bluuebunny/crossref_metadata_2025 huggingface dataset:
The quest for justice in education: capital and funds of knowledge
Authors: Gaete Alfredo , Luna Laura , Silva-Peña Ilich , Guerrero Patricia
Published: June 2023

This paper explores the funds of knowledge approach to pedagogy and educational research from a social justice perspective. In response to the suggestion made by some authors that the approach should be integrated with a capital perspective, we argue that this would work only if the concept of capital is understood in a certain way. Also, and more generally, we try to show that redistribution in education should not be thought of in terms of capital redistribution, but in terms of counteracting structural barriers to participatory parity which result in status differences among citizens. Finally, we suggest three concrete ways this can be achieved through pedagogies based on funds of knowledge.
Neonatal hypoglycemia: lack of evidence for a safe management
Authors: Roeper Marcia , Hoermann Henrike , Kummer Sebastian , Meissner Thomas
Published: June 2023

Neonatal hypoglycemia affects up to 15% of all newborns. Despite the high prevalence there is no uniform definition of neonatal hypoglycemia, and existing guidelines differ significantly in terms of when and whom to screen for hypoglycemia, and where to set interventional thresholds and treatment goals. In this review, we discuss the difficulties to define hypoglycemia in neonates. Existing knowledge on different strategies to approach this problem will be reviewed with a focus on long-term neurodevelopmental outcome studies and results of interventional trials. Furthermore, we compare existing guidelines on the screening and management of neonatal hypoglycemia. We summarize that evidence-based knowledge about whom to screen, how to screen, and how to manage neonatal hypoglycemia is limited – particularly regarding operational thresholds (single values at which to intervene) and treatment goals (what blood glucose to aim for) to reliably prevent neurodevelopmental sequelae. These research gaps need to be addressed in future studies, systematically comparing different management strategies to progressively optimize the balance between prevention of neurodevelopmental sequelae and the burden of diagnostic or therapeutic procedures. Unfortunately, such studies are exceptionally challenging because they require large numbers of participants to be followed for years, as mild but relevant neurological consequences may not become apparent until mid-childhood or even later. Until there is clear, reproducible evidence on what blood glucose levels may be tolerated without negative impact, the operational threshold needs to include some safety margin to prevent potential long-term neurocognitive impairment from outweighing the short-term burden of hypoglycemia prevention during neonatal period.
A solar irradiance estimation technique via curve fitting based on dual-mode Jaya optimization
Authors: Bi Ziqiang , Chu Guanying , Pan Xinyu , Guo Jichong , Gu Minming , Ban Jianmin
Published: June 2023

Solar irradiance is a crucial environmental parameter for optimal control of photovoltaic (PV) systems. However, precise measurements of the solar irradiance are difficult since the irradiation sensors (i.e., pyranometer or pyrheliometer) are expensive and hard to calibrate. This paper proposes a cost-effective and accurate method for estimating the solar irradiance with a PV module via curve fitting. A dual-mode Jaya (DM-Jaya) optimization algorithm is introduced to extract the real-time value of solar irradiance from the measured PV characteristics data by using two search strategies. The step sizes of a random walk are taken from even and Lévy distribution distributions in different searching phases. Compared with the traditional irradiance sensors, the proposed estimator does not require additional circuit and obtains relatively lower error rates. A comparative study of seven population-based optimization algorithms for the optimal design of the estimator is presented. These algorithms include particle swarm optimization (PSO), cuckoo search (CS), Jaya, simulated annealing (SA), genetic algorithm (GA), supply-demand-based optimization (SDO), and the proposed DM-Jaya algorithm. Simulations and experimental results reveal that DM-Jaya outperforms the other optimization algorithms in terms of the estimation speed and accuracy.
Effect of ecological civilization pilot demonstration area construction on urban land green use efficiency
Authors: Li Shaojie , Wang Duoduo , Wu Qin
Published: June 2023

Improvement of urban land green use efficiency (ULGUE) in the context of sustained economic growth is a major challenge for the regional sustainable development and ecological civilization construction in China. This study measures the ULGUE of 263 cities in China at the prefecture or above level, clarifies its spatio-temporal changes, investigates the effect of ecological civilization pilot demonstration area construction on ULGUE with the multi-period PSM-DID model and spatial Durbin difference model, and evaluates the spatial spillover effect of the policy. The results show that: 1) In terms of spatio-temporal changes, ULGUE shows a steady upward trend with time. From 2006 to 2019, the national mean value of ULGUE increases from 0.5284 to 0.6439, with an increase rate of 21.86%; in the spatial dimension, ULGUE is characterized by a pattern of eastern > national > central > western. 2) Ecological civilization pilot demonstration area construction has significantly improved the ULGUE of pilot cities by about 0.12% relative to that of non-pilot cities, which was validated by the robustness test. 3) Ecological civilization pilot demonstration area construction has significant positive spillover effects on the ULGUE of neighboring cities, which are related to the urban characteristics such as geographical location, resource endowment, and environmental protection intensity. 4) Ecological civilization pilot demonstration area construction has certain heterogeneity in its effect on ULGUE in different regions and cities, with a more significant promoting effect for non-eastern regions, non-resource-based cities, and non-key cities of environmental protection. Therefore, it is necessary to summarize the successful experience of ecological civilization pilot demonstration area construction and fully consider differential policies, so as to maximize the policy dividends while strengthening regional linkage, and further contribute to national popularization of this policy.
Construction and Validation of a Ferroptosis-Related Prognostic Model for Endometrial Cancer
Authors: Wang Hao , Wu Yingchen , Chen Shengfu , Hou Minzhi , Yang Yanning , Xie Meiqing
Published: June 2023

