bluuebunny/crossref_metadata_2025 huggingface dataset:
Coexistence of Relapsing Polychondritis and Sickle Cell Disease in a Child
Authors: Tetteh Bernard Ofoe , Yebuah Florence-Barbara , Amissah-Arthur Maame-Boatemaa , Dey Dzifa
Published: November 2021

Relapsing polychondritis (RP) is a rare, severe connective tissue disease of unknown etiology affecting cartilaginous and proteoglycan-rich structures in an episodic and inflammatory manner. Approximately a third of RP cases occur in conjunction with another disease usually systemic autoimmune rheumatic disease, or myelodysplastic syndrome. Sickle cell disease (SCD) is a common inherited hematologic condition characterized by the inheritance of two abnormal hemoglobins, of which one is a hemoglobin S, presenting with severe acute and chronic complications from vaso-occlusive phenomena, which can be difficult to differentiate from RP. The pathogenesis of RP is poorly understood but suggests an autoimmune mechanism with a link to sickle cell disease yet to be established. Treatment is empiric with steroids, anti-inflammatory, and disease-modifying antirheumatic drugs being the mainstay of therapy. Severe complications occur despite treatment, with respiratory involvement being the most catastrophic. This case report reviews a complex case of RP in an 11-year-old girl with sickle cell disease (SF genotype) presenting with bilateral red painful eyes, a painful swollen left ear, and knee pain. Laboratory findings revealed elevated inflammatory markers with negative immune serology. A diagnosis of RP was made based on the patient's symptomatology, presentation, and fulfillment of 5 out of the 6 clinical features using McAdam’s criteria. Management was instituted with a myriad of conventional and biologic DMARDs and other anti-inflammatory medications with no significant improvement and the development of complications of airway obstruction from disease activity and osteoporotic fracture from steroid therapy and underlying hemoglobinopathy. In children, the diagnosis of RP is delayed or overlooked due to its low incidence, variability in clinical symptoms, or sharing similar clinical features with other coexisting disease entities. This article reports its occurrence in the pediatric population and highlights the difficulty in managing such cases as there are no defined standard treatment protocols.
A Blockchain‐Based Auto Insurance Data Sharing Scheme
Authors: Liu Xiaoguang , Yang Hengzhou , Li Gaoping , Dong Hao , Wang Ziqing
Published: November 2021

Auto electronic insurance policy and electronic maintenance list record the entire process of auto owners purchasing auto insurance and repairs after accident, respectively. They play a vital role in auto owners’ applications for claims and insurance company’s judgment on whether to settle the claims. However, the privacy of insurance policy and the “information island” resulting from the nonsharing of data between users make the claim has low efficiency. The notable features of blockchain technology are decentralization and tamper‐proof, which can well solve data sharing and privacy protection. This paper proposes a blockchain‐based auto insurance data sharing scheme to improve the existing auto insurance claim system. The scheme includes four main bodies: auto owner, insurance company, 4S Shop, and government authority. In the proposed scheme, the data sharing of authorized users is realized through proxy reencryption. Finally, we have analyzed the security and performance of the solution. The analysis results show that the proposed scheme can meet many security features such as user access control and data tamper resistance and has an ideal calculation and communication cost.
Quality Evaluation of Ethiopian 100% Cotton Carded Ring Spun Yarn with Respect to USTER Standards
Authors: Adamu Biruk Fentahun , Atalie Desalegn , Liyew Erkihun Zelalem
Published: November 2021

Yarn quality influences both fabric production processes efficiency and export market. One method used to gauge competitiveness of an industry is to study its product quality. The aim of this research work is to evaluate the quality of Ethiopian textile spinning mills’ 100% cotton carded ring spun yarns in terms of its evenness (coefficient of mass variation, CVm), imperfections (thick and thin places, neps), and tensile properties with USTER Statistics 2018. Five spinning mills (B3, A0, A2, A4, and K3) of 15N, 20Ne, 25Ne, 30Ne, 35Ne, and 40Ne nominal yarn counts have been selected for the study. The yarn evenness and imperfections were measured using USTER tester 5 and tensile using a STATIMAT tester. The USTER statistical results showed 20.3Ne (mill B3), 32Ne (mill A4), and 36.2Ne (mill A2) had better overall quality, respectively. It was observed that most selected spinning mills had low evenness, imperfections, yarn strength, and good yarn elongation. Tensile properties of A2 (32.85Ne and 36.2Ne) had fallen under 5% USTER statistics percentile which indicates excellent yarn strength. Generally, from studied mills, it was seen that 61.5% of cotton yarn CVm and thin places falls at above 95% and 15% of yarn tenacity falls at ≤5% of Uster statistical percentile.
Valorization of Glycine max (Soybean) Seed Waste: Optimization of the Microwave-Assisted Extraction (MAE) and Characterization of Polyphenols from Soybean Meal Using Response Surface Methodology (RSM)
Authors: Woumbo Cerile Ypolyte , Kuate Dieudonné , Klang Mathilde Julie , Womeni Hilaire Macaire
Published: November 2021

