bluuebunny/crossref_metadata_2025 huggingface dataset:
Visit-to-Visit Heart Rate Variability Is Positively Associated With the Risk of Adverse Cardiovascular Outcomes
Authors: Zeng Rong , Wang Zuoguang , Cheng Wenli , Yang Kun
Published: March 2022

Introduction

Previous studies found visit-to-visit heart rate variability (VVHRV) may be positively associated with risks of several cardiovascular events, but whether VVHRV affected the benefit of intensive blood pressure control remained unknown. In this study, we assessed the risk of the composite cardiovascular outcomes associated with VVHRV among the older patients with hypertension and evaluated whether the benefit of intensive blood pressure control in the prevention of the composite cardiovascular outcomes was consistent in the context of elevated VVHRV.

Methods

This was a post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). We explored the relationship between VVHRV and the composite cardiovascular outcomes by multivariate Cox proportional hazard regressions. The primary endpoint was the composite cardiovascular outcomes, same as SPRINT, defined as a composite of myocardial infarction, stroke, heart failure, and/or death from cardiovascular causes. We used multiple adjustment models for all regressions.

Results

Nine thousand two hundred and fourty-seven patients from the SPRINT were included in our analysis. We found a positive association between VVHRV and the risk of composite cardiovascular outcomes among the elderly with hypertension. Per 1 CV increment in HRCV, the hazard ratio of the risk of composite cardiovascular outcomes was 1.04 (95CI: 1.03, 1.05) in the fully adjusted Model. The benefit of intensive blood pressure control in managing cardiovascular events was consistent in different VVHRV subgroups. There was no significant interaction in other confounders.

Conclusion

We found the VVHRV was associated with the composite cardiovascular outcomes among the elderly with hypertension, intensive blood pressure control did not change the above association, and the benefits of intensive blood pressure management were consistent across different VVHRV groups.
Preeclampsia and Venous Thromboembolism: Pathophysiology and Potential Therapy
Authors: Raia-Barjat Tiphaine , Edebiri Osasere , Ni Ainle Fionnuala
Published: March 2022

Preeclampsia (PET) is a multisystem inflammatory disorder that represents a leading cause of feto-maternal morbidity and mortality, complicating 2–5% of all pregnancies. PET incurs an increased risk of venous thromboembolism, which is one of the leading causes of death in pregnancy and in the postpartum period. This prothrombotic phenotype is attributable to the maternal phase of PET, which is characterized by a systemic inflammatory response and coagulation activation. Research continues to be undertaken in terms of preventative measures, however, currently revolves around pharmacological low dose aspirin initiated in the first trimester of pregnancy for those with risk factors. Treatment involves antenatal corticosteroids for fetal lung development in preterm birth, parenteral magnesium sulfate for fetal neuroprotection and maternal seizure prophylaxis, and timely birth of the fetus and placenta being the only definitive treatment of PET. Patients with a venous thromboembolism (VTE) risk deemed to be >1–3% are treated with pharmacological thromboprophylaxis in the form of low molecular weight heparin. Completing each woman’s VTE risk assessment is crucial, particularly in the setting of PET, as there is also a proven associated competing hemorrhagic risk.
Relationship Between Summer Compound Hot and dry Extremes in China and the Snow Cover Pattern in the Preceding Winter
Authors: Yao Haoxin , Zhao Liang , Shen Xinyong , Xiao Ziniu , Li Qingquan
Published: March 2022

With global warming, the probability of summer compound hot and dry extreme (CHDE) days, which are higher risk compared with single-factor extreme events, increases in some regions. However, there have been few studies on the winter precursor signals of such events. In this study, we found that summer CHDEs have generally increased in the last 20 years, with the increases in the middle and lower reaches of the Yangtze River region and Southwest China being more than double those in other regions of China. The dominant mode of summer CHDEs in China is characterized by more hot–dry days in the Yangtze–Huaihe River Basin (YHRB). Importantly, we found that there is an obvious cross-seasonal relationship between the first mode of winter snow cover in the Northern Hemisphere (NH) and summer CHDEs in China. When the mode of winter snow cover in the NH is in a positive phase with a negative-phase Arctic Oscillation (AO), i.e., more snow cover in Europe, Northeast China, and the northern United States, and less snow cover in central Asia and the midlatitudes in winter, more CHDEs in China in the following summer. Compared with the signals from the AO, these signals from winter snow can be better stored and transmitted into summer through the snow, soil and ocean, inducing a northward shift of the upper-level westerly jet and strengthening of South Asia high. Through the strong dynamic forcing of negative vorticity advection with the change of westerly jet, the subsidence movement in the western Pacific subtropical high (WPSH) region is strengthened, resulting in the stable maintenance of the WPSH in the YHRB. Under the synergy of a remote mid- and high-latitude wave train in summer, which also relates closely to winter snow cover, more CHDEs ultimately occur in the YHRB of China.
Development and Validation of Measure on Student-Teacher Relationship in the Indian Context
Authors: Yadav Shreshtha , Kohli Neena , Yadav Anil Kumar , Naveen  , Tiwari Trayambak , Mishra Tarun
Published: March 2022

