bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathological Results (Benign/Malignant) Can be Inferred from Macroscopic Findings for Breast Vacuum Associated Biopsy Specimens
Authors: Izumori Ayumi , Takahashi Masako , Sasa Soichiro , Inoue Hiroaki , Tangoku Akira , Sasa Mitsunori
Published: June 2021

Background: If the histopathological results could be inferred from the macroscopic findings for breast biopsy specimens, false-negative needle biopsies due to poor specimens could be prevented. However, no research on this has been reported to date.Methods: Biopsy specimens from 101 patients who underwent mammary gland Vacuum Associated Biopsy (VAB) were photographed with a smartphone, and the relationships between the macroscopic findings (presence/absence of turbidity, surface properties, presence/absence of white spots, and characteristic findings) and the pathological results (benign/malignant) were examined.Results: A significant difference was observed with regard to the presence/absence of turbidity: malignancy was detected in 33/37 (89%) specimens with turbidity and in 2/47 (4%) cases without turbidity (p<0.001). A significant difference was also observed regarding the surface properties: malignancy was detected in 14/70 (19%) smooth specimens and in 24/29 (83%) rough specimens (p<0.001). Also, malignancy was detected in 11/13 (85%) specimens with white spots, and the difference was significant (p<0.001).Conclusions: The pathological results (benign/malignant) were able to be predicted from the macroscopic findings for the breast VAB specimens. These findings warrant performance of reproducibility and prospective studies at multiple facilities.
Long-Term Macrolide Treatment for Non-Cystic Fibrosis Bronchiectasis in Children: A Meta-Analysis
Authors: Lee Eun , Sol In Suk , Kim Jong Deok , Yang Hyeon-Jong , Min Taek Ki , Jang Gwang Cheon , Hwang Yoon Ha , Cho Hyun-Ju , Suh Dong In , Kim Kyunghoon , Kim Hwan Soo , Kim Yoon Hee , Woo Sung Il , Lee Yong Ju , Jung Sungsu , Jeon You Hoon
Published: June 2021

Recurrent bacterial infection causes frequent exacerbations of Bronchiectasis (BE). The effectiveness and safety of macrolide long-term administration in BE remains controversial, especially in children with little treatment to prevent exacerbation. We conducted this meta-analysis to determine the usefulness of long-term macrolide in pediatric BE. We searched PubMed, Cochrane Library databases, Embase, KoreaMed, Igaku Chuo Zasshi, and Chinese National Knowledge Infrastructure databases. We identified randomized controlled trials (RCTs) on long-term macrolide treatment (≥ 4 weeks) in non-cystic fibrosis BE in children aged < 18 years. The primary outcome was frequency of acute exacerbation; secondary outcomes were changes in pulmonary function, sputum scores, and adverse events including bacterial resistance. We included four RCTs. Long-term macrolide treatment showed a significant decrease in the frequency of exacerbation (odds ratio [OR], 0.30; 95% confidence interval [CI], 0.10 to 0.87), mean number of exacerbations per patient (mean difference, -1.40; 95% CI, -2.26 to -0.54) and sputum purulence score (mean difference, -0.78; 95% CI, -1.32 to -0.24). However, long-term macrolide treatment was accompanied by increased carriage of azithromycin-resistant bacteria (OR, 7.13). Long-term macrolide administration prevents exacerbation of BE in children, but risks increasing antibiotic resistance. Benefits and risks should be weighed and determined on a patient-by-patient basis.
Development and Validation of a Radiomics-based Model to Predict Local Progression-free Survival After Chemo-radiotherapy in Patients With Esophageal Squamous Cell Cancer
Authors: Luo He-San , Chen Ying-Ying , Wu Sheng-Xi , Huang Shao-Fu , Xu Hong-Yao , Xue Ren-Liang , Du Ze-Sen , Li Xu-Yuan , Lin Lian-Xin , Huang He-Cheng
Published: June 2021

Purpose: To develop a nomogram model for predicting local progress-free survival (LPFS) in esophageal squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy. Methods: We collected the clinical data of ESCC patients treated with CCRT in our hospital. Eligible patients were randomly divided into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) with COX regression was performed to select optimal radiomics features calculating Rad-score for predicting LPFS in the training cohort. The univariate and multivariate analysis were performed to identify the predictive clinical factors for developing a nomogram model. The C-index was used to assess the performance of the predictive model and calibration curve was used to evaluate the accuracy.Results: A total of 221 ESCC patients were included in our study, with 155 patients in training cohort and 66 patients in validation cohort. After LASSO COX regression analysis, seventeen radiomics features were selected to calculate Rad-score for predicting LPFS. The patients with a Rad-score≥0.1411 had high risk of local recurrence, and those with a Rad-score<0.1411 had low risk of local recurrence. Multivariate analysis showed that N stage, CR status and Rad-score were independent predictive factors for LPFS. A nomogram model was built based on the result of multivariate analysis. The C-index of the nomogram was 0.745 (95%CI: 0.7700 -0.790) in training cohort and 0.723(95%CI：0.654-0.791) in validation cohort. The 3-year LPFS rate predicted by the nomogram model was highly consistent with the actual 3-year LPFS rate both in the training cohort and the validation cohort.Conclusion: We developed and validated a prediction model based on radiomics features and clinical factors, which can be used to predict LPFS of patients after CCRT. This model is conducive to making individualized chemoradiotherapy strategy and providing scientific basis for subsequent intensive adjuvant therapy for ESCC patients.
Design of a Low Power Hybrid Electro-Optic Plasmonic Modulator Based on ITO and Graphene
Authors: Abbaszadeh-Azar Omid , Abedi Kambiz
Published: June 2021

