bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Ferroptosis-Related lncRNA Signature Predicts the Prognosis of Bladder Cancer Patients
Authors: Chen Mei , Nie Zhenyu , Li Yan , Gao Yuanhui , Wen Xiaohong , Cao Hui , Zhang Shufang
Published: November 2021

Background: Ferroptosis is closely related to the occurrence and development of cancer. An increasing number of studies have induced ferroptosis as a treatment strategy for cancer. However, the predictive value of ferroptosis-related lncRNAs in bladder cancer (BC) still need to be further elucidated. The purpose of this study was to construct a predictive signature based on ferroptosis-related long noncoding RNAs (lncRNAs) to predict the prognosis of BC patients.

Methods: We downloaded RNA-seq data and the corresponding clinical and prognostic data from The Cancer Genome Atlas (TCGA) database and performed univariate and multivariate Cox regression analyses to obtain ferroptosis-related lncRNAs to construct a predictive signature. The Kaplan-Meier method was used to analyze the overall survival (OS) rate of the high-risk and low-risk groups. Gene set enrichment analysis (GSEA) was performed to explore the functional differences between the high- and low-risk groups. Single-sample gene set enrichment analysis (ssGSEA) was used to explore the relationship between the predictive signature and immune status. Finally, the correlation between the predictive signature and the treatment response of BC patients was analyzed.

Results: We constructed a signature composed of nine ferroptosis-related lncRNAs (AL031775.1, AL162586.1, AC034236.2, LINC01004, OCIAD1-AS1, AL136084.3, AP003352.1, Z84484.1, AC022150.2). Compared with the low-risk group, the high-risk group had a worse prognosis. The ferroptosis-related lncRNA signature could independently predict the prognosis of patients with BC. Compared with clinicopathological variables, the ferroptosis-related lncRNA signature has a higher diagnostic efficiency, and the area under the receiver operating characteristic curve was 0.707. When patients were stratified according to different clinicopathological variables, the OS of patients in the high-risk group was shorter than that of those in the low-risk group. GSEA showed that tumor- and immune-related pathways were mainly enriched in the high-risk group. ssGSEA showed that the predictive signature was significantly related to the immune status of BC patients. High-risk patients were more sensitive to anti-PD-1/L1 immunotherapy and the conventional chemotherapy drugs sunitinib, paclitaxel, cisplatin, and docetaxel.

Conclusion: The predictive signature can independently predict the prognosis of BC patients, provides a basis for the mechanism of ferroptosis-related lncRNAs in BC and provides clinical treatment guidance for patients with BC.
Microbiome-Mediated Immune Signaling in Inflammatory Bowel Disease and Colorectal Cancer: Support From Meta-omics Data
Authors: Pratt Molly , Forbes Jessica D. , Knox Natalie C. , Bernstein Charles N. , Van Domselaar Gary
Published: November 2021

Chronic intestinal inflammation and microbial dysbiosis are hallmarks of colorectal cancer (CRC) and inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis. However, the mechanistic relationship between gut dysbiosis and disease has not yet been fully characterized. Although the “trigger” of intestinal inflammation remains unknown, a wealth of evidence supports the role of the gut microbiome as a mutualistic pseudo-organ that significantly influences intestinal homeostasis and is capable of regulating host immunity. In recent years, culture-independent methods for assessing microbial communities as a whole (termed meta-omics) have grown beyond taxonomic identification and genome characterization (metagenomics) into new fields of research that collectively expand our knowledge of microbiomes. Metatranscriptomics, metaproteomics, and metabolomics are meta-omics techniques that aim to describe and quantify the functional activity of the gut microbiome. Uncovering microbial metabolic contributions in the context of IBD and CRC using these approaches provides insight into how the metabolic microenvironment of the GI tract shapes microbial community structure and how the microbiome, in turn, influences the surrounding ecosystem. Immunological studies in germ-free and wild-type mice have described several host-microbiome interactions that may play a role in autoinflammation. Chronic colitis is a precursor to CRC, and changes in the gut microbiome may be an important link triggering the neoplastic process in chronic colitis. In this review, we describe several microbiome-mediated mechanisms of host immune signaling, such as short-chain fatty acid (SCFA) and bile acid metabolism, inflammasome activation, and cytokine regulation in the context of IBD and CRC, and discuss the supporting role for these mechanisms by meta-omics data.
Collateral Victim or Rescue Worker?—The Role of Histone Methyltransferases in DNA Damage Repair and Their Targeting for Therapeutic Opportunities in Cancer
Authors: He Lishu , Lomberk Gwen
Published: November 2021

Disrupted DNA damage signaling greatly threatens cell integrity and plays significant roles in cancer. With recent advances in understanding the human genome and gene regulation in the context of DNA damage, chromatin biology, specifically biology of histone post-translational modifications (PTMs), has emerged as a popular field of study with great promise for cancer therapeutics. Here, we discuss how key histone methylation pathways contribute to DNA damage repair and impact tumorigenesis within this context, as well as the potential for their targeting as part of therapeutic strategies in cancer.
CRISPR Generated SIX6 and POU4F2 Reporters Allow Identification of Brain and Optic Transcriptional Differences in Human PSC-Derived Organoids
Authors: Wahlin Karl J. , Cheng Jie , Jurlina Shawna L. , Jones Melissa K. , Dash Nicholas R. , Ogata Anna , Kibria Nawal , Ray Sunayan , Eldred Kiara C. , Kim Catherine , Heng Jacob S. , Phillips Jenny , Johnston Robert J. , Gamm David M. , Berlinicke Cynthia , Zack Donald J.
Published: November 2021

