bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the Impact of Phenoconversion on Medications With Actionable Pharmacogenomic Guideline Recommendations in an Acute Aged Persons Mental Health Setting
Authors: Mostafa Sam , Polasek Thomas M. , Sheffield Leslie J. , Huppert David , Kirkpatrick Carl M. J.
Published: August 2021

Introduction: Polypharmacy and genetic variants that strongly influence medication response (pharmacogenomics, PGx) are two well-described risk factors for adverse drug reactions. Complexities arise in interpreting PGx results in the presence of co-administered medications that can cause cytochrome P450 enzyme phenoconversion.

Aim: To quantify phenoconversion in a cohort of acute aged persons mental health patients and evaluate its impact on the reporting of medications with actionable PGx guideline recommendations (APRs).

Methods: Acute aged persons mental health patients (N = 137) with PGx and medication data at admission and discharge were selected to describe phenoconversion frequencies for CYP2D6, CYP2C19 and CYP2C9 enzymes. The expected impact of phenoconversion was then assessed on the reporting of medications with APRs.

Results: Post-phenoconversion, the predicted frequency at admission and discharge increased for CYP2D6 intermediate metabolisers (IMs) by 11.7 and 16.1%, respectively. Similarly, for CYP2C19 IMs, the predicted frequency at admission and discharge increased by 13.1 and 11.7%, respectively. Nineteen medications with APRs were prescribed 120 times at admission, of which 50 (42%) had APRs pre-phenoconversion, increasing to 60 prescriptions (50%) post-phenoconversion. At discharge, 18 medications with APRs were prescribed 122 times, of which 48 (39%) had APRs pre-phenoconversion, increasing to 57 prescriptions (47%) post-phenoconversion.

Discussion: Aged persons mental health patients are commonly prescribed medications with APRs, but interpretation of these recommendations must consider the effects of phenoconversion. Adopting a collaborative care model between prescribers and clinical pharmacists should be considered to address phenoconversion and ensure the potential benefits of PGx are maximised.
Adverse Childhood Events and Health Biomarkers: A Systematic Review
Authors: Soares Sara , Rocha Vânia , Kelly-Irving Michelle , Stringhini Silvia , Fraga Sílvia
Published: August 2021

Background: This systematic review aimed to summarize evidence reporting epigenetic and/or neuro-immuno-endocrine embedding of adverse childhood events (ACEs) in children, with a particular focus on the short-term biological effect of those experiences.

Methods: A search was conducted in PsycINFO®, PubMed®, Isi Web of Knowledge and Scopus, until July 2019, to identify papers reporting the short-term biological effects of exposure to ACEs.

Results: The search identified 58 studies, that were included in the review. Regarding exposure, the type of ACE more frequently reported was sexual abuse (n = 26), followed by life stressors (n = 20) and physical abuse (n = 19). The majority (n = 17) of studies showed a positive association between ACEs and biomarkers of the immune system. Regarding DNA methylation 18 studies showed more methylation in participants exposed to ACEs. Two studies presented the effect of ACEs on telomere length and showed that exposure was associated with shorter telomere length.

Conclusion: Overall the associations observed across studies followed the hypothesis that ACEs are associated with biological risk already at early ages. This is supporting evidence that ACEs appear to get “under the skin” and induce physiological changes and these alterations might be strongly associated with later development of disease.
Does Industrial Agglomeration or Foreign Direct Investment Matter for Environment Pollution of Public Health? Evidence From China
Authors: Li Shi-Jie , Sun Bin , Hou Ding-Xia , Jin Wei-Jian , Ji Yun
Published: August 2021

This article focuses on the interaction between China's industrial agglomeration, foreign direct investment (FDI) and environmental pollution of public health in the past 15 years. By conducting theoretical and empirical research, we try to reveal the relationship and mechanism between the economic growth and public health from the perspective of environmental pollution. By constructing an embedded theoretical model of industrial agglomeration and FDI, this article combines other environmental pollution influencing factors, expounds the impact mechanism of industrial agglomeration on environmental pollution. Based on the provincial-level panel data of China on environmental pollution and industrial agglomeration, the empirical test is carried out through the threshold panel regression model. According to the results, industrial agglomeration can significantly rectify the regional environmental pollution, thereby benefiting public health. FDI has a phased impact on the relationship between industrial agglomeration and environmental pollution. Specifically, when the level of FDI is low, the positive improvement effect of industrial agglomeration on environmental pollution is relatively strong. This is mainly because industrial agglomeration can promote economic growth, technological progress, and enhance environmental awareness. When the level of FDI exceeds the first threshold and continues to rise, the positive improvement effect of industrial agglomeration is maximized. Before the level of FDI exceeds the second threshold, this effect gradually weakens. The population concentration and excessive expansion of city scale brought about by industrial agglomeration will lead to the increase of regional resource and energy consumption, thus aggravating environmental pollution. The policy implication is that while the government and enterprises are vigorously increasing the level of foreign investment, they must pay equal attention to economic growth and public health, and the level of industrial agglomeration should match the level of foreign investment so as to give full play to the positive improvement effect of industrial agglomeration on environmental pollution, and realize the coordinated development of the regional economy, environment and population health.
Surgical Outcomes of Robotic Resection for Sigmoid and Rectal Cancer: Analysis of 109 Patients From a Single Center in China
Authors: Peng Jianhong , Li Weihao , Tang Jinghua , Li Yuan , Li Xueying , Wu Xiaojun , Lu Zhenhai , Lin Junzhong , Pan Zhizhong
Published: August 2021

Background: Robotic colorectal surgery has been increasingly performed in recent years. The safety and feasibility of its application has also been demonstrated worldwide.However, limited studies have presented clinical data for patients with colorectal cancer (CRC) receiving robotic surgery in China. The aim of this study is to present short-term clinical outcomes of robotic surgery and further confirm its safety and feasibility in Chinese CRC patients.

