bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced PeriOperative Care and Health protection programme for the prevention of surgical site infections after elective abdominal surgery (EPO2CH): statistical analysis plan of a randomised controlled multicentre superiority trial
Authors:   for the EPO2CH study group, de Jonge S. W. , Wolfhagen N. , Zwinderman A. H. , Hollmann M. W. , Boermeester M. A. , Dijkgraaf M. G. W. 
Published: April 2021

Abstract
Background
Surgical site infections (SSI) are frequent complications after elective abdominal surgery. We designed the Enhanced PeriOperative Care and Health Protection programme (EPO2CH) care bundle, comprising of intraoperative high fractional inspired oxygen; intraoperative goal-directed fluid therapy; active preoperative, intraoperative and postoperative warming; glucose control and treatment of hyperglycaemia (> 10 mmol L− 1) in diabetics as well as non-diabetics; and wound irrigation before closure using an aqueous antiseptic. We hypothesise that EPO2CH added to standard care reduces the incidence of SSI compared to standard care alone for elective abdominal surgery.

Methods
This trial is designed as an open label, pragmatic randomised controlled parallel-group multicentre superiority trial. The primary endpoint is the incidence of SSI, defined by the Centers for Disease Control and prevention, within 30 days after surgery. The incidence of SSI is assessed using the Dutch national complication register and medical chart review. Secondary endpoints include the SSI incidence within 90 days, incidence of anastomotic leakage at 30 and 90 days, the incidence of incisional hernia within 1 year, mortality within 1 year and 5 years, quality of life, health and disability, and cost-effectiveness. Primarily, an intention-to-treat analysis will be performed to estimate the relative risk using a log binomial model. If not feasible, a logistic regression will be used to estimate the odds ratio. A per-protocol analysis will also be performed. Furthermore, the attributive effect of the distinct interventions will be explored.

Discussion
The results of the EPO2CH trial will determine if the EPO2CH bundle is effective to prevent SSI incidence for patients undergoing elective abdominal surgery. Details of the statistical analysis are described in this Statistical Analysis Plan (SAP).

Trial registration
Registration number: Dutch Trial Register Trial NL5572. Registered on March 3, 2016.
SAP version: V1.0, January 8, 2020. This SAP has been written based on study protocol V10.
Multisite transcranial direct current stimulation associated with cognitive training in episodic memory and executive functions in individuals with Alzheimer’s disease: a case report
Authors: Marchi Letícia Zanetti , Ferreira Rayssa Gabriela Dantas , de Lima Gabriella Nayara Siqueira , da Silva Jessyca Alves Silvestre , da Cruz Daniel Marinho Cezar , Fernandez-Calvo Bernardino , Andrade Suellen Mary Marinho dos Santos 
Published: April 2021

Abstract
Background
Dementia is among the most common chronic noncommunicable neurodegenerative diseases. In the long term, it causes disability and loss of autonomy and independence. It is estimated that there are 35.6 million people with Alzheimer’s disease worldwide. Several clinical aspects of this disease have been widely studied, but the main focus of study has been memory loss, which is one of the first symptoms. The present study proposes an innovative intervention that combines cognitive training and multisite transcranial direct current stimulation, which interferes with other clinical aspects of the subject.

Case presentation
In this study, we present two subjects diagnosed with mild Alzheimer’s disease. Subject 1 is an 82-year-old Brazilian Latin American woman with a high school education who was diagnosed with Alzheimer’s disease 8 years ago and uses an Exelon patch. Subject 2 is an 88-year-old Brazilian Latin American woman with an incomplete primary education who was diagnosed with Alzheimer’s disease 1 year ago and received medical orientation to temporarily discontinue medications for Alzheimer’s disease. Both participants were subjected to intermittent cognitive training sessions and concomitant transcranial stimulation in three weekly 30-minute sessions in which a brain area was stimulated every 10 minutes for a total of 24 sessions, with a 2-month follow-up. Transcranial stimulation was applied to six different regions of the cortex: the dorsolateral prefrontal cortex bilaterally, the somatosensory association cortex bilaterally and Broca’s and Wernicke’s areas. Comparing the results of tests performed before and after the treatment period, a 1-point improvement was observed for both subjects on the Word Recall task of the Alzheimer Disease Assessment Scale, which evaluates symptoms related to the decline of episodic memory. Improvement in the executive functions domain was also observed through the results of the Stroop test, Victoria version.

