scholarly journals HLA alleles measured from COVID-19 patient transcriptomes reveal associations with disease prognosis in a New York cohort

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12368
Author(s):  
René L. Warren ◽  
Inanc Birol
Keyword(s):  
Statistical Significance ◽  
Severe Disease ◽  
Significant Risk ◽  
Human Leukocyte ◽  
Negative Control ◽  
Control Group ◽  
Clinical Value ◽  
Hla Alleles ◽  
Disease Prognosis ◽  
Increased Risk

Background The Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants. Previously, we have identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small patient cohorts at the COVID-19 pandemic onset. Methods We have since analyzed a larger public patient cohort data (n = 126 patients) with controls, associated demographic and clinical data. By combining the predictive power of multiple in silico HLA predictors, we report on HLA-I and HLA-II alleles, along with their associated risk significance. Results We observe HLA-II DPA1*02:02 at a higher frequency in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p = 0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes, including admission to intensive care, reveal nominally significant risk associations with A*11:01 (FET p = 0.0078) and C*04:01 (FET p = 0.0087). The association with severe disease outcome is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0323). While prevalence of some of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with HLA-I C*04:01 tend to fare worse overall. This HLA allele may hold potential clinical value.

scholarly journals Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis

2020 ◽  
Author(s):  
René L. Warren ◽  
Inanç Birol
Keyword(s):  
In Silico ◽  
Statistical Significance ◽  
Significant Risk ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Negative Control ◽  
Control Group ◽  
Clinical Value ◽  
Disease Prognosis ◽  
Increased Risk

ABSTRACTBackgroundThe Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants.MethodsBy combining the predictive power of multiple in silico HLA predictors, we have previously identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small cohorts at the COVID-19 pandemic onset. Since then, newer and larger patient cohorts with controls and associated demographic and clinical data have been deposited in public repositories. Here, we report on HLA-I and HLA-II alleles, along with their associated risk significance in one such cohort of 126 patients, including COVID-19 positive (n=100) and negative patients (n=26).ResultsWe recapitulate an enrichment of DPA1*02:02 in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p=0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes reveal nominally significant risk associations with A*11:01 (FET p=0.0078), C*04:01 (FET p=0.0087) and DQA1*01:02 (FET p=0.0121).ConclusionsWhile enrichment of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with the latter three alleles tend to fare worse overall. This is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0023), and may hold potential clinical value.

scholarly journals Clinical value of a screening tool for tumor predisposition syndromes in childhood cancer patients (TuPS): a prospective, observational, multi-center study

2021 ◽  
Author(s):  
Floor A. M. Postema ◽  
Saskia M. J. Hopman ◽  
Corianne A. J. M. de Borgie ◽  
Cora M. Aalfs ◽  
Jakob K. Anninga ◽  
...  
Keyword(s):  
Screening Tool ◽  
Clinical Care ◽  
False Negative ◽  
Negative Control ◽  
Control Group ◽  
Clinical Value ◽  
Variant Of Uncertain Significance ◽  
Multi Center Study ◽  
Center Study ◽  
Genetic Consultation

AbstractRecognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-center study including children newly diagnosed with cancer from 2016 to 2019 in the Netherlands. Children in whom a TPS had been diagnosed before the cancer diagnosis were excluded. The screening tool consists of a checklist, 2D and 3D photographic series and digital assessment of these by a clinical geneticist. If a TPS was suspected, the patient was assessed positive and referred for routine genetic consultation. Primary aim was to assess the clinical value of this new screening tool. Of the 363 included patients, 57% (208/363) were assessed positive. In 15% of patients (32/208), the 2D photographic series with (n = 12) or without (n = 20) 3D photographs were decisive in the positive assessment. In 2% (4/208) of positive assessed patients, a TPS was diagnosed, and in an additional 2% (4/208) a germline variant of uncertain significance was found. Thirty-five negatively assessed patients were evaluated through routine genetic consultation as controls, in none a TPS was detected. Using the screening tool, 57% of the patients were assessed as suspected for having a TPS. No false negative results were identified in the negative control group in the clinical care setting. The observed prevalence of TPS was lower than expected, due to selection bias in the cohort.

scholarly journals The Connection of the Level of Estradiol in Serum and Obesity with the Endometrial Bleeding in Postmenopausal Women

