bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-free DNA Predicts Prolonged Response to Multi-agent Chemotherapy in Pancreatic Ductal Adenocarcinoma
Authors: Christenson Eric S. , Lim Su Jin , Durham Jennifer , De Jesus-Acosta Ana , Bever Katherine , Laheru Daniel , Ryan Amy , Agarwal Parul , Scharpf Robert B. , Le Dung T. , Wang Hao 
Published: October 2022

The treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) is frequently characterized by significant toxicity and rapid development of resistance to current approved therapies. More reliable biomarkers of response are needed to guide clinical decision making.We evaluated cell-free DNA (cfDNA) using a tumor-agnostic platform and traditional biomarkers (CEA and CA19-9) levels in 12 patients treated at Johns Hopkins University on NCT02324543 “Study of Gemcitabine/Nab-Paclitaxel/Xeloda (GAX) in Combination With Cisplatin and Irinotecan in Subjects With Metastatic Pancreatic Cancer.” The pretreatment values, levels after 2 months of treatment, and change in biomarker levels with treatment were compared with clinical outcomes to determine their predictive value.The variant allele frequency (VAF) of KRAS and TP53 mutations in cfDNA after 2 months of treatment was predictive of progression-free survival (PFS) and overall survival (OS). In particular, patients with a lower-than-average KRAS VAF after 2 months of treatment had a substantially longer PFS than patients with higher posttreatment KRAS VAF (20.96 vs. 4.39 months). Changes in CEA and CA19-9 after 2 months of treatment were also good predictors of PFS.Comparison via concordance index demonstrated KRAS or TP53 VAF after 2 months of treatment to be better predictors of PFS and OS than CA19-9 or CEA. This pilot study requires validation but suggests cfDNA measurement is a useful adjunct to traditional protein biomarkers and imaging evaluation and could distinguish between patients who are likely to achieve prolonged responses versus those that will have early progression and may benefit from a change in treatment approach.Significance:We report on the association of cfDNA with response durability for patients undergoing treatment with a novel metronomic chemotherapy regimen (gemcitabine, nab-paclitaxel, capecitabine, cisplatin, irinotecan; GAX-CI) for metastatic PDAC. This investigation offers encouraging evidence that cfDNA may prove to be a valuable diagnostic tool to guide clinical management.
Asymmetric Complexity in a Pupil Control Model With Laterally Imbalanced Neural Activity in the Locus Coeruleus: A Potential Biomarker for Attention-Deficit/Hyperactivity Disorder
Authors: Kumano Hiraku , Nobukawa Sou , Shirama Aya , Takahashi Tetsuya , Takeda Toshinobu , Ohta Haruhisa , Kikuchi Mitsuru , Iwanami Akira , Kato Nobumasa , Toda Shigenobu 
Published: October 2022

Abstract
Locus coeruleus (LC) overactivity, especially in the right hemisphere, is a recognized pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and may be related to inattention. LC activity synchronizes with the kinetics of the pupil diameter and reflects neural activity related to cognitive functions such as attention and arousal. Recent studies highlight the importance of the complexity of the temporal patterns of pupil diameter. Moreover, asymmetrical pupil diameter, which correlates with the severity of inattention, impulsivity, and hyperactivity in ADHD, might be attributed to a left-right imbalance in LC activity. We recently constructed a computational model of pupil diameter based on the newly discovered contralateral projection from the LC to the Edinger–Westphal nucleus (EWN), which demonstrated mechanisms for the complex temporal patterns of pupil kinetics; however, it remains unclear how LC overactivity and its asymmetry affect pupil diameter. We hypothesized that a neural model of pupil diameter control featuring left-right differences in LC activity and projections onto two opponent sides may clarify the role of pupil behavior in ADHD studies. Therefore, we developed a pupil diameter control model reflecting LC overactivity in the right hemisphere by incorporating a contralateral projection from the LC to EWN and evaluated the complexity of the temporal patterns of pupil diameter generated by the model. Upon comparisons with experimentally measured pupil diameters in adult patients with ADHD, the parameter region of interest of the neural model was estimated, which was a region in the two-dimensional plot of complexity versus left-side LC baseline activity and that of the right. A region resulting in relatively high right-side complexity, which corresponded to the pathophysiological indexes, was identified. We anticipate that the discovery of lateralization of complexity in pupil diameter fluctuations will facilitate the development of biomarkers for accurate diagnosis of ADHD.
On the Explainability of Graph Convolutional Network With GCN Tangent Kernel
Authors: Zhou Xianchen , Wang Hongxia 
Published: October 2022