Methods: The clinical data of 109 consecutive CRC patients who received robotic surgery at Sun Yat-sen University Cancer Center between June 2016 and May 2019 were retrospectively reviewed. Patient characteristics,tumor traits, treatment details, complications, pathological details, and survival status were evaluated.

Results: Among the 109 patients, 35 (32.1%) had sigmoid cancer, and 74 (67.9%) had rectal cancer. Thirty-seven (33.9%) patients underwent neoadjuvant chemoradiotherapy. Ten (9.2%) patients underwent sigmoidectomy, 38 (34.9%) underwent high anterior resection (HAR), 45 (41.3%) underwent low anterior resection (LAR), and 16 (14.7%) underwent abdominoperineal resection (APR). The median surgical procedure time was 270 min (range 120–465 min). Pathologically complete resection was achieved in all patients. There was no postoperative mortality. Complications occurred in 11 (10.1%) patients, including 3 (2.8%) anastomotic leakage, 1 (0.9%) anastomotic bleeding, 1 (0.9%) pelvic hemorrhage, 4 (3.7%) intestinal obstruction, 2 (1.8%) chylous leakage, and 1 (0.9%) delayed wound union. At a median follow-up of 17 months (range 1–37 months), 1 (0.9%) patient developed local recurrence and 5 (4.6%) developed distant metastasis, with one death due to disease progression.

Conclusions: Our results suggest that robotic surgery is technically feasible and safe for Chinese CRC patients, especially for rectal cancer patients who received neoadjuvant treatment. A robotic laparoscope with large magnification showed a clear surgical space for pelvic autonomic nerve preservation in cases of mesorectal edema.
Total Psoas Muscle Area as a Marker for Sarcopenia Is Related to Outcome in Children With Neuroblastoma
Authors: Ritz Annika , Froeba-Pohl Alexandra , Kolorz Julian , Vigodski Victor , Hubertus Jochen , Ley-Zaporozhan Julia , von Schweinitz Dietrich , Häberle Beate , Schmid Irene , Kappler Roland , Lurz Eberhard , Berger Michael
Published: August 2021

Background: Sarcopenia describes a generalized loss of skeletal muscle mass, strength, or function. Determined by measuring the total psoas muscle area (tPMA) on cross-sectional imaging, sarcopenia is an independent marker for poor post-surgical outcomes in adults and children. Children with cancer are at high risk for sarcopenia due to immobility, chemotherapy, and cachexia. We hypothesize that sarcopenic children with neuroblastoma are at higher risk for poor post-operative outcomes.

Patients and Methods: Retrospective analysis of children with neuroblastoma ages 1–15 years who were treated at our hospital from 2008 to 2016 with follow-up through March 2021. Psoas muscle area (PMA) was measured from cross-sectional images, using computed tomography (CT) and magnetic resonance imaging (MRI) scans at lumbar disc levels L3-4 and L4-5. tPMA is the sum of the left and right PMA. Z-scores were calculated using age- and gender-specific reference values. Sarcopenia was defined as a tPMA z-score below −2. A correlation of tPMA z-scores and sarcopenia with clinical variables and outcome was performed.

Results: One hundred and sixty-four children with workup for neuroblastoma were identified, and 101 children fulfilled inclusion criteria for further analysis, with a mean age of 3.92 years (SD 2.71 years). Mean tPMA z-score at L4-5 was −2.37 (SD 1.02). Correlation of tPMA z-score at L4-5 with weight-for-age z-score was moderate (r = 0.54; 95% CI, 0.38, 0.66). No association between sarcopenia and short-term outcome was observed. Sarcopenia had a sensitivity of 0.82 (95% CI, 0.62–0.93) and a specificity of 0.48 (95% CI 0.36–0.61) in predicting 5-year survival. In a multiple regression analysis, pre-operative sarcopenia, pre-operative chemotherapy in the NB2004 high-risk group, unfavorable tumor histology, and age at diagnosis were associated with 5-year survival after surgery, with hazard ratios of 4.18 (95% CI 1.01–17.26), 2.46 (95% CI 1.02–5.92), 2.39 (95% CI 1.03–5.54), and 1.01 (95% CI 1.00–1.03), respectively.

Conclusion: In this study, the majority of children had low tPMA z-scores and sarcopenia was a risk factor for decreased 5-year survival in children with neuroblastoma. Therefore, we suggest measuring the tPMA from pre-surgical cross-sectional imaging as a biomarker for additional risk stratification in children with neuroblastoma.
Ethnoveterinary Knowledge and Biological Evaluation of Plants Used for Mitigating Cattle Diseases: A Critical Insight Into the Trends and Patterns in South Africa
Authors: Chakale Mompati V. , Mwanza Mulunda , Aremu Adeyemi O.
Published: August 2021

