC progression and a potential therapeutic target as well as a prognostic marker.
The lncRNA ANRIL regulates endothelial dysfunction by targeting the let‐7b/TGF‐βR1 signalling pathway
Authors: Liu Xianglan , Li Shufeng , Yang Yi , Sun Yong , Yang Qingyuan , Gu Nan , Li Jing , Huang Tuo , Liu Ying , Dong Hui , Sun Song , Fu Guosheng , Wu Jian , Yu Bo
Published: August 2020

The long noncoding RNA antisense noncoding RNA in the INK4 locus (ANRIL) plays a critical role in the development of atherosclerosis. However, the precise effect of ANRIL on endothelial dysfunction remains unclear. In this study, we investigated ANRIL expression in patients with coronary artery disease and elucidated the molecular mechanism underlying its effect. ANRIL expression was detected in the blood plasma of 111 patients. We analysed the correlation between ANRIL and endothelial dysfunction markers. We also examined the effect of ANRIL on the regulation of endothelial dysfunction. ANRIL levels were increased in patients with acute coronary syndrome. The expression of ANRIL is associated with the inflammatory cytokines monocyte chemoattractant protein‐1 and interleukin‐10, which are secreted in response to endothelial dysfunction. Knockdown of ANRIL significantly promoted cell proliferation and tubule formation and inhibited inflammatory activation and apoptosis of human umbilical vein endothelial cells (HUVEC). ANRIL‐mediated inhibition of let‐7b regulates HUVEC dysfunction by targeting the TGF‐βR1/Smad signalling pathway. This study highlights a new therapeutic strategy for preventing endothelial dysfunction associated with cardiovascular disease.
The role of NOX4 in pulmonary diseases
Authors: Li Zi‐Ming , Xu Sheng‐Ya , Feng Yi‐Zhuo , Cheng Yu‐Rui , Xiong Jian‐Bing , Zhou Yong , Guan Cha‐Xiang
Published: August 2020

Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a subtype of the NOX family, which is mainly expressed in the pulmonary vasculature and pulmonary endothelial cells in the respiratory system. NOX4 has unique characteristics, and is a constitutively active enzyme that primarily produces hydrogen peroxide. The signaling pathways associated with NOX4 are complicated. Negative and positive feedback play significant roles in regulating NOX4 expression. The role of NOX4 is controversial because NOX4 plays a protective or damaging role in different respiratory diseases. This review summarizes the structure, enzymatic properties, regulation, and signaling pathways of NOX4. This review then introduces the roles of NOX4 in different diseases in the respiratory system, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis.
RPL41 sensitizes retinoblastoma cells to chemotherapeutic drugs via ATF4 degradation
Authors: Geng Wen , Ren Jiaxu , Shi Huimin , Qin Feng , Xu Xiaohe , Xiao Sheng , Jiao Yisheng , Wang Aiyuan
Published: August 2020

Retinoblastoma is the most common intraocular cancer with metastatic potential affecting infants and children. Although chemotherapy is available for retinoblastoma, side effects and drug resistance are frequent. Rpl41, encoding ribosomal protein L41 (RPL41), has been identified as a tumor suppressor gene, and its targeted degradation of activating transcription factor 4 (ATF4) produces an antitumor effect. The goal of the present study is to provide experimental evidence for the clinical application of a small peptide regimen in combination with chemotherapy for the treatment of retinoblastoma and to investigate the mechanism of their combined cytotoxicity. It was observed that treatment with the RPL41 peptide alone decreased the viability, migration, and invasion of retinoblastoma Y79 and Weri‐Rb1 cells, in addition to promoting cell apoptosis and cell cycle arrest. Furthermore, RPL41 protein levels showed a significantly decreased trend in retinoblastoma specimens, whereas ATF4 protein levels tended to be increased. Mechanistically, ATF4 degradation as a result of RPL41 peptide treatment was observed in retinoblastoma Y79 and Weri‐Rb1 cells. Most important, low‐dose administration of the RPL41 peptide significantly enhanced the antitumor effect of carboplatin, and further analysis confirmed their synergistic effect as anti‐retinoblastoma therapy, indicating that RPL41 sensitized Y79 and Weri‐Rb1 retinoblastoma cells to carboplatin. Thus, our data provide a preclinical rationale for the exploration of the RPL41 peptide as a potential adjuvant to carboplatin treatment in retinoblastoma.
Fetal myocardial performance index in pregnancies with idiopathic mildly increased amniotic fluid volume
Authors: Hashemi Attar Amirhossein , Hafezi Fatemeh
Published: August 2020

Purpose

To evaluate modified myocardial performance index (MPI), or Tei index, in fetuses of pregnancies with idiopathic mildly increased amniotic fluid index (AFI).

