bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Electronic Adherence Monitors and Associated Interventions for Routine HIV Antiretroviral Therapy in Uganda: Promising Findings
Authors: Haberer Jessica E. , Baijuka Robert , Tumuhairwe John Bosco , Tindimwebwa Edna B. , Tinkamanyire James , Tuhanamagyezi Ellyk , Musoke Lawrence , Garrison Lindsey E. , DelSignore Marisa , Musinguzi Nicholas , Asiimwe Stephen
Published: July 2022

Background

High, sustained adherence is critical for achieving the individual and public health benefits of HIV antiretroviral therapy (ART). Electronic monitors provide detailed adherence information and can enable real-time interventions; however, their use to date has largely been confined to research. This pilot study (NCT03825952) sought to understand feasibility and acceptability a relatively low-cost version of this technology and associated interventions for routine ART delivery in sub-Saharan Africa.

Methods

We provided two ART clinics in rural, southwestern Uganda with electronic adherence monitors for data-informed counseling as well as optional SMS messages to clients and/or social supporters (daily or triggered by missed or delayed doses) and/or an alarm. Clinic and ART client experiences were observed for 3 months per client, including time and motion studies. Qualitative interviews among clients, clinicians, and healthcare administrators were informed by the Consolidated Framework for Implementation Research.

Results

Fifty-one ART clients were enrolled; 57% were male and the median age was 34 years. Choice of associated intervention varied among participants. The median number of visits during follow-up was two per client. Counselors reviewed the adherence data with 90% of clients at least once; 67% reviewed data at all visits. Average adherence was 94%; four clients had adherence gaps >1 week. Acceptability was high; all but one client found the monitor "very useful” and all found SMS “very useful.” Clinic visits among clients with the intervention lasted 4 min longer on average than those in standard care. The monitors and daily SMS generally functioned well, although excess SMS were triggered, primarily due to cellular network delays. Overall, participants felt the technology improved adherence, clinic experiences, and clinician-client relationships. Few worried about stigma and privacy. Cost was a concern for implementation, particularly at scale.

Conclusion

We successfully implemented a relatively low-cost electronic ART adherence monitor and associated interventions for routine care in rural Uganda. Feasibility and acceptability were generally high, and individuals were identified who could benefit from adherence support. Future work should involve longitudinal follow-up of diverse populations, clinical outcomes, and detailed cost-effectiveness analysis to help drive policy decisions around the uptake of this technology for routine clinical care.

Clinical Trial Registration

identifier: NCT03825952.
Quantitatively Monitoring Bubble-Flow at a Seep Site Offshore Oregon: Field Trials and Methodological Advances for Parallel Optical and Hydroacoustical Measurements
Authors: Veloso-Alarcón Mario E. , Urban Peter , Weiss Tim , Köser Kevin , She Mengkun , Greinert Jens
Published: July 2022

Two lander-based devices, the Bubble-Box and GasQuant-II, were used to investigate the spatial and temporal variability and total gas flow rates of a seep area offshore Oregon, United States. The Bubble-Box is a stereo camera–equipped lander that records bubbles inside a rising corridor with 80 Hz, allowing for automated image analyses of bubble size distributions and rising speeds. GasQuant is a hydroacoustic lander using a horizontally oriented multibeam swath to record the backscatter intensity of bubble streams passing the swath plain. The experimental set up at the Astoria Canyon site at a water depth of about 500 m aimed at calibrating the hydroacoustic GasQuant data with the visual Bubble-Box data for a spatial and temporal flow rate quantification of the site. For about 90 h in total, both systems were deployed simultaneously and pressure and temperature data were recorded using a CTD as well. Detailed image analyses show a Gaussian-like bubble size distribution of bubbles with a radius of 0.6–6 mm (mean 2.5 mm, std. dev. 0.25 mm); this is very similar to other measurements reported in the literature. Rising speeds ranged from 15 to 37 cm/s between 1- and 5-mm bubble sizes and are thus, in parts, slightly faster than reported elsewhere. Bubble sizes and calculated flow rates are rather constant over time at the two monitored bubble streams. Flow rates of these individual bubble streams are in the range of 544–1,278 mm3/s. One Bubble-Box data set was used to calibrate the acoustic backscatter response of the GasQuant data, enabling us to calculate a flow rate of the ensonified seep area (∼1,700 m2) that ranged from 4.98 to 8.33 L/min (5.38 × 106 to 9.01 × 106 CH4 mol/year). Such flow rates are common for seep areas of similar size, and as such, this location is classified as a normally active seep area. For deriving these acoustically based flow rates, the detailed data pre-processing considered echogram gridding methods of the swath data and bubble responses at the respective water depth. The described method uses the inverse gas flow quantification approach and gives an in-depth example of the benefits of using acoustic and optical methods in tandem.
Revisiting Education: On the Role of Imagination, Intuition, and Other “Gifts” for Open Scholars
Authors: Class Barbara
Published: July 2022

