bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors and Influence of Postoperative Moderate-to-severe Pain of PACU in the Patients with Malignancy
Authors: Zhang Yu , Dai Qinxue , Xu Kaiwei , Fu Haifeng , Zhang Anqi , Du Wenwen
Published: March 2023

Background

This study was identied the risk factors for and designed to investigate influence of postoperative moderate-to-severe pain of post anaesthesia care unit (PACU) in patients with malignancy.

Methods

A retrospective study was performed on 22600 cancer patients with malignancy who underwent elective radical surgery in the Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, between October 2020 and December 2021. All patients were transferred to the PACU after tracheal extubation. Patients were divided into two groups according to a visual analogue scale (VAS) score of > 3: the no-moderate-severe-pain group and moderate-to-severe-pain group. Data pertaining to demographic, surgical, anaesthetic, and other factors were recorded. Logistic regression analysis was performed to explore the risk factors associated with postoperative moderate-to-severe pain of PACU in patients with malignancy.

Results

The incidence of postoperative moderate-to-severe pain of PACU in patients with malignancy was 1.42%. Multivariate logistic regression analysis showed that male sex, chest surgery, abdominal surgery, intraoperative haemorrhage, intraoperative use of non-steroidal anti-inflammatory drugs (NSAIDs), duration of anaesthesia, postoperative vomiting, and hypothermia were risk factors for postoperative moderate-to-severe pain of PACU in patients with malignancy. Female sex and intraoperative NSAID use were protective factors. The area under the curve was 0.85. Moderate-to-severe pain in the PACU correlated with hypertension, hyperglycaemia, dysphoria, and hypoxemia (P < 0.05).

Conclusions

Clinicians should actively provide preoperative pain education for men, patients undergoing chest or abdominal surgery, and patients who may experience massive haemorrhage during surgery. Active temperature monitoring and heat preservation, assisted analgesia with NSAIDS, and anti-nausea drugs were performed during surgery. Pain assessment and management should be conducted in time to reduce the occurrence of postoperative moderate-to-severe pain of PACU in patients with malignancy.
Trial registration
The study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (No.KY2021-097) and registered in the Chictr.org.cn registration system on 06/12/2021(ChiCTR2100054013).
Detection Mechanism in IoT framework using Artificial Neural Networks
Authors: Jain Rachna , Dhand Geetika , Sheoran Kavita , Kaur Amandeep , Puri Navyah , Jatana Nishtha , Jain Kashika , Bansal Hiti , Jain Panav
Published: March 2023

Internet of Things (IoT) applications are now used more frequently due to the rapid expansion of wireless networking and the digital revolution. IoT helps in user-to-machine and machine-to-machine interaction. IoT objects have gained popularity because they can be accessed from anywhere. Healthcare, agriculture, smart cities, and the military are different domains where IoT objects are communicating with each other. The goal of anomaly-based techniques is to figure out which patterns are normal and which are aberrant. This approach of intrusion detection has the benefit of detecting original works of authorship intrusions. However, this technique has the drawback of frequently producing false positive results. To increase the effectiveness of anomaly-based intrusion detection methods, machine learning techniques are being evaluated. Anomaly-based intrusion detection techniques can be used by machine learning algorithms to watch active behavior and compare it to known intrusion footprints in order to stay aware of potential future attacks. In a hybrid approach, different identifying methods are combined in the same scheme. This technique will eliminate the weaknesses of a particular operation while improving the overall IoT system's reliability. In this research, we study intrusion-based systems using comparative analysis of several machine learning and deep learning algorithms. In the proposed work one hot encoding technique is used to deal with the categorical data. Different parameters like accuracy, F-1 score, precision, and recall value have been calculated. Experimental results prove that ANN yields 99.61% accuracy over other hybrid models. However, in Machine Learning, RandomForestClassifier yields the best results.
Comparison of metagenomic next-generation sequencing and blood culture in patients with suspected bloodstream infection
Authors: Shi Wen , Zhou Yuhua , Wen Yi , Mao Enqiang , Ni Tongtian
Published: March 2023

Background
The application of metagenomic next-generation sequencing (mNGS) has gradually been carried out by clinical practitioner. However, few studies have compared it with blood cultures in patients suffering from suspected bloodstream infections. The purpose of this study was to compare the detection of pathogenic microorganisms by these two assays in patients with suspected bloodstream infection.
Methods
We retrospectively studied patients with fever, chills, antibiotic use for more than 3 days, suspected bloodstream infection, and admission to the emergency department of Ruijin Hospital from January 2020 to June 2022. All patients had blood drawn on the same day for blood mNGS and blood cultures. Clinical and laboratory parameters were collected on the day blood was drawn. The detection of pathogenic microorganisms by the two methods was compared. Risk factors and in-hospital mortality in patients with bloodstream infections were analysed separately for these two assays.
Results
In all 99 patients, the pathogenic microorganisms detection rate in blood mNGS was significantly higher than that in blood culture. Blood mNGS was consistent with blood culture in only 12.00% of all positive bacterial and fungal test results. The level of CRP is related to bacteraemia, fungaemia and viraemia detected by blood mNGS. No clear risk factors could be found in patients with a positive blood culture. In critically ill patients, both tests failed to improve patient outcomes.
Conclusion
In patients with suspected bloodstream infection, mNGS is not yet a complete replacement for blood cultures. The results of both tests could not improve in-hospital mortality.
KaiA regulates intracellular oxygen dynamics in unicellular diazotrophic cyanobacteria
Authors: Bandyopadhyay Anindita , Sengupta Annesha , Pakrasi Himadri
Published: March 2023

