bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying TNF and IL6 as potential hub genes and targeted drugs associated with scleritis: A bio-informative report
Authors: Yan Feiyue , Liu Yizong , Zhang Tianlu , Shen Yin
Published: March 2023

Background

Scleritis is a serious inflammatory eye disease that can lead to blindness. The etiology and pathogenesis of scleritis remain unclear, and increasing evidence indicates that some specific genes and proteins are involved. This study aimed to identify pivotal genes and drug targets for scleritis, thus providing new directions for the treatment of this disease.

Methods

We screened candidate genes and proteins associated with scleritis by text-mining the PubMed database using Python, and assessed their functions by using the DAVID database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to identify the functional enrichment of these genes and proteins. Then, the hub genes were identified with CytoHubba and assessed by protein-protein interaction (PPI) network analysis. And the serum from patients with active scleritis and healthy subjects were used for the validation of hub genes. Finally, the DGIdb database was used to predict targeted drugs for the hub genes for treating scleritis.

Results

A total of 56 genes and proteins were found to be linked to scleritis, and 65 significantly altered pathways were identified in the KEGG analysis (FDR < 0.05). Most of the top five pathways involved the categories “Rheumatoid arthritis,” “Inflammatory bowel disease”, “Type I diabetes mellitus,” and “Graft-versus-host disease”. TNF and IL6 were considered to be the top 2 hub genes through CytoHubba. Based on our serum samples, hub genes are expressed at high levels in active scleritis. Five scleritis-targeting drugs were found among 88 identified drugs.

Conclusions

This study provides key genes and drug targets related to scleritis through bioinformatics analysis. TNF and IL6 are considered key mediators and possible drug targets of scleritis. Five drug candidates may play an important role in the diagnosis and treatment of scleritis in the future, which is worthy of the further experimental and clinical study.
Interferon-β modulates microglial polarization to ameliorate delayed tPA-exacerbated brain injury in ischemic stroke
Authors: Kuo Ping-Chang , Weng Wen-Tsan , Scofield Barbara A. , Paraiso Hallel C. , Bojrab Paul , Kimes Brandon , Yu I-Chen Ivorine , Yen Jui-Hung Jimmy
Published: March 2023

Tissue plasminogen activator (tPA) is the only FDA-approved drug for the treatment of ischemic stroke. Delayed tPA administration is associated with increased risks of blood-brain barrier (BBB) disruption and hemorrhagic transformation. Studies have shown that interferon beta (IFNβ) or type I IFN receptor (IFNAR1) signaling confers protection against ischemic stroke in preclinical models. In addition, we have previously demonstrated that IFNβ can be co-administered with tPA to alleviate delayed tPA-induced adverse effects in ischemic stroke. In this study, we investigated the time limit of IFNβ treatment on the extension of tPA therapeutic window and assessed the effect of IFNβ on modulating microglia (MG) phenotypes in ischemic stroke with delayed tPA treatment. Mice were subjected to 40 minutes transient middle cerebral artery occlusion (MCAO) followed by delayed tPA treatment in the presence or absence of IFNβ at 3h, 4.5h or 6h post-reperfusion. In addition, mice with MG-specific IFNAR1 knockdown were generated to validate the effects of IFNβ on modulating MG phenotypes, ameliorating brain injury, and lessening BBB disruption in delayed tPA-treated MCAO mice. Our results showed that IFNβ extended tPA therapeutic window to 4.5h post-reperfusion in MCAO mice, and that was accompanied with attenuated brain injury and lessened BBB disruption. Mechanistically, our findings revealed that IFNβ modulated MG polarization, leading to the suppression of inflammatory MG and the promotion of anti-inflammatory MG, in delayed tPA-treated MCAO mice. Notably, these effects were abolished in MG-specific IFNAR1 knockdown MCAO mice. Furthermore, the protective effect of IFNβ on the amelioration of delayed tPA-exacerbated ischemic brain injury was also abolished in these mice. Finally, we identified that IFNβ-mediated modulation of MG phenotypes played a role in maintaining BBB integrity, because the knockdown of IFNAR1 in MG partly reversed the protective effect of IFNβ on lessening BBB disruption in delayed tPA-treated MCAO mice. In summary, our study reveals a novel function of IFNβ in modulating MG phenotypes, and that may subsequently confer protection against delayed tPA-exacerbated brain injury in ischemic stroke.
Development and validation of a new prognostic immune–inflammatory–nutritional score for predicting outcomes after curative resection for intrahepatic cholangiocarcinoma: A multicenter study
Authors: Zhu Jiang , Wang Denghui , Liu Chang , Huang Rui , Gao Fengwei , Feng Xuping , Lan Tian , Li Hui , Wu Hong
Published: March 2023

Background

Immune function, nutrition status, and inflammation influence tumor initiation and progression. This was a retrospective multicenter cohort study that investigated the prognostic value and clinical relevance of immune-, inflammatory-, and nutritional-related biomarkers to develop a novel prognostic immune–inflammatory–nutritional score (PIIN score) for patients with intrahepatic cholangiocarcinoma (ICC).

