bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-secreted lactate contributes to an immunosuppressive microenvironment and affects CD8 T-cell infiltration in glioblastoma
Authors: Wang Zeyu , Dai Ziyu , Zhang Hao , Liang Xisong , Zhang Xun , Wen Zhipeng , Luo Peng , Zhang Jian , Liu Zaoqu , Zhang Mingyu , Cheng Quan 
Published: April 2023

IntroductionGlioblastoma is a malignant brain tumor with poor prognosis. Lactate is the main product of tumor cells, and its secretion may relate to immunocytes’ activation. However, its role in glioblastoma is poorly understood. MethodsThis work performed bulk RNA-seq analysis and single cell RNA-seq analysis to explore the role of lactate in glioblastoma progression. Over 1400 glioblastoma samples were grouped into different clusters according to their expression and the results were validated with our own data, the xiangya cohort. Immunocytes infiltration analysis, immunogram and the map of immune checkpoint genes’ expression were applied to analyze the potential connection between the lactate level with tumor immune microenvironment. Furthermore, machine learning algorithms and cell-cell interaction algorithm were introduced to reveal the connection of tumor cells with immunocytes. By co-culturing CD8 T cells with tumor cells, and performing immunohistochemistry on Xiangya cohort samples further validated results from previous analysis.DiscussionIn this work, lactate is proved that contributes to glioblastoma immune suppressive microenvironment. High level of lactate in tumor microenvironment can affect CD8 T cells’ migration and infiltration ratio in glioblastoma. To step further, potential compounds that targets to samples from different groups were also predicted for future exploration.
Total severity score and age predict long-term hospitalization in COVID-19 pneumonia
Authors: Nasoufidou Athina , Kavelidou Marianthi , Griva Theodora , Melikidou Eleni , Maskalidis Charalampos , Machaira Konstantina , Nikolaidou Barbara 
Published: April 2023

BackgroundSevere COVID-19 pneumonia implies increased oxygen demands and length of hospitalization (LOS). We aimed to assess a possible correlation between LOS and COVID-19 patients' clinical laboratory data of admission, including the total severity score (TSS) from chest computed tomography (CT).MethodsData were assessed retrospectively at the General Hospital “Agios Pavlos” in Greece. Clinical laboratory data, TSS, and LOS were recorded.ResultsA total of 317 patients, 136 women and 181 men, with a mean age of 66.58 ± 16.02 years were studied. Significant comorbidities were hypertension (56.5%), dyslipidemia (33.8%), type 2 diabetes mellitus (22.7%), coronary heart disease (12.9%), underlying pulmonary disease (10.1%), and malignancy (4.4%). Inpatient time was related to age (p &lt; 0.001), TSS (p &lt; 0.001), time from symptom onset to hospitalization (p = 0.006), inhaled oxygen fraction (p &lt; 0.001), fibrinogen (p = 0.024), d-dimers (p &lt; 0.001), and C-reactive protein (p = 0.025), as well as a history of hypertension (p &lt; 0.001) and type 2 diabetes mellitus (p &lt; 0.008). The multivariate analysis showed a significant association of the LOS with age (p &lt; 0.001) and TSS (p &lt; 0.001) independent of the above-mentioned factors.ConclusionEarly identification of disease severity using the TSS and patients' age could be useful for inpatient resource allocation and for maintaining vigilance for those requiring long-term hospitalizations.
Development and characterization of ferret ex vivo tracheal injury and cell engraftment model
Authors: Ievlev Vitaly , Pai Albert C. , Dillon Drew S. , Kuhl Spencer , Lynch Thomas J. , Freischlag Kyle W. , Gries Caitlyn B. , Engelhardt John F. , Parekh Kalpaj R. 
Published: April 2023

