bluuebunny/crossref_metadata_2025 huggingface dataset:
Ivy sign in moyamoya disease
Authors: Yue Li , Li Wanjiang , Xia Chunchao , Tan Jing , Xiao Anqi , Liu Yi , Sun Haogeng
Published: November 2022

Background:Moyamoya disease can not be found commonly as a rare type compared to other vascular diseases, such as intracranial aneurysms. However, it can not be ignored for its high fatality and disability rate. In addition, the exact pathogenesis study of this disease is still on the way. The ivy sign is always observed in moyamoya disease (MMD), but the clinical importance of this sign in MMD isn't known. The main purpose of this research was to specifically investigate the clinical significance.Methods:The patients with moyamoya disease were hospitalized from January 2016 to 2020, it’s a retrospective cohort study to gather the baseline clinical and imaging study. The study was approved by the Institutional Review Board and Ethics Committee of West China Hospital, Sichuan University (No. 2018-219), Informed consent was obtained from all individual participants included in the study，all experiments were performed in accordance with relevant guidelines and regulations. In the analysis, univariate and multivariate logistic regression was utilized to testify whether ivy sign was independently associated with MMD characteristics, including cerebrovascular morphology, cerebral hemodynamics, cerebrovascular events, and postoperative collateral formation (PCF).Results:156 patients were included with 312 hemispheres (Table 1). As for the result of multivariate logistic regression analysis, we could discover a fact that ivy sign was tightly connected to the Suzuki stage ≥IV(OR,1.386;95%CI,1.055-1.822;p=0.019（Table2）), rCBF(cerebral blood flow) decreased type (OR,2.330;95%CI,1.733-3.133;p=0.000（Table3）), age acted as a protective factor for rCBF(OR, 0.966; 95%CI,0.946-0.986;p=0.001, the elder was more likely associated with decreased rCBF. ivy sign also played a significant role in Ischemic cerebrovascular events(OR,5.653;95%CI,3.092-10.336; p=0.003(Table5)), their remarkable connection could be seen in the study. We could also find that ivy was closely connected to good postoperative collateral formation (PCF)( OR,2.830;95%CI,1.329-6.027; p=0.007(Table4), we couldn't ignore that age was associated with good PCF as well(OR, 0.933;95%CI, 0.882-0.987; p=0.015).Discussion:We could be more aware of the connection between ivy signs and moyamoya disease from this study, to implement diagnosis, treatment, and prognosis more efficiently.
Preclinical evaluation of a brain penetrant PARP PET imaging probe in rat glioblastoma and nonhuman primates
Authors: Chen Baosheng , Ojha Devi Prasan , Toyonaga Takuya , Tong Jie , Pracitto Richard , Thomas Monique A. , Liu Michael , Kapinos Michael , Zhang Li , Zheng Ming-Qiang , Holden Daniel , Fowles Krista , Ropchan Jim , Nabulsi Nabeel , De Feyter Henk , Carson Richard E. , Huang Yiyun , Cai Zhengxin
Published: November 2022

Purpose Currently, there are multiple active clinical trials involving poly(ADP-ribose) polymerase (PARP) inhibitors in the treatment of glioblastoma. The noninvasive quantification of baseline PARP expression using positron emission tomography (PET) may provide prognostic information and lead to more precise treatment. Due to the lack of brain-penetrant PARP imaging agents, the reliable and accurate in vivo quantification of PARP in the brain remains elusive. Herein, we report the synthesis of a brain-penetrant PARP PET tracer, (R)-2-(2-methyl-1-(methyl-11C)pyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide ([11C]PyBic), and its preclinical evaluations in a syngeneic RG2 rat glioblastoma model and healthy nonhuman primates.
Methods We synthesized [11C]PyBic using veliparib as the labeling precursor, performed dynamic PET scans on RG2 tumor-bearing rats and calculated the distribution volume ratio (DVR) using simplified reference region method 2 (SRTM2) with the contralateral nontumor brain region as the reference region. We performed biodistribution studies, western blot, and immunostaining studies to validate the in vivo PET quantification results. We characterized the brain kinetics and binding specificity of [11C]PyBic in nonhuman primates on FOCUS220 scanner and calculated the volume of distribution (VT), nondisplaceable volume of distribution (VND), and nondisplaceable binding potential (BPND) in selected brain regions.
Results [11C]PyBic was synthesized efficiently in one step, with greater than 97% radiochemical and chemical purity and molar activity of 148 ± 85 MBq/nmol (n = 6). [11C]PyBic demonstrated PARP-specific binding in RG2 tumors, with 74% of tracer binding in tumors blocked by preinjected veliparib (i.v., 5 mg/kg). The in vivo PET imaging results were corroborated by ex vivo biodistribution, PARP1 immunohistochemistry and immunoblotting data. Furthermore, brain penetration of [11C]PyBic was confirmed by quantitative monkey brain PET, which showed high specific uptake (BPND > 3) and low nonspecific uptake (VND < 3 mL/cm3) in the monkey brain.
Conclusion [11C]PyBic is the first brain-penetrant PARP PET tracer validated in a rat glioblastoma model and healthy nonhuman primates. The brain kinetics of [11C]PyBic are suitable for noninvasive quantification of available PARP binding in the brain, which posits [11C]PyBic to have broad applications in oncology and neuroimaging.
Persistent high levels of carcinoembryonic antigen after tumor-resection are associated with poorer survival outcomes in patients with resected colorectal cancer
Authors: Muñoz-Montaño Wendy R. , López-Basave Horacio , Sánchez-Trejo Karen , Sandoval Rodrigo Catalán , Díaz-Romero Consuelo , Lino-Silva Leonardo , Diaz Andrea Maliachi , Ruiz-García Erika , Herrera-Martínez Marytere , Calderillo-Ruiz Germán , Castillo-Morales Carolina , Castillo-Morales Alison
Published: November 2022

