scholarly journals Analyzing master regulators and scRNA-seq of COVID-19 patients reveals an underlying anti-SARS-CoV-2 mechanism of ZNF proteins

2021 ◽  
Author(s):  
Shijie Qin ◽  
Weijun Xu ◽  
Canbiao Wang ◽  
Sizhu Jiang ◽  
Wei Dai ◽  
...  
Keyword(s):  
Immune Cells ◽  
Target Genes ◽  
Survival Outcome ◽  
Severe Illness ◽  
Protein Activity ◽  
Master Regulators ◽  
Female Patients ◽  
Significant Difference ◽  
Male Patients

AbstractStudies have demonstrated that both mortality and severe illness rates exist significant difference in different gender COVID-19 patients, but the reasons are still very mysterious to date. Here, we firstly find that the survival outcome of female patients is better to male patients through analyzing the 3044 COVID-19 cases. Secondly, we identify many important master regulators [e.g. STAT1/STAT2 and zinc finger (ZNF) proteins], in particular female patients can express more ZNF proteins and stronger transcriptional activities than male patients in response to SARS-CoV-2 infection. Thirdly, we discover that ZNF protein activity is significantly negative correlation with the SARS-CoV-2 load of COVID-19 patients, and ZNF proteins as transcription factors can also activate their target genes to participate in anti-SARS-CoV-2 infection. Fourthly, we demonstrate that ZNF protein activity is positive correlation with the abundance of multiple immune cells of COVID-19 patients, implying that the highly ZNF protein activity might promote the abundance and the antiviral activity of multiple immune cells to effectively suppress SARS-CoV-2 infection. Taken together, our study proposes an underlying anti-SARS-COV-2 role of ZNF proteins, and differences in the amount and activity of ZNF proteins might be responsible for the distinct prognosis of different gender COVID-19 patients.

Clinical Outcomes for “Suspicious” Category in Thyroid Fine-Needle Aspiration Biopsy: Patient's Sex and Nodule Size Are Possible Predictors of Malignancy

2009 ◽  
Vol 133 (5) ◽  
pp. 787-790
Author(s):  
Kirtee Raparia ◽  
Soo Kee Min ◽  
Dina R. Mody ◽  
Rose Anton ◽  
Mojgan Amrikachi
Keyword(s):  
Surgical Resection ◽  
Fine Needle Aspiration ◽  
Needle Aspiration ◽  
Cytologic Diagnosis ◽  
Fine Needle ◽  
Female Patients ◽  
Hürthle Cell ◽  
Significant Difference ◽  
Cell Neoplasm ◽  
Male Patients

Abstract Context.—Fine-needle aspiration (FNA) is recommended as an initial screening tool for the diagnosis of thyroid nodules. Approximately 10% of thyroid FNA diagnoses are “suspicious for neoplasm,” warranting surgical resection. Objectives.—To examine the role of a patient's age, sex, size of nodule, and morphologic features as possible predictors of malignancy in patients with cytologic diagnosis of “suspicious for neoplasm.” Design.—Cytopathology slides and reports of 402 consecutive thyroid FNAs from 2000–2005 interpreted as “suspicious” were reviewed. Of these, 180 cases that had subsequent surgical resection were selected. Results.—Of the 108 cases suspicious for follicular neoplasm on cytologic evaluation, histologic follow-up showed malignancy in 26 (24%). Of the 37 cases suspicious for Hürthle cell neoplasm, 15 (41%) had malignancy. Of the 35 cases suspicious for malignancy, 29 had malignant histologic diagnoses. Among cases with cytologic diagnoses of “suspicious for follicular or Hürthle cell neoplasm,” the rate of malignancy in female patients was 22% as compared to 43% in male patients (P = .02). The rate of malignancy in nodules less than 2 cm was 19% compared to 47% in nodules measuring 2 cm or larger (P < .001). These differences were statistically significant. No statistically significant difference was noted between the age of the patient and the rate of benign versus malignant diagnosis. Conclusions.—Malignant tumors were more frequent in male patients with a cytologic diagnosis of “suspicious for follicular or Hürthle cell neoplasm” than in female patients. Risk of malignancy was higher in nodules measuring 2 cm or larger. Age of the patient was not a predictor of malignancy.

