bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and influential factors of isolated hepatitis B core antibody positivity in a Chinese adult population
Authors: Wang Chengwei , Li Xiaoqin , Zhang Chuanmeng , Xiao Li , Xian Jianchun
Published: January 2024

Isolated anti-HBc (IAHBc) is defined by the presence of anti-HBc in the absence of HBsAg and hepatitis B surface antibody (anti-HBs). IAHBc is of great clinical significance as a specific pattern of HBV infection, but IAHBc has not been fully clarified. This study aimed to explore the prevalence and influential factors of IAHBc from routine examination results of inpatients.A total of 61,247 individuals were included in the study, with a median age of 55 years (range: 43–68), and a male-to-female ratio of 0.90:1. The prevalence of current HBV infection (HBsAg positive) was 6.82%, while the prevalence of previous HBV infection (HBsAg negative but anti-HBc positive) was 48.63%. The prevalence of IAHBc was 12.31%. Among them, the rates for males were 7.10%, 52.16%, and 13.70%, respectively, which were significantly higher than the rates for females at 6.56%, 45.45%, and 11.06% (P < 0.05). The prevalence rates mentioned above were significantly reduced after vaccination (P < 0.05). The prevalence of IAHBc increases with age, rising from 0.23% in the age group of 15–29 years to 13.57% in individuals aged 80 and above. After the age of 50, the prevalence of IAHBc closely parallels the previous infection rate but shows no significant association with the current infection rate (P > 0.05). Among IAHBc individuals, approximately 33.83% tested positive for anti-HBe, and their anti-HBc absorbance values were significantly higher compared to anti-HBe negative individuals (7.08 and 5.31, P < 0.01). The prevalence of anti-HBe positivity among IAHBc individuals does not vary with changes in the previous infection rate and age (P > 0.05).
ROR2 expression predicts human induced pluripotent stem cell differentiation into neural stem/progenitor cells and GABAergic neurons
Authors: Kuroda Takuya , Yasuda Satoshi , Matsuyama Satoko , Miura Takumi , Sawada Rumi , Matsuyama Akifumi , Yamamoto Yumiko , Morioka Masaki Suimye , Kawaji Hideya , Kasukawa Takeya , Itoh Masayoshi , Akutsu Hidenori , Kawai Jun , Sato Yoji
Published: January 2024

Despite the development of various in vitro differentiation protocols for the efficient derivation of specific cell types, human induced pluripotent stem cell (hiPSC) lines have varing ability to differentiate into specific lineages. Therefore, surrogate markers for accurately predicting the differentiation propensity of hiPSC lines may facilitate cell-based therapeutic product development and manufacture. We attempted to identify marker genes that could predict the differentiation propensity of hiPSCs into neural stem/progenitor cells (NS/PCs). Using Spearman’s rank correlation coefficients, we investigated genes in the undifferentiated state, the expression levels of which were significantly correlated with the neuronal differentiation propensity of several hiPSC lines. Among genes significantly correlated with NS/PC differentiation (P < 0.01), we identified ROR2 as a novel predictive marker. ROR2 expression in hiPSCs was negatively correlated with NS/PC differentiation tendency, regardless of the differentiation method, whereas its knockdown enhanced differentiation. ROR2 regulates NS/PC differentiation, suggesting that ROR2 is functionally essential for NS/PC differentiation. Selecting cell lines with relatively low ROR2 expression facilitated identification of hiPSCs that can differentiate into NS/PCs. Cells with ROR2 knockdown showed increased efficiency of differentiation into forebrain GABAergic neurons compared to controls. These findings suggest that ROR2 is a surrogate marker for selecting hiPSC lines appropriate for NS/PC and GABAergic neuronal differentiations.
Clinical significance of preoperative CALLY index for prognostication in patients with esophageal squamous cell carcinoma undergoing surgery
Authors: Feng Jifeng , Wang Liang , Yang Xun , Chen Qixun
Published: January 2024

The C-reactive protein-albumin-lymphocyte (CALLY) index has been identified as a useful and sensitive predictive tool for stratification in cancers. This investigation aimed to validate the prognostic ability of CALLY in esophageal squamous cell carcinoma (ESCC). Clinical characteristics of 318 patients with ESCC who underwent radical excision were gathered and analyzed retrospectively. A restricted cubic spline (RCS) model was used to determine an ideal threshold of CALLY due to the non-linear relation. To investigate the predictors, Cox hazard regression analysis was used. The recursive partitioning analysis (RPA), a method of risk categorization, was also developed for prognostic prediction. The receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were used to distinguish from the traditional TNM stage. Patients were compared by groups according to the optimal threshold of CALLY index, which was depicted by the non-linear relation between the cancer-specific survival (CSS) and CALLY index (P < 0.0001). Compared to those with high CALLY index, patients with low CALLY index experienced significantly worse 5-year CSS (21.8% vs. 62.6%, P < 0.001). At different TNM stages, patients with high CALLY index also had better 5-year CSS (I: P = 0.029; II: P < 0.001; III: P < 0.001) in subgroup analyses. The hazard ratio for CSS was 0.368 and CALLY index was an independent predictive factor (P < 0.001). Using TNM stage and CALLY-based RPA algorithms, a new staging was created. The RPA model considerably outperformed the TNM classification for prognostication using ROC (P < 0.001). The DCA also demonstrated that the new model outperformed the TNM stage with significantly improved accuracy for CSS. The prognostic value of CALLY in ESCC undergoing radical resection was initially determined in this study. CALLY was substantially related to prognosis and might be utilized in conjunction with TNM to evaluate ESCC prior to surgery.
Transport and retention of silica nanoparticles in glass-bead columns: effects of particle size, type, and concentration of ionic species
Authors: Daneshfar Reza , Ashoori Siavash , Soltani Soulgani Bahram
Published: January 2024

