bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors affecting pathways to care for children and adolescents with complex vascular malformations: parental perspectives
Authors: Sisk Bryan A. , Kerr Anna , King Katherine A. 
Published: July 2022

Abstract
Background
Complex vascular malformations (VMs) are rare disorders that can cause pain, coagulopathy, disfigurement, asymmetric growth, and disability. Patients with complex VMs experience misdiagnosis, delayed diagnosis, delayed or inappropriate treatments, and worsened health. Given the potential consequences of delaying expert care, we must identify the factors that impede or facilitate this access to care.

Results
We performed semi-structured interviews with 24 parents (21 mothers; 3 fathers; median age = 42.5 years) of children with complex VMs and overgrowth disorders living in the US, recruited through two patient advocacy groups – CLOVES Syndrome Community, and Klippel-Trenaunay Support Group. We performed thematic analysis to assess parental perspectives on barriers and facilitators to accessing expert care. We identified 11 factors, representing 6 overarching themes, affecting families’ ability to access and maintain effective care for their child: individual characteristics (clinician behaviors and characteristics, parent behaviors and characteristics), health care system (availability of specialist multidisciplinary teams, care coordination and logistics, insurance and financial issues, treatments and services), clinical characteristics (accuracy and timing of diagnosis, features of clinical presentation), social support networks, scientific progress, and luck and privilege. Additionally, access to information about VMs and VM care was a crosscutting theme affecting each of these factors. These factors influenced both the initial access to care and the ongoing maintenance of care for children with VMs.

Conclusion
Parents of children with VMs report multiple factors that facilitate or impede their ability to provide their child with optimal care. These factors represent possible targets for future interventions to improve care delivery for families affected by VMs.
Severity, symptomatology, and treatment duration for mental health disorders: a retrospective analysis from a conflict-affected region of northern Nigeria
Authors: Martínez Torre Santiago , Carreño Cristina , Sordo Luis , llosa Augusto E. , Ousley Janet , Waziri Abdulrauf , Mathela Richard , Umar Retsat Dazang , Usman Joshua , Sagrado María José 
Published: July 2022

AbstractBackgroundMental Health and psychosocial support (MHPSS) programs are essential during humanitarian crises and in conflict settings, like Nigeria’s Borno State. However, research on how types of traumatic stress and symptom severity affect clinical improvement is lacking in these contexts, as is consensus over how long these patients must engage in mental health care to see results.MethodsRecords from 11,709 patients from the MHPSS program in Pulka and Gwoza local government areas in Borno State, Nigeria from 2018 and 2019 were retrospectively analyzed. Patient information, symptoms, stress type, severity (CGI-S scale), and clinical improvement (CGI-I and MHGS scales) were assessed by the patient and counselor. Associations between variables were investigated using logistic regression models.ResultsClinical improvement increased with consultation frequency (OR: 2.5,p < 0.001 for CGI-I; OR: 2,p < 0.001 for MHGS), with patients who received three to six counseling sessions were most likely to improve, according to severity. Survivors of sexual violence, torture, and other conflict/violence-related stressors were nearly 20 times as likely to have posttraumatic stress disorder (PTSD) (OR: 19.7,p < 0.001), and depression (OR: 19.3,p < 0.001) symptomatology. Children exposed to conflict-related violence were also almost 40 times as likely to have PTSD (OR: 38.2,p = 0.002). Most patients presented an improvement in outcome at discharge, per both counselors (92%, CGI-I) and self-rating scores (73%, MHGS).ConclusionWe demonstrate a threshold at which patients were most likely to improve (3 sessions for mild or moderate patients; 6 sessions for severe). In addition, we identify the specific types of stress and symptom severity that affected the number of sessions needed to achieve successful outcomes, and highlight that some stress types (especially torture or having a relative killed) were specifically linked to PTSD and depression. Therefore, we emphasize the importance of classifying patient stress type and severity to identify the appropriate duration of care needed.
Emerging strategies to overcome resistance to third-generation EGFR inhibitors
Authors: Shi Kunyu , Wang Guan , Pei Junping , Zhang Jifa , Wang Jiaxing , Ouyang Liang , Wang Yuxi , Li Weimin 
Published: July 2022