scholarly journals Gender and Quality of Life After Cerebral Stroke

2010 ◽  
Vol 10 (2) ◽  
pp. 94-99 ◽  
Author(s):  
Amra Zalihić ◽  
Vedran Markotić ◽  
Dino Zalihić ◽  
Mirela Mabić
Keyword(s):  
Quality Of Life ◽  
Life Quality ◽  
Female Gender ◽  
Cerebral Stroke ◽  
Female Patients ◽  
Negative Prognostic Factor ◽  
Significant Difference ◽  
Medium Range ◽  
Male Patients

The aim of this work is to investigate the influence of gender on recovery after cerebral stroke.It is believed that functional outcome of cerebral stroke (CS) depends on gender. Female gender is mildly negative prognostic factor in after stroke results. Two hundred and two patients who had first ischemic cerebral stroke were questioned with help of, HADS and WHOQOL-Bref questionnaires, looking for differences in recovery depending on gender. Average patients' age was 72+/-13 (ME+/-IR) years. The youngest patient had 40 years, and the oldest 92 years, and medium range was 52 years. There were 112 males and 90 females. Quality of life was equally graded by both male and female after CS (p=0.208). Male patients had significantly better results in physical (p=0.035) and psychological (p=0.020) domain of life quality. After CS, male patients had better results only in memory dimension (p=0.003). Anxiety was statistically more frequent among female patients (p=0.009). Gender did not influence frequency of metabolic syndrome in patients with CS. Quality of life after CS was better in male patients, and statistically significant difference has been shown in physical, psychological domain and memory dimension. Female patients were more anxious then male after CS.

Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes

2013 ◽  
Vol 19 (8) ◽  
pp. 1035-1045 ◽  
Author(s):  
Jun-ichi Satoh ◽  
Hiroko Tabunoki
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Deep Sequencing ◽  
Immune Cells ◽  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Molecular Network ◽  
Genome Wide

Background: Vitamin D is a liposoluble vitamin essential for calcium metabolism. The ligand-bound vitamin D receptor (VDR), heterodimerized with retinoid X receptor, interacts with vitamin D response elements (VDREs) to regulate gene expression. Vitamin D deficiency due to insufficient sunlight exposure confers an increased risk for multiple sclerosis (MS). Objective: To study a protective role of vitamin D in multiple sclerosis (MS), it is important to characterize the global molecular network of VDR target genes (VDRTGs) in immune cells. Methods: We identified genome-wide VDRTGs collectively from two distinct chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) datasets of VDR-binding sites derived from calcitriol-treated human cells of B cell and monocyte origins. We mapped short reads of next generation sequencing (NGS) data on hg19 with Bowtie, detected the peaks with Model-based Analysis of ChIP-Seq (MACS), and identified genomic locations by GenomeJack, a novel genome viewer for NGS platforms. Results: We found 2997 stringent peaks distributed on protein-coding genes, chiefly located in the promoter and the intron on VDRE DR3 sequences. However, the corresponding transcriptome data verified calcitriol-induced upregulation of only a small set of VDRTGs. The molecular network of 1541 calcitriol-responsive VDRTGs showed a significant relationship with leukocyte transendothelial migration, Fcγ receptor-mediated phagocytosis, and transcriptional regulation by VDR, suggesting a pivotal role of genome-wide VDRTGs in immune regulation. Conclusion: These results suggest the working hypothesis that persistent deficiency of vitamin D might perturb the complex network of VDRTGs in immune cells, being responsible for induction of an autoimmune response causative for MS.

Subanalysis of the StiL NHL 1–2003 Study: Achievement of Complete Response with Bendamustine-Rituximab (B-R) and CHOP-R in the First-Line Treatment of Indolent and Mantle Cell Lymphomas Results in Superior Survival Compared to Partial Response.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2724-2724 ◽  
Author(s):  
Mathias J. Rummel ◽  
Norbert Niederle ◽  
Georg Maschmeyer ◽  
G.-Andre Banat ◽  
Ulrich von Grünhagen ◽  
...  
Keyword(s):  
Complete Response ◽  
Line Treatment ◽  
First Line ◽  
Female Patients ◽  
Significant Difference ◽  
Mantle Cell ◽  
Male Patients ◽  
The Impact ◽  
First Line Treatment

