bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic profiling of high- and low-spiking regions reveals novel epileptogenic mechanisms in focal cortical dysplasia type II patients
Authors: Srivastava Arpna , Kumar Krishan , Banerjee Jyotirmoy , Tripathi Manjari , Dubey Vivek , Sharma Devina , Yadav Nitin , Sharma M. C. , Lalwani Sanjeev , Doddamani Ramesh , Chandra P. Sarat , Dixit Aparna Banerjee 
Published: July 2021

AbstractFocal cortical dysplasia (FCD) is a malformation of the cerebral cortex with poorly-defined epileptogenic zones (EZs), and poor surgical outcome in FCD is associated with inaccurate localization of the EZ. Hence, identifying novel epileptogenic markers to aid in the localization of EZ in patients with FCD is very much needed. High-throughput gene expression studies of FCD samples have the potential to uncover molecular changes underlying the epileptogenic process and identify novel markers for delineating the EZ. For this purpose, we, for the first time performed RNA sequencing of surgically resected paired tissue samples obtained from electrocorticographically graded high (MAX) and low spiking (MIN) regions of FCD type II patients and autopsy controls. We identified significant changes in the MAX samples of the FCD type II patients when compared to non-epileptic controls, but not in the case of MIN samples. We found significant enrichment for myelination, oligodendrocyte development and differentiation, neuronal and axon ensheathment, phospholipid metabolism, cell adhesion and cytoskeleton, semaphorins, and ion channels in the MAX region. Through the integration of both MAX vs non-epileptic control and MAX vs MIN RNA sequencing (RNA Seq) data, PLP1, PLLP, UGT8, KLK6, SOX10, MOG, MAG, MOBP, ANLN, ERMN, SPP1, CLDN11, TNC, GPR37, SLC12A2, ABCA2, ABCA8, ASPA, P2RX7, CERS2, MAP4K4, TF, CTGF, Semaphorins, Opalin, FGFs, CALB2, and TNC were identified as potential key regulators of multiple pathways related to FCD type II pathology. We have identified novel epileptogenic marker elements that may contribute to epileptogenicity in patients with FCD and could be possible markers for the localization of EZ.
Challenges in the PREHOSPITAL emergency management of geriatric trauma patients – a scoping review
Authors: Eichinger Michael , Robb Henry Douglas Pow , Scurr Cosmo , Tucker Harriet , Heschl Stefan , Peck George 
Published: July 2021

Abstract
Background
Despite a widely acknowledged increase in older people presenting with traumatic injury in western populations there remains a lack of research into the optimal prehospital management of this vulnerable patient group. Research into this cohort faces many uniqu1e challenges, such as inconsistent definitions, variable physiology, non-linear presentation and multi-morbidity. This scoping review sought to summarise the main challenges in providing prehospital care to older trauma patients to improve the care for this vulnerable group.

Methods and findings
A scoping review was performed searching Google Scholar, PubMed and Medline from 2000 until 2020 for literature in English addressing the management of older trauma patients in both the prehospital arena and Emergency Department. A thematic analysis and narrative synthesis was conducted on the included 131 studies. Age-threshold was confirmed by a descriptive analysis from all included studies. The majority of the studies assessed triage and found that recognition and undertriage presented a significant challenge, with adverse effects on mortality. We identified six key challenges in the prehospital field that were summarised in this review.

Conclusions
Trauma in older people is common and challenges prehospital care providers in numerous ways that are difficult to address. Undertriage and the potential for age bias remain prevalent. In this Scoping Review, we identified and discussed six major challenges that are unique to the prehospital environment. More high-quality evidence is needed to investigate this issue further.
Function of ORFC of the polyketide synthase gene cluster on fatty acid accumulation in Schizochytrium limacinum SR21
Authors: Shi Yanyan , Chen Zhen , Li Yixin , Cao Xingyu , Yang Lijie , Xu Yiyuan , Li Zhipeng , He Ning 
Published: July 2021

Abstract
Background
As a potential source of polyunsaturated fatty acids (PUFA), Schizochytrium sp. has been widely used in industry for PUFA production. Polyketide synthase (PKS) cluster is supposed to be the primary way of PUFA synthesis in Schizochytrium sp. As one of three open reading frames (ORF) in the PKS cluster, ORFC plays an essential role in fatty acid biosynthesis. However, the function of domains in ORFC in the fatty acid synthesis of Schizochytrium sp. remained unclear.

