bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of RNA degradation in cell fate decision
Authors: Deng Mingqiang , Wang Xiwei , Xiong Zhi , Tang Peng
Published: March 2023

Cell fate is shaped by a unique gene expression program, which reflects the concerted action of multilayered precise regulation. Substantial research attention has been paid to the contribution of RNA biogenesis to cell fate decisions. However, increasing evidence shows that RNA degradation, well known for its function in RNA processing and the surveillance of aberrant transcripts, is broadly engaged in cell fate decisions, such as maternal-to-zygotic transition (MZT), stem cell differentiation, or somatic cell reprogramming. In this review, we first look at the diverse RNA degradation pathways in the cytoplasm and nucleus. Then, we summarize how selective transcript clearance is regulated and integrated into the gene expression regulation network for the establishment, maintenance, and exit from a special cellular state.
Getting cells into shape by calcium-dependent actin cross-linking proteins
Authors: Lehne Franziska , Bogdan Sven
Published: March 2023

The actin cytoskeleton represents a highly dynamic filament system providing cell structure and mechanical forces to drive a variety of cellular processes. The dynamics of the actin cytoskeleton are controlled by a number of conserved proteins that maintain the pool of actin monomers, promote actin nucleation, restrict the length of actin filaments and cross-link filaments into networks or bundles. Previous work has been established that cytoplasmic calcium is an important signal to rapidly relay information to the actin cytoskeleton, but the underlying mechanisms remain poorly understood. Here, we summarize new recent perspectives on how calcium fluxes are transduced to the actin cytoskeleton in a physiological context. In this mini-review we will focus on three calcium-binding EF-hand-containing actin cross-linking proteins, α-actinin, plastin and EFHD2/Swiprosin-1, and how these conserved proteins affect the cell’s actin reorganization in the context of cell migration and wound closure in response to calcium.
Anti-mold, self-cleaning superhydrophobic bamboo fiber/polypropylene composites with mechanical durability
Authors: Zhao He , Lin Xinxing , Lu Shengchang , Wu Hui , Zhou Xiaxing , Huang Liulian , Li Jianguo , Shi Jianping , Tong Wenxuan , Yuan Hongmei , Chen Lihui
Published: March 2023

Bamboo fiber/polypropylene composites (BPCs) have been widely used in buildings, interior decoration, and automobile components. However, pollutants and fungi can interact with the hydrophilic bamboo fibers on the surface of Bamboo fiber/polypropylene composites, degrading their appearance and mechanical properties. To improve their anti-fouling and anti-mildew properties, a superhydrophobic modified Bamboo fiber/polypropylene composite (BPC-TiO2-F) was fabricated by introducing titanium dioxide (TiO2) and poly(DOPAm-co-PFOEA) onto the surface of a Bamboo fiber/polypropylene composite. The morphology of BPC-TiO2-F was analyzed by XPS, FTIR, and SEM. The results showed that TiO2 particles covered on Bamboo fiber/polypropylene composite surface via complexation between phenolic hydroxyl groups and Ti atoms. Low-surface-energy fluorine-containing poly(DOPAm-co-PFOEA) was introduced onto the Bamboo fiber/polypropylene composite surface, forming a rough micro/nanostructure that endowed BPC-TiO2-F with superhydrophobicity (water contact angle = 151.0° ± 0.5°). The modified Bamboo fiber/polypropylene composite exhibited excellent self-cleaning properties, and a model contaminant, Fe3O4 powder, was rapidly removed from the surface by water drops. BPC-TiO2-F showed excellent anti-mold performance, and no mold was on its surface after 28 days. The superhydrophobic BPC-TiO2-F had good mechanical durability and could withstand sandpaper abrasion with a weight load of 50 g, finger wiping for 20 cycles, and tape adhesion abrasion for 40 cycles. BPC-TiO2-F showed good self-cleaning properties, mildew resistance, and mechanical resistance, giving it promising applications for automotive upholstery and building decoration.
Epidemiology and clinical characteristics of Epstein-Barr virus infection among children in Shanghai, China, 2017-2022
Authors: Ye Zhicheng , Chen Luxi , Zhong Huaqing , Cao Lingfeng , Fu Pan , Xu Jin
Published: March 2023

Objective

To investigate the epidemiology and infectious characteristics of Epstein-Barr virus (EBV) infection among children in Shanghai, China from 2017 to 2022.

Methods

We conducted a retrospective analysis of 10,260 inpatient patients who were subjected EBV nucleic acid testing from July 2017 to December 2022. Demographic information, clinical diagnosis, laboratory findings, etc. were collected and analyzed. EBV nucleic acid testing were performed by real-time PCR.

Results

A total of 2192 (21.4%) inpatient children were EBV-positive, with the average age of 7.3 ± 0.1 y. EBV detection was stable from 2017 to 2020 (26.9~30.1%), but showed essential decreases in 2021 (16.0%) and 2022 (9.0%). EBV was highest (>30%) detected from three quarters (Q) including 2018-Q4, 2019-Q4 and 2020-Q3. There were 24.5% of EBV coinfection with other pathogens, including bacteria (16.8%), other viruses (7.1%) and fungi (0.7%). EBV viral loads increased when coinfecting with bacteria ((142.2 ± 40.1) ×104/mL) or other viruses ((165.7 ± 37.4) ×104/mL). CRP significantly increased in EBV/fungi coinfection, while procalcitonin (PCT) and IL-6 showed remarkable increases in EBV/bacteria coinfection. Most (58.9%) of EBV-associated diseases belonged to immune disorders. The primary EBV-related diseases were systemic lupus erythematosus (SLE, 16.1%), immunodeficiency (12.4%), infectious mononucleosis (IM, 10.7%), pneumonia (10.4%) and Henoch-schonlein purpura (HSP, 10.2%). EBV viral loads were highest ((233.7 ± 27.4) × 104/mL) in patients with IM.