The present study aimed at determining the optimal conditions for extraction of total phenolic compounds from soybean (Glycine max) meal, a by-product of the soybean seeds industry, using a green protocol with microwave-assisted extraction (MAE). A face-centered composite design (FCCD) was used for optimization. Based on a screening aimed to determine the factors that significantly influenced the responses, a 50% hydro-ethanolic solution was used with solvent/dry matter ratio (60/1–110/1), power (120–270 W), and time (0–10 min) as factors, while the responses studied were total phenolic and flavonoid contents. FTIR, TLC, DPPH, and FRAP anti-oxidants tests were used to characterize the extracts obtained with optimum conditions. The factors that significantly influenced both responses were the individual effect of all factors, the interaction between solvent/dry matter ratio and extraction time, the quadratic effect of solvent/dry matter ratio, and power for total phenolic content, while only the quadratic effect of power significantly influenced the flavonoid content. The highest contents of phenols (13.09 mg GAE/g) and flavonoid (7.39 mg CE/g) were obtained at 120 W for 0.16 min with a solvent/dry matter ratio of 60/1. ATR-FTIR spectra indicated the presence of polyphenolic compounds in the extract, namely flavonoids. TLC indicated the presence of at least nine compounds in the extract, among which catechin and quercetin were identified with respective Rf of 0.98 and 0.93. DPPH assay showed the anti-oxidant capacity for the extract with an IC50 of 194.98 µg/ml. RSM permitted us to develop a green protocol for maximum extraction of polyphenols from soybean seeds waste using less solvent, low power, and a reduced time in MAE.
Remaining Useful Life Estimation of Aircraft Engines Using a Joint Deep Learning Model Based on TCNN and Transformer
Authors: Wang Hai-Kun , Cheng Yi , Song Ke
Published: November 2021

The remaining useful life estimation is a key technology in prognostics and health management (PHM) systems for a new generation of aircraft engines. With the increase in massive monitoring data, it brings new opportunities to improve the prediction from the perspective of deep learning. Therefore, we propose a novel joint deep learning architecture that is composed of two main parts: the transformer encoder, which uses scaled dot‐product attention to extract dependencies across distances in time series, and the temporal convolution neural network (TCNN), which is constructed to fix the insensitivity of the self‐attention mechanism to local features. Both parts are jointly trained within a regression module, which implies that the proposed approach differs from traditional ensemble learning models. It is applied on the Commercial Modular Aero‐Propulsion System Simulation (C‐MAPSS) dataset from the Prognostics Center of Excellence at NASA Ames, and satisfactory results are obtained, especially under complex working conditions.
[Retracted] PFNA‐II Internal Fixation Helps Hip Joint Recovery and Improves Quality of Life of Patients with Lateral‐Wall Dangerous Type of Intertrochanteric Fracture
Authors: Mu Weilu , Zhou Junlin
Published: November 2021

Objective. To analyze the effect of PFNA‐II internal fixation on hip joint recovery and quality of life (QOL) in patients with lateral‐wall dangerous type of intertrochanteric fracture. Methods. One hundred and twelve patients with lateral‐wall dangerous type of intertrochanteric fracture who underwent surgical treatment in our hospital from May 2017 to May 2019 were selected as the participants of the study. Based on the treatment method, all the enrolled patients were divided into two groups: proximal femoral nail antirotation (PFNA group; n = 59) who received closed reduction and minimally invasive PFNA internal fixation and dynamic hip screw group (DHS; n = 53) who received internal fixation. The clinical indicators, curative effect, hip function score, pain degree, postoperative QOL score, and complications were compared between the two groups. Results. The operation time, intraoperative blood loss, postoperative drainage volume, and the incidence of postoperative complications in PFNA group were statistically lower than those in DHS group (P < 0.05). The curative effect in PFNA group was notably better than that in DHS group. There were no significant differences in scores of hip function, visual analogue scale (VAS), and QOL between the two groups before operation (P > 0.05). However, the hip function score and QOL score increased in both groups after surgery, and the increase was more significant in the PFNA group, while the VAS score decreased in both groups, and the decrease in PFNA group was more significant (P < 0.05). Conclusion. PFNA internal fixation for the treatment of lateral‐wall dangerous type of intertrochanteric fracture has the advantages of short operation time, less intraoperative blood loss, effective improvement of hip joint function, and fewer postoperative complications, which is worthy of clinical application.
Comprehensive Analysis of the Immune and Prognostic Implication of MMP14 in Lung Cancer
Authors: Zheng Chun-long , Lu Qiang , Zhang Nian , Jing Peng-yu , Zhang Ji-peng , Wang Wu-ping , Li Gui-zhen
Published: November 2021

More and more studies have indicated an association between immune infiltration in lung cancer and clinical outcomes. Matrix metalloproteinase 14 (MMP14) has been reported to be dysregulated in many types of tumors and involved in the development and progression of tumors. However, its contribution to cancer immunity was rarely reported. In the study, we found that MMP14 expression was distinctly upregulated in lung cancer specimens compared with nontumor lung specimens. High MMP14 expression predicted a poor prognosis of lung squamous cell carcinoma (LUSC) patients. Increased MMP14 expressions were observed to be positively related to high immune infiltration levels in most of the immune cells. A pathway enrichment analysis of 32 MMP14-associated immunomodulators indicated the involvement of T cell receptor signaling pathway and Toll-like receptor signaling pathway. Based on MMP14-associated immunomodulators, we applied multivariate assays to construct multiple-gene risk prediction signatures. We observed that risk scores were independently associated with overall survival. These data highlighted that MMP14 was involved in tumor immunity, indicating that MMP14 could serve as a novel prognostic biomarker and therapeutic target for lung cancer. Our data suggest that the four genes identified in this study may serve as valuable biomarkers of lung cancer patient outcomes.
Research on Green Transport Mode of Chinese Bulk Cargo Based on Fourth-Party Logistics
Authors: Wu Jixiao , Wang Yinghui , Li Wenlu , Wu Haixia
Published: November 2021