Graphical Abstract

Analysis workflow chart.
Rethinking (again) Hardy-Weinberg and genetic drift in undergraduate biology
Authors: Klymkowsky Michael W.
Published: June 2023

Designing effective curricula is challenging. Content decisions can impact both learning outcomes and student engagement. As an example consider the place of Hardy-Weinberg equilibria (HWE) and genetic drift calculations in introductory biology courses, as discussed by Masel (2012). Given that population genetics, “a fairly arcane speciality”, can be difficult to grasp, there is little justification for introducing introductory students to HWE calculations. It is more useful to introduce them to the behavior of alleles in terms of basic features of biological systems, and that in the absence of selection recessive alleles are no “weaker” or preferentially lost from a population than are dominant alleles. On the other hand, stochastic behaviors, such as genetic drift, are ubiquitous in biological systems and often play functionally significant roles; they can be introduced to introductory students in mechanistic and probabilistic terms. Specifically, genetic drift emerges from the stochastic processes involved in meiotic chromosome segregation and recombination. A focus on stochastic processes may help counteract naive bio-deterministic thinking and can reinforce, for students, the value of thinking quantitatively about biological processes.
Case Report: Intercurrent infections in COVID-19-induced sustained immunodepression: is interferon gamma a suitable drug?
Authors: De Waard Aurianne , Lefebvre Laurent , Textoris Julien , Payen Didier
Published: June 2023

Acute immuno-depression syndrome (AIDs) had been observed in many life-threatening conditions leading to the Intensive Care Unit. and is associated with recurrent secondary infections. We report one COVID-19 patient with a severe ARDS, demonstrating acute immunodepression syndrome lasting for several weeks. The occurrence of secondary infections despite long treatment by antibiotics led to combined interferon γ (IFNγ) as reported previously. The response to IFNγ was evaluated by the flowcytometry HLA-DR expression on circulating monocytes, which was repeated from time to time. The severe COVID-19 patients responded well to IFNγ without adverse events.
When natural antibodies become pathogenic: autoantibodies targeted against G protein-coupled receptors in the pathogenesis of systemic sclerosis
Authors: Akbarzadeh Reza , Müller Antje , Humrich Jens Y. , Riemekasten Gabriela
Published: June 2023

Systemic sclerosis (SSc) is a chronic, multisystem connective tissue, and autoimmune disease with the highest case-specific mortality and complications among rheumatic diseases. It is characterized by complex and variable features such as autoimmunity and inflammation, vasculopathy, and fibrosis, which pose challenges in understanding the pathogenesis of the disease. Among the large variety of autoantibodies (Abs) present in the sera of patients suffering from SSc, functionally active Abs against G protein-coupled receptors (GPCRs), the most abundant integral membrane proteins, have drawn much attention over the last decades. These Abs play an essential role in regulating the immune system, and their functions are dysregulated in diverse pathological conditions. Emerging evidence indicates that functional Abs targeting GPCRs, such as angiotensin II type 1 receptor (AT1R) and the endothelin-1 type A receptor (ETAR), are altered in SSc. These Abs are part of a network with several GPCR Abs, such as those directed to the chemokine receptors or coagulative thrombin receptors. In this review, we summarize the effects of Abs against GPCRs in SSc pathologies. Extending the knowledge on pathophysiological roles of Abs against GPCRs could provide insights into a better understanding of GPCR contribution to SSc pathogenesis and therefore help in developing potential therapeutic strategies that intervene with pathological functions of these receptors.
Bioinformatic analysis of the molecular mechanisms underlying the progression of bone defects
Authors: Liu Hao , Zhao Xuan , Li Yin , Yi Jiang , Zhang Chenxi , Zheng Ziyang , Dai Siming , Yin Guoyong , Zhao Shujie
Published: June 2023

Background

The pathophysiology of bone defects (BDs) is complex, and the treatment for bone defects, in particular massive bone defects, remains a major clinical challenge. Our study was conducted to explore the molecular events related to the progression of bone defects a common clinical condition.

Methods

First, microarray data of GSE20980 were obtained from the Gene Expression Omnibus (GEO) database, where 33 samples in total were used to analyze the molecular biological processes related to bone defects. Next, the original data were normalized and differentially expressed genes (DEGs) were identified. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Finally, a protein–protein interaction (PPI) network was constructed and the trends of the different genes were confirmed.

Results

Compared with the samples of non-critical size defects (NCSD), the samples of critical size defects (CSD) had 2057, 827, and 1,024 DEGs at 7, 14, and 21 days post injury, respectively. At day 7, the DEGs were significantly enriched in metabolic pathways, at day 14 the DEGs were predominantly enriched in G-protein coupled signaling pathways and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, and at day 21 the DEGs were mainly enriched in circadian entrainment and synaptic-related functions. The PPI network showed similar results. Quantitative real-time PCR (qRT-PCR) and western blot (WB) were performed to validate the partial results of sequencing.