Methods

The clinical data of 571 patients (406 in the training set and 165 in the validation set) were collected from four large hepato-pancreatico-biliary centers of patients with ICC who underwent surgical resection between January 2011 and September 2017. Twelve blood biomarkers were collected to develop the PIIN score using the LASSO Cox regression model. The predictive value was further assessed using validation datasets. Afterward, nomograms combining the PIIN score and other clinicopathological parameters were developed and validated based on the calibration curve, time-dependent AUC curves, and decision curve analysis (DCA). The primary outcomes evaluated were overall survival (OS) and recurrence-free survival (RFS) from the day of primary resection of ICC.

Results

Based on the albumin–bilirubin (ALBI) grade, neutrophil- to- lymphocyte ratio (NLR), prognostic nutritional index (PNI), and systemic immune- inflammation index (SII) biomarkers, the PIIN score that classified patients into high-risk and low-risk groups could be calculated. Patients with high-risk scores had shorter OS (training set, p < 0.001; validation set, p = 0.003) and RFS (training set, p < 0.001; validation set, p = 0.002) than patients with low-risk scores. The high PIIN score was also associated with larger tumors (≥5 cm), lymph node metastasis (N1 stage), multiple tumors, and high tumor grade or TNM (tumor (T), nodes (N), and metastases (M)) stage. Furthermore, the high PIIN score was a significant independent prognostic factor of OS and RFS in both the training (p < 0.001) and validation (p = 0.003) cohorts, respectively. A PIIN-nomogram for individualized prognostic prediction was constructed by integrating the PIIN score with the clinicopathological variables that yielded better predictive performance than the TNM stage.

Conclusion

The PIIN score, a novel immune–inflammatory–nutritional-related prognostic biomarker, predicts the prognosis in patients with resected ICC and can be a reliable tool for ICC prognosis prediction after surgery. Our study findings provide novel insights into the role of cancer-related immune disorders, inflammation, and malnutrition.
Why human rights matter for marine conservation
Authors: Smallhorn-West Patrick , Allison Edward , Gurney Georgina , Karnad Divya , Kretser Heidi , Lobo Aaron Savio , Mangubhai Sangeeta , Newing Helen , Pennell Kamille , Raj Sushil , Tilley Alexander , Williams Haley , Peckham S. Hoyt
Published: March 2023

Human rights matter for marine conservation because people and nature are inextricably linked. A thriving planet cannot be one that contains widespread human suffering or stifles human potential; and a thriving humanity cannot exist on a dying planet. While the field of marine conservation is increasingly considering human well-being, it retains a legacy in some places of protectionism, colonialism, and fortress conservation. Here, we i) provide an overview of human rights principles and how they relate to marine conservation, ii) document cases where tensions have occurred between marine conservation goals and human rights, iii) review the legal and ethical obligations, and practical benefits, for marine conservation to support human rights, and iv) provide practical guidance on integrating human rights principles into marine conservation. We argue that adopting a human rights-based approach to marine conservation, that is integrating equity as a rights-based condition rather than a charitable principle, will not only help meet legal and ethical obligations to respect, protect, and fulfil human rights, but will also result in greater and more enduring conservation impact.
Artificial intelligence for clinical decision support for monitoring patients in cardiovascular ICUs: A systematic review
Authors: Moazemi Sobhan , Vahdati Sahar , Li Jason , Kalkhoff Sebastian , Castano Luis J. V. , Dewitz Bastian , Bibo Roman , Sabouniaghdam Parisa , Tootooni Mohammad S. , Bundschuh Ralph A. , Lichtenberg Artur , Aubin Hug , Schmid Falko
Published: March 2023

Background

Artificial intelligence (AI) and machine learning (ML) models continue to evolve the clinical decision support systems (CDSS). However, challenges arise when it comes to the integration of AI/ML into clinical scenarios. In this systematic review, we followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), the population, intervention, comparator, outcome, and study design (PICOS), and the medical AI life cycle guidelines to investigate studies and tools which address AI/ML-based approaches towards clinical decision support (CDS) for monitoring cardiovascular patients in intensive care units (ICUs). We further discuss recent advances, pitfalls, and future perspectives towards effective integration of AI into routine practices as were identified and elaborated over an extensive selection process for state-of-the-art manuscripts.

Methods

Studies with available English full text from PubMed and Google Scholar in the period from January 2018 to August 2022 were considered. The manuscripts were fetched through a combination of the search keywords including AI, ML, reinforcement learning (RL), deep learning, clinical decision support, and cardiovascular critical care and patients monitoring. The manuscripts were analyzed and filtered based on qualitative and quantitative criteria such as target population, proper study design, cross-validation, and risk of bias.

Results

More than 100 queries over two medical search engines and subjective literature research were developed which identified 89 studies. After extensive assessments of the studies both technically and medically, 21 studies were selected for the final qualitative assessment.

Discussion

Clinical time series and electronic health records (EHR) data were the most common input modalities, while methods such as gradient boosting, recurrent neural networks (RNNs) and RL were mostly used for the analysis. Seventy-five percent of the selected papers lacked validation against external datasets highlighting the generalizability issue. Also, interpretability of the AI decisions was identified as a central issue towards effective integration of AI in healthcare.
Characterization of the oral microbiome and gut microbiome of dental caries and extrinsic black stain in preschool children
Authors: Zheng Luoyuan , Cao Tingting , Xiong Puling , Ma Yulian , Wei Limin , Wang Jianfeng
Published: March 2023

Introduction

A lower prevalence of dental caries (hereafter termed “caries”) has been observed in children with dental extrinsic black stain (EBS).