The field of airway biology research relies primarily on in vitro and in vivo models of disease and injury. The use of ex vivo models to study airway injury and cell-based therapies remains largely unexplored although such models have the potential to overcome certain limitations of working with live animals and may more closely replicate in vivo processes than in vitro models can. Here, we characterized a ferret ex vivo tracheal injury and cell engraftment model. We describe a protocol for whole-mount staining of cleared tracheal explants, and showed that it provides a more comprehensive structural overview of the surface airway epithelium (SAE) and submucosal glands (SMGs) than 2D sections, revealing previously underappreciated structural anatomy of tracheal innervation and vascularization. Using an ex vivo model of tracheal injury, we evaluated the injury responses in the SAE and SMGs that turned out to be consistent with published in vivo work. We used this model to assess factors that influence engraftment of transgenic cells, providing a system for optimizing cell-based therapies. Finally, we developed a novel 3D-printed reusable culture chamber that enables live imaging of tracheal explants and differentiation of engrafted cells at an air-liquid interface. These approaches promise to be useful for modeling pulmonary diseases and testing therapies.Graphical abstract1,2. We describe here a method for differential mechanical injury of ferret tracheal explants that can be used to evaluate airway injury responses ex vivo. 3. Injured explants can be cultured at ALI (using the novel tissue-transwell device on the right) and submerged long-term to evaluate tissue-autonomous regeneration responses. 4. Tracheal explants can also be used for low throughput screens of compounds to improve cell engraftment efficiency or can be seeded with particular cells to model a disease phenotype. 5. Lastly, we demonstrate that ex vivo-cultured tracheal explants can be evaluated by various molecular assays and by immunofluorescent imaging that can be performed live using our custom-designed tissue-transwell.
Development of a real-time loop-mediated isothermal amplification method for monitoring Pseudomonas lurida in raw milk throughout the year of pasture
Authors: Zhang Shufei , Hu Lianxia , Xue Yuling , Zhang Dong , Zhang Yaoguang , Wang Shijie 
Published: April 2023

IntroductionThe psychrophilic bacterium Pseudomonas lurida (P. lurida) and its thermostable alkaline proteases can seriously damage raw milk quality.MethodsIn this study, specific primers were designed for P. lurida’s gyrB and aprX genes, and a real-time loop-mediated isothermal amplification (RealAmp) rapid detection method was developed for the early monitoring of P. lurida and its proteases in raw milk. A phylogenetic tree of the gyrB and aprX genes of P. lurida was constructed to analyze the homology of the design sequence of the RealAmp primer. The DNA of 2 strains of P. lurida and 44 strains of non-P. lurida were detected via RealAmp to analyze the specificity of the primer.ResultsIt was found that aprX-positive proteases were produced by P. lurida-positive strains only when Pseudomonas fluorescens was negative. The dissociation temperatures of gyrB and aprX in the RealAmp-amplified products were approximately 85.0°C and 90.0°C, respectively. Moreover, DNA was detected through a 10-fold dilution of P. lurida in a pure bacterial solution and artificially contaminated skimmed milk. The limit of detection of P. lurida DNA copy number in the pure bacterial solution was 8.6 copies/μL and that in the 10% skimmed milk was 5.5 copies/μL. Further, 144 raw milk samples throughout the year from three farms in Hebei province were analyzed using RealAmp. The highest detection rate of P. lurida was 56% in the first and third quarters, and that of proteases was 36% in the second quarter. The detection rates of P. lurida and its proteases were the highest in samples collected from pasture 2 (52 and 46%, respectively), and the ability of P. lurida to produce proteases reached 88%.DiscussionIn conclusion, RealAmp established an early and rapid method for the detection of P. lurida and its proteases in raw milk samples, allowing the identification and control of contamination sources in a timely manner to ensure the quality of milk and dairy products.
The correlation of retinal neurodegeneration and brain degeneration in patients with Alzheimer’s disease using optical coherence tomography angiography and MRI
Authors: Zhao Bingying , Yan Yibing , Wu Xingqi , Geng Zhi , Wu Yue , Xiao Guixian , Wang Lu , Zhou Shanshan , Wei Ling , Wang Kai , Liao Rongfeng 
Published: April 2023