Conclusion

EBV was prevalent among children in China, the viral loads increased when coinfecting with bacteria or other viruses. SLE, immunodeficiency and IM were the primary EBV-related diseases.
Impact of epicardial adipose tissue volume on hemodynamically significant coronary artery disease in Chinese patients with known or suspected coronary artery disease
Authors: Jin Xiangbo , Gao Beibei , Zheng Jiamin , Wu Xueer , Zhang Ning , Zhu Lijun , Zhu Xinyu , Xie Jianchang , Wang Zhen , Tong Guoxin , Huang Jinyu
Published: March 2023

Background

Epicardial adipose tissue (EAT) is directly related to coronary artery disease (CAD), but little is known about its role in hemodynamically significant CAD. Therefore, our goal is to explore the impact of EAT volume on hemodynamically significant CAD.

Methods

Patients who underwent coronary computed tomography angiography (CCTA) and received coronary angiography within 30 days were retrospectively included. Measurements of EAT volume and coronary artery calcium score (CACs) were performed on a semi-automatic software based on CCTA images, while quantitative flow ratio (QFR) was automatically calculated by the AngioPlus system according to coronary angiographic images.

Results

This study included 277 patients, 112 of whom had hemodynamically significant CAD and showed higher EAT volume. In multivariate analysis, EAT volume was independently and positively correlated with hemodynamically significant CAD [per standard deviation (SD) cm3; odds ratio (OR), 2.78; 95% confidence interval (CI), 1.86–4.15; P < 0.001], but negatively associated with QFRmin (per SD cm3; β coefficient, −0.068; 95% CI, −0.109 to −0.027; P = 0.001) after adjustment for traditional risk factors and CACs. Receiver operating characteristics curve analysis demonstrated a significant improvement in predictive value for hemodynamically significant CAD with the addition of EAT volume to obstructive CAD alone (area under the curve, 0.950 vs. 0.891; P < 0.001).

Conclusion

In this study, we found that EAT volume correlated substantially and positively with the existence and severity of hemodynamically significant CAD in Chinese patients with known or suspected CAD, which was independent of traditional risk factors and CACs. In combination with obstructive CAD, EAT volume significantly improved diagnostic performance for hemodynamically significant CAD, suggesting that EAT could be a reliable noninvasive indicator of hemodynamically significant CAD.
Sleep apnea-COPD overlap syndrome is associated with larger left carotid atherosclerotic plaques
Authors: Landete Pedro , Fernández-García Carlos Ernesto , Muñoz José M. , Friera Alfonsi , Ancochea Julio , González-Rodríguez Águeda , García-Monzón Carmelo
Published: March 2023

Background

Little is known about whether the overlap syndrome (OS) combining features of chronic obstructive pulmonary disease (COPD) and sleep apnea-hypopnea syndrome increases the risk of stroke associated with COPD itself.

Methods

We prospectively studied 74 COPD patients and 32 subjects without lung disease. Spirometry and cardiorespiratory polygraphy were used to assess the pulmonary function of the study population and ultrasound measurements of intima media thickness (IMT) as well as the volume of plaques in both carotid arteries were also evaluated.

Results

Polygraphic criteria of OS were met in 51% of COPD patients. We found that 79% of patients with OS and 50% of COPD patients without OS had atherosclerotic plaques in the left carotid artery (p = 0.0509). Interestingly, the mean volume of atherosclerotic plaques was significantly higher in the left carotid artery of COPD patients with OS (0.07 ± 0.02 ml) than in those without OS (0.04 ± 0.02 ml, p = 0.0305). However, regardless of the presence of OS, no significant differences were observed in both presence and volume of atherosclerotic plaques in the right carotid artery of COPD patients. Adjusted-multivariate linear regression revealed age, current smoking and the apnea/hypopnea index (OR = 4.54, p = 0.012) as independent predictors of left carotid atherosclerotic plaques in COPD patients.

Conclusions

This study suggests that the presence of OS in COPD patients is associated with larger left carotid atherosclerotic plaques, indicating that OS might be screened in all COPD patients to identify those with higher risk of stroke.
CURTAINs for your sliding window: Constructing unobserved regions by transforming adjacent intervals
Authors: Raine John Andrew , Klein Samuel , Sengupta Debajyoti , Golling Tobias
Published: March 2023

We propose a new model independent technique for constructing background data templates for use in searches for new physics processes at the LHC. This method, called Curtains, uses invertible neural networks to parameterise the distribution of side band data as a function of the resonant observable. The network learns a transformation to map any data point from its value of the resonant observable to another chosen value. Using Curtains, a template for the background data in the signal window is constructed by mapping the data from the side-bands into the signal region. We perform anomaly detection using the Curtains background template to enhance the sensitivity to new physics in a bump hunt. We demonstrate its performance in a sliding window search across a wide range of mass values. Using the LHC Olympics dataset, we demonstrate that Curtains matches the performance of other leading approaches which aim to improve the sensitivity of bump hunts, can be trained on a much smaller range of the invariant mass, and is fully data driven.
Modal analysis and harmonic response analysis of energy-absorbing and anti-scouring columns
Authors: Tang Zhi , Wu Hao , Wu Zhiwei , Jia Dunwei , Fu Yuejia
Published: March 2023

