bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compound heterozygous mutations in ABCG5 or ABCG8 causing Chinese familial Sitosterolemia
Authors: Sun Weiwei , Zhang Tian , Zhang Xiaoguang , Wang Jieyu , Chen Yuqing , Long Yun , Zhang Gong , Wang Yajian , Chen Ye , Fang Tao , Chen Mingwu 
Published: March 2020

AbstractBackgroundSitosterolemia (STSL), also known as phytosterolemia, is a rare autosomal recessive hereditary disease caused by mutations in the ABCG5 or ABCG8 genes. The disease is a result of disorders in lipoprotein metabolism, and is characterized by tendinous and tuberous xanthomas, elevated plasma cholesterol and phytosterol levels, and thrombocytopenia and hemolytic anemia in several patients. The manifestations of STSL are diverse and can easily be misdiagnosed. In recent years, cases of this disease in children have been reported in succession. There is therefore a need for clinicians to improve identification of STSL and perform early intervention.MethodsWe evaluated four children with STSL caused by genetic mutations in ABCG5 or ABCG8, as well as their family members, by analyzing their clinical characteristics and performing Trio‐whole exome sequencing. The biological consequences of the mutations were analyzed using various bioinformatics software. We also analyzed the consequences of a mutation commonly observed in STSL patients on the structure of the protein involved.ResultsWe identified five previously unreported pathogenic mutations of different phenotypes of STSL: ABCG5 NM_022436:c.1337G>A; ABCG8 NM_022437:c.965‐1G>A, c.323‐1G>C, c.1418C>G and c.1534G>A. We also report the structural changes brought about by a mutation common in STSL patients, as well as the possible consequences of these changes.ConclusionsOur findings further broaden the genotypic and phenotypic profiles of the onset of STSL in the pediatric population and provide information for the diagnosis and treatment of this disease.
Long term effects of stress on hippocampal function: Emphasis on early life stress paradigms and potential involvement of neuropeptide Y
Authors: Alviña Karina , Jodeiri Farshbaf Mohammad , Mondal Amit Kumar 
Published: March 2020

AbstractThe brain is both central in orchestrating the response to stress, and, a very sensitive target when such response is not controlled. In fact, stress has long been associated with the onset and/or exacerbation of several neuropsychiatric disorders such as anxiety, depression, and drug addiction. The hippocampus is a key brain region involved in the response to stress, not only due to its anatomical connections with the hypothalamic‐pituitary‐adrenal axis but also as a major target of stress mediators. The hippocampal dentate gyrus (DG)‐CA3 circuit, composed of DG granule cells axons (mossy fibers) synapsing onto CA3 pyramidal cells, plays an essential role in memory encoding and retrieval, functions that are vulnerable to stress. Although naturally excitatory, this circuit is under the inhibitory control of GABAergic interneurons that maintain the excitation/inhibition balance. One subgroup of such interneurons produces neuropeptide Y (NPY), which has emerged as a promising endogenous stress “resilience molecule” due to its anxiolytic and anti‐epileptic properties. Here we examine existing evidence that reveals a potential role for hilar NPY+ interneurons in mediating stress‐induced changes in hippocampal function. We will focus specifically on rodent models of early life stress (ELS), defined as adverse conditions during the early postnatal period that can have profound consequences for neurodevelopment. Collectively, these findings suggest that the long‐lasting effects of ELS might stem from the loss of GABAergic NPY+ cells, which then can lead to reduced inhibition in the DG‐CA3 pathway. Such change might then lead to hyperexcitability and concomitant hippocampal‐dependent behavioral deficits.
Similitude of cement‐bone micromechanics in cemented rat and human knee replacement
Authors: Mann Kenneth A. , Miller Mark A. , Tatusko Megan E. , Oest Megan E. 
Published: March 2020

