bluuebunny/crossref_metadata_2025 huggingface dataset:
A deep learning approach for automated diagnosis of pulmonary embolism on computed tomographic pulmonary angiography
Authors: Ajmera Pranav , Kharat Amit , Seth Jitesh , Rathi Snehal , Pant Richa , Gawali Manish , Kulkarni Viraj , Maramraju Ragamayi , Kedia Isha , Botchu Rajesh , Khaladkar Sanjay
Published: August 2022

Background
Computed tomographic pulmonary angiography (CTPA) is the diagnostic standard for confirming Pulmonary Embolism (PE). Since PE is a life-threatening condition, early diagnosis and treatment are critical to avoid PE-associated morbidity and mortality. However, the diagnosis of PE remains subject to misdiagnosis.
Methods
We retrospectively identified 251 CTPAs performed at a tertiary care hospital between January 2018 to January 2021. The scans were classified as positive (n = 55) and negative (n = 196) for PE based on the annotations made by board-certified radiologists. A fully anonymized CT slice served as input for detection of PE by the 2D segmentation model comprising U-Net architecture with Xception encoder. The diagnostic performance of the model was calculated at both the scan and the slice levels.
Results
The model correctly identified 44 out of 55 scans as positive for PE and 146 out of 196 scans as negative for PE with a sensitivity of 0.80 [95% CI: 0.68, 0.89], a specificity of 0.74 [95% CI: 0.68, 0.80], and an accuracy of 0.76 [95% CI: 0.70, 0.81]. On slice level, 4817 out of 5183 slices were marked as positive for the presence of emboli with a specificity of 0.89 [95% CI: 0.88, 0.89], a sensitivity of 0.93 [95% CI: 0.92, 0.94], and an accuracy of 0.89 [95% CI: 0.887, 0.890]. The model also achieved an AUROC of 0.85 [0.78, 0.90] and 0.94 [0.936, 0.941] at scan level and slice level, respectively for the detection of PE.
Conclusion
The development of an AI model and its use for the identification of pulmonary embolism will support healthcare workers by reducing the rate of missed findings and minimizing the time required to screen the scans.
RETRACTED: Quality testing of mifepristone and misoprostol in 11 countries
Authors: Bower Jason , Chinery Lester , Fleurent Alessandra , Gülmezoglu A. Metin , Im-Amornphong Wallada , Kilfedder Catherine , Procter Petra , Tomazzini Alessandra
Published: August 2022

The authors have requested that this preprint be removed from Research Square.
Construction of a prognostic model for hepatocellular carcinoma patients through bioinformatics analysis
Authors: Jia Jun , Li Dong , Zhang Dan , Cai Jiao , Li Fu , Duan Xue-zhang
Published: August 2022

Backgrounds: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Obesity is closely related to the incidence of various malignant tumors. However, the impact of obesity on tumor prognosis varies with tumor type. Our study used bioinformatics analysis to explore whether body mass index (BMI)-related genes influence the prognosis of hepatocellular carcinoma patients and its potential mechanism. Materials and Methods: We obtained HCC expression data from The Cancer Genome Atlas (TCGA) database and performed Least absolute shrinkage selection operator (LASSO) regression analysis to construct a prognostic model. The International Cancer Genome Consortium (ICGC)-HCC data were used as an independent validation dataset. Results: The prognosis of HCC patients with high BMI was significantly better than that of HCC patients with low BMI. We constructed a prognostic model composed of four genes (-0.092733248*ANXA10-0.168489516*CAPN3-0.204693987*PPP1R32 + 0.097937712*ZNF239) through LASSO regression analysis, which was performed on 101 significantly differentially expressed coding proteins between high- and low-BMI patients. Conclusion: We constructed a prognostic model for HCC patients using integrated bioinformatics analysis and identified four biomarkers that may be used as new therapeutic targets.
Vibrio cholerae circulating throughout a mass vaccination campaign in the Forcibly Displaced Myanmar National population in Cox’s Bazar, Bangladesh
Authors: Taylor-Brown Alyce , Afrad Mokibul , Khan Ashraful Islam , Lassalle Florent , Islam Md. Taufiqul , Tanvir Nabid Anjum , Thomson Nick , Qadri Firdausi
Published: August 2022

Over the last decade, the influx of Forcibly Displaced Myanmar Nationals (FDMNs) into Bangladesh has increased the population of Cox’s Bazar. Due to the already high population density coupled with poor living conditions, FDMNs and the host population of Bangladeshi Nationals (BGDNs) were at heightened risk of diarrhoeal disease outbreaks. Due to this, a nationwide sentinel surveillance programme was established, which revealed that there were seasonal localised sporadic cholera outbreaks in Cox’s Bazar. In this study, we aimed to infer the epidemic risk of the Vibrio cholerae strains circulating in the FDMN and BGDN populations, by determining if isolates linked to the current cholera pandemic were responsible for these outbreaks. Further, to better understand the dynamics of cholera before and during the mass oral cholera vaccination campaign conducted in Cox’s Bazar – the largest in the last decades – we also wanted to understand the links between these circulating strains and the current radiation of lineages causing disease in Haiti and Yemen – places in which reactive vaccination campaigns were conducted in response to outbreaks following humanitarian crises. To do this, we sequenced 223 V. cholerae isolates obtained from stool collected from ten intra-district surveillance sites in Cox’s Bazar, sampling both the FDMN and BGDN subpopulations over a period spanning the pre-and post-vaccination campaign (2014–2019). Phylogenetic analysis of these genomes showed that all isolates belonged to the epidemic “7PET” lineage – responsible for the current cholera pandemic – branching alongside V. cholerae that were circulating in Dhaka and Kolkata between 2014 and 2018. Two distinct sublineages of V. cholerae were present in Cox’s Bazar during the study period; one lineage (PG 1.3) that had radiated globally, and another lineage (PG 1.5) that was restricted to Asia and the Middle East. PG 1.3 was associated with a shorter duration of diarrhoea and lower relative risk of rice watery stool compared to PG 1.5. Given the nature and diversity of the V. cholerae isolated from the BGDN and FDMN subpopulations in Cox’s Bazar, without a vaccine intervention, the risk of local or widespread epidemics or even a pandemic was very high.
Competing Endogenous RNA Network Analysis of the Molecular Mechanisms of Ischemic Stroke
Authors: Chen Jian-Min , Li Xiao-Lu , Chen Qing-Fa , Yang Ye , Xu Sen-Ming , Xu Jianwen
Published: August 2022

