bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the association between income inequality in youth and deaths of despair in Canada: a population-based cohort study from 2006 to 2019
Authors: Benny Claire , Smith Brendan T , Hyshka Elaine , Senthilselvan Ambikaipakan , Veugelers Paul J , Pabayo Roman
Published: November 2022

Background

Deaths due to suicide, drug overdose and alcohol-related liver disease, collectively known as ‘deaths of despair’, have been markedly increasing since the early 2000s and are especially prominent in young Canadians. Income inequality has been linked to this rise in deaths of despair; however, this association has not yet been examined in a Canadian context, nor at the individual level or in youth. The study objective was to examine the association between income inequality in youth and deaths of despair among youth over time.

Methods

We conducted a population-based longitudinal study of Canadians aged 20 years or younger using data from the Canadian Census Health and Environment Cohorts. Baseline data from the 2006 Canadian Census were linked to the Canadian Vital Statistics Database up to 2019. We employed multilevel survival analysis models to quantify the association between income inequality in youth and time-to deaths of despair.

Results

The study sample included 1.5 million Canadians, representing 7.7 million Canadians between the ages of 0 and 19 at baseline. Results from the weighted, adjusted multilevel survival models demonstrated that income inequality was associated with an increased hazard of deaths of despair (adjusted HR (AHR) 1.35; 95% CI 1.04 to 1.75), drug overdose (AHR 2.38; 95% CI 1.63 to 3.48) and all-cause deaths (AHR 1.10; 95% CI 1.04 to 1.18). Income inequality was not significantly associated with suicide deaths (AHR 1.23, 95% CI 0.93 to 1.63).

Conclusion

The results show that higher levels of income inequality in youth are associated with an increased hazard of all-cause death, deaths of despair and drug overdose in young Canadians. This study is the first to reveal the association between income inequality and deaths of despair in youth and does so using a population-based longitudinal cohort involving multilevel data. The results of this study can inform policies related to income inequality and deaths of despair in Canada.
Virtual clinical trials of anti-PD-1 and anti-CTLA-4 immunotherapy in advanced hepatocellular carcinoma using a quantitative systems pharmacology model
Authors: Sové Richard J , Verma Babita K , Wang Hanwen , Ho Won Jin , Yarchoan Mark , Popel Aleksander S
Published: November 2022

Background

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is the third-leading cause of cancer-related death worldwide. Most patients with HCC are diagnosed at an advanced stage, and the median survival for patients with advanced HCC treated with modern systemic therapy is less than 2 years. This leaves the advanced stage patients with limited treatment options. Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) or its ligand, are widely used in the treatment of HCC and are associated with durable responses in a subset of patients. ICIs targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) also have clinical activity in HCC. Combination therapy of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) is the first treatment option for HCC to be approved by Food and Drug Administration that targets more than one immune checkpoints.

Methods

In this study, we used the framework of quantitative systems pharmacology (QSP) to perform a virtual clinical trial for nivolumab and ipilimumab in HCC patients. Our model incorporates detailed biological mechanisms of interactions of immune cells and cancer cells leading to antitumor response. To conduct virtual clinical trial, we generate virtual patient from a cohort of 5,000 proposed patients by extending recent algorithms from literature. The model was calibrated using the data of the clinical trial CheckMate 040 (ClinicalTrials.gov number,NCT01658878).

Results

Retrospective analyses were performed for different immune checkpoint therapies as performed in CheckMate 040. Using machine learning approach, we predict the importance of potential biomarkers for immune blockade therapies.

Conclusions

This is the first QSP model for HCC with ICIs and the predictions are consistent with clinically observed outcomes. This study demonstrates that using a mechanistic understanding of the underlying pathophysiology, QSP models can facilitate patient selection and design clinical trials with improved success.
Evaluation of the Disease Activity index for PSoriatic Arthritis (DAPSA) with a quick quantitative C reactive protein assay (Q-DAPSA) in patients with psoriatic arthritis: a prospective multicentre cross-sectional study
Authors: Proft Fabian , Schally Julia , Brandt Henning Christian , Brandt-Juergens Jan , Burmester Gerd Rüdiger , Haibel Hildrun , Käding Henriette , Karberg Kirsten , Lüders Susanne , Muche Burkhard , Protopopov Mikhail , Rademacher Judith , Rios Rodriguez Valeria , Torgutalp Murat , Verba Maryna , Zinke Silke , Poddubnyy Denis
Published: November 2022

Objectives

This study aimed to evaluate the Disease Activity index for PSoriatic Arthritis (DAPSA) based on a quick quantitative C reactive protein (qCRP) assay (Q-DAPSA) in a multicentre, prospective, cross-sectional study in patients with psoriatic arthritis (PsA).

Methods

The assessment of prospectively recruited study patients included joint examination and patient reported outcome (PRO) measures (patient global assessment, patient pain assessment). Following, the DAPSA based on a routine laboratory CRP measurement, Q-DAPSA and clinical DAPSA (cDAPSA) were calculated. Cross-tabulations and weighted Cohen’s kappa were performed to analyse the agreement of disease activity categories. Bland-Altman plots and intraclass correlation coefficients were used to determine the agreement of numerical values regarding CRP and qCRP as well as different disease activity scores.

