bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Performance Flip-Structure Enhancement-Mode HEMT with Face-to-Face Double Gates
Authors: Deng Siyu , Wei Jie , Zhang Cheng , Liao Dezun , Sun Tao , Yang Kemeng , Xi Lufan , Zhang Bo , Luo Xiaorong 
Published: August 2022

AbstractA novel double gates flip-structure enhancement-mode (E-mode) high electron mobility transistor with step field plate (DFF HEMT) is proposed. It features face-to-face double gates, including a top trench MIS gate with a step field plate and a bottom planar MIS gate, which is shorted together. In the on-state, the double gates not only can restore the 2DEG by the higher electric potential, but also can form the electron accumulation layers, and thus increase the saturation output current and reduce the on-resistance. The face-to-face double gates together deplete the 2DEG by using the work function difference to realize E-mode, instead of by etching the AlGaN layer under the gate for the conventional MIS gate E-mode HEMT. The double-gate structure not only avoids etch damage, but also maintains both high threshold voltage and low on-resistance. Meanwhile, the step gate field plate modulates E-field distribution to increase the BV. In order to easily fabricate, the trench gate with step field plate must be located on the top of device, forming the flip-structure. The flip-structure is also beneficial to decrease the leakage current in the substrate. The simulated Vth, BV and Id of the DFF HEMT are 0.8 V, 465 V and 494 mA/mm, respectively. The FOM of the DFF HEMT is 79.8% and 444.2% higher than those of the conventional MIS-FP HEMT and MIS HEMT.
Integration of protein context improves protein-based COVID-19 patient stratification
Authors: Gao Jinlong , He Jiale , Zhang Fangfei , Xiao Qi , Cai Xue , Yi Xiao , Zheng Siqi , Zhang Ying , Wang Donglian , Zhu Guangjun , Wang Jing , Shen Bo , Ralser Markus , Guo Tiannan , Zhu Yi 
Published: August 2022

Abstract
Background
Classification of disease severity is crucial for the management of COVID-19. Several studies have shown that individual proteins can be used to classify the severity of COVID-19. Here, we aimed to investigate whether integrating four types of protein context data, namely, protein complexes, stoichiometric ratios, pathways and network degrees will improve the severity classification of COVID-19.

Methods
We performed machine learning based on three previously published datasets. The first was a SWATH (sequential window acquisition of all theoretical fragment ion spectra) MS (mass spectrometry) based proteomic dataset. The second was a TMTpro 16plex labeled shotgun proteomics dataset. The third was a SWATH dataset of an independent patient cohort.

Results
Besides twelve proteins, machine learning also prioritized two complexes, one stoichiometric ratio, five pathways, and five network degrees, resulting a 25-feature panel. As a result, a model based on the 25 features led to effective classification of severe cases with an AUC of 0.965, outperforming the models with proteins only. Complement component C9, transthyretin (TTR) and TTR-RBP (transthyretin-retinol binding protein) complex, the stoichiometric ratio of SAA2 (serum amyloid A proteins 2)/YLPM1 (YLP Motif Containing 1), and the network degree of SIRT7 (Sirtuin 7) and A2M (alpha-2-macroglobulin) were highlighted as potential markers by this classifier. This classifier was further validated with a TMT-based proteomic data set from the same cohort (test dataset 1) and an independent SWATH-based proteomic data set from Germany (test dataset 2), reaching an AUC of 0.900 and 0.908, respectively. Machine learning models integrating protein context information achieved higher AUCs than models with only one feature type.

Conclusion
Our results show that the integration of protein context including protein complexes, stoichiometric ratios, pathways, network degrees, and proteins improves phenotype prediction.
CircWalk: a novel approach to predict CircRNA-disease association based on heterogeneous network representation learning
Authors: Kouhsar Morteza , Kashaninia Esra , Mardani Behnam , Rabiee Hamid R. 
Published: August 2022

