Whole-Exome sequencing analysis identified TMSB10/TRABD2A locus to be associated with carfilzomib-related cardiotoxicity among patients with multiple myeloma

BackgroundProteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-coding genes in CFZ-CVAE among MM patients using whole-exome sequencing (WES) analysis.MethodsExome-wide single-variant association analysis, gene-based analysis, and rare variant analyses were performed on 603,920 variants in 247 patients with MM who have been treated with CFZ and enrolled in the Oncology Research Information Exchange Network (ORIEN) at the Moffitt Cancer Center. Separate analyses were performed in European Americans and African Americans followed by a trans-ethnic meta-analysis.ResultsThe most significant variant in the exome-wide single variant analysis was a missense variant rs7148 in the thymosin beta-10/TraB Domain Containing 2A (TMSB10/TRABD2A) locus. The effect allele of rs7148 was associated with a higher risk of CVAE [odds ratio (OR) = 9.3 with a 95% confidence interval of 3.9—22.3, p = 5.42*10−7]. MM patients with rs7148 AG or AA genotype had a higher risk of CVAE (50%) than those with GG genotype (10%). rs7148 is an expression quantitative trait locus (eQTL) for TRABD2A and TMSB10. The gene-based analysis also showed TRABD2A as the most significant gene associated with CFZ-CVAE (p = 1.06*10−6).ConclusionsWe identified a missense SNP rs7148 in the TMSB10/TRABD2A as associated with CFZ-CVAE in MM patients. More investigation is needed to understand the underlying mechanisms of these associations

Medical prospects of cryptosporidiosis in vivo control using biofabricated nanoparticles loaded with Cinnamomum camphora extracts by Ulva fasciata

Background and Aim: Global efforts are continuing to develop preparations against cryptosporidiosis. This study aimed to investigate the efficacy of biosynthesized Ulva fasciata loading Cinnamomum camphora oil extract on new zinc oxide nanoparticles (ZnONPs shorten to ZnNPs) and silver nanoparticles (AgNPs) as alternative treatments for Cryptosporidium parvum experimental infection in rats. Materials and Methods: Oil extract was characterized by gas chromatography-mass spectrometry, loaded by U. fasciata on ionic-based ZnO and NPs, and then characterized by transmission electron microscopy, scanning electron microscopy, and X-ray diffraction. Biosafety and toxicity were investigated by skin tests. A total of 105 C. parvum oocysts/rat were used (n = 81, 2–3 W, 80–120 g, 9 male rats/group). Oocysts shedding was counted for 21 d. Doses of each preparation in addition to reference drug were administered daily for 7 d, starting on post-infection (PI) day (3). Nitazoxanide (100 mg) was used as the reference drug. After 3 weeks, the rats were sacrificed for postmortem examination and histopathological examination. Two blood samples/rat/group were collected on the 21st day. Ethylenediaminetetraacetic acid blood samples were also used for analysis of biochemistry, hematology, immunology, micronucleus prevalence, and chromosomal abnormalities. Results: C. camphora leaves yielded 28.5 ± 0.3 g/kg oil and 20 phycocompounds were identified. Spherical and rod-shaped particles were detected at 10.47–30.98 nm and 18.83–38.39 nm, respectively. ZnNPs showed the earliest anti-cryptosporidiosis effect during 7–17 d PI. Other hematological, biochemical, immunological, histological, and genotoxicity parameters were significantly fruitful; hence, normalized pathological changes induced by infestation were observed in the NPs treatments groups against the infestation-free and Nitazoxanide treated group. Conclusion: C. camphora, U. fasciata, ZnNPs, and AgNPs have refluxed the pathological effects of infection as well as positively improved host physiological condition by its anticryptosporidial immunostimulant regenerative effects with sufficient ecofriendly properties to be proposed as an alternative to traditional drugs, especially in individuals with medical reactions against chemical commercial drugs

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Monitoring the fluctuations of certain piercin sucking pests infesting cucumber plants at Sohag governorate, Egypt

The population fluctuations of five piercingsucking pests; melon aphid, Aphis gossypii (Glover); cotton whitefly, Bemisia tabaci (Genn.); potato leafhopper, Empoasca decipiens (Paoli); onion thrips, Thrips tabaci (Lind.) and two-spotted spider mite, Tetranychus urticae (Koch) were investigated on Hail cucumber variety during autumn and spring plantation from 2014 to 2016 seasons. As a result in autumn plantation, population of aphid and whitefly had one peak during 2014 and 2015 seasons , meanwhile, thrips population recorded three peaks in the same seasons. Otherwise, in spring plantationin 2015 and 2016 seasons, the populations of aphid and thrips recorded three peaks and one peak, respectively. In the meantime, the whitefly’s population showed three and two peaks, respectively. Leafhopper was the lowest sucking insect attacked cucumber during the two plantations throughout 2014, 2015 and 2016 growing seasons. The two-spotted spider mite only observed on spring plantation 2015 and 2016 and recorded one peak through the growing seasons. It could be concluded that planting date is effective on population fluctuations of piercing sucking pest and can be avoided by planting in late planting date

