bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination strategies to overcome resistance to the BCL2 inhibitor venetoclax in hematologic malignancies
Authors: Yue XiaoYan , Chen Qingxiao , He JingSong 
Published: October 2020

AbstractVenetoclax has been approved by the United States Food and Drug Administration since 2016 as a monotherapy for treating patients with relapsed/refractory chronic lymphocytic leukemia having 17p deletion. It has led to a breakthrough in the treatment of hematologic malignancies in recent years. However, unfortunately, resistance to venetoclax is inevitable. Multiple studies confirmed that the upregulation of the anti-apoptotic proteins of the B-cell lymphoma 2 (BCL2) family mediated by various mechanisms, such as tumor microenvironment, and the activation of intracellular signaling pathways were the major factors leading to resistance to venetoclax. Therefore, only targeting BCL2 often fails to achieve the expected therapeutic effect. Based on the mechanism of resistance in specific hematologic malignancies, the combination of specific drugs with venetoclax was a clinically optional treatment strategy for overcoming resistance to venetoclax. This study aimed to summarize the possible resistance mechanisms of various hematologic tumors to venetoclax and the corresponding clinical strategies to overcome resistance to venetoclax in hematologic malignancies.
Characterization of the serum levels of Meteorin-like in patients with inflammatory bowel disease and its association with inflammatory cytokines
Authors: Gholamrezayi Afsane , Mohamadinarab Maryam , Rahbarinejad Pegah , Fallah Soudabeh , Barez Shekufe Rezghi , Setayesh Leila , Moradi Nariman , Fadaei Reza , Chamani Elham , Tavakoli Tahmine 
Published: October 2020

Abstract

Background
Meteorin-like (Metrnl) is an adipokine with insulin sensitizing and anti-inflammatory properties that has been discovered recently. The relation among Metrnl, Inflammatory Bowel Disease (IBD), and obesity has been unexplored yet.

Methods
The present study was conducted on 54 healthy control, 42 Ulcerative Colitis (UC), and 43 Crohn’s disease (CD) patients who were diagnosed by pathological examination. In all participants, serum levels of adiponectin, Metrnl, interleukin (IL)-6, and Tumor necrosis factor (TNF-α) were measured using ELISA kits.

Results
Metrnl concentration was considerably lower in both UC (85.25 ± 36.55 pg/mL) and CD (76.93 ± 27.92 pg/mL) patients in comparison to control (107.52 ± 35.33 pg/mL). In addition, it was seen that both patient groups have a decreased level of adiponectin compared to the controls. Besides that, the level of IL-6 and TNF-α were significantly greater in the patient groups. Moreover, the result showed that the level of Metrnl is inversely correlated with body mass index (BMI) in the controls and the patients. Metrnl levels are also inversely associated with IL-6, and TNF-α in both of the patient groups.

Conclusions
The current study is the first one reporting the decreased levels of Metrnl in serum among patients with IBD, which is inversely related with BMI, TNF-α, and IL-6. These results suggested a possible relation of Metrnl with the pathogenesis of IBD, particularly through inflammatory process, although further studies are warranted to dissect the possible mechanism.
Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment
Authors: Liang Gaofeng , Wang Haojie , Shi Hao , Wang Haitao , Zhu Mengxi , Jing Aihua , Li Jinghua , Li Guangda 
Published: October 2020

Abstract
Multifunctional lanthanide-based upconversion nanoparticles (UCNPs), which feature efficiently convert low-energy photons into high-energy photons, have attracted considerable attention in the domain of materials science and biomedical applications. Due to their unique photophysical properties, including light-emitting stability, excellent upconversion luminescence efficiency, low autofluorescence, and high detection sensitivity, and high penetration depth in samples, UCNPs have been widely applied in biomedical applications, such as biosensing, imaging and theranostics. In this review, we briefly introduced the major components of UCNPs and the luminescence mechanism. Then, we compared several common design synthesis strategies and presented their advantages and disadvantages. Several examples of the functionalization of UCNPs were given. Next, we detailed their biological applications in bioimaging and disease treatment, particularly drug delivery and photodynamic therapy, including antibacterial photodynamic therapy. Finally, the future practical applications in materials science and biomedical fields, as well as the remaining challenges to UCNPs application, were described. This review provides useful practical information and insights for the research on and application of UCNPs in the field of cancer.
Direct oral anticoagulant use in left ventricular thrombus
Authors: Ali Zafar , Isom Nicholas , Dalia Tarun , Sami Farhad , Mahmood Uzair , Shah Zubair , Gupta Kamal 
Published: October 2020