In this paper, a hybrid plasmonic modulator based on ITO and graphene has been proposed and designed. Graphene and ITO are used in the active region, which increases the light-matter interaction and reduces the device's operating voltage in the proposed modulator. As a result, it increases the extinction ratio (ER), reduces power consumption and device footprint in the proposed modulator compared to similar modulators. The values of 14 dB/µm and 5.4 fJ are obtained for ER and power consumption, respectively. The time-domain finite-difference (FDTD) method is used to simulate the modulator. The integration of a modulator with high light-matter interaction and low power consumption in the silicon-on-insulator platform has significant potential for broadband, compact and efficient communication interconnects and circuits.
Association Between Nonalcoholic Fatty Liver Disease and the Incidence of Asthma in Adults: Finding from a Nationwide Study in Korea
Authors: Roh Jae-Hyung , Lee Hanbyul , Bae Yun-Jeong , Park Chan Sun , Kim Hyo-Jung , Yoon Sun-Young
Published: June 2021

Asthma and nonalcoholic fatty liver disease (NAFLD) are chronic diseases and are known to be associated with metabolic abnormalities. We aimed to clarify the association between NAFLD and the incidence of asthma in a large population-based cohort. We selected 160,603 healthy individuals without comorbidities from the National Health Insurance Service-National Sample cohort during 2009–2014. . NAFLD was defined by a surrogate marker, the fatty liver index (FLI). During a median of 5.08 years’ follow-up, 16,377 subjects (10.2%) were newly diagnosed with asthma and categorized into three groups according to FLI. The cumulative incidence of asthma was higher in subjects with higher vs. lower FLIs (FLI < 30 10.1%, 30 ≤ FLI < 60 10.8%, FLI ≥ 60 10.5% ). Higher FLI associated with an increased incidence of asthma (Harzard ratios (HR)highest vs. lowest FLI, 1.25; 95% CI, 1.15-1.36). The results using another definition of NAFLD as measured by hepatic steatosis index (HIS) are similar to the primary results. This association was more pronounced in women than in men (HR 1.46; 95% CI, 1.13-1.64 vs. HR 1.07; 95% CI, 0.94-1.20). This study demonstrated that NAFLD as measured by FLI and HIS may influence the incidence rates of asthma in adults, especially in women.
Health Complaints in Individual Visiting Primary Health Care: Population-Based National Electronic Health Records of Iran
Authors: Khatami Farnaz , Shariati Mohammad , Abbasi Zahra , Muka Taulant , Khedmat Leila , Saleh Narges
Published: June 2021

Background
The mission of medical schools is a sustainable commitment to orient education, research, and services based on the priorities and expectations of society. The most common complaints of patients from comprehensive health service centers (CHSCs) based on the data from electronic health records were identified to determine primary health care (PHC) priorities for the educational planning of medical students in Iran.
Methods
A population-based national study was designed to assess clinical complaints of patients in all age groups who were referred at least once to CHSCs to be visited by physicians. All the data in the census were extracted from electronic health records in PHC system during 2015–2020, classified by the International Classification of Primary Care (ICPC-2), and statistically analyzed. The total number of complaints that recorded in system was 17,430,139.
Results
59% of the referring patients were women. The highest number of referrals was related to the age group of 18–59 years (56.9%), while the lowest belonged to the elderly (13.3%). In all age and sex groups, the first ten complaints of patients with three top priorities in each category included process (follow-up, consultation, and results exam), digestive (toothache and gum complaint, abdominal pain, and diarrhea), respiratory (cough, sore throat, and runny nose), general (fever, pain, and weakness and fatigue), musculoskeletal (back pain, leg complaint, and knee injuries), endocrine and nutritional (weight gain, Feeding problem, and weight loss), cardiovascular (hypertension, palpitations, and Postural hypotension), neurological (headache, dizziness, and paralysis), sexual dysfunction (vaginal complaint, discharge, and irregular menstruation), and dermatological (pruritus, rash, and inflammation).
Conclusion
High priorities in referring to PHC had a key role in assessing the country's health needs. Since this study was in line with the national pattern of complaints and patients' profile, the present findings can be helpful to amend policy-making, educational planning and curricula development in medical schools.
The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury
Authors: Bretheau Floriane , Castellanos-Molina Adrian , Mailhot Benoit , Kusik Maxime , Belanger Dominic , Lessard Martine , Vallières Nicolas , Liu Xiaoyu , Quan Ning , Lacroix Steve
Published: June 2021

Spinal cord injury (SCI) triggers neuroinflammation, and subsequently secondary degeneration and oligodendrocyte (OL) death. We report that the alarmin interleukin (IL)-1α is released by damaged microglia after SCI. Intra-cisterna magna injection of IL-1α in mice rapidly induced neutrophil infiltration and OL death throughout the spinal cord, mimicking what is seen at sites of SCI. These effects were abolished by co-treatment with the IL-1R1 antagonist anakinra, as well as in IL-1R1-knockout mice which showed enhanced locomotor recovery after SCI. Conditional restoration of IL-1R1 expression in astrocytes or endothelial cells (ECs), but not in OLs or microglia, restored IL-1α-induced effects, while astrocyte- or EC-specific Il1r1 deletion reduced OL loss. Conditioned medium derived from IL-1α-stimulated astrocytes is toxic for OLs; further, IL-1α-stimulated astrocytes generate reactive oxygen species (ROS) and blocking ROS production in IL-1α-treated or SCI mice prevented OL loss. Thus, after SCI, microglia release IL-1α, which induces astrocyte- and EC-mediated OL degeneration.
Collision Detection Algorithm of Belt Grinding of the Blisk Based on Improved Octree Segmentation Method
Authors: Huang Zhi , Yang Xing , Min Jie , Wang Hongyan , Wei Pengxuan
Published: June 2021

