bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of lncRNA and mRNA Expression Profile in Relapsed Graves’ Disease
Authors: Yao Qiuming , Song Zhenyu , Wang Bin , Jia Xi , Song Ronghua , Zhang Jinan
Published: December 2021

Background: Graves’ disease (GD) is a common autoimmune disease, and its pathogenesis is unclear. Studies have found that the occurrence of GD is related to the immune disorder caused by the interaction of genetic susceptibility and environmental factors. The CD4+ T cell subset is closely related to the immune disorder of GD. LncRNAs are RNA molecules with a length of more than 200 nt and are involved in a variety of autoimmune diseases. However, the roles of lncRNAs in recurrent GD are still elusive. The purpose of this study is to identify lncRNA and mRNA expression profile in relapsed Graves’ disease.

Method: CD4+ T cells from 12 recurrent GD and 8 healthy controls were collected for high-throughput sequencing. The gene-weighted co-expression network analysis (WGCNA) was used to construct the co-expression module relevant to recurrent GD, and the key genes in the module were verified by RT-PCR.

Results: There are 602 upregulated lncRNAs and 734 downregulated lncRNAs in CD4+ T cells in recurrent GD patients compared with the healthy controls. The module most relevant to GD recurrence was constructed using WGCNA, and the key genes in the module were verified by RT-PCR. We found that the expression of RPL8, OAS2, NFAT5, DROSHA, NONHSAT093153.2, NONHSAT118924.2, and NONHSAT209004.1 was significantly decreased in GD group (p < 0.001, p < 0.001, p < 0.01, p < 0.05, p < 0.001, p < 0.05, and p < 0.01, respectively).

Conclusion: LncRNAs are closely related to the recurrence of GD. For the first time, we constructed the expression profile of lncRNAs and mRNAs in CD4+ T cells in recurrent GD patients.
Phospholipid Profiles for Phenotypic Characterization of Adipose-Derived Multipotent Mesenchymal Stromal Cells
Authors: Burk Janina , Melzer Michaela , Hagen Alina , Lips Katrin Susanne , Trinkaus Katja , Nimptsch Ariane , Leopold Jenny
Published: December 2021

Multipotent mesenchymal stromal cells (MSC) have emerged as therapeutic tools for a wide range of pathological conditions. Yet, the still existing deficits regarding MSC phenotype characterization and the resulting heterogeneity of MSC used in different preclinical and clinical studies hamper the translational success. In search for novel MSC characterization approaches to complement the traditional trilineage differentiation and immunophenotyping assays reliably across species and culture conditions, this study explored the applicability of lipid phenotyping for MSC characterization and discrimination. Human peripheral blood mononuclear cells (PBMC), human fibroblasts, and human and equine adipose-derived MSC were used to compare different mesodermal cell types and MSC from different species. For MSC, cells cultured in different conditions, including medium supplementation with either fetal bovine serum or platelet lysate as well as culture on collagen-coated dishes, were additionally investigated. After cell harvest, lipids were extracted by chloroform/methanol according to Bligh and Dyer. The lipid profiles were analysed by an untargeted approach using liquid chromatography coupled to mass spectrometry (LC-MS) with a reversed phase column and an ion trap mass spectrometer. In all samples, phospholipids and sphingomyelins were found, while other lipids were not detected with the current approach. The phospholipids included different species of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) in all cell types, whereas phosphatidylglycerol (PG) species were only present in MSC. MSC from both species showed a higher phospholipid species diversity than PBMC and fibroblasts. Few differences were found between MSC from different culture conditions, except that human MSC cultured with platelet lysate exhibited a unique phenotype in that they exclusively featured PE O-40:4, PG 38:6 and PG 40:6. In search for specific and inclusive candidate MSC lipid markers, we identified PE O-36:3 and PG 40:7 as potentially suitable markers across culture conditions, at which PE O-36:3 might even be used across species. On that basis, phospholipid phenotyping is a highly promising approach for MSC characterization, which might condone some heterogeneity within the MSC while still achieving a clear discrimination even from fibroblasts. Particularly the presence or absence of PG might emerge as a decisive criterion for future MSC characterization.
Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice
Authors: Li Yuanyuan , Mei Ning-Hua , Cheng Gui-Ping , Yang Jing , Zhou Li-Quan
Published: December 2021

Mitochondrion plays an indispensable role during preimplantation embryo development. Dynamic-related protein 1 (DRP1) is critical for mitochondrial fission and controls oocyte maturation. However, its role in preimplantation embryo development is still lacking. In this study, we demonstrate that inhibition of DRP1 activity by mitochondrial division inhibitor-1, a small molecule reported to specifically inhibit DRP1 activity, can cause severe developmental arrest of preimplantation embryos in a dose-dependent manner in mice. Meanwhile, DRP1 inhibition resulted in mitochondrial dysfunction including decreased mitochondrial activity, loss of mitochondrial membrane potential, reduced mitochondrial copy number and inadequate ATP by disrupting both expression and activity of DRP1 and mitochondrial complex assembly, leading to excessive ROS production, severe DNA damage and cell cycle arrest at 2-cell embryo stage. Furthermore, reduced transcriptional and translational activity and altered histone modifications in DRP1-inhibited embryos contributed to impeded zygotic genome activation, which prevented early embryos from efficient development beyond 2-cell embryo stage. These results show that DRP1 inhibition has potential cytotoxic effects on mammalian reproduction, and DRP1 inhibitor should be used with caution when it is applied to treat diseases. Additionally, this study improves our understanding of the crosstalk between mitochondrial metabolism and zygotic genome activation.
Mass Integration for Rigorous Process Modelling: A Sequential Approach for Direct Recycling
Authors: Marchione Filippo , Hungerbuehler Konrad , Papadokonstantakis Stavros
Published: December 2021

