bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of accuracy in identifying structural variants using third-generation sequencing for breast cancer in the absence of gold standard
Authors: Song Qianqian , Hu Taobo , Liang Baosheng , Zhang Zhen , Yang Liu , Wu Jinbo , Zhao Jin , Long Mengping , Lian Sheng , Fan Xiaodan , Wang Depeng , Wang Yang , Xie Fei , Yu Weichuan , Wang Shu , Zhou Xiaohua 
Published: October 2022

Abstract
Background: Detection of genomic structural variants (SVs) in breast cancer was of great clinical interest. Numerous methods were developed to call SVs from third-generation sequencing data, but the results and accuracy of various calling methods differ greatly. Thus, assessing the accuracy of these calling methods became important and challenging especially in the absence of gold standards. This study aimed to compare the performance of two SVs calling methods, denoted by T1 and T2 respectively, without gold standards of SVs.
Methods: A total of 155,566 structural variants detected by the two calling methods with third-generation sequencing were collected based on 20 breast cancer patients from Peking University People's Hospital. Utilizing a Bayesian approach that could take account of the dependency between calling results, we assessed the accuracy of T1 and T2 in detecting insertion, deletion, duplication, inversion, translocation, and copy number variant, respectively, in terms of sensitivity and specificity. Sensitivity analysis was conducted to evaluate the robustness of the comparison results.
Results: The estimated sensitivity and specificity of T2 were higher than that of T1 in detecting different SVs. The estimated sensitivity of T2 in detecting insertion, deletion, and duplication were 0.9438, 0.9440, and 0.9441, respectively, while the sensitivity of T1 were 0.8750, 0.8743, and 0.8843, respectively. Sensitivity analysis showed that the prior information is critical but the comparison results were robust in a certain range.
Conclusions: Results showed that T2 significantly outperforms T1 in a general comparison. The proposed model and obtained results are helpful to evaluate and select better SVs calling methods in the absence of gold standards, which in turn will be conducive to identifying new SVs associated with breast cancer or other diseases.
SurvExtrap: A tool to obtain precise parametric survival extrapolations
Authors: Gallacher Daniel 
Published: October 2022

Abstract
Background
Economic evaluation of emerging health technologies is mandated by agencies such as the National Institute of Health and Care Excellence (NICE) to ensure their cost is proportional to their benefit. To avoid bias, NICE stipulate that the benefit of a treatment is assessed across the lifetime of the patient population, which can be many decades. Unfortunately, follow-up from a clinical trial will not usually cover the required period and the observed follow-up will require extrapolation. For survival data this is typically done by selecting a preferred model from a set of candidate parametric models. This approach is limited in that the choice of model is restricted to those originally fitted. What if none of the models are consistent with clinical prediction or external data?
Results
This paper introduces SurvExtrap, a tool that estimates the parameters of common parametric survival models which interpolate key survival time co-ordinates specified by the user, which could come from external trials, real world data or expert clinical opinion. This is achieved by solving simultaneous equations which are rearranged from the survival functions of the parametric models. The application of SurvExtrap is shown through two examples where traditional parametric modelling did not produce models that were consistent with external data or clinical opinion.
Conclusions
SurvExtrap allows precise parametric survival models to be estimated and carried forward into economic models. It provides access to extrapolations that are consistent with multiple data sources such as observed data and clinical predictions, opening the door to exploration of regions of uncertainty/disagreement. SurvExtrap could avoid the need for post-hoc adjustments such as applying background mortality or treatment switching often applied to obtain a plausible survival model. Phase III clinical trials are not designed with extrapolation in mind, and so it is sensible to consider alternative approaches that incorporate external information.
BACE1 in PV interneuron tunes hippocampal CA1 local circuits and resets priming of fear memory extinction
Authors: Zheng Yan , Xiao Xuansheng , Wang Xiaotong , Zhu Ke , Li Lijuan , He Ying , Zhang Jinglan , Hu Hanning , Cui Yanqiu , Zhang Jianliang 
Published: October 2022