The discovery of nitrogen fixation in unicellular cyanobacteria provided the first clues for the existence of a circadian clock in prokaryotes. However, recalcitrance to genetic manipulation barred their use as model systems for deciphering the clock function. Here, we explore the circadian clock in the now genetically amenable Cyanothece 51142, a unicellular, nitrogen-fixing cyanobacterium. Unlike non-diazotrophic clock models, Cyanothece 51142 exhibits conspicuous self-sustained rhythms in various discernable phenotypes, offering a platform to directly study the effects of the clock on the physiology of an organism. Deletion of kaiA in this strain impacted regulation of oxygen cycling and hindered nitrogenase activity. Our findings imply a role for KaiA in regulating the intracellular oxygen dynamics in unicellular diazotrophic cyanobacteria and suggest that its addition to the KaiBC clock was likely an adaptive strategy that ensured optimal nitrogen fixation as microbes evolved from an anaerobic to an aerobic atmosphere under nitrogen constraints.
Recommendations for robust renovation strategies of Swiss residential buildings
Authors: Galimshina Alina , Moustapha Maliki , Hollberg Alexander , Lasvaux Sébastien , Sudret Bruno , Habert Guillaume
Published: March 2023

Building renovation is urgently required to reduce the environmental impact associated with the building stock. Typically, building renovation is performed by envelope insulation and/or changing the fossil-based heating system. Life cycle assessment and life cycle cost analysis are seen as suitable methods to evaluate the performance of a building in terms of environmental impacts and cost. However, the results are highly affected by uncertainty. The goal of this paper is to provide recommendations for robust renovation strategies considering uncertainties on future evolution of climate, energy grid, user behaviors. The method includes identifying optimal renovation options for the envelope and heating systems for building-representatives from all construction periods that are currently in need of retrofit in Switzerland. Conventional and bio-based materials are examined with inclusion of dynamic carbon storage potential. The results of the analysis show that heating system is a priority for building renovation for all the considered construction periods. The results also show that if only conventional materials are considered for building renovation, optimal solution does not prescribe deep renovation and higher energy consumption during life time is favored. However, when bio-based insulation materials can be used, the opposite conclusion is drawn and synergies between low environmental impact and low energy costs during life cycle are identified. Such renovation strategies pave the way for a just and low carbon transformation of the Swiss building stock.
Ultrafast inactivation of SARS-CoV-2 by 254-nm UV-C irradiation on porous and non-porous media of medical interest using an omnidirectional chamber
Authors: Maubert Bertrand , Theillère Camille , Jany Prescillia , Bourlet Thomas , Deschamps Jérôme , Pozzetto Bruno , Singh Fateh , Gadea Emilie
Published: March 2023

Covid-19 has spurred a renewed interest at decontamination techniques for air, objects and surfaces. Beginning 2020, a lot of effort was done in urgency to permit the reuse of UC-V for inactivating SARS-CoV-2. However, those studies diverged widely on the dose necessary to reach this goal; until today, the real value of the sensitivity of the virus to a 254-nm illumination is not known precisely. In this study, decontamination was performed in an original UV-C large decontamination chamber (UVCab, ON-LIGHT, France) delivering an omnidirectional irradiation with an average dose of 50 mJ/cm2 in 60 sec. Viral inactivation was checked by both cell culture and PCR test. SARS-CoV-2 was inactivated by UV-C light within 3 sec on both porous (disposable gown) and non-porous (stainless steel and apron) surfaces. For the porous surface, an irradiation of 5 min was needed to completely negative the PCR signal. The Z value estimating the sensitivity of SARS-CoV-2 to UV-C in the experimental conditions of our cabinet was shown to be > 0.5820 m2/J. These results illustrate the ability of this apparatus to inactivate rapidly and definitively high loads of SARS-CoV-2 deposited on porous or non-porous supports and open new perspectives on material decontamination using UV-C.
Investigating the spatial and temporal variation of Aerosols and Cloud Parameters over South Asia, using remote sensing.
Authors: malik mahnoor , Tariq Salman , Haq Zia Ul
Published: March 2023

Aerosol optical depth (AOD) is the most crucial factor in determining how aerosol at local, and regional levels are spatiotemporally distributed. In this study, data has been obtained from the Moderate Resolution Imaging Spectroradiometer (MODIS) onboard the Aqua satellite to examine spatiotemporal variations in aerosol optical depth (AOD) and their effects on the Angstrom Exponent (AE), and clouds parameters, namely cloud fraction (CF), cloud optical thickness (COT), cloud top pressure (CTP), cloud top temperature (CTT), ice cloud water path (ICWP), liquid cloud water path (LCWP), ice cloud effective radius (ICER), and liquid cloud effective radius (LCER) over South Asia from July 2002 to July 2021. The highest values of AOD (0.53–0.7) were observed in the Indo-Gangetic basin IGB region over South Asia. The highest values of AE (1.36 to 1.7) were observed in south-eastern India, Nepal, north-western Bangladesh, and Bhutan. The highest value of AOD is observed to be 0.7 in the IGB region during summer. The lowest value of AOD (0.2) was observed in winter. The highest mean value of AOD (0.63 ± 0.09) observed in Bangladesh is due to the noteworthy increase in agricultural activities. The negative correlation between AOD and AE was noticed in Karachi (-0.24), Lahore (-0.04), Rawalpindi (-0.08), Mumbai (-0.03), Kathmandu (-0.49), Colombo (-0.19), and in Kabul (-0.51). A positive correlation is observed in Delhi (0.21), Bangalore (0.09), and Dhaka (0.17).
Scalable Computer Interactive Teaching System Based on Large Scale Multimedia Data Analysis
Authors: Dong Zhang , Qi Zhu
Published: March 2023

