bluuebunny/crossref_metadata_2025 huggingface dataset:
Plant Pan-Genomics Comes of Age
Authors: Lei Li , Goltsman Eugene , Goodstein David , Wu Guohong Albert , Rokhsar Daniel S. , Vogel John P.
Published: April 2021

A pan-genome is the nonredundant collection of genes and/or DNA sequences in a species. Numerous studies have shown that plant pan-genomes are typically much larger than the genome of any individual and that a sizable fraction of the genes in any individual are present in only some genomes. The construction and interpretation of plant pan-genomes are challenging due to the large size and repetitive content of plant genomes. Most pan-genomes are largely focused on nontransposable element protein coding genes because they are more easily analyzed and defined than noncoding and repetitive sequences. Nevertheless, noncoding and repetitive DNA play important roles in determining the phenotype and genome evolution. Fortunately, it is now feasible to make multiple high-quality genomes that can be used to construct high-resolution pan-genomes that capture all the variation. However, assembling, displaying, and interacting with such high-resolution pan-genomes will require the development of new tools.
Understanding the Function of Mammalian Sirtuins and Protein Lysine Acylation
Authors: Wang Miao , Lin Hening
Published: April 2021

Protein lysine acetylation is an important posttranslational modification that regulates numerous biological processes. Targeting lysine acetylation regulatory factors, such as acetyltransferases, deacetylases, and acetyl-lysine recognition domains, has been shown to have potential for treating human diseases, including cancer and neurological diseases. Over the past decade, many other acyl-lysine modifications, such as succinylation, crotonylation, and long-chain fatty acylation, have also been investigated and shown to have interesting biological functions. Here, we provide an overview of the functions of different acyl-lysine modifications in mammals. We focus on lysine acetylation as it is well characterized, and principles learned from acetylation are useful for understanding the functions of other lysine acylations. We pay special attention to the sirtuins, given that the study of sirtuins has provided a great deal of information about the functions of lysine acylation. We emphasize the regulation of sirtuins to illustrate that their regulation enables cells to respond to various signals and stresses.
A Numerical Study of MHD Carreau Nanofluid Flow with Gyrotactic Microorganisms over a Plate, Wedge, and Stagnation Point
Authors: Muntazir R. M. Akram , Mushtaq M. , Jabeen K.
Published: April 2021

This article addresses the numerical exploration of steady and 2D flow of MHD Carreau nanofluid filled with motile microorganisms over three different geometries, i.e., plate, wedge, and stagnation point of a flat plate. The influence of magnetic field, viscous dissipation, thermophoresis, and Brownian motion is considered for both cases, i.e., shear thinning and shear thickening. A set of relevant similarity transformations are utilized to obtain dimensionless form of governing coupled nonlinear partial differential equations (PDEs). The transformed system of ordinary differential equations (ODEs) is then numerically solved by bvp4c via MATLAB based on shooting technique and Runge–Kutta–Fehlberg (RKF) scheme via MAPLE. Also, a numerical analysis has been made for skin friction factor, heat, and mass transfer rates. Results elucidate that all the profiles except velocity show decreasing behavior for higher values of magnetic field parameter. Among all three flow geometries for both shear thinning and shear thickening cases, the flow over a plate has lesser skin friction factor. The nanoparticle concentration and density of motile microorganism decrease in both the shear thinning and shear thickening cases, for increasing values of Brownian motion (Nb), but reverse trend is observed for rising values of thermophoresis parameter (Nt). Furthermore, it is observed that, as we increase the values of suction/injection parameter (S), the velocity of fluid increases but decreases the fluid temperature, concentration of mass and density of motile organisms over a plate, wedge, and stagnation point of a flat plate. Also, we observed that shear thinning nanofluid has higher rate of heat, mass, and motile microorganisms mass transfers than shear thickening fluid. Both shear thinning and thickening nanofluid have a low rate of heat/mass and gyrotactic microorganisms mass transfer over plate among wedge and stagnation point flow.
Hippocampal Subfield Volumes in Major Depressive Disorder Adolescents with a History of Suicide Attempt
Authors: Zhang Qi , Hong Su , Cao Jun , Zhou Yi , Xu Xiaoming , Ai Ming , Kuang Li
Published: April 2021

Suicidal behavior is a leading cause of death and often commences during adolescence/young adulthood (15~29 years old). The hippocampus, which consists of multiple functionally specialized subfields, may contribute to the pathophysiology of depression and suicidal behavior. We aimed to investigate the differences of hippocampal subfield volume between major depressive disorder (MDD) patients with and without suicide attempts and healthy controls in adolescents and young adults. A total of 40 MDD suicide attempters (MDD+SA), 27 MDD patients without suicide attempt (MDD‐SA), and 37 healthy controls (HC) were recruited. High‐resolution T1 MRI images were analyzed with the automated hippocampal substructure module in FreeSurfer 6.0. Volume differences among the groups were analyzed by a generalized linear model controlling for intracranial cavity volume (ICV). The relationship between hippocampal subfield volumes and clinical characteristics (HAM‐D and SSI scores) was assessed using two‐tailed partial correlation controlling for ICV in MDD+SA and MDD‐SA. We found that MDD‐SA had significantly smaller bilateral hippocampal fissure volume than HC and MDD+SA. No significant correlation was observed between hippocampal subfield volume and clinical characteristics (HAM‐D and SSI scores) in MDD+SA and MDD‐SA. Adolescent/young adult suicide attempters with MDD suicide attempters have larger bilateral hippocampal fissures than depressed patients without suicide attempts, independently from clinical characteristics. Within the heterogeneous syndrome of major depressive disorder that holds a risk for suicidality for subgroups, hippocampal morphology may help to explain or possibly predict such risk, yet longitudinal and functional studies are needed for understanding the biological mechanisms underlying.
An Empirical Study on the Agglomeration Characteristics of China’s Construction Industry Based on Spatial Autocorrelation and Spatiotemporal Transition
Authors: Zhao Likun , Tian Junsen , Liu Yanqi , Liu Rui
Published: April 2021