Background: In locoregional colon cancer, interindividual survival and recurrence rates following surgical resection are highly variable. The aim of the present study was to determine whether elevated preoperative and postoperative CEA values are useful prognostic biomarkers for patients with stage I - III colon cancer that underwent surgery with curative intent.
Methods: We conducted a retrospective study in patients with histologically confirmed stage I–III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico’s National Institute of Cancer, between 2008 and 2020. We determined preoperative and posoperative CEA, and to review the association of the score with poorer survival outcomes in patients with resected colorectal cancer: overall survival (OS) and disease-free survival (DFS).
Results: We included 640 patients with stages I and III colon cáncer, preoperative CEA levels were in the normal range in 460 (group A) and above the reference value in 180. Of the 180 patients with elevated preoperative CEA levels, 134 (group B) presented normalized CEA levels after surgery and 46 (group C) remained with CEA above reference values after surgery. Median follow- up was 46.4 months (range, 4.9–147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6-71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6-81.6)]; Group B: 75.7 months (95% CI 66.8-84.5) (p-value<0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8-76.3) months] than in group A [82.8 (95% CI 78.6-86.9 months] and group B [87.1 (95% CI 79.6-94.5 months] (p-value = 0.002) To identify whether change in CEA levels before and after surgery was an independent prongostic factor for survival outcomes, a Cox proportional hazard model was performed. In multivariate analysis, change in CEA level was a statistically significant independent prognostic factor for overall survival (p-value = 0.031)
Conclusions:When assessed in conjunction preoperative and postoperative CEA values are useful biomarkers for predicting survival outcomes in patients with resected CRC; prognosis is worse for patients with elevated pre and post-surgical CEA values; however, it is similar in patients with normal post-surgical values, regardless of their pre-surgery values.
Examining The Correlation between Patients with Atrial Fibrillation and eNOS G894 T Polymorphism
Authors: kargün kürşat
Published: November 2022

Objectives
Atrial fibrillation (AF) is the most common sustained arrhythmia. AF is a serious health problem since it causes discomfort, heart failures and strokes in patients. This study aims to identify the possible role of eNOS G894T polymorphisms in AF incidents.
Methods
73 individuals were included in the study with age average of 63.47 ± 9.10 who received EKG (electrocardiogram) at Elazig Training and Research Hospital Cardiology Department. 92 individuals with age average of 60.71 ± 9.14 who were confirmed to have no heart condition were included in the study as control group. The genomic DNAs of Control and AF groups were isolated from full blood. eNOS G894T polymorphism was detected with a real-time PZR device using kits. This study was conducted between the 2018 march and December. ethics committee university ethics committee 04/09/2018 Received with the management number 279476. This study was conducted between September and December 2018. It was received with the letter of the Ethics Committee of Fırat University Ethics Committee dated 04/09/2018 and numbered 279476.
Results
The significance of hypertension between AF patient and control groups was detected (p < 0,023), yet no significance was detected between diabetes, smoking and body mass index ((p > 0,004). Significant difference was observed between control group and AF group regarding eNOS G894T polymorphism (p < 0.0001).
Conclusions
As a result, it is concluded that variants of eNOS G894 T can be considered as a risk factor for AF.
Topic modeling for multi-omic integration in the human gut microbiome and implications for Autism
Authors: Tataru Christine , Peras Marie , Rutherford Erica , Dunlap Kaiti , Yin Xiaochen , Chrisman Brianna S. , DeSantis Todd Z. , Wall Dennis P. , Iwai Shoko , David Maude M.
Published: November 2022

While healthy gut microbiomes are critical to human health, pertinent microbial processes remain largely undefined, partially due to differential bias among profiling techniques. By simultaneously integrating multiple profiling methods, multi-omic analysis can define generalizable microbial processes, and is especially useful in understanding complex conditions such as Autism. Challenges with integrating heterogeneous data produced by multiple profiling methods can be overcome using Latent Dirichlet Allocation (LDA), a promising natural language processing technique that identifies topics in heterogeneous documents. In this study, we apply LDA to multi-omic microbial data (16S rRNA amplicon, shotgun metagenomic, shotgun metatranscrip-tomic, and untargeted metabolomic profiling) from the stool of 81 children with and without Autism. We identify topics, or microbial processes, that summarize complex phenomena occurring within gut microbial communities. We then subset stool samples by topic distribution, and identify metabolites, specifically neurotransmitter precursors and fatty acid derivatives, that differ significantly between children with and without Autism. We identify clusters of topics, deemed "cross-omic topics", which we hypothesize are representative of generalizable microbial processes observable regardless of profiling method. Interpreting topics, we find each represents a particular diet, and we heuristically label each cross-omic topic as: healthy/general function, age-associated function, transcriptional regulation, and opportunistic pathogenesis.
SOD2 promotes gastric tumorigenesis mediated by Helicobacter pylori and enhances resistance to 5-fluorouracil in gastric cancer
Authors: Fu Hongbing , Zhang Yu , Zhang Xin , Yao Jun , Yang Dejun , Wei Ziran , Zhu Zhenxin , Xu Jiapeng , Hu Zunqi , You Qing , Yan Ronglin , Wang Weijun
Published: November 2022

