bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Biomarkers Modulating Osteogenic Differentiation With Immune and Inflammation Landscapes in Mesenchymal Stem Cells: A Bioinformatics-based Comprehensive Study
Authors: Feng Ziyi , Su Xin , Wang Ting , Guo Shu
Published: January 2022

Background: Inducing osteogenic mesenchymal stem cell (MSC) differentiation brings a huge potential for clinical bone defect repair. This present study is aimed to identify novel key biomarkers for osteogenesis of MSCs, and analyze their possible regulation roles on immune and inflammation during this process.Results: Seven datasets (GSE159137, GSE159138, GSE114117, GSE88865, GSE153829, GSE63754, GSE73087) were obtained from the gene expression omnibus database, and 200 differentially expressed genes (DEGs) were identified from the train datasets. Biomarkers were screened through Logical regression of the selection operator algorithm, whose expressions and diagnostic performances were verified in the test datasets. FKBP prolyl isomerase 5 (FKBP5), insulin like growth factor binding protein 2, prostaglandin E receptor 2, SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) and transmembrane O-mannosyltransferase targeting cadherins 1 were established to be osteogenesis-related biomarkers. Finally, the DEGs of immune and inflammation in osteogenesis were detected, and their correlation with the hub biomarkers were analyzed. The five selected biomarkers are strongly associated with immune and inflammation related genes.Conclusion: Taken together, our manuscript identified five biomarkers related to stem cells osteogenesis and discussed their potential perspectives in immunoregulation, inflammation and tissue engineering during the process.
Rapid Centralised Randomisation in Emergency Setting Trials Using a Smartphone
Authors: Badurdeen Shiraz , Hodgson Kate , Santomartino Georgia A , Stevens Luke , Donath Susan , Roberts Calum , Manley Brett , Polglase Graeme R , Hooper Stuart B , Davis Peter G , Blank Douglas A
Published: January 2022

Randomised trials in emergency settings must quickly confirm eligibility and allocate participants to an intervention group without delaying treatment. We report rapid randomisation during two neonatal resuscitation trials using the non-commercial REDCap platform accessed via smartphone. This simple, reliable method has wide applicability for trials in emergency settings.
Inflammatory Modulation of miR-155 Inhibits Doxorubicin‑Induced Testicular Dysfunction Via Sirt1/Foxo1 Pathway: Insight to the Role of Acacetin and Bacillus Cereus Protease
Authors: Anwar Hend Mohamed , Hamad Sherin Ramadan , Salem Gad Elsayed Mohamed , Soliman Rania Hassan Mohamed , Elbaz Eman
Published: January 2022

Purpose Doxorubicin (DOX), a chemotherapeutic agent, can disrupt testicular function leading to male infertility. The present study aimed to explore the possible protective effect of natural flavone, acacetin (ACA), and protease of Bacillus Cereus bacteria (B. Cereus) as well as the potential role of miR-155/SIRT1/FOXO1 network in DOX-induced testicular toxicity. Methods Twenty-eight male Wistar rats were randomly allocated into four groups and treated as follows: Control (1% DMSO 1 mL/kg/day; p.o), DOX (1mg/kg, i.p) on every other day for 21 days with a cumulative dose equal to 10 mg/kg throughout the experimental period, pre-treated groups received ACA (5 mg/kg/day, p.o) or B. Cereus protease (36 mg/kg/day, p.o) for a week prior DOX administration. Results DOX challenge reduced serum testosterone, and testicular 17β-hydroxysteroid dehydrogenase (17β-HSD). DOX exhibited a significant increase in testicular oxidative stress, inflammatory and apoptotic markers. Aberrant testicular miR-34c, a germ-specific miRNA, and miR-155 expressions were observed, along with decreased protein expression of sirtuin1 (SIRT1) dependent forkhead box 1 (FOXO1) acetylation inducing apoptosis. Besides, abnormal histopathological architecture and a marked reduction in the testicular expression of proliferating cell nuclear antigen (PCNA) were detected. ACA or protease administration significantly improves the histopathological and immunohistochemical pictures compared to DOX alone and renovated testicular functions. Nevertheless, treatment with protease was more effective than treatment with ACA in ameliorating DOX-induced testicular toxicity. Conclusion This study reveals the prophylactic role of these two regimens on male fertility by exhibiting antioxidant, anti-inflammatory, and anti-apoptotic effects against DOX-elicited testicular toxicity, possibly via modulating miR-155/SIRT1/FOXO1 network.
Development and Pilot Testing of the 2019 Canadian Abortion Provider Survey
Authors: Renner Regina , Ennis Madeleine , Maazi Mahan , Dunn Sheila , Norman Wendy V , Kaczorowski Janusz , Guilbert Edith
Published: January 2022

