bluuebunny/crossref_metadata_2025 huggingface dataset:
A pathogenesis-related protein 1 of Cucurbita moschata responds to powdery mildew infection
Authors: Guo Wei-Li , Yang He-Lian , Zhao Jin-Peng , Bian Shi-Jie , Guo Yan-Yan , Chen Xue-Jin , Li Xin-Zheng
Published: August 2023

Pumpkin (Cucurbita moschata Duch.) productivity is severely hindered by powdery mildew (PM) worldwide. The causative agent of pumpkin PM is Podosphaera xanthii, a biotrophic fungus. Pathogenesis-related protein 1 (PR1) homolog was previously identified from transcriptomic analysis of a PM-resistant pumpkin. Here, we investigated the effects of CmPR1 gene from pumpkin for resistance to PM. Subcellular localization assay revealed that CmPR1 is a cytoplasmic protein in plants. The expression of CmPR1 gene was strongly induced by P. xanthii inoculation at 48 h and exogenous ethylene (ET), jasmonic acid (JA) and NaCl treatments, but repressed by H2O2 and salicylic acid (SA) treatments. Visual disease symptoms, histological observations of fungal growth and host cell death, and accumulation of H2O2 in transgenic tobacco plants indicated that CmPR1 overexpression significantly enhanced the resistance to Golovinomyces cichoracearum compared to wild type plants during PM pathogens infection, possibly due to inducing cell death and H2O2 accumulation near infected sites. The expression of PR1a was significantly induced in transgenic tobacco plants in response to G. cichoracearum, suggesting that CmPR1 overexpression positively modulates the resistance to PM via the SA signaling pathway. These findings indicate that CmPR1 is a defense response gene in C. moschata and can be exploited to develop disease-resistant crop varieties.
Primary microcephaly gene CENPE is a novel biomarker and potential therapeutic target for non-WNT/non-SHH medulloblastoma
Authors: Fang Huangyi , Zhang Yusong , Lin Chengyin , Sun Zhenkai , Wen Wei , Sheng Hansong , Lin Jian
Published: August 2023

Background

Non-WNT/non-SHH medulloblastoma (MB) is one of the subtypes with the highest genetic heterogeneity in MB, and its current treatment strategies have unsatisfactory results and significant side effects. As a member of the centromere protein (CENP) family, centromeric protein E (CENPE) is a microtubule plus-end-directed kinetochore protein. Heterozygous mutations in CENPE can leads to primary microcephaly syndrome. It has been reported that CENPE is upregulated in MB, but its role in MB development is still unknown.

Methods

We downloaded the relevant RNA seq data and matched clinical information from the GEO database. Bioinformatics analysis includes differential gene expression analysis, Kaplan-Meier survival analysis, nomogram analysis, ROC curve analysis, immune cell infiltration analysis, and gene function enrichment analysis. Moreover, the effects of CENPE expression on cell proliferation, cell cycle, and p53 signaling pathway of non-WNT/non-SHH MB were validated using CENPE specific siRNA in vitro experiments.

Results

Compared with normal tissues, CENPE was highly expressed in MB tissues and served as an independent prognostic factor for survival in non-WNT/non-SHH MB patients. The nomogram analysis and ROC curve further confirmed these findings. At the same time, immune cell infiltration analysis showed that CENPE may participate in the immune response and tumor microenvironment (TME) of non-WNT/non-SHH MB. In addition, gene enrichment analysis showed that CENPE was closely related to the cell cycle and p53 pathway in non-WNT/non-SHH MB. In vitro experimental validation showed that knockdown of CENPE inhibited cell proliferation by activating the p53 signaling pathway and blocking the cell cycle.

Conclusion

The expression of CENPE in non-WNT/non-SHH MB was positively correlated with poor prognosis. CENPE may affect tumor progression by regulating cell cycle, p53 pathway, and immune infiltration. Hence, CENPE is highly likely a novel biomarker and potential therapeutic target for non-WNT/non-SHH MB.
A meta-analysis of the Zilongjin tablets for non-small cell lung cancer and its network pharmacology of action against NSCLC and COVID-19
Authors: Yang Wuxia , Zhang Yichao , Gao Jing , Hu Pengcheng , Yang Yanjie , Xu Xiaoqing
Published: August 2023

Objective

To objectively evaluate the efficacy of the Zilongjin tablets in non-small cell lung cancer (NSCLC) and to explore its potential mechanism of action against NSCLC and COVID-19 based on network pharmacology.

Methods

The database was searched for randomized controlled trials (RCTs) of the Zilongjin tablets for NSCLC published up to 22 August 2022. The quality of included trials was assessed using Cochrane standard guidelines, and a meta-analysis was performed using Rev Man 5.3. Gene targets for intersections of NSCLC and COVID-19 (the NC) and drugs were obtained from the TCMSP database, HERB database, GeneCards database, and the NCBI database for network pharmacology research.

Results

Meta-analysis included 14 articles with 2,430 patients. The meta-analysis showed that the Zilongjin tablets combined with conventional chemotherapy were significantly more effective than chemotherapy alone in the treatment of NSCLC. A total of 29 drug-disease intersecting targets were identified in the network pharmacology. The “ingredient-target-pathway” diagram component-target-pathway network contained 119 nodes and 429 edges, with the majority of targets associated with inflammatory responses.