The emergence of computer interactive teaching system greatly facilitates the needs of students to learn anytime and anywhere at this stage. At the same time, the increase of online course video, voice, files and other teaching resources also puts forward higher requirements for the operation of the teaching system. Based on the actual needs of online teaching, this paper designs an extensible computer interactive teaching system with the aid of large-scale multimedia data analysis algorithm. Because of the complexity and large volume of the data in the teaching system, this paper uses the linear data feature extraction algorithm of principal component analysis to extract the most basic low dimensional features of the data, and reconstructs the data through the linear transformation method to achieve data prediction. Most online course resources are displayed in the form of multimedia. Therefore, this paper uses robust component analysis to process multimedia data, especially for some problems such as data missing and multimedia data interference. This paper uses RC ranking related evaluation method and R-value evaluation method to evaluate the prediction data, which proves that parameter selection plays an important role in controlling sparse regression. And the actual teaching system resources related video and picture data were tested, and the results showed that the algorithm used in this paper had the best data recognition performance when the number of theme models was 100, which provided an important reference for the design of the system. Finally, this paper designs a computer interactive teaching system which includes three modules: administrator, student and teacher, and tests the system, which proves the practical operation possibility and application value of the system.
An adaptive matrix material extrusion optimization model for in situ impregnated continuous fiber reinforced 3D printing
Authors: Yang Jinxiu , Ma Yingxin , Chen Ling , Zhang Lijing , Wu Huanxiao , Yao Yuan
Published: March 2023

In order to improve the strength and surface quality of fiber-reinforced composite 3D printed parts and reduce the overfilling and underfilling caused by the manufacturing process of molten filaments under continuous paths, a co-extrusion control and optimization method based on matrix adaptive feeding with printing speed and deposition spacing is proposed in this paper. The method not only achieves surface void filling under different paths, but also reduces the porosity of the printed parts and improves the strength of the printed parts by adjusting the matrix extrusion under different deposition spacings. Compared with the common co-extruded model, the tensile strength is increased by 18% , the bending strength is increased by 23.4% and the porosity decreased by 54.4%. The proposed method is applicable to models with arbitrary continuous infill patterns and improves the quality of fiber-reinforced printed parts, especially to avoid structural failure due to uneven filling.
Genome-Wide identification and expression analysis of the polygalacturonase gene family in sweetpotato
Authors: He Peiwen , Zhang Jingzhen , Lv Zunfu , Cui Peng , Xu Ximing , George Melvin Sidikie , Lu Guoquan
Published: March 2023

Background: Polygalacturonase (PG), a crucial enzyme involved in pectin degradation, is associated with various plants' developmental and physiological processes such as seed germination, fruit ripening, fruit softening and plant organ abscission. However, the members of PG gene family in sweetpotato (Ipomoea batatas) have not been extensively identiﬁed.
Results:In this study, there were 103 PG genes identified in sweetpotato genome, which were phylogenetically clustered into divergent six clades. The gene structure characteristics of each clade were basically conserved. Subsequently, we renamed these PGs according to their locations of the chromosomes. The investigation of collinearity between the PGs in sweetpotato and other four species, contained Arabidopsis thaliana, Solanum lycopersicum, Malus domestica and Ziziphus jujuba, revealed important clues about the potential evolution of the PG family in sweetpotato. Gene duplication analysis showed that IbPGs with collinearity relationships were all derived from segmental duplications, and these genes were under purifying selection. In addition, each promoter regionof IbPG proteins contained cis-acting elements related to plant growth and development processes, environmental stress responses and hormone responses. Furthermore, the 103 IbPGs were differentially expressed in various tissues (leaf, stem, proximal end, distal end, root body, root stock, initiative storage root and fiber root) and under different abiotic stresses (salt, drought, cold, SA, MeJa and ABA treatment). IbPG038 and IbPG039were down-regulated with salt, SA and MeJa treatment. According to the further investigation, we found that IbPG006, IbPG034 and IbPG099had different patterns under the drought and salt stress in fiber rootof sweetpotato, which provided insights into functional differences among these genes.
Conclusion: A total of 103 IbPGs were identified and classified into six clades from sweetpotato genome. The results of RNA-Seq and qRT-PCR suggested that IbPG006, IbPG034 and IbPG099 might play a significant role in tissue specificity as well as drought and salt stress responses, which showed valuable information for further functional characterization and application of the IbPGs.
A Three-Arm Randomized Controlled Trial Using Ecological Momentary Intervention, Community Health Workers, and Video Feedback at Family Meals to Improve Child Cardiovascular Health: The Family Matters Study Design
Authors: Berge Jerica M. , Trofholz Amanda C. , Aqeel Marah , Norderud Kristin , Tate Allan , Fertig Angela R. , Loth Katie , Mendenhall Tai , Neumark-Sztainer Dianne
Published: March 2023