AbstractBackgroundSeveral types of RNA in the cell are usually involved in biological processes with multiple functions. Coding RNAs code for proteins while non-coding RNAs regulate gene expression. Some single-strand RNAs can create a circular shape via the back splicing process and convert into a new type called circular RNA (circRNA). circRNAs are among the essential non-coding RNAs in the cell that involve multiple disorders. One of the critical functions of circRNAs is to regulate the expression of other genes through sponging micro RNAs (miRNAs) in diseases. This mechanism, known as the competing endogenous RNA (ceRNA) hypothesis, and additional information obtained from biological datasets can be used by computational approaches to predict novel associations between disease and circRNAs.ResultsWe applied multiple classifiers to validate the extracted features from the heterogeneous network and selected the most appropriate one based on some evaluation criteria. Then, the XGBoost is utilized in our pipeline to generate a novel approach, called CircWalk, to predict CircRNA-Disease associations. Our results demonstrate that CircWalk has reasonable accuracy and AUC compared with other state-of-the-art algorithms. We also use CircWalk to predict novel circRNAs associated with lung, gastric, and colorectal cancers as a case study. The results show that our approach can accurately detect novel circRNAs related to these diseases.ConclusionsConsidering the ceRNA hypothesis, we integrate multiple resources to construct a heterogeneous network from circRNAs, mRNAs, miRNAs, and diseases. Next, the DeepWalk algorithm is applied to the network to extract feature vectors for circRNAs and diseases. The extracted features are used to learn a classifier and generate a model to predict novel CircRNA-Disease associations. Our approach uses the concept of the ceRNA hypothesis and the miRNA sponge effect of circRNAs to predict their associations with diseases. Our results show that this outlook could help identify CircRNA-Disease associations more accurately.
Comprehensive analysis of RNA m6A methylation in pressure overload-induced cardiac hypertrophy
Authors: Li Weidong , Xing Chenxv , Bao Limeng , Han Shengna , Luo Tianxia , Wang Zhiju , Fan Hongkun 
Published: August 2022

Abstract
Aim
To analyze and compare the mRNA N6-methyladenosine modifications in transverse aortic constriction induced mice hearts and normal mice hearts.

Materials and methods
Colorimetric quantification was used to probe the changes in m6A modifications in the total RNA. The expression of m6A-related enzymes was analyzed via qRT-PCR and western blotting. RNA-seq and MeRIP-seq were performed to identify genes with differences in m6A modifications or expression in the transcriptome profile.

Results
Compared with the control group, the TAC group exhibited higher m6A methylation levels. FTO and WTAP were downregulated after TAC, while METTL3 was significantly downregulated at the protein level. MeRIP-seq revealed that 1179 m6A peaks were upmethylated and 733 m6A peaks were downmethylated, and biological analysis of these genes exhibited a strong relationship with heart function.

Conclusion
Our findings provide novel information regarding m6A modification and gene expression changes in cardiac hypertrophy, which may be fundamental for further research.
Patterns and trends of antibacterial treatment in patients with urinary tract infections, 2015–2019: an analysis of health insurance data
Authors: Schmiemann Guido , Hoffmann Falk , Hamprecht Axel , Jobski Kathrin 
Published: August 2022