The knowledge society is not a final state; rather, it is a collective task that we all must work towards. This reflective report, conducted in a Scholarship of Teaching and Learning approach by a scholar who teaches research methods and has been reflecting on research method education for a number of years, is a contribution to this endeavor. Its purpose is to share praxis, in the Freiran sense, on Open Education and Open Science as public good and commons through a specific example of Open Educational Practice (OEP). The report’s first finding involves documenting that OEP and providing some conceptual tools and suggestions for scholars who would like to move towards Openness. Its second finding, rooted in a previous SNSF research project, focuses on epistemology to raise awareness on the importance of philosophical and historical approaches to education. Without this knowledge, scholars find themselves closed in models that they replicate without consciously considering the values and methods they convey. The report’s third finding is a model of the knowledge creation process that considers knowledge as commons and incorporates a theoretical framework of absences and emergences that encompasses ignorance, inspiration, imagination, creativity, and intuition. Einstein called these faculties “gifts,” and we argue that scholars should learn to leverage them within an overall open framework.
The risk factors of type 2 diabetes in hypertensive subjects
Authors: Chen Yingqun , Ma Jiner , Lu Donghui , Fang Yefei
Published: July 2022

Objective

Hypertension (HTN) and type 2 diabetes (T2DM) share common risk factors and usually co-occur. This study examined the relationship between HTN history and T2DM incidence in a cohort of Chinese hypertensive subjects.

Methods

We recruited 443 cases (T2DM and HTN) and 443 sex- and age-matched controls (HTN). The history of peak systolic blood pressure (SBP) was divided into 140-159, 160-179, and ≥ 180 mmHg, and that of peak diastolic blood pressure (DBP) was divided into 90-99, 100-109, and ≥ 110 mmHg. Multiple binary logistic regression models were used to explore the association between controlled HTN status and T2DM.

Results

Creatinine concentrations were higher in the cases than in the controls (P < 0.05). The HTN duration was longer in the cases than in the controls (14.7 years vs. 13.2 years; P < 0.05). Significant differences were also found in the history of peak SBP and DBP between the cases and controls (both P < 0.05). Creatinine, HTN duration, and family history of T2DM were risk factors for T2DM in hypertensive subjects, with odds ratios (95% confidence intervals) of 1.013 (1.004-1.022), 1.025 (1.003-1.047), and 5.119 (3.266-8.026), respectively. Compared with the lowest level of peak DBP, the odds ratio for T2DM at the highest level of peak DBP was 1.757 (1.074-2.969). Subgroups analyses showed that the effect of the history of peak DBP on T2DM was significantly modified by sex (P-interaction = 0.037).

Conclusion

The highest DBP and the longest HTN duration were both independently associated with T2DM in hypertensive subjects.
Green Polymorphic Cooperative Formation Strategy of Low-Carbon Unmanned Surface Vessels
Authors: Lu Yuzhou , Shan Qihe , Xiao Geyang , Liang Yuan , Liu Wei
Published: July 2022

At the current stage of a global energy shortage, the optimization of marine energy consumption has received attention. In order to save marine energy consumption and reduce pollution, research on low-energy-consumption Unmanned Surface Vessels (USVs) and their green and low-carbon cooperative operation methods needs to be paid attention to. Due to the ever-changing environment of USVs in actual sea conditions and the increasingly complex tasks, the cooperation of a single swarm of USVs is incompetent. First, in order to cope with larger-scale and complex tasks, we construct the multilateral cooperative control system for USVs with topology scalability under a polymorphic network and propose the multilateral distributed control protocol. Second, in order to reduce the energy consumption of the cooperative operation of USVs, the low-energy-consumption and low-carbon USVs are selected with the lowest EEOI index as the optimization goal, and based on ad hoc on-demand distance vector routing (AODV), the optimal path between USVs is obtained. Then, the swarms are grouped by External Equitable Partition (EEP), and the green autonomous cooperative formation strategy is proposed. Finally, the simulation examples are used to verify the effectiveness of the method proposed in this article.
A novel data-driven multi-energy load forecasting model
Authors: Yao Yong , Li Shizhu , Wu Zhichao , Yu Chi , Liu Xinglei , Yuan Keyu , Liu JiaCheng , Wu Zeyang , Liu Jun
Published: July 2022

With the increasing concern on energy crisis, the coordination of multiple energy sources and low-carbon economic operation of integrated energy system (IES) have drawn more and more attention in recent years. In IES, accurate and effective multi-energy load forecasting becomes a research hotspot, especially using the high-performance data mining and machine learning algorithms. However, due to the huge difference in energy utilization between IES and traditional energy systems, the load forecasting of IES is more difficult and complex. In fact, in IES, load forecasting is not only related to external factors such as meteorological parameters and different seasons, but the correlation between energy consumption of different types of loads also plays an important role. In order to deal with the strong coupling and high uncertainty issues in IES, a novel data-driven multi-energy load forecasting model is proposed in this paper. Firstly, a feature extraction method based on Uniform Manifold Approximation and Projection (UMAP) for multi-energy load of the IES is developed, which reduces the dimension of the complex nonlinear input data. Then, considering multi-energy coupling correlation, a combined TCN-NBeats model is proposed for the joint prediction of multi-energy loads, aiming to improve the prediction accuracy through ensemble learning. Finally, the numerical case analysis using the multi-energy consumption data of an actual campus verifies the effectiveness and accuracy of the proposed data-driven multi-energy load forecasting model.
Impacts of renewable portfolio standard on carbon emission peaking and tradable green certificate market: A system dynamics analysis method
Authors: Zhang Yidi , Deng Hui , Yang Jiajia , Xu Chengwei , Zhou Ziqing , Wen Fushuan , Qi Donglian
Published: July 2022