Abstract
Left ventricular thrombus (LVT) is associated with a significant risk of ischemic stroke (IS) and peripheral embolization. Societal guidelines recommend the use of warfarin, with direct oral anticoagulants (DOACs) only for patients unable to tolerate warfarin. We studied the natural history of LVT with anticoagulation (AC) with emphasis on comparing warfarin and DOAC use. In this single center study, we identified patients with a confirmed LVT. Type and duration of anticoagulation, INR levels and clinical outcomes (bleeding, ischemic stroke or peripheral embolization, and thrombus resolution) were recorded. LVT was confirmed in a total of 110 patients. Mean age was 59 + 14 years. 79% were men. Underlying etiology was chronic ischemic cardiomyopathy in 58%, non-ischemic cardiomyopathy in 23%. AC was started in 96 (87%) patients. At 1 year follow up, 11 patients (10%) had a stroke while on any AC (2 had hemorrhagic stroke and 9 had IS). Of those with IS, 7 were on warfarin (71% of those had subtherapeutic INR) and 2 patients on DOACs had IS. The 1-year risk of any stroke was 15% in warfarin group (12% risk of ischemic stroke) compared to 6% in the DOACs group (p = 0.33). 37 (63%) patients on warfarin and 18 (53%) on DOACs had resolution of thrombus (p = 0.85). One-year risk of stroke with LVT is high (10%) even with AC. Most patients IS on warfarin had subtherapeutic INR. There was no statistical difference in stroke risk or rate of thrombus resolution between warfarin and DOACs treated patients.
Serum interleukin-6 is an indicator for severity in 901 patients with SARS-CoV-2 infection: a cohort study
Authors: Zhang Jing , Hao Yiqun , Ou Wuling , Ming Fei , Liang Gai , Qian Yu , Cai Qian , Dong Shuang , Hu Sheng , Wang Weida , Wei Shaozhong 
Published: October 2020

Abstract

Background
Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-19 patients, and report preliminary data on the efficacy of IL-6 receptor blockade.

Methods
We conducted a retrospective single-institutional study of 901 consecutive confirmed cases. Serum IL-6 concentrations were tested on admission and/or during hospital stay. Tocilizumab was given to 16 patients with elevated IL-6 concentration.

Results
366 patients were defined as common cases, 411 patients as severe, and 124 patients as critical according to the Chinese guideline on diagnosis and treatment of COVID-19. The median concentration of IL-6 was < 1.5 pg/ml (IQR < 1.50–2.15), 1.85 pg/ml (IQR < 1.50–5.21), and 21.55 pg/ml (IQR 6.47–94.66) for the common, severe, and critical groups respectively (P < 0.001). The follow-up kinetics revealed serum IL-6 remained high in critical patients even when cured. An IL-6 concentration higher than 37.65 pg/ml was predictive of in-hospital death (AUC 0.97 [95% CI 0.95–0.99], P < 0.001) with a sensitivity of 91.7% and a specificity of 95.7%. In the 16 patients who received tocilizumab, IL-6 concentrations were significantly increased after administration, and survival outcome was not significantly different from that of propensity-score matched counterparts (n = 53, P = 0.12).

Conclusion
Serum IL-6 should be included in diagnostic work-up to stratify disease severity, but the benefit of tocilizumab needs further confirmation.
Trial registration retrospectively registered.
Anti-Axl antibody treatment reduces the severity of experimental autoimmune encephalomyelitis
Authors: DuBois Juwen C. , Ray Alex K. , Davies Peter , Shafit-Zagardo Bridget 
Published: October 2020

Abstract

Background
Multiple sclerosis is an immune-mediated disease of the central nervous system (CNS) characterized by inflammation, oligodendrocytes loss, demyelination, and damaged axons. Tyro3, Axl, and MerTK belong to a family of receptor tyrosine kinases that regulate innate immune responses and CNS homeostasis. During experimental autoimmune encephalomyelitis (EAE), the mRNA expression of MerTK, Gas6, and Axl significantly increase, whereas Tyro3 and ProS1 remain unchanged. We have shown that Gas6 is neuroprotective during EAE, and since Gas6 activation of Axl may be necessary for conferring neuroprotection, we sought to determine whether α-Axl or α-MerTK antibodies, shown by others to activate their respective receptors in vivo, could effectively reduce inflammation and neurodegeneration.