Object Through the construction of a competing endogenous RNA (ceRNA) network, this study aimed to search for and investigate the possible molecular mechanisms of potential biomarkers associated with ischemic stroke (IS). Method Seven expression profiles of miRNA, mRNA, and lncRNA were downloaded from the NCBI GEO database. Following the exploration of the differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs), and mRNAs (DEmRNAs), the lncRNA–miRNA and miRNA–mRNA pairs were predicted with target prediction tools, and a ceRNA network was constructed. Subsequently, functional enrichment analyses were performed, a protein–protein interaction (PPI) network was constructed, and the immune cell infiltration landscapes were evaluated using the CIBERSORT algorithm. Finally, we identified the key lncRNAs, miRNAs, and mRNAs of IS using bioinformatics methods and assessed their diagnostic efficacy in the validation datasets. The expression of these key genes was also validated using the quantitative real-time polymerase chain reaction (qRT-PCR) in PC12 cells. Results We constructed the ceRNA network for IS. The DEmRNAs were mainly enriched in inflammatory signaling pathways through enrichment analysis. In the cerebral infarction group, the B cells naïve, T cells naïve, and monocytes had statistically different numbers compared with the control group. We used the criterion AUC > 0.7 to screen key miRNAs, mRNAs, and lncRNA. Finally, six key RNAs were identified. The verification results of the relative RNA expression by qRT-PCR were consistent with the results of the bioinformatics analysis. Conclusion Our results suggest that the ceRNA network exerted an important role in the inflammatory pathogenesis of IS and provided a new strategy to conduct IS research.
BETi enhance ATGL expression and its lipase activity to exert their antitumoral effects in triple-negative breast cancer (TNBC).
Authors: Rossi Teresa , Zamponi Raffaella , Chirico Mattea , Pisanu Maria Elena , Iorio Egidio , Torricelli Federica , Gugnoni Mila , Ciarrocchi Alessia , Pistoni Mariaelena
Published: August 2022

Background
Triple-Negative Breast Cancer (TNBC) is a subtype of breast cancer that differs from other types of invasive breast cancers in the faster spread and worse outcome and it presents limited treatment options. Bromodomain and extra-terminal domain (BET) family proteins are epigenetic readers that control the expression of different oncogenic proteins. BET inhibitors (BETi) are drugs that obstruct BET proteins’ function and are considered a promising anti-cancer strategy. Recent evidence also demonstrated that BET proteins exert their function in regulating metabolic processes.
Methods
RNA-sequencing analysis in TNBC cell lines showed differentially express genes involved in lipid metabolisms after BETi treatment. We mimicked ATGL activity with the short-chain fatty acid (FA) propionate and assessed ATGL function by the ATGL knockdown (KD) in TNBC cell lines. We evaluated ATGL KD effects by analyzing proliferation, the expression of several metabolic genes, lipolysis, mitochondrial function, and metabolic activity in the presence or absence of BETi. Chromatin Immunoprecipitation identified FoxO1 binding to the PNPLA2 promoter.
Results
Treatment of TNBC cells with two BETi markedly increased ATGL expression and lipolytic function, decreasing intracellular lipid content in the dose and time-dependent. The intracellular composition of FAs after BETi treatment reflected a significant reduction in neutral lipids. We confirmed the dependency of TNBC on FAs by mimicking ATGL activity with the short-chain FA propionate. We established that ATGL KD decreased ROS, upregulated SOD1 level, and reduced CPT1a. ATGL KD helps to switch from mitochondrial ß-oxidation to a glycolytic phenotype as their expression analysis revealed an upregulation of glycolytic markers and downregulation of ß-oxidation genes. The enhanced glycolysis reflected a marked increase in the mitochondrial metabolic activity measured by the MTT assay. Finally, we found FoxO1 upregulated upon JQ1 treatment. We established that FoxO1 binds the PNPLA2 promoter only after BETi usage and FoxO1 overexpression leads to ATGL induction. However, FoxO1 only partially prompted the induction of ATGL expression by BETi.
Conclusions
Although the anti-proliferative effects achieved by BETi are not dependent on ATGL mediating lipolysis, the results of this study showed that BETi promoted their antitumoral effects by altering mitochondrial dynamics through ATGL
CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR-140-5p/LMNB1 axis
Authors: Fu Wen , Wang Xianxing , Xiang Jifeng , Chen Shengkai , Xia Renpei , Qin Fanbo , Li Zhuo , Wang Huaizhi , Xie Chuanming , Liu Changjiang
Published: August 2022

