bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review of cognitive impairment and brain insult after mechanical ventilation
Authors: Bassi Thiago G. , Rohrs Elizabeth C. , Reynolds Steven C. 
Published: March 2021

AbstractWe conducted a systematic review following the PRISMA protocol primarily to identify publications that assessed any links between mechanical ventilation (MV) and either cognitive impairment or brain insult, independent of underlying medical conditions. Secondary objectives were to identify possible gaps in the literature that can be used to inform future studies and move toward a better understanding of this complex problem. The preclinical literature suggests that MV is associated with neuroinflammation, cognitive impairment, and brain insult, reporting higher neuroinflammatory markers, greater evidence of brain injury markers, and lower cognitive scores in subjects that were ventilated longer, compared to those ventilated less, and to never-ventilated subjects. The clinical literature suggests an association between MV and delirium, and that delirium in mechanically ventilated patients may be associated with greater likelihood of long-term cognitive impairment; our systematic review found no clinical study that demonstrated a causal link between MV, cognitive dysfunction, and brain insult. More studies should be designed to investigate ventilation-induced brain injury pathways as well as any causative linkage between MV, cognitive impairment, and brain insult.
Identification of pathogenic variants in cancer genes using base editing screens with editing efficiency correction
Authors: Huang Changcai , Li Guangyu , Wu Jiayu , Liang Junbo , Wang Xiaoyue 
Published: March 2021

AbstractBackgroundMillions of nucleotide variants are identified through cancer genome sequencing and it is clinically important to identify the pathogenic variants among them. By introducing base substitutions at guide RNA target regions in the genome, CRISPR-Cas9-based base editors provide the possibility for evaluating a large number of variants in their genomic context. However, the variability in editing efficiency and the complexity of outcome mapping are two existing problems for assigning guide RNA effects to variants in base editing screens.ResultsTo improve the identification of pathogenic variants, we develop a framework to combine base editing screens with sgRNA efficiency and outcome mapping. We apply the method to evaluate more than 9000 variants across all the exons ofBRCA1andBRCA2genes. Our efficiency-corrected scoring model identifies 910 loss-of-function variants forBRCA1/2, including 151 variants in the noncoding part of the genes such as the 5′ untranslated regions. Many of them are identified in cancer patients and are reported as “benign/likely benign” or “variants of uncertain significance” by clinicians. Our data suggest a need to re-evaluate their clinical significance, which may be helpful for risk assessment and treatment of breast and ovarian cancer.ConclusionsOur results suggest that base editing screens with efficiency correction is a powerful strategy to identify pathogenic variants in a high-throughput manner. Applying this strategy to assess variants in both coding and noncoding regions of the genome could have a direct impact on the interpretation of cancer variants.
Editing GWAS: experimental approaches to dissect and exploit disease-associated genetic variation
Authors: Rao Shuquan , Yao Yao , Bauer Daniel E. 
Published: March 2021

AbstractGenome-wide association studies (GWAS) have uncovered thousands of genetic variants that influence risk for human diseases and traits. Yet understanding the mechanisms by which these genetic variants, mainly noncoding, have an impact on associated diseases and traits remains a significant hurdle. In this review, we discuss emerging experimental approaches that are being applied for functional studies of causal variants and translational advances from GWAS findings to disease prevention and treatment. We highlight the use of genome editing technologies in GWAS functional studies to modify genomic sequences, with proof-of-principle examples. We discuss the challenges in interrogating causal variants, points for consideration in experimental design and interpretation of GWAS locus mechanisms, and the potential for novel therapeutic opportunities. With the accumulation of knowledge of functional genetics, therapeutic genome editing based on GWAS discoveries will become increasingly feasible.
Lack of detection of the Middle East respiratory syndrome coronavirus (MERS-CoV) nucleic acids in some Hyalomma dromedarii infesting some Camelus dromedary naturally infected with MERS-CoV
Authors: Hemida Maged Gomaa , Alhammadi Mohammed , Almathen Faisal , Alnaeem Abdelmohsen 
Published: March 2021