Results

Altogether, 104 patients with PsA could be included in the statistical analysis. With Q-DAPSA, 102 of 104 (98.1%) patients achieved identical disease activity categories in comparison to DAPSA with a weighted Cohen’s kappa of 0.980 (95% CI: 0.952 to 1.000). The agreement between DAPSA and cDAPSA was slightly lower with identical disease activity categories seen in 97 of 104 (93.3%) of patients and with a weighted Cohen’s kappa of 0.932 (95% CI 0.885 to 0.980).

Conclusions

The Q-DAPSA showed an almost perfect agreement with the conventional DAPSA regarding identical disease activity categories. Thus, the Q-DAPSA can be used as a timely available disease activity score in patients with PsA with the additional benefit of CRP involvement. Consequently, the Q-DAPSA could facilitate the implementation of the treat-to-target concept in clinical routine and clinical trials.
Systematic literature review informing the 2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases
Authors: Fragoulis George E , Dey Mrinalini , Zhao Sizheng , Schoones Jan , Courvoisier Delphine , Galloway James , Hyrich Kimme L , Nikiphorou Elena
Published: November 2022

Objective

To conduct a systematic literature review (SLR) on the screening and prophylaxis of opportunistic and chronic infections in autoimmune inflammatory rheumatic diseases (AIIRD).

Methods

SLR (inception-12/2021) based on the following search domains: (1) infectious agents, (2) AIIRD, (3) immunosuppressives/immunomodulators used in rheumatology, (4) screening terms and (5) prophylaxis terms. Articles were retrieved having the terms from (1) AND (2) AND (3) plus terms from (4) OR(5). Databases searched: PubMed, Embase and Cochrane Library. Exclusion criteria: studies on postoperative infections, paediatric AIIRD, COVID-19, vaccinations and non-Εnglish literature. Study quality was assessed with Newcastle-Ottawa scale for non-randomised controlled trials (RCTs), RoB-Cochrane for RCTs, AMSTAR2 for SLRs.

Results

From 5641 studies were retrieved, 568 full-text articles were assessed for eligibility, with 194 articles finally included. For tuberculosis, tuberculin skin test (TST) is affected by treatment with glucocorticoids and conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and its performance is inferior to interferon gamma release assay (IGRA). Agreement between TST and IGRA is moderate to low. For hepatitis B virus (HBV): risk of reactivation is increased in patients positive for hepatitis B surface antigen. Anti-HBcore positive patients are at low risk for reactivation but should be monitored periodically with liver function tests and/or HBV-viral load. Risk for Hepatitis C reactivation is existing but low in patients treated with biological DMARDs. ForPneumocystis jirovecii, prophylaxis treatment should be considered in patients treated with prednisolone ≥15–30 mg/day for >2–4 weeks.

Conclusions

Different screening and prophylaxis approaches are described in the literature, partly determined by individual patient and disease characteristics.
Seismic Response of Monopile-Supported OWT Structure Considering Effect of Long-Term Cyclic Loading
Authors: Sun Yilong , Xu Chengshun , Cui Chunyi , Naggar M. Hesham El , Du Xiuli
Published: November 2022

Offshore wind turbine (OWT) structures are subject to wave, wind, and seismic loading. Due to the cyclic nature of these loads, OWT foundations can be vulnerable to cumulative deformation and liquefaction triggered by waves and earthquakes. The effects of cumulative deformation and liquefaction on the monopile-supported OWT are not fully appreciated. This paper develops a three-dimensional numerical model for analyzing the seismic performance of large monopile-supported OWT under the long-term effect of cyclic loading. The numerical model was established employing FLAC3D and utilizing SANISAND constitutive model to simulate the soil behavior. The numerical model was validated by comparing its predictions with the results of dynamic triaxial tests and centrifuge tests. A simplified densification and subsidence site model was integrated into the numerical model to facilitate considering the long-term effect of cyclic loading. The numerical model was then used to conduct a comprehensive study to evaluate the influence of long-term cyclic loading on the natural frequency and seismic response of OWT structure. The results demonstrated that the densified subsidence zone around monopile increased the liquefaction resistance. However, the horizontal displacement of pile and the response acceleration of tower-top increased due to soil subsidence around monopile.
NETWORKS OF MUSIC GROUPS AS SUCCESS PREDICTORS
Authors: ZINOVIEV DMITRY
Published: November 2022

More than 4600 non-academic music groups had emerged in the USSR and post-Soviet independent nations during 1960–2015, performing in 275 genres. Some groups became legends and survived for decades, while others vanished and are known now only to the most dedicated music history scholars. To explain and predict success, we built a complex network of the groups and their almost 20,000 members based on performers’ sharing using the data from Wikipedia and Google. We calculated the primary network measures: centralities, degree assortativity, and clustering coefficient — and discovered that they could not accurately predict music group success, but they could distinguish between coarse measures of success, such as which groups were above or below the median. In particular, all centralities positively correlate with success, and the clustering coefficient non-linearly maximizes it. The proposed network-based success exploration and prediction methods are transferable to other arts and humanities areas with medium- or long-term team-based collaborations.
Conjoint Analysis Models of Digital Packaging Information Features in Customer Decision-Making
Authors: Płonka Marta , Grobelny Jerzy , Michalski Rafał
Published: November 2022