2019 ◽  
Vol 7 (1) ◽  
pp. 88-91 ◽  
Author(s):  
Valentina Tofiloska ◽  
Maria Krstevska ◽  
Ana Daneva-Markova ◽  
Viktorija Jovanovska
Keyword(s):  
Endometrial Cancer ◽  
Statistical Significance ◽  
Abnormal Uterine Bleeding ◽  
Control Group ◽  
Prospective Clinical Study ◽  
Study Group ◽  
Gynecology And Obstetrics ◽  
Increased Risk ◽  
Significant Difference ◽  
Post Menopausal

BACKGROUND: Postmenopausis is a period that begins one year after the last menstrual period. Abnormal uterine bleeding could be of different origins. AIM: This study aimed to determine the association of serum estrogen hormone levels and obesity with the occurrence of endometrial bleeding in post-menopausal women. MATERIAL AND METHODS: Prospective clinical study involving 120 postmenopausal patients treated at the University Clinic for Gynecology and Obstetrics-Skopje, divided into two groups: control and study. The control group consisted of 40 postmenopausal patients without endometrial bleeding, hospitalised and operated due to urogenital pathology. The study group consisted of 80 patients with endometrial bleeding who were divided into three subgroups according to the thickness of the endometrium: from 5-8 mm, 8-11 mm and above 11 mm. In all subjects, estradiol and BMI was determined. RESULTS: Estradiol levels were statistically higher in the study group compared to control while statistically significant difference among the three subgroups according to the thickness of the endometrium about the levels of estradiol in blood is not found. About BMI, the results showed that there was no statistical significance between the two examined groups. CONCLUSION: Patients with endometrial bleeding have increased levels of estradiol and are at increased risk of endometrial cancer about controls, the likelihood of endometrial cancer significantly increases by 1,108 times.

scholarly journals Analysis of Chronic Periodontitis in Tonsillectomy Patients: A Longitudinal Follow-Up Study Using a National Health Screening Cohort

2020 ◽  
Vol 10 (10) ◽  
pp. 3663 ◽  
Author(s):  
Soo Hwan Byun ◽  
Chanyang Min ◽  
Yong Bok Kim ◽  
Heejin Kim ◽  
Sung Hun Kang ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Chronic Periodontitis ◽  
Index Date ◽  
Statistical Significance ◽  
Significant Risk ◽  
Control Group ◽  
Follow Up Study ◽  
Region Of Residence ◽  
National Cohort

This study aimed to compare the risk of chronic periodontitis (CP) between participants who underwent tonsillectomy and those who did not (control participants) using a national cohort dataset. Patients who underwent tonsillectomy were selected from a total of 514,866 participants. A control group was included if participants had not undergone tonsillectomy from 2002 to 2015. The number of CP treatments was counted from the date of the tonsillectomy treatment. Patients who underwent tonsillectomy were matched 1:4 with control participants who were categorized based on age, sex, income, and region of residence. Finally, 1044 patients who underwent tonsillectomy were matched 1:4 with 4176 control participants. The adjusted estimated value of the number of post-index date (ID) CP did not reach statistical significance in any post-ID year (each of p > 0.05). In another subgroup analysis according to the number of pre- ID CP, it did not show statistical significance. This study revealed that tonsillectomy was not strongly associated with reducing the risk of CP. Even though the tonsils and periodontium are located adjacently, and tonsillectomy and CP may be related to bacterial inflammation, there was no significant risk of CP in patients undergoing tonsillectomy.

scholarly journals Outcomes of Infants with Mild Hypoxic Ischemic Encephalopathy Who Did Not Receive Therapeutic Hypothermia

2019 ◽  
Vol 4 (3) ◽  
pp. 1-9 ◽  
Author(s):  
Jonathan Reiss ◽  
Mridu Sinha ◽  
Jeffrey Gold ◽  
Julie Bykowski ◽  
Shelley M. Lawrence
Keyword(s):  
Therapeutic Hypothermia ◽  
Severe Disease ◽  
Significant Risk ◽  
Brain Magnetic Resonance Imaging ◽  
Adverse Outcomes ◽  
Hypoxic Ischemic Encephalopathy ◽  
Neurodevelopmental Outcomes ◽  
Specific Patient ◽  
Increased Risk ◽  
Ischemic Encephalopathy

