bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Central Corneal Thickness and Axial Length in Patients with Refractive Anomalies and Emmetropes
Authors: Ismaili Mimoza
Published: September 2023

Background: This study aimed to determine the correlation between central corneal thickness (CCT) and axial length (AL) in patients with refractive anomalies and emmetropes. Methods and Results: The study included 330 respondents, with a total of 660 eyes, divided into two groups. The test group (TG) included 180 respondents with refractive anomalies (65 respondents with hypertropia, 65 with myopia, and 50 with astigmatism); the control group (CG) included 150 respondents with uncorrected visual acuity – 6/6 in both eyes. The CCT values were higher in the hypermetropic group compared to the myopic group (561.5±25.3 vs. 517.9±37.3 mm, P<0.001), astigmatism group (561.5±25.3 vs. 528.3±35.3 mm, P<0.001) and the CG (561.5±25.3 vs. 553.3±18.5 mm, P<0.001). From 360 eyes in the TG with refractive anomalies, the lowest AL values were found in the hypermetropic group (21.7±1.0 mm) compared to the myopic group (P<0.001), the astigmatism group (P<0.001), and the CG (P<0.001). Similar differences were also found for the right eyes (OD): hypermetrops tend to have shorter AL than the astigmatic group (P<0.001), myopic group (P<0.001), and the CG (emmetrope) (P<0.001). Conclusion: The mean CCT value in the hyperopic group was higher than in the emmetropic group, while the CCT value of the myopic and astigmatic group was lower than that of the emmetropic group. AL values were the lowest in the hypermetropic group than in the myopic, astigmatic, and control groups.
Acute Vascular Events: Cellular and Molecular Mechanisms
Authors: Rao Varun , Shankar Rasika , Rao Gundu
Published: September 2023

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. An estimated 17.9 million individuals died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to heart attack and stroke. Cardiometabolic risks, such as hypertension, excess weight, obesity, type 2 diabetes, and vascular diseases, contribute significantly to the progression of coronary artery disease. Known sequelae of events that lead to these cardiometabolic diseases include oxidative stress, inflammation, development of dysfunction of vascular adipose tissue, altered blood pressure and blood lipids, altered glucose metabolism, hardening of the arteries, endothelial dysfunction, development of atherosclerotic plaques, and activation of platelet and coagulation pathways. The Framingham Heart Study Group has developed a Risk Score that estimates the risk of developing heart disease in a 10-year period. This group of experts has developed mathematical functions for predicting clinical coronary disease events. These prediction capabilities are derived by assigning weights to major CVD risk factors such as sex, age, blood pressure, total cholesterol, low-density lipoprotein, high-density lipoprotein cholesterol, smoking behavior, and diabetes status. Currently, there is a growing interest in the use of artificial intelligence and machine learning applications. AI-based mimetic pattern-based algorithms seem to be better than the conventional Framingham Risk Score, in predicting clinical events related to CVDs. However, there are limitations to these applications as they do not have access to data on the specific factors that trigger acute vascular events, such as heart attack and stroke. This overview briefly discusses some salient cellular and molecular mechanisms involved in precipitating thrombotic conditions. Further improvements in emerging technologies will provide greater opportunities for patient selection and treatment options. Several clinical studies have demonstrated that most CVDs can be prevented by addressing behavioral risk factors such as tobacco use, unhealthy diet and obesity, physical activity, and harmful use of alcohol. Early detection and better management of the modifiable risks seem to be the only way to reduce, reverse, or prevent these diseases.
Role of p53, Cancer Stem Cells, and Cellular Senescence in Radiation Response
Authors: Alamilla-Presuel Juan
Published: September 2023

Currently, radiotherapy has been identified as the most common cancer treatment. However, the efficacy of this treatment modality is low in several malignancies due to the resistance of cancer to radiation. Multiple mechanisms, including cell-cycle checkpoint function, DNA repair, and cell death pathways, modulate the radio-responsiveness of cancer cells. This review considered the role of p53, cancer stem cells (CSCs), and cellular senescence in radiation response.
The Impact of PET/MRI Fusion on the Diagnostic Imaging Industry
Authors: Aldahery Shrooq
Published: September 2023

The multimodal imaging technique has gained the spotlight in the present era due to its striking and immense applications. It is the combination of two or more modalities that complement one another to yield detailed information. Indubitably, it is an emerging and crucial technique due to its broad clinical and research applications. The diagnostic techniques with the dual modality are aligned for obtaining molecular data. Positron emission tomography (PET) is a progressive imaging technique in nuclear medicine. To flourish in the imaging industry, PET was combined with computed tomography (CT), but the fusion of the two provides some challenges, such as less soft tissue contrast and inefficiency of acquisition in simultaneous mode. As a result, another hybrid imaging technology, PET and MRI (PET/MRI), has been developed to provide more soft tissue contrast and less radiation dose exposure, leading this technique to be used extensively despite its shortcomings. This review study discusses the fusion of PET/MRI, technical challenges for their combination, commercially available models, and clinical applications observed in the wide areas of oncology, the cardiovascular system, the central nervous system, pediatrics, and inflammatory diseases.
Trends and Variability in Precipitation Across Turkey: A Multi-Method Statistical Analysis
Authors: Yetik Ali Kaan , Arslan Bilge , Şen Burak
Published: September 2023