Background: Numerous observational studies show associations between family meal frequency and markers of child cardiovascular health including healthful diet quality and lower weight status. Some studies also show the “quality” of family meals, including dietary quality of the food served and the interpersonal atmosphere during meals, is associated with markers of child cardiovascular health. Additionally, prior intervention research indicates that immediate feedback on health behaviors (e.g., ecological momentary intervention (EMI), video feedback) increases the likelihood of behavior change. However, limited studies have tested the combination of these components in a rigorous clinical trial. The main aim of this paper is to describe the Family Matters study design, data collection protocols, measures, intervention components, process evaluation, and analysis plan.
Methods/design: The Family Matters intervention utilizes state-of-the-art intervention methods including EMI, video feedback, and home visiting by Community Health Workers (CHWs) to examine whether increasing the quantity (i.e., frequency) and quality of family meals (i.e., diet quality, interpersonal atmosphere) improves child cardiovascular health. Family Matters is an individual randomized controlled trial that tests combinations of the above factors across three study Arms: (1) EMI; (2) EMI+Virtual Home Visiting with CHW+Video Feedback; and (3) EMI+Hybrid Home Visiting with CHW+Video Feedback. The intervention will be carried out across 6 months with children ages 5-10 (n=525) with increased risk for cardiovascular disease (i.e., BMI ≥75%ile) from low income and racially/ethnically diverse households and their families. Data collection will occur at baseline, post-intervention, and 6 months post-intervention. Primary outcomes include child weight, diet quality, and neck circumference.
Discussion: This study will be the first to our knowledge to use multiple innovative methods simultaneously including ecological momentary assessment, intervention, video feedback and home visiting with CHWs within the novel intervention context of family meals to evaluate which combination of intervention components are most effective in improving child cardiovascular health. The Family Matters intervention has high potential public health impact as it aims to change clinical practice by creating a new model of care for child cardiovascular health in primary care.
Trial Registration: This trial is registered in clinicaltrials.gov (Trial ID: NCT02669797). Date recorded 5/02/22.
Uncertainty Assessment of Future Climate Change Using Bias-Corrected High-Resolution Multi-Regional Climate Model Datasets over East Asia
Authors: Park Changyong , Shin Seok-Woo , Juzbašić Ana , Cha Dong-Hyun , Choi Youngeun , Min Seung-Ki , Kim Yeon-Hee , Chang Eun-Chul , Suh Myoung-Seok , Ahn Joong-Bae , Byun Young-Hwa
Published: March 2023

The quantitative assessment of the uncertainty components of future climate projections is critical for decision-makers and organizations to establish climate change adaptation and mitigation strategies at regional or local scales. This is the first study in which the changes in the uncertainty components of future temperature and precipitation projections are quantitatively evaluated using multiple regional climate models over East Asia, vulnerable to future climate change. For temperature, internal variability and model uncertainty were the main factors affecting the near-term projections. The scenario uncertainty continued to increase and was estimated to be the dominant factor affecting the uncertainty after the mid-term projections. Although precipitation has the same main uncertainty factors as the temperature in the near-term projections, it significantly differs from temperature because the internal variability notably contributes to the fraction to the total variance, even in the long-term projections. The internal variability of the temperature and precipitation in the near-term projections was predicted to be larger in Korea than that in East Asia. This was confirmed by regional climate models as well as previous studies using global climate models as to the importance of internal variability at smaller regional scales during the near-term projections. This study is of significance because it provides new possibilities with respect to the consideration of climate uncertainties to the establishment of climate change policies in more detail on the regional scale.
Characterization of immune checkpoints expression and lymphocyte densities of Iranian breast cancer patients; the co-expression status and clinicopathological associates
Authors: Pournabee Mohammadhossein , Keshavarz-Fathi Mahsa , Esmaeili Pooyesh , Sharif Pouya Mahdavi , Nili Fatemeh , Jahanbin Behnaz
Published: March 2023

Background
Breast malignancies are now the most common and deadliest type of neoplasms among women worldwide. Novel therapeutic approaches are needed to combat advanced stages of breast cancer. In this study, we aimed to investigate the expression and co-expression status of three immune checkpoints (PD-1, PD-L1, and LAG-3), as well as tumor-infiltrating lymphocytes (TIL) scores, and to further establish their potential correlations with clinicopathologic features.
Methods
We performed a retrospective study on 361 pathologic samples of breast cancer. Immunohistochemistry was performed to assess the status of the immune checkpoint markers, and H&E staining was used to score TILs. The correlations of the immune checkpoint markers of tumor cells and tumor-associated immune cells and TIL scores with clinicopathological characteristics were analyzed.
Results
Out of 361 assessed samples, LAG-3 was positive in 51%, while IC PD-L1 and TC PD-L1 were detectable in 36% and 8.9%, respectively. Moreover, both IC PD-L1 and LAG-3 stained positively in 24.4% of samples. IC PD-L1 expression was significantly higher in tumors with higher nuclear, mitotic, and overall grades and tubule formation. In addition, TC PD-L1 and LAG-3 exhibited a similar trend for higher overall grading. Tumors with positive estrogen- and progesterone-receptor (ER and PR) expression had significantly lower IC PD-L1 and TC PD-L1 staining, while LAG-3 positivity was more prevalent in HER2 positive samples. Tumors that were positive for these biomarkers had significantly higher Ki-67 scores. LAG-3 expression showed significant correlations with PD-1 and IC PD-L1 expression. Besides, the co-expression of LAG-3 and IC PD-L1 was significantly more encountered in luminal B and triple-negative subtypes, compared to the luminal A subtype. Regarding TILs, their scoring was significantly higher in ER and PR negative and HER2 positive samples. Intriguingly, samples with positive staining for LAG-3, IC PD-L1, and TC PD-L1 had significantly higher TIL scorings.
Conclusions
Immune checkpoints show differentially different levels of expression in certain molecular subtypes of breast cancer. Moreover, they reveal a meaningful correlation with each other, proliferation indices, and histologic grades. Finally, a sizable proportion of breast cancers co-express PD-L1 and LAG-3, which will make them appropriate targets for future combined ICIs.
Quantifiable impact: monitoring landscape restoration from space
Authors: Vliet Mendy van der , de Jeu Richard , Malbeteau Yoann , Ghent Darren , Veal Karen , de Haas Sander , Zaan Thijs van der , Sinha Rajiv , Dash Saroj , Houborg Rasmus
Published: March 2023