The notion that the student-teacher relationship is quintessential for the holistic development and success of students has been well established through various research. A considerable number of studies have been conducted in western countries, and various scales have been developed to measure student-teacher relationship. These scales have been extended to various cultural contexts. However, few studies have been found to focus on the suitability and applicability of these scales and theories of student-teacher relationship in the Indian context. In the western context, most of the studies on the student-teacher relationship were based on the attachment theory. In the context of Indian culture, student-teacher relationship functions beyond the boundaries of attachment theory. It is well acknowledged that Indian culture differs vastly from other cultures. Given the uniqueness of Indian culture, the present study advocated that nature of student-teacher relationship in the Indian context is significantly different from western countries. There was a need to develop a scale for measuring student-teacher relationship in the Indian context. This study intended to construct a scale on student-teacher relationship in the Indian context. Standard procedure was followed in the process of scale construction. Results of the first study illustrated a four factor (dedication, trust, respect, and obedience) model of student-teacher relationship, and a second study confirmed this model and ensured reliability and validity of the scale.
Navigating Education in the Context of COVID-19 Lockdowns and School Closures: Challenges and Resilience Among Adolescent Girls and Young Women in South Africa
Authors: Duby Zoe , Jonas Kim , Bunce Brittany , Bergh Kate , Maruping Kealeboga , Fowler Chantal , Reddy Tarylee , Govindasamy Darshini , Mathews Catherine
Published: March 2022

Gender related vulnerabilities and inequalities place female learners at high risk of school disengagement due to COVID-19 disruptions. Understanding the impacts of school closures and educational disruptions on female learners in South Africa is critical to inform appropriate, gender-sensitive policies, and programs, to mitigate further exacerbation of educational inequalities. We examined the effects that COVID-19 and lockdowns have had on the educational experiences of adolescent girls and young women (AGYW) aged 15–24, in six districts of South Africa characterized by high rates of HIV, teenage pregnancy and socio-economic hardship. Following a concurrent triangulation mixed-methods approach, we conducted a cross-sectional survey with 515 AGYW, and qualitative interviews with 50 AGYW. More than half of survey participants enrolled in education had been unable to continue with their studies. Factors associated with educational disruption included low socio-economic status, lack of cell phone access and household food insecurity. Qualitative narratives included challenges with online learning and studying at home in resource restricted settings, and insufficient support from schools and teachers. However, despite multiple barriers to continuing education, some AGYW demonstrated educational resilience, enabled by psychosocial and structural support, and resource access. Our findings lend support to an emerging evidence base showing that the closure of schools and tertiary institutions, combined with challenging home environments, and a lack of access to appropriate technology, has disproportionately impacted the most vulnerable AGYW, exacerbating pre-existing educational inequalities within the South African education system. Addressing structural barriers to educational equity, particularly in the pandemic context, including access of technology and the internet, is urgent.
Underestimated Prediabetic Biomarkers: Are We Blind to Their Strategy?
Authors: Luís Carla , Soares Raquel , Baylina Pilar , Fernandes Rúben
Published: March 2022

Type 2 Diabetes (T2D) is currently one of the fastest growing health challenging, a non-communicable disease result of the XXI century lifestyle. Given its growing incidence and prevalence, it became increasingly imperative to develop new technologies and implement new biomarkers for early diagnosis in order to promote lifestyle changes and thus cause a setback of the disease. Promising biomarkers have been identified as predictive of T2D development; however, none of them have yet been implemented in clinical practice routine. Moreover, many prediabetic biomarkers can also represent potential therapeutical targets in disease management. Previous studies have identified the most popular biomarkers, which are being thoroughly investigated. However, there are some biomarkers with promising preliminary results with limited associated studies; hence there is still much to be understood about its mechanisms and associations in T2D pathophysiology. This work identifies and discusses the promising results of Galectin-3, Ophthalmate and Fetuin-A.
miRNAs as Predictive Factors in Early Diagnosis of Gestational Diabetes Mellitus
Authors: Juchnicka Ilona , Kuźmicki Mariusz , Niemira Magdalena , Bielska Agnieszka , Sidorkiewicz Iwona , Zbucka-Krętowska Monika , Krętowski Adam Jacek , Szamatowicz Jacek
Published: March 2022

Introduction

Circulating miRNAs are important mediators in epigenetic changes. These non-coding molecules regulate post-transcriptional gene expression by binding to mRNA. As a result, they influence the development of many diseases, such as gestational diabetes mellitus (GDM). Therefore, this study investigates the changes in the miRNA profile in GDM patients before hyperglycemia appears.

Materials and Methods

The study group consisted of 24 patients with GDM, and the control group was 24 normoglycemic pregnant women who were matched for body mass index (BMI), age, and gestational age. GDM was diagnosed with an oral glucose tolerance test between the 24th and 26th weeks of pregnancy. The study had a prospective design, and serum for analysis was obtained in the first trimester of pregnancy. Circulating miRNAs were measured using the NanoString quantitative assay platform. Validation with real time-polymerase chain reaction (RT-PCR) was performed on the same group of patients. Mann-Whitney U-test and Spearman correlation were done to assess the significance of the results.

Results

Among the 800 miRNAs, 221 miRNAs were not detected, and 439 were close to background noise. The remaining miRNAs were carefully investigated for their average counts, fold changes, p-values, and false discovery rate (FDR) scores. We selected four miRNAs for further validation: miR-16-5p, miR-142-3p, miR-144-3p, and miR-320e, which showed the most prominent changes between the studied groups. The validation showed up-regulation of miR-16-5p (p<0.0001), miR-142-3p (p=0.001), and miR-144-3p (p=0.003).