Background: Helicobacter pylori (H. pylori) infection is the most common risk factor for gastric cancer (GC). The effect of the antioxidase manganese superoxide dismutase (SOD2 or MnSOD) in gastric tumorigenesis remains unclear.
Methods: We explored the molecular and mechanical links between H. pylori, inflammation, and SOD2 in GC. RNA sequencing was conducted to identify the differentially expressed mRNAs between H. pylori-infected and uninfected cells. The putative role of SOD2 in gastric tumorigenesis in response to H. pylori infection was investigated in vitro and in vivo.
Results: SOD2 is upregulated in GC. GC patients with high SOD2 expression clearly showed worse overall survival. H. pylori infection promoted SOD2 expression by activating the NF-κB signaling pathway. Knockdown of SOD2 led to increased levels of reactive oxygen species and oxidative stress in response to H. pylori infection. Meanwhile, the NF-κB binding site in the SOD2promoter region was evaluated through luciferase reporter and chromatin immunoprecipitation assays. SOD2 acted as an inhibitor of ferroptosis in GC cells, and SOD2 inhibition significantly sensitized GC cells to 5-fluorouracil treatment.
Conclusions: Our results suggest that activation of the NF-κB pathway in GC cells infected with H. pylori leads to the upregulation of SOD2. Considering the prosurvival oncogenic features of SOD2 overexpression, our study further supports a novel relationship between infection, inflammation, and gastric carcinogenesis. Our results indicate that SOD2 may be a promising therapeutic candidate for GC.
Tumor Collagens Predict Genetic Features and Patient Outcomes
Authors: Brodsky Alexander , Guo Kevin
Published: November 2022

The extracellular matrix (ECM) is a critical determinant of tumor fate that reflects the output from myriad cell types in the tumor.
The impact of ECM composition on patient outcomes remains largely unknown. Collagens constitute the principal substrate of
the tumor ECM and yet have been largely overlooked as simple structural proteins. When RNA transcription from solid tumors
in The Cancer Genome Atlas (TCGA) was retrospectively analyzed for expression patterns across the 43 human collagen
genes, strong associations with survival, specific immunoenvironments, somatic gene mutations, copy number variations, and aneuploidy were revealed in all cancer types. Clustering by matrisome and collagen expression grouped tumors by tissue of origin. We developed a machine learning classifier that predicts aneuploidy, and chromosome arm copy number alteration
(CNA) status based on collagen expression alone with high accuracy in many cancer types, suggesting a strong relationship
between ECM context and specific molecular alterations. These findings have broad implications in defining the relationship
between cancer-related genetic defects and the tumor microenvironment to improve prognosis and therapeutic targeting for patient care, opening new avenues of investigation to define tumor ecosystems.
Clinical Characteristics and Therapeutic Effects of Checkpoint Inhibitor-Related Pneumonitis in Patients with Non-Small Cell Lung Cancer
Authors: Pang Li , Xie Mei , Ma Xidong , Huang Aiben , Song Jialin , Yao Jie , Deng Hui , Zhang Duchao , Zang Xuelei , Ren Fangping , Gao Jie , Wu Chongchong , Wang Yuanyong , Zhang Xin , Bao Xinyu , Pan Lei , Xue Xinying
Published: November 2022

Background: With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects.
Methods: The clinical data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical and imaging data were analyzed; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized.
Results: 36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%) , nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%) , hypersensitiviy pneumonitis(HP) in 2 cases (6.3%) , diffuse alveolar damage in 1 case (3.1%) and atypical imaging anifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs.
Conclusion: We found that glucocorticoid 1-2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored.
The Toba eruption 74,000 years ago strengthened the Indian winter monsoon
Authors: Guballa Jose Dominick , Bollmann Jörg , Schmidt Katherine , Lueckge Andreas
Published: November 2022