Results
In this study, heterologous expression and overexpression were carried out to study the role of ORFC and its domains in fatty acid accumulation. Firstly, ORFC was heterologously expressed in yeast which increased the PUFA content significantly. Then, the dehydratase (DH) and enoyl reductase (ER) domains located on ORFC were overexpressed in Schizochytrium limacinum SR21, respectively. Fatty acids profile analysis showed that the contents of PUFA and saturated fatty acid were increased in the DH and ER overexpression strains, respectively. This indicated that the DH and ER domains played distinct roles in lipid accumulation. Metabolic and transcriptomic analysis revealed that the pentose phosphate pathway and triacylglycerol biosynthesis were enhanced, while the tricarboxylic acid cycle and fatty acids oxidation were weakened in DH-overexpression strain. However, the opposite effect was found in the ER-overexpression strain.

Conclusion
Therefore, ORFC was required for the biosynthesis of fatty acid. The DH domain played a crucial role in PUFA synthesis, whereas the ER domain might be related to saturated fatty acids (SFA) synthesis in Schizochytrium limacinum SR21. This research explored the role of ORFC in the PKS gene cluster in Schizochytrium limacinum and provided potential genetic modification strategies for improving lipid production and regulating PUFA and SFA content.
Epigenetic reprogramming of cell identity: lessons from development for regenerative medicine
Authors: Basu Amitava , Tiwari Vijay K. 
Published: July 2021

AbstractEpigenetic mechanisms are known to define cell-type identity and function. Hence, reprogramming of one cell type into another essentially requires a rewiring of the underlying epigenome. Cellular reprogramming can convert somatic cells to induced pluripotent stem cells (iPSCs) that can be directed to differentiate to specific cell types. Trans-differentiation or direct reprogramming, on the other hand, involves the direct conversion of one cell type into another. In this review, we highlight how gene regulatory mechanisms identified to be critical for developmental processes were successfully used for cellular reprogramming of various cell types. We also discuss how the therapeutic use of the reprogrammed cells is beginning to revolutionize the field of regenerative medicine particularly in the repair and regeneration of damaged tissue and organs arising from pathological conditions or accidents. Lastly, we highlight some key challenges hindering the application of cellular reprogramming for therapeutic purposes.
BMI trajectory in childhood is associated with asthma incidence at young adulthood mediated by DNA methylation
Authors: Rathod Rutu , Zhang Hongmei , Karmaus Wilfried , Ewart Susan , Kadalayil Latha , Relton Caroline , Ring Susan , Arshad S. Hasan , Holloway John W. 
Published: July 2021

Abstract
Purpose
Body mass index (BMI) is associated with asthma but associations of BMI temporal patterns with asthma incidence are unclear. Previous studies suggest that DNA methylation (DNAm) is associated with asthma status and variation in DNAm is a consequence of BMI changes. This study assessed the direct and indirect (via DNAm) effects of BMI trajectories in childhood on asthma incidence at young adulthood.

Methods
Data from the Isle of Wight (IoW) birth cohort were included in the analyses. Group-based trajectory modelling was applied to infer latent BMI trajectories from ages 1 to 10 years. An R package, ttscreening, was applied to identify differentially methylated CpGs at age 10 years associated with BMI trajectories, stratified for sex. Logistic regressions were used to further exclude CpGs with DNAm at age 10 years not associated with asthma incidence at 18 years. CpGs discovered via path analyses that mediated the association of BMI trajectories with asthma incidence in the IoW cohort were further tested in an independent cohort, the Avon Longitudinal Study of Children and Parents (ALSPAC).

