bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR/Cas13a-triggered entropy-driven amplification for colorimetric and fluorescent dual-mode detection of microRNA
Authors: Yu Juanchun , Zhang Junhong , Li Meng , You Yiqin , Zhang Chenchen
Published: November 2023

MicroRNAs (miRNAs) are crucial biomarkers for the early detection and monitoring of disease progression of chronic obstructive pulmonary disease (COPD). Herein, we have devised a method for detecting miRNA using a combination of colorimetric and graphene oxide-based fluorescent techniques. The target miRNA in our design could precisely activate the trans-cleavage activity of the CRISPR-Cas13a system. The activated Cas13a enzyme cuts the “rUrU” section in the P1 probe, generating a nicking site to induce entropy-driven amplification (EDA). One of the available EDA products has the capability to unfold the hairpin probe, thereby initiating the catalytic hairpin assembly, exposing the G-quadruplex structure, facilitating the subsequent color response. The fuel strand labeled with Cy3 successfully established a double-stranded DNA structure with DNA3, and consequently the Cy3 would not be quenched by graphene oxide (GO). The proposed dual-mode strategy provides a sensitive, precise, and selective method for miRNA detection. The implementation of the dual-mode technique in this method yields greater benefits in terms of improving the precision and consistency of the miRNA measurements. The developed method has the capability to fluorescently measure miRNA-21 levels down to a concentration of 5.8 fM. In addition, the analysis of miRNA targets from clinical samples using this method demonstrates its promising utility in the fields of biomedical research of COPD.
Study on the Long-term Quality of Life and Influencing Factors in Elderly Patients After Vertebroplasty Based on the EQ-5D Chinese Utility Score System: a retrospective study
Authors: Gao Min , Jiang Xiu-Li , Ge Jian-Yun , Zeng Zhen , Song Jie
Published: November 2023

Background The quality of life in elderly patients after vertebroplasty is influenced by various factors. Although the EQ-5D scale has been widely used to assess quality of life, the factors affecting the long-term postoperative quality of life of elderly vertebroplasty patients in China have not been thoroughly studied.
Methods This study is a retrospective research that included 519 patients aged 65 and above who underwent elective vertebroplasty. We collected baseline data from these patients and conducted telephone follow-ups 12 months post-operation to evaluate their EQ-5D health utility values and EQ-VAS scores. Univariate and multivariate linear regression models were used to analyze the factors affecting quality of life.
Results Of the 519 patients, the majority were female (78.0%), with ages ranging from 65 to 95 years and an average age of 75.2 years. Twelve months post-operation, pain/discomfort was the most commonly reported issue by 68.4% of patients. The median EQ-5D health utility value was 0.783, with a range between 0.450 and 0.887; the median VAS score was 75, ranging from 60 to 85. Multivariate linear regression analysis indicated that older age, hormone use, higher ASA grades, non-drinking habits, and low albumin levels were independent risk factors affecting the long-term quality of life in elderly patients after vertebroplasty. Additionally, a history of tumors, the number of vertebral compression fractures, and bone density were also crucial influencing factors.
Conclusions Based on the EQ-5D Chinese utility scoring system, we evaluated the quality of life of patients aged 65 and above 12 months after vertebroplasty. This study identified several factors related to the postoperative quality of life in elderly vertebroplasty patients, providing crucial evidence for further clinical decisions and patient education.
Incremental diagnostic value of SPECT/CT to post-radioiodine therapy planar whole-body scan in patients with papillary thyroid cancer
Authors: Zhu Liya , Son Junik , Lee Won Kee , Ahn Byeong-Cheol
Published: November 2023

Purpose
This study aimed to assess the value of adding single-photon emission computed tomography/computed tomography (SPECT/CT) to whole-body scan (WBS) in patients with papillary thyroid cancer (PTC).
Subjects and methods:
This study included 265 patients with PTC (aged > 20 years) who underwent WBS and SPECT/CT after radioiodine treatment. Patients were classified into non-metastasis, lymph node (LN) metastasis, and distant metastasis groups based on the diagnosis by the WBS. In addition, results of the WBS were compared with those of SPECT/CT to WBS, and according, the patients were divided into concordant and discordant subgroups.
Results
The addition of SPECT/CT changed the diagnosis of WBS in 28 (10.6%) of the 265 patients. The results of comparing the clinicopathological features of the subgroups suggested that the tumor size and serum thyroglobulin (TG) level in the discordant subgroup were significantly different from those in the concordant with the increasing trend in the non-metastasis group. In the distant metastasis group, the serum TG level in the discordant subgroup was significantly lower than that in the concordant subgroup, while the clinic-pathological factors were not different in the LN metastasis group. However, for the LN metastasis and distant metastasis groups, SPECT/CT changed the diagnosis of patients by 21.1% and 50.0%, respectively.
Conclusion
The results of this study suggest that the addition of SPECT/CT to WBS in patients who have PTC, large initial tumors, or high serum TG levels in the non-metastasis group may offer a more accurate diagnosis. Patients diagnosed with distant metastasis by the WBS and had low TG levels require additional SPECT/CT. Thus, SPECT/CT is recommended for patients diagnosed with LN metastasis and distant metastasis by WBS.
Hyperbaric oxygen therapy reduces the traumatic brain injury-mediated neuroinflammation through enrichment of Prevotella copri in the gut of male rats
Authors: Nyam Tee-Tau Eric , Wee Hsiao-Yue , Chiu Min-Hsi , Tu Kuan-Chi , Wang Che-Chuan , Yeh Yao-Tsung , Kuo Ching-Lung
Published: November 2023

