bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-like receptor-mediated innate immunity against herpesviridae infection: a current perspective on viral infection signaling pathways
Authors: Zheng Wenjin , Xu Qing , Zhang Yiyuan , E Xiaofei , Gao Wei , Zhang Mogen , Zhai Weijie , Rajkumar Ronaldjit Singh , Liu Zhijun 
Published: December 2020

AbstractBackgroundIn the past decades, researchers have demonstrated the critical role of Toll-like receptors (TLRs) in the innate immune system. They recognize viral components and trigger immune signal cascades to subsequently promote the activation of the immune system.Main bodyHerpesviridae family members trigger TLRs to elicit cytokines in the process of infection to activate antiviral innate immune responses in host cells. This review aims to clarify the role of TLRs in the innate immunity defense against herpesviridae, and systematically describes the processes of TLR actions and herpesviridae recognition as well as the signal transduction pathways involved.ConclusionsFuture studies of the interactions between TLRs and herpesviridae infections, especially the subsequent signaling pathways, will not only contribute to the planning of effective antiviral therapies but also provide new molecular targets for the development of antiviral drugs.
Clinicopathological and immunohistochemical study of 29 cases of solid-pseudopapillary neoplasms of the pancreas in patients under 20 years of age along with detailed review of literature
Authors: Din Nasir Ud , Rahim Shabina , Abdul-Ghafar Jamshid , Ahmed Arsalan , Ahmad Zubair 
Published: December 2020

Abstract
Background
Pancreatic Solid Pseudopapillary Neoplasms (SPNs) are rare low-grade malignant tumors with a marked preponderance for young females. Objective was to describe the morphology, differential diagnosis, and prognosis of SPNs in patients under 20 years of age and present a detailed review of literature.

Methods
A total of 29 cases in patients under 20 years of age reported as SPN during the period January 2014 to December 2019, were included in the study. These included 19 resection specimens, 4 incision biopsies and 6 cases received as blocks for second opinion. Hematoxylin and eosin (H&E) slides as well as immunohistochemistry (IHC) slides of all cases were retrieved and reviewed by the authors. TFE3 and Progesterone Receptor were performed retrospectively.

Results
Twenty-eight of the 29 patients were females. Ages of patients ranged from 12 to 19 years. Nineteen cases were resections. Tail was the commonest location. Mean tumor size was 9.5 cm. In 89.5% cases, tumor was confined to the pancreas. In 2 cases, distant metastasis was present. In 2 cases, extension beyond pancreas was seen. Solid and pseudopapillary areas were seen in all cases while other features were variable. Beta catenin and Cyclin D1 were positive in most cases while TFE3 was positive in 57% cases. Progesterone Receptor (PR) was positive in all 13 cases in which it was performed. Follow up was available in 14 patients. Follow up period ranged from 3 to 70 months. Twelve were alive and well without recurrence or metastasis while 2 were alive with recurrence and metastasis to liver and omentum respectively.

Conclusions
Although many studies on SPNs have been published, surgeons, oncologists and even pathologists in this part of the world are often not aware of these rare tumors leading to inaccuracies and delays in diagnosis. In addition, this paper focusses on the interesting observation that the majority of SPNs diagnosed in our department during study period occurred in patients under 20 years of age (29 versus 21 in patients over 20). However, clinico-epidemiological, morphologic and prognostic features were similar in both age groups. Possibility of SPNs should always be considered in case of pancreatic neoplasms occurring in patients under 20 years of age as well. We believe that this is a very interesting and helpful study for the clinicians as well as the pathologists.
Influence of a metaphyseal sleeve on the stress-strain state of a bone-tumor implant system in the distal femur: an experimental and finite element analysis
Authors: Li Jian-jun , Tian Dong-mu , Yang Li , Zhang Jing-yu , Hu Yong-cheng 
Published: December 2020

