bluuebunny/crossref_metadata_2025_split huggingface dataset:
LRRK2 Deficiency Protects Hearts from Myocardial Infarction Injury in Mice via the P53/HMGB1 Pathway
Authors: Liu Yuan , Chen Changgui , Chen Lu , Pei Xiaoxin , Tao Zekai , Xu Yawei , Li Ran 
Published: November 2021

Abstract
Purpose: LRRK2 is a Ser/Thr kinase with multiple functional domains. Current studies have shown that its mutations are closely related to hereditary Parkinson's disease. However, its role in cardiovascular disease, especially in myocardial infarction, is unclear. The aim of this study was to explore the functional role of LRRK2 in myocardial infarction. Methods: Wild-type and LRRK2 knockout mice were subjected to coronary artery ligation (left anterior descent) to establish a myocardial infarction mouse model. Neonatal rat cardiomyocytes were subjected to hypoxia to induce hypoxia injury in vitro. Results: We found increased LRRK2 expression levels in the infarct periphery of mouse hearts and hypoxic cardiomyocytes. LRRK2-deficient mice exhibited a decreased death rate and reduced infarction area compared to the wild-type controls 14 days after infarction. LRRK2-deficient mice showed reduced left ventricular fibrosis and inflammatory response, as well as improved cardiac function. In the in vitro study, LRRK2 silencing decreased the cleaved-caspase3 activity, reduced cardiomyocyte apoptosis, and diminished hypoxia-induced inflammation. However, LRRK2 overexpression enhanced the cleaved-caspase3 activity, increased the number of apoptotic cardiomyocytes, and caused remarkable hypoxia-induced inflammation. When exploring the related underlying mechanisms, we found that hypoxia induced an increase in HIFα expression, which enhanced LRRK2 expression. LRRK2 induced high expression of HMGB1 via P53. When blocking HMGB1 using the anti-HMGB1 antibody, the deteriorating effects caused by LRRK2 overexpression following hypoxia were inhibited in cardiomyocytes.Conclusions: In summary, LRRK2 deficiency protects hearts from myocardial infarction injury. The mechanism underlying this phenomenon involves the P53-HMGB1 pathway.
Yellow Light Decision Based On Driving Style: Day Or Night？
Authors: Wang Xuan , Mao Yan , Xiong Jing Jing , He Wu 
Published: November 2021

Abstract
Drivers' driving decisions at yellow lights are an important cause of accidents at intersections. According to previous studies driving style is an important basis for deciding whether a driver passes a yellow light or not. This study therefore aims to investigate the effect of different driving styles on driving decisions at yellow lights under different lighting conditions. In this paper, 64 licensed drivers were recruited to study the effect of different driving styles on the decision to drive through yellow lights under both daytime and nighttime lighting conditions using a driving simulator and a VR device. The results showed that maladjusted drivers were faster and more likely to pass the yellow light than adapted drivers (81.25% > 43.75%) in both day and night. Male drivers had higher overall driving style scores than female drivers, and male drivers were faster and more likely to pass a yellow light than female drivers (56.25% > 31.25%). The study also found that inexperienced drivers were faster and more likely to pass a yellow light than experienced drivers (50% > 37.5%). Overall, maladjusted drivers are more likely to pass yellow lights, and we can improve this situation by enhancing driving learning for maladjusted drivers.
Investigation of the Optimal Mouthpiece Material for Proton Therapy of Head and Neck Cancer
Authors: Suzuka Masaaki , Mori Takashi , Yamano Shigeru , Takeuchi Akiko , Shima Tomoka , Yasuda Koichi , Kinoshita Yurika , Minatogawa Hideki , Dekura Yasuhiro , Tomita Masayoshi , Aoyama Hidefumi , Minowa Kazuyuki 
Published: November 2021

