bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased populations will be exposed to the dangerous precipitation extremes across China in the future
Authors: Xu Huiwen , Chen Huopo , Wang Huijun
Published: August 2022

This study investigates the future changes in dangerous precipitation extremes with multiyear return periods and the population exposure across China at the 1.5–4°C warming levels via the latest simulations from the Coupled Model Intercomparison Project Phase 6 (CMIP6). The results show that the simulations project more frequent dangerous precipitation extremes across China under the warmer climate regardless of the shared socioeconomic pathway (SSP), with more substantial occurrence increases at the high warming levels. Consequently, the population exposure to dangerous precipitation extremes is anticipated to increase persistently in most regions of China except for some parts of northwestern China and the Tibetan Plateau. For the events estimated to occur once every 10 years, the 1.5, 2.0, 3.0, and 4.0°C warming relative to the current state will result in approximately 29.9, 47.8, 72.9, and 84.3% increases in the aggregated population exposure over China under the SSP5-8.5 scenario, respectively. However, the exposure change is somewhat subject to the emission scenarios, with larger proportional increases under the regional-rivalry scenario of SSP3-7.0 compared to the fossil-fueled development scenario of SSP5-8.5. The increased exposure under all the scenarios is primarily attributed to the climate change factor, and the population change and their interaction component make a minor contribution. Furthermore, compared to the 2.0°C warmer climate, the 0.5°C less warming under the 1.5°C climate can trigger remarkable decreases of 16.5–20.8% for exposure to once-in-decade events over China. Additionally, the changes in the occurrence and exposure are much larger for the rarer events. Hence, our analyses indicate that limiting warming to 1.5°C is beneficial to reducing the impacts associated with precipitation extremes across China, particularly for the more extreme events.
The relation of the “four properties” and fluid identification of the carboniferous weathering crust volcanic reservoir in the Shixi Oilfield, Junggar Basin, China
Authors: Fu Lei , Qin Zhangjin , Xie An , Chen Liang , Li Junfei , Wang Nan , Qin Qirong , Mao Kailan
Published: August 2022

This study addresses the poorly understood physical properties of the Shixi Oilfield reservoir, which consists of a weathered Carboniferous volcanic rocks with strong heterogeneity and in which logging identification and evaluation are difficult. Using the lithology, lithofacies, and reservoir space characteristics of volcanic materials, this comprehensive study uses core, well logging, mud logging, and production testing data to analyze the relationship among the lithology, physical properties, electrical properties, and oil-bearing properties (referred to as the “four properties”) of weathered Carboniferous volcanic crust in addition to fluid identification. 1) The lithology of Carboniferous volcanic crust is dominated by breccia lava, agglomerate, banded lava, and compact tuff, and the lithofacies are mainly effusive facies. Secondary pores and tectonic fissures are important reservoir spaces, and the corrosion-fracture pores are significant for reservoir properties. 2) The “four properties” of volcanic reservoirs in the study area have clear relationships. On this basis, data on the electrical properties of the material, such as interval transit time, density, and neutron, were used to establish a logging interpretation model of the properties and oil saturation of the volcanic rock. 3) Using the resistivity-porosity cross-plot method, normal probability distribution method, and Rt/Rxo-Rt cross-plot method, volcanic reservoir fluids were identified with coincidence rates of 80%, 63.63%, and 63.63%, respectively. The cross-plot method determines lower limits of the reservoir’s physical properties and oil saturation, yielding porosity>9%, permeability>0.2 mD, and oil saturation>45%.
Psychological Distress and Its Mediating Effect on Experiences of Online Risk: The Case for Vulnerable Young People
Authors: El-Asam Aiman , Lane Rebecca , Katz Adrienne
Published: August 2022

There is strong evidence showing that vulnerable children and adolescents, such as children who are carers for their family, in care themselves, or who have a physical disability or special educational needs, are at greater risk of mental health problems and poor social wellbeing. Recent research indicates this heterogenous but vulnerable group is also disadvantaged online and may be at greater risk of harm. This study aimed to examine participants’ vulnerability (vulnerable vs. non-vulnerable), psychological distress, parental e-safety support, and online lives, specifically their experiences of online risk. The roles of psychological distress and parental e-safety support were explored as possible mediators and moderators, respectively, for the relationship between vulnerability and online risk. Survey data was collected from 15,278 participants (11–17 years old; M = 12.60, SD = 1.44), 46.6% identified as females, 46.6% identified as males and 6% identified as “other”. Participants were recruited from schools/colleges in different parts of England, of whom 3,242 were categorised as vulnerable. Using Analysis of Variance (ANOVA) the results showed that, when compared to the non-vulnerable participants, the vulnerable groups (single or multiple vulnerabilities) experienced more psychological distress and online risks. They also received less e-safety support from parents or carers. Furthermore, mediation and moderated mediation analysis showed that the relationship between vulnerability and online risk was significantly and partially mediated by psychological distress. Parental e-safety support was found to moderate the relationship between psychological distress and online risk and between vulnerability and online risk. In conclusion, the results demonstrated that vulnerability offline is mirrored online. Psychological interventions and parental e-safety support are required to navigate the internet safely. Children’s services and practitioners should consider online risks in their assessments and interventions.
Association Between Vitamin D Supplementation and Fall Prevention
Authors: Wei Fei-Long , Li Tian , Gao Quan-You , Huang Yuli , Zhou Cheng-Pei , Wang Wen , Qian Ji-Xian
Published: August 2022

Background

Falls occur frequently among older individuals, leading to high morbidity and mortality. This study was to assess the efficacy of vitamin D in preventing older individuals from falling.