Human pluripotent stem cells (PSCs) represent a powerful tool to investigate human eye development and disease. When grown in 3D, they can self-assemble into laminar organized retinas; however, variation in the size, shape and composition of individual organoids exists. Neither the microenvironment nor the timing of critical growth factors driving retinogenesis are fully understood. To explore early retinal development, we developed a SIX6-GFP reporter that enabled the systematic optimization of conditions that promote optic vesicle formation. We demonstrated that early hypoxic growth conditions enhanced SIX6 expression and promoted eye formation. SIX6 expression was further enhanced by sequential inhibition of Wnt and activation of sonic hedgehog signaling. SIX6 + optic vesicles showed RNA expression profiles that were consistent with a retinal identity; however, ventral diencephalic markers were also present. To demonstrate that optic vesicles lead to bona fide “retina-like” structures we generated a SIX6-GFP/POU4F2-tdTomato dual reporter line that labeled the entire developing retina and retinal ganglion cells, respectively. Additional brain regions, including the hypothalamus and midbrain-hindbrain (MBHB) territories were identified by harvesting SIX6 + /POU4F2- and SIX6- organoids, respectively. Using RNAseq to study transcriptional profiles we demonstrated that SIX6-GFP and POU4F2-tdTomato reporters provided a reliable readout for developing human retina, hypothalamus, and midbrain/hindbrain organoids.
Rapid Gelling of Guar Gum Hydrogel Stabilized by Copper Hydroxide Nanoclusters for Efficient Removal of Heavy Metal and Supercapacitors
Authors: Zhu Xinwei , Chen Yingxi , Xie Renjian , Zhong Haijian , Zhao Weidong , Liu Yang , Yang Hui
Published: November 2021

In this paper, guar gum (GG) hydrogel has been successfully prepared by adding GG and Cu2+ mixture into an alkaline medium. The formation mechanism of the hydrogel has been investigated through various techniques. Results reveal GG facilitates the formation of ultrafine copper hydroxide clusters with a diameter of ∼3 nm. Moreover, these nanoclusters bring about a rapid gelling of GG within 10 ms. The synthesized hydrogel is applied to the adsorption of heavy metal ions from wastewater. The hydrogel shows excellent removal efficiency in removing various heavy metal ions. Besides, the hydrogel derived porous carbon exhibits high specific capacitance (281 F/g at 1 A/g) and excellent rate capacity. The high contaminant removal efficiency character and excellent electrochemical performance endow GG hydrogel with potential applications in the environmental and energy storage field.
Prognostic Potential of Liver Enzymes in Patients With COVID-19 at the Leishenshan Hospital in Wuhan
Authors: Liu Zeming , Hu Di , Li Jinpeng , Xia Qing , Gong Yan , Li Zhengwei , Wu Qian , Yi Meilin , Huang Yihui , Wu Meng , Guo Liang , Wu Xiaohui
Published: November 2021

Background

Coronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients.

Methods

Patient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality.

Results

Logistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19.

Conclusion

Elevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.
Bacterial Characteristics of Intestinal Tissues From Patients With Crohn’s Disease
Authors: Sun Desen , Ge Xiaolong , Tang Shasha , Liu Yaxin , Sun Jun , Zhou Yuping , Luo Liang , Xu Zhengping , Zhou Wei , Sheng Jinghao
Published: November 2021

Background and Aims

It is believed that intestinal bacteria play an indispensable role in promoting intestinal inflammation. However, the characteristics of these tissue-associated bacteria remain elusive. The aim of this study is to explore the bacterial loads, compositions, and structures in the noninflamed mucosa, inflamed mucosa, and creeping fat taken from patients with Crohn’s disease (CD).

Methods

Noninflamed mucosa, inflamed mucosa, and creeping fat samples were obtained from 10 surgical patients suffering from CD. Total bacterial DNA was extracted in a sterile environment using aseptic techniques. The V3–V4 regions of bacterial 16S rDNA were amplified and analysed using standard microbiological methods. qPCR was used to confirm the change in abundance of specific species in additional 30 independent samples.

Results

Inflamed mucosa exhibited the highest bacterial load (3.8 and 12 times more than that of non-inflamed mucosa and creeping fat) and species diversity. The relative abundance of Proteobacteria was dominant in most samples and was negatively associated with Firmicutes. Moreover, the relative abundances of Methylobacterium and Leifsonia in creeping fat significantly increased more than twice as much as other tissue types. The bacterial community structure analysis showed that the bacterial samples from the same individual clustered more closely.