Background
Gastrointestinal dysfunction frequently occurs following traumatic brain injury (TBI) and significantly increases posttraumatic complications. TBI can lead to alterations of gut microbiota. The neuroprotective effects of hyperbaric oxygen (HBO) have not been well recognized after TBI. The study aim was to link the impacts of HBO on the TBI-induced dysbiosis in the gut and the pathological changes in the brain after TBI.
Material and method
: Anesthetized male Sprague–Dawley rats were randomly assigned to 3 groups: sham surgery plus normobaric air (NBA) (21% oxygen at 1 ATA), TBI (2.0 atm) plus NBA, and TBI (2.0 atm) plus HBO (100% oxygen at 2.0 ATA) for 60 minutes immediately after TBI, 24 hours, and 48 hours later. The brain injury volume, TNF-α expression in the microglia and astrocyte, and neuronal apoptosis in the brain were consequently determined. The V3/V4 regions of 16S rRNA of the fecal samples were sequenced, and alterations of the gut microbiome were statistically analyzed. All parameters were evaluated at the 3rd day after TBI.
Results
Our results showed HBO improved TBI-induced neuroinflammation, brain injury volume and neuronal apoptosis. HBO appeared to increase the abundance of aerobic bacteria but inhibit anaerobic bacteria. Intriguingly, HBO reversed the TBI-mediated decrease of Prevotella copri and Deinococcus spp., which were both negatively correlated with neuroinflammation and brain injury volume. TBI increased the abundance of these gut bacteria in relation to NOD-like receptor signaling and Proteasome pathway, which also had a positive correlation trend to neuroinflammation and apoptosis. The abundance of Prevotella copri was negatively correlated to NOD-like receptor signaling and Proteasome pathway.
Conclusion
Our study demonstrated the neuroprotective effects of HBO after acute TBI might act through reshaping the TBI-induced gut dysbiosis and reversed the TBI-mediated decrease of Prevotella copri to reduce TBI-induced neuroinflammation through inhibition NOD-like receptor signaling and Proteasome pathway.
Deficiency of histone H3K36 methyltransferase SETD2 inhibits proliferation and migration of hepatocellular carcinoma through ERK pathway
Authors: Yang Yi , Zhang Linlin , Munyurangabo Gustave , Jin Hua , He Shuyang , Jia Yachun , Zhang Peihua , Yu Xiao , Yang Dan , Kong Guangyao
Published: November 2023

Background
Hepatocellular carcinoma (HCC) is one of the leading cause of cancer-related death worldwide. SETD2, as the only known methyltransferase for catalyzing trimethylation of histone H3 lysine 36 (H3K36), has been reported to be associated with several cancers. However, the function of SETD2 in HCC is ambiguous. This work aims to research the function and mechanism of SETD2 in HCC based on bioinformation analysis and cell experiments.
Methods
SETD2 expression and its relationship with prognosis in LIHC patients were evaluated based on the Cancer Genome Atlas (TCGA) database, the effect of SETD2 silencing and overexpression on HCC cell lines was explored according to CCK-8 assay, colony formation assay and wound healing assay. RNA-seq analysis, western blot and chromatin immunoprecipitation (ChIP) assay were used to explore the potential mechanism of SETD2 in HCC.
Results
The results indicated that SETD2 expression was upregulated and high SETD2 expression was related to poor prognosis in HCC. SETD2 silencing inhibited the proliferation and migration, and SETD2 overexpression promoted the proliferation and migration in HCC cells. RNA-seq data revealed that differentially expressed genes were dramatically enriched in fibroblast growth factor receptor signaling pathway. FGFBP1, as a FGF-binding protein, ranked in the top 10 among the DEGs. The expression of FGFBP1 in SETD2 silencing BEL-7402 cells was significantly decreased. As the downstream effector of FGFR, ERK phosphorylation level had positive correlation with SETD2. Besides, H3K36me3 directly bound to the promoter of FGFBP1 confirmed by ChIP-qPCR.
Conclusions
Our findings highlight the promotion role of SETD2/H3K36me3 in HCC proliferation and migration via FGFR-ERK signal pathway. Our studies will advance our understanding of epigenetic dysregulation at HCC progression and provide a rationale for SETD2 as potential diagnostic biomarker and therapeutic target in HCC.
Natto (fermented soybeans)-induced anaphylaxis in a surfer with the possibility of sensitization to poly(γ-glutamic acid) from cutaneous exposure to jellyfish sting: A case report
Authors: Shigeno Ayami , Suzuki Tsuyoshi , Obayashi Masakazu , Asada Kei , Matsushima Satoru
Published: November 2023