Methods

We searched the PubMed, Cochrane Library, and EMBASE databases systematically using the keywords “vitamin D” and “fall” for randomized controlled trials (RCTs) comparing the effects of vitamin D with or without calcium supplements with those of a placebo or no treatment on fall incidence in adults older than 50 years. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs) and 95% CIs with random-effects models.

Results

A total of 38 RCTs involving 61 350 participants fulfilled the inclusion criteria. Compared with placebo, high-dose vitamin D (≥ 700 IU) can prevent falls [RR, 0.87 (95% CI 0.79 to 0.96); ARD, -0.06 (95% CI, -0.10 to -0.02)]. Low-dose vitamin D (<700 IU) was not significantly associated with falls. Subgroup analysis showed that supplemental calcium, 25(OH) D concentration and frequency influenced the effect of vitamin D in preventing falls. Sensitivity analysis showed that vitamin D prevented falls, which was consistent with the primary analysis. In addition, the active form of vitamin D also prevented falls.

Conclusion

In this meta-analysis of RCTs, doses of 700 IU to 2000 IU of supplemental vitamin D per day were associated with a lower risk of falling among ambulatory and institutionalized older adults. However, this conclusion should be cautiously interpreted, given the small differences in outcomes.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42020179390.
Prognostic impact of coronary microvascular dysfunction assessed by caIMR in overweight with chronic coronary syndrome patients
Authors: Feng Cailin , Abdu Fuad A. , Mohammed Abdul-Quddus , Zhang Wen , Liu Lu , Yin Guoqing , Feng Yundi , Mohammed Ayman A. , Mareai Redhwan M. , Lv Xian , Shi Tingting , Xu Yawei , Yu Xuejing , Che Wenliang
Published: August 2022

Objective

Coronary microvascular dysfunction (CMD) may associate with adverse cardiovascular events in obese patients. Coronary angiography-derived index of microcirculatory resistance (caIMR) is proposed as a less-invasive and pressure-wire-free index to assess CMD. We aimed to investigate the impact of coronary microvascular function assessed by caIMR in patients with overweight and chronic coronary syndrome (CCS).

Methods

CCS patients who underwent coronary angiography between 2015 to 2018 were included. Overweight was defined as BMI≥24.0kg/m². Impaired coronary microvascular function was defined as caIMR≥25U. The patients were classified according to BMI and caIMR. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier and Cox regression analyses evaluated the association between caIMR and MACE.

Results

Two hundred and eighty-two CCS patients were enrolled. Among these, 169 (59.93%) were overweight. Impaired coronary microvascular function was higher in overweight patients than in patients with normal weight (49.70% vs. 38.05%; P=0.035). During 35 months of follow-up, 33 MACE had occurred. Among the total CCS population, MACE was higher in patients with high caIMR than in low caIMR (18.11% vs. 6.45%, P=0.003). In subgroups analysis, MACE was higher in overweight patients with high caIMR than low caIMR (20.24% vs. 7.06%, P=0.014), while there were no significant differences in normal-weight patients. Multivariate Cox analysis demonstrated that caIMR≥25 was independently associated with MACE in overweight patients (HR, 2.87; 95% CI, 1.12-7.30; P=0.027) but not in the normal-weight patients. In addition, caIMR showed a significant predictive value for adverse outcomes in overweight patients and provided an incremental prediction when added to a prediction model with BMI.

Conclusions

Impaired coronary microvascular function assessed by caIMR was common and is an independent predictor of MACE in overweight patients with CCS.
Changes in BMI and physical activity from youth to adulthood distinguish normal-weight, metabolically obese adults from those who remain healthy
Authors: Viitasalo A. , Pahkala K. , Lehtimäki T. , Viikari JSA. , Tammelin TH. , Raitakari O. , Kilpeläinen TO.
Published: August 2022

Highlights

Adults with MONW have a lower BMI during youth until young adulthood, but higher BMI after this than adults with metabolically healthy normal weight. Adults with MONW have a greater decrease in physical activity from youth to adulthood than other adults. Healthy lifestyle is important in the prevention of metabolic disorders, particularly in individuals who are slim in childhood.

Background

Individuals with metabolically obese normal-weight (MONW) have higher risk of cardiovascular events than those with obesity but a metabolically healthy status. Etiological factors leading to MONW are not well known. We hypothesized distinct trajectories of changes in BMI and physical activity may modify metabolic risk and distinguish individuals with MONW from those who remain healthy.

Methods

We compared the mean levels of BMI and physical activity at eight time points (1980, 1983, 1986, 1989, 1992, 2001, 2007, 2011) between MONW and healthy normal-weight adults using linear mixed-model analysis. The analyses included 1180 participants of the Cardiovascular Risk in Young Finns study, a population-based study that represents six different age cohorts 3, 6, 9, 12, 15 and 18 years of age at baseline.

