bluuebunny/crossref_metadata_2025 huggingface dataset:
Game-based digital therapeutics for children and adolescents: Their therapeutic effects on mental health problems, the sustainability of the therapeutic effects and the transfer of cognitive functions
Authors: Choi Eunhye , Yoon Eun-Ha , Park Min-Hyeon
Published: November 2022

Mental health problems in childhood and adolescence (e. g., attention deficits, problems in emotional understanding and subclinical levels of anxiety) are reported to develop further in adulthood and/or to increase the risk of developing mental health disorders in adulthood. Although it is important to provide treatment or prevention interventions for children and adolescents in order to reduce the risk of the further development of mental health problems, the pharmacological and behavioral treatments for this age group have limitations (e.g., limited access, unsustainable treatment effects and the lack of engagement in intervention). In order to overcome the limitations of conventional treatments, the use of digital technology, especially video games for this age group, is suggested. In order to be accepted as clinical interventions, objective evidence for the therapeutic effects of digital therapeutic that used video games to treat or prevent targeted mental health problems are required. Thus, this review aims to explore whether game-based digital therapeutics (DTx) for children and adolescents showed therapeutic effects on targeted mental health problems. As game-based DTx are suggested to show sustained therapeutic effects and the transfer of cognitive functions, it also reviews the maintenance of the therapeutic effects of DTx and the extent of the transfer of cognitive functions. Game-based DTx that are developed to treat or prevent mental health problems (e.g., attention deficit, depression) in children and adolescents are found to show therapeutic effects on targeted mental health problems despite the limitations (e.g., small sample size, limited investigation of the sustainability). This review would contribute to the understanding of whether there is objective evidence of the therapeutic effects of digital therapeutics using video games that deliver treatment or prevention interventions for mental health problems in children and adolescents.
How to promote grass roots medical treatment under China's graded diagnosis and treatment policy? — From the perspective of customer value theory
Authors: Tao Wanqiong , Chen Xiangrui , Gan Shuyu
Published: November 2022

Objectives

Based on the background of the implementation of graded diagnosis and treatment policy (GDT) in China, this paper studied the service optimization of primary medical institutions from the perspective of the primary medical treatment rate.

Methods

First, the difference-in-difference (DID) empirical strategy is used to analyze the impact of the implementation of the GDT on the improvement of the primary medical attendance rate, and the parallel trend test and the placebo test were used to test the robustness to illustrate the necessity of policy implementation. Second, combined with customer value theory, this paper used a logistic regression model to study the impact of customer value perception on grassroots medical care.

Results

The implementation of the GDT can indeed improve the rate of primary care (p = 0.028), but the impact is relatively small (0.042). From the perspective of value perception hierarchy, emotional value perception (p < 0.05) is the key factor that affects the behavior of grassroots medical treatment at this stage.

Conclusion

This paper fills the gaps in existing research, including empirical research on the grassroots medical treatment behavior of the masses under GDT and the impact of value perception on grassroots medical behavior. Furthermore, the recommendations are made for primary care institutions based on the results of the analysis, which promote the advancement of primary care services in China.
Power and resistance in schools: Implementing institutional change to promote health equity for sexual and gender minority youth
Authors: Shattuck Daniel , Richard Bonnie O. , Jaramillo Elise Trott , Byrd Evelyn , Willging Cathleen E.
Published: November 2022

Introduction

Schools in the United States are hierarchical institutions that actively (re)produce the power relations of the wider social world, including those associated with heteronormativity. Structural stigma, informed by heteronormativity and perpetuated through schools, contributes to the production of academic and health disparities among youth who are lesbian, gay, bisexual, transgender, queer, or of other gender and sexual identities (LGBTQ+). We draw upon 5 years of qualitative data from a cluster randomized controlled trial conducted in New Mexico that used implementation science frameworks to promote the uptake and sustainment of evidence-informed practices (EIPs) to examine how power operates to hinder or promote the ability of school staff to change school environments, disrupt structural stigma, and increase safety and support for LGBTQ+ youth.

Methods

Data sources included annual individual and small group qualitative interviews with school professionals (e.g., administrators, school nurses, teachers, and other staff), several of whom took part in Implementation Resource Teams (IRTs) charged with applying the EIPs. Other data sources included bi-weekly periodic reflections with implementation coaches and technical assistance experts. Data were recorded, transcribed, and analyzed using deductive and inductive coding techniques.

Results

The IRTs experienced variable success in implementing EIPs. Their efforts were influenced by: (1) constraining school characteristics, including staff turnover and resource scarcity; (2) community-based opposition to change and concerns about community backlash; (3) the presence or absence of supportive school leadership; and (4) variations in school, district, and state policies affecting LGBTQ+ students and attitudes about their importance. Findings illustrate how diverse power structures operated in and across outer and inner contexts to bound, shift, amplify, and otherwise shape how new practices were received and implemented.

Conclusion

Findings indicate that the efforts of IRTs were often a form of resistant power that operated within and against school hierarchies to leverage epistemic, discursive, and material power toward implementation. To improve health equity, implementation scientists must attend to the multiple real and perceived power structures that shape implementation environments and influence organizational readiness and individual motivation. Implementers must also work to leverage resistant power to counter the institutional structures and social norms that perpetuate inequities, like heteronormativity and structural stigma.
An Indigenous critique: Expanding sociology and recognizing unique Indigenous knowledge
Authors: Mackay Ried E
Published: November 2022

Introduction

This essay suggests that sociologists should integrate into their critical research work on the Americas an Indigenous critique/method based on Indigenous knowledge. As a mixed Indigenous scholar, I have been frustrated by the lack of frameworks based explicitly on Indigenous knowledge rather than merely referencing that knowledge.