Background
Substantial changes in abortion care regulations, available medications and national clinical practice guidelines have occurred since a 2012 national Canadian Abortion Provider Survey (CAPS). We developed and piloted the CAPs 2019 to explore changes of the abortion provider workforce, their clinical care as well as experiences with stigma and harassment.
Methods
We undertook development and piloting in three phases: (1) development of the preliminary survey sections and questions based on the 2012 survey instrument, (2) content validation and feasibility of including certain content aspects via a modified Delphi Method with panels of clinical and research experts, and (3) pilot testing of the draft survey for face validity and clarity of language; assessing usability of the web-based Research Electronic Data Capture platform including the feasibility of complex skip pattern functionality. We performed content analysis of phase 2 results and used a general inductive approach to identify necessary survey modifications.
Results
In Phase 1 we generated a survey draft that reflected the changes in Canadian abortion care regulations and guidelines and included questions for clinicians and administrators providing first and second trimester surgical and medical abortion. In phase 2, we held 6 expert panel meetings of 5-8 participants each representing clinicians, administrators and researchers to provide feedback on the initial survey draft. Due to the complexity of certain identified aspects, such as interdisciplinary collaboration and interprovincial care delivery differences, we revised the survey sections through an iterative process of meetings and revisions until we reached consensus on constructs and questions to include versus exclude for not being feasible. In phase 3 we made minor revisions based on pilot testing of the bilingual, web-based survey among additional experts chosen to be widely representative of the study population. We included complex branching logic so each respondent only viewed applicable questions based on their prior responses.
Conclusions
We developed and piloted the CAPS 2019 survey instrument suitable to explore characteristics of a complex multidisciplinary workforce, their care and experience with stigma on a national level, and that can be adapted to other countries.
Hazardous spent methanol synthesis catalyst, bauxite red mud and ground cooled ferrous slag application to produce sustainable ceramics
Authors: Mymrin Vsevolod , Alarcon Reinaldo H. G. , Guidolin Marilia A. , Klitzke Walderson , Avanci Monica A. , Rolim Paulo H.B. , Carvalho Karina Q. , Catai Rodrigo E.
Published: January 2022

New composites of sustainable ceramic composites from hazardous methanol synthesis catalyst waste, bauxite red mud and ground cooled ferrous slag were developed in this study. The ceramics were sintered at temperatures of 900°, 1000°, 1050°, 1100° and 1150°C for one hour. Almost all ceramic demonstrated fairly high properties, starting from a firing temperature of 1000°C. The best results were obtained after firing at 1050°С, which reached 25.98 MPa of flexural resistance, 8.80% of water absorption, 3.46 g/cm3 and 7.14% of linear shrinkage. Studies of physical – chemical processes of the ceramics’ structure formation by XRD, SEM / EDS / mapping and LAMMA methods show the synthesis of mainly amorphous new formations with strong glass-like structures. Therefore, the result of leaching and solubility of the initial components’ heavy metals in acid environment by the method of atom-absorption spectroscopy indicated their almost complete immobilization, which far exceeded the demands of Brazilian sanitary norms.
The Whole-Transcriptome Landscape of Diabetes-Related Sarcopenia Reveals the Specific Function of Novel lncRNA Gm20743
Authors: Yu Jing , Loh kim , Yang He-qin , Du Meng-ran , Wu Yong-xin , Liao Zhi-yin , Guo Ai , Yang Yun-fei , Chen Bo , Zhao Yu-xing , Chen Jin-liang , Zhou Jing , Sun Yue , Xiao Qian
Published: January 2022

Background: While the exact mechanism remains unclear, type 2 diabetes mellitus (T2DM) has been shown to increase the risk of sarcopenia that is characterized by decreased muscle mass, strength, and function. This study aimed to identify the pathophysiological role of lncRNAs in diabetic sarcopenia. Methods: Whole-transcriptome RNA sequencing was performed on the gastrocnemius from the overt diabetes-induced sarcopenia model of db/db mice. Informatics and co-expression networks were performed to predict key lncRNAs and their potential regulation circuits in diabetes-induced sarcopenia. To determine the specific function of lncRNA Gm20743, the detection of Mito-Sox, reactive oxygen species, Ethynyl-2′-deoxyuridine, and myosin heavy chain was performed in overexpressed-Gm20743 C2C12 cells. Results: RNA-seq data and informatics revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. Meanwhile, we characterized three core candidate lncRNAs Gm20743, Gm35438, and 1700047G03Rik and their potential function. Furthermore, the results suggested lncRNA Gm20743 may be involved in regulating mitochondrial function, oxidative stress, cell proliferation, and myotube differentiation in skeletal muscle cells. Conclusion: These findings significantly improve our understanding of lncRNAs that may mediate muscle mass, strength, and function in diabetes and represent potential therapeutic targets for diabetes-induced sarcopenia.
Molecular mapping and transfer of a novel brown planthopper resistance gene bph42 from Oryza rufipogon (Griff.) to cultivated rice (Oryza sativa L.)
Authors: Kaur pavneet , Neelam Kumari , Sarao Preetinder Singh , Babbar Anika , Kumar Kishor , vikal yogesh , Khanna Renu , Kaur Rupinder , Mangat G.S. , Singh Kuldeep
Published: January 2022

Brown planthopper (BPH), Nilaparvata lugens (Stål), is one of the most destructive pests of rice accounting for 52% of annual yield loss. Under severe conditions, BPH cause “hopper burn” leading to drying and lodging of the matured plant. Utilization of host-plant resistance from diverse germplasm is considered as cost-effective and environment-friendly approach for its management. The current study reports the identification and mapping of a novel source of resistance from wild species of rice O. rufipogon accession CR100441 against the BPH biotype 4. Genetic analysis was performed using 276 BC2F2 and 233 BC2F3 populations derived from a cross of O. rufipogon accession CR100441 and highly susceptible cultivar PR122. The segregation of susceptible to resistant plants 3:1 ratio (210:66, χ2c = 0.17 ≤ χ20.05,1=3.84) indicating the presence of single major recessive gene. Bulked segregant analysis (BSA) using 537 SSR markers mapped a BPH resistance gene (designated as bph42) on the short arm of chromosome 4 between RM16282 and RM16335. QTL analysis identified a peak marker RM16335 contributing 29% of phenotypic variance at 11.0 LOD. This marker co-segregates with the bph42 which could be efficiently used for marker-assisted selection (MAS) to transfer of the traits into elite rice cultivars.
Characteristics of Complete Mitochondrial Genomes Reveals a Potential Division of Genus Modiolus into Three Genera
Authors: Li Houmei , Ma Peizhen , Liu Yumeng , Li Cui , Li Chenghua , Wang Haiyan , Zhang Zhen
Published: January 2022