Background
We report a case of anaphylaxis induced by natto (fermented soybeans) allergy that occurred following dermal sensitization from a jellyfish sting.
Case presentation:
A 49-year-old male presented to the emergency room complaining of an acute onset of erythema with pruritis that appeared while he was surfing. Given that his heart rate dropped to ~ 40 bpm without a decline in blood pressure or oxygen saturation, we suspected anaphylaxis and administered 0.5 mg of adrenaline intramuscularly. Immediately after the muscular adrenaline injection, his heart rate recovered to ~ 60–70 bpm.
Conclusions
The major allergen that induces natto allergy is poly(γ-glutamic acid) (PGA), which is present in its mucilage. Given that PGA is also produced by jellyfish tentacles, it can be inferred that the PGA sensitization occurred via dermal exposure to jellyfish PGA. This is an example of a food allergy induced by animal stings. As PGA is a high-molecular-weight polymer, natto allergy, despite being IgE-mediated, often presents with late-onset anaphylaxis, which typically develops half a day after digestion. PGA has a wide range of applications in pharmaceuticals, cosmetics, and foods. Patients may develop allergic symptoms and experience repeated anaphylaxis with no known cause. Therefore, it is important to obtain a detailed medical history and individually instruct patients suspected of being allergic to PGA to avoid PGA-containing products.
An iterative matrix uncertainty selector for high-dimensional generalized linear models with measurement errors
Authors: Nono Betrand Fesuh , Nguefack-Tsague Georges , Kegnenlezom Martin , Nguéma Eugène-Patrice Ndong
Published: November 2023

Various regularization methods through penalization of parameters have been proposed for variable selection in high-dimensional regression analysis with measurement errors. Most of these techniques require knowledge of the measurement error distribution whose estimation can be computationally expensive or even unfeasible. A measurement error distribution free correction based on Rosenbaum and Tsybakov’s matrix uncertainty selector (MUS ) and Taylor expansion for generalized linear models (GLMs), termed generalized matrix uncertainty selector (GMUS), and its lasso variant, called generalized matrix uncertainty lasso (GMUL) have been proposed. Validation of the methods was mostly based on simulations, hence performance on real datasets remains to be verified. In this paper, we propose an iterative matrix uncertainty selector (IMUS) for high-dimensional GLMs which does not require knowledge of the measurement error distribution.The approach is grounded on the Rosenbaum and Tsybakov’s MUS and the derivation of the linear model underlying the iterative re-weighted least squares estimate in a GLM. Theoretical justifications have been given, alongside numerical comparison with the GMUS and GMUL with Taylor expansion truncated at first order. Simulations results and practical applications on three microarray real datasets demonstrate the effectiveness of our proposed method, producing comparable results for covariate selection in simulations or sometimes superior results in terms of convergence and well-defined elbow for all real datasets relative to the other methods. The IMUS algorithm is easily adaptable to all families as per the glm function in the stats R package.
Deep Learning-Based Automatic Measurement of Prostate Volume Using Two- Dimensional Transrectal Ultrasound: A Pilot Study
Authors: Yoon Heechul , Park Gihun , Hwang Inhyeok , Choi Moon Hyung , Song Tai-kyong
Published: November 2023

Purpose
The aim of this study is to automatically measure the prostate volume based on two-dimensional transrectal ultrasound (TRUS) images using deep learning.
Methods
A total of 1,645 ultrasound images were collected from 110 patients and partitioned into training and testing datasets at a 10:1 ratio. We introduced a method for automated prostate volume measurement using deep learning techniques on 2-D TRUS images. Initially, we applied a VGG-19-based model to classify the cross-sectional TRUS images into two types – transverse and sagittal images. These two groups of the categorized images were respectively fed into a U-Net-based model for segmentation. From the U-Net-based model, we obtained segmented images that are used to measure the prostate’s length and volume via an ellipsoid method. The measured volumes from our model were quantitatively evaluated by radiologist-measured results; the classification network was assessed based on accuracy and the segmentation network was assessed using intersection over union metrics, respectively.
Results
The classification network showed an accuracy of 99.35%, and the segmentation network exhibited a mean intersection over union value of 90.88%. The average error rate between the measured volume of the proposed method and the volume measured by the clinical assessment is 9.17%.
Conclusions
We have demonstrated that 2-D TRUS images, obtained through routine clinical diagnosis of prostate, can be effective and reliable in measurement of prostate volumes through a deep-learning-based approach with the ellipsoid formula. Our method can potentially address the previous challenges related to patient-dependent prostate shapes, ambiguous brightness patterns in TRUS, and inconsistencies among different operators when performing manual measurements.
Risk factors of renal insufficiency in patients with chronic obstructive pulmonary disease; A systematic review and meta-analysis
Authors: QIAN CAI HUA , MAO WEI , LU CHEN
Published: November 2023

Background
Chronic obstructive pulmonary disease (COPD) is a progressive, systematic inflammatory disorder. Chronic kidney disease (CKD) is frequently associated with COPD. A number of risk factors of CKD have been investigated among patients living with COPD. Conversely, the findings of the previous studies are contradictory and inconsistent. The present systematic review and meta-analysis revealed the risk of chronic renal insufficiency among patients living with COPD and patients-related and management-related risk factors.
Methods
Literature searching of twelve databases was performed on 14 July 2023. All clinical studies comparing the patients-related, COPD-related, and management-related variables among patients with COPD who developed chronic renal insufficiency and control groups were eligible. Studies reported the potential predictors of chronic renal insufficiency among patients with COPD were included.
Results
This meta-analysis included nine studies, encompassing 64289 patients with COPD. Of them, 10217 patients developed CKD, while 54072 had no-CKD. The risk of CKD after COPD was 22.5% (event rate 0.225, 95%CI; 17.2, 0.289; p < 0.001). Elderly patients (MD;5.50 years ,95%CI; 2.99, 8.02; p < 0.001), hypertensive patients (RR; 1.47, 95%CI; 1.16, 1.85; P = 0.001), diabetic patients (RR; 2.27, 95%CI; 1.52 to 3.38; P < 0.001), and patients with peripheral vascular disease (RR; 1.52, 95%CI; 1.45, 1.6; P < 0.001) were at higher risk of CKD.
Conclusions
The present meta-analysis pointed out the considerable risk of CKD among patients with COPD. Elderly patients with hypertension, diabetes mellitus, stroke, or peripheral vascular diseases were at higher risk of CKD.
Bioactivity and Toxicity of Biogenic Nickel Oxide Nanoparticles Using Punica granatum Seed Extract
Authors: Hussein Mohamed A. , Abdelkarim Esraa A. , Elsamahy Tamer , Sobhy Mabrouk , Bayomi Rasha M. El , Hafez Abd-Elsalam E.
Published: November 2023

