bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Abnormal Functional Connectivity in the Locus Coeruleus-Norepinephrine System Associated With Anxiety Symptom in Chronic Insomnia Disorder
Authors: Gong Liang , Shi Min , Wang Jian , Xu Ronghua , Yu Siyi , Liu Duan , Ding Xin , Zhang Bei , Zhang Xingping , Xi Chunhua 
Published: May 2021

BackgroundMental syndromes such as anxiety and depression are common comorbidities in patients with chronic insomnia disorder (CID). The locus coeruleus noradrenergic (LC-NE) system is considered to be crucial for modulation of emotion and sleep/wake cycle. LC-NE system is also a critical mediator of the stress-induced anxiety. However, whether the LC-NE system contributes to the underlying mechanism linking insomnia and these comorbidities remain unclear. This study aimed to investigate the LC-NE system alterations in patients with insomnia and its relationship with depression and anxiety symptoms.Materials and MethodsSeventy patients with CID and 63 matched good sleep control (GSC) subjects were recruited and underwent resting-state functional MRI scan. LC-NE functional network was constructed by using seed-based functional connectivity (FC) analysis. The alterations in LC-NE FC network in patients with CID and their clinical significance was explored.ResultsCompared with GSC group, the CID group showed decreased left LC-NE FC in the left inferior frontal gyrus, while they had increased LC-NE FC in the left supramarginal gyrus and the left middle occipital gyrus (MOG). For the right LC-NE FC network, decreased FC was found in left dorsal anterior cingulate cortex (dACC). Interesting, the increased LC-NE FC was located in sensory cortex, while decreased LC-NE FC was located in frontal control cortex. In addition, the FC between the left LC and left MOG was associated with the duration of the disease, while abnormal FC between right LC and left dACC was associated with the anxiety scores in patients with CID.ConclusionThe present study found abnormal LC-NE functional network in patients with CID, and the altered LC-NE function in dACC was associated with anxiety symptoms in CID. The present study substantially extended our understanding of the neuropathological basis of CID and provided the potential treatment target for CID patients who also had anxiety.
Neutral Effect of Increased Dairy Product Intake, as Part of a Lifestyle Modification Program, on Cardiometabolic Health in Adolescent Girls With Overweight/Obesity: A Secondary Analysis From a Randomized Controlled Trial
Authors: Skelly Lauren E. , Barbour-Tuck Erin N. , Kurgan Nigel , Calleja Melissa , Klentrou Panagiota , Falk Bareket , Josse Andrea R. 
Published: May 2021

Background:The presence of obesity and some cardiometabolic disease risk factors in childhood and adolescence track into adulthood. Intake of dairy products has been shown to be inversely related to adiposity and cardiometabolic variables in youth. However, limited research has examined cardiometabolic disease risk factors following increased dairy product consumption as part of a lifestyle modification intervention in youth with overweight/obesity. This secondary analysis aimed to determine whether 12 weeks of increased dairy consumption, as part of a lifestyle modification program, affects cardiometabolic variables in adolescent females (range: 10–18 years) with overweight/obesity (BMI &gt; 85th centile).Methods:Participants were randomized into two groups: higher dairy intake (RDa; four servings/day [to reflect previous Canada's Food Guide recommendations];n= 23) or low dairy intake (LDa; 0–2 servings/day;n= 23). Both RDa and LDa participated in a 12-week, eucaloric, lifestyle modification intervention consisting of exercise training, and nutritional counseling. Adiposity (percent body fat [%BF]), dietary intake, and measures of cardiometabolic health were measured pre- and post-intervention.Results:There were no significant changes over time within groups or differences over time between groups for triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), TC/HDL ratio, low-density lipoprotein cholesterol (LDL), glucose, insulin, homeostatic model assessment of insulin resistance, adiponectin, and tumor necrosis factor alpha (TNF-α) (main effects of time and interactions,p&gt; 0.05). Leptin decreased over the 12-week lifestyle intervention in both groups (main effect of time,p= 0.02). After combining the groups (n= 46), significant correlations were found between change in %BF and change in some cardiometabolic variables (HDL [r= −0.40], TC/HDL ratio [r= 0.42], LDL [r= 0.36], and TNF-α [r= 0.35],p&lt; 0.05). After controlling for change in dairy product intake, the correlations were unchanged.Conclusion:Our findings demonstrate that increased dairy product consumption, as part of a lifestyle modification, weight management intervention, had a neutral effect on cardiometabolic disease risk factors in adolescent females with overweight/obesity. Change in dairy product intake did not influence the relationships between change in adiposity and change in cardiometabolic variables. Future research designed to primarily assess the effect of increased dairy product consumption on cardiometabolic disease risk factors in this population is warranted.Clinical Trial Registration:Clinicaltrials.gov; NCT#02581813.