AbstractGraph convolutional network (GCN) is a powerful deep model in dealing with graph data. However, the explainability of GCN remains a difficult problem since the training behaviors for graph neural networks are hard to describe. In this work, we show that for GCN with wide hidden feature dimension, the output for semisupervised problem can be described by a simple differential equation. In addition, the dynamics of the behavior of output is decided by the graph convolutional neural tangent kernel (GCNTK), which is stable when the width of hidden feature tends to be infinite. And the solution of node classification can be explained directly by the differential equation for a semisupervised problem. The experiments on some toy models speak to the consistency of the GCNTK model and GCN.
Understanding the Drivers of Atlantic Multidecadal Variability Using a Stochastic Model Hierarchy
Authors: Liu Glenn , Kwon Young-Oh , Frankignoul Claude , Lu Jian 
Published: October 2022

Abstract
The relative importance of ocean and atmospheric dynamics in generating Atlantic multidecadal variability (AMV) remains an open question. Comparisons between climate models with a slab ocean (SLAB) and fully dynamic ocean components (FULL) are often used to explore this question, but cannot reveal how individual ocean processes generate these differences. We build a hierarchy of physically interpretable stochastic models to investigate the contribution of two upper-ocean processes to AMV: the role of seasonal variation and mixed-layer entrainment. This interpretability arises from the stochastic model’s simplified representation of sea surface temperature (SST), considering only the local upper-ocean response to white-noise atmospheric forcing and its impact on surface heat exchange. We focus on understanding differences between SLAB and FULL non-eddy-resolving preindustrial control simulations of the Community Earth System Model 1 (CESM), and estimate the stochastic model parameters from each respective simulation. Despite its simplicity, the stochastic model reproduces temporal characteristics of SST variability in the SPG, including reemergence, seasonal-to-interannual persistence, and power spectra. Furthermore, the unrealistically persistent SST of the CESM-SLAB ocean simulation is reproduced in the equivalent stochastic model configuration where the mixed-layer depth (MLD) is constant. The stochastic model also reveals that vertical entrainment primarily damps SST variability, thus explaining why SLAB exhibits larger SST variance than FULL. The stochastic model driven by temporally stochastic, spatially coherent forcing patterns reproduces the canonical AMV pattern. However, the amplitude of low-frequency variability remains underestimated, suggesting a role for ocean dynamics beyond entrainment.
Bone Marrow Adipokine Expression Was Associated With Decreased Erythroid Colony Growth After Trauma
Authors: Kelly Lauren S. , Kannan Kolenkode B. , Munley Jennifer A. , Pons Erick E. , Parvataneni Hari K. , Hagen Jennifer E. , Efron Philip A. , Mohr Alicia M. 
Published: October 2022

Background Proinflammatory and immunomodulatory adipokines are linked to inflammation in critically ill patients but are poorly studied after injury. We hypothesized that trauma would induce systemic adipokine release and influence erythroid suppression. Methods Blood and bone marrow (BM) were collected from trauma patients (ISS > 15, n = 90) and compared to patients undergoing elective hip replacement (n = 37). Plasma adipokine levels were measured, and BM was assayed for adipokine transcription and erythroid progenitor growth potential. Differences were detected using t-tests and correlations using simple linear regression. Results Trauma patients exhibited decreased adiponectin (1.8* vs 3.4 mg/mL) and increased leptin (7.8* vs 4.6 ng/mL) and resistin (3.1* vs 2.5 ng/mL), with sex- and age-specific differences. They also showed increased BM visfatin transcription. Adipokine transcription negatively correlated with erythroid progenitor growth. Conclusion Adipose tissue activity is linked to inflammatory responses after injury, with variability by age and sex. Bone marrow adipose tissue may influence erythroid recovery after trauma.
Paediatric manikins and school nurses as Basic Life Support coordinators: A useful strategy for schools?
Authors: Otero-Agra Martín , Rey-Fernández Luz , Pacheco-Rodríguez David , Fernández-Méndez Felipe , Barcala-Furelos Roberto , Greif Robert 
Published: October 2022