Backgrounds Mussels have been one of the most abundant and highly evolved marine biological groups with high level of genetic differentiation between and within species. The yellow-banded horse mussel, Modiolus modulaides (Röding, 1798), is an important economic species in Philippines and an endangered species in Japan, with no whole mitogenome characterized. Methods and Results In this study, we sequenced the whole mitochondrial genome of Modiolus modulaides (Röding, 1798), a medium-sized mussel collected from Guangxi, China. Result shows a 15,422 bp closed-circular DNA molecule, including 12 protein-coding genes, 22 transfer RNA genes and two ribosomal RNA genes. The genome composition is obviously A+T biased (62.5%), with 23.1% A, 39.4% T, 25.4% G and 12.0% C, making AT-skew and GC-skew being -0.26 and 0.36, respectively. Phylogenetic analysis of Modiolus modulaides and other 36 mussel species based on 12 protein-coding genes and two ribosomal RNAs of mitogenomes shows that Modiolus modulaides is most closely related with Modiolus phillippinum (Hanley, 1843).Conclusions A hypothesis that the current genus Modiolus should be separated three distinctive genera was raised based on morphological and phylogenetic characteristics, as well as gene patterns of mitogenomes. These results put forward new insight of phylogenetic relationship of Modiolus species and will help to further study the taxonomy and phylogeny of Mytilidae.
Urine exosomes biomarkers of Obesity treatment: A pilot study
Authors: Vijay Bhavya , Rao Satish P Ramachandra , Devkumar Poornima
Published: January 2022

BackgroundObesity is a raising risk factor for many diseases including Cardiovascular risks and Cancer. The present limitations and inaccuracy of anthropometric measures as well as treatment options demand research of integrative management strategies and identification of specific biomarkers of obesity. This study identifies the urine exosome biomarkers and its differential expression profile between 3-timepoints from female obese participants who underwent Ayurveda treatment.MethodologyUrine exosomes were isolated using PEG methods of isolation. The major proteins obtained were identified using label-free quantification in LC-MS/MS. The genes involved in pathway enrichment, functional annotation and disease manifestation were identified and shortlisted based on protein interaction network. The hub genes representing obesity are identified.ResultsThe exosomes isolated were validated using LC-MS/MS. Using UniProt as reference, a total of 210 exosome proteins were identified. 73 genes were overexpressed in pathway enrichment analysis. Further, GO functional annotation identified 15 common genes involved. Finally, the 8 genes common in obesity were identified and its differential expression profile was seen to have corrected at timepoints during treatment.ConclusionThis is the first study to isolate and identify urine exosomes profiles from female obese participants of India. The study results indicate the correction in the differential expression profile of 8 hub genes involved in obesity post treatment. The biomarker signature of the pilot study indicates the specificity of urine exosomes as diagnostic markers. The study also promotes the potential of integrative and complementary treatment approaches like Ayurveda in effective management of many metabolic diseases.
The KIDSCREEN-27 scale: translation and validation study of the Slovenian version
Authors: Budler Leona Cilar , Pajnkihar Majda , Ravens-Sieberer Ulrike , Barr Owen , Stiglic Gregor
Published: January 2022

Background: There are many methods available for measuring social support and quality of life (QoL) of adolescents, of these, the KIDSCREEN tools are most widely used. Thus, we aimed to translate and validate the KIDSCREEN-27 scale for the usage among adolescents aged between 10 and 19 years old in Slovenia.Methods: A cross-sectional study was conducted among 2 852 adolescents in primary and secondary school from November 2019 to January 2020 in Slovenia. 6-steps method of validation was used to test psychometric properties of the KIDSCREEN-27 scale. We checked descriptive statistics, performed a Mokken scale analysis, parametric item response theory, factor analysis, classical test theory and total (sub)scale scores.Results: All five subscales of the KIDSCREEN-27 formed a unidimensional scale with good homogeneity and reliability. The confirmatory factor analysis showed poor fit in user model versus baseline model metrics (CFI = 0.847; TLI = 0.862) and good fit in root mean square error (RMSEA = 0.072; p(χ2) < 0.001). A scale reliability was calculated using Cronbach's α (0.93), beta (0.86), G6 (0.95) and omega (0.93).Conclusions: The questionnaire showed good psychometric properties and can be used among adolescents in Slovenia to find out about their quality of life.
Photogenerated Reactive Oxygen Species and Hyperthermia by Cu3SnS4 Nanoflakes for Advanced Photocatalytic and Photothermal Antibacterial Therapy
Authors: Yang Yangzi , Wang Chengwei , Wang Ning , Li Jiaxin , Zhu Yingchun , Zai Jiantao , Fu Jingke , Hao Yongqiang
Published: January 2022