Silica nanoparticles (SiO2NPs) have garnered substantial attention as versatile additives in saline fluids, finding application in areas like environmental remediation, wastewater treatment, enhanced oil recovery, and carbon geo-sequestration. Despite their potential, the intricate interaction between electrolyzed nanoparticles and porous media remains inadequately researched in these contexts. This study delves into the pivotal yet underexplored aspect of silica nanoparticle absorption behavior within porous media, a key determinant of their practical effectiveness. The research focuses on silica particles with dimensions of 10 nm and 50 nm, synthesized via hydrolysis and condensation of tetraethyl orthosilicate (TEOS) in methanol. Employing packed glass bead columns as a surrogate for porous media, the study unravels the complex mechanisms governing nanoparticle transport and deposition. Comprehensive investigations encompass variations in particle sizes, ionic strength, and ionic species, resulting in the examination of 48 distinct flooding scenarios. UV/Vis spectrophotometry is used to quantify nanoparticle concentrations in effluents, elucidating their transport behavior within the porous media. Concurrently, pressure drop alterations across the media serve as indicators of particle plugging and changes in permeability. Intriguingly, specific conditions involving a nanofluid comprising 50 nm silica nanoparticles and 10,000 ppm of magnesium chloride exhibit pronounced permeability reduction, offering potential insights for optimizing applications. Particularly noteworthy is the unique reduction in silica particle retention on glass bead surfaces as salinity increases, especially in the presence of magnesium sulfate. A concentration of 5000 ppm magnesium sulfate induces a log-jamming mechanism, resulting in an amplified final-to-intermediate permeability ratio. Experimental outcomes align with observations from scanning electron microscopy, improving understanding of porous media retention mechanisms. This study contributes to a deeper understanding of interactions between nanoparticles and porous media, paving the way for enhanced application strategies.
The association between metabolic syndrome and major adverse cardiac and cerebrovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention
Authors: Hosseini Kaveh , Khalaji Amirmohammad , Behnoush Amir Hossein , Soleimani Hamidreza , Mehrban Saghar , Amirsardari Zahra , Najafi Kimia , Fathian Sabet Mehrshad , Hosseini Mohammadi Negin Sadat , Shojaei Shayan , Masoudkabir Farzad , Aghajani Hassan , Mehrani Mehdi , Razjouyan Hadie , Hernandez Adrian V.
Published: January 2024

Metabolic syndrome (MetS) poses an additional risk for the development of coronary artery disease and major adverse cardiac and cerebrovascular events (MACCE). In this study, we investigated the association between MetS and its components and MACCE after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). The presence of MetS was calculated at baseline using the NCEP-ATP III criteria. The primary outcome was MACCE and its components were secondary outcomes. Unadjusted and adjusted Cox Regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) of the association between MetS or its components and MACCE and its components. A total of 13,459 ACS patients who underwent PCI (MetS: 7939 and non-MetS: 5520) with a mean age of 62.7 ± 11.0 years (male: 72.5%) were included and median follow-up time was 378 days. Patients with MetS had significantly higher MACCE risk (adjusted HR [aHR] 1.22, 95% CI 1.08–1.39). The only component of MACCE that exhibited a significantly higher incidence in MetS patients was myocardial infarction (aHR 1.43, 95% CI 1.15–1.76). MetS components that were significantly associated with a higher incidence of MACCE were hypertension and impaired fasting glucose. Having three MetS components did not increase MACCE (aHR 1.12, 95% CI 0.96–1.30) while having four (aHR 1.32, 95% CI 1.13–1.55) or five (aHR 1.42, 95% CI 1.15–1.75) MetS components was associated with a higher incidence of MACCE. MetS was associated with a higher risk of MACCE in ACS patients undergoing PCI. Among MACCE components, myocardial infarction was significantly higher in patients with MetS. Impaired fasting glucose and hypertension were associated with a higher risk of MACCE. Identifying these patterns can guide clinicians in choosing appropriate preventive measures.
Imaging study of coccygeal morphology in adolescent idiopathic scoliosis
Authors: Zhang Haoyang , Pan Yingsen , Ju Chenhao , Shen Yi , Li Xiaoming , Ye Xin , Fan Binghua , Li Shuailin , Jiang Yongliang , Yao Benshun , Ying Xiaoming
Published: January 2024