Methods

We studied 25 cases (24‐40 weeks) with idiopathic mildly increased AFI, and 25 gestational age‐ and fetal gender‐matched healthy controls. Fetal echocardiographic variables and Doppler‐derived indices were recorded, including left and right MPI, left isovolumetric contraction time (IVCT), left ejection time (ET), left isovolumetric relaxation time (IVRT), aortic and pulmonary arterial peak systolic velocity (PSV), left and right E/A ratios, middle cerebral artery (MCA) pulsatility index (PI), and umbilical artery (UA) PI.

Results

The mean left MPI (0.52 vs 0.41, P < .0001) and right MPI (0.50 vs 0.42, P < .001) were higher, and mean IVCT (37.7 vs 25.9, P < .0001) was longer in cases than in controls. However, there were no significant differences between the two groups in IVRT (45.2 vs 43.2, P = .381), ET (160.2 vs 170.0, P = .079), aortic PSV (P = .073), left E/A (P = .080), pulmonary artery PSV (P = .061), right E/A (P = .054), MCA PI (P = .259), UA PI (P = .685), and cerebroplacental ratio (P = .645).

Conclusion

Pregnancies with idiopathic mildly increased AFI were associated with a significant increase in the fetal MPI of both left and right ventricles.
Impact of the etiology and Vitamin D receptor TaqI rs731236 gene polymorphism on the severity of acute pancreatitis
Authors: El‐Mahdy Reham I , Ramadan Haidi Karam‐Allah , Mohammed Hanan Sharaf EL_Deen , Ahmed Entsar H , Mokhtar Abeer A , Hosni Amal
Published: August 2020

Background/Purpose

This work aimed to assess the impact of different etiologies of acute pancreatitis (AP) and vitamin D receptor (VDR) TaqI rs731236 gene polymorphism on the severity of AP.

Methods

This case‐control study included 70 patients with AP and 40 healthy controls. Etiologies of AP were identified by imaging, ANA, cytomegalovirus (CMV) IgM, coxsackie B virus IgM, and IgG4. Genotyping of VDR TaqI rs731236 polymorphism, Laboratory tests and severity scores using Ranson, BISAP, Atlanta and APACHE II scores were determined.

Results

The age in AP patients was 36.03 ± 10.76, and females were 85.7%. The etiologies of AP were as follows: biliary (51.4%), coxsackievirus (22.9%), autoimmune (14.3%), post‐ERCP (8.6%) and 2.9% were idiopathic. The TT genotype of VDR polymorphism was significantly more common in AP than control (P = .001) and allele T dominated in AP group (OR = 2; 95% CI: 0.665–5.64). Most cases showed low severity scores with significant differences among etiologies and VDR genotypes. Biliary pancreatitis showed highest percentages of severe AP. However, etiologies and VDR polymorphism were not predictors of severity.

Conclusion

Etiology of AP could have impact on the disease severity. VDR gene polymorphism increases the risk of AP. Neither the etiology nor VDR gene polymorphism could predict AP severity.
Health‐related quality of life in paediatric patients with intoxication‐type inborn errors of metabolism: Analysis of an international data set
Authors: Bösch Florin , Landolt Markus A. , Baumgartner Matthias R. , Zeltner Nina , Kölker Stefan , Gleich Florian , Burlina Alberto , Cazzorla Chiara , Packman Wendy , V. D. Schwartz Ida , Vieira Neto Eduardo , Ribeiro Márcia G. , Martinelli Diego , Olivieri Giorgia , Huemer Martina
Published: August 2020