Chemical composition of rain water in Antwerp, Belgium

Abstract Understanding pediatric brain tumor biology is essential to help on disease stratification, and to find novel markers for early diagnosis. MicroRNA (miRNA) expression has been linked to clinical outcomes and tumor biology. Here, we aimed to detect the expression of different miRNAs in different pediatric brain tumor subtypes to discover biomarkers for early detection and develop novel therapies. Expression of 82 miRNAs was detected in 120 pediatric brain tumors from fixed-formalin paraffin-embedded tissues, low-grade glioma, high-grade glioma, ependymoma, and medulloblastoma, using quantitative real-time PCR. Low-expression of miR-221, miR-9, and miR-181c/d and over-expression of miR-101, miR-222, miR-139, miR-1827, and miR-34c was found in medulloblastoma; low expression of miR-10a and over-expression of miR-10b and miR-29a in ependymoma; low expression of miR-26a and overexpression of miR-19a/b, miR-24, miR-27a, miR- 584, and miR-527 in low-grade glioma. Cox regression showed differential miRNA expression between responders and non-responders. The most specific were miR-10a and miR-29a low expression in LGG non-responders, miR-135a and miR-146b over-expression in ependymoma non-responders, and miR-135b overexpression in medulloblastoma non-responders. MicroRNAs are differentially expressed in subtypes of brain tumors suggesting that they may help diagnosis. A greater understanding of aberrant miRNA in pediatric brain tumors may support development of novel therapies

Serum levels of Interleukin-33 and its soluble receptor ST2 in asthmatic patients

Interleukin-33 is a member of IL-1 family of cytokines and binds to two receptors: ST2 (IL-1-R1) and IL-1 receptor accessory protein (IL-1RAP). There are two isoforms of ST2 proteins: ST2L, a transmembrane form, and a soluble ST2 (sST2), a secreted form, that can serve as a decoy receptor of IL-33. The IL-33/ST2 signaling pathway activates airway eosinophils that exacerbate airway inflammation. The aim of this study was to analyze the serum level of IL-33 and its receptor sST2 in patients with bronchial asthma to assess if the serum level of IL-33 and/or sST2 may be a marker of the disease severity and potential therapeutic targets. Patients and methods: This study was carried out at the Microbiology & Immunology and Chest departements, Faculty of Medicine, Zagazig University Hospitals during the period from December 2012 to September 2013. The study included 30 patients diagnosed as bronchial asthma according to GINA 2012. Patients were classified into two groups: Group I: included 15 patients 8 males and 7 females with a mean age 36.2 ± 15.8 during exacerbation of bronchial asthma. Group 2: included 15 patients 8 male and 7 female with mean age 37.3 ± 12.8. They were stable asthmatic patients and the last exacerbation was one month ago. There were 30 normal healthy persons as a control group. All patients were subjected to, full medical history, general and local examination, Plain chest X-ray PA and lateral views, pulmonary function tests, Liver and kidney function tests, intradermal skin test, skin prick test, measurement of serum levels of IL-33 (WEKA MED), IL-33 Receptor (soluble ST2) (OmniKine) and total IgE (IMMUNOSPEC) by enzyme linked immunosorbent technique using commercial kits. Results: There was a highly significant increase in the serum level of IL-33 in both groups of patients (p1 < 0.001) with the highest level 960 ± 336 ng/ml in group 1 followed by 732.2 ± 68.3 ng/ml in group 2 while the normal control group serum level was 174 ± 41 ng/ml. As regards serum level of sST2, there was a highly significant increase in its level in both groups of patients (p1 < 0.001) with the highest level 96.8 ± 25 μg/ml in group 1 followed by 83.3 ± 5.3 μg/ml in group 2 while the normal control group serum level was 33.9 ± 9.6 μg/ml. In acute exacerbated patients there was significant −ve correlation between FEV1 and serum level of both total IgE and IL-33 and in stable asthmatic patients there was high significant +ve correlation between PEFR variability and serum level of sST2. Conclusion: The serum levels of IL-33 and its receptor sST2 were markedly elevated in patients with bronchial asthma and this supports the concept of sST2 and Interleukin-33 as a therapeutic target in asthma

The impact of using ovarian-adnexal reporting data system magnetic resonance imaging (O-RADS MRI) score on risk stratification of sonographically indeterminate adnexal masses