Abstract
Purpose: To investigate how the materials of mouthpieces used for proton therapy of head and neck cancer affect the dose distribution in surrounding normal tissue by focusing on the CT values of the materials.Methods: Six dental materials were used to measure CT values: temporary relining resin, tissue conditioner, vinyl polysiloxane, thermoplastic ethylene vinyl acetate copolymer splint, silicone rubber impression material, and a composite impression material. Among these materials, three of the dental materials were investigated further: one material with the CT value closest to water, and the materials with the highest and lowest CT values. Based on these results, we investigated the effect of the CT value of the mouthpiece on the dose distribution in 17 cases in which a mouthpiece was used during proton therapy for head and neck cancers, the treatment plans were recalculated by changing the CT values of the mouthpiece to that of the three identified dental materials. For each cancer case, the irradiation dose to normal tissue was calculated for the treatment plans. The evaluation indices were set to the mandible max dose (GyE), the mandible mean dose (GyE), the volume of the mandible irradiated above 60 GyE (mandible V-60GyE), the parotid affected side mean dose (GyE), the parotid unaffected side mean dose (GyE), and the oral mean dose (GyE). The Wilcoxon’s rank sum test was used to analyze the significance of the differences between treatment plans.Results: The temporary relining resin with the CT value closest to water was 36.9 HU, the vinyl polysiloxane with the highest CT value was 985 HU, and the thermoplastic ethylene vinyl acetate copolymer splint with the lowest CT value was -89.7 HU. The maximum absolute difference among the treatment plans per case was 4.18 GyE for the oral mean dose. The radiation dose for the evaluation indices did not differ significantly among the treatment plans. Conclusion: In the range of CT values from -89.7 HU to 985.0 HU covered in this study, the effect of the CT value of the mouthpiece on the dose distribution may be considered to have no clinical impact.
Time-To-Antibiotics and Clinical Outcomes in Patients With Sepsis and Septic Shock: A Prospective Nationwide Multicenter Cohort Study
Authors: Im Yunjoo , Kang Danbee , Ko Ryoung-Eun , Lee Yeon Joo , Lim Sung Yoon , Park Sunghoon , Na Soo Jin , Chung Chi Ryang , Park Mi Hyeon , Oh Dong Kyu , Lim Chae-Man , Suh Gee Young 
Published: November 2021

Abstract
Background
It is unclear whether the administration of antibiotics within 1 hour could improve patient outcomes in sepsis, and whether the association of time to antibiotics administration and clinical outcomes are different for sepsis and septic shock.
Methods
This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock.
Results
Overall, 3,035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI], 0.61–0.99; p=0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI, 0.44–0.99; p=0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI, 0.64–1.15; p=0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% (p=0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock.
Conclusion
Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.
Microstrip Based Pressure Sensor Antenna for Harsh Environment Applications
Authors: Alebachew Muhabaw Amare , Nayak Anil Kumar , Patnaik Amalendu 
Published: November 2021

Abstract
this paper is studied on a microstrip based pressure sensor for harsh environment applications which can sensing at a distance. A microstrip based pressure sensor for harsh environment was investigated with good results by using Rogers’s 3210 substrate material with a dielectric constant of 10.2, 1.28mm thickness and 2.4 GHz resonant frequency, and also both the patch side and the ground side are made from copper metal. The simulation of a proposed antenna was designed and tested by using HFSS software, the result of the designed antenna’s resonance frequency is inversely proportional with the displacement gap of the reflection plate and an antenna. The operating principles of this sensor, when a pressure (load) is applied on the reflection metal plate, the distance will decrease from the reflection plate and the resonant frequency will increase. Therefore, the applied pressure (load) can determined by measuring the changing resonance frequencies. Certainly, the simulation and the experimental results of performances and validates are clearly discussed.
The Expression of HPV E6/E7 mRNA in Situ Hybridization in HPV Typing-negative Cervical Cancer
Authors: Xu Yating , Sun Yonghong , Chang Hui , Cai Jingjing , Cao Chengcheng , Zhang Baogang , Zhang Youzhong , Liu Yuzhen 
Published: November 2021

