bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of adipokine and ghrelin levels on BMD and fracture risk: an updated systematic review and meta-analysis
Authors: Lee Seoyul , Kim Jeong Hun , Jeon Yun Kyung , Lee Jung Sub , Kim Keunyoung , Hwang Sun-Kyung , Kim Jae Ho , Goh Tae Sik , Kim Yun Hak 
Published: April 2023

ContextCirculating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed.ObjectiveThis study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis.Data sourcesStudies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed.Study selectionWe included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status.Data extractionWe extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies.Data synthesisA meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18).ConclusionsSerum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.
Case report: A novel mutation of RecQ-like helicase 5 in a Chinese family with early myocardial infarction, coronary artery disease, and stroke hemiplegia
Authors: Tang Yi , Wang Qian , Zhang Wei-Kai , Liu Yu-Xing , Zheng Zhao-Fen , Fan Liang-Liang , Liu Lv , He Jin 
Published: April 2023

Background: Myocardial infarction (MI) is a type of severe coronary artery disease (CAD) that can lead to heart failure and sudden cardiac death. The prevalence of heart failure globally is estimated at 1%–2%, of which ∼60% of cases are the consequence of MI as the primary cause. At present, several disease-causing genes have been identified that may be responsible for MI, such as autophagy-related 16-like 1 (ATG16L1) and RecQ-like helicase 5 (RECQL5).Methods: In this study, we enrolled a Chinese family with MI, CAD, and stroke hemiplegia. Whole-exome sequencing was applied to analyze the genetic lesion of the proband. Sanger sequencing was used to validate the candidate mutation in five family members and 200 local control cohorts.Results: After data filtering, we detected a novel mutation (NM_004259: c.1247T&gt;C/p.I416T) of RECQL5 in the proband. Sanger sequencing further validated that the novel mutation was existent in the affected individuals, including the proband’s younger sister and her mother, and absent in the other healthy family members and 200 local control cohorts. Furthermore, bioinformatics analysis confirmed that the novel mutation, located in a highly evolutionarily conserved site, was predicted to be deleterious and may change the hydrophobic surface area and aliphatic index of RECQL5.Conclusion: Here, we report the second mutation (NM_004259: c.1247T&gt;C/p.I416T) of RECQL5 underlying MI and CAD by whole-exome sequencing. Our study expanded the spectrum of RECQL5 mutations and contributed to genetic diagnosis and counseling of MI and CAD.
Compound heterozygous FAM20C gene variants in a patient with severe Raine syndrome: a case report
Authors: Chirteș Camelia , Bogliș Alina , Toth Andrea , Rac Corina , Bănescu Claudia 
Published: April 2023

Raine syndrome is a congenital disorder caused by biallelic mutations in the FAM20C gene. While most diagnosed cases of the syndrome are lethal in the first few months of life, there are also reports of non-lethal cases with Raine syndrome. The characteristic of this syndrome is typical facial dysmorphism and generalized osteosclerosis, as well as possible intracranial calcification, hearing loss, and seizures. We report a case of a 4-day-old patient at the time of examination, born with a distinct facial dysmorphism, short neck, narrow chest, and curved tibia. The parents, affirmative gypsy and non-consanguineous, had a previous male child born with the same phenotype who died at 4 months old. The computed tomography scan revealed choanal atresia, while transfontanelar ultrasound showed hypoplasia of the frontal and temporal lobes, corpus callosum dysgenesis, and multiple areas of intracranial hyperechogenicity. The chest X-Ray revealed generalized increased bone density. A skeletal disorders gene panel was performed which identified two variants in the FAM20C gene: a pathogenic variant c.1291C&gt;T (p.Gln431*) and a likely pathogenic variant (c.1135G&gt;A) (p.Gly379Arg), confirming the clinical diagnosis. The parents were also tested, and each was found to carry one of the variants. The particularity of this case is the severe phenotype in a compound heterozygous case that consists of FAM20C c.1291C&gt;T (p.Gln431*) variant that has recently been reported in the literature. Also, our case is one of the few compound-heterozygous mutations in the FAM20C gene that has been described in a non-consanguineous marriage.
Genome-wide analysis of RNA-binding proteins co-expression with alternative splicing events in mitral valve prolapse
Authors: Zhao Meng , Zhou Jingxin , Tang Yihu , Liu Mingzhu , Dai Yawei , Xie Hui , Wang Zihao , Chen Liang , Wu Yanhu 
Published: April 2023