Conclusion

This study provides some clues about the molecular mechanism behind bone defects, which should contribute to scientific research and clinical treatment of this condition.
Prevalence and risk factors of sarcopenia in idiopathic pulmonary fibrosis: a systematic review and meta-analysis
Authors: Li Jiaye , Lu Ye , Deng Mingming , Tong Run , Zhang Qin , Bian Yiding , Miao Jinrui , Wang Zilin , Zhou Xiaoming , Hou Gang
Published: June 2023

Background

Sarcopenia often occurs as a comorbidity in many diseases which ultimately affects patient prognosis. However, it has received little attention in patients with idiopathic pulmonary fibrosis (IPF). This systematic review and meta-analysis aimed at determining the prevalence and risk factors of sarcopenia in patients with IPF.

Methods

Embase, MEDLINE, Web of Science, and Cochrane databases were searched using relevant MeSH terms until December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used for quality assessment and data analysis were performed using Stata MP 17.0 (Texas, USA). A random effects model was adopted to account for differences between articles, and the I2 statistic was used to describe statistical heterogeneities. Overall pooled estimates obtained from a random effects model were estimated using the metan command. Forest plots were generated to graphically represent the data of the meta-analysis. Meta-regression analysis was used for count or continuous variables. Egger test was used to evaluate publication bias and, if publication bias was observed, the trim and fill method was used.

Main results

The search results showed 154 studies, and five studies (three cross-section and two cohort studies) with 477 participants were finally included. No significant heterogeneity was observed among studies included in the meta-analysis (I2 = 16.00%) and our study's publication bias is low (Egger test, p = 0.266). The prevalence of sarcopenia in patients with IPF was 26% (95% CI, 0.22–0.31). The risk factors for sarcopenia in patients with IPF were age (p = 0.0131), BMI (p = 0.001), FVC% (p < 0.001), FEV1% (p = 0.006), DLco% (p ≤ 0.001), and GAP score (p = 0.003).

Conclusions

The pooled prevalence of sarcopenia in patients with IPF was 26%. The risk factors for sarcopenia in IPF patients were age, BMI, FVC%, FEV1%, DLco%, and GAP score. It is important to identify these risk factors as early as possible to improve the life quality of patients with IPF.
Identification and validation of G protein-coupled receptors modulating flow-dependent signaling pathways in vascular endothelial cells
Authors: Qiu Dike , Xu Ke , Chung Namjin , Robbins Jennifer , Luo Robert , Lawrence Michael , He Aiqing , Yu Fei , Alt Andrew , Miller Michael M. , Hangeland Jon , Feder John N. , Seiffert Dietmar , Arey Brian J.
Published: June 2023

Vascular endothelial cells are exposed to mechanical forces due to their presence at the interface between the vessel wall and flowing blood. The patterns of these mechanical forces (laminar vs. turbulent) regulate endothelial cell function and play an important role in determining endothelial phenotype and ultimately cardiovascular health. One of the key transcriptional mediators of the positive effects of laminar flow patterns on endothelial cell phenotype is the zinc-finger transcription factor, krüppel-like factor 2 (KLF2). Given its importance in maintaining a healthy endothelium, we sought to identify endothelial regulators of the KLF2 transcriptional program as potential new therapeutic approaches to treating cardiovascular disease. Using an approach that utilized both bioinformatics and targeted gene knockdown, we identified endothelial GPCRs capable of modulating KLF2 expression. Genetic screening using siRNAs directed to these GPCRs identified 12 potential GPCR targets that could modulate the KLF2 program, including a subset capable of regulating flow-induced KLF2 expression in primary endothelial cells. Among these targets, we describe the ability of several GPCRs (GPR116, SSTR3, GPR101, LGR4) to affect KLF2 transcriptional activation. We also identify these targets as potential validated targets for the development of novel treatments targeting the endothelium. Finally, we highlight the initiation of drug discovery efforts for LGR4 and report the identification of the first known synthetic ligands to this receptor as a proof-of-concept for pathway-directed phenotypic screening to identify novel drug targets.
The micro and macro interactions in acute autoimmune encephalitis: a study of resting-state EEG
Authors: Luo Xin , Liao Jie , Liu Hong , Tang Qiulin , Luo Hua , Chen Xiu , Ruan Jianghai
Published: June 2023

Objective

Early recognition of autoimmune encephalitis (AIE) is often difficult and time-consuming. Understanding how the micro-level (antibodies) and macro-level (EEG) couple with each other may help rapidly diagnose and appropriately treat AIE. However, limited studies focused on brain oscillations involving micro- and macro-interactions in AIE from a neuro-electrophysiological perspective. Here, we investigated brain network oscillations in AIE using Graph theoretical analysis of resting state EEG.

Methods

AIE Patients (n = 67) were enrolled from June 2018 to June 2022. Each participant underwent a ca.2-hour 19-channel EEG examination. Five 10-second resting state EEG epochs with eyes closed were extracted for each participant. The functional networks based on the channels and Graph theory analysis were carried out.

Results

Compared with the HC group, significantly decreased FC across whole brain regions at alpha and beta bands were found in AIE patients. In addition, the local efficiency and clustering coefficient of the delta band was higher in AIE patients than in the HC group (P < 0.05). AIE patients had a smaller world index (P < 0.05) and higher shortest path length (P < 0.001) in the alpha band than those of the control group. Also, the AIE patients' global efficiency, local efficiency, and clustering coefficients decreased in the alpha band (P < 0.001). Different types of antibodies (antibodies against ion channels, antibodies against synaptic excitatory receptors, antibodies against synaptic inhibitory receptors, and multiple antibodies positive) showed distinct graph parameters. Moreover, the graph parameters differed in the subgroups by intracranial pressure. Correlation analysis revealed that magnetic resonance imaging abnormalities were related to global efficiency, local efficiency, and clustering coefficients in the theta, alpha, and beta bands, but negatively related to the shortest path length.

