bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laparotomy-Induced Peripheral Inflammation Activates NR2B Receptors on the Brain Mast Cells and Results in Neuroinflammation in a Vagus Nerve-Dependent Manner
Authors: Yang Jing , Dong Hong-Quan , Liu Yan-Hu , Ji Mu-Huo , Zhang Xun , Dai Hong-Yu , Sun Zhao-Chu , Liu Lu , Zhou Jian , Sha Huan-Huan , Qian Yan-Ning , Li Qing-Guo , Yao Hao , Li Na-Na 
Published: February 2022

Background: The pathophysiological mechanisms underlying postoperative cognitive dysfunction (POCD) remain unclear over the years. Neuroinflammation caused by surgery has been recognized as an important element in the development of POCD. Many studies also suggest that the vagus nerve plays an important role in transmitting peripheral injury signals to the central nervous system (CNS) and the resultant neuroinflammation. Previously, we have demonstrated that brain mast cells (BMCs), as the “first responders”, play a vital role in neuroinflammation and POCD. However, how the vagus nerve communicates with BMCs in POCD has not yet been clarified.Methods: In the current study, we highlighted the role of the vagus nerve as a conduction highway in surgery-induced neuroinflammation for the first time. In our model, we tested if mice underwent unilateral cervical vagotomy (VGX) had less neuroinflammation compared to the shams after laparotomy (LP) at an early stage. To further investigate the roles of mast cells and glutamate in the process, we employed KitW-sh mice and primary bone marrow-derived MCs to verify the glutamate-NR2B axis on MCs once again.Results: Our results demonstrated that there were higher levels of glutamate and BMCs activation as early as 4 h after LP. Meanwhile, vagotomy could partially block the increases and reduce neuroinflammation caused by peripheral inflammation during the acute phase. Excitingly, inhibition of NR2B receptor and knockout of mast cells can attenuateneuroinflammation induced by glutamate.Conclusion: Taken together, our findings indicate that the vagus is a high-speed pathway in the transmission of peripheral inflammation to the CNS. Activation of BMCs triggered a neuroinflammatory cascade. Inhibition of NR2B receptor on BMCs can reduce glutamate-induced BMCs activation, neuroinflammation, and memory impairment, suggesting a novel treatment strategy for POCD.
Diagnostic Delay and Its Predictors in Cluster Headache
Authors: Kim Byung-Su , Chung Pil-Wook , Kim Byung-Kun , Lee Mi Ji , Chu Min Kyung , Ahn Jin-Young , Bae Dae Woong , Song Tae-Jin , Sohn Jong-Hee , Oh Kyungmi , Kim Daeyoung , Kim Jae-Moon , Park Jeong Wook , Chung Jae Myun , Moon Heui-Soo , Cho Soohyun , Seo Jong-Geun , Kim Soo-Kyoung , Choi Yun-Ju , Park Kwang-Yeol , Chung Chin-Sang , Cho Soo-Jin 
Published: February 2022

ObjectiveCluster headache (CH) is a rare, primary headache disorder, characterized of excruciating, strictly one-sided pain attacks and ipsilateral cranial autonomic symptoms. Given the debilitating nature of CH, delayed diagnosis can increase the disease burden. Thus, we aimed to investigate the diagnostic delay, its predictors, and clinical influence among patients with CH.MethodsData from a prospective multicenter CH registry over a 4-year period were analyzed. CH was diagnosed according to the International Classification of Headache Disorders (ICHD)-3 criteria, and diagnostic delay of CH was assessed as the time interval between the year of the first onset and the year of CH diagnosis. Patients were classified into three groups according to the tertiles of diagnostic delay (1st tertile, &lt;1 year; 2nd tertile, 1–6 years; and 3rd tertile, ≥7 years).ResultsOverall, 445 patients were evaluated. The mean duration of diagnosis delay was 5.7 ± 6.7 years, (range, 0–36 years). Regarding the age of onset, majority of young patients (age &lt;20 years) belonged to the third tertile (60%), whereas minority of old patients (&gt;40 years) belonged to the third tertile (9.0%). For year of onset, the proportion of patients in the 3rd tertile was the highest for the groups before the publication year of the ICHD-2 (74.7%) and the lowest for the groups after the publication year of the ICHD-3 beta version (0.5%). Compared with the first CH, episodic CH [multivariable-adjusted odds ratio (aOR) = 5.91, 95% CI = 2.42–14.48], chronic CH (aOR = 8.87, 95% CI = 2.66–29.51), and probable CH (aOR = 4.12, 95% CI = 1.48–11.43) were associated with the tertiles of diagnostic delay. Age of onset (aOR = 0.97, 95% CI = 0.95–0.99) and PHQ-9 score (aOR = 0.96, 95% CI = 0.93–0.99) were inversely associated with the tertile of diagnostic delay. The prevalence of suicidal ideation was highest in the patients of the third tertile. The mean HIT-6 score increased significantly with the diagnostic delay (p = 0.041).ConclusionsPatients with a younger onset of CH have a higher risk of diagnostic delay. Nevertheless, the rate of delayed diagnosis gradually improved over time and with the publication of the ICHD criteria, supporting the clinical significance of diagnostic clinical criteria and headache education to reduce the disease burden of CH.
Automated Segmentation of Midbrain Structures in High-Resolution Susceptibility Maps Based on Convolutional Neural Network and Transfer Learning
Authors: Zhao Weiwei , Wang Yida , Zhou Fangfang , Li Gaiying , Wang Zhichao , Zhong Haodong , Song Yang , Gillen Kelly M. , Wang Yi , Yang Guang , Li Jianqi 
Published: February 2022