The global impact of the Youngest Toba Tuff (YTT) supereruption ~74,000 years (ka) ago is still heavily debated, ranging from having insignificant effects on climate to severely affecting modern human evolution. Climate models and terrestrial proxy records show that the YTT eruption may have caused cooling of the Asian landmass, thus impacting regional climate such as the Indian monsoon system. However, the immediate effect of the eruption on the Indian monsoon has not been indisputably demonstrated in any proxy record. Here, we present a nearly annual phytoplankton-based primary productivity (PP) record from the northeastern Arabian Sea and show that PP increased by ~65% for about 10–20 years after the eruption. The elevated PP is most likely linked to the deepening of the ocean mixed layer driven by strengthened northeasterly Indian winter monsoon winds, supporting previous modeling studies and demonstrating unequivocal evidence from a marine record for an Indian monsoon response to the YTT eruption. Conversely, the intensified winds might have decreased PP off Somalia as observed today during winter and reduced the marine food supply of early humans in the region—a factor that may have contributed to the postulated migration window during this time.
Real-world data on bio-clinical follow-up after vaccination with Pfizer-BioNT162b2 mRNA COVID-19 in 216 patients with hematological malignancies
Authors: Rossi Jean-François , Bonnet Emmanuel , Castelli Christel , Velensek Marion , Wisniewski Emma , Heraud Sophie , Boustany Rania , David Céleste , Dinet Jérôme , Sicard Roland , Daures Jean-Pierre , Bonifacy Marion , Mousset Lysiane , Goffart Emmanuel
Published: November 2022

Hematological malignancies patients (HM) have heterogeneous serological response after vaccination.
Real-world data.
216 patients with HM and 12 non-malignant hemopathies received BNT162b2 COVID-19 and monitored for >1 year. The first 43 patients had initial follow-up by telemedicine system (TM). Anti-Spike IgG antibodies were monitored 3-4 weeks post-1st vaccination and every 3-4 months, by 2 standard bioassays and a rapid serological test (RST). Vaccine boosts were given when the level was <7BAU/mL. Patients who did not seroconvert after 3-4 doses received tixagevimab/cilgavimab (TC).
Follow-up and results.
Tolerance using TM was good. 15 results were discordant between 2 standard bioassays. Good agreement was observed between standard and RST on 97 samples. After 2 doses, 68% were seroconverted (median 59 BAU/mL) with a median of 162 BAU/mL in untreated patients and 9 BAU/mL in treated patients (P<0.001), particularly for patients receiving rituximab. Patients with low levels of gammaglobulin levels (<5g/L) had reduced seroconversion (p=0.019). Median levels were 228 BAU/mL post-2nd dose if seroconverted post-1st and 2, if seronconverted only post-2nd. 68% of post-2nd negative patients were post-3rd positive. 16 pts received TC, 6 with non-severe symptomatic COVID-19 within 15-40 days.
Conclusion:
Personalized serological monitoring must be applicated particularly for HM patients.
The driving factors of water use and its decoupling relationship with economic development: A multi-sectoral perspective
Authors: Wang Tianzi , Jian Shengqi , Wang Huiliang , Yan Denghua
Published: November 2022

The water resource situation in China is severe, and conflicts between the supply and demand of water resources are prominent. Competition for water from key sectors, such as agriculture, industry, and domestic use, is widespread. The Yellow River, as one of the longest rivers in the world, is an important economic belt and an ecological barrier in China. This study considered the nine provinces along the Yellow River as the study area and the three major water-use sectors: agriculture, industry, and domestic as the research objects. The drivers of water consumption in each sector in the nine provinces along the Yellow River were analyzed using the Logarithmic Mean Divisia Index method. Based on this, a decoupling model was used to explore the relationship between water use in each sector and the corresponding level of economic development. It was found that water use intensity and economic development level were the largest negative and positive influencing factors on water use in each sector, respectively, and the opposite effects of the two may cause the Jevons paradox in water use. The overall agricultural water-saving level in the basin is high and has a large water-saving potential. The negative driving effect of the industrial structure was more significant in provinces with higher development levels. The positive driving effect of residents' consumption levels on domestic water use in rural areas was more obvious than in urban areas. The degree of decoupling between per capita and domestic water consumption in urban areas was the worst in the decoupling of water use in the agricultural, industrial, and domestic sectors and their corresponding levels of economic development. Therefore, focusing on areas with weak agricultural water conservation, promoting industrial structure upgrading, strengthening water conservation education in rural areas, and guiding the water-saving consumption habits of residents can promote the sustainable development of water resources in the provinces along the Yellow River. The research results provide insights into water conservation management in the Yellow River Basin.
Enhancement of pattern quality with loss modulation: Applying plasmonic lithography in sub-20 nm technology node and beyond
Authors: Wei Yayi , Han Dandan , Ye Tianchun , Deng Sen
Published: November 2022