The spatiotemporal agglomeration of industries is the most prominent geographical feature of economic activities. Based on the analysis of the spatiotemporal distribution of China’s construction industry agglomeration, this paper analyzes the characteristics and evolution trend of the spatiotemporal agglomeration of construction industry in 31 provinces and cities of China from 2010 to 2019 by using Moran’s index and the spatiotemporal transition measurement model. The findings are as follows: (1) China’s construction industry has experienced two stages in terms of time: steady rise and turbulent rise. Spatially, China’s construction industry, as a whole, the space takes the shape of one horizontal and two vertical, similar to the letter “H” being crossed. And the difference of “East‐West” two ends of the industrial agglomeration level is obvious. (2) The Yangtze River Delta Urban Agglomerations (Shanghai, Jiangsu, and Zhejiang), the Pearl River Delta Urban Agglomerations (Guangdong), Beijing‐Tianjin‐Hebei Urban Agglomerations, and the western region (Xinjiang and Tibet) have significant local features. The four major types of China’s construction industry cluster, which are H‐H, H‐L, L‐H, and L‐L, are formed. (3) The time‐space transition of China’s construction industry is dominated by the “stable transition” mode. The transition inertia is significant. The regional development has strong path dependence and spatial locking characteristics.
Study on Long‐Term Performance of Geogrid‐Reinforced and Pile‐Supported Embankment at Bridge Approach
Authors: Zhang Jun , Zhao Ziyang , Sun Zhijie
Published: April 2021

Bridges have been widely used in highway and railway engineering, especially in mountain areas. The differential settlement between bridge abutment and approach embankment is one of the most challenging problems, and it will result in “bumps” to affect the driving safety and comfortableness at the end of a bridge. The geogrid‐reinforced and pile‐supported embankment (GRPS embankment) is proposed to mitigate the differential settlement at the bridge approach. In this paper, the model tests and numerical studies are carried out to study the long‐term performance of the GRPS embankment considering the consolidation of subsoil. Firstly, a series of model tests are conducted to evaluate the long‐term performance of the GRPS embankment using a specially designed model box. Then, the numerical model is constructed using the finite element software MIDAS, and the numerical model is verified from the model test results. Finally, a parametric study is conducted to investigate the influences of pile net spacing, pile modulus, and filling modulus.
Differential Game Analysis of the Green Innovation Cooperation in Supply Chain under the Background of Dual-Driving
Authors: Zhu Guiju , Li Jialing , Zhang Yi , Liu Haiyun
Published: April 2021

Taking government environmental regulation and consumer’s green preference into a unified analytical framework, this study constructed a differential game model. With the joint effect of supplier and manufacturer green innovation efforts on the dynamic change of the product’s green level, it compared and analyzed the long-term dynamic equilibrium strategies of green innovation cooperation in a supply chain under decentralized and centralized decision-making situations. Accordingly, a scientific and reasonable profit-distribution contract was then proposed. On this basis, it further carried out a numerical simulation analysis on the dual-driving effects of the government and market. The results showed that the scientific and reasonable profit-distribution contract under the centralized decision-making situation, which was designed by using the Rubinstein bargaining game model, could effectively ensure that the supply chain members’ sharing profits would realize "Dual Pareto Improvements." With the increase of the environmental regulation’s intensity, the product’s green level kept rising and tended to be stable. However, the overall equilibrium profit of the supply chain was characterized by "U" fluctuation, which first descended and then ascended. In addition, the product’s green level, the green innovation investment and equilibrium (distributed) profits of supply chain members, and the overall profits of supply chain all increased with the consumers’ green preference.
On Cyclic-Vertex Connectivity of

n
,
k

-Star Graphs
Authors: Li Yalan , Zhang Shumin , Ye Chengfu
Published: April 2021

A vertex subset

F
 
⊆
 
V

G

is a cyclic vertex-cut of a connected graph

G

if

G
−
F

is disconnected and at least two of its components contain cycles. The cyclic vertex-connectivity

κ

c

G

is denoted as the cardinality of a minimum cyclic vertex-cut. In this paper, we show that the cyclic vertex-connectivity of the

n
,
k

-star network

S

n
,
k

is

κ

c

S

n
,
k

=
n
+
2
k
−
5

for any integer

n
≥
4

and

k
≥
2

.
Certain Class of Analytic Functions Connected with
q
-Analogue of the Bessel Function
Authors: Alessa Nazek , Venkateswarlu B. , Loganathan K. , Karthik T.S. , Reddy P. Thirupathi , Sujatha G.
Published: April 2021

The focus of this article is the introduction of a new subclass of analytic functions involving q-analogue of the Bessel function and obtained coefficient inequities, growth and distortion properties, radii of close-to-convexity, and starlikeness, as well as convex linear combination. Furthermore, we discussed partial sums, convolution, and neighborhood properties for this defined class.
Topical Applications of a Novel Emollient Inhibit Inflammation in Murine Models of Acute Contact Dermatitis
Authors: Wen Si , Sun Mengke , Ye Li , Yang Bin , Hu Lizhi , Man Mao-Qiang
Published: April 2021

