bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicles derived from macrophages: Current applications and prospects in tumors
Authors: Lou Kecheng , Feng Shangzhi , Luo Hui , Zou Junrong , Zhang Guoxi , Zou Xiaofeng
Published: December 2022

Macrophages (Mφs) are significant innate immune cells that perform a variety of tasks in response to different pathogens or stimuli. They are widely engaged in the pathological processes of various diseases and can contribute to tumorigenesis, progression and metastasis by regulating the tumor microenvironment and cancer cells. They are also the basis of chemoresistance. In turn, the tumor microenvironment and the metabolism of cancer cells can limit the differentiation, polarization, mobilization and the ability of Mφs to initiate an effective anti-tumor response. Extracellular vesicles (EVs) are small vesicles released by live cells that serve as crucial mediators of intercellular cell communication as well as a potential promising drug carrier. A growing number of studies have demonstrated that Mφs-EVs are not only important mediators in the pathological processes of various diseases such as inflammatory disorders, fibrosis and cancer, but also show significant potential in immunological modulation, cancer therapy, infectious defense and tissue repair. These natural nanoparticles (NPs) derived from Mφs are believed to be pleiotropic, stable, biocompatible and low immunogenic, providing novel alternatives for cancer treatment. This review provides an update on the pathological and therapeutic roles of Mφs-EVs in cancer, as well as their potential clinical applications and prospects.
IL-15 induced bystander activation of CD8+ T cells may mediate endothelium injury through NKG2D in Hantaan virus infection
Authors: Zhang Xiyue , Zhang Yusi , Liu He , Tang Kang , Zhang Chunmei , Wang Meng , Xue Manling , Jia Xiaozhou , Hu Haifeng , Li Na , Zhuang Ran , Jin Boquan , Zhang Fanglin , Zhang Yun , Ma Ying
Published: December 2022

Introduction

Hantaan virus (HTNV) can cause endothelium injury in hemorrhagic fever with renal syndrome (HFRS) patients. Bystander activation of CD8+ T cells by virus infection has been shown that was involved in host injury, but it is unclear during HTNV infection. This project aimed to study the effect of bystander-activated CD8+ T cell responses in HTNV infection.

Methods

The in vitro infection model was established to imitate the injury of endothelium in HFRS patients. Flow cytometry was performed to detect the expression of markers of tetramer+ CD8+ T cells and human umbilical vein endothelial cells (HUVECs). The levels of interleukin-15 (IL-15) in serum and supermanant were detected using ELISA kit. The expression of MICA of HUVECs was respectively determined by flow cytometry and western blot. The cytotoxicity of CD8+ T cells was assessed through the cytotoxicity assay and antibody blocking assay.

Results

EBV or CMV-specific CD8+ T cells were bystander activated after HTNV infection in HFRS patients. HTNV-infected HUVECs in vitro could produce high levels of IL-15, which was positively correlated with disease severity and the expression of NKG2D on bystander-activated CD8+ T cells. Moreover, the elevated IL-15 could induce activation of CD122 (IL-15Rβ)+NKG2D+ EBV/CMV-specific CD8+ T cells. The expression of IL-15Rα and ligand for NKG2D were upregulated on HTNV-infected HUVECs. Bystander-activated CD8+ T cells could exert cytotoxicity effects against HTNV-infected HUVECs, which could be enhanced by IL-15 stimulation and blocked by NKG2D antibody.

Discussion

IL-15 induced bystander activation of CD8+ T cells through NKG2D, which may mediate endothelium injury during HTNV infection in HFRS patients.
Benefit of vertical localization for sea surface temperature assimilation in isopycnal coordinate model
Authors: Wang Yiguo , Counillon François , Barthélémy Sébastien , Barth Alexander
Published: December 2022

Sea surface temperature (SST) observations are a critical data set for long-term climate reconstruction. However, their assimilation with an ensemble-based data assimilation method can degrade performance in the ocean interior due to spurious covariances. Assimilation in isopycnal coordinates can delay the degradation, but it remains problematic for long reanalysis. We introduce vertical localization for SST assimilation in the isopycnal coordinate. The tapering functions are formulated empirically from a large pre-industrial ensemble. We propose three schemes: 1) a step function with a small localization radius that updates layers from the surface down to the first layer for which insignificant correlation with SST is found, 2) a step function with a large localization radius that updates layers down to the last layer for which significant correlation with SST is found, and 3) a flattop smooth tapering function. These tapering functions vary spatially and with the calendar month and are applied to isopycnal temperature and salinity. The impact of vertical localization on reanalysis performance is tested in identical twin experiments within the Norwegian Climate Prediction Model (NorCPM) with SST assimilation over the period 1980–2010. The SST assimilation without vertical localization greatly enhances performance in the whole water column but introduces a weak degradation at intermediate depths (e.g., 2,000–4,000 m). Vertical localization greatly reduces the degradation and improves the overall accuracy of the reanalysis, in particular in the North Pacific and the North Atlantic. A weak degradation remains in some regions below 2,000 m in the Southern Ocean. Among the three schemes, scheme 2) outperforms schemes 1) and 3) for temperature and salinity.
Soluble tumor endothelial marker 1 in heart failure with reduced ejection fraction: A pilot study
Authors: Feng Wen-Han , Chen Po-Sheng , Chung Hsing-Chun , Lin Yi-Hsiung , Li Yi-Heng
Published: December 2022

Background

Tumor endothelial marker 1 (TEM1/CD248) is a transmembrane protein that expresses in mesenchymal lineage derived cells during embryogenesis and becomes undetectable in normal adults after birth. Re-expression of TEM1 is found in organ fibrosis, wound healing and cardiac remodeling indicating its potential role in heart failure (HF). The purpose of this study is to explore the role of soluble TEM1 (sTEM1) in patients with HF with reduced ejection fraction.

