bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-institutional Assessment of Pathologist scoring HER2 Immunohistochemistry
Authors: Robbins Charles , Fernandez Aileen , Han Gan , Wong Serena , Harigopal Malini , Podoll Mirna , Singh Kamaljeet , Ly Amy , Kuba Maria , Wen Hannah , Sanders Mary Ann , Brock Jane , Wei Shi , Fadare Oluwole , Hanley Krisztina , Jorns Julie , Snir Olivia , Yoon Esther , Rabe Kim , Soong T. , Reisenbichler Emily , Rimm David 
Published: July 2022

Abstract

The HercepTest was approved 20 + years ago as the companion diagnostic test for trastuzumab in HER2 amplified/overexpressing breast cancers. Subsequent HER2 immunohistochemistry (IHC) assays followed, including the now most common Ventana 4B5 assay. While this IHC assay has become the clinical standard, its reliability, reproducibility, and accuracy have largely been approved and accepted based on concordance between small numbers of pathologists without validation in a real-world setting. In this study, we evaluate the concordance and inter-rater reliability of scoring HER2 IHC in 170 breast cancer biopsies by 18 breast cancer-specialized pathologists from 15 institutions. We used the ONEST (Observers Needed to Evaluate Subjective Tests) method to determine the plateau of concordance and the minimum number of pathologists needed to estimate inter-rater agreement values for large numbers of raters, as seen in the real-world setting. We report substantial discordance within the intermediate categories (< 1% agreement for 1 + and 3.6% agreement for 2+) in the four-category HER2 IHC scoring system. The discordance within the IHC 0 cases is also substantial with an overall percent agreement (OPA) of only 25% and poor inter-rater reliability metrics (0.49 Fleiss’ kappa, 0.55 intraclass correlation coefficient). This discordance can be partially reduced by using a three-category system (28.8% vs. 46.5% OPA for four and three-category scoring systems respectively). ONEST plots suggest that the OPA for the task of determining a HER2 IHC score 0 from not 0 plateaus statistically around 59.4% at 10 raters. Conversely, at the task of scoring HER2 IHC as 3 + or not 3 + pathologists’ concordance was much higher with an OPA that plateaus at 87.1% with 6 raters. This suggests that legacy HER2 IHC remains valuable for finding HER2 gene amplified patients, but unacceptably discordant in assigning HER2-low or negative status for emerging HER2-low therapies.
ID-RDRL: A Deep Reinforcement Learning-based Feature Selection Intrusion Detection Model
Authors: Ren Kezhou , Zeng Yifan , Cao Zhiqin , Zhang Yingchao 
Published: July 2022

Abstract
Network assaults pose significant security concerns to network services; hence, new technical solutions must be used to enhance the efficacy of intrusion detection systems. Existing approaches pay insufficient attention to data preparation and inadequately identify unknown network threats. This paper presents a network intrusion detection model (ID-RDRL) based on RFE feature extraction and reinforcement learning. ID-RDRL filters the optimum subset of features using the RFE feature selection technique, feeds them into a neural network to extract feature information and then trains a classifier using DRL to recognize network intrusions. We utilized CSE-CIC-IDS2018 as a dataset and conducted tests to evaluate the model's performance, which is comprised of a comprehensive collection of actual network traffic. The experimental results demonstrate that the proposed ID-RDRL model can select the optimal subset of features, remove approximately 80 percent of redundant features, and learn the selected features through DRL to enhance the IDS performance for network attack identification. In a complicated network environment, it has promising application potential in IDS.
Risk of Iatrogenic Pneumothorax based on Location of Transbronchial Biopsy: A Retrospective Cohort Study
Authors: Ishak Mina , Chakraborty Debarati , Kassirian Shayan , Dhaliwal Inderdeep , Mitchell Michael A. 
Published: July 2022

