bluuebunny/crossref_metadata_2025 huggingface dataset:
Directional amplification and ground motion polarization in Casamicciola area (Ischia volcanic island) after the 21 August 2017 Md 4.0 earthquake
Authors: Pischiutta M. , Petrosino S. , Nappi R.
Published: December 2022

In this paper, we investigated ground motion directional amplification and horizontal polarization using ambient noise measurements performed in the northern sector of Ischia Island which suffered damage (VIII EMS) during the 21 August 2017, Md 4.0 earthquake. Over 70 temporary seismic stations were installed by the INGV EMERSITO task force, whose aim is to monitor site effects after damaging earthquakes in Italy. To investigate ground motion directional amplification effects, we have applied three different techniques, testing their performance: the HVSR calculation by rotating the two horizontal components, the covariance matrix analysis, and time–frequency domain polarization analysis. These techniques resulted in coherent outcomes, highlighting the occurrence of directional amplification and polarization effects in two main sectors of the investigated area. Our results suggest an interesting pattern for ground motion polarization, that is mainly controlled by recent fault activity and hydrothermal fluid circulation characterizing the northern sector of the Ischia Island.
Bioinformatics analyses for the identification of tumor antigens and immune subtypes of gastric adenocarcinoma
Authors: Wei Shuxun , Sun Qiang , Chen Jinshui , Li Xinxing , Hu Zhiqian
Published: December 2022

Background: Although mRNA vaccines have been effective against multiple cancers, their efficacy against stomach adenocarcinoma (STAD) remains undefined. Immunotyping can indicate the comprehensive immune status in tumors and their immune microenvironment, which is closely associated with therapeutic response and vaccination potential. The aim of this study was to identify potential antigens in STAD for mRNA vaccine development, and further distinguish immune subtypes of STAD to construct an immune landscape for selecting suitable patients for vaccination.

Methods: The gene expression and clinicopathological features of patients with gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx). 729 samples from GSE66229 and GSE84437 were downloaded through GEO and were used as the validation cohorts. Differential gene expression, genetic alterations and prognosis were analyzed using the R package, cBioPortal program and Kaplan-Meier. The relationship between tumor antigens and immune cells was evaluated and plotted by TIMER. ConsensusClusterPlus was used for consistency matrix construction and data clustering, and graph learning-based dimensional reduction was used to depict immune landscape. WGCNA was used to estimate the relationship between the color modules and immune subtypes.

Results: Two overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in STAD, including RAI14 and NREP. The immune subtypes showed distinct molecular, cellular and clinical characteristics. IS1 and IS2 exhibited immune-activated phenotypes and correlated to better survival compared to IS3, while IS3 tumors was immunologically cold. Immunogenic cell death modulators, immune checkpoints, and CA125, and CEA were also differentially expressed among the three immune subtypes. Finally, the immune landscape of STAD showed a high degree of heterogeneity between individual patients.

Conclusion: RAI14 and NREP are potential antigens for developing anti-STAD mRNA vaccine, and patients with IS1 and IS3 tumors may be suitable for vaccination.
A novel prognostic signature of cuproptosis-related genes and the prognostic value of FDX1 in gliomas
Authors: Zhu HuaXin , Wan Qinsi , Tan Jiacong , Ouyang Hengyang , Pan Xinyi , Li MeiHua , Zhao YeYu
Published: December 2022

Background: Gliomas are the most common malignant tumors of the central nervous system, with extremely bad prognoses. Cuproptosis is a novel form of regulated cell death. The impact of cuproptosis-related genes on glioma development has not been reported.

Methods: The TCGA, GTEx, and CGGA databases were used to retrieve transcriptomic expression data. We employed Cox’s regressions to determine the associations between clinical factors and cuproptosis-related gene expression. Overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were evaluated using the Kaplan-Meier method. We also used the least absolute shrinkage and selection operator (LASSO) regression technique.

Results: The expression levels of all 10 CRGs varied considerably between glioma tumors and healthy tissues. In glioma patients, the levels of CDKN2A, FDX1, DLD, DLAT, LIAS, LIPT1, and PDHA1 were significantly associated with the OS, disease-specific survival, and progression-free interval. We used LASSO Cox’s regression to create a prognostic model; the risk score was (0.882340) *FDX1 expression + (0.141089) *DLD expression + (–0.333875) *LIAS expression + (0.356469) *LIPT1 expression + (–0.123851) *PDHA1 expression. A high-risk score/signature was associated with poor OS (hazard ratio = 3.50, 95% confidence interval 2, –4.55, log-rank p < 0.001). Cox’s regression revealed that the FDX1 level independently predicted prognosis; FDX1 may control immune cell infiltration of the tumor microenvironment.

Conclusion: The CRG signature may be prognostic in glioma patients, and the FDX1 level may independently predict glioma prognosis. These data may afford new insights into treatment.
Serological, fragmentomic, and epigenetic characteristics of cell-free DNA in patients with lupus nephritis
Authors: Wang Fang , Miao Hai-bing , Pei Zhi-hua , Chen Zhen
Published: December 2022

Objectives

The biological characteristics of plasma circulating cell-free DNA (cfDNA) are related to the pathogenesis of lupus nephritis (LN). The aim of this study was to explore the biological characteristics of cfDNA in patients with LN in terms of serology, fragment omics, and epigenetics, and to discuss the possibility of liquid biopsy for cfDNA as an alternative to conventional tissue biopsy.

