Artificial intelligence-based locoregional markers of brain peritumoral microenvironment.

In malignant primary brain tumors, cancer cells infiltrate into the peritumoral brain structures which results in inevitable recurrence. Quantitative assessment of infiltrative heterogeneity in the peritumoral region, the area where biopsy or resection can be hazardous, is important for clinical decision making. Here, we derive a novel set of Artificial intelligence (AI)-based markers capturing the heterogeneity of tumor infiltration, by characterizing free water movement restriction in the peritumoral region using Diffusion Tensor Imaging (DTI)-based free water volume fraction maps. We leverage the differences in the peritumoral region of metastasis and glioblastomas, the former consisting of vasogenic versus the latter containing infiltrative edema, to extract a voxel-wise deep learning-based peritumoral microenvironment index (PMI). Descriptive characteristics of locoregional hubs of uniformly high PMI values are then extracted as AI-based markers to capture distinct aspects of infiltrative heterogeneity. The proposed markers are utilized to stratify patients' survival and IDH1 mutation status on a population of 275 adult-type diffuse gliomas (CNS WHO grade 4). Our results show significant differences in the proposed markers between patients with different overall survival and IDH1 mutation status (t test, Wilcoxon rank sum test, linear regression; p < 0.01). Clustering of patients using the proposed markers reveals distinct survival groups (logrank; p < 10-5, Cox hazard ratio = 1.82; p < 0.005). Our findings provide a panel of markers as surrogates of infiltration that might capture novel insight about underlying biology of peritumoral microstructural heterogeneity, providing potential biomarkers of prognosis pertaining to survival and molecular stratification, with applicability in clinical decision making.

3D-QCNet - A pipeline for automated artifact detection in diffusion MRI images.

Artifacts are a common occurrence in Diffusion MRI (dMRI) scans. Identifying and removing them is essential to ensure the accuracy and viability of any post-processing carried out on these scans. This makes quality control (QC) a crucial first step prior to any analysis of dMRI data. Several QC methods for artifact detection exist, however they suffer from problems like requiring manual intervention and the inability to generalize across different artifacts and datasets. In this paper, we propose an automated deep learning (DL) pipeline that utilizes a 3D-Densenet architecture to train a model on diffusion volumes for automatic artifact detection. Our method is validated on 9000 volumes sourced from 7 large clinical datasets spanning different acquisition protocols (with different gradient directions, high and low b-values, single-shell and multi-shell acquisitions) from multiple scanners. Additionally, they represent diverse subject demographics including age, sex and the presence or absence of pathologies. Our QC method is found to accurately generalize across this heterogenous data by correctly detecting 92% artifacts on average across our test set. This consistent performance over diverse datasets underlines the generalizability of our method, which currently is a significant barrier hindering the widespread adoption of automated QC techniques. Thus, 3D-QCNet can be integrated into diffusion pipelines to effectively automate the arduous and time-intensive process of artifact detection.

Comparing depression, anxiety, and quality of life in individuals with cardiac and non-cardiac chest pain.

Background: Psychological factors are often overlooked as potential contributors to cardiovascular disease. This study aimed to investigate the relationship between depression, anxiety, and quality of life with chest pain origin. Method: This cross-sectional study was performed from 2019 to 2020 and included participants from multiple medical centers across Shahrekord, Iran. Participants were recruited through advertisements in medical centers. Participants were divided into three groups: healthy control (n = 67), chest pain with cardiac origin (CCP) (n = 70), and chest pain with non-cardiac origin (NCCP) (n = 73). Data were collected using the Beck's Anxiety scale, Beck's Depression scale, and Short-Form Health Survey questionnaires. The chi-square, exact test, t-test, Kruskal-Wallis, and logistic regression models were used for statistical analysis. All analysis was performed using SPSS 26. Results: The mean scores of depression and anxiety in the NCCP group (depression = 17.03 ± 11.93, anxiety = 17.18 ± 11.37) were significantly higher than those in the CCP (depression = 9.73 ± 5.76, anxiety = 8.77 ± 5.96) and healthy (depression = 7.00 ± 7.61, anxiety = 6.18 ± 7.63) groups (p < 0.05). The mean score of quality of life in the NCCP group (54.87 ± 12.66) was significantly lower than that in the CCP (76.31 ± 12.49) and healthy (80.94 ± 15.78) groups (p < 0.05). Patients with NCCP had higher odds of having depression (adjusted OR = 4.39, 95% CI: 1.25, 15.35) and lower odds for having mental quality of life scores than the CCP and health groups, respectively (adjusted OR = 0.90, 95% CI: 0.87, 0.94). Conclusion: Our findings suggest that collaboration between psychiatrists and other specialists may be necessary to improve patients' health conditions and quality of life.

Distinct tumor signatures using deep learning-based characterization of the peritumoral microenvironment in glioblastomas and brain metastases.