Product packaging has a great influence on customers’ decision-making and shapes purchase intentions. The graphic message is the crucial component of this impact. Digital presentations of goods are ubiquitous, therefore understanding how graphical features influence customer decisions is of enormous theoretical and practical importance. Despite the interest, the role of specific factors and their combinations is still unclear, especially if medium-involvement products are concerned. Since only a few studies have considered this context, this research examines how eight variants of a digital presentation of cordless kettle packaging influence purchase willingness, which was derived from pairwise comparisons using eigenvectors. The experimental conditions differed in three factors: the existence of a product graphical context, a brief or extended product description, and white or black packaging background color. Results of analyses of variance and conjoint analyses revealed a significant role of all examined effects, with the background color being the least influential. The best-rated designs included graphical context and extended textual information. There were also some meaningful gender-related differences revealed by conjoint analyses. The black background color was much more important for females than males. The outcomes broaden our knowledge on people’s perception of packaging design graphical factors, and their impact on purchase decisions.
On the spectra of non-commuting graphs of certain class of groups
Authors: Kalita Jharna , Paul Somnath
Published: November 2022

Let [Formula: see text] be the center of a finite non-abelian group [Formula: see text] The non-commuting graph of [Formula: see text] is a simple undirected graph with vertex set [Formula: see text] and two vertices [Formula: see text] and [Formula: see text] are adjacent if and only if [Formula: see text] A group [Formula: see text] is called a CA-group if the centralizer [Formula: see text] for every non central element [Formula: see text] is abelian. In this paper, we investigate the distance, distance (signless) Laplacian spectra of non-commuting graphs of some CA-groups, and obtain some conditions on them so that the corresponding non-commuting graph is distance, distance (signless) Laplacian integral.
Wiki Loves Monuments: Crowdsourcing the Collective Image of the Worldwide Built Heritage
Authors: Azizifard Narges , Gelauff Lodewijk , Gransard-Desmond Jean-Olivier , Redi Miriam , Schifanella Rossano
Published: November 2022

The wide adoption of digital technologies in the cultural heritage sector has promoted the emergence of new, distributed ways of working, communicating, and investigating cultural products and services. In particular, collaborative online platforms and crowdsourcing mechanisms have been widely adopted in the effort to solicit input from the community and promote engagement. In this work, we provide an extensive analysis of the
Wiki Loves Monuments
initiative, an annual, international photography contest in which volunteers are invited to take pictures of the built cultural heritage and upload them to Wikimedia Commons. We explore the geographical, temporal, and topical dimensions across the 2010–2021 editions. We first adopt a set of CNN-based artificial systems that allow the learning of deep scene features for various scene recognition tasks, exploring cross-country (dis)similarities. To overcome the rigidity of the framework based on scene descriptors, we train a deep convolutional neural network model to label a photo with its country of origin. The resulting model captures the best representation of a heritage site uploaded in a country, and it allows the domain experts to explore the complexity of cross-national architectural styles. Finally, as a validation step, we explore the link between architectural heritage and intangible cultural values, operationalized using the framework developed within the World Value Survey research program. We observe that cross-country cultural similarities match to a fair extent the interrelations emerging in the architectural domain. We think this study contributes to highlighting the richness and the potential of the Wikimedia data and tools ecosystem to act as a scientific object for art historians, iconologists, and archaeologists.
Identification of Genetic Risk Factors for Monogenic and Complex Canine Diseases
Authors: Leeb Tosso , Bannasch Danika , Schoenebeck Jeffrey J.
Published: November 2022

Advances in DNA sequencing and other technologies have greatly facilitated the identification of genetic risk factors for inherited diseases in dogs. We review recent technological developments based on selected examples from canine disease genetics. The identification of disease-causing variants in dogs with monogenic diseases may become a widely employed diagnostic approach in clinical veterinary medicine in the not-too-distant future. Diseases with complex modes of inheritance continue to pose challenges to researchers but have also become much more tangible than in the past. In addition to strategies for identifying genetic risk factors, we provide some thoughts on the interpretation of sequence variants that are largely inspired by developments in human clinical genetics.
Compositionality in Computational Linguistics
Authors: Donatelli Lucia , Koller Alexander
Published: November 2022

Neural models greatly outperform grammar-based models across many tasks in modern computational linguistics. This raises the question of whether linguistic principles, such as the Principle of Compositionality, still have value as modeling tools. We review the recent literature and find that while an overly strict interpretation of compositionality makes it hard to achieve broad coverage in semantic parsing tasks, compositionality is still necessary for a model to learn the correct linguistic generalizations from limited data. Reconciling both of these qualities requires the careful exploration of a novel design space; we also review some recent results that may help in this exploration.
Heritage Languages: Language Acquired, Language Lost, Language Regained
Authors: Montrul Silvina
Published: November 2022

A heritage language is a sociopolitically minority and/or minoritized language acquired as the first or one of the first languages in a bilingual or multilingual context. Heritage languages are typically acquired under conditions of reduced exposure and are often used less than the majority language during late childhood and adolescence. Heritage languages show structural differences and changes at all levels of linguistic analysis from baseline grammars that arise from the complex interaction between the nature and quantity of input and the age of bilinguals. Although many situations give rise to heritage languages, this article focuses on immigrants and their children and reviews foundational studies of the linguistic properties of heritage languages; studies of age effects that have shed light on critical differences between first, second, and heritage language acquisition; and recent studies of heritage language relearning and reactivation. The implications of the study of heritage languages for bilingualism and society and for the language and cognitive sciences are discussed.
Update in Adult Transgender Medicine
Authors: Ramsay Alyxandra , Safer Joshua D.
Published: November 2022

