bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of Different Tumor Delineation Approaches for 18F-PSMA-1007 PET/CT Imaging in Prostate Cancer Patients
Authors: Mittlmeier Lena M. , Brendel Matthias , Beyer Leonie , Albert Nathalie L. , Todica Andrei , Zacherl Mathias J. , Wenter Vera , Herlemann Annika , Kretschmer Alexander , Ledderose Stephan T. , Schmidt-Hegemann Nina-Sophie , Kunz Wolfgang G. , Ricke Jens , Bartenstein Peter , Ilhan Harun , Unterrainer Marcus 
Published: May 2021

BackgroundDelineation of PSMA-positive tumor volume on PET using PSMA-ligands is of highest clinical interest as changes of PSMA-PET/CT-derived whole tumor volume (WTV) have shown to correlate with treatment response in metastatic prostate cancer patients. So far, WTV estimation was performed on PET using 68Ga-labeled ligands; nonetheless, 18F-labeled PET ligands are gaining increasing importance due to advantages over 68Ga-labeled compounds. However, standardized tumor delineation methods for 18F-labeled PET ligands have not been established so far. As correlation of PET-based information and morphological extent in osseous and visceral metastases is hampered by morphological delineation, low contrast in liver tissue and movement artefacts, we correlated CT-based volume of lymph node metastases (LNM) and different PET-based delineation approaches for thresholding on 18F-PSMA-1007 PET.MethodsFifty patients with metastatic prostate cancer, 18F-PSMA-1007 PET/CT and non-bulky LNM (short-axis diameter ≥10mm) were included. Fifty LNM were volumetrically assessed on contrast-enhanced CT (volumetric reference standard). Different approaches for tumor volume delineation were applied and correlated with the reference standard: I) fixed SUV threshold, II) isocontour thresholding relative to SUVmax (SUV%), and thresholds relative to III) liver (SUVliver), IV) parotis (SUVparotis) and V) spleen (SUVspleen).ResultsA fixed SUV of 4.0 (r=0.807, r2 = 0.651, p&lt;0.001) showed the best overall association with the volumetric reference. 55% SUVmax (r=0.627, r2 = 0.393, p&lt;0.001) showed highest association using an isocontour-based threshold. Best background-based approaches were 60% SUVliver (r=0.715, r2 = 0.511, p&lt;0.001), 80% SUVparotis (r=0.762, r2 = 0.581, p&lt;0.001) and 60% SUVspleen (r=0.645, r2 = 0.416, p&lt;0.001). Background tissues SUVliver, SUVparotis &amp; SUVspleen did not correlate (p&gt;0.05 each). Recently reported cut-offs for intraprostatic tumor delineation (isocontour 44% SUVmax, 42% SUVmax and 20% SUVmax) revealed inferior association for LNM delineation.ConclusionsA threshold of SUV 4.0 for tumor delineation showed highest association with volumetric reference standard irrespective of potential changes in PSMA-avidity of background tissues (e. g. parotis). This approach is easily applicable in clinical routine without specific software requirements. Further studies applying this approach for total tumor volume delineation are initiated.
Development and Interpretation of a Genomic Instability Derived lncRNAs Based Risk Signature as a Predictor of Prognosis for Clear Cell Renal Cell Carcinoma Patients
Authors: Yang Huiying , Xiong Xiaoling , Li Hua 
Published: May 2021