Results

Individuals with adult MONW had significantly lower BMI in childhood and young adulthood, but their BMI increased more than in other adults after this age (p<0.001for interaction between time and MONW status). Physical activity decreased relatively more since youth in individuals with adult MONW (p<0.001).

Conclusions

Relative leanness in youth and subsequent weight gain in young adulthood, and a gradual decrease in physical activity levels from youth to adulthood, predispose normal-weight individuals to metabolic impairments. The results highlight the importance of a healthy lifestyle in the prevention of metabolic disorders, particularly in individuals who are slim in childhood.
Comprehensive analysis of the m6A-related molecular patterns and diagnostic biomarkers in osteoporosis
Authors: Bai Qiong , Shi Min , Sun Xinli , Lou Qiu , Peng Hangya , Qu Zhuan , Fan Jiashuang , Dai Lifen
Published: August 2022

Background

N6-methyladenosine (m6A) modification is a critical epigenetic modification in eukaryotes and involves several biological processes and occurrences of diseases. However, the roles and regulatory mechanisms of m6A regulators in osteoporosis (OP) remain unclear. Thus, the purpose of this study is to explore the roles and mechanisms of m6A regulators in OP.

Methods

The mRNA and microRNA (miRNA) expression profiles were respectively obtained from GSE56815, GSE7158, and GSE93883 datasets in Gene Expression Omnibus (GEO). The differential expression of 21 m6A regulators between high-bone mineral density (BMD) and low-BMD women was identified. Then, a consensus clustering of low-BMD women was performed based on differentially expressed (DE)-m6A regulators. The m6A-related differentially expressed genes (DEGs), the differentially expressed miRNAs (DE-miRNAs), and biological functions were investigated. Moreover, a weighted gene co-expression network analysis (WGCNA) was constructed to identify the OP-related hub modules, hub genes, and the functional pathways. Then, an m6A regulator–target–pathway network and the competing endogenous RNA (ceRNA) network in key modules were constructed. A least absolute shrinkage and selection operation (LASSO) Cox regression model and a Support Vector Machine-Recursive Feature Elimination (SVM-RFE) model were constructed to identify the candidate genes for OP prediction. The receiver operator characteristic (ROC) curves were used to validate the performances of predictive models and candidate genes.

Results

A total of 10,520 DEGs, 13 DE-m6A regulators, and 506 DE-miRNAs between high-BMD and low-BMD women were identified. Two m6A-related subclusters with 13 DE-m6A regulators were classified for OP. There were 5,260 m6A-related DEGs identified between two m6A-related subclusters, the PI3K-Akt, MAPK, and immune-related pathways, and bone metabolism was mainly enriched in cluster 2. Cell cycle-related pathways, RNA methylation, and cell death-related pathways were significantly involved in cluster 1. Five modules were identified as key modules based on WGCNA, and an m6A regulator–target gene–pathway network and the ceRNA network were constructed in module brown. Moreover, three m6A regulators (FTO, YTHDF2, and CBLL1) were selected as the candidate genes for OP.

Conclusion

M6A regulators play an important role in the occurrences and diagnosis of OP.
Communicating leakage risk in the hydrogen economy: Lessons already learned from geoenergy industries
Authors: Stalker Linda , Roberts Jennifer J. , Mabon Leslie , Hartley Patrick G.
Published: August 2022

Hydrogen is set to play a part in delivering a net zero emissions future globally. However, previous research finds that risk perception issues are particularly challenging for emerging and potentially unfamiliar technologies. Hydrogen as a fuel falls into this category. Thus, while the hydrogen value chain could offer a range of potential environmental, economic and social benefits, it is imperative that the roll-out of hydrogen fits with societal expectations of how risk ought to be managed—and by whom. Communication and engagement are critical to ensure 1) communities and stakeholders are able to come to informed decisions on hydrogen and 2) developers, operators and regulators are able to respond to societal concerns and adapt practices appropriately.Within the hydrogen value chain, geological storage may be an important step, but could present challenges in terms of perceived safety. Lessons can be learned from international research and practice of CO2 and natural gas storage in geological formations [for carbon capture and storage (CCS) and power respectively] which may be relevant to hydrogen storage in salt caverns or porous sandstones. We draw on these analogues to present potential societal risk perception issues which may arise for geological storage of hydrogen. We argue that site-specific communication and engagement strategies, underpinned by broad-based principles covering the entire span of the project and a clear rationale for how hydrogen benefits the climate and the most vulnerable members of society under an energy crisis, will be critical to fostering societal support for geological hydrogen storage.
A Multi-Scale Time Method for the State of Charge and Parameter Estimation of Lithium-Ion Batteries Using MIUKF-EKF
Authors: Ji Shiyu , Sun Yi , Chen Zexing , Liao Wu
Published: August 2022

