bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical performance and failure modes of self-piercing riveted joints between AA6061 and solution-treated TC4 alloy
Authors: Huang Zhi-Chao , Lu Dao-Chun , Zhang Yong-Chao , Jiang Yu-Qiang , Lu Yan , Guo Yan-Wei 
Published: May 2023

Abstract
TC4 titanium alloy and AA6061 aluminum alloy are widely used in the transportation industry because of their excellent mechanical properties and lightweight. In this work, the TC4 titanium alloy was solution heat treated between 800 °C and 990 °C for 1 h, and water cooled to room temperature. The riveting and tensile tests at room temperature were conducted to evaluate the joint performance. The tensile strength and failure morphology were used to discuss the mechanical performance of joints. Solution heat treatment significantly improves the elongation, mechanical performance, and hardness of TC4 titanium alloy. Compared with the as-received material, the elongation of the treated TC4 titanium alloy is increased by 13% at the solution temperature of 900 °C, the tensile strength was added by 175 MPa at 930 °C, and the hardness was significantly increased. The optimal performance of the TC4 titanium alloy can be obtained at 930 °C. The tensile strength of the joint with the TC4 alloy solution heat treated at 930 °C is the highest of all joints. When the TC4 alloy was solution treated between 800 °C and 850 °C, the rivets were pulled from the AA6061. While at 900 °C and 930 °C, the AA6061 sheet was broken at the rivet. At 960 °C and 990 °C, the TC4 sheet was broken near the rivet. The crack size of TC4 titanium alloy gradually decreases from the rivet outward, and the crack spreads around the rivet. Severe friction can be found, which causes the peeling of the lower plate AA6061 alloy. The breaks of TC4 alloys were the plastic broken. The failure morphology of the TC4 alloy sheet is different under different solution heat treatment temperatures.
Impact of curing on the volumetric and mechanical properties of cold bitumen emulsion mix
Authors: Prasad Deepak , Suman Sanjeev Kumar 
Published: May 2023

Abstract
Cold bitumen emulsion mix (CBEM) is an emerging sustainable material for constructing the base or surface layer of flexible pavements, reducing energy consumption and global warming effects compared to hot mix asphalt. The main challenges associated with CBEM are low initial strength, moisture susceptibility, etc. This is primarily due to water encapsulation. The curing process allows the water to evaporate gradually over time, improving mechanical properties. This study investigates CBEM’s volumetric and mechanical properties under different curing conditions. CBEMs were prepared using low (50 blows) and high (75 blows) compaction efforts and cured at 25, 40, and 55 °C for 1 to 28 days. In volumetric characteristics, the air voids and voids in mineral aggregates decreased slightly with curing, while total binder volume decreased. Effective binder volume and voids filled with binder increased slightly, then decreased. The mechanical properties, i.e., Marshal Stability, Marshal Quotient, Indirect Tensile Strength (ITS), and Moisture Susceptibility parameters like the Indirect Tensile Strength Ratio (ITSR) and Retained Marshal Stability (RMS), were found to improve over time at each curing temperature. Using a high curing temperature further improved the mechanical characteristics of CBEM. The curing process was decelerated in case of CBEM prepared by high compactive efforts compared to CBEM prepared by low compactive efforts. The Michaelis-Menten model can be used to analyze moisture loss growth and the development of mechanical properties over time. The strength-maturity model can be developed by using ITS as strength parameters. There was a strong correlation between all mechanical characteristics and moisture loss.
Mapping confinement potentials and charge densities of interacting quantum systems using conditional generative adversarial networks
Authors: Pantis-Simut Calin-Andrei , Preda Amanda Teodora , Ion Lucian , Manolescu Andrei , Alexandru Nemnes George 
Published: May 2023

