bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-transcriptome analysis reveals virulence-specific pathogen−host interactions at the placenta in bovine neosporosis
Authors: Horcajo Pilar , Coronado Montserrat , Pastor-Fernández Iván , Collantes-Fernández Esther , Rico-San Román Laura , Reyes-Palomares Armando , Ortega-Mora Luis-Miguel
Published: July 2023

Research on bovine neosporosis has achieved relevant milestones, but the mechanisms underlying the occurrence of foetal death or protection against foetal death remain unclear. In a recent study, placentas from heifers challenged with the high-virulence isolate Nc-Spain7 exhibited focal necrosis and inflammatory infiltrates as soon as 10 days post-infection (dpi), although parasite detection was minimal. These lesions were more frequent at 20 dpi, coinciding with higher rates of parasite detection and the occurrence of foetal death in some animals. In contrast, such lesions were not observed in placentas from animals infected with the low-virulence isolate Nc-Spain1H, where the parasite was detected only in placenta from one animal at 20 dpi. This work aimed to study which mechanisms are triggered in the placentas (caruncles and cotyledons) of these pregnant heifers at early stages of infection (10 and 20 dpi) through whole-transcriptome analysis. In caruncles, infection with the high-virulence isolate provoked a strong proinflammatory response at 10 dpi. This effect was not observed in heifers infected with the low-virulence isolate, where IL-6/JAK/STAT3 signalling and TNF-alpha signalling via NF-κB pathways were down-regulated. Interestingly, the expression of E2F target genes, related to restraining the inflammatory response, was higher in these animals. At 20 dpi, more pronounced proinflammatory gene signatures were detectable in heifers infected with the high-virulence isolate, being more intense in heifers carrying dead fetuses. However, the low-virulence isolate continued without activating the proinflammatory response. In cotyledons, the response to infection with the high-virulence isolate was similar to that observed in caruncles; however, the low-virulence isolate induced mild proinflammatory signals at 20 dpi. Finally, a deconvolutional analysis of gene signatures from both placentome tissues revealed a markedly higher fraction of activated natural killers, M1 macrophages and CD8+ T cells for the high-virulence isolate. Therefore, our transcriptomic analysis supports the hypothesis that an intense immune response probably triggered by parasite multiplication could be a key contributor to abortion. Further studies are required to determine the parasite effectors that govern the distinct interactions of high- and low-virulence isolates with the host, which could help elucidate the molecular processes underlying the pathogenesis of neosporosis in cattle.
Crosstalk between ferroptosis and chondrocytes in osteoarthritis: a systematic review of in vivo and in vitro studies
Authors: Cao Siyang , Wei Yihao , Xu Huihui , Weng Jian , Qi Tiantian , Yu Fei , Liu Su , Xiong Ao , Liu Peng , Zeng Hui
Published: July 2023

Purpose

Recent scientific reports have revealed a close association between ferroptosis and the occurrence and development of osteoarthritis (OA). Nevertheless, the precise mechanisms by which ferroptosis influences OA and how to hobble OA progression by inhibiting chondrocyte ferroptosis have not yet been fully elucidated. This study aims to conduct a comprehensive systematic review (SR) to address these gaps.

Methods

Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020, we conducted a comprehensive search of the Embase, Ovid, ProQuest, PubMed, Scopus, the Cochrane Library, and Web of Science databases to identify relevant studies that investigate the association between ferroptosis and chondrocytes in OA. Our search included studies published from the inception of these databases until January 31st, 2023. Only studies that met the predetermined quality criteria were included in this SR.

Results

In this comprehensive SR, a total of 21 studies that met the specified criteria were considered suitable and included in the current updated synthesis. The mechanisms underlying chondrocyte ferroptosis and its association with OA progression involve various biological phenomena, including mitochondrial dysfunction, dysregulated iron metabolism, oxidative stress, and crucial signaling pathways.

Conclusion

Ferroptosis in chondrocytes has opened an entirely new chapter for the investigation of OA, and targeted regulation of it is springing up as an attractive and promising therapeutic tactic for OA.

Systematic review registration

https://inplasy.com/inplasy-2023-3-0044/, identifier INPLASY202330044.
Development and validation of prognostic risk prediction models for hepatocellular carcinoma patients treated with immune checkpoint inhibitors based on a systematic review and meta-analysis of 47 cohorts
Authors: Ma Delin , Liu Mingkun , Zhai Xiangyu , Li Xianzhi , Jin Bin , Liu Yang
Published: July 2023

Objective

To identify the risk factors associated with prognosis in patients with hepatocellular carcinoma (HCC) treated with immune checkpoint inhibitors (ICI) via meta-analysis. And to construct prediction models to aid in the prediction and improvement of prognosis.

Methods

We searched PubMed, Embase, Web of Science and Cochrane Library for relevant studies from inception to March 29, 2023. After completing literature screening and data extraction, we performed meta-analysis, sensitivity analysis, and subgroup analysis to identify risk factors associated with OS and PFS. Using the pooled hazard ratio value for each risk factor, we constructed prediction models, which were then validated using datasets from 19 centers in Japan and two centers in China, comprising a total of 204 patients.