Accurate state estimation is essential for the safe and reliable operation of lithium-ion batteries. However, the accuracy of the battery state estimation depends on the accuracy of the battery parameters. Because the state of charge (SOC) cannot be directly measured, estimation methods based on the Kalman filter are widely used. However, it is difficult to estimate SOC online and get high accuracy results. This article proposes a method for parameter identification and SOC estimation for lithium-ion batteries. Because the lithium-ion battery has slow-varying parameters (such as internal resistance, and polarization resistance), and the SOC has fast-varying characteristics, so a multi-scale multi-innovation unscented Kalman filter and extended Kalman filter (MIUKF-EKF) are used to perform online measurement of battery parameters and SOC estimation in this method. The battery parameters are estimated with a macro-scale, and the SOC is estimated with a micro-scale. This method can improve the estimation accuracy of the SOC in real-time. Results of experiments indicate that the algorithm has higher accuracy in online parameter identification and SOC estimation than in the dual extended Kalman filter (DEKF) algorithm.
Comparative analysis of MPPT techniques for enhancing a wind energy conversion system
Authors: Gaied Hajer , Naoui Mohamed , Kraiem Habib , Goud B. Srikanth , Flah Aymen , Alghaythi Mamdouh L. , Kotb Hossam , Ali Samia G. , Aboras Kareem
Published: August 2022

One of the most reliable and advanced renewable energy sources is wind energy. It is critical to harness as much wind energy as possible and maintain wind turbines operating at full capacity. Maximum power point tracking (MPPT) is a cutting-edge study that incorporates a variety of approaches. Because each MPPT technique has its own set of advantages and disadvantages, developing an accurate maximum power point tracking methodology for a certain case necessitates understanding. As a result, they must be checked thoroughly. This research tries to examine many algorithms that can be used to improve the wind energy system’s global MPPT performance. The traditional “Perturb and Observe” tool, the optimization method based on the “particle swarm optimization algorithm,” the neural network, and the “fuzzy logics” as intelligent tools are these techniques. The main objective of this research is to define and evaluate four different flexible algorithms that achieve the fundamental objective of this optimization. The advantages, drawbacks, and thorough analysis of MPPT systems are highlighted in terms of initial investment, responsiveness, and capacity to create maximum energy output. All of this comparison was made through simulation software, which is the MATLAB Simulink tool. The conclusions are supported by a comprehensive discussion and presentation of the results for a variety of situations and tests that reflect real-world behavior in any wind system.
Regional Groundwater Water Quality Assessment and Contamination Source Identification by a Self-Organizing Map and Entropy Method in Pinggu Basin, Northeast Beijing
Authors: Lv Shaojie , Zhang Zongwen , Sun Ning , Shi Zheming , Li Jia , Qu Shen
Published: August 2022

Groundwater quality assessment is important for understanding the suitability of groundwater resources for various purposes. Although many different methods have been proposed for this purpose, few methods have considered the spatial variation of groundwater components during the assessments. In this study, we proposed to combine the self-organizing map (SOM) and entropy-based weight determining method to assess groundwater quality. Totally, 955 water samples taken from 58 wells during 2010–2017 were used in the study. 22 hydrochemical components (K+, Na+, Ca2+, Mg2+, NH4+, Cl−, SO42-, F−, NO3−, Fe2+, Fe3+, Al, etc.) were used in the assessment for each sample. These sampling points can be classified into five clusters, which may be affected by four different sources: landfill sources (cluster 3), industrial and agricultural sources (cluster 5), and domestic sewage discharge sources (clusters 1, 2, and 4). The scores of the water quality of the five clusters that were calculated by the entropy method are 0.2658, 0.2634, 0.5737, 0.2608, and 0.5718, indicating that the groundwater affected by domestic sewage discharge sources (clusters 1, 2, and 4) are better than other two sources (clusters 3 and 5) in the study area. The results of this study provide insights for the protection of groundwater resources and the treatment of groundwater pollution in the future.
Combining L-band Synthetic Aperture Radar backscatter and TanDEM-X canopy height for forest aboveground biomass estimation
Authors: Khati Unmesh , Singh Gulab
Published: August 2022

Synthetic aperture radar (SAR) backscatter based above-ground biomass (AGB) estimates are limited by the saturation of the backscatter-AGB curve. This work explores the potential of combining backscatter with polarimetric SAR interferometry (PolInSAR) estimated forest stand height for improved AGB estimation. The models combining L-band backscatter and TanDEM-X height are compared with established backscatter based models. The models are also temporally cross-validated, i.e., trained on one acquisition date and validated for other dates. It is observed that with the input of height, the combined models perform significantly better than backscatter based models, with an improvement in root mean square error (RMSE) between 19% and 46%. The model utilizing HV-polarized backscatter and TanDEM-X PolInSAR height provide the best case AGB inversion with an R2 = 0.78 and an RMSE of 27.1 Mg/ha or 22% of mean AGB. The results demonstrate the potential of the synergistic combination of L-band PolSAR (backscatter) and X-band PolInSAR (height) products for AGB mapping over a tropical forest range in India.
Primary primitive neuroectodermal tumor of the cervix confirmed with molecular analysis in a pregnant woman: A case report and literature review
Authors: Wei Ding , Jianguo Zhao , Xiao Li , Pengpeng Qu
Published: August 2022