Analyzing trends in precipitation data is crucial for understanding the effects of climate change and making informed decisions about water management and crop patterns. The objective of the presented study was to investigate precipitation trends, analyze temporal and spatial variations, and identify potential change points in Turkey throughout the period from 1980 to 2019. Precipitation data were analyzed for both regional and 81 meteorological stations in Turkey on a monthly, seasonal and annual basis. Spearman rank correlation and Mann-Kendall tests were utilized to detect possible trends, and Sen's slope test to estimate the magnitude of change throughout the entire time series. The average precipitation amount of Turkey was determined 639.2 mm between 1980–2019 years. While Central Anatolian and Eastern Anatolian regions had below 639.2 mm, other regions were above. The range of seasonal precipitation values were found for winter 128.7-320.8 mm, 108.9–260.0 mm for spring, 43.9-109.3 mm for summer and 79.7-238.4 mm for autumn. The analysis of the data revealed no significant increase or decrease in annual values on a regional basis, with the greatest change on a seasonal basis being observed in the winter. The 40-yr trends of annual precipitation data belonging to 81 stations were decreasing in 23 provinces and increasing in 58 provinces, and 11 of them (14% of the total) were found to be statistically significant. Moreover, November was found to be a month of particular significance in terms of precipitation changes across the country, with a decrease observed in 80 out of 81 provinces. Spatial distribution analysis showed that the magnitude of variation in precipitation decreased as one moved from the southern to the northern regions of the country.
Genetic characterization, population genetics and demographics history of Bactrocera Zonata (Saunders) (Tephritidae: Diptera) of cox1 gene
Authors: juktihiremath shreedevi S , Biradar Shivaleela , C Srushti S , L Babu R
Published: September 2023

Background: (1)Bactrocera zonata (Saunders) (Tephritidae : Diptera), is one of destructive and invasive fruit fly species of the genus Bactrocera . In the present study, genetic structure, genetic diversity and demographic history of B.zonata was inferred from cytochrome oxidase I (cox1) gene sequence;
(2) Methods: Analysis of similarity test shows in DNA barcode with 100% accurate identification of B.zonata specimen which was differentiated from other Bactrocera species;
(3)Result: Descriptive statistic analysis of B.zonata revealed high genetic diversity through the indices [number of haplotypes (H), haplotype diversity (Hd), nucleotide diversity (p) and average number of nucleotide differences (k)]. Negative values of Tajima’s D and Fu’s Fs and star-like network of haplotypes inferred neutrality;
(4)Conclusion: Therefore, cytochrome oxidase 1 (cox1) barcode sequences generated in the present study could be a valuable source for the rapid identification and global population genetic study of B. zonata.
The Validity and IRT Psychometric Analysis of Chinese Version of Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10)
Authors: Du Jianhua , Wang Yufei , Wu Aoxue , Jiang Yinan , Duan Yanping , Geng Wenqi , Wan Lin , Li Jiarui , Hu Jiaojiao , Jiang Jing , Shi Lili , Wei Jing
Published: September 2023

Objective: The doctor-patient relationship (DPR) plays a crucial role in Chinese healthcare system, functioning in improve medical quality and reducing medical costs. This study examined the psychometric properties of the Chinese version of the Difficult Doctor-Patient Relationship Questionnaire (DDPRQ-10) among general hospital inpatients in China.
Methods: The research recruited 38 resident doctors responsible for 120 participants, and factor analyses were used to assess the construct validity of the scale. Convergent validity was evaluated by examining the correlation between DDPRQ-10 and depressive symptoms, burnout, and self-efficacy, using Patient Health Questionnaire Depression Scale-9 item (PHQ-9), and the Maslach Burnout Inventory (MBI). Both multidimensional item response theory (MIRT) and unidimensional item response theory (IRT) frameworks were used to estimate the parameters of each item.
Results: The Chinese version of DDPRQ-10 showed satisfactory internal consistency (Cronbach's alpha = 0.931), and fitted in a modified two-factor model of positive feelings and negative feelings (χ2/df = 1.494, GFI = 0.925, RMSEA = 0.071, SRMR = 0.008, CFI = 0.985, NFI = 0.958, NNFI = 0.980, TLI = 0.980, IFI = 0.986). Significant correlations with PHQ-9 with DDPRQ-10 and both subscales were revealed (r = 0.293~0.333, p < .001), while DDPRQ-10 score also significantly correlated with doctors’ MBI score (r = -0.467, p< .001). The MIRT model of full scale and IRT models of both subscales showed high discrimination of all items (a = 2.30~10.18), and the test information within the range of low-quality relationship was relatively high.
Conclusion: The Chinese version of DDPRQ-10 displayed satisfactory reliability and validity, and thus was appropriate for measuring the DPR in Chinese medical settings.
Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas
Authors: Aoki Hironori , Takasawa Akira , Yamamoto Eiichiro , Niinuma Takeshi , Yamano Hiro-o , Harada Taku , Kubo Toshiyuki , Yorozu Akira , Kitajima Hiroshi , Ishiguro Kazuya , Kai Masahiro , Katanuma Akio , Shinohara Toshiya , Nakase Hiroshi , Sugai Tamotsu , Osanai Makoto , Suzuki Hiromu
Published: September 2023

