bluuebunny/crossref_metadata_2025 huggingface dataset:
Returning to the Simplest Way: Clinical Results of Patients Undergoing Ivf in Natural Vs Modified Natural Cycles
Authors: Lopez Enrique Garcia , Calzada Alfonso Bermejo de la , Cabada Nereida Galajares , Martin Barbara Castro
Published: February 2022

Background
In recent years, natural cycle IVF has been undergoing a revival, gaining recognition as a safer, cheaper, and more comfortable option for patients. we define natural cicle IVF as the treatment in which oocytes are obtained from a spontaneous ovulatory cycle. When oral drugs are used (usually clomiphene citrate or letrozole), the process is referred to as modified natural cycle IVF. The aim of this study is to clarify whether the introduction of oral medication is beneficial for patients.
Methods
We retrospectively analysed all natural or modified IVF treatments that took place in our clinic during the studied period (January 2016 - December 2020). Descriptive variables were analysed with a t-test, and a chi-square test was performed on result variables.
Results
We found significant differences in the number of oocytes obtained after oocyte retrieval was (1.03 vs 1.63, p<0.001), number of mature oocytes (0.9 vs 1.3, p < 0.01), fertilization rate (0.7 vs 1.1, p < 0.01), and number of embryos available for transfer (0.5 vs 0.7, p < 0.01).However, we did not found signficant differences in terms of pregnancy rate (26,3% vs 19,6%, p=0.251) or live birth rate (16.3% vs 14,3%, p=0.7806)
Conclusions
although the numbers of oocytes and embryos available were higher in the group that used oral medication (which is similar to that obtained in previous studies), we did not find any differences in success rates in terms of pregnancy or live birth rate. Adding oral medication to natural cycle IVF, although reducing cancellation rates, does not seem to have an impact on the clinical results of the cycle. More studies are necessary, but we could reconsider the need to add oral medication since they suppose a higher cost for the patient.
Detection of Lysosomal Acid Lipase Deficiency in Tertiary Referral Centres
Authors: Kwok See , Soran Handrean , Barr Marianne
Published: February 2022

BackgroundLysosomal acid lipase deficiency (LALD) is a rare autosomal recessive metabolic disorder. Mutations in the LIPA gene that encodes LAL result in disrupted triglyceride metabolism. Presentations and severity of the disorder are diverse and are often non-specific. Characterisations of LALD include dyslipidaemia and abnormal liver function which can overlap with conditions such as familial hypercholesterolaemia and non-alcoholic fatty liver disease (NAFLD). The rarity of LALD may mean that the condition is unrecognised or misdiagnosed. The development of effective enzyme replacement therapy for LALD has provided motivation for identifying the condition clinically. Diagnosis of LALD by genetic testing is costly. However the relatively inexpensive assay of LAL activity in dried blood spot (DBS) has made the diagnosis of LALD in clinical practice more available. We studied LALD screening in 3 cohorts: patients from hospital Lipid and Diabetes Clinics selected using the current recommended criteria,1 patients from hospital Liver Clinic who either had histological features in their liver biopsies that were consistent with LALD or who had diagnoses of non-alcoholic steatohepatitis (NASH), NAFLD or cryptogenic cirrhosis, and genetic testing for patients found to have reduced LAL activity to detect LALD carriers.MethodEligible patients were consented for LALD screening. A single sample of blood was obtained either from a finger prick or from a venous blood sample. The blood was transferred to a DBS filter paper for processing. LAL activity <0.03 nmol/punch/h was diagnostic of LALD.Patients with reduced LAL activity were offered genetic testing. Consenting patients gave a venous blood sample of 3ml.Results1730 patients were screened for LALD from 8 centres in the UK. None of the patients in the cohort tested positive for LALD. 27 patients consented to have genetic testing. No abnormalities were detected. 100 patients in the Liver cohort were screened for LALD and none was positive for LALD.ConclusionUsing the eligibility criteria we adopted, the detection rate of LALD was meagre. In our cohorts, we did not identify any patient with undiagnosed LALD in hospital Lipid, Diabetes or Liver clinics.
Prevalence of subclinical mastitis, its associated bacterial isolates and risk factors among cattle in Africa: a systematic review and meta-analysis
Authors: Khasapane Ntelekwane George , Thekisoe Oriel Moeti Molifi , Byaruhanga Charles , Khumalo Zamantungwa , Nkhebenyane Sebolelo Jane
Published: February 2022

Background: Subclinical mastitis (SCM) is one of the most economically important diseases affecting the dairy industry. The SCM does not cause visible changes in the udder or physical changes of the milk as compared to clinical mastitis, and a clear overview of the prevalence and risk factors in the different regions of Africa is still lacking. The objective of this study was to investigate the prevalence of SCM and assess the associated risk factors and dominant bacterial pathogens among cattle in Africa. Materials and methods: Using a systematic review and meta-analysis approach, we gathered literature concerning SCM among cattle in Africa, published from 2020 through 2021in five databases. Results: A total of 1,560 records were retrieved and at the end of the screening, 38 studies were eligible for inclusion in the meta-analysis. The random-effects meta-analysis model showed that the weighted pooled prevalence of SCM in cattle in Africa was 51.5% (95% CI: 44.0-58.9%). Heterogeneity was high and significant as I2 (proportion of observed variation) was 98.4% (95% CI: 97.6-99.0%), τ2 was 0.0533 (95% CI: 0.035-0.089), and the Cochran Q statistic was 2244.97 (p<0.0001). Sub-group and meta-regression analyses showed that West Africa had the highest point estimate (85.3%), followed by East Africa (64.1%), and the least was for southern Africa (16.3%) (p=0.007). Other significant moderators for SCM were age (p<0.0001), breed (p=0.015) and parity (p=0.0001) of cattle. Staphylococcus species were the most predominant pathogens, followed by Streptococcus and Escherichia spp. Conclusions: The present study showed a high variation of subclinical mastitis prevalence in various parts of Africa. There is a need for more data on subclinical mastitis in some regions on the continent. The information gathered in this paper may be used to guide a multidisciplinary approach to the management, control and reduction of this infection.
The long non-coding RNA ‘TRASH’ is essential for cell survival in MAPK-driven melanoma
Authors: Feichtenschlager Valentin , Chen Linan , Zheng Yixuan , Ho Wilson , Sanlorenzo Martina , Vujic Igor , Fewings Eleanor , Lee Albert , Chen Christopher , Lin Kevin , Callanan Ciara , Vujic Marin , Hwang Yeonjoo , Lai Kevin , Chen Stephanie , Nguyen Thuan , Muñoz Denise , Kohwi Yoshinori , Posch Christian , Daud Adil , Rappersberger Klemens , Kohwi-Shigematsu Terumi , Coppé Jean-Philippe , Ortiz-Urda Susana
Published: February 2022