The biosynthesis of metal oxide nanoparticles has attracted attention because of their bioactivity, low cost, rapid reactivity, and simplicity. This study aims to synthesize and characterize the nickel oxide nanoparticles (NiO-NPs) by Punica granatum seed extract and evaluate their bioactivities and toxicity. The biosynthesized NiO-NPs physicochemical characteristics were explored using NTA, TGA, XRD, UV–Vis, and FT-IR, showing the formation of high-purity crystalline NPs with an average size of 10–60 nm. Furthermore, the antibacterial, antioxidant, and hemolytic activity of the biosynthesized NiO-NPs were explored. The results of this study showed that NiO-NPs possess a high antibacterial activity against Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive bacteria (methicillin-resistant Staphylococcus aureus and Aerococcus viridans). However, the NiO-NPs inhibitory effect on Gram-positive bacteria was higher than on Gram-negative bacteria. Moreover, NiO-NPs also showed a DPPH, ABTS, and H2O2 radical scavenging activity with non-hemolytic activity at low concentrations (< 250 mg/L) in a dose-dependent manner. Regarding the toxicity of NiO-NPs, an enhanced effect on seed development of Vigna radiate at low concentrations (5 mg/L) was observed, which can be utilized as an alternative to conventional agrochemicals. Also, the cytotoxicity analysis was performed in the L-929 normal fibroblast cell line using MTT assay and IC50 (125.5 mg/L), indicating that the biosynthesized NiO-NPs are biocompatible at different concentrations. The obtained data showed that the bioactivity of NiO-NPs might be due to their small size, which generates various active sites because of their high surface area. Generally, P. granatum seed extract showed ability as an efficient reducing and capping agent for NiO-NPs biosynthesis and played a vital role in enhancing their bioactivity.
Risk factors and a nomogram for predicting cognitive frailty in Chinese patients with lung cancer receiving drug therapy: a single-center cross-sectional study
Authors: Li Jinping , Wang Yan , Zhai Minfeng , Qin Mengyuan , Zhao Dandi , Xiang Qian , Shao Zaoyuan , Wang Panrong , Lin Yan , Dong Yiting , Liu Yan
Published: November 2023

Purpose
To identify independent factors of cognitive frailty and construct a nomogram to predict cognitive frailty risk in patients with lung cancer receiving drug therapy.
Methods
This is a cross-sectional study that enrolled patients with lung cancer undergoing drug therapy from October 2022 to July 2023. The collected data includes general demographic characteristics, clinical data characteristics and assessment of tools for cognitive frailty and other factors. Logistic regression was harnessed to determine the influencing factors, R software was used to establish a nomogram model to predict the risk of cognitive frailty. The enhanced Bootstrap method was employed for internal verification of the model. The performance of the nomogram was evaluated by using calibration curves, the area under the receiver operating characteristic curve, and decision curve analysis.
Results
A total of 372 patients were recruited, with a CF prevalence of 56.2%. Age, education background, diabetes Mellitus, insomnia, sarcopenia, and nutrition status were identified as independent factors by multivariate logistic regression analysis. Then, a nomogram model was constructed and patients were classified into high- and low-risk groups with a cutoff value of 0.552. For the entire cohort, the result of Hosmer-Lemeshow good of fit test was χ2 = 3.685 (P = 0.884), the area under the curve was 0.764 (95%CI:0.716–0.812), and the calibration curves presented good concordance with actual observations, which were consistent in both the training set and the validation set. Additionally, decision curve analysis demonstrated that the application of this nomogram could help improve clinical outcomes.
Conclusions
The prevalence of cognitive frailty was higher in lung cancer patients receiving drug therapy. The nomogram could identify the risk of cognitive frailty intuitively and simply in patients with lung cancer, so as to provide references for early screening and intervention for cognitive frailty at the early phases of drug treatment.
Online evolution of a phased array for ultrasonic imaging by a novel adaptive data acquisition method
Authors: Lukacs Peter , Stratoudaki Theodosia , Davis Geo , Gachagan Anthony
Published: November 2023