Methods

cfDNA was extracted from plasma samples of 127 patients with systemic lupus erythematosus (64 with LN, 63 without LN). The cfDNA concentration was determined using the Qubit method. Next-generation sequencing cfDNA methylation profiling was performed for three LN patients and six non-LN patients. The methylation panel was designed based on data from The Cancer Genome Atlas cohort. The fragmentation index, motif score, and DELFI score were calculated to explore the fragmentation profile of cfDNA in patients with LN. Statistical and machine learning methods were used to select features to calculate the methylation scores of the samples.

Results

Patients with LN had significantly lower cfDNA concentrations (P = 0.0347) than those without LN. This may be associated with the presence of anti-double-stranded DNA antibodies (r = –0.4189; P = 0.0296). The mean DELFI score (proportion of short fragments of cfDNA) in patients with LN was significantly higher than that in patients without LN (P = 0.0238). Based on the pan-cancer data, 73, 66, 8, and 10 features were selected and used to calculate the methylation scores. The mean methylation scores of these features in patients with LN differed significantly from those in patients without LN (P = 0.0238).

Conclusions

The specificity of cfDNA in patients with LN was identified using serological, fragmentomic, and epigenetic analyses. The findings may have implications for the development of new molecular markers of LN.
Innate immune function during antineoplastic treatment is associated with 12-months survival in non-small cell lung cancer
Authors: Ryssel Heidi , Egebjerg Kristian , Nielsen Susanne Dam , Lundgren Jens , Pøhl Mette , Langer Seppo W. , Kjaer Andreas , Ostrowski Sisse Rye , Fischer Barbara Malene
Published: December 2022

Introduction

The immune system has proven to be a key player in the progression as well as containment of cancer with new treatment strategies based on immunotherapy targeting this interaction. Assessing immune function could reveal critical information about the immune response to therapeutic interventions, revealing predictive biomarkers for tailored care and precision medicine.

Methods

We investigated immune function in 37 patients with inoperable non-small cell lung cancer (NSCLC) undergoing treatment with PD-L1 immune checkpoint inhibitor (ICI), chemotherapy (CT) or chemo-radiotherapy (CT/RT). Blood samples before (day 0) and during therapy (day 7, 21 and 80) were investigated by a standardized immunoassay, TruCulture®.

Results

Outcomes revealed a developing innate immune response induced by both immunotherapy and chemotherapy. NSCLC-patients displayed evidence of chronic innate immune activation and exhaustion prior to treatment. This pattern was particularly pronounced during treatment in patients dying within 12-months follow-up. Compared to treatment with CT, ICI demonstrated a higher ex vivo-stimulated release of proinflammatory cytokines.

Discussion

These preliminary findings may pave the way for tailored treatment and immune-monitoring.
Basophils from allergy to cancer
Authors: Poto Remo , Gambardella Adriana Rosa , Marone Gianni , Schroeder John T. , Mattei Fabrizio , Schiavoni Giovanna , Varricchi Gilda
Published: December 2022

Human basophils, first identified over 140 years ago, account for just 0.5-1% of circulating leukocytes. While this scarcity long hampered basophil studies, innovations during the past 30 years, beginning with their isolation and more recently in the development of mouse models, have markedly advanced our understanding of these cells. Although dissimilarities between human and mouse basophils persist, the overall findings highlight the growing importance of these cells in health and disease. Indeed, studies continue to support basophils as key participants in IgE-mediated reactions, where they infiltrate inflammatory lesions, release pro-inflammatory mediators (histamine, leukotriene C4: LTC4) and regulatory cytokines (IL-4, IL-13) central to the pathogenesis of allergic diseases. Studies now report basophils infiltrating various human cancers where they play diverse roles, either promoting or hampering tumorigenesis. Likewise, this activity bears remarkable similarity to the mounting evidence that basophils facilitate wound healing. In fact, both activities appear linked to the capacity of basophils to secrete IL-4/IL-13, with these cytokines polarizing macrophages toward the M2 phenotype. Basophils also secrete several angiogenic factors (vascular endothelial growth factor: VEGF-A, amphiregulin) consistent with these activities. In this review, we feature these newfound properties with the goal of unraveling the increasing importance of basophils in these diverse pathobiological processes.
Tumor necrosis factor is a necroptosis-associated alarmin
Authors: Pinci Francesca , Gaidt Moritz M. , Jung Christophe , Nagl Dennis , Kuut Gunnar , Hornung Veit
Published: December 2022

Necroptosis is a form of regulated cell death that can occur downstream of several immune pathways. While previous studies have shown that dysregulated necroptosis can lead to strong inflammatory responses, little is known about the identity of the endogenous molecules that trigger these responses. Using a reductionist in vitro model, we found that soluble TNF is strongly released in the context of necroptosis. On the one hand, necroptosis promotes TNF translation by inhibiting negative regulatory mechanisms acting at the post-transcriptional level. On the other hand, necroptosis markedly enhances TNF release by activating ADAM proteases. In studying TNF release at single-cell resolution, we found that TNF release triggered by necroptosis is activated in a switch-like manner that exceeds steady-state TNF processing in magnitude and speed. Although this shedding response precedes massive membrane damage, it is closely associated with lytic cell death. Further, we found that lytic cell death induction using a pore-forming toxin also triggers TNF shedding, indicating that the activation of ADAM proteases is not strictly related to the necroptotic pathway but likely associated with biophysical changes of the cell membrane upon lytic cell death. These results demonstrate that lytic cell death, particularly necroptosis, is a critical trigger for TNF release and thus qualify TNF as a necroptosis-associated alarmin.
Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model
Authors: Bishop Cameron R. , Caten Felipe Ten , Nakaya Helder I. , Suhrbier Andreas
Published: December 2022