MAPK-pathway up-regulation is responsible for over 40% of human cancer cases. Finding effective therapeutic targets for melanoma therapy continues to be a challenge due to drug resistance. Using a computational and experimental pipeline, we discovered the nuclear enriched long non-coding RNA (lncRNA) TRASH, which is induced upon MAPK-pathway-activation in melanoma. LncRNA hold essential regulatory functions in many cancer types. TRASH-targeting Antisense Oligonucleotides (TRASH-ASOs) greatly reduced cell-growth of melanoma cells in culture and systemic TRASH-ASO treatment significantly inhibited tumor growth of melanoma cell-line and patient-derived tumor xenografts without apparent side effects. We found that TRASH is essential for protein stability of the MAPK-pathway-regulating and apoptosis-inhibiting oncogene hnRNPA2/B1. TRASH knockdown induced apoptosis by down-regulating anti-apoptotic kinase activity and pro-survival signaling pathways. Compared to the well-studied oncogenic lncRNA MALAT1, the unique feature of TRASH is that it governs tumor cell-survival through maintaining activity of anti-apoptotic kinases and pro-survival signaling pathways in melanoma cells. TRASH-ASO treatment can bypass MEK-inhibitor (MEKi) resistance, and unlike MEKi, it does not induce early-onset treatment resistance. Furthermore, TRASH-ASO and MEKi combinations confer synergistic effects in melanoma treatment. Our findings show that TRASH-ASO treatment presents promising features for long lasting RNA-targeting melanoma therapy.
New paleoclimatic evidence of an extraordinary rise in temperature in the Northern Hemisphere in the last 3-4 decades.
Authors: Ogurtsov Maxim
Published: February 2022

Prognosis of temperature changes in the Northern Hemisphere for the period 1980-2020 was made using four temperature paleoreconstructions covering the last 1-2 millennia and ending 1979-1993. A part of paleodata before 1860 (prior to the beginning of a noticeable anthropogenic impact) was used as an information bank. Forecasts were made using nonlinear prediction method which is based on the reconstruction of the trajectory of the predicted series dynamic system in a pseudo-phase space. In all four cases, the forecast gave either a decrease or a very slight increase in temperature during 1980-2020. Statistical experiments performed with using prediction errors have shown that a rise in temperature by 0.15-0.20°C degrees in the indicated epoch is not excluded, but its probability is low (P <0.15). This means that if the climate in the 20th - early 21st century was controlled by the same dynamic system as before 1860, the noticeable warming of the Northern Hemisphere in 1980-2020 should not be observed. While the actual rise of the recorded temperature is sharp and reaches 1.0°C. Such divergence indicates that the climate of the Northern Hemisphere in the last 30-40 years was significantly affected by an additional factor that did not act in the previous 1-2 millennia. The possible influence of the problem of divergence in tree-ring research on the result obtained is discussed.
Gene Network Inference from Single-Cell Omics Data and Domain Knowledge for Constructing COVID-19-Specific ICAM1-Associated Pathways
Authors: Odaka Mitsuhiro , Magnin Morgan , Inoue Katsumi
Published: February 2022

ICAM-1 is critical for interactions between cells. Previous studies have suggested that ICAM-1 triggers cell-to-cell transmission of HIV-1 or HTLV-1. SARS-CoV-2 shares several features with these viruses in interactions between cells, and SARS-CoV-2 cell-to-cell transmission is associated with COVID-19 severity. However, ICAM-1 and its associated pathways are not identified as essential factors in interactions between cells in COVID-19. For example, the current COVID-19 Disease Map has no entry for those pathways. Therefore, discovering unknown ICAM-1 pathways will be indispensable for clarifying the mechanism of COVID-19. This study builds ICAM1-associated pathways by gene network inference from single-cell omics data and multiple knowledge bases. First, data analyses extracted coexpressed genes with significant differences in expression levels with spurious correlations removed. Second, knowledge bases validate models. Finally, mapping the models onto existing pathways identifies new ICAM1-associated pathways. These pathways indicate that (1) upstream pathways include proteins in noncanonical NF-kappaB pathway and that (2) downstream pathways contain integrins and cytoskeleton or motor proteins for cell transformation. In this way, data-driven and knowledge-based approaches are integrated into gene network inference for ICAM1-associated pathway construction. The results can contribute to repairing and completing the COVID-19 Disease Map, thereby improving our understanding of the mechanisms of COVID-19.
A Radiometrically Dated Record of Antarctic Ice Sheet Response to Millennial-Scale Climate Cycles during Glacials and Interglacials
Authors: Piccione Gavin , Blackburn Terrence , Tulaczyk Slawek , Rasbury Troy , Hain Mathis , Ibarra Daniel , Methner Katharina , Tinglof Chloe , Cheney Brandon , Northrup Paul , Licht Kathy
Published: February 2022