ObjectivesWe investigated the role and molecular mechanisms of RNA-binding proteins (RBPs) and their regulated alternative splicing events (RASEs) in the pathogenesis of mitral valve prolapse (MVP). MethodsFor RNA extraction, we obtained peripheral blood mononuclear cells (PBMCs) from five patients with MVP, with or without chordae tendineae rupture, and five healthy individuals. High-throughput sequencing was used for RNA sequencing (RNA-seq). Differentially expressed genes (DEGs) analysis, alternative splicing (AS) analysis, functional enrichment analysis, co-expression of RBPs, and alternative splicing events (ASEs) analysis were conducted.ResultsThe MVP patients exhibited 306 up-regulated genes and 198 down-regulated genes. All down- and up-regulated genes were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, MVP was closely associated with the top 10 enriched terms and pathways. In MVP patients, 2,288 RASEs were found to be significantly different, and four suitable RASEs (CARD11 A3ss, RBM5 ES, NCF1 A5SS, and DAXX A3ss) were tested. We identified 13 RNA-binding proteins (RBPs) from the DEGs and screened out four RBPs (ZFP36, HSPA1A, TRIM21, and P2RX7). We selected four RASEs based on the co-expression analyses of RBPs and RASEs, including exon skipping (ES) of DEDD2, alternative 3′ splice site (A3SS) of ETV6, mutually exclusive 3′UTRs (3pMXE) of TNFAIP8L2, and A3SS of HLA-B. Furthermore, the selected four RBPs and four RASEs were validated by reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and showed high consistency with RNA sequencing (RNA-seq).ConclusionDysregulated RBPs and their associated RASEs may play regulatory roles in MVP development and may therefore be used as therapeutic targets in the future.
Mesenchymal stem cell-derived exosomes for treatment of sepsis
Authors: Homma Kento , Bazhanov Nikolay , Hashimoto Kazuki , Shimizu Masaru , Heathman Thomas , Hao Qi , Nawgiri Ranjana , Muthukumarana Vidarshi , Lee Jae Woo , Prough Donald S. , Enkhbaatar Perenlei 
Published: April 2023

IntroductionThe pathogenesis of sepsis is an imbalance between pro-inflammatory and anti-inflammatory responses. At the onset of sepsis, the lungs are severely affected, and the injury progresses to acute respiratory distress syndrome (ARDS), with a mortality rate of up to 40%. Currently, there is no effective treatment for sepsis. Cellular therapies using mesenchymal stem cells (MSCs) have been initiated in clinical trials for both ARDS and sepsis based on a wealth of pre-clinical data. However, there remains concern that MSCs may pose a tumor risk when administered to patients. Recent pre-clinical studies have demonstrated the beneficial effects of MSC-derived extracellular vesicles (EVs) for the treatment of acute lung injury (ALI) and sepsis.MethodsAfter recovery of initial surgical preparation, pneumonia/sepsis was induced in 14 adult female sheep by the instillation of Pseudomonas aeruginosa (~1.0×1011 CFU) into the lungs by bronchoscope under anesthesia and analgesia. After the injury, sheep were mechanically ventilated and continuously monitored for 24 h in a conscious state in an ICU setting. After the injury, sheep were randomly allocated into two groups: Control, septic sheep treated with vehicle, n=7; and Treatment, septic sheep treated with MSC-EVs, n=7. MSC-EVs infusions (4ml) were given intravenously one hour after the injury.ResultsThe infusion of MSCs-EVs was well tolerated without adverse events. PaO2/FiO2 ratio in the treatment group tended to be higher than the control from 6 to 21 h after the lung injury, with no significant differences between the groups. No significant differences were found between the two groups in other pulmonary functions. Although vasopressor requirement in the treatment group tended to be lower than in the control, the net fluid balance was similarly increased in both groups as the severity of sepsis progressed. The variables reflecting microvascular hyperpermeability were comparable in both groups.ConclusionWe have previously demonstrated the beneficial effects of bone marrow-derived MSCs (10×106 cells/kg) in the same model of sepsis. However, despite some improvement in pulmonary gas exchange, the present study demonstrated that EVs isolated from the same amount of bone marrow-derived MSCs failed to attenuate the severity of multiorgan dysfunctions.
Stability of mental motor-imagery classification in EEG depends on the choice of classifier model and experiment design, but not on signal preprocessing
Authors: Rosenfelder Martin Justinus , Spiliopoulou Myra , Hoppenstedt Burkhard , Pryss Rüdiger , Fissler Patrick , della Piedra Walter Mario , Kolassa Iris-Tatjana , Bender Andreas 
Published: April 2023