Methods

Strong foundations of ancient Indigenous thought and philosophical tradition—which often differs dramatically from Western traditions—are identified and explored through three concepts: Ch'ixi, the Indigenous pragmatic, and Mexica concepts of Truth. These are identified and discussed using authoritative historical and contemporary sources. I provide potential pathways for usage of these concepts in the results and discussion. Arguments and controversy for accepting the validity of Indigenous sources are also addressed.

Results and discussion

Discussions of specific empirical questions and puzzles related to already familiar concepts and analyses such as systemic racism theory, multi-raciality, religion, and postcolonial theory are explored. The paper concludes that Indigenous theory is underexplored but is critical to liberation of Indigenous people and has legitimate academic value that scholars need to recognize.
Optimal integration of kinematic and ball-flight information when perceiving the speed of a moving ball
Authors: Nakamoto Hiroki , Fukuhara Kazunobu , Torii Taiga , Takamido Ryota , Mann David L.
Published: November 2022

In order to intercept a moving target such as a baseball with high spatio-temporal accuracy, the perception of the target's movement speed is important for estimating when and where the target will arrive. However, it is unclear what sources of information are used by a batter to estimate ball speed and how those sources of information are integrated to facilitate successful interception. In this study, we examined the degree to which kinematic and ball-flight information are integrated when estimating ball speed in baseball batting. Thirteen university level baseball batters performed a ball-speed evaluation task in a virtual environment where they were required to determine which of two comparison baseball pitches (i.e., a reference and comparison stimuli) they perceived to be faster. The reference and comparison stimuli had the same physical ball speed, but with different pitching movement speeds in the comparison stimuli. The task was performed under slow (125 km/h) and fast (145 km/h) ball-speed conditions. Results revealed that the perceived ball-speed was influenced by the movement speed of the pitcher's motion, with the influence of the pitcher's motion more pronounced in the fast ball-speed condition when ball-flight information was presumably less reliable. Moreover, exploratory analyses suggested that the more skilled batters were increasingly likely to integrate the two sources of information according to their relative reliability when making judgements of ball speed. The results provide important insights into how skilled performers may make judgements of speed and time to contact, and further enhance our understanding of how the ability to make those judgements might improve when developing expertise in hitting.
Effect of Allium sativum and Nigella sativa on alleviating aluminum toxicity state in the albino rats
Authors: Abdel Ghfar Sayed Soliman , Ali Montaser Elsayed , Momenah Maha Abdullah , Al-Saeed Fatimah A. , Al-Doaiss Amin A. , Mostafa Yasser Sabry , Ahmed Ahmed Ezzat , Abdelrahman Mohamed
Published: November 2022

The study objective was to evaluate Allium sativum's potential and Nigella Sativa's combination's potential to reduce aluminum toxicity and return to the normal state. In the present study, a hundred albino rats were randomly divided into five equal groups. The first group was used as a control group; the other four groups were exposed to aluminum 1,600 ppm. The second exposed to aluminum only; the third and fourth groups were treated with Allium sativum 5% and Nigella sativa 5%, respectively, while the fifth group was treated with a mix of Allium sativum 2.5% and Nigella sativa 2.5% for 8th weeks. After 8 weeks, the aluminum administration was stopped, and the second group was divided into three groups. The groups were treated with Allium sativum 5% and Nigella sativa 5%, and a mix of Allium sativum 2.5% and Nigella sativa 2.5%, respectively. The first group was the control group (continued from the first experiment). Garlic and Nigella sativa were crushed and added to feed while receiving aluminum chloride daily at a dose of 1.6 ml/l was added to the drinking water. Histopathological changes in the liver, kidney, and testes were investigated after 8 and 16 weeks, and blood samples were collected after 4, 8, and 16 weeks for biochemical blood parameters. The results showed that the histopathological examination of the liver, kidney, and testes showed signs of congestion in blood vessels after aluminum exposure. Meanwhile, the treatment with Allium sativum or Nigella sativum or the mixture between them had positive effects on evading the harmful effects of aluminum in the liver, Kidney, and testes tissues. In addition, there were protective effects for Allium sativum and Nigella sativa against aluminum on serum creatinine, urea, ALT, and AST concentrations. The present study concluded that supplementation with Allium sativum or Nigella sativa or their combination could reduce aluminum toxicity and return the liver, kidney, and testes to normal.
A Hybrid Exact–Local Search Approach for One-Machine Scheduling with Time-Dependent Capacity
Authors: Valouxis Christos , Gogos Christos , Dimitsas Angelos , Potikas Petros , Vittas Anastasios
Published: November 2022