Records of changing ice mass in offshore sediments and ice cores suggest that the West Antarctic ice sheet experienced millennial-scale ice loss during the last termination. However, the distal location and short temporal coverage of these records leads to uncertainty in both the spatial footprint of ice response, and whether this response persists outside of glacial terminations. Here we present a >100kyr archive of episodic Antarctic ice sheet basal melt events recorded by mineralogic variation in subglacial precipitates. 234U-230Th dates for two precipitates are used to build a time series of 32 opal-calcite transitions that correspond to Late Pleistocene millennial-scale climate cycles, with precipitation of opal during cold periods and calcite during warm periods. Geochemical data indicate that opal precipitation occurs via cryoconcentration of silica in brines beneath the ice sheet margin, while calcite precipitation is triggered by the addition of subglacial meltwater originating from the ice sheet interior. These freeze-flush cycles represent changes in subglacial hydrologic-connectivity driven by ice sheet velocity fluctuations, which likely occur in response to Southern Ocean thermal forcing acting on grounding lines within the Ross Embayment. Our results suggest that oscillating temperatures in the Southern Ocean affect the mass of the Antarctic ice sheet by regulating the delivery of heat to buttressing ice shelves and grounding lines on millennial timescales, regardless of the background climate state.
Numerical Study on Dynamic Response of RC Slabs Subjected to Cyclic Blast Loading
Authors: Wang Xinyu , Dong Bin , Gao Xicai , Hu Bin , Liang Yaozhe , Wang Junbo
Published: February 2022

Finite element (FE) model which can be used to investigate accumulated damage of the reinforced concrete (RC) slabs under cyclic blast loading is proposed. Firstly, accuracy of the FE model is verified through an experiment. Secondly, effects of the explosive inclination angle, standoff distance, and the explosive mass on the dynamic response of RC slabs are studied. At last, accumulated damage of the reinforced concrete (RC) slabs under cyclic blast loading is presented using the FE model. It is indicated that parameters of the explosive inclination angle, the scale distance, and the explosive mass have strong influences on the dynamic behavior of RC slabs. Under cyclic blast loading with small explosive charge, damage of the RC slab mainly appears in the first blast cycle. Displacement of the RC slab, axial force and strain of the rebars increase remarkably, which could be the mainly reason that damage evolution of the RC slab is not obvious, in the second blast cycle.
Parent training effects on emotion recognition in mothers rearing children with attention-deficit/hyperactivity disorder: A randomized controlled functional magnetic resonance imaging study
Authors: Makita Kai , Yao Akiko , Shimada Koji , Kasaba Ryoko , Fujisawa Takashi X , Mizuno Yoshifumi , Tomoda Akemi
Published: February 2022

This randomized controlled study aimed to examine neurological changes in socioemotional processing skills through parent training in caregivers of children with attention-deficit/hyperactivity disorder. Thirty mothers of children with ADHD were stratified into parental training and non-parental training groups. Functional magnetic resonance imaging was performed during the ‘Reading the Mind in the Eyes’ test, and parenting difficulties were evaluated using the Parenting Stress Index and Parenting Scale twice—before and after parental training. Parenting Stress Index and Parenting Scale scores significantly decreased after parental training. Activity in the left occipital fusiform gyrus increased during the task to estimate emotions from facial pictures, with decreased response time only seen after parental training. Therefore, brain activity changes and enhanced responses after parental training might reflect an increased sensitivity and responsivity to others’ mental state. The present results suggest that parental training promotes mothers’ understanding of problematic behavior in children with attention-deficit/hyperactivity disorder, which could help build a more nurturing environment, reduce parenting stress and a maladaptive parenting style, and improve the mother-child relationship.
Early Urine Infection Prediction Framework using XGBoost Ensemble Model in IoT-Fog Environment
Authors: Gupta Aditya , Singh Amritpal
Published: February 2022

Urine infections are one of the most prevalent concerns for the healthcare industry that may impair the functioning of the kidney and other renal organs. As a result, early diagnosis and treatment of such infections are essential to avert any future complications. Conspicuously, in the current work, an intelligent system for the early prediction of urine infections has been presented. The proposed framework uses IoTbased sensors for data collection, followed by data encoding and Infectious Risk Factor computation using the XGBoost algorithm over the fog computing platform. Finally, the analysis results along with the healthrelated information of users are stored in the cloud repository for future analysis. For performance validation, extensive experiments have been carried out and results are calculated based on real-time patients’ data. The statistical results of accuracy(91.45%), specificity(95.96%), sensitivity(84.79%), precision(95.49%), and f-score(90.12%) reveal the significantly improved performance of the proposed strategy over other baseline techniques.
A Heterogeneous Spatial Correlation Model for WSN Applications
Authors: kumar deo , kumar Sanjeet
Published: February 2022

In densely deployed Wireless Sensor Network, a large number of sensor nodes in an event area observes the event information and sends information to the sink. Due to physical properties related to sensed event, the sensor observations are highly spatially correlated with respect to location of sensor nodes. In this paper we have proposed a heterogeneous correlation model that exploits the spatial correlation between each sensor nodes. Heterogeneous WSNs consists of normal nodes and advance nodes with different sensing range. With the help of sensor coverage model and location of sensor nodes, heterogeneous correlation functions are derived to analyze the correlation characteristics of observed information’s by sensor nodes. The case studies using heterogeneous correlation functions are performed to study the spatial relationship among sensor nodes. Finally, a correlated clustering algorithm is proposed for efficient medium access and clustering protocol for heterogeneous WSNs.
TLR3 Gene Regulates Cataract-Related Mechanisms Through The Jagged-1/Notch Signaling Pathway
Authors: Chen Yu , Yang Rui
Published: February 2022