Methods
Mice received either α-Axl, α-MerTK, IgG isotype control, or PBS before the onset of EAE symptoms. EAE clinical course, axonal damage, demyelination, cytokine production, and immune cell activation in the CNS were used to determine the severity of EAE.

Results
α-Axl antibody treatment significantly decreased the EAE clinical indices of female mice during chronic EAE and of male mice during both acute and chronic phases. The number of days mice were severely paralyzed also significantly decreased with α-Axl treatment. Inflammatory macrophages/microglia and the extent of demyelination significantly decreased in the spinal cords of α-Axl-treated mice during chronic EAE, with no differences in the production of pro-inflammatory cytokines. α-MerTK antibody did not influence EAE induction or progression.

Conclusion
Our data suggests that the beneficial effect of Gas6/Axl signaling observed in mice administered with Gas6 can be partially preserved by administering an activating α-Axl antibody, but not α-MerTK.
Protocol of a study investigating breath-hold techniques for upper-abdominal radiation therapy (BURDIE): addressing the challenge of a moving target
Authors: Farrugia Briana , Khor Richard , Foroudi Farshad , Chao Michael , Knight Kellie , Wright Caroline 
Published: October 2020

Abstract

Background
Radiation therapy to upper abdominal sites is technically challenging due to motion of tumors and surrounding organs resulting from normal respiration. Breath-hold, using an Active Breathing Coordinator is one strategy used to reduce motion in these tumor sites. Though widely used, no studies have prospectively compared the different breath-hold techniques (inspiration, deep-inspiration and expiration) using ABC in the same patient cohort.

Methods
Patients planned for radiation therapy to upper abdominal tumors are invited to participate in this prospective study. Participants attempt three breath hold techniques: inspiration, deep-inspiration and expiration breath-hold, in random order. kV fluoroscopy images of the dome of diaphragm are taken of five consecutive breath-holds in each technique. Reproducibility and stability of tumour position are measured, and used to select the technique with which to proceed to planning and treatment. Reproducibility at planning and each treatment fraction is measured, along with breath hold time, treatment efficiency and patient experience.

Discussion
The screening method was validated after the first three participants. This screening process may be able to select the best breath-hold technique for an individual, which may lead to improved reproducibility. The screening process is being piloted as a prospective clinical trial.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR): 12618001691235. Registered 12th October 2018. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376109&isReview=true.
Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis
Authors: Wang Qi , Wang Chi , Hu Wenhao , Hu Fanqi , Liu Weibo , Zhang Xuesong 
Published: October 2020

Abstract

Background
Adolescents with scoliosis consistently demonstrate lower body weight, lean muscle mass, and bone mineral density than healthy adolescent counterparts. Recent studies have focused on understanding how leptin and ghrelin signaling may play a role in adolescent idiopathic scoliosis (AIS). In our current study, we aim to evaluate the serum levels of leptin, soluble leptin receptor (sOB-R), and ghrelin in AIS patients through systematic review and meta-analysis.

Methods
We conducted our systematic review by searching the keywords in online databases including PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to January 2020. Inclusion criteria were studies that measure leptin, soluble leptin receptor (sOB-R), and ghrelin levels in AIS patients. Selection of studies, assessment of study quality, and data extraction were performed by two reviewers independently. Then, data was analyzed to calculate the mean difference and 95% confidence interval (CI).

Results
Seven studies concerning leptin/sOB-R and three studies concerning ghrelin were qualified for meta-analysis (one study concerning both leptin and ghrelin). Serum leptin of patients with AIS were significantly lower when compared with healthy controls, with the weighted mean difference (WMD) of − 0.95 (95% CI − 1.43 to − 0.48, p < 0.0001) after reducing the heterogeneity using six studies for meta-analysis, while sOB-R and ghrelin level was significantly higher in AIS group when compared with control group, with the WMD of 2.64 (95% CI 1.60 to 3.67, p < 0.001) and 1.42 (95% CI 0.48 to 2.35, p = 0.003), respectively.