Conclusion

This study reveals the significant differences in bacterial load, species diversity, and composition among different intestinal tissue types of CD patients and confirms that the bacterial samples from the same individual are highly correlated. Our findings will shed light on fully revealing the characteristics of tissue-associated bacteria and their roles in CD pathogenesis.
Involvement of the Heat Shock Protein HtpG of Salmonella Typhimurium in Infection and Proliferation in Hosts
Authors: Dong Tao , Wang Weiwei , Xia Minhao , Liang Shujie , Hu Guangzhong , Ye Hui , Cao Qingyun , Dong Zemin , Zhang Changming , Feng Dingyuan , Zuo Jianjun
Published: November 2021

Salmonella Typhimurium is a common pathogen infecting the gastrointestinal tract of humans and animals, causing host gastroenteritis and typhoid fever. Heat shock protein (HtpG) as a molecular chaperone is involved in the various cellular processes of bacteria, especially under environmental stress. However, the potential association of HtpG with S. Typhimurium infection remains unknown. In this study, we clarified that HtpG could also play a role as an effector in S. Typhimurium infection. RNA-seq indicated that the flagellar assembly pathway, infection pathway, and chemotaxis pathway genes of S. Typhimurium were downregulated after the mutation of HtpG, which resulted in compromises of S. Typhimurium motility, biofilm formation, adhesion, invasion, and inflammation-inducing ability. In addition, HtpG recombinant protein was capable of promoting the proliferation of S. Typhimurium in host cells and the resultant inflammation. Collectively, our results illustrated an important role of HtpG in S. Typhimurium infection.
Administration of Adenosine Triphosphate Provides Additional Value Over Programmed Electrophysiologic Study in Confirmation of Successful Ablation of Atrioventricular Accessory Pathways
Authors: Wei Wei , Fang Xianhong , Shehata Michael , Wang Xunzhang , Zhan Xianzhang , Deng Hai , Liao Hongtao , Liao Zili , Liu Yang , Xue Yumei , Wu Shulin
Published: November 2021

Objectives: To study the benefit of adenosine triphosphate (ATP) in evaluating ablation endpoints of accessory pathways (AP) and subsequent long-term prognosis.

Methods: We reviewed consecutive patients with supraventricular tachycardias due to APs that underwent radiofrequency catheter ablation (RFCA) from January 2016 to September 2018 in our center. The patients were divided into two groups: the ATP group (who had passed both the ATP test and PES after ablation as the endpoint) and the non-ATP group (who had passed PES only after ablation as the endpoint). We reviewed the patients' intra-cardiac electrograms and analyzed their long-term outcomes.

Results: In total, 1,343 patients underwent successful RFCA. There were 215 patients in the ATP group with one lost to follow-up. There were 1,128 patients in the non-ATP group with 39 lost to follow-up. Twenty-three patients in the ATP group demonstrated additional electrophysiological entities due to ATP administration, including reappearance of the ablated APs in 16 patients, discovery of PES-undetected APs in 5, induction of atrial fibrillation in 5, premature atrial contractions in 1, and premature ventricular contractions in another. During the 7 to 39 months (average 24.4 ± 9.5 months) follow-up, the recurrence rate was 8.41% (18/214) in the ATP group and 6.80% (74/1,084) in the non-ATP group. In subjects with recurrence, 14 patients (14/18 = 77.8%) in the ATP group and 50 patients (50/74 = 67.6%) in the non-ATP group accepted redo ablations. Among the ATP-group, all the 14 redo APs were the old ones as before. Among the non-ATP-group, redo ablations confirmed that 39 APs were the old ones, while 20 APs were newly detected ones which had been missed previously. The difference in recurrent AP locations confirmed by redo procedures between the two groups was significant (p = 0.008). In the non-ATP group, 20 (40%) of redo cases were proven to have multiple APs, while 33 (3.3%) cases who did not suffer from recurrence had multiple APs. Existences of multiple APs in recurred cases were significantly higher than that in non-recurred ones in the non-ATP group (p < 0.001), while there was no such difference in the ATP group (p = 0.114).

Conclusions: The existence of multiple APs was more common in recurrent cases if ATP was not used for confirmation of ablation endpoints. ATP probably has additional value over PES alone by detecting weak AP conductions. ATP can evoke atrial and ventricular arrhythmias.
Anticoagulation Control in Different Ethnic Groups Receiving Vitamin K Antagonist for Stroke Prevention in Atrial Fibrillation
Authors: Zawawi Nur Azyyati , Abdul Halim Zaki Izzati , Ming Long Chiau , Goh Hui Poh , Zulkifly Hanis Hanum
Published: November 2021

Vitamin K antagonist such as warfarin reduces the risk of stroke in atrial fibrillation (AF) patients. Since warfarin has a narrow therapeutic index, its administration needs to be regularly monitored to avoid any adverse clinical outcomes such as stroke and bleeding. The quality of anticoagulation control with warfarin therapy can be measured by using time in therapeutic range (TTR). This review focuses on the prevalence of AF, quality of anticoagulation control (TTR) and adverse clinical outcome in AF patients within different ethnic groups receiving warfarin therapy for stroke prevention. A literature search was conducted in Embase and PubMed using keywords of “prevalence,” “atrial fibrillation,” “stroke prevention,” “oral anticoagulants,” “warfarin,” “ethnicities,” “race” “time in therapeutic range,” “adverse clinical outcome,” “stroke, bleeding.” Articles published by 1st February 2020 were included. Forty-one studies were included in the final review consisting of AF prevalence (n = 14 studies), time in therapeutic range (n = 18 studies), adverse clinical outcome (n = 9 studies) within different ethnic groups. Findings indicate that higher prevalence of AF but better anticoagulation control among the Whites as compared to other ethnicities. Of note, non-whites had higher risk of strokes and bleeding outcomes while on warfarin therapy. Addressing disparities in prevention and healthcare resource allocation could potentially improve AF-related outcomes in minorities.
The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels
Authors: Zhang Ren
Published: November 2021