Abstract
OBJECTIVE: Transbronchial lung biopsy (TBB) is a commonly performed procedure to obtain parenchymal lung tissue during bronchoscopy. Pneumothorax is among the most common serious complications of TBB. The objective of this study was to assess whether location of TBB correlated with development of post-procedural pneumothorax. We also sought to identify additional risk factors associated with pneumothorax development.This was a single-centre, retrospective cohort study. All TBB performed between 2010 to 2020 underwent subsequent chart review. The primary outcome was radiologist reported pneumothorax on post-procedure chest x-ray. Multivariable logistic regression model was created with included variables chosen a priori based on clinical significance.RESULTS: There were a total of 222 TBB performed that met inclusion criteria. Radiographic evidence of pneumothorax was reported in 38 patients (15.4%). Ten patients (4.1%) required a chest tube. In the multivariable analysis, risk of pneumothorax was significantly higher for biopsies obtained from the left upper lobe (OR 3.3; 95% CI 1.3 –9.1). There was an increased risk of pneumothorax following TBB when obtained from the left upper lobe. Clinicians should be aware of the increased risk and should consider alternative locations in patients with diffuse lung disease.
Effects of Subchronic aluminum exposure on learning, memory and neurotrophic factors in rats
Authors: Liu Wei , Liu Jiaxi , Gao Jie , Duan Xiaoxu , Zhang Lifeng 
Published: July 2022

Abstract
Aluminum (Al) is a neurotoxin that gradually accumulates in the brain in human life, resulting in oxidative brain injury related to Alzheimer's disease (AD) and other diseases. In this study, the learning and memory of rats exposed to different aluminum concentrations ( 0.0 g/L, 2.0 g/L, 4.0 g/L and 8.0 g/L) were studied, and the learning and memory of rats were observed by shuttle box experiment. With HE staining, Western Blot, Immunofluorescence, and RT-PCR, the morphology of nerve cells in the hippocampus of rat brain were observed, and the levels of activator protein-1 (AP-1) gene and protein, nerve growth factor (NGF), neurotrophin-3(NT3), glial cell line-derived neurotrophic factor (GDNF) gene and protein level, and brain-derived neurotrophic factor (BDNF) protein level, etc. The experimental results showed that subchronic aluminum exposure damaged learning and memory in rats. The cognitive function damage in rats was more evident after increasing the aluminum intake dose. The more aluminum intake, the more pronounced the histological changes in the hippocampus will be. The expression level and protein content of neurotrophic factors in the hippocampus of rats showed a negative correlation with aluminum intake. In this experiment, we explored the mechanism of aluminum exposure in learning and memory disorders, and provided some data reference for further elucidation of the damage mechanism of aluminum on the nervous system and subsequent preventive measures.
Latifolin enhances both survival and cardiomyocyte differentiation of bone marrow mesenchymal stem cells on rat myocardial infarction model
Authors: Zhang Ni , Lai Xiaoxiao , Chen Lanying , Li Wenhong , Luo Yingying , Li An , Liu Ronghua , Meng Xiaowei 
Published: July 2022

Abstract
Background: Myocardial infarction caused abundant loss of cardiomyocytes and myocardium limited self-repair ability. Mesenchymal stem cells (MSCs) were a promising option for cardiomyocyte regeneration therapies. However, low cardiomyocyte differentiation efficiency and poor cell survival limit application in myocardial infarction. Here, our study aimed to promote the survival and cardiomyocyte differentiation of BM-MSCs by latifolin from Dalbergiae Odoriferae. Methods: In vitro, cell survival was measured by MTT and apoptosis assays. BM-MSCs morphological differentiation was observed under microscope and TEM. Cardiac-specific genes and proteins were measured by RT-PCR and immunofluorescence staining. In vivo, cardiac function was assessed by LDH and CK-MB and echocardiography. The gross morphology and TTC were used to assess the LV infarct size. Masson’s trichrome was used to detect the extent of fibrosis. Histopathological changes were observed by HE staining. Immunofluorescence was used to detect the survival and cardiomyocyte differentiation of BM-MSCs. Immunohistochemistry was used to detect macrophage CD68 and neutrophils MPO expression. The protein expression of IL-6, p-NF-κB, β-catenin and HIF-1αwere detected by Western Blot. Results: In vitro, latifolin increased BM-MSCs viability and decreased apoptosis. Both atrial particles and myofilaments were precisely observed in the cytoplasm under TEM. Latifolin increased the cardiac-specific mRNA and proteins. In vivo, latifolin promoted BM-MSCs to reduce myocardial enzyme and improve cardiac function. Moreover, latifolin promoted BM-MSCs to reduces myocardial infarction size, myocardial fibrosis size, histopathological changes and macrophage infiltration in myocardial tissue. At the same time, latifolin promoted survival and cardiomyocyte differentiation of BM-MSCs. Latifolin up-regulated the protein expression of β-catenin and down-regulated the protein expression of IL-6, p-NF-κB, HIF-1α. Conclusion: Latifolin enhanced the effect of BM-MSCs to cure MI by promoting survival and cardiomyocyte differentiation after transplant in myocardial tissue though HIF-1α/NF-κB/IL-6 pathway and HIF-1α/β-catenin pathway. Such pro-differentiation and pro-survival might be a potential strategy to increase their regenerative efficacy.
System Dynamics based Carbon Footprint Assessment of Industrial Water and Energy Use
Authors: Karamouz Mohammad , Zare Mohammadreza , Ebrahimi Elham 
Published: July 2022

