bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standardization of Workflow and Flow Cytometry Panels for Quantitative Expression Profiling of Surface Antigens on Blood Leukocyte Subsets: An HCDM CDMaps Initiative
Authors: Kužílková Daniela , Puñet-Ortiz Joan , Aui Pei M. , Fernández Javier , Fišer Karel , Engel Pablo , van Zelm Menno C. , Kalina Tomáš 
Published: February 2022

BackgroundThe Human Cell Differentiation Molecules (HCDM) organizes Human Leukocyte Differentiation Antigen (HLDA) workshops to test and name clusters of antibodies that react with a specific antigen. These cluster of differentiation (CD) markers have provided the scientific community with validated antibody clones, consistent naming of targets and reproducible identification of leukocyte subsets. Still, quantitative CD marker expression profiles and benchmarking of reagents at the single-cell level are currently lacking.ObjectiveTo develop a flow cytometric procedure for quantitative expression profiling of surface antigens on blood leukocyte subsets that is standardized across multiple research laboratories.MethodsA high content framework to evaluate the titration and reactivity of Phycoerythrin (PE)-conjugated monoclonal antibodies (mAbs) was created. Two flow cytometry panels were designed: an innate cell tube for granulocytes, dendritic cells, monocytes, NK cells and innate lymphoid cells (12-color) and an adaptive lymphocyte tube for naive and memory B and T cells, including TCRγδ+, regulatory-T and follicular helper T cells (11-color). The potential of these 2 panels was demonstratedviaexpression profiling of selected CD markers detected by PE-conjugated antibodies and evaluated using 561 nm excitation.ResultsUsing automated data annotation and dried backbone reagents, we reached a robust workflow amenable to processing hundreds of measurements in each experiment in a 96-well plate format. The immunophenotyping panels enabled discrimination of 27 leukocyte subsets and quantitative detection of the expression of PE-conjugated CD markers of interest that could quantify protein expression above 400 units of antibody binding capacity. Expression profiling of 4 selected CD markers (CD11b, CD31, CD38, CD40) showed high reproducibility across centers, as well as the capacity to benchmark unique clones directed toward the same CD3 antigen.ConclusionWe optimized a procedure for quantitative expression profiling of surface antigens on blood leukocyte subsets. The workflow, bioinformatics pipeline and optimized flow panels enable the following: 1) mapping the expression patterns of HLDA-approved mAb clones to CD markers; 2) benchmarking new antibody clones to established CD markers; 3) defining new clusters of differentiation in future HLDA workshops.
The Impact of Breathing Hypoxic Gas and Oxygen on Pulmonary Hemodynamics in Patients With Pulmonary Hypertension
Authors: Carta Arcangelo F. , Lichtblau Mona , Berlier Charlotte , Saxer Stéphanie , Schneider Simon R. , Schwarz Esther I. , Furian Michael , Bloch Konrad E. , Ulrich Silvia 
Published: February 2022