Background
Growing evidence suggests that circular RNAs (circRNAs) are important factors in cancer progression. Nevertheless, the role of circRNAs in the progression of pancreatic ductal adenocarcinoma (PDAC) remains unclear.
Methods
CircPTPRA was identified based on our previous circRNA array data analysis. Wound healing, transwell and EdU assays were performed to investigate the effect of circPTPRA on the migration, invasion and proliferation of PDAC cells in vitro. RNA pull-down, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were conducted to verify the binding of circPTPRA with miR-140-5p. Subcutaneous xenograft models were constructed for in vivo experiments.
Results
CircPTPRA was significantly upregulated in PDAC tissues and cells compared to normal controls. Moreover, circPTPRA overexpression was positively correlated with lymph node invasion and worse prognosis in PDAC patients. In addition, overexpression of circPTPRA promoted PDAC migration, invasion, proliferation and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, circPTPRA upregulates LaminB1 (LMNB1) expression by sponging miR-140-5p and ultimately promots the progression of PDAC.
Conclusions
This study revealed that circPTPRA plays an important role in the progression of PDAC by sponging miR-140-5p. It can be explored as a potential prognostic marker and therapeutic target for PDAC.
Effects of repetitive twice-weekly tDCS stimulations on fatigue and fatigability in people with multiple sclerosis
Authors: Linnhoff Stefanie , Haghikia Aiden , Zaehle Tino
Published: August 2022

Fatigue is associated with a dramatically decreased quality of life in people with multiple sclerosis (pwMS). It refers to a constant subjective feeling of exhaustion and a performance decline, known as fatigability. However, inconsistency and heterogeneity in defining and assessing fatigue have led to limited advances in understanding and treating MS-associated fatigue. Transcranial direct current stimulation (tDCS) has emerged as a promising, non-pharmaceutical treatment strategy for subjective fatigue. However, whether repetitive tDCS also have long-term effects on time-on-task performance has not yet been investigated. Thus, this pseudorandomized, single-blinded, and sham-controlled study aimed to investigate tDCS effects on behavioral and electrophysiological parameters. PwMS received eight twice-weekly 30-minute tDCS stimulations over the left dorsolateral prefrontal cortex. Fatigability was operationalized as time-on-task-related changes in reaction time variability and P300 amplitude. Additionally, subjective trait and state fatigue ratings were assessed. The results revealed a significant tDCS effect on subjective trait fatigue ratings that lasted at least four weeks after the stimulations. However, the ratings declined after both anodal and sham tDCS. No effects were found on subjective state fatigue and objective fatigability parameters. Linear Mixed Models and Bayesian Regression models likewise favored the absence of a tDCS effect on fatigability parameters. Our results confirm the complex relationship between MS-associated fatigue and fatigability. Reliable and clinically relevant parameters need to be established to extend the potential of tDCS for treating fatigability. Furthermore, our results indicate that consecutive stimulations rather than twice-weekly stimulations should be the preferred stimulation scheme in future studies.
Enhanced pain facilitation rather than impaired pain inhibition in burning mouth syndrome female patients
Authors: Gremeau-Richard Christelle , Pionchon Paul , Mulliez Aurélien , Dualé Christian , Dallel Radhouane
Published: August 2022

Background
Deficient endogenous pain modulation has been implicated in the development and exacerbation of chronic orofacial pain. To date, relatively little is known regarding the function of the endogenous pain modulation in patients with burning mouth syndrome (BMS). This case-control study investigated endogenous pain modulation in women with BMS.
Methods
Conditioned pain modulation (CPM) was assessed upon temporal summation (TSP) of thermal pain. Forty female subjects, 20 BMS patients and 20 age-matched control subjects, were included in a 2 session-protocol. Mechanical and thermal pain thresholds were measured on the forearm and hand. TSP was obtained using repetitive laser-evoked thermal stimuli applied on the non-dominant hand, at an intensity yielding to moderate pain. During TSP, CPM was produced by immersing the contralateral foot in a water bath at painful cold (8°C) temperature. In control conditions, the foot was immersed in a water bath at not painful (30°C) temperature.
Results
BMS was not associated with any impairment in thermal as well as mechanical extracephalic pain thresholds. TSP and CPM efficacy were similar in BMS patients and control subjects. However, BMS patients exhibited enhanced extracephalic heat hyperalgesia.
Conclusion
This study reveals that there is no impairment of endogenous pain inhibition mechanisms in BMS patients, but rather an increase in pain facilitation.
Modelling of immune response in chronic myeloid leukemia patients suggests potential for treatment reduction prior to cessation
Authors: Karg Elena , Baldow Christoph , Zerjatke Thomas , Clark Richard , Roeder Ingo , Fassoni Artur , Glauche Ingmar
Published: August 2022