IntroductionPathological changes in Alzheimer’s disease can cause retina and optic nerve degeneration. The retinal changes are correlated with cognitive function. This study aimed to explore the relationship of retinal differences with neuroimaging in patients with Alzheimer’s disease, analyze the association of cognitive function with retinal structure and vascular density, and identify potential additional biomarkers for early diagnosis of Alzheimer’s disease.MethodWe performed magnetic resonance imaging (MRI) scans and neuropsychological assessments in 28 patients with mild Alzheimer’s disease and 28 healthy controls. Retinal structure and vascular density were evaluated by optical coherence tomography angiography (OCTA). Furthermore, we analyzed the correlation between neuroimaging and OCTA parameters in patients with mild Alzheimer’s disease with adjustment for age, gender, years of education, and hypertension.ResultsIn patients with mild Alzheimer’s disease, OCTA-detected retinal parameters were not significantly correlated with MRI-detected neuroimaging parameters after Bonferroni correction for multiple testing. Under multivariable analysis controlled for age, gender, years of education, and hypertension, the S-Hemi (0–3) sector of macular thickness was significantly associated with Mini-cog (β = 0.583, P = 0.002) with Bonferroni-corrected threshold at P &lt; 0.003.ConclusionOur findings suggested decreased macular thickness might be associated with cognitive function in mild AD patients. However, the differences in retinal parameters didn’t correspond to MRI-detected parameters in this study. Whether OCTA can be used as a new detection method mirroring MRI for evaluating the effect of neuronal degeneration in patients with mild Alzheimer’s disease still needs to be investigated by more rigorous and larger studies in the future.
RAGE and its ligand amyloid beta promote retinal ganglion cell loss following ischemia-reperfusion injury
Authors: Seyed Hosseini Fin Nafiseh , Georgevsky Dana , Sukkar Maria B. , Golzan S. Mojtaba 
Published: April 2023

IntroductionGlaucoma is a progressive neurodegenerative disease associated with age. Accumulation of amyloid-beta (Aß) proteins in the ganglion cell layer (GCL) and subsequent retinal ganglion cell (RGC) loss is an established pathological hallmark of the disease. The mechanism through which Aß provokes RGC loss remains unclear. The receptor for the advanced glycation end product (RAGE), and its ligand Aß, have been shown to mediate neuronal loss via internalizing Aß within the neurons. In this study, we investigated whether the RAGE–Aß axis plays a role in RGC loss in experimental glaucoma.MethodsRetinal ischemia was induced by an acute elevation of intraocular pressure in RAGE–/– and wild-type (WT) control mice. In a subset of animals, oligomeric Aß was injected directly into the vitreous of both strains. RGC loss was assessed using histology and biochemical assays. Baseline and terminal positive scotopic threshold (pSTR) were also recorded.ResultsRetinal ischemia resulted in 1.9-fold higher RGC loss in WT mice compared to RAGE–/– mice (36 ± 3% p &lt; 0.0001 vs. 19 ± 2%, p = 0.004). Intravitreal injection of oligomeric Aß resulted in 2.3-fold greater RGC loss in WT mice compared to RAGE–/– mice, 7-days post-injection (55 ± 4% p = 0.008 vs. 24 ± 2%, p = 0.02). We also found a significant decline in the positive scotopic threshold response (pSTR) amplitude of WT mice compared to RAGE–/– (36 ± 3% vs. 16 ± 6%).DiscussionRAGE–/– mice are protected against RGC loss following retinal ischemia. Intravitreal injection of oligomeric Aß accelerated RGC loss in WT mice but not RAGE–/–. A co-localization of RAGE and Aß, suggests that RAGE–Aß binding may contribute to RGC loss.
Development of a prognostic nomogram and risk stratification system for upper thoracic esophageal squamous cell carcinoma
Authors: Lin Yu , Zheng Binglin , Chen Junqiang , Huang Qiuyuan , Ye Yuling , Yang Yong , Chen Yuanmei , Chen Bijuan , You Mengxing , Wang Qifeng , Xu Yuanji 
Published: April 2023