AbstractEpidermal growth factor receptor (EGFR), the receptor for members of the epidermal growth factor family, regulates cell proliferation and signal transduction; moreover, EGFR is related to the inhibition of tumor cell proliferation, angiogenesis, invasion, metastasis, and apoptosis. Therefore, EGFR has become an important target for the treatment of cancer, including non-small cell lung cancer, head and neck cancer, breast cancer, glioma, cervical cancer, and bladder cancer. First- to third-generation EGFR inhibitors have shown considerable efficacy and have significantly improved disease prognosis. However, most patients develop drug resistance after treatment. The challenge of overcoming intrinsic and acquired resistance in primary and recurrent cancer mediated by EGFR mutations is thus driving the search for alternative strategies in the design of new therapeutic agents. In view of resistance to third-generation inhibitors, understanding the intricate mechanisms of resistance will offer insight for the development of more advanced targeted therapies. In this review, we discuss the molecular mechanisms of resistance to third-generation EGFR inhibitors and review recent strategies for overcoming resistance, new challenges, and future development directions.
Targeting purinergic pathway to enhance radiotherapy-induced immunogenic cancer cell death
Authors: Bao Xuhui , Xie Liyi 
Published: July 2022

AbstractEmerging evidence has demonstrated that radiotherapy (RT) can not only cause direct damage to cancer cells but also lead to immunogenic cell death (ICD), which involves the activation of host antitumor immune response in tumor immune microenvironment (TIME). RT-induced ICD comprises the release of damage-associated molecular patterns (DAMPs) from dying cancer cells that result in the activation of tumor-specific immunity to elicit long-term antitumor efficacy in both original and abscopal tumor sites. Adenosine triphosphate (ATP), as an important DAMP released by irradiated cancer cells and an essential factor within purinergic pathway, can be further hydrolyzed to adenosine (ADO) by two key ectonucleotidases, CD39 and CD73, to further modulate the antitumor immunity in TIME through purinergic signaling via the interaction to its specific receptors such as adenosine 2A receptor (A2AR) and A2BR widely expressed on the surface of the components in TIME, including cancer cells and many immune effector cells. In this review, we first introduced key components in purinergic pathway including ATP, ADO, their receptors, and essential ectonucleotidases. Then we reviewed the regulation of ATP and ADO levels and their main mechanisms by which they promote tumor growth and broadly suppress antitumor immunity through inhibiting the pro-inflammatory response of dendritic cells, cytotoxic T lymphocytes, and natural killer cells, while improving the anti-inflammatory response of regulatory T cells, macrophages, and myeloid-derived suppressor cells in TIME, especially after irradiation. Finally, we presented an overview of dozens of promising therapeutics including pharmacological antagonists and specific antibodies targeting ADO receptors and ectonucleotidases CD39 or CD73 investigated in the clinic for cancer treatment, especially focusing on the preclinical studies and clinical trials being explored for blocking the purinergic signaling to enhance RT as a combination antitumor therapeutic strategy, which has a robust potential to be translated to the clinic in the future.
PDIA3P1 promotes Temozolomide resistance in glioblastoma by inhibiting C/EBPβ degradation to facilitate proneural-to-mesenchymal transition
Authors: Gao Zijie , Xu Jianye , Fan Yang , Qi Yanhua , Wang Shaobo , Zhao Shulin , Guo Xing , Xue Hao , Deng Lin , Zhao Rongrong , Sun Chong , Zhang Ping , Li Gang 
Published: July 2022

Abstract
Background
Resistance to temozolomide (TMZ) is a major obstacle to preventing glioblastoma (GBM) recurrence after surgery. Although long noncoding RNAs (lncRNAs) play a variety of roles in GBM, the lncRNAs that regulate TMZ resistance have not yet been clearly elucidated. This study aims to identify lncRNAs that may affect TMZ treatment sensitivity and to explore novel therapeutic strategies to overcome TMZ resistance in GBM.

Methods
LncRNAs associated with TMZ resistance were identified using the Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) datasets. Quantitative real-time PCR (qRT–PCR) was used to determine the expression of PDIA3P1 in TMZ-resistant and TMZ-sensitive GBM cell lines. Both gain-of-function and loss-of-function studies were used to assess the effects of PDIA3P1 on TMZ resistance using in vitro and in vivo assays. Glioma stem cells (GSCs) were used to determine the effect of PDIA3P1 on the GBM subtype. The hypothesis that PDIA3P1 promotes proneural-to-mesenchymal transition (PMT) was established using bioinformatics analysis and functional experiments. RNA pull-down and RNA immunoprecipitation (RIP) assays were performed to examine the interaction between PDIA3P1 and C/EBPβ. The posttranslational modification mechanism of C/EBPβ was verified using ubiquitination and coimmunoprecipitation (co-IP) experiments. CompuSyn was leveraged to calculate the combination index (CI), and the antitumor effect of TMZ combined with nefllamapimod (NEF) was validated both in vitro and in vivo.