BackgroundAccurate delineation of the midbrain nuclei, the red nucleus (RN), substantia nigra (SN) and subthalamic nucleus (STN), is important in neuroimaging studies of neurodegenerative and other diseases. This study aims to segment midbrain structures in high-resolution susceptibility maps using a method based on a convolutional neural network (CNN).MethodsThe susceptibility maps of 75 subjects were acquired with a voxel size of 0.83 × 0.83 × 0.80 mm3 on a 3T MRI system to distinguish the RN, SN, and STN. A deeply supervised attention U-net was pre-trained with a dataset of 100 subjects containing susceptibility maps with a voxel size of 0.63 × 0.63 × 2.00 mm3 to provide initial weights for the target network. Five-fold cross-validation over the training cohort was used for all the models’ training and selection. The same test cohort was used for the final evaluation of all the models. Dice coefficients were used to assess spatial overlap agreement between manual delineations (ground truth) and automated segmentation. Volume and magnetic susceptibility values in the nuclei extracted with automated CNN delineation were compared to those extracted by manual tracing. Consistencies of volume and magnetic susceptibility values by different extraction strategies were assessed by Pearson correlation coefficients and Bland-Altman analyses.ResultsThe automated CNN segmentation method achieved mean Dice scores of 0.903, 0.864, and 0.777 for the RN, SN, and STN, respectively. There were no significant differences between the achieved Dice scores and the inter-rater Dice scores (p &gt; 0.05 for each nucleus). The overall volume and magnetic susceptibility values of the nuclei extracted by the automatic CNN method were significantly correlated with those by manual delineation (p &lt; 0.01).ConclusionMidbrain structures can be precisely segmented in high-resolution susceptibility maps using a CNN-based method.
A Nutrient Formulation Affects Developmental Myelination in Term Infants: A Randomized Clinical Trial
Authors: Schneider Nora , Bruchhage Muriel M. K. , O'Neill Barry V. , Hartweg Mickaël , Tanguy Jérôme , Steiner Pascal , Mutungi Gisella , O'Regan Jonathan , Mcsweeney Séamus , D'Sa Viren , Deoni Sean C. L. 
Published: February 2022

