bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resveratrol and Angiogenin-2 Combined With PEGDA/TCS Hydrogel for the Targeted Therapy of Hypoxic Bone Defects via Activation of the Autophagy Pathway
Authors: Fan Dehui , Liu Hengping , Zhang Zhenning , Su Meiyi , Yuan Zhixian , Lin Ying , Yang Shuquan , Li Wenqiang , Zhang Xintao 
Published: April 2021

The guarantee of cell survival under hypoxic conditions and rapid vascularization is a key in tissue engineering strategies for treating bone defects. Our study aimed to establish the protective role of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) in hypoxic conditions and realize rapid vascularization in bone defects. Resveratrol (Res), a non-flavonoid polyphenolic compound, and angiopoietin-2 (ANG2), a vascular activating factor, were applied to enhance BMSC and HUVEC survival, osteogenesis, and angiogenesis. The morphology, autophagy, viability, apoptosis, cycle, and osteogenic differentiation of BMSCs treated with Res were analyzed. The results indicated that Res could improve BMSC survival and differentiation via the autophagy pathway under hypoxic conditions. In addition, Res maintained HUVEC growth and proliferation in a hypoxic and ANG2 double-adverse environment via the autophagy pathway. To simulate a relatively hypoxic environment, small-aperture PEGDA/TCS hydrogels containing Res and ANG2 were prepared. BMSCs were cultured in the PEGDA/TCS scaffold and transplanted into a large tibial defect. CD31 immunofluorescence showed that the density and size of new blood vessels in the bone defect were significantly enhanced by ANG2 and Res at 8 weeks after surgery. H&amp;E, Masson, and immunohistochemical staining results indicated that ANG2 combined with Res could promote new bone formation in defects. All these results suggested that Res combined with ANG2 may be a novel strategy for the targeted therapy of hypoxic bone defects with tissue engineering scaffolds.
MGA Mutation as a Novel Biomarker for Immune Checkpoint Therapies in Non-Squamous Non-Small Cell Lung Cancer
Authors: Sun Lei , Li Man , Deng Ling , Niu Yuchun , Tang Yichun , Wang Yu , Guo Linlang 
Published: April 2021

Background: Immune checkpoint inhibitors have changed the treatment landscape for advanced non-small cell lung cancer. However, only a small proportion of patients experience clinical benefit from ICIs. Thus, the discovery of predictive biomarkers is urgently warranted. Evidence have shown that genetic aberrations in cancer cells can modulate the tumor immune milieu. We therefore explored the association between oncogenic mutations and efficacy to ICIs in non-squamous NSCLC.Methods: We curated genomic and clinical data of 314 non-squamous NSCLC patients receiving ICIs from four independent studies for the discovery cohort. For external validation, 305 patients from an ICI-treated cohort and 1,027 patients from two non-ICI-treated cohorts were used. Relations between oncogenic mutations and outcomes of immunotherapy were examined. Multivariate Cox regression models were applied to adjust confounding factors. Further investigation on tumor antigenicity and antitumor immunity was performed in The Cancer Genome Atlas lung adenocarcinoma cohort.Results: A total of 82 oncogenes/tumor suppressor genes according to the Oncology Knowledge base database with a frequency greater than 3% were identified and investigated in the discovery cohort. Within these genes, MGA mutations were enriched in patients with durable clinical benefit (p = 0.001, false discovery rate q &lt; 0.05). The objective response rate was also significantly higher in patients with MGA mutation (2.63-fold, p &lt; 0.001, FDR q &lt; 0.05). Longer progression-free survival was found in MGA-mutated patients (HR, 0.41; 95% CI, 0.23–0.73; p = 0.003), and the association remained significant after controlling for tumor mutational burden (TMB), programmed cell death ligand-1 expression, and treatment regimens. In the validation cohort, significant improvement in overall survival was found in patients harboring MGA mutation (HR, 0.39; 95% CI, 0.17–0.88; p = 0.02). Furthermore, the survival difference was not detected in non-ICI-treated cohorts. We also demonstrated that MGA mutation correlate with higher TMB, elevated neoantigen load and DNA damage repair deficiency. Gene set enrichment analysis revealed that gene sets regarding activated immune responses were enriched in MGA-mutated tumors.Conclusion: Our work provides evidence that MGA mutation can be used as a novel predictive biomarker for ICI response in non-squamous NSCLC and merits further clinical and preclinical validation.
Antiviral Activity of Isoimperatorin Against Influenza A Virus in vitro and its Inhibition of Neuraminidase
Authors: Lai Yanni , Han Tiantian , Zhan Shaofeng , Jiang Yong , Liu Xiaohong , Li Geng 
Published: April 2021