Sharp Downregulation of Hub Genes Associated With the Pathogenesis of Breast Cancer From Ductal Carcinoma In Situ to Invasive Ductal Carcinoma
Authors: Wang Yao , Liang Faqing , Zhou Yuting , Qiu Juanjuan , Lv Qing , Du Zhenggui 
Published: May 2021

IntroductionBreast atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) are precursor stages of invasive ductal carcinoma (IDC). This study aimed to investigate the pathogenesis of breast cancer by dynamically analyzing expression changes of hub genes from normal mammary epithelium (NME) to simple ductal hyperplasia (SH), ADH, DCIS, and finally to IDC.MethodsLaser-capture microdissection (LCM) data for NME, SH, ADH, DCIS, and IDC cells were obtained. Weighted gene co-expression network analysis (WGCNA) was performed to dynamically analyze the gene modules and hub genes associated with the pathogenesis of breast cancer. Tissue microarray, immunohistochemical, and western blot analyses were performed to determine the protein expression trends of hub genes.ResultsTwo modules showed a trend of increasing expression during the development of breast disease from NME to DCIS, whereas a third module displayed a completely different trend. Interestingly, the three modules displayed inverse trends from DCIS to IDC compared with from NME to DCIS; that is, previously upregulated modules were subsequently downregulated and vice versa. We further analyzed the module that was most closely associated with DCIS (p=7e−07). Kyoto Gene and Genomic Gene Encyclopedia enrichment analysis revealed that the genes in this module were closely related to the cell cycle (p= 4.3e–12). WGCNA revealed eight hub genes in the module, namely, CDK1, NUSAP1, CEP55, TOP2A, MELK, PBK, RRM2, and MAD2L1. Subsequent analysis of these hub genes revealed that their expression levels were lower in IDC tissues than in DCIS tissues, consistent with the expression trend of the module. The protein expression levels of five of the hub genes gradually increased from NME to DCIS and then decreased in IDC. Survival analysis predicted poor survival among breast cancer patients if these hub genes were not downregulated from DCIS to IDC.ConclusionsFive hub genes, RRM2, TOP2A, PBK, MELK, and NUSAP1, which are associated with breast cancer pathogenesis, are gradually upregulated from NME to DCIS and then downregulated in IDC. If these hub genes are not downregulated from DCIS to IDC, patient survival is compromised. However, the underlying mechanisms warrant further elucidation in future studies.