Methods

We examined endomyocardial biopsy specimens from three HF patients and blood samples from 48 patients admitted for acute decompensated HF (age 72 years, men 61.7%). The expression of TEM1 in cardiac tissue and concentrations of sTEM1 in plasma were evaluated. Cultured rat cardiomyocytes (H9c2) and human cardiac fibroblasts (HCF) were stimulated with hypoxia or transforming growth factor beta (TGF-β) to observe the release of sTEM1 into culture media. The conditioned media of hypoxia-stimulated H9c2 cells was harvested and added into cultured cardiac fibroblast to evaluate its biological effect.

Results

Immunofluorescence study of biopsy specimens from three HF patients showed TEM1 expression in cardiomyocytes and cardiac fibroblasts. The plasma level of sTEM1 was significantly higher in patients (0.90 ± 0.23 vs. 0.33 ± 0.10 ng/mL, p = 0.032) with LVEF ≤ 35% compared with those with LVEF 36–49%. The sTEM1 levels had correlations with HF biomarkers of cardiac fibrosis, including growth differentiation factor-15 (GDF-15) and galectin-3. There was a significant increase in sTEM1 levels in the cultured media of H9c2 and HCF after being stressed with hypoxia or TGF-β. The conditioned media derived from hypoxia-stimulated H9c2 cells significantly increased cell proliferation of cardiac fibroblasts. This effect was partially reversed by anti-TEM1 antibody.

Conclusion

This pilot study demonstrated that cardiac TEM1 expression was upregulated in HF. The levels of sTEM1 were significantly higher in HF patients with LVEF ≤ 35% and correlated with other biomarkers of cardiac fibrosis. In vitro study proved that functional sTEM1 was released into cultured media after stressing cardiomyocytes and HCF.
Apply pressure-strain loop to quantify myocardial work in pulmonary hypertension: A prospective cohort study
Authors: Wang Jian , Ni Chao , Yang Menghui , Zhang Xueming , Ruan Binqian , Sun Lingyue , Shen Xuedong , Shen Jieyan
Published: December 2022

Objectives

Pressure-strain loop (PSL) is a novel method to quantify myocardial work in many cardiovascular diseases. To investigate the value of myocardial work parameters derived from PSL for evaluating cardiac function and clinical prognosis in patients with pulmonary hypertension (PH).

Methods

A total of 52 patients with PH and 27 healthy controls were enrolled in this prospective study. PSLs determined by echocardiography were used to calculate global work index (GWI) of left ventricle (LV) and right ventricle (RV). Global constructive work (GCW) comprised the sum of myocardial work performed during shortening in systole and during lengthening in isovolumic relaxation. Global wasted work (GWW) comprised the sum of myocardial work performed during lengthening in systole and during shortening in isovolumic relaxation. Global work efficiency (GWE) was defined as GCW/(GCW + GWW).

Results

LVGWW, RVGWI, RVGCW and RVGWW were significantly higher in patients than controls (all P < 0.001). LVGWE, LVGWI, LVGCW, and RVGWE were lower in patients than controls (all P < 0.01). Myocardial work parameters correlated well with clinical and other conventional echocardiographic assessments (all P < 0.05). In binary logistic regression analysis, the combination of RVGWE and estimation of pulmonary arterial systolic pressure (ePASP) was the best model to predict clinical outcomes (OR = 0.803, P = 0.002 and OR = 1.052, P = 0.015, respectively). Receiver operating characteristic curv demonstrated the combination of RVGWE and ePASP was the best predictor of adverse events with 100% sensitivity and 76.3% specificity (AUC = 0.910, P < 0.001).

Conclusion

Myocardial work parameters derived from PSL are emerging markers of cardiac function. And the combination of RVGWE and ePASP is a useful predictor of clinical outcome in PH patients.
Novel and emerging therapies in pulmonary arterial hypertension
Authors: Cassady Steven J. , Soldin Danielle , Ramani Gautam V.
Published: December 2022

Pulmonary arterial hypertension (PAH), defined as a mean pulmonary artery pressure exceeding 20 mmHg with a pulmonary vascular resistance of 3 or more Wood units, is an incurable and progressive condition. The cornerstone of PAH treatment is pulmonary vasodilators, which act on the pulmonary vasculature to reduce pulmonary pressures and pulmonary vascular resistance and prevent progression to right heart failure. The number of available pulmonary vasodilator therapies has grown markedly in the last 10 years, alongside a rapidly expanding body of literature establishing strategies for their use. Up-front combination therapy, typically with two pulmonary vasodilator medications, has become the standard of care based on landmark trials showing superior outcomes over single therapies alone. Complex risk stratification matrices have begun to see widespread use as tools with which to guide changes in PAH therapies for individual patients. Strategies for using the pulmonary vasodilators in common use continue to be evaluated in trials exploring concepts such as up-front triple combination therapy and substitution of vasodilators for patients not meeting therapeutic goals. Alongside established pulmonary vasodilator therapies for PAH, there is a broad spectrum of experimental therapies that are being studied for the disease. These include both more conventional medications that act on pathways targeted by existing vasodilator therapies as well as non-vasodilator treatments with novel methods of action, that may act both to vasodilate and to address the detrimental changes of pulmonary arterial and right ventricular remodeling. Many of these emerging medications are the focus of active phase 2 and 3 trials. Finally, there has been significant interest in therapeutic pathways that are well established in left heart failure, with the hope of adapting strategies that may be efficacious in PAH and right heart failure as well. These include explorations of pathways treated by goal-directed medical therapy as well as device therapies such as pacing, resynchronization therapy, and cardiac monitoring devices. Many of these options show promise and may represent a complementary approach to treatment of PAH, allowing for multimodal therapy alongside pulmonary vasodilators to improve patient outcomes.
Effectiveness of in-class excel-based active learning activities for transportation engineering courses
Authors: Saha Promothes
Published: December 2022