Conclusion

We present changes in miRNA profile in the serum of GDM women, which may indicate significance in the pathophysiology of GDM. These findings emphasize the role of miRNAs as a predictive factor that could potentially be useful in early diagnosis.
Loss Prediction of Ultrahigh Voltage Transmission Lines Based on EEMD–LSTM–SVR Algorithm
Authors: Ding Can , Zhou Yiyuan , Ding Qingchang , Wang Zhenyi
Published: March 2022

Line loss prediction of ultrahigh voltage transmission lines is the key for ensuring the safe, reliable, and economical operation of the power system. However, the strong volatility of line loss brings challenges to the prediction of transmission line loss. For more accurate prediction, this article uses ensemble empirical mode decomposition (EEMD) to decompose the line loss and proposes the EEMD–LSTM–SVR prediction model. First of all, this article performs feature engineering on power flow, electric energy, and meteorological data and extracts the exponentially weighted moving average (EWMA) feature from the line loss. After the integration of the time dimension, this article mines the curve characteristics from the time series and constructs a multidimensional input dataset. Then, through ensemble empirical mode decomposition, the line loss is decomposed into high-frequency, low-frequency, and random IMFs. These IMFs and the standardized multidimensional dataset together constitute the final input dataset. In this article, each IMF fusion dataset is sent to LSTM and support vector regression models for training. In the training process, the incremental cross-validation method is used for model evaluation, and the grid search method is used for hyperparameter optimization. After evaluation, the LSTM algorithm predicts high-frequency IMF1 and 2 and random IMF4 and 5; the SVR algorithm predicts low-frequency IMF6 and 7 and random IMF3. Finally, the output value of each model is superimposed to obtain the final line loss prediction value. Also, the comparative predictions were performed using EEMD–LSTM, EEMD–SVR, LSTM, and SVR. Compared with the independent prediction models EEMD–LSTM and EEMD–SVR, the combined EEMD–LSTM–SVR algorithm has a decrease in mean absolute performance error% by 2.2 and 25.37, respectively, which fully demonstrates that the combined model has better prediction effect than the individual models. Compared with that of SVR, the MAPE% of EEMD–SVR decreases by 11.16. Compared with that of LSTM, the MAPE% of EEMD–LSTM is reduced by 32.72. The results show that EEMD decomposition of line loss series can effectively improve the prediction accuracy and reduce the strong volatility of line loss. Compared with that of the other four algorithms, EEMD–LSTM–SVR has the highest R-square of 0.9878. Therefore, the algorithm proposed in this article has the best effectiveness, accuracy, and robustness.
Design, Fabrication, and Thermal Evaluation of a Solar Cooking System Integrated With Tracking Device and Sensible Heat Storage Materials
Authors: Komolafe Clement A. , Okonkwo Clinton E.
Published: March 2022

Energy need for cooking in both the rural and urban areas all over the world is increasing every day as a result of an increase in population. The consequence of global warming due to the usage of fuels such as fossil fuel, firewood, and other biomass products for cooking necessitates innovative techniques that will improve the standard of living of people. In this study, the design, fabrication, and thermal evaluation of a solar cooking system integrated with an Arduino-based tracking device and sensible heat storage (SHS) materials was investigated. During the water boiling trials with black oil sensible material (BOSHSM), the obtained maximum temperatures for water, cooking box, and sensible heat storage material at 14:00 h when the solar radiation attained its peak value of 881.2 W/m2 were 64,52, and 54°C, respectively, while at 14:00 h with Black coated granite sensible heat storage material (BCGSHSM) at the solar radiation peak value of 890.4 W/m2, the maximum temperatures for water, cooking box, and sensible heat storage material were 73.5, 76, and 59°C, respectively. The maximum cooking power and thermal efficiency obtained from the water boiling trials were 48.4 and 56.4 W, and 31.6 and 35.8% respectively. Also, the results from the cooking of edibles revealed that the cooking power values ranged between 42.5 and 58.2, while that of efficiency ranged between 34.5 and 40.3% respectively. The maximum solar radiation during the cooking trial period was 986, 975, 956, and 953 W/m2. In general, from the results, the developed solar cooking system is a viable alternative to cooking with traditional/open burning of wood or other biomass products that pose a serious environmental and health-related threat to the people living in developing countries.
Performance and Economic Analysis of Organosolv Softwood and Herbaceous Lignins to Activated Carbons as Electrode Materials in Supercapacitors
Authors: Yu Lu , Seabright Kendhl , Bajaj Ishan , Keffer David J. , Alonso David M. , Hsieh Chien-Te , Li Mi , Chen Hao , Dai Sheng , Gandomi Yasser Ashraf , Maravelias Christos T. , Harper David P.
Published: March 2022

