bluuebunny/crossref_metadata_2025_split huggingface dataset:
sTNFRII-Fc modification protects human UC-MSCs against apoptosis/autophagy induced by TNF-α and enhances their efficacy in alleviating inflammatory arthritis
Authors: Zhao Yingjie , Yang Xuezhi , Li Siyu , Zhang Bingjie , Li Susu , Wang Xinwei , Wang Yueye , Jia Chengyan , Chang Yan , Wei Wei 
Published: October 2021

Abstract
Background
Tumor necrosis factor (TNF)-α inhibitors represented by Etanercept (a fusion protein containing soluble TNF receptor II (sTNFRII) and the Fc segment of human IgG1) play a pivotal role in Rheumatoid arthritis (RA) treatment. However, long-term use increases the risk of infection and tumors for their systemic inhibition of TNF-α, which disrupts the regular physiological function of this molecular. Mesenchymal stem cells (MSCs)-based delivery system provides new options for RA treatment with their “homing” and immune-regulation capacities, whereas inflammatory environment (especially TNF-α) is not conducive to MSCs' therapeutic effects by inducing apoptosis/autophagy. Here, we constructed a strain of sTNFRII-Fc-expressing MSCs (sTNFRII-MSC), aiming to offset the deficiency of those two interventions.

Methods
Constructed sTNFRII-Fc lentiviral vector was used to infect human umbilical cord-derived MSCs, and sTNFRII-MSC stable cell line was generated by monoclonal cultivation. In vitro and vivo characteristics of sTNFRII-MSC were assessed by coculture assay and an acute inflammatory model in NOD/SCID mice. The sTNFRII-MSC were transplanted into CIA model, pathological and immunological indicators were detected to evaluate the therapeutic effects of sTNFRII-MSC. The distribution of sTNFRII-MSC was determined by immunofluorescence assay. Apoptosis and autophagy were analyzed by flow cytometry, western blot and immunofluorescence.

Results
sTNFRII-Fc secreted by sTNFRII-MSC present biological activity both in vitro and vivo. sTNFRII-MSC transplantation effectively alleviates mice collagen-induced arthritis (CIA) via migrating to affected area, protecting articular cartilage destruction, modulating immune balance and sTNFRII-MSC showed prolonged internal retention via resisting apoptosis/autophagy induced by TNF-α.

Conclusion
sTNFRII-Fc modification protects MSCs against apoptosis/autophagy induced by TNF-α, in addition to releasing sTNFRII-Fc neutralizing TNF-α to block relevant immune-inflammation cascade, and thus exert better therapeutic effects in alleviating inflammatory arthritis.
Endometrial mesenchymal stem/stromal cells: The Enigma to code messages for generation of functionally active regulatory T cells
Authors: Aleahmad Mehdi , Bozorgmehr Mahmood , Nikoo Shohreh , Ghanavatinejad Alireza , Shokri Mohammad-Reza , Montazeri Samaneh , Shokri Fazel , Zarnani Amir-Hassan 
Published: October 2021

