bluuebunny/crossref_metadata_2025_split huggingface dataset:
STAU2 protein level is controlled by caspases and the CHK1 pathway and regulates cell cycle progression in the non-transformed hTERT-RPE1 cells
Authors: Condé Lionel , Gonzalez Quesada Yulemi , Bonnet-Magnaval Florence , Beaujois Rémy , DesGroseillers Luc 
Published: March 2021

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.
The efficacy, safety and cost-effectiveness of hydroxychloroquine, sulfasalazine, methotrexate triple therapy in preventing relapse among patients with rheumatoid arthritis achieving clinical remission or low disease activity: the study protocol of a randomized controlled clinical Trial (ESCoRT study)
Authors: Zhao Juan , Zhou Wei , Wu Yangfeng , Ji Ping , Yang Li , Yan Xiaoyan , Zhang Zhuoli 
Published: March 2021

Abstract
Background
Tumor necrosis factor α inhibitors (TNFi) is effective for rheumatoid arthritis (RA) patients who fail to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Because of high cost, the discontinuation is common but often lead to disease relapse. The study aims to investigate, if the combination therapy of csDMARDs is more effective in reducing disease relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi and MTX.

Methods
It will be a two-stage trial. In the first stage, all RA patients who failed to csDMARDs treatment [disease activity score 28 (DAS28)-CRP > 3.2] will receive MTX plus TNFi for no more than 12 weeks. Patients achieving DAS28-CRP < 3.2 during the first stage will be randomized into three groups at 1:1:1 ratio: (A) add hydroxychloroquine (HCQ) and sulfasalazine (SSZ) for the first 12 weeks and then remove TNFi but continue other treatments for the next 48 weeks; (B) maintain TNFi + MTX for 60 weeks; and (C) maintain TNFi + MTX for the first 12 weeks and then remove TNFi but continue MTX monotherapy for the next 48 weeks. The primary outcome will be disease relapse (DAS28-CRP increases by at least 0.6 and > 3.2). Secondary outcomes will include the incremental cost per reducing 1 case of relapse; patient reported intolerance to the treatment; adverse events; change of mean disease activity measured by DAS28, clinical disease activity index (CDAI) and simplified disease activity index (SDAI); the proportion of modified Sharp score increase < 0.3; ultrasound-detected remission in hands; Health Assessment Questionnaire Disability Index (HAQ-DI) and health related quality of life [the five-level EuroQol-5D (EQ-5D-5L) and short form-6D (SF-6D)].

Discussion
The aim of this trail will be to seek effective treatment options of preventing relapse of RA. The results of the current study may provide an instructive recommendation for more economical application of TNFi treatment in RA.
Trial registration NCT, NCT02320630. Registered on 16 December 2014. https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=3&cx=-jg9qo2.
Multiple aplasia cutis congenita type V and fetus papyraceous: a case report and review of the literature
Authors: Thadchanamoorthy V. , Dayasiri Kavinda , Thirukumar M. , Thamilvannan N. , Chandraratne S. H. 
Published: March 2021

Abstract
Background
Aplasia cutis congenita is regarded as congenital focal absence of skin in the newborn, and occurrence of more than three similar skin defects is rare. The etiology is thought to be multifactorial, and precise etiopathogenesis is unknown.

Case presentation
A 13-day-old newborn Sri Lankan Tamil girl was referred to the dermatologic clinic with multiple skin defects at birth. There were six lesions on the body, and two of them had healed during intrauterine period, leaving scars. This was a second twin of her pregnancy. Her first twin fetus had demised before 19 weeks of pregnancy and was confirmed to be fetus papyraceous based on ultrasound-guided fetal assessment. The said child was thoroughly investigated and found to have no other congenital abnormalities. Chromosomal studies yielded normal findings. She was treated with tropical antibacterial ointment, and all lesions resolved spontaneously within 4 weeks, leaving scars. Physiotherapy was commenced to prevent contracture formation, and follow-up was arranged in collaboration with the plastic surgical team.