Methods

We investigated the epidemiologic characterization of EBS and explored the possible role of the oral microbiome (OM) and gut microbiome (GM) in EBS formation and caries prevention. In an epidemiologic survey, 2,675 children aged 3–6 years were included. Thirty-eight of these children (7 children had both caries and EBS, 10 had EBS only, 11 had caries only, and 10 were healthy children) were recruited for 16S rRNA sequencing and collection of samples of supragingival plaque and feces. Collected plaque samples were divided into four groups: BCP (EBS+, caries+), BP (EBS+, caries−), CP (EBS−, caries+), and P (EBS−, caries−). Fecal samples were also divided into four groups: BCF (EBS+, caries+), BF (EBS+, caries−), CF (EBS−, caries+), and F (EBS−, caries−).

Results

EBS was observed in 12.10% of this population. Children with EBS had a significantly reduced prevalence of caries and a lower mean value of decayed–missing–filled teeth (dmft; p < 0.01). According to analyses of dental plaque, the P group had the most complex microbiome. The BCP group exhibited greater operational taxonomic unit (OTU) richness but a reduced evenness compared with the BP group, and the CP group showed greater OTU richness than the BP group. At the genus level, higher abundance of Actinomyces and Cardiobacterium species was observed in the BCP group. Higher abundance of Lautropia and Pesudopropionibacteriumin species was observed in the BP group compared with P and CP groups, respectively (p < 0.05). Veillonella species were significantly more common in P and CP groups than in BP groups, whereas Porphyromonas and Fusobacterium species were more common in the CP group (p < 0.05). With regard to the GM, the CF group exhibited greater OTU diversity than the BF group. The GM in the BCF group exhibited the most complex relationships across all fecal groups. GM groups could be distinguished by various unique biomarkers, such as Escherichia and Shigella species in the BCF group, Agathobacter and Ruminococcus species in the CF group, Lactobacillus species in the BF group, and Roseburia species in the F group. Our results suggest that EBS is a possible protective factor against early-childhood caries. Dental plaque and the GM may be relevant to EBS in primary dentition.
Morphological characterization, pathogenicity screening, and molecular identification of Fusarium spp. isolates causing post-flowering stalk rot in maize
Authors: Harish J. , Jambhulkar Prashant P. , Bajpai Ruchira , Arya Meenakshi , Babele Piyoosh K. , Chaturvedi Sushil K. , Kumar Anil , Lakshman Dilip K.
Published: March 2023

Post flowering stalk rot (PFSR) of maize caused by the Fusarium species complex is a serious threat to maize production worldwide. The identification of Fusarium species causing PFSR based on morphology traditionally relies on a small set of phenomic characteristics with only minor morphological variations among distinct Fusarium species. Seventy-one isolates were collected from 40 sites in five agro-climatic zones of India to assess the diversity of Fusarium spp. associated with maize crops showing symptoms of PFSR in the field. To investigate the pathogenicity of Fusarium spp. causing PFSR sixty isolates were toothpick inoculated between the first and second node at 55 days after sowing during the tassel formation stage of the crop in Kharif (Rainy season), and Rabi (Winter season) season field trials. Ten most virulent Fusarium isolates, based on the highest observed disease index, were identified by homology and phylogenetic analyses of partial sequences of the translation elongation factor 1 α (Tef-1α). Based on morphological traits such as mycelial growth patterns and mycelial pigmentation, Fusarium isolates were divided into nine clusters. The isolates were judged to be virulent based on their ability to decrease seedling vigour in in-vivo situations and high disease severity in field experiments. Pathogenicity test during the Kharif season showed 12 isolates with virulent disease symptoms with a mean severity ranging between 50 to 67 percent disease index (PDI) whereas in Rabi season, only five isolates were considered virulent, and the mean severity ranged between 52 to 67 PDI. Based on pathological characterization and molecular identification, 10 strains of Fusarium species namely, Fusarium acutatum (2/10), Fusarium verticillioides (Syn. Gibberella fujikuroi var. moniliformis) (7/10), Fusarium andiyazi (2/10) recorded the highest diseases index. All these species are part of the Fusarium fujikuroi species complex (FFSC). The distribution of virulent isolates is specific to a geographical location with a hot humid climate. Increased knowledge regarding the variability of Fusarium spp. responsible for PFSR of maize occurring across wide geographical locations of India will enable more informed decisions to be made to support the management of the disease, including screening for resistance in maize-inbred lines.
Role of asparagine biosynthesis pathway in Siniperca chuatsi rhabdovirus proliferation
Authors: Li Fangying , Fu Xiaozhe , Luo Xia , Lin Qiang , Liang Hongru , Niu Yinjie , Liu Lihui , Li Ningqiu
Published: March 2023