With the announcement of the carbon peaking and carbon neutrality target in China as well as the launch of the nationwide green power renewable generation trading, one of the key issues is how to design an effective renewable portfolio standard (RPS) and build an efficient tradable green certificate (TGC) market. The quota that stipulates the share of electricity supplied from qualified renewable energy (RE) sources has substantial impacts on the TGC market, the electricity market, and the occurred time of carbon emission peaking. However, few studies have been reported on effectively quantifying the impacts of quota variation. Given this background, this paper presents an innovative system dynamics (SD) model to evaluate the impacts of quota variation on the trading results of the TGC market and the trend of carbon emissions in China for the next decade. The proposed SD model takes factors such as the accommodating capability by the power system for RE generation, the policy-driven carbon emission reduction target as well as the decreasing fixed feed-in tariff (FIT) for RE generation as constraints for the first time. These factors are quantified in the constraints based on the current RE policies and market trading mechanism in China to improve the evaluation accuracy of the SD model. Using real-world data, simulations under various scenarios are carried out to validate the feasibility and efficiency of the proposed model. The methods for further improving the design of TGC market are also further explored, which are expected to effectively guide China to achieve the carbon peaking target.
Evaluating Barriers on Biogas Technology Adoption in China: The Moderating Role of Awareness and Technology Understanding
Authors: Ali Shahid , Yan Qingyou , Irfan Muhammad , Chen Zhenling
Published: July 2022

Biogas technology adoption is a challenge in developing countries like China. The primary objective of this study was to explore the major issues for farmers in adopting biogas plants. The sample size was identified through the snowball sampling method. A total of 51 respondents of biogas plant adopters participated in this study. The structured questionnaire was used to collect primary data through respondents. The formulated suppositions were assessed by partial least square structural equation modeling (PLS-SEM). The results indicated that all independent variables are significant and positively correlated with adopting biogas technology, reducing energy crises, and attaining cost-saving purposes. The results further indicated that the low cost and clear policy positively and significantly attract farmers to adopt biogas plants. The selected variables and their adopted moderation have a significant and positive impact on this conceptual model. The findings further indicate that major maintenance and day-to-day operations of biogas plants are expensive due to a lack of skilled operators, untrained or partially trained owners, and the unavailability of technicians. The results suggested that the government needs to plan a clear policy, provide short operation courses and technical support with skilled technicians to biogas plant owners, and launch a media campaign about maintenance to develop biogas plants.
Research on the Low-Carbon Development Path and Policy Options of China’s Transportation Under the Background of Dual Carbon Goals
Authors: Wang Xuecheng , Zhou Yalin , Bi Qinghua , Cao Zilong , Wang Baochun
Published: July 2022

Chinese government has proposed ambitious targets to combat climate change. As carbon emissions of China’s transportation have been rapidly increasing in past decades, massive efforts for carbon reduction need to be taken by transportation sector. Research on practical action paths for transportation sector’s low-carbon development are critical to achieving the Paris Agreement goals and China’s “Dual-Carbon” Target. Based on the transportation’s historical carbon emissions and the new possible trends in the future, this paper uses a forecast model to predict transportation’s carbon emission. Then we adopt a scenario analysis to analyze the total transportation demand in the transportation sector from 2021 to 2060. We quantitatively simulated the emission reduction effects of different policy measures under different scenarios, such as optimization of transportation structure, application of energy-saving and emission-reduction technologies, and new energy vehicles. The results provide paths and measures for the low-carbon development of transportation, and provides policy suggestion for the scientific formulation of the low-carbon development.
Assessing Factors Influencing Technology Adoption for Online Purchasing Amid COVID-19 in Qatar: Moderating Role of Word of Mouth
Authors: Al Halbusi Hussam , Al-Sulaiti Khalid , Abbas Jaffar , Al-Sulaiti Ibrahim
Published: July 2022

The COVID-19 pandemic developed new challenges for global consumers. In response to this disaster, digital technology users have faced the necessity to adopt and use specific technology apps for online shopping. This article examines how contingencies disrupt existing theoretical models and their implications for the post-COVID-19 era for online purchases. Customers prefer apps to use on the websites for search and purchase amid the COVID-19 crisis. The websites offer competitive advantages to apps for branding and CRM prospects. This motive keeps customers happy and satisfied with the website offers. This study focuses on consumer electronics and observes the comparative influence of fundamental elements (i.e., hedonic motivation, habits, perceived risk, technological trust, and technological awareness) on purchasing customer satisfaction. The study further examines the impact of customer satisfaction with online purchases with website continuance intention (WCI). Notably, this study explores the moderating effect of word-of-mouth (WOM) on the relationship between customer satisfaction with online purchases and website continuance intention. This study designed a web-based survey and recruited frequent visitors including international and citizens of Qatar for data collection. The study employed a purposive sampling technique and used three standardized psychological tools to obtain the data set needed to measure customer satisfaction with online purchases. The survey used a web link, distributed 600 questionnaires via email and social media, and received only 468 responses. After screening, only 455 were valid responses. The study showed a response rate of 75.83%. The study results showed that hedonic motivation, habits, perceived risk, and technological awareness were positively related to customer satisfaction with online purchasing. Besides, customer satisfaction with subsequent online purchases is also positively associated with website continuance intention (WCI). The results revealed that this relationship remained stronger when word-of-mouth (WOM) was higher. Hence, this shows that online shopping is seen as a vital and interesting activity in the Qatari context. The findings provide useful insights for future studies to explore the effects of COVID-19 on online purchase intentions.
Tax Avoidance Culture and Employees' Behavior Affect Sustainable Business Performance: The Moderating Role of Corporate Social Responsibility
Authors: Li Yan , Al-Sulaiti Khalid , Dongling Wang , Abbas Jaffar , Al-Sulaiti Ibrahim
Published: July 2022