Primary primitive neuroectodermal tumor (PNET) in the female tract is rare. Recently, a case of cervical PNET was diagnosed in our hospital. A 29-year-old pregnant woman presented with a cystic-solid cervical mass at the 7th week of gestation. The mass grew rapidly during follow-up and ruptured at the 22nd week. A biopsy was performed on the mass. Pathological examination revealed a malignant neoplasm composed of small cells which exhibited positive immunohistochemical (IHC) staining for CD99, SYN, and FLI1. Fluorescence in situ hybridization (FISH) displayed the presence of EWS-FLI1 fusion gene resulting from the chromosomal translocation t (11;22, q24;q12), which confirmed the diagnosis of cervical PNET. The reverse transcription-polymerase chain reaction (RT-PCR) results showed type 2 EWS-FLI1 fusion occurred in this tumor, suggesting a poor prognosis. The patient underwent surgical resection and was given adjuvant chemotherapy followed by pelvic radiotherapy. PNET arising from the genital tract, especially in the uterine cervix, is very rare and presents a diagnostic challenge. FISH and RT-PCR analysis are helpful for the diagnosis of such a tumor at an unusual site, as in the present case.
Comparative transcriptome analysis, unfolding the pathways regulating the seed-size trait in cultivated lentil (Lens culinaris Medik.)
Authors: Dutta Haragopal , Mishra Gyan P. , Aski Muraleedhar S. , Bosamia Tejas C. , Mishra Dwijesh C. , Bhati Jyotika , Sinha Subodh Kumar , Vijay Dunna , C. T. Manjunath Prasad , Das Shouvik , Pawar Prashant Anupama-Mohan , Kumar Atul , Tripathi Kuldeep , Kumar Ranjeet Ranjan , Yadava Devendra Kumar , Kumar Shiv , Dikshit Harsh Kumar
Published: August 2022

Market class, cooking time, quality, and milled grain yield are largely influenced by the seed size and shape of the lentil (Lens culinaris Medik.); thus, they are considered to be important quality traits. To unfold the pathways regulating seed size in lentils, a transcriptomic approach was performed using large-seeded (L4602) and small-seeded (L830) genotypes. The study has generated nearly 375 million high-quality reads, of which 98.70% were properly aligned to the reference genome. Among biological replicates, very high similarity in fragments per kilobase of exon per million mapped fragments values (R > 0.9) showed the consistency of RNA-seq results. Various differentially expressed genes associated mainly with the hormone signaling and cell division pathways, transcription factors, kinases, etc. were identified as having a role in cell expansion and seed growth. A total of 106,996 unigenes were used for differential expression (DE) analysis. String analysis identified various modules having certain key proteins like Ser/Thr protein kinase, seed storage protein, DNA-binding protein, microtubule-associated protein, etc. In addition, some growth and cell division–related micro-RNAs like miR3457 (cell wall formation), miR1440 (cell proliferation and cell cycles), and miR1533 (biosynthesis of plant hormones) were identified as having a role in seed size determination. Using RNA-seq data, 5254 EST-SSR primers were generated as a source for future studies aiming for the identification of linked markers. In silico validation using Genevestigator® was done for the Ser/Thr protein kinase, ethylene response factor, and Myb transcription factor genes. It is of interest that the xyloglucan endotransglucosylase gene was found differentially regulated, suggesting their role during seed development; however, at maturity, no significant differences were recorded for various cell wall parameters including cellulose, lignin, and xylose content. This is the first report on lentils that has unfolded the key seed size regulating pathways and unveiled a theoretical way for the development of lentil genotypes having customized seed sizes.
Statistical Methods Revisited for Estimating Daily Milk Yields: How Well do They Work?
Authors: Wu Xiao-Lin , Wiggans George R. , Norman H. Duane , Miles Asha M. , Van Tassell Curtis P. , Baldwin Ransom L. , Burchard Javier , Dürr João
Published: August 2022

Cost-effective milking plans have been adapted to supplement the standard supervised twice-daily monthly testing scheme since the 1960s. Various methods have been proposed to estimate daily milk yields (DMY), focusing on yield correction factors. The present study evaluated the performance of existing statistical methods, including a recently proposed exponential regression model, for estimating DMY using 10-fold cross-validation in Holstein and Jersey cows. The initial approach doubled the morning (AM) or evening (PM) yield as estimated DMY in AM-PM plans, assuming equal 12-h AM and PM milking intervals. However, in reality, AM milking intervals tended to be longer than PM milking intervals. Additive correction factors (ACF) provided additive adjustments beyond twice AM or PM yields. Hence, an ACF model equivalently assumed a fixed regression coefficient or a multiplier of “2.0” for AM or PM yields. Similarly, a linear regression model was viewed as an ACF model, yet it estimated the regression coefficient for a single milk yield from the data. Multiplicative correction factors (MCF) represented daily to partial milk yield ratios. Hence, multiplying a yield from single milking by an appropriate MCF gave a DMY estimate. The exponential regression model was analogous to an exponential growth function with the yield from single milking as the initial state and the rate of change tuned by a linear function of milking interval. In the present study, all the methods had high precision in the estimates, but they differed considerably in biases. Overall, the MCF and linear regression models had smaller squared biases and greater accuracies for estimating DMY than the ACF models. The exponential regression model had the greatest accuracies and smallest squared biases. Model parameters were compared. Discretized milking interval categories led to a loss of accuracy of the estimates. Characterization of ACF and MCF revealed their similarities and dissimilarities and biases aroused by unequal milking intervals. The present study focused on estimating DMY in AM-PM milking plans. Yet, the methods and relevant principles are generally applicable to cows milked more than two times a day.
A review on the role of miRNA-324 in various diseases
Authors: Kadkhoda Sepideh , Hussen Bashdar Mahmud , Eslami Solat , Ghafouri-Fard Soudeh
Published: August 2022