AbstractBackgroundUrinary tract infections are among the most common reason for encounter and subsequent antibiotic prescriptions. Due to the risk of collateral damage and increasing resistance rates, explicit recommendations against the use of fluoroquinolones like ciprofloxacin in uncomplicated urinary tract infections have been issued. However, to what extent these recommendations were followed and if there are relevant differences between the disciplines involved (general practitioners, urologists, paediatricians and gynaecologists) are unknown.MethodsWe used anonymized data from a local statutory health insurance (SHI) company, which covered about 38% of all SHI-insured persons in the federal state of Bremen, Germany between 2015—2019. Data included demographics, outpatient diagnoses and filled prescriptions on an individual level.ResultsOne-year prevalence of urinary tract infections was 5.8% in 2015 (females: 9.2%, males: 2.5%). Of all 102,715 UTI cases, 78.6% referred to females and 21.4% to males, 6.0% of cases were younger than 18 years. In females, general practitioners were the most common diagnosing speciality (52.2%), followed by urologists (20.0%) and gynaecologists (16.1%). Overall, fluoroquinolones were most often prescribed (26.3%), followed by fosfomycin (16.1%) and the combination of sulfamethoxazole and trimethoprim (14.2%). Fluoroquinolones were most often prescribed by urologists and general practitioners, while gynaecologists preferred fosfomycin. During the study period, shares of fluoroquinolones decreased from 29.4% to 8.7% in females and from 45.9% to 22.3% in males.ConclusionsDespite a clear trend toward a more guideline adherent prescription pattern, there is still room for improvement regarding the use of second-line antibiotics especially fluoroquinolones. The choice of antibiotics prescribed differs between specialities with higher uptake of guideline-recommended antibiotics by gynaecologists, mainly because of higher prescription shares of fosfomycin.
Inflammatory biomarkers and risk of breast cancer among young women in Latin America: a case-control study
Authors: Fontvieille Emma , His Mathilde , Biessy Carine , Navionis Anne-Sophie , Torres-Mejía Gabriela , Ángeles-Llerenas Angélica , Alvarado-Cabrero Isabel , Sánchez Gloria Inés , Navarro Edgar , Cortes Yorlany Rodas , Porras Carolina , Rodriguez Ana Cecilia , Garmendia Maria Luisa , Soto José Luis , Moyano Leonor , Porter Peggy L. , Lin Ming Gang , Guenthoer Jamie , Romieu Isabelle , Rinaldi Sabina ,   PRECAMA team, Tejeda Jenny , Lazcano María Felix , Franco Libia Zulema , Jaramillo Roberto , Angel Alberto , Ossa Carlos Andres , Arias William H. , Bedoya Gabriel , Cock-Rada Alicia , Echeverri Carolina , Herazo Fernando , Díaz-Yunez Israel , Hernández Angel , Cortes Bernal , Gonzalez Paula , Ocampo Rebecca , Guillen Diego , Loría Viviana , Vial Catalina , Diaz Lizette , Donato Elizabeth , Donn Thomas , Wirtala Kelly , Loucks Hailey 
Published: August 2022

Abstract
Background
Breast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer development, but data is limited in premenopausal women, especially in Latin America.

Methods
We investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors.

Results
IL-6 (ORper standard deviation (SD) = 1.33 (1.11–1.60)) and TNF-α (ORper SD = 1.32 (1.11–1.58)) were positively associated with breast cancer risk in fully adjusted models. Evidence of heterogeneity by estrogen receptor (ER) status was observed for IL-8 (P-homogeneity = 0.05), with a positive association in ER-negative tumors only. IL-8 (P-homogeneity = 0.06) and TNF-α (P-homogeneity = 0.003) were positively associated with risk in the largest tumors, while for leptin (P-homogeneity = 0.003) a positive association was observed for the smallest tumors only.

Conclusions
The results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women.
Bi-columnar locking plate fixation through a combined medial and lateral approach for the treatment of low transcondylar fractures of the distal humerus in the elderly
Authors: Park Sam-Guk , Seok Hyun-Gyu 
Published: August 2022

Abstract
Background
Low transcondylar fractures (LTFs) of the distal humerus are relatively uncommon elbow injuries in elderly patients after low-energy injuries. Although there is still debate regarding the method of fixation, several surgeons prefer bi-columnar fixation using pre-contoured locking plates. However, posterior approaches, which are usually used to perform the above procedure, have disadvantages, such as ulnar nerve neuropathy, damage to the extensor mechanism, and the need for general anesthesia. To solve these problems, the authors designed a combined medial and lateral approach. The purpose of this study was to present the outcomes of bi-columnar internal fixation through a combined medial and lateral approach for the treatment of LTFs of the distal humerus in the elderly.

Methods
A total of 46 patients diagnosed with distal humeral fractures between May 2017 and April 2020 were included. Thirty patients were excluded, and 16 patients who underwent open reduction and internal fixation by the medial and lateral approach were selected. We carried out all the surgeries under brachial plexus anesthesia. The clinical outcomes were assessed based on the visual analog scale (VAS) score, Mayo elbow performance score (MEPS), disabilities of the arm, shoulder, and hand (DASH) score, and range of motion (ROM) of the elbow joint. Standardized radiographs were obtained at 3, 6, and 12 months after surgery and at the last follow-up visit to evaluate for bony union and to check for complications, such as ulnar nerve neuropathy and heterotopic ossification.

Results
The mean age was 81 years (range, 65–91 years). Bony union was achieved in 15 out of 16 patients. The mean VAS score was 2.1 (range, 0–6), the mean MEPS was 84.4 (range, 70–100), and the mean DASH score was 20.6 (range, 9.5–33.6). There were three complications including reduction loss, skin necrosis, and stiffness of the elbow. There was no ulnar nerve neuropathy. The post-operative ROM was 100 degrees or higher in all cases, which did not cause any impairment in daily life.