Introduction

An adult wild-type C57BL/6J mouse model of chikungunya virus (CHIKV) infection and disease has been extensively used to study the alphaviral arthritic immunopathology and to evaluate new interventions. How well mouse models recapitulate the gene expression profiles seen in humans remains controversial.

Methods

Herein we perform a comparative transcriptomics analysis using RNA-Seq datasets from the C57BL/6J CHIKV mouse model with datasets obtained from adults and children acutely infected with CHIKV.

Results

Despite sampling quite different tissues, peripheral blood from humans and feet from mice, gene expression profiles were quite similar, with an overlap of up to ≈50% for up-regulated single copy orthologue differentially expressed genes. Furthermore, high levels of significant concordance between mouse and human were seen for immune pathways and signatures, which were dominated by interferons, T cells and monocyte/macrophages. Importantly, predicted responses to a series of anti-inflammatory drug and biologic treatments also showed cogent similarities between species.

Discussion

Comparative transcriptomics and subsequent pathway analysis provides a detailed picture of how a given model recapitulates human gene expression. Using this method, we show that the C57BL/6J CHIKV mouse model provides a reliable and representative system in which to study CHIKV immunopathology and evaluate new treatments.
Experimental and numerical analysis of the consolidation process for additive manufactured continuous carbon fiber-reinforced polyamide 12 composites
Authors: Zhilyaev Igor , Grieder Stefan , Küng Marco , Brauner Christian , Akermann Michael , Bosshard Jonas , Inderkum Petra , Francisco João , Eichenhofer Martin
Published: December 2022

Substitution of conventional metal structures with fiber-reinforced polymers is possible because of their sustainable performance. One of the primary disadvantages of these composite materials is their high cost due to labor-intensive manufacturing. Because the fiber path can be steered directly along the load path, structures can be manufactured in a near-net shape, and a high degree of reproducibility with low scrap rates can be achieved. Additive manufacturing of these composite structures could enable cost efficiency with a high degree of complexity. However, the high degree of porosity and high void content between the printed fiber filaments results in unacceptable structural performance. Following the printing process, a post-consolidation process (additive fusion) can be performed to improve the mechanical performance of the part and use fiber-reinforced polymers for load-bearing applications. Numerical simulation of the consolidation process enables the production of these complex parts without expensive prototyping iterations. Because of the rapid and local changes in material stiffness, the simulation of the consolidation process is combined with a set of numerical model convergence problems. An advanced finite-element numerical model for simulating the consolidation process of additive manufactured continuous fiber composite parts is presented in this paper. The additive fusion step simulation allows for the evaluation of process-induced deformations, final engineering constants, and porosity. The simulation workflow is demonstrated and validated using experimental data from the manufacturing process of a typical aerospace part, specifically a helicopter hinge element.
Coronavirus disease 2019 in patients with rheumatic immune-mediated diseases in a single University Hospital, matched case-control study and literature review
Authors: Martínez-López David , Ferraz-Amaro Ivan , Prieto-Peña Diana , Sánchez-Bilbao Lara , Herrero-Morant Alba , Álvarez-Reguera Carmen , Benavides-Villanueva Fabricio , Corrales-Selaya Cristina , Trigueros-Vázquez Martín , González-Gay Miguel Ángel , Blanco Ricardo
Published: December 2022

Background

COVID-19 may present different degrees of severity. Viral infections in patients with rheumatic inflammatory diseases (R-IMID) trend to present more severe disease. However, data comparing the severity of the disease between R-IMID and the general population are scarce.

Objectives

To compare predisposing factors, clinical, serological features, and severity of COVID-19 infection in patients with and without R-IMID.

Methods

Case-control study in a single University Hospital. We included all consecutive patients with a diagnosis of an R-IMID and COVID-19 infection up to March 31st, 2021. This cohort was compared to patients without R-IMID and not receiving immunosuppressive therapy, matched for sex and age (±5 years). Confirmed infection was defined if a patient had a positive nasopharyngeal swab for SARS-CoV-2. Severity was divided into mild, moderate, severe and critical according to the United States National Institute of Health (NIH) guidelines.

Results

We included 274 R-IMID patients (185 women/89 men), mean age 59.1 ± 18 years. More frequent R-IMID were: Rheumatoid arthritis (28.8%), Psoriatic Arthritis (20.1%), axial Spondyloarthritis (12.4%), Polymyalgia Rheumatica (8%) and Systemic Lupus Erythematosus (8%). Hypertension and dyslipidemia were more frequent in patients with R-IMID. Although most of the cases were mild, critical cases and deaths were more frequent in R-IMID. When adjusted by comorbidities, no statistical differences were observed.