Mass integration has been used for reducing the amount of process waste and environmental impact. Despite its long history, new challenges constantly arise with the use of process simulation tools offering platforms for rigorous process models. Therefore, the typical mass integration framework requires modifications to accurately account for the process performance. In this work, a novel sequential methodology is presented to realize a recycle network with rigorous process models. Initially, under the hypothesis of constant compositions of the process sources, an optimal ranking of the process sinks is determined. The optimal recycling network thus obtained is then used for a sequential methodology considering rigorous process models. The violations of process constraints are handled at each sequential step through the concept of “tightening constant”. The application of the sequential methodology to two case studies proves its ability to provide good approximations of the global optima with low computational effort.
Novel Pyrazine-Bridged D-A-D Type Charge Neutral Probe for Membrane Permeable Long-Term Live Cell Imaging
Authors: Liu Pei , Chen Suna , Zhao Wenxuan , Wang Qiutang , Wu Shuqi , Xu Liang , Bai Dan
Published: December 2021

A novel donor–acceptor–donor (D-A-D) type compound containing pyrazine as the acceptor and triphenylamine as the donor has been designed and synthesized. The photophysical properties and biocompatibility of this probe, namely (OMeTPA)2-Pyr for live cell imaging were systematically investigated, with observed large Stokes shifts, high photostability, and low cytotoxicity. Furthermore, we demonstrated that (OMeTPA)2-Pyr could permeate live cell membranes for labeling. The proposed mechanism of this probe was the binding and shafting through membrane integral transport proteins by electrostatic and hydrophobic interactions. These salient and novel findings can facilitate the strategic design of new pyrazine-fused charge-neutral molecular platforms as fluorescent probes, for long-term in situ dynamic monitoring in live cells.
The Role of Chaperone-Mediated Autophagy in Hepatitis C Virus-Induced Pathogenesis
Authors: Matsui Chieko , Yuliandari Putu , Deng Lin , Abe Takayuki , Shoji Ikuo
Published: December 2021

Lysosome incorporate and degrade proteins in a process known as autophagy. There are three types of autophagy; macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Although autophagy is considered a nonselective degradation process, CMA is known as a selective degradation pathway. All proteins internalized in the lysosome via CMA contain a pentapeptide KFERQ-motif, also known as a CMA-targeting motif, which is necessary for selectivity. CMA directly delivers a substrate protein into the lysosome lumen using the cytosolic chaperone HSC70 and the lysosomal receptor LAMP-2A for degradation. Hepatitis C virus (HCV) NS5A protein interacts with hepatocyte-nuclear factor 1α (HNF-1α) together with HSC70 and promotes the lysosomal degradation of HNF-1α via CMA, resulting in HCV-induced pathogenesis. HCV NS5A promotes recruitment of HSC70 to the substrate protein HNF-1α. HCV NS5A plays a crucial role in HCV-induced CMA. Further investigations of HCV NS5A-interacting proteins containing CMA-targeting motifs may help to elucidate HCV-induced pathogenesis.
A Workflow for Rapid Unbiased Quantification of Fibrillar Feature Alignment in Biological Images
Authors: Marcotti Stefania , Belo de Freitas Deandra , Troughton Lee D , Kenny Fiona N , Shaw Tanya J , Stramer Brian M , Oakes Patrick W
Published: December 2021

Measuring the organization of the cellular cytoskeleton and the surrounding extracellular matrix (ECM) is currently of wide interest as changes in both local and global alignment can highlight alterations in cellular functions and material properties of the extracellular environment. Different approaches have been developed to quantify these structures, typically based on fiber segmentation or on matrix representation and transformation of the image, each with its own advantages and disadvantages. Here we present AFT − Alignment by Fourier Transform, a workflow to quantify the alignment of fibrillar features in microscopy images exploiting 2D Fast Fourier Transforms (FFT). Using pre-existing datasets of cell and ECM images, we demonstrate our approach and compare and contrast this workflow with two other well-known ImageJ algorithms to quantify image feature alignment. These comparisons reveal that AFT has a number of advantages due to its grid-based FFT approach. 1) Flexibility in defining the window and neighborhood sizes allows for performing a parameter search to determine an optimal length scale to carry out alignment metrics. This approach can thus easily accommodate different image resolutions and biological systems. 2) The length scale of decay in alignment can be extracted by comparing neighborhood sizes, revealing the overall distance that features remain anisotropic. 3) The approach is ambivalent to the signal source, thus making it applicable for a wide range of imaging modalities and is dependent on fewer input parameters than segmentation methods. 4) Finally, compared to segmentation methods, this algorithm is computationally inexpensive, as high-resolution images can be evaluated in less than a second on a standard desktop computer. This makes it feasible to screen numerous experimental perturbations or examine large images over long length scales. Implementation is made available in both MATLAB and Python for wider accessibility, with example datasets for single images and batch processing. Additionally, we include an approach to automatically search parameters for optimum window and neighborhood sizes, as well as to measure the decay in alignment over progressively increasing length scales.
What Does Sleeping Brain Tell About Stress? A Pilot Functional Near-Infrared Spectroscopy Study Into Stress-Related Cortical Hemodynamic Features During Sleep
Authors: Liang Zilu
Published: December 2021