Results
We identified a lncRNA, PDIA3P1, which was upregulated in TMZ-resistant GBM cell lines. Overexpression of PDIA3P1 promoted the acquisition of TMZ resistance, whereas knockdown of PDIA3P1 restored TMZ sensitivity. PDIA3P1 was upregulated in MES-GBM, promoted PMT progression in GSCs, and caused GBMs to be more resistant to TMZ treatment. Mechanistically, PDIA3P1 disrupted the C/EBPβ-MDM2 complex and stabilized the C/EBPβ protein by preventing MDM2-mediated ubiquitination. Expression of PDIA3P1 was upregulated in a time- and concentration-dependent manner in response to TMZ treatment, and TMZ-induced upregulation of PDIA3P1 was mediated by the p38α-MAPK signaling pathway. NEF is a small molecule drug that specifically targets p38α with excellent blood–brain barrier (BBB) permeability. NEF blocked TMZ-responsive PDIA3P1 upregulation and produced synergistic effects when combined with TMZ at specific concentrations. The combination of TMZ and NEF exhibited excellent synergistic antitumor effects both in vitro and in vivo.

Conclusion
PDIA3P1 promotes PMT by stabilizing C/EBPβ, reducing the sensitivity of GBM cells to TMZ treatment. NEF inhibits TMZ-responsive PDIA3P1 upregulation, and NEF combined with TMZ provides better antitumor effects.
The ABCDE approach to difficult weaning from venoarterial extracorporeal membrane oxygenation
Authors: Meuwese Christiaan L. , Brodie Daniel , Donker Dirk W. 
Published: July 2022

AbstractVenoarterial extracorporeal membrane oxygenation (VA ECMO) has been increasingly applied in patients with cardiogenic shock in recent years. Nevertheless, many patients cannot be successfully weaned from VA ECMO support and 1-year mortality remains high. A systematic approach could help to optimize clinical management in favor of weaning by identifying important factors in individual patients. Here, we provide an overview of pivotal factors that potentially prevent successful weaning of VA ECMO. We present this through a rigorous approach following the relatable acronym ABCDE, in order to facilitate widespread use in daily practice.
Virtual reality (VR) to reduce anxiety in children in the plaster room: a study protocol for a randomised controlled trial
Authors: van der Water Lisa , Poppelaars Max A. , Koenraadt-van Oost Iris , Boele van Hensbroek Pieter , van Bergen Christiaan J. A. 
Published: July 2022

Abstract
Background
Paediatric fractures are highly prevalent and are most often treated with plaster. The removal of plaster is often an anxious experience for children. Virtual reality (VR) has proven to effectively distract children and reduce their anxiety in other clinical settings. This study aims to investigate the effect of VR on the anxiety level of children with fractures that undergo plaster removal or replacement in the plaster room.

Methods
This study is designed as a randomised controlled trial (RCT). The sample size is 270 patients, aged 5 to 17 years, with a fracture of the upper or lower extremity treated with plaster. The intervention group will be distracted with VR goggles and headphones during the replacement or removal of the plaster, whereas the control group will receive standard care. As a primary outcome, the level of anxiety will be measured with the Child Fear Scale (CFS). Secondary outcomes include anxiety reduction (difference between CFS after and CFS before plaster procedure) and Numeric Rating Scales (NRS) pain and satisfaction. Additionally, the children’s fastest heart rate during the procedure will be recorded. An unpaired samples t-test or a Mann-Whitney U test (depending on the data distribution) will be used to analyse the data.

Discussion
When completed, this trial will provide evidence on the potential role of VR in children with fractures treated with plaster. The purpose is to increase the quality of healthcare by decreasing anxiety and possibly pain perception of children during a plaster procedure.