Abstract
BACE1 is the rate-limiting enzyme for β-amyloid (Aβ) production and therefore is considered a prime drug target for treating Alzheimer’s disease (AD). Nevertheless, the BACE1 inhibitors failed in clinical trials, even exhibiting cognitive worsening, implying that BACE1 may function in regulating cognition-relevant neural circuits. Here, we found that parvalbumin-positive inhibitory interneurons (PV INs) in hippocampal CA1 express BACE1 at a high level. We designed and developed a mouse strain with conditional knockout of BACE1 in PV neurons. The CA1 fast-spiking PV INs with BACE1 deletion exhibited an enhanced response of postsynaptic N-methyl-D-aspartate (NMDA) receptors to local stimulation on CA1 oriens, with average intrinsic electrical properties and fidelity in synaptic integration. Intriguingly, the BACE1 deletion reorganized the CA1 recurrent inhibitory motif assembled by the heterogeneous pyramidal neurons (PNs) and the adjacent fast-spiking PV INs from the superficial to the deep layer. Moreover, the conditional BACE1 deletion impaired the AMPARs-mediated excitatory transmission of deep CA1 PNs. Further rescue experiments confirmed that these phenotypes require the enzymatic activity of BACE1. Above all, the BACE1 deletion resets the priming of the fear memory extinction. Our findings suggest a neuron-specific working model of BACE1 in regulating learning and memory circuits. The study may provide a potential path of targeting BACE1 and NMDAR together to circumvent cognitive worsening due to a single application of BACE1 inhibitor in AD patients.
Retinopathy of prematurity risk predictors in peripheral avascular areas after intravitreal ranibizumab treatment: Vascular outgrowth speed analysis
Authors: Chen Jinguo , Xiong Lichun , Ruan Guanyu , Hu Jianzhang 
Published: October 2022

Abstract
Objective
To explore the predictors of risk for peripheral avascular areas (PAR) in retinopathy of prematurity (ROP) after intravitreal ranibizumab (IVR) monotherapy
Methods
This retrospective study included 64 infants (118 eyes) who developed type 1 ROP and received IVR between July 2019 and March 2021. Retinal vascular outgrowth speed (RVOS) was assessed by measuring the disc diameter (DD) 2 months post-IVR. Potential risk factors were examined and recorded. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to determine risk factors and predict PAR values.
Results
Mean RVOS was 0.9 ± 0.6 DD/month in all eyes 2 months post-IVR; RVOS in treated eyes was higher than in non-treated eyes. Completed retinal vascularization was detected in 69 (58.5%) eyes, persistent PAR in 49 eyes (41.5%). Univariate logistic regression analysis showed that gestational age at birth, postnatal age (PNA) at surgery, cumulative clock hours (CCH) of the ROP lesion, RVOS after IVR, and ROP severity were individually associated with PAR. Multiple logistic regression analysis revealed that RVOS, CCH of the ROP lesion, and PNA at the time of surgery were independent risk factors for PAR. The ROC curve showed that the cutoff value for RVOS was 0.672 DD/month (area under the curve, 0.8184).
Conclusions
IVR treatment accelerates RVOS; RVOS is inversely related to PAR. RVOS < 0.672 DD/month was a potential predictor of PAR. CCH of the ROP lesion and PNA during surgery were independent risk factors for PAR.
Evaluation of toxicity and genotoxicity of concrete cast with steel slags using higher terrestrial plants
Authors: Alias Carlotta , Piovani Giovanna , Benassi Laura , Abbà Alessandro , Sorlini Sabrina , Gelatti Umberto , Zerbini Ilaria , Feretti Donatella 
Published: October 2022