HOXA13, Negatively Regulated by miR-139-5p, Decreases the Sensitivity of Gastric Cancer to 5-Fluorouracil Possibly by Targeting ABCC4
Authors: Chen Zhengqian , Qin Zhiwei , Li Lei , Wo Qi , Chen Xia 
Published: May 2021

PurposeChemoresistance remains a major challenge in the therapy of gastric cancer (GC). The homeobox (HOX) gene family has gained attention in carcinogenesis and chemoresistance. Here, this study aimed to explore the mechanism of HOXA13 in GC chemoresistance.MethodsQuantitative real-time PCR (qRT-PCR) and Western blot were used to evaluate the expression of HOXA13 in GC tissues. The Kaplan–Meier plotter database was mined for prognosis analysis of GC patients with different HOXA13 expression receiving 5-Fluorouracil (5-FU) therapy. The effects of HOXA13 on sensitivity of GC cells to 5-FU were investigated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2’-deoxyuridine (EdU) incorporation, flow cytometry and experiment in vivo. RNA-Sequencing analysis was performed to explore the underlying mechanism of HOXA13-mediated 5-FU resistance in GC. Chromatin immunoprecipitation (ChIP) and rescue experiments were applied to determine the relationship between HOXA13 and ABCC4. Luciferase reporter assay was performed to assess interaction of miR-139-5p and HOXA13.ResultsHOXA13 was upregulated in GC and its high expression was associated with poor prognosis of GC patients with 5-FU treatment. Overexpression of HOXA13 impaired the inhibitory effects of 5-FU on GC cells proliferation in vitro and vivo, and knockdown of HOXA13 exacerbated 5-FU-induced GC cells apoptosis. Mechanistically, HOXA13, directly targeted by miR-139-5p in GC, might upregulate ABCC4 expression, thereby accentuating 5-FU resistance of GC cells.ConclusionOur study suggests that HOXA13 attenuates 5-FU sensitivity of GC possibly by upregulating ABCC4. Thus, targeting HOXA13 would provide a novel prospective into the potential therapeutic strategy for reversing chemoresistance.
A Phase 2 Randomised Clinical Trial Assessing the Tolerability of Two Different Ratios of Medicinal Cannabis in Patients With High Grade Gliomas
Authors: Schloss Janet , Lacey Judith , Sinclair Justin , Steel Amie , Sughrue Michael , Sibbritt David , Teo Charles 
Published: May 2021

BackgroundCannabis for cancer is very topical and, given the use of illicit cannabis preparations used in this vulnerable population, research investigating standardised, quality-assured medicinal cannabis is critical to inform clinicians and assist patient safety.MethodsA randomized trial involving adult patients diagnosed with a high-grade glioma, no history of substance abuse, liver or kidney damage or myocardial infarction were eligible for inclusion in a tolerability study on two different ratios of medicinal cannabis. Baseline screening of brain morphology, blood pathology, functional status, and cognition was conducted. A retrospective control group was used for comparison for secondary outcomes.ResultsParticipants (n=88) were on average 53.3 years old. A paired t-test assessed the Functional Assessment of Cancer Therapy for Brain Cancer (FACT-Br) between groups from baseline to week 12 found that the 1:1 ratio favoured both physical (p=0.025) and functional (p=0.014) capacity and improved sleep (p=0.009). Analysis of changes from baseline to week 12 also found 11% of 61 participants had a reduction in disease, 34% were stable, 16% had slight enhancement, and 10% had progressive disease. No serious adverse events occurred. Side effects included dry mouth, tiredness at night, dizziness, drowsiness.ConclusionThis study demonstrated that a single nightly dose of THC-containing medicinal cannabis was safe, had no serious adverse effects and was well tolerated in patients. Medicinal cannabis significantly improved sleep, functional wellbeing, and quality of life.Clinical Trial RegistrationAustralian New Zealand Clinical Trials Registry (ANZCTR) http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373556&amp;isReview=true, identifier ACTRN12617001287325.