Objective: To evaluate cardiopulmonary resuscitation (CPR) skills performance and retention in schoolchildren aged 8 to 12 years following instruction by their teachers and with the guidance of a school nurse using paediatric manikins. Design: Descriptive simulation trial. Method: A school nurse provided support to six schoolteachers as they taught a modified 40-minute CPR course. Pupils were shown an out-of-hospital cardiac-arrest recognition video followed by a CPR simulation using paediatric manikins. 117 schoolchildren aged 8 to 12 years received the training. Both the schoolchildren and teachers completed a survey before and afterwards. Children completed an out-of-hospital cardiac-arrest recognition test and a 1-minute CPR test 1 week later. Results: After training, schoolchildren increased their self-efficacy as rescuers (8 ± 2 vs 10 ± 2; p < 0.001). Irrespective of age differences, 74% of schoolchildren performed the entire out-of-hospital cardiac-arrest recognition sequence correctly. Children aged 11 to 12 years and 10 to 11 years performed higher quality CPR (49% and 47%, respectively) compared to 8 to 9 year olds (14%, p = 0.008 and p = 0.014). Children aged 11 to 12 years outperformed younger children aged 8 to 9 years with respect to compression depth (48 ± 6 mm vs 43 ± 5 mm, p = 0.008) Conclusion: Schoolchildren’s teachers, who were guided by a nurse using paediatric manikins, taught children aged 10 to 12 years to perform high-quality CPR. We suggest integrating paediatric manikins as part of children’s CPR training as feedback from successful CPR performance increases motivation and confidence to act as a rescuer as well as improves skills retention.
Post-discharge experiences of patients with extracorporeal membrane oxygenation support: A qualitative study
Authors: Wang FengZhen , Zhang YuHao , Wu ShuJing , Xie HongYing , Lin DongMei , Wen XianMing , Duan ZhiSheng , Lu YuFeng , Liu ZiYou , Hu Shuo , Liu Jian 
Published: October 2022

Purpose To explore the life experiences of patients who have been discharged after undergoing extracorporeal membrane oxygenation (ECMO) support. Design A qualitative descriptive approach was used. Methods Patients who have undergone ECMO support and have been discharged were recruited. Thirteen participants were involved in this study. The data were collected through a semi-structured interview and analyzed using the Colaizzi method. Findings Four major themes in life experiences were reported by the participants: changes in physical function, changes in psychological state, active adaptation to daily life, and substantial rehabilitation needs. Conclusion Different, continuous, and convenient post-discharge physical and mental interventions, social support, spiritual support, and rehabilitation services should be provided according to the patient’s circumstances. We also call on the government to increase the patient reimbursement rate for ECMO treatment. These measures may help to improve the quality of life of patients.
Backscattered Electron Imaging: The Role in Calcified Tissue and Implant Analysis
Authors: Bloebaum Roy D. , Bachus Kent N. , Boyce Todd M. 
Published: October 2022

