bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated single-cell and spatial transcriptomic analyses unravel the heterogeneity of the prostate tumor microenvironment
Authors: Hirz Taghreed , Mei Shenglin , Sarkar Hirak , Kfoury Youmna , Wu Shulin , Verhoeven Bronte , Subtelny Alexander , Zlatev Dimitar , Wszolek Matthew , Salari Keyan , Murray Evan , Chen Fei , Macosko Evan , Wu Chin-Lee , Scadden David , Dahl Douglas , Baryawno Ninib , Saylor Philip , Kharchenko Peter , Sykes David
Published: April 2022

The treatment of primary prostate cancer delicately balances an active surveillance approach for low-risk disease with multimodal treatment including surgery, radiation therapy, and hormonal therapy for high-risk disease. Recurrence and development of metastatic disease remains a clinical problem, without a clear understanding of what drives immune escape and tumor progression. Here, we sought to comprehensively describe the tumor microenvironment of localized prostate cancer contrasting this with adjacent normal samples and healthy controls. We performed single-cell RNA sequencing and high-resolution spatial transcriptomic analysis. This revealed tumor context dependent changes in gene expression. Our data point towards an immune suppressive tumor microenvironment associated with suppressive myeloid populations and exhausted T-cells, in addition to high stromal angiogenic activity. We inferred cell-to-cell relationships at an unprecedented scale for ligand-receptor interactions within undissociated tissue sections. Our work provides a highly detailed and comprehensive resource of the prostate tumor microenvironment as well as tumor-stromal cell interactions.
Managing community engagement in research in Uganda: insights from practices in HIV/AIDS research
Authors: Barugahare John , Kass Nancy E.
Published: April 2022

Background: Community engagement (CE) in research is valuable for instrumental and intrinsic reasons. Despite existing guidance on how to ensure meaningful CE, much of what it takes to achieve this goal differs across settings. Considering the emerging trend towards mandating CE in many research studies, this study aimed at documenting how CE is conceptualized and implemented, and then providing context-specific guidance on how researchers and research regulators in Uganda could think about and manage CE in research. Methods: We conducted qualitative interviews and focus group discussions involving forty-one respondents who were experienced in HIV/AIDS biomedical research involving CE. Thirty-eight of these were directly or indirectly associated with Uganda’s leading research institution in the field of HIV/AIDS. They included Principal Investigators, Community Liaisons Officers, Research Ethics Committee members and Community Advisory Board Members. Three respondents were from Uganda National Council for Science and Technology. Data were collected between August 2019 and August 2020, using audio-taped focus group discussions and key informant interviews, transcribed and analyzed manually to generate themes and subthemes. Results: Three major themes emerged: goals-cum-value of CE; the means of CE, and, the evaluation of CE. Goals-cum-value of CE generated four subthemes that could be seen as overarching goals of CE: 1) promote communities’ agency; 2) generate and sustain trust; 3) protect and promote communities’ rights and interests; and, 4) help studies optimize participation in the form of enrolment and retention of participants. What usually comes under the nomenclatures of methods, strategies, and approaches of CE, such as town-hall meetings, sports events, drama, and the like, should simply be understood as the means of CE, and it is not desirable to hold pre-conceived and fixed ideas about the best means to conduct CE in research since a lot depend on the context. Finally, the study found that despite CE’s critical importance, which suggests the need to track and evaluate it, CE is currently intermittently evaluated, and for inadequate motivations. Conclusions: Existing guidance on how to conduct robust CE in research is no substitute for creativity, flexibility, and reflexivity on the part of both researchers and research regulators.
The influence of skin-to-skin contact on Cortical Activity during Painful procedures in preterm infants in the neonatal intensive care unit (iCAP mini): Study protocol for a randomized control trial.
Authors: Campbell-Yeo Marsha , Benoit Britney , Newman Aaron , Johnson Celeste , Bardouille Tim , Stevens Bonnie , Jiang Arlene
Published: April 2022

Background. Strong evidence suggests that maternal infant skin-to-skin contact (SSC) is effective in reducing behavioural responses to pain. Given the multi-sensory benefits of SSC, it is highly likely that SSC provided during pain in early life may reduce pain-induced brain activity. The aim of this study is to examine the effect of SSC compared to 24% sucrose on pain-induced activity in the preterm infant brain during a medically required heel lance. Secondary objectives include determining a) differences between behavioural pain response and noxious-related brain activity during heel lance; and b) rate of adverse events across groups.Methods. We will randomly assign 126 babies (32 to 36 completed weeks gestational age) admitted to the Neonatal Intensive Care Unit, and their mothers within the first seven days of age to receive: i) SSC plus sterile water; ii) 24% oral sucrose. Each baby will receive a medically indicated heel lance, following a no treatment baseline period. The primary outcome is noxious-related brain activity measured using an electroencephalogram (EEG) pain-specific event-related potential. Secondary outcomes include pain intensity measured using a bio-behavioural infant pain assessment tool (Premature Infant Pain Profile-Revised) and rate of adverse events.Discussion This will be the first clinical trial to compare the effect of SSC and 24% sucrose on pain-induced brain activity in the preterm infant brain during a clinical noxious stimulus, measured using EEG. Given the negative neurodevelopmental outcomes associated with unmanaged pain, it is imperative that preterm babies receive the most effective pain-reducing treatments to improve their health outcomes. Our findings will have important implications in informing optimal pain assessment and management in preterm infants.Trial registration: ClinicalTrials.gov NCT03745963. Date of registration: November 19, 2018.
Development of High-Speed Rail, Agglomeration of Productive Service Industry, and Industrial Pollution Emission: Analysis Based on Three Major Urban Agglomerations in the Yangtze River Economic Belt
Authors: Han Zi , Guoli Ou
Published: April 2022