Abstract
Background: High-risk human papilloma virus (HR-HPV) persistent infection is the major tumorigenesis factor for cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). However, the incidence of HPV-negative CC is approximately 5%-30% with different HPV detection methods. HR-HPV E6/E7 mRNA in situ hybridization (RISH) can detect HPV-driven tumours. Our study aimed to explore whether HPV typing-negative CC was caused by HPV infection.Methods: The records of CC patients with HPV typing results who had undergone cervical biopsies, cervical conization or hysterectomies were collected from April 2018 to September 2021 at the Affiliated Hospital of Weifang Medical University. RISH was detected using RNAscope chromogenicin in the tissues of patients with CC. Immunohistochemistry (IHC) was performed to evaluate the expression of p16INK4a and Ki67. CC patients with positive HPV typing in the same period were collected as controls.Results: A total of 308 women with HPV typing results were enrolled, and 30 (9.74%) cases of HPV typing were negative, including 22/30 (73.3%) cases of squamous cell carcinoma (SCC) and 8/30 (26.7%) cases of adenocarcinoma. In the CC patients who were HPV typing-negative, 28/30 (93.3%) were positive for RISH and p16INK4a block+ staining, which contained 22/22 (100%) SCCs and 6/8 (75%) adenocarcinomas. RISH was positive in 278/278 (100%) HPV typing-positive CCs, which included 232/232 (100%) SCCs and 46/46 (100%) adenocarcinomas. While 273/278 (98.2%) showed p16INK4a block+ staining, the five negative cases were SCC. Positive RISH in HPV typing-negative CC was significantly lower than in the HPV typing-positive group (P=0.002, 95% CI: 0.848-1.027). However, this significant difference only existed in adenocarcinoma, and positive RISH in HPV typing-negative SCC was the same as in the HPV typing-positive group. No significant differences were seen in the expression of p16INK4a and Ki67 (P=0.291, 95% CI: 0.863-1.047 and P=0.174, 95% CI: 0.905-1.033).Conclusions: HPV typing may cause misdiagnosis in 9.74% of CC patients, and HPV E6/E7 mRNA can detect the majority of CC with HPV-related status even in HPV typing-negative patients. This approach could provide a novel option to accurately detect HR-HPVs in cervical tumours and help to eliminate the percentage of misdiagnosed HPV-related cases.
PEG-Asparaginase Single-Agent Rescue in an Advanced Case of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma.
Authors: Barbieri Emiliano , Pozzi Stefano , Gelmini Roberta , Roncati Luca , Maccaferri Monica , Potenza Leonardo , Marasca Roberto , Luppi Mario , Leonardi Giovanna 
Published: November 2021

Abstract
MEITL is a very rare and highly aggressive peripheral T-cell lymphoma with poor prognosis and for which there is no standard treatment. Patients with relapsed/refractory disease have few treatment options and many still die of disease progression. Here we report the case of a 65-year-old woman affected by MEITL, progressing after initial treatment with an anthracycline-based chemotherapy and surgery, who received single-agent PEG-asparaginase salvage therapy at our institution. The treatment proved to be rapidly effective in controlling the disease and its associated paraneoplastic features. Nevertheless, toxicity was high and the patient died due to a treatment-related complication. The case we described brings new evidences on the effectiveness of PEG-asparaginase therapy in MEITL patients. Whether PEG-asparaginase should be included in the treatment course of MEITL patients could be the subject of future studies.
Effect of Hyaluronic Acid on Cytokines and Immune Cells Change in Patients of Knee Osteoarthritis
Authors: Jin Lixia , Xu Kangli , Liang Yun , Du Peng , Wan Shengcheng , Jiang Chang 
Published: November 2021

Abstract
Purpose To evaluate the changes of cytokines and immune cells after Intra-articular hyaluronic acid（IAHA）injections in patients with knee osteoarthritis (KOA).Patients and Methods Sixteen patients were included in the study, with a total of 63 IAHA injections. The Numeric Rating Scale (NRS) and Lysholm scores were evaluated at each visit. The immune cells and 14 cytokines of synovial fluid were analyzed at each visit. The association between immune cells and cytokines were examined Results IL-6 and IL-8 were the most common cytokines in the synovial fluid of KOA patients. The synovial fluid was orchestrated by macrophages (69%) and Lymphocytes (18%). Neutrophils were less to count of the total cell population (<2%). The cytokines decreased significantly after the first injection and then tended to be stable. Lymphocytes increased a lot, while Macrophages decreased in the early stage, then increased after multiple injections. The proposition of M1 decreased in the early stage, then increased after multiple injections, while M2 increased consistently. M1 and M2 were positively associated with IL-6 and IL-8.Conclusion The synovial fluid of KOA patients was orchestrated by macrophages (69%) and Lymphocytes (18%) and cytokines like IL-6 and IL-8. IAHA may play an anti-inflammatory functional role through the decreased production of IL-6 and IL-8 by macrophages through polarization. The results from this study provided new evidence for IAHA treatment in KOA patients, and therapies targeting pathogenic cytokines and immune cells might be used to attenuate the knee joint inflammation and release pain.Trial registrationChiCTR2100050133; date registered 17 August 2021.
Lupus Nephritis Correlates with B-Cell Interferon-β, Anti-Smith, and Anti-DNA: A Retrospective Study
Authors: Alduraibi Fatima , Fatima Huma , Hamilton Jennie , Chatham W.Winn , Hsu Hui-Chen , Mountz John 
Published: November 2021

