bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EXPRESSION OF HER-2 AND GALECTIN-3 IN COLORECTAL ADENOCARCINOMA AND THEIR RELATIONSHIP WITH CLINICOPATHOLOGICAL PARAMETERS
Authors: Lesmana Vienna Alodia 
Published: March 2021

Colorectal carcinoma (CRC) is the third most common cancer among worldwide. Data from WHO GLOBOCAN in 2018 show there were 1.8 million cases of CRC in the world, with mortality rates 861,000. Histopathology of tumor show 90% of CRC is adenocarcinoma and predominantly in men. Some proteins that are thought to play a role in tumor development are HER2 and Galectin-3. Correlation between expression of Human Epidermal Growth Factor Receptor 2 (HER2) and Galectin-3 with clinicopathology aspect are expected to help determine treatment options. The aim of this study was to investigate the correlation between expression levels of HER-2 and Galectin-3 in vary clinicopathological aspect of colorectal adenocarcinoma. Cross sectional study was conducted in 40 samples of colorectal adenocarcinoma in dr. Kariadi Central General Hospital from 1st January 2018 until 31st December 2018. Samples were analyzed regarding the expression of HER2 and Galectin-3 by immunohistochemical staining of paraffin-embedded material. Coexpression of HER-2, Galectin-3 and the clinicopathological parameters (gender, age, location, depth of invasion, lymph nodes metastase, distant metastase and stage) were analyzed using Chi square test and Spearmans correlation test. Positive HER-2 expression was found on 5% of samples, while strong expresion of Galectin-3 was found on 12.5% of samples. There was no significant correlation between HER-2 and Galectin-3 expression and clinicopathology aspect.
A Systematic Review of Tissue Engineering Scaffold in Tendon Bone Healing in vivo
Authors: Mao Zimu , Fan Baoshi , Wang Xinjie , Huang Ximeng , Guan Jian , Sun Zewen , Xu Bingbing , Yang Meng , Chen Zeyi , Jiang Dong , Yu Jiakuo 
Published: March 2021

Background: Tendon-bone healing is an important factor in determining the success of ligament reconstruction. With the development of biomaterials science, the tissue engineering scaffold plays an extremely important role in tendon-bone healing and bone tissue engineering.Materials and Methods: Electronic databases (PubMed, Embase, and the Web of Science) were systematically searched for relevant and qualitative studies published from 1 January 1990 to 31 December 2019. Only original articles that met eligibility criteria and evaluated the use of issue engineering scaffold especially biomaterials in tendon bone healing in vivo were selected for analysis.Results: The search strategy identified 506 articles, and 27 studies were included for full review including two human trials and 25 animal studies. Fifteen studies only used biomaterials like PLGA, collage, PCL, PLA, and PET as scaffolds to repair the tendon-bone defect, on this basis, the rest of the 11 studies using biological interventions like cells or cell factors to enhance the healing. The adverse events hardly ever occurred, and the tendon bone healing with tissue engineering scaffold was effective and superior, which could be enhanced by biological interventions.Conclusion: Although a number of tissue engineering scaffolds have been developed and applied in tendon bone healing, the researches are mainly focused on animal models which are with limitations in clinical application. Since the efficacy and safety of tissue engineering scaffold has been proved, and can be enhanced by biological interventions, substantial clinical trials remain to be done, continued progress in overcoming current tissue engineering challenges should allow for successful clinical practice.
Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension: A Protocol for an Acute, Randomized, Double-Blinded, Placebo-Controlled Cross-Over Trial
Authors: Tanghe Anouk , Celie Bert , Shadid Samyah , Rietzschel Ernst , Op ‘t Roodt Jos , Reesink Koen D. , Heyman Elsa , Calders Patrick 
Published: March 2021