Objective: Epithelial-mesenchymal transition (EMT) is the main cause of organ fibrosis and a common pathogenesis of most cataracts. Therefore, TLR3 may play a vital role in the progress of PCO EMT. This study aims to explore the molecular mechanism of TLR3 in the occurrence and development of post-cataract EMT, and to provide new ideas for the prevention and treatment of posterior capsule opacification (PCO).Materials and Methods: The expression of TLR3 and EMT-related factors in samples from normal and PCO patients was measured by qPCR. In the presence or absence of TLR3, human lens epithelial cell line SRA01/04 are treated with TGF-β2. The CCK-8 method measures cell proliferation, and the Transwell method detects migration and invasion. The expression of EMT-related molecules and Jagged-1/Notch signaling pathway was analyzed by Western blot and qPC experiments.Result: In terms of mechanism, the functional gain and loss experiments of human LEC show that TLR3 regulates the proliferation, migration, invasion of LEC and EMT induced by TGF-β2 by targeting the Jagged-1/Notch signaling pathway to affect the development of fibrotic cataract.Conclusion: These findings indicate that TLR3 prevents the progression of lens fibrosis by targeting the Jagged-1/Notch signaling pathway to regulate LEC proliferation, migration, invasion and TGF-β2-induced EMT. "TLR3-Jagged-1/Notch" signal axis may be a therapeutic target for the treatment of fibrotic cataract.
Commensal Lactobacillus Suppress Colon Tumorigenesis and Progression by Modulation of Sphingosine 1-Phosphate Signaling in Mice
Authors: Xu Fuqiang , Li Qiaoqiao , Wang Shuyang , Dong Miaoyin , Xiao Guoqing , Bai Jin , Wang Junkai , Sun Xisi
Published: February 2022

Background: Gut microbiota and their secreted metabolites influence the initiation, progression, and treatment responsiveness of colon cancer. Microbiota-based therapy regulated by probiotics has been considered as an effective strategy for prevention and therapeutic of colon cancer, whereas the antitumor mechanisms influenced by microbiota and their metabolites with intervention of probiotic remain further investigated.Results: Here, we investigated the preventive and therapeutic efficiency of commensal Lactobacillus in subcutaneous tumor models, and the underlying antitumor mechanism through the alteration of gut microbiota and their metabolites regulated by commensal Lactobacillus. Interestingly, we found that tumor formation rate in subcutaneous tumor models reduced 86.21% and 82.76%, in comparison to tumor controls when administrated with living or inactivated Lactobacillus (JY300-8 and JMR-01) for 20 days in advance. Subsequently, continuously oral administration for living or inactivated commensal Lactobacillus suppressed significantly the growth of tumor, and the tumor volumes declined 65.2% and 61.18%, respectively. Furthermore, microbiome and metabolome analyses revealed that commensal Lactobacillus suppressed colon tumorigenesis and progression through the modulation of gut microbiota and metabolites which included the down-regulation of secondary bile acids, sphingosine 1-phosphate (S1P) signaling in cancer and pyrimidine metabolism, as well as the production of anticarcinogenic compounds in tumor-bearing mice. Particularly, limitation the effects of S1P signaling via the modulation of sphingosine expression using probiotics, exerted antitumor efficiency.Conclusions: The work indicated the feasibility of using an effectively safe strategy to prevent the occurrence of colon cancer, and provided a potential therapeutic target for new therapeutics strategy via altering S1P signaling in cancer.
Association between the ELAVL1 gene single nucleotide polymorphisms and the Genetic Susceptibility to cervical cancer by high resolution melting in a Tunisian population
Authors: Boudhiba Najet , Sfar Sana , Helaoui Ahlem , Hołysz Marcin , Iwańczyk-Skalska Ewa , Bouchahda Haifa , Jagodziński Paweł piotr , KENANI Abderraouf
Published: February 2022

Background: Human papillomavirus infection is the major cause of cervical cancer, but only few cases develop into cancer. Although, HuR (ELAVL1) gene has been implicated in the oncogenesis of certain cancers. However, the correlation between the ELAVL1 gene and the risk of cervical cancer in Tunisian women remains unclear. Therefore, this study investigated the effect of ELAVL1 gene polymorphisms (SNPs) in cervical cancer development.Method: ELAVL1 gene SNPs: ELAVL1 rs12983784 T>C, ELAVL1 rs14394 T>C, ELAVL1 rs74369359 G>T, ELAVL1 rs35986520 G>A, ELAVL1 rs10402477 C>T, ELAVL1 rs12985234 A>G, ELAVL1 rs2042920 T>G, were genotyped by High resolution melting (HRM). SHEsis online software was used to perform linkage disequilibrium (LD) and haplotype analyses. Results: Comparing the cervical cancer patients with healthy control participants, the TC genotype of rs12983784 SNP (P=0.017, OR = 2.78, 95% CI = 1.2~6.45), the GT genotype of the rs74369359 SNP (P=0.004, OR = 9.4, 95% CI = 1.73~16.96) and the CT genotype of the rs10402477 SNP (P=0.002, OR = 5.89, 95% CI = 1.89~18.36) were associated with increased cervical cancer risk. TT genotype of rs12983784 SNP (P=0.005), GG genotype of the rs74369359 SNP (P=0.000) and CC genotype of the rs10402477 SNP (P=0.000) were considered as protective factors against cervical cancer in the Tunisian population. The haplotype analysis of the 7 SNPs of ELAVL1 gene suggested that “C C G G C A G” (P=0.02), “T T G G T A T” (P=0.01) and “T T T G C A T” (P=0.002) were a significant risk factor for cervical cancer. However, “TCGACAT” (P=0.04) and “TTGGCAT” (P=0.04) participated in the decrease of cervical cancer disease.The frequency of ELAVL1 haplotype rs10402477-rs2042920 TT was significantly higher in the cases group than in the control group (P=0.0001).Thus, this genotype increases cervical cancer risk among Tunisian women. Conclusion: The results of our study indicated that genetic variants in the ELAVL1 gene might be associated with susceptibility to cervical cancer in the Tunisian population.
PCSK9 Promotes Endothelial Dysfunction in Sepsis via TLR4/MyD88/NF-κB and NLRP3 Pathways
Authors: Huang Longxiang , Li Yuanjing , Cheng Zhe , Lv Zi , Luo Suxin , Xia Yong
Published: February 2022