Many field observations have found that damage to the support did not increase with the magnitude of the impact ground pressure. To enhance the impact protection performance of “support and surrounding rock” system. From the perspective of preventing the resonance of the “support and surrounding rock” system, the dynamic response of energy-absorbing and anti-scouring column is studied. Using the block theory, a dynamic model of the roadway enclosure-absorbing anti-scouring column under impact loading was established, and the dynamic response equation of the rock block at the support end was obtained. Based on the structural dynamics and Love shell theory, the characteristic equations of the energy-absorbing and anti-scouring column were derived, and the theoretical equations for the natural frequency and vibration mode function of the energy-absorbing and anti-scouring column were obtained. The ABAQUS numerical simulation method was used to carry out pre-stress modal analysis and harmonious response analysis of energy-absorbing and anti-scouring columns and conventional columns. We obtained the natural frequencies and vibration modes of the two columns and analyzed the effect of the setting load on the modalities of the columns. The column dynamic response law was determined by monitoring the displacement and velocity response curves at different positions. The results show that the natural frequency and vibration mode of the energy-absorbing and anti-scouring column are related to the density, elastic modulus, and length. The vibration of the energy-absorbing and anti-scouring column has two forms: beam vibration mode and cylindrical shell vibration mode, and the first four orders of vibration mode are transverse bend. The setting load has a small effect on the natural frequency and vibration mode of both types of columns, where the natural frequency decreases as the setting load increases. When the excitation frequency is close to the vibration frequency of the surrounding rock, the radial, axial, and circumferential response amplitudes of the primary and secondary columns of the energy-absorbing and anti-scouring column are the largest. Reinforcement and strengthening measures should be implemented to reduce the column deformation amplitude.
Epidemiology of chronic multimorbidity and temporary migration in a rural South African community in health transition: A cross-sectional population-based analysis
Authors: Dzomba Armstrong , Ginsburg Carren , Kabudula Chodziwadziwa W. , Yorlets Rachel R. , Ndagurwa Pedzisai , Harawa Sadson , Lurie Mark N. , McGarvey Stephen T. , Tollman Stephen , Collinson Mark A. , White Michael J. , Gomez-Olive Francesc X.
Published: March 2023

Introduction

In sub-Saharan African settings, the increasing non-communicable disease mortality is linked to migration, which disproportionately exposes sub-populations to risk factors for co-occurring HIV and NCDs.

Methods

We examined the prevalence, patterns, and factors associated with two or more concurrent diagnoses of chronic diseases (i.e., multimorbidity) among temporary within-country migrants. Employing a cross-sectional design, our study sample comprised 2144 residents and non-residents 18–40 years interviewed and with measured biomarkers in 2018 in Wave 1 of the Migrant Health Follow-up Study (MHFUS), drawn from the Agincourt Health and Demographic Surveillance System (AHDSS) in rural north-eastern South Africa. We used modified Poisson regression models to estimate the association between migration status and prevalent chronic multimorbidity conditional on age, sex, education, and healthcare utilisation.

Results

Overall, 301 participants (14%; 95% CI 12.6–15.6), median age 31 years had chronic multimorbidity. Multimorbidity was more prevalent among non-migrants (14.6%; 95% CI 12.8–16.4) compared to migrants (12.8%; 95% CI 10.3–15.7). Non-migrants also had the greatest burden of dual-overlapping chronic morbidities, such as HIV-obesity 5.7%. Multimorbidity was 2.6 times as prevalent (PR 2.65. 95% CI 2.07–3.39) among women compared to men. Among migrants, men, and individuals with secondary or tertiary education manifested lower prevalence of two or more conditions.

Discussion

In a rural community with colliding epidemics, we found low but significant multimorbidity driven by a trio of conditions: HIV, hypertension, and obesity. Understanding the multimorbidity burden associated with early adulthood exposures, including potential protective factors (i.e., migration coupled with education), is a critical first step towards improving secondary and tertiary prevention for chronic disease among highly mobile marginalised sub-populations.
Spatial–temporal pattern of urban ecological construction in the Yellow River basin and its optimization and promotion paths
Authors: Xiaohui Wang , Qian Che , Longsheng Wang , Guangyu Li , Haiyan Sun , Weishan Qin , Shuang Chen , Shimou Yao , Liwei Meng , Xiaoqian Yu
Published: March 2023

Introduction

Urban ecological instruction is an important method of sustainable development that couples the needs of the population and the environment, thus facilitating high-quality development. This study aimed to transform existing large-scale considerations of ecological urban construction to provide a more grounded evaluation framework. We constructed an integrated framework that considers economic, environmental, social, cultural, and ecological factors and their contribution to urban ecological construction.

Methods

We used methods of subjective and objective empowerment, exploratory spatial data analysis, and the obstacle degree model to explore spatiotemporal variations in urban ecological construction.