Conclusion

The efficacy and quality of life of the Zilongjin tablets combined conventional chemotherapy for NSCLC were significantly better than chemotherapy alone, alleviating various adverse effects. At the same time, the Zilongjin tablets may modulate the inflammatory response to alleviate NSCLC and COVID-19.
Deep convolutional neural network for rib fracture recognition on chest radiographs
Authors: Huang Shu-Tien , Liu Liong-Rung , Chiu Hung-Wen , Huang Ming-Yuan , Tsai Ming-Feng
Published: August 2023

Introduction

Rib fractures are a prevalent injury among trauma patients, and accurate and timely diagnosis is crucial to mitigate associated risks. Unfortunately, missed rib fractures are common, leading to heightened morbidity and mortality rates. While more sensitive imaging modalities exist, their practicality is limited due to cost and radiation exposure. Point of care ultrasound offers an alternative but has drawbacks in terms of procedural time and operator expertise. Therefore, this study aims to explore the potential of deep convolutional neural networks (DCNNs) in identifying rib fractures on chest radiographs.

Methods

We assembled a comprehensive retrospective dataset of chest radiographs with formal image reports documenting rib fractures from a single medical center over the last five years. The DCNN models were trained using 2000 region-of-interest (ROI) slices for each category, which included fractured ribs, non-fractured ribs, and background regions. To optimize training of the deep learning models (DLMs), the images were segmented into pixel dimensions of 128 × 128.

Results

The trained DCNN models demonstrated remarkable validation accuracies. Specifically, AlexNet achieved 92.6%, GoogLeNet achieved 92.2%, EfficientNetb3 achieved 92.3%, DenseNet201 achieved 92.4%, and MobileNetV2 achieved 91.2%.

Discussion

By integrating DCNN models capable of rib fracture recognition into clinical decision support systems, the incidence of missed rib fracture diagnoses can be significantly reduced, resulting in tangible decreases in morbidity and mortality rates among trauma patients. This innovative approach holds the potential to revolutionize the diagnosis and treatment of chest trauma, ultimately leading to improved clinical outcomes for individuals affected by these injuries. The utilization of DCNNs in rib fracture detection on chest radiographs addresses the limitations of other imaging modalities, offering a promising and practical solution to improve patient care and management.
Effect of smoking on the development of chronic obstructive pulmonary disease in young individuals: a nationwide cohort study
Authors: Chung Chiwook , Lee Kyu Na , Han Kyungdo , Shin Dong Wook , Lee Sei Won
Published: August 2023

Background

Cigarette smoking is an important risk factor for developing chronic obstructive pulmonary disease (COPD). However, the effect of smoking on the development of COPD in young individuals remains unclear. We aimed to evaluate the effect of smoking on COPD development in young individuals.

Methods

Using the Korean National Health Information Database, we screened individuals aged 20–39 years who participated in the national health check-up between 2009 and 2012. We defined physician-diagnosed COPD based on health insurance claims and searched the database until December 2019. We identified 6,307,576 eligible individuals, and 13,789 had newly developed COPD. We used multivariate Cox proportional hazards models to estimate the adjusted hazard ratio (aHR) of risk factors for COPD.

Results

The incidence rate for developing COPD was 0.26/1000 person-year. The risk of developing COPD was significantly higher in current smokers [aHR 1.46, 95% confidence interval (CI) 1.39–1.53] and former smokers (aHR 1.21, 95% CI 1.14–1.29) than in non-smokers. Furthermore, the risk increased with increasing smoking amounts (≥20 pack-years, aHR 2.24; 10–20 pack-years, aHR 1.55; <10 pack-years, aHR 1.27). Female participants had a higher relative risk of developing COPD due to smoking, compared with their male counterparts.

Conclusion

Cigarette smoking increased the risk of developing COPD in young individuals. Current and heavy smokers had higher risks of developing COPD than non-smokers. Female smokers were more likely to develop COPD than male smokers.
Chronic intermittent ethanol exposure during adolescence produces sex- and age-dependent changes in anxiety and cognition without changes in microglia reactivity late in life
Authors: Matthews Douglas B. , Scaletty Samantha , Trapp Sarah , Schreiber Areonna , Rossmann Gillian , Imhoff Bailey , Petersilka Quinn , Kastner Abigail , Pauly Jim , Nixon Kimberly
Published: August 2023

Binge-like ethanol exposure during adolescence has been shown to produce long lasting effects in animal models including anxiety-like behavior that can last into young adulthood and impairments in cognition that can last throughout most of the lifespan. However, little research has investigated if binge-like ethanol exposure during adolescence produces persistent anxiety-like behavior and concomitantly impairs cognition late in life. Furthermore, few studies have investigated such behavioral effects in both female and male rats over the lifespan. Finally, it is yet to be determined if binge-like ethanol exposure during adolescence alters microglia activation in relevant brain regions late in life. In the present study female and male adolescent rats were exposed to either 3.0 or 5.0 g/kg ethanol, or water control, in a chronic intermittent pattern before being tested in the elevated plus maze and open field task over the next ∼18 months. Animals were then trained in a spatial reference task via the Morris water maze before having their behavioral flexibility tested. Finally, brains were removed, sectioned and presumptive microglia activation determined using autoradiography for [3H]PK11195 binding. Males, but not females, displayed an anxiety-like phenotype initially following the chronic intermittent ethanol exposure paradigm which resolved in adulthood. Further, males but not females had altered spatial reference learning and impaired behavioral flexibility late in life. Conversely, [3H]PK11195 binding was significantly elevated in females compared to males late in life and the level of microglia activation interacted as a function of sex and brain regions, but there was no long-term outcome related to adolescent alcohol exposure. These data further confirm that binge-like ethanol exposure during adolescence produces alterations in behavior that can last throughout the lifespan. In addition, the data suggest that microglia activation late in life is not exacerbated by prior binge-like ethanol exposure during adolescence but the expression is sex- and brain region-dependent across the lifespan.
A decentralized, prospective, observational study to collect real-world data from patients with myasthenia gravis using smartphones
Authors: Steyaert Sandra , Lootus Meelis , Sarabu Chethan , Framroze Zeenia , Dickinson Harriet , Lewis Emily , Steels Jean-Christophe , Rinaldo Francesca
Published: August 2023

