bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of development speed and quality of blastocyst on singleton birthweight in single frozen-thawed blastocyst transfer cycles
Authors: Wang Xue , Xiao YaLing , Sun ZhengYi , Tao Tao
Published: January 2024

Background

Assisted reproductive technology (ART) has revolutionized infertility treatment, leading to a surge in ART-conceived children. Despite its success, ART-born offspring face higher risks of preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). The mechanisms behind these outcomes remain unclear, partly attributed to multiple embryo transfers. Recent advancements advocate single blastocyst transfers for improved outcomes. However, the influence of blastocyst quality and development speed on neonatal outcomes is underexplored.

Objective

This study investigated whether blastocyst development speed and quality affect singleton birthweight when the blastocyst is selected for single frozen-thawed blastocyst transfer (FBT).

Methods

Data from patients who performed an FBT cycle at our center from July 2011 to June 2021 were collected and analyzed. Based on the inclusion and exclusion criteria, 420 single FBT cycles were assessed. The women were divided into four groups, Group A (day 5, good-quality blastocysts), Group B (day 5, non-good-quality blastocysts), Group C (day 6, good-quality blastocysts), and Group D (day 6, non-good-quality blastocysts) according to the developmental speed and quality of the transferred blastocyst.

Results

The birthweight was relatively the highest in Group A, which developed rapidly and transferred good quality blastocysts. However, no significant difference existed among the groups (P>0.05). The prevalence of premature birth (PTB), low birth weight (LBW), very low birth weight (VLBW), or high birth weight (HBW) was similar among the four groups (P > 0.05). No correlation existed between birth weight and blastocyst development speed or quality after adjusting for possible confounders (P > 0.05 respectively). However, the difference in the proportion of males born among the four groups was significant, especially in Group D, which was significantly lower than that in Group A (adjusted odds ratio = 0.461, 95% confidence interval: 0.230–0.921, P < 0.05).

Conclusions

This retrospective cohort study suggests that the combined effect of blastocyst development speed and quality on neonatal birthweight is insignificant. The transfer of slow-growing, non-good-quality blastocysts increases the chance of a female baby being born.
Late age at first birth is a protective factor for oesophageal cancer and gastro-oesophageal reflux: the evidence from the genetic study
Authors: Su Yani , Xu Yiwei , Hu Yunfeng , Chang Yu , Wu Fangcai , Yang Mingyi , Peng Yuhui
Published: January 2024

Objective

The primary objective of this research endeavor was to examine the underlying genetic causality between the age at first birth (AFB) and four prevalent esophageal diseases, namely oesophageal obstruction (OO), oesophageal varices (OV), gastro-oesophageal reflux (GOR), and oesophageal cancer (OC).

Methods

We conducted a two-sample Mendelian randomization (MR) analysis to examine the causal association between AFB and four prevalent esophageal disorders. We employed eight distinct MR analysis techniques to evaluate causal relationships, encompassing random-effects inverse variance weighted (IVW), MR Egger, weighted median, simple mode, weighted mode, maximum likelihood, penalized weighted median, and fixed-effects IVW. The random-effects IVW method served as the primary approach for our analysis. Furthermore, we executed several sensitivity analyses to assess the robustness of the genetic causal inferences.

Results

The random-effects IVW analysis revealed a significant negative genetic causal association between AFB and both GOR (P < 0.001, Odds Ratio [OR] 95% Confidence Interval [CI] = 0.882 [0.828-0.940]) and OC (P < 0.001, OR 95% CI = 0.998 [0.998-0.999]). Conversely, there was insufficient evidence support to substantiate a genetic causal link between AFB and OO (P = 0.399, OR 95% CI = 0.873 [0.637-1.197]) or OV (P = 0.881, OR 95% CI = 0.978 [0.727-1.314]). The results of sensitivity analyses underscore the robustness and reliability of our MR analysis.

Conclusion

The findings of this investigation substantiate the notion that elevated AFB confers a protective effect against GOR and OC. In addition, no causative association was discerned between AFB and OO or OV at the genetic level.
Biomass and bioenergy perspectives of a coal region: status quo, potential and scenarios in Lusatia
Authors: Leuner Bruna , Hirschl Bernd
Published: January 2024

Coal has been one of the main fuels used in Europe. Its decreasing role due to the ongoing transformation of the energy system will create significant socio-economic challenges. The switch into renewable energy systems could be an alternative to maintain jobs and economic activities within the affected regions. Biomass use and bioenergy can play an important role in the energy transition. Instead of energy crops, forest and agricultural residues should be used as biogenic energy sources in the future to avoid impacts on land use and food security. The main objective of this article is to investigate the biomass potential of a coal region and to provide scenarios for the future development of bioenergy production. Due to the changing framework conditions and, as a result, the different biomass focuses, previous bioenergy potential estimates must be reviewed. The methods for determining the potential of biomass for energy production was used for Lusatia (in German: Lausitz), the second largest coal region in Germany. These methods can also be applied in other regions. As a first step, the regional status quo assessment of cultivated areas and yields had decisive relevance for calculating biomass potential ranges. In a second step, the current bioenergy facilities in the region were identified, with a focus on power and heat production. The third step was the estimation of future regional bioenergy use. Therefore, the regional potential was gathered with the generally supra-regional framework conditions. For this purpose, national scenario studies were used, which contain the relevant target values and framework conditions. Two scenarios were developed for future bioenergy estimations: a conservative path based on the current policies and a progressive path, derived from the goal of climate neutrality by 2045. The results show a qualitative comparison among both scenarios and the previously determined potential ranges. Bioenergy can probably contribute to achieving climate neutrality with an increase in wood-fired systems, while agricultural bioenergy potential is likely to decline. In the discussion section, however, the uncertainty of these results is pointed out, as future use of bioenergy will be heavily influenced by the regulatory framework, competition with material use and the influences of climate change.
Methylenetetrahydrofolate reductase polymorphic variants C677T and A1298C in rectal cancer in Slavic population: significance for cancer risk and response to chemoradiotherapy
Authors: Stanojevic Aleksandra , Spasic Jelena , Marinkovic Mladen , Stojanovic-Rundic Suzana , Jankovic Radmila , Djuric Ana , Zoidakis Jerome , Fijneman Remond J. A. , Castellvi-Bel Sergi , Cavic Milena
Published: January 2024

