bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell RNA datasets and bulk RNA datasets analysis demonstrated C1Q+ tumor-associated macrophage as a major and antitumor immune cell population in osteosarcoma
Authors: Tu Jihao , Wang Duo , Zheng XiaoTian , Liu Bin 
Published: February 2023

BackgroundOsteosarcoma is the most frequent primary bone tumor with a poor prognosis. Immune infiltration proved to have a strong impact on prognosis. We analyzed single-cell datasets and bulk datasets to confirm the main immune cell populations and their properties in osteosarcoma.MethodsThe examples in bulk datasets GSE21257 and GSE32981 from the Gene Expression Omnibus database were divided into two immune infiltration level groups, and 34 differentially expressed genes were spotted. Then, we located these genes among nine major cell clusters and their subclusters identified from 99,668 individual cells in single-cell dataset GSE152048 including 11 osteosarcoma patients. Especially, the markers of all kinds of myeloid cells identified in single-cell dataset GSE152048 were set to gene ontology enrichment. We clustered the osteosarcoma samples in the TARGET-OS from the Therapeutically Applicable Research to Generate Effective Treatments dataset into two groups by complete component 1q positive macrophage markers and compared their survival.ResultsCompared with the low-immune infiltrated group, the high-immune infiltrated group showed a better prognosis. Almost all the 34 differentially expressed genes expressed higher or exclusively among myeloid cells. A group of complete component 1q-positive macrophages was identified from the myeloid cells. In the bulk dataset TARGET-OS, these markers and the infiltration of complete component 1q-positive macrophages related to longer survival.ConclusionsComplete component 1q-positive tumor-associated macrophages were the major immune cell population in osteosarcoma, which contributed to a better prognosis.
Strong hydrodynamic processes observed in the Mediterranean Cassidaigne submarine canyon
Authors: Brun Lénaïg , Pairaud Ivane , Jacinto Ricardo Silva , Garreau Pierre , Dennielou Bernard 
Published: February 2023

IntroductionSubmarine canyons are incisive morphologies that play an important role in the exchange between shallow and deep waters. They interact with the general circulation and induce a specific circulation locally oriented by the morphology. The characteristics of the physical processes at play, the way they interact with each other and the influence of extreme events is still an open question as few observations are available. To answer this question and to improve the representation of submarine canyons in numerical models, it is key to understand the specific circulation patterns and their transitions in these specific environments.MethodsThis paper presents observations of currents, temperature and turbidity along the Cassidaigne canyon, northwestern Mediterranean Sea. Two oceanographic cruises carried out in 2017 and 2019 gathered data from the outer shelf and canyon head at 100-400 m depth to the base of the continental slope at 1900 m depth.Results and DiscussionThe circulation in the Cassidaigne area is subject to upwelling and downwelling-favorable winds, to the Northern Current and its associated mesoscale structures and is oriented by the local morphology. Upwellings occur both during stratified and non-stratified conditions. They are triggered by a wind forcing higher than 14 m s–1 and their consecutive relaxations are marked by a counter-current. Near the canyon head and on the shelf, the current orientation depends on the stratification, the wind, the bottom morphology and the general circulation. The mesoscale variability of the Northern Current can lead to its intrusion over the shelf leading to barotropic cross currents over the canyon. At 1700 m depth, a quasi-permanent residual up-canyon flow is observed in a narrow gorge area and can be extrapolated to the canyon body. Finally, turbidity currents were observed for the first time in connection with upwelling events, suggesting the key role of canyons’ internal hydrodynamics on shelf sedimentary processes.
Case report: A novel homozygous histidine triad nucleotide-binding protein 1 mutation featuring distal hereditary motor-predominant neuropathy with rimmed vacuoles
Authors: Jiang Nan , Vazquez Do Campo Rocio , Kazamel Mohamed 
Published: February 2023