Induction Chemotherapy Combined With Intensity-Modulated Radiotherapy for 129 Nasopharyngeal Carcinoma Patients With Synchronous Metastases: A Retrospective Study
Authors: Ni Mengshan , Geng Lijun , Kong Fangfang , Du Chengrun , Zhai Ruiping , Lyu Yingchen , Hu Chaosu , Ying Hongmei 
Published: May 2021

ObjectiveTo analyze the therapeutic effect and prognostic factors of nasopharyngeal carcinoma (NPC) patients with distant metastases at initial diagnosis receiving induction chemotherapy with intensity-modulated radiotherapy (IMRT).MethodsA total of 129 patients who underwent platinum-based induction chemotherapy followed by definitive IMRT with or without concurrent or adjuvant chemotherapy for newly diagnosed distant metastatic NPC in our center between March 2008 and November 2018 were retrospectively analyzed. 41 patients underwent local therapy for metastatic sites. Kaplan-Meier method was used to estimate survival rates, Log-rank test and Cox proportional hazards model were used to figure out independent prognostic factors of overall survival (OS).ResultsA total of 66 patients had been dead (median follow-up time, 51.5 months). The median overall survival (OS) time was 54.2 months (range, 7-136 months), and the 1-year, 2-year, 3-year, 5-year overall survival rates were 88.0%,71.0%,58.0%, and 47.0%. Multivariate analysis found that the factors correlated with poor overall survival were pre-treatment serum lactate dehydrogenase (SLDH) &gt;180U/L, chemotherapy cycles&lt;4, and M1 stage subdivision (M1b, single hepatic metastasis and/or multiple metastases excluding the liver; and M1c, multiple hepatic metastases). The 5-year OS rates for M1a, M1b and M1c were 62.6%,40.4% and 0%, respectively.ConclusionPlatinum-containing induction chemotherapy combined with IMRT seemed to be advantageous to prolong survival for some NPC patients with synchronous metastases at initial diagnosis. The independent factors to prognosticate OS were pre-treatment SLDH, number of chemotherapy cycles, and M1 subcategories. Prospective clinical trials are needed to confirm the result.
Preoperative nTMS and Intraoperative Neurophysiology - A Comparative Analysis in Patients With Motor-Eloquent Glioma
Authors: Rosenstock Tizian , Tuncer Mehmet Salih , Münch Max Richard , Vajkoczy Peter , Picht Thomas , Faust Katharina 
Published: May 2021

BackgroundThe resection of a motor-eloquent glioma should be guided by intraoperative neurophysiological monitoring (IOM) but its interpretation is often difficult and may (unnecessarily) lead to subtotal resection. Navigated transcranial magnetic stimulation (nTMS) combined with diffusion-tensor-imaging (DTI) is able to stratify patients with motor-eloquent lesion preoperatively into high- and low-risk cases with respect to a new motor deficit.ObjectiveTo analyze to what extent preoperative nTMS motor risk stratification can improve the interpretation of IOM phenomena.MethodsIn this monocentric observational study, nTMS motor mapping with DTI fiber tracking of the corticospinal tract was performed before IOM-guided surgery for motor-eloquent gliomas in a prospectively collected cohort from January 2017 to October 2020. Descriptive analyses were performed considering nTMS data (motor cortex infiltration, resting motor threshold (RMT), motor evoked potential (MEP) amplitude, latency) and IOM data (transcranial MEP monitoring, intensity of monopolar subcortical stimulation (SCS), somatosensory evoked potentials) to examine the association with the postoperative motor outcome (assessed at day of discharge and at 3 months).ResultsThirty-seven (56.1%) of 66 patients (27 female) with a median age of 48 years had tumors located in the right hemisphere, with glioblastoma being the most common diagnosis with 39 cases (59.1%). Three patients (4.9%) had a new motor deficit that recovered partially within 3 months and 6 patients had a persistent deterioration (9.8%). The more risk factors of the nTMS risk stratification model (motor cortex infiltration, tumor-tract distance (TTD) ≤8mm, RMTratio &lt;90%/&gt;110%) were detected, the higher was the risk for developing a new postoperative motor deficit, whereas no patient with a TTD &gt;8mm deteriorated. Irreversible MEP amplitude decrease &gt;50% was associated with worse motor outcome in all patients, while a MEP amplitude decrease ≤50% or lower SCS intensities ≤4mA were particularly correlated with a postoperative worsened motor status in nTMS-stratified high-risk cases. No patient had postoperative deterioration of motor function (except one with partial recovery) when intraoperative MEPs remained stable or showed only reversible alterations.ConclusionsThe preoperative nTMS-based risk assessment can help to interpret ambiguous IOM phenomena (such as irreversible MEP amplitude decrease ≤50%) and adjustment of SCS stimulation intensity.