Cattle farming is a traditional agricultural system that contribute to the rural economic, social and cultural values of the communities. Cattle as common with other livestock, are affected by many diseases that cause mortality and economic losses. In many rural households, the use of plants and associated knowledge are popular for managing cattle diseases especially in areas experiencing challenges with conventional veterinary medicine. Evidence on the documentation of indigenous knowledge and biological evaluation of plants used against cattle diseases remain understudied and fragmented. The aim of the review is to collate and analyse the ethnoveterinary knowledge and biological evaluation of plants used against cattle diseases in South Africa. Different scientific databases were systematically explored to extract data from 37 eligible studies. A total of 310 medicinal plants from 81 families used to treat 10 categories of cattle diseases across seven (7) provinces in South Africa. Leguminosae (Fabaceae), Compositae (Astereceae), Asparagaceae, and Xanthorrhoeaceae were the most frequently used plant families. Common plant parts used were leaves and roots. Twenty-seven (27) combination remedies involving 2–6 plants were identified as treatment regimes against cattle diseases. Common preparation methods were infusion and decoction while the administration mode was predominantly unspecified (52%) while oral and topical contributed 26 and 22%, respectively. In terms of diseases, the most treated ones were general systems infection, reproduction disorders and gastrointestinal problems. Currently, an estimated 21% of the 310 plants have been evaluated for diverse biological activities using relevant bioassays related to cattle diseases. Antibacterial activity remained the most studied biological activity. Evidence from the review revealed the significance of ethnoveterinary medicine against cattle diseases especially in rural areas of South Africa. Nevertheless, the use of plants for cattle diseases among other ethnic groups, particularly in the Northern Cape and Western Cape, remain under-studied.
Avances teoricos en las psicoterapias cognitivas
Authors: Mahoney Michael
Published: August 2021

los criterios actuales consideran a las psicoterapias cogniticas  como aplicaciones de las  ciencias cognitivas.
Relaciones tempranas y nacimiento del self
Authors: Sassaroli Sandra , Lorenzini Roberto
Published: August 2021

Este articulo  versa sobre nuestra hipotesis acerca del nacimiento  de la idea del otro y del Self en un sistema cognitivo que vive y aprende. Este nacimiento tiene origen en la relacion de vinculacion. Presentaremos nuestra hipotesis sobre la  filiacion de las relaciones de vinculacion y apego, que este de acuerdo con el principio motivacional .

El aumento de la capacidad predictiva y, sobre la base de  estas premisas, revisaremos las teorias tradicionales de la vinculacion desde Bowlby hasta la actualidad. Por ultimo, reexaminaremos nuestros trabajos previos y estableceremos nuevas  conexiones entre los tipos   de  relaciones de   vinculacion las  reglas   que   gobiernan la adquisicion  del conocimiento (criterios epistemologicos).
Los efectos patógenos de la psicoterapia
Authors: Semerari Antonio
Published: August 2021

Pademos considerar la psicoterapia como un proceso capaz de cambiar las estructuras de significado de una persona tanto para mejorar como para empeorar. Este articulo se propone superar una dimension anecdotica  de las errores en la terapia y afrontar los efectos patogenos a partir de observaciones clinicas intentando dar respuesta a tres tipos de cuestiones relativas  a:

a ) Determinar la fenomenologia clinica de la patologia indicada  por la psicaterapia .

b) Analizar primero de que mecanismos directos de relacion entre terapia y paciente pueden originarse. 

c )  Detectar los indicios precoces de cambia patogeno que pueden servir al terapeuta para modificar sus intervenciones.
Sobre la elaboracion del duelo en terapia familiar
Authors: Espina Alberto , Gago Josu , Pérez María Mar
Published: August 2021

La elaboracion del duelo desde los origenes de la psicologia y de la psicoterapia con la depresion .En este articulo se trata del estudio de los fenomenos de duelo  desde una perspectiva cientifica y con una aproximacion clinica de inspiracion sistemica .
Counseling y psicoterapia desde una perspectiva evolutiva
Authors: Marcia James E
Published: August 2021

En este articulo se vera la relacion entre tres enfoques teoricos en la psicologia evolutiva: la teoria psicoanalitica del ego. La teoria de las relaciones objetales, y la teoria del desarrollo cognitivo. Se parte del supuesto que los tres postulan objetivos con   procesos similares. Todos juntos ofrecen   el  marco de trabajo para el desarrollo del counseling de la psicoterapia. Se ilustran algunos puntos concretos con casos clinicos.
La entrevista evolutiva
Authors: Villegas Besora Manuel
Published: August 2021

En este articulo se considera la entrevista terapéutica como una  clase particular de discurso que puede ser analizado a dos niveles : a) expresivo, relativo a la complejidad epistemologica ‹le su enunciacion y b) constructivo, relativo al grado de desarrollo socio-cognitivo que manifiesta. Esta doble perspectiva, se basa en la descripcion constructivo-genética de Jean Piaget y su escuela, ofrece una vision evolutiva de la entrevista terapéutica y da origen a un modelo de analisis aplicable a cualquier entrevista, independientemente del modelo de adscripcion del terapeuta.
Los modelos teóricos , los tratamientos y las entrevistas de evaluación en la asistencia clínica en salud mental : informe sobre una encuesta realizada los C. A.P y C.A.P.I.P de Catalunya
Authors: Mitjavila Merce , Miró María Teresa , Bachs Jordi
Published: August 2021

El motivo de la realizacion de este estudio descriptivo parte de la reflexion , acerca de la diversidad de modelos en el campo de la  psicologia , psicologia cademica y psicologia aplicada.
Manual didactico para el tratamiento de disfunciones sexuales
Authors: Villegas Manuel
Published: August 2021