IntroductionRecessive mutations in the gene encoding the histidine triad nucleotide-binding protein 1 (HINT1) are associated with axonal motor-predominant Charcot–Marie–Tooth (CMT) disease with neuromyotonia. A total of 24 HINT1 gene mutations have been reported so far. Some of these cases had mild to moderate elevations of creatinine kinase with no earlier reports of muscle biopsy findings in these cases. In this study, we describe a patient with axonal motor-predominant neuropathy and myopathy with rimmed vacuoles, likely due to a novel HINT1 gene mutation.Case reportA 35-year-old African American man presented with insidious onset and progressive symmetric distal leg weakness followed by hand muscle atrophy and weakness since the age of 25. He had no muscle cramps or sensory complaints. His 38-year-old brother developed similar symptoms beginning in his early 30 s. On neurologic examination, the patient had distal weakness and atrophy in all limbs, claw hands, pes cavus, absent Achilles reflexes, and normal sensory examination. Electrodiagnostic studies revealed absent/reduced compound motor action potential amplitudes distally with normal sensory responses with no neuromyotonia. His sural nerve biopsy showed a chronic non-specific axonal neuropathy, and a biopsy of the tibialis anterior muscle demonstrated myopathic features and several muscle fibers harboring rimmed vacuoles without inflammation in addition to chronic denervation changes. A homozygous variant, p.I63N (c.188T &gt; A), in the HINT1 gene was found in both brothers.ConclusionWe describe a novel, likely pathogenic, HINT1 pI63N (c.188T &gt; A) homozygous variant associated with hereditary axonal motor-predominant neuropathy without neuromyotonia in two African American brothers. The presence of rimmed vacuoles on muscle biopsy raises the possibility that mutations in the HINT1 gene may also cause myopathy.
Analysis of characteristics of intracranial cavernous angioma and bleeding factors in middle-aged and elderly patients
Authors: Xiu Chao , Ni Donghe , Zhao Jincui , Yu Yang 
Published: February 2023

ObjectiveIntracranial cavernous angioma (ICA) is a cerebrovascular malformation. It causes local neurological dysfunction, epilepsy, intracranial hemorrhage (ICH) and other symptoms, seriously affecting the safety of patients. This study analyzed middle-aged and elderly patients with ICA in our hospital, summarized the characteristics of the disease and investigated the related factors of ICH.MethodsWe conducted a retrospective analysis of 120 middle-aged and elderly patients who were diagnosed with ICA by magnetic resonance imaging in our hospital from March 2018 to September 2021. The cases were assigned to either a bleeding group (i.e., the experimental group) or a non-bleeding group (i.e., the control group). The characteristics of the disease, including gender, age, number of lesions, form and symptoms of onset, distribution of lesions, blood supply vessels in the lesion area, size of the lesion and presence of bleeding, were summarized and analyzed. The relationship between these factors and ICH was investigated, and the data were analyzed using SPSS 25.0 software.ResultsThere were 56 cases in the experimental group and 64 cases in the control group. A univariate analysis showed that gender, age, body mass index, blood lipids, number of lesions, course of the disease, onset of symptoms and disease characteristics were not associated with ICH in the middle-aged and elderly patients with ICA (P &gt; 0.05). The maximum diameter, volume, location and blood supply area of the lesions were related to ICA complicated with ICH (P &lt; 0.05). A multivariate unconditional logistic regression analysis revealed that the maximum diameter, volume, location and blood supply area of the lesions were independent risk factors for ICH in the middle-aged and elderly patients with ICA. The odds ratio (OR) of the maximum diameter of the lesion was 4.410, the OR of the lesion volume was 7.316, the OR of the lesion site was 7.470, and the OR of the blood supply area was 1.6588.ConclusionIntracranial cavernous angioma lesions in middle-aged and elderly patients occur mainly in the supratentorial area, with a small part located in the infratentorial area. The main form of the disease is chronic recurrence. The occurrence of bleeding is related to the size, location and blood supply of the lesion.
Effects of a high-prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The “Gut Feelings” randomised controlled trial
Authors: Freijy Tanya M. , Cribb Lachlan , Oliver Georgina , Metri Najwa-Joelle , Opie Rachelle S. , Jacka Felice N. , Hawrelak Jason A. , Rucklidge Julia J. , Ng Chee H. , Sarris Jerome 
Published: February 2023

BackgroundPreliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health.Methods“Gut Feelings” was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures.ResultsA modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen’sd= −0.60, 95% confidence interval (CI) = −1.18, −0.03;p= 0.039]. There was no evidence of symptom improvement from the probiotic (d= −0.19, 95% CI = −0.75, 0.38;p= 0.51) or synbiotic treatments (d= −0.03, 95% CI = −0.59, 0.53;p= 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events.ConclusionA high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, though further evidence is required. Results are limited by the relatively small sample size.Clinical trial registrationhttps://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372753, identifier ACTRN12617000795392.
Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents
Authors: Invernizzi Azzurra , Rechtman Elza , Oluyemi Kristie , Renzetti Stefano , Curtin Paul , Colicino Elena , Ambrosi Claudia , Mascaro Lorella , Patrono Alessandra , Corbo Daniele , Cagna Giuseppa , Gasparotti Roberto , Reichenberg Abraham , Tang Cheuk Y. , Smith Donald R. , Placidi Donatella , Lucchini Roberto G. , Wright Robert O. , Horton Megan K. 
Published: February 2023