Abstract
Objective
The Middle East respiratory syndrome coronavirus (MERS-CoV) is one of the zoonotic coronaviruses [Hemida Peer J 7:e7556, 2019; Hemida et al. One Health 8:100102, 2019]. The dromedary camels remained the only known animal reservoir for this virus. Several aspects of the transmission cycle of the virus between animals, including arthropod-borne infection, is still largely unknown. The main objective of the current work was to study the possibility of MERS-CoV transmission through some arthropod vectors, particularly the hard ticks. To achieve this objective, we identified a positive MERS-CoV dromedary camel herd using the commercial available real-time PCR kits. We collected some arthropods, particularly the ticks from these positive animals as well as from the animal habitats. We tested these arthropods for the presence of MERS-CoV viral RNAs.

Results
Our results showing the absence of any detectable MERS-CoV-RNAs in these arthropods despite these animals were actively shedding the virus in their nasal secretions. Our results are confirming for the first the failure of detection of the MERS-CoV in ticks infesting dromedary camels. Failure of the detection of MERS-CoV in ticks infesting positive naturally infected MERS-CoV camels is strongly suggesting that ticks do not play roles in the transmission of the virus among the animals and close contact humans.
Mitochondrial activity regulates the differentiation of skin-derived mesenchymal stem cells into brown adipocytes to contribute to hypertension
Authors: Xi Wenda , Chen Wendong , Sun Weihong , Li Xiangxiao , Suo Zhimin , Jiang Gonghao , Gao Pingjin , Li Qun 
Published: March 2021

Abstract
Background
Brown adipocytes (BAs) are major components of brown adipose tissue (BAT), which is involved in blood pressure regulation. BAs are derived from multiple progenitors, including PDGFRα+ adipose-derived stem cells (ASCs). Skin-derived mesenchymal stem cells (S-MSCs) have the capacity to differentiate into adipocytes; however, their ability to differentiate into BAs remains unexplored. We aim to study the ability and regulatory mechanism of the differentiation of S-MSCs into BAs and the direct role of BAT in blood pressure regulation.

Methods
Protein expression was measured by flow cytometry or Western blotting, and gene mRNA levels were quantified by real-time quantitative PCR (RT-PCR). To induce the differentiation of S-MSCs into BAs, S-MSCs were stimulated with a brown adipogenic cocktail comprising insulin, IBMX, dexamethasone, triiodothyronine (T3), and rosiglitazone for the indicated periods. The oxygen consumption rate (OCR) was measured with an XF24 Extracellular Flux Analyzer. Mitochondrial mass was determined by flow cytometry and fluorescence staining. Hypertension was induced in WT mice by infusion of angiotensin II (Ang II), and systolic blood pressure (SBP) was measured using a tail cuff. Interscapular brown adipose tissue (iBAT)-deficient mice were generated by surgical removal of the iBAT depot, after which the animals were allowed to recover for 6 days. Aortic, iBAT, and heart tissue sections were analyzed by hematoxylin and eosin (HE) staining.

Results
We found that in vitro, S-MSCs isolated from the mouse dermis expressed the stem cell markers CD90/105 and PDGFRα and readily differentiated into BAs. Mitochondrial biogenesis and oxygen consumption were markedly increased during differentiation of S-MSCs into BAs. In vivo, iBAT was converted to white adipose tissue (WAT) in Ang II-induced hypertensive mice. We assessed the direct role of BAT in blood pressure (BP) regulation by using iBAT-deficient mice (generated by surgical removal of iBAT) and C57BL/6 (wild-type (WT)) mice and found that Ang II-induced BP elevation and vascular damage were markedly aggravated in iBAT-deficient mice compared with WT mice.

Conclusions
This study demonstrates that PDGFRα+ S-MSCs are able to differentiate into BAs and that this differentiation is regulated by mitochondrial activity. We also show that BAT plays a direct role in ameliorating Ang II-induced hypertension. The therapeutic potential of BAT for the prevention of hypertension-induced organ remodeling thus warrants further investigation.