Ecosystem conservation and restoration activities are critical to reduce the vulnerability of biodiversity to climate change. Although these activities need to be evaluated objectively and systematically, they are rarely analyzed from a global, multidimensional and multivariable perspective. Here we present a methodology to quantify the environmental impact of landscape restoration using long-term and high-resolution satellite observations. For two restoration areas in Tanzania, we find an increase in the amount of water retained by the soil (~0.01 m³ m⁻³, ~13% average increase), a soil temperature drop (~-0.5 °C) and an increase in surface greenness (~50% average increase) in 3,5 years. These datasets illuminate the impact of restoration initiatives on the landscape across their lifecycle, and support the reporting of comprehensive metrics to donors and partners. High quality satellite observations from commercial providers and space agencies are now achieving frequency, resolution, and accuracy that can effectively evaluate restoration activities.
Knowledge and practice of the physical activity prescription by generalists and specialist physicians of the City of Kinshasa: A cross-sectional study
Authors: Bowamou Christian Khalifa Emeka , Aliocha Nkodila Natuhoyila , Ekisawa Constant Nkiama , Jean-Paul Divengi Nzambi , Eleuthère Kintoki Vita , Benjamin Longo-Mbenza , Jean-Réné M’buyamba-kabangu , Bernard Kianu phanzu
Published: March 2023

Background
The health benefits of regular physical activity (PA) are well documented. However, several people in both developed and developing countries do not meet PA recommendations. Health professionals are believed to be potential PA promoters. The purpose of this study is to gain insight into general and specialist practitioners' knowledge, practices and PA prescription-related factors in private and public hospitals in Kinshasa.
Methods
A multicenter cross-sectional analytical study was conducted among general and specialist practitioners in the Democratic Republic of the Congo's capital using a declarative and anonymous questionnaire.
Results
Overall, 40.2% of the participants were interested in their patient’s PA, 2.3% prescribed PA, and 0.9% did it correctly. Specialist physicians (SPs) prescribed PA more frequently than general practitioners (GP), and private hospital physicians prescribed PA more frequently than public hospital physicians. Five factors were independently associated with participants in prescribing PA: being in a private hospital increased the likelihood of prescribing PA by twofold (aOR, 1.83; 95% CI, 0.99–3.39; p = 0.055), being an SP increased the likelihood by sixfold (aOR, 6.22; 95% CI, 3.78–10.51; p = 0.000), being an internist increase the likelihood by sixfold (aOR, 5.81; 95% CI, 3.45–9.78; p = 0.000), being cardiologist by a factor of 12 (aOR, 12.91; 95% CI, 4.37–38.15; p = 0.000) and knowing the benefits of PA by a factor of 2 (aOR, 2.29; 95% CI, 1.29–4.08; p = 0.006). The most common reason given for a lack of interest in patients' PA, followed by a lack of knowledge about current PA prescribing recommendations and a lack of time.
Conclusions
SPs and professionals in the private health sector were the most interested in their patients’ PA. A small portion of them actually prescribed it, and only a tiny proportion did it correctly. This bleak picture highlights a need to rethink the undergraduate medical curricula, especially about teachings on the importance and use of PA as a medicine in its own right in disease prevention and treatment.
Integrative Data Mining Pipeline for Identification of a Protein- Based Prognostic Signature in Lung Squamous Cell Carcinoma
Authors: Lei Ming , Shi Qiong , Chen Nan , Li Zhenhui , Lin Yichen , Wei Ying , Li Zhai
Published: March 2023