Abstract
Investigating links between water, energy, and carbon emissions require more attention on the path towards economic prosperity. This study aims to develop a framework for modeling water-energy-carbon interdependencies by considering the nonlinear relationships in their dynamic feedback processes. The main contribution of this research is the quantification of industrial water use carbon footprint through the development of an Industrial Water-Energy-Carbon (I-WEC) nexus model. The I-WEC model has a scenario-driven approach. The GDP as a representative of economic growth is assessed. The proposed methodology is tested on the Netherlands' industrial sector as a pilot due to the relatively good data structure. The results, based on policy-based complementary scenarios, show a 3% increase in total water use by 2030. The energy use and carbon emissions will fall as much as 10% and 25% in that year, respectively. The industrial GDP share could be maintained with a 0.76% loss that is close to the 0.5% loss that was projected by authorities. This study presents a unique approach that can be used in the other regions.
Development and validation of a brief measure of pathological dissociation: Laddis/Kira Pathological Dissociation Scale: Initial Psychometrics
Authors: Kira Ibrahim A. , Laddis Andreas , Kate Mary-Anne 
Published: July 2022

Abstract
The study developed the Laddis/Kira screening nine-item measure for pathological dissociation on a longitudinal sample of 228. Exploratory and confirmatory factor analysis found a one-factor structure. The measure had a large correlation with another measure of dissociation establishing its convergent validity, and a negative correlation with the will to exist, live, and survive establishing its divergent validity. It has a large correlation with complex PTSD (CPTSD) and executive function deficits establishing its predictive and criterion validity. It had good reliability and test-retest stability. The measure associated significantly higher with CPTSD compared with the comparable measure of DES-B. The study provided initial evidence of the measure's robust psychometrics.
Inhibition of K63 ubiquitination by G-Protein pathway suppressor 2 (GPS2) regulates mitochondria-associated translation
Authors: Gao Yuan , Kwan Julian , Orofino Joseph , English Justin , Hekman Ryan , Lyons Shawn M. , Emili Andrew , Cardamone Maria Dafne , Perissi Valentina 
Published: July 2022

Abstract
G-Protein Pathway Suppressor 2 (GPS2) is an inhibitor of non-proteolytic K63 ubiquitination mediated by the E2 ubiquitin-conjugating enzyme Ubc13. Previous studies have associated GPS2-mediated restriction of ubiquitination with the regulation of insulin signaling, inflammatory responses and mitochondria-nuclear communication across different tissues and cell types. However, a detailed understanding of the targets of GPS2/Ubc13 activity is lacking. Here, we have dissected the GPS2-regulated K63 ubiquitome in mouse embryonic fibroblasts and human breast cancer cells, unexpectedly finding an enrichment for proteins involved in RNA binding and translation on the outer mitochondrial membrane. Characterization of the RNA-binding protein PABPC1 as a target of GPS2-regulated ubiquitination within the mitochondrial compartment revealed a strategy for regulating the mitochondrial proteome via MUL1-mediated ubiquitination. Removal of GPS2-mediated inhibition, either via genetic deletion or stress-induced nuclear translocation, promotes the mitochondria-associated translation of selected mRNAs leading to increased expression of an adaptive antioxidant program. In light of GPS2 role in nuclear-mitochondria communication, these findings reveal an exquisite regulatory network for modulating mitochondrial gene expression through spatially coordinated transcription and translation.
Realization of optical logic gates using on-chip diffractive optical neural networks
Authors: ZAREI SANAZ , KHAVASI AMIN 
Published: July 2022