Abstract Abstract 2724 Background: The NHL 1 study, a prospective, multicenter, randomized, phase 3 study which compared B-R and CHOP-R as first-line treatment in indolent lymphomas and mantle cell lymphoma (MCL), demonstrated a significant benefit in progression-free survival (PFS) as well as improved tolerability for B-R compared with CHOP-R. Here we present an analysis of the impact of response quality on outcome. Methods: 514 patients (pts) with indolent or MCL were randomized to receive B-R or CHOP-R for a maximum of 6 cycles. Results: The overall response rate in the 514 pts (261 B-R; 253 CHOP-R) was 92.7% and 91.3% in the B-R and CHOP-R arms, respectively (as presented at the last ASCO meeting, J Clin Oncol 30, 2012 (suppl; abstr 3). A complete response (CR) was observed in 39.8% in the B-R arm and in 30% in the CHOP-R arm (p=0.021). The achievement of CR was associated with a significantly prolonged PFS and overall survival (OS) (Table 1). Analysis by treatment arm revealed a trend for superior PFS and a significantly improved OS for patients achieving CR following treatment with B-R. In the CHOP-R arm, patients in CR had a significantly superior PFS compared to those in PR with a trend to superior OS. Regardless of the quality of response, PFS was superior with B-R versus CHOP-R: For patients in CR, the median PFS was not reached with B-R, whereas for CHOP-R it was 53.7 months (p=0.0204). In patients achieving PR, treatment with B-R resulted in a median PFS of 57.2 months, and this was 30.9 months with CHOP-R (p=0.0002). We noted a statistically significant difference in CR rates between male (n=272, median age 63 years) and female (n=242, median age 64 years) patients. The CR rate was 28.6% in male patients and 42.1% in female patients (p=0.0016). Female patients had a longer median PFS (51.4 months) compared to male patients (38.6 months), however, this difference was not statistically significant (p=0.0866). Conclusions: Patients in CR following first-line treatment in our study had a significantly longer PFS and OS compared to those achieving a PR. Therefore, our results strongly suggest an association between quality of response and outcome. Disclosures: No relevant conflicts of interest to declare.

scholarly journals PARATHYROID HORMONE AND BIOCHEMICAL METABOLIC BONE MARKERS IN PATIENTS WITH β-THALASSEMIA MAJOR IN MISAN PROVINCE / IRAQ

2020 ◽  
Vol 17 (35) ◽  
pp. 65-72
Author(s):  
Noor AL-Huda Salah AL-ZUHAIRY ◽  
Zainab Abdul Jabbar Ridha AL-ALI
Keyword(s):  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Thalassemia Major ◽  
Control Group ◽  
Female Patients ◽  
Metabolic Bone ◽  
Significant Difference ◽  
Calcium Phosphorus ◽  
Male Patients ◽  
Serum Pth

Beta-thalassemia is a heterogeneous group of hereditary blood disorders characterized by defects in the synthesis of the β- chains of hemoglobin, resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. This study aims to assess the serum PTH, vitamin D, calcium, phosphorus, alkaline phosphatase, and magnesium levels in β-thalassemia major patients. A total of 50 (30 male and 20 female) patients with β- thalassemia major with ages range 11- 16 years and an equal number of sex-matched healthy adolescents as a control group were included in this study. A total of 52% of patients were lived in an urban area, and there was no significant difference between patients and the control group regarding residency. Male patients showed low statistically significant (P 0.05) mean serum PTH, vitamin D, and calcium levels, but mean serum phosphorus and alkaline phosphatase levels were significantly higher (P 0.05) as compared to the male control group. However, female patients had low, but without statistical significant (P>0.05) mean serum PTH level, whereas vitamin D and calcium levels were highly significant (P 0.05) reduced. The phosphorus and ALP levels were highly significantly (P 0.05) increased as compared to female controls. Regarding β- thalassemia major group, the current study showed male patients had non-significant (P 0.05) higher levels of PTH, calcium, phosphorus, and ALP. In contrast, vitamin D level was non-significantly (P 0.05) low in male patients as compared to female patients. Mean serum level of PTH had a negative correlation with phosphorus, but it had a positive association with vitamin D, calcium, ALP, and magnesium. In conclusion, this study demonstrated that β-thalassemia major patients have a markedly deranged biochemical metabolic bone profile. Regular monitoring of PTH and biochemical mineral profile is also recommended.

