bluuebunny/crossref_metadata_2025_split huggingface dataset:
High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies
Authors: Yuan Shunling , Liu Zhaoping , Xu Zhenru , Liu Jing , Zhang Ji 
Published: July 2020

AbstractHigh mobility group box 1 (HMGB1) is a nonhistone chromatin-associated protein that has been widely reported to play a pivotal role in the pathogenesis of hematopoietic malignancies. As a representative damage-associated molecular pattern (DAMP), HMGB1 normally exists inside cells but can be secreted into the extracellular environment through passive or active release. Extracellular HMGB1 binds with several different receptors and interactors to mediate the proliferation, differentiation, mobilization, and senescence of hematopoietic stem cells (HSCs). HMGB1 is also involved in the formation of the inflammatory bone marrow (BM) microenvironment by activating proinflammatory signaling pathways. Moreover, HMGB1-dependent autophagy induces chemotherapy resistance in leukemia and multiple myeloma. In this review, we systematically summarize the emerging roles of HMGB1 in carcinogenesis, progression, prognosis, and potential clinical applications in different hematopoietic malignancies. In summary, targeting the regulation of HMGB1 activity in HSCs and the BM microenvironment is highly beneficial in the diagnosis and treatment of various hematopoietic malignancies.
RETRACTED ARTICLE: M2 macrophage-derived extracellular vesicles promote gastric cancer progression via a microRNA-130b-3p/MLL3/GRHL2 signaling cascade
Authors: Zhang Yu , Meng Wenbo , Yue Ping , Li Xun 
Published: July 2020

Abstract
Background
Transfer of noncoding microRNAs (miRNAs) by extracellular vesicles (EVs) promotes the development of chemoresistance in many tumor types. Additionally, restoration or depletion of several miRNAs has been observed in multiple cancer types including gastric cancer (GC). In this present study, we aimed to investigate the mechanism of miR-130b-3p in M2 macrophage-derived EVs in the development of GC through regulation of mixed lineage leukemia 3 (MLL3) and grainyhead-like 2 (GRHL2).

Methods
Expression of miR-130b-3p and GRHL2 was quantified in 63 pairs of cancerous and noncancerous gastric tissues. The predicted binding between miR-130b-3p and MLL3, together with the enrichment of MLL3, H3K4me1, and H3K27ac in gene enhancer region, was verified by luciferase activity assay and chromatin immunoprecipitation. Effects of miR-130b-3p on GC cell proliferation, apoptosis, migration and invasion, as well as tube formation of human umbilical endothelial vein cells (HUEVCs) were further determined by gain- and loss-of function assays in vitro.

Results
miR-130b-3p was upregulated in GC tissues, and miR-130b-3p promoted survival, metastasis and angiogenesis of GC cells as well as enhanced tumor formation and angiogenesis in GC in vivo. Additionally, miR-130b-3p delivered in M2 macrophage-derived EVs promoted survival, migration, invasion, and angiogenesis of GC cells. Notably, MLL3 inhibited GC cell proliferation, migration, invasion, and vessel-like tube formation of HUEVCs by increasing GRHL2. Furthermore, downregulation of miR-130b-3p in M2 macrophage-derived EVs or upregulation of GRHL2 inhibited tumor formation and angiogenesis in GC.

Conclusion
This study highlights that EVs loaded with the specific miRNA cargo miR-130b-3p mediate communication between M2 macrophages and cancer cells in the tumor microenvironment through the modulation of MLL3 and GRHL2 in GC.
Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19
Authors: Ni Wentao , Yang Xiuwen , Yang Deqing , Bao Jing , Li Ran , Xiao Yongjiu , Hou Chang , Wang Haibin , Liu Jie , Yang Donghong , Xu Yu , Cao Zhaolong , Gao Zhancheng 
Published: July 2020

Abstract
An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1–7), and the ACE2/angiotensin-(1–7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1–7)/MAS may help attenuate organ injuries.

Graphical abstract
SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.
Preventive efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of Heartgard® Plus or Interceptor® Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs
Authors: Kryda Kristina , Holzmer Susan , Everett William R. , McCall John W. , Mahabir Sean P. , McTier Tom L. , Maeder Steven J. 
Published: July 2020

Abstract
Background
Recent reports indicated that increasing the monthly oral dosage and the number of consecutive monthly doses of moxidectin improved the efficacy against macrocyclic lactone (ML)-resistant Dirofilaria immitis. The two laboratory studies reported here evaluated the efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of either Heartgard® Plus (ivermectin/pyrantel) or Interceptor® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis strains.