Results

Our results showed that: (1) From 2006 to 2018, urban ecological construction in the Yellow River basin (YRB) exhibited a “polycentric” spatial differentiation pattern and a significant, gradually decreasing “center-periphery” spatial distribution trend. (2) High–high areas (with high agglomeration and high urban ecological construction) in the YRB are mainly distributed in Shandong Province and the adjacent regions, whereas low–low areas are mainly distributed in south–central Ningxia Province and southern Gansu Province. (3) Analysis of urban ecological construction characteristics across different city scales, functional types, spatial carriers, and basin locations shows that the urban ecological construction level is directly proportional to the scale of the city. The level of urban ecological construction is relatively higher in the Shandong Peninsula urban agglomeration, in the priority development area of the North China Plain, and in the downstream and right bank of the YRB. Spatial differences are mainly controlled by the net difference between regions from the upstream and midstream scales, as well as intra-regional differences between the left and right banks. (4) Marked differences can be observed in the obstacles to ecological construction in different types of cities.

Discussion

Typical barriers in cities in the YRB include the total water resources per capita, energy consumption per unit of GDP, the proportion of research and development investment in fiscal expenditure, the number of books in public libraries per 10,000 people, and land use efficiency. In the future, urban ecological construction should be based on the development conditions of each individual city, and should be improved according to local conditions to achieve the construction high-quality ecological cities.
Believe me! Why tesla’s recent alleged malfunction further highlights the need for transparent dialogue
Authors: Milford Stephen R. , Elger Bernice S. , Shaw David M.
Published: March 2023

On November the 13th, 2022 video footage was released purportedly showing a Tesla Model Y malfunctioning by speeding through the streets of a Chinese city killing two people. Video footage such as this has the potential to undermine trust in AVs. While Tesla has responded by stating they will get to the “truth,” there are questions as to how this truth is to be decided, and perhaps more importantly how the public can trust either Tesla or negative press. We explore the “facts” of the incident and discuss the challenges of building trust in new AVs systems based on transparency. In this article we argue that transparency is more than simply getting to the “truth.” It is fostering a relational dialogue between the facts and stakeholder. Using O’Brien’s window metaphor, this article explores the need for AV manufacturers to consider the content of such incidents, the different perceptions of stakeholders, and the medium through which the content is presented. Apart from the need for independent crash investigators, there is a need for AV manufacturers to go beyond simply’ getting to the truth’ and to engage with the public responsibly.
Case report: Homozygous variants of NEB and KLHL40 in two Arab patients with nemaline myopathy
Authors: Skrypnyk Cristina , Husain Aseel Ahmed , Hassan Hisham Y. , Ahmed Jameel , Darwish Abdulla , Almusalam Latifa , Ben Khalaf Noureddine , Al Qashar Fahad
Published: March 2023

Objective: Nemaline myopathies are a heterogeneous group of congenital myopathies caused by mutations in different genes associated with the structural and functional proteins of thin muscular filaments. Most patients have congenital onset characterized by hypotonia, respiratory issues, and abnormal deep tendon reflexes, which is a phenotype encountered in a wide spectrum of neuromuscular disorders. Whole-exome sequencing (WES) contributes to a faster diagnosis and facilitates genetic counseling.

Methods: Here, we report on two Arab patients from consanguineous families diagnosed with nemaline myopathy of different phenotype spectrum severities.

Results: Clinical assessment and particular prenatal history raised suspicion of neuromuscular disease. WES identified homozygous variants in NEB and KLHL40. Muscle biopsy and muscle magnetic resonance imaging studies linked the genetic testing results to the clinical phenotype. The novel variant in the NEB gene resulted in a classical type 2 nemaline myopathy, while the KLHL40 gene variant led to a severe phenotype of nemaline myopathy, type 8. Both patients were identified as having other gene variants with uncertain roles in their complex phenotypes.

Conclusions: This study enriches the phenotypic spectrum of nemaline myopathy caused by NEB and KLHL40 variants and highlights the importance of detailed prenatal, neonatal, and infancy assessments of muscular weakness associated with complex systemic features. Variants of uncertain significance in genes associated with nemaline myopathy may be correlated with the phenotype. Early, multidisciplinary intervention can improve the outcome in patients with mild forms of nemaline myopathies. WES is essential for clarifying complex clinical phenotypes encountered in patients from consanguineous families. Targeted carrier screening of extended family members would enable accurate genetic counseling and potential genetic prevention.
The immediate adverse drug reactions induced by ShenMai Injection are mediated by thymus-derived T cells and associated with RhoA/ROCK signaling pathway
Authors: Jiang Shan , Sun Bo , Zhang Yan , Han Jiayin , Zhou Yanyan , Pan Chen , Wang Hongjie , Si Nan , Bian Baolin , Wang Linna , Wang Lifang , Wei Xiaolu , Zhao Haiyu
Published: March 2023

Introduction

The mechanism of the immediate adverse drug reactions (ADRs) induced by ShenMai injection (SMI) has not been completely elucidated. Within 30 minutes, the ears and lungs of mice injected with SMI for the first time showed edema and exudation reactions. These reactions were different from the IV hypersensitivity. The theory of pharmacological interaction with immune receptor (p-i) offered a new insight into the mechanisms of immediate ADRs induced by SMI.