Transgender people often face barriers in health care due to lack of access to care, lack of knowledgeable healthcare professionals, discrimination, and gaps in medical and mental health research. Existing research on transgender health has focused heavily on mental health, HIV/AIDS, sexually transmitted diseases/infections, and substance abuse. Gender-affirming hormone therapy and/or surgery allows for some alignment of biology and gender identity. Gender-affirming care may offer quality-of-life benefits, which may outweigh modest concerns related to exogenous hormone therapy. The Endocrine Society treatment guidelines were revised in 2017, and this article reviews recent data that might inform a future guideline revision. Future longitudinal research is needed to close the gap in knowledge in the field of transgender medicine.
Effect of Ferric Nitrate on Semi-Insulating 4H-SiC (0001) Chemical Mechanical Polishing
Authors: Wang Weilei , Liu Weili , Song Zhitang , Xu Yonghui
Published: November 2022

Semi-insulating 4H-SiC (0001) has high hardness and high chemical inertness, making it difficult to obtain high material removal rates (MRR) during chemical mechanical polishing (CMP). In this paper, the role of chemical additive ferric nitrate in semi-insulating 4H-SiC(0001) chemical mechanical polishing with α-alumina as abrasive and KMnO4 as oxidant was discussed. The results showed that 0.5 wt% ferric nitrate can increase the removal rate of semi-insulating 4H-SiC(0001) by 34%, while the semi-insulating 4H-SiC(0001) surface roughness Ra was reduced from 0.123 nm to 0.110 nm. The key point was that the coefficient of friction of the polishing slurry was effectively reduced, which was very beneficial to the ploughing effect of the α-alumina abrasive with vermicular thin section morphology which had the highest removal rate. In the second place, the chemical composition of 4H-SiC(0001) corrosion layer was analyzed by XPS under different corrosion conditions. Si 2P spectrum analysis showed that O atoms only attack C atoms to produce Si–C–O structure under acidic conditions. Whereas with the addition of ferric nitrate, O atoms not only attacked C atoms, but also attacked Si atoms to produce softer SiO2 and Si-Ox-Cy structures. At the end of the paper, the chemical mechanical polishing mechanism of semi-insulating 4H-SiC(0001) was given.
Demonstration of Extended-Gate Structure for Ion Sensors based on Amorphous Indium-Gallium-Zinc Oxide Thin-Film Transistors
Authors: Iwamatsu Shinnosuke , Takechi Kazushige , Tanabe Hiroshi , Watanabe Yoshiyuki
Published: November 2022

This paper presents our work towards improving the reliability of high-sensitivity pH sensor based on the top-gate effect in an amorphous indium-gallium-zinc oxide thin-film transistor (a-InGaZnO TFT) and its application to the sensing of a sodium ion and a potassium ion. Here, we propose an extended-gate a-InGaZnO TFT pH sensor with an atomic layer deposition (ALD)-AlOx/sputtered-TaOx layered top-gate insulator and a Ti extended-gate electrode. We discuss our primary results for the extended-gate a-InGaZnO TFT pH sensor, including its pH sensitivity and ability to respond to a pH change of 0.001. The extended-gate a-InGaZnO TFT pH sensor resulted in over Nernstian pH sensitivity of 625 mV/pH. The pH sensor indicated the possibility of detecting a pH change of 0.001 with some signal processing techniques. Furthermore, we demonstrated the sensing of a sodium ion and a potassium ion with a-InGaZnO TFT and an ion-sensitive extended-gate electrode. The sensors indicated a clear response to the concentration changes of sodium and potassium ions with a sensitivity of 1030 mV/decade and 866 mV/decade, respectively. These results demonstrate that our extended-gate structure has the potential to detect with high sensitivity concentration changes in various ions just by replacing the extended-gate electrode with various ion-sensitive membranes.
Effect of Guiding Layers and Interdigitated Electrode Structures on the Frequency Behaviour of SAW Sensors
Authors: Xu Zhangliang , Luo Yang
Published: November 2022

The properties of surface acoustic wave (SAW) sensor can be optimized by using a rational structural design. In this work, simulation and experimental studies of ZnO/quartz structure are presented. The effect of the guiding layer on the propagation characteristic and surface displacement of the designed SAW sensor is mainly discussed. SAW sensors with different structures (different input-output interdigital transducer (IDT) ratio, different aperture and different guiding layer) are fabricated via conventional photolithography techniques and measured by network analyzer. The ZnO-based SAW sensor with symmetrical structure (50:50) and larger aperture (1800 μm) shows good frequency behaviour and obtains lower insertion loss. The experimental results are in agreement with the simulation results.
Memory decay and generalization following distinct motor learning mechanisms
Authors: Bao Shancheng , Lei Yuming
Published: November 2022

Motor skill learning is likely to involve error-based learning, use-dependent plasticity, and operant reinforcement. Here, we showed that these dissociable learning mechanisms exhibited distinct patterns of memory decay and generalization. With a better understanding of the characteristics of these learning mechanisms, it becomes possible to regulate each learning process separately to improve neurological rehabilitation.
Chronic intermittent hypoxia enhances glycinergic inhibition in nucleus tractus solitarius
Authors: Jia Shuping , Rybalchenko Nataliya , Kunwar Kishor , Farmer George E. , Little Joel T. , Toney Glenn M. , Cunningham J. Thomas
Published: November 2022