Results

A total of 47 studies, involving a total of 7649 ICI-treated HCC patients, were included in the meta-analysis. After analyzing 18 risk factors, we identified AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number, vascular invasion and combination therapy as predictors for OS prediction model, while AFP, ALBI, NLR, ECOG performance status, Child-Pugh stage, BCLC stage, tumor number and vascular invasion were selected as predictors for PFS model. To validate the models, we scored two independent cohorts of patients using both prediction models. Our models demonstrated good performance in these cohorts. In addition, in the pooled cohort of 204 patients, Our models also showed good performance with area under the curve (AUC) values of 0.712, 0.753, and 0.822 for the OS prediction model at 1-year, 2-year, and 3-year follow-up points, respectively, and AUC values of 0.575, 0.749 and 0.691 for the PFS prediction model Additionally, the calibration curve, decision curve analysis, and Kaplan-Meier curves in the pooled cohort all supported the validity of both models.

Conclusion

Based on the meta-analysis, we successfully constructed the OS and PFS prediction models for ICI-treated HCC patients. We also validated the models externally and observed good discrimination and calibration. The model’s selected indicators are easily obtainable, making them suitable for further application in clinical practice.
Antigen-specific cytokine profiles for pulmonary Mycobacterium avium complex disease stage diagnosis
Authors: Yamashita Yoshiro , Yasuda Ikkoh , Tanaka Takeshi , Ikeda Toru , Terada Mayumi , Takaki Masahiro , Tsuchihashi Yoshiko , Asoh Norichika , Ohara Yukiko , Enany Shymaa , Kobayashi Haruka , Matsumoto Sohkichi , Morimoto Konosuke
Published: July 2023

Introduction

Controlling pulmonary Mycobacterium avium complex (MAC) disease is difficult because there is no way to know the clinical stage accurately. There have been few attempts to use cell-mediated immunity for diagnosing the stage. The objective of this study was to characterize cytokine profiles of CD4+T and CD19+B cells that recognize various Mycobacterium avium-associated antigens in different clinical stages of MAC.

Methods

A total of 47 MAC patients at different stages based on clinical information (14 before-treatment, 16 on-treatment, and 17 after-treatment) and 17 healthy controls were recruited. Peripheral blood mononuclear cells were cultured with specific antigens (MAV0968, 1160, 1276, and 4925), and the cytokine profiles (IFN-γ, TNF-α, IL-2, IL-10, IL-13, and IL-17) of CD4+/CD3+ and CD19+ cells were analyzed by flow cytometry.

Results

The response of Th1 cytokines such as IFN-γ and TNF-α against various antigens was significantly higher in both the on-treatment and after-treatment groups than in the before-treatment group and control (P < 0.01–0.0001 and P < 0.05–0.0001). An analysis of polyfunctional T cells suggested that the presence of IL-2 is closely related to the stage after the start of treatment (P = 0.0309-P < 0.0001) and is involved in memory function. Non-Th1 cytokines, such as IL-10 and IL-17, showed significantly higher responses in the before-treatment group (P < 0.0001 and P < 0.01–0.0001). These responses were not observed with purified protein derivative (PPD). CD19+B cells showed a response similar to that of CD4+T cells.

Conclusion

There is a characteristic cytokine profile at each clinical stage of MAC.
Case Report: Intervention of radiotherapy improves the prognosis of rectal squamous cell carcinoma with high PD-L1 expression and enable patients to obtain NED status
Authors: Qu Fuyin , Xiao Linlin , Xiao Yuting , Gao Chao , Wang Xuan , Wang Yi , Gao Yuanhang , Wu Fengpeng , Liu Ming
Published: July 2023

Background

Rectal squamous cell carcinoma (RSCC) is a rare malignancy of the rectal tumor. Due to its extremely low incidence, there is still a lack of high-level treatment evidence and clinical consensus on this disease.

Case report

In this article, we report a treatment process of RSCC with high PD-L1 expression. Firstly, this patient received 2 cycles of Pembrolizumab immunotherapy, but the efficacy was less sanguine. Subsequently, 4 cycles of mFOLFOX6 chemotherapy were synchronously performed on the basis of the initial regimen. Although partial remission was achieved in the lymph nodes thereafter, the changes in the primary lesions were still not significant. After that, the patient received radiotherapy, and followed by 6 cycles of PC (Albumin-binding Paclitaxel and Nedaplatin) regimen chemotherapy combined with Pembrolizumab. Eventually, the patient achieved no evidence of disease (NED) status, and no signs of recurrence or metastasis were found after 12 months of follow-up.

Conclusion

This is the first report of a RSCC patient with high PD-L1 expression achieving a complete response. Looking back over the whole treatment process of this patient, we found that the participation of radiotherapy was the inflection point of prominent efficacy, which may provide a new idea for the selection of comprehensive treatment strategies for patients with RSCC.
Measurements of underwater operational noise caused by offshore wind turbine off the southwest coast of Korea
Authors: Yoon Young Geul , Han Dong-Gyun , Choi Jee Woong
Published: July 2023