IntroductionModern consciousness research has developed diagnostic tests to improve the diagnostic accuracy of different states of consciousness via electroencephalography (EEG)-based mental motor imagery (MI), which is still challenging and lacks a consensus on how to best analyse MI EEG-data. An optimally designed and analyzed paradigm must detect command-following in all healthy individuals, before it can be applied in patients, e.g., for the diagnosis of disorders of consciousness (DOC).MethodsWe investigated the effects of two important steps in the raw signal preprocessing on predicting participant performance (F1) and machine-learning classifier performance (area-under-curve, AUC) in eight healthy individuals, that are based solely on MI using high-density EEG (HD-EEG): artifact correction (manual correction with vs. without Independent Component Analysis [ICA]), region of interest (ROI; motor area vs. whole brain), and machine-learning algorithm (support-vector machine [SVM] vs. k-nearest neighbor [KNN]).ResultsResults revealed no significant effects of artifact correction and ROI on predicting participant performance (F1) and classifier performance (AUC) scores (allps &gt; 0.05) in the SVM classification model. In the KNN model, ROI had a significant influence on the classifier performance [F(1,8.939)= 7.585,p= 0.023]. There was no evidence for artifact correction and ROI selection changing the prediction of participants performance and classifier performance in EEG-based mental MI if using SVM-based classification (71–100% correct classifications across different signal preprocessing methods). The variance in the prediction of participant performance was significantly higher when the experiment started with a resting-state compared to a mental MI task block [X2(1)= 5.849,p= 0.016].DiscussionOverall, we could show that classification is stable across different modes of EEG signal preprocessing when using SVM models. Exploratory analysis gave a hint toward potential effects of the sequence of task execution on the prediction of participant performance, which should be taken into account in future studies.
Virtual simulation with AneuShape™ software for microcatheter shaping in intracranial aneurysm coiling: a validation study
Authors: Wu Zeng-Bao , Zeng Ying , Zhang Hua-Qiu , Shu Kai , Li Gao-Hui , Xiang Jian-Ping , Lei Ting , Zhu Ming-Xin 
Published: April 2023