Conclusion
LTFs of the distal humerus in the elderly can yield satisfactory results with bi-columnar internal fixation through a combined medial and lateral approach.
Knowledge, practice and perceived barriers towards chemotherapy induced nausea and vomiting in prophylaxis guideline adherence among nurses in oncology units at selected hospitals, in Addis Ababa, Ethiopia, a cross-sectional study
Authors: Gebre Deneke , Murugan Rajalakshmi , Bizuwork Ketema , Wurjine Teshome Habte 
Published: August 2022

Abstract
Background
Chemotherapy-induced emesis can be prevented by the use of recommended guidelines for antiemetic regimens but a research study indicates that in Ethiopia the use of standard antiemetic drug guidelines is very limited.

Objectives
To assess knowledge, practice, and perceived barriers towards chemotherapy-induced nausea and vomiting in prophylaxis guideline adherence among nurses in oncology units.

Methods
A cross-sectional study design was conducted among 81 oncology nurses selected in the two public hospitals of Addis Ababa, from March 1 to 30, 2020. The study participants were selected by using the population census method from the source population of nurses in oncology units. Data has collected by using semi-structured questionnaires with the self-administrated method. Data were analyzed by using Statistical Package for the Social Sciences software version 24. Descriptive statistics and logistic regression including bivariate and multivariate were conducted to examine the association between independent and outcome variables. The level of significance was determined at a p-value < 0.05 and a 95% confidence interval.

Result
Seventy-nine nurses participated with a 96% of response rate. All participants were aged greater than 24 with a mean age of 28.8 ± 6 years and nearly two-thirds of the respondents (60.8%) were females. Nurses were not trained in chemotherapy-induced nausea and vomiting management shows 54.4%. nurses’ knowledge of chemotherapy-induced nausea and vomiting prophylaxis Guidelines was 78.5%. The means score of oncology nurses’ practice toward guideline recommendation was 41.8%. Knowledge of nurses associated with the use of chemotherapy-induced nausea and vomiting prophylaxis guideline recommendations working in the outpatient department, inpatient ward, and chemotherapy administration unit has a significant association with chemotherapy-induced nausea and vomiting management knowledge. In the multiple logistic regression analysis, nurses who have trained for chemotherapy-induced nausea and vomiting management were 1.64-fold more aware than those who were not trained.

Conclusion
The study reveals that nurses working in the oncology unit of the study hospitals have a poor practice of Chemotherapy-Induced Nausea and Vomiting. Therefore, recommended providing Training for the Nurses working in the oncology unit and encourage them to apply standard guidelines.
Nectin-4 promotes osteosarcoma progression and metastasis through activating PI3K/AKT/NF-κB signaling by down-regulation of miR-520c-3p
Authors: Liu Yongheng , Li Guanghao , Zhang Yan , Li Lili , Zhang Yanting , Huang Xiaoyu , Wei Xianfu , Zhou Peng , Liu Ming , zhao Gang , Feng Jinyan , Wang Guowen 
Published: August 2022

AbstractPurposeNectin-4 is specifically up-regulated in various tumors, exert crucial effects on tumor occurrence and development. Nevertheless, the role and molecular mechanism of Nectin-4 in osteosarcoma (OS) are rarely studied.MethodsThe expression of Nectin-4 and its relationship with clinical characteristics of OS were investigated using OS clinical tissues, tissue microarrays, TCGA, and GEO databases. Moreover, the effect of Nectin-4 on cell growth and mobility was detected by CCK-8, colony formation, transwell, and wound-healing assays. The RT-qPCR, Western blotting, and luciferase reporter assays were performed to explore molecular mechanisms through which Nectin-4 mediates the expression of miR-520c-3p, thus modulating PI3K/AKT/NF-κB signaling. In vivo mice models constructed by subcutaneous transplantation and tail vein injection were used to validate the functional roles of Nectin-4 and miR-520c-3p.ResultsNectin-4 displayed a higher expression in OS tumor tissues compared with normal tissues, and its overexpression was positively associated with tumor stage and metastasis in OS patients. Functionally, Nectin-4 enhanced OS cells growth and mobility in vitro. Mechanistically, Nectin-4 down-regulated the levels of miR-520c-3p that directly targeted AKT-1 and P65, thus leading to the stimulation of PI3K/AKT/NF-κB signaling. In addition, the expression of miR-520c-3p was apparently lower in OS tissues than in normal tissues, and its low expression was significantly related to tumor metastasis. Furthermore, ectopic expression of miR-520c-3p markedly blocked the effect of Nectin-4 on OS cell growth and mobility. Knockdown of Nectin-4 could suppress the tumorigenesis and metastasis in vivo, which could be remarkably reversed by miR-520c-3p silencing.ConclusionsNectin-4 as an oncogene can promote OS progression and metastasis by activating PI3K/AKT/NF-κB signaling via down-regulation of miR-520c-3p, which could represent a novel avenue for identifying a potential therapeutic target for improving patient outcomes.
The geospatial and conceptual configuration of the natural environment impacts the association with health outcomes and behavior in children and adolescents
Authors: Nigg Carina , Niessner Claudia , Burchartz Alexander , Woll Alexander , Schipperijn Jasper 
Published: August 2022