Conclusion

These findings add to our understanding of how brain FC and graph parameters change and how the micro- (antibodies) scales interact with the macro- (scalp EEG) scale in acute AIE. The clinical traits and subtypes of AIE may be suggested by graph properties. Further longitudinal cohort studies are needed to explore the associations between these graph parameters and recovery status, and their possible applications in AIE rehabilitation.
A novel Dynamic Body Weight Support overground co-walker enabling variable unloading ratio and Motion Tracking
Authors: Zhang Xiaoqian , Shang Peng , Li Bing
Published: June 2023

Dynamic Body Weight Support (BWS) systems have gained attention in recent years for their potential in gait training. However, maintaining a natural gait and vertical unloading have been less explored. In our previous work, we developed a body Motion Tracking (MT) walker that can move with patients. In this study, we introduce a novel Motion Tracking Variable Body Weight Support (MTVBWS) system for overground walkers. This system utilizes Center of Mass (COM) tracking and gait phase detection to not only dynamically support the user's body weight in the vertical direction but also to facilitate movement in all directions. The system achieves this horizontal omnidirectional movement by employing active Mecanum wheels, guided by COM recognition. The validation experiments were implemented with the MT mode, passive mode, and BWS mode in “static,” “fixed unloading ratio (FUR),” and “variable unloading ratio (VUR)” settings with unloading force of 20 and 30%. The result shows that, compared to other modes, the proposed system in the MTVBWS mode can reduce the dragging effect in the horizontal plane caused by the walker. Moreover, the unloading force can be adjusted automatically to minimize the fluctuations in the force experienced by each lower limb during the rehabilitation walking training process. In comparison to natural walk, this mode presents smaller force fluctuations for each lower limb.
Neuron-astrocyte omnidirectional signaling in neurological health and disease
Authors: Pathak Dhruba , Sriram Krishnan
Published: June 2023

Astrocytes are an abundantly distributed population of glial cells in the central nervous system (CNS) that perform myriad functions in the normal and injured/diseased brain. Astrocytes exhibit heterogeneous phenotypes in response to various insults, a process known as astrocyte reactivity. The accuracy and precision of brain signaling are primarily based on interactions involving neurons, astrocytes, oligodendrocytes, microglia, pericytes, and dendritic cells within the CNS. Astrocytes have emerged as a critical entity within the brain because of their unique role in recycling neurotransmitters, actively modulating the ionic environment, regulating cholesterol and sphingolipid metabolism, and influencing cellular crosstalk in diverse neural injury conditions and neurodegenerative disorders. However, little is known about how an astrocyte functions in synapse formation, axon specification, neuroplasticity, neural homeostasis, neural network activity following dynamic surveillance, and CNS structure in neurological diseases. Interestingly, the tripartite synapse hypothesis came to light to fill some knowledge gaps that constitute an interaction of a subpopulation of astrocytes, neurons, and synapses. This review highlights astrocytes’ role in health and neurological/neurodegenerative diseases arising from the omnidirectional signaling between astrocytes and neurons at the tripartite synapse. The review also recapitulates the disruption of the tripartite synapse with a focus on perturbations of the homeostatic astrocytic function as a key driver to modulate the molecular and physiological processes toward neurodegenerative diseases.
Development and validation of platelet-to-albumin ratio as a clinical predictor for diffuse large B-cell lymphoma
Authors: Wang Jinghan , Li Linjie , Yu Fang , Zhang Junyu , Mao Liping , Chen Bocheng , Hu Xuelian , Zhou Hongmei , Xie Wanzhuo , Tong Hongyan , Jin Jie
Published: June 2023

Introduction

Diffuse large B-cell lymphoma (DLBCL) is the most common subtypes of lymphoma. Clinical biomarkers are still required for DLBCL patients to identify high-risk patients. Therefore, we developed and validated the platelet-to-albumin (PTA) ratio as a predictor for DLBCL patients.

Methods

A group of 749 patients was randomly divided into a training set (600 patients) and an internal validation set (149 cases). The independent cohort of 110 patients was enrolled from the other hospital as an external validation set. Penalized smoothing spline (PS) Cox regression models were used to explore the non-linear relationship between the PTA ratio and overall survival (OS) as well as progression-free survival (PFS), respectively.

Results

A U-shaped relation between the PTA ratio and PFS was identified in the training set. The PTA ratio less than 2.7 or greater than 8.6 was associated with the shorter PFS. Additionally, the PTA ratio had an additional prognostic value to the well-established predictors. What’s more, the U-shaped pattern of the PTA ratio and PFS was respectively validated in the two validation sets.