People with mental stress often experience disturbed sleep, suggesting stress-related abnormalities in brain activity during sleep. However, no study has looked at the physiological oscillations in brain hemodynamics during sleep in relation to stress. In this pilot study, we aimed to explore the relationships between bedtime stress and the hemodynamics in the prefrontal cortex during the first sleep cycle. We tracked the stress biomarkers, salivary cortisol, and secretory immunoglobulin A (sIgA) on a daily basis and utilized the days of lower levels of measured stress as natural controls to the days of higher levels of measured stress. Cortical hemodynamics was measured using a cutting-edge wearable functional near-infrared spectroscopy (fNIRS) system. Time-domain, frequency-domain features as well as nonlinear features were derived from the cleaned hemodynamic signals. We proposed an original ensemble algorithm to generate an average importance score for each feature based on the assessment of six statistical and machine learning techniques. With all channels counted in, the top five most referred feature types are Hurst exponent, mean, the ratio of the major/minor axis standard deviation of the Poincaré plot of the signal, statistical complexity, and crest factor. The left rostral prefrontal cortex (RLPFC) was the most relevant sub-region. Significantly strong correlations were found between the hemodynamic features derived at this sub-region and all three stress indicators. The dorsolateral prefrontal cortex (DLPFC) is also a relevant cortical area. The areas of mid-DLPFC and caudal-DLPFC both demonstrated significant and moderate association to all three stress indicators. No relevance was found in the ventrolateral prefrontal cortex. The preliminary results shed light on the possible role of the RLPCF, especially the left RLPCF, in processing stress during sleep. In addition, our findings echoed the previous stress studies conducted during wake time and provides supplementary evidence on the relevance of the dorsolateral prefrontal cortex in stress responses during sleep. This pilot study serves as a proof-of-concept for a new research paradigm to stress research and identified exciting opportunities for future studies.
Effect of NPC1L1 and HMGCR Genetic Variants With Premature Triple-Vessel Coronary Disease
Authors: Zhao Xueyan , Xu Jingjing , Tang Xiaofang , Huang Keyong , Li Jiawen , Liu Ru , Jiang Lin , Zhang Yin , Wang Dong , Sun Kai , Xu Bo , Zhao Wei , Hui Rutai , Gao Runlin , Song Lei , Yuan Jinqing
Published: December 2021

Background: Both Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) play a key role on dyslipidaemia. We aim to evaluate whether NPC1L1 and HMGCR genetic variants are associated with susceptibility of premature triple-vessel disease (PTVD).

Methods: Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, and rs2073547) of NPC1L1; and three SNPs (rs12916, rs2303151, and rs4629571) of HMGCR were genotyped in 872 PTVD patients (males ≤ 50 years old and females ≤ 60 years old), and 401 healthy controls.

Results: After adjusting for age and sex, rs12916 of HMGCR was associated with the risk of PTVD in dominance model [odds ratio (OR) = 1.68, 95% confidence intervals (CI): 1.29–2.18, P < 0.001], recessive model (OR = 1.43, 95% CI: 1.08–1.90, P = 0.013) and codominant model (OR = 1.38, 95% CI: 1.17–1.63, P < 0.001); meanwhile, rs4720470 of NPC1L1 was related to increased risk of PTVD in recessive model (OR = 1.74, 95% CI: 1.14–2.74, P = 0.013). Patients who carried both variant rs4720470 and rs12916 also had the risk of PTVD (P < 0.001); however, there were no correlation between these SNPs and the SNYTAX score (all P > 0.05).

Conclusions: This is the first report that rs4720470 is a novel polymorphism of the NPC1L1 gene associated with PTVD, and rs12916 of HMGCR gene appears to be a strong genetic marker of PTVD. Our study may improve the early warning, therapeutic strategies and drug development of PTVD.
Light Emitting Diodes Photobiomodulation Improves Cardiac Function by Promoting ATP Synthesis in Mice With Heart Failure
Authors: Zhang Wenwen , Gao Xinlu , Wang Xiuxiu , Li Desheng , Zhao Yiming , Zhang Tingting , Ne Jingwen , Xu Binbin , Li Shuainan , Jiang Zuke , Sun Hongyue , Ma Wenya , Yang Fan , Cai Benzhi , Yang Baofeng
Published: December 2021