BackgroundThe rapid spread of infectious bacteria has brought great challenges to public health. It is imperative to explore effective and environment-friendly antibacterial modality to defeat antibiotic-resistant bacteria with high biosafety and broad-spectrum antibacterial property. ResultsHerein, biocompatible Cu3SnS4 nanoflakes (NFs) were prepared by a facile and low-cost fabrication procedure. These Cu3SnS4 NFs could be activated by visible light, leading to visible light-mediated photocatalytic generation of a myriad of reactive oxygen species (ROS). Besides, the plasmonic Cu3SnS4 NFs exhibit strong near infrared (NIR) absorption and a high photothermal conversion efﬁciency of 55.7%. The ROS mediated cellular oxidative damage and the NIR mediated photothermal disruption of bacterial membranes collaboratively contributed to the advanced antibacterial therapy, which has been validated by the efficient eradication of both Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus strains in vitro and in vivo. Meanwhile, the exogenous copper ions metabolism from the Cu3SnS4 NFs facilitated the endothelial cell angiogenesis and collagen deposition, thus expediting the wound healing. Importantly, the inherent localized surface plasmon resonance effect of Cu3SnS4 NFs empowered them as an active substrate for surface-enhanced Raman scattering (SERS) imaging and SERS-labeled bacteria detection. ConclusionsThe low cost and biocompatibility together with the solar-driven broad-spectrum photocatalytic/photothermal antibacterial property of Cu3SnS4 NFs make them a candidate for sensitive bacteria detection and effective antibacterial treatment.
Designing A Provincial Surveillance and Support System for Childhood Cancer Survivors
Authors: Shuldiner Jennifer , Shah Nida , Reis Catherine , Chalmers Ian , Ivers Noah , Nathan Paul
Published: January 2022

Background Survivors of childhood cancer are at lifelong risk of morbidity (such as new cancers or heart failure) and premature mortality because of their cancer treatment. These are termed late effects. Therefore, they require lifelong, risk-tailored surveillance. However, most adult survivors of childhood cancer do not complete recommended surveillance tests such as mammograms or echocardiograms. Working with survivors, family physicians, and health-system partners, we are designing a provincial support system for high-priority tests, informed by principles of implementation science, behavioral science and design-thinking. Methods Our multi-phase process was as follows: Step 1: a qualitative study to explore intervention components essential to accessing surveillance tests; Step 2: a workshop with childhood cancer survivors, family physicians and health system stakeholders that used the Step 1 findings and ‘personas’ (a series of fictional but data-informed characters) to develop and tailor the intervention for different survivor groups Step 3: intervention prototype development; and step 4: iterative user-testing. Results The qualitative study of 30 survivors and 7 family physicians found a high desire for information on surveillance for late effects. Respondents indicated that in addition to providing personalized information, the intervention should help patients book appointments when they are due. Insights from the workshop included the importance of partnering with both family physicians and survivorship clinics and providing emotional support for survivors that may experience distress upon learning of their risk for late effects. In our user-testing process, prototypes went through iterations that incorporated feedback from users regarding usability and functionality. We sought to address the needs of survivors and physicians while balancing the capacity and infrastructure available for a life-long intervention via our health system partners. Conclusion In partnership with childhood cancer survivors, family physicians, and health-system partners, we elucidated the barriers and enablers to accessing guideline-recommended surveillance tests and designed a multi-faceted solution that will support survivors and their family physician. The next step is to evaluate the intervention in a pragmatic randomized control trial.
Not waiting for the death knell. A pilot study to examine supplementation and survivorship in a declining population of Tasmanian eastern quoll (Dasyurus viverrinus).
Authors: Hamer Rowena P , Robinson Natasha , Brewster Rob , Barlow Molly , Guinane Morrigan , Humphrey Morgan , Mifsud Adrian , Kutt Alex S.
Published: January 2022

Tasmanian populations of the eastern quoll Dasyurus viverrinus, which represent the last wild stronghold of this species after its extirpation from the Australian mainland, have experienced declines of more than 50% over the past three decades. In this pilot study, we investigate the feasibility of supplementing wild populations with captive-bred individuals to attempt to reverse observed declines. Our results are encouraging, in that we recorded high initial survival and low initial dispersal of captive-bred individuals relative to previous release attempts in mainland Australia. Further work is ongoing to determine long-term survival of released individuals and the genetic and population-level impacts on local populations. Our preliminary results support the use of population supplementation as an effective conservation action, which allows for early intervention to address species declines while simultaneously testing hypotheses about their underlying causes.
68Ga-FAPI improves tumor staging in patients with colorectal cancer: comparing to 18F-FDG PET/CT
Authors: Lin Xinfeng , Li Yingjie , Wang Shuailiang , Zhang Yan , Chen Xuetao , Wei Maomao , Zhu Hua , Wu Aiwen , Yang Zhi , Wang Xuejuan
Published: January 2022