IntroductionAdolescent exposure to neurotoxic metals adversely impacts cognitive, motor, and behavioral development. Few studies have addressed the underlying brain mechanisms of these metal–associated developmental outcomes. Furthermore, metal exposure occurs as a mixture, yet previous studies most often consider impacts of each metal individually. In this cross–sectional study, we investigated the relationship between exposure to neurotoxic metals and topological brain metrics in adolescents.MethodsIn 193 participants (53% females, ages: 15–25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of four metals (manganese, lead, copper, and chromium) in multiple biological media (blood, urine, hair, and saliva) and acquired resting–state functional magnetic resonance imaging scans. Using graph theory metrics, we computed global and local efficiency (global:GE; local:LE) in 111 brain areas (Harvard Oxford Atlas). We used weighted quantile sum (WQS) regression models to examine association between metal mixtures and each graph metric (GE or LE), adjusted for sex and age.ResultsWe observed significant negative associations between the metal mixture and GE and LE [βGE = −0.076, 95% CI (−0.122, −0.031); βLE= −0.051, 95% CI (−0.095, −0.006)]. Lead and chromium measured in blood contributed most to this association for GE, while chromium measured in hair contributed the most for LE.DiscussionOur results suggest that exposure to this metal mixture during adolescence reduces the efficiency of integrating information in brain networks at both local and global levels, informing potential neural mechanisms underlying the developmental toxicity of metals. Results further suggest these associations are due to combined joint effects to different metals, rather than to a single metal.
A bibliometric analysis of apoptosis in glaucoma
Authors: Zhang Jia-Heng , Wang Mei-Juan , Tan Ya-Ting , Luo Jia , Wang Shu-Chao 
Published: February 2023

BackgroundGlaucoma is the first irreversible and second blindness disease, which is characterized by the death of retinal ganglion cells (RGCs) and degeneration of the optic nerve. Previous works have indicated that apoptosis is the main reason for RGC death in glaucoma. Although many studies have investigated the mechanism of apoptosis and different strategies targeting apoptosis to protect the RGCs and finally recover the impaired vision in the glaucoma. However, the global trend and hotspots of apoptosis in glaucoma have not been well illustrated and discussed.MethodsDocuments were extracted from the Web of Science Core Collection on November 2, 2022. We selected articles and reviews published in English from January 1, 1999 to November 1, 2022 to perform visual analysis and statistical analysis of countries, institutions, authors, references and keywords by VOSviewer 1.6.18 and CiteSpace 5.8.ResultsThe publications about apoptosis in glaucoma show an increasing trend over time. Besides, the authors, institutions in the US and China published the most numbers of articles with the highest citation, which may be leading the research in the field of apoptosis in glaucoma. Last, series of advanced research results, technology and treatment for glaucoma, such as the discovery of key regulatory mechanisms on RGC apoptosis are emerging and will provide precise strategies for the treatment of glaucoma.ConclusionThis research will broaden our comprehension about the role of apoptosis in the process of glaucoma, and provide guidelines for us in basic research and disease treatment in the further.
Pharmacokinetics of single- and multiple-dose flumatinib in patients with chronic phase chronic myeloid leukemia
Authors: Jiang Bo , Qi Junyuan , Sun Mingyuan , Zheng Weiwei , Wei Yongyue , Wang Jianxiang , Zhang Fengkui 
Published: February 2023

IntroductionFlumatinib is a novel, oral breakpoint cluster region-abelson (BCR-ABL) tyrosine kinase inhibitor that has demonstrated manageable safety and promising efficacy in patients with newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML). MethodsThis study evaluated the pharmacokinetic (PK) profiles of flumatinib mesylate tablets at a dose of 400 mg and 600 mg in patients with CML-CP. The study was registered at chictr.org Identifier (ChiCTR2100044700). In this open-label, pharmacokinetic study, eligible patients were administered a single-dose of flumatinib 400 mg or 600 mg on day 1, followed by 2-day washout and 8 consecutive days of once-daily administration. Serial plasma samples were assayed for flumatinib and its metabolites (N-demethylate metabolite M1 and amide-bond hydrolytic metabolite M3).ResultsTwenty-nine patients were assigned to flumatinib 400 mg (n=14) or 600 mg (n=15). Serum concentrations of flumatinib reached maximum measured plasma concentration (Cmax) at a median time of 2 hours after each single dose, and then eliminated slowly with a mean apparent terminal disposition half-life (t1/2) from 16.0 to 16.9 hours. Following single- and multiple-dose administration, flumatinib exposure (Cmax, area under the concentration-time curve from 0 to t hours (AUC0-t), area under the concentration-time curve from 0 hours to infinity (AUC0-∞)) increased in an approximately dose-proportional manner. There was approximately 4.1- and 3.4- fold drug accumulation at steady-state after multiple-dose administration at 400 mg and 600 mg, respectively. The drug-related AEs associated with both treatments were primarily low-grade and tolerable events.ConclusionAnalysis of PK parameters indicated that flumatinib exposure increased in an approximately dose-proportional manner. Further research needs to be conducted in a large sample-size study.
Dynamic radiomics for predicting the efficacy of antiangiogenic therapy in colorectal liver metastases
Authors: Qu Hui , Zhai Huan , Zhang Shuairan , Chen Wenjuan , Zhong Hongshan , Cui Xiaoyu 
Published: February 2023