Conclusion

R-IMID have a very similar clinical presentation when compared to the general population. There is a trend to an increased severity of the disease in patients with R-IMID.
Comammox Nitrospira Clade B is the most abundant complete ammonia oxidizer in a dairy pasture soil and inhibited by dicyandiamide and high ammonium concentrations
Authors: Hsu Pei-Chun (Lisa) , Di Hong J. , Cameron Keith , Podolyan Andriy , Chau Henry , Luo Jiafa , Miller Blair , Carrick Sam , Johnstone Paul , Ferguson Scott , Wei Wenhua , Shen Jupei , Zhang Limei , Liu Hongbin , Zhao Tongke , Wei Wenxue , Ding Weixin , Pan Hong , Liu Yimeng , Li Bowen
Published: December 2022

The recent discovery of comammox Nitrospira, a complete ammonia oxidizer, capable of completing the nitrification on their own has presented tremendous challenges to our understanding of the nitrification process. There are two divergent clades of comammox Nitrospira, Clade A and B. However, their population abundance, community structure and role in ammonia and nitrite oxidation are poorly understood. We conducted a 94-day microcosm study using a grazed dairy pasture soil amended with urea fertilizers, synthetic cow urine, and the nitrification inhibitor, dicyandiamide (DCD), to investigate the growth and community structure of comammox Nitrospira spp. We discovered that comammox Nitrospira Clade B was two orders of magnitude more abundant than Clade A in this fertile dairy pasture soil and the most abundant subcluster was a distinctive phylogenetic uncultured subcluster Clade B2. We found that comammox Nitrospira Clade B might not play a major role in nitrite oxidation compared to the role of canonical Nitrospira nitrite-oxidizers, however, comammox Nitrospira Clade B is active in nitrification and the growth of comammox Nitrospira Clade B was inhibited by a high ammonium concentration (700 kg synthetic urine-N ha–1) and the nitrification inhibitor DCD. We concluded that comammox Nitrospira Clade B: (1) was the most abundant comammox in the dairy pasture soil; (2) had a low tolerance to ammonium and can be inhibited by DCD; and (3) was not the dominant nitrite-oxidizer in the soil. This is the first study discovering a new subcluster of comammox Nitrospira Clade B2 from an agricultural soil.
Gene expression, molecular docking, and molecular dynamics studies to identify potential antifungal compounds targeting virulence proteins/genes VelB and THR as possible drug targets against Curvularia lunata
Authors: Kamboj Himanshu , Gupta Lovely , Kumar Pawan , Sen Pooja , Sengupta Abhishek , Vijayaraghavan Pooja
Published: December 2022

Curvuluria lunata is a melanized fungus pathogenic to both plants and animals including humans, causing from mild, febrile to life-threatening illness if not well treated. In humans, it is an etiological agent of keratomycosis, sinusitis, and onychomycosis in immunocompromised and immunocompetent patients. The development of multiple-drug-resistant strains poses a critical treatment issue as well as public health problem. Natural products are attractive prototypes for drug discovery due to their broad-spectrum efficacy and lower side effects. The present study explores possible targets of natural antifungal compounds (α-pinene, eugenol, berberine, and curcumin) against C. lunata via gene expression analysis, molecular docking interaction, and molecular dynamics (MD) studies. Curcumin, berberine, eugenol, and α-pinene exhibited in vitro antifungal activity at 78 μg/ml, 156 μg/ml, 156 μg/ml, and 1250 μg/ml, respectively. In addition, treatment by these compounds led to the complete inhibition of conidial germination and hindered the adherence when observed on onion epidermis. Several pathogenic factors of fungi are crucial for their survival inside the host including those involved in melanin biosynthesis, hyphal growth, sporulation, and mitogen-activated protein kinase (MAPK) signalling. Relative gene expression of velB, brn1, clm1, and pks18 responsible for conidiation, melanin, and cell wall integrity was down-regulated significantly. Results of molecular docking possessed good binding affinity of compounds and have confirmed their potential targets as THR and VelB proteins. The docked structures, having good binding affinity among all, were further refined, and rescored from their docked poses through 100-ns long MD simulations. The MDS study revealed that curcumin formed a stable and energetically stabilized complex with the target protein. Therefore, the study concludes that the antifungal compounds possess significant efficacy to inhibit C. lunata growth targeting virulence proteins/genes involved in spore formation and melanin biosynthesis.
Case report: A novel variant in SLC25A46 causing sensorimotor polyneuropathy and optic atrophy
Authors: Kodal Louise Sloth , Hammer-Hansen Sophia , Holm-Yildiz Sonja , Grønskov Karen , Karstensen Helena Gásdal , Dysgaard Tina
Published: December 2022

SLC25A46 is a mitochondrial protein involved in mitochondrial dynamics. Recently, bi-allelic variants have been identified as a pathogenic cause in a spectrum of neurological syndromes. We report a novel homozygous SLC25A46 variant in two siblings, originating from Iraq. Both presented with optic atrophy and varying neurological symptoms. The neurological examination and nerve conduction studies were consistent with sensorimotor polyneuropathy, one having mild polyneuropathy and the other pronounced polyneuropathy. The cases illustrate the disease spectrum and provide substantial information to the knowledge of polyneuropathy caused by SLC25A46 variants. It further highlights the diagnostic potentials of whole exome sequencing which can improve future understanding of disease mechanisms.
ACLMHA and FML: A brain-inspired kinship verification framework
Authors: Li Chen , Bai Menghan , Zhang Lipei , Xiao Ke , Song Wei , Zeng Hui
Published: December 2022