Employees' behavior and corporate social responsibility (CSR) can affect firms’ profitability and increase the corporate economic burden. This current research endeavors to explore how business firms navigate employees' technology-driven behavior and CSR sustainable practices for tax avoidance to affect firms’ performance. This study examines how CSR sustainable practices moderate the relationship between employees' behavior and tax avoidance to achieve sustainable business performance. The study incorporated the Maximum Likelihood Estimator (MLE) for the purpose of data analysis using the structural equation modeling (SEM) technique that is suitable for this sample size. The study’s target population is employees of small and medium enterprises located in Pakistan. The study has drawn a sample of employees and applied a convenience sampling technique. The findings show that tax avoidance, employee behavior, and corporate social responsibility positively affect business firms’ performance. The results further indicate that sustainable CSR practices significantly moderate tax avoidance’s effect on business firms’ performance. However, there is no condition to identify the relationship between employee behavior and firm performance. In theory, this research contributes to the corporate strategy literature by answering how corporate social responsibility sustainable practices mediate the relationship between tax avoidance, employees' behavior, and sustainable business performance. It shows that socially responsible organizations will engage less in tax avoidance behaviors. The results exhibit that the study provides a systematic, holistic framework to attain sustainable firms’ performance. The findings' generalizability offers future direction with helpful insights for business managers and policymakers.
Genetic structure of wild rice Zizania latifolia in an expansive heterogeneous landscape along a latitudinal gradient
Authors: Wagutu Godfrey Kinyori , Fan Xiangrong , Fu Wenlong , Tengwer Miriam Chepkwemoi , Li Wei , Chen Yuanyuan
Published: July 2022

Global aquatic habitats are undergoing rapid degradation and fragmentation as a result of climate change and changes in land use. Understanding the genetic variability and adaptive potential of aquatic plant species is thus important for conservation purposes. In this study, we investigated the genetic diversity and structure of the extant natural populations of Zizania latifolia from five river basins in China based on 46 microsatellite markers. We tested isolation by environment (IBE), isolation by resistance (IBR), and isolation by distance (IBD) patterns using a reciprocal causal model (RCM). Furthermore, we elucidated the impact of the environment on Z. latifolia genetic diversity using generalized linear models (GLMs) and spatially explicit mixed models. Low genetic diversity (HE = 0.125–0.433) and high genetic differentiation (FST = 0.641, Øpt = 0.654) were found. Higher historical gene flow (MH = 0.212–2.354) than contemporary gene flow (MC = 0.0112–0.0247) and significant bottlenecks in almost all populations were identified, highlighting the negative impact of wetland fragmentation. The IBE model was exclusively supported for all populations and in three river basins. The IBD and IBR models were supported in one river basin each. The maximum temperature of the warmest month and precipitation seasonality were the plausible environmental parameters responsible for the observed pattern of genetic diversity. Local adaptation signatures were found, with nine loci identified as outliers, four of which were gene-linked and associated with environmental variables. Based on these findings, IBE is more important than IBD and IBR in shaping the genetic structure of Z. latifolia.
Water balance for gaged watersheds in the Central Sierra Nevada, California and Nevada, United States
Authors: Roche James W. , Wilson Kristen N. , Ma Qin , Bales Roger C.
Published: July 2022