Background
Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions.
Methods
SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (training set, n = 126; validation set, n = 73) and adjacent normal colonic tissues (n = 112).
Results
Mean immunohistochemistry scores in normal colonic tissues and tumors in a training set were as follows: normal colon, 24.2; hyperplastic polyp (HP), 21.6; SSL, 24.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 17.5; TSA, 7.3; low grade adenoma, 21.4; high grade adenoma, 11.7; high grade dysplasia (HGD), 12.1; EIC, 10.9. Abundant expression of SMOC1 in SSLs and significant downregulation of SMOC1 in TSAs were further confirmed in a validation set. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components.
Conclusion
Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.
A randomized trial of treatment for anterior cruciate ligament reconstruction by radial extracorporeal shock wave therapy
Authors: Song Yufeng , Che Xinle , Wang Zheyun , Li Mengshi , Zhang Runjie , Wang Dongming , Shi Qiongfang
Published: September 2023

Objective
The aim of this study was to explore the effects of radial extracorporeal shock wave therapy (rESWT) in patients with anterior cruciate ligament(ACL) reconstruction(ACLR).
Methods
We conducted a randomized, controlled trial involving 72 eligible patients with ACL reconstruction in which we compared two strategies: the experimental group was standard rehabilitation plus rESWT and the control group was standard rehabilitation plus sham rESWT. The outcome was the change from baseline to 24 weeks in the average score on Lysholm knee joint score (LKS), range of motion (ROM), visual analogue scale (VAS) and International Knee Literature Committee (IKDC).
Results
Of 36 subjects assigned to rehabilitation plus rESWT, 4 lost to follow up. Of 36 assigned to rehabilitation plus sham rESWT, 5 lost to follow up. The LKS, ROM and IKDC scores of the experimental group were markedly increased at 3 and 6 weeks after treatment (P < 0.001), and the VAS was notably decreased (P < 0.001). However, there were no significant differences in the LKS, ROM, IKDC and VAS between the groups at 24 weeks after treatment(P > 0.05).
Conclusion
The strategy of rehabilitation plus rESWT had better functional outcomes after ACL reconstruction. As such, our study demonstrates that rESWT is essential for patients with ACL reconstruction. Early use of rESWT can improve joint function, pain relief and ability of daily living. rESWT has a positive effect on the overall rehabilitation of patients.
Retro-MTGR: Molecule Retrosynthesis Prediction via Multi-Task Graph Representation Learning
Authors: Shi Jian-Yu , Zhao Pengcheng , Wei Xue-Xin , Wang Qiong , Wang Qi-Hao , Li Jia-Ning , Shang Jie , Lu Cheng
Published: September 2023

It is a vital bridging step to infer appropriate synthesis reaction routes (i.e., retrosynthesis) of newly-designed molecules. Unlike classical experience-based retrosynthesis approaches, artificial intelligence enables a cheap and fast retrosynthesis approach. Template-based models, limited in known synthesis templates, leverage substructure searching to infer candidate reaction centers (i.e., bonds). In contrast, both translation-based models (TransMs) and discriminative methods (DiscMs) are free to synthesis templates. TransM regards retrosynthesis as a translation from the target molecule to its reactants by generative algorithms. DiscM, directly inspired by chemical synthesis, performs reaction center recognition and leaving group identification in turn. Nevertheless, TransMs are redundant and weakly interpretable, while existing DiscMs neglect the associations between reaction centers and leaving groups. To address these issues, this paper elaborates a novel discriminative Multi-Task Graph Representation learning model of Retrosynthesis prediction (Retro-MTGR). It solves two major supervised discriminative tasks (i.e., the reaction center recognition and the leaving group identification respectively), and an auxiliary self-supervised task (i.e., atom embedding enhancer) simultaneously. The comparison with various state-of-the-art methods first demonstrates the superiority of Retro-MTGR. Then, the ablation studies reveal how its crucial components contribute to the prediction respectively, including the atom embedding enhancer, bond energies, and the leaving group co-occurrence graph. More importantly, comprehensive investigations validate its chemical interpretability by answering two questions: why a bond can be the reaction center or not, and what leaving groups are appropriate to given synthons. The answers demonstrate that Retro-MTGR can reflect five underlying chemical synthesis rules by characterizing molecule structures alone. Finally, two case studies demonstrate that the inferred retrosynthesis routes by Retro-MTGR are significantly consistent with those achieved by performed chemical synthesis assays. It’s anticipated that our Retro-MTGR can provide prior guidance for real retrosynthesis route planning. The code and data underlying this article are freely available at https://github.com/zpczaizheli/Retro-MTGR.
Changes in frailty and depressive symptoms among middle-aged and elderly Chinese: a nationwide cohort study
Authors: Sang Ni , Liu Rong-chao , Zhang Ming-hui , Lu Zong-Xiao , Zhang Meng-Yao , Li Bo-Han , Wei Meng , Pan Hai-Feng , Wu Guo Cui
Published: September 2023