The correlation between scoliosis and sagittal curvature of the cervical, thoracic, and lumbar spine have already been reported in previous studies. However, as a part of the spine, the change in coccygeal morphology in AIS patients has not yet been studied. In this study, a retrospective analysis was performed on 400 patients who were divided into a non-scoliotic group (206 patients) and an AIS group (194 patients). The Postacchini coccygeal radiological classification that was modified by Nathan was used to observe and compare the sagittal coccygeal morphology between the two groups. The results showed that the non-scoliotic group had the highest percentage (52.4%) of patients with type I and the lowest (3.4%) proportion of patients with type V; moreover, the AIS group had the highest percentage (69.1%) of patients with type I and the lowest (1.5%) proportion of patients with type V. The coccygeal morphology was significantly different between the non-scoliotic group and the AIS group (P = 0.001). No significant differences in coccygeal morphology were found between the males and females in the two groups (mild and moderate scoliosis and different segmental scoliosis). In addition, a significant correlation between coccygeal morphology and scoliosis (P = 0.035) was found. In conclusion, coccygeal morphology significantly differs between AIS patients and non-scoliotic adolescents. There was a smaller proportion of patients with a type I coccyx and a larger proportion of patients with a type II or type III coccyx in the AIS group than in the non-scoliotic group. In other words, the presence of a more pronounced coccygeal curve in AIS patients may be caused by an incorrect sitting position and an imbalance in the contraction of the pelvic muscles. It should be further studied whether correcting the sitting position and muscular imbalances could change coccygeal morphology and subsequently affect the development of AIS.
Non-contrast ultrasound image analysis for spatial and temporal distribution of blood flow after spinal cord injury
Authors: Routkevitch Denis , Soulé Zoe , Kats Nicholas , Baca Emily , Hersh Andrew M. , Kempski-Leadingham Kelley M. , Menta Arjun K. , Bhimreddy Meghana , Jiang Kelly , Davidar A. Daniel , Smit Constantin , Theodore Nicholas , Thakor Nitish V. , Manbachi Amir
Published: January 2024

Ultrasound technology can provide high-resolution imaging of blood flow following spinal cord injury (SCI). Blood flow imaging may improve critical care management of SCI, yet its duration is limited clinically by the amount of contrast agent injection required for high-resolution, continuous monitoring. In this study, we aim to establish non-contrast ultrasound as a clinically translatable imaging technique for spinal cord blood flow via comparison to contrast-based methods and by measuring the spatial distribution of blood flow after SCI. A rodent model of contusion SCI at the T12 spinal level was carried out using three different impact forces. We compared images of spinal cord blood flow taken using both non-contrast and contrast-enhanced ultrasound. Subsequently, we processed the images as a function of distance from injury, yielding the distribution of blood flow through space after SCI, and found the following. (1) Both non-contrast and contrast-enhanced imaging methods resulted in similar blood flow distributions (Spearman’s ρ = 0.55, p < 0.0001). (2) We found an area of decreased flow at the injury epicenter, or umbra (p < 0.0001). Unexpectedly, we found increased flow at the periphery, or penumbra (rostral, p < 0.05; caudal, p < 0.01), following SCI. However, distal flow remained unchanged, in what is presumably unaffected tissue. (3) Finally, tracking blood flow in the injury zones over time revealed interesting dynamic changes. After an initial decrease, blood flow in the penumbra increased during the first 10 min after injury, while blood flow in the umbra and distal tissue remained constant over time. These results demonstrate the viability of non-contrast ultrasound as a clinical monitoring tool. Furthermore, our surprising observations of increased flow in the injury periphery pose interesting new questions about how the spinal cord vasculature reacts to SCI, with potentially increased significance of the penumbra.
Tick-borne pathogens in questing adults Dermacentor reticulatus from the Eastern European population (north-eastern Poland)
Authors: Kubiak Katarzyna , Szymańska Hanna , Dziekońska-Rynko Janina , Tylkowska Agnieszka , Dmitryjuk Małgorzata , Dzika Ewa
Published: January 2024

Dermacentor reticulatus is tick species with an expanding geographical range in Europe, which creates the possibility of spreading microorganisms of significant veterinary and medical importance. The study aimed to investigate the prevalence and genetic diversity of Rickettsia spp., Babesia spp., Borrelia spp. and Anaplasma phagocytophilum in adult D. reticulatus ticks from the Eastern European population in the urban and the natural biotopes of north-eastern Poland. Microorganisms were detected by PCR and identified by DNA sequencing. The overall infection rate of at least one of the pathogens was 29.6%. The predominantly was Rickettsia spp. (27.1%) (with R. raoultii—9.1%) followed by Babesia spp. (2.4%) with B. canis (1.5%) as the most frequent. Based on 18S rRNA gene sequence, three B. canis genotypes were revealed. The prevalence of R. raoultii and B. canis was significantly higher in ticks from natural biotopes. The infection rates of B. afzelii and A. phagocytophilum were determined at 0.9% and 0.3%, respectively. Co-infections were detected in 3.8% of infected ticks. In diagnosing tick-borne diseases in humans, tick-borne lymphadenopathy should not be excluded. The prevalence of different genotypes of B. canis suggests differences in the clinical picture of canine babesiosis in the area.
Serine/threonine kinase 36 induced epithelial-mesenchymal transition promotes docetaxel resistance in prostate cancer
Authors: He Tao , Li Nan-Xing , Pan Zhao-Jun , Zou Zi-Hao , Chen Jie-Chuan , Yu Si-Zhe , Lv Fa , Xie Quan-Cheng , Zou Jun
Published: January 2024