Graphical abstract. Schematic of the in vitro differentiation of PDGFRα+ S-MSCs into BAs via a process regulated by mitochondrial activity. BAT plays a direct role in Ang II-induced hypertension and target organ remodeling
Initial inpatient management of adolescents and young adults admitted with severe malnutrition due to anorexia nervosa: protocol for a systematic review
Authors: Proulx-Cabana Stéphanie , Taddeo Danielle , Jamoulle Olivier , Frappier Jean-Yves , Tremblay-Racine Fannie , Stheneur Chantal 
Published: March 2021

Abstract
Background
Anorexia Nervosa (AN) is a highly prevalent disease in adolescents and young adults (AYAs). The quality of initial inpatient medical management in a patient with severe malnutrition due to AN is crucial to prevent further medical instability. This review aims to inventory evidence regarding initial refeeding and management of AYAs with AN in an inpatient setting, in order to avoid medical complications.

Methods
A systematic review will be conducted using PubMed, MEDLINE, All EBM Reviews, Embase, PsycINFO, Cochrane Database and CINAHL. The search strategy consists of terms related to anorexia, hospitalization and Pediatrics. Randomized controlled trials, case-control studies, cross-sectional and cohort studies will be included. Participants will include adolescents and adults 18–24 years old diagnosed with AN and meeting criteria for severe disease. The primary outcome will be any of the following complications: hypophosphatemia, refeeding syndrome, hypoglycemia, cardiac arrythmia, hepatic cytolysis or death. Data will be extracted and the risk of bias will be assessed by one author and reviewed by a second author. Results will be presented in a systematic narrative synthesis format. The quality of evidence for all outcomes will be evaluated using the GRADE methodology.

Discussion
This systematic review will examine current evidence on initial inpatient refeeding and help to document effectiveness of initial inpatient management in AYAs with severe AN in avoiding further medical complications.

Trial registration
This study is registered on PROSPERO under the reference number CRD42019123608.
Relationship between adiponectin, TNFα, and SHBG in prepubertal children with obesity
Authors: Ramon-Krauel Marta , Leal-Witt María Jesús , Osorio-Conles Óscar , Amat-Bou Montse , Lerin Carles , Selva David M. 
Published: March 2021

Abstract
Background
Sex hormone-binding globulin (SHBG) levels are low in adult subjects with obesity when compared to normal-weight individuals. Obesity is associated with higher tumor necrosis factor alpha (TNFα) plasma levels and lower adiponectin levels. Moreover, we have recently elucidated the molecular mechanisms by which TNFα and adiponectin regulate hepatic SHBG production.

Aim
The main objective of this study was to assess if the adult associations between TNFα, adiponectin, and SHBG are present in prepubertal children.

Methods
We determined several morphometric and biochemical parameters in normal-weight (n=15) and obese prepubertal (n=51) children, as well as quantified plasma SHBG, TNFα receptor 1 (TNFα-R1), and adiponectin levels.

Results
Our results showed that prepubertal children with obesity had decreased plasma SHBG levels compared to normal-weight controls (67 nmol/L vs 172 nmol/L). Importantly, SHBG plasma levels correlated significantly (P < 0.05) with TNFα (negatively, ßstd= − 0.31) and adiponectin (positively, ßstd= 0.58) suggesting an important role of these two cytokines in determining plasma SHBG levels in prepubertal children.

Conclusions
Our results suggest that plasma adiponectin levels may play a more important role than TNFα in influencing plasma SHBG levels in our prepubertal population with obesity.
Hydrochar from sugarcane industry by-products: assessment of its potential use as a soil conditioner by germination and growth of maize
Authors: Fregolente Laís G. , dos Santos João Vitor , Mazzati Felipe S. , Miguel Thaiz B. A. R. , de C. Miguel Emílio , Moreira Altair B. , Ferreira Odair P. , Bisinoti Márcia C. 
Published: March 2021

Abstract
Background
Hydrothermal carbonization (HTC) is a thermochemical process to convert biomass in carbon-rich materials (hydrochar). The use of sugarcane industry by-products in HTC has been evaluated, generating a hydrochar rich in nutrients, which could be used as a soil conditioner. We raised the hypothesis that the application of hydrochar in soil can improve its nutrient characteristics, bringing a better environment and favouring plant growth, expecting a development similar to that one observed in anthropogenic soils.