Introduction: Accurately diagnosing and treating infants with mild forms of hypoxic ischemic encephalopathy (HIE) is important, as the majority of neonates with signs and symptoms of HIE after birth do not meet clinical criteria for moderate or severe disease. Emerging evidence, however, suggests that infants with mild HIE (mHIE) have an increased risk for neurodevelopmental impairment (NDI). Methods: This retrospective descriptive study examined all inborn infants ≥35 week’s gestational age at a single, level III neonatal intensive care unit (NICU) in California between January 1, 2012, and December 31, 2015. International Classification of Diseases codes were used as a proxy to identify neonates with mHIE but who did not receive therapeutic hypothermia (TH). Short- and long-term neurodevelopmental outcomes were documented, including abnormal (1) brain magnetic resonance imaging within 10 days of birth suggestive of HIE, (2) electroencephalogram with electrographic seizures, (3) neurologic discharge examination, or (4) NDI following NICU discharge. Results: Over the 4-year study period, 25 infants met inclusion criteria. Eight of 25 (32%) infants demonstrated neurologic impairment, defined by an abnormality in at least one of the four categories. The remaining 17 infants were without documented evidence for adverse outcomes. Conclusion: Our results indicate that children with mHIE are at significant risk for neurologic injury and may benefit from more aggressive interventions. Further prospective studies should be completed to determine the efficacy of TH in this specific patient population.

scholarly journals BIOCHEMICAL AND HAEMATOLOGICAL CHANGES ASSOCIATED WITH TRANSPLACENTAL CONGENITAL MALARIA IN KOGI STATE, NORTH CENTRAL NIGERIA

2021 ◽  
Author(s):  
Shedrack Egbunu Akor ◽  
Dickson Achimugu Musa ◽  
Akogu SPO
Keyword(s):  
Cord Blood ◽  
Statistical Significance ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Blood Biochemical ◽  
Significant Difference ◽  
Haematological Changes ◽  
Haematological Indices ◽  
Congenital Malaria

Background: Transplacental congenital malaria is a vertical transplacental transmission of malaria parasites from the mother to the baby in utero or perinatally during labor. Cord blood that conveyed oxygen and nutrients from mother to fetus and return with carbon dioxide and other waste materials can transmit malaria pathogen. This study is aim to establish early diagnosis of transplacental congenital malaria using cord blood biochemical and haematological indices. Cord blood from 164 babies delivered at three hospitals in Kogi State between January and December, 2020 were microscopically investigated for malaria parasite. Biochemical and Haematological analyses were done using SYSMEX XP 300, Roche 9180 and VIS Spectrophotometer model 721. The data obtained were expressed as mean plus or minus standard deviation using SPSS 23. The indicator level of statistical significance was set at p<0.05. The results showed significant (p<0.05) decreased in values of WBC, platelet, sodium, potassium, urea, creatinine, RBC, PCV, haemoglobin and MCHC in malaria infected cord blood in comparison to malaria negative control group. Significant (P<0.05) increased activities of liver enzymes (AST, ALT, ALP), total protein, bicarbonate and chloride in malaria infected cord blood when compared with malaria negative group. However, no statistically significant difference in lymphocyte, MCV, MCH, neutrophil and mixed of both malaria infected and malaria negative cord blood. This study suggests that cord blood biochemical and haematological indices can be used to diagnose and manage transplacental congenital malaria in fetus and neonates. Keywords: Transplacental, Biochemical, Haematological and Congenital Malaria.

scholarly journals Effect of ZnO nanoparticles in treatment of broilers with Eimeria tenella. experimentally infected.

2021 ◽  
Author(s):  
Sadiya Aziz Anah ◽  
Khadeeja Abees Hmood ◽  
Saad Aziz Anah
Keyword(s):  
Zinc Oxide ◽  
Severe Disease ◽  
Treated Group ◽  
Positive Control ◽  
Negative Control ◽  
Eimeria Tenella ◽  
Positive Control Group ◽  
Economic Losses ◽  
Control Group ◽  
New Treatment