The benefits of emollients for eczematous dermatitis and psoriasis have been thought to be due to the improvements in epidermal function, including epidermal permeability barrier, stratum corneum hydration, and stratum corneum pH. We determined here whether emollient can direct inhibit cutaneous inflammation. Ear inflammation was induced by topical application of either 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) or 1‐fluoro‐2,4‐dinitrofluorobenzene (DNFB). Either 1% hydrocortisone cream or the novel emollient was applied to the right ear of the mice 45 min and 2 hours after TPA or DNFB application. The untreated left ear served as untreated controls. Both ear weight and ear thickness were measured 24 hours after TPA and DNFB application. Topical applications of either hydrocortisone cream or emollient significantly decreased both ear thickness and ear weight in comparison to untreated controls. In DNFB model, hydrocortisone significantly lowered expression levels of mRNA for IL‐1α, IL‐1β, and TNFα, while the emollient markedly decreased expression levels of IL‐1α and TNFα mRNA. In TPA model, both hydrocortisone and emollient significantly decreased expression levels of IL‐1α, IL‐1β, IL‐6, and TNFα mRNA. In parallel, inflammatory infiltration was also reduced by topical applications of either hydrocortisone or emollient. These results demonstrate that this novel emollient can directly inhibit cutaneous inflammation in murine models of both acute irritant contact dermatitis and acute allergic contact dermatitis. However, whether this emollient could also alleviate eczematous dermatitis in humans remains to be explored.
Rare Case of Multiple Perirenal, Extra-Adrenal Myelolipoma: Case Report, Current Management Options, and Literature Review
Authors: Benko Goran , Kopjar Andrina , Plantak Marin , Cvetko Danijel , Glunčić Vicko , Lukić Anita
Published: April 2021

Extra-adrenal myelolipomas are rare, asymptomatic entities, although large tumors may cause local symptoms or hemorrhage. When these lesions occur outside the adrenals in the retroperitoneum, they are radiographically easily confused with both primary and secondary retroperitoneal tumors, which tend to be aggressive. Although myelolipomas are benign and can be managed conservatively, if malignancy is suspected, a surgical procedure is an option. We report a case of a 68-year-old patient with multiple perirenal extra-adrenal myelolipomas. Initial abdominal ultrasound reviled an inhomogeneous mass surrounding the left kidney. Subsequent CT examination of the abdomen showed four separate, extrarenal, well-circumscribed, round-shaped, fat-containing retroperitoneal tumors. Given the significant size of the masses, that compressed major abdominal vessels and the suspicion of liposarcoma, a surgical excision of the lesions was performed. The tumors were easily separated, all surrounding structures were spared, and they were removed completely. Histologically, all masses consisted of hematopoietic and mature fat tissue and the final diagnosis was extra-adrenal myelolipoma. The patient was released from the hospital 7th day after surgery in good condition and at his baseline. Since myelolipomas are, by definition, nonfunctional benign tumors, there was no need for further follow-up. The radiological evaluation and fine needle biopsy are usually sufficient to establish the diagnosis, but in some cases of well-differentiated liposarcoma, the differentiation between myelolipoma and liposarcoma can be challenging. Therefore, considering that myelolipomas and liposarcomas have opposite prognoses, which affects the surgeon’s decision on the extent of surgical procedure and further treatment, we also emphasize the importance of intraoperative assessment of the tumor, both by the surgeon and by intraoperative pathology consultation.
Ordering Policies of a Deteriorating Item in an EOQ Model under Upstream Partial Order-Quantity-Dependent Trade Credit and Downstream Full Trade Credit
Authors: Molamohamadi Zohreh , Mirzazadeh Abolfazl
Published: April 2021

In the classical inventory systems, the retailer had to settle the accounts of the purchased items at the time they were received. But in practice, the supplier applies some strategic tools, such as trade credit contract, to enhance his sales channel and offers delay period to his customers to settle the account. Any member of the supply chain may offer full or partial trade credit contract to his downstream level. Full trade credit is the case that the latter is allowed to defer the whole payment to the end of the credit period. In partial trade credit, however, the downstream supply chain member must pay for a proportion of the purchased goods at first and can delay paying for the rest until the end of the credit period. This paper considers a two-level trade credit, where the supplier offers order-quantity-dependent partial trade credit to a retailer, who suggests full trade credit to his customers. An economic order quantity (EOQ) inventory model of a deteriorating item is formulated here, and the Branch and Reduce Optimization Navigator is applied to find the optimal replenishment policy. The sensitivity of the variables on different parameters has been analyzed by applying some numerical examples. The data reveal that increasing the credit periods of the retailer and the customers can decrease and increase the retailer’s total cost, respectively.
Peripheral Gangerene, an Unusual Presentation of Infantile Kawasaki: A Case Report and Literature Review
Authors: Tahghighi Fatemeh , Bakhtiari Koohsorkhi Maryam , Ziaee Vahid
Published: April 2021