In the process of belt grinding aero-engine Blisk(Bladed Disk), the abrasive belt can easily interfere with the Blisk, which will damage the valuable Blisk. Therefore, it is indispensable and significant to study the collision detection of belt grinding the Blisk. However, the application of traditional collision detection algorithms in this complicated realistic scene is difficult to obtain satisfactory results. In order to improve the accuracy and efficiency of the collision detection of grinding the Blisk, a collision detection algorithm based on the improved octree segmentation method is proposed in this paper. Firstly, the Oriented Bounding Box (OBB) is applied to establish the collision detection model for the abrasive belt. Secondly, the traditional octree segmentation method is optimized based on the k-means clustering algorithm, and an improved octree segmentation method is presented, in addition, the flow chart of the collision detection algorithm for belt grinding of the Bliskis given. Finally, algorithm verification and experimental verification are carried out based on a certain type of the Blisk. The results suggest that compared with the traditional method, the method in this paper not only promotes the accuracy of collision detection, but also promotes the efficiency of collision detection, and meets the requirements of object collision detection in this tanglesome scene with both accuracy and speed.
A Review of Unusual VLF Bursty-Patches Observed in Northern Finland
Authors: Martinez-Calderon Claudia , Manninen Jyrki K. , Manninen Jemina T. , Turunen Tauno
Published: June 2021

Using numerical ﬁltering techniques allowing to reduce noise from sferics, we are able to clearly study a new type of differently structured very low frequency (VLF) waves above f = 4 kHz at the ground station of Kannuslehto in northern Finland (KAN, MLAT=64.4°N, L=5.5). These emissions are intriguing since they are detected above the local equatorial electron gyrofrequency for the L-shell of Kannuslehto (fce ~ 5- 6 kHz). They are commonly observed at Kannuslehto, but have also been infrequently reported at other stations, sometimes under different names. Their possible common origin and manner of propagation is still under investigation. This paper unifies the nomenclature by regrouping all these waves detected at frequencies higher than the local equatorial 0.5 fce at the L-shell of observation under the name of VLF bursty-patches. We also give a review of the different characteristics of VLF bursty-patches observed by Kannuslehto, which at the moment, is the station with the highest observation rate. We will present recent observations between 2019 and 2021. While these waves have different spectral features, they appeared mostly composed of hiss bursts with durations of a few seconds to several minutes. They also show periodic features with varying periodicity and shape. They are sometimes characterized by single bursts covering very large frequency ranges of several kHz.
Real-Time Source-Independent Quantum Random Number Generator Based on a Cloud Superconducting Quantum Computer
Authors: Li Yuanhao , Wang Weilong , Fei Yangyang , Meng Xiangdong , Wang Hong , Duan Qianheng , Ma Zhi
Published: June 2021

Quantum random number generator (QRNG) relies on the intrinsic randomness of quantum mechanics to produce true random numbers which are important in information processing tasks. Due to the presence of the superposition state, quantum computer can be used as a true random number generator. However, in practice, the implementation of quantum computer is subject to various noise sources which affect the randomness of the generated random numbers. To solve this problem, we propose a source-independent QRNG (SI-QRNG) scheme based on quantum computer which is motivated by the SI-QRNG scheme in quantum optics. The scheme can provide certified randomness by estimating the preparation error of superposition states in real time even when the source is untrusted, under the assumption that the measurement operation is trusted. Our analysis takes into account the readout error of quantum state and further gives the final extracted number of random bits. And the estimation method of preparation error of superposition state in randomness source. We also provide a parameter optimization method to increase the generation rate of random bits. In addition, by utilizing the cloud superconducting quantum computer of IBM, we experimentally demonstrate the practicality of our SI-QRNG scheme and achieve the generation of true random numbers.
Internet Search Effort on Covid-19 and the Underlying Public Interventions and Epidemiological Status
Authors: Moustakas Aristides
Published: June 2021

This study aimed to quantify the relative importance of indices of personal freedom, economy, and epidemiology on the public interest on Covid-19 expressed by internet searches on the topic. The relationship between the effective reproduction rate Rt, news media cover, and web search effort was also quantified. Data of online search in Greece on Covid-19 topic for one year were analyzed using indices of social distancing, financial measures, and epidemiological variables using machine learning. Temporal autocorrelation of web search effort was quantified and control charts of web search, Rt, new cases and new deaths were employed. Results indicated that the trained model exhibited a fit of R2 = 91% between the actual and predicted web search effort. The top five variables for predicting web search effort were new deaths, the opening of international borders to non-Greek nationals, new cases, testing policy, and restrictions in internal movements. Web search had negligible temporal autocorrelation between weeks. Web search peaked during the same weeks that the Rt was peaking although new deaths or new cases were not peaking during those dates. The extent to which online searches may reflect the actual epidemiological situation is discussed.
Pulmonary Alveolar Microlithiasis and Pregnancy - A Case Report
Authors: AGARWAL MUKTA , SINGH RITU , Sinha Sudwita , Kumar Neeraj
Published: June 2021

Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive disease with a high penetrance characterized by widespread intra-alveolar accumulation of innumerable minute calculi called microliths. Pregnancy with PAM is even rarer. Here we are presenting the second case in India of 28yrs G2P1L1 37 weeks 1 day, known case of PAM with gestational hypothyroidism. She had difficulty in breathing which has increased from NYHA- grade II to NYHA- grade III from the fifth month of gestation. She had parrot beak (grade 3) clubbing. She was having intrauterine growth restriction with a growth discrepancy of four weeks. The patient was taken for cesarean section in view of a breech with premature rupture of the membrane with intrauterine growth restriction. Since lung function is compromised, oxygen supply to the baby is expected to be compromised, which can lead to intrauterine growth restriction, which is evident in this patient in both of her pregnancies.
Hexahedral Mesh Quality Improvement with Geometric Constraints
Authors: peng wei , Wu Xinguang , Bao Yidong , Zhang Chaoyang , Ji Weixi
Published: June 2021

Hexahedral mesh is of great value in the analysis of mechanical structure, and the mesh quality has an important impact on the efficiency and accuracy of the analysis. This paper presents a quality improvement method for hexahedral meshes, which consists of node classification, geometric constraints based single hexahedron regularization and local hexahedral mesh stitching. The nodes are divided into different types and the corresponding geometric constraints are established in single hexahedron regularization to keep the geometric shapes of original mesh. In contrast to the global optimization strategies, we perform the hexahedral mesh stitching operation within a few local regions surrounding elements with undesired quality, which can effectively improve the quality of the mesh with less consuming time. A number of mesh quality improvements for hexahedral meshes generated by a variety of methods are introduced to demonstrate the effectiveness of our method.
MiR-498 targets UBE2T to Inhibit Proliferation and Metastasis in Malignant Melanoma
Authors: Dang Ningning , Cao Wen , Li Pin , Huang Shuhong
Published: June 2021

BackgroundMalignant melanoma (MM) is a common malignant tumor and also one of the fastest growing malignancies. Considering that UBE2T could be a direct target of miR-498, we explore the ability of miR-498 to regulate MM cell progression by targeting UBE2T.MethodsWe detected the expression of miR-498 by quantitative real-time PCR assay. The cell proliferation, invasion and migration in MM cells were measured by cell counting kit-8, clone formation and transwell assays. Flow cytometry assay was used to detect the percentage of apoptotic cells. We explored the correction of miR-498 and UBE2T by dual-luciferase assays.ResultsDuring the study, we found that the overexpression of miR-498 inhibited proliferation, invasion, migration and induced cell apoptosis of M14 and A375 cells. In addition, the expression of epithelial-mesenchymal transition (EMT)-related factors was altered by overexpression of miR-498. Furthermore, UBE2T was differentially expressed in MM and normal tissues and high expression of UBE2T was strongly correlated with poor overall survival in patients with MM. We highlighted that overexpression of UBE2T reversed the inhibitory effects of miR-498 on MM cell progression.ConclusionsAltogether, our findings demonstrated that miR-498 significantly inhibited cell proliferation, invasion, migration and induced apoptosis, whilst confirming that miR-498 regulated MM cell progression by targeting UBE2T.
Critical Issue On The Extinction and Inattention Subtest of NIHSS Scale. An Analysis on Post-Acute Stroke Patients Attending Inpatient Rehabilitation
Authors: Basagni Benedetta , Hakiki Bahia , Campagnini Silvia , Salvadori Emilia , Grippo Antonello , Paperini Anita , Castagnoli Chiara , Hochleitner Ines , Politi Angela Maria , Gemignani Paola , Mosca Irene Eleonora , Franceschini Azzurra , Bonotti Enrico Bacci , Sodero Alessandro , Mannini Andrea , Pellicciari Leonardo , Poggesi Anna , Macchi Claudio , Carrozza Maria Chiara , Cecchi Francesca
Published: June 2021

Objectives
This study aims to evaluate the diagnostic performance of NIHSS extinction and inattention item, compared to the results of the Oxford Cognitive Screen (OCS) heart subtest. Additionally, the possible role of the NIHSS visual field subtest on the NIHSS extinction and inattention subtest performance is explored and discussed.
Methods
We analysed scores on NIHSS extinction and inattention subtest, NIHSS visual field subtest, and OCS heart subtest on a sample of 118 post-stroke patients.
Results
Compared to OCS heart subtest, the results on NIHSS extinction and inattention subtest showed an accuracy of 77.1% and a moderate agreement level (Cohen’s kappa = 0.455). Furthermore, a decrease in NIHSS accuracy detecting neglect (55.6%) was observed in patients with pathological scores in NIHSS visual field item.
Conclusions
Extreme caution is recommended for the diagnostic performance of extinction and inattention item of NIHSS. Signs of neglect may not be detected by NIHSS, and may be confused with visual field impairment.
Trial registration:
This study refers to an observational study protocol submitted to ClinicalTrials.gov with identifier: NCT03968627 (URL: https://www.clinicaltrials.gov/ct2/show/NCT03968627?term=Cecchi&cond=Stroke&draw=2&rank =2). The name of the registry is “Development of a National Protocol for Stroke Rehabilitation in a
A High Urinary Urobilinogen / Serum Total Bilirubin Ratio Reported in Abdominal Pain Patients Can Indicate Acute Hepatic Porphyria
Authors: Song Chengyuan , Sang Shaowei , Liu Yuan
Published: June 2021