Recently, transportation engineering industry members showed concern that students lacked the skills to solve real-world engineering problems using spreadsheet data analysis. In response to the circumstances shown by industry members, this study investigated how to engage students in a better way by incorporating spreadsheet analysis during class and helping them learn the course topics. Helping students link theoretical knowledge to real-world problems can be a challenge. In this effort, in-class activities and worksheets were redesigned to integrate with Excel to solve example problems using built-in tools, including cell references, equations, data analysis tool pack, solver tool, conditional formatting, charts, etc. The effectiveness of this technique was investigated using students’ evaluations of the course, enrollment data, and students’ comments. Based on the data of those criteria, it is evident that spreadsheet activities may increase student learning.
Teachers’ efforts to increase students’ confidence in speaking Indonesian in Sarolangun through language habituation
Authors: Nugraheni Aninditya Sri , Abroto
Published: December 2022

This research is aimed at investigating teachers’ habituation pattern as an effort to enhance students’ confidence in speaking Indonesian language in Sarolangun. It implements qualitative phenomenology approach to understand why and how an incident takes place. The data are collected through observation, interview, and documentation. The subjects of the research are Indonesian students and teachers from three different senior high schools in Sarolangun, Indonesia. The results reveal that students are low skilled in using Indonesian language, and they have low confidence in speaking in Indonesian due to bullying. The senior high school teachers in Sarolangun try to improve the students’ confidence in speaking Indonesian through encouragement, punishment for the bullies, and compulsory program to use Indonesian at school. These are considered as a proper policy in boosting students’ confidence. This research concludes that in the teaching of Indonesian, the language should not be used by a certain group of people but rather it could be used by all people regardless of their social class. Furthermore, Indonesian is the language used in academic and official context. Indonesia, indeed, constitutes of various tribes and languages. The aim of Indonesian language usage is to ease people from many different ethnicities and regions to communicate to each other.
Interactions and social identity of support teachers: An ethnographic study of the marginalisation in the inclusive school
Authors: Milani Marin Laura Emma , Jacomuzzi Alessandra Cecilia
Published: December 2022

Educational personnel are seen as agents of change toward inclusive schools. This research aims to examine the daily-based interactions through which inclusion is experienced by support teachers and how their social identity is constructed within a secondary school in a northern Italy province. The theoretical basis of this research is formed by the conceptual contributions of social identity approach and symbolic interactionism to understand self-categorization and identification processes, through the narratives of actors. An ethnographic design was implemented, with 4-month participant observation and 20 semi-structured interviews of long duration as the main data collection techniques. Fieldnotes and interviews transcriptions were inductively analyzed through a thematic approach to grounded theorising. Results show a school community in which there is a strong hierarchical relationship among main and support teachers, where support teachers experience strong feelings of inferiority and marginalisation, since they have entered school. These school interactions are also shaped by the school culture and management. However, support teachers have a potential avant-garde role as agents of change in the inclusion process. Future research should target this aspect to investigate best inclusive practices.
Overview of global publications on machine learning in diabetic retinopathy from 2011 to 2021: Bibliometric analysis
Authors: Shao An , Jin Kai , Li Yunxiang , Lou Lixia , Zhou Wuyuan , Ye Juan
Published: December 2022

Purpose

To comprehensively analyze and discuss the publications on machine learning (ML) in diabetic retinopathy (DR) following a bibliometric approach.

Methods

The global publications on ML in DR from 2011 to 2021 were retrieved from the Web of Science Core Collection (WoSCC) database. We analyzed the publication and citation trend over time and identified highly-cited articles, prolific countries, institutions, journals and the most relevant research domains. VOSviewer and Wordcloud are used to visualize the mainstream research topics and evolution of subtopics in the form of co-occurrence maps of keywords.

Results

By analyzing a total of 1147 relevant publications, this study found a rapid increase in the number of annual publications, with an average growth rate of 42.68%. India and China were the most productive countries. IEEE Access was the most productive journal in this field. In addition, some notable common points were found in the highly-cited articles. The keywords analysis showed that “diabetic retinopathy”, “classification”, and “fundus images” were the most frequent keywords for the entire period, as automatic diagnosis of DR was always the mainstream topic in the relevant field. The evolution of keywords highlighted some breakthroughs, including “deep learning” and “optical coherence tomography”, indicating the advance in technologies and changes in the research attention.

Conclusions

As new research topics have emerged and evolved, studies are becoming increasingly diverse and extensive. Multiple modalities of medical data, new ML techniques and constantly optimized algorithms are the future trends in this multidisciplinary field.
Joint analysis of m6A and mRNA expression profiles in the testes of idiopathic nonobstructive azoospermia patients
Authors: Tang Qiuqin , Wu Wei , Lu Yiwen , Zhou Yijie , Wu Wangfei , Li Jinhui , Pan Lianjun , Ling Xiufeng , Pan Feng
Published: December 2022

Background

Growing evidence has indicated that epigenetic factors might be associated with the pathophysiology of idiopathic nonobstructive azoospermia (iNOA). As the most common RNA modification, N6-methyladenosine (m6A) methylation has recently attracted more attention in the regulation of spermatogenesis; however, its role in the mechanisms of iNOA is still unclear.