Conclusion
Our current meta-analysis showed that serum level of leptin in AIS patients was significantly lower when compared with control subjects, while serum sOB-R and ghrelin levels were significantly higher in AIS patients. More clinical studies are still required to further validate the predictive value of leptin or ghrelin for the curve progression for AIS patients.
Metaphyseal anchoring short stem hip arthroplasty provides a more physiological load transfer: a comparative finite element analysis study
Authors: Yan Shuang G. , Chevalier Yan , Liu Fanxiao , Hua Xingyi , Schreiner Anna , Jansson Volkmar , Schmidutz Florian 
Published: October 2020

AbstractBackgroundShort stem total hip arthroplasty (SHA) preserves femoral bone stock and is supposed to provide a more natural load transfer compared to standard stem total hip arthroplasty (THA). As comparative biomechanical reference data are rare we used a finite element analysis (FEA) approach to compare cortical load transfer after implantations of a metaphyseal anchoring short and standard stem in native biomechanical femora.MethodsThe subject specific finite element models of biomechanical femora, one native and two with implanted metaphyseal anchoring SHA (Metha, B. Braun Aesculap) and standard THA (CLS, Zimmer-Biomet), were generated from computed tomography datasets. The loading configuration was performed with an axial force of 1400 N. Von Mises stress was used to investigate the change of cortical stress distribution.ResultsCompared to the native femur, a considerable reduction of cortical stress was recorded after implantation of SHA and standard THA. The SHA showed less reduction proximally with a significant higher metaphyseal cortical stress compared to standard THA. Moreover, the highest peak stresses were observed metaphyseal for the SHA stem while for the standard THA high stress pattern was observed more distally.ConclusionsBoth, short and standard THA, cause unloading of the proximal femur. However, the metaphyseal anchoring SHA features a clearly favorable pattern in terms of a lower reduction proximally and improved metaphyseal loading, while standard THA shows a higher proximal unloading and more distal load transfer. These load patterns implicate a reduced stress shielding proximally for metaphyseal anchoring SHA stems and might be able to translate in a better bone preservation.
External female genitalia of Triatoma jatai, Triatoma costalimai and Triatoma williami (Hemiptera: Reduviidae: Triatominae)
Authors: Teves Simone Caldas , Gonçalves Teresa Cristina Monte , de Freitas Simone Patrícia Carneiro , Lopes Catarina Macedo , Carbajal-de-la-Fuente Ana Laura , dos Santos-Mallet Jacenir Reis 
Published: October 2020

Abstract

Background
Taxonomic identification of triatomines is generally performed based on aspects of their external morphology. However, the use of a multidisciplinary approach, considering morphological aspects of the external genitalia, morphometry, genetics, and phylogeography has been suggested, especially for similar and/or cryptic species. The rupestral species Triatoma jatai Gonçalves et al., 2013, Triatoma costalimai Verano & Galvão, 1959 and Triatoma williami Galvão et al., 1965, which are morphologically similar, have been found naturally infected with Trypanosoma cruzi (Chagas, 1909) in wild, peridomestic, and intradomestic environments, representing a risk of new outbreaks of Chagas disease. This study presents morphological description complementation of these species, with an emphasis on the structures of the female external genitalia, using scanning electron microscopy.

Methods
The females of T. jatai and T. costalimai (n = 10 of each) were captured in the Brazilian municipalities of Paranã and Aurora do Tocantins and were identified with the use of a dichotomous key for the Matogrossensis subcomplex. Females of T. williami (n = 5), were obtained from a laboratory colony. The females were cut transversely at the sixth abdominal segment and examined under scanning electron microscopy (SEM) at the Oswaldo Cruz/Fiocruz Institute Electronic Microscopy Platform.

Results
It was possible to differentiate the three species based on the characteristics of urotergites VII, VIII and IX and urosternite VII, as well as the genital plaques, gonocoxites, and gonapophyses. To our knowledge, morphological differences in the spines present on gonapophysis 8 in triatomines are described here for the first time.