Methods
Dogs were inoculated 30 days prior to first treatment with 50 third-stage (L3) larvae of a ML-resistant strain of D. immitis, ZoeLA or JYD-34. In each study, dogs (six per group) were randomized to treatment with six monthly doses of placebo, four or six monthly doses of 24 µg/kg moxidectin, or six monthly doses of Heartgard® Plus or Interceptor® Plus at their label dose rates. Efficacy was evaluated by adult heartworm counts approximately nine months after L3 inoculation.

Results
All negative-control dogs were infected with adult heartworms (geometric mean, 35.6; range, 24–41) for ZoeLA and (geometric mean, 32.9; range, 30–37) for JYD-34. Efficacies against ZoeLA for moxidectin, Heartgard® Plus and Interceptor® Plus were ≥ 96.1%, 18.7% and 21.2%, respectively. Adult counts for both moxidectin-treated groups were significantly lower than negative control (P < 0.0001), significantly lower than Heartgard® Plus and Interceptor® Plus (P < 0.0001), but not significantly different from each other (P = 0.5876). Counts for Heartgard® Plus and Interceptor® Plus were not significantly different than negative control (P ≥ 0.2471). Efficacies against JYD-34 were ≥ 95.9%, 63.9% and 54.6% for moxidectin, Heartgard® Plus and Interceptor® Plus, respectively. Counts for all groups were significantly lower than negative control (P ≤ 0.0001). Counts for six monthly doses of moxidectin were significantly lower than those for four monthly doses (P = 0.0470), and the counts for both moxidectin-treated groups were significantly lower than Heartgard® Plus and Interceptor® Plus (P ≤ 0.0002).

Conclusions
Moxidectin administered orally at 24 µg/kg to dogs for four or six consecutive months was ≥ 95.9% effective in preventing the development of two ML-resistant heartworm strains and resulted in significantly fewer adult D. immitis than in dogs treated with Heartgard® Plus or Interceptor® Plus when administered for six consecutive months at their approved label dosages in two laboratory efficacy studies.
Highly accurate skin-specific methylome analysis algorithm as a platform to screen and validate therapeutics for healthy aging
Authors: Boroni Mariana , Zonari Alessandra , Reis de Oliveira Carolina , Alkatib Kallie , Ochoa Cruz Edgar Andres , Brace Lear E. , Lott de Carvalho Juliana 
Published: July 2020

Abstract
Background
DNA methylation (DNAm) age constitutes a powerful tool to assess the molecular age and overall health status of biological samples. Recently, it has been shown that tissue-specific DNAm age predictors may present superior performance compared to the pan- or multi-tissue counterparts. The skin is the largest organ in the body and bears important roles, such as body temperature control, barrier function, and protection from external insults. As a consequence of the constant and intimate interaction between the skin and the environment, current DNAm estimators, routinely trained using internal tissues which are influenced by other stimuli, are mostly inadequate to accurately predict skin DNAm age.

Results
In the present study, we developed a highly accurate skin-specific DNAm age predictor, using DNAm data obtained from 508 human skin samples. Based on the analysis of 2,266 CpG sites, we accurately calculated the DNAm age of cultured skin cells and human skin biopsies. Age estimation was sensitive to the biological age of the donor, cell passage, skin disease status, as well as treatment with senotherapeutic drugs.

Conclusions
This highly accurate skin-specific DNAm age predictor constitutes a holistic tool that will be of great use in the analysis of human skin health status/molecular aging, as well as in the analysis of the potential of established and novel compounds to alter DNAm age.
Quantification of the CM-Dil-labeled human umbilical cord mesenchymal stem cells migrated to the dual injured uterus in SD rat
Authors: Zheng Jia-Hua , Zhang Jing-Kun , Kong De-Sheng , Song Yan-Biao , Zhao Shuang-Dan , Qi Wen-Bo , Li Ya-Nan , Zhang Ming-le , Huang Xiang-Hua 
Published: July 2020

Abstract
Background
Human umbilical cord mesenchymal stem cell (hUC-MSC) therapy is considered as a promising approach in the treatment of intrauterine adhesions (IUAs). Considerable researches have already detected hUC-MSCs by diverse methods. This paper aims at exploring the quantitative distribution of CM-Dil-labeled hUC-MSCs in different regions of the uterus tissue of the dual injury-induced IUAs in rats and the underlying mechanism of restoration of fertility after implantation of hUC-MSCs in the IUA model.