Acute intoxication‐type inborn errors of metabolism (IT‐IEM) such as urea cycle disorders and non‐acute IT‐IEM such as phenylketonuria have a major impact on paediatric patients' life. Patients have to adhere to a strict diet but may face neurocognitive impairment and – in acute diseases – metabolic decompensations nevertheless. Research on the subjective burden of IT‐IEM remains sparse. Studies with appropriate sample sizes are needed to make valid statements about health‐related quality of life (HrQoL) in children and adolescents with IT‐IEM. Six international metabolic centres contributed self‐reports and proxy reports of HrQoL (assessed with the Paediatric Quality of Life Inventory) to the final data set (n = 251 patients; age range 2.3‐18.8 years). To compare HrQoL of the patient sample with norm data and between acute and non‐acute IT‐IEM, t tests were conducted. To examine the influence of child age, sex, diagnosis and current dietary treatment on HrQoL, multiple linear regression analyses were conducted. Self‐reports and proxy reporst showed significantly lower HrQoL total scores for children with IT‐IEM compared to healthy children. Current dietary treatment significantly predicted lower proxy reported total HrQoL. Children with non‐acute IT‐IEM reported significantly lower psychosocial health and emotional functioning than children with acute IT‐IEM. The patient sample showed significantly impaired HrQoL and a diet regimen remains a risk factor for lower HrQoL. Differences in HrQoL between acute and non‐acute IT‐IEM subgroups indicate that factors beyond symptom severity determine the perception of disease burden. Identifying these factors is of crucial importance to develop and implement appropriate interventions for those in need.
Mutational spectra of SARS‐CoV‐2 orf1ab polyprotein and signature mutations in the United States of America
Authors: Banerjee Shuvam , Seal Sohan , Dey Riju , Mondal Kousik Kr. , Bhattacharjee Pritha
Published: August 2020

The pandemic COVID‐19 outbreak has been caused due to SARS‐CoV‐2 pathogen, resulting in millions of infections and deaths worldwide, the United States being on top at the present moment. The long, complex orf1ab polyproteins of SARS‐CoV‐2 play an important role in viral RNA synthesis. To assess the impact of mutations in this important domain, we analyzed 1134 complete protein sequences of the orf1ab polyprotein from the NCBI virus database from affected patients across various states of the United States from December 2019 to 25 April 2020. Multiple sequence alignment using Clustal Omega followed by statistical significance was calculated. Four significant mutations T265I (nsp 2), P4715L (nsp 12), and P5828L and Y5865C (both at nsp 13) were identified in important nonstructural proteins, which function either as replicase or helicase. A comparative analysis shows 265 T→I, 5828 P→L, and 5865Y→C are unique to the United States and not reported from Europe or Asia; while one, 4715 P→L is predominant in both Europe and the United States. Mutational changes in amino acids are predicted to alter the structure and function of the corresponding proteins, thereby, it is imperative to consider the mutational spectra while designing new antiviral therapeutics targeting viral orf1ab.
A3G‐induced mutations show a low prevalence and exhibit plus‐strand regional distribution in hepatitis B virus DNA from patients with non‐hepatocellular carcinoma (HCC) and HCC
Authors: Ren FengLing , Li WeiNa , Zhao ShuDong , Wang Li , Wang Qin , Li Meng , Xiang An , Guo YanHai
Published: August 2020