Heart failure (HF) is the common consequences of various cardiovascular diseases, often leading to severe cardiac output deficits with a high morbidity and mortality. In recent years, light emitting diodes-based therapy (LEDT) has been widely used in multiple cardiac diseases, while its modulatory effects on cardiac function with HF still remain unclear. Therefore, the objective of this study was to investigate the effects of LED-Red irradiation on cardiac function in mice with HF and to reveal its mechanisms. In this study, we constructed a mouse model of HF. We found that LED-Red (630 nm) was an effective wavelength for the treatment of HF. Meanwhile, the application of LED-Red therapy to treat HF mice improved cardiac function, ameliorate heart morphology, reduced pulmonary edema, as well as inhibited collagen deposition. Moreover, LED-Red therapy attenuated the extent of perivascular fibrosis. Besides, LED-Red irradiation promoted calcium transients in cardiomyocytes as well as upregulated ATP synthesis, which may have positive implications for contractile function in mice with HF. Collectively, we identified that LED-Red exerts beneficial effects on cardiac function in HF mice possibly by promoting the synthesis of ATP.
Malnutrition and Frailty Are Critical Determinants of 6-Month Outcome in Hospitalized Elderly Patients With Heart Failure Harboring Surgically Untreated Functional Mitral Regurgitation
Authors: Miura Masakazu , Okuda Shinichi , Murata Kazuhiro , Nagai Hitoshi , Ueyama Takeshi , Nakao Fumiaki , Shimokawa Mototsugu , Yamamoto Takeshi , Ikeda Yasuhiro
Published: December 2021

Background: Hospitalized patients with acute decompensated heart failure (ADHF) frequently exhibit aggravating mitral regurgitation (MR). Those patients do not always undergo surgical mitral valve repair, but particularly in the elderly, they are often treated by conservative medical therapy. This study was aimed to investigate factors affecting 6-month outcomes in hospitalized patients with heart failure (HF) harboring surgically untreated MR.

Methods: We screened the presence of MR in hospitalized patients with HF between September 2017 and May 2020 in the Yamaguchi Prefectural Grand Medical (YPGM) center. At the time of discharge of these patients, individuals with surgically unoperated MR, including primary and secondary origin, were consequently recruited to this single-center prospective cohort study. The patients with severe MR who undergo surgical mitral valve treatment were not included in this study. The primary endpoint was all-cause readmission or all-cause death and the secondary endpoint was HF-related endpoint at 6 months after discharge. The Cox proportional hazard regression analyses were employed to assess the predictors for the composite endpoint.

Results: Overall, 489 patients with ADHF were admitted to the YPGM center. Of those, 146 patients (30% of total patients with HF) (median age 83.5 years, 69 men) were identified as harboring grade II MR or greater. Consequently, all the recruited patients were diagnosed as functional MR. During a median follow-up of 186.0 days, a total of 55 patients (38%) reached the primary or secondary endpoints (HF death and readmission in 31 patients, other in 24 patients). As a result of multivariate analysis, geriatric nutritional risk index [hazard ratio (HR) = 0.932; 95% CI = 0.887–0.979, p = 0.005], age (HR = 1.058; 95% CI = 1.006–1.112, p = 0.027), and left ventricular ejection fraction (HR = 0.971; 95% CI = 0.945–0.997, p = 0.030) were independent predictors of all-cause death or all-cause admission. Body mass index (HR = 0.793; 95% CI = 0.614–0.890, p = 0.001) and ischemic heart disease etiology (HR = 2.732; 95% CI = 1.056–7.067, p = 0.038) were also independent predictors of the HF-related endpoints.

Conclusion: Malnutrition and underweight were substantial predictors of adverse outcomes in elderly patients with HF harboring surgically untreated moderate-to-severe functional MR.
Spermidine Affects Cardiac Function in Heart Failure Mice by Influencing the Gut Microbiota and Cardiac Galectin-3
Authors: Chen Yufeng , Guo Zhiqin , Li Shaonan , Liu Zhen , Chen Pingan
Published: December 2021

Spermidine, which can be synthesized by the gut microbiota, can prevent cardiac hypertrophy and delay the progression to heart failure (HF). However, it is not clear whether the effect of spermidine on cardiac function is mediated by modulating the gut microbiota when HF occurs. Female HF Kunming mice induced by transverse aortic constriction were administered spermidine (HF+S group) or its antagonist (HF+SR group). Echocardiography, messenger ribonucleic acid (RNA) and protein expression of galectin-3 in the heart, cardiomyocyte apoptosis assays and gut microbiota analysis were detected. Left ventricular end-diastolic volume and diameter (LVVd and LVDd), and left ventricular end-systolic volume and diameter in the HF+SR group were significantly enlarged compared with those in the HF group (all P < 0.05). The HF+S group had a smaller LVDd and LVVd than the HF+SR group (5.01 ± 0.67 vs. 6.13 ± 0.45 mm, P = 0.033; 121.44 ± 38.74 vs. 189.94 ± 31.42 μL, P = 0.033). The messenger RNA and protein expression of galectin-3 and the number of apoptotic cardiomyocytes increased significantly in the HF+SR group compared to the HF group. Gut microbiota analysis showed that spermidine antagonists reduced the Firmicutes/Bacteroidetes ratio and changed the microbial community richness and diversity. In conclusion, spermidine can improve cardiac function in HF, and the regulation of gut microbiota and cardiac fibrosis may be a factor in the effect of spermidine on the improvement of cardiac function.
A Cloudier Picture of Ice-Albedo Feedback in CMIP6 Models
Authors: Sledd Anne , L’Ecuyer Tristan S.
Published: December 2021