Ultrasonic imaging using ultrasonic phased arrays has an enormous impact in science, medicine and society and is a widely used modality in many application fields. The maximum amount of information which can be captured by an array is provided by the data acquisition method capturing the complete data set of signals from all possible combinations of ultrasonic generation and detection elements of a dense array. However, capturing this complete data set requires long data acquisition time, large number of array elements and transmit channels and produces a large volume of data. All these reasons make such data acquisition unfeasible due to the existing phased array technology or non-applicable to cases requiring fast measurement time. This paper introduces the concept of an adaptive data acquisition process, the Selective Matrix Capture (SMC), which can adapt, dynamically, to specific imaging requirements for efficient ultrasonic imaging. SMC is realised experimentally using Laser Induced Phased Arrays (LIPAs), that use lasers to generate and detect ultrasound. The flexibility and reconfigurability of LIPAs enable the evolution of the array configuration, on-the-fly. The SMC methodology consists of two stages: a stage for detecting and localising regions of interest, by means of iteratively synthesising a sparse array, and a second stage for array optimisation to the region of interest. The delay-and-sum is used as the imaging algorithm and the experimental results are compared to images produced using the complete generation-detection data set. It is shown that SMC, without a priori knowledge of the test sample, is able to achieve comparable results, while preforming ∼10 times faster data acquisition and achieving ∼ 10 times reduction in data size.
Comparison of liver resection and radiofrequency ablation in long-term survival among patients with early-stage hepatocellular carcinoma: A meta-analysis of randomized trials and high-quality propensity score- matched studies
Authors: Hu Lingbo , Lin Jiangying , Wang Aidong , Shi Xingpeng , Qiao Yingli
Published: November 2023

Background
Whether radiofrequency ablation (RFA) and liver resection (LR) are comparable treatments for early-stage hepatocellular carcinoma (HCC) is controversial. We conducted this study to provide ample clinical evidence for the argument.
Methods
The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials (RCTs) and propensity score-matched (PSM) studies that compared long-term outcomes of both RFA and LR for patients with early-stage HCC. The hazard ratios (HRs) with 95% confidence intervals (95% CI) of overall survival (OS) and disease-free survival (DFS) were calculated.
Results
Thirty-six studies consisting of six RCTs and thirty PSM studies were included in this study, and a total of 7,384 patients were involved, with 3,694 patients being treated with LR and 3,690 patients with RFA. Meta-analysis showed that LR provided better OS and DFS than RFA (HR: 1.22, 95% CI: 1.13–1.31; HR: 1.56, 95% CI: 1.39–1.74, respectively). A sensitivity analysis indicated that the results were stable. For the subgroup of patients with BCLC 0 stage, RFA and LR resulted in similar OS and DFS. For the subgroup of patients with single tumor sizes less than 3 cm, RFA reached similar OS (HR: 1.19, 95% CI: 0.90–1.58) but worse DFS compared with LR (HR: 1.45, 95% CI: 1.11–1.90). For the subgroup of ablation margin larger than 0.5cm, LR still resulted in better OS than RFA (HR: 1.29, 95% CI: 1.09–1.53), while the ablation margin was larger than 1cm, both RFA and LR resulted in similar OS. The modality of RFA was also a factor that affected results. Subgroup analysis showed that patients receiving ultrasound-guided RFA had worse OS and DFS than LR (HR: 1.24, 95% CI: 1.14–1.36; HR: 1.44, 95% CI: 1.25–1.66, respectively).
Conclusions
Meta-analysis showed that LR provided better OS and DFS for patients with early-stage HCC. However, RFA and LR had similar effects on long-term survival in patients with BCLC 0 stage HCC. RFA and LR had similar effects on OS in patients with solitary HCC less than 3cm or when the ablation margin was larger than 1cm. The effects of different modalities of RFA on long-term survival are needed for further assessment.
Scholarship Schemes in Cambodian Higher Education: Unpacking Why Lower-Income Students Are Lagging Behind
Authors: Seyhakunthy HUN
Published: November 2023

The authors have requested that this preprint be removed from Research Square.
Determination of HLA class II risk alleles and prediction of self/non-self epitopes contributing Hashimotoˈs thyroiditis in a group of Iranian patients
Authors: Shirizadeh Ata , Borzouei Shiva , Razavi Zahra , Taherkhani Amir , Faradmal Javad , Solgi Ghasem
Published: November 2023

One of the probable hypotheses for the onset of autoimmunity is molecular mimicry. This study aimed to determine the HLA-II risk alleles for developing Hashimotoˈs thyroiditis (HT) in order to analyze the molecular homology between candidate pathogen-derived epitopes and potentially self-antigens (TPO) based on the presence of HLA risk alleles. HLA-DRB1/-DQB1 genotyping was performed in 100 HT patients and 330 ethnically matched healthy controls to determine the predisposing/protective HLA alleles for HT disease in our population. Then, insilico analysis was carried out to examine the sequence homology between epitopes derived from autoantigens and four potentially relevant pathogens and their binding capacity for HLA risk alleles based on peptide docking analysis. We identified HLA-DRB1*03:01, *04:02, *04:05 and *11:04 as predisposing alleles and DRB1*13:01 as potentially predictive allele for HT disease. Also, DRB1*11:04 ~ DQB1*03:01 (Pc = 0.002, OR:3.97) and DRB1*03:01 ~ DQB1*02:01 (Pc = 0.004, OR:2.24) haplotypes conferred a predisposing role for HT. Based on logistic regression analysis, carrying risk alleles increased the risk of HT development 4.5 times in our population (P = 7.09E-10). Also, ROC curve analysis revealed a high predictive power of those risk alleles in discrimination of susceptible from healthy individuals (AUC: 0.70, P = 6.6E-10). Analysis of peptide sequence homology between epitopes of TPO and epitopes derived from four candidate microorganisms revealed a homology between envelop glycoprotein D of herpes virus and sequence 151–199 of TPO with remarkable binding capacity to HLA-DRB1*03:01 allele. Our findings indicate the increased risk of developing HT in those individual carrying HLA risk alleles which can also be related to herpes virus infection.
Clinical characteristics and risk factors for plastic bronchitis in children with severe Mycoplasma pneumoniae pneumonia: a retrospective observational study
Authors: Mu Shiyin , Zou Yingxue , Guo Yongsheng , Huang Bing , Zhai Jia
Published: November 2023