BackgroundClear cell renal cell carcinoma (ccRCC) is a kind of frequently diagnosed cancer, leading to high death rate in patients. Genomic instability (GI) is regarded as playing indispensable roles in tumorigenesis and impacting the prognosis of patients. The aberrant regulation of long non-coding RNAs (lncRNAs) is a main cause of GI. We combined the somatic mutation profiles and expression profiles to identify GI derived lncRNAs (GID-lncRNAs) in ccRCC and developed a GID-lncRNAs based risk signature for prognosis prediction and medication guidance.MethodsWe decided cases with top 25% cumulative number of somatic mutations as genomically unstable (GU) group and last 25% as genomically stable (GS) group, and identified differentially expressed lncRNAs (GID-lncRNAs) between two groups. Then we developed the risk signature with all overall survival related GID-lncRNAs with least absolute shrinkage and selection operator (LASSO) Cox regression. The functions of the GID-lncRNAs were partly interpreted by enrichment analysis. We finally validated the effectiveness of the risk signature in prognosis prediction and medication guidance.ResultsWe developed a seven-lncRNAs (LINC00460, AL139351.1, AC156455.1, AL035446.1, LINC02471, AC022509.2, and LINC01606) risk signature and divided all samples into high-risk and low-risk groups. Patients in high-risk group were in more severe clinicopathologic status (higher tumor grade, pathological stage, T stage, and more metastasis) and were deemed to have less survival time and lower survival rate. The efficacy of prognosis prediction was validated by receiver operating characteristic analysis. Enrichment analysis revealed that the lncRNAs in the risk signature mainly participate in regulation of cell cycle, DNA replication, material metabolism, and other vital biological processes in the tumorigenesis of ccRCC. Moreover, the risk signature could help assess the possibility of response to precise treatments.ConclusionOur study combined the somatic mutation profiles and the expression profiles of ccRCC for the first time and developed a GID-lncRNAs based risk signature for prognosis predicting and therapeutic scheme deciding. We validated the efficacy of the risk signature and partly interpreted the roles of the seven lncRNAs composing the risk signature in ccRCC. Our study provides novel insights into the roles of genomic instability derived lncRNAs in ccRCC.
Assessment of Foveal Avascular Zone and Macular Vascular Plexus Density in Children With Unilateral Amblyopia: A Systemic Review and Meta-Analysis
Authors: Gao Lei , Gao Yang , Hong Fengrong , Zhang Peng , Shu Xiangwen 
Published: May 2021

Purpose: To examine the quantitative measurements of OCTA in children with amblyopia using the meta-analysis methodology.Methods: PubMed, Embase, and Cochrane library were searched for available papers up to March 2021. Weighted mean differences (WMD) were used to compare the retina parameters between the eyes with amblyopia and the contralateral eyes or healthy control eyes.Results: Twelve studies were included. When considering the parafovea, the microvessel density was reduced in amblyopic eyes compared with healthy control eyes in the superficial capillary plexus (SCP) in 6 × 6 volume scan (WMD = −2.12, 95%CI: −3.24, −0.99) but not SCP in 3 × 3 volume scan (WMD = −1.43, 95%CI: −2.96, 0.11). In the deep capillary plexus (DCP), amblyopia did not decrease vessel density in the 6 × 6 volume scan (WMD = −2.22, 95%CI: −5.86, 1.42; I2 = 79.6%, P = 0.008), but a difference was observed in the whole eye 3 × 3 (WMD = −1.95, 95%CI: −3.23, −0.67; I2 = 27.5%, P = 0.252). There were no significant differences in the foveal avascular zone area and foveal thickness between amblyopic eyes and healthy control eyes. There were no significant differences in microvessel density, foveal avascular zone area, and foveal thickness between amblyopic eyes and fellow eyes.Conclusion: According to OCTA, amblyopic eyes had lower vessel density in parafoveal SCP and DCP compared with healthy control eyes, but not compared with fellow eyes. There were no significant differences regarding the foveal avascular zone area and foveal thickness between amblyopic and non-amblyopic eyes.
The Synergistic Effects of 5-Aminosalicylic Acid and Vorinostat in the Treatment of Ulcerative Colitis
Authors: He Long , Wen Shuting , Zhong Zhuotai , Weng Senhui , Jiang Qilong , Mi Hong , Liu Fengbin 
Published: May 2021

Background: The drug 5-aminosalicylic acid (5-ASA) is the first-line therapy for the treatment of patients with mild-to-moderate ulcerative colitis (UC). However, in some cases, 5-ASA cannot achieve the desired therapeutic effects. Therefore, patients have to undergo therapies that include corticosteroids, monoclonal antibodies or immunosuppressants, which are expensive and may be accompanied by significant side effects. Synergistic drug combinations can achieve greater therapeutic effects than individual drugs while contributing to combating drug resistance and lessening toxic side effects. Thus, in this study, we sought to identify synergistic drugs that can act synergistically with 5-ASA.Methods: We started our study with protein-metabolite analysis based on peroxisome proliferator-activated receptor gamma (PPARG), the therapeutic target of 5-ASA, to identify more additional potential drug targets. Then, we further evaluated the possibility of their synergy with PPARG by integrating Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis, pathway-pathway interaction analysis, and semantic similarity analysis. Finally, we validated the synergistic effects with in vitro and in vivo experiments.Results: The combination of 5-ASA and vorinostat (SAHA) showed lower toxicity and mRNA expression of p65 in human colonic epithelial cell lines (Caco-2 and HCT-116), and more efficiently alleviated the symptoms of dextran sulfate sodium (DSS)-induced colitis than treatment with 5-ASA and SAHA alone.Conclusion: SAHA can exert effective synergistic effects with 5-ASA in the treatment of UC. One possible mechanism of synergism may be synergistic inhibition of the nuclear factor kappa B (NF-kB) signaling pathway. Moreover, the metabolite-butyric acid may be involved.
Multi-Scale Simulation of Two-Dimensional Chloride Transport Under the Effect of Bending Load in Concrete
Authors: Zhang Lijuan , Zhang Jianjian , Sun Guowen , Liu Zhiyong 
Published: May 2021