AbstractA preclinical rat knee replacement model was recently developed to explore the biological and mechanobiological changes of trabecular resorption for cement‐bone interdigitated regions. The goal here was to evaluate the relevance of this model compared with human knee replacement with regards to functional micromechanics. Eight nonsurvival, cemented knee replacement surgeries were performed, the interdigitated gap morphology was quantified, and interface micromotion between cement and bone was measured for 1 to 5 bodyweight loading. Computational fluid dynamics modeling of unit cell geometries with small gaps between trabeculae and cement was used to estimate fluid flow. Gap width (3.6 μm) was substantially smaller compared with cement‐bone gaps reported in human knee replacement (11.8 μm). Micromotion at the cement‐bone border was also decreased for the rat knee replacement (0.48 μm), compared with human (1.97 μm), for 1 bodyweight loading. However, the micromotion‐to‐gap width ratio (0.19 and 0.22 for, rat and human), and estimated fluid shear stress (6.47 and 7.13 Pa, for rat and human) were similar. Replicating the fluid dynamic characteristics of cement‐bone interdigitated regions in human knee replacements using preclinical models may be important to recapitulate trabecular resorption mechanisms due to proposed supraphysiologic fluid shear stress. Statement of clinical significance: local cement‐bone micromotion due to joint loading may contribute to the process of clinical loosening in total joint replacements. This work shows that while micromotion and gap morphology are diminished for the rat knee model compared to human, the motion‐to‐gap ratio, and corresponding fluid shear stress are of similar magnitudes
Outcomes of palliative‐intent surgery in retroperitoneal sarcoma—Results from the US Sarcoma Collaborative
Authors: Thalji Sam Z. , Tsai Susan , Gamblin T. Clark , Clarke Callisia , Christians Kathleen , Charlson John , Ethun Cecilia G. , Poultsides George , Grignol Valerie P. , Roggin Kevin K. , Votanopoulos Konstantinos , Fields Ryan C. , Abbott Daniel E. , Cardona Kenneth , Mogal Harveshp ,   other members of the US Sarcoma Collaborative
Published: March 2020

AbstractBackground and ObjectivesOutcomes of palliative‐intent surgery in retroperitoneal sarcomas (RPS) are not well understood. This study aims to define indications for and outcomes after palliative‐intent RPS resection.MethodsUsing a retrospective 8‐institution database, patients undergoing resection of primary/recurrent RPS with palliative intent were identified. Logistic regression and Cox‐proportional hazards models were constructed to analyze factors associated with postoperative complications and overall survival (OS).ResultsOf 3088 patients, 70 underwent 87 palliative‐intent procedures. Most common indications were pain (26%) and bowel obstruction (21%). Dedifferentiated liposarcoma (n = 17, 24%), leiomyosarcoma (n = 13, 19%) were predominant subtypes. Median OS was 10.69 months (IQR, 3.91‐23.23). R2 resection (OR, 8.60; CI, 1.42‐52.15; P = .019), larger tumors (OR, 10.87; CI, 1.44‐82.11; P = .021) and low preoperative albumin (OR, 0.14; CI, 0.04‐0.57; P = .006) were associated with postoperative complications. Postoperative complications (HR, 1.95; CI, 1.02‐3.71; P = .043) and high‐grade histology (HR, 6.56; CI, 1.72‐25.05; P = .006) rather than resection status were associated with reduced OS. However, in R2‐resected patients, development of postoperative complications significantly reduced survival (P = .042).ConclusionsPostoperative complications and high‐grade histology rather than resection status impacts survival in palliative‐intent RPS resections. Given the higher incidence of postoperative complications which may diminish survival, palliative‐intent R2 resection should be offered only after cautious consideration.
Sarcopenia is associated with increased mortality but not complications following resection and reconstruction of sarcoma of the extremities
Authors: Hendrickson Nathan R. , Mayo Zachary , Shamrock Alan , Kesler Kyle , Glass Natalie , Nau Peter , Miller Benjamin J. 
Published: March 2020