Background: Methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNPs) have been suggested as risk, prognostic, and predictive factors for colorectal cancer in various populations, but have not been validated so far. The aim of this study was to examine the association of MTHFR C677T (rs1801133) and A1298C (rs1801131) single nucleotide polymorphisms with the risk of rectal cancer as well as the response to neoadjuvant chemoradiotherapy (nCRT) based on 5-Fluorouracil (5-FU)/leucovorin (LV) in the locally advanced setting.

Patients and methods: This case-control study included 119 healthy controls and 97 patients with locally advanced rectal cancer (LARC). For MTHFR genotyping, restriction fragment length polymorphism analysis (PCR-RFLP) was employed.

Results:In silico analysis highlighted that SNPs C677T and A1298T correlate with MTHFR gene expression, and that gene expression profile correlates with cancer risk and stage. Using dominant and recessive models, it was found that the MTHFR 677CC vs. 677CT+677TT have increased risk of cancer development (odds ratio (OR): 2.27; 95% confidence interval (CI): 1.30–3.95, p = 0.002) as well as 677CC+677CT compared to 677TT (OR: 4.18, 95% CI: 1.16–14.99, p = 0.014). MTHFR 1298AA also shown increased risk for cancer development compared to 1298AC+1298CC (OR:2.0, 95% CI: 1.20–3.59, p = 0.035) Statistical analysis of combined genotypes highlighted the protective role of CT/AC combined genotype (OR: 3.15 95% CI: 1.576–6.279, p = 0.002) while the CC/AA genotype showed an increased risk for rectal cancer development (OR: 2.499, 95% CI: 1.246–5.081, p = 0.016) The carriers of the 677C/1298A haplotype had the highest risk for developing rectal cancer (OR: 1.74; 95% CI: 1.198–2.530, p = 0.002) while the 677T/1298C haplotype seems to provide a protective effect. (OR: 0.44; 95%CI 0.248–0.795, p = 0.003). No significant association with response to chemoradiotherapy was found.

Conclusion: Our data point to MTHFR 667C allele and 1298A alleles as low-penetrance risk factors for rectal cancer in our population. To the best of our knowledge, this is the first study of this type performed on the Slavic population in the Western Balkan, as various population-based factors might also be significant our findings can be used for future meta-analyses and the construction of genetic cancer risk prediction panels.
The crosstalk of CD8+ T cells and ferroptosis in cancer
Authors: Lin Zhengjun , Zou Songzhu , Wen Kunming
Published: January 2024

Ferroptosis is an iron-dependent, novel form of programmed cell death characterized by lipid peroxidation and glutathione depletion and is widespread in a variety of diseases. CD8+ T cells are the most important effector cells of cytotoxic T cells, capable of specifically recognizing and killing cancer cells. Traditionally, CD8+ T cells are thought to induce cancer cell death mainly through perforin and granzyme, and Fas-L/Fas binding. In recent years, CD8+ T cell-derived IFN-γ was found to promote cancer cell ferroptosis by multiple mechanisms, including upregulation of IRF1 and IRF8, and downregulation of the system XC-, while cancer cells ferroptosis was shown to enhance the anti-tumor effects of CD8+ T cell by heating the tumor immune microenvironment through the exposure and release of tumor-associated specific antigens, which results in a positive feedback pathway. Unfortunately, the intra-tumoral CD8+ T cells are more sensitive to ferroptosis than cancer cells, which limits the application of ferroptosis inducers in cancer. In addition, CD8+ T cells are susceptible to being regulated by other immune cell ferroptosis in the TME, such as tumor-associated macrophages, dendritic cells, Treg, and bone marrow-derived immunosuppressive cells. Together, these factors build a complex network of CD8+ T cells and ferroptosis in cancer. Therefore, we aim to integrate relevant studies to reveal the potential mechanisms of crosstalk between CD8+ T cells and ferroptosis, and to summarize preclinical models in cancer therapy to find new therapeutic strategies in this review.
Safety and efficacy of biliary stenting combined with iodine-125 seed strand followed by hepatic artery infusion chemotherapy plus lenvatinib with PD-1 inhibitor for the treatment of extrahepatic cholangiocarcinoma with malignant obstructive jaundice
Authors: Lin Long-Wang , Ke Kun , Chen Rong , Yang Wei-Zhu , Huang Ning , Wu Zheng-Zhong
Published: January 2024

Objectives

To evaluate the efficacy and safety of biliary stenting implantation with iodine-125 seed strand (SI) followed by hepatic artery infusion chemotherapy (HAIC) plus lenvatinib (Len) with programmed death-1 (PD-1) inhibitor for patients diagnosed with extrahepatic cholangiocarcinoma (ECC) and malignant obstructive jaundice (MOJ).