Introduction

We conducted a 3-month, prospective study in a population of patients with Myasthenia Gravis (MG), utilizing a fully decentralized approach for recruitment and monitoring (ClinicalTrials.gov Identifier: NCT04590716). The study objectives were to assess the feasibility of collecting real-world data through a smartphone-based research platform, in order to characterize symptom involvement during MG exacerbations.

Methods

Primary data collection included daily electronically recorded patient-reported outcomes (ePROs) on the presence of MG symptoms, the level of symptom severity (using the MG-Activities of Daily Living assessment, MG-ADL), and exacerbation status. Participants were also given the option to contribute data on their physical activity levels from their own wearable devices.

Results

The study enrolled and onboarded 113 participants across 37 US states, and 73% (N= 82) completed the study. The mean age of participants was 53.6 years, 60% were female. Participants were representative of a moderate to severe MG phenotype, with frequent exacerbations, high symptom burden and multiple comorbidities. 55% of participants (N=45) reported MG exacerbations during the study, with an average of 6.3 exacerbation days per participant. Median average MG-ADL scores for participants during self-reported exacerbation and non-exacerbation periods were 7 (interquartile range 4-9, range 1-19) and 0.3 (interquartile range 0-0.8, range 0-9), respectively. Analyses examining relationships between patient-reported and patient-generated health data streams and exacerbation status demonstrated concordance between self-reported MG-ADL scores and exacerbation status, and identified features that may be used to understand and predict the onset of MG symptom exacerbations, including: 1.) dynamic changes in day-to-day symptom reporting and severity 2.) daily step counts as a measure of physical activity and 3.) clinical characteristics of the patient, including the amount of time since their initial diagnosis and their active medications related to MG treatment. Finally, application of unsupervised machine learning methods identified unique clusters of exacerbation subtypes, each with their own specific representation of symptoms and symptom severity.

Conclusion

While these symptom signatures require further study and validation, our results suggest that digital phenotyping, characterized by increased multidimensionality and frequency of the data collection, holds promise for furthering our understanding of clinically significant exacerbations and reimagining the approach to treating MG as a heterogeneous condition.
Authenticity and brain health: a values-based perspective and cultural education approach
Authors: Stirland Lucy E. , Ayele Biniyam A. , Correa-Lopera Catherine , Sturm Virginia E.
Published: August 2023

This perspective paper discusses the concept of authenticity in relation to brain health and neurodegenerative diseases. We define authenticity as being true to oneself and consider it a social value of relevance to neuroscientists, clinicians, and caregivers. From a biological perspective, behaviors that can be interpreted as expressions of authenticity are produced by distributed brain networks. By understanding it as a dynamic process, we argue that harnessing authenticity across the lifespan can be protective by promoting resilience. We discuss the idea of authentic aging, which appreciates the complexity of human life within the world and can enhance positive views of later life. Authenticity is additionally applicable to caring for people with neurodegenerative diseases, both when understanding the behavior of people with dementia and the response of caregivers. Tailoring care to an individual’s personality and strengths may improve their brain health. Finally, we describe an interdisciplinary learning event, themed around masks, designed to engage participants in identifying authenticity in their own work. For scientists, care professionals, and caregivers, reflecting upon authenticity can aid understanding of the person with dementia and therefore improve care.
Dry eye in Parkinson's disease: a narrative review
Authors: Ungureanu Larisa , Chaudhuri K. Ray , Diaconu Stefania , Falup-Pecurariu Cristian
Published: August 2023

In Parkinson's disease (PD) patients, a wide range of ocular and visual disorders are present. Tear film instability, inflammation and dysfunction of the ocular surface, and the presence of symptoms of visual disturbance characterize dry eye, a multifactorial disease of the ocular surface. Based on a literature search, we discuss the frequency, pathogenesis, and influence on the quality of life of patients with dry eye in Parkinson's disease. Furthermore, we review the available means of diagnosis and management of dry eye. An improvement in awareness and recognition of dry eye is needed to provide suitable, personalized therapeutic options for PD patients, aiming to improve their quality of life, independence, and safety.
CACTUS: a computational framework for generating realistic white matter microstructure substrates
Authors: Villarreal-Haro Juan Luis , Gardier Remy , Canales-Rodríguez Erick J. , Fischi-Gomez Elda , Girard Gabriel , Thiran Jean-Philippe , Rafael-Patiño Jonathan
Published: August 2023