Due to the problems such as the excessive proportion of road transport and extreme carbon emission situation of China’s transport structure adjustment, this paper combines the fourth-party logistics with the bulk cargo green transport. It is advancing the adjustment of China’s bulk cargo transport structure using fourth-party logistics. This paper improves the particle swarm optimization algorithm to compare the integrated cost and carbon emissions of different bulk fourth-party transport networks to verify the benefits of the fourth-party logistics on bulk cargo transport networks’ cost reduction and emission reduction. The results show that using the fourth-party logistics model to promote the transfer of cargoes from road to rail can reduce the integrated cost of the transport network, reduce carbon emissions, and achieve green transport.
Effect of Low-Frequency Electric Pulse Technique Combined with Carboprost Methylate Suppositories on Recovery of Gastrointestinal Function and Postoperative Complications of Patients with Scarred Uterus Undergoing Secondary Cesarean Section
Authors: Yan Jinling , Liu Yongli , Jiao Ruifen , Li Meixiang , Zhao Liqin
Published: November 2021

The study aims to explore the effect of low-frequency electric pulse technique combined with carboprost methylate suppositories on recovery of gastrointestinal function and postoperative complications of patients with scarred uterus undergoing secondary cesarean section (C-section). The clinical data of 120 patients with scarred uterus undergoing secondary C-section treated in our hospital from February 2019 to February 2020 were retrospectively analyzed, and the patients were equally divided into experimental and control groups according to their admission order, where each group included 60 patients. After the operation, patients in the control group received routine nursing and conducted breastfeeding, and carboprost methylate suppositories were used for postoperative hemostasis. Those in the experimental group received low-frequency electric pulse technique for comprehensive treatment to compare their coagulation function indicators, recovery of gastrointestinal function, incidence rates of postoperative complications, and involution of uterus. No significant between-group differences in patients’ general information such as gestational weeks, gravidity, and number of times receiving C-section were observed (

P
>
0.05

). Compared with the control group after the operation, patients in the experimental group obtained significantly better coagulation function indicators (

P
<
0.001

) and presented better gastrointestinal function recovery (

P
<
0.001

), significantly lower incidence rates of postpartum hemorrhage, retention of urine, deep venous thrombosis of lower limb, rupture of uterus, and endometrial cavity fluid (

P
<
0.05

), and significantly better involution of uterus (

P
<
0.001

). In conclusion, combining low-frequency electric pulse technique with carboprost methylate suppositories can lower the incidence rates of postoperative complications for patients with scarred uterus undergoing secondary C-section, improve their coagulation function, promote the recovery of gastrointestinal function, and present the desirable involution of uterus, which should be promoted in practice.
Effect of Antioxidants in the Treatment of COPD Patients: Scoping Review
Authors: Orozco-Levi Mauricio , Colmenares-Mejía Claudia , Ruíz Jessica , Valencia-Barón Yurley Dayanna , Ramírez-Sarmiento Alba , Quintero-Lesmes Doris Cristina , Serrano Norma C.
Published: November 2021

Chronic obstructive pulmonary disease (COPD) is a common, preventable, treatable lung disease characterized by persistent respiratory symptoms and airflow limitation and multiorgan impact. This affects the nutritional status of patients and requires multidimensional interventions including nutritional interventions according to individual metabolic needs. Our scoping review determined the effects of antioxidants in the treatment of COPD patients and their role in the decrease in the probability of exacerbations, hospital readmissions, and changes in lung function. The sources MEDLINE, LILACS, and Google Scholar were consulted and 19 studies were selected. The most indicated antioxidants are N-Acetylcysteine, vitamins E and D, and Zinc. Other antioxidants from plants or fruits extracts are also being investigated. The beneficial effect of antioxidants in stable or exacerbated patients is not clear, but theoretical and biological arguments of benefit justify lines of research that specify the impact on reducing oxidative stress and negative effects in COPD.
Construction of Spatiotemporal Difference Image of the Impact of Financial Structure on China’s Total Factor Productivity
Authors: Yu Yong
Published: November 2021

My country’s current research on the influencing factors of total factor productivity has problems such as single evaluation method, low efficiency, and poor overall level in terms of evaluation methods and evaluation efficiency. Based on this, this study divides the financial structure into three traditional sections, banking, securities, and insurance, and uses the DEA model to study the temporal and spatial differences of the financial structure’s influence on the total factor productivity of the four major political and economic regions of China’s eastern, western, central, and northeastern China. First, establish a DEA model based on data mining algorithms, combine financial data comparisons over the years, to achieve a quantitative analysis of the financial structure’s impact on China’s total factor productivity, calculate financial efficiency, and then combine the DEA analysis data model with the grey correlation method. Analyze its internal influence rules, and design experiments for model verification analysis. The results show that the DEA analysis model can realize 8 iterations of data on the impact of financial structure on China’s total factor productivity, and its evaluation accuracy can reach more than 96.2%.
L

p

Smoothness on Weighted Besov–Triebel–Lizorkin Spaces in terms of Sharp Maximal Functions
Authors: Gürbüz Ferit , Loulit Ahmed
Published: November 2021

It is known, in harmonic analysis theory, that maximal operators measure local smoothness of

L

p

functions. These operators are used to study many important problems of function theory such as the embedding theorems of Sobolev type and description of Sobolev space in terms of the metric and measure. We study the Sobolev-type embedding results on weighted Besov–Triebel–Lizorkin spaces via the sharp maximal functions. The purpose of this paper is to study the extent of smoothness on weighted function spaces under the condition

M
α
#

f

∈

L

p
,
μ

, where

μ

is a lower doubling measure,

M
α
#

f

stands for the sharp maximal function of

f

, and

0
≤
α
≤
1

is the degree of smoothness.
Oxidative Stress Profile of Mothers and Their Offspring after Maternal Consumption of High‐Fat Diet in Rodents: A Systematic Review and Meta‐Analysis
Authors: Moraes-Souza R. Q. , Vesentini Giovana , Paula Verônyca Gonçalves , Sinzato Yuri Karen , Soares T. S. , Gelaleti Rafael Bottaro , Volpato Gustavo Tadeu , Damasceno Débora Cristina
Published: November 2021