Recent studies have revealed important functions of several microRNAs (miRNAs) in the pathogenesis of human diseases. miR-324 is an example of miRNAs with crucial impacts on the pathogenesis of a wide range of disorders. Gene ontology studies have indicated possible role of miR-324 in responses of cells to the leukemia inhibitory factor, long-term synaptic potentiation, positive regulation of cytokines production and sensory perception of sound. In human, miR-324 is encoded by MIR324 gene which resides on chromosome 17p13.1. In the current manuscript, we provide a concise review of the role of miR-324 in the pathogenesis of cancers as well as non-cancerous conditions such as aneurysmal subarachnoid hemorrhage, diabetic nephropathy, epilepsy, pulmonary/renal fibrosis, ischemic stroke and ischemia reperfusion injuries. Moreover, we summarize the role of this miRNA as a prognostic marker for malignant disorders.
The genetic interactions between non-alcoholic fatty liver disease and cardiovascular diseases
Authors: Chew Nicholas W.S. , Chong Bryan , Ng Cheng Han , Kong Gwyneth , Chin Yip Han , Xiao Wang , Lee Mick , Dan Yock Young , Muthiah Mark D. , Foo Roger
Published: August 2022

The ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the development of cardiovascular disease (CVD) has sparked interests in understanding the common mediators between the two biologically distinct entities. This comprehensive review identifies and curates genetic studies of NAFLD overlapping with CVD, and describes the colinear as well as opposing correlations between genetic associations for the two diseases. Here, CVD described in relation to NAFLD are coronary artery disease, cardiomyopathy and atrial fibrillation. Unique findings of this review included certain NAFLD susceptibility genes that possessed cardioprotective properties. Moreover, the complex interactions of genetic and environmental risk factors shed light on the disparity in genetic influence on NAFLD and its incident CVD. This serves to unravel NAFLD-mediated pathways in order to reduce CVD events, and helps identify targeted treatment strategies, develop polygenic risk scores to improve risk prediction and personalise disease prevention.
Strategies to overcome CAR-T cell resistance in clinical work: A single-institute experience
Authors: Nan Feifei , Fu Xiaorui , Chen Xinfeng , Li Ling , Li Xin , Wu Jingjing , Feng Xiaoyan , Wu Xiaolong , Yan Jiaqin , Zhang Mingzhi
Published: August 2022

The emergence of chimeric antigen receptor (CAR) T cell therapy has shifted the paradigm of malignant tumor treatment, especially the advent of CD19-directed CAR-T cell therapy for the treatment of relapsed/refractory (R/R) B-cell malignancies. Although CAR-T cell therapy has promising effects, some patients are resistant to this treatment, leaving them with limited options. Therefore, strategies to overcome resistance to CAR-T cell therapy are needed. We retrospectively studied three R/R diffuse large B-cell lymphoma patients who were resistant to CAR-T cell therapy and whose disease was controlled after receiving pembrolizumab, 21D4 CAR-T cells, or ibrutinib and venetoclax. Some promising prevention and treatment strategies to overcome treatment resistance are also discussed.
Persistent but atypical germinal center reaction among 3rd SARS-CoV-2 vaccination after rituximab exposure
Authors: Stefanski Ana-Luisa , Rincon-Arevalo Hector , Schrezenmeier Eva , Karberg Kirsten , Szelinski Franziska , Ritter Jacob , Chen Yidan , Meisel Christian , Jahrsdörfer Bernd , Ludwig Carolin , Schrezenmeier Hubert , Lino Andreia C. , Dörner Thomas
Published: August 2022

Background

Durable vaccine-mediated immunity relies on the generation of long-lived plasma cells and memory B cells (MBCs), differentiating upon germinal center (GC) reactions. SARS-CoV-2 mRNA vaccination induces a strong GC response in healthy volunteers (HC), but limited data is available about response longevity upon rituximab treatment.

Methods

We evaluated humoral and cellular responses upon 3rd vaccination in seven patients with rheumatoid arthritis (RA) who initially mounted anti-spike SARS-CoV-2 IgG antibodies after primary 2x vaccination and got re-exposed to rituximab (RTX) 1-2 months after the second vaccination. Ten patients with RA on other therapies and ten HC represented the control groups. As control for known long-lived induced immunity, we analyzed humoral and cellular tetanus toxoid (TT) immune responses in steady-state.