Background: Plastic bronchitis (PB) is a rare, underdiagnosed and potentially fatal condition that should not be overlooked in children, particularly in children with severe Mycoplasma pneumoniae pneumonia (SMPP). Therefore, we explored the risk factors for PB in children with SMPP and the diagnostic value for PB.
Methods: We retrospectively evaluated children with a clinical diagnosis of SMMP who were treated with bronchoscopy at Tianjin Children's Hospital from January 1, 2017, to December 31, 2021. According to the bronchoscopy and pathological examination results, the patients were divided into the PB group and the non-PB group. The clinical manifestations, laboratory data, imaging findings and treatments were analysed.
Results: Data from a total of 306 children with SMMP, including 109 children in the PB group and 197 children in the non-PB group, were reviewed. Procalcitonin (PCT), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), interleukin-6 (IL-6) and bronchial lavage fluid MP-DNA copy number levels were higher (P<0.05) while platelet (PLT) levels were lower (P<0.05) in the PB group. In addition, the incidence of pleural effusion, atelectasis, wheezing symptoms and hypoxemia in the PB group was significantly higher than that in the non-PB group (P<0.05). Multivariate logistic regression analysis showed that pleural effusion (odds ratio [OR], 3.148; 95% confidence interval [CI], 1.795-5.521; P<0.001), PLT (OR, 0.584; 95% CI, 0.439-0.776; P<0.001), and LDH (OR, 5.265; 95% CI, 1.488-18.630; P=0.011) were independent predictors of PB in children with SMPP. Receiver operating characteristic (ROC) curve analysis showed that the cut-off values for PLT and LDH in the diagnosis of PB were 242*109/L [sensitivity 57.80%; specificity 69.04%; area under the curve (AUC) 0.648; P<0.001] and 542 U/L (sensitivity 58.72%; specificity 64.97%; AUC 0.646, P<0.001), respectively. Children in the PB group had longer hospital stays and corticosteroid use durations than those in the non-PB group (P<0.05).
Conclusions: The PLT level (≤242*109/L), LDH level (>542 U/L) and pleural effusion were risk factors for PB in children with SMPP. This provides a basis for the early identification of PB in children with SMPP.
The Race Against Time: Evaluating the Speed of Gene Panel Result Delivery in NSCLC Patient Management
Authors: Kunimasa Kei , Tamiya Motohiro , Inoue Takako , Kawamura Takahisa , Miyazaki Akito , Kanzaki Ryu , Maniwa Tomohiro , Honma Keiichiro , Okami Jiro , Nishino Kazumi
Published: November 2023

Background
In this study, we aimed to compare the clinical utility of the Oncomine Dx® Target Test (Oncomine) with that of the AMOY Dx® Pan Lung Cancer PCR panel (AMOY), focusing on their turn-around times (TATs).
Methods
Data on the specimens, fresh-frozen (FF) or formalin-fixed paraffin-embedded (FFPE) tissue samples, the success rate and detected driver alterations, submitted for these gene panel analyses were also collected from medical records. Further, for the comparison of the two methods, TATs defined as: T1, the period from first visit to specimen submission at an external laboratory; T2, the period from first visit to when the attending physician ordered the gene panel test; and T3, the period from first visit until the availability of the analysis results, were measured.
Results
In total, 213 patients, with 157 and 56 who submitted specimens for Oncomine and AMOY, respectively, were enrolled. The success rate of the analyses were 98.0% for Oncomine and 100.0% for AMOY. Further, the detection rates of driver alterations were 57.9% and 50.9% for Oncomine and AMOY, respectively, and 95.9% specimens submitted for Oncomine were FFPE, while 78.2% of those submitted for AMOY were FF. Further, the TATs, T1, T2, and T3, tended to be significantly shorter in AMOY cases. Specifically, the median TAT for AMOY cases, particularly T3, was 12 days (range, 4–26 days).
Conclusions
AMOY showed shorter TATs and a higher success rate than Oncomine. Therefore, its application using FF specimens may be effectively utilized in oncologic emergencies.
Towards Effective Smartphone Pregnancy Apps: A Critical Evaluation of Quality, content and suitability in Freely Available Persian Pregnancy Apps
Authors: Asadollahi Fateme , Ebrahimzade samira , Roudsari Robab Latifnejad
Published: November 2023