Introduction: Patients with type 2 diabetes mellitus are at high risk to develop vascular complications resulting in high morbidity and mortality. Cocoa flavanols are promising nutraceuticals with possible beneficial vascular effects in humans. However, limited research is currently available on the vascular effects in a diabetic population with inconsistent results. Possible reasons for this inconsistency might be heterogeneity in the given intervention (dose per time and day, single dose vs. split-dose, placebo formula) and the studied population (blood pressure at baseline, duration of diabetes, use of vasoactive antihypertensive and antidiabetic drugs, sex). Therefore, we aimed to develop a randomized, double-blinded, placebo-controlled cross-over trial to investigate whether cocoa flavanols have an acute impact on blood pressure and vascular reactivity in patients with type 2 diabetes with and without arterial hypertension.Methods and Analysis: We will include participants in four groups: (i) patients with type 2 diabetes without arterial hypertension, (ii) patients with type 2 diabetes with arterial hypertension and 1 antihypertensive drug, (iii) non-diabetic participants with essential hypertension and 1 antihypertensive drug, and (iv) healthy controls. All participants will complete the same protocol on both testing days, consuming high-flavanol cocoa extract (790 mg flavanols) or placebo. Macrovascular endothelial function (flow-mediated dilation) and blood pressure will be measured before and after capsule ingestion. Forearm muscle vasoreactivity (near-infrared spectroscopy) and brachial artery blood flow (echo-doppler) will be assessed in response to a dynamic handgrip exercise test after capsule ingestion. Data will be analyzed with a random intercept model in mixed models.Clinical Trial Registration:www.Clinicaltrials.gov, identifier: NCT03722199.
Association of a Network of Immunologic Response and Clinical Features With the Functional Recovery From Crotalinae Snakebite Envenoming
Authors: Gerardo Charles J. , Silvius Elizabeth , Schobel Seth , Eppensteiner John C. , McGowan Lauren M. , Elster Eric A. , Kirk Allan D. , Limkakeng Alexander T. 
Published: March 2021

BackgroundThe immunologic pathways activated during snakebite envenoming (SBE) are poorly described, and their association with recovery is unclear. The immunologic response in SBE could inform a prognostic model to predict recovery. The purpose of this study was to develop pre- and post-antivenom prognostic models comprised of clinical features and immunologic cytokine data that are associated with recovery from SBE. Materials and MethodsWe performed a prospective cohort study in an academic medical center emergency department. We enrolled consecutive patients with Crotalinae SBE and obtained serum samples based on previously described criteria for the Surgical Critical Care Initiative (SC2i)(ClinicalTrials.gov Identifier: NCT02182180). We assessed a standard set of clinical variables and measured 35 unique cytokines using Luminex Cytokine 35-Plex Human Panel pre- and post-antivenom administration. The Patient-Specific Functional Scale (PSFS), a well-validated patient-reported outcome of functional recovery, was assessed at 0, 7, 14, 21 and 28 days and the area under the patient curve (PSFS AUPC) determined. We performed Bayesian Belief Network (BBN) modeling to represent relationships with a diagram composed of nodes and arcs. Each node represents a cytokine or clinical feature and each arc represents a joint-probability distribution (JPD).ResultsTwenty-eight SBE patients were enrolled. Preliminary results from 24 patients with clinical data, 9 patients with pre-antivenom and 11 patients with post-antivenom cytokine data are presented. The group was mostly female (82%) with a mean age of 38.1 (SD ± 9.8) years. In the pre-antivenom model, the variables most closely associated with the PSFS AUPC are predominantly clinical features. In the post-antivenom model, cytokines are more fully incorporated into the model. The variables most closely associated with the PSFS AUPC are age, antihistamines, white blood cell count (WBC), HGF, CCL5 and VEGF. The most influential variables are age, antihistamines and EGF. Both the pre- and post-antivenom models perform well with AUCs of 0.87 and 0.90 respectively.DiscussionPre- and post-antivenom networks of cytokines and clinical features were associated with functional recovery measured by the PSFS AUPC over 28 days. With additional data, we can identify prognostic models using immunologic and clinical variables to predict recovery from SBE.
Lipidomic Perturbations in Cynomolgus Monkeys are Regulated by Thyroid Stimulating Hormone
Authors: Xu Tao , Yang Yanling , Huang Xing , Ren Jianhong , Xu Ting , Xie Wei 
Published: March 2021