Abstract
Accurate and efficient tools for calculating the ground state properties of interacting quantum systems are essential in the design of nanoelectronic devices. The exact diagonalization method fully accounts for the Coulomb interaction beyond mean field approximations and it is regarded as the gold-standard for few electron systems. However, by increasing the number of instances to be solved, the computational costs become prohibitive and new approaches based on machine learning techniques can provide a significant reduction in computational time and resources, maintaining a reasonable accuracy. Here, we employ pix2pix, a general-purpose image-to-image translation method based on conditional generative adversarial network (cGAN), for predicting ground state densities from randomly generated confinement potentials. Other mappings were also investigated, like potentials to non-interacting densities and the translation from non-interacting to interacting densities. The architecture of the cGAN was optimized with respect to the internal parameters of the generator and discriminator. Moreover, the inverse problem of finding the confinement potential given the interacting density can also be approached by the pix2pix mapping, which is an important step in finding near-optimal solutions for confinement potentials.
Objective Analysis of Age-Related Changes in the Superficial Musculoaponeurotic System in Japanese Females Using Computed Tomography
Authors: Okuda Itsuko , Abe Katsuhiro , Yoshioka Naoki , Komemushi Takayoshi , Jinzaki Masahiro , Ohjimi Hiroyuki 
Published: May 2023

Abstract

Background
The superficial musculoaponeurotic system (SMAS) is an anatomical structure involved in facial aging.

Objectives
This study focused on SMAS thickness and aimed to establish age-related changes in SMAS thickness.

Methods
A total of 100 adult Japanese female participants (aged 20-79 years) were enrolled in the study. The participants were divided into 3 age groups: Y, M, and E, comprising 20 to 39, 40 to 59, and 60 to 79 years, respectively. Anatomical structures were used as landmarks to standardize the SMAS analysis sites. The SMAS in a fixed analysis area (FAA) was quantified using multi-detector computed tomography (MDCT), and the relationship between SMAS thickness and age, as well as BMI, was analyzed.

Results
In 96 participants (four were excluded due to imaging artifacts), a moderate yet significant negative correlation was found between the average (A)-SMAS thickness within the FAA and age. The A-SMAS thickness in groups M and E was significantly lower than that of group Y, and the mean value of group E was significantly lower than that of group M. SMAS thickness was greater in the young population. The SMAS gradually became thinner with aging. A statistically significant correlation was not found between SMAS thickness and BMI.

Conclusions
Using MDCT technology, age-related changes in SMAS were successfully analyzed. This highly objective analysis method corroborated the aesthetic surgical knowledge of the SMAS features related to facial aging. In clinical applications, our findings may help elucidate the mechanisms involved in facial aging.

Level of Evidence: 3
Structural diversification of fungal natural products by oxidative enzymes
Authors: Ozaki Taro 
Published: May 2023

ABSTRACT
Ascomycota and basidiomycota fungi are prolific producers of biologically active natural products. Fungal natural products exhibit remarkable structural diversity and complexity, which are generated by the enzymes involved in their biosynthesis. After the formation of core skeletons, oxidative enzymes play a critical role in converting them into mature natural products. Besides simple oxidations, more complex transformations, such as multiple oxidations by single enzymes, oxidative cyclization, and skeletal rearrangement, are often observed. Those oxidative enzymes are of significant interest for the identification of new enzyme chemistry and have the potential to be biocatalysts for the synthesis of complex molecules. This review presents selected examples of unique oxidative transformations that have been found in the biosynthesis of fungal natural products. The development of strategies for refactoring the fungal biosynthetic pathways with an efficient genome-editing method is also introduced.
Integrating multiple traits for improving polygenic risk prediction in disease and pharmacogenomics GWAS
Authors: Zhai Song , Guo Bin , Wu Baolin , Mehrotra Devan V , Shen Judong 
Published: May 2023