Increased solar absorption is an important driver of Arctic Amplification, the interconnected set of processes and feedbacks by which Arctic temperatures respond more rapidly than global temperatures to climate forcing. The amount of sunlight absorbed in the Arctic is strongly modulated by seasonal ice and snow cover. Sea ice declines and shorter periods of seasonal snow cover in recent decades have increased solar absorption, amplifying local warming relative to the planet as a whole. However, this Arctic albedo feedback would be substantially larger in the absence of the ubiquitous cloud cover that exists throughout the region. Clouds have been observed to mask the effects of reduced surface albedo and slow the emergence of secular trends in net solar absorption. Applying analogous metrics to several models from the 6thClimate Model Intercomparison Project (CMIP6), we find that ambiguity in the influence of clouds on predicted Arctic solar absorption trends has increased relative to the previous generation of climate models despite better agreement with the observed albedo sensitivity to sea ice variations. Arctic albedo responses to sea ice loss are stronger in CMIP6 than in CMIP5 in all summer months. This agrees better with observations, but models still slightly underestimate albedo sensitivity to sea ice changes relative to observations. Never-the-less, nearly all CMIP6 models predict that the Arctic is now absorbing more solar radiation than at the start of the century, consistent with recent observations. In fact, many CMIP6 models simulate trends that are too strong relative to internal variability, and spread in predicted Arctic albedo changes has increased since CMIP5. This increased uncertainty can be traced to increased ambiguity in how clouds influence natural and forced variations in Arctic solar absorption. While nearly all CMIP5 models agreed with observations that clouds delay the emergence of forced trends, about half of CMIP6 models suggest that clouds accelerate their emergence from natural variability. Isolating atmospheric contributions to total Arctic reflection suggests that this diverging behavior may be linked to stronger Arctic cloud feedbacks in the latest generation of climate models.
Internal Structure Characteristics and Formation Mechanism of Reverse Fault in the Carbonate Rock, A Case Study of Outcrops in Xike’er Area, Tarim Basin, Northwest China
Authors: Geng Feng , Wang Haixue , Hao Jianlong , Gao Pengbo
Published: December 2021

China’s Paleozoic deep carbonate effective reservoirs, mainly non-porous reservoirs, are generally formed under the interaction of late diagenesis, hydrothermal fluids, and structural fractures. Faults and their deformation mechanism and internal structure of fault zones play an important role in the formation of carbonate reservoirs and hydrocarbon accumulation. Based on the detailed analysis of outcrop data in Xike’er area, Tarim Basin, this paper systematically studies the deformation mechanism and internal structure of reverse fault in the carbonate rock, and discusses the reservoir characteristics, control factors and development rules. The study shows that the deformation mechanism of the fault in carbonate rocks is faulting and fracturing, and the dual structure of fault core and damage zone is developed. The fault core is mainly composed of fault breccia, fault gouge and calcite zone, and a large number of fractures are formed in the damage zone, which are cemented by calcite locally. The mineral composition and rare earth element tests show that the fault core has the dual effect of hydrothermal fluids and atmospheric fresh water, which is easy to be cemented by calcite; while the damage zone is dominated by atmospheric fresh water, which is a favorable zone for the development of fracture-vuggy reservoirs. Therefore, the damage zone is the “sweet spot” area of carbonate oil and gas enrichment, and generally shows strip distribution along the fault.
Ovarian Endometrioma Negatively Impacts Oocyte Quality and Quantity But Not Pregnancy Outcomes in Women Undergoing IVF/ICSI Treatment: A Retrospective Cohort Study
Authors: Wu Yaoqiu , Yang Rong , Lan Jie , Lin Haiyan , Jiao Xuedan , Zhang Qingxue
Published: December 2021

Purpose

To determine the impact of ovarian endometrioma per se on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes.

Methods

This retrospective study was conducted using two groups. The endometrioma group consisted of 862 women with infertility who had ovarian endometriomas and underwent their first ovarian stimulation for IVF/ICSI treatment between January 2011 to December 2019 at a public university hospital. A non-endometrioma comparison group, comprising 862 women with other infertility factors, was matched according to maternal age, body mass index (BMI), and infertility duration. Ovarian reserve and response and IVF/ICSI and pregnancy outcomes between the two groups were analyzed. Multivariate logistic regression (MLR) analysis was conducted on the basis of clinical covariates assessed for their association with live birth.

Results

The results showed that significantly lower antral follicle count (AFC), anti-Müllerian hormone (AMH), ovarian sensitivity index (OSI), oocyte maturation and fertilization rates, blastocyst rate, number of oocytes retrieved, and available embryos were found in women with endometrioma compared with the control, respectively (P < 0.05). The cumulative live birth rate per patient in women with endometrioma was lower than that of women without endometrioma (39.32% vs. 46.87%, P = 0.002). In women with endometrioma, those who underwent surgical intervention prior to IVF/ICSI treatment had higher maturation (86.03% vs. 83.42%, P = 0.003), fertilization (78.16% vs. 74.93%, P = 0.004), and top-quality embryo rates (42.94% vs. 39.93%, P = 0.097) but had fewer oocytes retrieved (8.01 ± 5.70 vs. 9.12 ± 6.69, P = 0.013) than women without surgery. However, live birth rates were comparable between women with endometrioma and women in the control group, regardless of whether they had a prior history of ovarian surgery. MLR analysis showed no correlation between endometrioma per se and live birth after being adjusted for number of top-quality embryos transferred and stage of embryo transfer.