Conclusions
The results from the two presented cases show that multisite transcranial stimulation associated with cognitive training is an effective adjuvant method for the treatment of patients diagnosed with mild Alzheimer’s disease. Its effects can benefit patients’ daily routines by reducing cognitive deficits by keeping intact areas active and/or compensating for lost functions.
Trial registration NCT02772185. Registered 13 May 2016, http://www.clinicaltrials.gov/ct2/show/NCT02772185. Retrospectively registered.
Efficient differentiation of human embryonic stem cells to retinal pigment epithelium under defined conditions
Authors: Limnios Ioannis J. , Chau Yu-Qian , Skabo Stuart J. , Surrao Denver C. , O’Neill Helen C. 
Published: April 2021

Abstract
Age-related macular degeneration (AMD) is a highly prevalent form of blindness caused by loss death of cells of the retinal pigment epithelium (RPE). Transplantation of pluripotent stem cell (PSC)-derived RPE cells is considered a promising therapy to regenerate cell function and vision.

Objective
The objective of this study is to develop a rapid directed differentiation method for production of RPE cells from PSC which is rapid, efficient, and fully defined and produces cells suitable for clinical use.

Design
A protocol for cell growth and differentiation from hESCs was developed to induce differentiation through screening small molecules which regulated a primary stage of differentiation to the eyefield progenitor, and then, a subsequent set of molecules to drive differentiation to RPE cells. Methods for cell plating and maintenance have been optimized to give a homogeneous population of cells in a short 14-day period, followed by a procedure to support maturation of cell function.

Results
We show here the efficient production of RPE cells from human embryonic stem cells (hESCs) using small molecules in a feeder-free system using xeno-free/defined medium. Flow cytometry at day 14 showed ~ 90% of cells expressed the RPE markers MITF and PMEL17. Temporal gene analysis confirmed differentiation through defined cell intermediates. Mature hESC-RPE cell monolayers exhibited key morphological, molecular, and functional characteristics of the endogenous RPE.

Conclusion
This study identifies a novel cell differentiation process for rapid and efficient production of retinal RPE cells directly from hESCs. The described protocol has utility for clinical-grade cell production for human therapy to treat AMD.
Transition technologies towards 6G networks
Authors: Raddo Thiago R. , Rommel Simon , Cimoli Bruno , Vagionas Chris , Perez-Galacho Diego , Pikasis Evangelos , Grivas Evangelos , Ntontin Konstantinos , Katsikis Michael , Kritharidis Dimitrios , Ruggeri Eugenio , Spaleniak Izabela , Dubov Mykhaylo , Klonidis Dimitrios , Kalfas George , Sales Salvador , Pleros Nikos , Tafur Monroy Idelfonso 
Published: April 2021

AbstractThe sixth generation (6G) mobile systems will create new markets, services, and industries making possible a plethora of new opportunities and solutions. Commercially successful rollouts will involve scaling enabling technologies, such as cloud radio access networks, virtualization, and artificial intelligence. This paper addresses the principal technologies in the transition towards next generation mobile networks. The convergence of 6G key-performance indicators along with evaluation methodologies and use cases are also addressed. Free-space optics, Terahertz systems, photonic integrated circuits, softwarization, massive multiple-input multiple-output signaling, and multi-core fibers, are among the technologies identified and discussed. Finally, some of these technologies are showcased in an experimental demonstration of a mobile fronthaul system based on millimeter 5G NR OFDM signaling compliant with 3GPP Rel. 15. The signals are generated by a bespoke 5G baseband unit and transmitted through both a 10 km prototype multi-core fiber and 4 m wireless V-band link using a pair of directional 60 GHz antennas with 10° beamwidth. Results shown that the 5G and beyond fronthaul system can successfully transmit signals with both wide bandwidth (up to 800 MHz) and fully centralized signal processing. As a result, this system can support large capacity and accommodate several simultaneous users as a key candidate for next generation mobile networks. Thus, these technologies will be needed for fully integrated, heterogeneous solutions to benefit from hardware commoditization and softwarization. They will ensure the ultimate user experience, while also anticipating the quality-of-service demands that future applications and services will put on 6G networks.
Research on task-offloading decision mechanism in mobile edge computing-based Internet of Vehicle
Authors: Cheng Jun , Guan Dejun 
Published: April 2021