Monte-Carlo diffusion simulations are a powerful tool for validating tissue microstructure models by generating synthetic diffusion-weighted magnetic resonance images (DW-MRI) in controlled environments. This is fundamental for understanding the link between micrometre-scale tissue properties and DW-MRI signals measured at the millimetre-scale, optimizing acquisition protocols to target microstructure properties of interest, and exploring the robustness and accuracy of estimation methods. However, accurate simulations require substrates that reflect the main microstructural features of the studied tissue. To address this challenge, we introduce a novel computational workflow, CACTUS (Computational Axonal Configurator for Tailored and Ultradense Substrates), for generating synthetic white matter substrates. Our approach allows constructing substrates with higher packing density than existing methods, up to 95% intra-axonal volume fraction, and larger voxel sizes of up to 500μm3 with rich fibre complexity. CACTUS generates bundles with angular dispersion, bundle crossings, and variations along the fibres of their inner and outer radii and g-ratio. We achieve this by introducing a novel global cost function and a fibre radial growth approach that allows substrates to match predefined targeted characteristics and mirror those reported in histological studies. CACTUS improves the development of complex synthetic substrates, paving the way for future applications in microstructure imaging.
Mesoscale calcium imaging in vivo: evolution and contribution to developmental neuroscience
Authors: Guillamón-Vivancos Teresa , Vandael Dorien , Torres Daniel , López-Bendito Guillermina , Martini Francisco J.
Published: August 2023

Calcium imaging is commonly used to visualize neural activity in vivo. In particular, mesoscale calcium imaging provides large fields of view, allowing for the simultaneous interrogation of neuron ensembles across the neuraxis. In the field of Developmental Neuroscience, mesoscopic imaging has recently yielded intriguing results that have shed new light on the ontogenesis of neural circuits from the first stages of life. We summarize here the technical approaches, basic notions for data analysis and the main findings provided by this technique in the last few years, with a focus on brain development in mouse models. As new tools develop to optimize calcium imaging in vivo, basic principles of neural development should be revised from a mesoscale perspective, that is, taking into account widespread activation of neuronal ensembles across the brain. In the future, combining mesoscale imaging of the dorsal surface of the brain with imaging of deep structures would ensure a more complete understanding of the construction of circuits. Moreover, the combination of mesoscale calcium imaging with other tools, like electrophysiology or high-resolution microscopy, will make up for the spatial and temporal limitations of this technique.
Interferon-induced transmembrane protein 3 in the hippocampus: a potential novel target for the therapeutic effects of recombinant human brain natriuretic peptide on sepsis-associated encephalopathy
Authors: Li Nan , Ma Rui-Hang , Zhang Er-Fei , Ge Feng , Fang De-Yu , Zhang Jing , Zhang Yan-Ning , Gao Yan , Hou Li-Chao , Jin Hong-Xu
Published: August 2023

Objective

This study aims to explore whether interferon-induced transmembrane protein 3 (IFITM3) is involved in recombinant human brain natriuretic peptide (rhBNP)-mediated effects on sepsis-induced cognitive dysfunction in mice.

Methods

The cellular localization and expression level of IFITM3 in the hippocampus were detected. The IFITM3 overexpression was achieved using an intracranial stereotactic system to inject an adeno-associated virus into the hippocampal CA1 region of mice. Field experiments, an elevated plus maze, and conditioned fear memory tests assessed the cognitive impairment in rhBNP-treated septic mice. Finally, in the hippocampus of septic mice, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining and Immunoblot were used to detect changes in the protein expression of cleaved Caspase-8 and cleaved Caspase-3 in apoptosis-related pathways, and toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) p65 in inflammatory pathways.

Results

Fourteen days after cecal ligation and puncture (CLP) surgery, IFITM3 localized in the plasma membrane and cytoplasm of the astrocytes in the hippocampus of septic mice, partially attached to the perivascular and neuronal surfaces, but not expressed in the microglia. The expression of IFITM3 was increased in the astrocytes and neurons in the hippocampus of septic mice, which was selectively inhibited by the administration of rhBNP. Overexpression of IFITM3 resulted in elevated anxiety levels and long-term learning and memory dysfunction, completely abolished the therapeutic effect of rhBNP on cognitive impairment in septic mice, and induced an increase in the number of neuronal apoptosis in the hippocampal CA1 region. The expression levels of cleaved Caspase-3 and cleaved Caspase-8 proteins were significantly increased in the hippocampus, but the expression levels of TLR4 and NF-κB p65 were not increased.

Conclusion

The activation of IFITM3 may be a potential new target for treating sepsis-associated encephalopathy (SAE), and it may be one of the key anti-apoptotic mechanisms in rhBNP exerting its therapeutic effect, providing new insight into the clinical treatment of SAE patients.
Alterations of PAC-based resting state networks in Parkinson’s disease are partially alleviated by levodopa medication
Authors: Mertiens Sean , Sure Matthias , Schnitzler Alfons , Florin Esther
Published: August 2023

Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder affecting the whole brain, leading to several motor and non-motor symptoms. In the past, it has been shown that PD alters resting state networks (RSN) in the brain. These networks are usually derived from fMRI BOLD signals. This study investigated RSN changes in PD patients based on maximum phase-amplitude coupling (PAC) throughout the cortex. We also tested the hypothesis that levodopa medication shifts network activity back toward a healthy state.

Methods

We recorded 23 PD patients and 24 healthy age-matched participants for 30 min at rest with magnetoencephalography (MEG). PD patients were measured once in the dopaminergic medication ON and once in the medication OFF state. A T1-MRI brain scan was acquired from each participant for source reconstruction. After correcting the data for artifacts and performing source reconstruction using a linearly constrained minimum variance beamformer, we extracted visual, sensorimotor (SMN), and frontal RSNs based on PAC.