Background: Due to its variable symptoms and nonspecific laboratory test results during routine examinations, acute hepatic porphyria (AHP) has always been a diagnostic dilemma for physicians. Misdiagnoses, missed diagnoses, and inappropriate treatments are very common. Correct diagnosis mainly depends on the detection of a high urinary porphobilinogen (PBG) level, which is not a routine test performed in the clinic and highly relies on the physician’s awareness of AHP. Therefore, identifying a more convenient indicator for use during routine examinations is required to improve the diagnosis of AHP.Results: In the present study, we retrospectively analyzed laboratory examinations in 12 AHP patients and 100 patients with abdominal pain of other causes as the control groups between 2015 and 2021. Compared with the control groups, AHP patients showed a significantly higher urinary urobilinogen level during the urinalysis (P < 0.05). However, we showed that the higher urobilinogen level was caused by a false-positive result due to a higher level of urine PBG in the AHP patients. Hence, we used serum total bilirubin, an upstream substance of urinary urobilinogen synthesis, for calibration. A remarkable increase in the urinary urobilinogen/serum total bilirubin ratio was observed in AHP patients when compared to the control groups. The area under the ROC curve of this ratio for AHP was 1.000 (95% confidence interval, 1.000–1.000, P < 0.01). A cutoff value of 3.22 for the urinary urobilinogen/serum total bilirubin ratio yielded a sensitivity of 100% and a specificity of 100% to distinguish AHP patients from the controls.Conclusion: A reported high urinary urobilinogen level that was adjusted by the serum total bilirubin level (urinary urobilinogen/serum total bilirubin ratio) could be used as a sensitive and specific screening marker for AHP in patients with abdominal pain.
Regulatory Network of miRNA, lncRNA, Transcription Factor and Target Immune Response Genes in Bovine Mastitis
Authors: Morenikeji Olanrewaju , Tucker Ashley , Salazar Nicole , Ayoola Adeola , Memili Erdogan , Thomas Bolaji
Published: June 2021

Pre- and post-transcriptional modifications of gene expression are emerging as foci of disease studies, with some studies revealing the importance of non-coding transcripts, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We hypothesize that TFs, lncRNAs and miRNAs can modulate the immune response in bovine mastitis and potentially serve as disease biomarkers and/or drug targets. With computational analyses, we identified candidate genes potentially regulated by miRNAs and lncRNAs base pair complementation and thermodynamic stability of binding regions. Remarkably, we found six miRNAs, two being bta-miR-223 and bta-miR-24-3p, to bind to several targets. NONBTAT027932.1 and XR_003029725.1, were identified to target several genes. Functional and pathway analyses revealed lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production and regulation of IL-23 production among others. The overarching interactome deserves further in vitro/in vivo explication for specific molecular regulatory mechanisms during bovine mastitis immune response and could lay the foundation for development of disease markers and therapeutic intervention.
Spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissues at genome scale and cellular level
Authors: Fan Rong , Deng Yanxiang , Bartosovic Marek , Ma Sai , Zhang Di , Liu Yang , Qin Xiaoyu , Su Graham , Xu Mina , Halene Stephanie , Craft Joseph , Castelo-Branco Goncalo
Published: June 2021

Cellular function in tissue is dependent upon the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context. The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping, but it remains elusive to capture spatial epigenetic information of tissue at cellular level and genome scale. Here we report on spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissue section via next-generation sequencing by combining in situ Tn5 transposition chemistry and microfluidic deterministic barcoding. Spatial chromatin accessibility profiling of mouse embryos delineated tissue region-specific epigenetic landscapes and identified gene regulators implicated in the central nerve system development. Mapping the accessible genome in human tonsil tissue with 20μm pixel size revealed spatially distinct organization of immune cell types and states in lymphoid follicles and extrafollicular zones. This technology takes spatial biology to a new realm by enabling spatially resolved epigenomics to improve our understanding of cell identity, state, and fate decision in relation to epigenetic underpinnings in development and disease.
Usefulness of the MADIT-ICD Benefit Score in a S-ICD Patient Cohort
Authors: Willy Kevin , Köbe Julia , Reinke Florian , Rath Benjamin , Ellermann Christian , Wolfes Julian , Lange Philipp S , Eckardt Lars , Frommeyer Gerrit
Published: June 2021

Background: The subcutaneous ICD (S-ICD) is used in an increasing number of patients for primary and secondary prevention of sudden cardiac death. Decision-making in primary prevention is not always trivial and many clinical scenarios are not reflected in current ICD guidelines. To help evaluating the patient’s individual risk, a new score trying to predict the benefit of an ICD implantation for primary prevention, the MADIT-ICD benefit score, which tries to predict occurrence of ventricular arrhythmias and non-arrhythmic death, has been proposed. We therefore aimed at examining its usefulness in a large single centre register of S-ICD patients Methods and results: All S-ICD patients with a primary preventive indication for ICD implantation from our large single centre database were included in the analysis (n=173). During a follow-up of 1227±978 days 27 patients developed sustained ventricular arrhythmias, while 6 patients died for non-arrhythmic reasons. Occurrence of ventricular arrhythmias could not sufficiently be predicted by the MADIT-ICD VT/VF score (p=0.3) in patients with (n=142, p=0.19) as well as patients without structural heart disease (n=31, p=0.88). However, there was a significant correlation for patients with ischemic cardiomyopathy (ICM) (n=29, p=0.04). Only one parameter (non-sustained ventricular tachycardia) was significantly associated with sustained ventricular arrhythmias (p=0.02). Of note, non-arrhythmic death could effectively be predicted by the proposed non-arrhythmic mortality score as part of the benefit score (p=0.001, r=0.3) also mainly driven by ICM patients. Age, diabetes mellitus, and a BMI <23 kg/m2 were key predictors of non-arrhythmic death implemented in the score.Conclusion: The MADIT-ICD benefit score adds a new option to evaluate expected benefit of ICD implantation for primary prevention. However, in our S-ICD cohort, the only group in which the score worked properly for prediction of sudden and non-sudden death were ICM patients, so that a larger validation in more heterogeneous cohorts in mandatory to claim general validity for this score in risk stratification for primary preventive ICD implantation.
Percutaneous Endoscopic Lumbar Discectomy for Treating Cauda Equina Syndrome Due To Lumbar Disc Herniation
Authors: He Hai-Chao , LV Xiao-qiang , Zhang Yong-Jin
Published: June 2021