Abstract Background Adnexal masses (AMs) are prevalent, leading to a substantial clinical effort including imaging for diagnosis, surgery, and pathology. Aim of the study The goal of this research was to evaluate the reliability of the Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) scale for diagnosing the sonographically indeterminate adnexal masses and to discriminate between malignant and benign ones using the O-RADS MRI scoring system. Methods This study included 72 cases with indeterminate adnexal masses in any age group. We excluded patients with previous history of operated adnexal lesion and patients who had contraindications for MRI as pacemakers or iron clips. Results Based on O-RADS MRI score, 44.4% of masses were diagnosed as O-RADS II indicating that they were almost certainly benign, 11.1% as O-RADS III indicating low risk malignancy, 8.3% as O-RADS IV indicating intermediate risk malignancy and 36.1% were diagnosed as O-RADS V indicating high risk malignancy. O-RADS MRI score for malignancy gave sensitivity of 92.31% (95%CI 63.97–99.81), specificity of 82.61% (95%CI 61.22–95.05), PPV of 75% (95%CI 54.84–88.11) and NPV of 95% (95%CI 74.12–99.21) with an overall accuracy of 86.11% (95%CI 70.50–95.33). Conclusions The O-RADS MRI score has excellent accuracy and validity in determining whether an AM is malignant or benign. Using this score in clinical practice may enable a tailored, patient-centered approach for masses that are sonographically indeterminate, avoiding unnecessary surgery, and in certain cases allows less extensive surgery, or even fertility preservation when appropriate

Differential Expression of Circulating miRNAs and Carfilzomib-Related Cardiovascular Adverse Events in Patients with Multiple Myeloma

This study investigates the association between circulating microRNA (miRNA) expression and cardiovascular adverse events (CVAE) in multiple myeloma (MM) patients treated with a carfilzomib (CFZ)-based regimen. A cohort of 60 MM patients from the Prospective Observation of Cardiac Safety with Proteasome Inhibitor (PROTECT) study was analyzed. Among these, 31 patients (51.6%) developed CVAE post-CFZ treatment. The Taqman OpenArray Human microRNA panels were used for miRNA profiling. We identified 13 differentially expressed miRNAs at baseline, with higher expressions of miR-125a-5p, miR-15a-5p, miR-18a-3p, and miR-152-3p and lower expression of miR-140-3p in patients who later developed CVAE compared to those free of CVAE, adjusting for age, gender, race, and higher B-type natriuretic peptide levels. We also identified three miRNAs, including miR-150-5p, that were differentially expressed in patients with and without CVAE post-treatment. Additionally, five miRNAs responded differently to CFZ treatment in CVAE vs. non-CVAE patients, including significantly elevated post-treatment expression of miR-140-3p and lower expressions of miR-598, miR-152, miR-21, and miR-323a in CVAE patients. Pathway enrichment analysis highlighted the involvement of these miRNAs in cardiovascular diseases and vascular processes. These findings suggest that specific miRNAs could serve as predictive biomarkers for CVAE and provide insights into the underlying mechanisms of CFZ-CVAE. Further investigation is warranted before these findings can be applied in clinical settings

Comorbidity of depression and anxiety with obstructive sleep apnea in a sample of Egyptian patients

Abstract Background Over the past 2 decades, sleep researchers have made significant advances in understanding sleep disorders including obstructive sleep apnea (OSA). OSA commonly coexists with psychiatric disorders encompassing mental health issues like depression, anxiety, bipolar, schizophrenia an others. This study aims to assess the comorbidity of OSA with depression and anxiety disorders among Egyptian patients. During the study, we conducted a cross-sectional study involving 92 adults diagnosed with OSA. Those patients were interviewed using a checklist to gather information regarding their chief complaints and other associated symptoms. The psychological status was assessed utilizing the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID I), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) scoring. The severity of the breathing disorder was classified as mild, moderate, or severe based on the respiratory disturbance index (RDI), which was confirmed through overnight polysomnography. Daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). Results The sample of patients as a whole shows that witnessed apneas represent the highest percentage (70.7%), followed by fatigue (69.6%), then non-refreshing sleep (67.4%), and snores (63.0%). The least frequent presenting symptom is frequent naps. The majority of OSA patients have a comorbid psychiatric disorder (65.0%). Among these, depressive disorders are the most prevalent (31.5%), followed by anxiety disorders (23.9%) and psychoses (6.5%). It is worth noting that 38% of OSA patients do not have any psychiatric disorders. In terms of anxiety disorders, the most common subtype observed is OCD (8.7%), followed by GAD (6.5%), panic (5%), and PTSD (3.3%). As regards depressive disorders, the predominant subtype present is depressive disorder not otherwise specified (11.9%), followed by dysthymic disorder and major depressive disorder (8.7% for each), and then bipolar disorder (depression) at 2.2%. Conclusions We conclude the following: 1. OSA patients are likely to present with comorbid depression and/or anxiety disorder(s). 2. Fatigue was found to be the most prevalent presenting symptom in OSA patients with comorbid anxiety compared to those without anxiety