Este articulo es un comentario de texto sobre las disfunciones sexuales
Mechanical Design and Performance Analyses of a Rubber-Based Peristaltic Micro-Dosing Pump
Authors: Zehetbauer Thomas , Plöckinger Andreas , Emminger Carina , Çakmak Umut D.
Published: August 2021

Low pressure fluid transport (1) applications often require low and precise volumetric flow rates (2) including low leakage to reduce additional costly and complex sensors. A peristaltic pump design (3) was realized, with the fluid’s flexible transport channel formed by a solid cavity and a wobbling plate comprising a rigid and a soft layer (4). In operation, the wobbling plate is driven externally by an electric motor, hence, the soft layer is contracted and unloaded (5) during pump-cycles transporting fluid from low to high pressure sides. A thorough characterization of the pump system is required to design and dimension the components of the peristaltic pump. To capture all these parameters and their dependencies on various operation-states, often complex and long-lasting dynamic 3D FE-simulations are required. We present, here, a holistic design methodology (6) including analytical as well as numerical calculations, and experimental validations for a peristaltic pump with certain specifications of flow-rate range, maximum pressures, and temperatures. An experimental material selection process is established and material data of candidate materials (7) (liquid silicone rubber, acrylonitrile rubber, thermoplastic-elastomer) are directly applied to predict the required drive torque. For the prediction, a semi-physical, analytical model was derived and validated by characterizing the pump prototype.
Physiological Traits of Thirty-Five Tomato Accessions in Response to Low Temperature
Authors: Rajametov Sherzod Nigmatullayevich , Lee Kwanuk , Jeong Hyo-Bong , Cho Myeong-Cheoul , Nam Chun-Woo , Yang Eun-Young
Published: August 2021

Tomato is often exposed to diverse abiotic stresses and cold stress is one of harsh environmental stresses. Abnormal low temperature affects tomato growth and development, leading to, e.g., physiological disorders, flower drops, and abnormal fruit morphology, and causing a decrease in tomato yield and fruit quality. It is important to identify low temperature-(LT) tolerant tomato (Solanum lycopersicum L.) cultivars relying on different fruit types. In this study, our focus was to analyze the physiological traits of 35 tomato accessions with three different fruit types (cherry, medium, and large sizes) under night temperature set-points of 15 °C for control temperature (CT) and 10 °C for LT, respectively. Plant heights (PH) of most tomato accessions in LT were remarkably decreased compared to those in CT. The leaf length (LL) and leaf width (LW) were reduced depending on the genotypes under LT. In addition, the number of fruits (NFR), fruit set (FS), fruit yield (FY), and marketable yield (MY) were negatively affected in LT. The variation was further investigated by the correlation, the principal component (PCA), and the cluster analysis. Interestingly, positive correlations between different vegetative and reproductive traits were uncovered. Multivariate analysis including the PCA and hierarchical clustering classified the LT-treated 35 tomato accessions into four major groups. The identified accessions were associated with vegetative and reproductive parameters on positive directions. The results might be utilized for establishing breeding programs on selecting LT-tolerant tomato cultivars with different selection indices relying on fruit types during vegetative and/or reproductive stages.
Effect of Inulin Source and a Probiotic Supplement in Pig Diets on Carcass Traits, Meat Quality and Fatty Acid Composition in Finishing Pigs
Authors: Grela Eugeniusz R. , Świątkiewicz Małgorzata , Florek Mariusz , Bąkowski Maciej , Skiba Grzegorz
Published: August 2021

In this experiment, we investigated the effect of the supplementation of probiotic bacteria in the diet with inulin or dried Jerusalem artichoke tubers on the performance, meat quality, and fatty acid composition in the meat and backfat of fatteners. One hundred and forty-four crossbred pigs (PIC × Penarlan P76) were divided into six groups and fattened from 30 to 114 kg. The meat proximate composition, pH, color, texture, shear force, water-holding capacity, sensory attributes, and thiobarbituric-acid-reactive substances were measured. Normal post-mortem meat glycolysis was demonstrated and no meat defects were present. The chemical constituents in muscle tissues were similar, except for intramuscular fat (IMF). The addition of the prebiotics resulted in a higher IMF level, whereas a significantly lower content was found after the probiotic supplementation. Meat from both prebiotic groups was lighter, less red, and more yellow and showed a higher hue angle. The addition of both prebiotics significantly improved the antioxidant status of meat (by approximately 16% and 18%) and the water-holding capacity (less free water and higher M/T ratios), but reduced shear force (by 17%, p ≤ 0.05) and hardness (by 39% and 35%, respectively, p ≤ 0.05). The addition of the prebiotics and probiotics had no effect on any of the evaluated sensory attributes.
Hyperphosphatemia-Induced Oxidant/Antioxidant Imbalance Impairs Vascular Relaxation and Induces Inflammation and Fibrosis in Old Mice
Authors: Asenjo-Bueno Ana , Alcalde-Estévez Elena , El Assar Mariam , Olmos Gemma , Plaza Patricia , Sosa Patricia , Martínez-Miguel Patricia , Ruiz-Torres María Piedad , López-Ongil Susana
Published: August 2021