As an extended research direction of face recognition, kinship verification based on the face image is an interesting yet challenging task, which aims to determine whether two individuals are kin-related based on their facial images. Face image-based kinship verification benefits many applications in real life, including: missing children search, family photo classification, kinship information mining, family privacy protection, etc. Studies presented thus far provide evidence that face kinship verification still offers many challenges. Hence in this paper, we propose a novel kinship verification architecture, the main contributions of which are as follows: To boost the deep model to capture various and abundant local features from different local face regions, we propose an attention center learning guided multi-head attention mechanism to supervise the learning of attention weights and make different attention heads notice the characteristics of different regions. To combat the misclassification caused by single feature center loss, we propose a family-level multi-center loss to ensure a more proper intra/inter-class distance measurement for kinship verification. To measure the potential similarity of features among relatives better, we propose to introduce the relation comparison module to measure the similarity among features at a deeper level. Extensive experiments are conducted on the widely used kinship verification dataset—Family in the Wild (FIW) dataset. Compared with other state-of-art (SOTA) methods, encouraging results are obtained, which verify the effectiveness of our proposed method.
Acupuncture and acupressure with improved cancer-related depression of retrospective studies
Authors: Wang Feiqing , Zhao Jianing , Li Yanju , Yang Xu , Wu Dan , Yang Bo , Zhang Chike , He Zhixu , Du Liang , Zhu Xiaodong , Ming Dong , Liu Yang , Tang Dongxin
Published: December 2022

Introduction

Acupuncture and acupressure are widely used for treating cancer pain and depression and recognized as safe and effective by the international medical community. In this study, we systematically evaluated the efficacy, safety, and clinical significance of acupuncture and acupressure in treating cancer-related depression.

Methods

We searched MEDLINE, PubMed, Science Direct, Google Scholar, Web of Science and Embase and Chinese-language databases for randomized clinical trials (RCTs). To assess efficacy, rating scales administered by clinicians or experts were preferred, including the Hamilton Depression Rating Scale (HAMD), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), and Quality of Life Questionnaire-Core 30 (QLQ-C30) and the total effective rate after treatment. In all, Sixteen RCTs involving 1019 cancer patients were included in the Meta-analysis.

Results

Eleven (69%) of these studies reported the post-treatment total effective rate. Three hundred fifty-three patients received antidepressants; the total effective rate was 72.5%. Three hundred sixty-one patients underwent acupuncture and acupressure; the total effective rate was 90%. Meta-analysis results showed I2 = 0%, no heterogeneity, (Z = 5.84, p < 0.00001); and combined OR = 3.55, (95% CI = 2.32 to 5.43).

Discussion

This study found that acupuncture and acupressure are as effective as medication in the treatment of cancer-related depression, provide a reliable basis for the clinical use of acupuncture to treat cancer-related depression, help promote nonpharmacological treatment for cancer-related complications. These approaches thus help reduce drug resistance and adverse reactions and improve patients’ quality of life.
The enigmatic helicase DHX9 as a candidate prognostic biomarker for resected pancreatic ductal adenocarcinoma
Authors: Chen Le-gao , Cui Ying , Lu Wei-qin , Wu Hao , Jiang Jin-song , Ding Ke-feng
Published: December 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, and current therapies have limited efficacy on PDAC. The DEAH-box helicase 9 (DHX9) is widely reported to influence cell biological behavior via regulating DNA replication, genomic stability, transcription, translation, and microRNA biogenesis. However, the prognostic role of DHX9 in PDAC remains unclear. Thus, the objective of this study is to investigate the prognostic value of DHX9 expression in PDAC patients.

Methods

Tumor specimens from PDAC patients with surgical resection were obtained, and DHX9 was stained and analyzed in this study. Univariate and multivariate Cox regression analyses were utilized to identify independent risk factors of overall survival (OS) and recurrence-free survival (RFS). The prognostic nomograms for predicting OS and RFS were established to obtain superior predictive power.

Results

Among the enrolled 110 patients, 61 patients were identified as having high expression of DHX9. The correlation analysis revealed that higher DHX9 expression in PDAC was prone to have advanced N stage (p = 0.010) and TNM stage (p = 0.017). For survival, the median OS (21.0 vs. 42.0 months, p < 0.001) and RFS (12.0 vs. 24.0 months, p < 0.001) of patients in the high DHX9 group were significantly shorter than those in the low DHX9 group. Within the univariate and multivariate analyses, American Joint Committee on Cancer (AJCC) N stage (p = 0.036) and DHX9 expression (p = 0.041) were confirmed as independent prognostic factors of OS, while nerve invasion (p = 0.031) and DHX9 expression (p = 0.005) were independent prognostic factors of RFS. Finally, the novel prognostic nomograms for OS and RFS were established and showed superior predictive accuracy.