AbstractBackground and ObjectivesEvidence regarding the impact of sarcopenia on operative outcomes in patients with sarcoma is lacking. We evaluated the relationship between sarcopenia and postoperative complications or mortality among patients undergoing tumor excision and reconstruction. ​MethodsWe retrospectively reviewed 145 patients treated with tumor excision and limb reconstruction for sarcoma of the extremities. Sarcopenia was defined as psoas index (PI) < 5.45 cm2/m2 for men and <3.85 cm2/m2 for women from preoperative axial CT. Regression analyses were used to assess the association between postoperative complications or mortality with PI, age, gender, race, body mass index, tumor histology, grade, depth, location, size, and neoadjuvant/adjuvant therapy.ResultsThere were 101 soft tissue tumors and 44 primary bone tumors. Sarcopenia was present in 38 patients (26%). Sarcopenic patients were older (median age: 72 vs 59 years, P = .0010) and had larger tumors (86.5%, >5 cm vs 77.7%, P = .023). Seventy‐three patients experienced complications (51%) and 18 patients died within 1 year. Sarcopenia and metastatic disease were associated with increased 12‐month mortality (hazard ratio [HR] = 6.68, P < .001; HR: 8.51, P < .001, respectively) but not complications (HR 1.45, P = .155, odds ratio, 1.32, P = .426, respectively).ConclusionsSarcopenia and metastatic disease were independently associated with postoperative mortality but no complications following surgery.
Comprehensive tumor profiling reveals unique molecular differences between peritoneal metastases and primary colorectal adenocarcinoma
Authors: Stein Matthew K. , Williard Forrest W. , Xiu Joanne , Tsao Miriam W. , Martin Michael G. , Deschner Benjamin W. , Dickson Paxton V. , Glazer Evan S. , Yakoub Danny , Shibata David , Grothey Axel F. , Philip Philip A. , Hwang Jimmy J. , Shields Anthony F. , Marshall John L. , Korn W. Michael , Lenz Heinz‐Josef , Deneve Jeremiah L. 
Published: March 2020

AbstractBackground and ObjectivesPeritoneal metastases (PM) from primary colorectal cancer (pCRC) are associated with poor outcomes; however, molecular differences are not well defined.MethodsWe compared unpaired tumor profiles of patients with pCRC and PM from Caris Life Sciences. Testing included next‐generation sequencing of 592 genes, microsatellite instability (MSI) and tumor mutational burden (TMB). Mutations were test‐defined as pathogenic (PATH).ResultsSix hundred seventeen pCRC and 348 PM patients had similar gender (55% male) and age (median 59). PATHs were similar between PM and pCRC in KRAS, BRAF, SMAD2, SMAD4, and PTEN. pCRC PATHs were increased in APC (76% vs 48%, P < .01), ARID1A (29% vs 12%, P < .05), TP53 (72% vs 53%, P < .01), PIK3CA (22% vs 15%, P < .05), and FBXW7 (13% vs 7%, P < .01) compared with PM. Mucinous PM had more PATHs in GNAS (19% vs 8%, P = .032) while nonmucinous PM had more PATHs in BRAF (13% vs 8%, P = .027). Right‐sided PM had decreased PATHs in APC (39% vs 68%, P < .0001), ARID1A (7% vs 38%, P < .004), and TP53 (48% vs 65%, P = .033) while there were no difference for left‐sided PM. Nine percent of pCRC and 6% of PM were MSI‐high (P = NS). There was no difference in TMB‐high, TMB‐intermediate, or TMB‐low between PM and pCRC.ConclusionsPM have similar rates of KRAS mutation with increased PATHs in GNAS (mucinous) and BRAF (nonmucinous) compared to pCRC. No differences in MSI or TMB were identified between PM and pCRC tumors. These findings inform future study into the molecular profile of PM.
Gradient Photonic Materials Based on One‐Dimensional Polymer Photonic Crystals
Authors: Schedl Andreas E. , Howell Irene , Watkins James J. , Schmidt Hans‐Werner 
Published: March 2020

AbstractIn nature, animals such as chameleons are well‐known for the complex color patterns of their skin and the ability to adapt and change the color by manipulating sophisticated photonic crystal systems. Artificial gradient photonic materials are inspired by these color patterns. A concept for the preparation of such materials and their function as tunable mechanochromic materials is presented in this work. The system consists of a 1D polymer photonic crystal on a centimeter scale on top of an elastic poly(dimethylsiloxane) substrate with a gradient in stiffness. In the unstrained state, this system reveals a uniform red reflectance over the entire sample. Upon deformation, a gradient in local strain of the substrate is formed and transferred to the photonic crystal. Depending on the magnitude of this local strain, the thickness of the photonic crystal decreases continuously, resulting in a position‐dependent blue shift of the reflectance peak and hence the color in a rainbow‐like fashion. Using more sophisticated hard‐soft‐hard‐soft‐hard gradient elastomers enables the realization of stripe‐like reflectance patterns. Thus, this approach allows for the tunable formation of reflectance gradients and complex reflectance patterns. Envisioned applications are in the field of mechanochromic sensors, telemedicine, smart materials, and metamaterials.
Design and manufacture of a high precision personalized electron bolus device for radiation therapy
Authors: Aldawood Faisal Khaled , Chang Sha X. , Desai Salil 
Published: March 2020