AbstractBackgroundRegulatory T cells (Tregs) play an important role in fine-tuning of immune responses and are pivotal for a successful pregnancy. Recently, the importance of mesenchymal stem cells in regulation of immune responses in general and Tregs in particular has been highlighted. Here, we hypothesized that menstrual stromal/stem cells (MenSCs) contribute to uterine immune system regulation through induction of functionally active Tregs.MethodsMenSCs were collected from 18 apparently healthy women and characterized. Bone marrow mesenchymal stem cells (BMSCs) served as a control. The effect of MenSCs on proliferation of anti-CD3/CD28-stimulated T CD4 + cells and generation of Tregs with or without pre-treatment with mitomycin C, IFN-γ and IL-1β was evaluated by flow cytometry. The potential role of IDO, PGE2, IL-6, IL-10, and TGF-β on proliferation of T CD4 + cells and generation of Tregs was assessed using blocking antibodies or agents. IDO activity was evaluated in MenSCs and BMSCs culture supernatants by a colorimetric assay. IL-10 and IFN-γ production in MenSCs-primed T CD4 + was measured using intracellular staining. To investigate the functional properties of Tregs induced by MenSCs, Treg cells were isolated and their functional property to inhibit proliferation of anti-CD3/CD28-stimulated PBMCs was assessed by flow cytometry.ResultsAccording to the results, proliferation of T CD4 + lymphocytes was enhanced in the presence of MenSCs, while pre-treatment of MenSCs with pro-inflammatory cytokines reversed this effect. PGE2 and IDO were the major players in MenSCs-induced T cell proliferation. Non-treated MenSCs decreased the frequency of Tregs, whereas after pre-treatment with IFN-γ and IL-1β, they induced functional Tregs with ability to inhibit the proliferation of anti-CD3/CD28-stimulated PBMCs. This effect was mediated through IL-6, IL-10, TGF-β and IDO. IFN-γ/IL-1β-treated MenSCs induced IL-10 and IFN-γ production in CD4 + T cells.ConclusionCollectively, these findings indicate that immunomodulatory impact of menstrual blood stem cells (MenSCs) on generation of Tregs and inhibition of T cells proliferation is largely dependent on pre-treatment with IFN-γ and IL-1β. This is the first report on immunomodulatory impact of MenSCs on Tregs and highlights the pivotal role of endometrial stem cells in regulation of local endometrial immune responses.
Sex and gender specific health topics in medical student learners: pulse check eight years later
Authors: Rydberg Ann , Buras Matthew R. , Quillen Jaxon , Miller Virginia , Kling Juliana M. 
Published: October 2021

Abstract
Background
An essential component of patient-centered, individualized medicine is considering how sex and gender affect mechanisms of health and disease.

Objectives
To assess medical students’ current knowledge of sex and gender specific health (SGSH) concepts compared to results from the same survey in 2012 to better inform development of curricular materials for medical education.

Methods
A previously designed survey tool, which assessed current knowledge of sex and gender-based medicine of medical students, was emailed to all Mayo Clinic Alix School of Medicine (MCASOM) students on Minnesota, Arizona, and Florida campuses in 2020. Descriptive and qualitative thematic results were compared to the same survey administered in 2012 to students enrolled in MCASOM. Changes in the inclusion of SGSH topics were assessed over the eight years.

Results
One hundred and one of 365 (27.7% response rate) surveys were returned with 2:1 female to male respondents with representation from all 4 years. The definitions of the terms “sex” and “gender” were correctly identified by most respondents (93.1%). However, only 36% (12/33) of questions related to other medical knowledge on SGSH topics had more than a 50% correct response rate. More than half of the students reported that SGSH topics were included in Gynecology, Cardiology, Pediatrics, and Immunology. SGSH topics were reported as not being routinely covered in Neurology and Nephrology, although more students said they were in 2020 then 2012. Sixty-two percent of students favored increasing SGSH in the current curriculum.

Conclusions
Medical students appear to understand the definition of and importance of SGSH in education. While some improvements in coverage by subject matter and topic area appear to have occurred as reported by medical students, opportunity remains to more fully integrate SGSH concepts in medical school curricula.
Sex differences in recovery of motor function in a rhesus monkey model of cortical injury
Authors: Bottenfield Karen R. , Bowley Bethany G. E. , Pessina Monica A. , Medalla Maria , Rosene Douglas L. , Moore Tara L. 
Published: October 2021

AbstractBackgroundStroke disproportionately affects men and women, with women over 65 years experiencing increased severity of impairment and higher mortality rates than men. Human studies have explored risk factors that contribute to these differences, but additional research is needed to investigate how sex differences affect functional recovery and hence the severity of impairment. In the present study, we used our rhesus monkey model of cortical injury and fine motor impairment to compare sex differences in the rate and degree of motor recovery following this injury.MethodsAged male and female rhesus monkeys were trained on a task of fine motor function of the hand before undergoing surgery to produce a cortical lesion limited to the hand area representation of the primary motor cortex. Post-operative testing began two weeks after the surgery and continued for 12 weeks. All trials were video recorded and latency to retrieve a reward was quantitatively measured to assess the trajectory of post-operative response latency and grasp pattern compared to pre-operative levels.ResultsPostmortem analysis showed no differences in lesion volume between male and female monkeys. However, female monkeys returned to their pre-operative latency and grasp patterns significantly faster than males.ConclusionsThese findings demonstrate the need for additional studies to further investigate the role of estrogens and other sex hormones that may differentially affect recovery outcomes in the primate brain.
An ontology network for Diabetes Mellitus in Mexico
Authors: Reyes-Peña Cecilia , Tovar Mireya , Bravo Maricela , Motz Regina 
Published: October 2021