Results

We found significant changes in all networks between healthy participants and PD patients in the medication OFF state. Levodopa had a significant effect on the SMN but not on the other networks. There was no significant change in the optimal PAC coupling frequencies between healthy participants and PD patients.

Discussion

Our results suggest that RSNs, based on PAC in different parts of the cortex, are altered in PD patients. Furthermore, levodopa significantly affects the SMN, reflecting the clinical alleviation of motor symptoms and leading to a network normalization compared to healthy controls.
The effects of acarbose treatment on cardiovascular risk factors in impaired glucose tolerance and diabetic patients: a systematic review and dose–response meta-analysis of randomized clinical trials
Authors: Zamani Mohammad , Nikbaf-Shandiz Mahlagha , Aali Yasaman , Rasaei Niloufar , Zarei Mahtab , Shiraseb Farideh , Asbaghi Omid
Published: August 2023

Acarbose (ACB) seems to be an effective drug in the management of cardiovascular risk factors. However, no previous meta-analysis of randomized controlled trials (RCTs) has been done to evaluate the effects of ACB on cardiovascular risk factors on impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2D), and type 1 diabetes mellitus (T1D). We comprehensively searched electronic databases including Scopus, Web of Science, and PubMed for RCTs for related keywords up to September 2022. A random-effects model was used to estimate the weighted mean difference (WMD) and 95% confidence interval (CI). The pooled analysis demonstrated that ACB treatment had a significant effect on fasting blood glucose (FBG) (WMD = −3.55 mg/dL; 95%CI: −6.29, −0.81;p = 0.011), fasting insulin (WMD = −6.73 pmoL/L; 95%CI: −10.37, −3.10;p < 0.001), HbA1c [WMD = −0.32%; 95%CI: −0.45, −0.20;p < 0.001], body weight (WMD = −1.25 kg; 95%CI: −1.79, −0.75;p < 0.001), body mass index (BMI) (WMD = −0.64 kg/m2; 95%CI: −0.92, −0.37;p < 0.001), tumor necrosis factor-alpha (TNF-α) (WMD = −2.70 pg/mL, 95%CI: −5.25, −0.16;p = 0.037), leptin (WMD = −1.58 ng/mL; 95%CI: −2.82, −0.35;p = 0.012), alanine transaminase (ALT) (WMD = 0.71 U/L; 95%CI: −0.31, 1.85;p = 0.164), triglyceride (TG) (WMD = −13.89 mg/dL; 95%CI: −20.69, −7.09;p < 0.001), total cholesterol (TC) (WMD = −2.26 mg/dL; 95%CI: −4.18, −0.34;p = 0.021), systolic blood pressure (SBP) (WMD = −1.29 mmHg; 95%CI: −2.44, −0.15;p = 0.027), and diastolic blood pressure (DBP) (WMD = 0.02 mmHg; 95%CI: −0.41, 0.45;p = 0.925) in an intervention group, compared with a placebo group. The non-linear dose–response analysis showed that ACB reduces the TC in trial duration by >50 weeks, and 180 mg/day is more effective for the decrement of CRP. ACB can improve lipid profiles, glycemic indices, anthropometric indices, and inflammatory markers in T2D, T1D, and IGT patients.
Case Report: Keratoacanthoma and type I diabetes secondary to treatment with PM8001, a bifunctional fusion protein targeting TGF-β and PD-L1
Authors: Qi Rongbin , Xu Hailing , Fu Xinyu , Yu Yingying , Lv Dongqing , Li Yujing , He Susu
Published: August 2023

Immune-related adverse reactions primarily involve the skin and the endocrine, digestive, and respiratory systems. In the endocrine system, these adverse effects mainly include hypophysitis, thyroiditis, hypoadrenalism, and rarely, diabetes mellitus. The most common symptoms in the skin are pruritus, rash, and infrequently, eruptive keratoacanthoma. Here, we report a case of a 67-year-old woman who developed eruptive keratoacanthoma of the skin 6 weeks after beginning treatment with a bispecific antibody (PM8001), targeting both programmed cell death receptor 1 and transforming growth factor β, as well as type I diabetes mellitus–induced ketoacidosis after 13 weeks. The type I diabetes appeared to stabilize after insulin treatment, and the keratoacanthoma gradually resolved after drug discontinuation. This case report describes a case of the effects of PM8001 immunotherapy on the endocrine glands and skin, together with a review of the relevant literature, and summarizes the different clinical characteristics of rare immune-related adverse events resulting from PM8001 immunotherapy to provide a reference for their early detection, diagnosis, and treatment.
Association of CCL4 rs10491121 and rs1634507 gene polymorphisms with cancer susceptibility: trial sequential analysis and meta-analysis
Authors: Yang Changsen , Song Tiangang , Mo Yajie , Wu Peixuan , Tian Haokun , Wen Lequan , Gao Yun
Published: August 2023

Background

Although numerous case-control studies have explored the association between CC cytokine ligand-4 (CCL4) expression and cancer susceptibility, their results have been conflicting. This study aimed to determine the still-unknown connection of CCL4 rs10491121 and rs163450 polymorphisms with cancer susceptibility.

Methods

Several databases, such as Web of Science, PubMed, and EMBASE, were searched for papers published since the creation of the database until November 2, 2022. Using RevMan 5.4 and StataMP 17 softwares, meta-analysis and subgroup analysis were performed after article screening and data extraction. For sensitivity analyses, one-by-one exclusion method was used, and then, the comprehensive effect was estimated and compared with that before exclusion. Trial sequential analysis (TSA)was performed using TSA 0.9.5.10 beta software.