Discontinuation of tyrosine kinase inhibitor (TKI) treatment is emerging as the main therapy goal for Chronic Myeloid Leukemia (CML) patients. The DESTINY trial showed that TKI dose reduction prior to cessation can lead to an increased number of patients achieving sustained treatment free remission (TFR). However, there has been no systematic investigation to evaluate how dose reduction regimens can further improve the success of TKI stop trials. Here, we apply an established mathematical model of CML therapy to investigate different TKI dose reduction schemes prior to therapy cessation and evaluate them with respect to the total amount of drug used and the expected TFR success. Our systematic analysis confirms clinical findings that the overall time of TKI treatment is a major determinant of TFR success, while highlighting that lower dose TKI treatment for the same duration is equally sufficient for many patients. Our results further suggest that a stepwise dose reduction prior to TKI cessation can increase the success rate of TFR, while substantially reducing the amount of administered TKI. Our findings illustrate the potential of dose reduction schemes prior to treatment cessation and suggest corresponding and clinically testable strategies that are applicable to many CML patients.
The Klotho-FGF23-CPP axis and cardiovascular outcomes in diabetic patients with chronic limb threatening ischemia: a prospective study
Authors: Biscetti Federico , Rando Maria Margherita , Cecchini Andrea Leonardo , Nicolazzi Maria Anna , Angelini Flavia , Iezzi Roberto , Eraso Luis H , Dimuzio Paul J , Pitocco Dario , Gasbarrini Antonio , Massetti Massimo , Flex Andrea
Published: August 2022

Background: Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-FGF23-CPP axis is associated with endothelial injury and cardiovascular risk.The aim of this study was to analyze the relationship between Klotho-FGF23-CPP serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI.Methods: Baseline levels of Klotho, FGF23, and CPP, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER.Results: A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs 446.4 ± 171.7 pg/mL, p<0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs 53.2 ± 15.4 pg/mL, p<0.01) and CPP (461.8 ± 168.6 pg/mL vs 269.3 ± 184.3 pg/mL, p<0.01) were significantly associated with the development of MACE. ROC analysis confirmed the predictive power of the Klotho-FGF23-CPP axis. Furthermore, decreased Klotho serum levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p<0.01).Conclusions: Klotho-FGF23-CPP axis imbalance is a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI.
A Novel Optimization Method for Belief Rule Base Expert System with Activation Rate
Authors: Xiang Gang , Wang Jie , Han XiaoXia , Tang Shuaiwen , Hu Guanyu
Published: August 2022

Although the belief rule base (BRB) expert system has many advantages, such as the effective use of semi-quantitative information, objective description of uncertainty, and efficient nonlinear modeling capability, it is always limited by the problem of combinatorial explosion. The main reason is that the optimization of a BRB with many rules will consume many computing resources, which makes it unable to meet the real-time requirements in some complex systems. Another reason is that the optimization process will destroy the interpretability of those parameters that belong to the inadequately activated rules given by experts. To solve these problems, a novel optimization method for BRB is proposed in this paper. Through the activation rate, the rules that have never been activated or inadequately activated are pruned during the optimization process. Furthermore, even if there is a complete data set and all rules are activated, the activation rate can also be used in the parallel optimization process of the BRB expert system, where the training data set is divided into some subprocesses. The proposed method effectively solves the combinatorial explosion problem of BRB and can make full use of quantitative data without destroying the original interpretability provided by experts. Case studies prove the advantages and effectiveness of the proposed method, which greatly expands the application fields of the BRB expert system.
Research on fractional order modeling and PIλ control strategy of CLLC bi-directional resonant converter
Authors: Li Di , Lv Qingquan , Zhang Zhenzhen , Huang Yunfan , Dong Haiying
Published: August 2022

There are problems such as insufficient modeling accuracy of the CLLC bi-directional resonant converter in integer order, failure to accurately describe the actual conditions of the system, poor dynamic performance of classical PI control strategy, and failure of the system to reach the stable state quickly and smoothly. First, based on the fractional order calculus theory, this paper proposes an extended describing function method based on fractional order, establishes the mathematical model of the fractional order and small signal model of the fractional order of the CLLC bi-directional resonant converter, obtains the fractional order transfer function of the system, constructs the PI λ control strategy of the fractional order of the CLLC bi-directional resonant converter, and builds the simulation model of the CLLC bi-directional resonant converter based on Matlab/Simulink software for simulation verification. Finally, a principle prototype was built in the laboratory to verify the correctness and feasibility of the CLLC bi-directional resonant converter of the fractional order and theoretical analysis of the PI λ control strategy of the fractional order.
Discovery of vaccine-like recombinant SARS-CoV-2 circulating in human
Authors: He Daniel Chang , He Cheng-Qiang
Published: August 2022

For viral diseases, vaccination with live attenuated vaccine (LAV) is one of the most effective means for fighting the diseases. However, LAVs are easy to spill from the vaccinated individuals and circulate in the population with unforeseen consequences. Currently, SARS-CoV-2 LAVs are undergoing clinical trials. In this study, we found that the recombinant viruses isolated from Indian SARS CoV-2 infected persons may be candidate LAV-derived strains, indicating the risk of SARS-CoV-2 LAV spillover from vaccinated persons, increasing the complexity of SARS-CoV-2 detection. In addition, the property of easy recombination of SARS-CoV-2 increases the chance of LAV virulence reversion. Therefore, how to distinguish the LAV viruses from the wild strain and how to avoid the recombination of the circulating vaccine strain and the wild strain are the challenges currently faced by SARS CoV-2 LAV development.
A post-quantum key exchange protocol from the intersection of quadric surfaces
Authors: Tullio Daniele Di , Gyawali Manoj
Published: August 2022