Abstract
Background
Medical experts in the domain of Diabetes Mellitus (DM) acquire specific knowledge from diabetic patients through monitoring and interaction. This allows them to know the disease and information about other conditions or comorbidities, treatments, and typical consequences of the Mexican population. This indicates that an expert in a domain knows technical information about the domain and contextual factors that interact with it in the real world, contributing to new knowledge generation. For capturing and managing information about the DM, it is necessary to design and implement techniques and methods that allow: determining the most relevant conceptual dimensions and their correct organization, the integration of existing medical and clinical information from different resources, and the generation of structures that represent the deduction process of the doctor. An Ontology Network is a collection of ontologies of diverse knowledge domains which can be interconnected by meta-relations. This article describes an Ontology Network for representing DM in Mexico, designed by a proposed methodology. The information used for Ontology Network building include the ontological resource reuse and non-ontological resource transformation for ontology design and ontology extending by natural language processing techniques. These are medical information extracted from vocabularies, taxonomies, medical dictionaries, ontologies, among others. Additionally, a set of semantic rules has been defined within the Ontology Network to derive new knowledge.

Results
An Ontology Network for DM in Mexico has been built from six well-defined domains, resulting in new classes, using ontological and non-ontological resources to offer a semantic structure for assisting in the medical diagnosis process. The network comprises 1367 classes, 20 object properties, 63 data properties, and 4268 individuals from seven different ontologies. Ontology Network evaluation was carried out by verifying the purpose for its design and some quality criteria.

Conclusions
The composition of the Ontology Network offers a set of well-defined ontological modules facilitating the reuse of one or more of them. The inclusion of international vocabularies as SNOMED CT or ICD-10 reinforces the representation by international standards. It increases the semantic interoperability of the network, providing the opportunity to integrate other ontologies with the same vocabularies. The ontology network design methodology offers a guide for ontology developers about how to use ontological and non-ontological resources in order to exploit the maximum of information and knowledge from a set of domains that share or not information.
Evaluation of intracellular processes in quinolinic acid-induced brain damage by imaging reactive oxygen species generation and mitochondrial complex I activity
Authors: Hosoi Rie , Fujii Yuka , Hiroyuki Ohba , Shukuri Miho , Nishiyama Shingo , Kanazawa Masakatsu , Todoroki Kenichiro , Arano Yasushi , Sakai Toshihiro , Tsukada Hideo , Inoue Osamu 
Published: October 2021

Abstract
Purpose
Our study aimed to elucidate the intracellular processes associated with quinolinic acid (QA)-induced brain injury by acquiring semiquantitative fluorescent images of reactive oxygen species (ROS) generation and positron emission tomography (PET) images of mitochondrial complex I (MC-I) activity.

Methods
Ex vivo fluorescent imaging with dihydroethidium (DHE) and PET scans with 18F-BCPP-EF were conducted at 3 h and 24 h after QA injection into the rat striatum. Immunohistochemical studies were performed 24 h after QA injection into the rat brain using monoclonal antibodies against neuronal nuclei (NeuN) and CD11b.

Results
A strong DHE-derived fluorescent signal was detected in a focal area within the QA-injected striatum 3 h after QA injection, and increased fluorescent signal spread throughout the striatum and parts of the cerebral cortex after 24 h. By contrast, 18F-BCPP-EF uptake in the QA-injected rat brain was unchanged after 3 h and markedly decreased after 24 h, not only in the striatum but also in the cerebral hemisphere. The fluorescent signal in the striatum 24 h after QA injection colocalised with microglial marker expression.