Conclusions

The data from this study supported the conclusion that ovarian endometrioma negatively impacts oocyte quality and quantity, but not overall pregnancy outcomes, in women undergoing IVF/ICSI treatment. Endometrioma lowers the cumulative live birth rate by decreasing the number of embryos. Surgical excision of endometrioma prior to IVF/ICSI can partly improve oocyte maturation and fertilization rates but not pregnancy outcomes.
Germline RET Leu56Met Variant Is Likely Not Causative of Multiple Endocrine Neoplasia Type 2
Authors: Hansen Anna Reimer , Borgwardt Line , Rasmussen Åse Krogh , Godballe Christian , Poulsen Morten Møller , Vieira Filipe G. , Mathiesen Jes Sloth , Rossing Maria
Published: December 2021

Activating variants in the receptor tyrosine kinase REarranged during Transfection (RET) cause multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominantly inherited cancer-susceptibility syndrome. The variant c.166C>A, p.Leu56Met in RET was recently reported in two patients with medullary thyroid cancer (MTC). The presence of a pheochromocytoma in one of the patients, suggested a possible pathogenic role of the variant in MEN 2A. Here, we present clinical follow up of a Danish RET Leu56Met cohort. Patients were evaluated for signs of MEN 2 according to a set of predefined criteria. None of the seven patients in our cohort exhibited evidence of MEN 2. Furthermore, we found the Leu56Met variant in our in-house diagnostic cohort with an allele frequency of 0.59%, suggesting that it is a common variant in the population. Additionally, none of the patients who harbored the allele were listed in the Danish MTC and MEN 2 registries. In conclusion, our findings do not support a pathogenic role of the Leu56Met variant in MEN 2.
Bone Turnover Markers in Response to Ultrasound-Guided Microwave Ablation for Primary Hyperparathyroidism
Authors: Ni Wenjing , Yuan Yue , Chu Xiaoqiu , Chen Guofang , Han Xue , Li Jie , Wu Xinping , Wang Jianhua , Liu Chao , Xu Shuhang
Published: December 2021

Objective

To assess the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperparathyroidism (PHPT), and to investigate whether MWA can improve the bone turnover and renal function.

Methods

A total of 20 consecutive PHPT patients with 21 parathyroid lesions treated with MWA in our center from May 2019 to March 2021 were recruited in this study. Serum parathyroid hormone (PTH), calcium and phosphorus levels before MWA and at 20 minutes, 4 hours, 1 day, 3 months, 6 months and 12 months after MWA were measured. Bone turnover biomarkers, renal function and lesion volume with volume reduction rate (VRR) before MWA and at the last follow-up were compared. Any complication related with MWA was evaluated. The technical and clinical success rates of MWA in the treatment of PHPT were calculated. Clinical success was defined as normal serum PTH and calcium without PHPT-associated manifestations at more than 6 months after ablation. Technical success was defined as complete ablation indicated by immediate postoperative contrast-enhanced ultrasound.

Results

The serum PTH, calcium and phosphorus levels at their respective follow-up time points dropped significantly after MWA (P <0.05). The volume of parathyroid lesions at the final examination was significantly reduced, compared with pre-ablation volume (P <0.001), with a median VRR reaching 89%. The technical and clinical success rates were 100% and 63.6%, respectively. Substantial changes of bone turnover biomarkers were observed before and after MWA (P <0.05), but the differences in renal function were not statistically significant. No major complications were reported in all cases. Pre-MWA serum PTH, lesion volume, maximum diameter of lesion and ablation time were significantly different between patients with successful and failed MWA.

Conclusions

PHPT can be effectively and safely treated by ultrasound-guided MWA, as proven by drop in serum PTH and reduction in the volume of parathyroid adenomas. Besides, MWA can impede bone remodeling to suppress hyperparathyroidism in the condition of PHPT.
Financialization of Water: Conceptual Analysis of the California Water Crisis
Authors: Orobello Christian , Cirella Giuseppe T.
Published: December 2021

Water is a rapidly shrinking commodity. As we continue to use water for industry, farming, and sustaining our own lives, we must realize its intrinsic value. In December of 2020, water was given a new value as a future on a commodities market. This paper aims to discuss the practical, ethical, and financial considerations of trading water in this manner. A thorough conceptual analysis of the literature and research from 2009 to 2020 related to commodities and their history was performed, and a more contemporary review of water policy and pricing. The goal is to develop a mixed solution that gives value to water without allowing it to be exploited to the detriment of the poor; water must be accessible and affordable if it is to be managed ethically. Approaching water as a high-value resource might create a market that makes it unobtainable for most of us; however, with a system that controls pricing, creates standards, and simultaneously works to increase the supply of water, we may be able to create a “market.” Our critique of the research and available solutions indicates rising water prices and mostly regressive policies. As a result, market controls need to be implemented to control pricing while ensuring water availability for all.
The Systematic Landscape of Nectin Family and Nectin-Like Molecules: Functions and Prognostic Value in Low Grade Glioma
Authors: Han Yunhe , Zou Cunyi , Zhu Chen , Liu Tianqi , Shen Shuai , Cheng Peng , Cheng Wen , Wu Anhua
Published: December 2021

Objective: Nectin and nectin-like molecules (Necls) are molecules that are involved in cell–cell adhesion and other vital cellular processes. This study aimed to determine the expression and prognostic value of nectin and Necls in low grade glioma (LGG).