Background and Aims:
The elderly population bears a severe burden of disease due to frailty and depressive symptoms, however, the results of association between the two in the elderly Chinese population have been conflicting. Therefore, this study aimed to investigate the developmental trajectories and interactions of frailty and depressive symptoms in the Chinese middle-aged and elderly population.
Methods
The study used three waves of data from 2011, 2013, and 2015 in the China Health and Retirement Longitudinal Study (CHARLS) database, focused on middle-aged and elderly people ≥ 45 years of age, and analyzed using latent growth models and cross-lagged models.
Results
According to the parallel latent growth model's findings, the initial level of depressive symptoms had a significant positive predictive effect on the initial level of frailty and a significant negative predictive effect on the rate of change in frailty. A substantial positive predictive relationship existed between the rate of change in depressive symptoms and the rate of change in response to frailty. The overall sample population, the middle-aged population, and the elderly population all showed evidence of a bidirectional causal connection between frailty and depressive symptoms as a result of cross-lagged analyses.
Conclusions
This study recommended advancing the age of concern for frailty and depressive symptoms to middle-aged adults. In the middle-aged and elderly Chinese population, the higher the initial level of frailty and the faster the rate of change, the higher the initial level of depressive symptoms and the faster the rate of change.
Genetic variations in MdSAUR36 participate in the negative regulation of mesocarp cell division and fruit size in Malus species
Authors: Tian Zhendong , Wu Bei , Liu Jing , Zhang Libo , Wu Ting , Wang Yi , Han Zhenhai , Zhang Xinzhong
Published: September 2023

Final fruit size of apple (Malus domestica) cultivars is related to both mesocarp cell division and cell expansion during fruit growth, but it is unclear whether the cell division and/or cell enlargement determine most the differences in fruit size between Malus species. In this study, by using an interspecific hybrid population between M. asiatica ‘Zisai Pearl’ and M. domestica cultivar ‘Red Fuji’, we found that the mesocarp cell number was the main causal factor of diversity in fruit size between Malus species. Rapid increase in mesocarp cell number occurred prior to 28 days after anthesis (DAA), while cell size increased gradually after 28 DAA until fruit ripening. Six candidate genes related to auxin signaling or cell cycle were predicted by combining the RNA-seq data and previous QTL data for fruit weight. Two InDels and 10 SNPs in the promoter of a small auxin upregulated RNA gene MdSAUR36 in ‘Zisai Pearl’ led to a lower promoter activity than that of ‘Red Fuji’. One non-synonymous SNP G/T at 379 bp downstream of the ATG codon of MdSAUR36, which was heterozygous in ‘Zisai Pearl’, exerted significant genotype effects on fruit weight, length, and width. Transgenic apple calli by over-expressing or RNAi MdSAUR36 confirmed that MdSAUR36 participated in the negative regulation of mesocarp cell division and thus apple fruit size. These results could provide new insights in the molecular mechanism of small fruit size in Malusaccession and be potentially used in molecular assisted breeding via interspecific hybridization.
Association between autoimmune disorders and prostate cancer: a Mendelian Randomization Study
Authors: Chen Peixian , Xiong Zhi , Luo Tianlong , Lai Yiming , Peng Shirong , Zhuang Ruilin , Li Kaiwen , Huang Hai
Published: September 2023

Background:
Although many epidemiological studies or meta-analyses have reported an association between autoimmune disorders and prostate cancer, no studies have reported a clear causal relationship and the direction of the association. The purpose of our research was to explore the potential causal relationship between autoimmune disorders and prostate cancer through mendelian randomization study(MR).
Method:
We retrieve literature through the pubmed using key words of "Autoimmune disorder" AND "cancer", and find that more than ten autoimmune disorders and cancer are potentially related. We continue to use the keywords of “autoimmune disorder” AND “prostate cancer” to find more clues on the correlation between prostate cancer and autoimmune disease. According to the above literature support, we selected 16 common autoimmune disorders that may be associated with prostate cancer. We extracted and selected disease-related single nucleotide polymorphisms (SNPs) from the largest and public genome-wide association study (GWAS) summary data. Inverse variance weighted (IVW) method was applied as our primary analyses for the two-sample Mendelian randomization and multivariate mendelian randomization analysis to estimate the OR value and 95% confidence interval. In addition, we conducted other two analyses to verify the reliability of the conclusion: weighted median method and MR-Egger method. We further verified the robustness of the conclusions by a series of sensitivity analyses.
Results:
The autoimmune diseases we selected included rheumatoid arthritis, ankylosing spondylitis, coxarthrosis, gonarthrosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary sclerosing cholangitis, asthma, type I diabetes, systemic lupus erythematosus, multiple sclerosis, autoimmune hyperthyroidism, psoriatic arthritis, and polymyalgia rheumatica. The results of IVW methods suggest that six immune diseases have been associated with the development of prostate cancer. Three diseases that may be significantly associated with higher risk of prostate cancer are rheumatoid arthritis (OR: 1.03, 95%CI,1.01-1.05, p=0.001), coxarthrosis (OR: 1.17, 95%CI,1.08-1.26, p < 0.001), and gonarthrosis (OR: 1.17, 95%CI,1.05-1.3, p=0.008). Three possible protective factors for prostate cancer are primary sclerosing cholangitis (OR: 0.97, 95%CI,0.95-0.99, p=0.001), autoimmune hyperthyroidism (OR: 0.97, 95%CI,0.94-0.99, p=0.011), and psoriatic arthritis (OR: 0.97, 95%CI,0.95-0.99, p=0.001). Multivariate Mendelian randomization found no association between Crohn's disease or ulcerative colitis and prostate cancer. Horizontal pleiotropy was not found in MR-Egger intercepts.
Conclusion:
Our findings provide genetic predictive evidence of an association between autoimmune disorders and prostate cancer, and these findings have important implications for screening and management in clinical practice.
1,25-dihydroxyvitamin D3 alleviates bisphenol A-induced apoptosis in KGN cells by improving mitochondrial activity and blocking the mitochondrial cytochrome c apoptotic pathway
Authors: Tang Liting , Luo Kaiming , Du Ke , Wang Long , Hua Fei
Published: September 2023