As interest in the development of renewable energy increases, a large number of offshore wind farms are being built worldwide. Accordingly, the potential impacts of underwater operational noise on marine ecosystems have become an issue, and thus it is necessary to understand the mechanisms and acoustic characteristics of underwater operational noise for the environmental impact assessment. For this paper, underwater noise was measured for about 10 days near a 3-MW wind turbine off the southwest coast of Korea, and the acoustic characteristics of the operational noise and its relationship with rotor speed were investigated. The tonal frequencies of the underwater operational noise varied with rotor speed, and particularly the peak level at a frequency of ~198 Hz increased by ~20 dB or more at the rated rotor speed. Additional experiments were conducted to determine the relationship between underwater noise and wind turbine tower vibration, and finally, the underwater noise correlated highly with the tower vibration acceleration signal, wind speed, and rotor speed, with correlation coefficients of 0.95 or higher.
Connectivity between white shark populations off Central California, USA and Guadalupe Island, Mexico
Authors: Kanive Paul E. , Rotella Jay J. , Chapple Taylor K. , Anderson Scot D. , Hoyos-Padilla Mauricio , Klimley Abbott Peter , Galván-Magaña Felipe , Andrzejaczek Samantha , Block Barbara A. , Jorgensen Salvador J.
Published: July 2023

Marine animals often move beyond national borders and exclusive economic zones resulting in a need for trans-boundary management spanning multiple national jurisdictions. Highly migratory fish vulnerable to over-exploitation require protections at international level, as exploitation practices can be disparate between adjacent countries and marine jurisdictions. In this study we collaboratively conducted an analysis of white shark connectivity between two main aggregation regions with independent population assessment and legal protection programs; one off central California, USA and one off Guadalupe Island, Mexico. We acoustically tagged 326 sub-adult and adult white sharks in central California (n=210) and in Guadalupe Island (n=116) with acoustic transmitters between 2008-2019. Of the 326 tagged white sharks, 30 (9.20%) individuals were detected at both regions during the study period. We used a Bayesian implementation of logistic regression with a binomial distribution to estimate the effect of sex, maturity, and tag location to the response variable of probability of moving from one region to the other. While nearly one in ten individuals in our sample were detected in both regions over the study period, the annual rate of trans-regional movement was low (probability of movement = 0.015 yr-1, 95% credible interval = 0.002, 0.061). Sub-adults were more likely than adults to move between regions and sharks were more likely to move from Guadalupe Island to central California, however, sex, and year were not important factors influencing movement. This first estimation of demographic-specific trans-regional movement connecting US and Mexico aggregations with high seasonal site fidelity represents an important step to future international management and assessment of the northeastern Pacific white shark population as a whole.
Target therapy for high-risk neuroblastoma treatment: integration of regulatory and scientific tools is needed
Authors: Ceci Adriana , Conte Rosa , Didio Antonella , Landi Annalisa , Ruggieri Lucia , Giannuzzi Viviana , Bonifazi Fedele
Published: July 2023

Introduction

Several new active substances (ASs) targeting neuroblastoma (NBL) are under study. We aim to describe the developmental and regulatory status of a sample of ASs targeting NBL to underline the existing regulatory gaps in product development and to discuss possible improvements.

Methods

The developmental and regulatory statuses of the identified ASs targeting NBL were investigated by searching for preclinical studies, clinical trials (CTs), marketing authorizations, pediatric investigation plans (PIPs), waivers, orphan designations, and other regulatory procedures.

Results

A total of 188 ASs were identified. Of these, 55 were considered ‘not under development' without preclinical or clinical studies. Preclinical studies were found for 115 ASs, of which 54 were associated with a medicinal product. A total of 283 CTs (as monotherapy or in combination) were identified for 70 ASs. Of these, 52% were at phases 1, 1/2, and 2 aimed at PK/PD/dosing activity. The remaining ones also included efficacy. Phase 3 studies were limited. Studies were completed for 14 ASs and suspended for 11. The highest rate of ASs involved in CTs was observed in the RAS-MAPK-MEK and VEGF groups. A total of 37 ASs were granted with a PIP, of which 14 involved NBL, 41 ASs with a waiver, and 18 ASs with both PIPs and waivers, with the PIP covering pediatric indications different from the adult ones. In almost all the PIPs, preclinical studies were required, together with early-phase CTs often including efficacy evaluation. Two PIPs were terminated because of negative study results, and eight PIPs are in progress. Variations in the SmPC were made for larotrectinib sulfate/Vitrakvi® and entrectinib/Rozlytrek® with the inclusion of a new indication. For both, the related PIPs are still ongoing. The orphan designation has been largely adopted, while PRIME designation has been less implemented.

Discussion

Several ASs entered early phase CTs but less than one out of four were included in a regulatory process, and only two were granted a pediatric indication extension. Our results confirm that it is necessary to identify a more efficient, less costly, and time-consuming “pediatric developmental model” integrating predictive preclinical study and innovative clinical study designs. Furthermore, stricter integration between scientific and regulatory efforts should be promoted.
Histopathological differences between vitiligo and lichen sclerosus et atrophicus using quantitative immunohistochemical analysis
Authors: Park Young Joon , Lee Heera , Park Hyoung Soo , Kim You Chan
Published: July 2023

Introduction

Lichen sclerosus et atrophicus (LS) is rare skin condition characterized by the presence of whitish patches primarily affecting the genital and perianal areas, though it can occur other parts of the body. LS may result in skin depigmentation without textural changes and should be differentiated from vitiligo. However, the histopathological features of hypopigmentation during vitiligo and LS have rarely been compared and have not been precisely described using quantitative immunohistochemical analysis. This study, therefore, aimed to investigate and compare the pigmentary characteristics of LS and vitiligo lesions using histochemical and immunohistochemical staining.