AbstractBackgroundAseptic loosening of distal femoral tumor implants significantly correlates with the resection length. We designed a new “sleeve” that is specially engaged in the metaphysis at least 5 cm proximal to the knee joint line to preserve as much bone stock as possible. This study investigates the influence of a metaphyseal sleeve on the stress-strain state of a bone tumor implant system in the distal femur.MethodsCortex strains in intact and implanted femurs were predicted with finite element (FE) models. Moreover strains were experimentally measured in a cadaveric femur with and without a sleeve and stem under an axial compressive load of 1000 N. The FE models, which were validated by linear regression, were used to investigate the maximal von Mises stress and the implanted-to-intact (ITI) ratios of strain in the femur with single-legged stance loading under immediate postoperative and osseointegration conditions.ResultsGood agreement was noted between the experimental measurements and numerical predictions of the femoral strains (coefficient of determination (R2) ≥ 0.95; root-mean-square error (RMSE%) ≈ 10%). The ITI ratios for the metaphysis were between 13 and 28% and between 10 and 21% under the immediate postoperative and osseointegration conditions, respectively, while the ITI ratios for the posterior and lateral cortices around the tip of the stem were 110% and 119% under the immediate-postoperative condition, respectively, and 114% and 101% under the osseointegration condition, respectively. The maximal von Mises stresses for the implanted femur were 113.8 MPa and 43.41 MPa under the immediate postoperative and osseointegration conditions, which were 284% and 47% higher than those in the intact femur (29.6 MPa), respectively.ConclusionsThis study reveals that a metaphyseal sleeve may cause stress shielding relative to the intact femur, especially in the distal metaphysis. Stress concentrations might mainly occur in the posterior cortex around the tip of the stem. However, stress concentrations may not be accompanied by periprosthetic fracture under the single-legged stance condition.
Plasma and local expressions of CircRNA CDR1as are linked with disease severity in patients with non-traumatic osteonecrosis of femoral head
Authors: Jiang Bin , Zhu Shu-Hua , Zeng Ji-Yong , Mao Zheng 
Published: December 2020

Abstract
Objective
To investigate the correlation of plasma and local expressions of Circ CDR1as with disease severity in patients with non-traumatic osteonecrosis of femoral head (ONFH).

Methods
Ninety-nine non-traumatic ONFH patients receiving surgery and 99 healthy individuals were enrolled in our study. Plasma and local Circ CDR1as were detected using real-time quantitative PCR (RT-qPCR). Radiographic progression was determined using Association Research Circulation Osseous (ARCO) classification system. Harris hip score (HHS) and visual analogue scale (VAS) were used to assess the clinical severity. Receiver operating characteristic (ROC) curve was carried out to evaluate the diagnostic value of plasma Circ CDR1as with regard to the radiographic severity.

Results
Plasma Circ CDR1as expressions were significantly higher in non-traumatic ONFH patients compared with healthy controls. In non-traumatic ONFH patients, there were no significant differences of CircCDR1as expressions between patients with alcohol-induced ONFH and steroid-induced ONFH. CircCDR1as in local necrotic tissue were significantly higher than adjacent non-affected tissue. Plasma and local Circ CDR1as expressions in patients with ARCO phase 4 were markedly upregulated compared with ARCO phase 3; plasma and local Circ CDR1as expressions in patients with ARCO phase 3 were markedly upregulated compared with ARCO phase 1/2. Plasma and local CircCDR1as expressions were positively associated with ARCO classification. In addition, plasma and local Circ CDR1as expressions were positively correlated with VAS and HHS scores. ROC curve analysis indicated that plasma Circ CDR1as may act as a decent marker for radiographic progression in non-traumatic ONFH patients.

Conclusions
Both plasma and local expressions of CircRNA CDR1as are linked with disease severity in patients with non-traumatic ONFH.
As an unusual traumatic presentation, acetabular fracture and concomitant ipsilateral intertrochanteric femur fracture: a retrospective case series of 18 patients
Authors: Liu Bo , Ma Wenhui , Liu Sikai , Chen Xiao , Li Mengnan , Huo Jia , Li Huijie , Han Yongtai 
Published: December 2020