Influenza A virus (IAV) poses a severe threat to human health and is a major public health problem worldwide. As global anti-influenza virus drug resistance has increased significantly, there is an urgent need to develop new antiviral drugs, especially drugs from natural products. Isoimperatorin, an active natural furanocoumarin, exhibits a broad range of pharmacologic activities including anticoagulant, analgesic, anti-inflammatory, antibacterial, anti-tumor, and other pharmacological effects, so it has attracted more and more attention. In this study, the antiviral and mechanistic effects of isoimperatorin on influenza A virus in vitro were studied. Isoimperatorin illustrated a broad-spectrum antiviral effect, especially against the A/FM/1/47 (H1N1), A/WSN/33 (H1N1, S31N, amantadine resistant), A/Puerto Rico/8/34 (H1N1), and A/Chicken/Guangdong/1996 (H9N2) virus strains. The experimental results of different administration modes showed that isoimperatorin had the best antiviral activity under the treatment mode. Further time-of-addition experiment results indicated that when isoimperatorin was added at the later stage of the virus replication cycle (6–8 h, 8–10 h), it exhibited an effective antiviral effect, and the virus yield was reduced by 81.4 and 84.6%, respectively. In addition, isoimperatorin had no effect on the expression of the three viral RNAs (mRNA, vRNA, and cRNA). Both the neuraminidase (NA) inhibition assay and CETSA demonstrated that isoimperatorin exerts an inhibitory effect on NA-mediated progeny virus release. The molecular docking experiment simulated the direct interaction between isoimperatorin and NA protein amino acid residues. In summary, isoimperatorin can be used as a potential agent for the prevention and treatment of influenza A virus.
On-Chip Broadband Mid-Infrared Supercontinuum Generation Based on Highly Nonlinear Chalcogenide Glass Waveguides
Authors: Xia Di , Huang Yufei , Zhang Bin , Yang Zelin , Zeng Pingyang , Shang Haiyan , Cheng Huanjie , Liu Linghao , Zhang Mingjie , Zhu Ying , Li Zhaohui 
Published: April 2021

On-chip mid-infrared (MIR) supercontinuum generation (SCG) covering the molecular functional spectral region (3–12 μm) offers the advantages of robustness, simplicity, and compactness. Yet, the spectral range still cannot be expanded beyond 10 μm. In this study, on-chip ultrabroadband MIR SCG in a high numerical aperture chalcogenide (ChG) waveguide is numerically investigated. The ChG waveguide with a Ge-As-Se-Te core and Ge-Se upper and lower cladding is designed to optimize the nonlinear coefficients and dispersion profile. Assisted by dispersive wave generation in both short- and long-wavelength range, broadband SCG ranging from 2 to 13 µm is achieved. Besides, a fabrication scheme is proposed to realize precise manipulation of dispersion design. Such results demonstrate that such sources are suitable for compact, chip-integrated molecular spectroscopy applications.
Forearm Volume Changes Estimated by Photo-Plethysmography During an Original Candlestick/Prayer Maneuver in Patients With Suspected Thoracic Outlet Syndrome
Authors: Hersant Jeanne , Ramondou Pierre , Chavignier Victoire , Chavanon Axelle , Feuilloy Mathieu , Picquet Jean , Henni Samir , Abraham Pierre 
Published: April 2021