Elevated triglyceride (TG) and reduced high-density lipoprotein-cholesterol (HDL-C) plasma levels are risk factors for atherosclerosis and cardiovascular disease. Therefore, a drug that simultaneously reduces TG and increases HDL-C plasma levels has the potential to prevent and treat these diseases. Angiopoietin-like 3 (ANGPTL3) regulates plasma TG and HDL-C levels by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL), respectively. ANGPTL3 inhibition of LPL requires complex formation with ANGPTL8, which is not required for its inhibition of EL. Therefore, the entire pool of plasma ANGPTL3 can be classified as ANGPTL8-associated ANGPTL3 and ANGPTL8-free ANGPTL3, where the former inhibits LPL and the latter inhibits EL. ANGPTL8 antibodies or inhibitors that block its interactions with ANGPTL3 can disrupt or preclude the ANGPTL3-8 complex formation, resulting in fewer ANGPTL3-8 complexes (reduced LPL inhibition), but more free ANGPTL3 (enhanced EL inhibition). Therefore, ANGPTL8 antagonism increases LPL activity while decreasing EL activity, thus leading to reduced plasma TG while simultaneously increasing HDL-C levels. In humans, carriers of ANGPTL8 truncating variants consistently have lower TG but higher HDL-C levels, supporting this hypothesis.
Projected Changes in Precipitation Extremes Over Jiulongjiang River Basin in Coastal Southeast China
Authors: Li Chang , Dike Victor Nnamdi , Lin Zhaohui , Gao Xuejie
Published: November 2021

The southeast coastal region of China is susceptible to challenges related to extreme precipitation events; hence, projection of future climate extremes changes is crucial for sustainable development in the region. Using the Regional Climate Model Version 4 (RegCM4), the future changes of summer precipitation extremes have been investigated over the Jiulongjiang River Basin (JRB), a coastal watershed in Southeast China. Comparison between the RegCM4 simulated and observed rainy season precipitation over JRB suggests that the RegCM4 can reasonably reproduce the seasonal precipitation cycle, the frequency distribution of precipitation intensity, and the 50-year return levels of precipitation extremes over JRB. Furthermore, the model projects an increase in daily maximum rainfall (RX1day) mostly over the northern part of the basin and a decrease over other parts of the basin, while projecting a widespread decrease for maximum consecutive 5-day precipitation amount (RX5day) relative to the present day. In terms of the 50-year return level of RX1day (RL50yr_RX1day), a general increase is projected over most parts of the basin in the near and far future of the 21st century, but a decrease can be found in the northeast and southwest parts of the JRB in the mid-21st century. The future change of the 50-year return level of RX5day (RL50yr_RX5day) shows a similar spatial pattern with that of RL50yr_RX1day in the near and mid-21st century, but with a larger magnitude. However, a remarkable decrease in RL50yr_RX5day is found in the south basin in the far future. Meanwhile, the projected changes in the 50-year return level for both RX1day and RX5day differ between the first and second rainy seasons in JRB. Specifically, the future increase in RL50yr_RX5day over the north basin is mainly contributed by the changes during the first-half rainy season, while the decrease of RL50yr_RX5day in the south is mostly ascribed to the future changes during the second-half rainy season. All above results indicate that the future changes of precipitation extremes in JRB are complicated, which might differ from extreme indices, seasons, and future projected periods. These will thus be of practical significance for flood risk management, mitigation, and adaptation measures in Jiulongjiang River Basin.
Study on Blasting Technology for Open-Pit Layering of Complex Mine Adjacent to High and Steep Slope
Authors: Wang Menglai , Li Xiaoshaung , Li Qihang , Hu Yunjin , Chen Qiusong , Jiang Song
Published: November 2021

In China, mining blasting vibration has seriously threatened the safety and stability of high and steep rock slopes. In this paper, taking the east mining area of Jianshan Phosphorus Mine as the research background, combined with field survey, field blasting test, numerical simulation and theoretical analysis, we systematically studied the adjacent high-steep rock slope and the layered blasting technology of complex ore. Based on wide hole spacing blasting numerical simulation and field tests, the use of 8 × 4 m hole network parameters, oblique line hole-by-hole initiation method, detonator delay using 35 ms between holes, 65 ms between rows and 500 ms within the holes, the rock mass rate was reduced and the drilling workload was decreased. In addition, regression analysis was carried out on a large amount of vibration test data, and the attenuation law and propagation law of blasting vibration of adjacent high and steep slopes were predicted, which provided a reference for mine production blasting. By establishing a mathematical model of cumulative damage of rock mass blasting, it shows that the depth of impact of mining blasting on the slope of Jianshan open-pit was 0–3.6m, but the blasting did not cause overall damage to the adjacent high and steep slopes. In the future, this model can be used to predict rock damage caused by subsequent blasting.
A Sediment Magnetic Record in the North Pacific Across the Mid-Pleistocene Transition and its Implication on Asian Dust Evolution
Authors: Shin Ji Young , Hyeong Kiseong , Kim Wonnyon
Published: November 2021