To investigate the role and potential mechanism of serine/threonine kinase 36 (STK36) in docetaxel resistance-prostate cancer (PCa). The expression of STK36 in PCa and the correlation with clinicopathological characteristics of PCa patients were analyzed using the data from different databases and tissue microarrays. To investigate the role of STK36 on cell proliferation, invasion, and migration, STK36 was overexpressed and silenced in DU-145 and PC-3 cell lines. Cell counting kit-8 (CCK8) was used to test cell proliferation. Cell invasion and migration were detected by cell wound scratch assay and trans well, respectively. The expression profile of STK36, E-Cadherin, and Vimentin was analyzed by Western blot. Cell apoptosis was detected by the TUNEL assay. STK36 expression was upregulated in PCa tissue compared with adjacent benign PCa tissue; it was higher in patients with advanced stages compared with lower stages and was significantly correlated with decreased overall survival. Up-regulation of STK36 significantly promoted the proliferation, invasion, and migration of DU-145 and PC-3 cells and compensated for the suppression caused by docetaxel treatment in vitro. A striking apoptosis inhibition could be observed when dealing with docetaxel, although the apoptosis of DU-145 and PC-3 cells was not affected by the STK36 exclusive overexpression. Besides, E-Cadherin expression was restrained while the expression levels of vimentin were all enhanced. The knockdown of STK36 reversed the above process. STK36 up-regulation could accelerate the biological behavior and docetaxel resistance of PCa by epithelial-mesenchymal transition (EMT) activation. STK36 may be potentially used as a target in PCa resolvent with docetaxel.
Declining hip fracture burden in Sweden 1998–2019 and consequences for projections through 2050
Authors: Michaëlsson Karl , Baron John A. , Byberg Liisa , Larsson Susanna C. , Melhus Håkan , Gedeborg Rolf
Published: January 2024

We aimed to estimate the absolute and age-standardized number of hip fractures in Sweden during the past two decades to produce time trends and future projections. We used nationwide register data from 1998 to 2019 and a validated algorithm to calculate the annual absolute and age-standardized number of incident hip fractures over time. The total hip fracture burden was 335,399 incident events over the 22 years, with a change from 16,180 in 1998 to 13,929 in 2019, a 14% decrease. One decade after the index hip fracture event, 80% of the patients had died, and 11% had a new hip fracture. After considering the steady growth of the older population, the decline in the age-standardized number of hip fractures from 1998 through 2019 was 29.2% (95% CI 28.1–30.2%) in women and 29.3% (95% CI 27.5–30.7%) in men. With a continued similar reduction in hip fracture incidence, we can predict that 14,800 hip fractures will occur in 2034 and 12,000 in 2050 despite doubling the oldest old (≥ 80 years). Without an algorithm, a naïve estimate of the total number of hip fractures over the study period was 539,947, with a second 10-year hip fracture risk of 35%. We note an ongoing decline in the absolute and age-standardized actual number of hip fractures in Sweden, with consequences for future projections.
Apalutamide versus bicalutamide in combination with androgen deprivation therapy for metastatic hormone sensitive prostate cancer
Authors: Ueda Takashi , Shiraishi Takumi , Miyashita Masatsugu , Kayukawa Naruhiro , Gabata Yusuke , Sako Satoshi , Ogura Ryota , Fujihara Atsuko , Okihara Koji , Ukimura Osamu
Published: January 2024

The objective of this study is to compare the efficacy of apalutamide and bicalutamide in combination with androgen deprivation therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We retrospectively collected the data of about 330 patients with metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and August 2023. Sixty-one patients were administered apalutamide (240 mg/day) with androgen deprivation therapy (group A), and 269 patients were administered bicalutamide (80 mg/day) with androgen deprivation therapy (group B). Propensity score matching was used to adjust for clinical background factors between the two groups. PSA progression-free survival and overall survival were significantly longer in group A than in group B among the matched patients. Apalutamide therapy was a significant independent factor for OS in matched patients. The second progression-free survival of group A was significantly longer than that of group B in matched patients. Patients treated with apalutamide achieved ≥ 90% PSA decline from baseline faster and in larger numbers than those with bicalutamide. Apalutamide combined with ADT may be superior to bicalutamide alone in terms of OS and PSA-PFS in patients with mHSPC.
The death rate of COVID-19 infection in different SARS-CoV-2 variants was related to C-reactive protein gene polymorphisms
Authors: Sadeghi Mofrad Sahar , Boozarjomehri Amnieh Shayan , Pakzad Mohammad Reza , Zardadi Mina , Ghazanfari Jajin Morteza , Anvari Enayat , Moghaddam Sina , Fateh Abolfazl
Published: January 2024

The serum level of C-reactive protein (CRP) is a significant independent risk factor for Coronavirus disease 2019 (COVID-19). A link was found between serum CRP and genetic diversity within the CRP gene in earlier research. This study examined whether CRP rs1205 and rs1800947 polymorphisms were associated with COVID-19 mortality among various severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) variants. We genotyped CRP rs1205 and rs1800947 polymorphisms in 2023 deceased and 2307 recovered patients using the polymerase chain reaction-restriction fragment length polymorphism method. There was a significant difference between the recovered and the deceased patients in terms of the minor allele frequency of CRP rs1205 T and rs1800947 G. In all three variants, COVID-19 mortality rates were associated with CRP rs1800947 GG genotype. Furthermore, CRP rs1205 CC and rs1800947 GG genotypes showed higher CRP levels. It was found that the G-T haplotype was prevalent in all SARS-CoV-2 variants. The C–C and C–T haplotypes were statistically significant in Delta and Omicron BA.5 variants, respectively. In conclusion, polymorphisms within the CRP gene may relate to serum CRP levels and mortality among COVID-19 patients. In order to verify the utility of CRP polymorphism correlation in predicting COVID-19 mortality, a replication of these results is needed.
Real-time fluorescence-guided adhesiolysis with indocyanine green in intra-abdominal surgery (with video)
Authors: Chen Qiangxing , Cai Yu , Cheng Ke , Chen Zixin , Li Jun , Wu Shangdi , Peng Bing
Published: January 2024