The purpose of this study is to use an integrated data mining approach, in which multi-omics, clinical information, and image information are considered together, and to develop a new prognosis prediction model for Lung Squamous Cell Carcinoma (LUSC). We analyzed Reverse Phase Protein Array (RPPA) data of LUSC samples (n = 328) from The Cancer Genome Atlas cohort (TCGA). Univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression analysis followed by multivariate Cox analysis were performed to identify key protein candidates and constructed a robust multiprotein prognostic model on the training set. The optimal cut-off value was obtained by the receiver operating characteristic (ROC) curve, which was employed to divide patients into a high- and a low-risk group. The model was evaluated using multiple statistical methods, including principal components analysis (PCA), Kaplan-Meier survival analysis, independent prognostic analysis, ROC analysis, and immunohistochemistry (IHC) staining. The co-expression analysis and bioinformatics enrichment analysis of gene function was adapted to evaluate the prognostic effect and biological pathways of the model. Four-protein (Histone-H3, HSP27_pS82, CHK2, and PAXILLIN) prognostic signature was able to stratify patients into high- and low-risk groups with statistical significance. The signature estimates poor overall survival for high-risk patients in both training and testing sets. Histone-H3, HSP27_pS82, and CHK2 were found to be protective, while PAXILLIN was associated with poor prognosis. Univariate and multivariate Cox regression analysis showed that the risk model was an independent risk factor for overall survival (univariate: HR = 3.558, 95%CI = 2.451–5.169, p< 0.001, multivariate: HR = 2.515, 95%CI = 1.750–3.615, p < 0.001). The area under the curve (AUC) of the risk scores was 0.742. The correlation heatmap provided a landscape for 455 proteins. The gene set enrichment analysis (GSEA) results revealed that adhesion molecular and cancer pathways were enriched in the high-risk group and the cytochrome P450 pathway was enriched in the low-risk groups. Our finding discovered a set of novel 4-related prognostic signatures could serve as a sensitive independent prognostic factor for individualized survival predictions.
Integrated microbiome-metabolome reveals thiram aggravates tibial dyschondroplasia through disturbing sphingolipid metabolism
Authors: Liu Yingwei , Wu Shouyan , Liu Kai , Li Ying , Liao Jiaozhao , Pan Jiaqiang , Hu Lianmei , Iqbal Mujahid , Mehmood Khalidx , Tang Zhaoxin , Zhang Hui
Published: March 2023

As a pesticide, thiram is widely used in agriculture to eliminate pests, and it also causes great environmental pollution and poses a certain threat to animal health. It’s well known that the contamination of feed with thiram in the environment can lead to tibial chondrogenesis(TD) in chickens. The imbalance of intestinal flora and related metabolites is closely related to bone development. Unfortunately, the relationship between the intestinal flora of TD broilers and serum metabolites is unclear. Our results demonstrated that broilers exposed to thiram showed typical lameness and the white cartilage thrombus in the growth plate, accompanied by hepatotoxicity and intestinal injury. We found that the intestinal flora of TD group was out of balance, the diversity was significantly increased with Corynebacterium significantly enriched. Moreover, the metabolome results showed alterations in 10 serum metabolites, with Glucosylceramide being considerably up-regulated, resulting in sphingolipid metabolism problem, which is critical in the etiology of TD. The comprehensive correlation analysis showed the relationship between intestinal microflora and Sphingolipid metabolism in TD broilers. Thiram aggravates tibial chondrodysplasia by affecting the changes in the composition and structure of the intestinal microflora of broilers and the disorder of sphingomyelin metabolism. Collectively, these findings provide novel insight into the pathogenesis of TD from the perspective of thiram-induced gut microbiota and metabolic disorders.
Development of cardiometabolic risk factors following endocrine therapy in women with breast cancer
Authors: Rillamas-Sun Eileen , Kwan Marilyn L. , Iribarren Carlos , Cheng Richard , Neugebauer Romain , Rana Jamal S. , Nguyen-Huynh Mai , Shi Zaixing , Laurent Cecile A. , Lee Valerie S. , Roh Janise M. , Huang Yuhan , Shen Hanjie , Hershman Dawn L. , Kushi Lawrence H. , Greenlee Heather
Published: March 2023

Purpose: Studies comparing the effect of aromatase inhibitor (AI) and tamoxifen use on cardiovascular disease (CVD) risk factors in hormone-receptor positive breast cancer (BC) survivors report conflicting results. We examined associations of endocrine therapy use with incident diabetes, dyslipidemia, and hypertension.
Methods: The Pathways Heart Study examines cancer treatment exposures with CVD-related outcomes in Kaiser Permanente Northern California members with BC. Electronic health records provided sociodemographic and health characteristics, BC treatment, and CVD risk factor data. Hazard ratios (HR) and 95% confidence intervals (CI) of incident diabetes, dyslipidemia, and hypertension in hormone-receptor positive BC survivors using AIs or tamoxifen compared with survivors not using endocrine therapy were estimated using Cox proportional hazards regression models adjusted for known confounders.
Results: In 8,985 BC survivors, mean baseline age and follow-up time was 63.3 and 7.8 years, respectively; 83.6% were postmenopausal. By treatment, 77.0% used AIs, 19.6% used tamoxifen, and 16.0% used neither. Postmenopausal women who used tamoxifen had an increased rate (HR: 1.43, 95% CI: 1.06-1.92) of developing hypertension relative to those who did not use endocrine therapy. Tamoxifen use was not associated with incident diabetes, dyslipidemia, or hypertension in premenopausal BC survivors. Postmenopausal AI users had higher hazard rates of developing diabetes (HR: 1.37, 95% CI: 1.05-1.80), dyslipidemia (HR: 1.58, 95% CI: 1.29-1.92) and hypertension (HR: 1.50, 95% CI: 1.24-1.82) compared with non-endocrine therapy users.
Conclusion: Hormone-receptor positive BC survivors treated with AIs may have higher rates of developing diabetes, dyslipidemia, and hypertension over an average 7.8 years post-diagnosis.
Hydrothermal synthesis of binary disulfide Co x Cu 1-x S 2 as cathode material for high-performance lithium thermal battery
Authors: Chen Chao , Gu Chengyu , Yang Yuli , Liu Haiping , Bi Sifu , Cao Lixin
Published: March 2023