Background and objectiveFor patients with advanced colorectal liver metastases (CRLMs) receiving first-line anti-angiogenic therapy, an accurate, rapid and noninvasive indicator is urgently needed to predict its efficacy. In previous studies, dynamic radiomics predicted more accurately than conventional radiomics. Therefore, it is necessary to establish a dynamic radiomics efficacy prediction model for antiangiogenic therapy to provide more accurate guidance for clinical diagnosis and treatment decisions.MethodsIn this study, we use dynamic radiomics feature extraction method that extracts static features using tomographic images of different sequences of the same patient and then quantifies them into new dynamic features for the prediction of treatmentefficacy. In this retrospective study, we collected 76 patients who were diagnosed with unresectable CRLM between June 2016 and June 2021 in the First Hospital of China Medical University. All patients received standard treatment regimen of bevacizumab combined with chemotherapy in the first-line treatment, and contrast-enhanced abdominal CT (CECT) scans were performed before treatment. Patients with multiple primary lesions as well as missing clinical or imaging information were excluded. Area Under Curve (AUC) and accuracy were used to evaluate model performance. Regions of interest (ROIs) were independently delineated by two radiologists to extract radiomics features. Three machine learning algorithms were used to construct two scores based on the best response and progression-free survival (PFS).ResultsFor the task that predict the best response patients will achieve after treatment, by using ROC curve analysis, it can be seen that the relative change rate (RCR) feature performed best among all features and best in linear discriminantanalysis (AUC: 0.945 and accuracy: 0.855). In terms of predicting PFS, the Kaplan–Meier plots suggested that the score constructed using the RCR features could significantly distinguish patients with good response from those with poor response (Two-sided P&lt;0.0001 for survival analysis).ConclusionsThis study demonstrates that the application of dynamic radiomics features can better predict the efficacy of CRLM patients receiving antiangiogenic therapy compared with conventional radiomics features. It allows patients to have a more accurate assessment of the effect of medical treatment before receiving treatment, and this assessment method is noninvasive, rapid, and less expensive. Dynamic radiomics model provides stronger guidance for the selection of treatment options and precision medicine.
Anti-AQP4–IgG-positive Leigh syndrome: A case report and review of the literature
Authors: Chen Jun , Wang Jianjun , Gan Jing , Luo Rong , Yang Zuozhen , Liang Mengmeng , Chen Xiaolu 
Published: February 2023

BackgroundLeigh syndrome (LS; OMIM: 256000) is a progressive neurodegenerative disease caused by genetic mutations resulting in mitochondrial oxidative phosphorylation defects. The prognosis is poor, with most children dying before the age of 2 years. MT-ATP6 variants are the most common mitochondrial DNA mutations in LS. MT-ATP6 variant-induced LS may trigger autoimmunity, and immunotherapy might be effective. Here, we present the first pediatric case of anti-aquaporin 4 (AQP4)–IgG-positive LS caused by an MT-ATP6 variant.CaseA 1-year-old boy was hospitalized due to recurrent fever, cough, and developmental regression. Two months previously, he had developed reduced responses to stimulation and psychomotor retardation. After admission, his condition deteriorated and respiratory failure ensued. Magnetic resonance imaging of the brain showed symmetrical small patchy abnormal signals around the third ventricle, pons, and dorsal periaqueductal gray matter in the dorsal medulla. Laboratory tests revealed anti-AQP4–IgG antibodies. Anti-infection, immunoglobulin, and glucocorticoid therapy were administered for symptomatic treatment. Genetic testing revealed a de novo homogeneous pathogenic variant of MT-ATP6 (m.9176T &gt; C, mutation ratio: 99.97%). The patient was diagnosed with anti-AQP4–IgG-positive LS, treated with “cocktail therapy” (vitamins B1, B2, C, and E, l-carnitine, and coenzyme Q10), and discharged after his condition improved. A literature review revealed that LS-induced mitochondrial defects can impact the immune system; hence, immunotherapy and early mitochondrial cocktail therapy may improve outcomes.ConclusionAnti-AQP4–IgG-positive LS is very rare. Patients with LS with the m.9176T  &gt; C variant of MT-ATP6 may be susceptible to autoimmune damage of the central nervous system. Early cocktail therapy combined with immunotherapy may improve their prognosis.