Viruses are non-living organisms that rely on host cellular metabolism to complete their life cycle. Siniperca chuatsi rhabdovirus (SCRV) has caused huge economic losses to the Chinese perch (Siniperca chuatsi) industry worldwide. SCRV replication is dependent on the cellular glutamine metabolism, while aspartate metabolism plays an important role in viral proliferation in glutamine deficiency. Herein, we investigated roles of asparagine metabolism in SCRV proliferation. Results showed that SCRV infection upregulated the expression of key enzymes in the aspartate metabolic pathway in CPB cells. And the key enzymes of malate-aspartic acid shuttle pathway upregulated during the virus invasion phase, and key enzymes of the asparagine biosynthesis pathway upregulated during the viral replication and release phase. When asparagine was added to the depleted medium, the SCRV copy number restored to 90% of those in replete medium, showing that asparagine and glutamine completely rescue the replication of SCRV. Moreover, inhibition of the aspartate- malate shuttle pathway and knockdown of the expression of key enzymes in the asparagine biosynthesis pathway significantly reduced SCRV production, indicating that the aspartic acid metabolic pathway was required to the replication and proliferation of SCRV. Above results provided references for elucidating pathogenic mechanism of SCRV by regulation of aspartate metabolism.
pOpsicle: An all-optical reporter system for synaptic vesicle recycling combining pH-sensitive fluorescent proteins with optogenetic manipulation of neuronal activity
Authors: Seidenthal Marius , Jánosi Barbara , Rosenkranz Nils , Schuh Noah , Elvers Nora , Willoughby Miles , Zhao Xinda , Gottschalk Alexander
Published: March 2023

pH-sensitive fluorescent proteins are widely used to study synaptic vesicle (SV) fusion and recycling. When targeted to the lumen of SVs, fluorescence of these proteins is quenched by the acidic pH. Following SV fusion, they are exposed to extracellular neutral pH, resulting in a fluorescence increase. SV fusion, recycling and acidification can thus be tracked by tagging integral SV proteins with pH-sensitive proteins. Neurotransmission is generally activated by electrical stimulation, which is not feasible in small, intact animals. Previous in vivo approaches depended on distinct (sensory) stimuli, thus limiting the addressable neuron types. To overcome these limitations, we established an all-optical approach to stimulate and visualize SV fusion and recycling. We combined distinct pH-sensitive fluorescent proteins (inserted into the SV protein synaptogyrin) and light-gated channelrhodopsins (ChRs) for optical stimulation, overcoming optical crosstalk and thus enabling an all-optical approach. We generated two different variants of the pH-sensitive optogenetic reporter of vesicle recycling (pOpsicle) and tested them in cholinergic neurons of intact Caenorhabditis elegans nematodes. First, we combined the red fluorescent protein pHuji with the blue-light gated ChR2(H134R), and second, the green fluorescent pHluorin combined with the novel red-shifted ChR ChrimsonSA. In both cases, fluorescence increases were observed after optical stimulation. Increase and subsequent decline of fluorescence was affected by mutations of proteins involved in SV fusion and endocytosis. These results establish pOpsicle as a non-invasive, all-optical approach to investigate different steps of the SV cycle.
Neural substrates of cognitive impairment in a NMDAR hypofunction mouse model of schizophrenia and partial rescue by risperidone
Authors: Delgado-Sallent Cristina , Gener Thomas , Nebot Pau , López-Cabezón Cristina , Puig M. Victoria
Published: March 2023

N-methyl D-aspartate receptor (NMDAR) hypofunction is a pathophysiological mechanism relevant for schizophrenia. Acute administration of the NMDAR antagonist phencyclidine (PCP) induces psychosis in patients and animals while subchronic PCP (sPCP) produces cognitive dysfunction for weeks. We investigated the neural correlates of memory and auditory impairments in mice treated with sPCP and the rescuing abilities of the atypical antipsychotic drug risperidone administered daily for two weeks. We recorded neural activities in the medial prefrontal cortex (mPFC) and the dorsal hippocampus (dHPC) during memory acquisition, short-term, and long-term memory in the novel object recognition test and during auditory processing and mismatch negativity (MMN) and examined the effects of sPCP and sPCP followed by risperidone. We found that the information about the familiar object and its short-term storage were associated with mPFC→dHPC high gamma connectivity (phase slope index) whereas long-term memory retrieval depended on dHPC→mPFC theta connectivity. sPCP impaired short-term and long-term memories, which were associated with increased theta power in the mPFC, decreased gamma power and theta-gamma coupling in the dHPC, and disrupted mPFC-dHPC connectivity. Risperidone rescued the memory deficits and partly restored hippocampal desynchronization but did not ameliorate mPFC and circuit connectivity alterations. sPCP also impaired auditory processing and its neural correlates (evoked potentials and MMN) in the mPFC, which were also partly rescued by risperidone. Our study suggests that the mPFC and the dHPC disconnect during NMDAR hypofunction, possibly underlying cognitive impairment in schizophrenia, and that risperidone targets this circuit to ameliorate cognitive abilities in patients.
Predicting the recurrence and overall survival of patients with glioma based on histopathological images using deep learning
Authors: Luo Chenhua , Yang Jiyan , Liu Zhengzheng , Jing Di
Published: March 2023

Background

A deep learning (DL) model based on representative biopsy tissues can predict the recurrence and overall survival of patients with glioma, leading to optimized personalized medicine. This research aimed to develop a DL model based on hematoxylin-eosin (HE) stained pathological images and verify its diagnostic accuracy.