Methods

In this single-center retrospective study, the data of ECC patients with MOJ from March 2015 to January 2023 was assessed. Using probability score matching (PSM), the selection bias of patients was reduced. Primary study outcomes included overall survival (OS) and progression-free survival (PFS). The OS and PFS were performed using the Kaplan–Meier method and evaluated with the log-rank test.

Results

A total of 104 patients were enrolled finally, including 52 patients treated with interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor (SI+HAIC+Len+P group) and 52 patients treated with interventional therapy (SI+HAIC) plus lenvatinib (SI+HAIC+Len group). 26 pairs of patients were matched after PSM analysis. After PSM analysis, the median OS and PFS in the SI+HAIC+Len+P group were significantly longer compared to those in the SI+HAIC+Len group (OS:16.6 vs. 12.3 months, P = 0.001; PFS:12.6 vs 8.5 months, P = 0.004). The DCR was significantly different between groups (P = 0.039), while ORR not (P = 0.548). The addition of PD-1 inhibitor was generally well tolerated without treatment-associated mortality.

Conclusion

Interventional therapy (SI+HAIC) plus Len with PD-1 inhibitor was effective for ECC patients accompanied by MOJ with a manageable safety profile.
Case report: A case of Acute Macular Neuroretinopathy secondary to Influenza A virus during Long COVID
Authors: Zhang Jiaqi , Xia Yihao , Li Xiaodong , He Runxi , Xie Xuejun
Published: January 2024

Ocular abnormalities have been reported in association with viral infections, including Long COVID, a debilitating illness caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This report presents a case of a female patient diagnosed with Acute Macular Neuroretinopathy (AMN) following an Influenza A virus infection during Long COVID who experienced severe inflammation symptoms and ocular complications. We hypothesize that the rare occurrence of AMN in this patient could be associated with the immune storm secondary to the viral infection during Long COVID.
Distinct RBC alloantibody responses in type 1 interferon-dependent and -independent lupus mouse models
Authors: Paul Kausik , Hernández-Armengol Rosario , Lee June Young , Chang Che-Yu , Shibata Tomohiro , Yamashita Michifumi , Jefferies Caroline , Gibb David R.
Published: January 2024

During transfusion of red blood cells (RBCs), recipients are exposed to both ABO and non-ABO ‘minor’ antigens. RBC donor units and recipient RBCs are not routinely matched for non-ABO antigens. Thus, recipients are exposed to many RBC alloantigens that can lead to RBC alloantibody production and subsequent clinically significant hemolysis. RBC alloantibodies also significantly limit the provision of compatible RBC units for recipients. Prior studies indicate that the frequency of RBC alloimmunization is increased during inflammatory responses and in patients with autoimmune diseases. Still, mechanisms contributing to alloimmune responses in patients with autoimmunity are not well understood. More than half of adult patients with systemic lupus erythematosus (SLE) produce type 1 interferons (IFNα/β) and express IFNα/β stimulated genes (ISGs). Previously, we reported that IFNα/β promote RBC alloimmune responses in the pristane mouse model, which develops a lupus-like phenotype that is dependent on IFNα/β signaling. However, it is unclear whether IFNα/β or the lupus-like phenotype induces alloimmunization in lupus models. Therefore, we tested the hypothesis that IFNα/β promotes RBC alloimmune responses in lupus by examining alloimmune responses in IFNα/β-independent (MRL-lpr) and IFNα/β-dependent (pristane) lupus models. Whereas pristane treatment significantly induced interferon-stimulated genes (ISGs), MRL-lpr mice produced significantly lower levels that were comparable to levels in untreated WT mice. Transfusion of murine RBCs that express the KEL antigen led to anti-KEL IgG production by pristane-treated WT mice. However, MRL-lpr mice produced minimal levels of anti-KEL IgG. Treatment of MRL-lpr mice with recombinant IFNα significantly enhanced alloimmunization. Collectively, results indicate that a lupus-like phenotype in pre-clinical models is not sufficient to induce RBC alloantibody production, and IFNα/β gene signatures may be responsible for RBC alloimmune responses in lupus mouse models. If these findings are extended to alternate pre-clinical models and clinical studies, patients with SLE who express an IFNα/β gene signature may have an increased risk of developing RBC alloantibodies and may benefit from more personalized transfusion protocols.
Gut microbiota in combination with blood metabolites reveals characteristics of the disease cluster of coronary artery disease and cognitive impairment: a Mendelian randomization study
Authors: Xu Shihan , Liu Yanfei , Wang Qing , Liu Fenglan , Xian Yanfang , Xu Fengqin , Liu Yue
Published: January 2024

Background

The coexistence of coronary artery disease (CAD) and cognitive impairment has become a common clinical phenomenon. However, there is currently limited research on the etiology of this disease cluster, discovery of biomarkers, and identification of precise intervention targets.