The hollow microsphere structure materials binary disulfide Co1-xCuxS2 (x = 0, 0.05, 0.10, 0.15, 0.20, 0.25) were synthesized by hydrothermal method with cobalt sulfate, copper sulfate, and sodium thiosulfate. The structure, morphology, and composition of Co1-xCuxS2 were characterized by X-ray diffraction (XRD), field emission scanning electron microscope (FESEM), and energy dispersive spectrometer (EDS). The influence of cobalt and copper content in Co1-xCuxS2 cathode material on the discharge performance of the cell was investigated. The experimental results show that the Co0.95Cu0.05S2 sample possesses the largest number of hollow microspheres, the internal resistance of the cell was lower and the specific capacity of the cell is higher. The results of constant current discharge showed that the optimal composition Co0.95Cu0.05S2 exhibits an ultra-high specific capacity of 531.8 mAh g-1 at 450℃ and the current density of 100 mA·cm-2 with the cut-off voltage of 1.5V. The best discharge temperature of Co0.95Cu0.05S2 was 450℃.
Nitrogen concentration, its uptake, use efficiency and yield of wheat (Triticum aestivum L.) As influenced by difference in rate of nitrogen application in Khumaltar, Nepal
Authors: Rawal Nabin , Vista Shree Prasad , Khadka Dinesh
Published: March 2023

Appropriate application of nitrogen (N) not only increases wheat production but also results in optimum N use efficiency (NUE). An experiment was conducted to determine N concentration, uptake, use efficiency and performance of wheat in response to N fertility levels at Khumaltar Lalitpur, Nepal during 2019/20 and 20020/21. The experiment involved 7 treatments; 6 levels of N (0, 50, 75, 100, 125, 150 kg ha− 1) with application of P2O5:K2O in 50:50 kg ha− 1 and zero plot (no fertilizer application) which was laid out in randomized complete block design and replicated three times. The varying N had significant influence on grain yield, N concentration, its uptake, NUE and economics of wheat production. Two years pooled grain yield showed that significantly (p ≤ 0.001) higher grain yield (6.52 Mg ha− 1) with B: C ratio of 2.6 was observed from application of 150 kg N ha− 1 which was at par with use of N @ 125 kg ha− 1 (6.32 Mg ha− 1). The two years mean N concentration in grain and straw of wheat were 13.98 and 3.49 g kg− 1, respectively. The data revealed that 4.9 Mg ha− 1 grain yield plus 5.56 Mg ha− 1 dry straw yield removed 81.7 kg N ha− 1. Likewise, N partition in wheat grain and straw were 75% and 25% respectively. The mean partial factor productivity, internal efficiency, physiological efficiency, recovery efficiency, and agronomic efficiency of N in wheat was found to be 61.8 kg kg− 1, 59.1 kg kg− 1, 53.1 kg kg− 1, 45.0%, and 22.5 kg kg− 1, respectively. N was limiting nutrient as added N fertilizer had considerable impact in wheat production and recommended to use 125 kg N ha− 1 under similar soil properties and ecology.
Pre-radiotherapy ctDNA liquid biopsy for risk stratification of oligometastatic non-small cell lung cancer
Authors: Chaudhuri Aadel , Semenkovich Nicholas , Samson Pamela , Badiyan Shahed , Vlacich Gregory , Stowe Hayley , Wang Yun , Star Rachel , Devarakonda Siddhartha , Govindan Ramaswamy , Waqar Saiama , Robinson Clifford , Pellini Bruna
Published: March 2023

The optimal treatment for patients with oligometastatic non-small cell lung cancer (NSCLC) remains unclear. Some patients with oligometastatic disease can experience prolonged remission after locally consolidative radiation therapy (RT), while others harbor micrometastatic disease (below current limits of detection by imaging) that may benefit from further prioritization of systemic therapy. To better risk-stratify this population and identify the patients most likely to benefit from locally consolidative radiation therapy, we performed a multi-institutional cohort study of patients with oligometastatic NSCLC undergoing liquid biopsy analysis of circulating tumor DNA (ctDNA).

Among this real-world cohort of 1,487 patients undergoing analysis (using the Tempus xF assay), a total of 1,880 ctDNA liquid biopsies along with paired clinical data were obtained across various timepoints. Approximately 20% (n=309) of patients had ctDNA obtained prior to RT and after their diagnosis of oligometastatic disease. Samples were de-identified and analyzed for mutational burden and variant frequencies of detectable deleterious (or likely deleterious) mutations in plasma.

Patients with undetectable ctDNA before RT had significantly improved progression-free survival and overall survival compared to patients with detectable ctDNA prior to RT. In patients that received RT, 598 pathogenic (or likely deleterious) variants were identified. ctDNA mutational burden pre-RT and ctDNA maximum variant allele frequency (VAF) pre-RT were both significantly inversely correlated with both progression-free (P = 0.0031 for mutational burden, P = 0.0084 for maximum VAF) and overall survival (P = 0.045 for mutational burden, P = 0.0073 for maximum VAF). Patients without detectable ctDNA prior to RT had significantly improved progression-free survival (P = 0.004) and overall survival (P = 0.03) compared to patients with detectable ctDNA prior to RT.