Materials and Methods: Differentially expressed nectin and Necls in LGG samples and the relationship of nectin family and Necls expression with prognosis, clinicopathological parameters, and survival were explored using The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and Repository of Molecular Brain Neoplasia Data (REMBRANDT) databases. Univariate and multivariate Cox analysis models were performed to construct the prognosis-related gene signature. Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves and multivariate Cox regression analysis, were utilized to evaluate the prognostic capacity of the four-gene signature. Gene ontology (GO)enrichment analysis and Gene Set Enrichment Analyses (GSEA) were performed to further understand the underlying molecular mechanisms. The Tumor Immune Estimation Resource (TIMER) was used to explore the relationship between the four-gene signature and tumor immune infiltration.

Results: Several nectin and Necls were differentially expressed in LGG. Kaplan–Meier survival analyses and Univariate Cox regression showed patients with high expression of NECTIN2 and PVR and low expression of CADM2 and NECTIN1 had worse prognosis among TCGA, CGGA, and REMBRANDT database. Then, a novel four-gene signature was built for LGG prognosis prediction. ROC curves, KM survival analyses, and multivariate COX regression indicated the new signature was an independent prognostic indicator for overall survival. Finally, GSEA and GO enrichment analyses revealed that immune-related pathways participate in the molecular mechanisms. The risk score had a strong negative correlation with tumor purity and data of TIMER showed different immune cell proportions (macrophage and myeloid dendritic cell) between high- and low-risk groups. Additionally, signature scores were positively related to multiple immune-related biomarkers (IL 2, IL8 and IFNγ).

Conclusion: Our results offer an extensive analysis of nectin and Necls levels and a four-gene model for prognostic prediction in LGG, providing insights for further investigation of CADM2, NECTIN1/2, and PVR as potential clinical and immune targets in LGG.
Genomic Uniqueness of Local Sheep Breeds From Morocco
Authors: Ouhrouch Abdessamad , Boitard Simon , Boyer Frédéric , Servin Bertrand , Da Silva Anne , Pompanon François , Haddioui Abdelmajid , Benjelloun Badr
Published: December 2021

Sheep farming is a major source of meat in Morocco and plays a key role in the country’s agriculture. This study aims at characterizing the whole-genome diversity and demographic history of the main Moroccan sheep breeds, as well as to identify selection signatures within and between breeds. Whole genome data from 87 individuals representing the five predominant local breeds were used to estimate their level of neutral genetic diversity and to infer the variation of their effective population size over time. In addition, we used two methods to detect selection signatures: either for detecting selective sweeps within each breed separately or by detecting differentially selected regions by contrasting different breeds. We identified hundreds of genomic regions putatively under selection, which related to several biological terms involved in local adaptation or the expression of zootechnical performances such as Growth, UV protection, Cell maturation or Feeding behavior. The results of this study revealed selection signatures in genes that have an important role in traits of interest and increased our understanding of how genetic diversity is distributed in these local breeds. Thus, Moroccan local sheep breeds exhibit both a high genetic diversity and a large set of adaptive variations, and therefore, represent a valuable genetic resource for the conservation of sheep in the context of climate change.
A Novel Nine-Gene Signature Associated With Immune Infiltration for Predicting Prognosis in Hepatocellular Carcinoma
Authors: Liu Rongqiang , Jiang ZeKun , Kong Weihao , Zheng Shiyang , Dai Tianxing , Wang Guoying
Published: December 2021

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, and its prognosis remains unsatisfactory. The identification of new and effective markers is helpful for better predicting the prognosis of patients with HCC and for conducting individualized management. The oncogene Aurora kinase A (AURKA) is involved in a variety of tumors; however, its role in liver cancer is poorly understood. The aim of this study was to establish AURKA-related gene signatures for predicting the prognosis of patients with HCC.

Methods: We first analyzed the expression of AURKA in liver cancer and its prognostic significance in different data sets. Subsequently, we selected genes with prognostic value related to AURKA and constructed a gene signature based on them. The predictive ability of the gene signature was tested using the HCC cohort development and verification data sets. A nomogram was constructed by integrating the risk score and clinicopathological characteristics. Finally, the influence of the gene signature on the immune microenvironment in HCC was comprehensively analyzed.

Results: We found that AURKA was highly expressed in HCC, and it exhibited prognostic value. We selected eight AURKA-related genes with prognostic value through the protein-protein interaction network and successfully constructed a gene signature. The nine-gene signature could effectively stratify the risk of patients with HCC and demonstrated a good ability in predicting survival. The nomogram showed good discrimination and consistency of risk scores. In addition, the high-risk group showed a higher percentage of immune cell infiltration (i.e., macrophages, myeloid dendritic cells, neutrophils, and CD4+T cells). Moreover, the immune checkpoints SIGLEC15, TIGIT, CD274, HAVCR2, and PDCD1LG2 were also higher in the high-risk group versus the low-risk group.