Purpose
This study explored whether and how 1,25-dihydroxyvitamin D3 (1,25(OH)2VD3) mitigates bisphenol A (BPA)-induced apoptosis in human ovarian granulosa KGN cells to obtain a theoretical basis for how vitamin D improves ovarian function in patients with polycystic ovary syndrome (PCOS).
Methods
The effect of different concentrations of BPA and 1,25(OH)2VD3 on KGN cell viability was clarified. Then, KGN cells were treated with BPA to induce apoptosis and subsequently exposed to 1,25(OH)2VD3. The apoptosis rate, reactive oxygen species (ROS) level, and mitochondrial function of the cells were assessed as well as the expression levels of genes related to apoptosis, antioxidant pathways, and mitochondrial biogenesis.
Results
BPA dose-dependently inhibited the proliferation and viability of the KGN cells, induced a significant increase in oxidative stress and apoptosis, and disrupted mitochondrial function. The expression levels of apoptotic genes in the mitochondrial cytochrome c (Cyt c) pathway were upregulated, and those of antioxidant and mitochondrial biogenesis genes were downregulated. 1,25(OH)2VD3 significantly ameliorated apoptosis and mitochondrial damage.
Conclusions
1,25(OH)2VD3 reduces BPA-induced KGN cell damage and apoptosis by improving mitochondrial activity and blocking the mitochondrial Cyt c apoptotic pathway. This indicates that the vitamin D levels in PCOS patients of childbearing age should be monitored.
Pseudomonas otitidis bacteremia in an immunocompromised patient with cellulitis: case report and literature review
Authors: Mori Takeo , Yoshizawa Sadako , Yamada Kageto , Sato Takahiro , Sasaki Masakazu , Nakamura Yusuke , Gen Ukyo , Murakami Hinako , Kashiwagi Katsuhito , Maeda Tadashi , Miyazaki Taito , Yamaguchi Tetsuo , Urita Yoshihisa , Ishii Yoshikazu , Tateda Kazuhiro
Published: September 2023

Background: Pseudomonas otitidis belongs to the genus Pseudomonas and causes various infections, including ear, skin, and soft tissue infections. P. otitidishas a unique susceptibility profile, being susceptible to penicillins and cephalosporins but resistant to carbapenems, due to the production of the metallo-β-lactamase called POM-1. This revealed genetic similarities with Pseudomonas aeruginosa, which can sometimes lead to misidentification.
Case presentation: We report the case of a 70-year-old Japanese male who developed cellulitis and bacteremia during chemotherapy for multiple myeloma. He was initially treated with meropenem, but blood culture later revealed gram-negative bacilli identified as P. otitidis using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Carbapenem resistance was predicted from previous reports; therefore, we switched to dual therapy with levofloxacin and cefepime, and favorable treatment results were obtained.
Conclusion: This is the first reported case of P. otitidis cellulitis and bacteremia in an immunocompromised patient. Carbapenems are typically used in immunocompromised patients and P. otitidis is often resistant to it. However, its biochemical properties are similar to those of Pseudomonas aeruginosa; therefore, its accurate identification is critical. In the present study, we rapidly identified P. otitidis using MALDI-TOF MS and switched from carbapenems to an appropriate antimicrobial therapy, resulting in a successful outcome.
Molecular and virulence characteristics of carbapenem-resistant Acinetobacter baumannii isolates: A prospective cohort study
Authors: Park Seung Min , Suh Jin Woong , Ju Yong Kuk , Kim Jeong Yeon , Kim Sun Bean , Sohn Jang Wook , Yoon Young Kyung
Published: September 2023