From the perspective of urban agglomeration, this paper studies the spatial correlation between pollution emission and industrial agglomeration and explores the impact of high-speed railway (HSR) development on urban industrial pollution emission and its internal mechanism. Based on the panel data of cities in three major urban agglomerations of the Yangtze River from 2007 to 2019, the entropy method is used to calculate the urban pollution reduction index, and the economic and environmental effects of HSR are investigated using combined double difference and spatial econometric techniques. The results show that: (1) HSR is helpful to alleviate pollution emissions; (2) HSR promotes the aggregation of local and neighboring producer services; (3) The accumulation of producer services plays an important intermediary role in the emission reduction effect of HSR and has positive spillover effects; (4) HSR has positive effects on the reduction of urban pollution in the Yangtze River Delta and Chengdu-Chongqing urban agglomeration, but it has negative effects on the middle reaches of the Yangtze River. The intermediary role of producer service agglomeration is more evident in the middle reaches of the Yangtze River and Yangtze River Delta.
Differential diagnosis of primary thyroid lymphoma and papillary thyroid carcinoma by ultrasound combined with computed tomography
Authors: Xu Dong , Peng Chanjuan , Yi Dan , Zhou Ying , Yao Jincao , Chen Bo , Yang Chen
Published: April 2022

Background: Primary thyroid lymphoma (PTL) and papillary thyroid carcinoma (PTC) are both thyroid malignancies, but their therapeutic methods and prognosis are different. This study aims to explore their sonographic and computed tomography （CT）features , and to improve the early diagnosis rate.Methods: The clinical and imaging data of 50 patients with PTL and 100 patients with PTC confirmed by pathology were retrospectively analysed.Results: There was no significant difference between PTL and PTC patients in gender ratio, echo texture, cystic change and aspect ratio (P>0.05), while the difference was significant in age, maximum diameter of nodule, asymmetric enlargement and Hashimoto's thyroiditis (P<0.001). PTL had a higher proportion than PTL in markedly hypoechoic, internal linear echogenic strands, posterior echo enhancement, rich vascularity, lack of calcification and homogeneous enhancement, with statistically significant difference (P<0.05), while PTC was proportionally higher than PTL in irregular border, circumscribed margin, capsular invasion and significant enhancement, also with statistically significant difference (P<0.001). Besides, PTL and PTC were significantly different in the non-contrast CT value mean, venous phase CT value mean, enhanced intensity and homogeneity of nodules (P<0.05). Multivariate logistic regression analysis showed that age, posterior echo enhancement, lack of calcification and homogeneous enhancement were independent risk factors (OR=1.226, 95%CI:1.056~1.423, P=0.007; OR=51.152, 95%CI: 2.934~891.738, P=0.007; OR=0.013, 95%CI: 0.000~0.400, P=0.013; OR=0.020, 95%CI: 0.001~0.507, P=0.018).Conclusions: Certain sonographic and CT features as the presence of posterior echo enhancement and lack of calcification, homogeneous enhancement were valuable for distinguishing PTL from PTC.
Female colon cancer: pattern and prognosis of distant metastases
Authors: Liu Yurong , Kang Rongbin , Zheng Huida , Wang Pengcheng , Jiang Weixin , Xiong Bin , Chen Jintao , Xu Jianhua
Published: April 2022

Background: The purpose of this study was to compare the metastatic pattern and prognosis of female colon cancer (FCC) to that of male colon cancer (MCC) to ascertain the independent factors impacting the prognosis of patients with FCC.Patients and Methods: The data of 135503 patients with colon cancer diagnosed between 2010 and 2017 with at least five years of follow-up were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The Pearson chi-square test and Fisher exact probability method were used to compare clinicopathological features. Kaplan-Meier analysis was used to compare survival differences. The Cox proportional risk model was utilized to evaluate the prognostic factors impacting overall survival.Results: A total of 22977 patients with metastatic colon cancer were identified;12172(53.0%) in males and 10805(47.0%) in females. Compared to non-metastatic FCC patients, a greater proportion of metastatic FCC patients, were less than 60 years of age, black race, and grade III-IV. The primary sites were mainly located on the left side. Compared to metastatic MCC patients, a higher proportion of metastatic FCC patients ranged over 60 years of age, black race, and chemotherapy, while the primary site was located on the right side. Among CC patients who had distant metastasis of a single organ, Liver and lung were the two most common sites, and patients with lung metastases had a better prognosis than those with other types of metastasizes. FCC patients with liver metastasis had a worse prognosis than their MCC counterparts and were more likely to develop lung metastases. Cox multivariate regression analysis showed that the risk ratio was higher in metastatic FCC patients compared to those without metastases.Conclusions: We report the survival comparison of metastatic FCC with non-metastatic FCC through the SEER database. Our results suggest that it has unique clinicopathologic features and differs from metastatic MCC. Furthermore, patients with liver metastatic FCC have a worse prognosis than those with MCC. Emphasis on screening for colon cancer in women and additional clinical care should be paid for, especially for patients with FCC with metastatic liver cancer.
Multivalent Binding Kinetics Resolved by Fluorescence Proximity Sensing
Authors: Schulte Clemens , Solda Alice , Spänig Sebastian , Adams Nathan , Bekic Ivana , Streicher Werner , Heider Dominik , Strasser Ralf , Maric Hans
Published: April 2022