In this work, yellow pine (YP, softwood) and switchgrass (SG, grass) lignins were extracted as a coproduct of an organosolv γ-valerolactone (GVL) biorefinery that also produces biofuels and furfural. The extracted lignins were converted to carbon precursors for synthesizing porous activated carbon electrodes for high energy-density supercapacitors. This research details the impact of lignin composition on the derived porous structures and electrochemical properties of activated carbons. Lignin precursors with various syringyl (S) to guaiacyl (G) contents were characterized using31P nuclear magnetic resonance (NMR) and two-dimensional1H‒13C NMR. A two-step activation process, using steam and carbon dioxide as the activating agents, enabled the formation of porous carbons structures with high surface area. The capacitive behavior of supercapacitors was systematically characterized by cyclic voltammetry, charge-discharge cycling, and electrochemical impedance spectroscopy. The specific capacitance of YP and SG capacitors reached 367 and 221 F g−1, respectively. Both types of capacitors demonstrated remarkably stable capacitance (capacitance retention >90%) along with excellent Coulombic efficiency (>99%) over 10,000 cycles. Compared to SG electrode, the better electrochemical performance achieved with YP electrodes was mainly due to shorter diffusion path, improved ionic mobility, and increased active surface area. The inexpensive lignin-based porous electrodes synthesized in this work can be used for various electrochemical devices for improved performance, decreased cost, and enhanced durability. This work also demonstrates that the selection of feedstock and appropriate processing conditions can tailor the structure of carbon composites for targeted applications. Techno-economic analysis indicates that YP and SG activated carbons can be produced at a minimum selling price of $8,493 and $6,670 per ton, respectively, which is competitive with the commercially available supercapacitor-grade activated carbons.
Assessing Hybridization Risk Between ESA-Listed Native Bull Trout (Salvelinus confluentus) and Introduced Brook Trout (S. fontinalis) Using Habitat Modeling
Authors: Manning Michael A. , Arismendi Ivan , Olivos J. Andres , Giannico Guillermo
Published: March 2022

The introduction of non-native species can negatively impact native species through reduced genetic fitness resulting from hybridization. The lack of spatiotemporal data on hybrid occurrences makes hybridization risk assessment difficult. Here, we developed a spatially-explicit Hybridization Risk Model (HRM) between native Oregon bull trout, an Endangered Species Act-listed Oregon species, and introduced brook trout by combining an intrinsic potential model (IPM) of brook trout spawning habitat and existing bull trout distribution and habitat use datasets in Oregon, United States. We created an expert-based brook trout IPM classification score (0–1) of streams based on the potential of geophysical attributes (i.e., temperature, discharge, gradient, and valley confinement) to sustain spawning habitats. The HRM included a risk matrix based on the presence/absence of both species as well as the type of habitat (spawning versus other) at 100-m stream segment resolution. We defined the hybridization risk as “extreme” when stream reaches contained bull trout spawning habitat and brook trout were present with IPM moderate or greater scores (IPM >0.5). Conversely, “low” risk reaches contained historic or non-spawning bull trout habitat, brook trout were absent, and IPM scores were low (IPM <0.25). Our HRM classified 34 km of streams with extreme risk of hybridization, 115 km with high risk, 178 km with moderate risk, and 6,023 km with low risk. Our HRM can identify a differential risk of hybridization at multiple spatial scales when either both species coexist in bull trout spawning habitat or are absent. The model can also identify stream reaches that would have higher risk of hybridization, but where brook trout are not currently present. Our modeling approach can be applied to other species, such as cutthroat trout and rainbow trout, Chinook and coho salmon, or similar species occurring elsewhere that potentially hybridize in freshwaters.
Winter Climate Variability, De-Icing Salt and Streetside Tree Vitality
Authors: Miron Justin , Millward Andrew A. , Vaziriyeganeh Maryamsadat , Zwiazek Janusz J. , Urban James
Published: March 2022

De-icing salts are applied to roads and walking surfaces to mitigate winter hazards resulting from ice, snow and freezing rain. The vitality of streetside trees, especially those growing in densely built urban areas, is compromised by repeated exposure to de-icing salts. Such trees already experience unfavorable establishment and growing conditions resulting from poor soil quality, inadequate moisture, physical abuse and air pollution−exposure to de-icing salt aggravates these challenges and can be an essential catalyst in tree mortality. Climate change is creating less predictable weather and, in some cases amplifying the intensity of winter storms. Cities that undertake snow and ice management may adopt modified approaches, and those less familiar with this practice may require its episodic adoption. We identify three pathways by which future climate warming may, counterintuitively, result in cities increasing their use of de-icing salt: (a) Warming winter temperatures in cities that were historically too cold to make effective use of sodium chloride (NaCl) for de-icing; (b) cities where daily high temperatures in winter may increase the frequency of freeze-thaw cycles; and, (c) cities in North America and Eurasia that may experience more severe winter weather resulting from greater variability in the circumpolar vortex (CPV). To offset potential damage to existing urban streetside trees and to ensure adequate soil and growing conditions for future trees, there is an immediate need for city foresters to collaborate with traffic safety and public works departments. We present a toolbox of approaches that can facilitate synchronized management efforts, including identifying the location of existing vulnerable trees and re-envisioning future infrastructure that would mitigate tree exposure to de-icing salts. At the same time, we call for the prioritization of research that investigates new potential pathways along which climate change may contribute to the novel adoption of de-icing salts.
Histone H3 Methylation and Autosomal vs. Sex Chromosome Segregation During Male Meiosis in Heteroptera
Authors: Toscani María Ayelen , Pigozzi María Inés , Papeschi Alba G. , Bressa María José
Published: March 2022