AbstractThis paper investigates a novel design and manufacturing methodology for an unmet need in radiation therapy—dose optimization of electron beam bolus. A thin‐walled bolus design was proposed which when filled with water, optimized the dose distribution for the electron beam radiation therapy. The fabrication of this design was accomplished by the fused deposition modelling (FDM) additive manufacturing (3D Printing) technique. Acrylonitrile butadiene styrene (ABS) and polycarbonate (PC) materials were employed for fabricating the electron boluses. Our data show that both the materials displayed expected radiation modulation. The designed boluses were subjected to higher radiation doses (50 Gy) and revealed permissible deformations based on the dimensional deviation analysis. Mechanical deformation tests were performed to evaluate the bolus design and materials under different loading conditions. The results showed that the ABS material had superior mechanical strength and deformation behaviour as compared to PC. Finite element analysis of the bolus designs revealed regions of stress concentration and potential failure modes which were validated by experimental results. The design of experiments analysis showed that bolus thickness and material type had a profound influence on the mechanical deformation of the bolus. The proposed radiation device technology is cost‐effective, eco‐friendly and amenable to changes in the tumour size and shape, compared to current methods. This paper provides a framework for the design and manufacture of radiation modulation devices that can be implemented for proton, electron and photon cancer therapies.
Whole exome sequencing identifies multiple novel candidate genes in familial gastroschisis
Authors: Salinas‐Torres Víctor M. , Gallardo‐Blanco Hugo L. , Salinas‐Torres Rafael A. , Cerda‐Flores Ricardo M. , Lugo‐Trampe José J. , Villarreal‐Martínez Daniel Z. , Ibarra‐Ramírez Marisol , Martínez de Villarreal Laura E. 
Published: March 2020

AbstractBackgroundGenetic association studies for gastroschisis have highlighted several candidate variants. However, genetic basis in gastroschisis from noninvestigated heritable factors could provide new insights into the human biology for this birth defect. We aim to identify novel gastroschisis susceptibility variants by employing whole exome sequencing (WES) in a Mexican family with recurrence of gastroschisis.MethodsWe employed WES in two affected half‐sisters with gastroschisis, mother, and father of the proband. Additionally, functional bioinformatics analysis was based on SVS–PhoRank and Ensembl–Variant Effect Predictor. The latter assessed the potentially deleterious effects (high, moderate, low, or modifier impact) from exome variants based on SIFT, PolyPhen, dbNSFP, Condel, LoFtool, MaxEntScan, and BLOSUM62 algorithms. The analysis was based on the Human Genome annotation, GRCh37/hg19. Candidate genes were prioritized and manually curated based on significant phenotypic relevance (SVS–PhoRank) and functional properties (Ensembl–Variant Effect Predictor). Functional enrichment analysis was performed using ToppGene Suite, including a manual curation of significant Gene Ontology (GO) biological processes from functional similarity analysis of candidate genes.ResultsNo single gene‐disrupting variant was identified. Instead, 428 heterozygous variations were identified for which SPATA17, PDE4DIP, CFAP65, ALPP, ZNF717, OR4C3, MAP2K3, TLR8, and UBE2NL were predicted as high impact in both cases, mother, and father of the proband. PLOD1, COL6A3, FGFRL1, HHIP, SGCD, RAPGEF1, PKD1, ZFHX3, BCAS3, EVPL, CEACAM5, and KLK14 were segregated among both cases and mother. Multiple interacting background modifiers may regulate gastroschisis susceptibility. These candidate genes highlight a role for development of blood vessel, circulatory system, muscle structure, epithelium, and epidermis, regulation of cell junction assembly, biological/cell adhesion, detection/response to endogenous stimulus, regulation of cytokine biosynthetic process, response to growth factor, postreplication repair/protein K63‐linked ubiquitination, protein‐containing complex assembly, and regulation of transcription DNA‐templated.ConclusionConsidering the likely gene‐disrupting prediction results and similar biological pattern of mechanisms, we propose a joint “multifactorial model” in gastroschisis pathogenesis.
A novel random discrete element analysis of rock fragmentation
Authors: Zhao Tao , Liu Yong 
Published: March 2020