Introduction. Diagnosing infantile Kawasaki disease with atypical symptoms is difficult, and it also has higher risk of coronary abnormalities which is one of the most common complications of KD. Other complications such as pericardial effusion, mitral insufficiency, congestive heart failure, myocardial systolic dysfunction, and systemic vasculitis were also reported. Peripheral gangrene and necrosis are among the rare complications of this systemic vasculitis. Case Presentation. We report an 8-month-old girl with prolonged fever, generalized petechial rash, cracked erythematous lips, edema, and coronary ectasia who received two doses of IVIG in another center, but short after her discharge, she started to develop a necrotic plaque on her knee. She was admitted in our hospital, and the repeat echocardiography showed sustained coronary ectasia. She received 3 doses of methylprednisolone pulse therapy and was discharged with aspirin and prednisolone. In the follow-up visits, the coronary ectasia was resolved and the necrotic ulcer was healing with a scar. Conclusions. The diagnosis of Kawasaki disease and echocardiographic evaluation of the coronary arteries should be considered in young infants with prolonged fever of unknown origin. Peripheral gangrene is a rare but important complication of infantile Kawasaki disease, although the exact mechanism in not fully understood.
Effect of Aluminum Sulfate and Succinic Acid on the Growth Law of α‐Calcium Sulfate Hemihydrate under Microwave Irradiation
Authors: Feng Yan , Guo Rongxin , Lin Zhiwei
Published: April 2021

The existing α‐hemihydrate gypsum preparation process has low production efficiency and high energy consumption. In this paper, α‐type hemihydrate gypsum was prepared by microwave irradiation using phosphogypsum as the raw material, calcium chloride solution as the reaction medium, and succinic acid and aluminum sulfate as crystal‐transforming agents. Both aluminum sulfate and succinic acid were studied to determine the mechanism influencing the effect on the growth of α‐type hemihydrate gypsum crystals. This study found that, without added succinic acid or aluminum ions, the crystal transformation rate of α‐calcium sulfate hemihydrate reached 96% with the average length‐diameter ratio reaching 21 after 1 h; when the dosage of succinic acid was 0.02%, the crystal transformation rate of α‐calcium sulfate hemihydrate reached 96% with the average length‐diameter ratio reaching 1.5 after 1.5 h; and when the aluminum ion dosage was 5 mM, the crystal transformation rate of α‐calcium sulfate hemihydrate reached 97% with the average length‐diameter ratio reaching 12.3 after 1 h. In addition, it was discovered that the reaction time was significantly shortened under microwave irradiation, and with an increase in succinic acid content, the regulation of the microscopic morphology of the calcium sulfate hemihydrate crystals was continuously enhanced and the aspect ratio of the crystals was continuously reduced. The EDS and Fourier transform infrared spectroscopy (FTIR) analysis showed that succinic acid did not adsorb onto the hemihydrate gypsum crystal during the reaction under microwave irradiation. The X‐ray photoelectron spectroscopy (XPS) analysis revealed that aluminum ions affected crystal growth by incorporating into calcium sulfate hemihydrate crystals after reacting with sulfate radicals.
Strong Convergence Analysis of Iterative Algorithms for Solving Variational Inclusions and Fixed-Point Problems of Pseudocontractive Operators
Authors: Yao Zhangsong , Wu Yan-Kuen , Wen Ching-Feng
Published: April 2021

Iterative methods for solving variational inclusions and fixed-point problems have been considered and investigated by many scholars. In this paper, we use the Halpern-type method for finding a common solution of variational inclusions and fixed-point problems of pseudocontractive operators. We show that the proposed algorithm has strong convergence under some mild conditions.
Management of Vasoproliferative Tumors of the Retina with Macular Complications by Pars Plana Vitrectomy Combined with Episcleral Cryotherapy
Authors: Zhang Wenhua , Qiang Zeyuan , Song Hao , Li Xiaoli , Dan Handong , Ge Keke , Li Pan , Huang Zixu , Wang Dongdong , Chen Feng , Zheng Bin , Song Zongming
Published: April 2021

Objective. To evaluate the efficacy of pars plana vitrectomy (PPV) combined with episcleral cryotherapy in treating vasoproliferative tumors of the retina (VPTR) with macular complications. Methods. In this retrospective noncomparative interventional case-series analysis, we included 11 eyes of ten patients diagnosed with VPTR. All patients underwent comprehensive ophthalmic examinations and were treated with PPV combined with episcleral cryotherapy. Best-corrected visual acuity (BCVA), tumor activity, retinal morphological structure, and postoperative complications were evaluated. Results. Macular complications included epimacular membrane (n = 10), macular hole (n = 3), and macular edema (n = 1). Tumors were treated with triple freeze-thaw episcleral cryotherapy during PPV. The mean logarithm of minimal angle of resolution (logMAR) BCVA dropped from 0.62 ± 0.58 to 0.39 ± 0.46. The difference between the mean values of logMAR BCVA before and after treatment was statistically significant (t = 2.48,P=0.033). The tumor activity was controlled effectively in nine cases. Compared with preoperative tumor activity, tumor activity after treatment was significantly lower (P<0.01). The increase of central retinal thickness and the disruption of retinal layers were associated with macular holes, macular edema, and retinal proliferative membrane. After the treatment, visual acuity improved in 91% of the cases, and 73% had no long-term complications. Conclusion. PPV combined with episcleral cryotherapy promoted tumor regression, preserved retinal integrity, and improved visual acuity. Thus, the combination of PPV with episcleral cryotherapy can be considered effective and safe for the management of VPTR with macular complications.
Computational Fluid Dynamics Analysis of Impingement Heat Transfer in an Inline Array of Multiple Jets
Authors: Singh Parampreet , Grover Neel Kanth , Agarwal Vivek , Sharma Shubham , Singh Jujhar , Sadeghzadeh Milad , Issakhov Alibek
Published: April 2021