Purpose
Gallium-68 (68Ga)-labeled fibroblast-activation protein inhibitor (FAPI) is a novel tracer that binds fibroblast-activation protein (FAP), which is overexpressed in colorectal cancers with a prominent stroma including cancer-associated fibroblasts (CAFs). The present study aimed to compare the diagnostic performance of 68Ga-FAPI positron emission tomography (PET)/computed tomography (CT) with that of fluorine-18 (18F)-fluorodeoxyglucose (FDG) PET/CT in primary and metastatic colorectal cancer lesions.
Methods
This prospective study included the image analyses of 37 patients with colorectal cancer who were sequentially evaluated using PET/CT with 18F-FDG and 68Ga-FAPI. Tracer uptakes were compared using Wilcoxon’s signed-rank test.
Results
The cohort comprised 37 patients, including 18 treatment-naïve patients and 19 post-treatment patients. In primary colorectal cancer lesions, the average 68Ga-FAPI and 18F-FDG maximum standardized uptake values (SUVmax) were 12.5 ± 4.8 and 13.2 ± 5.7 (P = 0.38), respectively, in the treatment-naïve group and 6.0 ± 4.3 and 7.9 ± 7.2, respectively, in the neoadjuvant chemotherapy group (P = 0.09); the detection rate was 100% with both tracers (18/18). The SUVmax value of 68Ga-FAPI in signet-ring/mucinous carcinomas (12.3 ± 5.2) was higher than that of 18F-FDG (8.3 ± 4.0) (P = 0.03). In addition, the average 68Ga-FAPI uptake was lower than that of 18F-FDG in poorly differentiated carcinomas (12.7 ± 3.7 vs. 18.1 ± 4.1, P = 0.04). Compared with 18F-FDG PET/CT, clinical TNM staging based on 68Ga-FAPI PET/CT led to upstaging in 6 patients (16.2%) and downstaging in 3 patients (8.1%). In peritoneal and liver metastases, both the SUVmax and the target/background ratio were higher with 68Ga-FAPI compared to 18F-FDG (3.7 vs. 2.6, P = 0.02, and 6.5 vs. 0.89, P = 0.01, respectively).
Conclusion
As a novel PET/CT tracer, 68Ga-FAPI showed its advantage in the detection of lymph nodes, and distant metastases, which improved staging of CRC.
International disparity of mental disorders burden: New trends of global mental health disparity
Authors: ZHU Huijie , JIANG Haojun , ZHU Zhiping , YAO Zhaoyu
Published: January 2022

Background: Mental illness had been a worldwide concern. Global Mental Health (GMH) had become a movement to fight for Global health inequality. In low-income country, adequate and quality mental health infrastructure, mental health services are not provided equitably to people with mental disorders.Methods: We used the data of global burden of 204countries from 1990 to 2019 in Global Burden of Disease database. The Years Lived with Disability (YLDs) due to mental disorders was treated as an indicator of national mental health. In the GBD Results Tool toolkit provided by the Institute of Health Measurement and Evaluation, retrieved and visualized the data in global burden of disease data. In addition, we used correlation analysis to analyze the correlation between the burden of mental illness and the level of national development.Results: It is found that, mental health had been a global issue which showing a gradual upward trend. There is a significant positive and moderate correlation between national development and the burden of mental disorder. The better the national development, the higher the YLDs Rate caused by mental disorders. The burden of mental illness in low-income countries is not high, but the rate of increase is relatively fast, while the burden of mental illness in low- and middle-income countries is relatively high, but the rate of decrease is apparent.Conclusion: The burden of mental disorders in developed countries is relatively high, but it has shown a downward trend. However, although the burden of mental disorders in developing countries is not large, the growth rate is relatively fast. This may be related to mental health policy. It is high time to notice that mental health had been a global issue. Global mental health movement should be done to narrow the gap between different countries, especially in developing countries.
Visualization of Learning-induced Synaptic Plasticity in Output Neurons of the Drosophila Mushroom Body γ-Lobe
Authors: Hancock Clare E. , Rostami Vahid , Nawrot Martin P. , Fiala André
Published: January 2022

By learning, through experience, which stimuli coincide with dangers, it is possible to predict outcomes and act pre-emptively to ensure survival. In insects, this process is localized to the mushroom body (MB), the circuitry of which facilitates the coincident detection of sensory stimuli and punishing or rewarding cues and, downstream, the execution of appropriate learned behaviors. Here, we focused our attention on the mushroom body output neurons (MBONs) of the γ-lobes that act as downstream synaptic partners of the MB γ-Kenyon cells (KCs) to ask how the output of the MB γ-lobe is shaped by olfactory associative conditioning, distinguishing this from non-associative stimulus exposure effects, and without the influence of downstream modulation. This was achieved by employing a subcellularly localized calcium sensor to specifically monitor activity at MBON postsynaptic sites. Therein, we identified a robust associative modulation within only one MBON postsynaptic compartment (MBON-γ1pedc>α/β), which displayed a suppressed postsynaptic response to an aversively paired odor. While this MBON did not undergo non-associative modulation, the reverse was true across the remainder of the γ-lobe, where general odor-evoked adaptation was observed, but no conditioned odor-specific modulation. In conclusion, associative synaptic plasticity underlying olfactory learning is localized to one distinct synaptic KC-to-MBON connection.
Whole-body Functional and Traditional Resistance Training are equally effective in increasing Muscular Fitness and Performance Variables in Untrained Young Men
Authors: zuo chongwen , Li Qing , Zhang Li , Bo Shumin
Published: January 2022

BackgroundFunctional resistance training (FRT) has been proposed as a safety alternative to traditional resistance training (TRT) for increasing neuromuscular adaptation capacity and improving certain muscular strength and competitive performance. The present study we sought to compare the effects of 6 weeks of whole-body functional and traditional resistance training on muscular fitness and performance variables in untrained young men.Methods29 untrained healthy young males aged 18–29 years who were randomly assigned to 6 weeks of functional resistance training (at 40% 1RM, 4-5sets of 20 repetitions, 3 times/week) or traditional training (at 70% 1RM, 4-5sets of 12 repetitions, 3 times/week). All subjects underwent numerous tests before and after the 6-week training such as upper and lower limb circumferences, maximal strength (barbell squat, bench press, dead lift, right leg flexion), power (throwing ability, jumping ability) and physical performance (sprint achievement, pull-up, handgrip strength). Internal training load variables was assessed by ratings of perceived exertion (RPE).Results(1) Both resistance training protocols improved muscular fitness and physical performance, no difference was observed between groups. However, only TRT protocols decreased body mass (-1.5kg, p < 0.05) and BMI (-0.5 kg/m2, p < 0.05). Internal training load variables between groups were no difference over a 6 weeks training period.ConclusionsIn conclusion, there is no difference between 6 weeks of whole-body functional resistance training compared to traditional resistance training on muscular fitness and performance.Trial registration: ChiCTR2100048485. Registered 09 July 2021, http://http://www.chictr.org.cn/
Mobile Phone Virtual Reality Game for Pediatric Home Burn Dressing Pain Management: A Randomized Feasibility Clinical Trial
Authors: Armstrong Megan , Lun Jonathan , Groner Jonathan I , Thakkar Rajan K , Fabia Renata , Noffsinger Dana , Ni Ai , Xiang Henry
Published: January 2022