Objective

To determine the differential expression of mRNA and m6A methylation status in the testes of iNOA patients.

Methods

Testes tissues from diagnosed iNOA and controlled obstructive azoospermia (OA) patients were collected and grouped according to the histological examinations. Total RNA was isolated and quantified by an m6A RNA Methylation Quantification Kit. The expression level of mRNAs was detected by qRT-PCR analysis. Differentially expressed m6A genes were analyzed using the human ArrayStar m6A epitranscriptomic microarray, and bioinformatics analyses were applied.

Results

A total of 36 iNOA and 8 controlled patients were included. The global expression of m6A in the iNOA group was significantly decreased. A dosage relationship was observed between the m6A decline and the degree of impaired spermatogenesis, with the successive process of normal spermatogeneis, hypospermatogenesis (HP), maturation arrest (MA), and Sertoli cell-only syndrome (SO). Four down-expressed genes (BDNF, TMEM38B, RPL3L, and C22orf42) displayed significantly lower expression of m6A methylation. Additionally, they also showed a gradually down-expressed tendency in the three groups (OA, HP, SO/MA groups). Moreover, m6A reader EIF3A was approved to have differential expression through microarrays analysis, which was consistent with the result from the qRT-PCR test.

Conclusions

The m6A expression was gradually downregulated in the testes tissue from iNOA patients in accordance with the degree of spermatogenic dysfunction. The determined differential expression of mRNA and m6A methylation status may represent potentially novel molecular targets for the mechanism study of iNOA in the epigenetic level, which could benefit the understanding of the pathophysiology of iNOA.
Comparison the effects of finerenone and SGLT2i on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus: A network meta-analysis
Authors: Li Xuefeng , Wu Hongli , Peng Huifang , Jiang Hongwei
Published: December 2022

Background

Finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to improve cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), while the relative efficacy has not been determined.

Methods

The databases of PubMed, Embase and Cochrane were searched for relevant cardiovascular or renal outcome trials of SGLT2i or finerenone. The end points were major adverse cardiovascular events (MACE), nonfatal stroke (NS), myocardial infarction (MI), hospitalization for heart failure (HHF), cardiovascular death (CVD), and renal composite outcome (RCO). Network meta-analysis was performed using Bayesian networks to obtain pooled hazard ratios (HR) and 95% confidence intervals (CI). The probability values for ranking active and placebo interventions were calculated using cumulative ranking curves.

Results

1024 articles were searched, and only 9 studies were screened and included in this meta-analysis with 71793 randomized participants. Sotagliflozin (HR 0.72 95%CI 0.59-0.88, SUCAR=0.93) and canagliflozin (HR 0.80 95%CI 0.67-0.97, SUCAR=0.73) can significantly reduce the risk of MACE compared with placebo. Canagliflozin (HR 0.64 95%CI 0.48-0.86, SUCAR=0.73), sotagliflozin (HR 0.66 95%CI 0.50-0.87, SUCAR=0.69) and empagliflozin (HR 0.65 95%CI 0.43-0.98, SUCAR=0.68) can significantly reduce the risk of HHF compared with placebo. Empagliflozin (HR 0.62 95%CI 0.43-0.89, SUCAR=0.96) can significantly reduce the risk of CVD compared with placebo. Empagliflozin (HR 0.61 95%CI 0.39-0.96, SUCAR=0.74), canagliflozin (HR 0.66 95%CI 0.46-0.92, SUCAR=0.63), and dapagliflozin (HR 0.53 95%CI 0.32-0.85, SUCAR=0.88) can significantly reduce the risk of RCO compared with placebo. Finerenone has reduced the risk of MACE, MI, HHF, CVD and RCO to varying degrees, but they do not show significant difference from placebo and each SGLT2i.

Conclusion

Both SGLT2i and finerenone could reduce the risk of MACE, HHF, MI, CVD, RCO. Finerenone has no obvious advantage than SGLT2i on the effects of cardiovascular and renal protective.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022375092.
An overview of walnuts application as a plant-based
Authors: Zhou Xingjian , Peng Xingyu , Pei Huan , Chen Yuhan , Meng Hui , Yuan Jiali , Xing Haijing , Wu Yueying
Published: December 2022

The plant-based refers to plant-based raw materials or products that are available as the source of protein and fat. Utilization and development of walnuts as a plant-based, resulting in a high-quality protein-rich walnut plant-based product: walnut protein powder and walnut peptides. Progress in research on the application of walnuts as a plant-based has been advanced, solving the problem of wasted resources and environmental pollution caused by the fact that walnut residue, a product of walnuts after oil extraction, is often thrown away as waste, or becomes animal feed or compost. This paper reviews and summarizes the research and reports on walnut plant-based at home and abroad, focusing on the application of walnut plant-based in the preparation process (enzymatic and fermentation methods) and the biological activity of the walnut protein and walnut peptide, to provide a theoretical basis for the further processing of walnuts as a walnut plant-based. It can make full use of walnut resources and play its nutritional and health care value, develop and build a series of walnut plant-based products, improve the competitiveness of walnut peptide products, turn them into treasure, and provide more powerful guidance for the development of food and medicine health industry in Yunnan.
Accelerated loss of trunk muscle density and size at L1 vertebral level in male patients with COPD
Authors: Wang Ying , Li Sidong , Zhang Zhenyi , Sun Shiqi , Feng Juntao , Chen Jinbiao , Pei Yigang , Peng Xianjing
Published: December 2022

Background and purpose

Weight loss and muscle mass loss are common in patients with chronic obstructive pulmonary disease (COPD). Muscle density and fat infiltration based on CT images may be more sensitive than muscle mass by DXA in the assessment of sarcopenia for COPD patients. However, the age-related changes of cross-sectional trunk muscle compositions based on lung CT scans are still unknown. Thus, we aimed to investigate over time the change in muscle density, size, and fat deposition of L1-level trunk muscles in patients with COPD.