Methods
In this study, we investigated the quantification of the CM-Dil-labeled hUC-MSCs migrated to the dual injured uterus in Sprague Dawley rats. Additionally, we investigated the differentiation of CM-Dil-labeled hUC-MSCs. The differentiation potential of epithelial cells, vascular endothelial cells, and estrogen receptor (ER) cells were assessed by an immunofluorescence method using CK7, CD31, and ERα. The therapeutic impact of hUC-MSCs in the IUA model was assessed by hematoxylin and eosin, Masson, immunohistochemistry staining, and reproductive function test. Finally, the expression of TGF-β1/Smad3 pathway in uterine tissues was determined by qRT-PCR and Western blotting.

Results
The CM-Dil-labeled cells in the stroma region were significantly higher than those in the superficial myometrium (SM) (71.67 ± 7.98 vs. 60.92 ± 3.96, p = 0.005), in the seroma (71.67 ± 7.98 vs. 23.67 ± 8.08, p = 0.000) and in the epithelium (71.67 ± 7.98 vs. 4.17 ± 1.19, p = 0.000). From the 2nd week of treatment, hUC-MSCs began to differentiate into epithelial cells, vascular endothelial cells, and ER cells. The therapeutic group treated with hUC-MSCs exhibited a significant decrease in fibrosis (TGF-β1/Smad3) as well as a significant increase in vascularization (CD31) compared with the untreated rats.

Conclusion
Our findings suggested that the distribution of the migrated hUC-MSCs in different regions of the uterine tissue was unequal. Most cells were in the stroma and less were in the epithelium of endometrium and gland. Injected hUC-MSCs had a capacity to differentiate into epithelial cells, vascular endothelial cells, and ER cells; increase blood supply; inhibit fibration; and then restore the fertility of the IUA model.
Radiobiological and dosimetric assessment of DNA-intercalated 99mTc-complexes bearing acridine orange derivatives
Authors: Belchior Ana , Di Maria Salvatore , Fernandes Célia , Vaz Pedro , Paulo António , Raposinho Paula 
Published: July 2020

Abstract
Background
Recently, a new family of 99mTc(I)-tricarbonyl complexes bearing an acridine orange (AO) DNA targeting unit and different linkers between the Auger emitter (99mTc) and the AO moiety was evaluated for Auger therapy. Among them, 99mTc-C3 places the corresponding radionuclide at a shortest distance to DNA and produces important double strand breaks (DSB) yields in plasmid DNA providing the first evidence that 99mTc can efficiently induce DNA damage when well positioned to the double helix. Here in, we have extended the studies to human prostate cancer PC3 cells using the 99mTc-C3 and 99mTc-C5 complexes, aiming to assess how the distance to DNA influences the radiation-induced biological effects in this tumoral cell line, namely, in which concerns early and late damage effects.

Results
Our results highlight the limited biological effectiveness of Auger electrons, as short path length radiation, with increasing distances to DNA. The evaluation of the radiation-induced biological effects was complemented with a comparative microdosimetric study based on intracellular dose values. The comparative study, between MIRD and Monte Carlo (MC) methods used to assess the cellular doses, revealed that efforts should be made in order to standardize the bioeffects modeling for DNA-incorporated Auger electron emitters.

Conclusions
99mTc might not be the ideal radionuclide for Auger therapy but can be useful to validate the design of new classes of Auger-electron emitting radioconjugates. In this context, our results highlight the crucial importance of the distance of Auger electron emitters to the target DNA and encourage the development of strategies for the fine tuning of the distance to DNA for other medical radionuclides (e.g., 111In or 161Tb) in order to enhance their radiotherapeutic effects within the Auger therapy of cancer.
FDG PET versus CT radiomics to predict outcome in malignant pleural mesothelioma patients
Authors: Pavic M. , Bogowicz M. , Kraft J. , Vuong D. , Mayinger M. , Kroeze S. G. C. , Friess M. , Frauenfelder T. , Andratschke N. , Huellner M. , Weder W. , Guckenberger M. , Tanadini-Lang S. , Opitz I. 
Published: July 2020

Abstract
Background
Careful selection of malignant pleural mesothelioma (MPM) patients for curative treatment is of highest importance, as the multimodal treatment regimen is challenging for patients and harbors a high risk of substantial toxicity. Radiomics—a quantitative method for image analysis—has shown its prognostic ability in different tumor entities and could therefore play an important role in optimizing patient selection for radical cancer treatment. So far, radiomics as a prognostic tool in MPM was not investigated.

Materials and methods
This study is based on 72 MPM patients treated with surgery in a curative intent at our institution between 2009 and 2017. Pre-treatment Fluorine-18 fluorodeoxyglucose (FDG) PET and CT scans were used for radiomics outcome modeling. After extraction of 1404 CT and 1410 FDG PET features from each image, a preselection by principal component analysis was performed to include only robust, non-redundant features for the cox regression to predict the progression-free survival (PFS) and the overall survival (OS). Results were validated on a separate cohort. Additionally, SUVmax and SUVmean, and volume were tested for their prognostic ability for PFS and OS.