Watershed managers require accurate, high-spatial-resolution evapotranspiration (ET) data to evaluate forest susceptibility to drought or catastrophic wildfire, and to determine opportunities for enhancing streamflow or forest resilience under climate warming. We evaluate an easily calculated product by using annual gridded precipitation (P) and measured discharge (Q), together with a gridded ET product developed from ET and P measured at flux towers plus Landsat NDVI (normalized difference vegetation index) to evaluate uncertainties in water balances across 52 watersheds with stream-gauge measurements in the Central Sierra Nevada. Watershed areas ranged from 5 to 4823 km2, and the study-area elevation range was 52–3302 m. Study-area P, ET, and Q averaged 1263, 634, and 573 mm yr–1 respectively, with precipitation at higher elevations up to five times that at lower elevations. We assessed uncertainty in water-balance components by applying a multiplier to P or Q values across the period of record for each watershed to align annual P-ET and Q values, resulting in average P-ET-Q = 0. Most year-to-year values of annual change in storage (ΔS), calculated as P-ET-Q for watersheds with well-constrained water balances, were within about + 300 mm. Across the study area we found that for each of 37 watersheds, applying a constant multiplier to either annual P or Q resulted in well-constrained water balances (average annual P-ET-Q = 0). Multiplicative adjustment of ET values for each watershed did not improve average water balances over the period of record, and would result in inconsistent values across adjacent and nested watersheds. For a given watershed, ET was relatively constant from year to year, with precipitation variability driving both interannual and spatial variability in runoff. These findings highlight the importance of evapotranspiration as a central metric of water-balance change and variability, and the strength of using high-confidence spatial- evapotranspiration estimates to diagnose uncertainties in annual water balances, and the components contributing to those uncertainties.
A combined approach for early in-field detection of beech leaf disease using near-infrared spectroscopy and machine learning
Authors: Fearer Carrie J. , Conrad Anna O. , Marra Robert E. , Georskey Caroline , Villari Caterina , Slot Jason , Bonello Pierluigi
Published: July 2022

The ability to detect diseased trees before symptoms emerge is key in forest health management because it allows for more timely and targeted intervention. The objective of this study was to develop an in-field approach for early and rapid detection of beech leaf disease (BLD), an emerging disease of American beech trees, based on supervised classification models of leaf near-infrared (NIR) spectral profiles. To validate the effectiveness of the method we also utilized a qPCR-based protocol for the quantification of the newly identified foliar nematode identified as the putative causal agent of BLD, Litylenchus crenatae ssp. mccannii (LCM). NIR spectra were collected in May, July, and September of 2021 and analyzed using support vector machine and random forest algorithms. For the May and July datasets, the models accurately predicted pre-symptomatic leaves (highest testing accuracy = 100%), but also accurately discriminated the spectra based on geographic location (highest testing accuracy = 90%). Therefore, we could not conclude that spectral differences were due to pathogen presence alone. However, the September dataset removed location as a factor and the models accurately discriminated pre-symptomatic from naïve samples (highest testing accuracy = 95.9%). Five spectral bands (2,220, 2,400, 2,346, 1,750, and 1,424 nm), selected using variable selection models, were shared across all models, indicating consistency with respect to phytochemical induction by LCM infection of pre-symptomatic leaves. Our results demonstrate that this technique holds high promise as an in-field diagnostic tool for BLD.
Transcriptome and Metabolome Analyses of Codonopsis convolvulacea Kurz Tuber, Stem, and Leaf Reveal the Presence of Important Metabolites and Key Pathways Controlling Their Biosynthesis
Authors: Yuan Fang , Yin Xiu , Zhao Kaihui , Lan Xiaozhong
Published: July 2022

Codonopsisconvolvulacea Kurz. var. vinciflora (Kom.) L.T. Shen is a member of Campanulaceae, which is used in traditional Chinese medicine. However, apart from a few Codonopsis species, no detailed knowledge is available on the metabolite composition and respective transcriptome signatures. We performed a combined transcriptome and metabolome analysis of the tuber, stem, and leaf of C. convolvulacea and found 1,144 metabolites and 231,840 unigenes in three experimental groups. The analysis revealed considerable variations in the three tissues. Tubers were rich in amino acids and derivatives, flavonoids, and organic acids, whereas the stems and leaves were rich in alkaloids and flavonoids, respectively. Transcriptome sequencing revealed candidate genes being involved in flavonoid, tryptophan, and alkaloid biosyntheses. In particular, we indicated that the variation in the isoflavone content is linked to the expressions of CHI, CYP73A, C3′H, F3H, CYP75B1, anthocyanidin synthase, and FLS. In a similar way, the levels of indole, L-tyrosine, and tryptamine were also consistent with the expressions of TDC/DDCs in the respective tissues. In addition, the expression levels of ASP5, ARO8, GOT, and AOC3 indicated that L-tryptophan is being converted to downstream metabolites. Overall, our datasets present a useful resource for future research on the uses of this medicinal plant and put forward many research questions.
A Four-MicroRNA Panel in Serum as a Potential Biomarker for Screening Renal Cell Carcinoma
Authors: Li Rongkang , Lu Chong , Li Xinji , Chen Xuan , Huang Guocheng , Wen Zhenyu , Li Hang , Tao Lingzhi , Hu Yimin , Zhao Zhengping , Chen Zebo , Lai Yongqing
Published: July 2022

Background: Renal cell carcinoma (RCC) has been a major health problem and is one of the most malignant tumors around the world. Serum microRNA (miRNA) profiles previously have been reported as non-invasive biomarkers in cancer screening. The aim of this study was to explore serum miRNAs as potential biomarkers for screening RCC.

Methods: A three-phase study was conducted to explore serum miRNAs as potential biomarkers for screening RCC. In the screening phase, 12 candidate miRNAs related to RCC were selected for further study by the ENCORI database with 517 RCC patients and 71 NCs. A total of 220 participants [108 RCC patients and 112 normal controls (NCs)] were enrolled for training and validation. The dysregulated candidate miRNAs were further confirmed with 30 RCC patients and 30 NCs in the training phase and with 78 RCC patients and 82 NCs in the validation phase. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used for assessing the diagnostic value of miRNAs. Bioinformatic analysis and survival analysis were also included in our study.