Discussion

A U-shaped association between the PTA ratio and PFS was found in patients with DLBCLs. The PTA ratio can be used as a biomarker, and may suggest abnormalities of both host nutritional aspect and systemic inflammation in DLBCL.
Clinicopathologic features, genomic profiles and outcomes of younger vs. older Chinese hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer patients
Authors: Wang Jinhao , Liu Yaxin , Liang Yuehua , Zhang Yue , Dong Hang , Zheng Tiantian , Yu Jianjun , Du Pan , Jia Shidong , King Bonnie L. , Wang Jing , Liu Xiaoran , Li Huiping
Published: June 2023

Background

Poor outcomes have been widely reported for younger vs. older breast cancer patients, but whether this is due to age itself or the enrichment of aggressive clinical features remains controversial. We have evaluated the clinicopathologic characteristics and genomic profiles of real-world hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) patients to examine the determinants of outcome for younger vs. older patients in a single clinical subtype undergoing treatment in the same clinic.

Patients and methods

This study included patients presenting at the Peking University Cancer Hospital with primary stage IV or first-line metastatic HR+/HER2- breast cancer who consented to an additional blood draw for genomic profiling prior to treatment. Plasma samples were analyzed with a targeted 152-gene NGS panel to assess somatic circulating tumor DNA (ctDNA) alterations. Genomic DNA (gDNA) extracted from peripheral blood mononuclear cells was analyzed for germline variants using a targeted 600-gene NGS panel. Kaplan-Meier survival analysis was performed to analyze disease free survival (DFS), progression free survival (PFS) and overall survival (OS) in association with clinicopathologic and genomic variables.

Results

Sixty-three patients presenting with HR+/HER2- MBC were enrolled in this study. Fourteen patients were < 40 years, 19 were 40-50 years, and 30 were > 50 years at the time of primary cancer diagnosis. No significant associations were observed between age and DFS, PFS or OS. Shorter OS was associated with de novo Stage IV disease (p = 0.002), Luminal B subtype (p = 0.006), high Ki67 index (p = 0.036), resistance to adjuvant endocrine therapy (p = 0.0001) and clinical stage (p = 0.015). Reduced OS was also observed in association with somatic alterations in FGFR1 (p = 0.008), CCND2 (p = 0.012), RB1 (p = 0.029) or TP53 (p = 0.029) genes, but not in association with germline variants.

Conclusion

In this group of real-world HR+/HER2- MBC breast cancer patients younger age was not associated with poor outcomes. While current guidelines recommend treatment decisions based on tumor biology rather than age, young HR+ breast cancer patients are more likely to receive chemotherapy. Our findings support the development of biomarker-driven treatment strategies for these patients.
Development, comparison, and validation of four intelligent, practical machine learning models for patients with prostate-specific antigen in the gray zone
Authors: Liu Taobin , Zhang Xiaoming , Chen Ru , Deng Xinxi , Fu Bin
Published: June 2023

Purpose

Machine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier for patients in the prostate-specific antigen gray zone are to be developed and compared, identifying valuable predictors. Predictive models are to be integrated into actual clinical decisions.

Methods

Patient information was collected from December 01, 2014 to December 01, 2022 from the Department of Urology, The First Affiliated Hospital of Nanchang University. Patients with a pathological diagnosis of prostate hyperplasia or prostate cancer (any PCa) and having a prostate-specific antigen (PSA) level of 4–10 ng/mL before prostate puncture were included in the initial information collection. Eventually, 756 patients were selected. Age, total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), fPSA/tPSA, prostate volume (PV), prostate-specific antigen density (PSAD), (fPSA/tPSA)/PSAD, and the prostate MRI results of these patients were recorded. After univariate and multivariate logistic analyses, statistically significant predictors were screened to build and compare machine learning models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier to determine more valuable predictors.

Results

Machine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier exhibit higher predictive power than individual metrics. The area under the curve (AUC) (95% CI), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score of the LogisticRegression machine learning prediction model were 0.932 (0.881–0.983), 0.792, 0.824, 0.919, 0.652, 0.920, and 0.728, respectively; of the XGBoost machine learning prediction model were 0.813 (0.723–0.904), 0.771, 0.800, 0.768, 0.737, 0.793 and 0.767, respectively; of the GaussianNB machine learning prediction model were 0.902 (0.843–0.962), 0.813, 0.875, 0.819, 0.600, 0.909, and 0.712, respectively; and of the LGBMClassifier machine learning prediction model were 0.886 (0.809–0.963), 0.833, 0.882, 0.806, 0.725, 0.911, and 0.796, respectively. The LogisticRegression machine learning prediction model has the highest AUC among all prediction models, and the difference between the AUC of the LogisticRegression prediction model and those of XGBoost, GaussianNB, and LGBMClassifier is statistically significant (p < 0.001).

Conclusion

Machine learning prediction models based on LogisticRegression, XGBoost, GaussianNB, and LGBMClassifier algorithms exhibit superior predictability for patients in the PSA gray area, with the LogisticRegression model yielding the best prediction. The aforementioned predictive models can be used for actual clinical decision-making.​
Tumor cuproptosis and immune infiltration improve survival of patients with hepatocellular carcinoma with a high expression of ferredoxin 1
Authors: Quan Yingyao , Li Wei , Yan Rongrong , Cheng Jing , Xu Heng , Chen Lin
Published: June 2023

Background

Cuproptosis is a novel cell death pathway dependent on cellular copper ions and ferredoxin 1 (FDX1). Hepatocellular carcinoma (HCC) is derived from healthy liver as a central organ for copper metabolism. It remains no conclusive evidence whether cuproptosis is involved in survival improvement of patients with HCC.