APOBEC3G (A3G) cytidine deaminase is an innate immune restriction factor that can edit and inhibit hepatitis B virus (HBV) replication. The preferred target of A3G is deamination of the third cytosine of 5′CCC to form a mutant marker 5′CC
C → K. However, the distribution of A3G‐induced mutations on HBV DNA during infection is not well characterized. To provide clarity, we obtained the HBV DNA sequences from HBV infected individuals with and without hepatocellular carcinoma (HCC and non‐HCC, respectively), from the NCBI database, and calculated the r values of A3G‐induced 5′CC
C → K mutation prevalence in HBV DNA. A3G‐induced mutations were weakly prevalent and mainly distributed in the plus strand of HBV DNA (r = 1.407). The mutations on the minus strand were weaker (r = .8189). There were A3G‐induced mutation regions in the 1200 to 2000 nt region of the plus strand and the 1600 to 1500 nt region of the minus strand. There was no significant difference in the r values of A3G‐induced mutations in HBV DNA between the HCC and non‐HCC groups. However, the rvalue of the plus strand 2400 to 2800 nt regions of HCC derived HBV DNA (r = 4.2) was significantly higher than that of the same regions of non‐HCC derived HBV DNA (r = 1.21). These findings clarify the weak prevalence and preferred plus‐strand distribution of A3G‐induced mutations on HBV DNA from HCC and non‐HCC. These findings may provide valuable clues regarding the interaction mechanism between A3G and HBV DNA and inform HCC screening.
The recombinant Newcastle disease virus Anhinga strain expressing human TRAIL exhibit antitumor effects on a glioma nude mice model
Authors: He Jinjiao , An Ying , Qi Jianying , Cui Lin , Yang Kai , Liu Mingyao , Qu Bo , Yan Shijun , Yin Jiechao , Jing Xiaohui , Dong Hui , Yu Qingzhong , Li Deshan , Wu Yunzhou
Published: August 2020

Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. However, the potential oncolytic ability of the recombinant newcastle disease virus (NDV) Anhinga strain carried with tumor necrosis factor‐related apoptosis inducing ligand (TRAIL) has not been fully explored at present. In the present study, the recombinant NDV/Anh‐TRAIL that secretes soluble TRAIL was constructed and the experiment results suggested NDV/Anh‐TRAIL as a promising candidate for glioma therapy. Growth kinetic and TRAIL secreted quantity of recombinant NDV/Anh‐TRAIL virus were measured. Cytotoxic and cell apoptosis were analyzed for its anti‐glioma therapy in vitro. Nude mice were used for the in vivo evaluation. Both tumor volume and mice behavior after injection were observed. The recombinant virus replicated with the same kinetics as the parental virus and the highest expression of TRAIL (77.8 ng/L) was found at 48 hours. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, a tetrazole and flow cytometry data revealed that the recombinant NDV/Anh‐TRAIL (56.1 ± 8.2%) virus could induce a more severe apoptosis rate, when compared with the NDV wild type (37.2 ± 7.0%) and mock (7.0 ± 1.8%) groups (P < .01), in U251 cells. Furthermore, in the present animal study, the average tumor volume was smaller in the NDV/Anh‐TRAIL group (97.21 mm3), when compared with the NDV wild type (205.03 mm3, P < .05) and PBS (310.30 mm3, P < .01) groups.
The effects of product development network positions on product performance and confidentiality performance
Authors: Lan Yingchao , Massimino Brett J. , Gray John V. , Chandrasekaran Aravind
Published: August 2020

Product development networks facilitate access to information, knowledge, and technologies that are otherwise difficult to obtain during innovation activities. Most current research on networks focuses on studying product performance benefits, but ignores the potential negative effects on confidentiality performance. Addressing this gap, we investigate how two key components of a firm's network position—network centrality and structural holes—affect both product and confidentiality performance. To do this, we assemble a panel of 1,468 electronic video games designed and developed by 591 developers over an 11‐year period. We find that higher network centrality relates to better product performance but worse confidentiality performance. Meanwhile, firms spanning more structural holes enjoy better performance across both dimensions. In an exploratory analysis, we find that product novelty strengthens the positive relationship between network centrality and product performance but mutes the positive relationship between structural holes and product performance. We discuss the importance of these findings to the literature on innovation in inter‐organizational networks.
Antioxidant quantification in different portions obtained during olive oil extraction process in an olive oil press mill
Authors: De Bruno Alessandra , Romeo Rosa , Piscopo Amalia , Poiana Marco
Published: August 2020

BACKGROUND

Different antioxidant compounds are generally transferred from olives to olive oil during the production process. This work characterized the principal total bioactive compounds (tocopherols and phenols) in olives, olive oil and by‐products of four cultivars grown in Calabrian areas (southern Italy), considering the effect of harvesting period. Antioxidant capacity, total and individual phenolic compounds were also analysed.

RESULTS

Drupes, olive paste, pomace and olive wastewater showed similar phenolic compounds, while olive oil possessed a different composition, suggesting that phenols are not only transferred from drupe to oil, but also they change during oil production. Tocopherols varied among cultivars and harvesting period: generally, they were more abundant in samples produced in the first harvesting period.