Abstract Coccidiosis is one of the common poultry diseases in Iraq and the world, which causes great economic losses. Therefore, this study aimed to use a new treatment represented by nanoparticles of zinc oxide and compare it with the drug (Amprolium). The Oocysts of Eimeria tenella were isolated from the feces of the briolers received at the Veterinary hospital in Diwaniyah Province and initially diagnosed by compound light microscopy,Then it was confirmed molecularly by PCR technique using the internal transcribed space ITS1 gene with a molecular weight of 409bp. The experiment was carried out on 120 birds of broilers, as the animals were divided into 6 groups with 20 birds per group. The first group(G1) was left as a negative control(uninfected), the second group(G2) was inoculated with 50,000 mature Oocysts and left as a positive control group,the third group(G3) was incubated with 50,000 Oocysts + Amprolium (anticoccidial), the fourth, fifth and sixth groups(G4,G5,G6) were also dosed with 50,000 Oocysts followed by an oral dose of nanoparticles of zinc oxide at a concentration of 20,40,60 mg/kg for each of fourth, fifth and sixth groups respectively. The current results showed that the briolers in G2 suffered from severe disease symptoms and high mortality occurred in the first week of infection, amounting to %10 compared to the anticoccidial (Amprolium group and the groups treated with nanoconcentrations 20,40,60 mg/kg respectively.G6 which was dosed with a concentration of 60 mg /kg, showed a significant decrease in the number of Oocysts excreted compared with the positive control group and the anticoccidial group, in addition to the appearance of mild symptoms and a mortality rate of %0.8,While there was a decrease in the number of Oocysts excreted during the second week in the anticoccidial group and the treated groups with the three nanoconcentrations with a decrease in the mortality rates of birds .The number of Oocysts excreted in the litter significantly decreased in the treated group with a concentration of 60 mg/kg compared to all other groups, and all birds of this group recovered during the second week of infection.

scholarly journals Socioeconomic Burden of Rising Methamphetamine-Associated Heart Failure Hospitalizations in California From 2008 to 2018

2021 ◽  
Author(s):  
Susan X. Zhao ◽  
Andres Deluna ◽  
Kate Kelsey ◽  
Clifford Wang ◽  
Aravind Swaminathan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Health Planning ◽  
Statistical Significance ◽  
Negative Control Group ◽  
International Classification Of Diseases ◽  
Negative Control ◽  
Control Group ◽  
Public Health Response ◽  
Classification Of Diseases ◽  
Age Adjusted Rates

BACKGROUND: Methamphetamine-associated cardiomyopathy/heart failure (MethHF) is an increasingly recognized disease entity in the context of a rising methamphetamine (meth) epidemic that most severely impacts the western United States. Using heart failure (HF) hospitalization data from the Office of Statewide Health Planning and Development, this study aimed to assess trend and disease burden of MethHF in California. METHODS: Adult patients (≥18 years old) with HF as primary hospitalization diagnosis between 2008 and 2018 were included in this study. The association with Meth (MethHF) and those without (non-MethHF) were determined by meth-related International Classification of Diseases -based secondary diagnoses. Statistical significance of trends in age-adjusted rates of hospitalization per 100 000 adults were evaluated using nonparametric analysis. RESULTS: Between 2008 and 2018, 1 033 076 HF hospitalizations were identified: 42 565 were MethHF (4.12%) and 990 511 (95.88%) were non-MethHF. Age-adjusted MethHF hospitalizations per 100 000 increased by 585% from 4.1 in 2008 to 28.1 in 2018, while non-MethHF hospitalizations decreased by 6.0% from 342.3 in 2008 to 321.6 in 2018. The rate of MethHF hospitalization increase more than doubled that of a negative control group with urinary tract infection and meth-related secondary diagnoses (7.82-fold versus 3.48-fold, P <0.001). Annual inflation–adjusted hospitalization charges because of MethHF increased by 840% from $41.5 million in 2008 to $390.2 million in 2018, as compared with an 82% increase for all HF hospitalization from $3.503 billion to $6.376 billion. Patients with MethHF were significantly younger (49.64±10.06 versus 72.20±14.97 years old, P <0.001), predominantly male (79.1% versus 52.4%, P <0.001), with lower Charlson Comorbidity Index, yet they had longer length of stay, more hospitalizations per patient, and more procedures performed during their stays. CONCLUSIONS: MethHF hospitalizations increased sharply during the study period and contributed significantly to the HF hospitalization burden in California. This emerging HF phenotype, which engenders considerable financial and societal costs, calls for an urgent and concerted public health response to contain its spread.

scholarly journals Carotid Arterial Stiffness and Cardiometabolic Profiles in Women with Fibromyalgia

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1786
Author(s):  
Yunkyung Kim ◽  
Geun-Tae Kim ◽  
Jihun Kang
Keyword(s):  
Risk Factors ◽  
Arterial Stiffness ◽  
Central Obesity ◽  
Cardiometabolic Risk ◽  
Statistical Significance ◽  
Cardiometabolic Risk Factors ◽  
Control Group ◽  
Increased Risk ◽  
Carotid Arterial ◽  
High Triglyceride