BackgroundPure oxygen breathing (hyperoxia) may improve hemodynamics in patients with pulmonary hypertension (PH) and allows to calculate right-to-left shunt fraction (Qs/Qt), whereas breathing normobaric hypoxia may accelerate hypoxic pulmonary vasoconstriction (HPV). This study investigates how hyperoxia and hypoxia affect mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with PH and whether Qs/Qt influences the changes of mPAP and PVR.Study Design and MethodsAdults with pulmonary arterial or chronic thromboembolic PH (PAH/CTEPH) underwent repetitive hemodynamic and blood gas measurements during right heart catheterization (RHC) under normoxia [fractions of inspiratory oxygen (FiO2) 0.21], hypoxia (FiO2 0.15), and hyperoxia (FiO2 1.0) for at least 10 min.ResultsWe included 149 patients (79/70 PAH/CTEPH, 59% women, mean ± SD 60 ± 17 years). Multivariable regressions (mean change, CI) showed that hypoxia did not affect mPAP and cardiac index, but increased PVR [0.4 (0.1–0.7) WU, p = 0.021] due to decreased pulmonary artery wedge pressure [−0.54 (−0.92 to −0.162), p = 0.005]. Hyperoxia significantly decreased mPAP [−4.4 (−5.5 to −3.3) mmHg, p &lt; 0.001] and PVR [−0.4 (−0.7 to −0.1) WU, p = 0.006] compared with normoxia. The Qs/Qt (14 ± 6%) was &gt;10 in 75% of subjects but changes of mPAP and PVR under hyperoxia and hypoxia were independent of Qs/Qt.ConclusionAcute exposure to hypoxia did not relevantly alter pulmonary hemodynamics indicating a blunted HPV-response in PH. In contrast, hyperoxia remarkably reduced mPAP and PVR, indicating a preserved vasodilator response to oxygen and possibly supporting the oxygen therapy in patients with PH. A high proportion of patients with PH showed increased Qs/Qt, which, however, was not associated with changes in pulmonary hemodynamics in response to changes in FiO2.
A Three-Dimensional Organoid Model of Primary Breast Cancer to Investigate the Effects of Oncolytic Virotherapy
Authors: Carter Mary E. , Hartkopf Andreas D. , Wagner Anna , Volmer Léa L. , Brucker Sara Y. , Berchtold Susanne , Lauer Ulrich M. , Koch André 
Published: February 2022

Background:Although several oncolytic viruses have already been tested in early-stage clinical studies of breast cancer, there is still an urgent need to develop patient-derived experimental systems that mimic the response of breast cancer to oncolytic agents in preparation of testing different oncolytic viruses in clinical trials. We addressed this need by developing a protocol to study the effects of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue.Methods:We used an established three-dimensional organoid model derived from tissue of 10 patients with primary breast cancer. We developed an experimental protocol for infecting organoid cultures with oncolytic viruses and compared the oncolytic effects of a measles vaccine virus (MeV) and a vaccinia virus (GLV) genetically engineered to express either green fluorescent protein (MeV-GFP) and red fluorescent protein (GLV-0b347), respectively, or a suicide gene encoding a fusion of cytosine deaminase with uracil phosphoribosyltransferase (MeV-SCD and GLV-1h94, respectively), thereby enabling enzymatic conversion of the prodrug 5-fluorocytosine (5-FC) into cytotoxic compounds 5-fluorouracil (5-FU) and 5-fluorouridine monophosphate (5-FUMP).Results:The method demonstrated that all oncolytic viruses significantly inhibited cell viability in organoid cultures derived from breast cancer tissue. The oncolytic effects of the oncolytic viruses expressing suicide genes (MeV-SCD and GLV-1h94) were further enhanced by virus-triggered conversion of the prodrug 5-FC to toxic 5-FU and toxic 5-FUMP.Conclusions:We were able to develop a protocol to assess the effects of two different types of oncolytic viruses in stable organoid cell cultures derived from breast cancer tissue. The greatest oncolytic effects were observed when the oncolytic viruses were engineered to express a suicide gene (MeV-SCD and GLV-1h94) in the presence of the prodrug 5-FC. The model therefore provides a promisingin vitromethod to help further testing and engineering of new generations of virotherapeutic vectors forin vivouse.
Feasibility of Telemedical HINTS (Head Impulse-Nystagmus-Test of Skew) Evaluation in Patients With Acute Dizziness or Vertigo in the Emergency Department of Primary Care Hospitals
Authors: von Martial Rascha , Leinweber Christina , Hubert Nikolai , Rambold Holger , Haberl Roman Ludwig , Hubert Gordian Jan , Müller-Barna Peter 
Published: February 2022