Abstract
Polygenic risk score (PRS) has been recently developed for predicting complex traits and drug responses. It remains unknown whether multi-trait PRS (mtPRS) methods, by integrating information from multiple genetically correlated traits, can improve prediction accuracy and power for PRS analysis compared with single-trait PRS (stPRS) methods. In this paper, we first review commonly used mtPRS methods and find that they do not directly model the underlying genetic correlations among traits, which has been shown to be useful in guiding multi-trait association analysis in the literature. To overcome this limitation, we propose a mtPRS-PCA method to combine PRSs from multiple traits with weights obtained from performing principal component analysis (PCA) on the genetic correlation matrix. To accommodate various genetic architectures covering different effect directions, signal sparseness and across-trait correlation structures, we further propose an omnibus mtPRS method (mtPRS-O) by combining P values from mtPRS-PCA, mtPRS-ML (mtPRS based on machine learning) and stPRSs using Cauchy Combination Test. Our extensive simulation studies show that mtPRS-PCA outperforms other mtPRS methods in both disease and pharmacogenomics (PGx) genome-wide association studies (GWAS) contexts when traits are similarly correlated, with dense signal effects and in similar effect directions, and mtPRS-O is consistently superior to most other methods due to its robustness under various genetic architectures. We further apply mtPRS-PCA, mtPRS-O and other methods to PGx GWAS data from a randomized clinical trial in the cardiovascular domain and demonstrate performance improvement of mtPRS-PCA in both prediction accuracy and patient stratification as well as the robustness of mtPRS-O in PRS association test.
Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia
Authors: Canals Isaac , Comella-Bolla Andrea , Cepeda-Prado Efrain , Avaliani Natalia , Crowe James A , Oburoglu Leal , Bruzelius Andreas , King Naomi , Pajares María A , Pérez-Sala Dolores , Heuer Andreas , Rylander Ottosson Daniella , Soriano Jordi , Ahlenius Henrik 
Published: May 2023

Abstract
Frontotemporal dementia (FTD) is the second most prevalent type of early-onset dementia and up to 40% of cases are familial forms. One of the genes mutated in patients is CHMP2B, which encodes a protein found in a complex important for maturation of late endosomes, an essential process for recycling membrane proteins through the endolysosomal system. Here, we have generated a CHMP2B-mutated human embryonic stem cell line using genome editing with the purpose to create a human in vitro FTD disease model. To date, most studies have focused on neuronal alterations; however, we present a new co-culture system in which neurons and astrocytes are independently generated from human embryonic stem cells and combined in co-cultures. With this approach, we have identified alterations in the endolysosomal system of FTD astrocytes, a higher capacity of astrocytes to uptake and respond to glutamate, and a neuronal network hyperactivity as well as excessive synchronization. Overall, our data indicates that astrocyte alterations precede neuronal impairments and could potentially trigger neuronal network changes, indicating the important and specific role of astrocytes in disease development.
Characteristics of amplitude of low-frequency fluctuations in the resting-state functional magnetic resonance imaging of alcohol-dependent patients with depression
Authors: Sun Fengwei , Yang Jihui , Liu Xiaoying , Huang Gengdi , Kong Zhi , Liu Yu , Zhu Yingmei , Peng Ying , Yang Mei , Jia Xiaojian 
Published: May 2023

Abstract
The high comorbidity of alcohol use disorder and depressive disorder is associated with poor patient prognosis. The mechanisms underlying this comorbidity, however, are largely unknown. By applying the amplitude of low-frequency fluctuations parameter in resting-state functional magnetic resonance imaging, this study investigated changes in the brain functioning of alcohol-dependent patients with and without depression. Alcohol-dependent patients (n = 48) and healthy controls (n = 31) were recruited. The alcohol-dependent patients were divided into those with and without depression, according to Patients Health Questionnaire-9 scores. Amplitude of low-frequency fluctuations in resting-state brain images were compared among the alcohol-dependent patients with depression, alcohol-dependent patients without depression, and healthy controls groups. We further examined associations between amplitude of low-frequency fluctuations alterations, alcohol-dependence severity, and depressive levels (assessed with scales). Compared with the healthy controls group, both alcohol groups showed amplitude of low-frequency fluctuations enhancement in the right cerebellum and amplitude of low-frequency fluctuations abatement in the posterior central gyrus. The alcohol-dependent patients with depression group had higher amplitude of low-frequency fluctuations in the right cerebellum than the alcohol-dependent patients without depression group. Additionally, we observed a positive correlation between amplitude of low-frequency fluctuations value and Patients Health Questionnaire-9 score in the right superior temporal gyrus in the alcohol-dependent patients with depression group. Alcohol-dependent subjects showed abnormally increased spontaneous neural activity in the right cerebellum, which was more significant in alcohol-dependent patients with depression. These findings may support a targeted intervention in this brain location for alcohol and depressive disorder comorbidity.
Bilateral inferior petrosal sinus sampling with human CRH stimulation in ACTH-dependent Cushing's syndrome: results from a retrospective multicenter study
Authors: Detomas Mario , Ritzel Katrin , Nasi-Kordhishti Isabella , Schernthaner-Reiter Marie Helene , Losa Marco , Tröger Viola , Altieri Barbara , Kroiss Matthias , Kickuth Ralph , Fassnacht Martin , Micko Alexander , Honegger Jürgen , Reincke Martin , Deutschbein Timo 
Published: May 2023