Conclusions
We successfully obtained functional images of focal ROS generation during the early period of excitotoxic injury, and microglial ROS generation and mitochondrial dysfunction were observed during the progression of the inflammatory response. Both ex vivo DHE imaging and in vivo 18F-BCPP-EF-PET were sufficiently sensitive to detect the respective processes of QA-induced brain damage. Our study contributes to the functional imaging of multiple events during the pathological process.
COVID-19 healthcare cost and length of hospital stay in Turkey: retrospective analysis from the first peak of the pandemic
Authors: Oksuz Ergun , Malhan Simten , Gonen Mustafa Sait , Kutlubay Zekayi , Keskindemirci Yilmaz , Tabak Fehmi 
Published: October 2021

AbstractBackgroundDuring the COVID-19 pandemic, health care systems are under extreme pressure. This study analyzed health care resource use (HCRU) and costs in patients admitted to the hospital for COVID-19 and aimed to estimate the one-year direct medical cost of the disease in Turkey.MethodsThis retrospective cohort study was conducted between March and July 2020 in a tertiary hospital (n = 1056) in Istanbul. Patient demographics, clinical and treatment characteristics at admission, comorbidities, disease severity, and costs from a payer perspective were evaluated using the microcosting method. The results include LOS, hospital costs, and univariate and generalized linear models to investigate influencing factors. The data were extrapolated to provide a country-level estimate.ResultsThe mean length of stay was 9.1 days (SD 6.9). The mean length of stay was 8.0 days (4.7) for patients hospitalized in wards versus 14.8 days (SD 12.0) for patients hospitalized in the ICU. In univariate analysis, several factors, including O2therapy (+ 3.7 days), high CRP > 41.8 mg/L (+ 3.8 days), and elevated ferritin (+ 3.5), were found to be associated with a longer LOS (p < 0.05).The direct annual medical cost of COVID-19 was estimated at PPP$ 2.1 billion. The COVID-19 pandemic resulted in a direct medical burden that corresponds to 2.0% of the government health expenditures and 0.8 per thousand of Turkey’s gross domestic product (GDP).ConclusionsEstimating the impact of this pandemic in terms of HCRU and costs to the health care system can help design strategies to manage the pandemic.
RhoA enhances osteosarcoma resistance to MPPa-PDT via the Hippo/YAP signaling pathway
Authors: Zhan Fangbiao , He Tao , Chen Zhiyu , Zuo Qiang , Wang Yang , Li Qiaochu , Zhong Shenxi , Ou Yunsheng 
Published: October 2021

Abstract
Background
Osteosarcoma (OS) is the most prevalent primary bone malignancy affecting adolescents, yet the emergence of chemoradiotherapeutic resistance has limited efforts to cure affected patients to date. Pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) is a recently developed, minimally invasive treatment for OS that is similarly constrained by such therapeutic resistance. This study sought to explore the mechanistic basis for RhoA-activated YAP1 (YAP)-mediated resistance in OS.

Methods
The relationship between YAP expression levels and patient prognosis was analyzed, and YAP levels in OS cell lines were quantified. Immunofluorescent staining was used to assess YAP nuclear translocation. OS cell lines (HOS and MG63) in which RhoA and YAP were knocked down or overexpressed were generated using lentiviral vectors. CCK-8 assays were used to examine OS cell viability, while the apoptotic death of these cells was monitored via Hoechst staining, Western blotting, and flow cytometry. Tumor-bearing nude mice were additionally used to assess the relationship between lentivirus-mediated alterations in RhoA expression and MPPa-PDT treatment outcomes. TUNEL and immunohistochemical staining approaches were leveraged to assess apoptotic cell death in tissue samples.