BackgroundAcute dizziness, vertigo and imbalance are common symptoms in emergency departments. Stroke needs to be distinguished from vestibular diseases. A battery of three clinical bedside tests (HINTS: Head Impulse Test, Nystagmus, Test of Skew) has been shown to detect stroke as underlying cause with high reliability, but implementation is challenging in primary care hospitals. Aim of this study is to prove the feasibility of a telemedical HINTS examinationviaa remotely controlled videooculography (VOG) system.MethodsThe existing video system of our telestroke network TEMPiS (Telemedic Project for Integrative Stroke Care) was expanded through a VOG system. This feature enables the remote teleneurologist to assess a telemedical HINTS examination based on inspection of eye movements and quantitative video head impulse test (vHIT) evaluation. ED doctors in 11 spoke hospitals were trained in performing vHIT, nystagmus detection and alternating cover test. Patients with first time acute dizziness, vertigo or imbalance, whether ongoing or resolved, presented to the teleneurologist were included in the analysis, as long as no focal neurological deficit according to the standard teleneurological examination or obvious internal medicine cause was present and a fully trained team was available. Primary outcome was defined as the feasibility of the telemedical HINTS examination.ResultsFrom 01.06.2019 to 31.03.2020, 81 consecutive patients were included. In 72 (88.9%) cases the telemedical HINTS examination was performed. The complete telemedical HINTS examination was feasible in 46 cases (63.9%), nystagmus detection in all cases (100%) and alternating covert test in 70 cases (97.2%). The vHIT was recorded and interpretable in 47 cases (65.3%). Results of the examination with the VOG system yielded clear results in 21 cases (45.7%) with 14 central and 7 peripheral lesions. The main reason for incomplete examination was the insufficient generation of head impulses.ConclusionIn our analysis the telemedical HINTS examination within a telestroke network was feasible in two thirds of the patients. This offers the opportunity to improve specific diagnostics and therapy for patients with acute dizziness and vertigo even in primary care hospitals. Improved training for spoke hospital staff is needed to further increase the feasibility of vHIT.
Bee Venom Effect on Glioblastoma Cells Viability and Gelatinase Secretion
Authors: Małek Agata , Kocot Joanna , Mitrowska Kamila , Posyniak Andrzej , Kurzepa Jacek 
Published: February 2022

BackgroundThe involvement of MMP-2 and MMP-9 in the pathogenesis of various kinds of cancers including glioblastoma is well documented. The evaluation of the anticancer potential of honey bee (Apis mellifera) venom (BV) consisting of the inhibition of MMP-2 and MMP-9 secretion in a glioblastoma cell culture model was the aim of the study.Methods8-MG-BA and GAMG human primary glioblastoma cell lines vs. HT-22 mouse hippocampal neuronal cells were applied for the study. The BV dose (0.5, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, and 5.0 μg/ml) and time-dependent (24, 48, 72 h) cytotoxicity was evaluated with the tetrazolium-based colorimetric assay (MTT test). MMP-2 and MMP-9 activities in the cell culture medium under different BV concentrations were determined by gelatin zymography.ResultsA dose and time-dependent BV effect on cytotoxicity of both glioblastoma cell lines and hippocampus line was observed. The weakest, but statistically important effect was exerted by BV on HT-22 cells. The greatest cytotoxic effect of BV was observed on the 8-MG-BA line, where a statistically significant reduction in viability was observed at the lowest BV dose and the shortest incubation time. The reduction of both gelatinases secretion was observed at 8-MG-BA and GAMG lines without significant effect of HT-22 cell line.ConclusionIn vitro studies indicate that BV has both cytotoxic and inhibitory effects on the secretion of MMP-2 and MMP-9 in selected lines of glioma, suggesting anticancer properties of BV.
Dynamics of the Gut Bacteria and Fungi Accompanying Low-Carbohydrate Diet-Induced Weight Loss in Overweight and Obese Adults
Authors: Yu Dan , Xie Libin , Chen Wei , Qin Jin , Zhang Jingjing , Lei Min , Wang Yue , Tang Hongge , Xue Sujuan , Liang Xinxiu , Miao Zelei , Xiao Congmei , Shang Meishuang , Lu Jie , Di Hailing , Fu Yuanqing 
Published: February 2022