Methods

We included 31 and 46 patients diagnosed with LS and vitiligo, respectively, at Ajou University Hospital between March 2009 and March 2020 in this study. Their medical charts and skin biopsy specimens were retrospectively reviewed. Additionally, Fontana–Masson staining for melanin and immunohistochemical staining for Melan-A, NKI/beteb, tyrosinase, and microphthalmia-associated transcription factor was performed.

Results

The melanin content, as well as the number of melanocytes was, in general, significantly higher in the epidermis of patients in the LS group compared with that in the vitiligo group. However, 22.6% of LS tissues showed less melanin pigmentation, 25.8% of LS specimens exhibited a lower number of melanocytes, and 29.0% of LS specimens demonstrated less melanocyte activity when compared with the average of vitiligo specimens.

Conclusion

As lower melanin pigmentation and the near absence number of melanocytes were also observed in several LS specimens, both the clinical and histological findings must be comprehensively reviewed to differentiate vitiligo from LS.
TRIM3 attenuates cytokine storm caused by Dabie bandavirus via promoting Toll-like receptor 3 degradation
Authors: Jin Ke , Dai Yan , Ouyang Ke , Huang Huaying , Jiang Zhengyi , Yang Zhan , Zhou Tingting , Lin Hong , Wang Chunhui , Wang Chunyan , Sun Xuewei , Lu Dafeng , Liu Xiaoguang , Hu Nannan , Zhu Chuanlong , Zhu Jin , Li Jun
Published: July 2023

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by the Dabie bandavirus (DBV), and it has become a global public health threat. Cytokine storm is considered to be an important pathogenesis of critical SFTS. Tripartite motif-containing 3 (TRIM3), as a member of the TRIM protein family, may contribute to the regulation of the immune and inflammatory responses after viral infection. However, whether TRIM3 plays a major role in the pathogenesis of SFTS has not yet been investigated.

Methods

TRIM3 mRNA levels were detected in PBMCs between 29 SFTS patients and 29 healthy controls by qRT-PCR. We established the pathogenic IFNAR−/− SFTS mouse model successfully by inoculating subcutaneously with DBV and testing the expression levels of TRIM3 mRNA and protein by qRT-PCR and immunofluorescence in the livers, spleens, lungs, and kidneys. TRIM3OE THP-1 cells and peritoneal macrophages extracted from TRIM3−/− mice were infected with DBV. The effect of TRIM3 on cytokines was detected by qRT-PCR and ELISA. Then we examined Toll-like receptor 3 (TLR3) and protein phosphorylation in the MAPK pathway after DBV infection using Western blot. Flow cytometry was used to verify TLR3 expression on peripheral blood monocytes in SFTS patients. We further explored the interaction between TRIM3 and TLR3 using CO-IP and Western blot.

Results

Compared to healthy controls, TRIM3 mRNA expression in PBMCs is decreased in SFTS patients, especially in severe cases. TRIM3 mRNA and protein were synchronously reduced in the livers, spleens, lungs, and kidney tissues of the IFNAR−/− SFTS mice model. In the DBV-infected cell model, TRIM3 overexpression can inhibit the DBV-induced release of IL-1β, IL-6, and TNF-α, the expression of TLR3, and protein phosphorylation in the MAPK pathway, which plays an anti-inflammatory role, while TRIM3 deficiency exacerbates the pro-inflammatory effects. We further found that TRIM3 can promote TLR3 degradation through K48-linked ubiquitination.

Conclusion

TRIM3 can inhibit the production of cytokines by regulating the degradation of TLR3 through K48-linked ubiquitination, which can be a therapeutic target for improving the prognosis of SFTS.
Wild-type Lactococcus lactis producing bacteriocin-like prophage lysins
Authors: Takala Timo M. , Mokhtari Samira , Ahonen Susanna L. , Wan Xing , Saris Per E. J.
Published: July 2023

Introduction

Lactococcus is a genus of lactic acid bacteria used in the dairy industry as a starter. Lactococci have been found to produce altogether more than 40 different bacteriocins, ribosomally synthesized antimicrobial proteins. All known Lactococcus spp. bacteriocins belong to classes I and II, which are mainly heat-resistant peptides. No class III bacteriocins, bigger heat-sensitive proteins, including phage tail-like bacteriocins, have been found from the Lactococcus spp. Unlike phage tail-like bacteriocins, prophage lysins have not been regarded as bacteriocins, possibly because phage lysins contribute to autolysis, degrading the host's own cell wall.

Methods

Wild-type Lactococcus lactis strain LAC460, isolated from spontaneously fermented idli batter, was examined for its antimicrobial activity. We sequenced the genome, searched phage lysins from the culture supernatant, and created knock-out mutants to find out the source of the antimicrobial activity.

Results and discussion

The strain LAC460 was shown to kill other Lactococcus strains with protease- and heat-sensitive lytic activity. Three phage lysins were identified in the culture supernatant. The genes encoding the three lysins were localized in different prophage regions in the chromosome. By knock-out mutants, two of the lysins, namely LysL and LysP, were demonstrated to be responsible for the antimicrobial activity. The strain LAC460 was found to be resistant to the lytic action of its own culture supernatant, and as a consequence, the phage lysins could behave like bacteriocins targeting and killing other closely related bacteria. Hence, similar to phage tail-like bacteriocins, phage lysin-like bacteriocins could be regarded as a novel type of class III bacteriocins.
Insight into the acid tolerance mechanism of Acetilactobacillus jinshanensis subsp. aerogenes Z-1
Authors: Li Qin , Hu Kaidi , Mou Juan , Li Jianlong , Liu Aiping , Ao Xiaolin , Yang Yong , He Li , Chen Shujuan , Zou Likou , Guo Mingye , Liu Shuliang
Published: July 2023