These data suggest that in patients with oligometastatic NSCLC, pre-radiotherapy ctDNA analysis can potentially identify the patients most likely to benefit from locally consolidative RT and experience prolonged progression-free and overall survival. Similarly, ctDNA may be useful to identify those patients with undiagnosed micrometastatic disease, in whom it may be appropriate to prioritize systemic therapy.
Biodynamic Substrate for the Optimization of Biomass and Constitution of Metabolites of Plectranthus Ornatus
Authors: Suárez-Barreiro jovanna , Romero María , Velásquez Camilo , Tobon Felipe , Leguizamón Adriana
Published: March 2023

ThePlectranthus ornatusCodd. (also known as acetaminofem and boldo) has been found to have various pharmaceutical uses, including insecticidal properties. The metabolite composition of P. ornatus varies depending on soil and climatic conditions. The objective of this study was to optimize the growth and metabolite composition of P. ornatus (N = 72) through biodynamic substrate cultivation in Machetá-Cundinamarca, Colombia, located at 1850 masl, over a period of 60 days. Four different substrates were tested: sandy, vermicompost, horse manure, and biodynamic substrate, with the aim of identifying significant differences that would indicate optimization.The study evaluated root growth, plant material growth, and relative metabolite amounts (%) present in an ethanolic extract obtained under the same conditions. Additionally, the volatile fraction was identified using HS-SPME/GC-MS, and soil analysis was performed. The results showed that the plants grown in the biodynamic substrate had the highest growth in plant material and root (p < 0.05), while the plants grown in the sandy substrate had the highest concentration of volatile fraction in the extract. Furthermore, the plants grown in the biodynamic substrate exhibited greater vitality, and the physicochemical/microbiological composition of this substrate at the end of the trial showed a higher concentration of nutrients required for aromatics cultivation and a higher concentration of nitrogen-fixing bacteria.In conclusion, this study suggests that in the long term, the biodynamic substrate may be more efficient in obtaining metabolites of pharmaceutical interest, and a combination with sandy substrate should be considered for optimal results.
Evolution of periodic wave and dromion-like structure solutions in the variable-coefficients coupled high-order complex Ginzburg-Landau system
Authors: Yan Yuanyuan , Liu Wenjun , Wang Haotian , Liu Xiaoyan , Meng Xiankui , Yang Hujiang , Tian Ye
Published: March 2023

In this paper, the propagation characteristics of an ultrashort pulse in the birefringent fiber expressed by the variable-coefficients coupled high-order complex Ginzburg-Landau (HCGL) equations are analyzed. Firstly, the one-soliton solution of the coupled HCGL equations is obtained by the asymmetric method. And this is the first time that the coupled Ginzburg-Landau (GL) equations are successfully solved by the asymmetric method, which further expands the scope of application of the asymmetric method. Then, the evolution process and dynamic characteristics of special types of solitons such as the periodic wave and dromion-like structure in the variable-coefficients coupled HCGL system are discussed by examples. Furthermore, the combination of traditional bright soliton and dromon-like structure is constructed for the first time. These works are expected to promote the research on multi-soliton solutions in HCGL systems, which is still an unsolved problem, and are likely to contribute some theoretical guidance to the optimization of Wavelength Division Multiplexing (WDM) systems and the preparation of special types of soliton pairs in fiber lasers, so as to promote the development of optical soliton research and elevate information transmission rate in optical communication systems.
Patients, payers and developers of Orphan Medicinal Products: lessons learned from 10 years’ multi-stakeholder dialogue on improving access in Europe via MoCA
Authors: Cavaller-Bellaubi Maria , Hughes-Wilson Wills , Kubinová Šárka , De Casteele Marc Van , Lente Evert Jan Van , Degortes Emanuele , Pontén Johan , Eichler Hans-Georg , Cam Yann Le , Boselli Simone , Bucsics Anna
Published: March 2023

Background: The Mechanism of Coordinated Access to orphan medicinal products (MoCA) was established in 2013 with the intention of developing a coordinated mechanism between volunteering EU stakeholders and developers of Orphan Medicinal Products (OMPs) to support the exchange of information aimed at enabling informed decisions on pricing and reimbursement at Member State level and to evaluate the value of an OMP based on a Transparent Value Framework. The objective of the collaborative approach was to support more equitable access to authorised therapies for people living with rare diseases, rational prices for payers and more predictable market conditions for OMP developers. Over the past 10 years, the MoCA has conducted a series of pilot projects, examining a variety of different products and technologies at different stages of development; and with contributions from a variety of patient representatives, participation from EU payers from a range of Member States; and, recently, with EUnetHTA members and the EMA participating in the meetings as observers.
Results: 10 years on from the establishment of the MoCA, the European landscape has significantly evolved, not only in the field of drug development with increasingly transformative therapies based on novel technologies, but also in terms of larger numbers of approved treatments, increased budget impact and the resulting associated uncertainties; as well as in terms of stakeholder collaboration and interactions. The value of early dialogue with OMP developers, including the EU payer community via their national decision-making authorities, is a key element within this early interaction and contributes to identifying, managing and reducing uncertainties allowing a prospectively planned approach earlier in development and, consequently, to support more timely, sustainable and equitable access to new OMPs, particularly where there is a high unmet medical need.
Conclusions: The voluntary, informal nature of the MoCA interactions creates a flexible framework for non-binding dialogue. A forum for such interactions is needed to achieve the aims of the MoCA and to support both healthcare systems in planning as well as to underpin timely, equitable and sustainable access for patients with rare diseases to new therapies within the EU.