Machine scheduling is a hard combinatorial problem having many manifestations in real life. Due to the schedule followed, the possibility of installations of machines operating sub-optimally is high. In this work, we examine the problem of a single machine with time-dependent capacity that performs jobs of deterministic durations, while for each job, its due time is known in advance. The objective is to minimize the aggregated tardiness in all tasks. The problem was motivated by the need to schedule charging times of electric vehicles effectively. We formulate an integer programming model that clearly describes the problem and a constraint programming model capable of effectively solving it. Due to the usage of interval variables, global constraints, a powerful constraint programming solver, and a heuristic we have identified, which we call the “due times rule”, the constraint programming model can reach excellent solutions. Furthermore, we employ a hybrid approach that exploits three local search improvement procedures in a schema where the constraint programming part of the solver plays a central role. These improvement procedures exhaustively enumerate portions of the search space by exchanging consecutive jobs with a single job of the same duration, moving cost-incurring jobs to earlier times in a consecutive sequence of jobs or even exploiting periods where capacity is not fully utilized to rearrange jobs. On the other hand, subproblems are given to the exact constraint programming solver, allowing freedom of movement only to certain parts of the schedule, either in vertical ribbons of the time axis or in groups of consecutive sequences of jobs. Experiments on publicly available data show that our approach is highly competitive and achieves the new best results in many problem instances.
Inhibition of GSK3β Promotes Proliferation and Suppresses Apoptosis of Porcine Muscle Satellite Cells
Authors: Park Jinryong , Choi Hyunwoo , Shim Kwanseob
Published: November 2022

As the global population increases, interest in cultured meat (a new research field) is gradually increasing. The main raw material for the production of cultured meat is muscle stem cells called satellite cells isolated from livestock. However, how to mass proliferate and maintain satellite cells in vitro without genetic manipulation remains unclear. In the present study, we isolated and purified porcine muscle satellite cells (PMSCs) from the femur of a 1-day-old piglet and cultured PMSCs by treating them with an inhibitor (XAV939, Tankyrase (TNKS) inhibitor) or an activator (CHIR99021, glycogen synthase kinase 3 beta (GSK3β) inhibitor) of Wnt signaling. The CHIR group treated with 3 μM CHIR99021 showed a significantly increased proliferation rate of PMSCs compared to the SC group (control), whereas the XAV group treated with 1 μM XAV939 showed a significantly decreased proliferation rate of PMSCs. CHIR99021 also inhibited the differentiation of PMSCs by reducing the expression of MyoD while maintaining the expression of Pax7 and suppressed apoptosis by regulating the expression of apoptosis-related proteins and genes. RNA sequencing was performed to obtain gene expression profiles following inhibition or activation of the Wnt signaling pathway and various signaling mechanisms related to the maintenance of satellite cells were identified. Our results suggest that inhibition of GSK3β could dramatically improve the maintenance and mass proliferation ability of PMSCs in vitro by regulating the expression of myogenic markers and the cell cycle.
Physiological Assessment of the Health and Welfare of Domestic Cats—An Exploration of Factors Affecting Urinary Cortisol and Oxytocin
Authors: Nagasawa Takumi , Kimura Yuichi , Masuda Koji , Uchiyama Hidehiko
Published: November 2022

Physiological samples are beneficial in assessing the health and welfare of cats. However, most studies have been conducted in specialized environments, such as shelters or laboratories, and have not focused on cats living in domestic settings. In addition, most studies have assessed physiological stress states in cats based on cortisol, and none have quantified positive indicators, such as oxytocin. Here, we collected urine samples from 49 domestic cats and quantified urinary cortisol, oxytocin, and creatinine using ELISA. To identify factors influencing hormone levels, owners responded to questionnaires regarding their housing environment, individual cat information, and the frequency of daily interactions with their cats. Using principal component analysis, principal component scores for daily interactions were extracted. These results showed that the frequency of tactile and auditory signal-based communication by owners was positively correlated with the mean concentration of oxytocin in the urine. Additionally, this communication was more frequent in younger cats or cats that had experienced a shorter length of cohabitation with the owner. However, no factors associated with urinary cortisol concentration were identified. Our study indicates that interactions and relationships with the owner influence the physiological status of cats and suggests that oxytocin is a valuable parameter for assessing their health and welfare.
Evolutionary Impacts of Pattern Recognition Receptor Genes on Carnivora Complex Habitat Stress Adaptation
Authors: Wu Xiaoyang , Chen Jun , Wang Xibao , Shang Yongquan , Wei Qinguo , Zhang Honghai
Published: November 2022

Many mammals develop specific immune responses owing to the changes in their ecological niche and diet that are essential for animal survival. However, pattern recognition receptors (PRRs) serve as the first line of defense in innate immunity and generate immune responses in the host. However, the evolutionary impacts on PRR genes in Carnivora are not well studied. Herein, we explored the evolution of 946 PRR gene sequences in 43 Carnivora species to elucidate the molecular mechanisms of carnivore adaptation to complex habitats. We found that the PRRs were relatively conserved, and different gene families showed different evolutionary patterns. PRRs were highly purified based on their overall roles in Carnivora species but interspersed with positive-selection patterns during evolution. Different niche types may have jointly driven the evolution of PRR genes. In particular, the selection pressure of toll-like receptor (TLR) 10 was relaxed in seven species with pseudogenes, which may have emerged during recent evolutionary events. We speculated that a “functional compensation” mechanism may exist for genes with overlapping functions in the TLR gene family. Additionally, TLR2, TLR4, NLRC5, and DECTIN1 were subject to positive selection in semi-aquatic species, and the adaptive evolution of these genes may have been related to the adaptation to semi-aquatic environments. In summary, our findings offer valuable insights into the molecular and functional evolution of PRR genes, which are important for immune adaptations in Carnivora.
Effects of Dietary Quinoa Seeds on Cecal Microorganisms and Muscle Fatty Acids of Female Luhua Chickens
Authors: Wu Tao , Jiang Xiaofan , Yang Farong , Wei Yuming , Zhao Shengguo , Jiao Ting
Published: November 2022