Abstract
Background: In systemic lupus erythematosus (SLE), detection of interferon-β (IFNβ)in B cells was found to be most prominent in patients with high anti-Smith (Sm) and renal disease, but a mechanistic connection was not clear. The objective of the present study is to determine the association of IFNβ in peripheral blood naïve B cells with the histopathological features of lupus nephritis (LN).Methods: The percentage of IFNβ+ cells in IgD+CD27− naïve CD19+ B cells (B-cell IFNβ) among peripheral blood mononuclear cells (PBMCs) from 80 SLE patients were analyzed using flow cytometry. Serological and clinical data were collected. The correlations of B-cell IFNβ with LN classification and with histopathological findings (light, electron and immunofluorescence [IF] microscopic analyses for deposition of IgM, IgG, IgA, C1q, and C3) were determined in 23 available biopsy specimens.Results: B-cell IFNβ is positively associated with anti-Sm (p = 0.001), anti-DNA (p = 0.010), and LN (p = 0.001), but was negatively associated with oral/nasal ulcer (p = 0.003) and photosensitivity (p = 0.045). B-cell IFNβ positively correlated with immune complex (IC) deposit in the glomerular basement membrane (GBM) (p = 0.002) but not in the mesangial (p = 0.107) or tubular region (p = 0.313). Patients with high B-cell IFNβ had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B-cell IFNβ (p < 0.0001). Histopathological features positively associated with increased B-cell IFNβ included active glomerular lesions as determined by fibrocellular crescents (p = 0.023), chronic glomerular lesions indicated by segmental sclerosis (p = 0.033), and a membranous pattern of renal damage indicated by spike/holes (p = 0.015).Conclusion: B-cell IFNβ correlates with severe LN, glomerular basement membrane (GBM) IC deposition, and anatomical features of both active and chronic glomerular lesions.
Addressing catastrophic forgetting for medical domain expansion
Authors: Gupta Sharut , Singh Praveer , Chang Ken , Qu Liangqiong , Aggarwal Mehak , Arun Nishanth , Vaswani Ashwin , Raghavan Shruti , Agarwal Vibha , Gidwani Mishka , Hoebel Katharina , Patel Jay , Lu Charles , Bridge Christopher , Chen Jimmy , Chan R. V. Paul , Chiang Michael , Campbell John , Rubin Daniel , Kalpathy-Cramer Jayashree 
Published: November 2021

Abstract
Model brittleness is a key concern when deploying deep learning models in real-world medical settings. A model that has high performance at one dataset may suffer a significant decline in performance when tested at on different datasets. While pooling datasets from multiple hospitals and re-training may provide a straightforward solution, it is often infeasible and may compromise patient privacy. An alternative approach is to fine-tune the model on subsequent datasets after training on the original dataset. Notably,this approach degrades model performance at the original datasets, a phenomenon known as catastrophic forgetting. In this paper, we develop an approach to address catastrophic forgetting based on elastic weight consolidation combined with modulation of batch normalization statistics under three scenarios: 1) for expanding the domain from one imaging system’s data to another imaging system’s 2) for expanding the domain from a large multi-hospital dataset to another single hospital dataset 3) for expanding the domain from dataset from one geographic region to a dataset from another geographic region. Focusing on the clinical uses cases of mammographic breast density detection and retinopathy of prematurity stage diagnosis, we show that our approach outperforms several other state-of-the-art approaches and provide theoretical justification for the efficacy of batch normalization modulation. The results of this study are generally applicable to the deployment of any clinical deep learning model which requires domain expansion.
Growth in Infants, Children and Adolescents with Unilateral and Bilateral Cerebral Palsy
Authors: Brunner Maria de las Mercedes Ruiz , Cuestas Eduardo , Heinen Florian , Schroeder Andreas Sebastian 
Published: November 2021