Several lactic acid bacteria (LAB) are double-edged swords in the production of Sichuan bran vinegar; on the one hand, they are important for the flavour of the vinegar, but on the other hand, they result in vinegar deterioration because of their gas-producing features and their acid resistance. These characteristics intensify the difficulty in managing the safe production of vinegar using strains such as Acetilactobacillus jinshanensis subsp. aerogenes Z-1. Therefore, it is necessary to characterize the mechanisms underlying their acid tolerance. The results of this study showed a survival rate of 77.2% for Z-1 when exposed to pH 3.0 stress for 1 h. This strain could survive for approximately 15 days in a vinegar solution with 4% or 6% total acid content, and its growth was effectively enhanced by the addition of 10 mM of arginine (Arg). Under acidic stress, the relative content of the unsaturated fatty acid C18:1 (n-11) increased, and eight amino acids accumulated in the cells. Meanwhile, based on a transcriptome analysis, the genes glnA, carA/B, arcA, murE/F/G, fabD/H/G, DnaK, uvrA, opuA/C, fliy, ecfA2, dnaA and LuxS, mainly enriched in amino acid transport and metabolism, protein folding, DNA repair, and cell wall/membrane metabolism processes, were hypothesized to be acid resistance-related genes in Z-1. This work paves the way for further clarifying the acid tolerance mechanism of Z-1 and shares applicable perspectives for vinegar brewing.
A stochastic B cell affinity maturation model to characterize mechanisms of protection for tetravalent dengue vaccine constructs
Authors: Pannala Venkat R. , Nguyen Hung D. , Wallqvist Anders
Published: July 2023

Dengue annually infects millions of people from a regionally and seasonally varying dengue virus population circulating as four distinct serotypes. Effective protection against dengue infection and disease requires tetravalent vaccine formulations to stimulate a balanced protective immune response to all four serotypes. However, this has been a challenge to achieve, and several clinical trials with different leading vaccine candidates have demonstrated unbalanced replication and interference of interindividual serotype components, leading to low efficacy and enhanced disease severity for dengue-naïve populations. Production of serotype-specific neutralizing antibodies is largely viewed as a correlate of protection against severe dengue disease. However, the underlying mechanisms that lead to these protective immune responses are not clearly elucidated. In this work, using a stochastic model of B cell affinity maturation, we tested different live-attenuated vaccine constructs with varied viral replication rates and contrasted the initiation and progress of adaptive immune responses during tetravalent vaccination and after dengue virus challenge. Comparison of our model simulations across different disease-severity levels suggested that individual production of high levels of serotype-specific antibodies together with a lower cross-reactive antibody are better correlates for protection. Furthermore, evolution of these serotype-specific antibodies was dependent on the percent of viral attenuation in the vaccine, and production of initial B cell and T cell populations pre- and post-secondary dengue infection was crucial in providing protective immunity for dengue-naïve populations. Furthermore, contrasting disease severity with respect to different dengue serotypes, our model simulations showed that tetravalent vaccines fare better against DENV-4 serotype when compared to other serotypes.
Identification of novel gene signatures and immune cell infiltration in intervertebral disc degeneration using bioinformatics analysis
Authors: Tang Tao , He Zhongyuan , Zhu Zhengya , Wang Fuan , Chen Hongkun , Zhang Fu , Zhou Jiaxiang , Wang Jianmin , Li Baoliang , Liu Xizhe , Zhou Zhiyu , Liu Shaoyu
Published: July 2023

Background: Intervertebral disc degeneration (IDD) is the leading cause of lower back pain, and an overall understanding of the molecular mechanisms related to IDD is still lacking. The purpose of this study was to explore gene signatures and immune cell infiltration related to IDD via bioinformatics analysis.

Methods: A total of five expression profiles of mRNA and non-coding RNA were downloaded from the Gene Expression Omnibus (GEO) database. The potentially involved lncRNA/circRNA–miRNA–mRNA networks and protein-protein interaction networks were constructed by miRNet, circBank, STRING, and the Cytoscape database. Gene ontology, Kyoto Encyclopaedia of Genes and Genomes Analysis, Gene Set Enrichment Analysis, Gene Set Variation Analysis, Immune Infiltration Analysis, and Drug-Gene Interaction were used to analyse the top 20 hub genes. RT-qPCR was conducted to confirm the 12 differential expressions of genes both in the nucleus pulposus and annulus fibrosus tissues

Results: There were 346 differentially expressed mRNAs, 12 differentially expressed miRNAs, 883 differentially expressed lncRNAs, and 916 differentially expressed circRNAs in the GEO database. Functional and enrichment analyses revealed hub genes associated with platelet activation, immune responses, focal adhesion, and PI3K-Akt signalling. The apoptotic pathway, the reactive oxygen species pathway, and oxidative phosphorylation play an essential role in IDD. Immune infiltration analysis demonstrated that the Treg cells had significant infiltration, and three levels of immune cells, including dendritic cells, Th2 cells, and tumour-infiltrating lymphocytes, were inhibited in IDD. Drug-gene interaction analysis showed that COL1A1 and COL1A2 were targeted by collagenase clostridium histolyticum, ocriplasmin, and PDGFRA was targeted by 66 drugs or molecular compounds. Finally, 24 cases of IDD tissues and 12 cases of normal disc tissues were collected, and the results of RT-qPCR were consistent with the bioinformatics results.