Methods

We explored the causal connections between gut microbiota, blood metabolites, and the disease cluster of CAD combined with cognitive impairment through two-sample Mendelian randomization (TSMR). Additionally, we determine the gut microbiota and blood metabolites with the strongest causal associations using Bayesian model averaging multivariate Mendelian randomization (MR-BMA) analysis. Furthermore, we will investigate the mediating role of blood metabolites through a two-step Mendelian randomization design.

Results

We identified gut microbiota that had significant causal associations with cognitive impairment. Additionally, we also discovered blood metabolites that exhibited significant causal associations with both CAD and cognitive impairment. According to the MR-BMA results, the free cholesterol to total lipids ratio in large very low density lipoprotein (VLDL) was identified as the key blood metabolite significantly associated with CAD. Similarly, the cholesteryl esters to total lipids ratio in small VLDL emerged as the primary blood metabolite with a significant causal association with dementia with lewy bodies (DLB). For the two-step Mendelian randomization analysis, we identified blood metabolites that could potentially mediate the association between genus Butyricicoccus and CAD in the potential causal links.

Conclusion

Our study utilized Mendelian randomization (MR) to identify the gut microbiota features and blood metabolites characteristics associated with the disease cluster of CAD combined with cognitive impairment. These findings will provide a meaningful reference for the identification of biomarkers for the disease cluster of CAD combined with cognitive impairment as well as the discovery of targets for intervention to address the problems in the clinic.
Electrochemotherapy combined with immunotherapy – a promising potential in the treatment of cancer
Authors: Hadzialjevic Benjamin , Omerzel Masa , Trotovsek Blaz , Cemazar Maja , Jesenko Tanja , Sersa Gregor , Djokic Mihajlo
Published: January 2024

Electrochemotherapy is a novel, locoregional therapy that is used to treat cutaneous and deep-seated tumors. The electric pulses used in electrochemotherapy increase the permeability of the cell membranes of the target lesion and thus enhance the delivery of low-permeant cytotoxic drugs to the cells, leading to their death. It has also been postulated that electrochemotherapy acts as an in situ vaccination by inducing immunogenic cell death. This in turn leads to an enhanced systemic antitumor response, which could be further exploited by immunotherapy. However, only a few clinical studies have investigated the role of combined treatment in patients with melanoma, breast cancer, hepatocellular carcinoma, and cutaneous squamous cell carcinoma. In this review, we therefore aim to review the published preclinical evidence on combined treatment and to review clinical studies that have investigated the combined role of electrochemotherapy and immunotherapy.
The novel mechanism facilitating chronic hepatitis B infection: immunometabolism and epigenetic modification reprogramming
Authors: Wang Zhengmin , Liu Nan , Yang Yang , Tu Zhengkun
Published: January 2024

Hepatitis B Virus (HBV) infections pose a global public health challenge. Despite extensive research on this disease, the intricate mechanisms underlying persistent HBV infection require further in-depth elucidation. Recent studies have revealed the pivotal roles of immunometabolism and epigenetic reprogramming in chronic HBV infection. Immunometabolism have identified as the process, which link cell metabolic status with innate immunity functions in response to HBV infection, ultimately contributing to the immune system’s inability to resolve Chronic Hepatitis B (CHB). Within hepatocytes, HBV replication leads to a stable viral covalently closed circular DNA (cccDNA) minichromosome located in the nucleus, and epigenetic modifications in cccDNA enable persistence of infection. Additionally, the accumulation or depletion of metabolites not only directly affects the function and homeostasis of immune cells but also serves as a substrate for regulating epigenetic modifications, subsequently influencing the expression of antiviral immune genes and facilitating the occurrence of sustained HBV infection. The interaction between immunometabolism and epigenetic modifications has led to a new research field, known as metabolic epigenomics, which may form a mutually reinforcing relationship with CHB. Herein, we review the recent studies on immunometabolism and epigenetic reprogramming in CHB infection and discuss the potential mechanisms of persistent HBV infection. A deeper understanding of these mechanisms will offer novel insights and targets for intervention strategies against chronic HBV infection, thereby providing new hope for the treatment of related diseases.
Numerical simulation on dynamic compression properties of sandstone under axial static preload
Authors: Xu Ying , Zhang Zhongyi , Li Chengjie , Ge Jinjin
Published: January 2024

In this study, through a series of static mechanical tests and split Hopkinson pressure bar (SHPB) dynamic impact tests, the static and dynamic mechanical parameters of yellow sandstone are determined, and the Holmquist–Johnson–Cook model parameters of the rock are determined by the test data and theoretical calculation. The feasibility of a numerical model is verified, based on which the SHPB impact process under different axial pressure is subjected to numerical analysis. The results show that with increasing impact load, the degree of rock breakage increases, and the dynamic compressive strength and dynamic elastic modulus increase continuously. With the application and increase of axial pressure, the dynamic compressive strength and dynamic elastic modulus of the rock decrease gradually under the same impact load, and the maximum cumulative strain keeps increasing, indicating that under the influence of axial pressure, micro-cracks in the rock have initially developed and expanded. With increasing axial pressure, the rock is more vulnerable to breakage, and its weakening degree keeps increasing. The energy utilization rate of one-dimensional dynamic and static combined loading is affected by the axial compression ratio and impact load. At low axial compression ratio, the rock has high impact resistance but high energy utilization rate; at high axial compression ratio, the rock has low impact resistance but low energy utilization rate. Therefore, the combination of axial compression ratio and impact velocity can improve the crushing effect and energy utilization rate on the premise of clear crushing form requirements.
Tongbian decoction restores intestinal microbiota and activates 5-hydroxytryptamine signaling: implication in slow transit constipation
Authors: Li Hongjia , Lv Na , Li Dongna , Qian Yunzhi , Si Xianghuan , Hua Yuanqing , Wang Yujuan , Han Xiaojuan , Xu Tianshu
Published: January 2024