Background

In recent decades, endoscopic techniques to treat lumbar disc herniation (LDH) have gained popularity in clinical practice. However, there is little literature on the use of percutaneous endoscopic lumbar discectomy (PELD) to treat cauda equina syndrome (CES) due to LDH. This study aims to evaluate the feasibility and clinical efficacy of PELD for treating CES caused by disc herniation, and as well as to report some technical strategies.
Methods

Between October 2012 and April 2018, 15 patients with CES caused by LDH at the early and intermediate stages of Shi’s classification were selected as the subjects of study, and underwent PELD. All patients were followed up for at least two years. The patients’ back pain and leg pain were evaluated using visual analogue scale (VAS) scores and the Oswestry Disability Index (ODI). Patient satisfaction was evaluated using the MacNab outcome scale. Clinical outcomes were measured preoperatively and at 3 days, 3 months, 6 months and the last follow-up.
Results

The VAS score for back pain, leg pain and ODI score significantly decreased from preoperatively scores of 6.67 ± 1.05, 7.13 ± 1.19 and 62.0 ± 6.85 respectively, to postoperatively cores of 1.80 ± 0.41, 1.47 ± 0.52 and 12.93 ± 1.03 at the last follow-up postoperatively. These postoperative scores were all significantly different compared with preoperative scores (P < 0.01). According to the modified MacNab outcome scale, 86.67% of these patients had excellent and good outcomes at the final follow-up. Complications included one patient with cerebrospinal fluid leakage and one patient who developed recurrent herniation; the latter patient finally achieved satisfactory results after reoperation.
Conclusion

PELD could be used as an alternative surgical method for the treatment of CES due to LDH in properly selected cases and appropriate patient selection. However, the operator should pay attention to foraminoplasty to enlarge the working space.
Aldosterone and Renin Concentration Abnormally Elevated in a Cohort of Normotensive Pregnant Women
Authors: Pasten Valentina , TAPIA-CASTILLO ALEJANDRA , Fardella Carlos E. , Leiva Andrea , Carvajal Cristian A.
Published: June 2021

During pregnancy the renin-angiotensin-aldosterone system (RAAS) undergo major changes to preserve normal blood pressure (BP), placenta blood flow and ensure a good pregnancy outcome. Abnormal aldosterone-renin metabolism is a risk factor for arterial hypertension and cardiovascular risk, but its association to pathological conditions in pregnancy remains unknown. Hence, clinical and subclinical novel biomarkers associated to these pathological conditions are encouraged to be identified. Aim: To study a cohort of normotensive pregnant women according to their serum aldosterone and plasma renin levels and assay their small extracellular vesicles (sEV) and a specific protein-cargo (LCN2, AT1R). Methods: A cohort of 54 normotensive pregnant women at term gestation. We determined the BP, serum aldosterone and plasma renin concentration. In a subgroup, we isolated their plasma sEVs and semi-quantify two EV-proteins (AT1R, LCN2). Results: We set a normal range of aldosterone and renin based in the interquartile range. We identified 5/54(9%) pregnant women with elevated aldosterone and low renin levels, and 5/54(9%) other pregnant women with low aldosterone and elevated renin levels. No differences were found in sEV-LCN2 nor sEV-AT1R. Conclusion: We found 18% normotensive pregnant women having either high aldosterone or high renin levels, suggesting a subclinical status similar to a primary aldosteronism or a hyperreninemia. Both would evolve to pathological conditions in presence a second challenge affecting the maternal vascular physiology or the BP. sEVs and its specific cargo are encouraged to be further studied in order to clarify its role as potential biomarkers of RAAS alterations in pregnant women.
Identifying the Chemical Profile and Pharmacological Mechanism of Xinbao Pill against Myocardial Ischemia-Reperfusion Injury Using Ultra-Fast Liquid Chromatography-Quadrupole-Time-Of-Flight Tandem Mass Spectrometry Coupled with Network Pharmacology-Based Investigation
Authors: Yang Ying , Chen Ting , Liu Jiaming , Chen Sixuan , Cai Rongqing , Wu Liqiong , Hu Jiexiong , Lin Qiongying , Qi Xiaoxiao , Liu Zhongqiu , Cheng Yuanyuan
Published: June 2021