Qualitative and quantitative differences in phenolic composition and antioxidant activity were significantly found among cultivars in all the matrices.

CONCLUSION

The highest amount of total phenolic antioxidants ended up in olive wastewater with variability due to the olive cultivar, while only a small part of them finished in the oil. This work shows evidence that the availability of bioactive compounds in different portions from the olive oil extraction belong to different varietal origins. In particular, new information was acquired on Ottobratica Calipa, a new olive clone, that produced an olive oil with an interesting antioxidant amount. © 2020 Society of Chemical Industry
Clinical relevance of performing endoscopic ultrasound‐guided fine‐needle biopsy for pancreatic neuroendocrine tumors less than 2 cm
Authors: Heidsma Charlotte M. , Tsilimigras Diamantis I. , Rocha Flavio , Abbott Daniel E. , Fields Ryan , Smith Paula M. , Poultsides George A. , Cho Cliff , van Eijck Casper , van Dijkum Elisabeth Nieveen , Maithel Shishir K. , Pawlik Timothy M. ,   the US Neuroendocrine Tumor Study Group
Published: August 2020

Background

We sought to define the diagnostic yield and concordance rates between endoscopic ultrasound (EUS)‐fine‐needle aspiration (FNA) and surgical pathology specimen following resection of pancreatic neuroendocrine tumors (pNET) less than 2 cm.

Methods

Patients with a pNET less than 2 cm who underwent EUS‐FNA were identified using a multi‐institutional international database. Tumor differentiation, and Ki‐67 index, as determined through EUS‐FNA were examined and concordance rates between EUS‐FNA and the surgical pathology were assessed.

Results

Among 628 patients with a pNET less than 2 cm, 57.2% of patients had an EUS‐FNA performed. Patients who underwent EUS had slightly smaller size tumors (1.3 vs 1.4 cm), and the pNETs were less likely to be functional (15.3% vs 26.8%) or symptomatic (48.5% vs 56.5%) (both P < .05). Among 314 patients with a pNET less than 2 cm who had an EUS‐FNA performed at the time of diagnosis, 243 (73.2%) had the diagnosis confirmed by preoperative EUS‐FNA. Tumor differentiation and Ki‐67 could be determined by EUS‐FNA in only 26.4% and 20.1% of patients, respectively. Concordance rate between EUS‐FNA and pathology was high relative to tumor differentiation (92.7%) and Ki‐67 (81.0%).

Conclusion

Tumor differentiation and Ki‐67 index could be determined by EUS‐FNA in only 26.4% and 20.1% of cases, respectively. Further studies should focus on EUS techniques to optimize diagnostic yield and cell extraction in the preoperative setting.
Prognostic impact of lymphovascular invasion in pT1‐T3 gallbladder adenocarcinoma
Authors: Dominguez Dana A. , Aversa John G. , Hagerty Brendan L. , Diggs Laurence P. , Raoof Mustafa , Davis Jeremy L. , Hernandez Jonathan M. , Blakely Andrew M.
Published: August 2020

Background

Most gallbladder cancers are diagnosed after cholecystectomy for presumed benign disease, and nodal staging to inform subsequent treatment is therefore often lacking. We evaluated the association of lymphovascular invasion (LVI) with regional lymph node involvement in gallbladder adenocarcinoma and its impact on survival.

Methods

The National Cancer Database was queried to identify patients with resected gallbladder adenocarcinoma and with available staging and LVI status. Patients with pT4 and M1 disease were excluded. Univariable and multivariable regression identified factors associated with positive lymph nodes. Cox proportional hazards model was used to evaluate overall survival (OS).

Results

Of 1649 patients with available LVI status, 1142 (69.7%) had at least one positive lymph node and 765 (46.4%) had LVI. On multivariable regression, presence of LVI was the strongest predictor of positive lymph nodes (odds ratio, 3.69; P < .001). The positive predictive value of LVI for positive lymph nodes in pT2 and pT3 tumors was 80.1% and 90.5%, respectively. LVI was independently associated with decreased OS (hazard ratio, 1.21; P = .001), as were node‐positive disease and increasing T stage.