Multivalent protein interactors are an attractive modality for probing protein function and exploring novel pharmaceutical strategies. The throughput and precision of state-of-the-art methodologies and workflows for the effective development of multivalent binders is currently limited by surface immobilization, fluorescent labelling and sample consumption. Using the gephyrin protein, the master regulator of the inhibitory synapse, as benchmark, we exemplify the application of Fluorescence proximity sensing (FPS) for the systematic kinetic and thermodynamic optimization of multivalent peptide architectures. High throughput synthesis of +100 peptides with varying combinatorial dimeric, tetrameric, and octameric architectures combined with direct FPS measurements resolved on-rates, off-rates, and dissociation constants with high accuracy and low sample consumption compared to three complementary technologies. The dataset and its machine learning-based analysis deciphered the relationship of specific architectural features and binding kinetics and thereby identified binders with unprecedented protein inhibition capacity thus, highlighting the value of precise on- and off-rate determination for the rational engineering of multivalent inhibitors.
A Novel Method to Achieve the Most Accurate Classification Success Using Covid-19 Images in Machine Learning Algorithms
Authors: AVUÇLU Emre
Published: April 2022

The COVID-19 pandemic started with the first case from China in December 2019 and continues to pose a major threat to the world's health. COVID-19 spread around the world in a short time and negatively affected people's lives in every aspect. Due to the rapid spread of COVID-19, the healthcare sectors of many countries have been caught off guard. This situation created a very heavy workload for doctors and healthcare professionals. Due to the importance of COVID-19, many studies have been conducted in the literature. These studies have been carried out and continue to be done to help experts to diagnose COVID-19 more accurately and to use appropriate treatment methods for this diagnosis. Computer aided diagnosis systems should be developed to alleviate this workload. Machine Learning Algorithms (MLAs) are of great importance in the development of computer-aided early and accurate diagnosis systems in medicine today. In this study, a method is proposed for more accurate diagnosis of COVID-19 patients using COVID-19 image data. Feature extraction was performed using the RGB values of the images. These features were used in train and test operations for MLAs. Six different MLAs were used in experimental studies (k Nearest Neighbor (k-NN), Decision Tree (DT), Multinominal Logistic Regression (MLR), Naive Bayes (NB) and Support Vector Machine (SVM), Minimum Mean Distance Classifier (MMDC)). The following accuracy rates were obtained in train operations for MLAs, respectively; 1, 1, 1, 0.81159, 0.94927, 0.81884. In test operations, accuracy results were obtained as follows; 0.83673, 0.93877, 0.97959, 0.85714, 0.87142, 0.85714. After the application of the proposed method, the test success rate for MLR increased to 1. The results obtained were given in the experimental studies section in detail. The results proved to be very promising. According to the results, it was seen that the proposed method could be used effectively in future studies.
Voluntary exercise attenuates mice anxiety after traumatic brain injury via inhibiting NLRP3 inflammasome activation
Authors: Hu Xiaoxuan , Ou Yuhang , Li Jiashuo , Sun Meiqi , Ge Qian , Pan Yongqi , Cai Zhenlu , Tan Ruolan , Wang Wenyu , An Jing , Lu Haixia , Wu Gang
Published: April 2022

Background: Psychological disorders, particularly the anxiety after traumatic brain injury (TBI) have received great attention both in clinical practice and experimental investigation. New therapeutic strategies are urgently required nowadays to improve mental condition of TBI patients. Neuroinflammation is the typical adaptive response that played important roles in psychiatric illness after brain tissue damage. Therefore, the immune-targeted therapy has aroused attention. Voluntary exercise has been considered as the most essential rehabilitative intervention following TBI. However, there were some experiments showed opposite effects, which varies with different time windows. Whether and when the voluntary exercise should be taken after TBI remain to be defined. The aim of the current study was to elucidate whether in-time voluntary exercise could improve the neurological recovery and reduce the anxiety of TBI mice by inhibiting the neuroinflammation via attenuating the activation of NLRP3 inflammasome.Methods: Kunming mice (8 weeks) were subjected to TBI and randomly divided into 4 groups One week voluntary wheel running (VWR) was applied to TBI mice soon after trauma - at 2nd day after injury. The neurofunction of TBI mice was detected by neurological severity score (NSS) and beam walking assay. Anxiety behavior was evaluated by open-field (OF) test and elevated plus maze (EPM) test. The cellular inflammatory signal, including IL-12, IFN-γ, CCL2, IL-10 and TGF-β, as well as the activation of microglia and NLRP3 inflammasome in the perilesional cortex were investigated.Results: After one week VWR, neurological function recovery was enhanced while the anxiety behavior of TBI mice was significantly eased. Accompanied with this, anti-inflammatory signaling, IL-10 in particular, greatly elevated. NLRP3 expression, caspase-1 activation and pro-inflammatory cytokines IL-1β/ IL-18 secretion were significantly inhibited. All these alterations were consistent with reduced microglia activation in the perilesional site and positively correlated with the weaken of anxiety behavior.Conclusion: In-time VWR could be a high potential therapeutic strategy for neuropsychiatric disorders following TBI by targeting neuroinflammation.
Blink Rate Variability as a Measure of Computer Vision Syndrome
Authors: Hossain Gahangir , Bello Mukhtar , Faiyazuddin Musab
Published: April 2022