Conclusion

This study identified the independent prognostic value of DHX9 for RFS and OS in resected PDAC patients, and higher DHX9 expression was prone to have an earlier recurrence and shorter OS. Therefore, DHX9 may be a promising and valuable biomarker and a potential target for treating PDAC. More accurate and promising predictive models would be achieved when DHX9 is incorporated into nomograms.
Vascular invasion and lymph node metastasis mediate the effect of CA242 on prognosis in hilar cholangiocarcinoma patients after radical resection
Authors: Heng Gang , Huang Benqi , Shen Yanbing , wang Dan , Lan Zhen , Yao Yuxuan , Zhang Jianxin , Jia Jiankun , Zhang Chengcheng
Published: December 2022

Background

Carbohydrate antigen 242 has been clinically used as a diagnostic biomarker for pancreatic cancer. However, the prognostic role of CA242 in hilar cholangiocarcinoma (HCCA) has not been identified. Also, it remains unclear to what extents the vascular invasion and lymph node metastasis mediate the effect of serum CA242 on prognosis.

Objective

This study aimed to investigate whether vascular invasion and lymph node metastasis mediate the relationship between CA242 levels and clinical prognosis in HCCA patients after radical resection.

Methods

Data of 234 HCCA patients who accepted radical resection from March 2008 to December 2014 were analyzed. Vascular invasion and lymph node metastasis were assessed by postoperative pathological examinations. Mediation analysis was performed to study the potential causal relationship between CA242 and overall survival (OS) and relapse-free survival (RFS). Survival analysis was performed using the Kaplan-Meier method.

Results

Among 234 HCCA patients, 104 patients (44.4%) with normal CA242 levels (≤ 20 IU/ml) had significantly better OS (p=0.004) and RFS (p=0.001) than those 130 patients (55.6%) with elevated CA242 levels (>20 IU/ml). The logistic analysis showed that elevated CA242 was an independent risk factor for vascular invasion (p=0.006) and lymph nodes metastasis (p=0.040). The causal mediation analysis indicated that the vascular invasion (p=0.012 for OS; p=0.036 for RFS) and lymph nodes metastasis (p=0.024 for OS; p=0.014 for RFS) played significant roles in mediating the effect of serum CA242 on OS and RFS.

Conclusion

Serum elevated CA242 could be a novel marker for prognosis prediction in HCCA patients. Vascular invasion and lymph node metastasis mediated the relationship between CA242 and clinical prognosis.
Use of period analysis to timely assess 5-year relative survival for breast cancer patients from Taizhou, Eastern China
Authors: Li Runhua , Zheng Yabing , Huang Jiajia , Lei Huijun , Xu Mingzhi , Wang Liangyou , Zhang Luyao , Cheng Yongran , Jiang Xiyi , Tang Huijuan , Shi Zheng , Chen Gang , Zhou Huijuan , Dai Zhijun , Lu Dalin , Chen Tianhui
Published: December 2022

Objectives

While timely assessment of long-term survival for patients with breast cancer is essential for evaluation on early detection and screening programs, those data are extremely scant in China. We aimed to derive most up-to-date survival estimates and to predict future survival using the cancer registry data from Taizhou city, Eastern China.

Methods

Patients diagnosed with breast cancer during 2004-2018 from four cancer registries with high-quality data from Taizhou, Eastern China were included. Period analysis was used to calculate 5-year relative survival (RS) for the overall population and according to the stratification factors sex, age at diagnosis and geographic region. We further predict the upcoming 5-year RS during 2019-2023, using continuous data from three 5-year periods (2004-2008, 2009-2013 and 2014-2018) and a model-based period approach.

Results

Overall 6159 patients diagnosed with breast cancer during 2004-2018 were enrolled. The 5-year RS for breast cancer in 2014-2018 reached 88.8%, while women were higher compared to men (90.5% versus 83.7%) and urban areas were higher compared to rural areas (91.9% versus 86.7%). Additionally, we found a clear gradient by age at diagnosis, ranging from 94.8% for age<45 years to 83.3% for age>74 years. Projected overall 5-year RS for the upcoming 2019-2023 could reach 91.5% (84.8% for men and 93.5% for women).

Conclusions

We provided, for first time in China, using period analysis, most up-to-date 5-year RS (88.8%) for patients with breast cancer from Taizhou, Eastern China. We also demonstrate the 5-year RS has improved greatly over last 15 years, which has important implications for timely evaluation of early detection and screening programs.
Evaluation of short-term intraocular pressure changes after intravitreal injection of Conbercept in patients with diabetic macular edema
Authors: Hu Yunyan , Zeng Yunkao , Yang Jing , Zeng Xiaomin , Cao Dan , Ou Biqun , Zhang Guanrong , Zhang Liang
Published: December 2022

Background: The study concerning the influence of Conbercept, which is an anti-Vascular endothelial growth factor (VEGF) agent, in intraocular pressure (IOP) spike is limited and warrants further investigation. The current study aimed to investigate the changes of intraocular pressure after intravitreal injection (IVI) of Conbercept and evaluate the risk factors associated with intraocular pressure spikes.

Methods: Patients with diabetic macular edema receiving intravitreal injection of 0.05 ml (0.5 mg) Conbercept were involved in the study. All patients underwent slit lamp examination to determine the status of phakia/pseudophakia. The axial length was measured using IOL Master 500 before intravitreal injection. Patients underwent a Conbercept intravitreal injection with a 30-gauge needle in a standard fashion. The intraocular pressure was measured 2 min before injection, and 2, 10, 30 min, 1, 2, 5, 24 h after injection using a rebound tonometer. The changes of intraocular pressure and the relevant risk factors were evaluated. Patients were subdivided into phakic group and pseudophakic group to analyze the effect of lens status on intraocular pressure changes.