Materials and methods

129 male COPD patients with a second chest CT scan (from 2013-2019 to 2014-2020) were enrolled. The CT images at first and second CT scans are analyzed by OsiriX software. Trunk muscles at the level of the 1st lumbar vertebrae were selected for analysis. Attenuation of lumbar vertebrae 1 was also measured from chest CT images. The pulmonary function values were calculated based on forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).

Results

The mean age of the 129 patients with COPD was 69.7 years. The durations of COPD of this cohort were from 8-17 years. The mean area and density of L1 trunk muscles were 85.5 cm2 and 36.4 HU. At baseline, muscle area and density and vertebral density were negatively associated with age (p<0.0001), while the intermuscular fat area and the fat infiltration ratio were not significantly associated with age (p>0.05). The per-year loss of trunk muscle area was 2.83 cm2 (p<0.0001) which accounts for 3.3% decrease per year, and the per-year decrease of trunk muscle density was 2.41 HU (p<0.0001) which accounts for 6.6% decrease per year. The per-year increase of intermuscular fat in trunk muscles was 0.57 cm2 (p=0.006) which accounts for 11.1% increase per year. The bone density loss was 5.63 HU/per year (p<0.0001).

Conclusion

Men with COPD had accelerated muscle loss as well as increased fat infiltration. Compared to muscle quantity loss, the decline in muscle quality is much larger, indicating the importance of relevant interventions focusing on improving muscle quality.
Clinical characteristics and molecular etiology of partial 17α-hydroxylase deficiency diagnosed in 46,XX patients
Authors: Zhang Duoduo , Yao Fengxia , Luo Min , Wang Yanfang , Tian Tiffany , Deng Shan , Tian Qinjie
Published: December 2022

Introduction

Complete 17α-hydroxylase deficiency (17OHD) is relatively common, with typical juvenile female genitalia, severe hypertension, hypokalemia, and the absence of sexual development, but partial (or non-classical) 17OHD (p17OHD) is extremely rare. The p17OHD patients can present with a broad spectrum of symptoms in 46,XX karyotype including various degree of spontaneous breast development after puberty, recurrent ovarian cysts, oligomenorrhea and infertility depending on specific gene mutations and other influencing factors.

Methods

This paper is a retrospective analysis of p17OHD cases from 1997 to 2021 in a Chinese tertiary hospital. Eight patients were recruited from unrelated families according to clinical data. Genotypes of patients were determined by sequencing the CYP17A1 genes. Clinical characteristics were summarized based on manifestations, hormone profiles, and responses to treatments.

Results

All seven post-pubertal patients had abnormal menses. All patients had enlarged multilocular ovaries, and six (6/8) had a history of ovarian cystectomy prior to a definite diagnosis of p17OHD. All eight patients’ sex hormone levels were in accord to hypogonadism with mildly elevated follicle-stimulating hormone levels, and oral contraceptives effectively suppressed the ovarian cysts. Of the four patients who underwent plasma renin activity tests, all showed results below the reference range. Fourteen alleles with a CYP17A1 mutation were found. Exon 6 was the most frequent mutation site (5/14), and four out of these five mutations were c.985_987delTACinsAA, being the most common one. In Case 2, c.1220dupA was a newly reported mutation of CYP17A1.

Conclusions

46,XX p17OHD patients were born with highly fragile ovarian reserve due to diverse mutations of CYP17A1. However, their multi-ovarian cysts can be managed conservatively for fertility preservation. This study focuses on p17OHD in 46,XX by locating the complex genetic causes in novel mutations, summarizing the puzzling spectrum of clinical manifestations, and illustrating the significance of fertility preservation in these scarce cases.
The vulnerability of springs and phreatophyte communities to groundwater level declines in Oregon and Nevada, 2002–2021
Authors: Saito Laurel , Freed Zach , Byer Sarah , Schindel Michael
Published: December 2022

Increased groundwater demand is causing aquifer declines that impact viability of groundwater-dependent ecosystems (GDEs) like springs and phreatophyte communities. To understand which springs and phreatophyte communities may be stressed by groundwater level declines in Oregon and Nevada, we assessed groundwater level trends in nearby monitoring wells. Very few springs and phreatophyte communities were near monitoring wells with adequate data. Less than 1% of >50,000 springs in Nevada and Oregon were within 800 m of analyzed wells, and only 52 springs were near a shallow (<30 m below ground surface) well. Among springs near analyzed wells, 56% in Nevada and 29% in Oregon were near wells with declining groundwater level trends, and percentages were similar among springs that were within 800 m of analyzed shallow wells. Less than 22% of all phreatophyte communities in Nevada and Oregon were near analyzed wells, and only 9.6% were within 800 m of a shallow well. Of phreatophyte communities near analyzed wells, 48% and 57% were near wells with declining trends in Nevada and Oregon, respectively. Differences among GDE types could reflect more groundwater development where phreatophytes exist. Differences between states in proportion of springs near wells with declining trends could be due to more surface water capture in Oregon or increased pressure for groundwater development in Nevada. State-specific policies and administration of groundwater rights and monitoring affect data availability and trends observed in the two states. More groundwater level data are essential for understanding impacts of groundwater withdrawals to GDEs.
Benchmarking a fast and simple on-site detection assay for the oak wilt pathogen Bretziella fagacearum
Authors: Bourgault Émilie , Gauthier Marie-Krystel , Potvin Amélie , Stewart Don , Chahal Karandeep , Sakalidis Monique L. , Tanguay Philippe
Published: December 2022