Conclusions: This gene signature may be useful prognostic markers and therapeutic targets in patients with HCC.
Exome-Sequencing Identifies Novel Genes Associated with Recurrent Pregnancy Loss in a Chinese Cohort
Authors: Xiang Huifen , Wang Chunyan , Pan Hong , Hu Qian , Wang Ruyi , Xu Zuying , Li Tengyan , Su Yezhou , Ma Xu , Cao Yunxia , Wang Binbin
Published: December 2021

Recurrent pregnancy loss (RPL) is a common reproductive problem affecting around 5% of couples worldwide. At present, about half of RPL cases remained unexplained. Previous studies have suggested an important role for genetic determinants in the etiology of RPL. Here, we performed whole-exome sequencing (WES) analysis on 100 unrelated Han Chinese women with a history of two or more spontaneous abortions. We identified 6736 rare deleterious nonsynonymous variants across all patients. To focus on possible candidate genes, we generated a list of 95 highly relevant genes that were functionally associated with miscarriage according to human and mouse model studies, and found 35 heterozygous variants of 28 RPL-associated genes in 32 patients. Four genes (FOXA2, FGA, F13A1, and KHDC3L) were identified as being strong candidates. The FOXA2 nonsense variant was for the first time reported here in women with RPL. FOXA2 knockdown in HEK-293T cells significantly diminished the mRNA and protein expression levels of LIF, a pivotal factor for maternal receptivity and blastocyst implantation. The other genes, with 29 variants, were involved in angiogenesis, the immune response and inflammation, cell growth and proliferation, which are functionally important processes for implantation and pregnancy. Our study identified several potential causal genetic variants in women with RPL by WES, highlighting the important role of genes controlling coagulation, confirming the pathogenic role of KHDC3L and identifying FOXA2 as a newly identified causal gene in women with RPL.
Identification of Two Immune Related Genes Correlated With Aberrant Methylations as Prognosis Signatures for Renal Clear Cell Carcinoma
Authors: Yao Zhi-Yong , Xing Chaoqung , Liu Yuan-Wu , Xing Xiao-Liang
Published: December 2021

Almost 75% of renal cancers are renal clear cell carcinomas (KIRC). Accumulative evidence indicates that epigenetic dysregulations are closely related to the development of KIRC. Cancer immunotherapy is an effective treatment for cancers. The aim of this study was to identify immune-related differentially expressed genes (IR-DEGs) associated with aberrant methylations and construct a risk assessment model using these IR-DEGs to predict the prognosis of KIRC. Two IR-DEGs (SLC11A1 and TNFSF14) were identified by differential expression, correlation analysis, and Cox regression analysis, and risk assessment models were established. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.6907. In addition, we found that risk scores were significantly associated with 31 immune cells and factors. Our present study not only shows that two IR-DEGs can be used as prognosis signatures for KIRC, but also provides a strategy for the screening of suitable prognosis signatures associated with aberrant methylation in other cancers.
Pan-Cancer Analysis of the Solute Carrier Family 39 Genes in Relation to Oncogenic, Immune Infiltrating, and Therapeutic Targets
Authors: Qu Yi-Yuan , Guo Rong-Yan , Luo Meng-Ling , Zhou Quan
Published: December 2021

Background: Emerging pieces of evidence demonstrated that the solute carrier family 39 (SLC39A) members are critical for the oncogenic and immune infiltrating targets in multiple types of tumors. However, the precise relationship between the SLC39A family genes and clinical prognosis as well as the pan-cancer tumor cell infiltration has not been fully elucidated.

Methods: In this study, the pan-cancer expression profile, genetic mutation, prognostic effect, functional enrichment, immune infiltrating, and potential therapeutic targets of the SLC39A family members were investigated by analyzing multiple public databases such as the Oncomine, TIMER, GEPIA, cBioPortal, KM-plotter, PrognoScan, GeneMANIA, STRING, DAVID, TIMER 2.0, and CellMiner databases.

Results: The expression levels of most SLC39 family genes in the tumor tissues were found to be significantly upregulated compared to the normal group. In mutation analysis, the mutation frequencies of SLC39A4 and SLC39A1 were found to be higher among all the members (6 and 4%, respectively). Moreover, the overall mutation frequency of the SLC39A family genes ranged from 0.8 to 6% pan-cancer. Also, the function of the SLC39A highly related genes was found to be enriched in functions such as zinc II ion transport across the membrane, steroid hormone biosynthesis, and chemical carcinogenesis. In immune infiltration analysis, the expression level of the SLC39A family genes was found to be notably related to the immune infiltration levels of six types of immune cells in specific types of tumors. In addition, the SLC39A family genes were significantly related to the sensitivity or resistance of 63 antitumor drugs in a variety of tumor cell lines.

Conclusion: These results indicate that the SLC39 family genes are significant for determining cancer progression, immune infiltration, and drug sensitivity in multiple cancers. This study, therefore, provides novel insights into the pan-cancer potential targets of the SLC39 family genes.