BackgroundThe shaping of an accurate and stable microcatheter plays a vital role in the successful embolization of intracranial aneurysms. Our study aimed to investigate the application and the role of AneuShape™ software in microcatheter shaping for intracranial aneurysm embolization.MethodsFrom January 2021 to June 2022, 105 patients with single unruptured intracranial aneurysms were retrospectively analyzed with or without AneuShape™ software to assist in microcatheter shaping. The rates of microcatheter accessibility, accurate positioning, and stability for shaping were analyzed. During the operation, fluoroscopy duration, radiation dose, immediate postoperative angiography, and procedure-related complications were evaluated.ResultsCompared to the manual group, aneurysm-coiling procedures involving the AneuShape™ software exhibited superior results. The use of the software resulted in a lower rate of reshaping microcatheters (21.82 vs. 44.00%, p = 0.015) and higher rates of accessibility (81.82 vs. 58.00%, p = 0.008), better positioning (85.45 vs. 64.00%, p = 0.011), and higher stability (83.64 vs. 62.00%, p = 0.012). The software group also required more coils for both small (&lt;7 mm) and large (≥7 mm) aneurysms compared to the manual group (3.50 ± 0.19 vs. 2.78 ± 0.11, p = 0.008 and 8.22 ± 0.36 vs. 6.00 ± 1.00, p = 0.081, respectively). In addition, the software group achieved better complete or approximately complete aneurysm obliteration (87.27 vs. 66.00%, p = 0.010) and had a lower procedure-related complication rate (3.60 vs. 12.00%, p = 0.107). Without this software, the operation had a longer intervention duration (34.31 ± 6.51 vs. 23.87 ± 6.98 min, p &lt; 0.001) and a higher radiation dose (750.50 ± 177.81 vs. 563.53 ± 195.46 mGy, p &lt; 0.001).ConclusionsSoftware-based microcatheter shaping techniques can assist in the precise shaping of microcatheters, reduce operating time and radiation dose, improve embolization density, and facilitate more stable and efficient intracranial aneurysm embolization.
Endovascular thrombectomy is cost-effective in acute basilar artery occlusion stroke
Authors: Schwarting Julian , Rühling Sebastian , Bodden Jannis , Schwarting Stéphanie K. , Zimmer Claus , Mehrens Dirk , Kirschke Jan S. , Kunz Wolfgang G. , Boeckh-Behrens Tobias , Froelich Matthias F. 
Published: April 2023

ObjectiveEndovascular thrombectomy is a long-established therapy for acute basilar artery occlusion (aBAO). Unlike for anterior circulation stroke, cost-effectiveness of endovascular treatment has not been evaluated and is urgently needed to calculate expected health benefits and financial rewards. The aim of this study was therefore to simulate patient-level costs, analyze the economic potential of endovascular thrombectomy in patients with acute basilar artery occlusion (aBAO), and identify major determinants of cost-effectiveness.MethodsA Markov model was developed to compare outcome and cost parameters between patients treated by endovascular thrombectomy and patients treated by best medical care, based on four recent prospective clinical trials (ATTENTION, BAOCHE, BASICS, and BEST). Treatment outcomes were derived from the most recent literature. Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. Willingness to pay per QALY thresholds were set at 1x gross domestic product per capita, as recommended by the World Health Organization.ResultsEndovascular treatment of acute aBAO stroke yielded an incremental gain of 1.71 quality-adjusted life-years per procedure with an incremental cost-effectiveness ratio of $7,596 per QALY. This was substantially lower than the Willingness to pay of $63,593 per QALY. Lifetime costs were most sensitive to costs of the endovascular procedure.ConclusionEndovascular treatment is cost-effective in patients with aBAO stroke.
Beta band oscillations in the motor thalamus are modulated by visuomotor coordination in essential tremor patients
Authors: Basha Diellor , Kalia Suneil K. , Hodaie Mojgan , Lopez Rios Adriana L. , Lozano Andres M. , Hutchison William D. 
Published: April 2023

IntroductionBeta oscillations in sensorimotor structures contribute to the planning, sequencing, and stopping of movements, functions that are typically associated with the role of the basal ganglia. The presence of beta oscillations (13–30 Hz) in the cerebellar zone of the thalamus (the ventral intermediate nucleus – Vim) indicates that this rhythm may also be involved in cerebellar functions such as motor learning and visuomotor adaptation.MethodsTo investigate the possible role of Vim beta oscillations in visuomotor coordination, we recorded local field potential (LFP) and multiunit activity from the Vim of essential tremor (ET) patients during neurosurgery for the implantation of deep brain stimulation (DBS) electrodes. Using a computer, patients performed a visuomotor adaptation task that required coordinating center-out movements with incongruent visual feedback imposed by inversion of the computer display.ResultsThe results show that, in ET, Vim beta oscillations of the LFP were lower during the incongruent center-out task than during the congruent orientation. Vim firing rates increased significantly during periods of low beta power, particularly on approach to the peripheral target. In contrast, beta power in the subthalamic nucleus of Parkinson’s disease (PD) patients did not differ significantly between the incongruent and the congruent orientation of the center-out task.DiscussionThe findings support the hypothesis that beta oscillations of the Vim are modulated by novel visuomotor tasks. The inverse relationship between the power of Vim-LFP beta oscillations and Vim firing rates suggest that the suppression of beta oscillations may facilitate information throughput to the thalamocortical circuit by modulation of Vim firing rates.
Estimating complete cancer prevalence in Europe: validity of alternative vs standard completeness indexes
Authors: Demuru Elena , Rossi Silvia , Ventura Leonardo , Dal Maso Luigino , Guzzinati Stefano , Katalinic Alexander , Lamy Sebastien , Jooste Valerie , Di Benedetto Corrado , De Angelis Roberta ,   the EUROCARE-6 Working Group
Published: April 2023