Conclusion: Our data indicated that the 20 hub genes and immune cell infiltration were involved in the pathological process of IDD. In addition, the PDGFRA and two potential drugs were found to be significant in IDD development.
PINNet: a deep neural network with pathway prior knowledge for Alzheimer's disease
Authors: Kim Yeojin , Lee Hyunju
Published: July 2023

Introduction

Identification of Alzheimer's Disease (AD)-related transcriptomic signatures from blood is important for early diagnosis of the disease. Deep learning techniques are potent classifiers for AD diagnosis, but most have been unable to identify biomarkers because of their lack of interpretability.

Methods

To address these challenges, we propose a pathway information-based neural network (PINNet) to predict AD patients and analyze blood and brain transcriptomic signatures using an interpretable deep learning model. PINNet is a deep neural network (DNN) model with pathway prior knowledge from either the Gene Ontology or Kyoto Encyclopedia of Genes and Genomes databases. Then, a backpropagation-based model interpretation method was applied to reveal essential pathways and genes for predicting AD.

Results

The performance of PINNet was compared with a DNN model without a pathway. Performances of PINNet outperformed or were similar to those of DNN without a pathway using blood and brain gene expressions, respectively. Moreover, PINNet considers more AD-related genes as essential features than DNN without a pathway in the learning process. Pathway analysis of protein-protein interaction modules of highly contributed genes showed that AD-related genes in blood were enriched with cell migration, PI3K-Akt, MAPK signaling, and apoptosis in blood. The pathways enriched in the brain module included cell migration, PI3K-Akt, MAPK signaling, apoptosis, protein ubiquitination, and t-cell activation.

Discussion

By integrating prior knowledge about pathways, PINNet can reveal essential pathways related to AD. The source codes are available at https://github.com/DMCB-GIST/PINNet.
Online detection of compensatory strategies in human movement with supervised classification: a pilot study
Authors: Das Neha , Endo Satoshi , Patel Sabrina , Krewer Carmen , Hirche Sandra
Published: July 2023

Introduction

Stroke survivors often compensate for the loss of motor function in their distal joints by altered use of more proximal joints and body segments. Since this can be detrimental to the rehabilitation process in the long-term, it is imperative that such movements are indicated to the patients and their caregiver. This is a difficult task since compensation strategies are varied and multi-faceted. Recent works that have focused on supervised machine learning methods for compensation detection often require a large training dataset of motions with compensation location annotations for each time-step of the recorded motion. In contrast, this study proposed a novel approach that learned a linear classifier from energy-based features to discriminate between healthy and compensatory movements and identify the compensating joints without the need for dense and explicit annotations.

Methods

Six healthy physiotherapists performed five different tasks using healthy movements and acted compensations. The resulting motion capture data was transformed into joint kinematic and dynamic trajectories. Inspired by works in bio-mechanics, energy-based features were extracted from this dataset. Support vector machine (SVM) and logistic regression (LR) algorithms were then applied for detection of compensatory movements. For compensating joint identification, an additional condition enforcing the independence of the feature calculation for each observable degree of freedom was imposed.

Results

Using leave-one-out cross validation, low values of mean brier score (<0.15), mis-classification rate (<0.2) and false discovery rate (<0.2) were obtained for both SVM and LR classifiers. These methods were found to outperform deep learning classifiers that did not use energy-based features. Additionally, online classification performance by our methods were also shown to outperform deep learning baselines. Furthermore, qualitative results obtained from the compensation joint identification experiment indicated that the method could successfully identify compensating joints.

Discussion

Results from this study indicated that including prior bio-mechanical information in the form of energy based features can improve classification performance even when linear classifiers are used, both for offline and online classification. Furthermore, evaluation compensation joint identification algorithm indicated that it could potentially provide a straightforward and interpretable way of identifying compensating joints, as well as the degree of compensation being performed.
Identifying risk factors for in-stent restenosis in symptomatic intracranial atherosclerotic stenosis: a systematic review and meta-analysis
Authors: Wang Ning , Lu Yuning , Feng Lei , Lin Dongdong , Gao Yuhai , Wu Jiong , Wang Ming , Wan Shu
Published: July 2023

Background

In-stent restenosis (ISR) is an adverse and notable event in the treatment of intracranial atherosclerotic stenosis (ICAS) with percutaneous transluminal angioplasty and stenting (PTAS). The incidence and contributing factors have not been fully defined. This study was performed to evaluate factors associated with ISR after PTAS.

Data source

We identified studies on ISR after PTAS from an electronic search of articles in PubMed, Ovid MEDLINE, and the Cochrane Central Database (dated up to July 2022).

Results

A total of 19 studies, including 452 cases of ISR after 2,047 PTAS, were included in the meta-analysis. The pooled incidence rate of in-stent restenosis was 22.08%. ISR was more likely to occur in patients with coronary artery disease (OR = 1.686; 95% CI: 1.242–2.288; p = 0.0008), dissection (OR = 6.293; 95% CI: 3.883–10.197; p < 0.0001), and higher residual stenosis (WMD = 3.227; 95% CI: 0.142–6.311; p = 0.0404). Patients treated with Wingspan stents had a significantly higher ISR rate than those treated with Enterprise stents (29.78% vs. 14.83%; p < 0.0001).