AbstractObjectiveBilateral inferior petrosal sinus sampling (BIPSS) is regarded as the gold standard to differentiate between Cushing´s disease (CD) and ectopic Cushing's syndrome (ECS). However, published data on the diagnostic value of additional prolactin analysis are controversial. Thus, we evaluated the diagnostic performance of BIPSS with and without prolactin in a multicenter study.Design and methodsRetrospective study in five European reference centers. Patients with overt adrenocorticotropin (ACTH)-dependent Cushing's syndrome at the time of BIPSS with human corticotropin–releasing hormone stimulation were eligible. Cut-offs for the inferior petrosal sinus (IPS) to peripheral (P) ACTH ratio and the normalized ACTH:prolactin IPS:P ratio were calculated via receiver operator characteristic analyses (reference: CD).Results156 patients with BIPSS were identified. Of these, 120 patients (92 [77%] females; 106 [88%] CD, 14 [12%] ECS) had either histopathologically confirmed tumors or biochemical remission and/or adrenal insufficiency after surgery; only this subgroup was analyzed by ROC analysis. The optimal cut-offs for the ACTH IPS:P ratio were ≥1.9 at baseline (sensitivity 82.1% [95% CI, 73.2-88.6], specificity 85.7% [95% CI, 56.2-97.5], AUC 0.86) and ≥2.1 at 5 minutes post-CRH (sensitivity 91.3% [95% CI, 83.6-95.7], specificity 92.9% [95% CI, 64.1-99.6], AUC 0.96). A subgroup underwent additional prolactin analysis. An optimal cut-off of ≥1.4 was calculated for the normalized ACTH:prolactin IPS:P ratio (sensitivity 96.0% [95% CI, 77.7-99.9], specificity 100% [95% CI, 56.1-100], AUC 0.99).ConclusionOur study confirms the high accuracy of BIPSS in the differential diagnosis of ACTH-dependent Cushing's syndrome and suggests that the simultaneous measurement of prolactin might further improve the diagnostic performance of this test.
C18 A FISTULA BETWEEN LVOT AND LEFT ATRIUM: AN UNKNOWN ORIGIN
Authors: Cosimo R , Palomba C , Malvezzi Caracciolo D‘Aquino M , Scognamiglio G , Sperlongano S , Liccardo B , Golino P 
Published: May 2023