Methods

In this study, we determined that the ADRs were mediated by thymus-derived T cells through the different reactions of BALB/c mice (thymus-derived T cell normal) and BALB/c nude mice (thymus-derived T cell deficient) after injecting SMI. The flow cytometric analysis, cytokine bead array (CBA) assay and untargeted metabolomics were used to explain the mechanisms of the immediate ADRs. Moreover, the activation of the RhoA/ROCK signaling pathway was detected by western blot analysis.

Results

In BALB/c mice, the vascular leakage and histopathology results showed the occurrence of the immediate ADRs induced by SMI. The flow cytometric analysis revealed that CD4+ T cell subsets (Th1/Th2, Th17/Treg) were imbalanced. And the levels of cytokines such as IL-2, IL-4, IL12P70 and INF-γ increased significantly. However, in BALB/c nude mice, all the indicators mentioned above have not changed significantly. The metabolic profile of both BALB/c mice and BALB/c nude mice was significantly changed after injecting SMI, and the notable increase in lysolecithin level might have a greater association with the immediate ADRs induced by SMI. The Spearman correlation analysis revealed that LysoPC (18:3(6Z,9Z,12Z)/0:0) showed a significant positive correlation with cytokines. After injecting SMI, the levels of RhoA/ROCK signaling pathway-related protein increased significantly in BALB/c mice. Protein-protein interaction (PPI) showed that the increased lysolecithin levels might be related to the activation of the RhoA/ROCK signaling pathway.

Discussion

Together, the results of our study revealed that the immediate ADRs induced by SMI were mediated by thymus-derived T cells, and elucidated the mechanisms of such ADRs. This study provided new insights into the underlying mechanism of immediate ADRs induced by SMI.
Proteotranscriptomic analyses reveal distinct interferon-beta signaling pathways and therapeutic targets in choroidal neovascularization
Authors: Hu Yuxiang , Qi Siyi , Zhuang Hong , Zhuo Qiao , Liang Yu , Kong Hongyu , Zhao Chen , Zhang Shujie
Published: March 2023

Aim

To investigate the molecular mechanism underlying the onset of choroidal neovascularization (CNV).

Methods

Integrated transcriptomic and proteomic analyses of retinas in mice with laser-induced CNV were performed using RNA sequencing and tandem mass tag. In addition, the laser-treated mice received systemic interferon-β (IFN-β) therapy. Measurements of CNV lesions were acquired by the confocal analysis of stained choroidal flat mounts. The proportions of T helper 17 (Th17) cells were determined by flow cytometric analysis.

Results

A total of differentially expressed 186 genes (120 up-regulated and 66 down-regulated) and 104 proteins (73 up-regulated and 31 down-regulated) were identified. The gene ontology and KEGG pathway analyses indicated that CNV was mainly associated with immune and inflammatory responses, such as cellular response to IFN-β and Th17 cell differentiation. Moreover, the key nodes of the protein–protein interaction network mainly involved up-regulated proteins, including alpha A crystallin and fibroblast growth factor 2, and were verified by Western blotting. To confirm the changes in gene expression, real-time quantitative PCR was performed. Furthermore, levels of IFN-β in both the retina and plasma, as measured by enzyme-linked immunosorbent assay (ELISA), were significantly lower in the CNV group than in the control group. IFN-β treatment significantly reduced CNV lesion size and promoted the proliferation of Th17 cells in laser-treated mice.

Conclusions

This study demonstrates that the occurrence of CNV might be associated with the dysfunction of immune and inflammatory processes and that IFN-β could serve as a potential therapeutic target.
Perspectives of vector management in the control and elimination of vector-borne zoonoses
Authors: Wong Meng Li , Zulzahrin Zulhisham , Vythilingam Indra , Lau Yee Ling , Sam I-Ching , Fong Mun Yik , Lee Wenn-Chyau
Published: March 2023

The complex transmission profiles of vector-borne zoonoses (VZB) and vector-borne infections with animal reservoirs (VBIAR) complicate efforts to break the transmission circuit of these infections. To control and eliminate VZB and VBIAR, insecticide application may not be conducted easily in all circumstances, particularly for infections with sylvatic transmission cycle. As a result, alternative approaches have been considered in the vector management against these infections. In this review, we highlighted differences among the environmental, chemical, and biological control approaches in vector management, from the perspectives of VZB and VBIAR. Concerns and knowledge gaps pertaining to the available control approaches were discussed to better understand the prospects of integrating these vector control approaches to synergistically break the transmission of VZB and VBIAR in humans, in line with the integrated vector management (IVM) developed by the World Health Organization (WHO) since 2004.
Effects of bilirubin on the development and electrical activity of neural circuits
Authors: Wu Cuiping , Jin Yuefan , Cui Yaqi , Zhu Yidan , Yin Shankai , Li Chunyan
Published: March 2023

In the past several decades, bilirubin has attracted great attention for central nervous system (CNS) toxicity in some pathological conditions with severely elevated bilirubin levels. CNS function relies on the structural and functional integrity of neural circuits, which are large and complex electrochemical networks. Neural circuits develop from the proliferation and differentiation of neural stem cells, followed by dendritic and axonal arborization, myelination, and synapse formation. The circuits are immature, but robustly developing, during the neonatal period. It is at the same time that physiological or pathological jaundice occurs. The present review comprehensively discusses the effects of bilirubin on the development and electrical activity of neural circuits to provide a systematic understanding of the underlying mechanisms of bilirubin-induced acute neurotoxicity and chronic neurodevelopmental disorders.
Quantitative association of cerebral blood flow, relaxation times and proton density in young and middle-aged primary insomnia patients: A prospective study using three-dimensional arterial spin labeling and synthetic magnetic resonance imaging
Authors: Luo Xiao-Wen , Li Quan-Xi , Shen Li-Shan , Zhou Xiang , Zou Feng-Yun , Tang Wen-Jie , Guo Ruo-Mi
Published: March 2023

Objectives

To quantitatively measure the T1 value, T2 value, proton density (PD) value, and cerebral blood flow (CBF) in young and middle-aged primary insomnia (PI) patients, and analyze the correlations between relaxation times, PD, and CBF to explore potential brain changes.