BackgroundLow-carbohydrate (e.g., Atkins) dietary pattern is one of the most effective diets for weight loss, but little is known about the characteristics of the gut microbiota accompanying low-carbohydrate diets-induced weight loss. This study aims to profile dynamics of gut bacteria and fungi accompanying modified Atkins diets-induced weight loss among overweight and obese adults.MethodsOverweight and obese adults were screened to follow a modified Atkins diet plan (30% of energy from protein, 40% from carbohydrate and 30% from fat). We longitudinally profiled dynamics of gut bacteria and fungi based on 16S rRNA and ITS rRNA gene sequencing data, respectively.ResultsA total of 65 participants followed the modified Atkins diets for 20–231 days, with 61 and 27 participants achieving a weight loss of at least 5 and 10%, respectively. Most of the participants who achieved 10% weight loss also experienced improvements on metabolic health. The diversity of gut bacteria and fungi increased after a weight loss of 5% and kept stable thereafter. Bacteria genera including Lachnoclostridium and Ruminococcus 2 from Firmicutes phylum were depleted, while Parabacteroides and Bacteroides from Bacteroidetes phylum were enriched after weight loss. The inter-kingdom analysis found an intensive covariation between gut fungi and bacteria, involving more than half of the weight loss-associated bacteria.ConclusionsThis study confirmed the modulation of bacterial and fungal composition during weight loss with the low-carbohydrate diets and showed previously unknown links between intestinal bacteria and fungi accompanying the weight loss.
Real-World Outcomes of Hodgkin Lymphoma: A Multi-Centric Registry From India
Authors: Bhurani Dinesh , Nair Reena , Rajappa Senthil , Rao Suparna Ajit , Sridharan Nithya , Boya Rakesh Reddy , Raman Ganapathi S. , Menon Hari , Seshachalam Arun , Nimmagadda Ramesh 
Published: February 2022

BackgroundHodgkin’s lymphoma (HL) is one of the most curable malignancies with a 5-year survival of over 80%. Most published literature from low-middle income countries comes from single institute experience.MethodologyThe OncoCollect Lymphoma group registry was set up in 2017 and has 9 major participating sites across India. Data of newly diagnosed classical HL (CHL) patients, treated between 2011 and 2017, were collected using OncoCollect software. The clinical features, subtypes, prognostic stratification, treatment patterns, response to first-line treatment, and 5-year outcomes were analyzed. All statistical analysis was done using Microsoft R Open statistical software linked to OncoCollect software.ResultsThere were 939 newly diagnosed CHL patients with a median age of 38 (range, 18–99) years at presentation. The male-to-female ratio was 2.07:1. Histological subtypes included mixed cellularity, CHL (MC, CHL), nodular sclerosis, CHL (NS, CHL), lymphocyte-rich, CHL (LR, CHL), and lymphocyte-depleted, CHL (LD, CHL), in 60.60%, 26.94%, 9.80%, and 2.66%, respectively. At presentation, 50.43% had B symptoms and 53.35% had advanced disease. 29.71% of advanced-stage patients had high Hodgkin IPI score. 79% and 21% of patients received 1st-line treatment with chemotherapy alone or combined modality treatment with chemotherapy and radiotherapy. The most common first-line chemotherapy was ABVD-based regimen (94.68%). The overall response rate was 93.48%. Complete response rates among early-stage favorable and unfavorable risk groups were 92.73% and 86.79%, and those among advanced-stage low- and high-risk groups were 76.64% and 69.78%, respectively. The median relapse-free follow-up duration was 51 months (IQR 22–69). A significant difference was found in 5-year EFS between the early- and advanced-stage disease 83.53% and 73.55% (p = 0.00087), respectively. Similarly, significant difference was found in EFS among early-stage patients treated with a combination of 4-cycle chemotherapy and radiotherapy vs. chemotherapy alone 88.57% and 66.33% (p = 0.0042), respectively.ConclusionsIn this large cohort from India, survival of patients with HL was comparable to the developed world. With a median follow-up of 51 months, the 5-year EFS and OS of all patients were 78.24% and 83.63%, respectively.
Long-Term Outcome of Centrally Located Hepatocellular Carcinomas Treated by Radical Resection Combined With Intraoperative Electron Radiotherapy (IOERT)
Authors: Wu Yan-Ling , Zhai Yirui , Li Minghui , Cai Jian-Qiang , Ma Pan , Wang Li-Ming , Wu Xiu-Hong , Wang Xiao-dan , Wu Fan , Zeng Qiang , Chen Bo , Li Ye-Xiong , Wu Jian-Xiong , Feng Qinfu 
Published: February 2022