Investigation of Biliary Canal Variations as a Cause of Stone Formation in the Choledochal Canal

2020 ◽  
Vol 2 (2) ◽  
pp. 77-85
Author(s):  
Yusuf Atakan Baltrak ◽  
M. Sabri Medişoğlu ◽  
Çolak Tuncay ◽  
Yalnız Ahmet ◽  
Çam İsa ◽  
...  
Keyword(s):  
Gall Bladder ◽  
Surgical Procedures ◽  
Stone Formation ◽  
Age Group ◽  
Female Patients ◽  
Duct Diameter ◽  
Significant Difference ◽  
Group A ◽  
Male Patients ◽  
Choledochal Duct

The present study aimed to investigate if there is an association between the diameter of the choledochal duct and choledochal duct stone formation. The present study consisted of 79 patients who had endoscopic interventions and MRCP procedure with surgery history. Some followed due to disorders of the liver, gall bladder, and biliary tract and some of whom presented hepatobiliary complaints between 2017 and 2019. The choledochal duct diameter measured from MRCP images and choledochal duct stone had examined; the type classified according to Huang classification. Among the cases classified, 29 patients, was Huang Type A1, 27 patients were Huang Type A2, 16 patients were Huang Type A3, and seven patients were Huang Type A4. There was not any statistically significant association in terms of choledochal diameter regarding the types. Choledochal duct diameter was statistically higher in female patients than male patients (p<0.05). According to the age group, a statistically significant difference detected for choledochal duct stone formation; individuals over 45 years of age present an increase for choledochal duct stone (p<0.05). The choledochal duct diameter was found higher in female patients compared with male patients; stone formation has found increased in both gender over 45 years of age. It should consider before surgical procedures and radiological tests.

Association of PD-L1 expression with tumor infiltrating immune cells and mutation burden in the high grade neuroendocrine carcinoma of the lung.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8564-8564 ◽  
Author(s):  
Hye Sook Kim ◽  
Ji-Youn Han
Keyword(s):  
Neuroendocrine Carcinoma ◽  
Immune Cells ◽  
Progression Free Survival ◽  
Large Cell ◽  
High Grade ◽  
Free Survival ◽  
Mutation Burden ◽  
Programmed Death ◽  
Significant Difference

8564 Background: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high grade neuroendocrine carcinoma of the lung and remain among the most fatal malignancies. Programmed death-ligand 1 (PD-L1) is expressed in a group of cancers that may be suitable for specific immunotherapy. We retrospectively investigated PD-L1 expression in tumor cells (TC) and tumor infiltrating immune cells (IC) and correlated this with mutation burden and clinical outcome. Methods: A total of 192 patients with LCNEC (n = 72) and SCLC (n = 120) were explored. PD-L1 expression was scored by immunohistochemistry in TC and IC. We used the Ion AmpliSeq Comprehensive Cancer Panel to identify mutation in all exons in 409 cancer-related genes. Results: The overall prevalence of PD-L1 expression on TC was 15.1 % (29/192). No significant difference was observed between LCNEC and SCLC (16.7% vs. 14.2%, p = 0.365). Tumor-infiltrating IC and PD-L1 positive immune cells (IC) were observed in 34.4% (66/192) and 31.3% (60/192), respectively. The prevalence of tumor-infiltrating IC and PD-L1 expression on IC were significantly higher in LCNEC compared to SCLC (57.6% vs. 23.3%, p < .001; 45.8% vs. 22.5%, p = .001, respectively). Tumor-infiltrating IC and PD-L1 expression on IC were correlated with higher nonsynonymous mutational load (p = 0.048 and 0.038, respectively). Tumor-infiltrating immune cells (median 11.3 vs. 6.8 months, p = 0.005), and its correlated PD-L1 expression on IC (median 11.3 vs. 7.0 months, p = 0.024) were related with better progression free survival. There was no relevance between biomarker status and overall survival. Conclusions: These findings suggest that the PD-1/PD-L1 pathway is activated in a fraction of HGNEC of lung with correlating higher mutational burden. Further studies are needed to determine the PD-L1 expression and correlated clinical features to refine role of anti-PD1 treatments in these patient population.

Bioinformatic Analysis of Transcriptional Regulation by Nur77 in Central Nervous System and Immune System

2021 ◽  
Author(s):  
Montserrat Olivares Costa ◽  
Fernando Faunes ◽  
María Estela Andrés
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Immune Cells ◽  
Binding Sites ◽  
Target Genes ◽  
Bioinformatic Analysis ◽  
Neuronal Stem Cells

Abstract ObjectiveThe objectives of this work were to find genes regulated by Nur77 in neurons and to evaluate the possible common role of this transcription factor in neurons and lymphatic cells using published experimentally generated databases of ChIP-Seq and a microarray. We also characterized Nur77 binding throughout the genome. ResultsWe identified 113 Nur77 target genes in neuronal stem cells and 116 in neuronal cells. Cell adhesion and anchoring processes emerged as regulated by Nur77 in neurons and lymphatic cells. We found 9 common genes regulated by Nur77. Finally, we described a significant distribution of Nur77 binding sites in strong enhancers and active promoters. This work is a first step to understand the role of Nur77 and its common targets in neurons and immune cells.