Aging impairs vascular function, but the mechanisms involved are unknown. The aim of this study was to analyze whether aging-related hyperphosphatemia is implied in this effect by elucidating the role of oxidative stress. C57BL6 mice that were aged 5 months (young) and 24 months (old), receiving a standard (0.6%) or low-phosphate (0.2%) diet, were used. Isolated mesenteric arteries from old mice showed diminished endothelium-dependent vascular relaxation by the down-regulation of NOS3 expression, increased inflammation and increased fibrosis in isolated aortas, compared to those isolated from young mice. In parallel, increased Nox4 expression and reduced Nrf2, Sod2-Mn and Gpx1 were found in the aortas from old mice, resulting in oxidant/antioxidant imbalance. The low-phosphate diet improved vascular function and oxidant/antioxidant balance in old mice. Mechanisms were analyzed in endothelial (EC) and vascular smooth muscle cells (SMCs) treated with the phosphate donor ß-glycerophosphate (BGP). In EC, BGP increased Nox4 expression and ROS production, which reduced NOS3 expression via NFκB. BGP also increased inflammation in EC. In SMC, BGP increased Collagen I and fibronectin expression by priming ROS production and NFκB activity. In conclusion, hyperphosphatemia reduced endothelium-dependent vascular relaxation and increased inflammation and vascular fibrosis through an impairment of oxidant/antioxidant balance in old mice. A low-phosphate diet achieved improvements in the vascular function in old mice.
Effect of Water-Based Acrylic Acid Microcapsules on the Properties of Paint Film for Furniture Surface
Authors: Yan Xiaoxing , Peng Wenwen , Qian Xingyu
Published: August 2021

In this paper, self-healing microcapsules with urea formaldehyde coated Nippon water-based acrylic acid were prepared, and the performance of water-based topcoat paint film added with self-healing microcapsules and the repair effect of microcapsules were investigated. The results show that when the content of microcapsules in water-based topcoat paint film on the surface of wood increased, the color difference and hardness rose gradually, the gloss and adhesion declined gradually, the impact resistance and tensile strength at break rose first and then declined. The 0.67:1 core-wall ratio microcapsules had a better micromorphology, and the water-based topcoat paint film with 0.67:1 microcapsules had a certain repair effect. The microcapsules were added to the water-based topcoat paint film to repair the coating to a certain extent, which provide technical reference for prolonging the service life of water-based topcoat paint film for the furniture surface.
Simulation and Analysis of the Impact of Cylinder Deactivation on Fuel Saving and Emissions of a Medium-Speed High-Power Diesel Engine
Authors: Liu Ying , Kuznetsov Alexandr , Sa Bowen
Published: August 2021

The potential benefit of cylinder deactivation (CDA) on power and emission performances has been numerically investigated on a locomotive 16-cylinder diesel engine. A 1D model combined with a predictive friction model and a 3D combustion model based and validated on experimental data have been developed to simulate engine working processes by deactivating half of the cylinders by cutting off the fuel supply and maintaining/cutting off valve motions. The results demonstrate that CDA with the valves closed decreases the BSFC by 11% at 450 rpm and by 14% at 556 rpm with a load of 1000 N∙m, due to increased indicated efficiency and reduced mechanical losses. After deactivating cylinders, frictional losses of piston rings increase in the active cylinders because of the raised gas pressure and the lubricating oil temperature decrease. Friction losses of the main bearings and big-end connecting rod bearings decrease due to the overall load drop. In comparison with the normal operation, CDA with the valves closed decreases the BSCO emission by 75.26% and the BSsoot emission by 62.9%. As the EGR rate is 30%, CDA with the valves closed effectively reduces the BSNOx emission to 4.2 g/(kW·h) at the cost of a 0.8% increase in the BSFC and without the rise in the BSCO emission.
Cranial Implant Design Applying Shape-Based Interpolation Method via Open-Source Software
Authors: Abdullah Johari Yap , Abdullah Abdul Manaf , Hueh Low Peh , Husein Adam , Hadi Helmi , Rajion Zainul Ahmad
Published: August 2021

Reconstructing a large skull defect is a challenge, as it normally involves the use of sophisticated proprietary image processing and expensive CAD software. As an alternative, open-source software can be used for this purpose. This study aimed to compare the 3D cranial implants reconstructed from computed tomography (CT) images using the open-source MITK software with commercial 3-matic software for ten decompressive craniectomy patients. The shape-based interpolation method was used, in which the technique of segmenting every fifth and tenth slice of CT data was performed. The final design of patient-specific implants from both software was exported to STL format for analysis. The results of the Kruskal–Wallis test for the surface and volume of cranial implants designed using 3-matic and the two MITK techniques showed no significant difference, p > 0.05. The results of the Hausdorff Distance (HD) and Dice Similarity Coefficient (DSC) analyses for cranial implants designed using 3-matic software and the two different MITK techniques showed that the average points distance for 3-matic versus MITK was 0.28 mm (every tenth slice) and 0.15 mm (every fifth slice), and the similarity between 3-matic and MITK on every tenth and fifth slices were 85.1% and 89.7%, respectively. The results also showed that the open-source MITK software is comparable with the commercial software for designing patient-specific implants.
A Unified Theory for 3D Gear and Thread Metrology
Authors: Stein Martin , Keller Frank , Przyklenk Anita
Published: August 2021