Eolian dust deposited in the North Pacific is an important archive of the evolutionary history of Asian interior source regions and climate system. Here, we present a ∼1 Myr sediment magnetic record from the central North Pacific to characterize eolian dust properties since the middle Pleistocene. For the studied sediments, magnetic components are mainly identified as biogenic magnetite and detrital magnetic minerals (dust and volcanic origins) based on coercivity analysis, microscopic observations, and sedimentological information. The detrital magnetic component is characterized by high coercivity (>100 mT) and shows a long-term increase in concentration since ∼1 Ma. In particular, the concentration shows a considerable increase at ∼0.8–0.7 Ma compared to the inorganic silicate fraction, indicative of magnetic mineral enrichment in detrital sediment fraction. At the same time, the coercivity distribution of the detrital component also decreases, which can be attributed to an increase in the ferrimagnetic mineral contribution. As the detrital sediments are primarily wind-blown particles, such ferrimagnetic enrichment implies a change in dust source materials after ∼0.8 Ma, which could be explained by the reorganization of atmospheric circulation and/or regional aridification in source regions across the mid-Pleistocene transition. The dust property change in source areas is likely to be synchronized across the North Pacific based on the similarity of the long-term trend of magnetic signals.
Substrate Treatment Evaluation and Their Impact on Printing Results for Wearable Electronics
Authors: Khan Saleem , Ali Shawkat , Khan Arshad , Wang Bo , Al-Ansari Tareq , Bermak Amine
Published: November 2021

This paper presents a comparative study on the treatment techniques for flexible polymeric substrates and their impact on the printing results. Substrate treatments are central to optimization of the printing processes and a strict set of requirements are needed to achieve uniform and acceptable printing results. Therefore, this research is highlighting the most significant treatment methods used for fine-tuning the surface properties of different polymeric substrates. Besides the two commonly used treatment techniques of oxygen plasma and ultraviolet ozone, a new method of using surface cleaning liquid is applied for rapid treatment of polymeric substrates. Comparative study is carried out on the basis of cleaning steps required for substrate preparation, processing, robustness as well as on the final printed results on the substrates. All the three treatment techniques with similar processing protocol are applied on a single type of polyimide (PI) substrate. To further validate the applicability and manufacture of practical devices, the liquid cleaning method is also applied on Polyethylene terephthalate substrates for making proof-of-concept wearable temperature sensor. From the study it is concluded that the liquid surface cleaning method is advantageous in terms of easy processing, robustness and producing uniform printing results on diverse polymeric substrates.
24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency
Authors: Turcu Adina F. , Mallappa Ashwini , Nella Aikaterini A. , Chen Xuan , Zhao Lili , Nanba Aya T. , Byrd James Brian , Auchus Richard J. , Merke Deborah P.
Published: November 2021

Background

Optimal management of androgen excess in 21-hydroxylase deficiency (21OHD) remains challenging. 11-oxygenated-C19 steroids (11-oxyandrogens) have emerged as promising biomarkers of disease control, but data regarding their response to treatment are lacking.

Objective

To compare the dynamic response of a broad set of steroids to both conventional oral glucocorticoids (OG) and circadian cortisol replacement via continuous subcutaneous hydrocortisone infusion (CSHI) in patients with 21OHD based on 24-hour serial sampling.

Participants and Methods

We studied 8 adults (5 women), ages 19-43 years, with poorly controlled classic 21OHD who participated in a single-center open-label phase I–II study comparing OG with CSHI. We used mass spectrometry to measure 15 steroids (including 11-oxyandrogens and Δ5 steroid sulfates) in serum samples obtained every 2 h for 24 h after 3 months of stable OG, and 6 months into ongoing CSHI.

Results

In response to OG therapy, androstenedione, testosterone (T), and their four 11-oxyandrogen metabolites:11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone (11KT) demonstrated a delayed decline in serum concentrations, and they achieved a nadir between 0100-0300. Unlike DHEAS, which had little diurnal variation, pregnenolone sulfate (PregS) and 17-hydoxypregnenolone sulfate peaked in early morning and declined progressively throughout the day. CSHI dampened the early ACTH and androgen rise, allowing the ACTH-driven adrenal steroids to return closer to baseline before mid-day. 11KT concentrations displayed the most consistent difference between OG and CSHI across all time segments. While T was lowered by CSHI as compared with OG in women, T increased in men, suggesting an improvement of the testicular function in parallel with 21OHD control in men.

Conclusion

11-oxyandrogens and PregS could serve as biomarkers of disease control in 21OHD. The development of normative data for these promising novel biomarkers must consider their diurnal variability.
Utility of Three Adiposity Indices for Identifying Left Ventricular Hypertrophy and Geometric Remodeling in Chinese Children
Authors: Wang Huan , Zhao Min , Magnussen Costan G. , Xi Bo
Published: November 2021

Background

Previous studies have shown that waist-to-height ratio (WHtR) performed similarly well when compared to body mass index (BMI) and waist circumference (WC) for identifying cardiovascular risk factors. However, to our knowledge, the performance of these three adiposity indices for identifying left ventricular hypertrophy (LVH) and left ventricular geometric (LVG) remodeling in youth has not been assessed. We aimed to determine the utility of BMI, WC and WHtR for identifying LVH and LVG in Chinese children.