Results
OS patients exhibited higher levels of YAP expression, and these were correlated with a poor prognosis. MPPa-PDT induced apoptosis in OS cells, and such MPPa-PDT-induced apoptosis was enhanced following YAP knockdown whereas it was suppressed by YAP overexpression. RhoA and YAP expression levels were positively correlated in OS patients, and both active and total RhoA protein levels rose in OS cells following MPPa-PDT treatment. When RhoA was knocked down, levels of unphosphorylated YAP and downstream target genes were significantly reduced, while RhoA/ROCK2/LIMK2 pathway phosphorylation was suppressed, whereas RhoA overexpression resulted in the opposite phenotype. MPPa-PDT treatment was linked to an increase in HMGCR protein levels, and the inhibition of RhoA or HMGCR was sufficient to suppress RhoA activity and to decrease the protein levels of YAP and its downstream targets. Mevalonate administration partially reversed these reductions in the expression of YAP and YAP target genes. RhoA knockdown significantly enhanced the apoptotic death of OS cells in vitro and in vivo following MPPa-PDT treatment, whereas RhoA overexpression had the opposite effect.

Conclusions
These results suggest that the mevalonate pathway activates RhoA, which in turn activates YAP and promotes OS cell resistance to MPPa-PDT therapy. Targeting the RhoA/ROCK2/LIMK2/YAP pathway can significantly improve the efficacy of MPPa-PDT treatment for OS.
Joint spectral efficiency optimization of uplink and downlink for massive MIMO-enabled wireless energy harvesting systems
Authors: Sun Wenfeng , Liu Chen , Qian Mujun , Chen Yan , Xu Shu 
Published: October 2021

AbstractThis paper investigated the spectral efficiency (SE) in massive multiple-input multiple-output systems, where all terminals have no fixed power supply and thus need to replenish energy via the received signals from the base station. The hybrid wireless energy harvesting (EH) protocol is applied for each terminal, which can switch to either existing time-switching (TS) protocol or power-splitting (PS) protocol. Based on the hybrid wireless EH protocol, a general system model is developed, which can switch to either only uplink data transmission or only downlink data transmission. As a result, a general analytical framework is formulated. Then, closed-form lower bound expressions on SE for each terminal are obtained on the uplink and downlink, respectively. According to these expressions, the joint SE of uplink and downlink maximization problem is designed with some practical constraints. As the designed optimization problem is non-linear and non-convex, it is hard to solve directly. To provide a solution, an iteration algorithm is proposed by utilizing one-dimensional search technique and successive approximation method based on geometric program. Additionally, the convergence and complexity of the proposed algorithm are discussed as well. Finally, the feasibility of the proposed algorithm is analyzed by simulations. Numerical results manifest that the proposed algorithm can provide good SE by optimizing relevant system parameters, and the system model can help to discuss the TS, PS or hybrid protocol for only uplink data transmission, only downlink data transmission or joint data transmission of uplink and downlink in the considered system.
On Lipschitz continuity with respect to the Poincaré metric of linear contractions between Möbius gyrovector spaces
Authors: Watanabe Keiichi 
Published: October 2021

AbstractFor every linear operator between inner product spaces whose operator norm is less than or equal to one, we show that the restriction to the Möbius gyrovector space is Lipschitz continuous with respect to the Poincaré metric. Moreover, the Lipschitz constant is precisely the operator norm.
A fractional q-integral operator associated with a certain class of q-Bessel functions and q-generating series
Authors: Al-Omari Shrideh , Suthar Dayalal , Araci Serkan 
Published: October 2021

AbstractThis paper deals with Al-Salam fractional q-integral operator and its application to certain q-analogues of Bessel functions and power series. Al-Salam fractional q-integral operator has been applied to various types of q-Bessel functions and some power series of special type. It has been obtained for basic q-generating series, q-exponential and q-trigonometric functions as well. Various results and corollaries are provided as an application to this theory.
Blow-up of solutions for a quasilinear system with degenerate damping terms
Authors: Boulaaras Salah , Choucha Abdelbaki , Agarwal Praveen , Abdalla Mohamed , Idris Sahar Ahmed 
Published: October 2021

AbstractIn this work, we consider a quasilinear system of viscoelastic equations with degenerate damping and general source terms. According to some suitable hypothesis, we study the blow-up of solutions. This is the general case of the recent results of Boulaaras’ works (Bull. Malays. Math. Sci. Soc. 43:725–755, 2020) and (Appl. Anal. 99:1724–1748, 2020).