Endothelial dysfunction often accompanies sepsis. We aimed to explore the role of PCSK9 in septic endothelial dysfunction. Sepsis was induced by Lipopolysaccharide (LPS) treatment on human umbilical vein endothelial cells (HUVECs) in vitro and Cecal ligation and puncture (CLP) surgery mice in vivo. Evolocumab (EVC) and Pep 2-8, PCSK9 inhibitors, was subsequently used to determine the role of PCSK9 in septic endothelial dysfunction in vitro and in vivo, respectively. And TLR4 agonist, Kdo2-Lipid A ammonium (KLA), was used to determine the related mechanism. Expression of eNOS, VE-Cadherin, PCSK9, TLR4, MYD88, p-p65, p65, NLRP3, ASC and Caspase1 p20 in the aortas and HUVECs were measured by Western blot and mRNA expression of TNFα, IL-1 and IL-6 were determined by PCR. Nitric oxide (NO) content in the medium and cell viability were examined. Vasodilation function of the aorta was detected by vascular reactivity experiments. The 48-h survival rate after CLP was observed. The results demonstrated that the expression of eNOS and VE-Cadherin decreased and PCSK9 expression increased in septic HUVECs or mice. Nevertheless, inhibition of PCSK9 could improve the eNOS and VE-Cadherin expression. The activation of TLR4/MyD88/NF-κB and NLRP3 pathways should be responsible for the PCSK9-induced endothelial dysfunction in sepsis. Vascular reactivity test and survival study shows that inhibiting PCSK9 could prevent the decline of endothelium-dependent vasodilation function and improve the survival rates of septic mice. In summary, our results suggest that increased PCSK9 in sepsis activates the TLR4/MyD88/NF-κB and NLRP3 pathways to induce inflammation, which results in vascular endothelial dysfunction and decrease of survival rates. However, inhibition of PCSK9 could improve the vascular endothelial function in sepsis, which may be a potential way for clinical treatment.
Effect and Mechanism of LncRNA-PBC11 in Regulating EMT Progression of Prostate Cancer Cells
Authors: Cui Haoyu , Xie Xuefeng , Hou Chuansheng , Ma Qiang , Chen Zhuo
Published: February 2022

The invasion and metastasis of prostate cancer is the main reason for its poor prognosis. Up to now, ADT (androgen deprivation therapy, ADT), whether surgical or drug therapy, is the basic method for the treatment of prostate cancer. However, ADT therapy is generally not recommended for the clinical treatment of metastatic prostate cancer. EMT (epithelial-to-mesenchymal transition, EMT) of tumor cells is the internal driving factor of tumor invasion and metastasis. Therefore, in-depth study on the regulation mechanism of EMT in prostate cancer cells will help us develop the new prevention and treatment plan for prostate cancer. Here, we will demonstrate and elaborate an lncRNA-PBC11 closely related to EMT of prostate cancer cells. The research data show that the content of PBC11 in metastatic prostate tumors increases significantly compared to non-metastatic, and can competitively bind hsa-miR-137 with 3'UTR of Twist1 in the form of miRNA sponge, thereby weakening the antitumor activity of hsa-miR-137. Our functional experiments confirmed that PBC11 knockdown is an important means for the normal operation of EMT inhibitory pathway hsa-miR-137/Twist1 in prostate cancer cells, and PBC11 knockdown combined with hsa-miR-137 overexpression showed excellent resistance to EMT in prostate cancer cells induced by TGF-β1. In a word, our study shows that PBC11 up-regulates the expression of Twist1 protein by blocking hsa-miR-137/ Twist1 pathway and promotes the progress of EMT in prostate cancer cells, overexpression of PBC11 can effectively inhibit EMT in prostate cancer cells by restoring the negative regulation of Twist1 by hsa-miR-137.
Novel gene loci associated with susceptibility or cryptic quantitative resistance to Pyrenopeziza brassicae in Brassica napus
Authors: Fell Heather , Ali Ajisa Muthayil , Wells Rachel , Mitrousia Georgia K. , Woolfenden Hugh , Schoonbeek Henk-jan , Fitt Bruce D. L. , Ridout Christopher J. , Stotz Henrik
Published: February 2022