Results

Seven case-control studies encompassing 3559 cases and 4231 controls were included. The P value was greater than 0.05 for all models, indicating the absence of an evident relationship of CCL4 gene rs10491121 and rs1634507 polymorphisms with cancer susceptibility. However, in the subgroup analysis of rs10491121, the P values in all models studied by us except GA vs. AA were <0.05 considering the Chinese subgroup, suggesting that the G allele is a risk factor for cancer in the Chinese population. Besides, in the subgroup analysis of rs1634507 considering oral cancer, the co-dominant model GG vs. TT, dominant model GG + GT vs. TT, and allele model G vs. T groups showed OR < 1 and P < 0.05, indicating that the G allele was a protective factor of oral cancer. However, for other cancer types, all the models studied by us except GG vs. GT showed OR > 1 and P < 0.05, indicating that the G allele was a risk factor for these other cancers. Despite the statistically significant results, sensitivity analysis had some stability limitations, and TSA results suggested the possibility of false positives.

Conclusion

For rs10491121, we identified an association between the G allele and increased cancer risk in the Chinese population. For rs1634507, the G allele was not found to be associated with reduced risk of oral cancer and increased risk of other cancers studied by us.
TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck
Authors: Rubió-Casadevall Jordi , Cirauqui Cirauqui Beatriz , Martinez Trufero Javier , Plana Serrahima Maria , García Castaño Almudena , Carral Maseda Alberto , Iglesias Docampo Lara , Pérez Segura Pedro , Ceballos Lenza Isaac , Gutiérrez Calderón Vanesa , Fuster Salvà José , Pena Álvarez Carolina , Hernandez Irene , del Barco Morillo Edel , Chaves Conde Manuel , Martínez Galán Joaquina , Durán Sánchez Marisa , Quiroga Vanesa , Ortega Eugenia , Mesia Ricard
Published: August 2023

Objectives

The aim of this study was to confirm the efficacy of the ERBITAX scheme (paclitaxel 80 mg/m2 weekly and cetuximab 400 mg/m2 loading dose, and then 250 mg/m2 weekly) as first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who are medically unfit for cisplatin-based (PT) chemotherapy.

Materials and methods

This retrospective, non-interventional study involved 16 centers in Spain. Inclusion criteria were to have started receiving ERBITAX regimen from January 2012 to December 2018; histologically confirmed SCCHN including oral cavity, oropharynx, hypopharynx, and larynx; age ≥18 years; and platinum (PT) chemotherapy ineligibility due to performance status, comorbidities, high accumulated dose of PT, or PT refractoriness.

Results

A total of 531 patients from 16 hospitals in Spain were enrolled. The median age was 66 years, 82.7% were male, and 83.5% were current/former smokers. Patients were ineligible to receive PT due to ECOG 2 (50.3%), comorbidities (32%), PT cumulative dose ≥ 225 mg/m2 (10.5%), or PT refractoriness (7.2%). Response rate was 37.7%. Median duration of response was 5.6 months (95% CI: 4.4–6.6). With a median follow-up of 8.7 months (95% CI: 7.7–10.2), median PFS and OS were 4.5 months (95% CI: 3.9–5.0) and 8.9 months (95% CI: 7.8–10.3), respectively. Patients treated with immunotherapy after ERBITAX had better OS with a median of 29.8 months compared to 13.8 months for those who received other treatments. The most common grade ≥ 3 toxicities were acne-like rash in 36 patients (6.8%) and oral mucositis in 8 patients (1.5%). Five (0.9%) patients experienced grade ≥ 3 febrile neutropenia.

Conclusion

This study confirms the real-world efficacy and tolerability of ERBITAX as first-line treatment in recurrent/metastatic SCCHN when PT is not feasible. Immunotherapy after treatment with ERBITAX showed remarkable promising survival, despite potential selection bias.
AI-powered discovery of a novel p53-Y220C reactivator
Authors: Zhou Shan , Chai Dafei , Wang Xu , Neeli Praveen , Yu Xinfang , Davtyan Aram , Young Ken , Li Yong
Published: August 2023

Introduction

The p53-Y220C mutation is one of the most common mutations that play a major role in cancer progression.

Methods

In this study, we applied artificial intelligence (AI)-powered virtual screening to identify small-molecule compounds that specifically restore the wild-type p53 conformation from p53-Y220C. From 10 million compounds, the AI algorithm selected a chemically diverse set of 83 high-scoring hits, which were subjected to several experimental assays using cell lines with different p53 mutations.

Results

We identified one compound, H3, that preferentially killed cells with the p53-Y220C mutation compared to cells with other p53 mutations. H3 increased the amount of folded mutant protein with wild-type p53 conformation, restored its transcriptional functions, and caused cell cycle arrest and apoptosis. Furthermore, H3 reduced tumorigenesis in a mouse xenograft model with p53-Y220C-positive cells.

Conclusion

AI enabled the discovery of the H3 compound that selectively reactivates the p53-Y220C mutant and inhibits tumor development in mice.
Dyskeratosis congenita: natural history of the disease through the study of a cohort of patients diagnosed in childhood
Authors: Uria-Oficialdegui M. L. , Navarro S. , Murillo-Sanjuan L. , Rodriguez-Vigil C. , Benitez-Carbante M. I. , Blazquez-Goñi C. , Salinas J. A. , Diaz-de-Heredia C.
Published: August 2023

Background

Dyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time.