In this paper, we present a new key exchange protocol in which Alice and Bob have secret keys given by quadric surfaces embedded in a large ambient space by means of the Veronese embedding and public keys given by hyperplanes containing the embedded quadrics. Both of them reconstruct the isomorphism class of the intersection which is a curve of genus 1, and is uniquely determined by the j-invariant. An eavesdropper, to find this j-invariant, has to solve problems which are conjecturally quantum resistant.
Fast sensorimotor learning in middle-aged adults
Authors: Kyriazis Diana , Uji Makoto , Bouyagoub Samira , Cercignani Mara , Ford Paul , Sigala Natasha
Published: August 2022

Cognitive training offers a potential approach for the prevention of cognitive decline in later life. Repetition of targeted exercises may improve, or at least preserve, both specific domain and general cognitive abilities by strengthening neural connections and promoting neuroprotective processes within brain networks. Importantly, middle-aged adults have been omitted from the cognitive training literature. In this experiment, we investigated short-term training (1 session) on a perceptual-cognitive-motor task in middle-aged adults. Furthermore, we examined the functional and structural neural correlates of this training. Twenty-one healthy middle-aged adults between the age of 40 and 50 years underwent one scanning session during which they learned and performed the perceptual-cognitive-motor task. We compared performance and functional imaging on the Early and Late Learning phases of the task. We used diffusion MRI to examine baseline microstructural variation in the brain in relation to training outcome. The diffusion indices included fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), and orientation dispersion index (ODI). We found a significant improvement in performance following training on the task. There were also significant training-induced changes in functional activity in cortical and subcortical brain regions. Furthermore, significant correlations were found between the diffusion indices of FA, MD, and ODI and training outcome. These results show fast neuroplasticity in the middle-aged brain, and that variation in brain microstructure underpins fast motor learning.
Teaching-learning in Clinical Education Based on Epistemological Orientations: A Multi- method Study
Authors: Khani Hamed , Ahmady Soleiman , Sabet Babak , Zandi Shirdel , Mohammadimehr Mojgan , Niakan Somayeh
Published: August 2022

IntroductionTeaching-learning is the heart of medical education in the clinical setting. The objective of this research was to develop a conceptual model of effective clinical teaching in undergraduate medical education and conceptualize its operational framework based on the best fit approach.MethodsThis research consisted of three sub-studies conducted using a multi-method approach. The first sub-study was conducted using a qualitative meta-synthesis approach. The second sub-study used Clarke's situational analysis approach as a postmodern version of grounded theory. Finally, the third sub-study was designed in two stages. First, it was conducted using the expert panel, in the second step, framework of synthesis based on best fit, and the framework of Ottenhoff- de Jonge et al., which formed the basis of this study.ResultsIn the first sub-study, qualitative evidence on the factors of effective teaching-learning in clinical education was synthesized into five dimensions. Based on the second sub-study, the clinical teaching-learning situation in undergraduate medical education in Iran was represented in three maps, including situational, social worlds/arenas, and positional. Finally, in the third sub-study, based on model modification and development in the expert panel, the effective teaching-learning dimensions were developed into behavioral, social, pedagogical, technology, contextual, educational leadership, and financial dimensions. In the second step, based on the framework of Ottenhoff- de Jonge et al., a three-dimensional matrix was developed concerning epistemological orientations about teaching and learning.DiscussionMoving from a single teaching-centered and learning-centered orientation to a teaching-learning-centered orientation is required for effective teaching-learning in clinical medical education.
Social Support in Schools and Related Outcomes for LGBTQ Youth: A Scoping Review
Authors: Leung Enoch , Gomez Gabriela Kassel , Sullivan Samantha , Murahara Flavio , Flanagan Tara
Published: August 2022

Recent research has increasingly focused on positive factors and supports for LGBTQ youth. This scoping review explores existing social support for LGBTQ youth in schools through the ecological systems approach to respond to the following four objectives: 1) define social support systems in schools, 2) identify current research on outcomes for LGBTQ youth, 3) identify barriers to support LGBTQ youth in schools, and 4) identify areas for future research for LGBTQ youth and social support in schools. A systematic search (Arksey & O’Malley, 2005) between 2007 through 2021 resulted in 94 articles. This review gave rise to an organizational framework to consolidate various systems of social support for LGBTQ youth in schools. Social support consisted of seven social support systems (family, curriculum, family, peers, school policies, GSAs and programs, and school climate) that are positively associated with the promotion of positive socioemotional, behavioural, and educational outcomes for LGBTQ youth. Though the literature has been clear surrounding the risks associated with LGBTQ youth, this scoping review provides a positive outlook on LGBTQ youth’s school experiences and how these systems of social support allow for LGBTQ youth to act as active participants to foster a positive school climate and sense of safety.
Nuclear-anchored FGFR regulates cell proliferation and cisplatin resistance in pancreatic ductal adenocarcinoma
Authors: Yue Zhi-qiang
Published: August 2022