Abstract
Background
Studies investigating associations between natural environments and health outcomes or health behaviors in children and adolescents yielded heterogenous results to date. This may be the result of different geospatial configurations of the natural environment and confounding characteristics of the study population. Thus, we investigated how the relationship between the natural environment and mental health, muscular fitness, and physical activity varies depending on the geospatial configuration of nature and children’s and adolescents’ characteristics.

Methods
Data were derived from the German Motorik-Modul (MoMo) cohort study (2018–2020) that investigates physical activity, muscular fitness, and health parameters in a national sample of children and adolescents (N = 2843) between four and 17 years (Mage = 10.46 ± 3.49 years; 48.3% girls). Mental health was assessed via questionnaire, muscular fitness via standing long jump, and physical activity with 7-day accelerometer measurement. Using geographic information systems, land cover, and land use data, three different nature definitions were applied. Both circular buffers (100–1000 m) and street-network buffers (1000–5000 m) were created for each of the nature definitions. Associations were explored with linear regression models, and interaction analysis was used to investigate how those relationships vary by gender, age, and socio-economic status.

Results
The relationship between the three outcomes and the natural environment varied considerably depending on the nature definition, buffer size, and buffer type, as well as socio-demographic characteristics. Specifically, when comparing youth with a high socio-economic status to those with a medium socio-economic status, smaller circular buffer distances were related to less physical activity, but larger street-network buffer distances were related to greater mental health problems. Distinct relationships also occurred for youth with low socio-economic status in those relationships, with the pattern being less clear.

Conclusions
For future health research studies that investigate the role of the natural environment, we argue for the development of an a-priori model that integrates both geospatial considerations (nature definition, buffer type, and buffer size) and conceptual considerations (health outcome/behavior, sample characteristics) based on potentially underlying mechanisms that link the natural environment and the health outcome or behavior under investigation to theoretically underpin the geospatial configuration of the natural environment.
Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment
Authors: Gu Jun , Zhao Gang , Yu Jiangkun , Xu Pei , Yan Jiabin , Jin Zhengshuai , Chen Sheng , Wang Yong , Zhang Leshuai W. , Wang Yangyun 
Published: August 2022

AbstractAlthough combination chemoimmunotherapy shows promising clinical results for cancer treatment, this approach is largely restricted by variable objective response rate and severe systemic adverse effects of immunotherapeutic antibody and chemotherapeutic drugs. Therefore, an in situ-formed therapeutic silk-chitosan composite scaffold is fabricated in this study to allow local release of the chemotherapeutic drug doxorubicin (DOX) and JQ1 (small molecular inhibitor used for the extraterminal protein BRD4 and bromodomain) with control release kinetics. DOX-JQ1@Gel contains a pH-degradable group that releases therapeutics in a weak acidic tumor microenvironment. The released DOX could directly kill tumor cells or lead to immunogenic cell death, thereby triggering the response of antitumor immunity. Meanwhile, chemotherapy-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to trigger the response of antitumor immunity. Finally, the DOX-JQ1@Gel is locally injected to evaluate its synergistic cancer therapeutic effect, which is expected to improve objective response rate of immunotherapy and minimize systemic side effects.
Graphical Abstract