Material and methods

Multicenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020).

Results

Fourteen patients were diagnosed with DC between the ages of 3 and 17 years (median, 8.5 years). They all had hematologic manifestations at diagnosis, and nine developed mucocutaneous manifestations during the first decade of life. Seven presented severe DC variants. All developed non-hematologic manifestations during follow-up. Mutations were identified in 12 patients. Thirteen progressed to bone marrow failure at a median age of 8 years [range, 3–18 years], and eight received a hematopoietic stem cell transplant. Median follow-up time was 9 years [range, 2–24 years]. Six patients died, the median age was 13 years [range, 6–24 years]. As of November 2022, eight patients were still alive, with a median age of 18 years [range, 6–32 years]. None of them have developed myeloblastic syndrome or cancer.

Conclusions

DC was associated with high morbidity and mortality in our series. Hematologic manifestations appeared early and consistently. Non-hematologic manifestations developed progressively. No patient developed cancer possibly due to their young age. Due to the complexity of the disease multidisciplinary follow-up and adequate transition to adult care are essential.
Abnormal changes of bone metabolism markers with age in children with cerebral palsy
Authors: Xing Wen , Liang Lin , Dong Na , Chen Liang , Liu Zhizhong
Published: August 2023

Cerebral palsy (CP) is a broad range of diseases with permanent and nonprogressive motor impairments, carrying a high cost for both the individual and the society. The characteristics of low bone mineral density and high risk of fractures suggest that bone metabolism disorders are present in CP. This study aims to investigate the association between indicators of bone metabolism and children with CP. A total of 139 children (75 children with CP and 64 healthy controls) were included in this cross-sectional study. Participants were divided into three age groups (0–2 years, 2.1–4 years, and 4.1–7 years). All children with CP were diagnosed according to clinical criteria and furtherly divided into clinical subtypes. The levels of total procollagen type I N-terminal propeptide (TPINP), N-MID osteocalcin (OC), beta-crosslaps (β-CTX), 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) in the serum were measured with corresponding detection kits according to the manufacturer's instructions. Serum levels of TPINP and 25-OHD were lower with older age, whereas β-CTX and PTH were higher with older age. In the CP group, TPINP (age 0–2 years and 2.1–4 years) and OC (age 2.1–4 years) levels were higher, while β-CTX (age 2.1–4 years and 4.1–7 years) and PTH (age 2.1–4 years) values were lower than the control group. In addition, there were no statistically significant differences in the levels of these indicators among the CP subgroups with different clinical characteristics. Our study shows that bone turnover markers, indicators of bone metabolism, in children with CP differ significantly from healthy controls. The indicators we studied changed with age, and they did not correlate with disease severity.
Neurotoxicology of alcohol: a bibliometric and science mapping analysis
Authors: Mendes Paulo Fernando Santos , Baia-da-Silva Daiane Claydes , Melo Wallacy Watson Pereira , Bittencourt Leonardo Oliveira , Souza-Rodrigues Renata Duarte , Fernandes Luanna Melo Pereira , Maia Cristiane do Socorro Ferraz , Lima Rafael Rodrigues
Published: August 2023

Alcohol consumption is common in many societies and has increased considerably, resulting in many socioeconomic and public health problems. In this sense, studies have been carried out in order to understand the mechanisms involved in alcohol consumption and related harmful effects. This study aimed to identify and map the knowledge and to perform bibliometric analysis of the neurotoxicology of alcohol based on the 100 most cited articles. A search was carried out in the Web of Science Core Collection database and information was extracted regarding the journal, authors, keywords, year of publication, number of citations, country and continent of the corresponding author. For each selected manuscript, the study design, alcohol exposure model, dose, period of exposure, and effect on the central nervous system and research hotspots were mapped. The journal with the highest number of publications was Alcoholism: Clinical and Experimental Research (n = 11 papers), the author who contributed the most was Crews FT (n = 8 papers), the studies had a total of 288 keywords and 75% of the publications were from the United States of America. The experimental studies evaluated the effects of prenatal and postnatal exposure and were conducted in rats and mice using doses ranging from 2.5 to 14 g/kg/day, with administration by subcutaneous, intraperitoneal, intragastric, or inhalation route or with free access through drinking bottles. Among the studies mapped, the oldest one (1989) aimed to understand the systemic damage and mechanisms of action involved, while the most recent focused on understanding the receptors and mechanisms involved in addiction, as well as genetic factors. Our results show the panorama of the most widespread scientific production in the scientific community on the neurotoxicology of ethanol, a high prevalence was observed in studies that addressed fetal alcohol syndrome and/or the effects of ethanol on neurodevelopment.
Qubit energy tuner based on single flux quantum circuits
Authors: Geng Xiao , He Kaiyong , Huang Rutian , Liu Jianshe , Chen Wei
Published: August 2023