Background
The rise of health apps in the digital health landscape has created opportunities for health promotion, particularly in pregnancy. However, despite pregnancy mobile apps' wide distribution and popularity, there is limited data on their quality and content. This review aimed to evaluate the Quality, content, and suitability of the most popular and freely available Persian smartphone pregnancy-related apps.
Methods
163 apps were screened from Google Play and Cafebazaar app store using the search term pregnancy app until July 2023. Apps in the Farsi language, freely available, downloaded more than 10,000 times, and designed for pregnant women were included. Finally, only nine apps met the inclusion criteria, downloaded on mobile phones and assessed by two independent reviewers using the Mobile App Rating Scale (MARS), the Coverage and Depth of Information Scale, and the Suitability Assessment of Materials (SAM).
Results
The mean of the four MARS subscale scores across all nine apps was 3.55 ± 0.61 out of a maximum of 5. Aesthetics and functionality subscales were rated the highest, followed by engagement and information subscales. Overall, 66% of apps were rated poor for coverage and depth of health information, 33% as adequate, and no app received a superior level. Regarding SAM, 44% of apps were rated superior, 55% adequate, and no app received a poor score.
Conclusions
This evaluation highlights the importance of evaluating the quality and content of pregnancy apps before recommending them to pregnant women. Healthcare providers should suggest high-quality pregnancy apps with appropriate content for pregnant women.
Simultaneous Production of Vitamin K2 and Iturin A by Bacillus velezensis ND
Authors: Shen Yeqiao , Cao Xiaojie , Tang Zhongmin , Gao Yuqiu , Zhang Huili
Published: November 2023

Bacillus velezensis is known to produce a diverse array of secondary metabolites, including the ability to synthesize lipopeptides such as iturin A, and additionally produce higher amounts of vitamin K2. Consequently, we sought to employ co-production fermentation to simultaneously generate vitamin K2 and iturin A. In order to significantly reduce fermentation costs and enhance substrate utilization efficiency, this article initially established a straightforward and effective product extraction method that enables the separate collection of vitamin K2 and iturin A from the fermentation broth. Simultaneously, the impacts of glycerol, soybean meal powder, yeast extract powder, and L-glutamic acid sodium, employed as carbon and nitrogen sources in the culture medium, on the co-production of vitamin K2 and iturin A were refined by optimizing factors such as culture temperature, initial pH and the concentrations of trace elements Na+ and K+, as well as additional additives L-glutamic acid sodium. It was discerned that glycerol, soybean meal powder, yeast extract powder, and L-glutamic acid sodium significantly influenced the concurrent production of vitamin K2 and iturin A. As a result, a novel process for the efficient co-production fermentation of vitamin K2 and iturin A was established, thereby enhancing the value-added aspect of the fermentation process. Furthermore, the implementation of a two-compartment biofilm reactor synergistically elevated the co-production efficiency. The yields of vitamin K2 and iturin A reached 46.88 mg/L and 5.58 g/L, respectively. This study provides a theoretical framework and practical implications for the integrated double-product fermentation process.
Innovative, simple and efficient algorithms for logarithms with adjustable accuracy
Authors: Gepner Paweł , Moroz Leonid , Samotyy Volodymyr , Kokosiński Zbigniew , Gavkalova Nataliia , Kocot Bartłomiej
Published: November 2023

The computation of logarithmic functions is essential for many computational applications in science and engineering. Various computational techniques have been developed to approximate these functions. In this article, we present a simple and efficient algorithm for calculating the logarithmic function using IEEE 754 standard arithmetic types that minimises the number of arithmetic operations compared to previous implementations. Our starting point is Mitchell’s linear approximation, which reduces the computation of the logarithm to just the addition of the exponent and the significand. We developed a parameterised framework for choosing the number of segments in a piecewise polynomial approximation scheme in combination with polynomial degree and bit manipulation techniques, which allows a tradeoff between the accuracy and efficiency. We measured a speedup by a factor of 3--20 with respect to the C/C++ library software implementation while keeping the absolute error at a low level. This article presents and discusses our proposed implementation, compares it to other logarithm realisations and tests these realisations on various platforms.
Repetitive mild traumatic brain injury elicits a reactive microglial morphology and elevates serum neurofilament light levels, independent of NLRP3 inflammasome inhibition
Authors: O'Brien William , Green Tabitha R.F. , Pham Louise , Bain Jesse , Sobey Christopher G , Robertson Avril A B , O’Brien Terence J. , Monif Mastura , Shultz Sandy R , Rowe Rachel K. , McDonald Stuart J.
Published: November 2023

There is growing evidence that a second mild traumatic brain injury (mTBI) sustained prior to cellular and neurological recovery from the first increases risk of cumulative pathological and neurological deficits. Despite this, the pathophysiology of single and repeated mTBI (rmTBI) is not well understood, and as such, no therapeutic interventions are available to mitigate the cumulative deficits induced. The Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome is an intracellular protein complex that is critical to the innate immune response. Although neuroinflammation is a key feature of mTBI pathophysiology, little is known about the role of the inflammasome in rmTBI. To investigate this, we used a clinically relevant rat model of mTBI and assessed whether pharmacologically inhibiting NLRP3 with the specific NRLP3 inhibitor MCC950, reduced inflammasome activation in the brain and thereby improved acute behavioural and molecular outcomes. We hypothesised that rmTBI would result in up-regulation of inflammasome-associated genes, a reactive microglial phenotype, axonal injury, and neurobehavioural deficits, and that these factors would be attenuated by NLRP3 inflammasome inhibition with MCC950. We found that rmTBI increased hippocampal apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) mRNA expression, increased microglia cell number in the motor cortex, sensorimotor cortex, hippocampus, corpus callosum and thalamus, and elevated serum neurofilament light (NfL) levels that correlated with both the number of microglia in the corpus callosum, and sensorimotor deficits. These changes were not mitigated by MCC950 treatment. This study provides evidence that the NLRP3 inflammasome does not play a significant role in the acute neuroinflammatory response following rmTBI; however further studies are required to investigate its role chronically.
Clinical Efficacy and Central Mechanisms of Electroacupuncture Treatment for Low Back Pain in Primary Osteoporosis: Study Protocol for a Randomized Controlled Trial
Authors: Huang Chihuan , Liu Jing , Wang Zun , Zhang Di , Guo Zhijie , Wei Liyu , Liu Shaowei , Liu Lanying , Xu Daoming
Published: November 2023