Results
For the PFS a concordance index (c-index) of 0.67 (95% CI 0.52–0.82) and 0.66 (95% CI 0.57–0.78) for the training cohort (n = 36) and internal validation cohort (n = 36), respectively, were obtained for the PET radiomics model. The PFS advantage of the low-risk group translated also into an OS advantage. On CT images, no radiomics model could be trained. SUV max and SUV mean were also not prognostic in terms of PFS and OS.

Conclusion
We were able to build a successful FDG PET radiomics model for the prediction of PFS in MPM. Radiomics could serve as a tool to aid clinical decision support systems for treatment of MPM in future.
Recommendations for the surveillance of multidrug-resistant bacteria in Italian long-term care facilities by the GLISTer working group of the Italian Association of Clinical Microbiologists (AMCLI)
Authors: Aschbacher Richard , Pagani Leonardo , Migliavacca Roberta , Pagani Laura ,   the GLISTer (Gruppo di Lavoro per lo Studio delle Infezioni nelle Residenze Sanitarie Assistite e Strutture Assimilabili) working group, Confalonieri Massimo , Farina Claudio , Fazii Paolo , Luzzaro Francesco , Rigoli Roberto , Spalla Melissa 
Published: July 2020

AbstractLong-term care facilities (LTCFs) are an important reservoir of multidrug-resistant organisms (MDROs). Colonization of LTCF residents by MDROs is generally higher in Italy compared to other European countries. The present review by the working group for the study of infections in LTCFs (GLISTer) of the Italian Association of Clinical Microbiologists (AMCLI) aims to propose criteria for a laboratory-based surveillance of MDROs in Italian LTCFs.We recommend the adhesion to three levels of laboratory-based MDROs surveillance in LTCFs: i) mandatory MDRO surveillance by cumulative retrospective analysis of antimicrobial susceptibility data, obtained as part of routine care of clinical specimens. ii) strongly recommended surveillance by active rectal swab cultures or molecular screening to determine colonization with carbapenemase-producing Enterobacterales, should a resident be proven infected. iii) voluntary surveillance by prospective MDRO surveys, mainly based on point prevalence colonization studies, allowing to determine the MDROs baseline prevalence in the facility.Laboratory-based surveillance of MDROs in LTCFs is aimed at providing useful epidemiological information to healthcare providers operating in the facility, but it is only effective if the collected data are used for infection prevention and control purposes, targeting the peculiar aspects of LTCFs.
Science-society dialogue from the start: Participatory research agenda-setting by Science Cafés
Authors: Balázs Bálint , Horváth Janka , Pataki György 
Published: July 2020

AbstractThis empirical paper presents a case of a participatory agenda-setting exercise for green care services in Hungary. Science Cafés were utilised as a participatory agenda-setting tool within the framework of the InSPIRES H2020 project. The objectives were to collect perceptions of research needs from key actors in the green care field in Hungary, to generate collaborative research projects on green care services and to initiate social dialogue around green care in Hungary. The main research question was as follows: how can we co-create a research agenda on green care by eliciting responses from concerned citizens and experts in a very open and democratic setting? While a growing body of evidence supports the need for, and benefits of, green care services, there is not much research in Hungary addressing diverse knowledge needs of the multiple social actors in the green care field. Science Café as developed for institutionalising an informal and lively dialogue between science and society proved to be a useful tool to co-generate a research agenda for such a relatively neglected but socially highly beneficial theme as green care.
Training or Synergizing? Complex Systems Principles Change the Understanding of Sport Processes
Authors: Pol Rafel , Balagué Natàlia , Ric Angel , Torrents Carlota , Kiely John , Hristovski Robert 
Published: July 2020

AbstractThere is a need to update scientific assumptions in sport to promote the critical thinking of scientists, coaches, and practitioners and improve their methodological decisions. On the basis of complex systems science and theories of biological evolution, a systematization and update of theoretical and methodological principles to transform the understanding of sports training is provided. The classical focus on learning/acquiring skills and fitness is replaced by the aim of increasing the diversity/unpredictability potential of teams/athletes through the development of synergies. This development is underpinned by the properties of hierarchical organization and circular causality of constraints, that is, the nestedness of constraints acting at different levels and timescales. These properties, that integrate bottom-up and top-down all dimensions and levels of performance (from social to genetic), apply to all types of sport, ages, or levels of expertise and can be transferred to other fields (e.g., education, health, management). The team as the main training unit of intervention, the dynamic concept of task representativeness, and the co-adaptive and synergic role of the agents are some few practical consequences of moving from training to synergizing.