Background and ObjectivesObservational studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning. The study aims to investigate the efficacy of a blend of docosahexaenoic acid (DHA), arachidonic acid (ARA), iron, vitamin B12, folic acid, and sphingomyelin (SM) from a uniquely processed whey protein concentrate enriched in alpha-lactalbumin and phospholipids compared with a control formulation on myelination, cognitive, and behavioral development in the first 6 months of life.MethodsThese are 6-month results from an ongoing two-center, randomized controlled trial with a 12-month intervention period (completed for all participants). In this study, full term, neurotypical infants of both sexes (N = 81) were randomized into investigational (N = 42) or control groups (N = 39). In addition, non-randomized breast-fed children (N = 108) serve as a natural reference group. Main outcomes are myelination (MRI), cognitive (Bayley Scales of Infant and Toddler Development, 3rd edition [Bayley-III]), social-emotional development (Ages and Stages Questionnaires: Social-Emotional, 2nd edition [ASQ:SE-2]), sleep (Brief Infant Sleep Questionnaire [BISQ]), and safety (growth and adverse events [AEs]).ResultsThe full analyses set comprises N = 66 infants. Significant differences in myelin structure, volume, and rate of myelination were observed in favor of the investigational myelin blend at 3 and 6 months of life. Effects were demonstrated for whole brain myelin and for cerebellar, parietal, occipital, and temporal regions, known to be functionally involved in sensory, motor, and language skills. No statistically significant differences were found for early behavior and cognition scores.ConclusionsThis is the first study demonstrating the efficacy of a myelin nutrient blend in well-nourished, term infants on developmental myelination, which may be foundational for later cognitive and learning outcomes.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03111927.
The Prognostic Role of Glycemia in Patients With Pancreatic Carcinoma: A Systematic Review and Meta-Analysis
Authors: Wang Xiaofang , Xu Wanfeng , Hu Xiaoru , Yang Xianghong , Zhang Mingming 
Published: February 2022

BackgroundFasting blood glucose and glycated hemoglobin (HbA1c) levels are associated with the risk of pancreatic cancer.AimTo examine the relationship between perioperative glucose and HbA1c levels and prognosis in patients with pancreatic cancer.MethodsPubMed, Embase, and the Cochrane Library were queried for potentially eligible studies published up to May 2021. The exposures were perioperative fasting glucose and HbA1c levels. The primary outcome was survival. The secondary outcome was complications. All analyses were performed using the random-effects model.ResultsTen studies (48,424 patients) were included. The pre-operative (HR=1.10, 95%CI: 0.89-1.35; I2 = 45.1%, Pheterogeneity=0.078) and postoperative (HR=1.19, 95%CI: 0.92-1.54; I2 = 67.9%, Pheterogeneity=0.001) blood glucose levels were not associated with the survival to pancreatic cancer. Similar results were observed for HbA1c (HR=1.09, 95%CI: 0.75-1.58; I2 = 64.2%, Pheterogeneity=0.039), fasting blood glucose (FBG)/HbA1c (HR=1.16, 95%CI: 0.67-1.68; I2 = 0.0%, Pheterogeneity=0.928), and FBG (HR=1.75, 95%CI: 0.81-3.75; I2 = 79.4%, Pheterogeneity=0.008). Pre-operative blood glucose levels were not associated with postoperative complications (OR=0.90, 95%CI: 0.52-1.56), but postoperative glucose levels were associated with postoperative complications (OR=3.06, 95%CI: 1.88-4.97; I2 = 0.0%, Pheterogeneity=0.619).ConclusionBlood glucose, FBG, and HbA1c levels are not associated with the survival of patients with pancreatic cancer. Postoperative blood glucose levels could predict postoperative complications.
Trends in Surgical Morbidity and Survival Outcomes for Radical Hysterectomy in West China: An 11-Year Retrospective Cohort Study
Authors: Jing Huining , Yang Ying , Liu Yinxia , Zou Peijun , Li Zhengyu 
Published: February 2022

ObjectivesTo vertically analyze the trend of surgical approaches, demographics, surgical morbidity, and long-term survival outcomes of early-stage cervical cancer over the past 11 years and to determine whether there have been any significant changes.MethodsA total of 851 patients with consecutive International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA–IIA cervical cancer diagnosed between January 2008 and June 2018 at a single center in China were included in this retrospective study. Trends in the rate of minimally invasive surgery (MIS), demographics, surgical morbidities, and long-term survival outcomes were determined. We categorized patients into two groups according to their year of operation. The demographics, pathological factors, surgical morbidity, and long-term survival outcomes were compared between these two groups.ResultsRegarding the surgical approach, there was a significant increase in the rate of laparoscopic radical hysterectomy (LRH) performed over the study period, from 7.8% in 2008 to 72.5% in 2018 (p &lt; 0.0001). The mean age of patients who underwent abdominal radical hysterectomy (ARH) has increased slightly from 2008 to 2018, and those who underwent ARH in the second half of the study period (2014–2018) were significantly older (45.01 vs. 47.50 years; p = 0.001). The most impressive changes over the past 11 years have occurred in the surgical morbidity in both the ARH and LRH groups. The overall surgical morbidity decreased from 29.2% in 2008 to 11.9% in 2018, with an annual rate of 1.57%. The median estimated blood loss volume of the ARH group was 500 ml (range 50–2,000) in the first few years compared to 400 ml (30–2500) in the last few years of the study period (p &lt; 0.0001), which in the LRH group was 350 ml (range 150–800) and 150 ml (range 5–1,000), respectively (p &lt; 0.0001). Similarly, allogeneic blood transfusions and hospital stay have all decreased dramatically over time in both approaches. On the other hand, our study did not reveal any significant statistical changes in long-term survival outcomes over the follow-up period in either group.ConclusionsThe findings of our study demonstrate that great progress in surgically managed cervical cancer has been made over the last decade in West China. Our retrospective study demonstrated that the year of operation does not appear to influence the long-term survival, but the surgical morbidity impressively decreased over the study period in both the ARH and LRH groups, which reflects that the higher hospital surgical volume for radical hysterectomy (RH) was not associated with lower survival outcomes but related to the reduction of surgical morbidity.
Potential Influence of Anesthetic Interventions on Breast Cancer Early Recurrence According to Estrogen Receptor Expression: A Sub-Study of a Randomized Trial
Authors: Li Mohan , Zhang Yuelun , Pei Lijian , Zhang Zhiyong , Tan Gang , Huang Yuguang 
Published: February 2022