Abstract
Steel slags (SS), by-products of the steel industry, may be used as recycled materials. However, their reuse may generate the potential release of harmful compounds into the environment. The aim of this study was to assess the potential impact of concrete mixtures cast with SS as partial replacement of natural aggregate on the terrestrial ecosystem, in terms of toxicity and genotoxicity, by using a battery of bioassays composed of higher plants. Four concrete mixtures, each one cast with the replacement of natural aggregates by 30% of four different SS and a mixture with natural aggregates only (reference concrete) were submitted to the monolithic leaching test (UNI EN 15863). The leachates were assayed for phytotoxicity by using seeds of Lepidium sativum, Cucumis sativus, and Allium cepa. The emerged seedlings of L. sativum and A. cepa were used for the evaluation of the DNA damage through the Comet test. The genotoxicity of the leachates was also analysed by means of bulbs of A. cepa applied through the Comet and the chromosomal aberrations tests. None of the samples caused phytotoxic effects towards the tested seeds. Rather, almost all the samples support the seedlings emergence, demonstrated by germination indexes (GI%) between 90% and 120%. Moreover, two leachates from concrete cast with SS and the one from the reference concrete were able to promote the germination and root elongation of C. sativus and A. cepa. DNA damage in L. sativum and A. cepa seedlings was significantly increased only by the sample from reference concrete, while the four leachates from concrete cast with SS did not differ by the controls. Conversely, the DNA damage on A. cepa bulbs was significantly improved by leachate from reference concrete, but also by that from a sample of concrete with SS. Moreover, all the leachates caused the rise of chromosomal aberrations in bulbs of A. cepa. Despite some genotoxic effects of concrete on plant cells, the partial replacement of SS does not seem to make concrete any more hazardous than the reference one in terms of global toxicological assessment, suggesting the potential use of SS as reliable recycled material, leading to a reduction of the impact of the anthropic activities on the environment.
Does Family Functioning contribute to the Life Satisfaction among Female University Students during COVID-19 Outbreak?
Authors: Zarei Salman , Fooladvand Khadijeh 
Published: October 2022

Abstract
Background: Literature review has showed that family functioning is positively associated with satisfaction with life. However, the internal mechanisms of this relationship are still unclear, especially during the COVID-19. This study examined the mediating role of hope and resilience in the association between family functioning and life satisfaction of female university students in COVID-19 pandemics.
Methods: A cross-sectional online study was done throughout the fifth wave of the COVID-19 outbreak in Iran. A total of 480 female students were recruited from Lorestan University. Data was collected by the State Hope Scale (SHS), Satisfaction with Life Scale (SWLS), Family APGAR Index, and Connor-Davidson Resilience Scale (CD-RISC). Data analysis were based on structural equation modeling.
Results: Family functioning exerted a significant direct effect on hope, on resilience and on life satisfaction. Also, according to the findings, hope and resilience pose a significant mediating effect in the association between family functioning and life satisfaction.
Conclusion: This study provides a better perspective regarding the protective role of hope, family functioning, and resilience on life satisfaction among female university students during the COVID-19 pandemic. Training of such skills is needed to increase life satisfaction in female university students.
Use of mouse primary epidermal organoids for USA300 infection modeling and drug screening
Authors: xie xiaorui , Tong Xuebo , Li Zhihong , Cheng Quan , Wang Xiaowei , Long Yin , Liu Fangbo , Wang Yonghui , Wang Juan , Liu Li 
Published: October 2022

Abstract
Skin infections caused by drug-resistant Staphylococcus aureus occur at high rates nationwide. Mouse primary epidermal organoids (mPEOs) possess stratified histological and morphological characteristics of epidermis and are highly similar to their derived tissue at the transcriptomic and proteomic levels. Herein, the susceptibility of mPEOs to methicillin-resistant S. aureus USA300 infectionwas investigated. The results show that mPEOs support USA300 colonization and invasion, exhibiting swollen epithelial squamous cells with nuclear necrosisand secreting inflammatory factors such as IL-1β. Meanwhile mPEOs beneficial to observe the process of USA300 colonization with increasing infection time, and USA300 induces mPEOs to undergo pyroptosis and autophagy. In addition, we performed a drug screen for the mPEOinfection model and showed that vancomycin restores cell viability and inhibits bacterial internalization in a concentration-dependent manner. In conclusion, we establish an in vitro skin infection model that contributes to the examination of drug screening strategies and antimicrobial drug mechanisms.
Kruppel-like factor 4 promotes autophagy in human monocytes leukemia cells under high glucose conditions by inhibiting AKT/mTOR signaling pathway
Authors: Zhang Rui , Chen Sisi , Wang Tongdan , Yu Pei 
Published: October 2022