Quantitative disease resistance (QDR) can provide durable control of pathogens in crops in contrast to resistance (R) gene-mediated resistance which can break down due to pathogen evolution. QDR is therefore a desirable trait in crop improvement but little is known about the causative genes and so it is difficult to incorporate into breeding programmes. Light leaf spot, caused by Pyrenopeziza brassicae, is an important disease of oilseed rape (canola, Brassica napus). To identify new QDR gene loci, we used a high-throughput screening pathosystem with P. brassicae on 196 lines of B. napus combined with an association transcriptomics platform. We show that all resistance against P. brassicae was associated with QDR and not R gene-mediated. We used genome-wide association analysis with an improved B. napus population structure to reveal four gene loci significantly (P = 0.0001) associated with QDR in regions showing linkage disequilibrium. On chromosome A09, enhanced resistance was associated with heterozygosity for a cytochrome P450 gene co-localising with a previously-described locus for seed glucosinolate content. In addition, eight significant gene expression markers with a false discovery rate of 0.001 were associated with QDR against P. brassicae. For seven of these, expression was positively correlated with resistance whereas for one, a HXXXD-type acyl-transferase, negative correlation indicated a potential susceptibility gene. The study identifies novel QDR loci for susceptibility and resistance, including novel cryptic QDR genes associated with heterozygosity, that will inform future crop improvement.
Research advances in the diagnosis and treatment of Chiari malformations: a bibliometric analysis
Authors: Rangel India , Singh Rohin , McLelland Marissa D. , Dodd Armaan , Shlobin Nathan A. , Meyer Jenna H. , Hudson Miles , Gottfried Oren
Published: February 2022

Chiari malformation is a relatively rare condition involving herniation of the brain out of the skull and into the spinal canal. The purpose of this review was to identify top contributors to the world of Chiari research, as well as to highlight the publications which have shaped our perception of this condition.We performed a search of the Web of Science between the years 1900 and 2021 using the terms “Chiari I malformation”, “Arnold Chiari malformation”, “Chiari II malformation”, “Chiari malformation type 1”, and “Chiari malformation type 2”. After screening for duplicates and assessing for relevance using two independent reviewers, the top 100 most frequently cited articles were collected and sorted. These articles were published between the years 1938 and 2015 and were cited 145.7 times on average, ranging from 79 to 724 citations per article. Authored by Milhorat et al., the 1999 Neurosurgery article “Chiari I Malformation Redefined: Clinical and Radiographic Findings for 364 Symptomatic Patients” received most citations (724 citations). Journal of Neurosurgery contributed the most articles to the top-100 with 21 publications. The University of California system accounted for the most articles by institution (8 of 100) and the USA was the highest contributing country (62%). In this study, we identified and analyzed the most cited articles on Chiari malformations to gain a better understanding of the publications contributing our knowledge of this disorder. This analysis serves both as a way of gauging the current state of research and of recognizing gaps where further research is necessary.
Infective Endocarditis With Oral Bacteria: Association With Findings During Oral Infection Screening
Authors: Thoresen Therese , Jordal Stina , Lie Stein-Atle , Wünsche Friederike , Jacobsen Martha Rolland , Lund Bodil
Published: February 2022

Background: Oral streptococci represent the causing microorganism for infective endocarditis (IE) in many patients. The impact of oral infections is questioned, and it has been suggested that bacteraemia due to daily routines may play a bigger part in the aetiology of IE. The aim of this study was to examine the association between oral health and infective endocarditis caused by oral viridans streptococci. Methods: A retrospective study was conducted at Haukeland University Hospital (HUH) from 2006- 2015. All consecutive adult patients admitted to hospital for treatment of IE and subjected to an oral focus screening including orthopantomogram, were included. The clinical, radiological and laboratory characteristics of the patients, collected during oral infectious focus screening, were analysed. Patient survival was calculated using Kaplan-Meier and mortality rates were compared using Cox-regression. Results: A total of 208 patients were included, 77% (n=161) male patients and 23% (n=47) female, mean age was 58 years. A total of 67 (32%) had IE caused by viridans streptococci. No statistically significant correlation could be found between signs of oral infection and IE caused by viridans streptococci. The overall mortality at 30 days was 4.3 % (95% CI: 1.6-7.0). There was no statistical difference in mortality between IE caused by viridans streptococci or S. aureus (HRR=1.16, 95% CI: 0.57-2.37, p=0.680). Conclusion: The benefit of oral infection screening and elimination in patients admitted with IE seems uncertain. Based on this study it cannot be concluded that oral conditions and oral infection influence the overall mortality for patients with endocarditis.
LncRNA MIR181A2HG Negatively Regulates Human Keratinocytes Proliferation by Binding SRSF1
Authors: Fan Xiaomei , Yue Pengpeng , Li Mingzhao , Chen Fangru , Fang Jingxian , Deng Xueling , Liu Xiaoyu , Wei Zhida , Gan Shaoqin , Weng Chengke , Gao Jintao
Published: February 2022

Psoriasis is a common chronic inflammatory skin disease. Abnormal proliferation of keratinocytes plays an important role in the pathogenesis of psoriasis. Long non-coding RNAs (lncRNAs) are involved in the regulation of a variety of cell biological processes. The purpose of this study was to investigate the potential role of lncRNA MIR181A2HG in the proliferation of human keratinocytes. qRT-PCR was performed to measure the expression levels of MIR181A2HG, SRSF1, miR-181a, miR-181b, KRT6 and KRT6 in tissue specimens and cells. Cell Counting Kit-8 (CCK-8) was used to measure cell viability. RNA pulldown-mass spectrometry (MS) was applied to identify the proteins interacting with MIR181A2HG. RNA pulldown-Western blotting and RNA immunoprecipitation (RIP)-qRT-PCR were used to confirm the interaction between MIR181A2HG and SRSF1. In this study, we found MIR181A2HG was decreased in psoriatic lesions. Knockdown of MIR181A2HG promoted the proliferation of human keratinocytes, while overexpression of MIR181A2HG inhibited the proliferation of human keratinocytes. 356 proteins were identified to interact with MIR181A2HG potentially. SRSF1 was finally determined to interact with MIR181A2HG. In addition, silencing of SRSF1 inhibited keratinocytes proliferation, which could be reversed with knockdown of MIR181A2HG. In summary, MIR181A2HG negatively regulates keratinocytes proliferation by binding SRSF1, suggesting that MIR181A2HG and SRSF1 may serve as potential targets for the treatment of psoriasis.
Benefit of Adjuvant Radiotherapy for Gallbladder Cancer: A Comparability-Based Metaanalysis
Authors: Choi Seo Hee , RIM CHAI HONG , Shin In-Soo , Yoon Won Sup , Koom Woong Sub , Seong Jinsil
Published: February 2022