Methods

Cranial magnetic resonance (MR) images of 44 PI patients and 30 healthy subjects were prospectively collected for analysis. The T1, T2, PD, and CBF values of the frontal lobe, parietal lobe, temporal lobe, and occipital lobe were independently measured using three-dimensional arterial spin labeling (3D-ASL), synthetic magnetic resonance imaging (syMRI) and a whole-brain automatic segmentation method. The differences of these imaging indices were compared between PI patients and healthy subjects. Follow-up MR images were obtained from PI patients after 6 months to compare with pre-treatment images. The Wilcoxon signed rank test and Spearman rank were used for statistical analysis.

Results

Bilateral CBF asymmetry was observed in 38 patients, with significant differences in both the T2 value and CBF between the four lobes of the brain (p < 0.01). However, no significant difference was found in the T1 and PD values between the bilateral lobes. A negative correlation was found between CBF and T2 values in the right four lobes of patients with primary insomnia (PI). During follow-up examinations, five PI patients showed a disappearance of insomnia symptoms and a decrease in CBF in both brain lobes.

Conclusion

Insomnia symptoms may be associated with high CBF, and most PI patients have higher CBF and lower T2 values in the right cerebral hemispheres. The right hemisphere appears to play a critical role in the pathophysiology of PI. The 3D-ASL and syMRI technologies can provide a quantitative imaging basis for investigating the brain conditions and changes in young and middle-aged PI patients.
Indices of Mediterranean diet adherence and breast cancer risk in a community-based cohort
Authors: Yiannakou Ioanna , Singer Martha R. , Moore Lynn L.
Published: March 2023

Introduction

A Mediterranean-style dietary pattern is believed to have cancer-protective effects. We compared the prospective associations between adherence to four established Mediterranean diet indices and breast cancer risk (including total, postmenopausal, and hormone receptor positive cases) in women in the Framingham Offspring Study.

Methods

The four indices used two different approaches to measuring adherence to a Mediterranean diet: (a) scores based on the population-specific median intakes of Mediterranean diet-related foods in a given population (i.e., alternate Mediterranean Diet (aMED) index and Mediterranean Diet Score (MDS) index), and (b) scores based on compliance with recommended intakes of relevant foods from the Mediterranean diet pyramid [i.e., Mediterranean Diet (MeDiet) index and Mediterranean Style Dietary Pattern (MSDP) index]. Dietary data were derived from semiquantitative food frequency questionnaires collected in 1991-95. Participants included 1579 women aged ≤ 30 years who were free of prevalent cancer. Women were followed through 2014, and Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for various confounders.

Results

During a median follow-up of approximately 18 years, 87 breast cancer cases were documented. Women in the highest (vs. lowest) score category of the pyramid-based scores (i.e., MeDiet or MSDP) had approximately 45% statistically significantly lower breast cancer risks. These effects were even stronger for any hormone receptor positive cases using the MeDiet index (highest vs. lowest score categories: HR = 0.45, 95% CI: 0.22–0.90). Neither of the median intake-based scores (i.e., aMED, MDS) was associated with breast cancer risk.

Discussion

Our results suggest that the methodology and the composition of Mediterranean diet indices influence their ability to assess conformity to this specific diet pattern and predict breast cancer risk.
Choline PET/CT in recurrent prostate cancer
Authors: Detti Beatrice , Carnevale Maria Grazia , Lucidi Sara , Burchini Luca , Caini Saverio , Orsatti Carolina , Bertini Niccolò , Roghi Manuele , di Cataldo Vanessa , Fondelli Simona , Ingrosso Gianluca , Francolini Giulio , Scartoni Daniele , Sardaro Angela , Pisani Antonio , Scoccianti Silvia , Aristei Cynthia , Livi Lorenzo
Published: March 2023

Purpose

Biochemical recurrence (BR) occurs in up to 40% of patients with prostate cancer (PCa) treated with primary radical prostatectomy (RP). Choline PET/CT may show, in a single-step examination, the site of tumor recurrence earlier than traditional imaging methods, particularly at low prostate-specific antigen (PSA) levels, thus influencing subsequent treatment.

Methods/patients

Patients with recurrent and non-metastatic prostate cancer (nmPCa), who were assessed with choline PET/CT, were included in the analysis. Based on imaging results, the following therapeutic strategies were chosen: radiotherapy to the prostatic bed, androgen deprivation therapy (ADT), and chemotherapy or stereotactic body radiotherapy (SBRT) to either the pelvic lymph nodes or distant metastases. We assessed the impact of age, PSA levels, Gleason score (GS), and adjuvant therapy on oncological outcomes.