To study the effects of adding quinoa seed (raw grain) to the diet of the Luhua chicken on the cecal microorganism abundance and fatty acid composition of muscle, 120 49-day-old healthy female dewormed Luhua chickens (body weight 1476.21 ± 101.39 g) were randomly divided into 4 groups, with 3 replicates in each group and 10 chickens in each repetition. The control group (CK group) was fed a basal diet and the experimental groups were fed with 4% (Q4), 8% (Q8), and 12% (Q12) quinoa seed (raw grain) added to the basal diet for 75 days. After 121 days of age, the animals were slaughtered and the 16S rRNA characteristics of cecal flora, as well as composition and content of fatty acids in muscle, were determined and analyzed. The content of unsaturated fatty acids (UFAs), docosahexaenoic acid (C22:6n3; DHA) and n-3 polyunsaturated fatty acids (n-3 PUFAs) in the breast and leg muscles significantly increased in the experimental groups supplemented with quinoa seeds (p < 0.05). However, the content of saturated fatty acids (SAFs) and ratio of n-6/n-3 in breast muscle and leg muscle significantly decreased (p < 0.05). In addition, adding a certain percentage of quinoa seeds in the diet can also affect the community composition and content of microorganisms in the ceca of Luhua chickens. At the phylum level, the Proteobacteria, Actinobacteria, Synergistetes and Melainabacteria in experimental groups (Q4, Q8 and Q12) were significantly lower than those in the CK group (p < 0.05). At the genus level, Desulfovibrio, Synergistes, Olsenella, Parabacteroides, Mailhella, Sutterella and Ruminiclostridiu in group Q4 were significantly lower than those in group CK (p < 0.05) while Faecalibacterium in Q8 group, and Lawsonia and Faecalibacterium in Q12 group were significantly higher than those in the CK group (p < 0.05). Enrichment analysis of the microbial function showed that compared with the CK group, Metabolism and Enzyme Families were significantly enriched in the Q4 group (p < 0.05). Cellular Processes and Signaling were significantly enriched in the Q8 group (p < 0.05). The association analysis of fatty acids with microorganisms showed that the abundance of Faecalibacterium, Lawsonia and Meagmonas was significantly correlated with partial SFAs and UFAs (p < 0.05). In conclusion, adding quinoa seeds to diets significantly increased the content of muscle DHA, UFAs and n-3 PUFAs. The content of SAFs and the n-6/n-3 ratio were significantly reduced. Taken together, quinoa can effectively improve the cecal microbiota structure, inhibit the number of harmful bacteria and increase the number of beneficial bacteria, regulating the intestinal environment and promoting the body health of female Luhua chickens.
Special Issue on Requirements Engineering, Practice and Research
Authors: Rodrigues da Silva Alberto , Olsina Luis
Published: November 2022

With recent developments in cloud and mobile computing technologies, the growing need for secure, trustworthy, and cost-efficient software and the shortage of highly skilled professional software developers have given rise to a new generation of problems that require improved forms of specification and representation of such systems at multiple abstraction levels, with various concerns and stakeholder perspectives [...]
Mathematical Computations of Long-Term Settlement and Bearing Capacity of Soil Bases and Foundations near Vertical Excavation Pits
Authors: Ter-Martirosyan Zaven G. , Ter-Martirosyan Armen Z. , Vanina Yulia V.
Published: November 2022

The present paper describes and provides an analytical solution for the problem of evaluating the settlement and load-bearing capacity of weighty soil layers of limited thickness resting upon incompressible soil bases and an excavation pit wall, upon exposure of the foundation to a distributed load in the vicinity of a wall. The authors developed a method for determining the stressed state component in the reduced engineering problem based on the Ribere–Faylon trigonometric series, accounting for the nonlinear deformation properties of soils. To determine the settlement over time of the foundation near the pit, we used the A.Z. Ter-Martirosyan’s model to describe shear deformations and the Kelvin–Voigt model to describe volume deformations, assuming that ε·z(t) = ε·v(t) + ε·γ(t), according to the Hencky’s system of physical equations. The obtained solutions make it possible to assess the long-term deformation of soil bases and the long-term load-bearing capacity with respect to nonlinear rheological properties in a way that accurately corresponds to the actual performance of subsoils exposed to loading. The theoretical results were followed by numerical experiments to prove their validity.
Noncoding RNAs Are Promising Therapeutic Targets for Diabetic Retinopathy: An Updated Review (2017–2022)
Authors: Wang Mengchen , Li Qiaoyu , Jin Meiqi , Wang Zhen , Zhang Xuelian , Sun Xiaobo , Luo Yun
Published: November 2022