Methods

Our study retrospectively collected 162 patients with glioma and randomly divided them into a training set (n = 113) and a validation set (n = 49) to build a DL model. The HE-stained slide was segmented into a size of 180 × 180 pixels without overlapping. The patch-level features were extracted by the pre-trained ResNet50 to predict the recurrence and overall survival. Additionally, a light-strategy was introduced where low-size digital biopsy images with clinical information were inputted into the DL model to ensure minimum memory occupation.

Results

Our study extracted 512 histopathological features from the HE-stained slides of each glioma patient. We identified 36 and 18 features as significantly related to disease-free survival (DFS) and overall survival (OS), respectively, (P < 0.05) using the univariate Cox proportional-hazards model. Pathomics signature showed a C-index of 0.630 and 0.652 for DFS and OS prediction, respectively. The time-dependent receiver operating characteristic (ROC) curves, along with nomograms, were used to assess the diagnostic accuracy at a fixed time point. In the validation set (n = 49), the area under the curve (AUC) in the 1- and 2-year DFS was 0.955 and 0.904, respectively, and the 2-, 3-, and 5-year OS were 0.969, 0.955, and 0.960, respectively. We stratified the patients into low- and high-risk groups using the median hazard score (0.083 for DFS and−0.177 for OS) and showed significant differences between these groups (P < 0.001).

Conclusion

Our results demonstrated that the DL model based on the HE-stained slides showed the predictability of recurrence and survival in patients with glioma. The results can be used to assist oncologists in selecting the optimal treatment strategy in clinical practice.
Associations between diet and incidence risk of lung cancer: A Mendelian randomization study
Authors: Yan Haihao , Jin Xiao , Zhang Changwen , Zhu Changjun , He Yucong , Du Xingran , Feng Ganzhu
Published: March 2023

Background

Observational studies have revealed associations between diet and lung cancer. However, it is unclear whether the association is disturbed by confounding factors. We used a two-sample Mendelian randomization (MR) method to characterize the associations between diet and the lung cancer risk (including 3 subtypes: lung adenocarcinoma (LA), squamous cell lung carcinoma (SqCLC), and small cell lung cancer (SCLC)).

Materials and methods

Data on 20 diets were screened from the UK Biobank. Lung cancer data came from a large meta-analysis of 85,716 individuals. The inverse-variance weighted method was used as the main analysis. Sensitivity analysis was also used to explain the different multiplicity patterns of the final model.

Results

Our results showed significant evidence that 3 diets were associated with lung cancer [odds ratio (OR): 0.271, 95% confidence interval (CI): 0.150–0.488, p = 1.46 × 10−4, dried fruit; OR: 3.010, 95% CI: 1.608–5.632, p = 5.70 × 10−4, beer] and SqCLC (OR: 0.135, 95% CI: 0.062–0.293, p = 2.33 × 10−5, dried fruit; OR: 0.485, 95% CI: 0.328–0.717, p = 2.9 × 10−4, cheese). There were also suggestive correlations between 5 dietary intakes and lung cancer (OR: 0.441, 95% CI: 0.250–0.778, p = 0.008, cereal; OR: 2.267, 95% CI: 1.126–4.564, p = 0.022, beef), LA (OR: 0.494, 95% CI: 0.285–0.858, p = 0.012, dried fruit; OR: 3.536, 95% CI: 1.546–8.085, p = 0.003, beer) and SCLC (OR: 0.006, 95% CI: 0.000–0.222, p = 0.039, non-oily fish; OR: 0.239, 95% CI: 0.086–0.664, p = 0.006, dried fruit). No other association between diet and lung cancer was observed.

Conclusion

Our study preliminary found that cheese, dried fruit, and beer intake were significantly associated with the risk of lung cancer or its subtypes, while cereal, beef, and non-oily fish intake were suggestively associated with the risk of lung cancer or its subtypes. Well-designed prospective studies are still needed to confirm our findings in the future.
Upregulation of the ferroptosis-related STEAP3 gene is a specific predictor of poor triple-negative breast cancer patient outcomes
Authors: Yuan Lifang , Liu Jiannan , Bao Lei , Qu Huajun , Xiang Jinyu , Sun Ping
Published: March 2023

Objective

This study was designed to assess ferroptosis regulator gene (FRG) expression patterns in patients with TNBC based on data derived from The Cancer Genome Atlas (TCGA). Further, it was utilized to establish a TNBC FRG signature, after which the association between this signature and the tumor immune microenvironment (TIME) composition was assessed, and relevant prognostic factors were explored.

Methods

The TCGA database was used to obtain RNA expression datasets and clinical information about 190 TNBC patients, after which a prognostic TNBC-related FRG signature was established using a least absolute shrinkage and selection operator (LASSO) Cox regression approach. These results were validated with separate data from the Gene Expression Omnibus (GEO). The TNBC-specific prognostic gene was identified via this method. The STEAP3 was then validated through Western immunoblotting, immunohistochemical staining, and quantitative real‐time polymerase chain reaction (RT-qPCR) analyses of clinical tissue samples and TNBC cell lines. Chemotherapy interactions and predicted drug sensitivity studies were investigated to learn more about the potential clinical relevance of these observations.