A device called the qubit energy tuner (QET), based on single flux quantum (SFQ) circuits, has been proposed for Z control of superconducting qubits. The QET is created by improving flux digital-to-analog converters (flux DACs). It can set the energy levels or frequencies of qubits, particularly flux-tunable transmons, and perform gate operations requiring Z control. The circuit structure of the QET is elucidated, consisting of an inductor loop and flux bias units for coarse or fine-tuning. The key feature of the QET is analyzed to understand how SFQ pulses change the inductor loop current, which provides external flux for qubits. Three simulations were performed to verify QET functionality. The first simulation verified the responses of the inductor loop current to SFQ pulses, showing a relative deviation of approximately 4.259% between the analytical solutions of the inductor loop current and the solutions from the WRSpice time-domain simulation. The second and third simulations, using QuTip, demonstrated how to perform a Z gate and an iSWAP gate using the QET, respectively, with corresponding fidelities of 99.99884% and 99.93906% for only one gate operation to specific initial states. These simulations indicate that the SFQ-based QET could act as an efficient component of SFQ-based quantum–classical interfaces for digital Z control of large-scale superconducting quantum computers.
Comparative analysis of tumor biology and prognosis in mucinous and signet-ring cell colon cancers versus classical adenocarcinoma
Authors: Liu Yang , Yin Wenxin , Li Xiaoxia , Li Bowen , Liu Fang , Kang Pengcheng
Published: August 2023

Background: Limited information is currently available on the natural history and prognosis of two distinct histological subtypes of adenocarcinoma (AC) in the colon: mucinous adenocarcinoma (MAC) and signet-ring cell carcinoma (SRCC). Therefore, the aim of this study is to examine the clinicopathological characteristics of colon MAC and SRCC, comparing them to classical AC, using a large cohort of cases from the United States.

Methods: Patients diagnosed with colon AC, MAC, or SRCC from the SEER database between 2000 and 2018 were included in our study. Incidence trends, patient demographics, tumor characteristics, treatment, and survival were analyzed.

Results: In our study, we analyzed a total of 310,813 patients with colon cancers, including 271,382 cases of classical AC, 34,750 cases of MAC, and 4,681 cases of SRCC. Over the study period, we observed a decline in the age-adjusted incidence rates of colon AC, MAC, and SRCC. Notably, the MAC and SRCC cohorts differed significantly from AC in terms of patient characteristics, tumor locations, and treatment patterns. Patients with MAC and SRCC had poorer survival outcomes compared to those with AC. Factors associated with worse survival included older age, male sex, poorly differentiated tumors, advanced stage, and the presence of MAC or SRCC histology. On the other hand, surgical intervention was associated with improved survival.

Conclusion: Our study underscores the significance of recognizing the distinct features and outcomes associated with different histological subtypes of colon cancer. Further research is warranted to delve into the underlying biological traits that contribute to these differences and to develop more tailored treatment strategies.
Breaking the cycle of emotional flooding: the protective role of women’s emotional intelligence in couple’s conflict
Authors: Berenguer-Soler María , García del Castillo-López Álvaro , Pineda David
Published: August 2023

Introduction

One of the most damaging aspects, both for people’s well-being and for close relationships, is conflict. Beyond different stressors, the emotions evoked, their regulation and an appropriate conflict resolution strategy will reduce negative consequences. Emotional Intelligence facilitates social relationships, but little applied research has been done on the relationship with couple conflict and emotional flooding, particularly from the perspective of women. Therefore, the present study analyzes the role of Perceived Emotional Intelligence (PEI) and the mediating effect of Positive Conflict Resolution strategies (PCR) in couples’ conflicts from women’s perspective, examining its effect on Emotional Flooding (EF) and Satisfaction.

Methods

Through a cross-sectional design, the relationships between variables were analyzed using group comparisons and means of a structural equation model (SEM) in a sample of 692 women.

Results

Significant differences were found between the groups by age, length of relationship, and motherhood. The SEM revealed a good fit. PEI predicted 71.8% of the variance in EF and 35% in Satisfaction through PCR and Conflict.
Using iterative random forest to find geospatial environmental and Sociodemographic predictors of suicide attempts
Authors: Pavicic Mirko , Walker Angelica M. , Sullivan Kyle A. , Lagergren John , Cliff Ashley , Romero Jonathon , Streich Jared , Garvin Michael R. , Pestian John , McMahon Benjamin , Oslin David W. , Beckham Jean C. , Kimbrel Nathan A. , Jacobson Daniel A.
Published: August 2023

Introduction

Despite a recent global decrease in suicide rates, death by suicide has increased in the United States. It is therefore imperative to identify the risk factors associated with suicide attempts to combat this growing epidemic. In this study, we aim to identify potential risk factors of suicide attempt using geospatial features in an Artificial intelligence framework.

Methods

We use iterative Random Forest, an explainable artificial intelligence method, to predict suicide attempts using data from the Million Veteran Program. This cohort incorporated 405,540 patients with 391,409 controls and 14,131 attempts. Our predictive model incorporates multiple climatic features at ZIP-code-level geospatial resolution. We additionally consider demographic features from the American Community Survey as well as the number of firearms and alcohol vendors per 10,000 people to assess the contributions of proximal environment, access to means, and restraint decrease to suicide attempts. In total 1,784 features were included in the predictive model.

Results

Our results show that geographic areas with higher concentrations of married males living with spouses are predictive of lower rates of suicide attempts, whereas geographic areas where males are more likely to live alone and to rent housing are predictive of higher rates of suicide attempts. We also identified climatic features that were associated with suicide attempt risk by age group. Additionally, we observed that firearms and alcohol vendors were associated with increased risk for suicide attempts irrespective of the age group examined, but that their effects were small in comparison to the top features.

Discussion

Taken together, our findings highlight the importance of social determinants and environmental factors in understanding suicide risk among veterans.