Trial registration
Netherlands Trial Register NL9065. Registered on 27 November 2020
Metabolic engineering of Ashbya gossypii for limonene production from xylose
Authors: Muñoz-Fernández Gloria , Martínez-Buey Rubén , Revuelta José Luis , Jiménez Alberto 
Published: July 2022

Abstract
Background
Limonene is a cyclic monoterpene that has applications in the food, cosmetic, and pharmaceutical industries. The industrial production of limonene and its derivatives through plant extraction presents important drawbacks such as seasonal and climate issues, feedstock limitations, low efficiency and environmental concerns. Consequently, the implementation of efficient and eco-friendly bioprocesses for the production of limonene and other terpenes constitutes an attractive goal for microbial biotechnology. In this context, novel biocatalysts with the ability to produce limonene from alternative carbon sources will help to meet the industrial demands of limonene.

Results
Engineered strains of the industrial fungus Ashbya gossypii have been developed to produce limonene from xylose. The limonene synthase (LS) from Citrus limon was initially overexpressed together with the native HMG1 gene (coding for HMG-CoA reductase) to establish a limonene-producing platform from a xylose-utilizing A. gossypii strain. In addition, several strategies were designed to increase the production of limonene. Hence, the effect of mutant alleles of ERG20 (erg20F95W and erg20F126W) were evaluated together with a synthetic orthogonal pathway using a heterologous neryl diphosphate synthase. The lethality of the A. gossypii double mutant erg20F95W−F126W highlights the indispensability of farnesyl diphosphate for the synthesis of essential sterols. In addition, the utilization of the orthogonal pathway, bypassing the Erg20 activity through neryl diphosphate, triggered a substantial increase in limonene titer (33.6 mg/L), without critically altering the fitness of the engineered strain. Finally, the overexpression of the native ERG12 gene further enhanced limonene production, which reached 336.4 mg/L after 96 h in flask cultures using xylose as the carbon source.

Conclusions
The microbial production of limonene can be carried out using engineered strains of A. gossypii from xylose-based carbon sources. The utilization of a synthetic orthogonal pathway together with the overexpression of ERG12 is a highly beneficial strategy for the production of limonene in A. gossypii. The strains presented in this work constitute a proof of principle for the production of limonene and other terpenes from agro-industrial wastes such as xylose-rich hydrolysates in A. gossypii.
Identifying metabolic syndrome in migrant Asian Indian adults with anthropometric and visceral fat action points
Authors: Sluyter John D. , Plank Lindsay D. , Rush Elaine C. 
Published: July 2022

AbstractBackgroundMetabolic syndrome (MetS) is a clustering of metabolic risk factors, including large waist circumference (WC). Other anthropometric parameters and visceral fat mass (VFM) predicted from these may improve MetS detection. Our aim was to assess the ability of such parameters to predict this clustering in a cross-sectional, diagnostic study.MethodParticipants were 82 males and 86 females, aged 20–74 years, of Asian Indian ethnicity. VFM was estimated by dual-energy X-ray absorptiometry (DXA) through identification of abdominal subcutaneous fat layer boundaries. Non-anthropometric metabolic risk factors (triglycerides, HDL cholesterol, blood pressure and glucose) were defined using MetS criteria. We estimated the ability of anthropometry and VFM to detect ≥ 2 of these factors by receiver operating characteristic (ROC) and precision-recall curves.ResultsTwo or more non-anthropometric metabolic risk factors were present in 45 (55%) males and 29 (34%) females. The area under the ROC curve (AUC) to predict ≥ 2 of these factors using WC was 0.67 (95% confidence interval: 0.55–0.79) in males and 0.65 (0.53–0.77) in females. Optimal WC cut-points were 92 cm for males (63% accuracy) and 79 cm for females (53% accuracy). VFM, DXA-measured sagittal diameter and suprailiac skinfold thickness yielded higher AUC point estimates (by up to 0.06), especially in females where these measures improved accuracy to 69%, 69% and 65%, respectively. Pairwise combinations that included WC further improved accuracy.ConclusionOur findings indicate that cut-points for readily obtained measures other than WC, or in combination with WC, may provide improved detection of MetS risk factor clusters.
Cystic liver lesions: a pictorial review
Authors: Chenin Mégane , Paisant Anita , Lebigot Jérôme , Bazeries Paul , Debbi Kawtar , Ronot Maxime , Laurent Valérie , Aubé Christophe 
Published: July 2022