Oak wilt is a vascular disease of oak trees caused by the fungus Bretziella fagacearum. Once infected, trees may die in a few weeks. Although the disease is currently only found in the United States, it has been reported within just a few hundred meters of the Canada–USA border. To limit the establishment and spread of oak wilt in Canada, the development of an on-site, quick and reliable method to detect B. fagacearum is critical. In this study, we developed and validated a new qPCR TaqMan® assay that can detect B. fagacearum in a laboratory setting with great specificity and sensitivity. Using this test as a reference, we also developed and validated a new DETECTR assay that can detect B. fagacearum under 1 h from a variety of environmental samples, such as mycelium mats and insect vectors, using minimal laboratory equipment. While there are still some limitations to the sensitivity of this assay, we believe that its ease of use, flexibility and accuracy will provide an essential tool in efforts to reduce the spread of oak wilt.
Emissions of isoprenoids from dominant tree species in subtropical China
Authors: Zeng Jianqiang , Song Wei , Zhang Yanli , Mu Zhaobin , Pang Weihua , Zhang Huina , Wang Xinming
Published: December 2022

Emission factors (Es) are among the major sources of uncertainty in regional or global emission estimates of biogenic volatile organic compounds (BVOCs). Tropical vegetation contributes approximately 70% of global BVOC emissions, yet in situ measurements of BVOC emissions from tropical tree species, especially naturally grown mature trees, are quite limited. In this study, BVOC emissions from twenty mature trees (15 evergreen broad-leaved and 5 evergreen needle-leaved) were measured using dynamic chambers, and the emitted BVOCs were collected using sorbent tubes and speciated with a thermal desorption-gas chromatography/mass spectrometry system (TD-GC/MS). Twenty BVOC compounds including, isoprene, 14 monoterpene (MT) species and 9 sesquiterpene (SQT) species were quantified to calculate their Es. The results showed that Eucalyptus urophylla had the largest Es of isoprene (26.47 ± 3.70 μg g–1 h–1) among all the measured trees, followed by Ficus hispida (20.74 ± 1.78 μg g–1 h–1), Syzygium hainanense (20.49 ± 1.36 μg g–1 h–1), Casuarina equisetifolia (18.70 ± 2.91 μg g–1 h–1), and Mangifera indica (11.71 ± 7.04 μg g–1 h–1). α-Pinene, β-pinene, and limonene were the most abundant MTs, of which the largest Es were observed for Magnolia denudata (8.33 ± 2.05 μg g–1 h–1), Castanopsis hystrix (5.29 ± 3.24 μg g–1 h–1), and Magnolia denudata (3.11 ± 1.07 μg g–1 h–1), respectively. The Es of SQTs for the measured trees were lower than 0.50 μg g–1 h–1 except for Magnolia denudata (1.10 ± 0.41 μg g–1 h–1). β-Caryophyllene was the most common SQT, with Magnolia denudata having the highest Es of 0.09 ± 0.03 μg g–1h–1. The localized Es for dominant tree species could be used to update BVOC emission factors for typical vegetation types and help improve BVOC emission estimates in typical subtropical regions and narrow their uncertainties.
Longitudinal immune profiling after radiation-attenuated sporozoite vaccination reveals coordinated immune processes correlated with malaria protection
Authors: Duffy Fergal J. , Hertoghs Nina , Du Ying , Neal Maxwell L. , Oyong Damian , McDermott Suzanne , Minkah Nana , Carnes Jason , Schwedhelm Katharine V. , McElrath M. Juliana , De Rosa Stephen C. , Newell Evan , Aitchison John D. , Stuart Ken
Published: December 2022

Background

Identifying immune processes required for liver-stage sterilizing immunity to malaria remains an open problem. The IMRAS trial comprised 5x immunizations with radiation-attenuated sporozoites resulting in 55% protection from subsequent challenge.

Methods

To identify correlates of vaccination and protection, we performed detailed systems immunology longitudinal profiling of the entire trial time course including whole blood transcriptomics, detailed PBMC cell phenotyping and serum antigen array profiling of 11 IMRAS radiation-attenuated sporozoite (RAS) vaccinees at up to 21 timepoints each.

Results

RAS vaccination induced serum antibody responses to CSP, TRAP, and AMA1 in all vaccinees. We observed large numbers of differentially expressed genes associated with vaccination response and protection, with distinctly differing transcriptome responses elicited after each immunization. These included inflammatory and proliferative responses, as well as increased abundance of monocyte and DC subsets after each immunization. Increases in Vδ2 γδ; T cells and MAIT cells were observed in response to immunization over the course of study, and CD1c+ CD40+ DC abundance was significantly associated with protection. Interferon responses strongly differed between protected and non-protected individuals with high interferon responses after the 1st immunization, but not the 2nd-5th. Blood transcriptional interferon responses were correlated with abundances of different circulating classical and non-classical monocyte populations.