Background: Virtual Reality (VR) gaming is considered a safe and effective alternative to standard pain alleviation in the hospital. This study will address the effectiveness and feasibility of a VR game that was developed by our research team for repeated at-home burn dressing changes. Methods: A randomized clinical trial was conducted among patients recruited from the outpatient burn clinic of a large American Burn Association–verified pediatric burn center between September 2019 and June 2021. We included English-speaking burn patients 5-17 years old requiring daily dressing changes for at least one week after first outpatient dressing change. One group played an interactive VR game during dressing changes, while the other utilized standard distraction techniques available in the home for up to a week. Both child and caretaker were asked to assess perceived pain on a scale of 1-10. For the VR group, patients were also asked to rate various aspects of the VR game on a scale of 1-10 and caregivers were asked questions assessing ease of use.Results: A total of 35 children were recruited for this study with 24 fully completing study measures. The majority of participants were male (54.3%), White (82.9%), and with second degree burns (94.4%). Children and caregivers in the VR group reported less pain than the control group at the 4th dressing change. Participants in the VR group showed a clinically meaningful (≥30%) reduction in child reported overall pain (33.3%) and caregiver reported worst pain (31.6%). Children’s satisfaction with the VR remained at a high level across dressing changes, with reported realism and engagement increasing over time. Over half of the children (54.5%) enjoyed playing the game and did not report any challenges.Conclusions: Subjects found the VR to be a useful distraction during home dressing changes and reported no challenges. VR should be considered as a nonpharmacologic companion for pain management during at-home burn dressing changes.Trial Registration: ClinicalTrials.gov Identifier: NCT04548635. Registered September 14, 2020 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04548635
A Pan-Genome Data Structure Induced by Pooled Sequencing Facilitates Variant Mining in Heterogeneous Germplasm
Authors: Reeves Patrick A. , Richards Christopher M.
Published: January 2022

Valuable genetic variation lies unused in gene banks due to the difficulty of exploiting heterogeneous germplasm accessions. Advances in molecular breeding, including transgenics and genome editing, present the opportunity to exploit hidden sequence variation directly. Here we describe the pangenome data structure induced by wholegenome sequencing of pooled individuals from wild populations of Patellifolia spp., a source of disease resistance genes for the related crop species sugar beet (Beta vulgaris). We represent the pangenome of a heterogeneous population sample as a set of phased reads mapped to a reference genome assembly derived from the sequence pool or other sources. We show that this basic data structure can be queried by homology to identify short haplotypic variants present in the wild relative, at genes of agronomic interest in the crop. Further we demonstrate the possibility of cataloging short haplotypic variation in all Patellifolia genomic regions that have corresponding single copy orthologous regions in sugar beet. The data structure, termed a "phased read archive", can be produced, altered, and queried using standard tools to facilitate discovery of agronomicallyimportant sequence variation in heterogeneous germplasm.
Discovery of Canine Drug Toceranib Phosphate as a Repurposed Agent against Human Hepatocellular Carcinoma
Authors: qiao ling , Qin Siyuan , Weng Ningna , Li Bowen , Luo Maochao , Zhang Zhe , Zhou Li , Jiang Cen , Huang Canhua
Published: January 2022

Background
Human hepatocellular carcinoma (HCC) is an aggressive malignancy worldwide with a poor clinical outcome. There are limited therapeutic options currently available for those diagnosed with terminal HCC and therefore incorporating novel agents into standard-of-care regimens is urgently needed. In contrast to de novo drug discovery, the strategy of repurposing already-approved compounds initially designed to treat animals, which share similarities in disease-associated characteristics with humans (i.e., dogs), might yield substantial advantages in terms of efficacy and safety. Given the evidence for clinical efficacy of toceranib phosphate (TOC) against canine carcinomas, we aimed to investigate its potential therapeutic effects on human HCC and the mechanisms involved.
Methods
We evaluated the antitumor effects of TOC using human HCC cell-line and cell line-derived xenograft models. Changes in autophagic response upon TOC exposure were quantified through immunoblotting and immunofluorescence analysis. The role of TOC-triggered autophagy was addressed via pharmacological and genetic inhibition.
Results
TOC, an approved canine drug, exhibited potent antitumor activity against human HCC cells by stimulating apoptosis in vitro and in vivo, which was accompanied by a concomitant increase in autophagic flux. Artificially blocking the TOC-triggered autophagy, either by pharmacologically using autophagy inhibitors or genetic interference, significantly inhibited cellular proliferation in vitro and decreased tumor burden in vivo, indicating a protective role of autophagy against TOC-mediated HCC cell death. This role played by TOC-induced autophagy was further linked to the inactivation of Akt/mTOR pathway that can be largely attributed to the upregulation of matricellular protein Cyr61 in HCC cells. Moreover, in vivo and in vitro treatment with standard systemic therapeutic sorafenib plus TOC resulted in pronounced synergistic effects on HCC cells.
Conclusions
Our results elucidate a newly identified therapeutic potential of TOC in treating HCC, sparking a growing interest in repurposing such canine drugs for human use.
Human Umbilical Cord Mesenchymal Stem Cells Grown in 3D Micro-environment Ameliorate Acute Liver Injury by Immunoregulation and Proliferation Promotion
Authors: Zhang Junhong , Zhou Junqi , Peng Yan , Mohsin Ali , Luo Yanxia , Zhuang Yingpng , Guo Meijin
Published: January 2022