Introduction

Slow transit constipation (STC) is a type of functional constipation. The detailed mechanism of STC, for which there is currently no effective treatment, is unknown as of yet. Tongbian decoction (TBD), a traditional Chinese medicinal formula, is commonly used to treat STC in clinical settings. However, the potential impact of TBD on the management of STC via modulation of the gut microbiota remains unclear.

Methods

Pseudo-germ-free rats were constructed after 6 days of treatment with bacitracin, neomycin, and streptomycin (abbreviated as ABX forthwith). Based on the successful construction of pseudo-germ-free rats, the STC model (ABX + STC) was induced using loperamide hydrochloride. After successful modeling, based on the different sources of donor rat microbiota, the ABX + STC rats were randomly divided into three groups: Control → ABX + STC, STC → ABX + STC, and STC + TBD → ABX + STC for fecal microbiota transplant (FMT). Body weight, fecal water content, and charcoal power propelling rate of the rats were recorded. Intestinal microbiota was detected by 16S rRNA sequencing, and the 5-hydroxytryptamine (5-HT) signaling pathway was examined by western blots, immunofluorescence, and immunohistochemical analysis.

Results

After treatment with fecal bacterial solutions derived from rats treated with Tongbian decoction (TBD), there was an increase in body weight, fecal water content, and the rate of charcoal propulsion in the rats. Additionally, activation of the 5-hydroxytryptamine (5-HT) signaling pathway was observed. The 16S rRNA sequencing results showed that the fecal bacterial solution from TBD-treated rats affected the intestinal microbiota of STC rats by increasing the proliferation of beneficial bacteria and suppressing the expansion of harmful bacteria.

Conclusion

Our study showed that TBD alleviated constipation in STC rats by modulating the structure of the intestinal microbiota.
Causal relationship between gut microflora and dementia: a Mendelian randomization study
Authors: Fu Jinjie , Qin Yuan , Xiao Lingyong , Dai Xiaoyu
Published: January 2024

Background

Numerous pertinent investigations have demonstrated a correlation between gut microflora (GM) and the occurrence of dementia. However, a causal connection between GM and dementia and its subtypes has not yet been clarified.

Objective

To explore the causal association between GM and dementia, including its subtypes, a two-sample Mendelian randomization (TSMR) analysis was used.

Methods

Our data comes from the Genome-Wide Association Study (GWAS). The principal approach employed for the Mendelian randomization study was the inverse-variance weighted method, supplemented by four methods: MR-Egger, weighted median, simple mode, and weighted mode. This was followed by Cochrane’s Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out as sensitivity analysis validation.

Results

Twenty-one GMs associated with any dementia, Alzheimer’s disease, vascular dementia, Lewy body dementia, Parkinson’s disease, and dementia under other disease classifications were derived from the analysis, and 21 passed sensitivity tests.

Conclusion

We confirmed the causal relationship between GM and dementia and its subtypes, derived specific flora associated with increased or decreased risk of dementia, and provided new ideas for preventive, diagnostic, and therapeutic interventions for dementia mediated by gut microbiota.
Fully synthetic phosphorylated Tau181, Tau217, and Tau231 calibrators for Alzheimer’s disease diagnosis
Authors: Li Xinyu , Zeng Huimei , Durairaj Pradeepraj , Wen Weihuan , Li Tianpeng , Zhao Yanru , Liu Yang , Liu Xue , Zhan Lingpeng , Rao Lang , Yuan Wen , Guo Tengfei , Shen Weijun , Cai Hui , Chen Zhicheng
Published: January 2024

Background

The calibrator in immunoassay plays an essential role in diagnosing Alzheimer’s disease (AD). Presently, the most well-studied biomarkers for AD diagnosis are three phosphorylated Tau (p-Tau): p-Tau231, p-Tau217, and p-Tau181. Glycogen synthase-3beta (GSK3β)-phosphorated Tau-441 is the most commonly used calibrator for p-Tau immunoassays. However, the batch-to-batch inconsistency issue of the commonly used GSK3β-phosphorylated Tau-441 limits its clinical application.

Methods

We have successfully generated and characterized 61 Tau monoclonal antibodies (mAbs) with distinct epitopes by using the hybridoma technique and employed them as capture or detection antibodies for p-Tau immunoassays. Through chemical synthesis, we synthesized calibrators, which are three peptides including capture and detection antibody epitopes, for application in immunoassays that detect p-Tau231, p-Tau217, and p-Tau181. The novel calibrators were applied to Enzyme-linked immunosorbent assay (ELISA) and Single-molecule array (Simoa) platforms to validate their applicability and establish a range of p-Tau immunoassays.