IntroductionComparable indicators on complete cancer prevalence are increasingly needed in Europe to support survivorship care planning. Direct measures can be biased by limited registration time and estimates are needed to recover long term survivors. The completeness index method, based on incidence and survival modelling, is the standard most validated approach.MethodsWithin this framework, we consider two alternative approaches that do not require any direct modelling activity: i) empirical indices derived from long established European registries; ii) pre-calculated indices derived from US-SEER cancer registries. Relying on the EUROCARE-6 study dataset we compare standard vs alternative complete prevalence estimates using data from 62 registries in 27 countries by sex, cancer type and registration time.ResultsFor tumours mostly diagnosed in the elderly the empirical estimates differ little from standard estimates (on average less than 5% after 10-15 years of registration), especially for low prognosis cancers. For early-onset cancers (bone, brain, cervix uteri, testis, Hodgkin disease, soft tissues) the empirical method may produce substantial underestimations of complete prevalence (up to 20%) even when based on 35-year observations. SEER estimates are comparable to the standard ones for most cancers, including many early-onset tumours, even when derived from short time series (10-15 years). Longer observations are however needed when cancer-specific incidence and prognosis differ remarkably between US and European populations (endometrium, thyroid or stomach).DiscussionThese results may facilitate the dissemination of complete prevalence estimates across Europe and help bridge the current information gaps.
Misdiagnosis analysis of 2291 cases of haematolymphoid neoplasms
Authors: Deng Jing , Zuo Xiaona , Yang Liuyi , Gao Zifen , Zhou Chunju , Guo Ligai 
Published: April 2023

ObjectiveTo retrospectively analyze the reasons for misdiagnosis of haematolymphoid neoplasms and provide experience for improving the diagnostic level in China.MethodsA retrospective analysis was performed on 2291 cases of haematolymphoid diseases evaluated by the Department of Pathology of our hospital from 1 July 2019 to 30 June 2021. All 2291 cases were reviewed by two hematopathologist experts and classified according to the 2017 revised WHO classification criteria, supplemented immunohistochemistry (IHC), molecular biology and genetic information as needed. The diagnostic discordance between primary and expert review was evaluated. The possible causes of the diagnostic discrepancies were analyzed for each step involved in the procedure of diagnosis.ResultsIn total, 912 cases did not conform to the expert diagnoses among all the 2291 cases, with a total misdiagnosis rate of 39.8%. Among them, misdiagnosis between benign and malignant lesions accounted for 24.3% (222/912), misdiagnosis between haematolymphoid neoplasms and non-haematolymphoid neoplasms accounted for 3.3% (30/912), misdiagnosis among lineages accounted for 9.3% (85/912), misclassification in lymphoma subtypes accounted for 60.8% (554/912), and other misdiagnoses among benign lesions accounted for 2.3% (21/912) of cases, among which misclassification of lymphoma subtypes was the most common.ConclusionThe accurate diagnosis of haematolymphoid neoplasms is challenging, involving various types of misdiagnosis and complicated causes, however, it is important for precise treatment. Through this analysis, we aimed to highlight the importance of accurate diagnosis, avoid diagnostic pitfalls and to improve the diagnostic level in our country.