Objective: Hemodynamic investigations in thoracic outlet syndrome (TOS) remain difficult, even in trained hands. Results are generally reported as either presence or absence of venous compression. In fact, in patients with suspected TOS but without chronic venous occlusion, the forearm volume changes may result from various combinations of forearm position from heart level, arterial inflow, and/or venous outflow positional impairment.Design: Cross sectional, retrospective, single center study, accessible on Clinicaltrial.gov under reference NCT04376177.Material: We used venous photo-plethysmography (V-PPG) in 151 patients with suspected TOS. The subjects elevated their arms to the “candlestick” (Ca) position for 30 s and then kept their arm elevated in front of the body for an additional 15 s (“prayer” position; Pra). This CA–Pra procedure was repeated three times by each patient with recording of both arms.Method: We classified V-PPG recordings using an automatic clustering method.Result: The blinded clustering classification of 893 V-PPG recordings (13 missing files) resulted in four out of seven clusters, allowing the classification of more than 99% of the available recordings. Each cluster included 65.73, 6.16, 17.13, and 10.8% of the recordings, respectively.Conclusion: Venous hemodynamic profiles in TOS are not only either normal or abnormal. With V-PPG, four clusters were observed to be consistent with, and assumed to result from, the four possible associations of presence/absence of arterial inflow/venous outflow positional impairment: (1) normal response (maximal emptying in Ca and Pra), (2) isolated inflow impairment (emptying in Ca and filling in Pra due to post-ischemic vasodilation), (3) isolated venous outflow impairment (emptying then filling in Ca due to arterial inflow and emptying in Pra), and (4) simultaneous inflow/outflow impairment (emptying in Ca but no filling due to concomitant inflow impairment and further emptying in Pra).
The Prevalence of Hyperpalatable Baby Foods and Exposure During Infancy: A Preliminary Investigation
Authors: Kong Kai Ling , Fazzino Tera L. , Rohde Kaitlyn M. , Morris Katherine S. 
Published: April 2021

Objective:To characterize the prevalence of hyperpalatable foods (HPF) among baby foods in the U.S. and examine the prevalence of HPF exposure and consumption from both baby food and adult food sources among infants aged 9–15 months.Methods:A U.S. baby food database as well as baby foods from three 24-h dietary recalls of 147 infants were used to identify baby foods as HPF per previous publication. HPF exposure was defined as intake of any HPF during the 3-day measurement period. To determine the extent of HFP consumption, % kilocalorie (kcal) intake from HPF was characterized.Results:Only 12% of baby foods were HPF; however, nearly all participants (&gt;90%) consumed HPF, primarily through exposure to adult foods. Younger infants (&lt;12 months) consumed 38% [standard deviation (SD) = 23.6%] of their daily food kcal from HPF and older infants (≥12 months) consumed 52% (SD = 16.4%) of daily food kilocalorie from HPF. Most younger infants (68%) and older infants (88%) had repeated exposure to the same HPF across the measurement period.Conclusions:The prevalence of HPF among baby foods in the U.S. is low. However, almost all infants were exposed to HPF, and HPF comprised a substantial percentage of daily food kilocalorie in infants' diets. Findings highlight the transition to solid food consumption during complimentary feeding period is a critical time for early HPF exposure.
Changes in Nursing Students' Career Choices Following the COVID-19 Pandemic in China
Authors: Bai Wei , Xi Hai-Tao , Zhu Qianqian , Wang Zhiwen , Han Lin , Chen Pan , Cai Hong , Zhao Yan-Jie , Chen Li , Ge Zong-Mei , Ji Mengmeng , Zhang Hongyan , Yang Bing-Xiang , Liu Shuo , Cheung Teris , Ungvari Gabor S. , An Fengrong , Xiang Yu-Tao 
Published: April 2021

Background: Health professionals including nurses have experienced heavy workload and great physical and mental health challenges during the coronavirus disease 19 (COVID-19) pandemic, which may affect nursing students' career choices. This study examined the changes in nursing students' career choices after the onset of the COVID-19 pandemic in China.Methods: This study was conducted in five University nursing schools in China between September 14, 2020 and October 7, 2020. Career choices before and after the COVID-19 pandemic were collected and analyzed.Results: In total, 1,070 nursing students participated in the study. The reported choice of nursing as future career increased from 50.9% [95% confidence interval (CI): 47.9–53.9%] before the COVID-19 pandemic to 62.7% (95%CI: 59.8–65.6%) after the onset of COVID-19 pandemic. Students who chose nursing as their future career following the COVID-19 outbreak had less severe depression and anxiety compared to those who did not choose nursing, but the associations of depression and anxiety with career choice disappeared in multivariable analyses. Binary logistic regression analysis revealed that male gender [odds ratio (OR) = 0.68, 95% CI: 0.50–0.91], rural residence (OR = 1.53, 95%CI: 1.17–2.00), fourth year students (OR = 0.50, 95%CI: 0.35–0.72), negative experiences during the COVID-19 pandemic (OR = 0.66, 95%CI: 0.47–0.92), and good health (OR = 4.6, 95%CI: 1.78–11.87) were significantly associated with the choice of nursing as future career after the onset of the COVID-19 pandemic.Conclusions: The COVID-19 pandemic appeared to have a positive influence on the career choice of nursing among Chinese nursing students.
Low Incidence and Mortality by SARS-CoV-2 Infection Among Healthcare Workers in a Health National Center in Mexico: Successful Establishment of an Occupational Medicine Program
Authors: Salazar Miguel Ángel , Chavez-Galan Leslie , Castorena-Maldonado Armando , Mateo-Alonso Maribel , Diaz-Vazquez Nadia Otilia , Vega-Martínez Ana María , Martínez-Orozco José Arturo , Becerril-Vargas Eduardo , Sosa-Gómez Fernando Manuel , Patiño-Gallegos Hilda , Alonso-Martínez Delfino , López-Segundo Enrique , Vidal Fernando , Velasco-González Luis Joan , Pérez-Pulido Silvia , Santillán-Doherty Patricio , Regalado-Pineda Justino , Salas-Hernández Jorge , Buendía-Roldán Ivette 
Published: April 2021

Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Healthcare workers (HCWs) constitute a population which is significantly affected by SARS-CoV-2 infection worldwide. In Mexico, the Instituto Nacional de Enfermedades Respiratorias (INER) is the principal national reference of respiratory diseases.Aim: To evaluate the efficiency of the INER-POL-TRAB-COVID19 program to mitigate the SARS-CoV-2 infection risk among the INER-healthcare workers (INER-HCW).Methods: Currently, the INER has 250 beds and 200 respiratory ventilators to support COVID-19 patients in critical condition. On March 1st, 2020, the INER-POL-TRAB-COVID19 program was launched to mitigate the SARS-CoV-2 infection risk among the INER-HCW.Findings: From March 1st to October 1st, 2020, 71.5% of INER-HCWs were tested for SARS-CoV-2 infection, and 77% of them were frontline workers. Among the tested INER-HCWs, 10.4% were positive for SARS-CoV-2 infection. Nonetheless, nosocomial infection represented only 3.8% of the cases and the mortality was null. Fifty-three of INER-HCWs positive to SARS-CoV-2 had a negative test 42–56 days post-diagnosis and were returned to service. Finally, although a change in the PPE implemented on May 11th, 2020, the incidence of SARS-CoV-2 infection was not affected.Conclusion: INER has a lower incidence of HCWs infected with SARS-CoV-2 as compared to the mean of the national report. The implementation of the INER-POL-TRAB-COVID19 program is efficient to decrease the risk of infection among the HCWs. Our findings suggest that the implementation of a similar program at a national level can be helpful to provide a safe environment to HCWs and to prevent the collapse of health institutions.
PubMed-Scale Chemical Concept Embeddings Reconstruct Physical Protein Interaction Networks
Authors: Škrlj Blaž , Kokalj Enja , Lavrač Nada 
Published: April 2021

PubMed is the largest resource of curated biomedical knowledge to date, entailing more than 25 million documents. Large quantities of novel literature prevent a single expert from keeping track of all potentially relevant papers, resulting in knowledge gaps. In this article, we present CHEMMESHNET, a newly developed PubMed-based network comprising more than 10,000,000 associations, constructed from expert-curated MeSH annotations of chemicals based on all currently available PubMed articles. By learning latent representations of concepts in the obtained network, we demonstrate in a proof of concept study that purely literature-based representations are sufficient for the reconstruction of a large part of the currently known network of physical, empirically determined protein–protein interactions. We demonstrate that simple linear embeddings of node pairs, when coupled with a neural network–based classifier, reliably reconstruct the existing collection of empirically confirmed protein–protein interactions. Furthermore, we demonstrate how pairs of learned representations can be used to prioritize potentially interesting novel interactions based on the common chemical context. Highly ranked interactions are qualitatively inspected in terms of potential complex formation at the structural level and represent potentially interesting new knowledge. We demonstrate that two protein–protein interactions, prioritized by structure-based approaches, also emerge as probable with regard to the trained machine-learning model.
FORMS AND METHODS OF TEACHING HEALTH SAVING TO STUDENTS OF MEDICAL INSTITUTIONS OF HIGHER EDUCATION
Authors: DONCHENKO V. 
Published: April 2021