Conclusion

In patients with gallbladder adenocarcinoma, LVI is independently associated with regional lymph node metastases and abbreviated OS. LVI status may help risk‐stratify patients following initial cholecystectomy and inform subsequent treatment.
Bronchoscopic procedures during COVID‐19 pandemic: Experiences in Turkey
Authors: Ozturk Ayperi , Sener Melahat U. , Yılmaz Aydın
Published: August 2020

Background

Globally, coronavirus disease‐2019 (COVID‐19) is a new, highly contagious, and life‐threatening virus. We aimed to demonstrate how we proceeded with bronchoscopic procedures without published guidelines at the inception of the pandemic period.

Materials and Methods

All bronchoscopic procedures applied from the first case seen in Turkey (11 March‐15 May) were evaluated retrospectively. Patient data on indications, diagnosis, types of procedures, and the results of COVID‐19 tests were recorded.

Results

This study included 126 patients; 36 required interventional bronchoscopic techniques (28.6%), 74 required endobronchial ultrasonography (EBUS; 58.7%), and 16 required flexible fiberoptic bronchoscopy (12.7%). All interventional rigid bronchoscopic techniques were performed for emergent indications: malignant airway obstruction (66.7%), tracheal stenosis (25%), and bronchopleural fistula (8.3%). Malignancy was diagnosed in 59 (79.7%), 12 (50%), and 4 (25%) patients who underwent EBUS, interventional procedures, and fibreoptic bronchoscopy, respectively. All personnel wore personal protective equipment and patients wore a surgical mask, cap, and disposable gown. Of the patients, 31 (24.6%) were tested for COVID‐19 and all the results were negative. COVID‐19 was not detected in any of the patients after a 14‐day follow‐up period.

Conclusion

This study was based on our experiences and demonstrated that EBUS and/or bronchoscopy should not be postponed in patients with known or suspected lung cancer.
Characterization of bovine and canine animal model cartilage endplates and comparison to human cartilage endplate structure, matrix composition, and cell phenotype
Authors: Lakstins Katherine , Arnold Lauren , Gunsch Gilian , Khan Safdar , Moore Sarah , Purmessur Devina
Published: August 2020

There is a need to further explore mechanisms of cartilage endplate (CEP) degeneration, due to its role in the onset and progression of intervertebral disc degeneration and low back pain. Therefore, the goal of this study was to evaluate structure, matrix composition, and cell phenotype between the human and bovine or canine, both clinically relevant animal models currently used to study the intervertebral disc, CEP. This information may be used in addition to other relevant studies, to help determine optimal animal models for use in studying the role of the CEP in intervertebral disc degeneration and back pain. Endplate structure, matrix composition, cell morphology, and gene expression were evaluated using a picrosirius red/alcian blue and hematoxylin and eosin stain, a dimethylmethylene blue assay, and quantitative reverse transcription polymerase chain reaction. The bovine and canine CEPs were thinner with more rounded cells and thicker bony endplates. The canine CEP contained significantly more sulfated glycosaminoglycans. The bovine CEP demonstrated higher expression of ACAN, COL1, and COL2 and lower expression of T, FBLN1, and collagen X (COLX) compared to the human CEP. The canine CEP had higher COL2 and lower COL1, KRT19, MKX, FBLN1, COLX expression compared to human. These similarities and differences between human and bovine or canine CEP are important to consider when evaluating which animal model is most optimal to use in future studies, interpreting research findings using these animal models and assessing translatability to the human condition.
Posttraumatic Perfusion Analysis of Quadriceps, Patellar, and Achilles Tendon Regeneration With Dynamic Contrast‐Enhanced Ultrasound and Dynamic Contrast‐Enhanced Magnetic Resonance Imaging
Authors: Fischer Christian , Miska Matthias , Jung Andreas , Weber Marc‐André , Saure Daniel , Schmidmaier Gerhard , Weimer Andreas , Moghaddam Arash , Doll Julian
Published: August 2020

Objectives

The healing process of tendons after surgical treatment of tendon ruptures mainly depends on the perfusion of the tendon and its surrounding tissue. Dynamic contrast‐enhanced ultrasound (DCE‐US) and dynamic contrast‐enhanced MRI (DCE‐MRI) can provide additional information about the local microperfusion. In this pilot study, the feasibility of these techniques to assess the vascularization during tendon regeneration was evaluated.