Results: Compared to NCs, six miRNAs (miR-18a-5p, miR-138-5p, miR-141-3p, miR-181b-5p, miR-200a-3p, and miR-363-3p) in serum were significantly dysregulated in RCC patients. A four-miRNA panel was built by combining these candidate miRNAs to improve the diagnostic value with AUC = 0.908. ABCG1 and RNASET2, considered potential target genes of the four-miRNA panel, may play a significant role in the development of RCC.

Conclusion: A four-miRNA panel in serum was identified for RCC screening in our study. The four-–miRNA panel has a great potential to be a non-invasive biomarker for RCC screening.
Key LncRNAs Associated With Oxidative Stress Were Identified by GEO Database Data and Whole Blood Analysis of Intervertebral Disc Degeneration Patients
Authors: Jiang Xueliang , Wu Junfei , Guo Chunhui , Song Wenhui
Published: July 2022

Background: Intervertebral disc degeneration (IDD) is a major cause of low back pain, but the onset and progression of IDD are unknown. Long non-coding RNA (lncRNA) has been validated to play a critical role in IDD, while an increasing number of studies have linked oxidative stress (OS) to the initiation and progression of IDD. We aim to investigate key lncRNAs in IDD through a comprehensive network of competing endogenous RNA (ceRNA) and to identify possible underlying mechanisms.

Methods: We downloaded IDD-related gene expression data from the Gene Expression Omnibus (GEO) database and obtained differentially expressed-lncRNAs (DE-lncRNA), -microRNAs (DE-miRNA), and -messenger RNAs (DE-mRNA) by bioinformatics analysis. The OS-related lncRNA-miRNA-mRNA ceRNA interaction axis was constructed and key lncRNAs were identified based on ceRNA theory. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses on mRNAs regulated by lncRNAs in the ceRNA network. Single sample gene set enrichment analysis (ssGSEA) was used to reveal the immune landscape. Expression of key lncRNAs in IDD was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Results: In this study, 111 DE-mRNAs, 20 DE-lncRNAs, and 502 DE-miRNAs were identified between IDD patients and controls, and 16 OS-related DE-lncRNAs were also identified. The resulting lncRNA-miRNA-mRNA network consisted of eight OS-related DE-lncRNA nodes, 24 DE-miRNA nodes, 70 DE-mRNA nodes, and 183 edges. Functional enrichment analysis suggested that the ceRNA network may be involved in regulating biological processes related to cytokine secretion, lipid, and angiogenesis. We also identified four key lncRNAs, namely lncRNA GNAS-AS1, lncRNA MIR100HG, lncRNA LINC01359, and lncRNA LUCAT1, which were also found to be significantly associated with immune cells.

Conclusion: These results provide novel insights into the potential applications of OS-related lncRNAs in patients with IDD.
Human muscle in gene edited pigs for treatment of volumetric muscle loss
Authors: Greising Sarah M. , Weiner Joshua I. , Garry Daniel J. , Sachs David H. , Garry Mary G.
Published: July 2022

Focusing on complex extremity trauma and volumetric muscle loss (VML) injuries, this review highlights: 1) the current pathophysiologic limitations of the injury sequela; 2) the gene editing strategy of the pig as a model that provides a novel treatment approach; 3) the notion that human skeletal muscle derived from gene edited, humanized pigs provides a groundbreaking treatment option; and 4) the impact of this technologic platform and how it will advance to far more multifaceted applications. This review seeks to shed insights on a novel treatment option using gene edited pigs as a platform which is necessary to overcome the clinical challenges and limitations in the field.
Characterization of Histone H3 Gene Family Reveals That GmHH3-3 is Associated With Higher Seed Weight in Glycine max
Authors: Fatima Chahat , Tahir Muhammad Hammad Nadeem , Ikram Rao Muhammad , Khan Zulqurnain , Sajjad Muhammad , Qanmber Ghulam , Darwish Essam , Geng Zhide , Xiangkuo Gao , Ur Rehman Shoaib
Published: July 2022

The main function of histone protein is to provide support to the structure of chromosomes. It helps in binding a long thread of DNA into a more condensed shape to fit into the nucleus. From histone variants, histone H3 (HH3) plays a crucial role in plant growth and development. Characterization of histones has not been reported in Glycine max till now. The objective of this study was to characterize the HH3 gene family for molecular breeding of G. max. In this study, 17 HH3 members in G. max were identified by performing local BLASTp using HH3 members from Arabidopsis as a query. Phylogenetic analysis classified HH3 genes in seven clades. Sequence logo analysis among Arabidopsis thaliana, Oryza sativa, and Glycine max showed a higher level of similarity in amino acids. Furthermore, conserveness of G. max HH3 genes was also confirmed by Gene Structure Display. Ten paralogous gene pairs were identified in GmHH3 genes in the Glycine max genome by conducting collinearity analysis. G. max HH3 genes have experienced strong purifying selection pressure, with limited functional divergence originating from the segmental and whole-genome duplication, as evidenced by the Ka/Ks ratio. The KASP marker was developed for GmHH3-3 gene. Genotyping was performed on 46 G. max genotypes. This differentiation was based upon the presence of either GmHH3-3-C or GmHH3-3-T allele in the CDS region. The results showed that G. max accessions containing the GmHH3-3-T allele at respective locus showed higher thousand seed weight than that of those accessions that contain the GmHH3-3-C allele. This research provides the basic information to further decipher the function of HH3 in soybean.
Characterization of KRAS Mutational Regression in Oligometastatic Patients
Authors: Ottaiano Alessandro , de Vera d’Aragona Roberta Penta , Trotta Anna Maria , Santorsola Mariachiara , Napolitano Maria , Scognamiglio Giosuè , Tatangelo Fabiana , Grieco Paolo , Zappavigna Silvia , Granata Vincenza , Perri Francesco , Luce Amalia , Savarese Giovanni , Ianniello Monica , Casillo Marika , Petrillo Nadia , Belli Andrea , Izzo Francesco , Nasti Guglielmo , Caraglia Michele , Scala Stefania
Published: July 2022