Results: Forty patients with a mean age of 62.48 ± 12.22 years were included in the study. The mean intraocular pressure values at baseline and 2, 10, 30 min, 1, 2, 5, 24 h after injection were 14.81 ± 3.13 mmHg, 26.80 ± 9.43 mmHg, 18.76 ± 6.16 mmHg, 16.54 ± 5.94 mmHg, 15.64 ± 3.75 mmHg, 14.46 ± 3.03 mmHg, 14.10 ± 1.88 mmHg, 14.23 ± 2.71 mmHg respectively. The intraocular pressure after injection for 2, 10 min was significantly higher than baseline (p < 0.001, p = 0.001, respectively). The intraocular pressure between baseline and post-injection for 30 min or beyond were comparable (all p > 0.05). No significant difference was found between the phakic group and pseudophakic group (p = 0.422). The changes of intraocular pressure were positively correlated with age (r = 0.329, p = 0.038), but negatively with axial length (r = −0.472, p = 0.002).

Conclusion: intravitreal injection of Conbercept may cause rapid spike of intraocular pressure, but is safe with respect to short-term changes. The intraocular pressure in patients with older age and shorter axial length is more likely to be higher after intravitreal injection.
Sleep loss effects on physiological and cognitive responses to systemic environmental hypoxia
Authors: Fabries Pierre , Gomez-Merino Danielle , Sauvet Fabien , Malgoyre Alexandra , Koulmann Nathalie , Chennaoui Mounir
Published: December 2022

In the course of their missions or training, alpinists, but also mountain combat forces and mountain security services, professional miners, aircrew, aircraft and glider pilots and helicopter crews are regularly exposed to altitude without oxygen supplementation. At altitude, humans are exposed to systemic environmental hypoxia induced by the decrease in barometric pressure (<1,013 hPa) which decreases the inspired partial pressure of oxygen (PIO2), while the oxygen fraction is constant (equal to approximately 20.9%). Effects of altitude on humans occur gradually and depend on the duration of exposure and the altitude level. From 1,500 m altitude (response threshold), several adaptive responses offset the effects of hypoxia, involving the respiratory and the cardiovascular systems, and the oxygen transport capacity of the blood. Fatigue and cognitive and sensory disorders are usually observed from 2,500 m (threshold of prolonged hypoxia). Above 3,500 m (the threshold for disorders), the effects are not completely compensated and maladaptive responses occur and individuals develop altitude headache or acute altitude illness [Acute Mountain Sickness (AMS)]. The magnitude of effects varies considerably between different physiological systems and exhibits significant inter-individual variability. In addition to comorbidities, the factors of vulnerability are still little known. They can be constitutive (genetic) or circumstantial (sleep deprivation, fatigue, speed of ascent.). In particular, sleep loss, a condition that is often encountered in real-life settings, could have an impact on the physiological and cognitive responses to hypoxia. In this review, we report the current state of knowledge on the impact of sleep loss on responses to environmental hypoxia in humans, with the aim of identifying possible consequences for AMS risk and cognition, as well as the value of behavioral and non-pharmacological countermeasures.
Adiponectin, leptin, cortisol, neuropeptide Y and profile of mood states in athletes participating in an ultramarathon during winter: An observational study
Authors: Kienast Camilla , Biere Katharina , Coker Robert H. , Genov Nikolai N. , Jörres Marc , Maggioni Martina Anna , Mascarell-Maricic Lea , Schalt Adriane , Genov Magdalena , Gunga Hanns-Christian , Steinach Mathias
Published: December 2022

Background:The Montane®Yukon Arctic Ultra (YAU) is one of the longest (690 km) and coldest (+10.6°C–43.9°C) ultramarathons worldwide. Taking part in an ultramarathon is associated with great physiological and psychological stress, which can affect one’s mood, level of hormones, and peptides. The current study aimed to identify relationships between peptides, hormones, and mood states in participants during this ultramarathon.

Methods:The study cohort consisted of 36 participants (19 men, 17 women, 38.64 ± 9.12 years) split into a finisher (n= 10), non-finisher (n= 19), and control group (n= 7). Data were collected at four time points: baseline (PRE), during (D1 after 277 km, D2 after 383 km), and after the race (POST). Questionnaires were used to assess ratings of perceived exertion (RPE), total quality of recovery (TQR), and profile of mood states (POMS-SF). Serum NPY, leptin, adiponectin, and cortisol were measured.

Results:Among non-finishers, scores for confusion, anger, depression, and tension-anxiety (PRE vs. D2,p< 0.05) increased, while vigor decreased (PRE vs. D1,p< 0.05). In contrast, finishers’ tension-anxiety scores decreased (PRE vs. D1,p< 0.05). Fatigue increased in finishers (PRE vs. POST,p< 0.05) and non-finishers (PRE vs. D1,p< 0.05). In non-finishers, depressive mood correlated positively with leptin, anger, and confusion at several time points (p< 0.001). In finishers, NPY correlated with TQR at PRE (p< 0.05), while leptin correlated negatively with TQR at POST (p< 0.05). Tension-anxiety correlated highly with perceived exertion in non-finishers (p< 0.001) and with cortisol in finishers (p< 0.05) and non-finishers (p< 0.001). In finishers, confusion correlated negatively with NPY (p< 0.01).