Diabetic retinopathy (DR) is the most common complication of diabetes. It is also the main cause of blindness caused by multicellular damage involving retinal endothelial cells, ganglial cells, and pigment epithelial cells in adults worldwide. Currently available drugs for DR do not meet the clinical needs; thus, new therapeutic targets are warranted. Noncoding RNAs (ncRNAs), a new type of biomarkers, have attracted increased attention in recent years owing to their crucial role in the occurrence and development of DR. NcRNAs mainly include microRNAs, long noncoding RNAs, and circular RNAs, all of which regulate gene and protein expression, as well as multiple biological processes in DR. NcRNAs, can regulate the damage caused by various retinal cells; abnormal changes in the aqueous humor, exosomes, blood, tears, and the formation of new blood vessels. This study reviews the different sources of the three ncRNAs—microRNAs, long noncoding RNAs, and circular RNAs—involved in the pathogenesis of DR and the related drug development progress. Overall, this review improves our understanding of the role of ncRNAs in various retinal cells and offers therapeutic directions and targets for DR treatment.
EPIAMNE: A New Scoring System for Differentiating Transient EPIleptic AMNEsia from Transient Global Amnesia
Authors: Sancetta Biagio Maria , Ricci Lorenzo , Assenza Giovanni , Boscarino Marilisa , Narducci Flavia , Vico Carlo , Di Lazzaro Vincenzo , Tombini Mario
Published: November 2022

Transient epileptic amnesia (TEA) is a rare cause of acute amnestic syndromes (AAS), often misdiagnosed as transient global amnesia (TGA). We proposed a scoring system—the EPIlepsy AMNEsia (EPIAMNE) score—using quantitative EEG (qEEG) analysis to obtain a tool for differentiating TEA from TGA. We retrospectively reviewed clinical information and standard EEGs (stEEG) of 19 patients with TEA and 21 with TGA. We computed and compared Power Spectral Density, demonstrating an increased relative theta power in TGA. We subsequently incorporated qEEG features in EPIAMNE score, together with clinical and stEEG features. ROC curve models and pairwise ROC curve comparison were used to evaluate and compare the diagnostic accuracy for TEA detection of EPIAMNE score, presence of symptoms atypical for TGA (pSymAT) and identification of anomalies (interictal epileptiform or temporal focal spiky transients) at stEEG (PosEEG). Area Under the Curve (AUC) of EPIAMNE score revealed to be higher than PosEEG and pSymAT (AUCEPIAMNE = 0.95, AUCpSymAT = 0.85, AUCPosEEG = 0.67) and this superiority proved to be statistically significant (p-valueEPIAMNE-PosEEG and p-valueEPIAMNE-pSymAT < 0.05). In conclusion, EPIAMNE score classified TEA with higher accuracy than PosEEG and pSymAT. This approach could become a promising tool for the differential diagnosis of AAS, especially for early TEA detection.
The Value of Semiquantitative Parameters Derived from 18F-FDG PET/CT for Predicting Response to Neoadjuvant Chemotherapy in a Cohort of Patients with Different Molecular Subtypes of Breast Cancer
Authors: Urso Luca , Evangelista Laura , Alongi Pierpaolo , Quartuccio Natale , Cittanti Corrado , Rambaldi Ilaria , Ortolan Naima , Borgia Francesca , Nieri Alberto , Uccelli Licia , Schirone Alessio , Panareo Stefano , Arnone Gaspare , Bartolomei Mirco
Published: November 2022

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is a strong prognostic factor in breast cancer (BC). The aim of this study was to investigate whether semiquantitative parameters derived from baseline [18F]Fluorodeoxyglucose ([18F]FDG) positron emission computed tomography/computed tomography (PET/CT) could predict pCR after NAC and survival outcomes in patients affected by different molecular subtypes of BC. We retrospectively retrieved patients from the databases of two Italian hospitals (Centre A: University Hospital of Ferrara; Centre B: University of Padua) meeting the following inclusion criteria: (1) diagnosis of BC; (2) history of NAC; (3) baseline [18F]FDG PET/CT performed before the first cycle of NAC; (4) available follow-up data (response after NAC and survival information). For each [18F]FDG PET/CT scan, semiquantitative parameters (SUVmax, SUVmean, MTV and TLG) related to the primary tumor (B), to the reference lesion for both axillary (N) and distant lymph node (DN), and to the whole-body burden of disease (WB) were evaluated. Patients enrolled were 133: 34 from centre A and 99 from centre B. Patients’ molecular subtypes were: 9 luminal A, 49 luminal B, 33 luminal B + HER-2, 10 HER-2 enriched, and 32 triple negative (TNBC). Luminal A and HER-2 enriched BC patients were excluded from the analysis due to the small sample size. pCR after NAC was achieved in 47 patients (41.2%). [18F]FDG PET/CT detected the primary tumor in 98.3% of patients and lymph node metastases were more frequently detected in Luminal B subgroup. Among Luminal B patients, median SUVmean_B values were significantly higher (p = 0.027) in responders (7.06 ± 5.9) vs. non-responders (4.4 ± 2.1) to NAC. Luminal B + HER-2 non-responders showed a statistically significantly higher median MTV_B (7.3 ± 4.2 cm3 vs. 3.5 ± 2.5 cm3; p = 0.003) and TLG_B (36.5 ± 24.9 vs. 18.9 ± 17.7; p = 0.025) than responders at baseline [18F]FDG PET/CT. None of the semiquantitative parameters predicted pCR after NAC in TNBC patients. However, among TNBC patients who achieved pCR after NAC, 4 volumetric parameters (MTV_B, TLG_B, MTV_WB and TLG_WB) were significantly higher in patients dead at follow-up. If confirmed in further studies, these results could open up a widespread use of [18F]FDG PET/CT as a baseline predictor of response to NAC in luminal B and luminal B + HER-2 patients and as a prognostic tool in TNBC.
DNA-Methylation Analysis as a Tool for Thymoma Classification
Authors: Gaiser Timo , Hirsch Daniela , Porth Isabel , Sahm Felix , Ströbel Philipp , von Deimling Andreas , Marx Alexander
Published: November 2022