Results

These data revealed that 87 FRGs were differentially expressed when comparing TNBC tumors and healthy tissue samples (87/259, 33.59%). Seven of these genes (CA9, CISD1, STEAP3, HMOX1, DUSP1, TAZ, HBA1) are significantly related to the overall survival of TNBC patients. Kaplan-Meier analyses and established FRG signatures and nomograms identified CISD1 and STEAP3 genes of prognostic relevance. Prognostic Risk Score values were positively correlated with the infiltration of CD4+ T cells (p = 0.001) and myeloid dendritic cells (p =0.004). Further evidence showed that STEAP3 was strongly and specifically associated with TNBC patient OS (P<0.05). The results above were confirmed by additional examinations of STEAP3 expression changes in TNBC patient samples and cell lines. High STEAP3 levels were negatively correlated with half-maximal inhibitory concentration (IC50) values for GSK1904529A (IGF1R inhibitor), AS601245 (JNK inhibitor), XMD8−85 (Erk5 inhibitor), Gefitinib, Sorafenib, and 5-Fluorouracil (P < 0.05) in patients with TNBC based on information derived from the TCGA-TNBC dataset.

Conclusion

In the present study, a novel FRG model was developed and used to forecast the prognosis of TNBC patients accurately. Furthermore, it was discovered that STEAP3 was highly overexpressed in people with TNBC and associated with overall survival rates, laying the groundwork for the eventually targeted therapy of individuals with this form of cancer.
Fluid overload–associated large B-cell lymphoma with primary biliary cirrhosis: A case report
Authors: Wang Huan , Zhang Quan , Liu Qin , Wu Xian , Ma Ke
Published: March 2023

The 5th edition of World Health Organization Classification of Haematolymphoid Tumours (WHO-HAEM5) is characterized by its hierarchical system for classification and novel entities/types. Considering the significant discrepancy in clinical manifestations and prognosis, fluid overload–associated large B-cell lymphoma (FOALBCL) has been a new addition to the WHO-HAEM5, being distinct from the traditional diagnosis of primary effusion lymphoma. In this manuscript, we report a patient who was diagnosed with FOALBCL that a novel entity introduced in the WHO-HAEM5. It is an instance of a successful application of the updated WHO-HAEM5 and indicates that the ′Blue Book′ could confer convenience and benefits on both patients and clinicians. Moreover, the patient combined primary biliary cirrhosis (PBC), which is a relatively rare condition compared to the underlying medical condition of viral cirrhosis. Due to atypical clinical symptoms and invasive biopsy of lymphoma, sometimes, diagnoses might be undesired, which eventually leads to a poor prognosis. With this case report, it reminds not just hematologists but also other specialists to pay attention to the updates and revisions of the classifications of lymphoma.
Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway
Authors: Sheng Mingyue , Chen Xun , Yu Yan , Wu Qi , Kou Junping , Chen Gangling
Published: March 2023

Backgrounds: The circadian clock protein Rev-erbα is a crucial regulator of circadian rhythms that affects multiple molecular, cellular, and physiology pathways that control susceptibility, injury, and recovery in the neurological disorders. Emerging evidence suggest that Rev-erbα plays a key role in the inflammation and oxidative stress, two pivotal mechanisms in the pathogenesis, progression, and recovery process of ischemic stroke. However, it remains inconclusive whether Rev-erbα activation is protective against ischemic brain damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a master regulator of inflammatory and oxidative responses. Our study aimed to determine whether pharmacological activation of Rev-erbα by SR9009 protects against acute ischemic brain damage partly via Nrf2 pathway.

Methods: Adult mice were pretreated with SR9009 or Nrf2 inhibitor all-trans-retinoic acid (ATRA) for 3 days prior to Sham or middle cerebral artery occlusion (MCAO) operation. After ischemia for 1 h and reperfusion for 24 h, the neurological function and cerebral infarction volume were determined, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and glutathione peroxidase (GSH-PX) activity in serum were detected by kit. The mRNA and/or protein level of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), Period (Per)1, Brain and muscle arnt-like1 (Bmal1), Circadian locomotor output cycles kaput (Clock), Rev-erbα, Nrf2, heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO1) in cerebral cortex were detected by q-PCR and Western blot.

Results: We confirmed that SR9009 activated Rev-erbα gene in the cerebral cortex under basal condition. At 24 h after reperfusion, SR9009 ameliorated acute neurological deficits, reduced infarct volume. Meanwhile, the inflammatory TNF-α, IL-1β, iNOS and MDA content levels were significant decreased, SOD and GSH-PX activity were obviously increased, which were markedly blunted (or abolished) by ATRA. SR9009 enhanced the induction of Nrf2 and its downstream target genes HO-1 and NQO1 after ischemic insult. In addition, we found that SR9009 restored Rev-erbα, Bmal1, Clock, Per1 genes expression in the cerebral cortex under ischemic condition.

Conclusion: Taken together, Rev-erbα activation by SR9009 protects against ischemic stroke damage, at least, partly through Nrf2 pathway.
Impact of selenium biofortification on production characteristics of forages grown following standard management practices in Oregon
Authors: Hall Jean A. , Bobe Gerd , Filley Shelby J. , Bohle Mylen G. , Pirelli Gene J. , Wang Guogie , Davis T. Zane , Bañuelos Gary S.
Published: March 2023

Introduction

Low selenium (Se) concentrations in soils and plants pose a health risk for ruminants consuming locally-grown forages. Previous studies have shown that Se concentrations in forages can be increased using soil-applied selenate amendments. However, the effects of foliar selenate amendments applied with traditional nitrogen-phosphorus-potassium-sulfur (NPKS) fertilizers on forage yields, and nutrient contents, and agronomic efficiencies are unknown.