AbstractBackgroundAcetabular fracture and concomitant ipsilateral intertrochanteric femur fracture has been suggested as an unusual traumatic presentation and rarely reported in the literature. The aims of this study were (1) to identify the etiological characteristics, (2) to summarize the treatment strategy, and (3) to present the mid- to long-term results of patients with this rare traumatic presentation.MethodsIn this retrospective study, 18 patients (15 males, 3 females; mean age = 42.77 ± 17.74 years, range = 16 to 87 years) who were diagnosed and treated for simultaneous acetabular fracture and ipsilateral intertrochanteric fracture were included. Injury mechanisms, fracture classifications, and treatment strategies were noted. To assess functional status, the Harris score was used. To evaluate pain intensity, visual analogous scale (VAS) was used. The reduction quality of acetabular fractures was examined as per Matta’s standard. Postoperative complications were also recorded.ResultsThe mean follow-up was 10.04 ± 3.38 (range = 6.2 to 16 years). The most common injury mechanism was traffic accident, followed by falling from a tall height. As per the Evans classification, intertrochanteric fractures were defined as type 3 in 13 patients, type 2 in one patient, and type 4 in 4 patients. In acetabular fracture site, the most common fractures were posterior wall fractures, followed by anterior column fractures. All patients received internal fixation for their intertrochanteric fractures. Ten out of 18 patients also received internal fixation for their acetabular fracture. However, for the remaining patients, acetabular fractures were treated conservatively or with fracture fragment resection. Bony healing was achieved in all but one patient who died postoperatively. Twelve patients achieved excellent and good results (Harris score ≥ 80 points) whereas five patients achieved fair and poor results (Harris score < 80 points). The proportion of patients who achieved an excellent-good Harris score was 70.6%. Dislocation of the hip was found to be an independent risk factor (HR = 9.194, 95% CI = 1.024-82.515) for the poor patient outcome.ConclusionTo sum up, high-impact trauma is the main cause of acetabular fracture and concomitant ipsilateral intertrochanteric femur fracture. For patients who have undergone surgical treatment, fracture healing is usually achieved. However, the occurrence of complications, especially avascular necrosis, is the major cause of a poor prognosis. Dislocation of the hip joint at the time of injury is considered to be an important risk factor for a poor prognosis.
Spectrum of movement disorders in GNAO1 encephalopathy: in-depth phenotyping and case-by-case analysis
Authors: Kim Soo Yeon , Shim YoungKyu , Ko Young Joon , Park Soojin , Jang Se Song , Lim Byung Chan , Kim Ki Joong , Chae Jong-Hee 
Published: December 2020

Abstract
Background
GNAO1 encephalopathy is a rare neurodevelopmental disorder characterized by distinct movement presentations and early onset epileptic encephalopathy. Here, we report the in-depth phenotyping of genetically confirmed patients with GNAO1 encephalopathy, focusing on movement presentations.

Results
Six patients who participated in Korean Undiagnosed Disease Program were diagnosed to have pathogenic or likely pathogenic variants in GNAO1 using whole exome sequencing. All medical records and personal video clips were analyzed with a literature review. Three of the 6 patients were male. Median follow-up duration was 41 months (range 7–78 months) and age at last examination was 7.4 years (range 3.3–16.9 years). Initial complaints were hypotonia or developmental delay in 5 and right-hand clumsiness in 1 patient, which were noticed at median age of 3 months (range 0–75 months). All patients showed global developmental delay and 4 had severely retarded development. Five patients (5/6, 83.3%) had many different movement symptoms with various onset and progression. The symptoms included stereotyped hands movement, non-epileptic myoclonus, dyskinesia, dystonia and choreoathetosis. Whole exome sequencing identified 6 different variants in GNAO1. Three were novel de novo variants and atypical presentation was noted in a patient. One variant turned out to be inherited from patient’s mother who had mosaic variant. Distinct and characteristics movement phenotypes in patients with variant p.Glu246Lys and p.Arg209His were elucidated by in-depth phenotyping and literature review.