Backscattered electron (BSE) imaging is being developed into an accurate and useful technique for determining changes in bone morphology, histometry, and mineral content. BSE is currently used as a tool for quantifying the response of mineralized tissue to biomaterials. This paper briefly discusses the physics of BSE imaging and its application to mineralized tissue and biomaterials research. Original research is reported which better defines the errors that are imposed by changes in specimen working distance and tilt. Two parameters, the backscattered electron profile and the weighted mean graylevel, were introduced and developed so that BSE imaging could be used as a reproducible, quantitative technique for studying mineral content changes in bone. Results demonstrated that the working distance to a cortical bone surface can vary up to 300 μm or tolerate a tilt of up to 10 degrees without altering weighted mean graylevel values by more than 2 percent. Calibration of the BSE signal would allow for reproducible, quantitative mineral content analysis to be conducted on bone and bone/implant interfaces. Bone substitutes and pure metals were investigated to determine their potential as BSE graylevel calibration standards. Pure metals appear to be the most promising materials for standardizing BSE graylevels, due to their greater homogeneity. Finally, interrelationships between compressive strength and stiffness, histometry, and mineral content of individual trabecula in cancellous bone are investigated. Failure site trabecular thickness and minimum trabecular thickness, two new histometric parameters defined in this study, were found to statistically correlate with cancellous bone strength and stiffness.
Numerical Investigation of Natural Convection in Horizontal Porous Media Heated from Below—Comparisons with Experiments
Authors: Shankar V. , Hagentoft C.-E. 
Published: October 2022

Thick layers of highly permeable loose-fill insulation are used to thermally insulate attics in modern building technology. Since the use of highly permeable insulation leads to an increase in air movement not only in the porous layer (insulation) but also in the fluid layer (attics), it is therefore of paramount interest to determine the influence of the complex heat transfer phenomena due to natural and forced convection on the thermal properties of insulating porous medium with air cavity. With the help of CFD (Computational Fluid Dynamics), the combined effect of air movement inside the insulation and the air cavity is investigated. The paper deals with the CFD analysis, carried out in order to predict the effects of natural convection on the thermal performance of the building envelope. The results obtained from the numerical computations are compared with experimental findings.
Effect of Polymer Structure on the Long-Term Aging of Rigid Polyurethane Foam
Authors: Moore S. E. 
Published: October 2022

The effect of polymer structure on both initial and aged thermal conductivity ( K-factor) or thermal resistivity ( R-value) was explored by using a new procedure to estimate the long-term thermal resistance of gas-filled cellular plastics proposed by Norton [1], Edgecombe [2] and Bomberg [3]. This method uses a semi-logarithmic plot of thermal resistivity versus time that produces two distinct stages in the data, thermal drift and plateau with a break point separating the two stages. The plateau stage was fit with a straight line in order to estimate the long-term thermal resistance or K-factor of the foam. This concept was employed on the fourteen CFC-11 blown foams [4] in this study. The effect of me two major types of isocyanates, Specialty TDI (toluene diisocyanate) and PMDI (polymeric diphenylmethane diisocyanate), was isolated and compared. The significance of seven different types of polyol initiators was also evaluated with respect to K-factor and K-factor aging. In the case of the PMDI foams, the data correlated well with the model and the 20-year K-factor predictions appear to be reasonable when compared to the raw data curves. In the case of the TDI foams, however, it was more difficult to find a break point which would define the plateau region in the data. Most of these foams did contain break points, but the break point occurs at a slightly longer time. The 20-year K-factors of these foams could be predicted with reasonable confidence when there was a break point in the resistivity versus log (T) curves.
Morphometry of thenar muscles by water bath ultrasonography in trapeziometacarpal osteoarthritis: intra- and inter-rater reliability
Authors: Karademir Feray , Ayhan Kuru Cigdem , Arın Gamze , Soylu Ruhi 
Published: October 2022

We studied the intra- and inter-rater reliability of muscle thickness and cross-sectional area measurements of thenar muscles with a water bath ultrasonography technique in eight healthy volunteers and 16 patients with trapeziometacarpal osteoarthritis. Thickness and cross-sectional area of the opponens pollicis, abductor pollicis brevis, flexor pollicis brevis, first dorsal interosseous and adductor pollicis muscle were measured. The results showed changes in the morphometric properties of the thenar muscles in patients with trapeziometacarpal osteoarthritis (TMC OA) compared with the healthy volunteers. In the dominant-sided patients ( n = 14), there were lower cross-sectional area values for the abductor pollicis brevis and opponens pollicis muscles. In the non-dominant-sided patients ( n = 10), there were lower cross-sectional area values for the abductor pollicis brevis and flexor pollicis brevis and lower muscle thickness of the abductor pollicis brevis. The water bath ultrasonography technique could be used to diagnose and treat diseases where changes in thenar muscle thickness and cross-sectional area can be expected. Level of evidence: III
Optimal Design and Experimental Verification of Low Radiation Noise of Gearbox
Authors: Liu Lan , Kang Kun , Xi Yingjie , Hu Zhengxi , Gong Jingyi , Liu Geng 
Published: October 2022