Due to the COVID-19 pandemic and working from home with portable devices, we are spending a longtime on the device screen. Prolonged focus on devices like computer screens, tablets, e-readers, and cellphones – Video Display Terminals (VDTs) has been linked with vision problems which affect over 60 million people globally. The computer related ocular problem is collectively called Computer Vision Syndrome (CVS) [1]. CVS is multidirectional as it affects people differently and with varying associated symptoms. The goal of this research is to analyze Electroencephalograph (EEG) signals and affirm that our hypothesis that if eye Blink rate variability (BRV) is a good indicator of human attentiveness then human attention can be directly correlated to CVS. Two EEG signals were analyzed with one recorded from participant while engaged in a cognitive demanding task and compared with a control data set when participant was in a less attentive. A significant decrease in eye blink rate from 20 to 16 was observed in the signals collected from the participants engaged in cognitive task.
QTL mapping of maize kernel traits under low phosphorus stress
Authors: Jiang Tao , Zhang Chenghua , Zhang Zhi , Wen Min , Qiu Hongbo
Published: April 2022

Low phosphorus stress significantly impacts the development of maize kernels. In this study, the 082 maize genotype, which has high phosphorus use efficiency, and the Ye107 maize genotype, which has low phosphorus use efficiency, were utilized to construct an F2:3 population. QTL mapping was then employed to determine the genetic basis of differences in the maize kernel traits of the two parents in a low-phosphorus environment. This analysis revealed several major QTLs that control environmental impacts on kernel length, kernel width, kernel thickness, and kernel weight. These QTLs were detected in all three environments and were distributed on five genome segments of chromosomes 3, 5, 6, and 9. Most environmental insensitive QTLs had stable effects in all low-phosphorus environments, indicating that they may be broadly applicable to breeding efforts designed to generate germplasm with higher phosphorus use efficiency.
Sensitivity and Selectivity of Fluorescent Chemosensor for the Detection of Fe 3+ and its Cell Images
Authors: Marimuthu Pitchai , Ramu Andy
Published: April 2022

A simple probe (Z)-N'-((8-hydroxyquinolin-2-yl) methylene)nicotine hydrazide (8-HQC-NH) has been synthesized and realized as a “turn-off” fluorescent chemosensor for the detection for Fe3+ ion over the competitive metal ions in ethanol medium. The fluorescent intensity of the 8-HQC-NH probe intensely illustrated that the “turn-off” selective quenching upon the addition of Fe3+ owing to the chelation-enhanced fluorescence quenching (CHEQ) effect. The probe of 8-HQC-NH exhibited an ample linear response towards Fe3+ concentration rangingbetween 0 to 75 µM with satisfactory lower detection limits of 7x10− 8 M. Furthermore, the developed 8-HQC-NH probe offers many advantages like good biocompatibility, negligible cytotoxicity, being promising efficient fluorescent probe to recognize Fe3+ions in living cells. These features explore the way for the design of simple and efficient fluorescent method for the bio-sensing applications.
WITHDRAWN: HDAC9 promotes the susceptibility of diabetes to Contrast-induced acute kidney injury by regulating TXNIP/Trx1 pathway
Authors: Lu Heng-Cheng , Dai Wen-Ni , Liu Zhi-Wen , xiao Li , Liu Hong , sun lin , He Li-Yu
Published: April 2022