Intra-abdominal adhesions have consistently posed a challenge for surgeons during procedures. This study aims to investigate the feasibility of utilizing indocyanine green (ICG) in conjunction with near-infrared imaging for the detection of intra-abdominal adhesions. In vitro, we analyzed factors affecting ICG fluorescence. We divided SD rats into groups to study ICG excretion in different digestive tract regions. Additionally, we reviewed surgical videos from previous cholecystectomy cases, categorizing them by ICG injection timing and assessing fluorescence imaging in various digestive tract regions. Finally, we preoperatively injected ICG into two cholecystectomized patients with abdominal adhesions, guiding intraoperative adhesiolysis with near-infrared fluorescence imaging. In vitro, we observed a significant influence of protein and ICG concentrations on ICG fluorescence intensity. Our rat experiments unveiled a strong and highly significant correlation (Kendall’s tau-b = 1, P < 0.001) between the timing of ICG injection and the farthest point of intestinal fluorescence. A retrospective case analysis further validated this finding (Kendall’s tau-b = 0.967, P < 0.001). Under the guidance of fluorescence navigation, two cholecystectomized patients with intra-abdominal adhesions successfully underwent adhesiolysis, and no postoperative complications occurred. The intraoperative combination of ICG with near-infrared fluorescence imaging effectively enhances the visibility of the liver, bile ducts, and various segments of the gastrointestinal tract while providing real-time navigation. This real-time fluorescence guidance has the potential to aid surgeons in the dissection of intra-abdominal adhesions.
An experimental and numerical study of the strength development of layered cemented tailings backfill
Authors: Chiloane Nhleko Monique , Sengani Fhatuwani , Mulenga Francois
Published: January 2024

The behaviour of a stratified backfilled stope in terms of strength development and stress distribution has not been well established in the field of rock engineering. Yet, the mining industries with massive ore bodies are looking into high production with a high standard of safety which is mainly governed by large excavation with backfill as a support system. It is difficult to fill these large excavations at one time. Therefore, a subsequent backfilling of the stope layer by layering is adopted, which results in a layered backfill structure. The purpose of this study was to explore the strength development, stress distribution and deformation across the stope supported by both layered and non-layered backfill. It has been observed that the backfill support system gain its strength with time, however, the layered backfill support system loses its strength when more layers are introduced, this is due to the shearing effect around the interfaces of the backfill layers. The impact of layering was validated by 3D numerical simulation. It is therefore concluded that non layered backfill support system are more suitable for stoping mining methods rather than layered support system.
Machine learning models for early prediction of potassium lowering effectiveness and adverse events in patients with hyperkalemia
Authors: Huang Wei , Zhu Jian-Yong , Song Cong-Ying , Lu Yuan-Qiang
Published: January 2024

The aim of this study was to develop a model for early prediction of adverse events and treatment effectiveness in patients with hyperkalemia. We collected clinical data from patients with hyperkalemia in the First Hospital of Zhejiang University School of Medicine between 2015 and 2021. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to analyze the predictors on the full dataset. We randomly divided the data into a training group and a validation group, and used LASSO to filter variables in the training set. Six machine learning methods were used to develop the models. The best model was selected based on the area under the curve (AUC). Shapley additive exPlanations (SHAP) values were used to explain the best model. A total of 1074 patients with hyperkalemia were finally enrolled. Diastolic blood pressure (DBP), breathing, oxygen saturation (SPO2), Glasgow coma score (GCS), liver disease, oliguria, blood sodium, international standardized ratio (ISR), and initial blood potassium were the predictors of the occurrence of adverse events; peripheral edema, estimated glomerular filtration rate (eGFR), blood sodium, actual base residual, and initial blood potassium were the predictors of therapeutic effect. Extreme gradient boosting (XGBoost) model achieved the best performance (adverse events: AUC = 0.87; therapeutic effect: AUC = 0.75). A model based on clinical characteristics was developed and validated with good performance.
EPYC functions as a novel prognostic biomarker for pancreatic cancer
Authors: Yang Zhen , Li Honglin , Hao Jie , Mei Hanwei , Qiu Minghan , Wang Huaqing , Gao Ming
Published: January 2024

Pancreatic cancer (PC) has become a worldwide challenge attributed to its difficult early diagnosis and rapid progression. Treatments continue to be limited besides surgical resection. Hence, we aimed to discover novel biological signatures as clinically effective therapeutic targets for PC via the mining of public tumor databases. We found that epiphycan (EPYC) could function as an independent risk factor to predict the poor prognosis in PC based on integrated bioinformatics analysis. We downloaded associated PC data profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) online websites, then applied the software Rstudio to filter out genes under the strict criteria. After the batch survival analysis using Log-rank test and univariate cox regression, we obtained 39 candidate genes. Subsequently, we narrowed the scope to 8 genes by establishing a Lasso regression model. Eventually, we focused on 2 genes (EPYC and MET) by further building a multivariate cox regression model. Given that the role of EPYC in PC remains obscure, we then performed a series of molecular functional experiments, including RT-qPCR, CCK8, EdU, colony formation, Transwell, western blot, cell live-dead staining, subcutaneous tumor formation, to enhance our insight into its underlying molecular mechanisms. The above results demonstrated that EPYC was highly expressed in PC cell lines and could promote the proliferation of PCs via PI3K-AKT signaling pathway in vivo and in vitro. We arrived at a conclusion that EPYC was expected to be a biological neo-biomarker for PC followed by being a potential therapeutic target.
Effects of AST-120 on mortality in patients with chronic kidney disease modeled by artificial intelligence or traditional statistical analysis
Authors: Lee Chia-Lin , Liu Wei‑Ju , Tsai Shang-Feng
Published: January 2024