Conclusions
Aplasia cutis congenita is a rare condition of uncertain etiology, but consanguinity may play a role. This report described a newborn with type V cutis aplasia congenita in whom the diagnosis was confirmed based on clinical features and revision of antenatal history. The management depends on the pattern, extent, location, severity, underlying causes, and associated anomalies.
On a class of stochastic fractional kinetic equation with fractional noise
Authors: Lu Min , Liu Junfeng 
Published: March 2021

AbstractIn this article we study a class of stochastic fractional kinetic equations with fractional noise which are spatially homogeneous and are fractional in time with$H>1/2$H>1/2. The diffusion operator involved in the equation is the composition of the Bessel and Riesz potentials with any fractional parameters. We prove the existence of the solution under some mild conditions which generalized some results obtained by Dalang (Electron. J. Probab. 4(6):1–29, 1999) and Balan and Tudor (Stoch. Process. Appl. 120:2468–2494 , 2010). We study also its Hölder continuity with respect to space and time variables with$b=0$b=0. Moreover, we prove the existence for the density of the solution and establish the Gaussian-type lower and upper bounds for the density by the techniques of Malliavin calculus.
Economic burden of eating disorders in South Korea
Authors: Lee Sang Min , Hong Minha , Park Saengryeol , Kang Won Sub , Oh In-Hwan 
Published: March 2021

Abstract
Background
Few studies have investigated the epidemiology of eating disorders using national representative data. In this study, we investigated the treatment prevalence and economic burden of eating disorders in South Korea.

Methods
The aim of this study was to estimate the treatment prevalence and the medical expenditure of diagnosed eating disorders (ICD F50.x) in South Korea between 2010 and 2015. We also examined the economic costs of eating disorders, including the direct medical cost, direct non-medical costs, and indirect costs, in order to calculate the economic burden of such disorders.

Results
The total treatment prevalence of eating disorders in South Korea was 12.02 people (per 100,000) in 2010, and 13.28 in 2015. The cost of medical expenditures due to eating disorders increased from USD 1229724 in 2010 to USD 1843706 in 2015. The total economic cost of eating disorders was USD 5455626 in 2015. In 2015, the economic cost and prevalence of eating disorders was the highest in the 20–29 age group.

Conclusions
The results showed the eating disorders are insufficiently managed in the medical insurance system. Further research is therefore warranted to better understand the economic burdens of each type of eating disorder.
Inhibition of BCL11B induces downregulation of PTK7 and results in growth retardation and apoptosis in T-cell acute lymphoblastic leukemia
Authors: Li Kehan , Chen Cunte , Gao Rili , Yu Xibao , Huang Youxue , Chen Zheng , Liu Zhuandi , Chen Shaohua , Luo Gengxin , Huang Xin , Przybylski Grzegorz K. , Li Yangqiu , Zeng Chengwu 
Published: March 2021

AbstractT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of leukemia with poor prognosis, and biomarkers and novel therapeutic targets are urgently needed for this disease. Our previous studies have found that inhibition of the B-cell leukemia/lymphoma 11B (BCL11B) gene could significantly promote the apoptosis and growth retardation of T-ALL cells, but the molecular mechanism underlying this effect remains unclear. This study intends to investigate genes downstream of BCL11B and further explore its function in T-ALL cells. We found that PTK7 was a potential downstream target of BCL11B in T-ALL. Compared with the healthy individuals (HIs), PTK7 was overexpressed in T-ALL cells, and BCL11B expression was positively correlated with PTK7 expression. Importantly, BCL11B knockdown reduced PTK7 expression in T-ALL cells. Similar to the effects of BCL11B silencing, downregulation of PTK7 inhibited cell proliferation and induced apoptosis in Molt-4 cells via up-regulating the expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and p27. Altogether, our studies suggest that PTK7 is a potential downstream target of BCL11B, and downregulation of PTK7 expression via inhibition of the BCL11B pathway induces growth retardation and apoptosis in T-ALL cells.
On two extensions of the canonical Feller–Spitzer distribution
Authors: Vinogradov Vladimir Vladimirovich , Paris Richard Bruce 
Published: March 2021

AbstractWe introduce two extensions of the canonical Feller–Spitzer distribution from the class of Bessel densities, which comprise two distinct stochastically decreasing one-parameter families of positive absolutely continuous infinitely divisible distributions with monotone densities, whose upper tails exhibit a power decay. The densities of the members of the first class are expressed in terms of the modified Bessel function of the first kind, whereas the members of the second class have the densities of their Lévy measure given by virtue of the same function. The Laplace transforms for both these families possess closed–form representations in terms of specific hypergeometric functions. We obtain the explicit expressions by virtue of the particular parameter value for the moments of the distributions considered and establish the monotonicity of the mean, variance, skewness and excess kurtosis within the families. We derive numerous properties of members of these classes by employing both new and previously known properties of the special functions involved and determine the variance function for the natural exponential family generated by a member of the second class.
MicroRNAs in central nervous system disorders: current advances in pathogenesis and treatment
Authors: Hussein Mona , Magdy Rehab 
Published: March 2021