Abstract

Optical computing is highly desired as a potential strategy for circumventing the performance limitations of semiconductor-based electronic devices and circuits. Optical logic gates are considered as fundamental building blocks for optical computation and they enable logic functions to be performed extremely quickly without the generation of heat and crosstalk. Here, we discuss the design of a multi-functional optical logic gate based on an on-chip diffractive optical neural network that can perform AND, NOT and OR logic operations at the wavelength of 1.55µm. The wavelength-independent operation of the multi-functional logic gate at seven wavelengths (over a bandwidth of 60nm) is also studied which paves the way for wavelength division multiplexed parallel computation. This simple, highly-integrable, low-loss, energy-efficient and broadband optical logic gate provides a path for the development of high-speed on-chip nanophotonic processors for future optical computing applications.
Effects of short-term and perioperative antiviral therapy on prognosis after hepatectomy for hepatitis B virus-related hepatocellular carcinoma
Authors: Mu Fan , Zhao Zhen , Xu Kun , Hu Liangshuo , Guo Kun , Shi Jianhua , Yu Liang , Lv Yi , Wang Bo 
Published: July 2022

Abstract
Background: Although the benefits of antiviral therapy against hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the difference in outcomes among patients who receive short-term (at least 24 weeks) or perioperative antiviral therapy after liver hepatectomy for HBV-related HCC. Methods: A retrospective study of patients who underwent hepatectomy for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were divided into perioperative (control group, n=108) and short-term antiviral therapy groups (n=108). Results: Baseline clinical and laboratory tests and tumor characteristics were compared between the two groups. The Kaplan–Meier analysis showed a significant difference in overall survival (P<0.0001) and disease-free survival (P=0.035) between the two groups. Multivariate analysis demonstrated that short-term antiviral treatment was independently related to enhanced survival outcome in OS (hazard ratio =0.27; 95% confidence interval= 0.08–0.88, P=0.030). Conclusions: In patients with HBV-related HCC, receiving short-term antiviral therapy for at least 24 weeks resulted in enhanced outcomes.
Mediterranean heat waves and wildfires of July-August 2021 in the southern part of Turkey
Authors: Acar Zahide , Gonencgil Barbaros , Halis Onur 
Published: July 2022

Abstract
Extreme weather events are experienced more frequently across the earth due to the effects of climate change. The high frequency of extreme weather events increases vulnerability in sensitive areas. In the Mediterranean Basin, which is one of the most sensitive areas, many countries have experienced wildfires in recent years. Turkey is one of the countries where forest fires occur frequently in the Mediterranean basin. Although the causes of the fire vary over the years, the problems caused by forest fires draw attention every year. Since 1990, there have been many forest fires across the country and the most areal losses caused by the Fires occurred in 1994, 2000 and 2008. The largest forest fires after these dates occurred in the summer of 2021.The area where Turkey is most sensitive to fire is the Mediterranean climate region. Most of the fires, especially in this area, occur in an unnatural way such as negligence-accident, unsolved and intentional. The control mechanism in the spatial expansion of fires mostly depends on atmospheric conditions. Within the scope of the study, it was aimed to draw attention to the atmospheric conditions during the period of wildfires in many parts of Turkey in the summer of 2021 for various reasons. According to the calculations, the air temperatures before the start of the fire in the provinces of Antalya and Muğla are above the long-term averages of the stations here. In addition, the effects of the heat wave were observed at many stations before the fire.
Substrate Effects on Spin Relaxation in Two-Dimensional Dirac Materials with Strong Spin-Orbit Coupling
Authors: Ping Yuan , Xu Junqing 
Published: July 2022