Results

Data from 410 consecutive nmPCa patients with BR who underwent RP as primary treatment were analyzed. One hundred seventy-six (42.9%) patients had a negative choline PET/CT, and 234 (57.1%) patients resulted positive. In the multivariate analysis, only chemotherapy and PSA at recurrence were significant independent prognostic factors on overall survival (OS). In the PET-positive subgroup, the number of relapses, PSA post-prostatectomy, and chemotherapy impacted on OS. PSA (post-surgery and at recurrence) affected progression-free survival (PFS) in the univariate analysis. In the multivariate analysis, GS, the number of relapse sites, and PSA (post-surgery and at recurrence) were significant prognostic factors for disease-free survival (DFS).

Conclusion

Choline PET/CT provides better accuracy than conventional imaging for the assessment of nmPCa with BR after prostatectomy, thereby enabling salvage strategies and improving quality of life.
Case report: Bilateral carotid body tumors with a concomitant skull-base paraganglioma
Authors: Liu Zhixuan , Yue Ruimin , Sun Cuiyun , Wang Junping
Published: March 2023

Background

Bilateral carotid body tumors with a concomitant skull-base paraganglioma are extremely rare, of which only one case has been reported in the literature to date.

Case presentation

We present the case of a 35-year-old male with 1 year of hypertension and high levels of dopamine and 3-methoxytyramine. Magnetic resonance imaging (MRI) scans demonstrated three separate masses at the left middle cranial fossa floor and bilateral carotid bifurcation. Genetic testing showed succinate dehydrogenase complex subunit D mutation. The patient underwent the resection of the left skull base mass. Histopathology and immunohistochemistry confirmed the presence of a skull-base paraganglioma.

Conclusions

Succinate dehydrogenase complex subunit D mutation-associated bilateral carotid body tumors with a concomitant skull-base paraganglioma accompanied by abnormal dopamine and hypertension are extremely rare, which not only provides ideas for considering the association of gene mutations, biochemical abnormalities and clinical symptoms but also provides an expanded diagnostic spectrum for paraganglioma in atypical locations.
An update on immunological and molecular tests and their impact in infectious uveitis
Authors: Thomas Joanne , Nguyen Nam V. , Fashina Tolulope , Huang Ye , Yeh Steven , Conrady Christopher D.
Published: March 2023

Early diagnosis of infectious uveitis can lead to prompt initiation of treatment to minimize vision-threatening sequelae. As various infectious etiologies of uveitis share similar clinical features, advancements in polymerase chain reaction (PCR) and metagenomic next-generation sequencing (MDS) have shown significant promise in improving diagnostic capabilities. Various techniques of PCR, including real-time, multiplex, comprehensive, and broad-range, have increased the armamentarium for infectious uveitis diagnosis. Additionally, metagenomic deep sequencing technology has provided a methodology to identify causative pathogens as well as novel etiologies of uveitis. This review discusses the diagnostic tools available for infectious uveitis and highlights the advantages and disadvantages of the techniques.
Regional blocks for pain control at the end of life in pediatric oncology
Authors: Cuviello Andrea , Cianchini de la Sota Ashley , Baker Justin , Anghelescu Doralina
Published: March 2023

Background

Pain management at the end of life is a fundamental aspect of care and can improve patients' quality of life. Interventional approaches may be underutilized for pediatric cancer patients.

Objective

To describe a single institution's 10 years of experience with regional pain management at the end of life in pediatric oncology.

Methods

A retrospective cohort study of 27 patients with pediatric cancer who died between April 2011 and December 2021 and received continuous nerve block (CNB) catheters or single-shot nerve blocks (SSBs) during their last three months of life. The type of blocks, analgesic efficacy, and palliative care involvement were evaluated.

Results

Twenty-two patients (81.5%) had solid tumor diagnoses, including carcinomas, sarcomas, and neuroblastoma. Most (59%) patients received CNB catheters, and 12 patients (44%) received SSBs for pain control. The mean pain score decreases for CNB catheters and SSBs after interventions were −2.5 and −2.8, respectively, on an 11-point scale. Decreases in opioid patient-controlled analgesia dosing requirements were noted in 56% of patients with CNB catheters; likewise, in 25% of patients with SSBs at 24 h and in 8% at 5 days after interventions. Nearly all patients had PC involvement and received care from pain specialists (96% and 93%, respectively). Twenty-three (85%) had physician orders for scope of treatment orders completed before death.

Conclusion

Regional pain control interventions can be effective and safe for relieving regional pain and suffering in dying children and young adults. The collaboration between palliative care and pain management specialists at the end of life can help alleviate suffering and improve quality of life.
Case report: Child chronic nonbacterial osteomyelitis with rapid progressive scoliosis-an association with disease?
Authors: Shi Xiaojun , Hou Xiujuan , Hua Haiqin , Dong Xia , Liu Xiaoping , Cao Fengjiao , Li Chen
Published: March 2023

Background

Chronic nonbacterial osteomyelitis (CNO) is an auto-inflammatory bone disease that usually develops in childhood. Spinal involvement is a common manifestation of CNO, but it is rare for CNO to lead to rapid progression of scoliosis deformity. Here we present a 9-year-old girl with acute scoliosis with CNO and scoliosis progressed rapidly in 2 months.