PurposeTo explore the feasibility and safety of centrally located hepatocellular carcinoma (CL-HCC) treated by narrow-margin resection combined with intraoperative electron radiotherapy (IOERT).Methods and MaterialsFrom November 2009 to November 2016, 37 consecutive patients were treated with IOERT as adjuvant treatment during narrow-margin resection for CL-HCC. Long-term outcomes, adverse events for surgery, and acute and chronic toxicities were analyzed.ResultsThe median follow-up was 57.82 months (range, 3.75-111.41 months). A total dose of 15 Gy (range 12 to 17Gy) (prescribed at the 90% isodose) was delivered with a 0.9cm (range 0.8-1.2 cm) median treatment depth targeting the narrow-margin. The 1-year, 3-year and 5-year OS rates were 91.39%, 88.34% and 88.34%, respectively. The 1-year, 3-year and 5-year DFS rates were 80.81%, 68.59% and 54.17%, respectively. In the univariate analysis, none of the treatment characteristics were predictive of overall survival. Fifteen (40.5%) patients suffered from a recurrence event. No patient had marginal recurrence. The 1-year, 3-year and 5-year intrahepatic recurrence rates were 19.75%, 25.92% and 39.58%, respectively. The 1-year, 3-year and 5-year extrahepatic recurrence rates were 2.7%, 5.95% and 9.87%, respectively. There was no 30-day surgical-related death. Three patients had grade 4, and 28 patients had grade 3 alanine aminotransferase (ALT) levels, and seven patients had grade 4, and 30 patients had grade 3 aspartate transaminase (AST) levels. All of them returned to normal within four months. There was no acute radiation-induced liver injury during follow-up. There were no acute or chronic toxicities associated with IOERT.ConclusionIOERT for narrow-margin CL-HCC may achieve good long-term survival outcomes, without significantly increasing acute and chronic toxicities. An IOERT dose of 15Gy may be the safest and most feasible. IOERT might be considered as an adjuvant therapy for CL-HCC patients with a narrow-margin.
Epidemiology and Survival of Patients With Optic Pathway Gliomas: A Population-Based Analysis
Authors: Liu Huanbing , Chen Yong , Qin Xiaowei , Jin Zheng , Jiang Yining , Wang Yubo 
Published: February 2022