Plasmonic lithography, which uses the evanescent electromagnetic (EM) fields to image beyond the diffraction limit, has been successfully demonstrated as a main candidate for recording integrated circuits (IC) with sub-10 nm resolution. However, as the feature size continuously down-scaling, the corresponding photoresist profile in general exhibits a very poor pattern fidelity due to the near-field optical proximity effect (OPE), far below the minimum requirement for nanofabrication. The importance of the near-field OPE formation and its minimization for nanodevice fabrication with high dense feature and fidelity necessitates a systematic study of the phenomenon and its origins. In this work, a point-spread function (PSF) generated by a plasmonic bowtie nanoridge aperture (BNA) is employed to account for all physical and chemical phenomena involved in the near-field patterning process. The achievable resolution of plasmonic lithography has successfully been enhanced to approximately 4 nm with numerical simulations. A field enhancement factor (F) as a function of gap size is defined to quantitatively evaluate the strong near-field enhancement effect excited by a plasmonic BNA, which also revels that the high enhancement of evanescent field is due to the strong resonant coupling between the plasmonic waveguide and the surface plasmon waves (SPWs). However, based on the investigation of the physical origin of the near-field OPE, and the theoretical calculations indicate that the evanescent-field-induced high-k information loss is the main optical contributor for the near-field OPE. Furthermore, an analytic formula is introduced to quantitatively analyze the effect of the rapidly decaying feature of the evanescent field on the final exposure pattern profile. Notably, a fast and effective optimization method based on the compensation principle of exposure dose is proposed to relax the pattern distortion by modulating the exposure map with dose leveling. The proposed pattern quality enhancement method can open new possibilities in the manufacture of nanostructures with ultrahigh pattern quality via plasmonic lithography, which would find potentially promising applications in high density optical storage, biosensors, plasmonic nanofocusing, and so forth.
Identification of stable sources of rate-reducing resistance to Septoria lactucae in lettuce germplasm
Authors: Perdomo David Nataren , Torres Tiago Bezerra , Santos Cleberly Evangelista , Cabral Cleia Santos , Reis Ailton , Boiteux Leonardo Silva
Published: November 2022

Septoria leaf spot, caused by Septoria lactucae, is one of the major open-field diseases of lettuce (Lactuca sativa) in tropical and subtropical regions. However, there are few available studies dealing with the identification of useful sources of resistance to this disease. Here, a genetically diverse collection of 42 lettuce accessions was evaluated for Septoria leaf spot reaction under open-field conditions (natural inoculum) during the rainy season. The experimental design was randomized blocks with three replications (16 plants each). Although no immunity-like source was detected, 21 accessions displayed superior levels of rate-reducing resistance with significant lower Area Under Disease Progress Curve (AUDPC) values, encompassing seven accessions of the ‘Crispy green loose-leaf’, eight of the ‘Crispy purple loose-leaf’, two of the ‘Cos/Romaine’, two of the ‘Loose-leaf super crispy’, one accession of the ‘Butterhead’, and one accession of the ‘Iceberg’ morphotype. A subgroup of nine accessions with the highest levels of field resistance was also inoculated under greenhouse conditions with four S. lactucae isolates (collected in distinct geographic areas) in two assays at two distinct phenological stages. The cultivars ‘BRS Mediterrânea’ and ‘Vanda’ displayed lowest AUDPC values at the late vegetative/reproductive phenological phase. The remaining accessions displayed intermediate values of AUDPC, with the exception of the cultivar ‘Rubi’ (control), which exhibited moderate levels of susceptibility. The availability for lettuce breeding programs of genetic sources with higher and stable levels of resistance to S. lactucae will enable the development of more adapted commercial cultivars, increasing the sustainability of this crop across Neotropical regions.
Ultrasound-Based Nomogram for predicting the Risk of Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma
Authors: Duan Sensen , Wei Gang , Chen Songhao , Hu Xi’e , Bao Guoqiang
Published: November 2022

Background
Although Prophylactic central compartment lymph node dissection (CLND) can reduce thyroid cancer recurrence, it can also cause surgical complications. Previous studies examining this issue have focused on papillary thyroid carcinoma rather than papillary thyroid microcarcinoma (PTMC) and lacked external validation, thus limiting their clinical applications. In this research, we retrospectively assessed independent predictors to produce a nomogram that can quantify the risk of central compartment lymph node metastasis (CLNM) in patients with PTMC to determine which patients should undergo CLND.
Objective
In this study, we intend to develop and validate a machine learning-based nomogram to predict the risk of central lymph node metastasis in papillary thyroid microcarcinoma and provide surgical recommendations to clinicians.
Methods
Patients with PTMC who received cervical lymph node biopsy at the Tangdu Hospital were included in the study sets. Demographic characteristics, ultrasonography results, and biochemical indicators were assessed. Multiple logistic regression was adopted as the basis for the nomogram. Concordance index (C-index), receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA) were employed to evaluate the nomogram’s distinguishability, accuracy, and clinical availability.
Results
In our univariate logistic regression analysis, young age, large tumor size, calcification, aspect ratio ≥ 1, multifocality, indistinct lymphatic hilus, high free thyroxine (FT4), and low thyroid peroxidase antibody (TPOAb) were independent risk predictors for CLNM. Combining these predictors, the nomogram shows strong predictive capacity with C-index and accuracy of 0.784 and 0.713 in the training set and 0.779 and 0.709 in the validation set. DCA indicated that the nomogram had a well clinical application value.
Conclusions
We established a reliable, inexpensive, reproducible, and non-invasive preoperative prediction model that provides a potential tool for reducing the overtreatment of patients with PTMC.
MYOC/p.G367R mutation induces cell dysfunction of the trabecular meshwork and retina via impairment of the protein degradation mechanism
Authors: Zhu Yihua , Zhou Biting , Chen Xiaole , Yao Yihua , Zeng Yuping , Zhang Jingjin , Cao Zongfu , Ye Qin , Zhang Nanwen , Yang Juhua
Published: November 2022