Method

A 365–liver hepatocellular carcinoma (LIHC) cohort with RNA sequencing data and paired clinical and survival information was obtained from the The Cancer Genome Atlas (TCGA) dataset. A retrospective cohort of 57 patients with HCC with stages I/II/III was collected by Zhuhai People’s Hospital from August 2016 to January 2022. Low- or high-FDX1 groups were divided according to the median value of FDX1 expression. Cibersort, single-sample gene set enrichment analysis, and multiplex immunohistochemistry analyzed immune infiltration in LIHC and HCC cohorts. Cell proliferation and migration of HCC tissues and hepatic cancer cell lines were evaluated using the Cell Counting Kit-8. Quantitative real-time PCR and RNA interference measured and downregulated FDX1 expression. Statistical analysis was conducted by R and GraphPad Prism software.

Results

High FDX1 expression significantly enhanced survival of patients with LIHC from the TCGA dataset, which was also demonstrated through a retrospective cohort with 57 HCC cases. Immune infiltration was different between the low– and high–FDX1 expression groups. Natural killer cells, macrophages, and B cells were significantly enhanced, and PD-1 expression was low in the high-FDX1 tumor tissues. Meanwhile, we found that a high expression of FDX1 decreased cell viability in HCC samples. HepG2 cells with FDX1 expression are sensitive to Cu2+, and interference of FDX1 promoted proliferation and migration of tumor cells. The consistent results were also demonstrated in Hep3B cells.

Conclusion

This study reveals that cuproptosis and tumor immune microenvironment were together involved in improvement of survival in patients with HCC with a high expression of FDX1.
Governor vessel moxibustion for cancer-related fatigue in colorectal patients: a randomized trial
Authors: Li Huakang , Huang Wei , Du Kangming , Liu Wei , Wu Ziliang , Xu Bo , Li Qiang , Wang Yue , Lin Bing
Published: June 2023

Objective

This study aimed to investigate the efficacy and mechanism of action of Governor Vessel Moxibustion (GVM) in the treatment of Cancer-Related Fatigue (CRF) in patients who have completed treatment for colorectal cancer.

Methods

We randomly assigned 80 CRF patients in a 1:1 ratio to either the experimental group or the control group. During the three-week treatment period, both groups of patients received usual care for CRF provided by professional nurses. The experimental group received additional GVM treatment (three times a week, nine times total). The primary outcome was the mean change in total fatigue score from baseline to the end of treatment, assessed using the Chinese version of the Piper Fatigue Scale.

Results

At baseline, the total fatigue scores were 6.20 ± 0.12 in the experimental group and 6.16 ± 0.14 in the control group. At the end of treatment, the total fatigue scores decreased by 2.03 points (32.7% decrease from baseline) in the experimental group and by 0.99 points (15.6% decrease from baseline) in the control group. The absolute reduction in total fatigue scores in the experimental group was 1.04 points higher than in the control group (95% CI, 0.93 to 1.15; P<0.001), corresponding to a relative difference of 17.1% (95% CI, 15.2% to 18.9%; P<0.001). At the end of treatment, the experimental group showed greater reductions in interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels compared to the control group. No serious adverse events related to GVM treatment were observed.

Conclusion

GVM appears to be safe and effective for alleviating CRF in patients who have completed colorectal cancer treatment, which may be related to the modulation of IL-6 and TNF-α levels.

Trial registration

Chinese Clinical Trials Registry: ChiCTR2300069208.
Network targets for therapeutic brain stimulation: towards personalized therapy for pain
Authors: Motzkin Julian C. , Kanungo Ishan , D’Esposito Mark , Shirvalkar Prasad
Published: June 2023

Precision neuromodulation of central brain circuits is a promising emerging therapeutic modality for a variety of neuropsychiatric disorders. Reliably identifying in whom, where, and in what context to provide brain stimulation for optimal pain relief are fundamental challenges limiting the widespread implementation of central neuromodulation treatments for chronic pain. Current approaches to brain stimulation target empirically derived regions of interest to the disorder or targets with strong connections to these regions. However, complex, multidimensional experiences like chronic pain are more closely linked to patterns of coordinated activity across distributed large-scale functional networks. Recent advances in precision network neuroscience indicate that these networks are highly variable in their neuroanatomical organization across individuals. Here we review accumulating evidence that variable central representations of pain will likely pose a major barrier to implementation of population-derived analgesic brain stimulation targets. We propose network-level estimates as a more valid, robust, and reliable way to stratify personalized candidate regions. Finally, we review key background, methods, and implications for developing network topology-informed brain stimulation targets for chronic pain.
A meta-analysis: single or double dartos flap layer in tubularized incised plate urethroplasty to prevent urethrocutaneous fistula?
Authors: Yuan Yi , Wang Yu-wen , Liang Yan-nei , Wang Yu-ying , Ho Jun-jie , Peng Tong-yu , Zhao Zhang , Deng Nan
Published: June 2023

Backgrounds

Urethrocutaneous fistula is one of the most common complications after urethroplasty. This meta-analysis aims to evaluate the superiority of double dartos flap to single dartos flap in preventing fistula during tubularized incised plate urethroplasty (TIPU), which is one of the most frequently used operations for hypospadias.

Methods

We extracted clinical trials under the following included criteria: (1) children with TIPU; (2) a comparison of single and double flap layer; and (3) record of complications with the following excluded criteria: (1) non-comparison and (2) lack of data. Finally, 13 studies from PubMed, Cochrane Library, Scopus, and Embase have been investigated, with a total of 1,185 patients from 2005 to 2022. The quality assessment was conducted according to the Cochrane handbook and the Newcastle–Ottawa scale. A mixed-effect model was utilized to weigh the risk of fistula, phallic rotation, meatal stenosis, and wound dehiscence by the Review Manager V.5.4 software.