Background & purpose: The benefits of adjuvant radiotherapy (ART) in gallbladder cancer (GBC) treatment remain inconclusive owing to the rarity of GBC and lack of randomized studies.Methods: PubMed, Medline, Embase, and Cochrane Library were systematically searched until March 2021. The primary endpoint was overall survival (OS). Comparative clinical studies that reported survival outcomes in GBC patients treated with or without ART were included. The comparability of each study was assessed by considering all possible clinical indicators (group 2: ART arm with poor clinical profile; group 1: ART arm with statistically similar profile or no evidence of having inferior clinical factors compared to non-ART arm).Results: Twenty-one studies involving 6876 GBC patients were reviewed. In pooled analyses of OS, the odds ratio (OR) was 1.26 ( p =0.111). In subgroup analyses considering comparability, the OR significantly favored the ART arm (1.92, p =0.008) among comparability group 1 studies, whereas it was 1.03 ( p =0.865) in comparability group 2 studies. The pooled rate of 5-yr OS in the ART vs. non-ART arms was 44.9% vs. 20.9% in group 1 and 34.1% vs. 40.0% in group 2. With ART, significant reduction in locoregional recurrence (OR: 0.21, p =0.001) but not in distant metastasis (OR: 1.32, p =0.332) was noted.Conclusion: ART not only showed benefits in patients with a similar clinical profile to those treated without ART but also yielded comparable survival in patients with an inferior clinical profile. Our results strongly support the more active application of ART in GBC treatment.Protocol registration: This study is registered in PROSPERO (CRD4202124062, available at: https://www.crd.york.ac.uk/).
Post Treatment Mastalgia is a Common Complaint But Not an Indication of Recurrence
Authors: Komenaka Ian , Hsu Chiu-Hsieh , Ramos Gilbert , Nodora Jesse , Martinez Maria Elena
Published: February 2022

Purpose: Post-treatment mastalgia is a common complaint in up to 68% of patients after treatment. This symptom is worrisome to patients as many believe it is a sign of recurrence. The current study was performed to evaluate if post-treatment mastalgia is associated with breast cancer recurrence.Methods: Patients included were seen from January 1, 2000 to December 31, 2020. All patients who were treated for breast cancer and then presented with breast pain during follow up were considered to have post-treatment mastalgia. All patients who were diagnosed with a second breast cancer but did not experience post-treatment mastalagia were also evaluated.Results: 1799 patients had a mean age 52.9 years. 36% of patients experienced post-treatment mastalgia. Of patients who complained of post-treatment mastalgia, 19 were diagnosed with a chest wall recurrence (CW), ipsilateral breast tumor recurrence (IBTR), or contralateral breast cancer (CBC). 17 of the 19 patients had breast pain after the second diagnosis and treatment were completed. The average duration between their second diagnosis and initial complaint of breast pain was 6.2 years. The two patients who complained of breast pain prior to their second diagnosis did not have mastalgia at the time of their second diagnosis. Local recurrence or contralateral breast cancer were more common in patients without post treatment mastalgia (10.1% vs 0.3%, p < 0.0001) during follow up.Conclusions: Post treatment mastalgia is not associated with recurrence. Interval or repeat imaging does not appear necessary and instead patient education and reassurance are important in its management.
Circumscription and typification of sphagnicolous omphalinoid species of Arrhenia (Hygrophoraceae) in Newfoundland and Labrador: three obligate and one facultative species
Authors: Voitk Andrus , Saar Irja , Moncada Bibiana , Lickey Edgar B.
Published: February 2022

Molecular studies of sphagnicolous arrhenias in Newfoundland and Labrador created four clades in Arrhenia, three obligate sphagnophiles (two scaly-capped and one smooth-capped) and one facultative (smooth-capped). Nomenclatural review recovered 16 names applied to omphalinoid sphagnicolous taxa in the past. Critical review of these left five as suitable to this group. One scaly obligate sphagnophilic clade contained the type for Arr. gerardiana and the other the type for Clitocybe gerardiana var. fusca; the latter we introduce as the novel species Arr. bigelowii. It differed from the first by longer spores and a darkening reaction in 10% of collections. The smooth-capped third obligate sphagnophilic clade contained the types of Ag. telmatiaeus and Omphalina fusconigra; we recombined it as Arr. telmatiaea. This is the darkest species of the group, with a more northern distribution. The facultative sphagnophile was identified as Arr. philonotis, a lighter smooth-capped species also with a more northern distribution. In addition, we collected an unidentified smooth-capped facultatively sphagnophilic species of Omphalina of the O. pyxidata complex. All five species are distributed in both Europe and North America. We describe each species of Arrhenia with a sequenced type, providing new type material where needed, and add an informal description of the Omphalina. Overall, this study adds new sequences from 82 specimens of sphagnicolous arrhenias to the two existing in GenBank when we began, 11 new sequences of the unidentified species of Omphalina, and several other arrhenias.
Genetic Diversity and Relationships Among Nopalea sp. and Opuntia spp. Accessions Revealed by RAPD, ISSR and ITS Molecular Markers
Authors: Bezerra Janieire Dorlamis Cordeiro , de Andrade Alberício Pereira , Rêgo Mailson Monteiro do , Silva Divan Soares da , Júnior José Ribamar Silva do Nascimento , Araújo Fernando dos Santos , Valença Roberta de Lima , Rêgo Elizanilda Ramalho do , Pessoa Angela Maria dos Santos , Bruno Riselane de Lucena Alcântara , de Medeiros Ariosvaldo Nunes
Published: February 2022