Methods

This study included 1,492 Chinese children aged 6-11 years. Adiposity indices assessed were BMI, WC and WHtR. LVH and high relative wall thickness (RWT) were defined using sex- and age-specific 90th percentile values of left ventricular mass index and RWT, respectively, based on the current population. LVG remodeling included concentric remodeling (CR), eccentric hypertrophy (EH) and concentric hypertrophy (CH), which was defined based on the combination of LVH and high RWT.

Results

The magnitude of association of central obesity defined by WHtR with LVH [odds ratio (OR) =10.09, 95% confidence interval (CI) =6.66-15.29] was similar with general obesity defined by BMI (OR=10.49, 95% CI=6.97-15.80), and both were higher than central obesity defined by WC (OR=6.87, 95% CI=4.57-10.33). Compared with BMI, WHtR had better or similar predictive utility for identifying LVH, EH, and CH [the area under the curve (AUC): 0.84 vs. 0.79; 0.84 vs. 0.77; 0.87 vs. 0.88, respectively]; WC had worse or similar discriminatory utility with AUCs of 0.73, 0.70, 0.83, respectively.

Conclusion

WHtR performed similarly or better than BMI or WC for identifying LVH and LVG remodeling among Chinese children. WHtR provides a simple and convenient measure of central obesity that might improve the discrimination of children with cardiac structural damage.
On the Road Without a Map: Why We Need an “Ethic of Road Ecology”
Authors: Moore Lauren J. , Arietta A. Z. Andis , Spencer Daniel T. , Huijser Marcel P. , Walder Bethanie L. , Abra Fernanda D.
Published: November 2021

Over the past two decades, our knowledge of the ecological impacts of roads has increased rapidly. It is now clear that the environmental effects of transportation infrastructure are inextricable from transportation benefits to economic, social, and cultural values. Despite the necessity of optimizing these multiple values, road planners, scientists, and practitioners have no established methodology or pluralistic approach to address growing ethical complexities. We articulate five ethical issues that could be addressed by developing an ethic of road ecology in order to facilitate the identification, reasoning, and harmonization of ethical dimensions of road planning and development. This inquiry into road ecology can draw lessons from existing applied ethics, such as in ecological restoration and urban planning, to build a narrative that is informed by both science and ethics. We illustrate five ethical issues presented through case studies that elaborate on the motivations, responsibilities, and duties that should be considered in ethically and scientifically complicated road building decisions. To address these issues, we encourage the development of a code of ethics, dedicated intellectual forums, and practical guidance to assist road planners, and more broadly transportation practitioners, to resolve complex ethical quandaries systematically. We hope this perspective encourages conversation for a holistic yet pragmatic approach to this applied ethics problem, while also assisting responsible parties as they navigate difficult moral terrain.
Epstein–Barr Virus+ B Cells in Breast Cancer Immune Response: A Case Report
Authors: Aran Andrea , Peg Vicente , Rabanal Rosa Maria , Bernadó Cristina , Zamora Esther , Molina Elisa , Arribas Yago A. , Arribas Joaquín , Pérez José , Roura-Mir Carme , Carrascal Montserrat , Cortés Javier , Martí Mercè
Published: November 2021

EBV-specific T cells have been recently described to be involved in fatal encephalitis and myocarditis in cancer patients after immune checkpoint therapies. Here, we report the study of a human triple-negative breast cancer tumor (TNBC) and EBV-transformed B cells obtained from a patient-derived xenograft (PDX) that progressed into a lymphocytic neoplasm named xenograft-associated B-cell lymphoma (XABCL). T-cell receptor (TCR) high-throughput sequencing was performed to monitor the T-cell clonotypes present in the different samples. Forty-three T-cell clonotypes were found infiltrating the XABCL tissue after three passes in mice along 6 months. Eighteen of these (42%) were also found in the TNBC biopsy. TCR infiltrating the XABCL tissue showed a very restricted T-cell repertoire as compared with the biopsy-infiltrating T cells. Consequently, T cells derived from the TNBC biopsy were expanded in the presence of the B-cell line obtained from the XABCL (XABCL-LCL), after which the TCR repertoire obtained was again very restricted, i.e., only certain clonotypes were selected by the B cells. A number of these TCRs had previously been reported as sequences involved in infection, cancer, and/or autoimmunity. We then analyzed the immunopeptidome from the XABCL-LCL, to identify putative B-cell-associated peptides that might have been expanding these T cells. The HLA class I and class II-associated peptides from XABCL-LCL were then compared with published repertoires from LCL of different HLA typing. Proteins from the antigen processing and presentation pathway remained significantly enriched in the XABCL-LCL repertoire. Interestingly, some class II-presented peptides were derived from cancer-related proteins. These results suggest that bystander tumor-infiltrating EBV+ B cells acting as APC may be able to interact with tumor-infiltrating T cells and influence the TCR repertoire in the tumor site.
Type 1 Innate Lymphoid Cells Limit the Antitumoral Immune Response
Authors: Vienne Margaux , Etiennot Marion , Escalière Bertrand , Galluso Justine , Spinelli Lionel , Guia Sophie , Fenis Aurore , Vivier Eric , Kerdiles Yann M.
Published: November 2021