Methods

Using a split plot design, we determined the effects of springtime sodium selenate foliar amendment rates (0, 45, and 90 g Se ha-1) and NPKS application (none, NPK for grasses/PK for alfalfa, and NPKS/PKS fertilization at amounts adapted to meet local forage and soil requirements) on forage growth and N, S, and Se concentrations, yields, and agronomic efficiencies. This 2-year study was conducted across Oregon on four representative forage fields: orchardgrass (Dactylis glomerata L.) in Terrebonne (central Oregon), grass-clover mixture in Roseburg (southwestern Oregon), and both grass mixture and alfalfa (Medicago sativa L.) fields in Union (eastern Oregon).

Results

Grasses grew poorly and were low in N content without NPK fertilization. Fertilization with NPK/PK promoted forage growth, increased forage N concentrations, and had to be co-applied with S when plant available S was low. Without Se amendment, forage Se concentrations were low and further decreased with NPKS/PKS fertilization. Selenate amendment linearly increased forage Se concentration without adversely affecting forage yields, N and S concentrations, or N and S agronomic efficiencies.

Discussion

Importantly, S fertilization did not interfere with Se uptake in Se amended plots. In conclusion, co-application of NPKS/PKS fertilizers and foliar sodium selenate in springtime is an effective strategy to increase forage total Se concentrations, while maintaining optimal growth and quality of Oregon forages.
Neuropsychological monitoring of cognitive function and ICF–based mental components in patients with malignant brain tumours
Authors: Pilarska Agnieszka , Pieczyńska Anna , Hojan Katarzyna
Published: March 2023

Background

Cognitive deficits are one of the important clinical features of patients with brain tumours, which can affect up to 30–90% of patients before treatment. The consequence is a significant and rapid degradation of the patient’s intellectual functioning, seizures, paralysis and other symptoms that prevent independent functioning. This results in a reduced quality of life and a psychological crisis not only for the patient but also for their relatives. Maintaining the patient’s function at the highest level for as long as possible is particularly important, given that long-term remission or a cure is unlikely or accompanied by significant disability.

Purpose

This paper aims to provide a narrative review to the neuropsychological procedure for monitoring cognitive function in patients with brain tumours, which may be helpful in developing adequate clinical practice and appropriate management procedures.

Methods

A narrative review was applied to search broadly across disciplines, retrieving literature from several databases (PubMed, Web of Science, and EBSCOhost).

Results

(1) discussing the methodological aspects of neuropsychological tools for monitoring cognitive function in brain tumour patients, (2) identifying the most commonly used tools and (3) their practical applicability according to the cognitive function components of the International Classification of Functioning, Disability and Health (ICF).

Conclusion

This article points to the need to systematise research tools or develop new ones, adapted to diagnostic needs with high psychometric characteristics, with particular attention to memory processes and learning effect. Rehabilitation of patients is also an important issue, which requires the use of adequate tools to assess functional disability. The International Classification of Functioning, Disability and Health (ICF) seems to be useful in this respect. The ICF has the advantage of targeting actions to improve the condition of the individual and to keep them as long as possible in a state of well-being that allows them to function effectively in society or to return to work. This is particularly important in view of the ageing population and the increasing number of diagnoses related to brain tumours.
Language athletes: Dual-language code-switchers exhibit inhibitory control advantages
Authors: Gosselin Leah , Sabourin Laura
Published: March 2023

Recent studies have begun to examine bilingual cognition from more nuanced, experienced-based perspectives. The present study adds to this body of work by investigating the potential impact of code-switching on bilinguals’ inhibitory control abilities. Crucially, our bilingual participants originated from a predominantly dual-language environment, the interactional context which is believed to require (and therefore, potentially train) cognitive control processes related to goal-monitoring and inhibition. As such, 266 French Canadian bilinguals completed an online experiment wherein they were asked to complete a domain-general (Flanker) and a language-specific (bilingual Stroop) inhibitory control task, as well as extensive demographic and language background questionnaires. Stepwise multiple regressions (including various potential demographic and linguistic predictors) were conducted on the participants’ Flanker and Stroop effects. The results indicated that the bilinguals’ propensity to code-switch consistently yielded significant positive (but unidirectional) inhibitory control effects: dual-language bilinguals who reported more habitual French-to-English switching exhibited better goal-monitoring and inhibition abilities. For the language-specific task, the analysis also revealed that frequent unintentional code-switching may mitigate these inhibition skills. As such, the findings demonstrate that dual-language code-switchers may experience inhibitory control benefits, but only when their switching is self-reportedly deliberate. We conclude that the bilinguals’ interactional context is thus of primary importance, as the dual-language context is more conducive to intentional code-switching. Overall, the current study highlights the importance of considering individualistic language experience when it comes to examining potential bilingual executive functioning advantages.
Strategies for reducing meat consumption within college and university settings: A systematic review and meta-analysis
Authors: Chang Kenjin B. , Wooden Alyssa , Rosman Lori , Altema-Johnson Daphene , Ramsing Rebecca
Published: March 2023

Introduction

Despite the considerable public and planetary health benefits associated with reducing the amount of meat consumed in high-income countries, there is a limited empirical understanding of how these voluntary changes in food choice can be effectively facilitated across different settings. While prior reviews have given us broad insights into the varying capacities of behavior change strategies to promote meaningful reductions in meat consumption, none have compared how they perform relative to each other within a uniform dining context.