Heteropteran insects exhibit a remarkable diversity of meiotic processes, including coexistence of different chromosomes types with different behavior during the first meiotic division, non-chiasmatic segregation, and inverted meiosis. Because of this diversity they represent suitable models to study fundamental questions about the mechanisms of chromosome behavior during cell division. All heteropteran species possess holokinetic chromosomes and in most of them the autosomal chromosomes synapse, recombine, and undergoe pre-reductional meiosis. In contrast, the sex chromosomes are achiasmatic, behave as univalents at metaphase I and present an inverted or post-reductional meiosis. An exception to this typical behavior is found in Pachylis argentinus, where both the autosomes and the X-chromosome divide reductionally at anaphase I and then divide equationally at anaphase II. In the present report, we analyzed the distribution of histones H3K9me2 and H3K9me3 in P. argentinus and in five species that have simple and multiple sex chromosome systems with typical chromosome segregation, Belostoma elegans, B. oxyurum, Holhymenia rubiginosa, Phthia picta, and Oncopeltus unifasciatellus. We found that H3K9me3 is a marker for sex-chromosomes from early prophase I to the end of the first division in all the species. H3K9me2 also marks the sex chromosomes since early prophase but shows different dynamics at metaphase I depending on the sex-chromosome segregation: it is lost in species with equationally dividing sex chromosomes but remains on one end of the X chromosome of P. argentinus, where chromatids migrate together at anaphase I. It is proposed that the loss of H3K9me2 from the sex chromosomes observed at metaphase I may be part of a set of epigenetic signals that lead to the reductional or equational division of autosomes and sex chromosomes observed in most Heteroptera. The present observations suggest that the histone modifications analyzed here evolved in Heteroptera as markers for asynaptic and achiasmatic sex chromosomes during meiosis to allow the distinction from the chiasmatic autosomal chromosomes.
Principles of Nanoparticle Design for Genome Editing in Plants
Authors: Sharma Pushkal , Lew Tedrick Thomas Salim
Published: March 2022

Precise plant genome editing technologies have provided new opportunities to accelerate crop improvement and develop more sustainable agricultural systems. In particular, the prokaryote-derived CRISPR platforms allow precise manipulation of the crop genome, enabling the generation of high-yielding and stress-tolerant crop varieties. Nanotechnology has the potential to catalyze the development of a novel molecular toolbox even further by introducing the possibility of a rapid, universal delivery method to edit the plant genome in a species-independent manner. In this Perspective, we highlight how nanoparticles can help unlock the full potential of CRISPR/Cas technology in targeted manipulation of the plant genome to improve agricultural output. We discuss current challenges hampering progress in nanoparticle-enabled plant gene-editing research and application in the field, and highlight how rational nanoparticle design can overcome them. Finally, we examine the implications of the regulatory frameworks and social acceptance for the future of nano-enabled precision breeding in the developing world.
HSPB8 is a Potential Prognostic Biomarker that Correlates With Immune Cell Infiltration in Bladder Cancer
Authors: Tan Zhiyong , Fu Shi , Huang Yinglong , Duan Xianzhong , Zuo Yigang , Zhu Xiaorui , Wang Haifeng , Wang Jiansong
Published: March 2022

Background: Heat shock protein B8 (HSPB8) is expressed in various cancers. However, the functional and clinicopathological significance of HSPB8 expression in bladder cancer (BC) remains unclear. The present study sought to elucidate the clinicopathological features and prognostic value of HSPB8 in BC.

Methods: A BC RNA-seq data set was obtained from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) database, and the external validation dataset GSE130598 was downloaded from the GEO database. Samples in the TCGA-BLCA were categorized into two groups based on HSPB8 expression. Differentially expressed genes (DEGs) between the two groups were defined as HSPB8 co-expressed genes. Gene set enrichment analysis (GSEA), protein-protein interaction networks, and mRNA-microRNA (miRNA) interaction networks were generated to predict the function and interactions of genes that are co-expressed with HSPB8. Finally, we examined immune cell infiltration and constructed a survival prediction model for BC patients.

Results: The expression level of HSBP8 has a significant difference between cancer samples and normal samples, and its diagnosis effect was validated by the ROC curve. 446 differential expressed genes between HSBP8 high-expression and HSBP8 low expression groups were identified. Gene enrichment analysis and GSEA analysis show that these differential gene functions are closely related to the occurrence and development of BC and the metabolic pathways of BC. The cancer-related pathways included Cytokine-cytokine receptor Interaction, Focal adhesion, and Proteoglycans in cancer. PPI and protein-coding gene-miRNA network visualized the landscape for these tightly bounded gene interactions. Immune cell infiltration shows that B cells, CD4+T cells, and CD8+T cells have strongly different infiltration levels between the HSBP8 high exp group and low exp group. The survival prediction model shows that HSBP8 has strong prognosis power in the BLCA cohort.

Conclusion: Identifying DEGs may enhance understanding of BC development’s causes and molecular mechanisms. HSPB8 may play an essential role in BC progression and prognosis and serve as a potential biomarker for BC treatment.
Comprehensive Genetic Analysis of Tuberculosis and Identification of Candidate Biomarkers
Authors: Wen Zilu , Wu Liwei , Wang Lin , Ou Qinfang , Ma Hui , Wu Qihang , Zhang Shulin , Song Yanzheng
Published: March 2022

Purpose: The purpose of this study is to use the data in the GEO database to analyze, screen biomarkers that can diagnose tuberculosis, and verification of candidate biomarkers.