Background
Mesenchymal stem cells (MSCs) have been widely used for inflammatory diseases like acute liver injury (ALI) and COVID-19 diseases. However, most MSCs instead of the cell-matrix are cultured in 2 D plates, resulting in degeneration of some key functions along with a limited understanding of the immune response in tissue repairing. Herein, we obtained the human umbilical cord MSCs grown on microcarriers in 3 D suspension culture (3 D hUCMSCs) that proved more appreciative than 2 D hUCMSCs for the ALI therapy.
Methods
hUCMSCs were isolated and respectively cultured in 2 D plates and 3 D microcarriers in vitro, and acute liver injury model in mice was used to evaluate tissue repairing ability of the transplanted hUCMSCs. Nitric oxide production, cell proliferation and the relative protein expression level were comprehensively evaluated. Besides, the cytokine expression level in the of serum mice was detected by quantitative RT-PCR and cytokine antibody chip.
Results
When transplanted with 3 D hUCMSCs in ALI mice, the injured liver tissues have a significantly-increased histological scores and enhanced animal’s body/liver weight, superior to the 2 D hUCMSCs and control group. Pro-inflammatory cytokines (IL-6, IL-1β, IL-17, IL-22 and TNF-α), apoptosis promoter IFN-g, and NO production declined when transplanted with 3D hUCMSCs compared to the control group. Besides, anti-inflammatory cytokines (IL-10) was up-regulated.
Conclusion
Both the 3 D hUCMSCs and the conditioned medium were more favorable for the therapy of acute liver injury (ALI). Triple regulatory roles of the 3 D hUCMSCs include the effective promotion of M1/M2 macrophage switch through increased secreting of anti-inflammatory cytokines, ameliorating proliferation and NO downregulation of macrophage. A balance of these cytokines in the conditioned medium of 3 D hUCMSCs played a key role in ALI repairing. It was proven that the 3 D hUCMSCs could trigger the mitogen-activated protein kinases (MAPKs) and STAT3 signaling pathways. Conclusively, the revelation of the superior moderating effect of 3 D hUCMSCs and possible regulatory mechanisms will improve the clinical efficacy of stem cell therapy for inflammatory and immunological diseases.
HMGN5 escorts oncogenic STAT3 signaling by regulating chromatin landscape in tumorigenesis of breast cancer
Authors: Mou Jiahui , Huang Meijun , Wang Feifei , Xu Xiaoding , Xie Hanqi , Lu Henglei , Li Mingyang , Li Yu , Kong Weiwen , Chen Jing , Xiao Ying , Chen Yiding , Wang Chaochen , Ren Jin
Published: January 2022

Background: Cancer progression is highly dependent on the ability of cancer cell tumor formation, in which epigenetic modulation plays an essential role. However, the epigenetic factors promoting breast tumor formation are less known. Screened from 3D-sphere tumor formation model, HMGN5 which regulates chromatin structures became the candidate therapeutic targets in breast cancer, though its role is obscure. Methods: The differential molecular profiles of 2D- and 3D-cultured breast cancer cell spheres were analyzed by mass spectrometry. Meanwhile, the prognostic relevance of HMGN5 was evaluated by examining the expression of HMGN5 in TCGA and a tissue microarray. Then, the oncogenic role of HMGN5 was investigated by CCK-8, trans-well, tumor sphere formation assays in vitro, and xenograft tumor growth and invasion assays in vivo. RNA-seq, Cut & Tag and bioinformatics analysis were performed to explore the molecular mechanism of HMGN5 in tumorigenesis. Luciferase reporter assays and ChIP-qPCR were performed to study the regulation of HMGN5 by STAT3. Moreover, nanoparticle-packaged siRNAs targeting HMGN5 were used to test the therapeutic effect in xenograft tumor model.Results: HMGN5 is highly expressed in 3D-spheres of breast cancer cells and clinical tumors, also an unfavorable prognostic marker in patients. Furthermore, HMGN5 controls tumor formation and metastasis of breast cancer cells in vitro and in vivo. Mechanistically, HMGN5 is governed by active STAT3 transcriptionally and further escorts STAT3 to shape oncogenic chromatin landscape and transcriptional program. More importantly, interference of HMGN5 by nanoparticle-packaged siRNA effectively inhibit tumor growth in breast cancer cell-derived xenograft mice model. Conclusion: Our findings reveal a novel feed-forward circuit between HMGN5 and STAT3 in promoting breast cancer tumorigenesis and suggest HMGN5 as a novel epigenetic therapeutic-target in STAT3-hyperactive breast cancer.
Occupations on the map: Using a super learner algorithm to downscale labor statistics
Authors: Dijk Michiel van , de Lange Thijs , Leeuwen Paul van , Debie Philippe
Published: January 2022