Maternal exposure to the high‐fat diet (HFD) during gestation or lactation can be harmful to both a mother and offspring. The aim of this systematic review was to identify and evaluate the studies with animal models (rodents) that were exposed to the high‐fat diet during pregnancy and/or lactation period to investigate oxidative stress and lipid and liver enzyme profile of mothers and their offspring. The electronic search was performed in the PUBMED (Public/Publisher MEDLINE), EMBASE (Ovid), and Web of Science databases. Data from 77 studies were included for qualitative analysis, and of these, 13 studies were included for meta‐analysis by using a random effects model. The pooled analysis revealed higher malondialdehyde levels in offspring of high‐fat diet groups. Furthermore, the pooled analysis showed increased reactive oxygen species and lower superoxide dismutase and catalase in offspring of mothers exposed to high‐fat diet during pregnancy and/or lactation. Despite significant heterogeneity, the systematic review shows oxidative stress in offspring induced by maternal HFD.
Dipeptidyl Peptidase (DPP)-4 Inhibitor Impairs the Outcomes of Patients with Type 2 Diabetes Mellitus After Curative Resection for Colorectal Cancer
Authors: Saito Akira , Kitayama Joji , Horie Hisanaga , Koinuma Koji , Kawashima Rie , Ohzawa Hideyuki , Yamaguchi Hironori , Kawahira Hiroshi , Mimura Toshiki , Lefor Alan Kawarai , Sata Naohiro
Published: November 2021

Dipeptidyl peptidase IV inhibitor (DPP-4i) has been shown to act either as a promoter or as a suppressor for cancer. Although epidemiologic studies suggest that DPP-4i does not correlate with the development of malignancies, its effects on cancer metastases are controversial. We evaluated the impact of DPP-4i on postoperative outcomes of the diabetic patients with colorectal cancer and microscopic features of the resected tumors. In 260 consecutive patients with type 2 diabetes mellitus (T2DM) who underwent curative resection of colorectal cancer, the correlation between DPP-4i use and prognosis was retrospectively examined. Expression of Zeb1 on tumor cells and density of infiltrating immune cells were quantitatively evaluated with multicolor IHC in 40 tumors from DPP-4i users, 40 tumors from propensity score–matched users, and 40 tumors from nonusers. Postoperative disease-free survival (DFS) was significantly lower in 135 patients treated with DPP-4i compared with 125 nontreated patients [5-year DFS, 73.7% vs. 87.4%; HR, 1.98; 95% confidence interval (CI), 1.05–3.71; P = 0.035]. IHC revealed that the number of Zeb1+ tumor cells increased in tumors from DPP-4i–treated patients than tumors from nonusers (P < 0.01). The densities of CD3+ and CD8+ T cells were significantly lower in tumors from DPP-4i users (P < 0.01) with decreased density of tertiary lymphoid structures (P < 0.001). However, the density of M2-type tumor-associated macrophages with CD68+ CD163+ phenotypes was significantly higher (P < 0.01) in tumors from DPP-4i users. Exposure of colorectal cancer to DPP-4i may accelerate epithelial-to-mesenchymal transition (EMT) creating a tumor-permissive immune microenvironment, which might impair the outcomes of the patients with colorectal cancer and T2DM.

Significance:

DPP-4i has been shown to enhance the antitumor effects of immunotherapy. However, we found that DPP-4i significantly impairs the outcomes of patients with colorectal cancer who underwent curative resection, possibly through acceleration of EMT and creation of a tumor-permissive immune microenvironment. This suggests that DPP-4i must be used with caution until its safety is fully confirmed by further studies of the mechanistic effects on existing cancers in humans.
Mapping Sequential IgE-Binding Epitopes on Major and Minor Egg Allergens
Authors: Suprun Maria , Sicherer Scott H. , Wood Robert A. , Jones Stacie M. , Leung Donald Y.M. , Burks A. Wesley , Dunkin David , Witmer Marc , Grishina Galina , Getts Robert , Suárez-Fariñas Mayte , Sampson Hugh A.
Published: November 2021

Introduction: Molecular studies of hen’s egg allergens help define allergic phenotypes, with IgE to sequential (linear) epitopes on the ovomucoid (OVM) protein associated with a persistent disease. Epitope profiles of other egg allergens are largely unknown. The objective of this study was to construct an epitope library spanning across 7 allergens and further evaluate sequential epitope-specific (ses-)IgE and ses-IgG4 among baked-egg reactive or tolerant children. Methods: A Bead-Based Epitope Assay was used to identify informative IgE epitopes from 15-mer overlapping peptides covering the entire OVM and ovalbumin (OVA) proteins in 38 egg allergic children. An amalgamation of 12 B-cell epitope prediction tools was developed using experimentally identified epitopes. This ensemble was used to predict epitopes from ovotransferrin, lysozyme, serum albumin, vitellogenin-II fragment, and vitellogenin-1 precursor. Ses-IgE and ses-IgG4 repertoires of 135 egg allergic children (82 reactive to baked-egg, the remaining 52 tolerant), 46 atopic controls, and 11 healthy subjects were compared. Results: 183 peptides from OVM and OVA were screened and used to create an aggregate algorithm, improving predictions of 12 individual tools. A final library of 65 sequential epitopes from 7 proteins was constructed. Egg allergic children had higher ses-IgE and lower ses-IgG4 to predominantly OVM epitopes than both atopic and healthy controls. Baked-egg reactive children had similar ses-IgG4 but greater ses-IgE than tolerant group. A combination of OVA-sIgE with ses-IgEs to OVM-023 and OVA-028 was the best predictor of reactive phenotype. Conclusion: We have created a comprehensive epitope library and showed that ses-IgE is a potential biomarker of baked-egg reactivity.
Oncological Outcomes of Transoral Laryngeal Microsurgery with Fiber-Optic Diode Laser for Early Glottic Cancer: A Single-Center Experience
Authors: Korkmaz Mehmet Hakan , Bayır Ömer , Hatipoğlu Esra Bozkurt , Tatar Emel Çadalli , Han Ünsal , Öcal Bülent , Keseroğlu Kemal , Karahan Sevilay , Saylam Güleser
Published: November 2021