Amid all convective heat transfer augmentation methods employing single phase, jet impingement heat transfer delivers significantly higher coefficient of local heat transfer. The arrangement leading to nine jets in square array has been used to cool a plate maintained at constant heat flux. Numerical study has been carried out using RANS-based turbulence modeling in commercial CFD Fluent software. The turbulent models used for the study are three different “k-ε” models (STD, RNG, and realizable) and SST “k-ω” model. The numerical simulation output is equated with the experimental results to find out the most accurate turbulence model. The impact of variation of Reynolds number, inter-jet spacing, and separation distance has been considered for the geometry considered. These parameters affect the coefficient of heat transfer, temperature, and turbulent kinetic energy related to flow. The local “h” values have been noticed to decline with the rise in separation distance “H/D.” The SST “k-ω” model has been noticed to be in maximum agreement with the experimental results. The average value of heat transfer coefficient “h” reduces from 210 to 193 W/m2K with increase in “H/D” from 6 to 10 at “Re” = 9000 and S/D of 3. As per numerical results, inter-jet spacing “S/D” of 3 has been determined to be the most optimum value.
Role of Microalbuminuria and Hypoalbuminemia as Outcome Predictors in Critically Ill Patients
Authors: Nour Mahmoud , hegazy Abdelhaleem , mosbah Abeer , Abdelaziz Ahmed , Fawzy Mohamed
Published: April 2021

Background. Assessment of microalbuminuria and hypoalbuminemia can be used as a good tool for the prediction of the ICU outcome in critically ill patients. Purpose. To evaluate and compare the prognostic significance of microalbuminuria (albumin creatinine ratio (ACR)) and serum albumin level done on admission and after twenty-four hours for the critically ill patients. Methodology. Sixty ICU patients were involved in a prospective cohort study (mean age was 44.4 ± 16.7 years, and 78.3% were males). Patients were divided into 2 groups according to mortality (survivors and nonsurvivors) and were subjected to laboratory measurement of the mentioned biomarkers on admission and after twenty-four hours. Results. There were 34 patients (56.67%) in group A (survivors) and 26 patients (43.33%) in group B (nonsurvivors). Albumin creatinine ratio on admission (ACR1) and albumin creatinine ratio after 24 hours (ACR2) were significantly lower in survivors than nonsurvivors (

P

values were <0.001 for both). Serum albumin level after 24 hours of admission was significantly higher in survivors than nonsurvivors (

P

value 0.02) while admission serum albumin was not significantly different between both groups (

P

value was 0.1). There was a positive correlation between ACR2 and ICU stay and mechanical ventilatory support with a strong positive correlation with the use of vasopressor therapy (r: 0.35, 0.58, and 0.73, respectively).

P

values were 0.005, <0.0001, and <0.0001, respectively. There was a positive correlation between ACR2 with APACHE II and SOFA scores (r: 0.46 and 0.43, respectively);

P

values were 0.001 and <0.0001, respectively. There was a moderate negative correlation between serum albumin on admission and after 24 hours and the duration of mechanical ventilation (r: −0.4 and −0.39, respectively) (

P

values were 0.001 and 0.002, respectively). By Cox regression analysis, two parameters were found to be an independent predictor of mortality in ICU patients which were age and using vasopressor treatment (

P

values = 0.01 and <0.001), while the other parameters were not independent predictors of mortality (

P

values were more than 0.05). Conclusions. Microalbuminuria on admission and after 24 hours of ICU admission could be a good predictor of mortality in critically ill patients. The serum albumin level after 24 hours of admission can predict poor outcomes in critically ill patients.
Therapeutic Value of miRNAs in Coronary Artery Disease
Authors: Ali Sheikh Md Sayed , Alduraywish A. , Almaeen A. , Alruwali Mubarak , Alruwaili Raed , Alomair Basil Mohammed , Salma Umme , Hedeab Gomaa Mostafa , Bugti Najeebullah , A.M.Abdulhabeeb Ibrahim
Published: April 2021

Atherosclerotic ischemic coronary artery disease (CAD) is a significant community health challenge and the principal cause of morbidity and mortality in both developed and developing countries for all ethnic groups. The progressive chronic coronary atherosclerosis is the main underlying cause of CAD. Although enormous progress occurred in the last three decades in the management of cardiovascular diseases, the prevalence of CAD continues to increase worldwide, indicating the need for discovery of deeper molecular insights of CAD mechanisms, biomarkers, and innovative therapeutic targets. Recently, several research groups established that microRNAs essentially regulate various cardiovascular development and functions, and a deregulated cardiac enriched microRNA profile plays a vital role in the pathogenesis of CAD and its biological aging. Numerous studies established that over‐ or downregulation of a single miRNA gene by ago‐miRNA or anti‐miRNA is enough to modify the CAD disease process, significantly prevent age‐dependent cardiac cell death, and markedly improve cardiac function. In the light of more recent experimental and clinical evidences, we briefly reviewed and discussed the involvement of miRNAs in CAD and their possible diagnostic/therapeutic values. Moreover, we also focused on the role of miRNAs in the initiation and progression of the atherosclerosis plaque as the strongest risk factor for CAD.
Extending the Utility of UTAUT2 for Hospital Patients’ Adoption of Medical Apps: Moderating Effects of e-Health Literacy
Authors: Chang Yung-Tzung , Chao Cheng-Min , Yu Chen-Wei , Lin Fang-Chen
Published: April 2021