Natural killer (NK) cells are known to be able to kill established tumor cell lines, but important caveats remain regarding their roles in the detection and elimination of developing primary tumors. Using a genetic model of selective ILC1 and NK cell deficiency, we showed that these cells were dispensable for tumor immunosurveillance and immunoediting in the MCA-induced carcinogenesis model. However, we were able to generate primary cell lines derived from MCA-induced tumors with graded sensitivity to NK1.1+ cells (including NK cells and ILC1). This differential sensitivity was associated neither with a modulation of intratumoral NK cell frequency, nor the capacity of tumor cells to activate NK cells. Instead, ILC1 infiltration into the tumor was found to be a critical determinant of NK1.1+ cell-dependent tumor growth. Finally, bulk tumor RNAseq analysis identified a gene expression signature associated with tumor sensitivity to NK1.1+ cells. ILC1 therefore appear to play an active role in inhibiting the antitumoral immune response, prompting to evaluate the differential tumor infiltration of ILC1 and NK cells in patients to optimize the harnessing of immunity in cancer therapies.
Impact of Patient Age on Clinical Efficacy and Toxicity of Checkpoint Inhibitor Therapy
Authors: Wong Selina K. , Nebhan Caroline A. , Johnson Douglas B.
Published: November 2021

The addition of immune checkpoint inhibitors (ICIs) to the therapeutic armamentarium for solid malignancies has resulted in unprecedented improvements in patient outcomes in many cancers. The landscape of ICIs continues to evolve with novel approaches such as dual immune checkpoint blockade and combination therapies with other anticancer agents including cytotoxic chemotherapies and/or antiangiogenics. However, there is significant heterogeneity seen in antitumor responses, with certain patients deriving durable benefit, others experiencing initial benefit followed by acquired resistance necessitating change in therapy, and still others who are primarily refractory to ICIs. While generally better tolerated than traditional cytotoxic chemotherapy, ICIs are associated with unique toxicities, termed immune-related adverse events (irAEs), which can be severe or even lethal. As a disease of aging, older individuals make up a large proportion of patients diagnosed with cancer, yet this population is often underrepresented in clinical trials. Because ICIs indirectly target malignant cells through T cell activation, it has been hypothesized that age-related changes to the immune system may impact the efficacy and toxicity of these drugs. In this review, we discuss differences in the clinical efficacy and toxicity of ICIs in patients at the extremes of age.
Sediment Resuspension and Associated Extracellular Enzyme Activities Measured ex situ: A Mechanism for Benthic-Pelagic Coupling in the Deep Gulf of Mexico
Authors: Ziervogel Kai , Sweet Julia , Juhl Andrew R. , Passow Uta
Published: November 2021

Sediment resuspension caused by near-bed currents mediates exchange processes between the seafloor and the overlying water column, known as benthic-pelagic coupling. To investigate the effects of sediment resuspension on microbial enzyme activities in bottom waters (<500 m), we conducted onboard erosion experiments using sediment cores taken with a multi-corer from six deep-sea sites in the northern Gulf of Mexico. We then incubated the core-top water with resuspended sediments in roller tanks to simulate bottom water conditions following sediment resuspension. Bacterial cell abundance, particulate organic matter content, and potential rates of three hydrolytic enzymes (leucine aminopeptidases – PEP; β-glucosidases – GLU, lipases – LIP) were monitored during the experimentally-generated erosion events and subsequently in the roller tanks to examine whether resuspension of deep-sea sediments enhances activities of extracellular enzymes in overlying waters. Surficial sediments were resuspended at critical shear stress velocities between 1.4 and 1.7 cm s–1, which parallel bottom water currents of 28 and 34 cm s–1. Only one of our nine cores resisted experimentally generated bottom shear stresses and remained undisturbed, possibly as a result of oil residues from natural hydrocarbon seeps at the investigated site. The most notable enzymatic responses to sediment resuspension were found for LIP activities that increased in overlying waters of all eight of our resuspended cores and remained at high levels during the roller tank incubations. PEP and GLU showed orders of magnitude lower rates and more variable responses to experimentally resuspended sediments compared with LIP. We also found a disconnect between enzyme activities and bacterial cell numbers, indicating a major role of extracellular enzymes physically disconnected from microbial cells in our experiments. Our results demonstrate that sediment resuspension may promote organic matter breakdown in bottom waters by supplying extracellular enzymes without requiring a bacterial growth response. The marked increase in LIP activity suggests that resuspended enzymes may affect the degradation of petroleum hydrocarbons, including those from the natural seeps that are abundant in the investigation area.
Wind Waves in the Mediterranean Sea: An ERA5 Reanalysis Wind-Based Climatology
Authors: Barbariol Francesco , Davison Silvio , Falcieri Francesco Marcello , Ferretti Rossella , Ricchi Antonio , Sclavo Mauro , Benetazzo Alvise
Published: November 2021