We propose a unified theory for the metrological treatment of helical machine elements such as cylindrical and conical gears, worms, and screw threads. The main idea is to introduce a universal 3D geometry model for threaded components that provides for distinct parameterization using a unique set of geometry parameters and that offers and a functional description of the transverse profile. Using modern 3D coordinate measuring technology, a holistic evaluation algorithm yields the actual geometry as the result of a high dimensional best-fit procedure and form deviations as corresponding residuals. All determinants and evaluation parameters can then be calculated from the set of actual geometry parameters. By applying certain constraints to the model to be fitted, the novel method can be reduced to the established 2D methods and hence meets demands for the comparison of the two procedures. The results of the novel approach have proven to be very stable and they enable the evaluation of areal measurements with no loss of information.
Thioredoxin-1 and Correlations of the Plasma Cytokines Regarding Aortic Valve Stenosis Severity
Authors: Tretjakovs Peteris , Lurins Juris , Svirskis Simons , Gersone Gita , Lurina Dace , Rozenberga Ulla , Blumfelds Leons , Bahs Guntis , Lejnieks Aivars , Mackevics Vitolds
Published: August 2021

Aortic valve stenosis (AS) develops not only with a pronounced local inflammatory response, but also oxidative stress is involved. The aim of this study was to evaluate the plasma levels of thioredoxin-1 (TRX1), myeloperoxidase (MPO), chemerin, growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), fibroblast growth factor 21 (FGF-21), and metalloproteinase (MMP)-1, -3, and -9 in acquired AS patients as well as to clarify the correlations of TXR1 and the plasma inflammatory biomarkers regarding AS severity. AS patients were classified into three groups: 16 patients with mild AS stenosis, 19 with moderate and 11 with severe AS, and 30 subjects without AS were selected as a control group. AS patients had significantly higher plasma levels of TRX1 compared to controls, but the highest difference was found in mild AS patients compared to the controls. We conclude that AS is associated with significantly increased plasma TRX1 levels, and TRX1 might serve as a specific and sensitive biomarker of AS. TRX1 and also chemerin, GDF-15, VEGF-A, FGF-2 and FGF-21 significantly correlate with AS severity degrees. TRX1 also showed positive association with FGF-2, VEGF-A, and MMP-3 in all AS patients.
Poloxamer 188 Exerts Direct Protective Effects on Mouse Brain Microvascular Endothelial Cells in an In Vitro Traumatic Brain Injury Model
Authors: Lotze Felicia P. , Riess Matthias L.
Published: August 2021

Traumatic Brain Injury (TBI), the main contributor to morbidity and mortality worldwide, can disrupt the cell membrane integrity of the vascular endothelial system, endangering blood–brain barrier function and threatening cellular subsistence. Protection of the vascular endothelial system might enhance clinical outcomes after TBI. Poloxamer 188 (P188) has been shown to improve neuronal function after ischemia/reperfusion (I/R) injury as well as after TBI. We aimed to establish an in vitro compression-type TBI model, comparing mild-to-moderate and severe injury, to observe the direct effects of P188 on Mouse Brain Microvascular Endothelial Cells (MBEC). Confluent MBEC were exposed to normoxic or hypoxic conditions for either 5 or 15 h (hours). 1 h compression was added, and P188 was administered during 2 h reoxygenation. A direct effect of P188 on MBEC was tested by assessing cell number/viability, cytotoxicity/membrane damage, metabolic activity, and total nitric oxide production (tNOp). While P188 enhanced cell number/viability, metabolic activity, and tNOp, an increase in cytotoxicity/membrane damage after mild-to-moderate injury was prevented. In severely injured MBEC, P188 improved metabolic activity only. P188, present during reoxygenation, influenced MBEC function directly in simulated I/R and compression-type TBI.
Novel Orthogonally Hydrocarbon-Modified Cell-Penetrating Peptide Nanoparticles Mediate Efficient Delivery of Splice-Switching Antisense Oligonucleotides In Vitro and In Vivo
Authors: Bazaz Safa , Lehto Tõnis , Tops Rahel , Gissberg Olof , Gupta Dhanu , Bestas Burcu , Bost Jeremy , Wiklander Oscar P. B. , Sork Helena , Zaghloul Eman M. , Mamand Doste R. , Hällbrink Mattias , Sillard Rannar , Saher Osama , Ezzat Kariem , Smith C. I. Edvard , Andaloussi Samir EL , Lehto Taavi
Published: August 2021

Splice-switching therapy with splice-switching oligonucleotides (SSOs) has recently proven to be a clinically applicable strategy for the treatment of several mis-splice disorders. Despite this, wider application of SSOs is severely limited by the inherently poor bioavailability of SSO-based therapeutic compounds. Cell-penetrating peptides (CPPs) are a class of drug delivery systems (DDSs) that have recently gained considerable attention for improving the uptake of various oligonucleotide (ON)-based compounds, including SSOs. One strategy that has been successfully applied to develop effective CPP vectors is the introduction of various lipid modifications into the peptide. Here, we repurpose hydrocarbon-modified amino acids used in peptide stapling for the orthogonal introduction of hydrophobic modifications into the CPP structure during peptide synthesis. Our data show that α,α-disubstituted alkenyl-alanines can be successfully utilized to introduce hydrophobic modifications into CPPs to improve their ability to formulate SSOs into nanoparticles (NPs), and to mediate high delivery efficacy and tolerability both in vitro and in vivo. Conclusively, our results offer a new flexible approach for the sequence-specific introduction of hydrophobicity into the structure of CPPs and for improving their delivery properties.
Research on Bonding Performance of Anchorage Caisson Foundation with Different Contact Surfaces and Grouting Bed
Authors: Geng Tiesuo , Chen Shuanghua , Zhao Liuqun , Zhang Zhe
Published: August 2021