Results
Germination studies were performed expecting a species-dependent response, using maize and tomato seeds, whose development was assessed in two soluble fractions obtained from hydrochar aiming to evaluate different rhizosphere conditions. The results showed a better development of maize, especially in the aqueous soluble fraction, whose nutrient concentration was lower than that of the acid soluble fraction, as well as the organic composition. Maize growth in soils showed a better initial development in ultisol compared to oxisol, this being inferred by root:shoot biomass ratio and by scanning electron microscopy (SEM) images. However, the development of maize was better in anthropogenic soil compared to soils that received hydrochar.

Conclusion
The maize growth, compared with that carried out in anthropogenic soil, suggests that during the period evaluated the addition of hydrochar in soil did not have a negative effect upon maize development in its initial phase, and could have even favoured rooting in ultisol.
The effectiveness of an online grammar study scheme for Chinese undergraduate students
Authors: Windsor Ryan John 
Published: March 2021

AbstractThis paper outlines and describes the effectiveness of a virtual learning environment (VLE) as a grammar learning resource for first year students at a university in southern China over two academic years. The resource, named the Independent Grammar Study Scheme (IGSS), offered short grammar exercises that were completed over a 14-week period by two cohorts of year one students. The results of this study suggest that IGSS was successful in raising the grammar test scores of participants in both 2018 and 2019; that IGSS was more beneficial to students with lower English proficiency in 2018 but not in 2019; and that the VLE has been of great benefit to the university and to around one thousand students thus far.
Prognosis of hepatocellular carcinoma metastasizing to the oral cavity
Authors: Hong Jun-Hee , Lee Keonmo , Kim Jinhong , Ahn Kang-Min 
Published: March 2021

Abstract
Background
Oral metastasis by hepatocellular carcinoma (OMHCC) is extremely rare, and the prognosis had been reported quite poor due to simultaneous multiple organ metastases. In this study, we report clinical features and survival of 10 new cases of OMHCC and suggest the criteria for palliative surgery.

Methods
A retrospective clinical study including 10 new cases of oral OMHCC between 2006 and 2016 was performed. Clinical features and survival analysis were examined. The recorded variables were age, sex, site of oral metastases, size of oral tumor (largest diameter), and survival after oral histopathologic diagnosis.

Results
There was male (n=8) predilection of OMHCC. The mean survival time was 16.9 months. Patient age ranged from 40 to 71 years (mean 56.5). Eight mandibular and two maxillary lesions were found. One patient showed simultaneously the maxilla and the oral tongue involvement. The most often encountered symptoms were swelling (80%) followed by pain (60%), numbness (60%), bleeding (10%), and tooth mobility (10%). Four patients underwent operation due to spontaneous bleeding and swelling of the cancer. Overall (from onset of hepatocellular carcinoma) and truncated survival (from onset of OMHCC) were 71.9 and 13.1 months respectively.

Conclusion
The prognosis of OMHCC was quite poor. Oral and jaw bone examination should be included in patients with multiple metastasis of HCC. Palliative surgery might be performed in patients who reported spontaneous bleeding, severe pain, and oral dysphasia due to tumor enlargement.
The increasing expression of GPX7 related to the malignant clinical features leading to poor prognosis of glioma patients
Authors: Yao Jiawei , Chen Xin , Liu Zhendong , Zhang Ruotian , Zhang Cheng , Yang Quan , Yao Penglei , Jiang Qiuyi , Wu Jianing , Zhao Shiguang 
Published: March 2021

Abstract
Background
Glioma is the most common malignant brain tumor in adults. The standard treatment scheme of glioma is surgical resection combined alternative radio- and chemotherapy. However, the outcome of glioma patients was unsatisfied. Here, we aimed to explore the molecular and biological function characteristics of GPX7 in glioma.

Methods
The multidimensional data of glioma samples were downloaded from Chinese Glioma Genome Atlas (CGGA). RT-qPCR method was used to identify the expression status of GPX7. Kaplan–Meier curves and Cox regression analysis were used to explore the prognostic value of GPX7. Gene Set Enrichment Analysis (GSEA) was applied to investigate the GPX7-related functions in glioma.