Abstract
History of presentation A 76–year–old woman presented to our EchoLab for worsening exertional dyspnea. Few weeks prior the patient underwent cardiological examination that showed heart failure with preserved ejection fraction (HFpEF) with bilateral pleuric effusion, severe mitralic regurgitation (MR), moderate tricuspid regurgitation (TR) with an estimated systolic pulmonary artery pressure (sPAP) of 50 mmHg and a mildly increased mean gradient on bioprothesic aortic valve (26 mmHg). Past medical history The patient had a medical history significant for arterial hypertension, hyperlipidemia, diabetes mellitus, permanent atrial fibrillation and HCV–related liver disease. She received double surgical aortic valve replacement in 2015 and 2019, the second procedure was complicated by intraoperatory stretching of mitral anterior leaflet and atrioventricular block treated with implantation of bicameral PMK. In the following weeks, the patient was admitted to hospital for exposure of the PMK generator pocket associated to catether cultures positivity for S. Aureus oxacilline–resistant, thus undergoing to device removal and positioning of a new PMK. Investigations The cardio–thoracic auscultation revealed a bilateral basal reduction of vesicular breath sounds, an apical sweet systolic murmur (suggestive of MR) and a systolic small aortic murmur best heard at the second intercostal space. The transthoracic echocardiography showed a blood flow apparently originating from interatrial septum heading towards the free left atrial wall. The Transoesophageal Echocardiography (TEE) with bubble test ruled out any interatrial communication. The 3D TEE acquisitions clarified that the shunt arose from the left ventricular outflow tract (LVOT), thus allowing the diagnosis of fistula between the LVOT and the left atrium. Follow–up and conclusions The patient underwent a procedure of percutaneous closure of the fistula. One month after this intervention, the patient presented to our department for the cardiological follow–up. We noticed that the closure had been successful with no left residual shunts and a reduction of the transprothesic mean aortic gradient (18 mmHg). This case report highlights the importance of the 3D echocardiography in order to settle uncertain diagnostics whereas the 2D echocardiography alone is not sufficient. Nevertheless, the diagnostic challenge that remains open is to understand whether the etiology of the fistula is iatrogenic or post–infectious.
C66 PRIMARY RESULTS FROM APOLLO–B, A PHASE 3 STUDY OF PATISIRAN IN PATIENTS WITH TRANSTHYRETIN–MEDIATED AMYLOIDOSIS WITH CARDIOMYOPATHY
Authors: Longhi S , Maurer M , Fontana M , Berk J , Gustafsson F , Simões M , Grogan M , Fernandes F , Gottlieb R , Kubanek M , Poulsen S , Damy T , Diemberger I , Tahara N , Yu W , Tang W , Obici L , González–Duarte A , Sekijima Y , White M , Yureneva E , Jay P , Vest J , Gillmore J 
Published: May 2023

Abstract

Introduction
Transthyretin–mediated (ATTR) amyloidosis is a progressive, multisystem, fatal disease. Patisiran, an IV RNAi therapeutic, is approved for the treatment of hereditary ATTR amyloidosis with polyneuropathy. The safety and efficacy of patisiran in patients with wild–type or hereditary ATTR amyloidosis with cardiomyopathy (CM) is being investigated in the ongoing APOLLO–B study.

Methods
Patients were 18–85 yrs old with evidence of cardiac amyloidosis by echocardiography, and ATTR amyloid by tissue biopsy or fulfilling nonbiopsy diagnostic criteria for ATTR amyloidosis with CM. Medical history of heart failure (HF) due to ATTR amyloidosis with ≥1 prior hospitalization or current clinical evidence of HF was required. Patients were randomized 1:1 to patisiran IV 0.3 mg/kg or placebo Q3W for 12 months. The primary endpoint was change from baseline in 6–MWT at Month 12 (M12) with patisiran vs placebo.

Results
APOLLO–B enrolled 360 patients (patisiran, n=181; placebo, n=179): median age (range), 76.0 (41, 85) yrs; male, 89%; wtATTR, 80%. Baseline characteristics were consistent between patients on tafamidis at baseline (91/360 [25%]) and those who were not. Patisiran achieved a rapid and sustained reduction in serum TTR, irrespective of baseline tafamidis treatment. At M12, patisiran showed a significant benefit vs placebo in 6–MWT (median [95% CI] change from baseline: patisiran, –8.15 [–16.42, 1.50]; placebo, –21.35 [–34.05, –7.52]; HL estimate of median difference: 14.69 [0.69, 28.69]; p=0.0162) and KCCQ–OS (LS mean [SEM] change from baseline: patisiran, 0.300 [1.263]; placebo, –3.408 [1.277]; LS mean [SEM] difference: 3.709 [1.796]; p=0.0397). Consistent benefits with patisiran in 6–MWT and KCCQ–OS were observed across predefined patient subgroups. Time to first event of all–cause hospitalization, urgent HF visit, or death directionally favored patisiran vs placebo (HR [95% CI], 0.839 [0.557, 1.263]), as did all–cause mortality (HR [95% CI], 0.355 [0.110, 1.138]), but all composite outcomes endpoints did not achieve statistical significance over 12 months. Patisiran was well tolerated; most AEs were mild or moderate in severity, and there were no cardiac safety concerns.

Conclusions
Benefits at 12 months were observed with patisiran vs placebo in functional capacity, and health status and quality of life, in patients with ATTR amyloidosis with CM. The efficacy and safety of patisiran continues to be studied in the APOLLO–B open–label extension.