AbstractMicroRNAs (miRNAs) are a class of short, non-coding, regulatory RNA molecules that function as post transcriptional regulators of gene expression. Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer’s disease, Parkinson’s disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease. miRNAs are implicated in the pathogenesis of excitotoxicity, apoptosis, oxidative stress, inflammation, neurogenesis, angiogenesis, and blood–brain barrier protection. Consequently, miRNAs can serve as biomarkers for different neurological disorders. In recent years, advances in the miRNA field led to identification of potentially novel prospects in the development of new therapies for incurable CNS disorders. MiRNA-based therapeutics include miRNA mimics and inhibitors that can decrease or increase the expression of target genes. Better understanding of the mechanisms by which miRNAs are implicated in the pathogenesis of neurological disorders may provide novel targets to researchers for innovative therapeutic strategies.
Alveolar cleft and maximum cleft width as predictors for difficult laryngoscopy and intubation in patients with unilateral complete cleft lip and palate
Authors: Abdelhameed Gamal A. , Ghanem Wael A. , Armanios Simon H. , Abdelrahman Tamer Nabil 
Published: March 2021

Abstract
Background
Cleft lip and palate is one of the commonest congenital anomalies, which have an impact on feeding, speech, and dental development away from the significant psychosocial sequel. Early surgical repair aims to restore appearance and function, and the modern techniques can leave many defects undetectable. Therefore, the anesthetic challenge facing the pediatric airway with such abnormalities is still of a great impact. The aim of our study among 189 patients enrolled is to correlate alveolar gap and maximum cleft width measurements as predictors of difficult laryngoscopy and intubation in infants with unilateral complete cleft lip/palate aging from 1 to 6 months. As a secondary outcome, their weight is to be correlated too as another parameter.

Results
The alveolar gap and maximum cleft width are both of equal high predictive power (p value ≤ 0.001) with 100% sensitivity for both and specificity of 76.10% and 82.39% respectively, with a cut off value of ≤ 10 mm and 11 mm for these dimensions respectively, and odds ratio of incidence of difficult intubation is 4.18 and 5.68 respectively, while body weight ≤ 5.75 kg has an odds ratio of 2.32.

Conclusion
Alveolar cleft and maximum cleft width can be used as predictors for anticipation of difficult laryngoscopy and intubation infant patients with unilateral complete cleft lip and palate, while body weight ≤ 5.75 kg increases the risk more than twice.
Steroids—has the time come to extend their use to AML?
Authors: Farrugia Mariah , Cutajar Catriona , Agius Jean Calleja , Wismayer Pierre Schembri 
Published: March 2021

Abstract
Background
In 2018, leukaemia accounted for 2.6% of all new cancers, it being the 13th most common cause of cancer and the 10th most common cause of cancer death. Glucocorticoids are commonly used in lymphoid leukaemia treatment, where they are cytotoxic. The aim of this review is to highlight ongoing research of steroid use in myeloid leukaemias.

Main text
Glucocorticoids increase infection risks in acute myeloid leukaemia, but with adequate antifungal cover, they can help in hyperleucocytic disease. They also show some benefits in sensitising multidrug-resistant AML cell lines to cytotoxic agents, induce differentiation marker expression and can also induce CD38 expression, making AML cells possible targets of daratumumab.
Cardiotonic steroids, like digitalis, are being recognised as sensitising AML cells to the chemotherapeutic effects of many cytotoxic agents, primarily by inhibiting efflux pumps, thus minimising AML resistance.
Ecdysteroids enhance sensitivity in multidrug-resistant AML, but also in non-resistant AML cell lines, through pathways including the activation of mitochondrial apoptosis. Their anti-apoptotic effects on non-malignant cell lines help their target specificity. Sensitisation is chemotherapy-specific, enhancing the effects of doxorubicin and tubulin inhibitors but increasing resistance to cisplatinum.

Short conclusion
Cardiotonic steroids and ecdysteroids both show chemosensitisation to the cytotoxic effects of chemotherapy on AML cell lines. It is likely time to consider clinical trials to assess whether these, as well as traditional glucocorticoids, can contribute to the AML armamentarium, particularly in chemo-resistant disease.
Impact of silver nanoparticles as antibacterial agent derived from leaf and callus of Celastrus paniculatus Willd
Authors: Solanki Anita , Rathod Dipika , Patel Illa C. , Panigrahi Jitendriya 
Published: March 2021

Abstract
Background
Celastrus paniculatus Willd. is a rich source of numerous active constituents such as celapanigin, celapagin, malkangunin, celapanin, zeylasteral, pristimerin, and zeylasterone which render medicinal properties to its various parts. Therefore, the present work provides a protocol for the synthesis of AgNPs from in vivo leaf and in vitro developed callus extract of C. paniculatus and both the extracts have great antibacterial potential, which may give immense support for the drug preparation using AgNPs prepared from this valuable medicinal plant.