Results

The double dartos flap layer group excels in descending the risk of postoperative fistula [odds ratio (OR) = 9.56; 95% confidence interval (CI) (4.76, 19.22); P < 0.00001] and phallic rotation [OR = 31.26; 95% CI (9.60, 101.84); P < 0.00001], while there are no differences in the rate of meatal stenosis [OR = 1.49; 95% CI (0.73, 2.70); P = 0.31] and wound dehiscence [OR = 2.30; 95% CI (0.80, 6.63); P = 0.12].

Conclusions

The routine utility of a double dartos flap layer is recommended as a potential treatment during the tubularized incised plate urethroplasty.

Systematic Review Registration

identifier PROSPERO CRD42022366294.
Management of tetralogy of Fallot in the pediatric intensive care unit
Authors: Hammett Owen , Griksaitis Michael J.
Published: June 2023

Tetralogy of Fallot (ToF) is one of the most common congenital cyanotic heart lesions and can present to a variety of health care professionals, including teams working in pediatric intensive care. Pediatric intensive care teams may care for a child with ToF pre-operatively, peri-operatively, and post-operatively. Each stage of management presents its own unique challenges. In this paper we discuss the role of pediatric intensive care in each stage of management.
Efficacy and safety of consolidation durvalumab after chemoradiation therapy for stage III non-small-cell lung cancer: a systematic review, meta-analysis, and meta-regression of real-world studies
Authors: Zhang Yatong , Tian Yumei , Zheng Li , Sun Xuelin , Zhao Zinan , Zheng Yujing , Tian Jinhui
Published: June 2023

Background: The current review aimed to pool real-world evidence on the efficacy and toxicity of consolidation durvalumab for stage III unresectable non-small cell lung cancer (NSCLC) after curative chemoradiotherapy.

Methods: PubMed, CENTRAL, ScienceDirect, Embase, and Google Scholar were searched for observational studies reporting the use of durvalumab for NSCLC till 12th April 2022. Twenty-three studies with 4,400 patients were included.

Results: The pooled 1-year overall survival (OS) and progression-free survival rates (PFS) were 85% (95% CI: 81%–89%) and 60% (95% CI: 56%–64%) respectively. Pooled incidence of all-grade pneumonitis, grade ≥3 pneumonitis and discontinuation of durvalumab due to pneumonitis were 27% (95% CI: 19%–36%), 8% (95% CI: 6%–10%) and 17% (95% CI: 12%–23%) respectively. The pooled proportion of patients experiencing endocrine, cutaneous, musculoskeletal, and gastrointestinal adverse events was 11% (95% CI: 7%–18%), 8% (95% CI: 3%–17%), 5% (95% CI: 3%–6%), and 6% (95% CI: 3%–12%), respectively.

Conclusion: Meta-regression indicated that performance status significantly influenced PFS, while age, time to durvalumab, and programmed death-ligand 1 status significantly affected pneumonitis rates. Real-world evidence suggests that the short-term efficacy and safety of durvalumab are consistent with that of the PACIFIC trial. The congruence of results lends support to durvalumab use in improving outcomes of unresectable stage III NSCLC.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324663, identifier CRD42022324663.
N-linoleyltyrosine resisted the growth of non-small cell lung cancer cells via the regulation of CB1 and CB2 involvement of PI3K and ERK pathways
Authors: Hu Yan , Zhao Zhe , Liu Yuan-Ting , Xu Ze-Cheng , Li Jing-Yi , Yang Zheng-Yu , Rui-Wang  , Yang Yun-Qi , Zhang Jia-Hui , Qiu Si-Yuan , He Tao , Wu Yi-Ying , Liu Sha
Published: June 2023

Background: N-linoleyltyrosine (NITyr), one of the anandamide analogs, exerts activity via the endocannabinoid receptors (CB1 and CB2), which showed anti-tumor effects in various tumors. Therefore, we speculated that NITyr might show anti-non-small cell lung cancer (NSCLC) effects via the CB1 or CB2 receptor. The purpose of the investigation was to reveal the anti-tumor ability of NITyr on A549 cells and its mechanisms.

Methods: The viability of A549 cells was measured by MTT assay, and the cell cycle and apoptosis were both examined by flow cytometry; in addition, cell migration was tested by wound healing assay. Apoptosis-related markers were measured by immunofluorescence. The downstream signaling pathways (PI3K, ERK, and JNK) of CB1 or CB2 were examined through Western blotting. The expressions of CB1 and CB2 were detected by immunofluorescence. Finally, the AutoDock software was used to validate the binding affinity between the targets, such as CB1 and CB2, with NITyr.