Background

We previously reported rare regressive genetic trajectories of KRAS pathogenic mutations as a specific hallmark of the genuine oligometastatic status in colorectal cancer (CRC).

Methods

Survival and prognostic impact of disease extent in 140 metastatic CRC patients were evaluated through the Kaplan–Meyer curves and the Log-Rank test. KRAS mutations were assessed through the Illumina NovaSeq 6000 platform and TruSight™ Oncology 500 kit. HLA typing was carried out by PCR with sequence-specific oligonucleotides. Lymphocyte densities in tumors were expressed as cells per square millimeter. NKs isolated and CD8+ from NK-depleted PBMCs were characterized through flow cytometry. CD107a externalization was evaluated as NKs/CD8 cytotoxicity toward human colon cancer cells HT29, SW620, HCT116, and LS174T carrying different KRAS mutations.

Results

The oligometastatic status was a strong and independent variable for survival (HR: 0.08 vs. polymetastatic disease; 95% CI: 0.02–0.26; p < 0.001). Eighteen oligometastatic patients were selected. Twelve were alive at the last follow-up, and 9 were characterized. Genetic regression of KRAS was observed in 3 patients: patient (PAT)2, PAT5, and PAT8. PAT2 and PAT5 presented the highest levels of GrzB+ lymphocytes in the tumor cores of the metastases (120 ± 11.2 and 132 ± 12.2 cells/mm2, respectively). Six out of 9 patients (67%), including PAT2 and PAT5, expressed HLA-C7. Twopatients (PAT2 and PAT5) presented high CD3+/CD8+-dependent cytotoxicity against HLA-C7+ SW620 cells (p.G12V-mutated cells), which was consistent with their observed mutational regression (p.G12V/p.G13D in primary→p.G13D in metastatic tumor).

Conclusions

We provide evidence that CD3+/CD8+ lymphocytes from oligometastatic CRC patients display differential cytotoxicity against human colon cancer cells carrying KRAS mutations. This could provide an interesting basis for monitoring oligometastatic disease and developing future adoptive immunotherapies.
The Impact of Proton Pump Inhibitors on the Development of Gastric Neoplastic Lesions in Patients With Autoimmune Atrophic Gastritis
Authors: Dilaghi Emanuele , Bellisario Mario , Esposito Gianluca , Carabotti Marilia , Annibale Bruno , Lahner Edith
Published: July 2022

Introduction

Proton pump inhibitors (PPIs) have been widely prescribed as a primary treatment for acid-related disorders. A large body of literature reported several adverse outcomes due to PPI therapy, including an increased risk of gastric cancer (GC). Autoimmune atrophic gastritis (AAG) is a chronic inflammatory disorder affecting the oxyntic mucosa, leading to mucosal atrophy, intestinal metaplasia, and reduced gastric acid secretion, up to the possible development of dysplasia and intestinal-type GC. Whether PPI use may increase the GC risk in AAG patients has not yet been investigated. We conducted a case–control study in AAG patients to assess the association between the PPI use before AAG diagnosis and the development of GC at follow-up (FU).

Materials and Methods

Patients were included from a prospective cohort of AAG patients (diagnosed 1992–2021) in a referral center for gastric autoimmunity; all patients adhered to an endoscopic–histological FU program according to Management of precancerous conditions and lesions in the stomach (MAPS) I/II (management of epithelial precancerous conditions) guidelines. At diagnosis, clinical/biochemical data and PPI use before AAG diagnosis (withdrawn at the time of diagnosis), for at least 12 months, were evaluated. Patients who developed gastric neoplastic lesions (GNLs) at FU were considered as cases; patients without a diagnosis of GNLs at FU were considered as controls. At a total FU of 2.3 years (1–13), 35 cases were identified, and controls were matched 2:1 by age ( ± 3 years), gender, and years of FU (n=70); therefore, a total of n=105 patients were included in the study.