Background Contrast-induced acute kidney injury (CIAKI) is the third most common cause of hospital-acquired AKI. Diabetes mellitus (DM) is a major risk factor for CIAKI. Nevertheless, the mechanism of its role in diabetes susceptibility to CIAKI remains unclear. This study aimed to explore the role played by HDAC9 during the susceptibility of diabetic model to CIAKI. Methods Both in vitro and in vivo model of diabetes were induced by treating human renal tubular epithelial cells (HK-2) with high glucose (HG, 50mM) and by feeding mice with a high-fat diet (HFD) followed by intraperitoneal injection of streptozotocin (STZ), respectively. CIAKI mice models were constructed by contrast-media (iohexol), and iohexol also was treated HK-2 cells. Then, BRD-4354 (an inhibitor of HDAC9) was added into treated cells and mice. Finally, knockdown HDAC9 in HK-2 cultured with HG, and iohexol was added. The pathological changes, oxidative stress and apoptosis levels in mice kidney tissues were assessed. Meanwhile, cellular reactive oxygen species and the activity of HK-2 cells was measured. Western blot was used to determine the expression of HDAC9 and TXNIP/Trx1/P-ASK1/p38MAPK signaling pathways in cells and kidneys. Results HDAC9 was increased in both diabetic kidney tissues and HGinduced HK-2 cells. In vitro experiment indicated that HK-2 exposed to HG attenuated further damage to apoptosis and oxidative stress by iohexol via knockdown and inhibiting HDAC9. In vivo assay revealed that BRD4354 reduced diabetic mice sensitivity to CI-AKI. Mechanically, HDAC9 could activate TXNIP/Trx1/P-ASK1/p38MAPK signaling pathway involving in the susceptibility of diabetes to CIAKI. Conclusion HDAC9 promotes the sensitivity of diabetes to CIAKI; and may be involved in oxidative stress and apoptosis through regulation of the TXNIP/Trx1/P-ASK1/p38MAPK pathway.
Comparison of horizontal wind observed by wind profiler radars with ERA5 reanalysis data in Anhui, China
Authors: Deng Xueliang , He Dongyan , Zhang Guangyuan , Zhu Song , Dai Rui , Jin Xiaolong , Fu Wei , Shen Weiwei , Chen Jian , Fan Yingxiang , Wei Chunxuan , Li Xin
Published: April 2022

The wind profiler radar network at Anhui province in China was completely constructed for improving warning capacity of meteorological disasters in 2019. In order to verify its proper performance, vertical profiles of horizontal winds were compared with ERA5 reanalysis data during the period January to December in 2021. The wind profiler radars behave good capability in measuring the atmospheric wind with high data collection rates (> 80%). Furthermore, data availabilities of WPRs decrease with the increase of altitudes and they are mostly greater than 90% below 3km in day without precipitation, indicating that the annual mean of the effective detection height is about 2-3km with maximum value (4-6km) in summer and minimum value (around 2km) in winter. More importantly, the WPRs shows excellent agreement with the ERA5 zonal (correlation coefficients > 0.89 and standard deviations < 2.57m/s) and meridional winds (correlation coefficients > 0.76 and standard deviations < 3.26 m/s) in most stations. Also, the biases show a broadly Gaussian character in zonal winds and meridional winds and they are all close to zero. The differences of horizontal wind between wind profiler radars and ERA5 present a function of altitude. Normally, not only zonal winds but also meridional winds at low level can performance better than those at upper level. Meanwhile, due to the difference of atmospheric turbulent between day and night, statistical parameters of comparison during day time behave better than those at night. The result shows that the wind profiler radar network at Anhui is capable of providing good quality wind data in PBL for numerical model and weather processes studies in future.
Exploring deep learning methods for recognizing rare diseases and their clinical manifestations from texts
Authors: Segura-Bedmar Isabel , Camino-Perdones David , Guerrero-Aspizua Sara
Published: April 2022

Background and Objective:: Although rare diseases are characterized by low prevalence, approximately 400 million people are affected by a rare disease. The early and accurate diagnosis of these conditions is a major challenge for general practitioners, who do not have enough knowledge to identify them. In addition to this, rare diseases usually show a wide variety of manifestations, which might make the diagnosis even more difficult. A delayed diagnosis can negatively affect the patient’s life. Therefore, there is an urgent need to increase the scientific and medical knowledge about rare diseases. Natural Language Processing (NLP) and Deep Learning can help to extract relevant information about rare diseases to facilitate their diagnosis and treatments. Methods:: The paper explores several deep learning techniques such as Bidirectional Long Short Term Memory (BiLSTM) networks or deep contextualized word representations based on Bidirectional Encoder Representations from Transformers (BERT) to recognize rare diseases and their clinical manifestations (signs and symptoms). Results:: BioBERT, a domain-specific language representation based on BERT and trained on biomedical corpora, obtains the best results with an F1 of 85.2% for rare diseases. Since many signs are usually described by complex noun phrases that involve the use of use of overlapped, nested and discontinuous entities, the model provides lower results with an F1 of 57.2%. Conclusions:: While our results are promising, there is still much room for improvement, especially with respect to the identification of clinical manifestations (signs and symptoms).
Multi-scale Analysis of the Multi Source DEMs and Derived Topographic Parameters for Suitability of Avalanche Hazard Mapping
Authors: Dewali Sanjay Kumar , Jain Kamal , Singh Dhiraj Kumar
Published: April 2022