Abstract
Background
Diabetic atherosclerosis (AS) is the main cause of disability and death in diabetes. In the progression of AS, autophagic activity plays an important role. Kruppel-like factor 4 (KLF4) is a member of zinc finger protein transcription factor family and is believed to play a protective role in the pathogenesis of atherosclerosis. This study aimed to explore the role of KLF4 in diabetic atherosclerosis and the autophagic mechanism.
Methods
After the diabetic mouse model induced by streptozotocin (STZ), we gave mice a high-fat and sugar diet. Aortic arches were dissected from the iliac bifurcation to remove external fatty deposits and detected the level of KLF4 protein expression in diabetic group compared to the non-diabetic group. On the other hand, KLF4 lentiviral vector and small interfering RNA (siRNA) were constructed for in vitro experiments. Oil red staining and cholesterol content assay was used to determinate the cholesterol content in human monocytes leukemia cells (THP-1). Cell apoptosis was determined using TUNEL assay. Immunofluorescence staining, western blotting and reverse transcription-PCR analysis were utilized to evaluate the expressions of autophagy-related proteins as well as AKT/mTOR signaling pathway-related proteins after the transfection of KLF4 siRNA or lentiviral vector.
Results
The expression level of KLF4 protein was decreased in the aorta of diabetic mice, while KLF4 overexpression in THP-1 cells under high glucose can significantly decrease cellular cholesterol accumulation, increase beclin-1 expression and decrease P62/SQSTM1 expression, respectively. Meanwhile, microtubule-associated protein 1 light chain 3 (LC3) fluorescence intensity in KLF4 lentiviral vector group is significantly enhanced with increased cell apoptosis. Phosphorylated mammalian target of rapamycin (p-mTOR) and phosphorylated AKT (p-AKT) expression was decreased in KLF4 overexpressed group. On the contrary, after transfection of KLF4 siRNA, the expression levels of p-mTOR and p-AKT were increased in THP-1 cells.
Conclusion
KLF4 can decrease cellular cholesterol accumulation and induce autophagy in THP-1 cells under high glucose conditions by inhibiting the AKT/mTOR pathway, which may slow the progression of diabetic atherosclerosis.
Hippocampal organotypic cultures as ex vivo model for tissue response to upconverting nanoparticles
Authors: Zajdel Karolina , Janowska Justyna , Frontczak-Baniewicz Małgorzata , Sypecka Joanna , Sikora Bozena 
Published: October 2022

Abstract
In the last few years, rare-earth-doped upconverting nanoparticles (UCNPs) have been widely used in different life sciences due to their unique properties. Nanoparticles have become a multifunctional and promising new approach to neurobiological disorders and have shown extraordinary application potential to overcome problems related to conventional treatment strategies. This study evaluated the internalization mechanisms, bio-distribution, and neurotoxicity of NaYF4:20%Yb3+,2%Er3+ UCNPs in rat organotypic hippocampal slices. TEM results showed that UCNPs were easily internalized by hippocampal cells and co-localized with selected organelles inside neurons and astrocytes. Moreover, we found that UCNPs were taken into the neurons via clathrin- and caveolae-mediated endocytosis. Propidium iodide staining and TEM analysis did not confirm the adverse effects of UCNPs on hippocampal slice viability and morphology. Therefore, UCNPs may be a potent tool for bio-imaging and testing new therapeutic strategies for brain diseases in the future.
General nonlinear Hall current in magnetic insulators beyond the quantum anomalous Hall effect
Authors: Kaplan Daniel , Holder Tobias , Yan Binghai 
Published: October 2022