Chronic intermittent hypoxia (CIH) has been used to mimic the hypoxemia associated with sleep apnea and determine how these hypoxemias influence neural function. The nucleus of the solitary tract is the main site for chemoreceptor input to the CNS, but how CIH influences NTS inhibition has not been determined. These studies show that CIH increases glycine-mediated miniature IPSCs through mechanisms that depend on protein trafficking and astrocyte activation.
HSPB1 overexpression improves hypoxic-ischemic brain damage by attenuating ferroptosis in rats through promoting G6PD expression
Authors: Dai Yi , Hu Lan
Published: November 2022

HSPB1 and G6PD were overexpressed in the hippocampus tissues of HI rats. High expression of HSPB1 in HI rats mitigated infarction rate and iron accumulation. HSPB1 overexpression reduced ferritin level, attenuated apoptosis, yet augmented GPX4, SLC7A11, and TFR1 levels in the hippocampus tissues of HI rats. G6PD deletion impaired the protective role of HSPB1 overexpression against HI brain damage-induced ferroptosis.
Differential changes in somatosensory evoked potentials and motor performance: pursuit movement task versus force matching tracking task
Authors: Ambalavanar Ushani , Delfa Nicholas La , McCracken Heather , Zabihhosseinian Mahboobeh , Yielder Paul , Murphy Bernadette
Published: November 2022

This study demonstrates neurophysiological differences in cerebellar and somatosensory cortex pathways when learning a motor task requiring visuomotor tracking versus a task that requires force-matching modulation, in healthy individuals. The clear neurophysiological differences in early somatosensory evoked potentials associated with cortical somatosensory processing, cerebellar input, and sensorimotor integration between these two tasks demonstrate some of the neural correlates of force modulation and validate the force-matching task for use in future work.
Using Machine Learning Techniques to Predict Learner Drop-out Rate in Higher Educational Institutions
Authors: Dake Delali Kwasi , Buabeng-Andoh Charles
Published: November 2022

Recently, students dropping out of school at the tertiary level without prior notice or permission has intrigued deep concern among academic authorities, instructors, and counsellors. It has therefore become necessary to understand factors that lead to high attrition rates among learners and identify at-risk students for urgent academic counselling. In providing a proactive response to learner attrition, the study deployed a machine learning algorithm with high model accuracy to predict students’ drop-out rates and identify dominant attributes that affect learner attrition and retention. An attrition model was built and validated among support vector machine, decision tree, multilayer perceptron, and random forest algorithms. The machine learning algorithms were tested for accuracy, precision, recall, F-measure, and ROC using the 10-fold and the 5-fold comparative cross-validation techniques. In addition to the cross-validation technique, the chi-square feature selection mechanism was implemented to understand the algorithms’ training time and accuracy. The random forest emerged as the best-performing algorithm, with an accuracy of 70.98% and 69.74% for the 10-fold and the 5-fold cross-validation implementations, respectively.
A High-Accurate Time Integration Method for Solving Structural Vibration Responses
Authors: Lei Xiangsheng , Wang Yanfeng , Wang Xinghua , Lin Gang , Qin Xinyan
Published: November 2022

A time integration method for the equations of motion is developed based on the Gauss implicit Runge-Kutta method to high-accurate solving the responses in structural vibration. The present method possesses the features of unconditional stability and self-starting and can achieve fourth-order accuracy in displacement, velocity, and acceleration simultaneously. The algorithm is a matrix form and no need to iterate in the calculation. The convergent accuracy is verified by a numerical example, and the effectiveness is also verified by solving the dynamic responses of a vibration isolation system and the vibration responses of a pylon structure with cyclic loads and earthquake loads.
Some Bianchi Type Viscous Holographic Dark Energy Cosmological Models in the Brans–Dicke Theory
Authors: Santhi M. Vijaya , Chinnappalanaidu T. , Madhu S. Srivani , Gusu Daba Meshesha
Published: November 2022

In this article, we analyze Bianchi type–II, VIII, and IX spatially homogeneous and anisotropic space-times in the background of the Brans–Dicke theory of gravity within the framework of viscous holographic dark energy. To solve the field equations, we have used the relation between the metric potentials as

R
=

S

n

and the relation between the scalar field

ϕ

and the scale factor

a

as

ϕ
=

a

m

. Also, we have discussed some of the dynamical parameters of the obtained models, such as the deceleration parameter

q

, the jerk parameter

 
j

, the EoS parameter

ω

v
h
d
e

, the density parameter

Ω

vhde

, Om-diagnostic, squared speed of sound

v
s
2

, EoS plane

ω

v
h
d
e

−

ω

v
h
d
e

′

, and statefinder plane

r
 
−
 
s

through graphical representation, which are significant in the discussion of cosmology. Furthermore, all the models obtained and graphically presented shown an expanding and accelerating Universe, which is in better agreement with the latest experimental data. The viscous holographic dark energy models are compatible with explaining the present cosmic accelerated expansion.
Facial Recognition of Cattle Based on SK-ResNet
Authors: Gong He , Pan Haohong , Chen Lin , Hu TianLi , Li Shijun , Sun Yu , Mu Ye , Guo Ying
Published: November 2022