Hospitals have begun to provide their own apps to improve the efficiency of hospital services. This study investigated the factors influencing the adoption of medical apps by hospital patients by using a theoretical model that combines the extended unified theory of acceptance and use of technology (UTAUT) with the concept of e-health literacy and personal innovativeness (PI). Data were obtained from responses to a paper-based self-reported questionnaire issued to patients at a hospital in Taoyuan, Taiwan. Of the 650 distributed questionnaires, we received 629 completed questionnaires, yielding a response rate of 96.8%. The responses to the completed questionnaires were analyzed using structural equation modeling (SEM). Partial least squares regression was used for model and hypothesis testing. The data were analyzed using an SEM approach to test ten hypotheses; significant support was observed for five of these hypotheses. The results indicated that habit, performance expectancy, facilitating conditions, and PI had significant positive effects on the usage intention (UI) of individuals, thereby confirming that e-health literacy moderates the association between performance expectancy and UI. This research contributes to the current understanding of adoption of hospital medical apps by patients. The findings are expected to assist hospitals in deciding whether to consider medical apps when investing in information technology.
Abstract IA-017: Chromatin and gene transcription in hypoxia
Authors: Batie Michael , Frost Julianty , Rocha Sonia
Published: April 2021

Oxygen is essential for the life of most multicellular organism and changes in oxygen availability have implications in physiological and pathophysiological conditions. In response to hypoxia (low oxygen availability) transcriptional changes are induced. The transcriptional response to hypoxia is mediated primarily by the Hypoxia Inducible Factor (HIF) family of transcription factors. HIFs are activated in hypoxia via inhibition of prolyl hydroxylases (PHDs), a group of molecular dioxygenases, which require oxygen for their activity. Whilst the role of HIFs in the transcriptional response to hypoxia is well characterized, little is known with regards to chromatin structure in low oxygen stress and how this coordinates the transcriptional response. It was recently shown that chromatin is sensitive to oxygen levels, with hypoxia altering histone methylation at hypoxia responsive genes via inhibition of specific JmjC histone demethylases. To further investigate chromatin structure and its role in hypoxia induced gene transcription, we have performed ATAC-seq and RNA-seq in human cancer cell lines in acute and prolonged hypoxia. We find that acute hypoxia leads to increased promoter accessibility at a subset of hypoxia inducible genes, and this mostly precedes changes in mRNA expression, with further changes in chromatin structure after prolonged hypoxia. In addition, ChIP-seq data on histone methylation marks (H3K4me and H3K36me3), revealed similar earlier patterns of genomic distribution. Furthermore, we dissected the impact of HIF in the observed changes using a chemical probe and specific HIF1beta depletion analysis of ATAC-seq. This work gives insights into the role of chromatin dynamics in regulating the transcriptional response to hypoxia and elucidating the mechanisms behind these changes may lead to targeted therapies for hypoxia driven diseases.

Citation Format: Michael Batie, Julianty Frost, Sonia Rocha. Chromatin and gene transcription in hypoxia [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-017.
Differential DNA Methylation of the IMMP2L Gene in Families with Maternally Inherited 7q31.1 Microdeletions is Associated with Intellectual Disability and Developmental Delay
Authors: Vasilyev Stanislav A. , Skryabin Nikolay A. , Kashevarova Anna A. , Tolmacheva Ekaterina N. , Savchenko Renata R. , Vasilyeva Oksana Yu. , Lopatkina Maria E. , Zarubin Alexei A. , Fishman Veniamin S. , Belyaeva Elena O. , Filippova Miroslava O. , Shorina Asia R. , Maslennikov Arkadiy B. , Shestovskikh Olga L. , Gayner Tatyana A. , Čulić Vida , Vulić Robert , Nazarenko Lyudmila P. , Lebedev Igor N.
Published: April 2021

Most copy number variations (CNVs) in the human genome display incomplete penetrance with unknown underlying mechanisms. One such mechanism may be epigenetic modification, particularly DNA methylation. The IMMP2L gene is located in a critical region for autism susceptibility on chromosome 7q (AUTS1). The level of DNA methylation was assessed by bisulfite sequencing of 87 CpG sites in the IMMP2L gene in 3 families with maternally inherited 7q31.1 microdeletions affecting the IMMP2L gene alone. Bisulfite sequencing revealed comparable levels of DNA methylation in the probands, healthy siblings without microdeletions, and their fathers. In contrast, a reduced DNA methylation index and increased IMMP2L expression were observed in lymphocytes from the healthy mothers compared with the probands. A number of genes were upregulated in the healthy mothers compared to controls and downregulated in probands compared to mothers. These genes were enriched in components of the ribosome and electron transport chain, as well as oxidative phosphorylation and various degenerative conditions. Differential expression in probands and mothers with IMMP2L deletions relative to controls may be due to compensatory processes in healthy mothers with IMMP2L deletions and disturbances of these processes in probands with intellectual disability. The results suggest a possible partial compensation for IMMP2L gene haploinsufficiency in healthy mothers with the 7q31.1 microdeletion by reducing the DNA methylation level. Differential DNA methylation of intragenic CpG sites may affect the phenotypic manifestation of CNVs and explain the incomplete penetrance of chromosomal microdeletions.
Trimetazidine Protects from Mercury-Induced Kidney Injury
Authors: Hazelhoff María Herminia , Bulacio Romina Paula , Torres Adriana Monica
Published: April 2021