Topography is the most essential input in process of avalanche hazard modelling, simulation and mapping. Formation of the avalanches and their movement through mountainous terrain is governed by the topographic parameters and their scales. Digital Elevation Model (DEM) is the only source for deriving various topographic parameters spatially. Spatial resolution and elevation accuracy of the DEMs depend on the DEM sources. In the present work a multi-scale and multi resolution analysis is carried out using six different DEMs (SRTM -90m, ASTER- 30m, TOPO-30m, ALOS-12.5m, CartoSat 1-10m, and Airborne Survey DEM -1m) of the Manali-Dhundi area, India. The objective of present work is to understand the variation and sensitivity of various topographic parameters (point and local) at different cell sizes and neighbourhood sizes and also to identify the most suitable scales of different contributing topographic parameters for identification of the avalanche prone areas. High resolution airborne derived DEM elevation is compared with DGPS elevation value and high coefficient of correlation (R2 =0.97), and low RMSE (~0.97 m) and MAE (~0.04 m) has been observed. Further, various topographic variables (i.e. elevation, slope, aspect, curvature, terrain ruggedness) and avalanche simulation parameters (i.e. avalanche release area and debris extents in xyz direction) derived from DEMs were evaluated with the reference DEM at various spatial scales for avalanche sites of study area. Analysis results suggests that, ALOS and ASTER DEM produces fairly matching representation of actual terrain and debris extent with respect to reference DEM. However, TOPO DEM provide good accuracy for calculation of release area as compared to other DEMs. Slope and ruggedness derived from ADS DEM at 5m to 10m resolution provide fairly good representation of avalanche terrain. Extraction of topographic curvature was found most suitable at ≥ 30m resolution for avalanche terrain. Suitable scales for identification of avalanche release area and estimation of avalanche flow extents were found between 5 to 10m. In the present work validation of the estimated release area and flow extent was carried out with the limited point observations from the field. Detailed field investigation using geospatial approach of data collection will be taken in future for detailed and multiple profile-based validation of these results.
Immunogenicity, efficacy, and safety of SARS-CoV-2 vaccine dose fractionation: a systematic review and meta-analysis
Authors: Yang Bingyi , Huang Xiaotong , Gao Huizhi , Leung Nancy , Tsang Tim , Cowling Benjamin
Published: April 2022

Dose fractionation of Coronavirus Disease 2019 (COVID-19) vaccine could effectively accelerate global vaccine coverage, while supporting evidence of efficacy, immunogenicity, and safety are needed, especially with emerging variants. We reviewed clinical trials reported dose-finding results to estimate the dose-response relationship of neutralizing antibodies (nAbs) of COVID-19 vaccines. We further predict the vaccine efficacy against both ancestral and variants, using previously reported correlates of protection and cross-reactivity. We also reviewed and compared T-cell responses and safety profiles between fractional and standard dose groups. We found that dose fractionation of mRNA and protein subunit vaccines could induce SARS-CoV-2 specific nAbs and T-cells that likely confer a reasonable level of protection (i.e., vaccine efficacy > 50%) against ancestral strains and variants. Safety profiles of fractional doses were non-inferior to the standard dose. Dose fractionation of mRNA and protein subunit vaccines may be safe and effective.
Serum metabolomics profiling reveals metabolic alterations prior to the diagnosis with non-small cell lung cancer among Chinese community residents: a prospective nested case-control study
Authors: Xiang Yu , Zhao Qi , Wu Yilin , Liu Xing , Zhu Junjie , Yu Yuting , Su Xuyan , Xu Kelin , Jiang Yonggen , Zhao Genming
Published: April 2022

Background: The present high mortality of lung cancer in China stems mainly from the lack of feasible, noninvasive early disease detection biomarkers. Serum metabolomics profiling prior to diagnosis to reveal metabolic alterations could expedite the disease detection process and suggest patients harboring disease. We identified differential expressed metabolites and their involved biological processes of non-small cell lung cancer (NSCLC) among the Chinese community residents. Methods: Using a nested case-control design, we applied ultra-high-performance liquid chromatography / mass spectrometry (LC-MS)-based serum metabolomics to reveal metabolomic alterations and indicate the NSCLC presence using serum samples collected prior to their disease diagnoses. Studied serum samples were collected from 41 patients before NSCLC diagnosis (within 3.0 y) and 38 matched cancer-free controls from the prospective Shanghai Suburban Adult Cohort recruited from April 2016 to October 2017 at Songjiang District, Shanghai, China. Results: NSCLC patients presented markedly cellular metabolism alterations in serum samples collected prior to their disease diagnoses compared with cancer-free controls. In total, we identified 18 significantly expressed metabolites whose relative abundance showed either an upward or a downward trend, with most of them where lipid and lipid-like molecules, organic acids, and nitrogen compounds. Choline metabolism in cancer exhibits a markedly metabolic disturbance in NSCLC patients, followed by sphingolipid and glycerophospholipid metabolism. Our data point to the aforementioned metabolisms and related metabolites as potential vital targets for cancer interventions and could improve the early diagnosis of NSCLC patients. Our results demonstrate the potential feasibility of LC-MS-based serum metabolomics to predict the presence of NSCLC combined with characteristics including smoking habits and the exposure history of second-hand smoking. With further validation, metabolomic techniques could be used as an effective but less-invasive tool to supplement the screening programs of NSCLC in the Chinese population. Interpretation: Chol­­­­­ine metabolism in cancer, sphingolipid, and glycerophospholipid metabolism emerge as the significant metabolic disturbance of NSCLC. Metabolites involved in these biological processes may be the distinctive features associated with NSCLC prior to diagnosis.
Effects of using first principle of instruction on content and language integrated learning class
Authors: Hao Hao , Susono Hitoshi , Geng Xuewang , Chen Li , Yamada Masanori
Published: April 2022