Results

By employing the hybridoma technique, 49 mAbs recognizing Tau (1–22), nine mAbs targeting p-Tau231, one mAb targeting p-Tau217, and two mAbs targeting p-Tau181 were developed. Peptides, including recognition epitopes of capture and detection antibodies, were synthesized. These peptides were used as calibrators to develop 60 immunoassays on the ELISA platform, of which six highly sensitive immunoassays were selected and applied to the ultra-sensitive Simoa platform. Remarkably, the LODs were 2.5, 2.4, 31.1, 32.9, 46.9, and 52.1 pg/ml, respectively.

Conclusion

Three novel p-Tau calibrators were successfully generated and validated, which solved the batch-to-batch inconsistency issue of GSK3β-phosphorylated Tau-441. The novel calibrators exhibit the potential to promote the standardization of clinical AD diagnostic calibrators. Furthermore, we established a series of highly sensitive and specific immunoassays on the Simoa platform based on novel calibrators, which moved a steady step forward in p-Tau immunoassay application for AD diagnosis.
ID-YOLOv7: an efficient method for insulator defect detection in power distribution network
Authors: Chen Bojian , Zhang Weihao , Wu Wenbin , Li Yiran , Chen Zhuolei , Li Chenglong
Published: January 2024

Insulators play a pivotal role in the reliability of power distribution networks, necessitating precise defect detection. However, compared with aerial insulator images of transmission network, insulator images of power distribution network contain more complex backgrounds and subtle insulator defects, it leads to high false detection rates and omission rates in current mainstream detection algorithms. In response, this study presents ID-YOLOv7, a tailored convolutional neural network. First, we design a novel Edge Detailed Shape Data Augmentation (EDSDA) method to enhance the model's sensitivity to insulator's edge shapes. Meanwhile, a Cross-Channel and Spatial Multi-Scale Attention (CCSMA) module is proposed, which can interactively model across different channels and spatial domains, to augment the network's attention to high-level insulator defect features. Second, we design a Re-BiC module to fuse multi-scale contextual features and reconstruct the Neck component, alleviating the issue of critical feature loss during inter-feature layer interaction in traditional FPN structures. Finally, we utilize the MPDIoU function to calculate the model's localization loss, effectively reducing redundant computational costs. We perform comprehensive experiments using the Su22kV_broken and PASCAL VOC 2007 datasets to validate our algorithm's effectiveness. On the Su22kV_broken dataset, our approach attains an 85.7% mAP on a single NVIDIA RTX 2080ti graphics card, marking a 7.2% increase over the original YOLOv7. On the PASCAL VOC 2007 dataset, we achieve an impressive 90.3% mAP at a processing speed of 53 FPS, showing a 2.9% improvement compared to the original YOLOv7.
Altered dynamic effective connectivity of the default mode network in type 2 diabetes
Authors: Xu Kun , Wang Jun , Liu Guangyao , Yan Jiahao , Chang Miao , Jiang Linzhen , Zhang Jing
Published: January 2024

Introduction

Altered functional connectivity of resting-state functional magnetic resonance imaging (rs-fMRI) within default mode network (DMN) regions has been verified to be closely associated with cognitive decline in patients with Type 2 diabetes mellitus (T2DM), but most studies neglected the fluctuations of brain activities—the dynamic effective connectivity (DEC) within DMN of T2DM is still unknown.

Methods

For the current investigation, 40 healthy controls (HC) and 36 T2DM patients have been recruited as participants. To examine the variation of DEC between T2DM and HC, we utilized the methodologies of independent components analysis (ICA) and multivariate granger causality analysis (mGCA).

Results

We found altered DEC within DMN only show decrease in state 1. In addition, the causal information flow of diabetic patients major affected areas which are closely associated with food craving and metabolic regulation, and T2DM patients stayed longer in low activity level and exhibited decreased transition rate between states. Moreover, these changes related negatively with the MoCA scores and positively with HbA1C level.

Conclusion

Our study may offer a fresh perspective on brain dynamic activities to understand the mechanisms underlying T2DM-related cognitive deficits.
Exploring the utility of a latent variable as comprehensive inflammatory prognostic index in critically ill patients with cerebral infarction
Authors: Shu Chang , Zheng Chenguang , Zhang Guobin
Published: January 2024

Objective

We introduce the comprehensive inflammatory prognostic index (CIPI), a novel prognostic tool for critically ill cerebral infarction patients, designed to meet the urgent need for timely and convenient clinical decision-making in this high-risk patient group.

Methods

Using exploratory factor analysis on selected indices—neutrophil to lymphocyte ratio (NLR), systemic inflammation response index (SIRI), and systemic immune inflammation index (SIII)—we derived CIPI, a latent variable capturing their combined predictive power. Data from 1,022 patients in the Medical Information Mart for Intensive Care (MIMIC)-IV database were used to develop CIPI-based survival models, with the robustness and area under the receiver operating characteristic curve (AUC) performance of CIPI validated against an independent dataset of 326 patients from the MIMIC-III CareVue subset. The CIPI’s predictive power for in-hospital and intensive care unit (ICU) mortality was assessed through Kaplan–Meier analysis, univariate and multivariate Cox regression models, and time-dependent AUC analysis. Linearity, subgroup sensitivity analyses and interaction effects with CIPI were also evaluated.