A climatology of the wind waves in the Mediterranean Sea is presented. The climate patterns, their spatio-temporal variability and change are based on a 40-year (1980–2019) wave hindcast, obtained by combining the ERA5 reanalysis wind forcing with the state-of-the-art WAVEWATCH III spectral wave model and verified against satellite altimetry. Results are presented for the typical (50th percentile) and extreme (99th percentile) significant wave height and, for the first time at the regional Mediterranean Sea scale, for the typical and extreme expected maximum individual wave height of sea states. The climate variability of wind waves is evaluated at seasonal scale by proposing and adopting a definition of seasons for the Mediterranean Sea states that is based on the satellite altimetry wave observations of stormy (winter) and calm (summer) months. The results, initially presented for the four seasons and then for winter and summer only, show the regions of the basin where largest waves occur and those with the largest temporal variability. A possible relationship with the atmospheric parameter anomalies and with teleconnection patterns (through climate indices) that motivates such variability is investigated, with results suggesting that the Scandinavian index variability is the most correlated to the Mediterranean Sea wind-wave variability, especially for typical winter sea states. Finally, a trend analysis shows that the Mediterranean Sea typical and extreme significant and maximum individual wave heights are decreasing during summer and increasing during winter.
Fabrication and Mechanical Performance of Graphene Nanoplatelet/Glass Fiber Reinforced Polymer Hybrid Composites
Authors: Yao Xudan , Kinloch Ian A. , Bissett Mark A.
Published: November 2021

Glass fiber reinforced polymer (GFRP) composites are promising alternatives for the traditional carbon steel pipes used in the oil and gas industry due to their corrosion and chemical resistance. However, the out-of-plane mechanical properties of GFRPs still need further improvement to achieve this goal. Hence, in this work, two methods combining either vacuum mixing or spray coating with vacuum-assisted resin infusion were studied to fabricate graphene nanoplatelet (GNP)/GFRP hybrid composites. The former method resulted in a severe filtering effect, where the GNPs were not evenly distributed throughout the final composite, whereas the latter process resulted in a uniform GNP distribution on the glass fabrics. The addition of GNPs showed no modest contribution to the tensile performance of the GFRP composites due to the relatively high volume and in-plane alignment of the glass fibers. However, the GNPs did improve the flexural properties of GFRP with an optimal loading of 0.15 wt% GNPs, resulting in flexural strength and modulus increases of 6.8 and 1.6%, respectively. This work indicates how GNPs can be advantageous for out-of-plane mechanical reinforcement in fiber-reinforced composites.
Psoriasis to Psoriatic Arthritis: The Application of Proteomics Technologies
Authors: Qi Fei , Tan Yaqi , Yao Amin , Yang Xutong , He Yanling
Published: November 2021

Psoriatic disease (PsD) is a spectrum of diseases that affect both skin [cutaneous psoriasis (PsC)] and musculoskeletal features [psoriatic arthritis (PsA)]. A considerable number of patients with PsC have asymptomatic synovio-entheseal inflammations, and approximately one-third of those eventually progress to PsA with an enigmatic mechanism. Published studies have shown that early interventions to the very early-stage PsA would effectively prevent substantial bone destructions or deformities, suggesting an unmet goal for exploring early PsA biomarkers. The emergence of proteomics technologies brings a complete view of all involved proteins in PsA transitions, offers a unique chance to map all potential peptides, and allows a direct head-to-head comparison of interaction pathways in PsC and PsA. This review summarized the latest development of proteomics technologies, highlighted its application in PsA biomarker discovery, and discussed the possible clinical detectable PsA risk factors in patients with PsC.
Bibliometric Analysis and Systematic Review of Global Coronavirus Research Trends Before COVID-19: Prospects and Implications for COVID-19 Research
Authors: Yan Peijing , Li Meixuan , Li Jing , Lu Zhenxing , Hui Xu , Bai Yuping , Xun Yangqin , Lao Yongfeng , Wang Shizhong , Yang Kehu
Published: November 2021

Coronaviruses (CoV) cause respiratory and intestinal infections. We conducted this bibliometric analysis and systematical review to explore the CoV-related research trends from before COVID-19. We systematically searched the Ovid MEDLINE, Ovid Embase, and Web of Science (WOS) databases for published bibliometric analyses of CoV from database inception to January 24, 2021. The WOS Collection was searched from inception to January 31, 2020, to acquire the CoV-related publications before COVID-19. One-Way ANOVA and Bonferroni multiple-comparison tests were used to compare differences. Visualization mapping and keyword cluster graphs were made to illustrate the research topics and hotpots. We included 14,141 CoV-related publications for the bibliometric analysis and 16 (12 articles) CoV-related bibliometric analyses for the systematic review. Both the systematic review and bibliometric analysis showed (1) the number of publications showed two steep upward trajectories in 2003–2004 and in 2012–2014; (2) the research hotpots mainly focused on the mechanism, pathology, epidemiology, clinical diagnosis, and treatment of the coronavirus in MERS-CoV and SARS-Cov; (3) the USA, and China; the University of Hong Kong; and Yuen KY, came from the University of Hong Kong contributed most; (4) the Journal of Virology had the largest number of CoV related studies. More studies should focus on prevention, diagnosis, and treatment in the future.