Background
In natural physiological conditions, FGF is a pleiotropic growth factor with multiple bio-activities and FGF/FGFR system has many important biological functions and roles. Interestingly, more and more evidences show that FGF/FGFR system plays an important role in the occurrence and development of pancreatic ductal adenocarcinoma.
Methods
In our study, we explored the cellular characteristics of FGF/FGFR system in pancreatic ductal adenocarcinoma cells. In addition, we also investigated the relationship between nuclear localized FGF/FGFR and cisplatin resistance. A series of experimental techniques including indirect immunofluorescence, Western-blot and ELISA were used to analyze the cellular characteristics of FGF/FGFR. We systematically assessed the cell behavior of IGF-1/IGF-1R in the Pancreatic ductal adenocarcinoma cell model.
Results
We have three main findings: First, we found that IGF-1R could transport into the cell nuclei of Pancreatic ductal carcinoma cell, and the nuclear-localized FGF/FGFR was closely related to the proliferation of Pancreatic ductal carcinoma cells. Additionally, we also found that the nuclear-localized FGF/FGFR might be closely associated with cisplatin resistance in pancreatic ductal adenocarcinoma, this may be a potential mechanism of cisplatin resistance; Secondly, we found that the nuclear-localized FGF/FGFR showed a positive correlation with the intensity of AKT signaling.
Conclusions
Taken together, this work lays the foundation for further research on the relationship between the nuclear FGF/FGFR and the pancreatic ductal adenocarcinoma development or cisplatin resistance in pancreatic ductal adenocarcinoma.
Typical and anomalous pathways of surface-floating material in the northern North Atlantic and Arctic Ocean
Authors: Herman Agnieszka , Wesławski Jan Marcin
Published: August 2022

Surface waters of the oceans carry large amounts of material, including sediment grains, plankton organisms, ice crystals, as well as pollutants, e.g., oil and plastic. Transport and spatio-temporal distribution of that material depend on its properties and on the dynamical processes in the ocean mixed layer – currents, waves, turbulence, and convective mixing – acting at a wide range of scales. Due to its importance for marine physics, biogeochemistry and ecology, substantial research effort has been put in recent years into observations and modelling of ocean material transport, especially in the context of marine plastic pollution. Nevertheless, many important questions remain unanswered. In this work, numerically simulated trajectories of surface-floating particles in the period 1993–2020 are used to analyze usual and anomalous transport pathways in the northern North Atlantic and the Arctic Ocean. Lagrangian trajectories are computed based on surface currents from a hydrodynamic model and Stokes drift from a spectral wave model. It is shown that due to high amplitudes of Stokes drift (comparable with wind-induced currents in ice-free parts of the domain of study), combined with its high directional variability, it substantially modifies the drifting paths, underlying the important role of wave-induced currents in surface material transport. A statistical analysis of ∼1.6·108 trajectories reveals patterns of connections between nearshore locations in the domain of study, the associated drift times and path sinuosity. Seasonal variability of transport, different in the Arctic Ocean and the North Atlantic, is found for typical transport routes following the larger-scale circulation patterns. Crucially, in both sub-domains episodic, but very strong transport events between otherwise isolated locations occur, associated with anomalous atmospheric circulation and, arguably, providing ‘windows of opportunity’ for dispersal of various organisms to new locations. It is shown for two examples in the North Atlantic region that an unusual combination of atmospheric circulation indices explains the anomalous transport, thus providing a predictive tool for future events. In the Arctic, analogous phenomena are modified by the state of the sea ice cover.
A Selective LVQ Algorithm for Improving Instance Reduction Techniques and its Application for Text Classification
Authors: Hayel Rafa , Hindi Khalil El , Hosny Manar , Alharbi Rawan , Alsalman Hussien
Published: August 2022

Instance-Based learning, such as the k Nearest Neighbor (kNN), is a simple yet effective machine learning algorithm for text classification. However, it may take long classification time and large memory requirement which motivated the development of instance reduction techniques that discard irrelevant and noisy instances. This usually comes at the expense of reducing the classification accuracy. This work proposes a Selective Learning Vector Quantization algorithm (SLVQ) and uses it to fine-tune the reduced datasets in a way that improves their representation of the full dataset. Unlike classical Learning Vector Quantization (LVQ) algorithms, SLVQ can deal with nominal attributes, while using the instances in the reduced datasets as the initial codebook vectors and using the original dataset to fine-tune them. The algorithm addresses the problem of dealing with nominal values, which is crucial, since many real-world datasets contain nominal attributes and require the use of an appropriate distance measure, such as the Value Distance Measure (VDM). SLVQ modifies the Value Difference Metric (VDM) distances between nominal values instead of modifying the weight vectors themselves. Our experimental results using four instance reduction algorithms and 17 text classification datasets demonstrate our approach’s effectiveness in improving the classification accuracy of the reduced sets.
Comparison of pneumonia incidence between long-acting muscarinic antagonist and inhaled corticosteroid plus long-acting beta agonist in patients with COPD : A retrospective cohort study in a real-world setting
Authors: Lee Eung Gu , Kim Youlim , Hwang Yong Il , Yoo Kwang Ha , Lee So Eun , Jung Kyung Yoon , Lee Doik , Park Yong Bum , Rhee Chin Kook
Published: August 2022