Results

After 3rd vaccination, 5/7 seroconverted RTX patients revealed lower anti-SARS-CoV-2 IgG levels but similar neutralizing capacity compared with HC. Antibody levels after 3rd vaccination correlated with values after 2nd vaccination. Despite significant reduction of circulating total and antigen-specific B cells in RTX re-exposed patients, we observed the induction of IgG+ MBCs upon 3rd vaccination. Notably, only RTX treated patients revealed a high amount of IgA+ MBCs before and IgA+ plasmablasts after 3rd vaccination. IgA+ B cells were not part of the steady state TT+ B cell pool. TNF-secretion and generation of effector memory CD4 spike-specific T cells were significantly boosted upon 3rd vaccination.

On the basis of pre-existing affinity matured MBCs within primary immunisation, RTX re-exposed patients revealed a persistent but atypical GC immune response accompanied by boosted spike-specific memory CD4 T cells upon SARS-CoV-2 recall vaccination.
IFN-γ, should not be ignored in SLE
Authors: Liu Wenping , Zhang Shumin , Wang Jibo
Published: August 2022

Systemic lupus erythematosus (SLE) is a typical autoimmune disease with a complex pathogenesis and genetic predisposition. With continued understanding of this disease, it was found that SLE is related to the interferon gene signature. Most studies have emphasized the important role of IFN-α in SLE, but our previous study suggested a nonnegligible role of IFN-γ in SLE. Some scholars previously found that IFN-γ is abnormally elevated as early as before the classification of SLE and before the emergence of autoantibodies and IFN-α. Due to the large overlap between IFN-α and IFN-γ, SLE is mostly characterized by expression of the IFN-α gene after onset. Therefore, the role of IFN-γ in SLE may be underestimated. This article mainly reviews the role of IFN-γ in SLE and focuses on the nonnegligible role of IFN-γ in SLE to gain a more comprehensive understanding of the disease.
Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer
Authors: Zou Ruoyao , Jiang Qidi , Jin Tianqiang , Chen Mo , Yao Liangqing , Ding Hongda
Published: August 2022

Background

Cancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment (TME). These cells play a supportive role throughout cancer progression. Their ability to modulate the immune system has also been noted. However, there has been limited investigation of CAFs in the TME of epithelial ovarian cancer (EOC).

Methods

We comprehensively evaluated the CAF landscape and its association with gene alterations, clinical features, prognostic value, and immune cell infiltration at the pan-cancer level using multi-omic data from The Cancer Genome Atlas (TCGA). The CAF contents were characterized by CAF scores based on the expression levels of seven CAF markers using the R package “GSVA.” Next, we identified the molecular subtypes defined by CAF markers and constructed a CAF riskscore system using principal component analysis in the EOC cohort. The correlation between CAF riskscore and TME cell infiltration was investigated. The ability of the CAF riskscore to predict prognosis and immunotherapy response was also examined.

Results

CAF components were involved in multiple immune-related processes, including transforming growth factor (TGF)-β signaling, IL2-STAT signaling, inflammatory responses, and Interleukin (IL) 2-signal transducer and activator of transcription (STAT) signaling. Considering the positive correlation between CAF scores and macrophages, neutrophils, and mast cells, CAFs may exert immunosuppressive effects in both pan-cancer and ovarian cancer cohorts, which may explain accelerated tumor progression and poor outcomes. Notably, two distinct CAF molecular subtypes were defined in the EOC cohort. Low CAF riskscores were characterized by favorable overall survival (OS) and higher efficacy of immunotherapy. Furthermore, 24 key genes were identified in CAF subtypes. These genes were significantly upregulated in EOC and showed a strong correlation with CAF markers.

Conclusions

Identifying CAF subtypes provides insights into EOC heterogeneity. The CAF riskscore system can predict prognosis and select patients who may benefit from immunotherapy. The mechanism of interactions between key genes, CAF markers, and associated cancer-promoting effects needs to be further elucidated.
Phenotypic, functional, and metabolic heterogeneity of immune cells infiltrating non–small cell lung cancer
Authors: Aramini Beatrice , Masciale Valentina , Samarelli Anna Valeria , Dubini Alessandra , Gaudio Michele , Stella Franco , Morandi Uliano , Dominici Massimo , De Biasi Sara , Gibellini Lara , Cossarizza Andrea
Published: August 2022

Lung cancer is the leading cancer in the world, accounting for 1.2 million of new cases annually, being responsible for 17.8% of all cancer deaths. In particular, non–small cell lung cancer (NSCLC) is involved in approximately 85% of all lung cancers with a high lethality probably due to the asymptomatic evolution, leading patients to be diagnosed when the tumor has already spread to other organs. Despite the introduction of new therapies, which have improved the long-term survival of these patients, this disease is still not well cured and under controlled. Over the past two decades, single-cell technologies allowed to deeply profile both the phenotypic and metabolic aspects of the immune cells infiltrating the TME, thus fostering the identification of predictive biomarkers of prognosis and supporting the development of new therapeutic strategies. In this review, we discuss phenotypic and functional characteristics of the main subsets of tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating myeloid cells (TIMs) that contribute to promote or suppress NSCLC development and progression. We also address two emerging aspects of TIL and TIM biology, i.e., their metabolism, which affects their effector functions, proliferation, and differentiation, and their capacity to interact with cancer stem cells.
Trend detection by innovative polygon trend analysis for winds and waves
Authors: Akçay Fatma , Bingölbali Bilal , Akpınar Adem , Kankal Murat
Published: August 2022