Methods

To address this gap in the literature, we synthesized the available research on university-implemented meat reduction interventions and examined the variations in the success rates and effect estimates associated with each of the three approaches identified in our systematic review.

Results

From our analyses of the 31 studies that met our criteria for inclusion (n = 31), we found that most were successful in reducing the amount of meat consumed within university settings. Moreover, independent of the number of individual strategies being used, multimodal interventions were found to be more reliable and effective in facilitating these changes in food choice than interventions targeting the choice architecture of the retail environment or conscious decision-making processes alone.

Discussion

In addition to demonstrating the overall value of behavior change initiatives in advancing more sustainable dining practices on college and university campuses, this study lends further insights into the merits and mechanics underlying strategically integrated approaches to dietary change. Further investigations exploring the persistence and generalizability of these effects and intervention design principles are needed.

Systematic review registration

https://doi.org/10.17605/OSF.IO/DXQ5V, identifier: 10.17605/OSF.IO/DXQ5V.
Case report: Successful and effective percutaneous closure of a deep femoral artery pseudoaneurysm using proglide device
Authors: Jiaxin Liu , Yan Li , Sheng Zhang , Zhiyi Dong , Jichang Wang , Shaoying Lu
Published: March 2023

A 61-year-old man developed severe swelling in the left lower extremity after interventional embolization of liver tumor. Ultrasound examination showed a pseudoaneurysm and thrombosis in the upper thigh on the left. To recognize the causes and determine the effective therapy, lower extremity arteriography was performed. The results revealed a pseudoaneurysm arised from deep femoral artery. Considering of the size of cavity and symptoms of patient, a new method was tried instead of traditional treatment using PROGLIDE device. Postoperative angiography showed a powerful blocking effect. This case study provide us a specific treatment for pseudoaneurysm, and this method provide us a new therapeutic strategy in clinical practice.
Soil Fertility Management for Sustainable Crop Production
Authors: Mi Wenhai , Ma Qingxu , Cao Xiaochuang , Wu Lianghuan
Published: March 2023

To feed the growing world population, which is expected to reach 9 [...]
The Domestication and Dispersal of Large-Fruiting Prunus spp.: A Metadata Analysis of Archaeobotanical Material
Authors: Dal Martello Rita , von Baeyer Madelynn , Hudson Mark , Bjorn Rasmus G. , Leipe Christian , Zach Barbara , Mir-Makhamad Basira , Billings Traci N. , Muñoz Fernández Irene M. , Huber Barbara , Boxleitner Kseniia , Lu Jou-Chun , Chi Ko-An , Liu Hsiao-Lei , Kistler Logan , Spengler Robert N.
Published: March 2023

The Prunus genus contains many of the most economically significant arboreal crops, cultivated globally, today. Despite the economic significance of these domesticated species, the pre-cultivation ranges, processes of domestication, and routes of prehistoric dispersal for all of the economically significant species remain unresolved. Among the European plums, even the taxonomic classification has been heavily debated over the past several decades. In this manuscript, we compile archaeobotanical evidence for the most prominent large-fruiting members of Prunus, including peach, apricot, almonds, sloes, and the main plum types. By mapping out the chronology and geographic distributions of these species, we are able to discuss aspects of their domestication and dispersal more clearly, as well as identify gaps in the data and unanswered questions. We suggest that a clearer understanding of these processes will say a lot about ancient peoples, as the cultivation of delayed return crops is an indicator of a strong concept of land tenure and the specialization of these cultivation strategies seems to be tied to urbanism and reliable markets. Likewise, the evolution of domestication traits in long-generation perennials, especially within Rosaceae, represents awareness of grafting and cloning practices.
Placing Management of Sunflower Downy Mildew (Plasmopara halstedii (Farl.) Berl. et de Toni) under an Integrated Pest Management (IPM) System Approach: Challenges and New Perspectives
Authors: Bán Rita , Kiss József , Pálinkás Zoltán , Körösi Katalin
Published: March 2023

Sunflower is one of the major oil crops in the world. Diseases such as sunflower downy mildew (Plasmopara halstedii (Farl.) Berl. et de Toni) constitute a significant risk factor during sunflower production. Integrated pest management (IPM) is considered an essential tool against sunflower downy mildew; however, the pathogen variability repeatedly affects the efficacy of control measures. This article evaluates some vital elements of the management of sunflower downy mildew disease and analyzes current challenges. In addition, we outlined the options for the future integration of recent research and achievements related to sunflower downy mildew to achieve more sustainable sunflower production. Finally, a SWOT analysis was performed to consider internal factors, such as strengths (S) and weaknesses (W), and external factors, such as opportunities (O) and threats (T) connected to the topic.