Chloride transport in marine concrete under loading is the main cause of its structural deterioration. The traditional numerical simulation assumes that the coefficient of chloride transport is constant, resulting in a large deviation in the prediction results. Based on the porous medium theory, micromechanics theory, and the idea of equivalent homogenization, a multi-scale model of the effective diffusion variable coefficient of chloride transport under bending load was established, which was calculated and programmed by the numerical analysis. The results show that the prediction values of the two-dimensional variable coefficient model are basically consistent with those in the literature, and the prediction accuracy is significantly improved. In addition, the theoretical simulation proves that the bending load affects the porosity of the cement matrix, and then the diffusion coefficient of chloride is changed in concrete. The compression zone can slow down the chloride transport process, while tension zone will accelerate it. The chloride concentration under tension zone is 42.1% higher than that under compression zone when the diffusion time is 200 days and the concrete depth is 15 mm.
Emergency Medicine Cases in Underwater and Hyperbaric Environments: The Use of in situ Simulation as a Learning Technique
Authors: Paganini Matteo , Mormando Giulia , Savino Sandro , Garetto Giacomo , Tiozzo Giulia , Camporesi Enrico M. , Fabris Fabrizio , Bosco Gerardo 
Published: May 2021

IntroductionHyperbaric chambers and underwater environments are challenging and at risk of serious accidents. Personnel aiming to assist patients and subjects should be appropriately trained, and several courses have been established all over the world. In healthcare, simulation is an effective learning technique. However, there have been few peer-reviewed articles published in the medical literature describing its use in diving and hyperbaric medicine.MethodsWe implemented the curriculum of the Master’s degree in hyperbaric and diving medicine held at the University of Padova with emergency medicine seminars created by the faculty and validated by external experts. These seminars integrated traditional lectures and eightin situsimulation scenarios.ResultsFor the hyperbaric medicine seminar, simulations were carried out inside a real hyperbaric chamber at the ATIP Hyperbaric Treatment Centre, only using air and reproducing compression noise without pressurization to avoid damages to the manikins. The four scenarios consisted of hyperoxic seizures, pneumothorax, hypoglycemia, and sudden cardiac arrest. Furthermore, we added a hands-on session to instruct participants to prepare an intubated patient undergoing hyperbaric oxygen treatment with a checklist and simulating the patient transfer inside and outside the hyperbaric chamber. The diving medicine seminar was held at the Y-40 The Deep Joy pool in Montegrotto Terme (Italy), also involving SCUBA/breath-hold diving (BHD) instructors to rescue subjects from the water. These diving medicine scenarios consisted of neurologic syndrome (“taravana/samba”) in BHD, drowning of a breath-hold diver, pulmonary barotrauma in BHD, and decompression illness in a SCUBA diver.ConclusionWith this experience, we report the integration of simulation in the curriculum of a teaching course in diving and hyperbaric medicine. Future studies should be performed to investigate learning advantages, concept retention, and satisfaction of participants.
Retrospective Analysis of Training and Its Response in Marathon Finishers Based on Fitness App Data
Authors: Zrenner Markus , Heyde Christian , Duemler Burkhard , Dykman Solms , Roecker Kai , Eskofier Bjoern M. 
Published: May 2021