In view of the first domestic offshore suspension bridge with caisson foundation, this paper mainly studies the bonding properties between underwater pre-filled aggregate grouting bed and anchorage caisson foundation. Through the test, the cohesive force of adding ordinary concrete between the anchorage caisson foundation and the grouting bed, the cohesive force of adding paper base asphalt felt between the anchorage caisson foundation and the grouting bed, and the cohesive force of adding geotextile between the anchorage caisson foundation and the grouting bed are measured, respectively. When the contact surface is concrete and geotextile, the fracture form of the specimen was analyzed by numerical simulation, and the AE variation trend of the two specimens have been studied. The results of this article can provide references for other projects.
Experimental Campaigns on Mechanical Properties and Seismic Performance of Unstabilized Rammed Earth—A Literature Review
Authors: Perić Ana , Kraus Ivan , Kaluđer Jelena , Kraus Lucija
Published: August 2021

Earthen architecture has a significant share in the world’s fund of both residential architecture and cultural heritage. It provides a home to more than half of the world’s population and can be found in seismically active areas. Empirically acquired knowledge on building with rammed earth (RE) has usually been passed down from generation to generation by word of mouth, with no written scientific grant for the load-bearing capacity and resistance of structural elements. Today, many countries still do not have standards for the design of RE structures. In the development of new as well as existing design standards, the results of experimental research play a significant role. The focus of this study was on unstabilized RE, which is locally available material with low embodied energy. This paper elaborates experimental campaigns, within which meticulous techniques were employed to provide new knowledge on RE for use in earthquake-prone areas. Furthermore, this paper includes: (i) ranges of values of mechanical properties determined on RE specimens from all over the world; (ii) a comparative summary of experimental research conducted on walls and buildings to assess their seismic performance; (iii) an overview of standards and testing methods used in experiments; and (iv) recommendations for further research.
Integrating Serum Biomarkers into Prediction Models for Biochemical Recurrence Following Radical Prostatectomy
Authors: Moghaddam Shirin , Jalali Amirhossein , O’Neill Amanda , Murphy Lisa , Gorman Laura , Reilly Anne-Marie , Heffernan Áine , Lynch Thomas , Power Richard , O’Malley Kieran J. , Taskèn Kristin A. , Berge Viktor , Solhaug Vivi-Ann , Klocker Helmut , Murphy T. Brendan , Watson R. William
Published: August 2021

This study undertook to predict biochemical recurrence (BCR) in prostate cancer patients after radical prostatectomy using serum biomarkers and clinical features. Three radical prostatectomy cohorts were used to build and validate a model of clinical variables and serum biomarkers to predict BCR. The Cox proportional hazard model with stepwise selection technique was used to develop the model. Model evaluation was quantified by the AUC, calibration, and decision curve analysis. Cross-validation techniques were used to prevent overfitting in the Irish training cohort, and the Austrian and Norwegian independent cohorts were used as validation cohorts. The integration of serum biomarkers with the clinical variables (AUC = 0.695) improved significantly the predictive ability of BCR compared to the clinical variables (AUC = 0.604) or biomarkers alone (AUC = 0.573). This model was well calibrated and demonstrated a significant improvement in the predictive ability in the Austrian and Norwegian validation cohorts (AUC of 0.724 and 0.606), compared to the clinical model (AUC of 0.665 and 0.511). This study shows that the pre-operative biomarker PEDF can improve the accuracy of the clinical factors to predict BCR. This model can be employed prior to treatment and could improve clinical decision making, impacting on patients’ outcomes and quality of life.
TYK2 in Cancer Metastases: Genomic and Proteomic Discovery
Authors: Borcherding Dana C. , He Kevin , Amin Neha V. , Hirbe Angela C.
Published: August 2021

Advances in genomic analysis and proteomic tools have rapidly expanded identification of biomarkers and molecular targets important to cancer development and metastasis. On an individual basis, personalized medicine approaches allow better characterization of tumors and patient prognosis, leading to more targeted treatments by detection of specific gene mutations, overexpression, or activity. Genomic and proteomic screens by our lab and others have revealed tyrosine kinase 2 (TYK2) as an oncogene promoting progression and metastases of many types of carcinomas, sarcomas, and hematologic cancers. TYK2 is a Janus kinase (JAK) that acts as an intermediary between cytokine receptors and STAT transcription factors. TYK2 signals to stimulate proliferation and metastasis while inhibiting apoptosis of cancer cells. This review focuses on the growing evidence from genomic and proteomic screens, as well as molecular studies that link TYK2 to cancer prevalence, prognosis, and metastasis. In addition, pharmacological inhibition of TYK2 is currently used clinically for autoimmune diseases, and now provides promising treatment modalities as effective therapeutic agents against multiple types of cancer.
The Effect of Gold Nanoparticles on the Catalytic Activity of NiTiO3 for Hydrodeoxygenation of Guaiacol
Authors: Zhao Bin , Zhang Guanghui , Mao Jingbo , Wang Yanli , Yang Hong , Guo Xinwen
Published: August 2021

Guaiacol is a typical model compound used to investigate and understand the hydrodeoxygenation behaviour of bio-oils, which is critical to their application as an alternative to fossil resources. While extensive research has been carried out on developing catalysts for guaiacol hydrodeoxygenation, the true active sites in these catalysts are often illusive. This study investigated the effect of Au-loading on the catalytic activity of NiTiO3 for the hydrodeoxygenation of guaiacol. It showed that metallic Ni formed by the partial reduction in NiTiO3 was responsible for its catalytic activity. Au-loading in NiTiO3 effectively reduces the temperature required for the NiTiO3 reduction from 400 °C to 300 °C. Consequently, at an Au-loading of 0.86 wt%, the 0.86 Au/NiTiO3-300 °C catalyst was found to deliver a guaiacol conversion of ~32%, more than 6 times higher than that of the pure NiTiO3-300 °C catalyst.
Conversion of Residual Palm Oil into Green Diesel and Biokerosene Fuels under Sub- and Supercritical Conditions Employing Raney Nickel as Catalyst
Authors: Falabella Sousa-Aguiar Eduardo , Zanon Costa Carolina , Peixoto Gimenes Couto Maria Antonieta , de Almeida Azevedo Débora , Filho José Faustino Souza de Carvalho
Published: August 2021