Conclusions

The present study provides the current estimates of the robust effects of some risk factors for in-stent restenosis in intracranial atherosclerotic stenosis. The Enterprise stent had advantages compared with the Wingspan stent for ISR. The significant risk factors for ISR were coronary artery disease, dissection, and high residual stenosis. Local anesthesia was a suspected factor associated with ISR.
Case report: Expanding the phenotype of FOXP1-related intellectual disability syndrome and hyperkinetic movement disorder in differential diagnosis with epileptic seizures
Authors: Cesaroni Carlo Alberto , Pollazzon Marzia , Mancini Cecilia , Rizzi Susanna , Cappelletti Camilla , Pizzi Simone , Frattini Daniele , Spagnoli Carlotta , Caraffi Stefano Giuseppe , Zuntini Roberta , Trimarchi Gabriele , Niceta Marcello , Radio Francesca Clementina , Tartaglia Marco , Garavelli Livia , Fusco Carlo
Published: July 2023

Objective

We aimed to report on previously unappreciated clinical features associated with FOXP1-related intellectual disability (ID) syndrome, a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, and language delay, with or without autistic features.

Methods

We performed whole-exome sequencing (WES) to molecularly characterize an individual presenting with ID, epilepsy, autism spectrum disorder, behavioral problems, and facial dysmorphisms as major features.

Results

WES allowed us to identify a previously unreported de novo splice site variant, c.1429-1G>T (NM_032682.6), in the FOXP1 gene (OMIM*605515) as the causative event underlying the phenotype. Clinical reassessment of the patient and revision of the literature allowed us to refine the phenotype associated with FOXP1 haploinsufficiency, including hyperkinetic movement disorder and flat angiomas as associated features. Interestingly, the patient also has an asymmetric face and choanal atresia and a novel de novo variant of the CHD7 gene.

Conclusion

We suggest that FOXP1-related ID syndrome may also predispose to the development of hyperkinetic movement disorders and flat angiomas. These features could therefore require specific management of this condition.
Listening efficiency in adult cochlear-implant users compared with normally-hearing controls at ecologically relevant signal-to-noise ratios
Authors: Perea Pérez Francisca , Hartley Douglas E. H. , Kitterick Pádraig T. , Zekveld Adriana A. , Naylor Graham , Wiggins Ian M.
Published: July 2023

Introduction

Due to having to work with an impoverished auditory signal, cochlear-implant (CI) users may experience reduced speech intelligibility and/or increased listening effort in real-world listening situations, compared to their normally-hearing (NH) peers. These two challenges to perception may be usefully integrated in a measure of listening efficiency: conceptually, the amount of accuracy achieved for a certain amount of effort expended.

Methods

We describe a novel approach to quantifying listening efficiency based on the rate of evidence accumulation toward a correct response in a linear ballistic accumulator (LBA) model of choice decision-making. Estimation of this objective measure within a hierarchical Bayesian framework confers further benefits, including full quantification of uncertainty in parameter estimates. We applied this approach to examine the speech-in-noise performance of a group of 24 CI users (M age: 60.3, range: 20–84 years) and a group of 25 approximately age-matched NH controls (M age: 55.8, range: 20–79 years). In a laboratory experiment, participants listened to reverberant target sentences in cafeteria noise at ecologically relevant signal-to-noise ratios (SNRs) of +20, +10, and +4 dB SNR. Individual differences in cognition and self-reported listening experiences were also characterised by means of cognitive tests and hearing questionnaires.

Results

At the group level, the CI group showed much lower listening efficiency than the NH group, even in favourable acoustic conditions. At the individual level, within the CI group (but not the NH group), higher listening efficiency was associated with better cognition (i.e., working-memory and linguistic-closure) and with more positive self-reported listening experiences, both in the laboratory and in daily life.

Discussion

We argue that listening efficiency, measured using the approach described here, is: (i) conceptually well-motivated, in that it is theoretically impervious to differences in how individuals approach the speed-accuracy trade-off that is inherent to all perceptual decision making; and (ii) of practical utility, in that it is sensitive to differences in task demand, and to differences between groups, even when speech intelligibility remains at or near ceiling level. Further research is needed to explore the sensitivity and practical utility of this metric across diverse listening situations.
Obstructive sleep apnea event detection using explainable deep learning models for a portable monitor
Authors: Alarcón Ángel Serrano , Madrid Natividad Martínez , Seepold Ralf , Ortega Juan Antonio
Published: July 2023

Background

Polysomnography (PSG) is the gold standard for detecting obstructive sleep apnea (OSA). However, this technique has many disadvantages when using it outside the hospital or for daily use. Portable monitors (PMs) aim to streamline the OSA detection process through deep learning (DL).

Materials and methods

We studied how to detect OSA events and calculate the apnea-hypopnea index (AHI) by using deep learning models that aim to be implemented on PMs. Several deep learning models are presented after being trained on polysomnography data from the National Sleep Research Resource (NSRR) repository. The best hyperparameters for the DL architecture are presented. In addition, emphasis is focused on model explainability techniques, concretely on Gradient-weighted Class Activation Mapping (Grad-CAM).

Results

The results for the best DL model are presented and analyzed. The interpretability of the DL model is also analyzed by studying the regions of the signals that are most relevant for the model to make the decision. The model that yields the best result is a one-dimensional convolutional neural network (1D-CNN) with 84.3% accuracy.