Chronic kidney disease (CKD) imposes a substantial burden, and patient prognosis remains grim. The impact of AST-120 (AST-120) on the survival of CKD patients lacks a consensus. This study aims to investigate the effects of AST-120 usage on the survival of CKD patients and explore the utility of artificial intelligence models for decision-making. We conducted a retrospective analysis of CKD patients receiving care in the pre-end-stage renal disease (ESRD) program at Taichung Veterans General Hospital from 2000 to 2019. We employed Cox regression models to evaluate the relationship between AST-120 use and patient survival, both before and after propensity score matching. Subsequently, we employed Deep Neural Network (DNN) and Extreme Gradient Boosting (XGBoost) models to assess their performance in predicting AST-120's impact on patient survival. Among the 2584 patients in our cohort, 2199 did not use AST-120, while 385 patients received AST-120. AST-120 users exhibited significantly lower mortality rates compared to non-AST-120 users (13.51% vs. 37.88%, p < 0.0001) and a reduced prevalence of ESRD (44.16% vs. 53.17%, p = 0.0005). Propensity score matching at 1:1 and 1:2 revealed no significant differences, except for dialysis and all-cause mortality, where AST-120 users exhibited significantly lower all-cause mortality (p < 0.0001), with a hazard ratio (HR) of 0.395 (95% CI = 0.295–0.522). This difference remained statistically significant even after propensity matching. In terms of model performance, the XGBoost model demonstrated the highest accuracy (0.72), specificity (0.90), and positive predictive value (0.48), while the logistic regression model showed the highest sensitivity (0.63) and negative predictive value (0.84). The area under the curve (AUC) values for logistic regression, DNN, and XGBoost were 0.73, 0.73, and 0.69, respectively, indicating similar predictive capabilities for mortality. In this cohort of CKD patients, the use of AST-120 is significantly associated with reduced mortality. However, the performance of artificial intelligence models in predicting the impact of AST-120 is not superior to statistical analysis using the current architecture and algorithm.
Synergistic observation of FY-4A&4B to estimate CO concentration in China: combining interpretable machine learning to reveal the influencing mechanisms of CO variations
Authors: Chen Bin , Hu Jiashun , Wang Yixuan
Published: January 2024

Accurately estimating the concentration of carbon monoxide (CO) with high spatiotemporal resolution is crucial for assessing its meteorological-environmental-health impacts. Although machine learning models have high predictive ability in environmental research, there are relatively few explanations for model outputs. Utilizing the top-of-atmosphere radiation data of China’s new generation geostationary satellites (FY-4A and FY-4B) and interpretable machine learning models, the 24-hour near-surface CO concentrations in China was conducted (resolution: 1 hour, 0.04°). The model improved by 6.6% when using the all-sky dataset (cloud-contained model, R2 = 0.759) compared to the clear-sky dataset (cloud-removed model). The interpretability analysis of the CO estimation model used two methods, namely ante-hoc (model feature importance) and post-hoc (SHapley Additive exPlanations). The importance of daytime meteorological factors increased by 51% compared to nighttime. Combining partial dependency plots, the impact of key meteorological factors on CO was elucidated to gain a deeper understanding of the spatiotemporal variations of CO.
Role of PLK1/NUMB/NOTCH in epithelial-mesenchymal transition in human melanoma
Authors: Chhabra Gagan , Singh Chandra K. , Ndiaye Mary A. , Su Shengqin , Shirley Carl A. , Ahmad Nihal
Published: January 2024

Polo-like kinase 1 (PLK1), a serine/threonine kinase, is overexpressed in melanoma and its expression has been associated with poor disease prognosis. PLK1 has been shown to interact with NUMB, a NOTCH antagonist. However, the exact role of PLK1, NUMB, and NOTCH signaling in epithelial-mesenchymal transition (EMT) in melanoma progression is unclear. In this study, Affymetrix microarray analysis was performed to determine differentially expressed genes following shRNA-mediated knockdown of PLK1 in human melanoma cells that showed significant modulations in EMT and metastasis-related genes. Using multiple PLK1-modulated melanoma cell lines, we found that PLK1 is involved in the regulation of cell migration, invasion, and EMT via its kinase activity and NOTCH activation. In vitro kinase assay and mass spectrometry analysis demonstrated a previously unknown PLK1 phosphorylation site (Ser413) on NUMB. Overexpression of non-phosphorylatable (S413A) and phosphomimetic (S413D) mutants of NUMB in melanoma cells implicated the involvement of NUMB-S413 phosphorylation in cell migration and invasion, which was independent of NOTCH activation. To determine the clinical relevance of these findings, immunohistochemistry was performed using melanoma tissue microarray, which indicated a strong positive correlation between PLK1 and N-cadherin, a protein required for successful EMT. These findings were supported by TCGA analysis, where expression of high PLK1 with low NUMB or high NOTCH or N-cadherin showed a significant decrease in survival of melanoma patients. Overall, these results suggest a potential role of PLK1 in EMT, migration, and invasion of melanoma cells. Our findings support the therapeutic targeting of PLK1, NUMB, and NOTCH for melanoma management.
Artificial intelligence-enabled ECG for left ventricular diastolic function and filling pressure
Authors: Lee Eunjung , Ito Saki , Miranda William R. , Lopez-Jimenez Francisco , Kane Garvan C. , Asirvatham Samuel J. , Noseworthy Peter A. , Friedman Paul A. , Carter Rickey E. , Borlaug Barry A. , Attia Zachi I. , Oh Jae K.
Published: January 2024