Results
Two BMI trajectories (high vs. normal) were identified. Of the 442,474 CpG sites, DNAm at 159 CpGs in males and 212 in females were potentially associated with BMI trajectories. Assessment of their association with asthma incidence identified 9 CpGs in males and 6 CpGs in females. DNAm at 4 of these 15 CpGs showed statistically significant mediation effects (p-value < 0.05). At two of the 4 CpGs (cg23632109 and cg10817500), DNAm completely mediated the association (i.e., only statistically significant indirect effects were identified). In the ALSPAC cohort, at all four CpGs, the same direction of mediating effects were observed as those found in the IoW cohort, although statistically insignificant.

Conclusion
The association of BMI trajectory in childhood with asthma incidence at young adulthood is possibly mediated by DNAm.
Submandibular lymph node metastasis of occult thyroid carcinoma first suspected to be a salivary gland tumor: a case report
Authors: Kaneko Hiroyuki , Deguchi Mami , Yano Hisashi 
Published: July 2021

Abstract
Background
When diagnosing and treating neck masses, various diseases need to be considered, including benign or malignant tumors, lymph node-related diseases, and cysts. Thus, there may be cases in which making a definitive diagnosis is difficult on the basis of blood testing and imaging alone.

Case presentation
The patient was an 80-year-old Japanese female who presented with swelling in the right submandibular area. Magnetic resonance imaging and ultrasonography revealed a solid tumor with inhomogeneous content continuous with the submandibular gland. Therefore, the clinical diagnosis was salivary gland tumor. Surgical treatment was performed, and intraoperative frozen-section examination demonstrated submandibular lymph node metastasis of thyroid carcinoma. After surgical treatment, blood test for thyroid gland function yielded normal results except for increased thyroglobulin levels. Further positron-emission tomography–computed tomography and ultrasonography were performed, in addition to fine-needle aspiration biopsy of the thyroid gland and other tests; however, no other thyroid abnormalities were observed. Fine-needle aspiration biopsy revealed no carcinomatous components. Close observational follow-up has been continued without thyroid gland treatment, and as of approximately 8 years postoperation, no recurrence, metastases, or thyroid carcinoma have developed.

Conclusion
The mass was lymph node metastasis of occult thyroid carcinoma. In general, occult thyroid carcinoma metastasizes to level II–V. To the best of our knowledge, this is the first report of submandibular lymph node metastasis alone of occult thyroid carcinoma.
Preservation of nautilid soft parts inside and outside the conch interpreted as central nervous system, eyes, and renal concrements from the Lebanese Cenomanian
Authors: Klug Christian , Pohle Alexander , Roth Rosemarie , Hoffmann René , Wani Ryoji , Tajika Amane 
Published: July 2021

AbstractNautilid, coleoid and ammonite cephalopods preserving jaws and soft tissue remains are moderately common in the extremely fossiliferous Konservat-Lagerstätte of the Hadjoula, Haqel and Sahel Aalma region, Lebanon. We assume that hundreds of cephalopod fossils from this region with soft-tissues lie in collections worldwide. Here, we describe two specimens of Syrionautilus libanoticus (Cymatoceratidae, Nautilida, Cephalopoda) from the Cenomanian of Hadjoula. Both specimens preserve soft parts, but only one shows an imprint of the conch. The specimen without conch displays a lot of anatomical detail. We homologise the fossilised structures as remains of the digestive tract, the central nervous system, the eyes, and the mantle. Small phosphatic structures in the middle of the body chamber of the specimen with conch are tentatively interpreted as renal concrements (uroliths). The absence of any trace of arms and the hood of the specimen lacking its conch is tentatively interpreted as an indication that this is another leftover fall (pabulite), where a predator lost parts of its prey. Other interpretations such as incomplete scavenging are also conceivable.
Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy
Authors: Bandara Ranmal Avinash , Chen Ziyan Rachel , Hu Jim 
Published: July 2021