Background: Thymomas are malignant thymic epithelial tumors that are difficult to diagnose due to their rarity and complex diagnostic criteria. They represent a morphologically heterogeneous class of tumors mainly defined by “organo-typical” architectural features and cellular composition. The diagnosis of thymoma is burdened with a high level of inter-observer variability and the problem that some type-specific morphological alterations are more on the continuum than clear-cut. Methylation pattern-based classification may help to increase diagnostic precision, particularly in borderline cases. Methods and Results: We applied array-based DNA methylation analysis to a set of 113 thymomas with stringent histological annotation. Unsupervised clustering and t-SNE analysis of DNA methylation data clearly segregated thymoma samples mainly according to the current WHO classification into A, AB, B1, B2, B2/B3, B3, and micronodular thymoma with lymphoid stroma. However, methylation analyses separated the histological subgroups AB and B2 into two methylation classes: mono-/bi-phasic AB-thymomas and conventional/“B1-like” B2-thymomas. Copy number variation analysis demonstrated methylation class-specific patterns of chromosomal alterations. Interpretation: Our study demonstrates that the current WHO classification is generally well reflected at the methylation level but suggests that B2- and AB-thymomas are (epi)genetically heterogeneous. Methylation-based classifications could help to refine diagnostic criteria for thymoma classification, improve reproducibility, and may affect treatment decisions.
Dietary Polyphenol Intake and Gastric Cancer: A Systematic Review and Meta-Analysis
Authors: Fagundes Marcela de Araújo , Silva Alex Richard Costa , Fernandes Gisele Aparecida , Curado Maria Paula
Published: November 2022

Background: Phenolic compound consumption may have a protective effect against gastric cancer (GC). Most GC studies focus on the flavonoids class, but results are conflicting and knowledge gaps remain for other classes and total polyphenol intake. This study aimed to assess the association between polyphenol intake (total, flavonoids, and other classes) and GC. Methods: In this systematic review and meta-analysis, the PubMed, Embase, Scopus, LILACS, Web of Science, and OpenGrey databases were searched for studies published up to 20 March 2022. Case–control and cohort studies analyzing the association between polyphenol intake and GC were included. For the meta-analysis, pooled summary estimates were calculated using a random-effects model, and the estimates extracted adjusted for most variables. Subgroup analyses were performed for subclass (e.g., flavonoids and other classes), sex, geographical area, study design, anatomical subtype, histological subtype, family history of GC and fruit and/or vegetable intake. The study was registered with PROSPERO (#CRD42022306014). Findings: The search identified 2752 records, of which 19 studies published during the period 1999–2021 including a total of 1,197,857 subjects were eligible. Polyphenol consumption reduced GC risk by 29% (RR = 0.71; 95% CI: 0.62–0.81; I2 = 60.5%); while flavonoid intake decreased GC risk by 28% (RR = 0.72; 95% CI: 0.61–0.85; I2 = 64.3%), similar to the reduction fort other classes (RR = 0.65; 95% CI: 0.54–0.79; I2 = 72.0%). Protective effects against GC were observed in both sexes (male, RR = 0.79; 95% CI: 0.67–0.94, I2 = 31.6%; female, RR = 0.65; 95% CI: 0.48–0.87, I2 = 49.7%) and for intestinal subtype (RR = 0.65; 95% CI: 0.52–0.82, I2 = 0.0%). By continent, polyphenol consumption reduced GC risk in both Europe (RR = 0.67; 95% CI: 0.57–0.79, I2 = 44.2%) and Asia (RR = 0.67; 95% CI: 0.51–0.89, I2 = 60.7%). Conclusions: Dietary polyphenol intake decreased GC risk. The reduction was greatest in females. Most previous studies were carried out in Europe and Asia. Further studies investigating polyphenol consumption and GC in Latin American populations are warranted.
Follistatin Is a Novel Chemoattractant for Migration and Invasion of Placental Trophoblasts of Mice
Authors: Li Jing , Qi Yan , Yang Ke , Zhu Linjing , Cui Xueling , Liu Zhonghui
Published: November 2022

Follistatin (FST) as a gonadal protein is central to the establishment and maintenance of pregnancy. Trophoblasts’ migration and invasion into the endometrium are critical events in placental development. This study aimed to elucidate the role of FST in the migration and invasion of placental trophoblasts of mice. We found that FST increased the vitality and proliferation of primary cultured trophoblasts of embryonic day 8.5 (E8.5) mice and promoted wound healing of trophoblasts. Moreover, FST significantly induced migration of trophoblasts in a microfluidic device and increased the number of invasive trophoblasts by Matrigel-coated transwell invasion assay. Being treated with FST, the adhesion of trophoblasts was inhibited, but intracellular calcium flux of trophoblasts was increased. Western blotting results showed that FST had no significant effects on the level of p-Smad3 or the ratio of p-Smad3/Smad3 in trophoblasts. Interestingly, FST elevated the level of p-JNK; the ratio of p-JNK/JNK; and expression of migration-related proteins N-cadherin, vimentin, ezrin and MMP2 in trophoblasts. Additionally, the migration of trophoblasts and expression of N-cadherin, vimentin, and MMP2 in trophoblasts induced by FST were attenuated by JNK inhibitor AS601245. These findings suggest that the elevated FST in pregnancy may act as a chemokine to induce trophoblast migration and invasion through the enhanced JNK signaling to maintain trophoblast function and promote placental development.
LASP1 in Cellular Signaling and Gene Expression: More than Just a Cytoskeletal Regulator
Authors: Butt Elke , Howard Cory M. , Raman Dayanidhi
Published: November 2022