Results
The results indicated that the expression of GPX7 in glioma was higher compared to that in normal brain tissue. Univariate and multivariate Cox regression analyses confirmed that the expression value of GPX7 was an independent prognostic factor in glioma. The GSEA analysis showed that GPX7 was significantly enriched in the cell cycle pathway, ECM pathway, focal adhesion pathway, and toll-like receptor pathway.

Conclusions
The GPX7 was recommended as an independent risk factor for patients diagnosed with glioma for the first time and GPX7 could be potentially used as the therapy target in future. Furthermore, we attempted to explore a potential biomarker for improving the diagnosis and prognosis of patients with glioma.
Insomnia in neurological diseases
Authors: Mayer Geert , Happe Svenja , Evers Stefan , Hermann Wiebke , Jansen Sabine , Kallweit Ulf , Muntean Maria-Lucia , Pöhlau Dieter , Riemann Dieter , Saletu Michael , Schichl Melanie , Schmitt Wolfgang J. , Sixel-Döring Friederike , Young Peter 
Published: March 2021

AbstractInsomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances for sleep with impairment of daytime performance. These components of insomnia – namely persistent sleep difficulties despite of adequate sleep opportunity resulting in daytime dysfunction - appear secondary or co-morbid to neurological diseases. Comorbid insomnia originates from neurodegenerative, inflammatory, traumatic or ischemic changes in sleep regulating brainstem and hypothalamic nuclei with consecutive changes of neurotransmitters. Symptoms of neurological disorders (i.e motor deficits), co-morbidities (i.e. pain, depression, anxiety) and some disease-specific pharmaceuticals may cause insomnia and/or other sleep problems.This guideline focuses on insomnias in headaches, neurodegenerative movement disorders, multiple sclerosis, traumatic brain injury, epilepsies, stroke, neuromuscular disease and dementia.The most important new recommendations are: Cognitive behavioral therapy (CBTi) is recommended to treat acute and chronic insomnia in headache patients. Insomnia is one of the most frequent sleep complaints in neurodegenerative movement disorders. Patients may benefit from CBTi, antidepressants (trazodone, doxepin), melatonin and gaba-agonists. Insomnia is a frequent precursor of MS symptoms by up to 10 years. CBTi is recommended in patients with MS, traumatic brain injury and. Melatonin may improve insomnia symptoms in children with epilepsies. Patients with insomnia after stroke can be treated with benzodiazepine receptor agonists and sedating antidepressants. For patients with dementia suffering from insomnia trazodone, light therapy and physical exercise are recommended.
Mathematical analysis of a generalized epidemic model with nonlinear incidence function
Authors: Ogunmiloro O. M. , Kareem H. 
Published: March 2021

AbstractBackgroundThough different forms of control measures have been deployed to curtail disease transmission, which are mostly through vaccination, treatment, isolation, etc., using mathematical models. Therefore, there is a need to consider the strict compliance or attendance of human individuals to medical awareness program through media outlets like radio, television, etc. In this work, a generalized mathematical model of two groups of infectious individuals who are compliant and non-compliant to medical awareness program is studied.ResultsA generalized Susceptible-Exposed-Infected-Recovered (SEIR) model with two groups of infectious individuals who attend or are compliant and those who do not attend or are non-compliant to medical awareness program is established. The analytical results of the model shows that the model is positive, well-posed, and epidemiologically reasonable. The two equilibria and the basic reproduction numberRrof the model is computed and analyzed and it is shown that the disease-free equilibrium is locally and globally asymptotically stable whenRr < 1 and the endemic equilibrium is globally stable whenRr > 1. Simulations are carried out by varying some parameters whenRris less and above unity. The simulations suggest that control interventions are to be implemented and medical awareness program scaled up to mitigate the spread of diseases. Furthermore, two numerical methods of Runge-Kutta and Differential Transform Method (DTM) are employed to obtain the approximate solutions of the model system equations, and it is observed that the results of the two methods agreeably compare with each other in terms of efficiency and convergence.ConclusionThis work should be taken into consideration by health policy makers and bio-mathematicians, because existing literature only take into consideration, how diseases spread and its management without considering the impact of strict compliance to consistent awareness program to mitigate the spread of diseases, which has been considered in this work. The limitation of this work is the unavailability of data on individuals in disease endemic regions who always and who do not comply with medical awareness programs.