BackgroundEffects of anesthetic interventions on cancer prognosis remain controversial. There is evidence that estrogen receptor (ER)-negative breast cancer patients have an early recurrence peak. We aimed to assess the potential benefit of regional anesthesia-analgesia versus general anesthesia regarding early recurrence in breast cancer according to ER expression.MethodsBased on a multicenter randomized controlled trial (clinicaltrials.gov, NCT00418457), we included all the patients from Peking Union Medical College Hospital research center in this study. The primary outcome was breast cancer recurrence after surgery. The Cox proportional hazard model was used to compare recurrence between groups.ResultsIn total, 1,253 breast cancer patients were included in this sub-study, among whom the median follow-up time was 53 months. In this sub-study, 320 patients were ER-negative, and 933 were ER-positive. As for ER-negative patients, the recurrence risk in the PPA (paravertebral blocks and propofol general anesthesia) group showed no statistical difference compared with the GA (sevoflurane and opioids general anesthesia) group (19.1% versus 23.4%; adjusted HR: 0.80, 95% CI: 0.50–1.30; P = 0.377). In the first 18 months after breast cancer surgery, which is considered as the classical early peak of recurrence, after adjustment for menstruation and the pathological stage of tumor, the decrease of early recurrence observed in the PPA group was not significant compared with the GA group (adjusted HR: 0.63, 95% CI: 0.34–1.14; P = 0.127).ConclusionsIn our study, the effects of early recurrence after breast cancer surgery in both ER-negative and ER-positive patients were similar between regional anesthesia-analgesia and general anesthesia. Large samples of ER-negative patients will be needed to clarify the effects of anesthetic interventions.
Operative Choice for Length-Unstable Femoral Shaft Fracture in School-Aged Children: Locking Plate vs. Monolateral External Fixator
Authors: Hong Pan , Rai Saroj , Tang Xin , Liu Ruikang , Li Jin 
Published: February 2022

BackgroundLocking plate (LP) is a good choice in the treatment of length-unstable femoral shaft fracture in children. Monolateral external fixator (EF) has been reported for this condition for decades. This study aims to compare the clinical outcomes of school-aged children with length-unstable femoral shaft fracture treated with LP vs. EF.MethodsPatients aged 5–11 years old with length-unstable femoral shaft fractures treated at our institute from January 2014 to January 2018 were retrospectively reviewed and categorized into LP and EF groups. The preoperative data, including baseline information of the patients, radiographic parameters, and types of surgical procedure, were collected from the hospital database, and postoperative data, including complications, were collected during the follow-up visits.ResultsOverall, 36 patients (average, 8.2 ± 2.1 years; male, 20; female, 16) in the LP group and 35 patients (average, 8.3 ± 2.3 years; male 20, female 15) in the EF group were included. There was significantly less operative time for EF (45.4 ± 7.8 min) compared with LP (67.8 ± 11.3 min) (P &lt; 0.001). As for the frequency of fluoroscopy, there was a significant difference between the EF (13.9 ± 2.4) and LP (16.5 ± 3.2) groups (p &lt; 0.001). The rate of major complications was not significantly different between these two groups. There was a significant difference between the EF group (11.2 ± 5.8 mm) and the LP group (7.5 ± 1.6 mm) group concerning limb length discrepancy (P &lt; 0.001).ConclusionBoth LP and EF produce satisfactory outcomes in school-aged children with length unstable femoral shaft fractures. External fixation remains a viable choice without the necessity of secondary surgery for hardware removal.
Protective SARS-CoV-2 Antibody Response in Children With Inflammatory Bowel Disease
Authors: Bosa Luca , Di Chiara Costanza , Gaio Paola , Cosma Chiara , Padoan Andrea , Cozzani Sandra , Perilongo Giorgio , Plebani Mario , Giaquinto Carlo , Donà Daniele , Cananzi Mara 
Published: February 2022