Detailed and accurate labor market statistics are fundamental to support social policies that aim to improve the match between labor supply and demand, and support the creation of jobs. Despite overwhelming evidence that labor activities are distributed unevenly across space, detailed statistics on the geographical distribution of labor and work are not readily available. To fill this gap, we demonstrated an approach to create fine-scale gridded occupation maps by means of downscaling district-level labor statistics informed by remote sensing and other spatial information. We applied a super learner algorithm that combines the results of different machine learning models to predict the shares of six major occupation categories and the labor force participation rate at a resolution of 30 arc seconds (1x1 km) in Vietnam. The results are subsequently combined with gridded information on the working-age population to produce maps of the number of workers per occupation. The super learners outperform (n =4) or have similar (n = 3) accuracy in comparison to best-performing single machine learning algorithms. A comparison with an independent high-resolution wealth index showed that the shares of the four low-skilled occupation categories (91% of the labor force), were able to explain between 27% and 45% of the spatial variation in wealth in Vietnam, pointing at a strong spatial relationship between work, income and wealth. The proposed downscaling approach can also be applied to produce maps of other (labor) statistics, which are only available at aggregated levels
Zinc Tellurite Glass System Incorporated with Erbium Oxide and Silver Oxide as Ultra-Broad (S+C+L) Bands Optical Communication
Authors: Nazrin S. N. , Halimah M. K. , Yee S. P. , Boukhris Imed , Kebaili Imen
Published: January 2022

Melt-quenching method was used to synthesize a series of zinc tellurite glasses doped with erbium oxide and silver oxide. At room temperature, X-ray diffraction (XRD) and density measurement were implemented to characterize the prepared glass samples. The amorphous nature of the glass samples is proven from the XRD spectra obtained in this work. The density of the glass showed an increment trend from 4.4673 to 4.9705 g/cm3 when adding more silver oxide, which can prove that the glass strength is higher. For photoluminescence analysis, blue, green and red emissions were found in the glass series under 375 nm excitation wavelength. According to McCumber theory, higher emission cross-section and higher FWHM are efficient for both broadband amplifier and laser application. More extensive and flatter gain with a maximum gain difference has covered both C and L bands for optical communication, providing a few channels in the wavelength division multiplex network (WDM). The high efficiency of optical amplification is justified with a higher gain figure of merit and larger gain bandwidth. According to McCumber’s theory, all the results proved that 0.03 molar fraction of silver oxide is the most optimum concentration to be applied in the optical application. In Judd-Ofelt analysis, spectroscopic quality factor and shorter lifetime is a crucial parameter for obtaining intense laser transition, strong emission probabilities and encouraging the laser optical transition, which was successfully attained in all glass samples. The present glass system is also applicable for white light application since the standard equal energy point from all glass samples were located near the center of the CIE diagram (0.33, 0.33). In the meantime, higher values of CCT range from 6761 to 6937 K produce light with a better image as compared to lower CCT. Higher CCT is commercially used in LCD (liquid crystal display) and CRT (cathode ray tube) screens. The colour purity is a parameter for better white LED application, whereas low colour purity is for pure white light emission. Therefore, lower colour purity was found around 10.7 around 18.8% in all glass samples.
Pathological Count of Igg4-Positive Plasmacytes Suggests Extraophthalmic Involvement And Relapse In Patients With Igg4-Related Ophthalmic Disease: A Retrospective Study
Authors: Yuan Yiqun , Meng Fengxi , Ren Hui , Yue Han , Xue Kang , Zhang Rui
Published: January 2022

Background: IgG4-related ophthalmic disease (IgG4ROD) is a phenotype of IgG4-related disease (IgG4RD) with ophthalmic involvement. The pathological IgG4+ plasmacyte count has only been used for diagnosis. We aimed to explore its possible clinical value in the management of IgG4ROD.Methods: Fifty-five pathologically diagnosed IgG4ROD patients were included, and their clinical, pathological, serological, and radiological findings and treatment outcomes were reviewed and analyzed. The pathological IgG4+ plasmacyte counts in lesions from different anatomic sites were compared, and their association with serum IgG4 concentrations, systemic involvement and relapse risk was analyzed.Results: The patients were divided into groups according to the anatomic site of their biopsied lesions, namely, the lacrimal gland, extraocular muscle and orbital soft tissue. No significant difference was found in the pathological IgG4+ plasma cell counts among these groups (p=0.975). The pathological IgG4+ plasmacyte count positively correlated with the IgG4 concentration in peripheral blood (R2=0.5469, p<0.001). The serum IgG4 concentration and the pathological infiltrating IgG4+ plasmacyte count were significantly higher in patients with extraophthalmic involvement (p<0.001 and p=0.005, respectively). The areas under the receiver operating characteristic (ROC) curve (AUCs) of the serum IgG4 level and pathological IgG4+ plasmacyte count for identifying systemic involvement were 0.897 (p<0.001) and 0.759 (p=0.015), respectively. The patients with relapse had higher levels of serum IgG4, more germinal centers (GCs), and infiltrating IgG4+ plasmacytes in lesions. Multivariate Cox regression analysis revealed that a pathological IgG4+ plasmacyte count of >150/high-power field (HPF) and an elevated serum IgG4 level of >500 mg/dL were risk factors for relapse after steroid treatment.Conclusions: Lesions from different ophthalmic sites in IgG4ROD patients have similar counts of IgG4+ and IgG+ plasmacytes. The quantity of pathological IgG4+ plasmacytes corresponded to the serum IgG4 concentration in patients with IgG4ROD and could be meaningful in identifying systemic involvement and predicting subsequent relapse.