It is known that densely populated coastal areas may be adversely affected as a result of the climate change effects. In this respect, for coastal protection, utilization, and management it is critical to understand the changes in wind speed (WS) and significant wave height (SWH) in coastal areas. Innovative approaches, which are one of the trend analysis methods used as an effective way to examine these changes, have started to be used very frequently in many fields in recent years, although not in coastal and marine engineering. The Innovative Polygon Trend Analysis (IPTA) method provides to observe the one-year behavior of the time series by representing the changes between consecutive months as well as determining the trends in each individual month. It is not also affected by constraints such as data length, distribution type or serial correlation. Therefore, the main objective of this study is to investigate whether using innovative trend methods compared to the traditional methods makes a difference in trends of the climatological variables. For this goal, trends of mean and maximum WS and SWH series for each month at 33 coastal locations in Black Sea coasts were evaluated. Wind and wave parameters WS and SWH were obtained from 42-year long-term wave simulations using Simulating Waves Nearshore (SWAN) model forced by the Climate Forecast System Reanalysis (CFSR). Monthly mean and maximum WS and SWH ​​were calculated at all locations and then trend analyses using both traditional and innovative methods were performed. Low occurrence of trends were detected for mean SWH, maximum SWH, mean WS, and maximum WS according to the Mann-Kendall test in the studied months. The IPTA method detected more trends, such as the decreasing trend of the mean SWH at most locations in May, July and November December. The lowest (highest) values were seen in summer (winter), according to a one-year cycle on the IPTA template for all variables. According to both methods, most of the months showed a decreasing trend for the mean WS at some locations in the inner continental shelf of the southwestern and southeastern Black Sea. The IPTA method can capture most of the trends detected by the Mann-Kendall method, and more missed by the latter method.
Serum ferritin as a crucial biomarker in the diagnosis and prognosis of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease: A systematic review and meta-analysis
Authors: Wen Huai , Hun Marady , Zhao Mingyi , Han Phanna , He Qingnan
Published: August 2022

Background

Early identification and treatment are paramount for intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) in patients with Kawasaki disease (KD). Unfortunately, there is no single crucial biomarker to identify these patients in a timely manner, which makes KD the most common cause of acquired heart disease in children in developed countries. Recently, many studies have focused on the association between serum ferritin (SF), IVIG resistance, and CALs in KD. We thus performed a systematic review and meta-analysis to ascertain the diagnostic and prognostic values of SF in predicting IVIG resistance and CALs in KD in the acute phase.

Methods

The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) were extracted from the data to evaluate the SF levels in KD. The hazard ratios (HRs) of related risk factors and their corresponding 95% confidence intervals (CIs) were applied to compute the pooled assessments of the outcomes.

Results

A total of 11 eligible articles were included in this meta-analysis, including twenty studies for diagnosis and five studies for prognosis. In terms of diagnostic values, SF could identify KD patients in the overall studies with a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.76 (95% CI: 0.69–0.82), 0.82 (95% CI: 0.76–0.88), 4.33 (95% CI: 3.07–6.11), 0.29 (95% CI: 0.22–0.38), 15.0 (95% CI: 9.00–25.00), and 0.86 (95% CI: 0.83–0.89), respectively. In studies comparing KD patients and controls, there were a relatively high pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 0.79 (95% CI: 0.72–0.84), 0.84 (95% CI: 0.79–0.91), 4.61 (95% CI: 3.27–6.51), 0.26 (95% CI: 0.20–0.34), 20.82 (95% CI: 11.83–36.64), and 0.89 (95% CI: 0.86–0.91), respectively. For the prognostic values, we found poor survival outcomes based on KD patients (HR = 1.31, 95% CI: 1.07–1.59, P = 0.008).

Conclusion

Our meta-analysis suggests that SF may be used as a workable and critical biomarker for the diagnosis and prognosis of IVIG resistance and CALs in patients with KD. We also propose that maintaining the dynamic balance between iron, SF, and ferroptosis will be an important therapeutic strategy to reduce the morbidity of CALs.

Systematic review registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022279157].
The role of kidney biopsy in immune checkpoint inhibitor nephrotoxicity
Authors: Moss Emily M. , Perazella Mark A.
Published: August 2022

Immune checkpoint inhibitors, medications that boost host immune response to tumor cells, are now at the forefront of anti-cancer therapy. While efficacious in the treatment of patients with advanced cancer, immune checkpoint inhibitors can lead to serious autoimmune side effects involving any organ in the body. Immune checkpoint inhibitor nephrotoxicity is an increasingly recognized cause of acute kidney injury in patients with cancer. This review discusses the clinical and histopathologic diagnosis of immune checkpoint inhibitor nephrotoxicity, highlighting the need for more reliable non-invasive diagnostic testing. We focus on the controversy surrounding the role of kidney biopsy in diagnosis and management of suspected immune checkpoint inhibitor toxicity with inclination toward pursuing kidney biopsy in certain outlined circumstances. Finally, we briefly discuss treatment of immune checkpoint inhibitor nephrotoxicity and the decision to re-challenge immunotherapy in patients who experience these adverse events.