Backgroud/Objectives: Transoral laser laryngeal microsurgery (LTLM) has been widely used in the treatment of early-stage glottic laryngeal squamous cell carcinoma (LSCC) for the past few decades. Although T stage, tumor grade, anterior commissure involvement, type of cordectomy, positive surgical margin, and postoperative additional therapies were accused as the prognostic factors for recurrence, there is still controversy about these data in the literature. The purpose of this study was to evaluate the oncological results of our patients with early glottic LSCC treated with LTLM as a single-modality therapy in a single-center study. Methods: Patients with early-stage (Tis-1–2/N0) glottic LSCC who underwent LTLM as a primary treatment from 2011 to 2019 were retrospectively reviewed. The clinicopathological factors and oncologic outcomes were analyzed. Results: One hundred and sixty-one patients were enrolled in this study. The 5-year overall (OS), disease-specific (DSS), disease-free (DFS), and laryngectomy-free survival rates were 84.5%, 97.9%, 79.2%, and 93.5%, respectively. The most common stage, histopathological type, and type of endoscopic cordectomy were T1 stage, well-differentiated cancer, and type 2 cordectomy, respectively. A positive surgical margin was defined in 20 (12.4%) patients. There was a significant relationship between histopathological grade and positive surgical margins (p = 0.038). OS and DSS rates of “wait and see” modality were lower, while DFS of radiotherapy was lower than that of other treatment modalities in patients with positive surgical margins, but the differences were not statistically significant. Nineteen (11.8%) patients had a recurrence. DSS was statistically significantly lower in patients with recurrence (p < 0.001). Conclusion: The results of our study showed that anterior commissure involvement, surgical margin positivity, and higher T stage statistically did not reduce survival rates in early-stage LSCC patients treated with LTLM. As the histopathological grade of the tumor worsens, the risk of surgical margin positivity increases. RT may have a negative effect on recurrence and organ preservation in the additional treatment of patient with positive surgical margins.
Increased Plasma GDF15 Is Associated with Altered Levels of Soluble VEGF Receptors 1 and 2 in Symptomatic Multiple Myeloma
Authors: Hidman Josefin , Larsson Anders , Thulin Måns , Karlsson Torbjörn
Published: November 2021

Introduction: In multiple myeloma, there is an increase in bone marrow microvascular density and enhanced renal lymphangiogenesis. Increased levels of the proangiogenic protein growth differentiation factor-15 (GDF15) have previously been reported to be associated with poor prognosis in myeloma. A possible association between GDF15 and the soluble forms of vascular endothelial growth factor receptors (sVEGFR) 1 and 2 has not yet been investigated, and a role for these receptors in pathological angiogenesis in myeloma is still to be defined. Methods: Plasma levels of GDF15 and sVEGFR1 and 2 were determined by ELISA in patients with smouldering multiple myeloma (sMM), patients with symptomatic multiple myeloma (abbreviated as MM), and healthy controls. The levels were compared between the three groups, and correlation coefficients were calculated, as were Kaplan-Meier curves for GDF15 and sVEGFR1 and sVEGFR2. Results: Levels of GDF15 were significantly higher in MM than in both patients with sMM and controls. A gradual decrease in mean sVEGFR1 concentration was observed, with MM > sMM > controls. Mean sVEGFR2 was lower in patients with MM than in controls. There was a positive correlation between GDF15 and sVEGFR1, and GDF15 correlated negatively with sVEGFR2. High GDF15 (>3 ng/mL) was associated with poor prognosis. Conclusion: In multiple myeloma, increased expression of GDF15 correlates positively with sVEGFR1 and negatively with sVEGFR2. It is possible that the altered levels of sVEGFR1 and 2 contribute to the increased angio- and lymphangiogenesis observed in myeloma.
Introducing a Group Therapy Program (PLAN D) for Young Outpatients with Derealization and Depersonalization: A Pilot Study
Authors: Flückiger Rahel , Schmidt Stefanie J. , Michel Chantal , Kindler Jochen , Kaess Michael
Published: November 2021

Depersonalization and derealization (DD) cause significant distress and are associated with poor role and social functional outcomes. Despite the relatively high prevalence of DD symptoms and the chronic course in those suffering from a DD disorder, there still exists a need for effective interventions. Preliminary evidence indicates that cognitive behavioral therapy (CBT) delivered in an individual setting demonstrates some positive intervention effects for patients with DD regarding their symptom levels. By considering DD-specific treatment needs, a group therapy program was developed as an add-on therapy based on CBT techniques called PLAN D comprising the following elements: psychoeducation, lifestyle interventions, acceptance and mindfulness training, and new patterns of DD-related cognitions. In a pilot study, we present an 8-week group intervention for adolescents and young adults with DD disorder. To our knowledge, no standardized group intervention program for DD exists so far. Thus, this novel intervention represents a promising opportunity to positively influence long-term outcomes and course of DD.
Tryptase and IL-33 in Bronchoalveolar Lavage Fluid May Predict the Types of Eosinophilic Pneumonia and Disease Recurrence
Authors: Akaba Tomohiro , Kondo Mitsuko , Hara Kaori , Mizobuchi Rie , Abe Kazuhiro , Miyoshi Azusa , Yagi Osamitsu , Tagaya Etsuko
Published: November 2021