Abstract
Can a generic magnetic insulator exhibit a Hall current? The quantum anomalous Hall effect (QAHE) is one example of an insulating bulk carrying a quantized Hall conductivity and other insulators (with zero Chern number) present zero Hall conductance in the linear response regime. Here, we find that a general magnetic insulator possesses a nonlinear Hall conductivity quadratic to the electric field if the system breaks inversion symmetry. This conductivity originates from an induced orbital magnetization due to virtual interband transitions. We identify three contributions to the wavepacket motion, a velocity shift, a positional shift, and a Berry curvature renormalization. In contrast to the crystalline solid, we find that this nonlinear Hall conductivity vanishes for Landau levels of a 2D electron gas, indicating a fundamental difference between the QAHE and the Integer quantum Hall effect.
MRCP and microincision of the cystic duct can prevent residual gallstones: A single-center experience
Authors: Huang Yonghong , Peng Fei , Zhou Binxian , Duo A 
Published: October 2022

Abstract
Background: Residual gallstones are an infrequent but troublesome complication after laparoscopic cholecystectomy (LC). This study aimed to explore the feasibility of routine preoperative magnetic resonance cholangiopancreatography (MRCP) examination and intraoperative microincision of the cystic duct in preventing residual gallstones after LC surgery.
Methods: This report presents a summary and analysis of 1217 cases of gallbladder stones treated by LC in the People's Hospital of Nyingchi from January 2016 to August 2021. According to the different measures taken to prevent residual gallstones, it is divided into 3 phases. In phase 1, there is no preoperative MRC examination P and intraoperative microincision. In phase 2, preoperative MRCP examination was performed without intraoperative microincision. In phase 3, both preoperative MRCP examination and intraoperative microincision were performed. Then the differences in residual gallstones at different phases were analyzed. And further analysis of preoperative MRCP and intraoperative microincision case data was performed to assess feasibility in phase 3, including the extra cost posed by the MRCP examination, operation time, volume of blood loss, and presence of residual gallstones after surgery.
Results: In phase 1, 0.63% (3/473) of patients had residual gallstones after LC surgery; in phase 2, 0.24% (1/418) of patients had residual gallstones; in phase 3, no patients residual gallstones were present (0/326). Feasibility analysis for Phase 3 showed that 7.98% of cases of silent choledocholithiasis that were not detected by abdominal ultrasound were detected by MRCP, and MRCP examination only accounted for 9.45% of the total hospitalization expenses, which could effectively reduce the missed diagnosis of cholecystolithiasis combined with choledocholithiasis. The average time of microincision and squeezing of the cystic duct during the operation was 3 to 5 minutes, and the bleeding volume was 1 to 3 ml, indicating that microincision of the cystic duct was safe and easy to perform. Sedimentary stones or flocs could be squeezed out by this technique in 21% of LC cases, which could effectively reduce the risk of secondary choledocholithiasis stones after surgery.
Conclusion: These data show that routine preoperative MRCP examination and intraoperative microincision of the cystic duct can effectively prevent residual gallstones after LC.
Controlling THz generation in nonlinear metasurfaces through coupling: amplitude-tuning, handedness-selectivity and holography
Authors: Han Jiaguang , Wang Qingwei , Zhang Xueqian , Xu Quan , Feng Xi , Lu Yongchang , Niu Li , Plum Eric , Gu Jianqiang , Yang Quanlong , Fang Ming , Huang Zhixiang , Zhang Shuang , Zhang Weili 
Published: October 2022

Abstract
Generation and manipulation of THz waves are of vital importance to advance THz technology. Nonlinear metasurfaces allow effective integration of both processes into a single compact device. However, the existing THz generator-manipulators offer limited control over the generated field. Here, we demonstrate that coupling between meta-atoms provides additional degrees of freedom: achiral coupling can provide full control over the amplitude of the generated THz field, while chiral coupling makes the THz generation sensitive to the handedness of the pump polarization. Based on chiral coupling, we realize meta-molecules that only generate THz waves when pumped with circularly polarized light of one handedness. This enables independent generation of different holograms with left-handed and right-handed pump light. As an example, we generate THz beams with different orbital angular momenta with a handedness-selective metasurface.