Background
Pneumonia is an infectious disease commonly associated with chronic obstructive pulmonary disease (COPD). However, few studies have directly compared the incidence of pneumonia in patients on common COPD treatments such as long-acting muscarinic antagonists (LAMA) with those on inhaled corticosteroids and long-acting β2-agonist (ICS/LABA). Moreover, risk factors for pneumonia in COPD are still unclear. We compared the incidence of pneumonia in COPD patients on LAMA and those on ICS/LABA and explored the risk factors associated with pneumonia.
Methods
This nationwide cohort study used Korean National Health Insurance claim data from January 2002 to April 2016. Patients who received COPD medication, either LAMA or ICS/LABA, with the COPD diagnostic code, were selected. We enrolled patients with good compliance (medication possession ratio ≥ 80%). The primary outcome was pneumonia in COPD patients initiating LAMA or ICS/LABA. We investigated the risk factors associated with pneumonia, including the sub-types of ICS treatments. The observation period was a minimum of 12 months and a maximum of 136 months.
Results
After propensity score matching, the incidence rate per 1,000 person-years of pneumonia was 93.96 for LAMA (n = 1,003) and 136.42 for ICS/LABA (n = 1,003) patients (p < 0.001). The adjusted hazard ratio (HR) for pneumonia in patients on fluticasone/LABA was 1.496 (95% confidence interval [CI] 1.204–1.859) compared with LAMA (p < 0.001). In multivariable analysis, a history of pneumonia was a risk factor associated with pneumonia (HR, 2.123; 95% CI, 1.580–2.852; p < 0.001).
Conclusions
The incidence of pneumonia was higher in COPD patients on ICS/LABA compared with those on LAMA. It is recommended that ICS use be avoided in COPD patients with high pneumonia risk.
Mine tailings-based geopolymers: Durability, microstructure, thermal and leaching properties
Authors: Akeed Mahmoud
Published: August 2022

The mining industry produces a considerable amount of stone waste and tailings, posing an ecological danger. This industrial waste is often disposed of via landfill, which leads to soil degradation and water and air pollution while obtaining valuable land. It can be recycled via a variety of methods, including the promising geopolymerization approach, which converts waste into value. This research investigates recent advancements in the production of geopolymer composites derived from industrial waste and mine tailings as a potential sustainable construction material. This research also provides in-depth analyses of the features and behaviours of mine tailings mixtures utilized in geopolymer production, such as their durability, microstructure, thermal and leaching capabilities. This study also reveals an information gap that must be addressed to progress mine tailings composites for cementitious materials.
The effects of coriander seed supplementation on serum glycemic indices, lipid profile and parameters of oxidative stress in patients with type 2 diabetes mellitus: a randomized double-blind placebo-controlled clinical trial
Authors: Zamany Sanaz , Mahdavi Aida Malek , Pirouzpanah Saeed , Barzegar Ali
Published: August 2022

Background: This research aimed to study the effect of coriander seed supplementation on serum glycemic indices, lipid profile and oxidative stress parameters in patients with type 2 diabetes mellitus (T2DM).Methods: In this randomized double-blinded, placebo-controlled trial, eligible 40 T2DM patients aged 30-60 years were recruited from Sina Hospital (Tabriz, Iran) and randomly assigned into two groups to receive either coriander seed powder (1000 mg/day, n=20) or placebo (1000 mg/day, n=20) for 6 weeks. Anthropometric measurements, dietary intake, and biochemical parameters including fasting blood sugar (FBS), serum insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), high- and low-density lipoprotein cholesterols (HDL-C and LDL-C), malondialdehyde (MDA), and total antioxidant capacity (TAC) were assessed before and after supplementation.Results: Anthropometric measurements were not significantly different between intervention and placebo groups. Coriander seed supplementation led to significant within-group reductions in FBS (156.15±23.19 to 130.30±21.15), serum insulin (17.72±0.47 to 17.12±0.76), HOMA-IR (6.82±0.95 to 5.52±0.99), TC (183.85±55.68 to 145.20±31.36), TG (152.50±37.59 to 130.40 ±27.96), LDL-C (127.35±23.45 to 111.40±25.71), and MDA (1.65±0.15 to 1.49±0.15), whereas there were significant increases observed in serum TAC (1.93±0.12 to 1.97±0.09) (P<0.05). Post-dose comparisons showed significant between-group differences for FBS, serum insulin, HOMA-IR, TC, TG, LDL-C, MDA, and TAC levels after adjusting for baseline values (P<0.05).Conclusions: Coriander seed supplementation was able to improve glycemic indices, lipid profile and oxidative stress status in T2DM and it may be useful complementary treatment in management of these patients.Trial registration: The study protocol was registered on the Iranian Registry of Clinical Trials website (IRCT20190224042821N2) on 2019/Oct/11.
Optimization of analgesia algorithm in strabismus surgery in children: a single-center randomized controlled prospective study
Authors: Oleshchenko I. G. , Iureva T. N. , Bachaldina L. N. , Mankov A. V. , Zabolotskii Dmitrii V.
Published: August 2022