Treatment for Flexible Flatfoot in Children With Subtalar Arthroereisis and Soft Tissue Procedures
Authors: Li Bing , He Wenbao , Yu Guangrong , Zhou Haichao , Xia Jiang , Zhao Youguang , Zhu Hui , Yu Tao , Yang Yunfeng 
Published: May 2021

Background: Children with flexible flatfoot is common in clinics and there is no unified conclusion on surgical treatment. And for some patients with severe deformities, the correction of the subtalar joint arthroereisis combine the release of the Achilles tendon or gastrocnemius muscle release is still not satisfactory. The main aim of the present study was to investigate the therapeutic outcomes of subtalar arthroereisis combined with Achilles tendon or gastrocnemius recession and medial soft tissue (spring ligament, talonavicular joint capsule, tibionavicular ligaments and tibiospring ligaments) tightening for treating flexible flatfoot with severe deformities.Methods: Thirty patients (32 feet) with pediatric flexible flatfoot who underwent subtalar arthroereisis and soft tissue procedures during January 2016 to January 2018. There were 18 males (20 feet) and 12 females (12 feet) with an average age of 9.5 years (range, 8–12 years). We used the AOFAS scores and VAS scores combined with angles measure to evaluate the pre-operative and post-operative status.Results: Thirty patients (32 feet) were followed up for 25.3 months on average (range, 18–36 months). There was no infection. Post-operative foot pain, arch collapse, and other symptoms improved. At last follow-up, the Meary angle was decreased from 17.5° ± 4.4° to 4.1° ± 1.2° (P &lt; 0.05), the talar-first metatarsal (AP) was decreased from 15.3° ± 3.1° to 4.8° ± 1.3°(P &lt; 0.05), The mean AOFAS score was rose from 66.6 ± 5.8 to 88.6 ± 7.9 (P &lt; 0.05), the mean VAS score was decreased from 6.6 ± 0.6 to 1.7 ± 0.3 (P &lt; 0.05).Conclusion: The subtalar arthroereisis combined with soft tissue procedures can effectively correct flexible flatfoot in children and it is a significant method for severe forefoot abduction reconstruction.Level of Evidence: IV
Efficacy of Chinese Herbal Injections for Elderly Patients With pneumonia—A Bayesian Network Meta-analysis of Randomized Control Trials
Authors: Yuan Yang , Zheng Quan , Si Zhilin , Liu Juhua , Li Zhi , Xiong Lian , Liu Pan , Li Xu , He Chengshi , Liang Jinghong 
Published: May 2021

Background: Pneumonia is a prevalent and complicated disease among adults, elderly people in particular, and the debate on the optimal Chinese herbal injections (CHIs) is ongoing. Our objective is to investigate the comparative effectiveness of various CHIs strategies for elderly patients with pneumonia.Methods: A comprehensive search strategy was executed to identify relevant randomized controlled trials (RCTs) by browsing through several databases from their inception to first, Feb 2020; All of the direct and indirect evidence included was rated by Network meta-analysis under a Bayesian framework.Results: We ultimately identified 34 eligible randomized controlled trials that involved 3,111 elderly participants and investigated 4 CHIs combined with Western medicine (WM) (Xiyanping injection [XYP]+WM, Yanhuning injection [YHN]+WM, Tanreqing injection [TRQ]+WM, Reduning injection [RDN]+WM), contributing 34 direct comparisons between CHIs. Seen from the outcome of Clinical effective rate and time for defervescence, patients taking medicine added with CHIs [Clinical effective rate, XYP + WM(Odd ratio (OR): 0.74, 95%Credible intervals (CrIs):0.55–0.98), YHN + WM(OR: 0.66, 95%CrI: 