Results: We found that NITyr inhibited cell viability, hindered the cell cycle, resulted in apoptosis, and inhibited migration. The CB1 inhibitor, AM251, and the CB2 inhibitor, AM630, weakened the aforementioned phenomenon. The immunofluorescence assay suggested that NITyr upregulated the expression of CB1 and CB2. Western blot analysis indicated that NITyr upregulated the expression of p-ERK, downregulated the expression of p-PI3K, and did not affect p-JNK expression. In conclusion, NITyr showed a role in inhibiting NSCLC through the activation of CB1 and CB2 receptors involved in PI3K and ERK pathways.
Paraben exposure through drugs in the neonatal intensive care unit: a regional cohort study
Authors: Iacobelli Silvia , Commins Marie , Lorrain Simon , Gouyon Beatrice , Ramful Duksha , Richard Magali , Grondin Anthony , Gouyon Jean-Bernard , Bonsante Francesco
Published: June 2023

Background and objectives: Environmental factors influence the development of very preterm infants (VPIs, born at less than 32 weeks of gestation). It is important to identify all potential sources of paraben exposure in these vulnerable infants. We aimed to quantify paraben exposure via drug administration in a cohort of VPI cared for in neonatal intensive care units (NICUs).

Methods: A prospective, observational study was carried out over a five-year period in a regional setting (two NICUs using the same computerized order-entry system). The main outcome was exposure to paraben-containing drugs. The secondary outcomes were: time of the first exposure, daily intake, number of infants exceeding paraben acceptable daily intake (ADI: 0–10 mg/kg/d), duration of exposure, and cumulative dose.

Results: The cohort consisted of 1,315 VPIs [BW 1129.9 (±360.4) g]. Among them, 85.5% were exposed to paraben-containing drugs. In 40.4% of infants, the first exposure occurred during the second week of life. Mean paraben intake and duration of exposure were, respectively, 2.2 (±1.4) mg/kg/d and 33.1 (±22.3) days. The cumulative paraben intake was 80.3 (±84.6) mg/kg. The ADI was exceeded in 3.5% of exposed infants. Lower GA was associated with higher intake and longer exposure (p < 0.0001). The main molecules involved in paraben exposure were: sodium iron feredetate, paracetamol, furosemide, and sodium bicarbonate + sodium alginate.

Conclusion: Commonly used drugs are potential source of parabens, and ADI can be easily exceeded in VPIs cared for in NICUs. Efforts are needed to identify paraben-free alternative formulations for these vulnerable infants.
Cold water immersion of the hand and forearm during half-time improves intermittent exercise performance in the heat
Authors: Iwahashi Manami , Chaen Yudai , Yanaoka Takuma , Kurokawa Yasutsugu , Hasegawa Hiroshi
Published: June 2023

The present study aimed to investigate the effect of cold water immersion of the hand and forearm during half-time (HT) on intermittent exercise performance and thermoregulation by imitating intermittent athletic games in the heat. In a randomized crossover design, 11 physically active men performed the first half (first and second block) and second half (third and fourth block) intermittent cycling exercise protocol, which consisted of a 5-s maximal power pedalling (body weight × 0.075 kp) every minute separated by 25-s of unloaded pedalling and rest (30 s) in the heat (33°C, 50% relative humidity). The two-halves were separated by a 15-min HT. During HT, the participants were assigned to the CON (sedentary resting) or COOL (immersion of hands and forearms in cold water at 15–17°C) condition. The mean power output in the second half was significantly greater (third and fourth block:p< 0.05) in the COOL than in the CON condition. Moreover, there was a significant decrease in the rectal (0.54 ± 0.17°C,p< 0.001) and mean skin (1.86 ± 0.34°C,p< 0.05) temperatures of the COOL condition during HT. Furthermore, the heart rate (16 ± 7 bpm,p< 0.05) and skin blood flow (40.2 ± 10.5%,p< 0.001) decreased at the end of HT in the COOL condition. In the second half, thermal sensation was more comfortable in the COOL condition (p< 0.001). Cold water immersion of the hand and forearm during HT improved physiological and reduced perceived heat stress. Moreover, it prevented a reduction in intermittent exercise performance in the second half.
Genetic diversity and population structure of bermudagrass (Cynodon spp.) revealed by genotyping-by-sequencing
Authors: Singh Lovepreet , Wu Yanqi , McCurdy James D. , Stewart Barry R. , Warburton Marilyn L. , Baldwin Brian S. , Dong Hongxu
Published: June 2023

Bermudagrass (Cynodon spp.) breeding and cultivar development is hampered by limited information regarding its genetic and phenotypic diversity. To explore diversity in bermudagrass, a total of 206 Cynodon accessions consisting of 193 common bermudagrass (C. dactylon var. dactylon) and 13 African bermudagrass (C. transvaalensis) accessions of worldwide origin were assembled for genetic characterization. Genotyping-by-sequencing (GBS) was employed for genetic marker development. With a minor allele frequency of 0.05 and a minimum call rate of 0.5, a total of 37,496 raw single nucleotide polymorphisms (SNPs) were called de novo and were used in the genetic diversity characterization. Population structure analysis using ADMIXTURE revealed four subpopulations in this germplasm panel, which was consistent with principal component analysis (PCA) and phylogenetic analysis results. The first three principal components explained 15.6%, 10.1%, and 3.8% of the variance in the germplasm panel, respectively. The first subpopulation consisted of C. dactylon accessions from various continents; the second subpopulation was comprised mainly of C. transvaalensis accessions; the third subpopulation contained C. dactylon accessions primarily of African origin; and the fourth subpopulation represented C. dactylon accessions obtained from the Oklahoma State University bermudagrass breeding program. Genetic diversity parameters including Nei’s genetic distance, inbreeding coefficient, and Fst statistic revealed substantial genetic variation in the Cynodon accessions, demonstrating the potential of this germplasm panel for further genetic studies and cultivar development in breeding programs.