Introduction: Eosinophilic pneumonia (EP) is characterized by a marked accumulation of eosinophils in the lungs and blood. Eosinophils and mast cells play an important role in the pathogenesis of EP via release of biomarkers such as tryptase and interleukin (IL)-33. However, the potential role of these biomarkers is not fully understood. Objectives: We aimed to evaluate the differences among the levels of tryptase and IL-33 in bronchoalveolar lavage fluid (BALF) from several types of EP. We evaluated the differences between the levels of these biomarkers in the recurrent and nonrecurrent cases. Method: We prospectively collected the clinical data of patients with EP, diagnosed between 2006 and 2015 in our institution. Bronchoscopy was performed before steroid treatment; BALF was collected. The clinical characteristics of EP patients and the levels of tryptase and IL-33 in BALF were evaluated. Results: We enrolled 15 patients with chronic EP (CEP), 5 with acute EP (AEP), 10 with drug-induced EP, and 6 with angiitis-related EP. Tryptase levels in the CEP group were significantly higher than that in the drug-induced EP group (p = 0.048), while the AEP group had the highest IL-33 levels. Recurrence of EP was noted in 67% of patients with CEP. The levels of tryptase and IL-33 were notably higher in the recurrent cases than that in the nonrecurrent CEP group (p = 0.004, p = 0.04, respectively). Furthermore, there was a positive correlation between the levels of tryptase and IL-33 in the BALF of patients with CEP (ρ = 0.69, p = 0.004). Conclusions: Tryptase and IL-33 in BALF are useful biomarkers for the assessment of EP types. These biomarkers could be used to predict disease recurrence.
BRAF V600E Mutation in Triple-Negative Breast Cancer: A Case Report and Literature Review
Authors: Wang Liye , Lu Qianyi , Jiang Kuikui , Hong Ruoxi , Wang Shusen , Xu Fei
Published: November 2021

Background: The B-Raf proto-oncogene (BRAFV600E) gene mutation has been identified in a variety of malignancies, but no evidence of the efficacy of vemurafenib treatment in BRAFV600E mutant breast cancer (BC) has been reported. Case Presentation: We reported a 60-year-old woman with confirmed triple-negative BC with BRAFV600E mutation. Progression-free survival (PFS) for first-line chemotherapy was 7 months. The patient received vemurafenib and albumin-bound paclitaxel as second-line therapy, exhibiting regression of some pulmonary metastatic lesions with concomitant progression of other lesions, and achieved 4.4 months of PFS. Genetic testing of the progressed pulmonary lesion revealed the BRAFV600E mutation, and acquired new mutations and AR amplification. The patient ultimately died of multiple organ failure and achieved 12 months of overall survival. Conclusions: The BRAFV600E mutation may be a potential prognostic factor and therapeutic target for BC.
The Effect of Sex-Mismatched Red Blood Cell Transfusion on Endothelial Cell Activation in Critically Ill Patients
Authors: Alshalani Abdulrahman , van Manen Lisa , Boshuizen Margit , van Bruggen Robin , Acker Jason P. , Juffermans Nicole P.
Published: November 2021

Background: Observational studies suggest that sex-mismatched transfusion is associated with increased mortality. Mechanisms driving mortality are not known but may include endothelial activation. The aim of this study is to investigate the effects of sex-mismatched red blood cell (RBC) transfusions on endothelial cell activation markers in critically ill patients. Study Design and Methods: In patients admitted to the intensive care unit who received a single RBC unit, blood samples were drawn before (T0), 1 h after (T1), and 24 h after transfusion (T24) for analysis of soluble syndecan-1, soluble intercellular adhesion molecule-1, soluble thrombomodulin (sTM), von Willebrand factor antigen, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα). Changes in the levels of these factors were compared between sex-matched and sex-mismatched groups. Results: Of 69 included patients, 32 patients were in the sex-matched and 37 patients were in the sex-mismatched group. Compared to baseline, sex-matched transfusion was associated with significant reduction in sTM level (p value = 0.03). Between-group comparison showed that levels of syndecan-1 and sTM were significantly higher in the sex-mismatched group compared to the sex-matched group at T24 (p value = 0.04 and 0.01, respectively). Also, TNFα and IL-6 levels showed a statistically marginal significant increase compared to baseline in the sex-mismatched group at T24 (p value = 0.06 and 0.05, respectively), but not in the sex-matched group. Discussion: Transfusion of a single sex-mismatched RBC unit was associated with higher syndecan-1 and sTM levels compared to transfusion of sex-matched RBC unit. These findings may suggest that sex-mismatched RBC transfusion is associated with endothelial activation.
Prognoses in Pathologically Confirmed T1 Lower Rectal Cancer Patients with or without Preoperative Therapy: An Analysis Using the Surveillance, Epidemiology, and End Results Database
Authors: Taira Tetsuro , Nozawa Hiroaki , Kawai Kazushige , Sasaki Kazuhito , Murono Koji , Emoto Shigenobu , Kishikawa Junko , Ozawa Tsuyoshi , Yokoyama Yuichiro , Abe Shinya , Nagai Yuzo , Anzai Hiroyuki , Sonoda Hirofumi , Ishihara Soichiro
Published: November 2021