This study aimed to characterise the molecular features and virulence profile of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. Clinical CRAB isolates were obtained from blood cultures of adult patients with CRAB bacteraemia, collected between July 2015 and July 2021 in a Korean hospital. Real-time polymerase chain reaction was used to detect 13 virulence genes, genotyping was conducted via multilocus sequence typing (MLST), and a Tenebrio molitor infection model was selected for survival analysis. A total of 170 clinical CRAB isolates harboured the blaOXA−23 and blaOXA−51 genes. MLST genotyping identified 11 CRAB sequence types (STs), of which ST191 was the most predominant (25.7%). Virulence genes were distributed as follows: basD, 58.9%; espA, 15.9%; bap, 92.4%; ata, 86.5%; chop, 7.1%; ompA, 77.1%; pbpG; 93.5%; bfmR, 92.9%; fhaB, 70.6%; abeD, 99.4%; cpaA, 0.6%; lipA, 99.4%; and recA, 100%. In the T. molitor model, ST195 showed a significantly higher mortality rate (73.3% vs. 66.7%, p = 0.015) and ST451 displayed a lower mortality rate (60.0% vs. 73.3%, p = 0.007) compared to counterpart groups. Our findings provided insight on the microbiological features of CRAB blood isolates. A potential framework for using a T. molitor infection model to characterise CRAB pathogen virulence is suggested.
The draft genome of the Temminck's tragopan (Tragopan temminckii) with evolutionary implications
Authors: Li Xuejuan , Wang Xiaoyang , Yu Xiaoping , Yang Chao , Lin Liliang , Huang Yuan
Published: September 2023

Background
High-quality genome data of birds play a significant role in systematic studying their origin and adaptive evolution. The Temminck's tragopan (Tragopan temminckii) (Galliformes, Phasianidae), a larger pheasant, is one of the most abundant and widely distributed species of the genus Tragopan, and was defined as class II of the list of national key protected wild animals in China. The limited genomic data restricted evolutionary trait studies of this taxa.
Results
The whole genome of the Temminck's tragopan was sequenced using Illumina and PacBio platform, and then de novo assembled and annotated. The genome size was 1.06 Gb, with a contig N50 of 4.17 Mb. A total of 117.22 Mb (11.00%) repeat sequences were identified. 16,414 genes were predicted using three
methods
, with 16,099 (98.08%) annotated as functional genes based on five databases. In addition, comparative genome analyses were conducted across 12 Galliformes species. The
results
indicated that T. temminckii formed a basal position of the clade including Lophura nycthemera, Phasianus colchicus, Chrysolophus pictus, Syrmaticus mikado, Perdix hodgsoniae, and Meleagris gallopavo, with a corresponding divergence time of 31.43 million years ago (MYA). Expanded gene families associated with immune response and energy metabolism were identified. Genes and pathways associated with plumage color and feather development, immune response, and energy metabolism were found in positively selected genes (PSGs).
Conclusions
A genome draft of the Temminck's tragopan was reported, genome feature and comparative genome analysis were described, and genes and pathways related to plumage color and feather development, immune response, and energy metabolism were identified. The genomic data of the Temminck's tragopan considerably contribute to the genome evolution and phylogeny of the genus Tragopan and the whole Galliformes species underlying ecological adaptation strategies.
Effect of ticagrelor versus clopidogrel after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome——Propensity score matching analysis
Authors: Zhao Yinan , Yang Yuxin , Guo Lei , Shen Dapeng , Dong Zhichao , Lin Yajuan , Liu Hao , Wei Yushan , Zhang Bo
Published: September 2023

Background
The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not.
Methods
A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately.
Results
After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model.
Conclusion T
he benefit of ticagrelor was attenuated in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion.
Data-Mining Analysis of Media Frame Effects on Social Perception of Schizophrenia Renaming in Korea
Authors: Kim Il Bin , Choi Joonho , Park Seon-Cheol , Koike Shinsuke , Kwon Jun Soo , Sun Choi Hyo , Yeon Lee Ju , Lee Yu Sang , Kim Eunkyung
Published: September 2023

Background
In 2011, Korean Neuropsychiatric Association renamed schizophrenia from ‘mind split disorder’ (‘Jungshinbunyeolbyung’ in Korean) to ‘attunement disorder’ (‘Johyeonbyung’ in Korean), in a strategic way to reduce social stigma toward people with schizophrenia. However, there remains an elusive consensus that how the renaming effort has contributed to changes in the social perception of schizophrenia in Korea.
Methods
With this regard, we explored whether media frames alter the social perception, in ways of respecting or disrespecting schizophrenia patients before and after the renaming. This study extensively investigated media keywords related to schizophrenia across the time by applying both language and epidemiologic analyses.
Results
In results, the media keywords have been negatively described for schizophrenia patients both before and after the renaming. Further, from an analysis using the regression model, a significant correlation was observed between the frequency of negative keywords and the hospitalization frequency of schizophrenia patients. In addition, the negative keywords deciphering schizophrenia were also significantly more shown under Korean media frames after a specific murder case committed by a schizophrenia patient.
Conclusions
These findings suggest that the social perception of schizophrenia has been scarcely changed, but rather remained negatively biased against schizophrenia patients, in spite of the renaming effort. Notably, the biased media frames have been demonstrated to negatively impact on the social perception, and even on the medical use patterns of general schizophrenia patients. In conclusion, we suggest that the unbiased media frames along with the renaming effort may collectively help reduce the negative social perception of schizophrenia.
Trial registration
This study was approved from the Institute of Review Board (IRB) of the Yoing-In Mental Hospital (IRB No. YIMH-IRB-2019-02).
The causality between C-reactive protein and asthma: A Two-Sample Mendelian Randomization Analysis
Authors: Mou Yong , Cao Wenhao , Wang Rujuan , Liu Xiaofan , Yang Xiuwen , Zhu Jing
Published: September 2023