Assessment of left ventricular diastolic function plays a major role in the diagnosis and prognosis of cardiac diseases, including heart failure with preserved ejection fraction. We aimed to develop an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to identify echocardiographically determined diastolic dysfunction and increased filling pressure. We trained, validated, and tested an AI-enabled ECG in 98,736, 21,963, and 98,763 patients, respectively, who had an ECG and echocardiographic diastolic function assessment within 14 days with no exclusion criteria. It was also tested in 55,248 patients with indeterminate diastolic function by echocardiography. The model was evaluated using the area under the curve (AUC) of the receiver operating characteristic curve, and its prognostic performance was compared to echocardiography. The AUC for detecting increased filling pressure was 0.911. The AUCs to identify diastolic dysfunction grades ≥1, ≥2, and 3 were 0.847, 0.911, and 0.943, respectively. During a median follow-up of 5.9 years, 20,223 (20.5%) died. Patients with increased filling pressure predicted by AI-ECG had higher mortality than those with normal filling pressure, after adjusting for age, sex, and comorbidities in the test group (hazard ratio (HR) 1.7, 95% CI 1.645–1.757) similar to echocardiography and in the indeterminate group (HR 1.34, 95% CI 1.298–1.383). An AI-enabled ECG identifies increased filling pressure and diastolic function grades with a good prognostic value similar to echocardiography. AI-ECG is a simple and promising tool to enhance the detection of diseases associated with diastolic dysfunction and increased diastolic filling pressure.
Genetic effects on variability in visual aesthetic evaluations are partially shared across visual domains
Authors: Bignardi Giacomo , Smit Dirk J. A. , Vessel Edward A. , Trupp MacKenzie D. , Ticini Luca F. , Fisher Simon E. , Polderman Tinca J. C.
Published: January 2024

The aesthetic values that individuals place on visual images are formed and shaped over a lifetime. However, whether the formation of visual aesthetic value is solely influenced by environmental exposure is still a matter of debate. Here, we considered differences in aesthetic value emerging across three visual domains: abstract images, scenes, and faces. We examined variability in two major dimensions of ordinary aesthetic experiences: taste-typicality and evaluation-bias. We build on two samples from the Australian Twin Registry where 1547 and 1231 monozygotic and dizygotic twins originally rated visual images belonging to the three domains. Genetic influences explained 26% to 41% of the variance in taste-typicality and evaluation-bias. Multivariate analyses showed that genetic effects were partially shared across visual domains. Results indicate that the heritability of major dimensions of aesthetic evaluations is comparable to that of other complex social traits, albeit lower than for other complex cognitive traits. The exception was taste-typicality for abstract images, for which we found only shared and unique environmental influences. Our study reveals that diverse sources of genetic and environmental variation influence the formation of aesthetic value across distinct visual domains and provides improved metrics to assess inter-individual differences in aesthetic value.
σE of Streptomyces coelicolor can function both as a direct activator or repressor of transcription
Authors: Pospíšil Jiří , Schwarz Marek , Ziková Alice , Vítovská Dragana , Hradilová Miluše , Kolář Michal , Křenková Alena , Hubálek Martin , Krásný Libor , Vohradský Jiří
Published: January 2024

σ factors are considered as positive regulators of gene expression. Here we reveal the opposite, inhibitory role of these proteins. We used a combination of molecular biology methods and computational modeling to analyze the regulatory activity of the extracytoplasmic σE factor from Streptomyces coelicolor. The direct activator/repressor function of σE was then explored by experimental analysis of selected promoter regions in vivo. Additionally, the σE interactome was defined. Taken together, the results characterize σE, its regulation, regulon, and suggest its direct inhibitory function (as a repressor) in gene expression, a phenomenon that may be common also to other σ factors and organisms.
Mendelian randomization identifies circulating proteins as biomarkers for age at menarche and age at natural menopause
Authors: Yazdanpanah Nahid , Jumentier Basile , Yazdanpanah Mojgan , Ong Ken K. , Perry John R. B. , Manousaki Despoina
Published: January 2024

Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating proteins associated with altered ANM and AAM using an unbiased two-sample Mendelian randomization (MR) and colocalization approach. By testing causal effects of 1,271 proteins on AAM, we identified 22 proteins causally associated with AAM in MR, among which 13 proteins (GCKR, FOXO3, SEMA3G, PATE4, AZGP1, NEGR1, LHB, DLK1, ANXA2, YWHAB, DNAJB12, RMDN1 and HPGDS) colocalized. Among 1,349 proteins tested for causal association with ANM using MR, we identified 19 causal proteins among which 7 proteins (CPNE1, TYMP, DNER, ADAMTS13, LCT, ARL and PLXNA1) colocalized. Follow-up pathway and gene enrichment analyses demonstrated links between AAM-related proteins and obesity and diabetes, and between AAM and ANM-related proteins and various types of cancer. In conclusion, we identified proteomic signatures of reproductive ageing in women, highlighting biological processes at both ends of the reproductive lifespan.
Proinflammatory chemokine CXCL14 activates MAS-related G protein-coupled receptor MRGPRX2 and its putative mouse ortholog MRGPRB2
Authors: Al Hamwi Ghazl , Namasivayam Vigneshwaran , Büschbell Beatriz , Gedschold Robin , Golz Stefan , Müller Christa E.
Published: January 2024

Patients with idiopathic pulmonary fibrosis show a strongly upregulated expression of chemokine CXCL14, whose target is still unknown. Screening of CXCL14 in a panel of human G protein-coupled receptors (GPCRs) revealed its potent and selective activation of the orphan MAS-related GPCR X2 (MRGPRX2). This receptor is expressed on mast cells and − like CXCL14 − upregulated in bronchial inflammation. CXCL14 induces robust activation of MRGPRX2 and its putative mouse ortholog MRGPRB2 in G protein-dependent and β-arrestin recruitment assays that is blocked by a selective MRGPRX2/B2 antagonist. Truncation combined with mutagenesis and computational studies identified the pharmacophoric sequence of CXCL14 and its presumed interaction with the receptor. Intriguingly, C-terminal domain sequences of CXCL14 consisting of 4 to 11 amino acids display similar or increased potency and efficacy compared to the full CXCL14 sequence (77 amino acids). These results provide a rational basis for the future development of potential idiopathic pulmonary fibrosis therapies.
Two-photon excitation fluorescence microspectroscopy protocols for examining fluorophores in fossil plants
Authors: Stoneman Michael R. , McCoy Victoria E. , Gee Carole T. , Bober Katherine M. M. , Raicu Valerică
Published: January 2024

Fluorescence emission is common in plants. While fluorescence microscopy has been widely used to study living plants, its application in quantifying the fluorescence of fossil plants has been limited. Fossil plant fluorescence, from original fluorophores or formed during fossilization, can offer valuable insights into fluorescence in ancient plants and fossilization processes. In this work, we utilize two-photon fluorescence microspectroscopy to spatially and spectrally resolve the fluorescence emitted by amber-embedded plants, leaf compressions, and silicified wood. The advanced micro-spectroscope utilized, with its pixel-level spectral resolution and line-scan excitation capabilities, allows us to collect comprehensive excitation and emission spectra with high sensitivity and minimal laser damage to the specimens. By applying linear spectral unmixing to the spectrally resolved fluorescence images, we can differentiate between (a) the matrix and (b) the materials that comprise the fossil. Our analysis suggests that the latter correspond to durable tissues such as lignin and cellulose. Additionally, we observe potential signals from chlorophyll derivatives/tannins, although minerals may have contributed to this. This research opens doors to exploring ancient ecosystems and understanding the ecological roles of fluorescence in plants throughout time. Furthermore, the protocols developed herein can also be applied to analyze non-plant fossils and biological specimens.
Precise determination of molecular adsorption geometries by room temperature non-contact atomic force microscopy
Authors: Brown Timothy , Blowey Philip James , Sweetman Adam
Published: January 2024

High resolution force measurements of molecules on surfaces, in non-contact atomic force microscopy, are often only performed at cryogenic temperatures, due to needing a highly stable system, and a passivated probe tip (typically via CO-functionalisation). Here we show a reliable protocol for acquiring three-dimensional force map data over both single organic molecules and assembled islands of molecules, at room temperature. Isolated cobalt phthalocyanine and islands of C60 are characterised with submolecular resolution, on a passivated silicon substrate (B:Si(111)-$$(\sqrt{3}\times \sqrt{3})R3{0}^{\circ }$$

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). Geometries of cobalt phthalocyanine are determined to a ~ 10 pm accuracy. For the C60, the protocol is sufficiently robust that areas spanning 10 nm × 10 nm are mapped, despite the difficulties of room temperature operation. These results provide a proof-of-concept for gathering high-resolution three-dimensional force maps of networks of complex, non-planar molecules on surfaces, in conditions more analogous to real-world application.
An all-in-one seismic phase picking, location, and association network for multi-task multi-station earthquake monitoring
Authors: Si Xu , Wu Xinming , Li Zefeng , Wang Shenghou , Zhu Jun
Published: January 2024

Earthquake monitoring is vital for understanding the physics of earthquakes and assessing seismic hazards. A standard monitoring workflow includes the interrelated and interdependent tasks of phase picking, association, and location. Although deep learning methods have been successfully applied to earthquake monitoring, they mostly address the tasks separately and ignore the geographic relationships among stations. Here, we propose a graph neural network that operates directly on multi-station seismic data and achieves simultaneous phase picking, association, and location. Particularly, the inter-station and inter-task physical relationships are informed in the network architecture to promote accuracy, interpretability, and physical consistency among cross-station and cross-task predictions. When applied to data from the Ridgecrest region and Japan, this method showed superior performance over previous deep learning-based phase-picking and localization methods. Overall, our study provides a prototype self-consistent all-in-one system of simultaneous seismic phase picking, association, and location, which has the potential for next-generation automated earthquake monitoring.