BackgroundTo date, there's no evidence of an increased risk of SARS-CoV-2 infection or more severe COVID-19 in patients with inflammatory bowel disease (IBD). However, whether COVID-19 alters the clinical course of IBD or whether IBD treatment affects the immunological response to SARS-CoV-2 is still under investigation, especially in children.AimTo assess the serological response to SARS-CoV-2 in children with IBD, and to evaluate the impact of COVID-19 on the clinical course of IBD.Material and MethodsThis prospective study enrolled children (0–18 years) followed-up at the University Hospital of Padova for IBD, who acquired a confirmed SARS-CoV-2 infection between 02.2020 and 02.2021. The anti-SARS-CoV-2 S-RBD IgG titer was evaluated at 3 months after infection and compared to that of a control group of healthy children matched for age, sex, and COVID-19 severity.ResultsTwelve children with IBD (M = 5; median age 14 years) contracted COVID-19 during the study period. 11/12 patients were under immunomodulatory treatment (4/12 steroids; 6/12 azathioprine; 3/12 anti-TNFs; 2 vedolizumab; 1 ustekinumab). SARS-CoV-2 infection remained asymptomatic in 4/12 children and caused mild COVID-19 in the remaining 8. Mean anti-SARS-CoV-2 IgG S-RBD titer was similar between IBD patients and controls (27.3 ± 43.8 vs. 36.8 ± 35.3 kAU/L, p = ns). No children experienced IBD flares nor required gastroenterological support during the infection period.DiscussionChildren with IBD can mount a protective humoral response against SARS-CoV-2, which is comparable to that of their healthy peers regardless of ongoing immunomodulatory treatment. This study also supports the favorable course of PIBD during COVID-19 and vice-versa.
Blocking VCAM-1 Prevents Angiotensin II-Induced Hypertension and Vascular Remodeling in Mice
Authors: Yin Liangqingqing , Bai Jie , Yu Wei-Jia , Liu Ying , Li Hui-Hua , Lin Qiu-Yue 
Published: February 2022

Adhesion of monocytes to the vascular endothelium frequently leads to an inflammatory response, which contributes to hypertension and vascular remodeling. Vascular cellular adhesion molecule-1 (VCAM-1) plays an important role in leukocyte adhesion and migration during inflammatory diseases. However, its role in angiotensin (Ang) II -induced hypertension and vascular dysfunction remains largely unknown. Wild-type (WT) mice were administered a VCAM-1 neutralizing antibody (0.1 or 0.2 mg/mouse/day) or IgG control and then infused with Ang II (490 ng kg−1 min−1) or saline continuously for 14 days. Systolic blood pressure (SBP) was measured with a tail-cuff system, pathological changes in the aorta were assessed by histological staining, and vascular relaxation was analyzed an aortic ring assay. Our results indicated that compared with saline infusion, Ang II infusion significantly upregulated VCAM-1 expression in the mouse aorta and serum. Moreover, Ang II infusion markedly increased arterial hypertension, wall thickness, fibrosis, infiltration of Mac-2+ macrophages, reactive oxygen species (ROS) production and vascular relaxation dysfunction. Conversely, blockade of VCAM-1 with a neutralizing antibody substantially alleviated these effects. In vitro experiments further confirmed that the VCAM-1 neutralizing antibody inhibited Ang II-induced macrophage adhesion and migration and DNA damage and oxidative stress in endothelial cells (ECs). In conclusion, these results indicate that blockade of VCAM-1 exerts a protective effect against Ang II-induced arterial hypertension and dysfunction by regulating monocytes adhesion and infiltration into the endothelium and represents a novel therapeutic approach for hypertension.