Conclusions

This study has revealed multiple coordinated immunological processes induced by vaccination and associated with protection. Our work represents the most detailed immunological profiling of a RAS vaccine trial performed to date and will guide the design and interpretation of future malaria vaccine trials.
Transcriptional inhibition of STAT1 functions in the nucleus alleviates Th1 and Th17 cell-mediated inflammatory diseases
Authors: Park Jiyoon , Son Min-Ji , Ho Chun-Chang , Lee Su-Hyeon , Kim Yuna , An Jaekyeung , Lee Sang-Kyou
Published: December 2022

T helper 1 cells (Th1 cells) and T helper 17 cells (Th17 cells) play pivotal roles in the pathogenesis of various autoimmune diseases, including psoriasis and inflammatory bowel disease (IBD). Signal transducer and activator of transcription 1 (STAT1) regulates the Th1 and Th17 cell lineage commitment at an early stage and maintains their immunological functions in vitro and in vivo. The previous strategies to block STAT1 functions to treat autoimmune diseases inhibit Th1 cell activity but simultaneously cause hyper-activation of Th17 cells. Herein, to modulate the functions of pathogenic Th1 and Th17 cells without genetic modification in normal physiological conditions, we generated the nucleus-deliverable form of the transcription modulation domain of STAT1 (ndSTAT1-TMD), which can be transduced into the nucleus of the target cells in a dose- and time-dependent manner without affecting the cell viability and T cell activation signaling events. ndSTAT1-TMD significantly blocked the differentiation of naïve CD4+ T cells into Th1 or Th17 cells via competitive inhibition of endogenous STAT1-mediated transcription, which did not influence Th2 and Treg cell differentiation. When the gene expression profile of Th1 or Th17 cells after ndSTAT1-TMD treatment was analyzed by mRNA sequencing, the expression of the genes involved in the differentiation capacity and the immunological functions of Th1 or Th17 cells were substantially reduced. The therapeutic potential of ndSTAT1-TMD was tested in the animal model of psoriasis and colitis, whose pathogenesis is mainly contributed by Th1 or/and Th17 cells. The symptoms and progression of psoriasis and colitis were significantly alleviated by ndSTAT1-TMD treatment, comparable to anti-IL-17A antibody treatment. In conclusion, our study demonstrates that ndSTAT1-TMD can be a new therapeutic reagent for Th1/17 cell-mediated autoimmune diseases by modulating the functions of pathogenic Th1 and Th17 cells together.
The blood pressure targets in sepsis patients with acute kidney injury: An observational cohort study of multiple ICUs
Authors: Zhao Lina , Fan Yan , Wang Zhiwei , Wei Zhiyong , Zhang Ying , Li Yun , Xie Keliang
Published: December 2022

Background

The maintenance of blood pressure is pivotal in preventing sepsis with acute kidney injury (AKI). Especially in sepsis patients treated with vasopressors. The optimal the blood pressure has been controversial to maintain renal perfusion. This study aims to explore the blood pressure target in sepsis with AKI.

Methods

We retrieved patient data from the MIMIC IV and eICU databases. The Lasso regression model was used to identify the relationship between blood pressure and sepsis in patients with AKI and remove collinearity among variables. Generalized additive models were used to estimate the blood pressure range in patients with sepsis with AKI. Statistical methods such as multivariable logistic regression, propensity score analysis, inversion probability-weighting, and doubly robust model estimation were used to verify the target blood pressure for patients with sepsis and AKI.

Results

In total, 17874 patients with sepsis were included in this study. the incidence of AKI may be related to the level of mean article pressure (MAP) and diastolic blood pressure (DBP) in sepsis patients. The range of MAPs and DBPs may be 65-73 mmHg and 50-60 mmHg in AKI patients without hypertension. The range of MAPs and DBPs may be 70-80 mmHg and 54-62 mmHg in AKI patients with hypertension. The prognosis of sepsis with AKI was unaffected by MAP or DBP. Systolic blood pressure is not associated with sepsis in patients with AKI.

Conclusions

To ensure renal perfusion, AKI patients with hypertension may require a higher MAP [70-80] versus (65-73), mmHg] and DBP [(54-62) vs (50-60), mmHg] than patients without hypertension.
Prospects for NK-based immunotherapy of chronic HBV infection
Authors: Jin Xiaomeng , Bi Jiacheng
Published: December 2022

Effective and long-term treatment is required for controlling chronic Hepatitis B Virus (HBV) infection. Natural killer (NK) cells are antiviral innate lymphocytes and represent an essential arm of current immunotherapy. In chronic HBV (CHB), NK cells display altered changes in phenotypes and functions, but preserve antiviral activity, especially for cytolytic activity. On the other hand, NK cells might also cause liver injury in the disease. NK -based immunotherapy, including adoptive NK cell therapy and NK -based checkpoint inhibition, could potentially exploit the antiviral aspect of NK cells for controlling CHB infection while preventing liver tissue damage. Here, we review recent progress in NK cell biology under the context of CHB infection, and discuss potential NK -based immunotherapy strategies for the disease.
Histone lysine-specific demethylase 1 regulates the proliferation of hemocytes in the oyster Crassostrea gigas
Authors: Gu Xiaoyu , Qiao Xue , Yu Simiao , Song Xiaorui , Wang Lingling , Song Linsheng
Published: December 2022

Background

Lysine-specific demethylase 1 (LSD1) is an essential epigenetic regulator of hematopoietic differentiation, which can specifically mono-methylate H3K4 (H3K4me1) and di-methylate H3K4 (H3K4me2) as a transcriptional corepressor. Previous reports have been suggested that it participated in hematopoiesis and embryonic development process. Here, a conserved LSD1 (CgLSD1) with a SWIRM domain and an amino oxidase (AO) domain was identified from the Pacific oyster Crassostrea gigas.