Conclusions
We reported 6 patients with GNAO1 encephalopathy showing an extremely diverse clinical spectrum on video. Some characteristic movement features identified by careful inspection may also provide important diagnostic insight and practice guidelines.
Effect of ciliary neurotrophic factor on neural differentiation of stem cells of human exfoliated deciduous teeth
Authors: Zeng Sujuan , Zhao Xuedan , Zhang Lingling , Pathak Janak L. , Huang Wenyan , Li Yunyang , Guan Hongbing , Zhao Wanghong , Ge Lihong , Shu Yan 
Published: December 2020

AbstractThe stem cells of human exfoliated deciduous teeth (SHEDs) are considered to be one of the main sources of seed cells in stem cell therapy. The aim of this study was to examine the effect of ciliary neurotrophic factor (CNTF) on neurogenic differentiation of SHEDs. With the consent of parents, SHEDs from 6 to 8 year old children were isolated and cultured. The mesenchymal stemness and the potential of multidirectional (adipogenic and osteogenic) differentiation for the isolated SHEDs were firstly determined. The effect of CNTF on specific neurogenic differentiation of SHEDs was then examined by detecting the expression of marker genes and proteins via RT-PCR, immunoblotting, and immunofluorescence microscopy. The isolated SHEDs expressed specific surface markers of mesenchymal stem cells, and their potential of osteogenic and adipogenic differentiation were confirmed. CNTF promoted the differentiation of SHEDs into neuron-like cells with a high expression of acetylcholine transferase (CHAT), a marker of cholinergic neurons. The expression of other neuron markers including nestin, microtubule-associated protein 2 (MAP 2), and β-tublin III was also detected. Interestingly, the expression of neurogenic markers was maintained at a high level after neurogenic induction. SHEDs can be induced by CNTF to differentiate into cholinergic neuron-like cells under appropriate culture conditions. Our findings have laid a foundation for future use of SHEDs to treat neurological diseases.
Spectrum of thrombotic complications and their outcomes in Chinese children with primary nephrotic syndrome
Authors: Lv Yan-Li , Guan Na , Ding Jie , Yao Yong , Xiao Hui-Jie , Zhong Xu-Hui , Wang Fang , Liu Xiao-Yu , Zhang Hong-Wen , Su Bai-Ge , Xu Ke 
Published: December 2020

AbstractBackgroundThromboembolism is a life-threatening, limb-threatening or organ-threatening complication that occurs in patients with primary nephrotic syndrome (NS). There are few studies on the spectrum, complications and outcomes of thrombosis in children with NS. This study aimed to determine the spectrum of thrombosis and its relationship with the nephrotic state, treatment and outcomes in children and adolescents with primary NS.MethodsThe medical records of subjects aged 1–18 years with NS complicated with thromboembolism treated at our centre within the last 26 years were retrieved. Data on the status of NS, site, symptoms and signs, laboratory investigations, diagnosis, treatment, complications and outcomes of thrombosis were collected and reviewed retrospectively. A severe complication was defined as a condition associated with thrombosis requiring a special diagnostic modality to confirm or a specific treatment such as surgical intervention. The outcome of thrombosis was defined as the status of thrombosis, as determined by imaging methods and the functional status with respect to the anatomic sites of thrombosis at the last follow-up. The permanent dysfunction of an organ or limb related to thrombosis was defined as a sequela.ResultsWe observed thrombosis in 1.4% (27/1995) of subjects with NS during the study period. There were 27 subjects with thrombosis, including 21 males and 6 females. Thrombosis was observed in 51.9% (14/27) of the study participants with steroid resistant NS. Most episodes of thrombosis occurred during the active stage of NS; however, 7.4% of thrombosis cases occurred during the remission of proteinuria. Renal vein thrombosis (33.3%) and pulmonary embolism (25.9%) were the most common types of thrombosis. Among the 17 subjects biopsied, minimal change disease and membranous nephropathy were the two most common findings. Six (22.2%) subjects experienced severe complications or sequelae; 1 had persistent intracranial hypertension, 1 had intestinal perforation, 1 had hypoxemia and pulmonary hypertension, 1 had lameness, 1 had epilepsy, and 1 had an askew mouth due to facial paralysis. In 19 (70.4%) subjects, the symptoms resolved completely or improved without severe complications or sequelae.ConclusionsThrombosis mostly occurred in males of school age during the active stage of NS. Renal vein thrombosis and pulmonary embolism were the most common types of thrombosis. In most patients with thrombosis, the symptoms improved completely without complications with standard anticoagulation therapy. However, 22.2% had severe complications or sequelae requiring an advanced diagnostic modality and aggressive treatment.
Opportunities and challenges of delivering digital clinical trials: lessons learned from a randomised controlled trial of an online behavioural intervention for children and young people
Authors: Hall Charlotte L. , Sanderson Charlotte , Brown Beverly J. , Andrén Per , Bennett Sophie , Chamberlain Liam R. , Davies E. Bethan , Khan Kareem , Kouzoupi Natalie , Mataix-Cols David , McKenzie Caitlin , Murphy Tara , Townsend Mark , Hollis Chris , Murray Elizabeth 
Published: December 2020