With the gradual increase of the scale of the breeding industry in recent years, the intelligence level of livestock breeding is also improving. Intelligent breeding is of great significance to the identification of livestock individuals. In this paper, the cattle face images are obtained from different angles to generate the cow face dataset, and a cow face recognition model based on SK_ResNet is proposed. Based on ResNet-50 and using a different number of sk_Bottleneck, this model integrates multiple receptive fields of information to extract facial features at multiple scales. The shortcut connection part connects to the maximum pooling layer to reduce information loss; the ELU activation function is used to reduce the vanishing gradient, prevent overfitting, accelerate the convergence speed, and improve the generalization ability of the model. The constructed bovine face dataset was used to train the SK-ResNet-based bovine face recognition model, and the accuracy rate was 98.42%. The method was tested on the public dataset and the self-built dataset. The accuracy rate of the model was 98.57% on the self-built pig face dataset and the public sheep face dataset. The accuracy rate was 97.02%. The experimental results verify the superiority of this method in practical application, which is helpful for the practical application of animal facial recognition technology in livestock.
Lysosomal-Associated Transmembrane Protein 5 Promotes Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma
Authors: Huang Ruo-Hui , Ge Zi-Lu , Xu Gang , Zeng Qing-Ming , Xia Wei , Xiao Guan-Cheng , Zou Xiao-Feng , Zhang Bin-Bin
Published: November 2022

Clear cell renal cell carcinoma (ccRCC) is the most aggressive and deadly cancer of the urinary system and is regulated by multiple signaling pathways. However, the specific molecular mechanisms underlying ccRCC have not been fully studied or demonstrated. This study aimed to elucidate the function of lysosomal-associated transmembrane protein 5 (LAPTM5) in ccRCC cell lines and animal models and determine the potential underlying mechanisms. Our results demonstrated that LAPTM5 expression in patients with ccRCC was significantly higher in the tumor group than that in the adjacent nontumor group. Moreover, LAPTM5 promoted proliferation, migration, and invasion of ccRCC cells through the gain and loss of the function of LAPTM5 in 786-0 and Caki-1 cell lines. Similar results regarding LAPTM5 overexpression were obtained in BALB/c nude mice. In addition, LAPTM5 activated the Jun N-terminal kinase (JNK)/p38 signaling cascade by interacting with Ras-related C3 botulinum toxin substrate 1 (RAC1). Treatment with an RAC1 inhibitor eliminated the effects of LAPTM5 in ccRCC. In conclusion, these results indicate that LAPTM5 may be a new therapeutic target for ccRCC via activation of the RAC1-JNK/p38 axis.
Early Post-Operative Endoscopy Is Associated with Lower Surgical Recurrence of Crohn’s Disease: A Retrospective Study of Three Successive Cohorts
Authors: Amicone Caroline , Marques Carla Coimbra , Reenaers Catherine , Van Kemseke Catherine , Seidel Laurence , Louis Edouard
Published: November 2022

Background. The severity of endoscopic recurrence during the first year after intestinal resection for Crohn’s disease is predictive of clinical recurrence. The aim of our study was to assess the impact of the implementation of an ileocolonoscopy during the first year after surgery on surgical recurrence. Methods. All patients who underwent a first intestinal resection for Crohn’s disease between 1992 and 2018 at the University Hospital of Liège were retrospectively included. The time to surgical recurrence was compared in three successive groups of patients operated on in the period 1992–2001 (group A), 2002–2011 (group B), and 2012–2020 (group C) using the Kaplan–Meier method and the Log-Rank test. To identify independent prognostic factors, a multivariate analysis was used via the Cox model. Results. 223 patients (group A = 69, group B = 94, group C = 60) were included. Probabilities of surgical recurrence were significantly lower in group C (2.2% and 4.7% at 3 and 5 years, respectively) compared with group B (4.2% and 7.6% at 3 and 5 years, respectively) and with group A (9% and 18.2% at 3 and 5 years, respectively) (

p
=
0.0089

). Ileocolonoscopy during the year after surgery was associated with a significantly reduced surgical recurrence rate in univariate and multivariate analysis (HR = 0.31,

p
=
0.0049

). Conclusion. The implementation of an early ileocolonoscopy after surgery for Crohn’s disease since early 2000 has been associated with a reduced surgical recurrence over the last 30 years.
The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models
Authors: Hebron Katie E. , Wan Xiaolin , Roth Jacob S. , Liewehr David J. , Sealover Nancy E. , Frye William J.E. , Kim Angela , Stauffer Stacey , Perkins Olivia L. , Sun Wenyue , Isanogle Kristine A. , Robinson Christina M. , James Amy , Awasthi Parirokh , Shankarappa Priya , Luo Xiaoling , Lei Haiyan , Butcher Donna , Smith Roberta , Edmondson Elijah F. , Chen Jin-Qiu , Kedei Noemi , Peer Cody J. , Shern Jack F. , Figg W. Douglas , Chen Lu , Hall Matthew D. , Difilippantonio Simone , Barr Frederic G. , Kortum Robert L. , Robey Robert W. , Vaseva Angelina V. , Khan Javed , Yohe Marielle E.
Published: November 2022

Purpose:

PAX-fusion negative rhabdomyosarcoma (FN RMS) is driven by alterations in the RAS/MAP kinase pathway and is partially responsive to MEK inhibition. Overexpression of IGF1R and its ligands is also observed in FN RMS. Preclinical and clinical studies have suggested that IGF1R is itself an important target in FN RMS. Our previous studies revealed preclinical efficacy of the MEK1/2 inhibitor, trametinib, and an IGF1R inhibitor, BMS-754807, but this combination was not pursued clinically due to intolerability in preclinical murine models. Here, we sought to identify a combination of an MEK1/2 inhibitor and IGF1R inhibitor, which would be tolerated in murine models and effective in both cell line and patient-derived xenograft models of RAS-mutant FN RMS.