AbstractAs a technology integrated with Internet of things, mobile edge computing (MEC) can provide real-time and low-latency services to the underlying network and improve the storage and computation ability of the networks instead of central cloud infrastructure. In mobile edge computing-based Internet of Vehicle (MEC-IoV), the vehicle users can deliver their tasks to the associated MEC servers based on offloading policy, which improves the resource utilization and computation performance greatly. However, how to evaluate the impact of uncertain interconnection between the vehicle users and MEC servers on offloading decision-making and avoid serious degradation of the offloading efficiency are important problems to be solved. In this paper, a task-offloading decision mechanism with particle swarm optimization for MEC-IoV is proposed. First, a mathematical model to calculate the computation offloading cost for cloud-edge computing system is defined. Then, the particle swarm optimization is applied to convert the offloading of task into the process and obtain the optimal offloading strategy. Furthermore, to avoid falling into local optimization, the inertia weight factor is designed to change adaptively with the value of the objective function. The experimental results show that the proposed offloading strategy can effectively reduce the energy consumption of terminal devices while guarantee the service quality of users.
Existence of radial solutions for a $p(x)$-Laplacian Dirichlet problem
Authors: Ragusa Maria Alessandra , Razani Abdolrahman , Safari Farzaneh 
Published: April 2021

AbstractIn this paper, using variational methods, we prove the existence of at least one positive radial solution for the generalized$p(x)$p(x)-Laplacian problem$$ -\Delta _{p(x)} u + R(x) u^{p(x)-2}u=a (x) \vert u \vert ^{q(x)-2} u- b(x) \vert u \vert ^{r(x)-2} u $$−Δp(x)u+R(x)up(x)−2u=a(x)|u|q(x)−2u−b(x)|u|r(x)−2uwith Dirichlet boundary condition in the unit ball in$\mathbb{R}^{N}$RN(for$N \geq 3$N≥3), wherea,b,Rare radial functions.
An efficient HILIC-MS/MS method for the trace level determination of three potential genotoxic impurities in aripiprazole active drug substance
Authors: Mullangi Sumanth , Ravindhranath Kunta , Panchakarla Ravi Kiran 
Published: April 2021

AbstractA sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method was developed and validated for trace analysis of potential genotoxic impurities (PGIs): 2,3-dichloroaniline (PGI-1), bis(2-chloroethyl) amine (PGI-2), and 2-chloroethylamine (PGI-3), in aripiprazole (APZ) active drug substance. Separation of analytes was achieved on ACE HILIC–N Column (HILN-5-1046U, 100 × 4.6 mm, 5 μm) in gradient elution mode with mobile phase A [acetonitrile:ammonium formate buffer (95:5 v/v)] and mobile phase B [acetonitrile:ammonium formate buffer (50:50 v/v)] at a flow rate of 0.8 mL/min. Developed method was linear in the concentration range of 8–100 ppm for PGI-1, 11–100 ppm for PGI-2, and 12.5–100ppm for PGI-3 with R2 > 0.996. The developed method was accurate for quantification of each PGI with percent recoveries greater than 96% and RSD (%) not more than 5%. The developed method was precise for quantification of PGIs in aripiprazole with RSD (%) of not more than 4% for any of the PGIs. There was no interference of diluent peaks at the retention time of the PGIs and APZ in the method. All the PGIs and sample solutions were found to be stable at ambient laboratory temperature (25 ± 5 °C) and refrigerated condition (2–8 °C) for a period of 48 h. The developed HILIC-MS/MS method can be used for trace quantification of PGIs in aripiprazole drug in quality control laboratories of the pharmaceutical industry.
Death after discharge: prognostic model of 1-year mortality in traumatic brain injury patients undergoing decompressive craniectomy
Authors: Cui Wenxing , Ge Shunnan , Shi Yingwu , Wu Xun , Luo Jianing , Lui Haixiao , Zhu Gang , Guo Hao , Feng Dayun , Qu Yan 
Published: April 2021

Abstract
Background
Despite advances in decompressive craniectomy (DC) for the treatment of traumatic brain injury (TBI), these patients are at risk of having a poor long-term prognosis. The aim of this study was to predict 1-year mortality in TBI patients undergoing DC using logistic regression and random tree models.