AbstractReducing the radiated noise of a gearbox is a difficult problem in aviation, navigation, machinery, and other fields. Structural improvement is the main means of noise reduction for a gearbox, and it is realized primarily through contribution analysis and structure optimization. However, these approaches have certain limitations. In this study, a low-noise design method for a gearbox that combines the two approaches is proposed, and experimental verification is performed. First, a finite element/boundary element model is established using a single-stage herringbone gearbox. Considering the vibration excitation of the gear system, the radiation noise of a single-stage gearbox is predicted based on the modal acoustic transfer vector (MATV) method. Subsequently, the maximum field point of the radiated noise is determined, and the acoustic transfer vector (ATV) analysis and modal acoustic contribution (MAC) analysis are conducted to determine the region that contributes significantly to the radiated noise of the field point. The optimization region is selected through the panel acoustic contribution (PAC) analysis. Next, to reduce the normal speed in the optimization region, topology optimization is performed. According to the topology optimization results, four different noise reduction structures are added to the gearbox, and the low-noise optimization models are established respectively. Finally, by measuring the radiated noise of the gearbox before and after optimization under a given working condition, the validity of the radiated noise prediction method and the low-noise optimization design method are verified by comparing the simulation and experimental data. A comparison of the four optimization models proves that the noise reduction effect can be achieved only by adding a noise reduction structure to the center of the density nephogram.
Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1–7) as a sensitizer for chemotherapy and immunotherapy in breast cancer
Authors: Mei Jie , Cai Yun , Xu Rui , Yu Xinqian , Han Xu , Weng Miaomiao , Chen Lingyan , Ma Tao , Gao Tianshu , Gao Fei , Xia Tiansong , Zhu Yichao , Zhang Yan 
Published: October 2022

Abstract
Background
Angiotensin-converting enzyme 2 (ACE2) is known as a tumor suppressor and lowly expressed in most cancers. The expression pattern and role of ACE2 in breast cancer (BC) have not been deeply elucidated.

Methods
A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). The correlation of ACE2 expression and immunological characteristics in the BC tumor microenvironment (TME) was evaluated. The role of ACE2 in predicting the response to therapeutic options was estimated. Moreover, the pharmacodynamic effect of angiotensin-(1–7) (Ang-1–7), the product of ACE2, on chemotherapy and immunotherapy was evaluated on the BALB/c mouse BC model. In addition, the plasma samples from BC patients receiving neoadjuvant chemotherapy were collected and subjected to the correlation analysis of the expression level of Ang-1–7 and the response to neoadjuvant chemotherapy.

Results
ACE2 was lowly expressed in BC tissues compared with that in adjacent tissues. Interestingly, ACE2 was shown the highest correlation with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, immune checkpoints, and tumor mutation burden (TMB) in BC. In addition, a high level of ACE2 indicated a low response to endocrine therapy and a high response to chemotherapy, anti-ERBB therapy, antiangiogenic therapy and immunotherapy. In the mouse model, Ang-1–7 sensitized mouse BC to the chemotherapy and anti-PD-1 immunotherapy, which revealed its significant anti-tumor effect. Moreover, a high plasma level of Ang-1–7 was associated with a better response to neoadjuvant chemotherapy.

Conclusions
ACE2 identifies immuno-hot tumors in BC, and its enzymatic product Ang-1–7 sensitizes BC to the chemotherapy and immunotherapy by remodeling the TME.