MYOC mutations are the leading genetic causes of primary open-angle glaucoma (POAG). We previously identified a recurrent Gly367Arg mutant myocilin (MYOC/p.G367R) associated with juvenile open-angle glaucoma (JOAG) in a large Chinese family, but the pathogenic mechanism remains unclear. The MYOC/p.G367R carrier presented a high intraocular pressure and typic POAG phenotype, including an open anterior angle, a thinning retina nerve fiber layer, and a tubular visual field. Trabecular meshwork (TM) cell lines (iHTMCs) and primary TM cells (pHTMCs) expressing wild-type or mutant (G367R) myocilin were constructed to further verify the disease-causing roles of MYOC/p.G367R mutation in the TM. The G367R mutant had no effect on cytoskeletal arrangement or fibronectin production. Consistently, the combination of G367R-myocilin with the chaperones Grp94 and CRYAB impaired the intracellular degradation mechanism and caused aggregation of myocilin in the ER. The excessive accumulation of mutated myocilin in the ER resulted in chronic ER stress, and apoptosis. Moreover, autophagy plays an essential role in regulating the pathogenesis of MYOC mutations. Rapamycin activated autophagy and decreased intracellular myocilin accumulation. Chloroquine inhibited autophagy and promoted intracellular myocilin retention, exacerbating ER stress and oxidative stress in TM cells. Meanwhile, the retinal cell line 661W was used to study the effect of MYOC/p.G367R mutation in retinal cells. Similar to TM cells, the autophagic activity of 661W cells expressing G367R-myocilin was inhibited. In addition, MYOC/p.G367R mutation induced mitochondrial dysfunction and promoted superoxide onion generation in 661W cells. Together, our findings suggest that G367R mutant myocilin induces cell dysfunction of the TM and retina through excessive intracellular accumulation of mutant myocilin caused by impairment of protein clearance mechanisms. Furthermore, autophagy may serve as a therapeutic target to promote the degradation of mutant myocilin and alleviate cell dysfunction.
Electronic and optical spectroscopic insights into 2.3.4-trimethyl pentane conformations by long-range corrected DFT calculations, experimental low frequency Raman and IR temperature sensitivity and scaled vibrational assignment
Authors: Hachim Mouhi Eddine , Sadik Karima , Byadi Said , Tebbaai Hajar , Hamdani Naoual El , Aboulmouhajir Aziz
Published: November 2022

Conformational, spectroscopic and electronic behaviors of the 2.3.4-trimethyl pentane (2.3.4-TMP) molecule were carried out based on density functional theory DFT calculations with the long-range dispersion correction through CAM-B3LYP and WB97XD levels at aug-cc-pvtz basis set. Electronic properties of this molecule, such as HOMO-LUMO, molecular static polarizability, hyperpolarizability parameters, and molecular electrostatic surface potential (MEP) are also investigated. Deep and multiple spectroscopic investigations were used to characterize and differentiate between the stable conformers of 2.3.4-TMP. The experimental Fourier Transform infrared (FTIR) and Raman spectra were recorded. The spectral temperature sensitivity and scaled vibrational assignment for all the five lowest conformers A-E were carried out. A good correlation between experimental and calculated frequencies was observed with a standard deviation (RMS) of 4 cm-1 below 1500 cm-1 and 6 cm-1 for all other frequencies.1H and 13C NMR spectra were simulated using GIAO-WB97XD/aug-cc-pvtz in Dimethyl Sulfoxide (DMSO) solvent, and the observed results agreed well with their experimental counterparts. Electronic transitions were analyzed using TD-WB97XD/aug-cc-pvtz simulated to have the UV-Vis spectra of the five conformers.
BejaGNN: Behavior-based Java Malware Detection via Graph Neural Network
Authors: Feng Pengbin , Yang Li , Lu Di , Xi Ning , Ma Jianfeng
Published: November 2022

As a popular platform-independent language, Java is widely used in enterprise applications. In the past few years, language vulnerabilities exploited by Java malware have become increasingly prevalent, which cause threats for multi-platform. Security researchers continuously propose various approaches for fighting against Java malware programs. However, the presence of complex hidden techniques, such as code obfuscation, makes identifying complicated Java malware become challenging. Therefore, there is an urgent need to develop new approaches for resisting hidden techniques. In this paper, we present BejaGNN, a novel behavior-based Java malware detection method using static analysis, word embedding technique, and graph neural network. Specifically, BejaGNN leverages static analysis techniques to extract ICFGs from Java program files and then prunes these ICFGs to remove noisy instructions. Then, work embedding techniques are adopted to learn semantic representations for Java bytecode instructions. Finally, BejaGNN builds a graph neural network classifier to determine the maliciousness of Java programs. Experimental results on a public Java bytecode benchmark demonstrate that BejaGNN achieves high F1 98.8% and is superior to existing Java malware detection approaches, which verifies the promise of graph neural network in Java malware detection.
Statins suppress cell-to-cell propagation of α-synuclein by lowering cholesterol
Authors: Min Joo-Ok , Ho Hoang-Anh , Lee Wonjae , Jung Byung Chul , Park Sung Jun , Kim Seokjoong , Lee Seung-Jae
Published: November 2022