AbstractSince CRISPR/Cas9 was harnessed to edit DNA, the field of gene therapy has witnessed great advances in gene editing. New avenues were created for the treatment of diseases such as Cystic Fibrosis (CF). CF is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Despite the success of gene editing with the CRISPR/Cas9 in vitro, challenges still exist when using CRISPR/Cas9 in vivo to cure CF lung disease. The delivery of CRISPR/Cas9 into lungs, as well as the difficulty to achieve the efficiency required for clinical efficacy, has brought forth new challenges. Viral and non-viral vectors have been shown to deliver DNA successfully in vivo, but the sustained expression of CFTR was not adequate. Before the introduction of Helper-Dependent Adenoviral vectors (HD-Ad), clinical trials of treating pulmonary genetic diseases with first-generation viral vectors have shown limited efficacy. With the advantages of larger capacity and lower immunogenicity of HD-Ad, together with the versatility of the CRISPR/Cas9 system, delivering CRISPR/Cas9 to the airway with HD-Ad for lung gene therapy shows great potential. In this review, we discuss the status of the application of CRISPR/Cas9 in CF gene therapy, the existing challenges in the field, as well as new hurdles introduced by the presence of CRISPR/Cas9 in the lungs. Through the analysis of these challenges, we present the potential of CRISPR/Cas9-mediated lung gene therapy using HD-Ad vectors with Cystic Fibrosis lung disease as a model of therapy.
Sex differences in CRT device implantation rates, efficacy, and complications following implantation: protocol for a systematic review and meta-analysis of cohort studies
Authors: Dewidar Omar , Birnie David , Podinic Irina , Welch Vivian , Wells George A. 
Published: July 2021

Abstract
Introduction
There is abundant evidence for sex differences in the diagnosis, implantation, and outcomes for cardiac resynchronization therapy (CRT) devices. Controversial data suggesting women are less likely to receive the device regardless of the greater benefit. The aim of this review is to assess sex differences in the implantation rate, clinical effectiveness, and safety of patients receiving CRT devices.

Methods
We will conduct a systematic literature search of MEDLINE, Embase, and Web of Science to identify cohort studies that meet our eligibility criteria. Title and full text screening will be conducted in duplicate independently. Eligible studies report clinical effectiveness or safety of patients receiving CRT device while providing sex-disaggregated data. Implantation rate will be extracted from the baseline characteristics tables of the studies. The effectiveness outcomes include the following: all-cause death, hospitalization, peak oxygen consumption (pVO2), quality of life (QoL), 6-min walk test, NYHA class reduction, LVEF, and heart failure hospitalization. The complication outcomes include the following: contrast-induced nephropathy, pneumothorax, pocket-related hematoma, pericardial tamponade, phrenic nerve stimulation, device infection, death, pulmonary edema, electrical storm, cardiogenic shock, and hypotension requiring resuscitation. Description of included studies will be reported in detail and outcomes will be meta-analyzed and presented using forest plots when feasible. Risk of bias will be assessed using the Newcastle-Ottawa Scale (NOS) by two review authors independently. GRADE approach will be used to assess the certainty of evidence.

Discussion
The aim of this review is to determine the presence of differences in CRT implantation between women and men as well as differences in clinical effectiveness and safety of CRT after device implantation. Results from this systematic review will provide important insights into sex differences in CRT devices that could contribute to the development of sex-specific recommendations and inform policy.

Systematic review registration
PROSPERO CRD42020204804
Access to systemic anti-cancer therapies for women with secondary breast cancer—protocol for a mixed methods systematic review
Authors: Pearson Sally Anne , Taylor Sally , Marsden Antonia , Yorke Janelle 
Published: July 2021

Abstract
Background
It is well recognised that access and receipt of appropriate guideline recommended treatment with systemic anti-cancer therapies for secondary breast cancer is a key determinant in overall survival. Where there is disparity in access this may result in unwarranted variation and disparity in outcomes. Individual, clinical and wider contextual factors have been associated with these disparities, however this remains poorly understood for women with secondary breast cancer. The purpose of the review is to examine individual, clinical and contextual factors which influence access to evidence-based systemic anti-cancer therapies for women with secondary breast cancer. This will include barriers and facilitators for access and receipt of treatment and an exploration of women and clinicians experience and perspectives on access.