Objective: Finishing a marathon requires to prepare for a 42.2 km run. Current literature describes which training characteristics are related to marathon performance. However, which training is most effective in terms of a performance improvement remains unclear.Methods: We conducted a retrospective analysis of training responses during a 16 weeks training period prior to an absolved marathon. The analysis was performed on unsupervised fitness app data (Runtastic) from 6,771 marathon finishers. Differences in training volume and intensity between three response and three marathon performance groups were analyzed. Training response was quantified by the improvement of the velocity of 10 km runs Δv10 between the first and last 4 weeks of the training period. Response and marathon performance groups were classified by the 33.3rd and 66.6th percentile of Δv10 and the marathon performance time, respectively.Results: Subjects allocated in the faster marathon performance group showed systematically higher training volume and higher shares of training at low intensities. Only subjects in the moderate and high response group increased their training velocity continuously along the 16 weeks of training.Conclusion: We demonstrate that a combination of maximized training volumes at low intensities, a continuous increase in average running speed up to the aimed marathon velocity and high intensity runs ≤ 5 % of the overall training volume was accompanied by an improved 10 km performance which likely benefited the marathon performance as well. The study at hand proves that unsupervised workouts recorded with fitness apps can be a valuable data source for future studies in sport science.
The Alteration of Salivary Immunoglobulin A in Autism Spectrum Disorders
Authors: Gong Wuyi , Qiao Yanan , Li Bosheng , Zheng Xiaoguo , Xu Ruihuan , Wang Mingbang , Mi Xiaohui , Li Yongming 
Published: May 2021

Objectives: Autism spectrum disorders (ASD) are neurodevelopmental disorders with changes in the gut and oral microbiota. Based on the intimate relationship between the oral microbiota and oral mucosal immunity, this study aimed to investigate changes in salivary immunoglobulin A (IgA) level in ASD and the underlying mechanism for any such changes.Methods: We recruited 36 children diagnosed with ASD and 35 normally developing children and measured their salivary IgA content using enzyme-linked immunosorbent assay (ELISA). The valproate (VPA) -treated ASD mouse model was established by prenatal exposure to valproate and mouse salivary IgA content was also quantified by ELISA. The submandibular glands of VPA and control mice were isolated and analyzed using qRT-PCR, immunofluorescence staining, and flow cytometry. ASD-related Streptococci were co-incubated with the human salivary gland (HSG) cell line, and western blotting was used to detect the levels of relevant proteins.Results: We found that salivary IgA content was significantly decreased in patients with ASD and had a significant ASD diagnostic value. The salivary IgA content also decreased in VPA mice and was significantly correlated with autistic-like behaviors among them. The mRNA and protein levels of the polymeric immunoglobulin receptor (Pigr) were downregulated in the submandibular glands of VPA mice and the Pigr mRNA level was positively correlated with mouse salivary IgA content. HSG cells treated with ASD-related Streptococci had reduced PIGR protein level.Conclusion: Therefore, protective IgA levels were reduced in the saliva of individuals with ASD, which correlated with the bacteria-induced downregulation of Pigr in salivary glands. This study suggests a new direction for ASD diagnosis and prevention of oral diseases in ASD cohorts and provides evidence for the ASD mucosal immunophenotype in the oral cavity.
Attention Enhancement for Exoskeleton-Assisted Hand Rehabilitation Using Fingertip Haptic Stimulation
Authors: Li Min , Chen Jiazhou , He Guoying , Cui Lei , Chen Chaoyang , Secco Emanuele Lindo , Yao Wei , Xie Jun , Xu Guanghua , Wurdemann Helge 
Published: May 2021

Active enrollment in rehabilitation training yields better treatment outcomes. This paper introduces an exoskeleton-assisted hand rehabilitation system. It is the first attempt to combine fingertip cutaneous haptic stimulation with exoskeleton-assisted hand rehabilitation for training participation enhancement. For the first time, soft material 3D printing techniques are adopted to make soft pneumatic fingertip haptic feedback actuators to achieve cheaper and faster iterations of prototype designs with consistent quality. The fingertip haptic stimulation is synchronized with the motion of our hand exoskeleton. The contact force of the fingertips resulted from a virtual interaction with a glass of water was based on data collected from normal hand motions to grasp a glass of water. System characterization experiments were conducted and exoskeleton-assisted hand motion with and without the fingertip cutaneous haptic stimulation were compared in an experiment involving healthy human subjects. Users’ attention levels were monitored in the motion control process using a Brainlink EEG-recording device and software. The results of characterization experiments show that our created haptic actuators are lightweight (6.8 ± 0.23 g each with a PLA fixture and Velcro) and their performance is consistent and stable with small hysteresis. The user study experimental results show that participants had significantly higher attention levels with additional haptic stimulations compared to when only the exoskeleton was deployed; heavier stimulated grasping weight (a 300 g glass) was associated with significantly higher attention levels of the participants compared to when lighter stimulated grasping weight (a 150 g glass) was applied. We conclude that haptic stimulations increase the involvement level of human subjects during exoskeleton-assisted hand exercises. Potentially, the proposed exoskeleton-assisted hand rehabilitation with fingertip stimulation may better attract user’s attention during treatment.
A Combined “Hanging Liver Maneuver” and “Intrahepatic Extra-Glissonian Approach” for Anatomical Right Hepatectomy: Technique Standardization, Results, and Correlation With Portal Pedicle Anatomy
Authors: Makdissi Fabio Ferrari , Mattos Bruno Vinicius Hortences de , Kruger Jaime Arthur Pirola , Jeismann Vagner Birk , Coelho Fabricio Ferreira , Herman Paulo 
Published: May 2021