Abstract
Understanding substrate effects on spin dynamics and relaxation in two-dimensional (2D) materials
is of key importance for spintronics and quantum information applications. However, the key
factors that determine the substrate effect on spin relaxation, in particular for materials with strong
spin-orbit coupling, have not been well understood. Here we performed first-principles real-time
density-matrix dynamics simulations with spin-orbit coupling (SOC) and quantum descriptions of
electron-phonon and electron-impurity scattering for the spin lifetimes of supported/free-standing
germanene, a prototypical strong SOC 2D Dirac material. We show that the effects of different
substrates on spin lifetime can surprisingly differ by two orders of magnitude. We find that such
huge difference seems to be mostly caused by substrate-induced modifications of spin-flip scattering
matrix elements, in sharp contrast to the substrate effects on weak SOC materials like graphene.
Liver fibrosis indices predict length of hospitalization and mortality in SARS-CoV-2 infected patients
Authors: Crudele Lucilla , Novielli Fabio , Petruzzelli Stefano , Battaglia Stefano , Giuliano Antonio , Melodia Rosa , Morano Chiara , Dell'Aquila Paola , Moretti Renata , Castorani Luigi , Salvia Roberto , Inglese Gianfranco , Susca Nicola , dell'Olio Lucrezia , Falcone Francesca , Castaldo Mariapaola , De Matteis Carlo , Moschetta Antonio 
Published: July 2022

Abstract
Background: The ongoing COVID-19 pandemic has challenged health systems under multiple aspects. The deep understanding of risk and prognostic factors for this disease may help not only in reducing severity and mortality but also in targeting therapies considering patients’ individual features. Liver Fibrosis is considered a complication in Non-alcoholic Fatty Liver Disease (NAFLD), being a feature of steatohepatitis (NASH), and it had already been related to an increased risk for a wide range of diseases. Methods: Here, we analysed a sample of 271 patients with moderate-to-severe SARS-CoV-2-related respiratory failure, hospitalized in a sub-intensive care Unit, with the aim of unveiling if any condition may predict their prognosis and mortality. Results: We found that non-invasive scores of liver fibrosis such as AAR, FIB-4 and mFIB-4, Forns, and AARPRI strongly predict not only in-hospital mortality but also the length of hospitalization and the eventual admission to intensive care units. Conclusions: Thus, pre-existing liver metabolic disease is a net predictor of poor prognosis in SARS-CoV-2 infected patients admitted to Sub-Intensive Care Unit.
The proposal of boundary setting for the posterior to level V region and the theoretical feasibility of prophylactic irradiation dose reduction of level Va in nasopharyngeal carcinoma: A retrospective study in a single-center
Authors: Jiang Chaoyang , Li Xiaokai , Zhang Ling , Gong Baolin , Gao Hui , Li Zhihui , Zhang Tao , Wang Juan 
Published: July 2022

Abstract
Background: The lymph node involvement in the posterior to level V (PLV) region is mainly observed in nasopharyngeal carcinoma (NPC). Recently, we have reported the distribution of metastatic lymph nodes in the PLV region and there are correlations between the neck node levels (NNL) of NPC, but what is the boundary of the PLV region and how to delineate it remains unclear, and we further to elaborate whether the bilateral level Va should be covered as intermediate-risk clinical target volumes (CTVn2, about 60 Gy equivalent) for all T and N categories based on these correlations.Methods: A total of 1021 consecutive NPC patients with N1-3 stage from January 2012 to December 2020 were reviewed. The lymph node metastasis level of each patient was evaluated according to the updated guidelines proposed in 2013. According to the distribution pattern of lymph node metastasis and the anatomical structure in the PLV region, the boundaries of PLV region was delineated, and whether it is appropriate to cover the bilateral level Va as CTVn2 for all the NPC patients was further discussed.Results: The cranial boundary of PLV region is the caudal border of cricoid cartilage, the caudal boundary is the plane serratus anterior muscle begins to appear, the anterior boundary is the anterior border of trapezius, and the posterior boundary is the convergence of levator scapulae and trapezius. Laterally, the PLV region is limited by the medial edge of trapezius and medially by the lateral surface of levator scapulae. The nodal spread in level Va is based on the lymph node metastasis of level IIb in NPC.Conclusions: The PLV region is a missing NNL of head and neck tumors, especially in NPC. The proposed boundaries of the PLV region can provide a preliminary proposal for the further revision of NNL in head and neck tumors. It is theoretically feasible to reduce the prophylactic irradiation dose of the bilateral level Va in patients with N0 stage or with isolated metastases in level VIIa.