Background: The present study aimed to evaluate the association between FM and cardiometabolic risk factors and carotid arterial stiffness in FM patients. Methods: The cardiometabolic risk profile was defined based on the Adult Treatment Panel III panel. Carotid intimal media thickness (cIMT) and arterial stiffness were assessed using high-resolution ultrasonography. Multivariate logistic analysis was performed to estimate the association between FM and cardiometabolic risk factors. We used a general linear regression to compare the cIMT and carotid beta-index between the participants with and without FM. Pearson’s coefficient was calculated to evaluate the potential correlation between cardiometabolic risk profiles, cIMT, and arterial stiffening in FM. Results: FM participants showed a higher risk of central obesity (odds ratio [OR] = 3.21, 95% confidence interval [CI] 1.49, 6.91), high triglyceride (OR = 4.73, 95% CI 2.29, 9.79), and impaired fasting glucose (IFG) (OR = 4.27, 95% CI 2.07, 8.81) compared to the control group. The FM group exhibited higher beta-index values than the control group (p = 0.003). Although IFG and triglyceride glucose index showed a tendency to correlate with the beta-index, statistical significance was not observed. Conclusions: FM was associated with an increased risk of central obesity, high triglyceride levels, and IFG. Furthermore, advanced arterial stiffness of the carotid artery was observed in FM, which might be correlated with insulin resistance.

scholarly journals Circulating Extracellular MicroRNAs in Blood and Saliva Are a New Source of Biomarkers in the Assessment of Health Effects of Traditional Korean Diet (P15-003-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sang-Woon Choi ◽  
Myung-Sunny Kim ◽  
Dae Young Kwon ◽  
Hae-Jeung Lee ◽  
Seon-Joo Park ◽  
...  
Keyword(s):  
Health Effects ◽  
Dietary Intervention ◽  
Metabolic Diseases ◽  
Statistical Significance ◽  
Diet Group ◽  
Control Group ◽  
Rt Pcr ◽  
Alcoholic Fatty Liver ◽  
Altered Expression ◽  
Increased Risk

Abstract Objectives Over the past decades current Korean diet has been rapidly modified to the Western style, which might be responsible for the increased risk of metabolic diseases in Korea, whereas the traditional Korean diet (K-diet) has been reported as metabolically and epigenetically healthy diet. MicroRNAs (miRs) are small, single-stranded, non-coding RNAs that affect posttranscriptional regulation and circulating miRs have been regarded as next generation biomarkers of many health conditions. We therefore determined whether extracellular miRs can be useful biomarkers to determine the health effects of K-diet. Methods Ten obese perimenopausal women were recruited and randomly divided into either K-diet group (n = 5) or control diet (a Westernized Korean diet) group (n = 5). Subjects were housed in a metabolic unit like condition for 2 weeks of dietary intervention. Blood and saliva samples were collected before and after the intervention and circulating miRs were extracted using Qiagen miRNeasy kit. After 84 circulating miRs were detected with miScript miRNA PCR Array, miRs with statistical significance were validated with individual RT-PCRs. Results In the K-diet group significantly down-regulated plasma miRs were hsa-miR126-3p, hsa-miR18a-5p, hsa-miR19b-3p, hsa-miR107, hsa-miR148a-3p, hsa-miR26b-5p, hsa-miR374a-5p and hsa-miR26a-5p, which are known to be associated with type 1 or 2 diabetes or non-alcoholic fatty liver disease. Among them hsa-miR126-3p (P = 0.0158) and hsa-miR26a-5p (P = 0.0348) were validated by RT-PCR. In the control group plasma hsa-miR25-3p was down-regulated and hsa-miR-148a-3p was up-regulated. Only hsa-miR-25-3p (P = 0.0407), which is known to be associated with cardiovascular disease, was validated. In the K diet group 5 saliva miRs, hsa-miR-92-3p , hsa-miR-17-3p, hsa-miR-25b-3p, hsa-miR-122a-5p and hsa-miR-193a-5p, were significantly down-regulated by the array, while only hsa-miR-92-3p (P = 0.0381) and hsa-miR-122a-5p (P = 0.0242) were validated by RT-PCR. In the control group 3 saliva miRs (hsa-miR-25-3p, hsa-miR-31-5p and hsa-miR-200a-3p) showed significantly altered expression by the array but not by RT-PCR. Conclusions Circulating miRs can be a new source of biomarkers to determine the health effects of K-diet. Funding Sources Korea Food Research Institute.

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