Methods

We conducted a comprehensive analysis by various means to verify the function of CgLSD1 in hematopoietic process, including quantitative real-time PCR (qRT-PCR) analysis, western blot analysis, immunofluorescence assay, RNA interference (RNAi) and flow cytometry.

Results

The qRT-PCR analysis revealed that the transcripts of CgLSD1 were widely expressed in oyster tissues with the highest level in the mantle. And the transcripts of CgLSD1 were ubiquitously expressed during larval development with the highest expression level at the early D-veliger larvae stage. In hemocytes after Vibrio splendidus stimulation, the transcripts of CgLSD1 were significantly downregulated at 3, 6, 24, and 48 h with the lowest level at 3 h compared to that in the Seawater group (SW group). Immunocytochemical analysis showed that CgLSD1 was mainly distributed in the nucleus of hemocytes. After the CgLSD1 was knocked down by RNAi, the H3K4me1 and H3K4me2 methylation level significantly increased in hemocyte protein. Besides, the percentage of hemocytes with EdU-positive signals in the total circulating hemocytes significantly increased after V. splendidus stimulation. After RNAi of CgLSD1, the expression of potential granulocyte markers CgSOX11 and CgAATase as well as oyster cytokine-like factor CgAstakine were increased significantly in mRNA level, while the transcripts of potential agranulocyte marker CgCD9 was decreased significantly after V. splendidus stimulation.

Conclusion

The above results demonstrated that CgLSD1 was a conserved member of lysine demethylate enzymes that regulate hemocyte proliferation during the hematopoietic process.
Inconsistency between non-invasive prenatal testing (NIPT) and conventional prenatal diagnosis due to confined placental and fetal mosaicism: Two case reports
Authors: Kang Kyung Min , Kim Soo Hyun , Park Ji Eun , Kim Hyunjin , Jang Hee Yeon , Go Minyeon , Yang So Hyun , Ryu Sang Woo , Bae Sung Mi , Cha Dong Hyun , Shim Sung Han
Published: December 2022

We aimed to identify the causes of inconsistent results between non-invasive prenatal testing (NIPT) and invasive testing methods for trisomy 21. In the first case, NIPT was performed at 11 weeks of pregnancy, and the result showed a high risk of trisomy 21 [fetal fraction (FF) = 6.98%, 21 chromosome Z-score = 3.6]. The patient underwent quantitative fluorescent (QF)-PCR and karyotyping at 14 + 0 weeks of pregnancy through CVS showing mosaicism of 47, XX, + 21[11] and 46, XX [39] in karyotyping. The patient underwent amniocentesis at 15 + 6 weeks, showing a normal pattern in QF-PCR and 46, XX karyotyping in long term culture. The second case underwent NIPT at 16 + 5 weeks of pregnancy (FF = 7.52%, 21 chromosome Z-score = 2.503). She underwent an invasive test at 19 weeks through amniotic fluid sampling. As a result, trisomy 21 was detected by QF-PCR, and mosaicism of XX, +21[22]/46, XX [4] was identified by karyotyping. Despite significant advances in fetal chromosome analysis using NIPT, invasive testing is still needed as placenta-derived DNA does not reflect 100% fetal genetic information. Placental mosaicism can be detected by NIPT, but more research is needed to increase its sensitivity. Therefore, if the NIPT result is positive, an invasive test can confirm the result, and continuous monitoring is required even if the NIPT result is negative.
Peripheral blood cell anomalies in COVID-19 patients in the United Arab Emirates: A single-centered study
Authors: Elemam Noha Mousaad , Talaat Iman M. , Bayoumi Fatehia A. , Zein Dima , Georgy Ramy , Altamimi Abdalrahman , Alkhayyal Noura , Habbal Alaa , Al Ali Feda , ElKhider Alaa , Ahmed Abdallah , Abusnana Salah , Bendardaf Riyad
Published: December 2022

Introduction

In this study, we aimed at exploring the morphologic and quantitative abnormalities in the peripheral blood counts of coronavirus disease 2019 (COVID-19) patients.

Methods

A cohort of 131 COVID-19 patients was recruited at University Hospital Sharjah (UHS), UAE. Their peripheral blood smears were examined for morphological evaluation. Also, their clinical laboratory investigations and radiological findings were retrieved from the medical records. Our cohort consisted of 63 males and 68 females with an age of 63.6 ± 18.6 years.

Results

The presence of atypical lymphocytes was observed in around 80% of the recruited COVID-19 patients. Further, monocytes with toxic cytoplasmic vacuoles were identified in 55% of the cases. Neutrophil-associated changes, including pseudo-Pelger-Huët, bands, and long nuclear endoplasm, were reported in around 25–35% of the patients. RBCs associated changes such as microcytic and hypochromic RBCs, as well as targetoid, dacrocytes, ovalocytes, echinocytes/burr cells, and schistocytes, were described. According to disease severity, RBCs chromicity was found to be significantly different between stable and critical patients. COVID-19 patients with CO-RADS 5 showed a similar change in RBCs as well as a decrease in the neutrophils with hypogranular cytoplasm.

Conclusion

Peripheral blood smear assessment in COVID-19 patients could provide information about the disease state and pulmonary involvement.