Results

CIPI was an independent prognostic factor, demonstrating a statistically significant association with in-hospital and ICU mortality, when assessed as a continuous and a categorical variable. It showed a linear relationship with mortality rates and demonstrated stability across most subgroups, with no significant interactions observed. Its predictive capabilities for in-hospital and ICU mortality among critically ill cerebral infarction patients matched those of established prognostic indices in the MIMIC database.

Conclusion

Our study indicates that CIPI is a reliable and effective prognostic tool for critically ill cerebral infarction patients in predicting in-hospital and ICU mortality. Its straightforward calculation, rooted in routine blood tests, enhances its practicality, promising significant utility in clinical settings.
Response to experimental cold-induced pain discloses a resistant category among endurance athletes, with a distinct profile of pain-related behavior and GABAergic EEG markers: a case–control preliminary study
Authors: Peier Franziska , Mouthon Michael , De Pretto Michael , Chabwine Joelle Nsimire
Published: January 2024

Pain is a major public health problem worldwide, with a high rate of treatment failure. Among promising non-pharmacological therapies, physical exercise is an attractive, cheap, accessible and innocuous method; beyond other health benefits. However, its highly variable therapeutic effect and incompletely understood underlying mechanisms (plausibly involving the GABAergic neurotransmission) require further research. This case–control study aimed to investigate the impact of long-lasting intensive endurance sport practice (≥7 h/week for the last 6 months at the time of the experiment) on the response to experimental cold-induced pain (as a suitable chronic pain model), assuming that highly trained individual would better resist to pain, develop advantageous pain-copying strategies and enhance their GABAergic signaling. For this purpose, clinical pain-related data, response to a cold-pressor test and high-density EEG high (Hβ) and low beta (Lβ) oscillations were documented. Among 27 athletes and 27 age-adjusted non-trained controls (right-handed males), a category of highly pain-resistant participants (mostly athletes, 48.1%) was identified, displaying lower fear of pain, compared to non-resistant non-athletes. Furthermore, they tolerated longer cold-water immersion and perceived lower maximal sensory pain. However, while having similar Hβ and Lβ powers at baseline, they exhibited a reduction between cold and pain perceptions and between pain threshold and tolerance (respectively −60% and − 6.6%; −179.5% and − 5.9%; normalized differences), in contrast to the increase noticed in non-resistant non-athletes (+21% and + 14%; +23.3% and + 13.6% respectively). Our results suggest a beneficial effect of long-lasting physical exercise on resistance to pain and pain-related behaviors, and a modification in brain GABAergic signaling. In light of the current knowledge, we propose that the GABAergic neurotransmission could display multifaceted changes to be differently interpreted, depending on the training profile and on the homeostatic setting (e.g., in pain-free versus chronic pain conditions). Despite limitations related to the sample size and to absence of direct observations under acute physical exercise, this precursory study brings into light the unique profile of resistant individuals (probably favored by training) allowing highly informative observation on physical exercise-induced analgesia and paving the way for future clinical translation. Further characterizing pain-resistant individuals would open avenues for a targeted and physiologically informed pain management.
Consumption of ultra-processed foods and risk for Alzheimer’s disease: a systematic review
Authors: Claudino Paola Alves , Bueno Nassib Bezerra , Piloneto Sabrina , Halaiko Dieniffer , Azevedo de Sousa Leticia Priscila , Barroso Jara Maia Cassia Helena , Netto Bárbara Dal Molin
Published: January 2024

Objective

To investigate the association of the consumption of ultra-processed foods with the risk of developing Alzheimer’s disease in adults and the elderly. The review protocol was registered on PROSPERO (CRD42022375944).

Methods

This is a systematic review reported according to PRISMA guidelines. Observational studies were included without language or publication year restrictions. Studies assessing only other types of dementia as outcomes, not considering Alzheimer’s disease, were excluded. The research was carried out in the Medline, Embase, Lilacs databases, and a survey of the gray literature between April and November 2023, in addition to citation search in the included studies. Data extraction was performed by two independent reviewers. The risk of bias and methodological quality of the included studies were assessed using the Joanna Briggs Institute checklist for cohort studies.

Results

A total of 5 studies involving 617,502 adults and elderly people were included. All studies had a cohort design and were considered of high methodological quality. Of the included studies, 4 demonstrated a risk association between the consumption of ultra-processed foods and the development of Alzheimer’s disease, while 1 study showed a risk association only with the development of cognitive decline.

Discussion

The association between ultra-processed foods consumption and the risk of developing Alzheimer’s disease is a recent topic in scientific studies, given that the oldest study identified by our review dates back to 2017. Of the four included studies, three showed a significant association between ultra-processed foods consumption and the risk of developing Alzheimer’s disease.
Clear cell renal cell carcinoma: immunological significance of alternative splicing signatures
Authors: Zhang Jiayu , Jiang Hongyi , Rao Dapang , Jin Xishi
Published: January 2024

Background

Renal cell carcinoma (RCC) accounts for 90% of renal cancers, of which clear cell carcinoma (ccRCC) is the most usual histological type. The process of alternative splicing (AS) contributes to protein diversity, and the dysregulation of protein diversity may have a great influence on tumorigenesis. We developed a prognostic signature and comprehensively analyzed the role of tumor immune microenvironment (TIME) and immune checkpoint blocking (ICB) treatment in ccRCC.