Methods
This was a retrospective analysis of TBI patients undergoing DC from January 1, 2015, to April 25, 2019. Patient demographic characteristics, biochemical tests, and intraoperative factors were collected. One-year mortality prognostic models were developed using multivariate logistic regression and random tree algorithms. The overall accuracy, sensitivity, specificity, and area under the receiver operating characteristic curves (AUCs) were used to evaluate model performance.

Results
Of the 230 patients, 70 (30.4%) died within 1 year. Older age (OR, 1.066; 95% CI, 1.045–1.087; P < 0.001), higher Glasgow Coma Score (GCS) (OR, 0.737; 95% CI, 0.660–0.824; P < 0.001), higher d-dimer (OR, 1.005; 95% CI, 1.001–1.009; P = 0.015), coagulopathy (OR, 2.965; 95% CI, 1.808–4.864; P < 0.001), hypotension (OR, 3.862; 95% CI, 2.176–6.855; P < 0.001), and completely effaced basal cisterns (OR, 3.766; 95% CI, 2.255–6.290; P < 0.001) were independent predictors of 1-year mortality. Random forest demonstrated better performance for 1-year mortality prediction, which achieved an overall accuracy of 0.810, sensitivity of 0.833, specificity of 0.800, and AUC of 0.830 on the testing data compared to the logistic regression model.

Conclusions
The random forest model showed relatively good predictive performance for 1-year mortality in TBI patients undergoing DC. Further external tests are required to verify our prognostic model.
Methylation as a critical epigenetic process during tumor progressions among Iranian population: an overview
Authors: Akhlaghipour Iman , Bina Amir Reza , Abbaszadegan Mohammad Reza , Moghbeli Meysam 
Published: April 2021

AbstractCancer is one of the main health challenges and leading causes of deaths in the world. Various environmental and genetic risk factors are associated with tumorigenesis. Epigenetic deregulations are also important risk factors during tumor progression which are reversible transcriptional alterations without any genomic changes. Various mechanisms are involved in epigenetic regulations such as DNA methylation, chromatin modifications, and noncoding RNAs. Cancer incidence and mortality have a growing trend during last decades among Iranian population which are significantly related to the late diagnosis. Therefore, it is required to prepare efficient molecular diagnostic panels for the early detection of cancer in this population. Promoter hyper methylation is frequently observed as an inhibitory molecular mechanism in various genes associated with DNA repair, cell cycle regulation, and apoptosis during tumor progression. Since aberrant promoter methylations have critical roles in early stages of neoplastic transformations, in present review we have summarized all of the aberrant methylations which have been reported during tumor progression among Iranian cancer patients. Aberrant promoter methylations are targetable and prepare novel therapeutic options for the personalized medicine in cancer patients. This review paves the way to introduce a non-invasive methylation specific panel of diagnostic markers for the early detection of cancer among Iranians.
3D rock minerals by correlating XRM and automated mineralogy and its application to digital rock physics for elastic properties
Authors: Hao Jin , Li Guoliang , Su Jiao , Yuan Yuan , Du Zhongming , Niu Suyun , Yang Jijin 
Published: April 2021