SummaryThis paper presents a novel probabilistic approach of random discrete element analysis (RDEA) to investigate the mechanism of rock fragmentation under uniaxial compression. This model combines the advantages of both random field theory and discrete element method in characterizing the spatial variation and uncertainty of microscopic material properties. The numerical results reveal that the stress‐strain curves of a group of tests can match well the general trend of the experimental data, with the mean uniaxial compressive strength (UCS) of 10.18 MPa and the mean Young modulus of 1.73 GPa. The coefficient of variation (COV) for the rock samples is much lower than that of the initial random fields of particles because of the averaging effect of microscopic material property in obtaining the bulk values. The rock fragmentation is initiated by the breakage of weak particles within the rock mass, and it develops rapidly as the vertical loading stress approaches the UCS. The final damage zone resides dominantly in the weak region of the rock sample, and the distribution of material property coefficients follows a similar beta distribution as the corresponding initial random field. Rock samples with persistent “pillar‐like” structures of strong particles can effectively resist the normal compression, resulting in high rock strengths. The traditional DEM simulation with a set of constant material properties can only represent one extreme realization of random field, which could significantly overestimate the rock strength. The proposed RDEA approach can effectively capture the uncertainty and complex interactions of rock fragmentation in a more realistic and reliable way.
Effectiveness and robustness revisited for a preconditioning technique based on structured incomplete factorization
Authors: Xin Zixing , Xia Jianlin , Cauley Stephen , Balakrishnan Venkataramanan 
Published: March 2020

SummaryIn this work, we provide new analysis for a preconditioning technique called structured incomplete factorization (SIF) for symmetric positive definite matrices. In this technique, a scaling and compression strategy is applied to construct SIF preconditioners, where off‐diagonal blocks of the original matrix are first scaled and then approximated by low‐rank forms. Some spectral behaviors after applying the preconditioner are shown. The effectiveness is confirmed with the aid of a type of two‐dimensional and three‐dimensional discretized model problems. We further show that previous studies on the robustness are too conservative. In fact, the practical multilevel version of the preconditioner has a robustness enhancement effect, and is unconditionally robust (or breakdown free) for the model problems regardless of the compression accuracy for the scaled off‐diagonal blocks. The studies give new insights into the SIF preconditioning technique and confirm that it is an effective and reliable way for designing structured preconditioners. The studies also provide useful tools for analyzing other structured preconditioners. Various spectral analysis results can be used to characterize other structured algorithms and study more general problems.
Function and mutual interaction of BiP‐, PERK‐, and IRE1α‐dependent signalling pathways in vascular tumours
Authors: Anspach Laura , Tsaryk Roman , Seidmann Larissa , Unger Ronald E , Jayasinghe Caren , Simiantonaki Nektaria , Kirkpatrick C James , Pröls Felicitas 
Published: March 2020

AbstractSpontaneously regressing infantile haemangiomas and aggressive angiosarcomas are vascular tumours with excessive angiogenesis. When analysing haemangiomas and angiosarcomas immunohistochemically with respect to their chaperone profiles we found that angiosarcomas have significantly elevated protein levels of binding immunoglobulin protein (BIP) and PERK with concomitant attenuated IRE1α levels, whereas haemangioma tissue exhibits the same pattern as embryonal skin tissue. We show that BiP is essential for the maintenance of VEGFR2 protein, which is expressed in the endothelium of both tumour types. When studying the effects of BiP, the IRE1α/Xbp1 ‐, and PERK/ATF4‐signalling pathways on the migration and tube‐forming potential of endothelial cells, we show that downregulation of BiP, as well as inhibition of the kinase activity of IRE1α, inhibit in vitro angiogenesis. Downregulation of PERK (PKR‐like kinase; PKR = protein kinase R) levels promotes Xbp1 splicing in endoplasmic reticulum (ER)‐stressed cells, indicating that in angiosarcoma the elevated PERK levels might result in high levels of unspliced Xbp1, which have been reported to promote cell proliferation and increase tumour malignancy. The data presented in this study revealed that in addition to BiP or PERK, the kinase domains of IRE1α and Xbp1 could be potential targets for the development of novel therapeutic approaches for treating angiosarcomas and to control tumour angiogenesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.