A comprehensive study of the thermal deoxygenation of palm residue under sub- and supercritical water conditions using Raney nickel as a heterogeneous catalyst is presented in this paper. Hydrothermal technology was chosen to replace the need for hydrogen as a reactant, as happens, for example, in catalytic hydrotreatment. Several experiments were carried out at different reaction temperatures (350, 370, and 390 °C) and were analyzed with different times of reaction (1, 3.5, and 6 h) and catalyst loads (5, 7.5, 10 wt.%). No hydrogen was introduced in the reactions, but it was produced in situ. The results showed the selectivity of biokerosene ranged from 2% to 67%, and the selectivity of diesel ranged from 5% to 98%. The best result was achieved for 390 °C, 10 wt.% catalyst load, and 3.5 h of reaction, when the selectivities equal to 67% for biokerosene and 98% for diesel were obtained. The Raney nickel catalyst demonstrated a tendency to promote the decarboxylation reaction and/or decarbonylation reaction over the hydrodeoxygenation reaction. Moreover, the fatty acid and glycerol reforming reaction and the water−gas shift reaction were the main reactions for the in situ H2 generation. This study demonstrated that a hydrothermal catalytic process is a promising approach for producing liquid paraffin (C11−C17) from palm residue under the conditions of no H2 supply.
Calcium Signaling Regulates Autophagy and Apoptosis
Authors: Sukumaran Pramod , Nascimento Da Conceicao Viviane , Sun Yuyang , Ahamad Naseem , Saraiva Luis R , Selvaraj Senthil , Singh Brij B
Published: August 2021

Calcium (Ca2+) functions as a second messenger that is critical in regulating fundamental physiological functions such as cell growth/development, cell survival, neuronal development and/or the maintenance of cellular functions. The coordination among various proteins/pumps/Ca2+ channels and Ca2+ storage in various organelles is critical in maintaining cytosolic Ca2+ levels that provide the spatial resolution needed for cellular homeostasis. An important regulatory aspect of Ca2+ homeostasis is a store operated Ca2+ entry (SOCE) mechanism that is activated by the depletion of Ca2+ from internal ER stores and has gained much attention for influencing functions in both excitable and non-excitable cells. Ca2+ has been shown to regulate opposing functions such as autophagy, that promote cell survival; on the other hand, Ca2+ also regulates programmed cell death processes such as apoptosis. The functional significance of the TRP/Orai channels has been elaborately studied; however, information on how they can modulate opposing functions and modulate function in excitable and non-excitable cells is limited. Importantly, perturbations in SOCE have been implicated in a spectrum of pathological neurodegenerative conditions. The critical role of autophagy machinery in the pathogenesis of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, would presumably unveil avenues for plausible therapeutic interventions for these diseases. We thus review the role of SOCE-regulated Ca2+ signaling in modulating these diverse functions in stem cell, immune regulation and neuromodulation.
Occurrence and Antigenic Specificity of Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (P-ANCA) in Systemic Autoimmune Diseases
Authors: Argyropoulou Ourania D. , Goules Andreas V. , Boutzios Georgios , Tsirogianni Alexandra , Sfontouris Charalampos , Manoussakis Menelaos N. , Vlachoyiannopoulos Panayiotis G. , Tzioufas Athanasios G. , Kapsogeorgou Efstathia K.
Published: August 2021

Perinuclear anti-neutrophilic cytoplasmic antibodies (P-ANCA) recognize heterogeneous antigens, including myeloperoxidase (MPO), lactoferrin, elastase, cathepsin-G and bactericidal/permeability-increasing protein. Although P-ANCA have diagnostic utility in vasculitides, they may also be found in patients with various other systemic autoimmune rheumatic diseases (SARDs). Nevertheless, the clinical significance and the targets recognized by P-ANCA in such patients remain unclear. For this purpose, herein we investigated the occurrence of ANCA-related antigenic specificities in 82 P-ANCA-positive sera by multiplex ELISA, as well as their association with other autoantibodies. The P-ANCA-positive sera corresponded to patients with vasculitides (n = 24), systemic lupus erythematosus (n = 28), antiphospholipid syndrome (n = 5), Sjögren’s syndrome (n = 7), rheumatoid arthritis (n = 3), systemic scleroderma (n = 1), sarcoidosis (n = 1) and Hashimoto′s thyroiditis (n = 13). In most P-ANCA-positive patients studied (51/82, 62.3%), these autoantibodies occurred in high titers (>1:160). The analysis of P-ANCA-positive sera revealed reactivity to MPO in only 50% of patients with vasculitides, whereas it was infrequent in the other disease groups studied. Reactivity to other P-ANCA-related autoantigens was also rarely detected. Our findings support that high P-ANCA titers occur in SARD. The P-ANCA-positive staining pattern is associated with MPO specificity in vasculitides, while in other autoimmune diseases, it mostly involves unknown autoantigens.