Introduction: The presence of mercury in the environment is a worldwide concern. Inorganic mercury is present in industrial materials, is employed in medical devices, is widely used in batteries, is a component of fluorescent light bulbs, and it has been associated with human poisoning in gold mining areas. The nephrotoxicity induced by inorganic mercury is a relevant health problem mainly in developing countries. The primary mechanism of mercury toxicity is oxidative stress. Trimetazidine (TMZ) is an anti-ischemic drug, which inhibits cellular oxidative stress, eliminates oxygen-free radicals, and improves lipid metabolism. The aim of this study was to evaluate whether the administration of TMZ protects against mercuric chloride (HgCl2) kidney damage. Methods: Adult male Wistar rats received only HgCl2 (4 mg/kg bw, sc) (Hg group, n = 5) or TMZ (3 mg/kg bw, ip) 30 min before HgCl2 administration (4 mg/kg bw, sc) (TMZHg group, n = 7). Simultaneously, a control group of rats (n = 4) was studied. After 4 days of HgCl2 injection, urinary flow, urea and creatinine (Cr) plasma levels, Cr clearance, urinary glucose, and sodium-dicarboxylate cotransporter 1 (NaDC1) in urine were determined. Lipid peroxidation (MDA) and glutathione (GSH) levels were measured in kidney homogenates. Results: Rats only treated with HgCl2 showed an increase in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, and NaDC1 urinary excretion as compared with the control group and a decrease in Cr clearance. TMZHg group showed a decrease in urea and Cr plasma levels, urinary flow, fractional excretion of water, glucosuria, NaDC1 urinary excretion, and an increase in Cr clearance when compared to the Hg group. Moreover, MDA and GSH levels observed in Hg groups were decreased and increased, respectively, by TMZ pretreatment. Conclusion: TMZ exerted a renoprotective action against HgCl2-induced renal injury, which might be mediated by the reduction of oxidative stress. Considering the absence of toxicity of TMZ, its clinical application against oxidative damage due to HgCl2-induced renal injury should be considered. The fact that TMZ is commercially available should simplify and accelerate the translation of the present data “from bench to bedside.” In this context, TMZ become an interesting new example of drug repurposing.
Periungual Mycobacterium marinum Infection following a Fish Manicure
Authors: Vanhooteghem Olivier , Theate Ivan , De Schaetzen Viriginie
Published: April 2021

Fish pedicures and/or fish manicures are treatments performed in spas involving the use of the living fish Garra rufa. In the last decade, the use of G. rufa for cosmetic and therapeutic reasons has become increasingly popular. The patients are placed into a bath to control psoriasis, eczema, or other skin conditions, but there is no scientific proof of their effectiveness. Most of the infections described in association with fish spas result from minor skin injury and contact with fish carrying such bacteria as Staphylococcus aureus, Aeromonas sobria, and Mycobacterium marinum. Therefore, fish spas in general should not be recommended, particularly for diabetic patients, immunocompromised patients, or patients treated with biological agents.
Innate Immune Cells in the Adipose Tissue in Health and Metabolic Disease
Authors: Michailidou Zoi , Gomez-Salazar Mario , Alexaki Vasileia Ismini
Published: April 2021

Metabolic disorders, such as obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease, are characterized by chronic low-grade tissue and systemic inflammation. During obesity, the adipose tissue undergoes immunometabolic and functional transformation. Adipose tissue inflammation is driven by innate and adaptive immune cells and instigates insulin resistance. Here, we discuss the role of innate immune cells, that is, macrophages, neutrophils, eosinophils, natural killer cells, innate lymphoid type 2 cells, dendritic cells, and mast cells, in the adipose tissue in the healthy (lean) and diseased (obese) state and describe how their function is shaped by the obesogenic microenvironment, and humoral, paracrine, and cellular interactions. Moreover, we particularly outline the role of hypoxia as a central regulator in adipose tissue inflammation. Finally, we discuss the long-lasting effects of adipose tissue inflammation and its potential reversibility through drugs, caloric restriction, or exercise training.
Repetitive Mild Traumatic Brain Injury in a Perinatal Nicotine Exposure Mouse Model of Attention Deficit Hyperactivity Disorder
Authors: Zhang Lin , Levenson Cathy W. , Salazar Valentina Cea , McCarthy Deirdre M. , Biederman Joseph , Zafonte Ross , Bhide Pradeep G.
Published: April 2021

Attention deficit hyperactivity disorder (ADHD) increases the risk for concussion or mild traumatic brain injury (mTBI). At the same time, recommendations for the management of ADHD include participation in sports and other organized physical activities, including those that carry an increased risk of mTBI. Very little work has been done to determine the extent to which untreated ADHD adversely impacts behavioral outcomes of repeated mild concussions. Here, we used a perinatal nicotine exposure (PNE) mouse model of ADHD combined with a closed-head, repetitive mTBI model. The PNE mouse model carries significant construct, face, and predictive validity as a preclinical model of ADHD. Two-month-old PNE and control mice were subjected to closed-head repetitive mTBI or sham procedure once daily for 5 days. Object-based attention, novel object recognition memory, spatial working memory, and depression-like behavior were analyzed 1 day and 2 weeks following repeated mTBI. Consistent with our previous reports, mice in the PNE group showed significant deficits in object-based attention and working memory prior to mTBI. These deficits persisted following the repeated mTBI. Repeated mTBI produced a transient attention deficit in the control group but did not exacerbate the attention deficit that is characteristic of the PNE group. Although neither PNE nor repetitive mTBI alone influenced immobility in the tail suspension test, when PNE mice were subjected to mTBI, there was a transient increase in this measurement suggesting a synergistic effect of ADHD and mTBI on depression-like behavior. Thus, our data using the PNE mouse model suggest that ADHD may be a risk factor for transient depression following repeated mTBI and that repeated mTBI may be a risk factor for transient attention deficit.
The Kidney-Heart Connection in Obesity
Authors: García-Carrasco Almudena , Izquierdo-Lahuerta Adriana , Medina-Gómez Gema
Published: April 2021