The aim of this study was to examine the effects of content and language integrated learning (CLIL) designed according to the First Principle of Instruction (FPI). Fifteen hours Japanese CLIL course was implemented. A total of 16 university students attended the course and multiple data sources, including learning tests, questionnaire feedback, and dialogue of the group discussion, were collected and examined. As a result, students' learning outcomes, including basic Japanese proficiency, intercultural communication content, and writing skills, were statistically significantly improved. Students have a high level of awareness of the elements of FPI designed in the course. In addition, all the FPI elements had a positive impact on basic Japanese proficiency except for the application element: the problem-centered, application, and integration elements positively impacted intercultural communication content and writing skills. The results showed that students had individual differences in using the worksheet to summarize their writing ideas. Students spent most of the time in the group discussions in their native language. Even when Japanese was used, Japanese words were used rather than whole sentences in most cases. The results of the quantitative and qualitative analyses showed that the use of problem-centered theory FPI had a positive impact on the design of the CLIL. However, attention needs to be paid to students' individual differences and the guidance of students in applying basic language knowledge in problem-centered learning activities. Finally, it puts forward some points that should be considered when designing CLIL in the future.
In Silico Analysis of Aberrant Gene Expression Profiles in Haematologic Malignancies and their Impact on Mismatch Repair Functions
Authors: Bhattacharya Priyanjali , Patel Trupti
Published: April 2022

Background - The tissue microenvironment in cancers involves complex network of biomolecular interactions. Differentially expressed genes (DEGs) in diseased conditions have crucial role in cancer diagnosis. Here, we mined expression profiles (Affymetrix microarray datasets) of six different haematologic malignancies from Gene Expression Omnibus (GEO). We filtered the common DEGs across all the six profiles and developed an interactome between these abnormally expressed genes and nine mismatch repair (MMR) genes using STRING. Results - The functional relevance was inferred for 12 DEGs which were prominently altered, and their impact direct/ indirect impact on MMR functions was prognosticated. Overall results demonstrated that these genes have a significant biological role and their functional disruption resulted in cellular incompetency and disturbances in DNA repair, which may contribute to oncologic transformation. The overexpressed gene-products - flt3, myc, rad52, and hdac9 were computationally docked to All-trans retinoic acid (ATRA), an anti-cancer drug and natural ATRA like Compound 3 from black turmeric to test their efficacy on protein modulation in cancer. Conclusion - A predictive pathway was drawn elucidating the outcomes of disturbed DEG-MMR dynamics in myeloid and lymphoid malignancies. The molecular docking revealed potency of black turmeric compound in modulating an abnormally expressed gene.
Ovarian status modulates endocrine and neuroinflammatory responses to a murine mammary tumor
Authors: Strehle Lindsay D. , Russart Kathryn L.G. , Burch Valerie , Grant Corena V. , Pyter Leah M.
Published: April 2022

In breast cancer patients, behavioral comorbidities reduce quality of life, increase mortality, and may persist years into remission. These side effects are associated with increased circulating and brain inflammatory markers in patients and rodent tumor models, respectively. The prevalence and severity of these behavioral comorbidities stratify by menopausal status, suggesting an underlying mechanistic role of estrogen. Here, we manipulated “menopause” status (ovary-intact and ovariectomized) in a mouse mammary tumor model to determine the extent to which ovarian status modulates: 1) tumor effects on estrogen concentrations and signaling in the brain, 2) tumor effects on estrogen-associated neurobiology and inflammation, and 3) the ability for tumor resection to resolve the effects of a tumor. As estrogens are anti-inflammatory and beneficial to cognitive and emotional behavior, we hypothesized that reduced circulating estradiol (E2) following ovariectomy exacerbates tumor-induced peripheral and central inflammation. Notably, we observed ovarian-dependent modulation on tumor-induced peripheral outcomes, including E2-dependent processes and, to a lesser degree, circulating inflammatory markers. In the brain, ovariectomy exacerbated neuroinflammatory markers in select brain regions and modulated E2-related neurobiology due to a tumor and/or resection. Overall, our data suggest that ovarian status has moderate implications for tumor-induced alterations in neuroendocrinology and neuroinflammation and mild effects on peripheral inflammatory outcomes in this murine mammary tumor model.
Fracture Prediction of Inconel Sheet Deformed under Different Stress States
Authors: Morchhale Ayush , Ural U Sachin , Arvikar Siddhant , Pandre Sandeep , Kotkunde Nitin , Singh Swadesh Kumar
Published: April 2022

The present work focuses on the prediction of onset of fracture for thin-walled metallic sheets used for forming complex shape and lightweight components for aerospace applications. The Lou-Huh ductile damage model has been used along with Barlat 1989 anisotropic yielding function for the prediction of fracture limits of Inconel alloy in different stress states, namely, pure shear, uniaxial tension, pure strain and equi-biaxial tension. Nine different types of specimens have been deformed experimentally till the occurrence of fracture using simple tensile test and stretch forming setup. The principal stresses at the onset of fracture have been determined experimentally and numerically and plotted in the major-minor strain space and, further, have been transformed into the effective plastic strain to fracture vs. stress triaxiality space. The fracture sites in the numerical simulations have been found to be consistent with the experimental results. Cockcroft-Latham, Brozzo, Oh and Rice-Tracey model have also been used for determining the fracture locus but the Lou–Huh model has only been found to accurately predict the fracture limit in all the stress states for a wide range of stress triaxiality as it considers the effect of shear-linkage of voids.
The genetic and epigenetic regulation of CD55 and its pathway analysis in colon cancer
Authors: Liu Jiawei , Fu Ning , Wu Hongjiao , Jin Ye , Li Ang , Song Qinqin , Ji Shanshan , Zhang Zhi , Zhang Xuemei
Published: April 2022