Experimental Design:

Using proliferation and apoptosis assays, we studied the factorial effects of trametinib and ganitumab (AMG 479), a mAb with specificity for human and murine IGF1R, in a panel of RAS-mutant FN RMS cell lines. The molecular mechanism of the observed synergy was determined using conventional and capillary immunoassays. The efficacy and tolerability of trametinib/ganitumab was assessed using a panel of RAS-mutated cell-line and patient-derived RMS xenograft models.

Results:

Treatment with trametinib and ganitumab resulted in synergistic cellular growth inhibition in all cell lines tested and inhibition of tumor growth in four of six models of RAS-mutant RMS. The combination had little effect on body weight and did not produce thrombocytopenia, neutropenia, or hyperinsulinemia in tumor-bearing SCID beige mice. Mechanistically, ganitumab treatment prevented the phosphorylation of AKT induced by MEK inhibition alone. Therapeutic response to the combination was observed in models without a mutation in the PI3K/PTEN axis.

Conclusions:

We demonstrate that combined trametinib and ganitumab is effective in a genomically diverse panel of RAS-mutated FN RMS preclinical models. Our data also show that the trametinib/ganitumab combination likely has a favorable tolerability profile. These data support testing this combination in a phase I/II clinical trial for pediatric patients with relapsed or refractory RAS-mutated FN RMS.
Biology and Targetability of the Extended Spectrum ofPIK3CAMutations Detected in Breast Carcinoma
Authors: Rugo Hope S. , Raskina Kira , Schrock Alexa B. , Madison Russell W. , Graf Ryon P. , Sokol Ethan S. , Sivakumar Smruthy , Lee Jessica K. , Fisher Virginia , Oxnard Geoffrey R. , Tukachinsky Hanna
Published: November 2022

Purpose:

Alpelisib is a PI3K alpha (PI3Kα)-selective inhibitor approved for the treatment of hormone receptor–positive/HER2-negative (HR+/HER2−) PIK3CA-mutated advanced breast cancer (ABC) based on the SOLAR-1 trial, which defined 11 substitutions in exons 7, 9, and 20 in PIK3CA (SOLAR1m). We report alpelisib effectiveness for ABC harboring SOLAR1m, as well as other pathogenic PIK3CA mutations (OTHERm) using comprehensive genomic profiling (CGP).

Experimental Design:

A total of 33,977 tissue and 1,587 liquid biopsies were analyzed using hybrid capture–based CGP covering the entire coding sequence of PIK3CA. Clinical characteristics and treatment history were available for 10,750 patients with ABC in the deidentified Flatiron Health-Foundation Medicine clinico-genomic database (FH-FMI CGDB).

Results:

PIK3CAm were detected in 11,767/33,977 (35%) of tissue biopsies, including 2,300 (7%) samples with OTHERm and no SOLAR1m. Liquid biopsy had 77% sensitivity detecting PIK3CAm, increasing to 95% with circulating tumor DNA fraction ≥2%. In patients with HR+/HER2− ABC and PIK3CAm receiving alpelisib/fulvestrant (ALP+FUL; n = 182) or fulvestrant alone (FUL; n = 119), median real-world progression-free survival (rwPFS) was 5.9 months on ALP+FUL [95% confidence interval (CI): 5.1–7.4] versus 3.1 months on FUL (95% CI: 2.7–3.7; P < 0.0001). In patients with OTHERm, median rwPFS was 4.0 months on ALP+FUL (95% CI: 2.8–10.1) versus 2.5 months on FUL (95% CI: 2.2–3.7; P = 0.0054).

Conclusions:

CGP detects diverse PIK3CAm in a greater number of patients with ABC than PCR hotspot testing; 20% of patients with PIK3CAm do not have SOLAR1m. These patients may derive benefit from alpelisib.

See related commentary by Tau and Miller, p. 989
Triple Positive Antiphospholipid Antibody Syndrome in Pregnancy with High Frequency Plasma Exchange: A Case Report
Authors: Cottrell Jesse , Al Sanani Ahlim , Ogu Iheanyichukwu , Chaffin David
Published: November 2022

Introduction: Triple antibody positive antiphospholipid syndrome during pregnancy carries a poor prognosis. The placental vasculature is particularly vulnerable to these antibodies resulting in a marked increased risk of fetal growth restriction, placental infarction, abruption, stillbirth, and preterm severe preeclampsia. Case Presentation: We report a case of a primigravida with triple antibody positive antiphospholipid syndrome that demonstrated placental insufficiency and fetal compromise at a previable gestation. The patient underwent plasma exchange every 48 h for 11 weeks resulting in delivery of a viable infant. Placental blood flow was improved after complete absence of end-diastolic flow in the fetal umbilical artery. Conclusion: Scheduled plasmapheresis every 48 h can be considered in select cases of antiphospholipid antibody syndrome.
Efficacy and Safety of a Drug-Free, Barrier-Forming Nasal Spray for Allergic Rhinitis: Randomized, Open-Label, Crossover Noninferiority Trial
Authors: Nehrig Julian , Grosse Nicole , Hohenfeld Ilja P. , Hohlfeld Jens M. , Badorrek Philipp
Published: November 2022