BackgroundThe study aimed to develop a nomogram model to predict overall survival (OS) and construct a risk stratification system of upper thoracic esophageal squamous cell carcinoma (ESCC).MethodsNewly diagnosed 568 patients with upper ESCC at Fujian Medical University Cancer Hospital were taken as a training cohort, and additional 155 patients with upper ESCC from Sichuan Cancer Hospital Institute were used as a validation cohort. A nomogram was established using Cox proportional hazard regression to identify prognostic factors for OS. The predictive power of nomogram model was evaluated by using 4 indices: concordance statistics (C-index), time-dependent ROC (ROCt) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI).ResultsIn this study, multivariate analysis revealed that gender, clinical T stage, clinical N stage and primary gross tumor volume were independent prognostic factors for OS in the training cohort. The nomogram based on these factors presented favorable prognostic efficacy in the both training and validation cohorts, with concordance statistics (C-index) of 0.622, 0.713, and area under the curve (AUC) value of 0.709, 0.739, respectively, which appeared superior to those of the American Joint Committee on Cancer (AJCC) staging system. Additionally, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the nomogram presented better discrimination ability to predict survival than those of AJCC staging. Furthermore, decision curve analysis (DCA) of the nomogram exhibited greater clinical performance than that of AJCC staging. Finally, the nomogram fairly distinguished the OS rates among low, moderate, and high risk groups, whereas the OS curves of clinical stage could not be well separated among clinical AJCC stage.ConclusionWe built an effective nomogram model for predicting OS of upper ESCC, which may improve clinicians’ abilities to predict individualized survival and facilitate to further stratify the management of patients at risk.
A TCAD study on the effect of process parameters on silicon optical phase shifter performance
Authors: Mishra Darpan , Sonkar Ramesh Kumar 
Published: April 2023

On-chip integrated optical phase shifters are an important part of optical phase modulators. The performance of such modulators relies heavily on the phase shifter performance, which in turn depends on multiple process parameters. This paper reports the study of the effect of different process parameters on the performance of a silicon PN optical phase shifter obtained by process simulation using Silvaco® TCAD. The effect of dopant implantation dose, implantation energy, annealing temperature and time, wafer temperature, wafer tilt and rotation, and pre-amorphization on the phase and absorption of light is discussed. The 3-dB modulation bandwidth of a lumped phase shifter and the dependency of the performance metrics on different process parameters are presented. Monte Carlo numerical simulation shows that the free-carrier absorption has a much greater dependency on the process parameters than the phase shift. The study shows that ion channeling poses a limiting factor on the phase shifter performance, which can be improved by tilting the wafer or using a pre-amorphized substrate for implantation. The study shows that the 3-dB modulation bandwidth is highly dependent on the wafer tilt angle, rotation angle, and the lattice structure of the solid substrate. A bandwidth improvement of more than 5× is observed with 1.7× lower absorption for a pre-amorphized sample at −5 V compared to a crystalline sample with the same process flow.
Research on on-line assembly and calibration system based on laser scanning and optical fiber sensor
Authors: Ding Weijie , Li Meixuan , Liang Fang , Gao Yan , Qin Wei , Zhang Hong 
Published: April 2023

In order to improve the degree of assembly automation, an online assembly calibration system is designed based on laser scanning and optical fiber sensors. The optical fiber sensing module is used to obtain the stress field information, and the laser scanning module is used to obtain the point cloud information of the assembly structure. The position offset caused by the stress field can be compensated to the 3D point cloud for improving the target reconstruction accuracy. It consists of laser scanning module, optical fiber sensor module, demodulator, data analysis module, etc. Analyzing the structural characteristics of the module, the stress field distribution of the module structure is obtained through simulation analysis, and an appropriate optical fiber sensor network layout is constructed. When the force is applied in different directions, the stress field distribution of the assembly structure is simulated and analyzed. The results show that the magnitude and direction of the residual stress have an impact on the distribution of the stress field. At the same time, the stress field diffusion degree had been also analyzed in different strength conditions. In the calibration test of FBG sensor, the functional relationship between wavelength variation and stress is about 0.0011 nm/N. In the assembly test, the stress test trends of different FBGs were obtained, and the relative error was concentrated between 4.0% and 9.0%, which had good stability. After correcting the position of the point cloud for optical fiber sensing data, the position deviation between the test point and the digital analog has been significantly reduced, with the average value decreasing from 2.953. to 0.095 mm. It has good applicability in factories with large interference of working environment, and can improve the application field of intelligent assembly.
The impact of attention-deficit/hyperactivity disorder and specific learning disorders on academic performance in Spanish children from a low-middle- and a high-income population
Authors: Español-Martín Gemma , Pagerols Mireia , Prat Raquel , Rivas Cristina , Ramos-Quiroga Josep Antoni , Casas Miquel , Bosch Rosa 
Published: April 2023