BackgroundWe aimed to analyze the epidemiology and outcomes of pediatric patients and adult patients with optic pathway gliomas in the United States using a population-based method.MethodsData for patients with optic pathway gliomas diagnosed between 2000 and 2018 were extracted from the SEER database. We divided the patients into a pediatric group and an adult group. Descriptive analyses were conducted to analyze demographic and clinical characteristics and treatment. We used the chi-square test to evaluate differences between pediatric and adult patients with optic pathway gliomas. The possible prognostic indicators were analyzed by Kaplan–Meier curves and Cox proportional hazards models.ResultsOptic pathway gliomas represented 86.6% of all lesions originating from the optic pathway. In total, 1257 cases of optic pathway gliomas were included in our study. Pediatric patients accounted for 83.7% in this cohort, and most of the patients were diagnosed at 1-4 years old. Chemotherapy was chosen most often for pediatric patients, but radiation therapy was chosen most often for adult patients. Pilocytic astrocytoma accounted for 59.1% of pediatric patients and 37.5% of adult patients. The overall survival (OS) rates were 94.8% 5 years after diagnosis and 93.0% 10 years after diagnosis. Survival analysis showed that surgery, radiation and chemotherapy did not help patients obtain a better prognosis. Overall, pediatric patients had a better prognosis.ConclusionOptic pathway gliomas are relatively rare lesions with good prognosis. They mostly affect children, and pilocytic astrocytoma is the most common histological diagnosis. Highly individualized treatment is essential for such patients.
Improving the Quality of Human Upper Urinary Tract Specimens by Cryobiopsy
Authors: Klein Jan T. , John Axel , Bohnert Lars , Enderle Markus D. , Linzenbold Walter , Bolenz Christian 
Published: February 2022

ObjectiveThe quality of histopathological specimens obtained from the upper urinary tract with conventional flexible ureterorenoscopic biopsy needs to be improved. We investigated the feasibility and biopsy quality of specimens obtained by cryobiopsy, compared with standard ureterorenoscopic biopsy techniques in a human ex vivo model.Materials and MethodsHuman ureters obtained from nephrectomy specimens (N=12) were dissected and canulated with an ureteral access sheath. Ureterorenoscopic biopsies were randomly obtained from different sites of the renal pelvic caliceal system using different types of instruments. The performance of two newly developed flexible cryoprobes with outer diameters of 1.1 mm (CB11) and 0.9 mm (CB09) was compared with that of the biopsy forceps(FB) and Bigopsy®(BiG) and two different Dormia baskets N‐Gage (NG) and Zero‐Tip (ZT). We assessed the feasibility of the various biopsy techniques based on the number of biopsy attempts needed to obtain macroscopically discernible biopsies. The specimens were examined histopathologically for size, biopsy quality, presence of various artifact types, and representativeness.ResultsBiopsies taken with the cryoprobes showed a higher biopsy quality than biopsies taken with the comparative instruments. The CB11 provided significantly larger biopsies than forceps biopsies and also than biopsies with ZT. The CB09 was able to collect larger samples when compared with the FB and BiG biopsy forceps. There were no significant differences in artifact area, except for the CB11 cryoprobe compared with the NG. To clarify the results a subdivision of larger or smaller than 20% artifact area was performed. A significant difference was found between CB11 and the forceps biopsies, as well as between CB11 and NG and ZT in favor of the cryoprobe. The representation of the histopathological sample was also determined. Biopsies taken with CB11 were more representative compared with forceps biopsies BiG and FB and basket biopsies NG and ZT.ConclusionsIn a standardized comparative ex vivo setting, larger biopsies were obtained by using the cryobiopsy technique with the CB11 probe. Qualitatively, cryobiopsy specimens were overlaid by fewer artifacts and a higher biopsy quality was achieved in histopathologic examination compared with standard instrumentation. Further stepwise development will transfer the promising cryobiopsy technique into the clinical setting.
Integrin-Mediated Tumorigenesis and Its Therapeutic Applications
Authors: Li Qingling , Lan Ting , Xie Jian , Lu Youguang , Zheng Dali , Su Bohua 
Published: February 2022

Integrins, a family of adhesion molecules generally exist on the cell surface, are essential for regulating cell growth and its function. As a bi-directional signaling molecule, they mediate cell-cell and cell-extracellular matrix interaction. The recognitions of their key roles in many human pathologies, including autoimmunity, thrombosis and neoplasia, have revealed their great potential as a therapeutic target. This paper focuses on the activation of integrins, the role of integrins in tumorigenesis and progression, and advances of integrin-dependent tumor therapeutics in recent years. It is expected that understanding function and signaling transmission will fully exploit potentialities of integrin as a novel target for tumors.