Thyroid disease affects an estimated 200 million people worldwide, and is commonly associated with increased blood lipid levels. However, the mechanism by which thyroid-stimulating hormone (TSH) affects lipid profiles is not clear. Twenty-four cynomolgus monkeys were treated with a novel exogenous recombinant human TSH (rhTSH) (SNA001) at 9 μg kg−1, 22 μg kg−1, or 54 μg kg−1, and reference rhTSH (Thyrogen®) at 22 μg kg−1. The primary TSH (SNA001) pharmacokinetic (PK) parameters increased in a dose-dependent manner across the dose range of 9 μg kg−1, 22 μg kg−1, or 54 μg kg−1. Peak triiodothyronine (T3) and thyroxine (T4) levels were reached within 24 h after rhTSH administration, which was delayed by approximately 20 h. In total, 420 lipid species were detected and quantified by ultra-performance liquid chromatography high resolution spectrometry (UPLC-HR-MS)-based lipidomics. Notably, peak levels of lipid accumulation, particularly sphingomyelin (SM) and triglycerides (TG), appeared at 4 and 24 h, which was consistent with the pattern of TSH and T3/T4 levels, respectively. According to weighted correlation network analysis (WGCNA), perturbations of many lipid species were strongly correlated with TSH and T3/T4 levels. TSH and the stimulated T3/T4 levels and lipid profiles following SNA001 administration were comparable to those after administration of the reference rhTSH (Thyrogen®). The plasma lipidome and changes in lipid levels after rhTSH stimulation were associated with TSH and T3/T4 concentrations. T3/T4 and lipid profiles were delayed after TSH stimulation. Such phenomena require further exploration.
A New Classification of Anterior Choroidal Artery Aneurysms and Its Clinical Application
Authors: Duan Yu , Qin Xuanfeng , An Qinqzhu , Liu Yikui , Li Jian , Chen Gong 
Published: March 2021

Background and Purpose: The aim of this study was to compare the different subtypes of anterior choroidal artery (AChoA) aneurysm based on a new classification and to analyze the risk factors according to individual endovascular treatment (EVT).Methods: In the new classification, AChoA aneurysms are classified into independent type (I type) and dependent type (II type) based on the relationship between the AChoA and the aneurysm. II type aneurysms have three subtypes, IIa (neck), IIb (body), and IIc (direct). We retrospectively analyzed 52 cases of AChoA aneurysm treated in our center between 2015 to 2019. There were 13 (25.0%) I type aneurysms, 24 (46.2%) IIa aneurysms, 15 (28.8%) IIb aneurysms, and no IIc type; 28 cases had a subarachnoid hemorrhage. According to our preoperative EVT plan for the different subtypes: II type should achieve Raymond-Roy Occlusion Class 1 (RROC 1) where possible. To protect the AChoA, it is best to preserve the neck of the IIa type aneurysms (RROC 2), and RROC 3 is enough for IIb type.Results: Ten asymptomatic cases with minimal aneurysms were treated conservatively. Of the other cases, 42 were treated with individualized EVT (26 with a simple coil, 6 with balloon-assisted coiling, 7 with stent-assisted coiling, and 3 by flow diverter. Different subtypes had different RROC (Z = 14.026, P = 0.001). IIb type aneurysms (χ2 = 7.54, P = 0.023) were one of the factors related to temporary or permanent AChoA injury during surgery. Overall, two patients (IIa = 1, IIb = 1) developed contralateral hemiparesis.Conclusions: The new classification diagram clearly shows the features of all types of AChoA aneurysm and makes EVT planning more explicit. The II type (particularly IIb) was a potential risk factor for AChoA injury.
Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein–Barr Virus-Specific T Cell Therapy
Authors: Ioannides Zara A. , Csurhes Peter A. , Douglas Nanette L. , Mackenroth Gem , Swayne Andrew , Thompson Kate M. , Hopkins Tracey J. , Green Kerryn A. , Blum Stefan , Hooper Kaye D. , Wyssusek Kerstin H. , Coulthard Alan , Pender Michael P. 
Published: March 2021

Background: Increasing evidence indicates a role for Epstein–Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment.Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy.Methods: We assessed participants 2 and 3 years after completion of T cell therapy.Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product.Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.
Assisted Suicide in Parkinsonian Disorders
Authors: Nuebling Georg S. , Butzhammer Elisabeth , Lorenzl Stefan 
Published: March 2021