Conclusion

The use of PMs using machine learning techniques for detecting OSA events still has a long way to go. However, our method for developing explainable DL models demonstrates that PMs appear to be a promising alternative to PSG in the future for the detection of obstructive apnea events and the automatic calculation of AHI.
Abnormal spontaneous brain activity in females with autism spectrum disorders
Authors: Xie Jiapei , Zhang Weidong , Shen Yu , Wei Wei , Bai Yan , Zhang Ge , Meng Nan , Yue Xipeng , Wang Xinhui , Zhang Xianchang , Wang Meiyun
Published: July 2023

Objectives

To date, most studies on autism spectrum disorder (ASD) have focused on sample sets that were primarily or entirely composed of males; brain spontaneous activity changes in females remain unclear. The purpose of this study was to explore changes in the brain spontaneous neural activity in females with ASD.

Methods

In this study, resting-state functional magnetic resonance images (rs-fMRI) of 41 females with ASD and 41 typically developing (TD) controls were obtained from the ABDIE database. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) of the two groups were calculated to detect the regional brain activity. A two independent sample t-test was used to analyze differences between the ASD and TD groups and a p-value <0.05 was considered statistically significant after false discovery rate (FDR) correction. Pearson correlation analysis was conducted between social responsiveness scale (SRS) scores and the local activity of significantly different brain regions.

Results

Compared with the typically developing (TD) group, the values of ALFF and ReHo were significantly increased in the left superior temporal gyrus (STG), while the values of ReHo were significantly decreased in the left superior frontal gyrus (SFG), left middle occipital gyrus (MOG), bilateral superior parietal lobule (SPL), and bilateral precuneus in the females with ASD group. Correlation analysis showed that the ReHo of the right precuneus was positively correlated to the total SRS, social communication, and autistic mannerisms.

Conclusion

Spontaneous activity changes in females with ASD involved multiple brain regions and were related to clinical characteristics. Our results may provide some help for further exploring the neurobiological mechanism of females with ASD.
Prevalence and prognostic value of malnutrition in patients with acute coronary syndrome and chronic kidney disease
Authors: Ni Weicheng , Guo Kun , Shi Sanling , Cheng Ling , Zhou Yimin , Zhang Fengyu , Xu Jiachen , Lin Ken , Chen Changxi , Gao Zhan , Zhou Hao
Published: July 2023

Background

Malnutrition is a rising global health issue associated with unfavorable outcomes of a variety of disorders. Currently, the prevalence and prognostic significance of malnutrition to patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) remained largely unclear.

Methods

A total of 705 patients diagnosed with ACS and CKD in the First Affiliated Hospital of Wenzhou Medical University between 2013 and 2021 were included in this retrospective cohort study. Malnutrition was assessed by the Controlling Nutritional Status (CONUT), the Geriatric Nutritional Risk Index (GNRI), and the Prognostic Nutritional Index (PNI), respectively. The relationships between malnutrition and all-cause mortality and major cardiovascular events (MACEs) were analyzed.

Results

During a median follow-up of 31 months, 153 (21.7%) patients died, and 165 (23.4%) had MACEs. The prevalence of malnutrition was 29.8, 80.6, and 89.8% for the PNI, CONUT, and GNRI, respectively. All the malnutrition indexes were correlated with each other (r = 0.77 between GNRI and PNI, r = −0.72 between GNRI and CONUT, and r = −0.88 between PNI and CONUT, all p < 0.001). Compared with normal nutrition, malnutrition was independently associated with an increased risk for all-cause mortality (adjusted hazard ratio for moderate and severe degrees of malnutrition, respectively: 7.23 [95% confidence interval (CI): 2.69 to 19.49] and 17.56 [95% CI: 5.61 to 55.09] for the CONUT score, 2.18 [95% CI: 0.93 to 5.13] and 3.16 [95% CI: 1.28 to 7.79] for the GNRI, and 2.52 [95% CI: 1.62 to 3.94] and 3.46 [95% CI: 2.28 to 5.25] for the PNI score. p values were lower than 0.05 for all nutritional indexes, except for moderate GNRI p value = 0.075). As for MACEs, similar results were observed in the CONUT and PNI. All the risk scores could improve the predictive ability of the Global Registry of Acute Coronary Events (GRACE) risk score for both all-cause mortality and MACEs.

Conclusion

Malnutrition was common in patients with ACS and CKD regardless of the screening tools used, and was independently associated with all-cause mortality and MACEs. Malnutrition scores could facilitate risk stratification and prognosis assessment.
A literature review on the impact of disasters on healthcare systems, the role of nursing in disaster management, and strategies for cancer care delivery in disaster-affected populations
Authors: Wang Wen , Li Hui , Huang Miao
Published: July 2023

This review article highlights the critical role of nurses in disaster management, with a specific focus on addressing blood tumors in disaster-affected populations. Disasters have a significant impact on healthcare systems and populations, and nurses play a crucial role in disaster preparedness, response, and recovery. The article provides case studies and successful examples of nursing interventions in disaster settings and tumor management, emphasizing the challenges and opportunities in providing cancer care in disaster settings. Recommendations for future research and practice in disaster nursing and blood tumor care are also presented. This information is essential for healthcare professionals and policymakers involved in disaster management, as well as researchers and clinicians working in the field of cancer care.