Background: C-reactive protein (CRP) plays a critical role in asthma development and is usually elevated in asthmatic patients. However, the causal association between CRP and asthma remains unknown.
Results: We utilized single nucleotide polymorphisms (SNPs) associated with both CRP and outcomes of asthma, allergic asthma and obesity related asthma as genetic variables via genome-wide summary association study (GWAS). In our study, 42 SNPs were identified as instrumental variables (Ivs) for mendelian randomization (MR) analyses. According to the primary inference results by inverse variance weighted (IVW)methods, the circulating CRP was demonstrated to be significantly associated with risk of asthma (OR=1.046, 95%CI 1.004-1.090, P=0.030) and obesity related asthma (OR=1.072, 95%CI 1.009-1.138, P=0.025), whereas no distinct causality with allergic asthma (OR=1.051, 95%CI 0.994-1.112, P=0.081). Sensitivity analyses indicated that there’s no horizontal pleiotropy among IVs, and the MR results were proved to be robust by leave-one-out sensitivity analysis, despite of the presence of heterogeneity.
Conclusions:The present study suggested that genetically determined circulating CRP showed an increased risk of developing asthma and obesity related asthma, without causality with allergic asthma.
Deep embedded clustering generalisability and adaptation for mixed datatypes: two critical care cohorts
Authors: de Kok Jip , Rosmalen Frank van , Koeze Jacqueline , Keus Frederik , Kuijk Sander van , Forte José Castela , Schnabel Ronny , Driessen Rob , Herpt Thijs van , Sels Jan-Willem , Bergmans Dennis , Lexis Chris , Doorn William van , Meex Steven , Xu Minnan , Borrat Xavier , Cavill Rachel , Horst Iwan van der , Bussel Bas van
Published: September 2023

We propose X-DEC, a novel deep clustering technique that can integrate mixed datatypes (in this study numerical and categorical variables). Deep Embedded Clustering (DEC) is a promising technique capable of managing extensive sets of variables and non-linear relationships. Nevertheless, DEC cannot adequately handle mixed datatypes. Therefore, we created X-DEC by replacing the autoencoder with an X-shaped variational autoencoder (XVAE) and optimising hyperparameters for cluster stability. We compared DEC and X-DEC by reproducing a previous study that used DEC to identify clusters in a population of intensive care patients. We assessed internal validity based on cluster stability on the development dataset. Since generalisability of clustering models has insufficiently been validated on external populations, we assessed external validity by investigating cluster generalisability onto an external validation dataset. We concluded that both DEC and X-DEC resulted in clinically recognisable and generalisable clusters, but X-DEC produced much more stable clusters.
The role of DNA methylation in chondrogenesis of human iPSCs as a stable marker of cartilage quality
Authors: Hajmousa Ghazaleh , de Almeida Rodrigo Coutinho , Bloks Niek , Ruiz Alejandro Rodríguez , Bouma Marga , Slieker Roderick , Kuipers Thomas B , Nelissen Rob GHH , Ito Keita , Freund Christian , Ramos Yolande F.M. , Meulenbelt Ingrid
Published: September 2023

Background
Lack of insight into factors that determine purity and quality of human iPSC (hiPSC)-derived neo-cartilage precludes applications of this powerful technology towards regenerative solutions in the clinical setting. Here we set out to generate methylome-wide landscapes of hiPSC derived neo-cartilages from different tissues-of-origin and integrated transcriptome-wide data to identify aberrant set-points of transcription.
Methods
We applied in vitro chondrogenesis using hiPSCs generated from two different tissue sources; skin fibroblasts and articular cartilage. Upon differentiation towards chondrocytes these are referred to as hFiCs and hCiC, respectively. Genome-wide DNA methylation and RNA sequencing datasets were generated of the hiPSC-derived neo-cartilages, and the epigenetically-regulated transcriptome was compared to that of neo-cartilage deposited by human primary articular cartilage (hPAC).
Results
Methylome-wide landscapes of neo-cartilages of hiPSCs reprogrammed from two different somatic tissues were 85% similar to that of hPACs. By integration of transcriptome-wide data, changes in transcriptionally active CpGs between hCiC relative to hPAC were prioritized. Among CpG-gene pairs lower expressed in hCiCs relative to hPACs, we identified genes such as MGP, GDF5, and CHAD enriched in closely related pathways and involved in cartilage development that likely mark phenotypic differences in chondrocyte states. Vice versa, among CpG-gene pairs higher expressed, we identified genes such as KIF1A or NKX2-2 enriched in neurogenic pathways and likely reflected off target differentiation.
Conclusions
We did not find significant variation between the different tissue sources of the hiPSCs, suggesting that application of a robust differentiation protocol such as we applied here is more important as compared to the epigenetic memory of the cells of origin. Results of our study could be further exploited to improve quality, purity, and maturity of hiPSC derived neo-cartilage matrix, ultimately to realize introduction of sustainable, hiPSC derived neo-cartilage implantation into clinical practice.
The implications of lipids mobility, drug-enhancers (surfactants)-skin interaction and TRPV1 on licorice flavonoids permeability
Authors: Wang Zhuxian , Hu Yi , Xue Yaqi , Wu Yufan , Zeng Quanfu , Chen Hongkai , Guo Yinglin , Liang Peiyi , Shen Chunyan , Jiang Cuiping , Liu Li , Shen Qun , Zhu Hongxia , Liu Qiang
Published: September 2023