Background
Primary osteoporosis is a common disease in the elderly, often causing low back pain and limited mobility. Electroacupuncture is considered a combination of traditional acupuncture and modern transcutaneous electrical nerve stimulation. Due to its strong stimulation, it has shown certain efficacy in relieving low back pain associated with primary osteoporosis (POP). It has the potential to be a complementary or alternative treatment for drug therapy of POP-related low back pain. However, the underlying mechanisms have not been fully elucidated. Therefore, this study, by evaluating the efficacy of electroacupuncture in treating POP-related low back pain, aims to explore the potential central mechanisms using resting-state functional magnetic resonance imaging (rs-fMRI).
Methods
This study is a randomized controlled trial in which 60 patients were randomly divided into two groups: the calcium group (n = 30) and the calcium + electroacupuncture group (n = 30). The study lasted for 17 weeks, including a 1-week baseline, 4 weeks of treatment, and 12 weeks of follow-up (at the 4th and 12th week after treatment). The primary outcome measure is McGill Pain Questionnaire (MPQ), and secondary outcome measures include the Oswestry dysfunction index(ODI), Young's Modulus, and the use of analgesic medications after treatment. These measures will be used to evaluate the clinical efficacy of the two intervention methods for treating low back pain associated with primary osteoporosis (POP). Twenty patients from each group will be randomly selected for rs-fMRI examinations to observe changes in brain functional activity and correlate them with changes in pain severity.
Discussion
This study aims to evaluate the clinical efficacy and potential central mechanisms of electroacupuncture in treating low back pain associated with POP. Provided that we obtain imaging-based evidence of the effectiveness of electroacupuncture intervention for POP-related low back pain, this study will provide supporting evidence for the clinical application of electroacupuncture in the treatment of low back pain associated with POP.
Trial registration:
Chinese Clinical Trial Registry ChiCTR2300075736. Registered on 14 September 2023
Assessing the Value of Disulfide Death-Associated Genes in the Prognosis and Treatment of Glioma
Authors: Wu HaoYuan , Yang ZhiHao , Chang ChenXi , Wang ZhiWei , Zhang DeRan , Guo QingGuo , Zhao Bing
Published: November 2023

Background
"Disulfide death," a form of cellular demise, is triggered by the abnormal accumulation of intracellular disulfides under conditions of glucose deprivation. However, its role in the prognosis of glioma remains undetermined. Therefore, the main objective of this study is to establish prognostic signature based on disulfide death-related genes and to provide new solutions in choosing the effective treatment of glioma.
Methods
The combined analysis utilizes data from the Atlas of Cancer Genome (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Genotype-Tissue Expression (GTEx) databases to screen disulfide death-related genes. Then, TCGA and CGGA serve to construct and verify prognostic signature. In addition, the immunological characteristics of the model and the potential predictive value of immune and chemotherapeutic responses were further explored. Finally, the effect of Importin-4(IPO4) on gliomas has been further confirmed through functional experiments.
Results
7 genes associated with disulfide death were obtained and two subgroups of patients with different prognosis and clinical characteristics were identified. Risk signature was subsequently developed and proved to serve as an independent predictor. The high-risk group exhibited immunosuppressive microenvironment, and was characterized by high concentration of M2 macrophages and regulatory T cells (Tregs). Patients in high-risk group may benefit more from immunotherapy and chemotherapy. In addition, in vitro experiments have shown that inhibition of the expression of IPO4 leads to a significant reduction in the proliferation, migration, and invasion of glioma cells.
Conclusion
This study constructed the first prognostic disulfide death-related gene signature in glioma with the ability to optimize the choice of patients receiving immuno- and chemotherapies and provided a potential therapeutic target for glioma.
200 years of taxonomic confusion: Sporendonema and allies
Authors: Kandemir Hazal , Decock Cony , Hernández-Restrepo Margarita , Labuda Roman , Houbraken Jos , Ilkit Macit , Hoog GS Sybren
Published: November 2023

The genus Sporendonema was introduced in 1827 with the type species S. casei. for a red mold on cheese. Cheese is a consistent niche for this species. Sphaerosporium equinum is another species classified in Gymnoascaceae (Onygenales) and has also been reported from cheese. Recently, other habitats have been reported for both Sporendonema casei and Sphaerosporium equinum. The present study aimed to investigate the taxonomy of Sporendonema and Sphaerosporium, as well as a close neighbor, Arachniotus. Hormiscium aurantiacum, another related cheese-associated species was also included in the analyses. Strains were evaluated in terms of colony morphology, micromorphology, salt tolerance, growth rate at different temperatures, casein degradation, cellulase activity and multilocus phylogeny with sequences of the nuclear ribosomal internal transcribed spacer region, the D1-D2 region of the large subunit and partial β-tubulin locus sequences. The results showed that the analysed species were congeneric, and the generic names Arachniotus and Sphaerosporium should be reduced to the synonymy of Sporendonema. Therefore, four new combinations as well as one lectotype and one epitype were designated in Sporendonema. Two strains attributed to Sphaerosporium equinum from substrates other than cheese were found to be phylogenetically and morphologically deviant and were introduced as a new species named Sporendonema isthmoides.