INTRODUCTION. The postoperative period during strabismus surgery in children is often complicated by pain syndrome of different intensity and postoperative nausea and vomiting (PONV), which negatively affects postoperative rehabilitation. Intraoperative regional techniques have a sufficiently high analgesic profile, which serves as a justification for their use. Subtenon blockade refers to minimally invasive interventions. OBJECTIVES. To evaluate the efficacy of subtenone blockade for postoperative anesthesia of children after strabismus surgery. MATERIALS AND METHODS. A single-center open randomized controlled prospective longitudinal study was conducted in parallel groups. Group 1 — 36 patients, acetaminophen 1.5 mg/kg was used for postoperative anesthesia; Group 2 — 38 patients, a subtenon blockade was performed at the end of surgery. The main indicators of hemodynamics at the stages of the study, the level of cortisol and the redox coefficient, the level of pain and the frequency of PONV were taken into account. RESULTS. After surgery, patients reported of pain of different intensity 4 hours after surgery: Group 1 — 66.6 % of patients, Group 2 — 5.2 % of patients. PONV was present in 6 (16.6 %) patients of Group 1. There were no PONV in Group 2. The cortisol level in the group with subtenon blockade after 4 hours was 32 % lower (p ˂ 0.05) than in patients of the 1st group. In Group 2, the FORT/FORD coefficient significantly increased 4 hours after surgery from 0.45 ± 0.5 to 0.62 ± 0.2 (p ˂ 0.005). CONCLUSIONS. The use of subtenone blockade in strabismus surgery at the end of the operation allows to achieve pronounced and prolonged analgesia, to limit the manifestation of PONV in the postoperative period, as well as to limit the level of surgical stress in general, which in turn reduces the degree of inflammatory reaction of the eye.
Perioperative management of elderly and senile patients. Recommendations
Authors: Zabolotskikh Igor B. , Gorobets E. S. , Grigoryev E. V. , Kotovskaya Yu. V. , Lebedinskii K. M. , Musaeva T. S. , Mkhitaryan E. A. , Ovechkin A. M. , Ostapenko V. S. , Rozanov A. V. , Runikhina N. K. , Tkacheva O. N. , Trembach N. V. , Khoronenko V. E. , Cherdak M. A.
Published: August 2022

Perioperative management of elderly patients remains one of the most difficult tasks of modern anesthesiology. Compared with younger patients, people over 60 years of age have a higher risk of developing adverse postoperative outcomes, as a result of age-related decline in physiological functions, the presence of several concomitant diseases, polypragmasia, cognitive dysfunction and specific geriatric syndromes, such as frailty. More than 25 % of this category of people have several chronic diseases of the cardiovascular, nervous, endocrine, hematopoietic, musculoskeletal systems, respiratory, digestive and other systems. In the process of aging, there is also a decrease and some perversion of metabolic processes, a decrease in the reactivity of the body. All of the above, along with the surgical intervention, increases the risk of postoperative complications and perioperative mortality.
The recommendations present the definition of the category of elderly and senile patients, provide information about age-related changes in their body that affect anesthesia and intensive care. The main clinical syndromes and symptoms useful in predicting the unfavorable course of the perioperative period are indicated, including frailty, nutritional insufficiency, sarcopenia and cognitive dysfunction. Methods for assessing functional activity and the risk of falls are given separately. Attention is paid to the causes, diagnosis, prevention and treatment of delirium, cardiovascular, respiratory complications. The principles of choosing the method of anesthesia and management of the perioperative period in elderly and senile patients, depending on the features of interventions and concomitant pathology, are described.
Effect of assisted lung ventilation on the level of serum biomarkers of lung injury after robot-assisted surgery: a prospective randomized study
Authors: Klimov A. A. , Chotchaeva A. A. , Pankratova M. A. , Subbotin Valerii V.
Published: August 2022

INTRODUCTION. It is uncertain whether assisted lung ventilation versus pressure control–volume guaranteed ventilation reduces ventilation-induced pulmonary injury and inflammation during anaesthesia for robotic surgery. OBJECTIVES. To compare Pressure support ventilation Pro (PSVpro) with moderate neuromuscular block (NMB) with protective pressure control–volume guaranteed ventilation (PCV-VG) with intensive neuromuscular block during anaesthesia for robotics abdominal surgery respect to biomarkers levels of lung injury and inflammation. MATERIALS AND METHODS. Design: randomized clinical trial. 35 patients scheduled for elective robotic radical prostatectomy under general anesthesia were randomized into two groups. Group 1 — moderate and shallow NMB (TOF 1–4, TOF ratio T4/T1 < 40 %) and pressure support ventilation — PSVpro (n = 19), Group 2 — intensive NMB (TOF 0, PTC < 2) and protective pressure control–volume guaranteed ventilation — PCV-VG (n = 16). The primary outcome was the changes in serum levels of inflammation biomarkers (Tumor necrosis factor α (TNF-α), Interleukin-6 (IL-6) and Interleukin-6 (IL-8)) and lung injury biomarker (Surfactant Protein D (SP-D)) 1 hour after the end of surgery. RESULTS. The levels of serum IL-6, IL-8, TNF-a and SP-D, before and after surgery were 2.1 [1.125; 16.215], 30.9 [12.85; 50.7]; 10.6 [8.04; 14.75], 13 [8.585; 21.25]; 4 [4; 4.035], 4 [4; 4]; 66.2 [39.2; 91.1], 65.4 [57; 109.6] in the Group 1 and 2.20 [1.55; 5.33], 26.15 [18.175; 42.875]; 10.45 [8.6425; 16.35], 19.15 [9.77; 31.35]; 4 [4; 4.815], 4 [4; 4]; 60.65 [49.56; 106.73], 63.20 [56.5; 106.65] in the Group 2 respectively. Changes in serum biomarkers levels were not significantly different between the two ventilation strategies. CONCLUSIONS. Pressure support ventilation Pro with moderate neuromuscular block compare to protective mandatory lung ventilation with intense neuromuscular block does not affect changes in serum levels of biomarkers for inflammation and lung injury IL-6, IL-8, SP-D and TNF-α in patients undergoing elective robotic prostatectomy.