Methods

To identify prognosis-related AS events, univariate Cox regression was used and functional annotation was performed using gene set enrichment analysis (GSEA). In this study, prognostic signatures were developed based on multivariate Cox, univariate Cox, and LASSO regression models. Moreover, to assess the prognostic value, the proportional hazards model, Kruskal–Wallis analysis, and ROC curves were used. To obtain a better understanding of TIME in ccRCC, the ESTIMATE R package, single sample gene set enrichment analysis (ssGSEA) algorithm, CIBERSORT method, and the tumor immune estimation resource (TIMER) were applied. The database was searched to verify the expression of C4OF19 in tumor and normal samples. Regulatory networks for AS-splicing factors (SFs) were visualized using Cytoscape 3.9.1.

Results

There were 9,347 AS cases associated with the survival of ccRCC patients screened. A total of eight AS prognostic signatures were developed with stable prognostic predictive accuracy based on splicing subtypes. In addition, a qualitative prognostic nomogram was developed, and the prognostic prediction showed high effectiveness. In addition, we found that the combined signature was significantly associated with the diversity of TIME and ICB treatment-related genes. C4ORF19 might become an important prognostic factor for ccRCC. Finally, the AS-SF regulatory network was established to clearly reveal the potential function of SFs.

Conclusion

We found novel and robust indicators (i.e., risk signature, prognostic nomogram, etc.) for the prognostic prediction of ccRCC. A new and reliable prognostic nomogram was established to quantitatively predict the clinical outcome. The AS-SF networks could provide a new way for the study of potential regulatory mechanisms, and the important roles of AS events in the context of TIME and immunotherapy efficiency were exhibited. C4ORF19 was found to be a vital gene in TIME and ICB treatment.
Summary of the evidence of best practices for the prevention and treatment of embolism syndrome after TACE in primary liver cancer
Authors: Yao Yanrong , Huang Xi , Zhao Chengsi , Wang XiaoYan , Mi Guangli , Liu Jingli
Published: January 2024

Objective

This study aims to retrieve, evaluate, and summarize domestic and foreign evidence on the prevention and treatment of embolism syndrome following transcatheter arterial chemoembolization (TACE) for primary liver cancer and to provide an evidence-based foundation for clinical practice.

Methods

Utilizing the “6S” model, we conducted a systematic search of UpToDate, BMJ Best Practice, domestic and foreign guidelines, and related databases on the prevention and treatment of embolism syndrome following TACE for primary liver cancer. This search included clinical decision-making, guidelines, systematic reviews, evidence summaries, randomized controlled trials, and expert consensus. The search time frame extended from January 1, 2013 to May 1, 2023. Evidence was synthesized after an independent review of the included studies by two investigators.

Results

A total of 11 articles were included in the analysis, comprising one clinical decision-making article, three clinical guidelines, six expert consensus articles, and one randomized controlled trial. We summarized 31 pieces of evidence across three categories: preoperative preparation, intraoperative interventions, and postoperative symptom management.

Conclusion

This study presents a comprehensive summary of the best available evidence on the prevention and treatment of embolism syndrome following TACE for primary liver cancer. These findings can serve as a valuable reference for clinical practitioners, enabling nurses to deliver individualized care based on the symptoms and specific needs of liver cancer patients.

Systematic review registration

http://ebn.nursing.fudan.edu.cn, identifier ES20232398.
Robotic assisted minimally invasive esophagectomy versus minimally invasive esophagectomy
Authors: Xue Mengchao , Liu Junjie , Lu Ming , Zhang Huiying , Liu Wen , Tian Hui
Published: January 2024

Background

Esophagectomy is the gold standard treatment for resectable esophageal cancer; however, there is insufficient evidence to indicate potential advantages over standard minimally invasive esophagectomy (MIE) in treating thoracic esophageal cancer. Robot-assisted minimally invasive esophagectomy (RAMIE) bridges the gap between open and minimally invasive surgery. In this single-center retrospective review, we compare the clinical outcomes of EC patients treated with MIE and RAMIE.

Method

We retrospectively reviewed the clinical data of patients with esophageal cancer who underwent surgery at Qilu Hospital between August 2020 and August 2022, including 159 patients who underwent MIE and 35 patients who received RAMIE. The intraoperative, postoperative, and preoperative patient characteristics in both groups were evaluated.

Results

Except for height, the MIE and RAMIE groups showed no significant differences in preoperative features (P>0.05). Further, there were no significant differences in intraoperative indices, including TNM stage of the resected tumor, tumor tissue type, or ASA score, between the two groups. However, statistically significant differences were found in some factors; the RAMIE group had a shorter operative time, less intraoperative bleeding, and more lymph nodes removed compared to the MIE group. Patients in the RAMIE group reported less discomfort and greater chest drainage on the first postoperative day than patients in the MIE group; however, there were no differences in other features between the two datasets.

Conclusion

By comparing the clinical characteristics and outcomes of RAMIE with MIE, this study verified the feasibility and safety of RAMIE for esophageal cancer. Overall, RAMIE resulted in more complete lymph node clearance, shorter operating time, reduced surgical hemorrhage, reduced postoperative discomfort, and chest drainage alleviation in patients. To investigate the function of RAMIE in esophageal cancer, we propose undertaking a future clinical trial with long-term follow-up to analyze tumor clearance, recurrence, and survival after RAMIE.