Materials and methods: GSE158767 dataset were used to process WGCNA analysis, differential gene analysis, Gene ontology and KEGG analysis, protein-protein network analysis and hub genes analysis. Based on our previous study, the intersect between WGCNA and differential gene analysis could be used as candidate biomarkers. Then, the enzyme-linked immunosorbent assay was used to validate candidate biomarkers, and receiver operating characteristic was used to assess diagnose ability of candidate biomarkers.

Results: A total of 412 differential genes were screened. And we obtained 105 overlapping genes between DEGs and WGCNA. GO and KEGG analysis showed that most of the differential genes were significantly enriched in innate immunity. A total of 15 hub genes were screened, and four of them were verified by Enzyme-linked immunosorbent assay. CCL5 performed well in distinguishing the healthy group from the TB group (AUC = 0.723). And CCL19 performed well in distinguishing the TB group from the ORD groups (AUC = 0.811).

Conclusion: CCL19, C1Qb, CCL5 and HLA-DMB may play important role in tuberculosis, which indicated four genes may become effective biomarkers and could be conveniently used to facilitate the individual tuberculosis diagnosis in Chinese people.
Neutralisation Hierarchy of SARS-CoV-2 Variants of Concern Using Standardised, Quantitative Neutralisation Assays Reveals a Correlation With Disease Severity; Towards Deciphering Protective Antibody Thresholds
Authors: Cantoni Diego , Mayora-Neto Martin , Nadesalingam Angalee , Wells David A. , Carnell George W. , Ohlendorf Luis , Ferrari Matteo , Palmer Phil , Chan Andrew C.Y. , Smith Peter , Bentley Emma M. , Einhauser Sebastian , Wagner Ralf , Page Mark , Raddi Gianmarco , Baxendale Helen , Castillo-Olivares Javier , Heeney Jonathan , Temperton Nigel
Published: March 2022

The rise of SARS-CoV-2 variants has made the pursuit to define correlates of protection more troublesome, despite the availability of the World Health Organisation (WHO) International Standard for anti-SARS-CoV-2 Immunoglobulin sera, a key reagent used to standardise laboratory findings into an international unitage. Using pseudotyped virus, we examine the capacity of convalescent sera, from a well-defined cohort of healthcare workers (HCW) and Patients infected during the first wave from a national critical care centre in the UK to neutralise B.1.1.298, variants of interest (VOI) B.1.617.1 (Kappa), and four VOCs, B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta), including the B.1.617.2 K417N, informally known as Delta Plus. We utilised the WHO International Standard for anti-SARS-CoV-2 Immunoglobulin to report neutralisation antibody levels in International Units per mL. Our data demonstrate a significant reduction in the ability of first wave convalescent sera to neutralise the VOCs. Patients and HCWs with more severe COVID-19 were found to have higher antibody titres and to neutralise the VOCs more effectively than individuals with milder symptoms. Using an estimated threshold for 50% protection, 54 IU/mL, we found most asymptomatic and mild cases did not produce titres above this threshold.
Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting
Authors: Guo Ruiting , Lu Wenyi , Zhang Yi , Cao Xinping , Jin Xin , Zhao Mingfeng
Published: March 2022

With the gradual improvement of treatment regimens, the survival time of multiple myeloma (MM) patients has been significantly prolonged. Even so, MM is still a nightmare with an inferior prognosis. B-cell maturation antigen (BCMA) is highly expressed on the surface of malignant myeloma cells. For the past few years, significant progress has been made in various BCMA-targeted immunotherapies for treating patients with RRMM, including anti-BCMA mAbs, antibody-drug conjugates, bispecific T-cell engagers, and BCMA-targeted adoptive cell therapy like chimeric antigen receptor (CAR)-T cell. The 63rd annual meeting of the American Society of Hematology updated some information about the application of BCMA in MM. This review summarizes part of the related points presented at this conference.
Sex Differences in Use of Low Tidal Volume Ventilation in COVID-19—Insights From the PRoVENT–COVID Study
Authors: Swart Pien , Nijbroek Sunny G. L. H. , Paulus Frederique , Neto Ary Serpa , Schultz Marcus J.
Published: March 2022

The purpose of this study was to compare and understand differences in the use of low tidal volume ventilation (LTVV) between females and males with acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). This is a post-hoc analysis of an observational study in invasively ventilated patients with ARDS related to COVID-19 in 22 ICUs in the Netherlands. The primary endpoint was the use of LTVV, defined as having received a median tidal volume (VT) ≤6 ml/kg predicted body weight (PBW) during controlled ventilation. A mediation analysis was used to investigate the impact of anthropometric factors, next to the impact of sex per se. The analysis included 934 patients, 251 females and 683 males. All the patients had ARDS, and there were no differences in ARDS severity between the sexes. On the first day of ventilation, females received ventilation with a higher median VT compared with males [6.8 (interquartile range (IQR) 6.0–7.6 vs. 6.3 (IQR 5.8–6.9) ml/kg PBW; p < 0.001]. Consequently, females received LTVV less often than males (23 vs. 34%; p = 0.003). The difference in the use of LTVV became smaller but persisted over the next days (27 vs. 36%; p = 0.046 at day 2 and 28 vs. 38%; p = 0.030 at day 3). The difference in the use LTVV was significantly mediated by sex per se [average direct effect of the female sex, 7.5% (95% CI, 1.7–13.3%); p = 0.011] and by differences in the body height [average causal mediation effect, −17.5% (−21.5 to −13.5%); p < 0.001], but not by the differences in actual body weight [average causal mediation effect, 0.2% (−0.8 to 1.2%); p = 0.715]. In conclusion, in this cohort of patients with ARDS related to COVID-19, females received LTVV less often than males in the first days of invasive ventilation. The difference in the use of LTVV was mainly driven by an anthropometric factor, namely, body height. Use of LTVV may improve by paying attention to correct titration of VT, which should be based on PBW, which is a function of body height.
A Resampling Method to Improve the Prognostic Model of End-Stage Kidney Disease: A Better Strategy for Imbalanced Data
Authors: Shi Xi , Qu Tingyu , Van Pottelbergh Gijs , van den Akker Marjan , De Moor Bart
Published: March 2022