Introduction: Symptoms of allergic rhinitis can be reduced by nonpharmacological nasal sprays that create a barrier between allergens and the nasal mucosa. A new nasal spray (AM-301) containing the clay mineral bentonite was tested for its ability to reduce symptoms of grass pollen. Methods: This open-label, crossover, noninferiority trial compared the efficacy and safety of AM-301 to that of hydroxypropyl methylcellulose (HPMC; Nasaleze® Allergy Blocker), an established barrier method. Adults with seasonal allergic rhinitis were exposed to Dactylis glomerata pollen, in a controlled setting, the Fraunhofer allergen challenge chamber, first without protection and then protected by HPMC or AM-301 (7 days apart). Efficacy was assessed from total nasal symptom score (TNSS), nasal secretion weight, and subjective rating. The primary endpoint was the difference, between AM-301 and HPMC, in least square mean change in TNSS over a 4-h exposure to allergen. Results: The study enrolled 36 persons, and 35 completed all study visits. The mean TNSS was 5.91 (SD = 1.45) during unprotected exposure, 5.20 (SD = 1.70) during protection with HPMC, and 4.82 (SD = 1.74) during protection with AM-301. The difference in least square means between the two treatments was −0.39 (95% CI: −0.89 to 0.10), establishing the noninferiority of AM-301. No difference in mean weight of nasal secretions was observed between the treatments. Efficacy was rated as good or very good for AM-301 by 31% and for HPMC by 14% of subjects. Sixteen subjects reported adverse events with a relationship to AM-301 or HPMC; most adverse events were mild, and none was serious. Discussion/Conclusion: AM-301 demonstrated noninferiority toward HPMC in the primary endpoint and was perceived better in subjective secondary endpoints. Both barrier-forming products had a persisting protective effect over 4 h and were safe.
Guidelines for the Management of Atopic Dermatitis in Children: A Systematic Review
Authors: Wang Qi , Liu Lamei , Gao Shujing , Su Shaoyu
Published: November 2022

Introduction: Numerous guidelines have been published for atopic dermatitis management in children in recent years. To date, the quality of the newest guidelines has not been appraised. This study aimed to identify and evaluate guidelines for the management of atopic dermatitis in children. Methods: We reviewed the literature retrieved from PubMed, Web of Science, Ovid, ScienceDirect, Embase, China National Knowledge Infrastructure, WanFang Data, and guidelines websites. Search period from January 1, 2016, to December 31, 2021. The following keywords were used for searching: “atopic dermatitis,” “atopic eczema,” “eczema,” “guideline,” and “consensus.” The quality of the guidelines was assessed by two assessors using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument independently, and domain scores >60% were considered to have sufficient quality. The guideline recommendations were reviewed. Results: Nineteen guidelines were included in the study. Three guidelines had a graded A level, which was recommended for use in practice. Eleven guidelines had a graded B level, which was recommended for use in revision. The remaining five guidelines were rated with C level, which was not recommended. The average score of six domains of AGREE II was 64.76%, 48.53%, 42.35%, 73.83%, 32.23%, and 70.17%, respectively. A consistency test showed an intraclass correlation coefficient range of 0.497 (95% CI: 0.105, 0.705) to 0.970 (95% CI: 0.93, 0.987) based on the two assessors’ test results for the guidelines. Conclusions: Most guidelines were recommended for use with revision. No significant changes were observed in the primary management of atopic dermatitis in children compared to previous evidence. New biological agents and complementary alternative medicine are increasingly available, but the evidence for the treatment of atopic dermatitis in children is still limited.
Early MOnitoring of REsponse (MORE) to Golimumab Therapy: Results of a Multicentre, Prospective Observational Trial
Authors: Helwig Ulf , Krause Thomas Helmut , Maaser Christian , Büning Jürgen , Drabik Attyla , Blömacher Margit , Plachta-Danielzik Sandra , Teich Niels , Krummenerl Annette , Sturm Andreas , Schwab Matthias , Schreiber Stefan ,   on behalf of the German IBD Study Group (GISG)
Published: November 2022

Background: The therapeutic goal of clinical remission in patients with moderate to severe ulcerative colitis (UC) is achieved after biological therapy only in 16–39%. Individualization of therapeutic intervention would benefit from prediction of early response. Study Objective: The primary objective of our study was to assess golimumab (GLM) trough serum level of ≥2.5 μg/mL in combination with a reduction of faecal calprotectin (FC) of ≥50% at week 6 compared to baseline to predict clinical response at week 26 after regular GLM intake. Methods: Patients with moderate to severe active UC and planned GLM treatment were recruited for a prospective, multicentre, observational study in Germany. Prediction of clinical response was assessed by FC and GLM trough level. Missing data were imputed as therapy failure according to the last observation carried forward method. Results: Fifty nine patients have been enrolled. 54% of patients were anti-TNF naïve. Clinical response at week 6 was a significant predictor for achieving clinical response at week 26 (odds ratio [OR] 10.97, confidence interval [CI], 2.96–40.68; p < 0.001). Moreover, patients with a GLM trough level of ≥2.5 μg/mL and a ≥50% reduction of FC at week 6 had an OR of 5.33 (95% CI, 0.59–47.84) to achieve clinical response at week 26. Conclusion: Clinical response at week 6 is the best predictive marker for achieving clinical response at week 26. Consideration of significant reduction of FC and trough GLM serum levels could improve prediction of response.