The complex of developmental methods is systematized in the article, sent to development of medical education in the field of health saving. These include: cognitive (dialogical teaching methods, seminars-discussions, problem-based learning, cognitive counseling, cognitive maps, instrumental-logical training, reflection training, etc.); activity (methods of projects and guiding tests, contextual learning, organizational-activity games, complex didactic tasks, technological maps, simulation-game modeling, etc.); motivational (interactive and simulation games, development trainings, developmental psychodiagnostics, etc.).
The process of teaching students of medical institutions of higher education is based on the introduction of a set of methods with an emphasis on the formation of students' readiness for creative professional activity in the field of health (social adaptation, individual work, group, control testing, training). Methods, forms and means (active, passive, interactive) of learning are considered and analyzed. They are extremely effective in increasing the level of students' cognitive interest reducing the time to assess the knowledge of all students in each class, focus their behavior on the acquisition of values, knowledge, skills and abilities. Particular attention is paid to the use of computer information technology as a highly effective learning tool.
The importance of all methods and forms of education and their necessity for the formation of readiness of students of medical institutions of higher education to use health-saving technologies in future professional activities is determined.
THEORETICAL ASPECTS OF THE PROFESSIONAL TRAINING OF PILOT INSTRUCTORS IN CIVIL AVIATION OF UKRAINE
Authors: ROZHNOVA T. , KONOVALOV O. 
Published: April 2021

The article substantiates the theoretical principles of the professional training of pilot instructors in civil aviation of Ukraine. It covers the analysis of significant scientific researches and publications concerning training of civil aviation specialists and highlights the relevance of the topic of research. Considerable attention is given to the terminological apparatus in the context of aviation professional education. The article provides interpretations of such terms as professional training, pedagogical system, pedagogical conditions and competence.
There is a serious demand to educate a sufficient number of qualified flight instructors, who would be able to deal with the intensive scientific and technical transformations of the aviation industry. This matter is of particular relevance to our country, where the civil aviation industry may become a factor in the revival of an efficient economy.
Professional civil aviation pilot training has been a research subject of many Ukrainian scientists, such as: V. Asriyan I. Galimska, O. Moskalenko, T. Plachinda, G. Puhalska and others. However, the problem of professional civil aviation pilot instructor training in Ukraine has remained out of scientists’ attention.
Scientists suggest considering professional training of aviation specialists as an integrated system of interdisciplinary knowledge and skills, provided by the use of a set of theoretical and flight training activities, that teach to solve practical problems during professional duties. The essence of such training can be determined as an integrated pedagogical process that contributes to the formation of psychophysiological qualities, resistance to extreme factors of professional activity and achievement of a high level of efficiency by civil aviation pilots.
In this study, professional training of instructor pilots is also considered as a part of the overall education system of aviation specialists, which involves acquiring general and professional competencies that provide mastery of knowledge and skills of the future instructor. It is aimed at a full professional self-realization of the individual and is focused on the formation of pedagogical competence of an instructor. Successful functioning of elements of such a system is impossible without fulfillment of certain pedagogical conditions.
We have researched only some theoretical aspects of professional civil aviation pilot training in Ukraine. The next stage of our study will cover the legal regulations that describe professional training of pilot instructors in Ukraine.
The Effects of Allopurinol on Glutathione Sulfhydryl (GSH) Serum Level, Six Minute Walking Test, and CAT Score of COPD Patients
Authors: Samuel Samuel , Suradi Suradi , Sutanto Yusup Subagio 
Published: April 2021

Background: Stress oxidative in COPD impairs striated muscle thus worsening COPD symptoms. Allopurinol as antioxidant reduces stress oxidative so it can improve exercise capacity and clinical symptoms. The aims of this study were to analyze the effects of allopurinol on GSH serum level, six minute walking test (6MWT), and COPD assessment test (CAT) score of COPD patients.
Methods: This study was a pre and post test clinical trial held in pulmonology outpatient clinic in Dr. Moewardi General Hospital Surakarta from January to February 2018 using purposive sampling. The COPD group C and D patients were cathegorized as intervention group which received allopurinol 300 mg/day for 4 weeks and control group which did not receive allopurinol. Glutathione sulfhydryl serum level, 6MWT, and CAT score were measured at baseline and after 4 weeks in both groups.
Results: A total of 37 stable COPD group C and D patients were included in this study. The intervention group showed decreased GSH level (52.58±38.39) µg/ml and CAT score (10.37±4.46) which were statistically significant compared to control group (P