Background
CD55 played an important role in the development of colon cancer. This study aims to evaluate the expression of CD55 in colon cancer and discover how it was regulated by transcriptional factor and miRNA.
Methods
The expression of CD55 was explored by Tumor Immune Estimation Resource2.0 (TIMER 2.0), Human Protein Altas (HPA), and UALCAN databases. TRANSFAC and Contra v3 programs were used to predict the potential binding transcription factors in the CD55 promoter. TargetScan and Starbase v2.0 were used to predict potential binding ability of miRNAs to the 3’ untranslated region (3’UTR) of CD55. SurvivalMeth was used to explore the differentially methylated sites of CD55 promoter in colon cancer. Dual-luciferase reporter assay was performed to determine the targeting relationship of TFCP2, NF-κB, or miR-27a-3p with CD55. CD55 related genes was explored by constructing a protein-protein interaction (PPI) network. The pathway analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.
Results
CD55 was significantly highly expressed in colon cancer tissues when compared with that in adjacent normal colon tissues. Dual luciferase reporter assays for CD55 promoter region showed that after knocking down TFCP2, the relative luciferase activity was decreased by 21% (P < 0.05); after inhibiting NF-κB, the relative luciferase activity was decreased by 70% (P < 0.01). The reporter gene activity assay presented that luciferase activity affected by 3’UTR of CD55 was decreased by 46% in the presence of targeting miR-27a-3p (P < 0.001). PPI network assay revealed a set of CD55-related genes, which including CFP, CFB, C4A, C4B, C5AR1, C3, C3AR1, C2, EGF, LCK, CD59, PIGA, PGAP1, ICAM1, EMR2 and CD97. GO and KEGG analysis revealed that the target genes occurred more frequently in immune-related pathways.
Conclusion
Our results indicated that CD55 was regulated by TFCP2, NF-κB, miR-27a-3p and several immune-related genes, which in turn affects colon cancer.
An Adaptive Interactional Technique Based on the Five-Dimensional Emotional Model for Webpage Interface Design
Authors: Zhang Hanzhong , Yin Jibin , Qin Haonan
Published: April 2022

The five-dimensional emotional model has been proposed for the recognition of emotions. This paper presents an adaptive emotional technique for webpage interface design based on it, which adaptively adjusts the presentation of various elements of web user interfaces by recognizing the changes in a user’s facial expression. The adjustments in the web interface, in turn, affect the user’s emotions. An experiment was designed and conducted to examine the relationship between interface elements and users’ emotional dimensions. The experimental results showed that there was a significant correlation between the layouts of the web user interfaces and the users’ emotions. Using a multi-layer perceptron, a neural network model was then trained to transform the values of the users’ emotional dimensions and interface element values, and a quantifiable transformation relationship between the webpage elements and users’ emotions was obtained. Finally, design guidelines based on our proposed adaptive technique are provided for web user interfaces.
Quality of life and the impact from sociodemographic and clinical parameters in Chinese chronic lymphocytic leukemia patients: an observational cohort study
Authors: Li Heng , Lian Qiaoping , Luo Ming , Wang Peilong , Yin Le , Zhang Donghua , Wang Jun , Li Wei , Wu Cuicui , Deng Shibin , Wu Daxing , Peng Hongling
Published: April 2022

Background: Relatively few studies have reported quality of life (QoL) and psychosocial distress in patients with chronic lymphocytic leukemia (CLL). This study aims to assess the QoL and psychological distress and the impact from sociodemographic and clinical parameters in the Chinese context.Methods: Taking advantage of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire with QLQ-CLL17 module and DASS-21 questionnaire, a total of 50 Chinese patients with CLL completed self-reported questionnaires, assessing the level of depression, anxiety, stress and QoL.Results: A significantly higher proportion of patients in the active-treatment group had impaired physical function than the “watch and wait” group (90% vs. 65%, P=0.03). Patients with active treatment reported a significantly lower QoL in the role functioning subscale (84.44±25.50 vs. 95.83±9.17, P=0.031) and cognitive functioning subscale (76.67±18.88 vs. 89.17±12.42, P=0.007). The symptom scales had a negative impact on the functioning subscale. A dramatically high proportion of patients reported psychological distress. With regard to sociodemographic parameters, gender, age, education background and income had certain impact on functional subscales. 5 patients retested the questionnaires after median 8（2-18）months. Compared to the initial assessment, they scored significantly worse on the emotional scales (P=0.0237).Conclusions: There are unique correlates of QoL and disease status among Chinese CLL patients. This finding illuminates individual differences that may be associated with QoL. Therefore, psychosocial interventions and survivorship care plans should be made in the management of CLL survivors.