LIM and SH3 protein 1 was originally identified as a structural cytoskeletal protein with scaffolding function. However, recent data suggest additional roles in cell signaling and gene expression, especially in tumor cells. These novel functions are primarily regulated by the site-specific phosphorylation of LASP1. This review will focus on specific phosphorylation-dependent interaction between LASP1 and cellular proteins that orchestrate primary tumor progression and metastasis. More specifically, we will describe the role of LASP1 in chemokine receptor, and PI3K/AKT signaling. We outline the nuclear role for LASP1 in terms of epigenetics and transcriptional regulation and modulation of oncogenic mRNA translation. Finally, newly identified roles for the cytoskeletal function of LASP1 next to its known canonical F-actin binding properties are included.
Microwave-Assisted Synthesis, Characterization and Tribological Properties of a g-C3N4/MoS2 Nanocomposite for Low Friction Coatings
Authors: Saxena Mukul , Sharma Anuj Kumar , Srivastava Ashish Kumar , Singh Rabesh Kumar , Dixit Amit Rai , Nag Akash , Hloch Sergej
Published: November 2022

This study explores the tribological performance of microwave-assisted synthesized g-C3N4/MoS2 coatings. The two-dimensional transition metal dichalcogenide (TMD) nanosheet is getting prominence in the study of tribology due to its layered structure. The graphitic carbon nitride (g-C3N4) nanosheet was made using the calcination method and its nanocomposite with molybdenum disulfide (MoS2) was produced using a microwave-assisted method. The structure and morphology of the samples were characterized by some well-known methods, and tribological properties were studied by a pin-on-disc (POD) apparatus. Morphological analysis revealed that graphitic carbon nitride and molybdenum disulfide coexisted, and the layer structured MoS2 was well dispersed on graphitic carbon nitride nanosheets. BET analysis was used to determine the pore volume and specific surface area of the synthesized materials. The inclusion of MoS2 nanoparticles caused the composite’s pore volume and specific surface area to decrease. The reduction in g-C3N4 pore volume and specific surface area confirmed that the pores of calcinated graphitic carbon nitride were filled with MoS2 nanoparticles. The tribological property of g-C3N4/MoS2 nanocomposite was systematically investigated under different factors such as applied loads (5N to 15N), sliding speed (500 to 1000 mm/s) and material composition (uncoated, MoS2-coated, 9 wt.% of g-C3N4 and 20 wt.% of g-C3N4 in the composite). The optimal composite material ratio was taken 9%, by weight of g-C3N4 in the g-C3N4/MoS2 composite for a variety of levels of loads and sliding speeds. The results indicates that the incorporation of g-C3N4 in nanocomposites could reduce friction and improve wear life, which were better than the results with single MoS2. This study demonstrates a solution to broaden the possible uses of g-C3N4 and MoS2-based materials in the field of tribology.
Efficacy and Safety of the “Trisection Method” Training System for Robot-Assisted Radical Cystectomy at a Single Institution in Japan
Authors: Nakane Keita , Yamada Toyohiro , Tomioka-Inagawa Risa , Sugino Fumiya , Kumada Naotaka , Kawase Makoto , Takeuchi Shinichi , Kawase Kota , Kato Daiki , Takai Manabu , Iinuma Koji , Koie Takuya
Published: November 2022

To maintain a surgeon’s concentration, reduce fatigue, and train young surgeons, surgical procedures for bladder cancer are divided into the following parts: robot-assisted radical cystectomy (RARC), bowel reconstruction, and totally intracorporeal urinary diversion (ICUD) (RARC+ICUD). Each part is performed by a different surgeon (Trisection method). We retrospectively evaluated the efficacy and safety of this approach at a single institution in Japan. One hundred consecutive patients who underwent RARC+ICUD at Gifu University Hospital between November 2018 and August 2022 were included in this study. The patient background, surgical outcomes, and postoperative complications were compared between surgeries by first-, second-, and third-generation surgeons. The overall survival (OS) and recurrence-free survival (RFS) were compared between surgeries by each generation. Of the 100 patients, 19, 38, and 43 RARCs were performed by first-, second-, and third-generation surgeons, respectively. There were 35, 25, and 39 patients who underwent ileal conduit, neobladder, and ureterocutaneostomy, respectively. No significant differences were found among the patients respective to the type of ICUDs. Although the first-generation surgeon had a significantly shorter operative time with RARC, the surgical time for bowel reconstruction, length of hospital stays, and incidence of postoperative complications were not significantly different among the groups. Additionally, OS and RFS did not differ significantly among the generations. The “Trisection method” is an effective and safe concept with no difference in outcomes between the generations of surgeons.
Planar Gas Expansion under Intensive Nanosecond Laser Evaporation into Vacuum as Applied to Time-of-Flight Analysis
Authors: Morozov Alexey , Titarev Vladimir
Published: November 2022