Abstract
PURPOSE: To compare growth patterns during infancy, childhood and adolescence in children with unilateral and bilateral cerebral palsy (CP) phenotype and to assess the association with gross motor impairment, dysphagia and gestational age. METHODS: We retrospectively studied 389 children with CP from a single center population in Munich, Germany. 1536 measurements of height and weight were tabulated and z-scored from 6 to 180 months of age. Generalized linear mixed model were used to examine the association between growth, GMFCS, dysphagia and gestational age by CP phenotype. RESULTS: Children with unilateral CP tend to grow similarly to their typically developed peers. In the main effect model, bilateral CP phenotype was significantly associated with decreased mean z-scores for height (β[95% CI] = -0.953 [-1.145, -0.761], p < 0.001), weight (−0.999 [−1.176, −0.807], p < 0.001) and BMI (β[95% CI] = −0.437 [−0.799, −0.075]), compared with unilateral CP phenotype.This association remained significant in the interaction models. The height-for-age z-scores, weight-for-age decreased z-scores and BMI-for-age z-scores of children with bilateral CP and GMFCS III–V or dysphagia decreased more significantly than those of children with unilateral CP. Preterm birth was not significantly associated with decreased growth in height, weight and BMI.CONCLUSION: Reduced growth in children with bilateral CP was strongly associated with moderate to severe impairment in gross motor function (GMFCS III–V) and dysphagia.
Enhancement of the haemostatic effect of platelets in the presence of high normal concentrations of von Willebrand factor
Authors: Hermann Goetz , Blum Andrea , Bolliger Daniel , Achermann Rita , Estermann Anna , Gebhard Caroline , Henn Anne , Huber Jan , Singh Jasprit , Todorov Atanas , Zehnder Tatjana Stefanie , Zellweger Nuria , Buser Andreas , Tsakiris Dimitrios , Hollinger Alexa , Siegemund Martin 
Published: November 2021

Abstract
Introduction: Von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surface of damaged endothelia. To the best of our knowledge, no trial exists that investigated the effect of platelet transfusion in combination with the administration of balanced vWF in severe blood loss, despite being widely used in clinical practice. The Basel Will-Plate study will investigate the impact of timely administration of balanced vWF (1:1 vWF and FVIII) in addition to platelet transfusion on need for blood and coagulation factor transfusion in patients admitted to the intensive care unit (ICU) who suffer from severe bleeding. The study hypothesis is based on the assumption that by adding balanced vWF to platelets will reduce the overall need of transfusion of blood products compared to transfusion of platelets alone. Methods and Analysis: The Will-Plate study is an investigator-initiated, single-centre, double-blinded randomised controlled clinical trial in 120 critically ill patients needing platelet transfusion. The primary outcome measure will be the number of fresh frozen plasma (FFP) and red blood cell (RBC) transfusions according to groups. Secondary outcome measures include number of platelet concentrates transfused within the first 48 h after treatment of study medication, quantity of blood loss in the first 48 hours after treatment with the study medication, length of stay in ICU and hospital, number of revision surgeries for haemorrhage control, ICU mortality, hospital mortality, 30-day mortality and one-year mortality. Patients will be followed after 30 days and 1 year for activities of daily living and mortality assessment. Sample size was calculated to detect a 50% reduction of the number of blood products subsequently transfused within two days in patients with Wilate® compared to placebo. Ethics and dissemination: This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the ICH-GCP or ISO EN 14155 (as far as applicable) as well as all national legal and regulatory requirements. Study results will be presented in international conferences and published in a peer-reviewed journal. Trials registration: ClinicalTrials.gov Identifier: NCT04555785 Protocol version: Clinical Study Protocol Version 2, 01.11.2020