Results
High frequencies of calli induced from leaves and its counterpart, i.e., the natural part leaf were selected as the experimental materials for the green synthesis. The collected data exhibited gradual color variations started with whitish color, creamish, and after 8 weeks it ultimately turns into a solid mass of brownish callus. The silver nanoparticles (AgNPs) were synthesized using in vivo fresh leaves and in vitro developed callus extracts with an indication of brown colored complex. Further confirmation of AgNPs synthesis in both the samples was done using UV-visible spectral analysis followed by X-ray diffraction (XRD) analysis, Fourier transformation infrared spectroscopy (FTIR), and scanning electron microscopic (SEM) analysis.

Conclusion
The antibacterial activity of both extracts reflected the presence of the zone of inhibition in both gram-positive and gram-negative bacteria. AgNPs derived from callus extract showed better results with 24.00 ± 1.00 mm zones of inhibition. This protocol deserves the recognition of the antibacterial potential of AgNPs synthesized from CP plant extracts.
Integer Programming Formulations for Minimum Spanning Tree Interdiction
Authors: Wei Ningji , Walteros Jose L. , Pajouh Foad Mahdavi 
Published: March 2021

We consider a two-player interdiction problem staged over a graph where the attacker’s objective is to minimize the cost of removing edges from the graph so that the defender’s objective, that is, the weight of a minimum spanning tree in the residual graph, is increased up to a predefined level r. Standard approaches for graph interdiction frame this type of problems as bilevel formulations, which are commonly solved by replacing the inner problem by its dual to produce a single-level reformulation. In this paper, we study an alternative integer program derived directly from the attacker’s solution space and show that this formulation yields a stronger linear relaxation than the bilevel counterpart. Furthermore, we analyze the convex hull of the feasible solutions of the problem and identify several families of facet-defining inequalities that can be used to strengthen this integer program. We then proceed by introducing a different formulation defined by a set of so-called supervalid inequalities that may exclude feasible solutions, albeit solutions whose objective value is not better than that of an edge cut of minimum cost. We discuss several computational aspects required for an efficient implementation of the proposed approaches. Finally, we perform an extensive set of computational experiments to test the quality of these formulations, analyzing and comparing the benefits of each model, as well as identifying further enhancements.Summary of Contribution: Network interdiction has received significant attention over the last couple of decades, with a notable peak of interest in recent years. This paper provides an interesting balance between the theoretical and computational aspects of solving a challenging network interdiction problem via integer programming. We present several technical developments, including a detailed study of the problem's solution space, multiple formulations, and a polyhedral analysis of the convex hull of feasible solutions. We then analyze the results of an extensive set of computational experiments that were used to validate the effectiveness of the different methods we developed in this paper.
Level of hemoglobin among cow milk and camel milk consuming young children: A comparative study
Authors: Abdurahman Ahmed , Gashu Dawd 
Published: March 2021

BackgroundCow milk is an important source of macro-and micronutrients. However, it has low iron content but high content of casein and calcium thus could negatively influence hemoglobin synthesis. On the other hand, camel milk contains higher iron concentration than cow milk. In addition, the majority of iron in camel milk is associated with the lower molecular fraction of casein suggesting better bioavailability. Furthermore, vitamin C concentration, a useful iron absorption enhancer, is more than three-fold greater in camel milk than cow milk. This study compared hemoglobin concentration among young children consuming consistently cow milk or camel milk.MethodsHemoglobin concentration of young children (aged 6–59 mo) from settled pastoralist communities of the Somali region, Ethiopia, consistently consuming cow milk (n = 166) or camel milk (n = 166) was determined. In addition, socio-demographic and water, sanitation, and hygienic (WASH) conditions of study participants’ households were captured. Furthermore, dietary intake and anthropometric characteristics of participating children were assessed.ResultsAmong the participating children, 38.6% were underweight, 33.4% were stunted, and 34.5% were wasted. In addition, 77.4% of children were anemic. The present study households had poor WASH conditions. Only 0.6% of children had the minimum acceptable dietary diversity. There was small but significant mean hemoglobin difference among camel milk and cow milk consuming children (9.6±1.8 g/dl vs 9.1±2.2 g/dl; p = 0.012). In addition, the odds of low hemoglobin concentration was greater among cow milk consuming children than camel milk consuming children [AOR 2.17; 95 CI; 1.39, 3.37; p = 0.001]. However, the overall anemia prevalence among the two groups was similar.ConclusionCamel milk consumption is associated with better hemoglobin concentration but may not be sufficient to prevent anemia in populations from resource poor settings. The etiology of anemia is multifactorial thus further studies on the link between milk consumption and hemoglobin concentration are important.