Background: Xinbao Pill (Xin-Bao-Wan, XBW) is a traditional Chinese herbal formula, which is widely used in clinical treatment for cardiovascular diseases; however, the therapeutic effect of XBW on myocardial ischemia-reperfusion injury (MI/RI) is unclear. In this study, we evaluated the cardioprotective effect and molecular mechanism of XBW against MI/RI.Methods: A phytochemistry-based network pharmacology analysis was used to uncover the mechanism of XBW against MI/RI. Firstly, ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) method was used to identify chemicals in XBW. MI/RI-related targets of XBW were predicted using TargetNet database, OMIC database and reported literatures. GO and KEGG pathway enrichment analyses were performed using String database. Left anterior descending artery (LAD) ligation-induced MI/RI rat model and oxygen glucose deprivation-reperfusion (OGD/R)-induced H9c2 cell model were used to evaluate the cardioprotective effect and potential mechanism of XBW.Results: 37 chemicals were identified in XBW by using UHPLC-QTOF-MS; 50 MI/RI-related targets of XBW were predicted using TargetNet database, OMIC database and reported literatures. In vivo study, XBW (180 mg/kg) significantly reduced myocardial infarct size and creatine kinase MB (CK-MB) level induced by MI/RI in rat model; in vitro study, XBW protected H9c2 cells against OGD/R injury in a dose-dependent manner. GO and KEGG pathway enrichment analyses showed that the cardioprotective effect of XBW was associated with 5 significant pathways including autophagy, apoptosis, HIF-1 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway. Experimental investigation also verified that XBW could suppress apoptosis, autophagy and endoplasmic reticulum (ER) stress.Conclusion: XBW showed therapeutic effects against MI/RI mainly via attenuating apoptosis though suppressing excessive autophagy and ER stress.
A Retrospective Study on Incidence, Diagnosis, and Clinical Outcome of Gastric-type Endocervical Adenocarcinoma in a Single Institution
Authors: Radomska Anna , Lee Daniel , Neufeld Heather , Korte Nancy , Torlakovic Emina , Agrawal Anita , Chibbar Rajni
Published: June 2021

Background: Gastric-type endocervical adenocarcinoma is rare but the most common subtype of cervical adenocarcinoma not associated with human papillomavirus. It is more aggressive with a shorter five-year survival rate compared to human papillomavirus-associated usual type endocervical adenocarcinoma. The objectives of our study were to determine the incidence and clinical-pathological characteristics of Gastric-type endocervical adenocarcinoma in a single institution. Methods: Twenty four cases of invasive cervical adenocarcinoma were identified between January 2000 and December 2015, from the Saskatoon Health Region pathology database using International Endocervical Adenocarcinoma Criteria and Classification to retrospectively classify endocervical adenocarcinoma. Immunohistochemistry was performed with antibodies for Gastric mucin-6 (MUC-6), p16INK4a, cyclin-dependent kinase inhibitor 2A (p16), p53 protein (p53), estrogen and progesterone receptors. Clinical and pathological data was retrieved from pathology reports and charts. Statistical analysis was performed using Mann-Whitney U test and Chi-Square test.Results: Using the International Endocervical Adenocarcinoma Criteria and Classification criteria, 19 cases (79.2%) were classified as human papillomavirus-associated usual type endocervical adenocarcinoma, and five cases (20.8%) as Gastric-type endocervical adenocarcinoma. In our study 40% of Gastric-type endocervical adenocarcinoma cases presented at stage III compared to none of the usual type endocervical carcinoma cases. All the Gastric-type endocervical adenocarcinoma cases were positive for MUC-6, and negative for p16. 60% Gastric-type endocervical adenocarcinoma cases demonstrated mutant type p53 staining. In contrast, 84.2% of human papillomavirus-associated usual type endocervical adenocarcinoma cases showed block like nuclear and cytoplasmic positivity with p16 antibodies. The Gastric-type endocervical adenocarcinoma group had significantly shorter median survival time than human papillomavirus-associated usual type endocervical adenocarcinoma group, Gastric-type endocervical adenocarcinoma is 22 months compared to human papillomavirus-associated usual type endocervical adenocarcinoma at 118 months (p = 0.043). Conclusions: In this study, Gastric-type endocervical adenocarcinoma accounted for 20.8% of all cervical adenocarcinoma with higher stage at presentation and shorter overall survival. Histomorphology and immunohistochemistry for MUC-6 and p16 could differentiate between Gastric-type endocervical adenocarcinoma and human papillomavirus-associated usual type endocervical adenocarcinoma.
Recurrent Pancreatic Follicular Dendritic Cell Sarcoma: A Case Report and Literature Review
Authors: Li Jia , Zhou Wenyang , Lv Ying , Hu Rong
Published: June 2021

Background: Follicular Dendritic Cell Sarcoma (FDCS) is a rare malignant tumor originated from follicular dendritic cells. Presently radical resection is the standard treatment; however there is no clear optimal chemotherapy for unresectable lesions. We presented the clinical data, pathological features, imaging features, diagnosis and treatment of a very rare patient with recurrence and metastasis after radical resection of pancreatic FDCS. Case presentation: A 64-year-old male patient was delivered to hospital due to intermittent chest tightness and pain. A pancreatic mass was found after thorough physical examination. Enhanced MRI showed a round solid mass in the head and neck of pancreas. The patient underwent radical resection. The pathological diagnosis was FDCS. CHP regimen was used for consolidation chemotherapy for 6 cycles. Two years later, due to a large amount of effusion, the patient was confirmed to have relapse and extensive abdominal metastasis. Both CHOP regimen and bendamustine were ineffective.Conclusions: FDCS of pancreas is very rare, and its imaging findings are not specific. If the disease relapses or metastases, though applies a variety of chemotherapy regimens, it is difficult to obtain satisfactory curative effect, and long-term prognosis is pessimistic. This is the first reported case that bendamustine was ineffective in the treatment of FDCS.
Metastatic Pattern of Truncal and Extremity Leiomyosarcoma: Retrospective Analysis of Predictors, Outcomes, and Detection
Authors: Tigchelaar Seth Stravers , Frey Christopher , Segovia Nicole A. , Mohler David G. , Steffner Robert J. , Avedian Raffi S.
Published: June 2021