Background

Prognostic models can help to identify patients at risk for end-stage kidney disease (ESKD) at an earlier stage to provide preventive medical interventions. Previous studies mostly applied the Cox proportional hazards model. The aim of this study is to present a resampling method, which can deal with imbalanced data structure for the prognostic model and help to improve predictive performance.

Methods

The electronic health records of patients with chronic kidney disease (CKD) older than 50 years during 2005–2015 collected from primary care in Belgium were used (n = 11,645). Both the Cox proportional hazards model and the logistic regression analysis were applied as reference model. Then, the resampling method, the Synthetic Minority Over-Sampling Technique-Edited Nearest Neighbor (SMOTE-ENN), was applied as a preprocessing procedure followed by the logistic regression analysis. The performance was evaluated by accuracy, the area under the curve (AUC), confusion matrix, and F3 score.

Results

The C statistics for the Cox proportional hazards model was 0.807, while the AUC for the logistic regression analysis was 0.700, both on a comparable level to previous studies. With the model trained on the resampled set, 86.3% of patients with ESKD were correctly identified, although it was at the cost of the high misclassification rate of negative cases. The F3 score was 0.245, much higher than 0.043 for the logistic regression analysis and 0.022 for the Cox proportional hazards model.

Conclusion

This study pointed out the imbalanced data structure and its effects on prediction accuracy, which were not thoroughly discussed in previous studies. We were able to identify patients with high risk for ESKD better from a clinical perspective by using the resampling method. But, it has the limitation of the high misclassification of negative cases. The technique can be widely used in other clinical topics when imbalanced data structure should be considered.
The Clinical Phenotype of Chinese Patients With Autoimmune Pancreatitis Differs Significantly From Western Patients
Authors: Jin Qiwen , Ge Yongpeng , Chen Xixia , Tan Chang , Huang Zhenguo , Wang Bei , Zhang Bo , Peng Qinglin , Wang Xiaodi , Wang Guochun
Published: March 2022

Aim

To characterize the clinical features of autoimmune pancreatitis (AIP) in China and compare differences between our Chinese cohort and Western cohorts.

Methods

This was a retrospective study of patients with AIP that was carried out in the China-Japan Friendship Hospital between January 2010 and April 2021. We included a total of 50 patients (46 males and 4 females) aged between 27 and 86 years who fulfilled the international Consensus Diagnostic (ICD) Criteria. For comparative purposes, we included data from seven representative Western cohorts.

Result

When comparing Chinese and Western patients, we found that obstructive jaundice was the most frequent initial symptom (68 vs. 43%, P < 0.001). Extra-pancreatic organ involvement was more common in Chinese patients (68 vs. 30%, P < 0.001). Sclerosing cholangitis was the most frequent extrapancreatic lesion (48 vs. 24%, P = 0.001). The elevation of serum IgG4 was more obvious in our cohort (86 vs. 49%, P < 0.001). Conversely, the rates of ANA-positivity were significantly higher in Western populations (17 vs. 50%, P = 0.006). With regards to imaging, diffuse swelling was significantly more common in China (44 vs. 27%, P = 0.021). Steroid therapy was used more frequently in our Chinese patients (84 vs. 59%, P = 0.001). The steroid-response rate was also significantly higher in our Chinese patients (85 vs. 54%, P = 0.001); However, the rate of resection was higher in Western cohorts (2 vs. 31%, P < 0.001). There was no significant difference between the two populations with regards to recurrence rate (33 vs. 33%, P = 1.000).

Conclusion

This study identified significant differences between Chinese and Western populations of patients with AIP. Within the Chinese population, AIP was more likely to have jaundice and extra-pancreatic organ involvement, and elevated serum IgG4 levels. Chinese patients were also showed favorable responses to treatment with glucocorticoids.
Development and Validation of Prognostic Nomogram for Postpartum Hemorrhage After Vaginal Delivery: A Retrospective Cohort Study in China
Authors: Song Zixuan , Wang Xiaoxue , Zhou Yangzi , Wang Yuting , Zhang Dandan
Published: March 2022

Background

Postpartum hemorrhage (PPH) is a common complication following vaginal delivery and in severe cases can lead to maternal death. A straightforward predictive model is required to enable prenatal evaluations by obstetricians to prevent PPH complications.

Methods

Data of patients who delivered vaginally after 37 weeks of gestation were retrospectively collected from the medical database at Shengjing Hospital of China Medical University for the period 2016 to 2020. PPH was defined as blood loss of 500 mL or more within 24 h of delivery, and important independent prognostic factors were determined using univariate and multivariate logistic regression analyses to construct nomograms regarding PPH.