A computational investigation of the dynamics of gas expansion due to intense nanosecond laser evaporation into vacuum has been carried out. The problem is solved in a one-dimensional approximation, which simplifies calculations and at the same time allows one to analyze the main features of the expansion dynamics. For analysis we use three different approaches. Two of them are based on kinetic analysis via the direct simulation Monte Carlo (DSMC) method and numerical solution of the model Bhatnagar–Gross–Krook (BGK) equation. The third one focuses on derivation of an analytical continuum solution. Emphasis is placed on the analysis of the velocity distribution function and the average energy of particles passing through the time-of-flight detector on the normal to the evaporation surface, which is important for interpreting experimental measurements. The formulated problem is quite difficult as the considered flow is time-dependent, contains discontinuities in boundary conditions and involves large variations of local Knudsen numbers as well as steep gradients of the velocity distribution function. Data were obtained on the particle energy in the time-of-flight distribution for the range of regimes from the free molecular flow to continuum one. The maximum attainable average energy of particles in the time-of-flight distribution is determined. The non-monotonicity of the energy increase was found, which is explained based on analysis of the velocity distribution of particles.
Canonical Density Matrices from Eigenstates of Mixed Systems
Authors: Kourehpaz Mahdi , Donsa Stefan , Lackner Fabian , Burgdörfer Joachim , Březinová Iva
Published: November 2022

One key issue of the foundation of statistical mechanics is the emergence of equilibrium ensembles in isolated and closed quantum systems. Recently, it was predicted that in the thermodynamic (N→∞) limit of large quantum many-body systems, canonical density matrices emerge for small subsystems from almost all pure states. This notion of canonical typicality is assumed to originate from the entanglement between subsystem and environment and the resulting intrinsic quantum complexity of the many-body state. For individual eigenstates, it has been shown that local observables show thermal properties provided the eigenstate thermalization hypothesis holds, which requires the system to be quantum-chaotic. In the present paper, we study the emergence of thermal states in the regime of a quantum analog of a mixed phase space. Specifically, we study the emergence of the canonical density matrix of an impurity upon reduction from isolated energy eigenstates of a large but finite quantum system the impurity is embedded in. Our system can be tuned by means of a single parameter from quantum integrability to quantum chaos and corresponds in between to a system with mixed quantum phase space. We show that the probability for finding a canonical density matrix when reducing the ensemble of energy eigenstates of the finite many-body system can be quantitatively controlled and tuned by the degree of quantum chaos present. For the transition from quantum integrability to quantum chaos, we find a continuous and universal (i.e., size-independent) relation between the fraction of canonical eigenstates and the degree of chaoticity as measured by the Brody parameter or the Shannon entropy.
Evaluation of the Flourish Dashboard for Context-Aware Fault Diagnosis in Industry 4.0 Smart Factories
Authors: Kaupp Lukas , Nazemi Kawa , Humm Bernhard
Published: November 2022

Cyber-physical systems become more complex, therewith production lines become more complex in the smart factory. Every employed system produces high amounts of data with unknown dependencies and relationships, making incident reasoning difficult. Context-aware fault diagnosis can unveil such relationships on different levels. A fault diagnosis application becomes context-aware when the current production situation is used in the reasoning process. We have already published TAOISM, a visual analytics model defining the context-aware fault diagnosis process for the Industry 4.0 domain. In this article, we propose the Flourish dashboard for context-aware fault diagnosis. The eponymous visualization Flourish is a first implementation of a context-displaying visualization for context-aware fault diagnosis in an Industry 4.0 setting. We conducted a questionnaire and interview-based bilingual evaluation with two user groups based on contextual faults recorded in a production-equal smart factory. Both groups provided qualitative feedback after using the Flourish dashboard. We positively evaluate the Flourish dashboard as an essential part of the context-aware fault diagnosis and discuss our findings, open gaps, and future research directions.
Assessing Green Infrastructures Using GIS and the Multi-Criteria Decision-Making Method: The Case of the Al Baha Region (Saudi Arabia)
Authors: Mobarak Babikir , Shrahily Raid , Mohammad Alsharif , Alzandi Abdulrhman Ali
Published: November 2022

Among the Saudi Vision 2030 programs is the Green Saudi Initiative, which aims to protect the environment, energy conversion, and sustainability projects to build a sustainable future. In the present paper, Green Infrastructures (GI) were assessed, analyzed, and mapped using GIS and Analytic Hierarchy Process-based-Multi-Criteria Decision-Making Method (AHP-MCDM). Ten criteria were selected to elaborate the GI suitability map (DEM, slope, topographic position index, rainfall, distance to the water lines, topographic wetness index, distance to the road, wind speed, housing income group high (high-income people) map, employment in the agricultural sector, and land use land change). The results revealed four classes of suitability: Poor, Fair, Good, and Excellent. The “Excellent” area for GI planning was estimated at 983 km2 (9%), whereas the “Good” area covered 36% (3987 km2). The excellent and good areas for GI were more localized in the central part of the Al Baha region in the areas of Al Bahah, Elmandaq, Alatawlah, and the central part of Buljurshi. According to the obtained results, the southern part of the study is not suitable for GI planning; this is explained by the large area of barren land and sand. The results obtained by this research may help managers and decision-makers in future planning for GI areas in the Al Baha region.