BackgroundLeiomyosarcomas (LMS) are a heterogenous group of malignant mesenchymal neoplasms with smooth muscle origin and are classified as either non-uterine (NULMS) or uterine (ULMS). Metastatic pattern, prognostic factors, and ideal staging/surveillance studies for truncal and extremity LMS have not been defined.MethodsA retrospective analysis of patients diagnosed with histopathology-confirmed truncal or extremity LMS between 2009-2019 was conducted. Data collected included demographics, tumor characteristics, staging, surveillance, and survival endpoints. Primary site was defined as either 1. Extremity, 2. Flank/Pelvis, or 3. Chest wall/Spine.ResultsWe identified 73 patients, 23.3% of which had metastatic LMS at primary diagnosis, while 68.5% developed metastatic disease at any point. The mean metastatic-free survival from primary diagnosis of localized LMS was 3.0±2.8 years. Analysis of prognostic factors revealed that greater age (≥50 years) at initial diagnosis (OR=3.74, p=0.0003) and higher tumor grades II (OR=16, p=0.019) and III (OR=13, p=0.025) were significantly associated with metastases.ConclusionsTruncal and peripheral extremity LMS is an aggressive tumor with high metastatic potential. While there is a significant risk of metastases to lungs, extra-pulmonary tumors are relatively frequent. Older patients and patients with higher-grade (II/III) tumors carry an increased risk of developing metastatic disease.
A novel clinical nomogram for predicting 3-month unfavorable outcomes of stroke patients treated with mechanical thrombectomy
Authors: Zhang Xiao-Guang , Wang Jia-Hui , Yang Wen-Hao , Zhu Xiao-Qiong , Xue Jie , Li Zhi-Zhang , Kong Yu-Ming , Hu Liang , Jiang Shan-Shan , Xu Xu-Shen , yue yun-hua
Published: June 2021

Background: Mechanical thrombectomy (MT) is an effective treatment for large-vessel occlusion in acute ischemic stroke, however, only some revascularized patients have a good prognosis. For stroke patients undergoing MT, predicting the risk of unfavorable outcomes and adjusting the treatment strategies accordingly can greatly improve prognosis. Therefore, we aimed to develop and validate a nomogram that can predict 3-month unfavorable outcomes for individual stroke patient treated with MT. Methods: We analyzed 238 patients with acute ischemic stroke who underwent MT from January 2018 to October 2020. The primary outcome was a 3-month unfavorable outcome, assessed using the modified Rankin Scale (mRS), 3-6. A nomogram was generated based on a multivariable logistic model. We used the area under the receiver-operating characteristic curve to evaluate the discriminative performance and used the calibration curve and Spiegelhalter’s Z-test to assess the calibration performance of the risk prediction model. Results: After multivariable logistic regression, six variables (gender, bridging therapy, postoperative mTICI, stroke-associated pneumonia, preoperative creatinine and Na) remained independent predictors of 3-month unfavorable outcomes in stroke patients treated with MT, thus forming a nomogram. The area under the nomogram curve was 0.848 with good calibration performance (P = 0.946 for the Spiegelhalter’s Z-test). Conclusions: A novel nomogram consisting of gender, bridging therapy, postoperative mTICI, stroke-associated pneumonia, preoperative creatinine and Na can predict the 3-month unfavorable outcomes in stroke patients treated with MT.
A combined miR-34a and arsenic trioxide nanodrug delivery system for synergistic inhibition of HCC progression after microwave ablation
Authors: Hu Jian , Pei Wenceng , Jiang Zhenyou , Li Zihuang
Published: June 2021

Background
Microwave ablation (MWA) has become an alternative treatment for unresectable surgery for hepatocellular carcinoma (HCC), but it still faces the risk of recurrence and metastasis after treatment. Recent studies have found that miR-34a presents decreased gene expression in residual tumours after ablation therapy and can increase the therapeutic effect of arsenic trioxide on HCC, which brings new opportunities for its treatment.
Methods
A pH-sensitive charge inversion material was used to construct a nanotargeted delivery system that presents the synergistic effect of miR-34a and As2O3. We established in vitro and in vivo models of microwave ablation of HCC and performed in-depth research on dual drug systems to inhibit the rapid progression of HCC after microwave ablation in cell pyroptosis.
Results
The antitumour effect was enhanced with double-drug nanoparticles relative to a single formulation, and the therapeutic efficacy of the nanoparticles was more significant in a weakly acidic environment. Dual-drug nanoparticles could increase the N-terminal portion of GSDME, decrease the expression of Cyt-c and c-met.
Conclusions
Dual-drug nanoparticles may improve the therapeutic efficacy of HCC with insufficient ablation through Cyt-c and GSDME-N and decrease the expression levels of c-met. It is expected to provide new treatment methods for residual liver cancer after microwave ablation, prolong the survival of patients and improve quality of life.