Licorice flavonoids (LFs) attained a considerable interest in cosmetic and skin ailments treatments, however, their lipophilic nature restricts their application. In this paper, we systematically investigated the enhancement efficacy and mechanisms of different penetration enhancers (surfactants) on ten LFs compounds. Herein, the aim was to unveil how seven different enhancers modified the stratum corneum (SC) surface and influence the drug-enhancers-skin interaction, and to relate these effects to permeation enhancing effects of ten LFs compounds in the liquids. The enhancing efficacy was evaluated by ERpermeation, ERretention and ERcom, which was conducted on the porcine skin. It was summarized that heat capsaicin (CaP) and lipophilic Plurol® Oleique CC 497 (POCC) caused the most significance of SC lipids fluidity, SC water loss and surface structures alterations, thereby resulting in a higher permeation enhancing effects than other surfactants. Moreover, CaP could completely occupied drug-skin interaction sites, while POCC only occupied most drug-skin interactions. The enhancing efficacy of both POCC and capsaicin was dependent on the log P values of LFs. For impervious LFs with low drug solubility, enhancing their drug solubility helped them permeate into the SC interface. For high-permeation LFs, their permeation was hardly enhanced or inhibited ascribed to the strong drug-enhancer-skin strength in the SC. More importantly, drug-surfactant-skin energy possessed a good negative correlation with the LFs permeation amount for most LFs molecules. Additionally, transient receptor potential vanilloid 1 (TRPV1) rather than transient receptor potential melastatin 8 (TRPM8) mediated LFs permeation enhancement by capsaicin. The study provided novel insights for drug permeation enhancement from the viewpoint of molecular pharmaceutics, as well as the scientific utilization of LFs compounds and surfactants in topical or transdermal formulations.
Characteristics and survival of multifocal/multicentric breast cancer: a retrospective study of 415 cases
Authors: Tong Ying , Zhang Chuanpeng , Yang Susu , Liu Yitao , Sun Feixiang , Yu Ziyi , Fu Ziyi , Zhao Yi
Published: September 2023

Objectives: This study was to compare the clinicopathological and prognostic characteristics of multifocal/multicentric (MF/MC) with unifocal (UF) breast cancer to study the determinants of cancer multiplicity in survival.
Methods: A retrospective analysis of 83 MF/MC and 332 UF breast cancer patients was conducted. Clinicopathological characteristics and prognostic indicators were compared.
Results: MF/MC breast cancer were more likely to have lymph node metastasis and lymph vascular/perineural invasion. There was a statistically significant difference in the LRFS rate. Cancer multiplicity was not an independent prognostic factor.
Conclusion: MF/MC breast cancer are more aggressive. However, cancer multiplicity did not affect prognosis.
Unit of attentional refreshing in multiple identity tracking: Object and Boolean map
Authors: Lin Juntian , Jia Jianrong , Yu Huadong , Wu Shujie , Zhang Yu , Li Jie
Published: September 2023

Tracking multiple distinct moving objects requires periodically refreshing the objects’ identity-location bindings. Classic theories assume that individual object is the unit of refreshing. Considering that features and locations can be represented as Boolean maps, in the present study we investigated whether Boolean map can also serve as the unit of refreshing in multiple identity tracking (MIT). We used an adapted MIT paradigm, in which every two targets shared the same identity and thus could be represented in one Boolean map. A cue was used to guide the refreshing when tracking was about to end. We examined whether only the cued target was refreshed (i.e., object-based refreshing) or the other target sharing the same identity was also refreshed (i.e., Boolean-map-based refreshing). In Experiment 1, all objects moved randomly. The results showed that while the cued target showed significantly better performance than uncued targets, no significant advantage was observed for the other same-identity target relative to other targets, revealing no Boolean-map-based refreshing. In Experiment 2, same-identity targets moved along parallel trajectories, so that the spatial relationship within each Boolean map remain unchanged during motion. The results showed that the same-identity target, as well as the cued target, was tracked better than other targets, revealing a same-Boolean-map advantage. Taken together, the results indicate that Boolean map can be used as the unit for attentional refreshing in MIT, but only in the circumstance where spatial relationship within each Boolean map remain unchanged as objects move, otherwise the refreshing is based on individual object.