Background
Dactylopius opuntiae (Cockerell) (carmine cochineal) is an insect pest highly noxious that has spread through cactus pear crops in the Brazilian semiarid region. Knowledge of diversity and genetic relationships of the cactus pear accessions is fundamental to create new varieties resistance to carmine cochineal. Therefore, this investigation was undertaken to assess the genetic diversity and genetic relationships that existed in between cactus pear (Nopalea sp. and Opuntia spp.) accessions with contrasting resistance to D. opuntiae.
Methods
We conducted a molecular analysis in seven cactus pear accessions from the “reference collection” of the Agronomic Institute of Pernambuco, Brazil using RAPD, ISSR and ITS molecular markers.
Results
A total of 242 bands were detected from 26 polymorphic primers. The high percentage of polymorphism by RAPD (89.8%), ISSR (81.2%) and ITS (75%) markers suggests that the cactus pear accessions have high genetic diversity. The combined analysis of markers enabled the accessions discrimination of about the genus and ploidy, but were incongruous in relation to resistance level to D. opuntiae.
Conclusions
The resistant accessions (IPA-200016, IPA-200149, IPA-100004, IPA-200205) are genetically divergent, therefore could be potentially incorporated into any further breeding programs directed to create new varieties of cactus pear resistant to D. opuntiae.
Extraction and preconcentration of parabens in liquid pharmaceutical samples by Dispersive Liquid-Liquid Microextraction based on deep eutectic solvent
Authors: sahebian SAMANEH , Razavi N. , Foroutan F. , Khaki J.Vahdati
Published: February 2022

In this paper dispersive liquid-liquid microextraction using deep eutectic solvent, as one of extraction solvent was considered for preconcentration and determination of parabens in liquid pharmaceutical samples. Deep eutectic solvent (DES) composed of choline chloride (ChCl) hydrogen bond acceptor) and hydrogen bond donor (glucose) was provided the highest extraction efficiency. Thermogravimetry analysis (TGA), X-ray diffraction and Fourier-transform infrared spectroscopy (FT-IR) were selected to prove that the synthesis of DES was done successfully. The Liquid chromatography with photodiode array detection (HPLC-DAD) was used for analysis of paraben species. Parameters affecting the extraction efficiency were studied and optimized through univariate analysis and experimental design. Under the optimal conditions (pH of aqueous solution: 4.5, ethanol as the disperser solvent, glucose DES as the extraction solvent) the linearity range of 0.1-5000 ng mL−1 was obtained with the coefficient of determination (R2) ranging in 0.993-0.9962. Limits of detection (LOD) ranged from 0.04 – 0.15 ng mL−1 with the relative standard deviations from 1.78–6.85%. The developed method was applied to determination of parabens in liquid pharmaceuticals such as ampule, syrups and nose drop samples. The relative recoveries in these real samples were in the range of 80.95-103.12%.
Toxoplasma Gondii Dense Granule Protein 3 Promotes Endoplasmic Reticulum Stress-Induced Apoptosis by Activating the PERK Pathway
Authors: Obed Cudjoe , Wu Minmin , Chen Ying , An Ran , Cai Haijian , Luo Qingli , Yu Li , Wang Jie , Liu Fang , Shen Jilong , Du Jian
Published: February 2022

Background
Toxoplasma gondii is a neurotropic single-celled parasite that can infect mammals and birds. Central nervous system infection with T. gondii infection can lead to Toxoplasma encephalitis. Toxoplasma infection can cause endoplasmic reticulum (ER) stress and unfolded protein response (UPR) activation, which ultimately can lead to apoptosis of host cells. The dense granule protein GRA3 has been identified as one of the secretory proteins that contribute to the virulence of T. gondii; however, the mechanism remains enigmatic.
Methods
The expression of GRA3 gene in RH, ME49, Wh3 and Wh6 strains were determined using quantitative real-time PCR (qRT–PCR). pEGFP-GRA3Wh6 was created by inserting Chinese 1 Wh6 GRA3 (GRA3Wh6) cDNA into a plasmid encoding the enhanced GFP. Mouse neuro2a (N2a) cells were transfected with either pEGFP or pEGFP-GRA3Wh6 and incubated for 24-36 hr. N2a cell apoptosis- and ER stress-associated proteins were determined using flow cytometry and immunoblotting. Furthermore, N2a cells were pretreated with GSK2656157 and Z-ATAD-FMK before pEGFP-GRA3Wh6 transfection, and the effect of the inhibitors on GRA3Wh6-induced ER stress and apoptosis was investigated.
Results
GRA3 gene expression was higher in the avirulent strains of type II ME49 and type Chinese 1 Wh6 strains compared to the virulent strains of type I RH strain and type Chinese 1 Wh3 strain. Transfection with pEGFP-GRA3Wh6 induced neuronal apoptosis and increased the expression of GRP78, p-PERK, cleaved caspase-12, cleaved caspase-3, and CHOP compared to pEGFP. Pretreatment with GSK2656157 and Z-ATAD-FMK decreased apoptosis in N2a cells, and similarly, ER stress- and apoptosis-associated protein levels were significantly decreased.
Conclusion
GRA3 induces neural cell apoptosis via the ER stress signaling pathway, which could play a role in Toxoplasmic encephalitis.