Background: Due to the high prevalence of suicidal ideation in Parkinson's Disease (PD) and exploratory data indicating a similar prevalence in atypical Parkinsonian disorders (APD), we sought to determine the frequency of assisted suicide (AS) as well as factors driving these decisions in PD and APD.Methods: Retrospective chart analysis (2006-2012) at a Swiss Right-to-Die organization. Patients with PD and APD who completed AS were analyzed concerning disease state, symptom burden, medication, and social factors.Results: We identified 72 patients (PD = 34, PSP = 17, MSA = 17, CBS = 4; 7.2% of all AS cases), originating mainly from Germany (41.7%), Great Britain (29.2%), and the US (8.3%). Predominant symptoms at the time of application were immobility (PD/APD: 91%/97%), helplessness (63%/70%), pain (69%/19%), dysarthria (25%/32%), and dysphagia (19%/59%). APD patients generally showed a higher symptom burden and a higher frequency of diagnosed depression (8.8%/28.9%). While most patients with diagnosed depression received antidepressants (80%), other symptoms such as pain (59%) were treated less consistently. Of note, time from diagnosis to application differed greatly between PD (8.5 ± 6.8 years) and APD (1.5 ± 1.3 years, p &lt; 0.0001).Conclusions: In our analysis, Parkinsonian disorders appeared to be overrepresented as a cause of AS considering the prevalence of these diseases. The observation that assisted suicide is sought early after initial diagnosis in APD implies the need for early comprehensive psychological support of these patients and their relatives.
The Insula Is a Hub for Functional Brain Network in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Authors: Li Chunyan , Pang Xiaomin , Shi Ke , Long Qijia , Liu Jinping , Zheng Jinou 
Published: March 2021

BackgroundIn recent years, imaging technologies have been rapidly evolving, with an emphasis on the characterization of brain structure changes and functional imaging in patients with autoimmune encephalitis. However, the neural basis of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and its linked cognitive decline is unclear. Our research aimed to assess changes in the functional brain network in patients with anti-NMDAR encephalitis and whether these changes lead to cognitive impairment.MethodsTwenty-one anti-NMDAR encephalitis patients and 22 age-, gender-, and education status-matched healthy controls were assessed using resting functional magnetic resonance imaging (fMRI) scanning and neuropsychological tests, including the Hamilton Depression Scale (HAMD24), the Montreal Cognitive Assessment (MoCA), and the Hamilton Anxiety Scale (HAMA). A functional brain network was constructed using fMRI, and the topology of the network parameters was analyzed using graph theory. Next, we extracted the aberrant topological parameters of the functional network as seeds and compared causal connectivity with the whole brain. Lastly, we explored the correlation of aberrant topological structures with deficits in cognitive performance.ResultsRelative to healthy controls, anti-NMDAR encephalitis patients exhibited decreased MoCA scores and increased HAMA and HAMD24scores (p&lt; 0.05). The nodal clustering coefficient and nodal local efficiency of the left insula (Insula_L) were significantly decreased in anti-NMDAR encephalitis patients (p&lt; 0.05 following Bonferroni correction). Moreover, anti-NMDAR encephalitis patients showed a weakened causal connectivity from the left insula to the left inferior parietal lobe (Parietal_Inf_L) compared to healthy controls. Conversely, the left superior parietal lobe (Parietal_sup_L) exhibited an enhanced causal connectivity to the left insula in anti-NMDAR encephalitis patients compared to controls. Unexpectedly, these alterations were not correlated with any neuropsychological test scores.ConclusionThis research describes topological abnormalities in the functional brain network in anti-NMDAR encephalitis. These results will be conducive to understand the structure and function of the brain network of patients with anti-NMDAR encephalitis and further explore the neuropathophysiological mechanisms.
Primary Tumor Resection for Rectal Cancer With Unresectable Liver Metastases: A Chance to Cut Is a Chance for Improved Survival
Authors: Chen Jia-nan , Shoucair Sami , Wang Zheng , Habib Joseph R. , Zhao Fu-qiang , Yu Jun , Liu Zheng , Liu Qian 
Published: March 2021