Results

A total of 24,833 patients who delivered vaginally were included in this study. The training cohort included 22,302 patients who delivered between 2016 and 2019 and the external validation cohort included 2,531 patients who delivered during 2020. Nomogram was created using data such as age, race, occupation, parity, gestational weeks, labor time, neonatal weight, analgesic delivery, gestational diabetes mellitus, premature rupture of membranes, anemia, hypertension, adenomyosis, and placental adhesion. The nomogram has good predictive power and clinical practicality through the analysis of the area under the curve and decision curve analysis. Internal verification was performed on the nomogram for PPH, demonstrating consistency between the nomogram's predicted probability and actual probability.

Conclusions

The developed and validatable nomogram is a good predictor of PPH in vaginal delivery and can be used in clinical practice to guide obstetricians to administer preventive therapies before delivery.
Cyclosporine Monotherapy in Pediatric Patients With Non-severe Aplastic Anemia: A Retrospective Analysis
Authors: Li Hongmin , Fu Lingling , Yang Bixi , Chen Hui , Ma Jie , Wu Runhui
Published: March 2022

Objective

The management of children with non-severe aplastic anemia (NSAA) is undefined and the efficacies and benefits of immunosuppressive therapy remain inconsistent. The study aimed to investigate the efficacy of Cyclosporine (CsA) monotherapy for pediatric NSAA.

Methods

Clinical data of children with NSAA who had been treated with CsA monotherapy at the outpatient department of Beijing Children's Hospital, Capital Medical University, National Children's Medical Center from January 2017 to March 2021 was collected retrospectively. Patients who had been treated <1 years until the end of follow-up were excluded. Transfusion-independent NSAA was further divided into moderate NSAA and mild NSAA according to the degree of cytopenia. Progression was defined as the development of transfusion-dependent AA or SAA and relapse was considered when treatment failed after initial response.

Results

A total of 95 pediatric patients with NSAA were enrolled in this study with 49 (51.6%) patients confirmed as mild NSAA, 38 (40%) as moderate NSAA and 8 (8.4%) as transfusion-dependent NSAA. The median treatment time of CsA was 22 (12–44) months. The overall response rate (ORR) was 57.9%, with 30.5% CR and 27.4% PR. Unexpectedly, patients with mild NSAA acquired lowest ORR (46.9%), then patients with moderate NSAA (63.2%), while 8 patients who were transfusion-dependent all had an active response to CsA. The granulocyte and megakaryocyte response was 46.9 and 55.8% respectively, while the erythrocyte response rate was as low as 22.5%. Univariate analyses revealed that patients with lower platelet count and higher interleukin 10 level predict an active response to CsA while higher level of fetal hemoglobin (HbF) tended to be a negative factor. Data of Treg cells before and after 1 year's treatment was available in a total number of 40 patients. Paired comparison found that the percentage of Treg cells in CD4+ T cells was decreased after 1 year's treatment of CsA (6.78 ± 2.72 vs. 5.23 ± 2.06, P = 0.001),both in responders and non-responders. The degree of decline in Treg cells between two distinctive response groups had no significant difference (P>0.05). With a median follow-up time of 22 months, 10.9% of responders relapsed and maintained NSAA while 27.5% of non-responders progressed to SAA or became transfusion-dependent. The overall progression rate was 11.6%.

Conclusion

CsA monotherapy had heterogeneous effects in the treatment of children NSAA Treatment approaches should be hierarchical and individual in clinical. Patients with lower platelet count and higher interleukin 10 level predicted an active response to CsA. While higher level of fetal hemoglobin (HbF) tended to be a negative factor. The percentage of Treg cells in CD4+ T cells was decreased broadly after treatment.
Plasma Homocysteine as a Potential Marker of Early Renal Function Decline in IgA Nephropathy
Authors: Wang Yan-Na , Xia Han , Song Zhuo-Ran , Zhou Xu-Jie , Zhang Hong
Published: March 2022

Hyperhomocysteinemia (HHcy) is very common among patients with chronic kidney disease (CKD), and related to the risk of cardiovascular events and mortality in these patients. However, the prevalence of HHcy in primary causes of CKD and its role in kidney disease progression are not well-understood. In this study, we investigated the prevalence of HHcy in different CKD stages in 221 patients with IgA nephropathy (IgAN) and 194 patients with other primary glomerular diseases. We also evaluated the association of homocysteine (Hcy) [after adjusted for estimated glomerular filtration rate (eGFR)] with CKD progression event, defined as ESKD or 50% decline in eGFR, in a cohort of 365 patients with IgAN. The prevalence of HHcy was 67.9% (150/221), 53.5% (76/142), 51.5% (17/33), and 42.1% (8/19) in patients with IgAN, membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, respectively. The Hcy/eGFR ratio was significantly associated with pathologic features of IgAN, including the proportion of global glomerulosclerosis (r = 0.38, p < 0.001), the proportion of ischemia originated glomerular sclerosis (r = 0.32, p < 0.001), and the severity of tubular atrophy/interstitial fibrosis (r = 0.57, p < 0.001). Importantly, Hcy/eGFR ratio was an independent risk factor for CKD progression event (hazard ratio, 1.38; 95% confidence interval, 1.13–1.68; p = 0.002). The risk of CKD progression events continuously increased with the Hcy/eGFR ratio, but reached a plateau when Hcy/eGFR ratio was >1.79. Our findings suggest that elevated Hcy/eGFR ratio may be an early marker of poor renal outcome in IgAN.