Results

The proportion of PPI users before AAG diagnosis was significantly higher in cases than in controls (54.3% vs. 18.6%, p<0.001). At logistic regression, considering as a dependent variable the development of GNLs at FU, a positive association was shown for PPI use before AAG diagnosis (OR 9.6, 95%CI 2.3–40.3), while other independent variables as the use of antiplatelets/anticoagulants (OR 2.8, 95%CI 0.7–12.0), age ≥ 50 years (OR 2.0, 95%CI 0.2–18.1), 1st-degree family history for GC (OR 2.4, 95%CI 0.4–15.2), and smoking habit (OR 0.4, 95%CI 0.1–2.1) were not associated.

Conclusions

PPI use before the diagnosis of AAG appears to considerably increase the risk of subsequent GNL development. Considering the common misuse of PPIs, physicians should regularly reevaluate the appropriateness of ongoing PPI therapy, in particular in patients with a clinical suspicion of or already diagnosed AAG.
Case Report: Suspected Case of Brucella-Associated Immune Reconstitution Inflammatory Syndrome
Authors: Qu Chunmei , Xu Nannan , Niu Dehong , Wen Sai , Yang Hui , Wang Shanshan , Wang Gang
Published: July 2022

Human brucellosis is one of the most prevalent zoonoses. There are many similarities between the pathogenesis of Mycobacterium tuberculosis (MTB) infection and that of brucellosis. Immune reconstitution inflammatory syndrome (IRIS) may occur during the treatment of MTB infection, but it has not been reported in brucellosis cases thus far. We report the case of a 40-year-old male whose condition initially improved after adequate anti-Brucella therapy. However, 3 weeks later, the patient presented with exacerbation of symptoms and development of a paravertebral abscess. After exclusion of other possible causes of clinical deterioration, immune reconstitution inflammatory syndrome (IRIS) with brucellosis was presumed. After supplementation with anti-Brucella treatment with corticosteroids, the abscess disappeared, and the symptoms completely resolved. Our case suggests that it is necessary to be aware of the possible occurrence of IRIS in patients with brucellosis in clinical practice.
Intestinal alkaline phosphatase (IAP, IAP Enhancer) attenuates intestinal inflammation and alleviates insulin resistance
Authors: Gao Chenzhe , Koko Marwa Yagoub Farag , Ding Mingxing , Hong Weichen , Li Jianping , Dong Na , Hui Mizhou
Published: July 2022

In this study, we investigated the effects of intestinal alkaline phosphatase (IAP) in controlled intestinal inflammation and alleviated associated insulin resistance (IR). We also explored the possible underlying molecular mechanisms, showed the preventive effect of IAP on IR in vivo, and verified the dephosphorylation of IAP for the inhibition of intestinal inflammation in vitro. Furthermore, we examined the preventive role of IAP in IR induced by a high-fat diet in mice. We found that an IAP + IAP enhancer significantly ameliorated blood glucose, insulin, low-density lipoprotein, gut barrier function, inflammatory markers, and lipopolysaccharide (LPS) in serum. IAP could dephosphorylate LPS and nucleoside triphosphate in a pH-dependent manner in vitro. Firstly, LPS is inactivated by IAP and IAP reduces LPS-induced inflammation. Secondly, adenosine, a dephosphorylated product of adenosine triphosphate, elicited anti-inflammatory effects by binding to the A2A receptor, which inhibits NF-κB, TNF, and PI3K-Akt signalling pathways. Hence, IAP can be used as a natural anti-inflammatory agent to reduce intestinal inflammation-induced IR.
Natural fish oil improves the differentiation and maturation of oligodendrocyte precursor cells to oligodendrocytes in vitro after interaction with the blood–brain barrier
Authors: Piatek Paweł , Lewkowicz Natalia , Michlewska Sylwia , Wieczorek Marek , Bonikowski Radosław , Parchem Karol , Lewkowicz Przemysław , Namiecinska Magdalena
Published: July 2022

The blood–brain barrier (BBB) tightly controls the microenvironment of the central nervous system (CNS) to allow neurons to function properly. Additionally, emerging studies point to the beneficial effect of natural oils affecting a wide variety of physiological and pathological processes in the human body. In this study, using an in vitro model of the BBB, we tested the influence of natural fish oil mixture (FOM) vs. borage oil (BO), both rich in long-chain polyunsaturated fatty acids (LC-PUFAs) and monounsaturated fatty acids (MUFAs) such as oleic acid (C18:1n9c) or nervonic acid (NA), on human oligodendrocyte precursor cells (hOPCs) during their maturation to oligodendrocytes (OLs) regarding their ability to synthesize myelin peptides and NA. We demonstrated that FOM, opposite to BO, supplemented endothelial cells (ECs) and astrocytes forming the BBB, affecting the function of hOPCs during their maturation. This resulted in improved synthesis of myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), proteolipid protein (PLP), and NA in mature OLs. This effect is probably the result of BBB cell and hOPC stimulation via free fatty acid receptors (FFARs), which increases insulin growth factor-1 (IGF-1), ciliary neurotrophic factor (CNTF), and brain-derived neurotrophic factor (BDNF) and inhibits fibroblast growth factor 2 (FGF-2) synthesis. The unique formula of fish oil, characterized by much more varied components compared to those of BOs, also improved the enhancement of the tight junction by increasing the expression of claudin-5 and VE-cadherin on ECs. The obtained data justify consideration of naturally derived fish oil intake in human diet as affecting during remyelination.