Background: About half of the patients with rectal cancer will develop liver metastasis during the course of their illness. Unfortunately, a large proportion of these metastases are unresectable. Surgical resection of the primary tumor vs. palliative treatment in patients with unresectable synchronous liver metastases remains controversial.Methods: Patients with rectal cancer with surgically unresectable liver metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2015. According to different treatment modalities, patients were divided into a primary tumor resection group and a non-resection group. Rates of primary tumor resection and survival were calculated for each year. Kaplan–Meier methods and Cox regression models were used to assess long-term survival. Multivariable logistic regression models were used to evaluate factors potentially associated with primary tumor resection.Results: Among 1,957 patients, 494 (25.2%) had undergone primary tumor resection. Patients with primary tumor resection had significantly better 5-year survival rate (27.2 vs. 5.6%, P &lt; 0.001) compared to the non-resection group. Chemoradiotherapy with primary site resection was associated with the longest mean and 5-year OS (44.7 months, 32.4%). The Cox regression analyses of the subgroup indicated that patients who underwent primary tumor resection had improved survival compared with those who did not undergo resection in all 25 subgroups. Factors associated with primary tumor resection were well or moderately differentiated tumor grade, undergoing radiation, and primary tumor size &lt;5 cm.Conclusions: The majority of patients with rectal cancer with unresectable liver metastases did not undergo primary tumor resection. Our results indicate that resection of the primary tumor appears to offer the greatest chance of survival. Prospective studies are needed to confirm these results.
Protective Factors for Early Childhood Caries in 3-Year-Old Children in Poland
Authors: Olczak-Kowalczyk Dorota , Gozdowski Dariusz , Turska-Szybka Anna 
Published: March 2021

Background: Early childhood caries (ECC) remains highly prevalent in preschool children worldwide. Dental caries affects every second 3-year-olds in Poland. The aim of the study was to assess protective factors for ECC in 3-year-olds.Methods: A cross-sectional survey was conducted in 2017 among 3-year-olds attending kindergartens in all 16 provinces of Poland. The questionnaire included socioeconomic factors, and oral health behaviors. Decayed, missing due to caries and filled teeth and surfaces were assessed. Caries indices (dmft and dmfs), percentage of caries-free and severe ECC (S-ECC) were calculated. The Student's t-test, Spearman correlation, univariate and multivariate logistic regression (the odds ratios (OR) and adjusted odds ratios (AOR): confounding factors: socioeconomic conditions, oral health behaviors) were performed; p &lt; 0.05.Results: A total of 1,638 children were included. ECC was confirmed in 41.1%; S-ECC in 23.4%. The dmft index was 1.85 ± 3.14, dmfs = 2.99 ± 6.56. Spearman correlation [socioeconomic factors, especially mother's education (r = −0.148, p &lt; 0.001) and family's economic status (r = −0.071, p = 0.004)], despite were statistically significant, indicate very weak relationships with dmft index. After 12th month of life not giving any beverages before bedtime and at night, but water or unsweetened milk only, healthy snacking (sandwiches, fresh fruit), or water on a daily basis decreases the probability of caries development (for S-ECC: OR = 0.37, AOR = 0.47, AOR2 = 0.37; p &lt; 0.01), even if inappropriate dietary behaviors or hygiene practices were simultaneously present. Brushing of a child's teeth twice a day lowered the odds of caries (for S-ECC: OR = 0.78, p = 0.031; AOR = 0.81, p = 0.081; AOR2 = 0.84, p = 0.131), but this effect was less intense when inappropriate dietary behaviors were accounted for. Children of parents with good self-assessment of their teeth were more often caries-free (61.4 vs. 42.9%; p = 0.006) and had lower dmft indices (1.67 vs. 2.93; p = 0.002).Conclusions: Preventing a child after 12th month of life from getting any beverages before bedtime, water or unsweetened milk only, sandwiches and fresh fruit as snacks, or water given to on a daily basis, tooth brushing twice a day decrease the odds of caries in 3-year-olds. Diet appears to have primary significance in the etiology of ECC, since tooth brushing can only partly attenuate the impact of inappropriate dietary behaviors on dental caries. Children are more often caries-free and have lower severity of caries if their parents' dentition is self-assessed as healthy.