Introduction: Preoperative chemoradiotherapy (CRT) is the standard therapy for downstaging in locally advanced lower rectal cancer. However, it remains unclear whether rectal cancers downstaged by preoperative therapy show similar prognoses to those of the same stage without preoperative therapy. We previously demonstrated that preoperative CRT did not affect prognosis of rectal cancer with pathological T1N0 (pT1N0) stage in a single institute. Here, using a larger dataset, we compared prognoses of (y)pT1 rectal cancer stratified by the use of preoperative therapy and analyzed prognostic factors. Methods: Cases of pT1N0 rectal cancer, registered between 2004 and 2016, were extracted from the Surveillance, Epidemiology, and End Results database. Patients were categorized as the “ypT1 group” if they had undergone preoperative therapy before surgery or as the “pT1 group” if they had undergone surgery alone. Overall survival (OS) and cancer-specific survival (CSS) between these groups of patients were compared. Factors associated with CSS and OS were identified by univariate and multivariate analyses. Results: Among 3,757 eligible patients, ypT1 and pT1 groups comprised 720 and 3,037 patients, respectively. While ypT1 patients showed poorer CSS than ypT1 patients, there was no significant difference in OS. Preoperative therapy was not an independent prognostic factor for CSS or OS. Multivariate analysis identified age and histological type as significant factors associated with CSS. Sex, age, race, and number of lymph nodes dissected were identified as significant factors associated with OS. Conclusions: Prognosis among patients with (y)p T1N0 rectal cancer was similar irrespective of whether they underwent preoperative therapy, which is consistent with our previous observations.
Diagnostic Value of VDR in Bone Metastasis and Prognosis of Patients with Breast Cancer and Expression Correlation between Vitamin D Receptor and Hairless Protein
Authors: Ding Pan , Du XiaoMing , Wan LiHui , Zhao XueKe , Zhang DeRui , Huang ZeLing , Cao Ge , Zhou XuYang , Zheng YuQin , Cao YuWen
Published: November 2021

Background: Breast cancer is more likely to metastasize to the bone. Previous researches have revealed that the vitamin D receptor (VDR) contributes to breast cancer progression and bone metastasis in mouse and human breast cells, and hairless (Hr) protein interacts with VDR in the mammalian hair cycle. This study aimed to explore the expression of VDR/Hr in breast cancer, and the correlation between VDR/Hr and prognosis, bone metastasis, and metastasis-related prognosis. Methods: The expression of VDR and Hr was analyzed on 119 breast cancer tissues and corresponding normal breast tissue from each of the breast cancer samples by immunohistochemistry staining, and the databases were supplemented as well. Results: The expression of the VDR protein was significantly decreased in breast cancer patients (p < 0.05), inversely, the UALCAN (p = 0.000) and GEPIA (p > 0.05) databases showed that the VDR mRNA expression tended to be higher in tumor tissues. The Hr protein was expressed at a low level within breast cancer specimens (p < 0.05), which was in agreement with the level of Hr mRNA in UALCAN (p = 0.005) and GEPIA (p > 0.05). The protein levels of VDR and Hr were positively correlated (p > 0.05), while the mRNA levels suggested a close relationship with GEPIA (p < 0.05). Low expression of Hr protein displayed a tendency for longer overall survival (OS) and recurrence-free survival (RFS), and its mRNA data also revealed the same trend in the Kaplan-Meier dataset (both p > 0.05). However, VDR protein and mRNA with low expression had markedly shorter OS and RFS (both p < 0.05). The downregulation of VDR protein was significantly associated with an advanced stage (p < 0.05). Low VDR protein was an independent risk factor for poor prognosis (p < 0.05) and was negatively correlated with bone metastasis (p < 0.05). VDR protein and mRNA levels were both downregulated in breast cancer with bone metastasis (both p < 0.05). The area under ROC curve (AUC) for VDR protein expression to identify patients with bone metastasis was 0.661 (p < 0.05) and the AUC for VDR level to predict 1-year, 3-year, and 5-year OS was 0.621, 0.664, and 0.805 in patients with bone metastasis, respectively (p < 0.05). VDR with low expression accelerated bone metastasis and metastasis-related poor survival (both p < 0.05). Conclusion: VDR expression is a notable prognostic factor in primary breast cancer patients for predicting bone metastases and unfavorable clinical outcome.
Discurso em resenha
Authors: Pimenta Pedro Paulo , Galé Pedro , Pimentel Lara
Published: November 2021

Discurso em resenha
AKAP18δ Anchors and Regulates CaMKII Activity at Phospholamban-SERCA2 and RYR
Authors: Carlson Cathrine R. , Aronsen Jan Magnus , Bergan-Dahl Anna , Moutty Marie Christine , Lunde Marianne , Lunde Per Kristian , Jarstadmarken Hilde , Wanichawan Pimthanya , Pereira Laetitia , Kolstad Terje R.S. , Dalhus Bjørn , Subramanian Hariharan , Hille Susanne , Christensen Geir , Müller Oliver J. , Nikolaev Viacheslav , Bers Donald M. , Sjaastad Ivar , Shen Xin , Louch William E. , Klussmann Enno , Sejersted Ole M.
Published: November 2021

Background:

The sarcoplasmic reticulum (SR) Ca
2+
-ATPase 2 (SERCA2) mediates Ca
2+
reuptake into SR and thereby promotes cardiomyocyte relaxation, whereas the ryanodine receptor (RYR) mediates Ca
2+
release from SR and triggers contraction. Ca
2+
/CaMKII (CaM [calmodulin]-dependent protein kinase II) regulates activities of SERCA2 through phosphorylation of PLN (phospholamban) and RYR through direct phosphorylation. However, the mechanisms for CaMKIIδ anchoring to SERCA2-PLN and RYR and its regulation by local Ca
2+
signals remain elusive. The objective of this study was to investigate CaMKIIδ anchoring and regulation at SERCA2-PLN and RYR.

Methods:

A role for AKAP18δ (A-kinase anchoring protein 18δ) in CaMKIIδ anchoring and regulation was analyzed by bioinformatics, peptide arrays, cell-permeant peptide technology, immunoprecipitations, pull downs, transfections, immunoblotting, proximity ligation, FRET-based CaMKII activity and ELISA-based assays, whole cell and SR vesicle fluorescence imaging, high-resolution microscopy, adenovirus transduction, adenoassociated virus injection, structural modeling, surface plasmon resonance, and alpha screen technology.