Case Presentation

A 9-year-old girl presented bilateral shoulder inequality with pain in the left hypochondrium for 2 months. Standing spinal x-rays showed right convex scoliosis with a 25° Cobb angle. Chest magnetic resonance imaging (MRI) showed that the T8 vertebra was flattened and local bone was destroyed with bone marrow edema. The bone biopsy showed evidence of fibrosis and chronic inflammatory changes with no specific diagnosis. One month later, her scoliosis and bone destruction deteriorated obviously. Thoracic vertebra MRI showed that the T8 vertebra had a compression fracture. 99mTc-MDP whole-body bone scintigraphy showed intense uptake at T8/9 and the right sacroiliac joint. She was diagnosed with CNO accompanied by rapidly progressive scoliosis. The scoliosis was successfully treated with adalimumab and zoledronic acid, which showed significant improvement after 6 months of follow-up.

Conclusion

Zoledronic acid and adalimumab successfully treated CNO with rapidly progressive scoliosis, but could not prevent vertebral compression.
Building an antimicrobial stewardship program: A narrative of six years under the Donabedian perspective
Authors: Fonseca Medeiros Amanda , Margotto Bertollo Caryne , Moreira Reis Adriano Max , Costa Monica Aparecida , Meireles Leite Edna Marilea , da Silva Gonçalves Simony , Nogueira Guimarães de Abreu Mauro Henrique , Pedra de Souza Renan , Parreiras Martins Maria Auxiliadora
Published: March 2023

Introduction: Antimicrobial resistance (AMR) is increasing and represents one of the world’s major challenges. AMR increase morbimortality, length of hospital stay and costs. Antimicrobial Stewardship Programs (ASP) are one of the key strategies to promote the rational use of antimicrobials since AMR is mostly driven by antimicrobial consumption.

Objective: To describe the ASP implementation in a teaching hospital from the perspective of Donabedian quality assessment and the Brazilian regulatory requirements.

Method: This was a descriptive study with secondary data collection, including document review of the ASP. The study setting was a general public 392-bed hospital. The ASP activities were performed by the hospital infection control committee (HICC), hospital pharmacy (HP) and diagnostic support laboratory (DSL). The description of the three services mainly involved in the ASP was based on a quality assessment model involving the dimensions of “structure”, “process” and “result” proposed by Donabedian. The distribution among dimensions was guided by the checklist of essential elements of the ASP that compose the Brazilian regulatory requirements. The checklist was applied in July, 2022, and the ASP results described from 2016 to 2021.

Results: ASP actions have been gradually implemented since 2008 with the implementation of HICC and improved over the years. Regarding structure, the investments in technology were mapped, quantifying 26 computers and three software programs employed to computerize the ASP processes performed in specific physical areas by HICC, HP and DSL. Institutional guidelines used by HICC, HP and DSL guided clinical practices to operationalize ASP. The evaluation metrics improved for 10 indicators and worsened for four indicators. From the 60 items composing the checklist, the hospital met the requirements in 73.3% of the items (n = 44).

Conclusion: This study described the implementation of ASP in a teaching hospital, applying the Donabedian perspective. Although the hospital still does not have a classic ASP model, there were investments to improve structure, processes and results, aiming to comply with international guidelines. A high proportion of key elements of ASP in the hospital were followed according to the Brazilian regulatory requirements. Aspects related to antimicrobial consumption and the emergence of microbial resistance deserve further investigations.
Real-world efficacy and safety of pyrotinib in patients with HER2-positive metastatic breast cancer: A prospective real-world study
Authors: Zhang Qiongwen , He Ping , Tian Tinglun , Yan Xi , Huang Juan , Zhang Zhang , Zheng Hong , Zhong Xiaorong , Luo Ting
Published: March 2023

Background: Pyrotinib, a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor, shows encouraging anticancer activity and acceptable tolerability in multiple phase II and phase III randomized clinical trials, but the real-world data of pyrotinib, especially the outcomes in HER2-positive metastatic breast cancer, have been rarely reported. Here, we evaluated the treatment outcomes of pyrotinib in real-world practice in patients with HER2-positive metastatic breast cancer (MBC).

Methods: This was a prospective, real-world, observational cohort study. Through the Breast Cancer Information Management System, HER-2 positive MBC patients treated with pyrotinib between 2017/06 and 2020/09 were included. Provider-reported objective response rate, progression-free survival (PFS), and overall survival (OS) were considered in the assessment of treatment outcomes. Tumor responses to pyrotinib treatment were calculated using RECIST 1.1. Adverse events were evaluated using clinical records.

Results: The trial involved 113 individuals who were receiving pyrotinib treatment, with an average age of 51 years. Complete response, partial response and stable disease were observed in 9 (8.0%), 66 (58.4%), and 17 (15.0%) patients, respectively, while progressive disease was recorded in 20 (17.7%) patients. After a median follow-up of 17.2 months, the median PFS was 14.1. The most common adverse events of any grade were diarrhea (87.6%), vomiting (31.9%), and palmar-plantar erythrodysesthesia (26.6%). Among the patients with brain metastases, the median PFS and OS were 15.2 and 19.8 months, respectively. In addition, pyrotinib has similar efficacy in various subtypes of HER2-positive MBC patients, as shown by the lack of a significant difference of PFS and OS among pyrotinib-treated patients with or without brain metastases, or patients using pyrotinib as first-line, second-line, third-line or beyond therapies.

Conclusion: Our real-world results demonstrated equivalent clinical efficacy in HER-2 positive MBC patients compared to phase II and phase III clinical trials with pyrotinib, and promising outcomes in patients with brain metastases.