Methods

Between 2013 and 2015, 23 patients with surgical treatment of traumatic rupture of quadriceps, patellar, and Achilles tendons were involved. All patients received clinical follow‐up examinations at 6, 12, and at least 52 weeks postoperatively. Dynamic contrast‐enhanced US and DCE‐MRI examinations were performed 6 and 12 weeks postoperatively. Dynamic contrast‐enhanced US perfusion was quantified by the parameters peak enhancement, wash‐in area under the curve, rise time, and initial area under the curve. Correlations between these parameters were examined via the Spearman rank correlation. The clinical and functional outcomes were assessed via the Lysholm Knee Score and Knee and Osteoarthritis Outcome Score at 12 and 52 weeks postoperatively.

Results

Fourteen patients with quadriceps (n = 8), patellar (n = 4) and Achilles (n = 2) tendon ruptures with complete follow‐up were available. The microperfusion could be successful assessed. We could detect a strong correlation of DCE‐US (peak enhancement) parameters with DCE‐MRI (initial area under the curve) parameters after 6 and 12 weeks.

Conclusions

In this pilot study, DCE‐US was able to visualize the microperfusion of healing tendons with a strong correlation with DCE‐MRI. Our initial results are in favor of DCE‐US as a potential quantitative imaging tool for evaluating the vascularization in tendon regeneration as a complementary method.
Chidamide acts on the histone deacetylase‐mediated miR‐34a/Bcl‐2 axis to regulate NB4 cell line proliferation and apoptosis
Authors: Peng Jie , Li Shu‐Jun , Fu Xiao , Liu Yi , Zhao Xie‐Lan
Published: August 2020

Acute promyelocytic leukemia (APL), a biologically and clinically distinct variant of acute myelogenous leukemia, is characterized by the fusion of the N‐terminus of promyelocytic leukemia protein to the C terminus of retinoic acid receptor alpha, mostly due to chromosomal translocation t(15;17). Chidamide, a synthetic analogue of MS‐275 identified from a group of benzamide‐type compounds, has been found to have efficient anticancer activity in basic and clinical research studies. However, the concrete role and underlying mechanism of Chidamide in the treatment of APL has not been well characterized. Our data demonstrate that Chidamide inhibited the expression of histone deacetylase (HDAC) to induce apoptosis and suppress proliferation in NB4 cells. Mechanistically, Chidamide increases the expression of miR‐34a by suppressing HDAC. Furthermore, B‐cell lymphoma‐2 (Bcl‐2) is a direct target of miR‐34a, the expression of which is regulated by miR‐34a. Functionally, Chidamide inhibits cell proliferation and promotes apoptosis through miR‐34a/Bcl‐2. Chidamide exerts its anticancer effect via the HDAC‐mediated miR‐34a/Bcl‐2 axis, providing potential targets for APL therapy.
Antiviral Activity of Nanomaterials against Coronaviruses
Authors: Muhammad Wali , Zhai Zihe , Gao Changyou
Published: August 2020

One of the challenges facing by world nowadays is the generation of new pathogens that cause public health issues. Coronavirus (CoV) is one of the severe pathogens that possess the RNA (ribonucleic acid) envelop, and extensively infect humans, birds, and other mammals. The novel strain “SARS‐CoV‐2” (severe acute respiratory syndrome coronavirus‐2) causes deadly infection all over the world and presents a pandemic situation nowadays. The SARS‐CoV‐2 has 40 different strains that create a worrying situation for health authorities. The virus develops serious pneumonia in infected persons and causes severe damage to the lungs. There is no vaccine available for this virus up to present. To cure this type of infections by making vaccines and antiviral drugs is still a major challenge for researchers. Nanotechnology covering a multidisciplinary field may find the solution to this lethal infection. The interaction of nanomaterials and microorganisms is considered as a potential treatment method because the nanomaterials owe unique physicochemical properties. The aim of this review is to present an overview of previous and recent studies of nanomaterials against coronaviruses and to provide possible new strategies for upcoming research using the nanotechnology platform.