Results:

Our results show that AKAP18δ anchors and directly regulates CaMKIIδ activity at SERCA2-PLN and RYR, via 2 distinct AKAP18δ regions. An N-terminal region (AKAP18δ-N) inhibited CaMKIIδ through binding of a region homologous to the natural CaMKII inhibitor peptide and the Thr17-PLN region. AKAP18δ-N also bound CaM, introducing a second level of control. Conversely, AKAP18δ-C, which shares homology to neuronal CaMKIIα activator peptide (N2B-s), activated CaMKIIδ by lowering the apparent Ca
2+
threshold for kinase activation and inducing CaM trapping. While AKAP18δ-C facilitated faster Ca
2+
reuptake by SERCA2 and Ca
2+
release through RYR, AKAP18δ-N had opposite effects. We propose a model where the 2 unique AKAP18δ regions fine-tune Ca
2+
-frequency-dependent activation of CaMKIIδ at SERCA2-PLN and RYR.

Conclusions:

AKAP18δ anchors and functionally regulates CaMKII activity at PLN-SERCA2 and RYR, indicating a crucial role of AKAP18δ in regulation of the heartbeat. To our knowledge, this is the first protein shown to enhance CaMKII activity in heart and also the first AKAP (A-kinase anchoring protein) reported to anchor a CaMKII isoform, defining AKAP18δ also as a CaM-KAP.
Alternative Splicing Mediated by RNA-Binding Protein RBM24 Facilitates Cardiac Myofibrillogenesis in a Differentiation Stage-Specific Manner
Authors: Lu Serena Huei-An , Lee Kang-Zheng , Hsu Paul Wei-Che , Su Liang-Yu , Yeh Yu-Chen , Pan Chien-Yuan , Tsai Su-Yi
Published: November 2021

Background:

Mutations in genes encoding sarcomeric proteins lead to failures in sarcomere assembly, the building blocks of contracting muscles, resulting in cardiomyopathies that are a leading cause of morbidity and mortality worldwide. Splicing variants of sarcomeric proteins are crucial at different stages of myofibrillogenesis, accounting for sarcomeric structural integrity. RBM24 (RNA-binding motif protein 24) is known as a tissue-specific splicing regulator that plays an essential role in cardiogenesis. However, it had been unclear if the developmental stage-specific alternative splicing facilitated by RBM24 contributes to sarcomere assembly and cardiogenesis. Our aim is to study the molecular mechanism by which RBM24 regulates cardiogenesis and sarcomere assembly in a temporal-dependent manner.

Methods:

We ablated
RBM24
from human embryonic stem cells (hESCs) using CRISPR/Cas9 techniques.

Results:

Although
RBM24
−/−
hESCs still differentiated into sarcomere-hosting cardiomyocytes, they exhibited disrupted sarcomeric structures with punctate Z-lines due to impaired myosin replacement during early myofibrillogenesis. Transcriptomics revealed >4000 genes regulated by
RBM24
. Among them, core myofibrillogenesis proteins (eg, ACTN2 [α-actinin 2], TTN [titin], and MYH10 [non-muscle myosin IIB]) were misspliced. Consequently, MYH6 (muscle myosin II) cannot replace nonmuscle myosin MYH10, leading to myofibrillogenesis arrest at the early premyofibril stage and causing disrupted sarcomeres. Intriguingly, we found that the ABD (actin-binding domain; encoded by exon 6) of the Z-line anchor protein ACTN2 is predominantly excluded from early cardiac differentiation, whereas it is consistently included in human adult heart. CRISPR/Cas9-mediated deletion of exon 6 from
ACTN2
in hESCs, as well as forced expression of full-length ACTN2 in
RBM24
−/−
hESCs, further corroborated that inclusion of exon 6 is critical for sarcomere assembly. Overall, we have demonstrated that RBM24-facilitated inclusion of exon 6 in
ACTN2
at distinct stages of cardiac differentiation is evolutionarily conserved and crucial to sarcomere assembly and integrity.

Conclusions:

RBM24 acts as a master regulator to modulate the temporal dynamics of core myofibrillogenesis genes and thereby orchestrates sarcomere organization.
Evolving Multimodal Robot Behavior via Many Stepping Stones with the Combinatorial Multiobjective Evolutionary Algorithm
Authors: Huizinga Joost , Clune Jeff
Published: November 2021

An important challenge in reinforcement learning is to solve multimodal problems, where agents have to act in qualitatively different ways depending on the circumstances. Because multimodal problems are often too difficult to solve directly, it is often helpful to define a curriculum, which is an ordered set of subtasks that can serve as the stepping stones for solving the overall problem. Unfortunately, choosing an effective ordering for these subtasks is difficult, and a poor ordering can reduce the performance of the learning process. Here, we provide a thorough introduction and investigation of the Combinatorial Multiobjective Evolutionary Algorithm (CMOEA), which allows all combinations of subtasks to be explored simultaneously. We compare CMOEA against three algorithms that can similarly optimize on multiple subtasks simultaneously: NSGA-II, NSGA-III, and ε-Lexicase Selection. The algorithms are tested on a function-optimization problem with two subtasks, a simulated multimodal robot locomotion problem with six subtasks, and a simulated robot maze-navigation problem where a hundred random mazes are treated as subtasks. On these problems, CMOEA either outperforms or is competitive with the controls. As a separate contribution, we show that adding a linear combination over all objectives can improve the ability of the control algorithms to solve these multimodal problems. Lastly, we show that CMOEA can leverage auxiliary objectives more effectively than the controls on the multimodal locomotion task. In general, our experiments suggest that CMOEA is a promising algorithm for solving multimodal problems.