Conclusions
The results show that external genitalia of females are useful structures to differentiate T. costalimai, T. jatai and T. williami. SEM analysis contributes to and corroborates, together with other tools morphological and molecular, the distinction of the three species.
A novel dynamic source routing (DSR) protocol based on minimum execution time scheduling and moth flame optimization (MET-MFO)
Authors: Almazok Salem A. , Bilgehan Bülent 
Published: October 2020

Abstract
In general, the conventional routing approaches in mobile ad hoc networks (MANETs) provide a route between the source and the target with a minimum hop count. Dynamic source routing (DSR) as a typical prototype of routing protocols relies on the minimum hop count parameter to provide the path without considering any other factors such as energy consumption and node energy level, which significantly affect the routing algorithm performance. To enhance the performance of the DSR, a novel and efficient routing mechanism based on a hybrid approach using the minimum execution time (MET) scheduling and moth flame optimization (MFO) scheme is proposed. This hybridization version of DSR is called the (MET-MFODSR) algorithm, and it aims to improve the routing mechanism through establishing an optimal route with minimum energy consumption, which increases the network lifetime and reduces route failure issues. The proposed MET-MFODSR protocol is implemented using the MATLAB platform, analyzed and evaluated in different simulation environments. The simulation results demonstrate that the suggested routing algorithm is applicative and practicable, and its performance exceeds the performance of the existing Bee DSR (BEEDSR) and Bee-inspired protocol (BeeIP) algorithms.
The solvability of a kind of generalized Riemann–Hilbert problems on function spaces $H_{\ast }$
Authors: Li Pingrun 
Published: October 2020

Abstract
In this paper, we study a kind of generalized Riemann–Hilbert problems (R-HPs) with several unknown functions in strip domains. We mainly discuss methods of solving R-HPs with two unknown functions and obtain general solutions and conditions of solvability on function spaces $H_{\ast }$

H
∗

. At the end of this paper, we consider in detail the behavior of the solution at ∞ and in different domains. Thus the results in this paper generalize and improve the theory of the classical Riemann–Hilbert problems.
Approximate solutions for a fractional hybrid initial value problem via the Caputo conformable derivative
Authors: Amara Abdelkader , Etemad Sina , Rezapour Shahram 
Published: October 2020

Abstract
Our main purpose in this work is to derive an existence criterion for a Caputo conformable hybrid multi-term integro-differential equation equipped with initial conditions. In this way, we consider a partially ordered Banach space, and, by applying the lower solution property, the existence and successive approximations of solutions for the mentioned hybrid initial problem are investigated. Eventually, we formulate an illustrative example for this hybrid IVP to support our findings from a numerical point of view. Moreover, we plot the sequence of the obtained approximate solutions for different values of noninteger orders.
Fibroblast-like cells change gene expression of bone remodelling markers in transwell cultures
Authors: Hartmann Eliza S. , Schluessel Sabine , Köhler Miriam I. , Beck Felicitas , Redeker Julia I. , Summer Burkhard , Schönitzer Veronika , Fottner Andreas , Mayer-Wagner Susanne 
Published: October 2020

AbstractIntroductionPeriprosthetic fibroblast-like cells (PPFs) play an important role in aseptic loosening of arthroplasties. Various studies have examined PPF behavior in monolayer culture systems. However, the periprosthetic tissue is a three-dimensional (3D) mesh, which allows the cells to interact in a multidirectional way. The expression of bone remodeling markers of fibroblast-like cells in a multilayer environment changes significantly versus monolayer cultures without the addition of particles or cytokine stimulation. Gene expression of bone remodeling markers was therefore compared in fibroblast-like cells from different origins and dermal fibroblasts under transwell culture conditions versus monolayer cultures.MethodsPPFs from periprosthetic tissues (n = 12), osteoarthritic (OA) synovial fibroblast-like cells (SFs) (n = 6), and dermal fibroblasts (DFs) were cultured in monolayer (density 5.5 × 103/cm2) or multilayer cultures (density 8.5 × 105/cm2) for 10 or 21 days. Cultures were examined via histology, TRAP staining, immunohistochemistry (anti-S100a4), and quantitative real-time PCR.ResultsFibroblast-like cells (PPFs/SFs) and dermal fibroblasts significantly increased the expression of RANKL and significantly decreased the expression of ALP, COL1A1, and OPG in multilayer cultures. PPFs and SFs in multilayer cultures further showed a higher expression of cathepsin K, MMP-13, and TNF-α. In multilayer PPF cultures, the mRNA level of TRAP was also found to be significantly increased.ConclusionThe multilayer cultures are able to induce significant expression changes in fibroblast-like cells depending on the nature of cellular origin without the addition of any further stimulus. This system might be a useful tool to get more in vivo like results regarding fibroblast-like cell cultures.