Background: The hanging liver maneuver and intrahepatic extra-Glissonian approach are distinct modalities to facilitate safe anatomical liver resections. This study reports a standardized combination of these techniques focusing on safety, results and correlation with portal pedicle anatomy in oncological patients.Method: Combined hanging liver maneuver and intrahepatic extra-Glissonian approach for anatomic right hepatectomy was described stepwise. Portal pedicle anatomy was correlated with the Glissonian approach failure and complications. Clinical characteristics of patients, perioperative outcomes, short and long-term survival rates were analyzed.Results: Thirty colorectal liver metastases patients submitted to the combined approach were evaluated. Anatomical variations of the right portal pedicle were present in 26.6%. Hanging liver maneuver was feasible in 100%, and Glissonian approach in 96.7% despite portal pedicle variations. Mean operative time was 326 min. Mean blood loss was 507 ml. Mean hospital stay was 8 days. There was no 90-day operative mortality and no significant morbidity. Oncological surgical margins were free. Overall and disease-free 5-year survival were 59 and 37%.Conclusion: Regardless of frequent anatomical variations of the right portal pedicle, the hanging liver maneuver, and intrahepatic extra-Glissonian approach can be combined, being useful for anatomical right hepatectomies in a safe and reproducible way in most patients.
Pharmacoeconomic Analysis of Heartworm Preventive Compliance and Revenue in Veterinary Practices in the United States
Authors: Mwacalimba Kennedy , Amodie Deborah , Swisher Lisa , Moldavchuk Marina , Brennan Christopher , Walther Claire , Bowman Kelly 
Published: May 2021

Background: Heartworm disease (HWD) is a potentially fatal condition caused by the nematode Dirofilaria immitis. It is endemic in North America, and the American Heartworm Society recommends that owned dogs be on a Food and Drug Administration-approved HWD preventive year-round. The objective of this study was to compare the 12-month HWD preventive purchase compliance rates of injectable moxidectin (ProHeart® 6) and the dose equivalent in monthly HWD preventives and their associated economic value to the veterinary hospital.Methods: This study used retrospective anonymized transactional data of 7,926,392 unique dogs from 3,737 companion animal practices across the US for the period 2014–2017. Compliance was defined using American Heartworm Society guidelines. Comparisons were purchases of a 6-month moxidectin injection or six doses of any monthly HWD or HWD combination preventive product, tracked for the next preventive purchase 5–7 months later. Total revenue, HWD prevention cost, 12-month repurchase compliance, and patient retention were calculated. Data were expressed on an annualized basis. Compliance comparisons were calculated based on proportion analysis with the SAS ProbNorm function (SAS 9.4, Cary, NC), using a two-sided t-test, at the 5% level of significance (P &lt; 0.05).Results: At 51.7%, annual compliance with injectable moxidectin was higher than the dose equivalent in monthly HWD preventives, which was 24.4% (P = 0.0001). Eighty-five percent of patients on injectable moxidectin recorded additional transactions during the first visit (average invoice of $161), compared with only 55% of pet owners who purchased monthly HWD prevention (average invoice $141) or monthly HWD combination (average invoice of $171). The average costs of 6 months of HWD preventives were as follows: injectable moxidectin, $48 (29.7% of the total visit invoice); monthly HWD prevention, $45 (31.0% of the total invoice); and monthly HWD combination, 95 (55.6% of the total visit invoice). Finally, dogs receiving injectable moxidectin had a higher proportion of patients with repeat injections within 12 months between 2014 and 2017, with 68% retention rate after 4 years. In comparison, the six-dose monthly HWD cohort retention rate dropped to 55% by 2017.Conclusions: Dogs receiving injectable moxidectin had higher HWD preventive compliance, generated more practice revenue, and had a higher rate of practice retention compared with monthly HWD products.