scholarly journals Role of Platelets in Rheumatic Mitral Stenosis: An Observational Study

2018 ◽  
Vol 03 (04) ◽  
pp. 225-230
Author(s):  
Shravan Chetti ◽  
Santhimayee Kalivela ◽  
Suresh Yerra ◽  
Indrani Garre ◽  
Achukatla Kumar
Keyword(s):  
Mitral Stenosis ◽  
Left Atrial ◽  
Clot Formation ◽  
Male Population ◽  
Distribution Width ◽  
Significant Difference ◽  
Laboratory Investigations ◽  
Male Patients ◽  
Group 2

Abstract Background As previous studies demonstrated, the mean platelet volume (MPV) is one of the determinant factors for the development of left atrial appendage (LAA) clot. The authors wanted to see other parameters such as platelet distribution width (PDW) along with MPV in patients with chronic rheumatic heart disease (CHRD) in whom transesophageal echocardiogram (TEE) was done. Methods Total 50 consecutive CRHD patients with predominantly mitral stenosis (MS) came for cardiac outpatient department (OPD) for balloon valvuloplasty and were enrolled. Transthoracic echocardiography (TTE) and TEE were performed for each patient. Laboratory investigations included all biochemical parameters. In addition MPV and PDW were noted. Results Most of the 50 patients enrolled in this study were middle-aged women (n = 37), with mean age of 40.18 ± 9.50 years. Patients were divided into two groups: with left atrial (LA) clot (n = 24, group 1) and without LA clot (n = 26, group 2). Out of them, male population with severe MS was more prone for LA clot formation (p = 0.031). When comparing severity of MS with electrocardiographic (ECG) rhythm (normal vs. atrial fibrillation), no statistically significant difference was observed with clot formation (p = −0.44). In this study, presence of clot is more when the patient has larger-size platelets, that is, higher MPV, which is statistically significant (9.823 ± 0.759 vs. 10.996 ± 0.534; p = 0.000). Severe MS is associated with high normal PDW whether the clot is present or not but statistically not significant (p = −0.926). Conclusion Severity of MS in CRHD patients is an independent determinant of LA clot formation irrespective of rhythm abnormalities and higher MPV value. Male patients with severe MS are more prone to LA clot formation.

scholarly journals Evolution of Hominin Detoxification: Neanderthal and Modern Human Ah Receptor Respond Similarly to TCDD

2020 ◽  
Author(s):  
Jac M M J G Aarts ◽  
Gerrit M Alink ◽  
Henk J Franssen ◽  
Wil Roebroeks
Keyword(s):  
Codon Usage ◽  
Modern Human ◽  
Ah Receptor ◽  
Coding Region ◽  
Modern Humans ◽  
Protein Activity ◽  
Response Curves ◽  
Human Dose ◽  
Significant Difference

Abstract In studies of hominin adaptations to fire use, the role of the aryl hydrocarbon receptor (AHR) in the evolution of detoxification has been highlighted, including statements that the modern human AHR confers a significantly better capacity to deal with toxic smoke components than the Neanderthal AHR. To evaluate this, we compared the AHR-controlled induction of cytochrome P4501A1 (CYP1A1) mRNA in HeLa human cervix epithelial adenocarcinoma cells transfected with an Altai-Neanderthal or a modern human reference AHR expression construct, and exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We compared the complete AHR mRNA sequences including the untranslated regions (UTRs), maintaining the original codon usage. We observe no significant difference in CYP1A1 induction by TCDD between Neanderthal and modern human AHR, whereas a 150–1,000 times difference was previously reported in a study of the AHR coding region optimized for mammalian codon usage and expressed in rat cells. Our study exemplifies that expression in a homologous cellular background is of major importance to determine (ancient) protein activity. The Neanderthal and modern human dose–response curves almost coincide, except for a slightly higher extrapolated maximum for the Neanderthal AHR, possibly caused by a 5′-UTR G-variant known from modern humans (rs7796976). Our results are strongly at odds with a major role of the modern human AHR in the evolution of hominin detoxification of smoke components and consistent with our previous study based on 18 relevant genes in addition to AHR, which concluded that efficient detoxification alleles are more dominant in ancient hominins, chimpanzees, and gorillas than in modern humans.

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