Cell-to-cell propagation of protein aggregates has been implicated in the progression of neurodegenerative diseases. However, the underlying mechanism and modulators of this process are not fully understood. Here, we screened a small-molecule library in a search for agents that suppress the propagation of α-synuclein and mutant huntingtin (mHtt). These screens yielded several molecules, some of which were effective against both α-synuclein and mHtt. Among these molecules, we focused on simvastatin and pravastatin. Simvastatin administration in a transgenic model of synucleinopathy effectively ameliorated behavioral deficits and α-synuclein accumulation, whereas pravastatin had no effect. Because only simvastatin enters the brain effectively, these results suggest that inhibition of brain cholesterol synthesis is important in simvastatin effects. In cultured cells, accumulation of intracellular cholesterol, induced by genetic ablation of the NPC1 gene or by pharmacological treatment with U18666A, increased α-synuclein aggregation and secretion. In contrast, lowering cholesterol using methyl-β-cyclodextrin or statins reversed α-synuclein aggregation and secretion in NPC1-knockout cells. Consistent with these observations, feeding a high-fat diet aggravated α-synuclein pathology and behavioral deficits in the preformed fibril-injected mouse model, an effect that was also reversed by simvastatin administration. These results suggest that statins suppress propagation of protein aggregates by lowering cholesterol in the brain.
Testicular cancer knowledge amongst Lebanese university students and the effect of a social media awareness campaign
Authors: Kanbar Anthony , Abdessater Maher , Khoury Joey El , Halabi Rami , Assaf Serge , Mina Anthony , Breidy Sabine , Awad Toufic , Khoury Raghid El
Published: November 2022

Background
Testicular cancer (TC) is the most common malignancy in men between 15–40 years. Testicular self-examination (TSE) leads to early diagnosis. We aimed, in this study, to evaluate the knowledge among young Lebanese male university students concerning TC and their practice of TSE. We also evaluated the use of social media (SM) for an awareness campaign.
Methods
Using an online survey, we evaluated male students' knowledge at our university and the factors associated with increased knowledge and practice of TSE. Then we conducted an entirely virtual awareness campaign using social media and an awareness video and evaluated its effect.
Results
Only 14% (N=115) had previously received awareness about TC, and 31% (N=254) previously had a testicular examination by a healthcare professional (HCP). Risk factors were identified correctly by 13% (N=160). Factors that were associated with the increased practice of TSE were medical studies (OR = 8.55, CI [3.93-19.50]), previous awareness about TC (OR=3.35, CI [1.90-5.92]), and high TC knowledge score (OR=1.38, CI [1.07-1.77]). Higher knowledge scores were associated with studying for seven years (OR=1.93, CI [1.23-3.05]) or more (OR=1.55, CI [1.09-2.19]). After the awareness campaign, 70% of the student practiced TSE, 15% talked with their HCP about TC, and 43% transmitted knowledge to others. About 4.6% of students discovered that they have risk factors for TC. The median amount of knowledge learned by the students was 8 over 10 (IQR 7-9). Most students (90%) had a good experience using social media for awareness.
Conclusions
Young university students in Lebanon have poor knowledge about TC and its risk factors. TSE is poorly practiced in non-medical students, especially in the most concerned men with risk factors. Education about TC increases the practice of TSE. The use of social media is an effective method for awareness campaigns and can improve health-related practices.
Childhood Vaccine Hesitancy in Two Regions with Different Socioeconomic Backgrounds in Turkey
Authors: SARIKAHYA Selma DURMUŞ , GÜDEN Emel , YORULMAZ Deniz Sümeyye
Published: November 2022

The authors have requested that this preprint be removed from Research Square.
Effects of Cross-linking of Rice Protein with Ferulic Acid on Digestion and Absorption of Ferulic Acid
Authors: Ling Xiao , Zhang Jiajia , Teng Jian-Wen , Huang Li , Xia Ning
Published: November 2022

Though rice proteins have been applied to improve the stability of phenolic compounds, the effects of rice proteins on the digestibility and bioavailability of phenolic acid have not been clear. This study devoted to understanding the effects of protein interaction with ferulic acid on the digestion and absorption of ferulic acid in gastrointestinal environment. Ferulic acid were formed complexes with rice proteins with and without the presence of laccase at room temperature. It was found that rice protein could protect ferulic acid from degradation in simulated oral fluid and remain stable in gastrointestinal fluids. With the hydrolysis of pepsin and pancreatin, rice protein-ferulic acid complexes degraded and released ferulic acid in gastrointestinal environment. The DPPH scavenging activity digested rice protein-ferulic acid complexed was maintained while that of digested ferulic acid was significantly decreased. Moreover, the permeability coefficient of ferulic acid was not affected by rice peptides. Thus, rice protein is a promising food matrix to protect ferulic acid in digestion tract and maintain the antioxidant functions of ferulic acid.
Limitation of life-sustaining therapies in critically-ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study
Authors: Giabicani Mikhael , Terrier Christophe Le , Poncet Antoine , Guidet Bertrand , Rigaud Jean-Philippe , Quenot Jean-Pierre , Mamzer Marie-France , Pugin Jérôme , Weiss Emmanuel , Bourcier Simon
Published: November 2022