Conclusion:The study reveals an essential interplay between hormones and mood states affecting performance: Leptin was associated with anger and a depressive mood state in non-finishers and worse recovery in finishers. In contrast, NPY appeared linked to a lower confusion score and heightened recovery in finishers. A simultaneous increase in depressed mood, anger, tension-anxiety, and confusion might harm performance and lead to race failure.
A nomogram for predicting lung-related diseases among construction workers in Wuhan, China
Authors: Chen Xuyu , Yin Wenjun , Wu Jie , Luo Yongbin , Wu Jing , Li Guangming , Jiang Jinfeng , Yao Yong , Wan Siyu , Yi Guilin , Tan Xiaodong
Published: December 2022

Objective

To develop a prediction nomogram for the risk of lung-related diseases (LRD) in construction workers.

Methods

Seven hundred and fifty-two construction workers were recruited. A self- designed questionnaire was performed to collected relevant information. Chest X-ray was taken to judge builders' lung health. The potential predictors subsets of the risk of LRD were screened by the least absolute shrinkage and selection operator regression and univariate analysis, and determined by using multivariate logistic regression analysis, then were used for developing a prediction nomogram for the risk of LRD. C-index, calibration curve, receiver operating characteristic curve, decision curve analysis (DCA) and clinical impact curve analysis (CICA) were used to evaluation the identification, calibration, predictive ability and clinical effectiveness of the nomogram.

Results

Five hundred and twenty-six construction workers were allocated to training group and 226 to validation group. The predictors included in the nomogram were symptoms, years of dust exposure, work in shifts and labor intensity. Our model showed good discrimination ability, with a bootstrap-corrected C index of 0.931 (95% CI = 0.906–0.956), and had well-fitted calibration curves. The area under the curve (AUC) of the nomogram were (95% CI = 0.906–0.956) and 0.945 (95% CI = 0.891–0.999) in the training and validation groups, respectively. The results of DCA and CICA indicated that the nomogram may have clinical usefulness.

Conclusion

We established and validated a novel nomogram that can provide individual prediction of LRD for construction workers. This practical prediction model may help occupational physicians in decision making and design of occupational health examination.
The experience of hate incidents across racial and ethnic groups during the COVID-19 pandemic
Authors: Fan Carolyn A. , Hara-Hubbard KeliAnne K. , Barrington Wendy E. , Baquero Barbara
Published: December 2022

Introduction

Racism is a root cause of ill health for communities of color, and hate incidents are one manifestation of racism. Marginalized racial and ethnic groups, including but not limited to Asian Americans, have been the target of highly publicized violence, hate, and discrimination which has been amplified during the COVID-19 pandemic.

Objectives

This paper investigates (1) the prevalence of hate incidents across racial and ethnic groups, and (2) the relationship between race and ethnicity and hate incidents during the first year of the COVID-19 pandemic. We also seek to (3) situate study findings within theories of racism.

Methods

This study utilizes national data from the Understanding America Study (UAS) COVID-19 Longitudinal Survey from June 10, 2020 to March 30, 2021 (n = 8,436). Hate incidents in six categories were examined: being treated with less courtesy, receiving poorer service, others acting as if they were not smart, others acting as if they were afraid of them, being threatened or harassed, and experiencing any of the previous categories of hate incidents. Main analyses were conducted via population averaged logistic panel regression.

Results

The majority of members of all six marginalized racial and ethnic groups reported at least one hate incident during the first year of the COVID-19 pandemic. In addition, all marginalized racial or ethnic groups had statistically significant higher odds of experiencing at least two categories of hate incidents compared to white individuals. Asian, AI/AN, Black, and Multiracial groups had significantly higher odds of experiencing each category of hate incident. All marginalized racial and ethnic groups had significantly higher odds of receiving poorer service and others acting as if they were afraid of them.

Conclusion

All marginalized racial and ethnic groups experienced significant levels of hate incidents within the first year of the COVID-19 pandemic. The public health community must continue to research, monitor, treat, and prevent hate incidents as a public health issue while recognizing the social and historical contexts of structural and interpersonal racism in the US.
Towards better-informed dispersal probabilities in historical biogeography: Arachnids as a model lineage
Authors: Kuntner Matjaž , Turk Eva
Published: December 2022

Historical biogeography is an integrative scientific field critical for testing evolutionary hypotheses pertinent to organismal distributions, but despite recent theoretical and analytical advances, biogeographic reconstructions continue to struggle with accuracy and rigor. Most modern studies include the three elements needed for historical biogeographic inference, namely a time-calibrated phylogeny, contemporary taxonomic distributions, and estimations of organismal dispersal probabilities. The latter, we argue, are particularly vague, and historical biogeography would greatly benefit from dispersal probability estimations that are better informed and biologically meaningful. To achieve that goal, next-generation biogeography should ideally consider: a) dispersal-related traits; b) ecology; c) geological histories; and d) geographical factors. We briefly recap the three case studies on spiders that have pioneered this approach. Due to their old age and mega-diversity—considering both phylogenetic and life style diversity—arachnids are an ideal animal lineage for modern biogeographic research. There is no reason, however, that the concept should not be applied to all life. Further modifications of the proposed concept and, particularly, methodological implementation are needed to render this biogeographic framework widely useful.