There is a strong relationship between the kidney and the heart, where if one of these organs fails, so does the other, in the so-called cardiorenal syndrome (CRS). Besides, there are also interactions with the rest of the body leading to a metabolic state that establishes a feedback loop that is perpetuated. The CRS is characterized by hemodynamic changes, activation of neuro-humoral systems, natriuretic peptides, and changes in mineral metabolism. In this scenario, the kidney and heart, connected by a dysfunctional endothelium, inevitably fail. In obesity, this syndrome is exacerbated due to the complications of adipose tissue dysfunction, in the so-called cardiorenal metabolic syndrome (CRMetS). Obesity promotes adipose tissue dysfunction because it exceeds lipid storage capacity and leads to a lipotoxic state, characterized by inflammation, hypertension, insulin resistance and dyslipidemia, oxidative stress, and hyperuricemia, among others, that affect different organs other than the adipose tissue. In addition, the pro-inflammatory gut microbiota present in obese patients releases uremic toxins, contributing to oxidative stress and inflammation, perpetuating and accelerating the progression of this pathology. In this article, we describe the contribution of obesity, the factors and mechanisms implicated in the development of the CRMetS. Despite the great knowledge about the CRS, more research is needed to characterize the CRMetS given the global obesity epidemic.
Infliximab Therapeutic Drug Monitoring in Inflammatory Bowel Disease Virtual Biologics Clinic Leads to Durable Clinical Results
Authors: Sagar Rebecca , Lenti Marco V. , Clark Tanya , Rafferty Helen J. , Gracie David J. , Ford Alexander C. , O’Connor Anthony , Ahmad Tariq , Hamlin P. John , Selinger Christian P.
Published: April 2021

Background: Therapeutic drug monitoring (TDM) of infliximab (IFX) trough levels and anti-drug antibodies in conjunction with symptoms, disease history, and investigations can aid decision-making. This study evaluated 1-year outcomes of patients with decisions that were altered on the basis of TDM results, in order to investigate whether outcomes from TDM-based decisions to adjust or stop IFX treatment are durable. Methods: We retrospectively collected clinical outcomes 12 months post treatment decisions based on proactive TDM. Patients whose initial treatment decisions were altered on the basis of TDM results were compared with those where the decision remained unchanged. Events of interest were inpatient admissions with active inflammatory bowel disease (IBD), further changes to biologic therapy, and IBD-related health-care costs. Results: Of 189 patients, 54 (28%) had initial treatment decisions altered in the light of TDM results. The 135 patients whose initial decision was not altered in light of TDM results served as the comparator. There were no differences in hospitalization rates or subsequent biologic switches between the altered decision groups and the comparator group. IBD-related health-care costs were higher in those whose initial decision was altered (median GBP 7,912 vs. GBP 6,521; p < 0.0001) due to higher drug costs (median GBP 7,062 vs. GBP 6,012; p < 0.0001). Conclusion: Our study demonstrates good outcomes from changes to IFX treatment based on TDM. Patients with a decision to stop, switch, or continue with an adjusted IFX dose experienced comparable clinical outcomes but had higher drug-related expenditure than those whose treatment decision was not altered in light of TDM.
Antithrombotic Management in Ischemic Stroke with Essential Thrombocythemia: Current Evidence and Dilemmas
Authors: Das Shubhabrata , Deb Anasua , Pal Tanmoy
Published: April 2021

Thrombotic diseases like ischemic stroke are common complications of essential thrombocythemia (ET) due to abnormal megakaryopoiesis and platelet dysfunction. Ischemic stroke in ET can occur as a result of both cerebral arterial and venous thrombosis. Management of ET is aimed at preventing vascular complications including thrombosis. Acute management of ischemic stroke in ET is the same as that in the general population without myeloproliferative disorders. However, an ET patient with ischemic stroke is at high risk for rethrombosis and is therefore additionally managed with cytoreductive therapy and antithrombotic agents. Given abnormal platelet production in ET, there is suboptimal suppression of platelets with the standard recommended dose of aspirin for cardiovascular (CV) prevention. Hence, for optimal CV protection in ET, low-dose aspirin is recommended twice daily in an arterial thrombotic disease like atherothrombotic ischemic stroke in presence of the following risk factors: age >60 years, Janus kinase2 V617F gene mutation, and presence of CV risk factors. In the presence of the same risk factors, concurrent antiplatelet and anticoagulant therapy is suggested for venous thrombosis. However, increased risk of bleeding with dual antithrombotic agents poses a significant challenge in their use in cerebral venous thromboembolism or atrial fibrillation in presence of the above-mentioned risk factors. We discuss these dilemmas regarding antithrombotic management in ischemic stroke in ET in this case-based review of literature in the light of current evidence.