Methods
A mixed methods approach with a segregated design will be used to examine and explore factors which influence access to systemic anti-cancer therapies for women with secondary breast cancer. Electronic databases to be searched from January 2000 onwards will be EBSCO CINAHL Plus, Ovid MEDLINE, Ovid EMBASE, PsychINFO and the Cochrane Library and JBI database. This will include NHS Evidence which will be searched for unpublished studies and gray literature.
Title and abstract citations and full-text articles will be screened by the author and second reviewer. Data will be extracted by the author and validated by the second reviewer.
An overarching synthesis will be produced which brings together quantitative and qualitative findings. Methodological quality and risk of bias will be assessed using the Mixed Methods Appraisal Tool.

Discussion
Understanding individual, clinical and wider contextual factors associated with access and receipt of systemic anti-cancer therapies for secondary breast cancer is a complex phenomenon. These will be examined to determine any association with access. Review findings will be used to guide future research in this area and the development of an evidence-based service level intervention designed to address unwarranted variation in access based upon the Medical Research Council (MRC) approach to the development, implementation and evaluation of complex interventions.

Systematic review registration
The review protocol has been registered in PROSPERO CRD42020196490.
Finite-time stability of linear stochastic fractional-order systems with time delay
Authors: Mchiri Lassaad , Ben Makhlouf Abdellatif , Baleanu Dumitru , Rhaima Mohamed 
Published: July 2021

AbstractThis paper focuses on the finite-time stability of linear stochastic fractional-order systems with time delay for $\alpha \in (\frac{1}{2},1)$
α
∈
(

1

2

,
1
)
. Under the generalized Gronwall inequality and stochastic analysis techniques, the finite-time stability of the solution for linear stochastic fractional-order systems with time delay is investigated. We give two illustrative examples to show the interest of the main results.
“I was eating more fruits and veggies than I have in years”: a mixed methods evaluation of a fresh food prescription intervention
Authors: Heasley Cole , Clayton Becca , Muileboom Jade , Schwanke Anna , Rathnayake Sujani , Richter Abby , Little Matthew 
Published: July 2021

AbstractBackgroundFood insecurity is associated with poor nutritional health outcomes. Prescribing fresh fruits and vegetables in healthcare settings may be an opportunity to link patients with community supports to promote healthy diets and improve food security. This mixed methods study evaluated the impacts of a fresh food prescription pilot program.MethodsThe study took place at two Community Health Centre locations in Guelph, Ontario, Canada. Sixty food insecure patients with ≥1 cardio-metabolic condition or micronutrient deficiency participated in the intervention. Participants were prescribed 12 weekly vouchers to Community Food Markets. We conducted a one-group pre-post mixed-methods evaluation to assess changes in fruit and vegetable intake, self-reported health, food security, and perceived food environments. Surveys were conducted at baseline and follow-up and semi-structured interviews with participants were conducted following the intervention.ResultsFood security and fruit and vegetable consumption improved following the intervention. Food security scores increased by 1.6 points, on average (p < 0.001). Consumption of fruits and ‘other’ vegetables (cucumber, celery, cabbage, cauliflower, squashes, and vegetable juice) increased from baseline to follow-up (p < 0.05). No changes in self-reported physical or mental health were observed. Qualitative data suggested that the intervention benefited the availability, accessibility, affordability, acceptability, and accommodation of healthy foods for participating households.ConclusionsFresh food prescription programs may be a useful model for healthcare providers to improve patients’ food environments, healthy food consumption, and food security.