AbstractHepatic cysts (HC) are sac-like structures mainly filled with liquid and showing a distinct membrane. They are usually found incidentally through imaging. A wide spectrum of imaging patterns may be observed for common and uncommon, neoplastic and non-neoplastic diseases. While simple hepatic cysts occur frequently and do not require any treatment or follow-up, non-typical cysts should be carefully analysed to avoid misdiagnosing a lesion that would require appropriate management. Therefore, adequate knowledge of all the relevant imaging patterns is critical to secure an accurate diagnosis. The aim of this review is to describe the imaging features of the different types of hepatic cysts.
Morphologic CT and MRI features of primary parotid squamous cell carcinoma and its predictive factors for differential diagnosis with mucoepidermoid carcinoma
Authors: Ban Xiaohua , Hu Huijun , Li Yue , Yang Lingjie , Wang Yu , Zhang Rong , Xie Chuanmiao , Zhou Cuiping , Duan Xiaohui 
Published: July 2022

AbstractBackgroundPrimary parotid squamous cell carcinoma (SCC) is a rare entity with a poor prognosis. Pathologically, the diagnosis of it requires the exclusion of parotid mucoepidermoid carcinoma (MEC). Currently, the imaging features of primary parotid SCC and the predictive indicators for differential diagnosis of the two entities have not been well reported. Our purpose was to identify the imaging characteristics of primary parotid SCC and to determine the predictive factors for its’ differential diagnosis.ResultsThirty-one participants with primary parotid SCC and 59 with primary parotid MEC were enrolled. Clinical, CT and MRI features were reviewed and compared by univariate analysis. Then, multinomial logistic regression was used to determine the predictors to distinguish parotid SCC from MEC. Most primary parotid SCCs exhibited irregular shape, ill-defined margin, incomplete or no capsule, heterogeneous and marked or moderate enhancement, necrosis, local tumor invasiveness (LTI). Age, maximal dimension, shape, degree of enhancement, gradual enhancement, necrosis, and LTI were different between the primary parotid SCCs and MECs in univariate analysis (p < 0.05). While in multinomial logistic regression analysis, only age and necrosis were the independent predictors for distinguishing parotid SCC from MEC, and this model exhibited an area under curve of 0.914 in ROC curve analysis.ConclusionsPrimary parotid SCC has some distinct imaging features including the large tumor size, irregular shape, ill-defined margin, and particularly the marked central necrosis. Patients with age ≥ 51.5 years and necrosis on the image of the primary tumor in the parotid gland could be more likely to be SCCs than MECs.
Ultra-low-dose computed tomography for torsion measurements of the lower extremities in children and adolescents
Authors: Waelti Stephan , Fischer Tim , Griessinger Jennifer , Cip Johannes , Dietrich Tobias Johannes , Ditchfield Michael , Allmendinger Thomas , Messerli Michael , Markart Stefan 
Published: July 2022

Abstract
Background
Quantifying femoral and tibial torsion is crucial in the preoperative planning for derotation surgery in children and adolescents. The use of an ultra-low-dose computed tomography (CT) protocol might be possible for modern CT scanners and suitable for reliable torsion measurements even though the bones are not completely ossified.

Methods
This is a retrospective review of 77 children/adolescents (mean age 12.7 years) who underwent a lower extremity CT for torsion measurements on a 64-slice scanner. A stepwise dose reduction (70%, 50%, 30% of the original dose) was simulated. Torsion measurements were performed on all image datasets, and image noise, interrater agreement and subjective image quality were evaluated. Effective radiation dose of each original scan was estimated. As proof of concept, 24 children were scanned with an ultra-low-dose protocol, adapted from the 30% dose simulation, and the intra-class correlation coefficient (ICC) was determined. Ethics approval and informed consent were given.

Results
Torsion measurements at the simulated 30% dose level had equivalent interrater agreement compared to the 100% dose level (ICC ≥ 0.99 for all locations and dose levels). Image quality of almost all datasets was rated excellent, regardless of dose. The mean sum of the effective dose of the total torsion measurement was reduced by simulation from 0.460/0.490 mSv (boys/girls) at 100% dose to 0.138/0.147 mSv at 30%. The ICC of the proof-of-concept group was as good as that of the simulated 30% dose level.

Conclusion
Pediatric torsion measurements of the lower extremities can be performed using an ultra-low-dose protocol without compromising diagnostic confidence.