Digital rock physics (DRP) is an emerging technique that has rapidly become an indispensable tool to estimate elastic properties. The success of DRP mainly depends on three factors: acquiring a 3D rock structure image, accurately identifying 3D minerals, and using a proper numerical simulation method. Shales present a substantial challenge for DRP owing to their heterogeneous structure, composition, and properties from micron to centimeter scale. To obtain a sufficiently large field-of-view (FOV) image of a sample that reflects the detailed and representative internal structure and composition, we have developed a new DRP workflow to obtain large-FOV high-resolution digital rocks with 3D mineralogical information. Using the “divide-and-stitch” technique, a long shale sample is divided into several subunits, imaged separately by high-resolution X-ray microscopy (XRM), and then stitched to obtain a large-FOV 3D digital rock. An FOV of a rock cylinder (736 μm in diameter, 2358 μm in height, and 1 μm resolution) is used as an example. By correlating XRM and automated mineralogy, a large-FOV 3D mineral digital rock is obtained from a shale sample. Six mineral phases are identified and verified by automated mineralogy, and four laminae are detected according to the grain size, which offer a new perspective to study sedimentary processes and heterogeneities at the millimeter scale. The finite-difference method is used to compute the elastic properties of the large-FOV 3D mineral digital rock, and the results of Young’s modulus are within the limit of the Voigt/Reuss bounds. It also reveals that there is a difference in simulated elastic properties in the four laminae. The large-FOV 3D mineral digital rock offers the potential to explore the relationship between elastic properties and mineral phases, as well as the heterogeneities of elastic properties at the millimeter scale.
Development of a Pediatric Relative Bioavailability/Bioequivalence Database and Identification of Putative Risk Factors Associated With Evaluation of Pediatric Oral Products
Authors: Pawar Gopal , Wu Fang , Zhao Liang , Fang Lanyan , Burckart Gilbert J. , Feng Kairui , Mousa Youssef M. , Naumann Franci , Batchelor Hannah K. 
Published: April 2021

AbstractGenerally, bioequivalence (BE) studies of drug products for pediatric patients are conducted in adults due to ethical reasons. Given the lack of direct BE assessment in pediatric populations, the aim of this work is to develop a database of BE and relative bioavailability (relative BA) studies conducted in pediatric populations and to enable the identification of risk factors associated with certain drug substances or products that may lead to failed BE or different pharmacokinetic (PK) parameters in relative BA studies in pediatrics. A literature search from 1965 to 2020 was conducted in PubMed, Cochrane Library, and Google Scholar to identify BE studies conducted in pediatric populations and relative BA studies conducted in pediatric populations. Overall, 79 studies covering 37 active pharmaceutical ingredients (APIs) were included in the database: 4 bioequivalence studies with data that passed BE evaluations; 2 studies showed bioinequivalence results; 34 relative BA studies showing comparable PK parameters, and 39 relative BA studies showing differences in PK parameters between test and reference products. Based on the above studies, common putative risk factors associated with differences in relative bioavailability (DRBA) in pediatric populations include age-related absorption effects, high inter-individual variability, and poor study design. A database containing 79 clinical studies on BE or relative BA in pediatrics has been developed. Putative risk factors associated with DRBA in pediatric populations are summarized.
Two UV-sensitive targets in dorsoanterior specification of frog embryos
Authors: Elinson Richard P. , Pasceri Peter 
Published: April 2021

ABSTRACT
Previous work has shown that ultraviolet (UV) irradiation of fertilized frog eggs yields embryos that lack dorsal and anterior structures. The eggs fail to undergo the cortical/cytoplasmic rotation that specifies dorsoventral polarity, and they lack an array of parallel microtubules associated with the rotation. These eggs can be rescued by tilting with respect to gravity, and normal dorsoanterior development occurs. We find here that UV irradiation of Xenopus prophase I oocytes or Rana metaphase I oocytes also causes the dorsoanterior deficient syndrome, but the UV target is different from that in fertilized eggs. Tilting eggs, irradiated as oocytes, with respect to gravity, does not rescue dorsoanterior development, although lithium treatment does. The UV dose required to produce dorsoanterior deficiency for Rana metaphase I oocytes is much less than that for fertilized eggs, and the oocytes can form the array of parallel microtubules and undergo the cortical/ cytoplasmic rotation after fertilization. Despite these features of normal development, no dorsoanterior structures form. While the UV target in fertilized eggs is thought to be the parallel microtubules (Elinson & Rowning, 1988; Devi Biol. 128, 185–197), the UV target in the oocytes may be a dorsal determinant.