Background: Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, timing, modalities, and factors associated with LST decisions in critically-ill COVID-19 patients.
Methods: We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions.
Results: Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3–21). Median ICU load at the patient level was 126%. Age, clinical frailty score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1–11) after LST limitations.
Conclusions: Prevalence of LST limitations in critically-ill COVID-19 patients was similar to data reported pre-pandemic and not increased by stress on ICU capacities.
A machine learning model for flank wear prediction in face milling of Inconel 718
Authors: Banda Tiyamike , Liu Yu-chen , Farid Ali Akhavan , Lim Chin Seong
Published: November 2022

Optimization of flank wear width (VB) progression during face milling of Inconel 718 is challenging due to the synergistic effect of cutting parameters on the complex wear mechanisms and failure modes. The lack of quantitative understanding between VB and the cutting conditions limits the development of the tool life extension. In this study, a Gaussian kernel ridge regression was employed to develop the VB progression model for face milling of Inconel 718 using multi-layer physical vapor deposition-TiAlN/NbN coated carbide inserts with the input feature of cutting speed, feed rate, axial depth of cut, and cutting length. The model showed a root-mean-square error of 30.9 (49.7) µm and R2 of 0.93 (0.81) in full fit (5-fold cross-validation test). The statistics along with the cross-plot analyses suggested that the model had a high predictive ability. A new promising condition at the cutting speed of 40 m/min, feed rate of 0.08 mm/tooth, and axial depth of cut of 0.9 mm was designed and experimentally validated. The measured and predicted VB agreed well with each other. This model is thus applicable for VB prediction and optimization in the real face milling operation of Inconel 718.
The standardized muscle contractive stiffness is correlated to physical performance in hospitalized older adults
Authors: Tang Xinyi , Huang Li , Yue Jirong , Qiu Li
Published: November 2022

Background
Shear wave elastography (SWE) can quantify muscle stiffness to reflect the muscle quality, and we explored the application of SWE in assessing physical performance in hospitalized older adults.
Methods
A total of 98 older adults, including 55 men and 43 women, were recruited in this cross-sectional study. Short physical performance battery (SPPB) and time-up-and-go (TUG) test were used to evaluate physical performance, and a dynamic SWE imaging for the flexor digitorum superficialis in the process of using grip strength meter was documented. The peak strength and peak shear wave velocities (SWV) were recorded, and the ratio of peak SWV to peak strength was defined as the standardized muscle contractive stiffness.
Results
For men, the peak SWV was negatively correlated to SPPB scores (r=-0.351 to -0.448, all P < 0.01) and positively correlated to TUG time (r = 0.299 to 0.369, all P < 0.05), and the standardized muscle contractive stiffness was significantly negatively correlated to SPPB scores (r== -0.501 to -0.532, all P < 0.01) and positively correlated to TUG time (r = 0.424 to 0.462, all P < 0.01). For women, the peak SWV was not correlated to physical performance, and the standardized muscle contractive stiffness was correlated to the TUG time (r = 0.312 for Cmax and 0.310 for Cmean, both P < 0.05). Those participants with decreased physical performance had significant higher standardized muscle contractive stiffness in both men and women (all P < 0.05).
Conclusion
SWE can be applied in evaluating muscle function and the muscle contractive stiffness standardized by grip strength can be a potential indicator.
The effects of photon-induced photoacoustic streaming during root canal treatment of symptomatic irreversible pulpitis: a randomized clinical trial.
Authors: Wu Shengxuan , Chen Minle , Zhao Jian , Li Yang , Wen Cheng , Yang Li , Jiang Qianzhou
Published: November 2022

Objectives

The authors of this study aimed to evaluate the effects of photon-induced photoacoustic streaming (PIPS) on antibacterial activity, residual pulp removal and postoperative pain in teeth with symptomatic irreversible pulpitis during root canal treatment (RCT).

Materials and Methods

In this superiority randomized clinical trial (ClinicalTrials.gov ID: ChiCTR2000037446), sixty patients with symptomatic irreversible pulpitis in need of RCT were selected. After preparation, they were randomly assigned into two groups according to final irrigation protocol: conventional needle irrigation (CNI) or PIPS. Bacterial suspensions in root canals were assessed using an Adenosine 5'-triphosphate (ATP) assay kit. The effect of root canal irrigation on residual pulp removal was evaluated by NaOCl-induced bubble formation. Patients were asked to register their pain intensity in the visual analogue scale (VAS) document after 1-day and 7-day intervals.

Results

Compared to CNI group, PIPS irrigation showed a greater antibacterial efficacy than the CNI group (P = 0.046). And the PIPS irrigation significantly reduced the NaOCl-induced bubble count(P<0.001). On Day 1 post operation, pain intensity was significantly lower in the PIPS group (0.34 ± 0.75) compared to the CNI group (1.24 ± 1.27) (P = 0.004). NaOCl-induced bubble count showed statistically correlated to the maximum postoperative pain on Day 1 (P<0.001), while the ATP values seemed not to be statistically correlated to the intensity of postoperative pain (P = 0.684).

Conclusions

Irrigation with 1% NaOCl delivered with PIPS could decrease bacterial levels, enhance root canal cleaning effect and lessen postoperative pain after root canal preparation.

Clinical Relevance

The PIPS is a safe and effective final irrigation protocol for teeth with symptomatic irreversible pulpitis during RCT.