IntroductionPast research has demonstrated that attention-deficit/hyperactivity disorder (ADHD), specific learning disorders (SLD), and socioeconomic status (SES) affect a host of educational outcomes. However, there are no studies examining whether SES moderates the association between these neurodevelopmental disorders (ND) and the academic achievement of children and adolescents. The present investigation examined the impact of ADHD and SLD on academic performance in 1,287 Spanish students aged 5–17 from a low-middle (LM)- and a high-income population, when adjusted for comorbidity and demographic factors that may influence educational functioning.MethodsParents completed a questionnaire regarding demographic data along with the Strengths and Difficulties Questionnaire. Additionally, teachers provided information on learning difficulties trough the Protocol for Detection and Management of Dyslexia. Teacher’s Version. Academic performance across multiple domains (i.e., first language, foreign language, mathematics) was obtained from school records. ND were determined using standardized diagnostic methods based on the Diagnostic and Statistical Manual of Mental Disorders criteria. To examine the effects of ADHD and SLD on academic achievement and the potential moderating role of SES, a series of ordinal logistic regressions were conducted.ResultsEmotional/behavioral problems, learning difficulties, and ND were more frequent among individuals from the LM-income population. After controlling for gender, age, parental divorce/separation, grade retention, frequency of screen use, and daily meals, both ADHD and SLD were associated with worse educational outcomes. Lower SES also increased the risk for academic impairment, although the interactions with ADHD or SLD were not significant.ConclusionThese findings indicate that ADHD and SLD exert a pervasive impact on academic performance across different socioeconomic backgrounds. Therefore, early detection and effective intervention strategies aimed at students with these ND are crucial to improve their educational functioning and mitigate the negative consequences related to academic problems.
Biomass fuel usage for cooking and frailty among older adults in China: a population-based cohort study
Authors: Song Quhong , Dai Miao , Lin Taiping , Zhao Yanli , Peng Xuchao , Liang Rui , Su Qiaoli , Yue Jirong 
Published: April 2023

BackgroundAlthough outdoor air pollution is reported to have a negative effect on frailty, evidence involving household air pollution is sparse.MethodsA cohort study on older participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey was conducted between 2011/2012 and 2014. Household cooking fuel types were determined by self-reported questionaries, and were dichotomized into clean or biomass fuels. The frailty status was evaluated via a 46-item frailty index (FI) and the FRAIL scale, respectively. Frailty was identified if FI &gt;0.21 or FRAIL score ≥3. Cox proportional hazards models were employed to examine the relationship between cooking fuels and incident frailty. And the effects of swapping cooking fuels on frailty risk were also explored.ResultsAmong 4,643 participants (mean age at baseline 80.9 ± 9.6 years, 53.7% male) totaling 11,340 person-years, 923 (19.9%) incident frailty was identified using FI. Compared to clean fuels, cooking with biomass fuels was intricately linked to a 23% rise in frailty risk (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.06–1.43). A similar association was detected between biomass cooking fuels and frailty measured by the FRAIL scale (HR 1.24, 95% CI 1.04–1.50). Sensitive analyses supported the independent relationship between biomass fuels and frailty. Stratified analyses revealed that the frailty risk was higher among town residents (HR 1.44, 95% CI 1.13–1.84) and participants not exercising regularly (HR 1.35, 95% CI 1.11–1.64). In comparison with persistent biomass fuels usage, switching to clean fuels had a trend to reduce the frailty risk, and the opposite effect was observed when swapping from clean to biomass fuels.ConclusionCooking with biomass fuels was associated with an increased frailty risk in older adults, especially amongst those living in town and those lacking regular exercise. More studies are needed to confirm our findings and to evaluate the potential benefits of reducing indoor biomass fuel usage.