Abstract
Background
Despite being the gold standard of research to determine effectiveness, randomised controlled trials (RCTs) often struggle with participant recruitment, engagement and retention. These issues may be exacerbated when recruiting vulnerable populations, such as participants with mental health issues. We aimed to update understanding of the scope of these problems in trials of health technology and identify possible solutions through reflecting on experiences from an exemplar trial (Online Remote Behavioural Intervention for Tics; ORBIT).

Method
We extracted anonymised data on recruitment, retention and requests for more funding and time from trials funded by the largest funder of health technology trials in the UK (the National Institute of Health Research Health Technology Assessment) between 2010 and 2020, and compared these with data from a recent, successful trial (ORBIT). ORBIT aimed to assess the clinical- and cost-effectiveness of blended online and human behavioural therapy for tics in young people. Many of the trial procedures, including recruitment, the intervention and data collection, were undertaken online.

Results
Data were extracted on 51 trials conducted between 2010 and 2020. Sixty per cent of trials failed to reach their original recruitment target and only 44% achieved their follow-up in the specified time frame. In contrast, ORBIT recruited to target and achieved 90% follow-up. We posit that these achievements are related to (a) judicious use of digital technology for trial procedures and (b) adequate numbers of highly trained and motivated trial staff. We provide details of both these to help other research teams plan and cost for successful trials.

Conclusion
An approach combining human and online methods may be advantageous in facilitating trial delivery, particularly in paediatric mental health services. Given the importance of successful clinical trials in advancing healthcare delivery and the waste of human and economic resources associated with unsuccessfully delivered trials, it is imperative that trials are appropriately costed and future research focusses on improving trial design and delivery.

Trial registration
The ORBIT trial is registered with ISRTCN (ISRCTN70758207) Registered on March 20, 2018. and ClinicalTrials.gov (NCT03483493). Registered on March 30, 2018.
Variation in sugarcane biomass composition and enzymatic saccharification of leaves, internodes and roots
Authors: Mason Patrick J. , Furtado Agnelo , Marquardt Annelie , Hodgson-Kratky Katrina , Hoang Nam V. , Botha Frederik C. , Papa Gabriella , Mortimer Jenny C. , Simmons Blake , Henry Robert J. 
Published: December 2020

Abstract
Background
The composition of biomass determines its suitability for different applications within a biorefinery system. The proportion of the major biomass fractions (sugar, cellulose, hemicellulose and lignin) may vary in different sugarcane genotypes and growth environments and different parts of the plant. This study investigated the composition of mature and immature internodes, roots and mature leaves of sugarcane.

Results
Internodes were found to have a significantly larger alcohol-soluble component than leaves and roots. The primary difference between the immature and mature internodes was the ratio of soluble sugars. In mature tissues, sucrose content was significantly higher, whereas in immature internodal tissues there was lower sucrose and heightened concentrations of reducing sugars. Carbon (C) partitioning in leaf tissues was characterised by low levels of soluble components and high “other” and cell wall fractions. Root tissue had low ratios of soluble fractions relative to their cell wall contents, indicating a lack of storage of soluble carbon. There was no significant difference in the ratio of the major cell wall fractions between the major organ types. Characterisation of individual non-cellulosic monomers indicated leaf and root tissues had significantly higher arabinose and galactose fractions. Significantly larger proportions of syringyl lignin compounds and the hydroxycinnamic compound, p-coumaric acid were observed in mature internodal tissues compared to the other tissue types. Tissue-specific differences in composition were shown to greatly affect the recalcitrance of the cell wall to enzymatic saccharification.

Conclusions
Overall, this study displayed clear evidence of the differential partitioning of C throughout the sugarcane plant in specific organs. These organ-specific differences have major implications in their utility as a bioproduct feedstock. For example, the inclusion of trash (leaves) with the culms (internodes) may alter processing efficiency.