0.45–0.95), TRQ + WM(OR: 0.65, 95%CrI: 0.50–0.83), RDN + WM(OR: 0.60, 95%CrI: 0.40–0.89); Time for defervescence, YHN + WM(Mean difference (MD): −2.11, 95%CrI: −3.26 to −0.98), XYP + WM(MD: −2.06, 95%CrI: −3.08 to −1.09), RDN + WM(MD: −1.97, 95%CrI: −3.61 to −0.35), TRQ + WM(MD: −1.69, 95%CrI: −2.27 to −1.04)] showed statistically better effect compared with participants in the Control group (CG) who only took WM. Meanwhile, based on the time for disappearance of cough, 3 out of 4 CHIs [TRQ + WM(MD: −2.56, 95%CrI: −3.38 to −1.54), YHN + WM(MD: −2.36, 95%CrI: −3.86 to −1.00) and XYP + WM(MD: −2.21, 95%CrI: −3.72 to −1.10)] strategies indicated improvement of clinical symptoms. Only XYP + WM(MD −1.78, 95%CrI: −3.29 to −0.27) and TRQ + WM (MD: −1.71, 95%CrI: −2.71 to −0.73) could significantly shorten the time for disappearance of pulmonary rales.Conclusion: According to the statistical effect size (The surface under the cumulative ranking), we found that XYP + WM was presumably to be the preferable treatment for treating elderly patients with pneumonia compared with WM alone in terms of clinical effective rate. Our findings were based on very limited evidence and thus should be interpreted with caution. The application of the findings requires further research.
Dexmedetomidine Protects Human Cardiomyocytes Against Ischemia-Reperfusion Injury Through α2-Adrenergic Receptor/AMPK-Dependent Autophagy
Authors: Xiao Yingying , Li Junpeng , Qiu Lisheng , Jiang Chuan , Huang Yanhui , Liu Jinfen , Sun Qi , Hong Haifa , Ye Lincai 
Published: May 2021

Background: Ischemia-reperfusion injury (I/R) strongly affects the prognosis of children with complicated congenital heart diseases (CHDs) who undergo long-term cardiac surgical processes. Recently, the α2-adrenergic receptor agonist Dexmedetomidine (Dex) has been reported to protect cardiomyocytes (CMs) from I/R in cellular models and adult rodent models. However, whether and how Dex may protect human CMs in young children remains largely unknown.Methods and Results: Human ventricular tissue from tetralogy of Fallot (TOF) patients and CMs derived from human-induced pluripotent stem cells (iPSC-CMs) were used to assess whether and how Dex protects human CMs from I/R. The results showed that when pretreated with Dex, the apoptosis marker-TUNEL and cleaved caspase 3 in the ventricular tissue were significantly reduced. In addition, the autophagy marker LC3II was significantly increased compared with that of the control group. When exposed to the hypoxia/reoxygenation process, iPSC-CMs pretreated with Dex also showed reduced TUNEL and cleaved caspase 3 and increased LC3II. When the autophagy inhibitor (3-methyladenine, 3-MA) was applied to the iPSC-CMs, the protective effect of Dex on the CMs was largely blocked. In addition, when the fusion of autophagosomes with lysosomes was blocked by Bafilomycin A1, the degradation of p62 induced by Dex during the autophagy process was suspended. Moreover, when pretreated with Dex, both the human ventricle and the iPSC-CMs expressed more AMP-activated protein kinase (AMPK) and phospho AMPK (pAMPK) during the I/R process. After AMPK knockout or the use of an α2-adrenergic receptor antagonist-yohimbine, the protection of Dex and its enhancement of autophagy were inhibited.Conclusion: Dex protects young human CMs from I/R injury, and α2-adrenergic receptor/AMPK-dependent autophagy plays an important role during this process. Dex may have a therapeutic effect for children with CHD who undergo long-term cardiac surgical processes.