Tumor types are classically distinguished based on biopsies of the tumor itself, as well as a radiological interpretation using diverse MRI modalities. In the current study, the overarching goal is to demonstrate that primary (glioblastomas) and secondary (brain metastases) malignancies can be differentiated based on the microstructure of the peritumoral region. This is achieved by exploiting the extracellular water differences between vasogenic edema and infiltrative tissue and training a convolutional neural network (CNN) on the Diffusion Tensor Imaging (DTI)-derived free water volume fraction. We obtained 85% accuracy in discriminating extracellular water differences between local patches in the peritumoral area of 66 glioblastomas and 40 metastatic patients in a cross-validation setting. On an independent test cohort consisting of 20 glioblastomas and 10 metastases, we got 93% accuracy in discriminating metastases from glioblastomas using majority voting on patches. This level of accuracy surpasses CNNs trained on other conventional DTI-based measures such as fractional anisotropy (FA) and mean diffusivity (MD), that have been used in other studies. Additionally, the CNN captures the peritumoral heterogeneity better than conventional texture features, including Gabor and radiomic features. Our results demonstrate that the extracellular water content of the peritumoral tissue, as captured by the free water volume fraction, is best able to characterize the differences between infiltrative and vasogenic peritumoral regions, paving the way for its use in classifying and benchmarking peritumoral tissue with varying degrees of infiltration.

Parasite-derived microRNAs as a diagnostic biomarker: potential roles, characteristics, and limitations.

MicroRNAs (miRNAs), a subclass of small regulatory RNAs that present from ancient unicellular protozoans to parasitic helminths and parasitic arthropods. MiRNAs' mode of action has attracted wide attention as a result of their unique functional importance. MiRNAs play a role in diverse physiological and pathological processes ranging from organ development, immune function to apoptosis and cancer at the post-transcription gene expression. Thus, miRNAs are known to be targets for clinical treatment and therapy. The discovery of the high stability of circulating miRNA in various types of host body fluids, such as whole blood, serum, plasma, saliva, and urine has increased great interest among researchers in the potential of circulating miRNA as a prognosis/diagnosis of infectious. Some circulating miRNAs biomarkers advanced to clinical applications related to human diseases. However, this idea starts to come only in the fields of infectious disease. The goal of this review is to enhance the current understanding of these molecules and their applicability in the field of medicine. A detailed review of the available literature consulting tools performed in online repositories such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate. This review summarizes an overview of preclinical studies using circulating miRNAs biomarkers against infectious diseases affecting humans. The use of miRNA as a safe and potential tool is encouraging news, considering that until now, guidelines for the use of miRNA in clinical practice are still lacking.

QC-Automator: Deep Learning-Based Automated Quality Control for Diffusion MR Images.

Quality assessment of diffusion MRI (dMRI) data is essential prior to any analysis, so that appropriate pre-processing can be used to improve data quality and ensure that the presence of MRI artifacts do not affect the results of subsequent image analysis. Manual quality assessment of the data is subjective, possibly error-prone, and infeasible, especially considering the growing number of consortium-like studies, underlining the need for automation of the process. In this paper, we have developed a deep-learning-based automated quality control (QC) tool, QC-Automator, for dMRI data, that can handle a variety of artifacts such as motion, multiband interleaving, ghosting, susceptibility, herringbone, and chemical shifts. QC-Automator uses convolutional neural networks along with transfer learning to train the automated artifact detection on a labeled dataset of ∼332,000 slices of dMRI data, from 155 unique subjects and 5 scanners with different dMRI acquisitions, achieving a 98% accuracy in detecting artifacts. The method is fast and paves the way for efficient and effective artifact detection in large datasets. It is also demonstrated to be replicable on other datasets with different acquisition parameters.

Cross-platform and cross-interaction study of user personality based on images on Twitter and Flickr.

Assessing the predictive value of different social media platforms is important to understand the variation in how users reveal themselves across multiple platforms. Most social media platforms allow users to interact in multiple ways: by posting content to the platform, liking others' posts, or building a user profile. While prior studies offer insights into how language use differs across platforms, differences in image usage is less well understood. In this study, we analyzed variation in image content with user personality across three interaction types (posts, likes and profile images) and two platforms, using a unique data set of users who are active on both Twitter and Flickr. Usage patterns on these two social media platforms revealed different aspects of users' personality. Cross-platform data fusion is thus shown to improve personality prediction performance.

Relationship of SNP rs2645429 in Farnesyl-Diphosphate Farnesyltransferase 1 Gene Promoter with Susceptibility to Lung Cancer.

BACKGROUND AND PURPOSE: The mevalonate pathway is one of the major metabolic pathways that use acetyl-CoA to produce sterols and isoprenoids. These compounds can be effective in the growth and development of tumors. One of the enzymes involved in the mevalonate pathway is FDFT1. Different variants of this gene are involved in the risk of suffering various diseases. The present study examined the relationship between FDFT1 rs2645429 polymorphism and the risk of nonsmall cell lung cancer (NSCLC) in a population from southern Iran. METHOD: The genotypes of rs2645429 polymorphism of FDFT1 gene were examined in 95 samples: 34 patients with NSCLC and 61 healthy individuals by RFLP method. RESULTS: The results of this study indicated that C allele of this polymorphism was effectively associated with the risk of NSCLC in the Iranian population (p value = 0.023; OR = 2.71; 95% CI = 1.12-6.59) and CC genotype has significant relation with susceptibility to NSCLC (p value = 0.029; OR = 3.02; 95% CI = 1.09-8.39). This polymorphism is located in the promoter region FDFT1 gene, and CC genotype may increase the activity of this promoter. This study also found a significant relationship between C allele and metastatic status. C allele was more common in NSCLC patients. (p = 0.04). CONCLUSION: C allele of FDFT1 rs2645429 polymorphism gene can be a risk factor for NSCLC, whereas T allele probably has a low protective role.

Evaluation of altered expression of miR-9 and miR-106a as an early diagnostic approach in gastric cancer.

BACKGROUND: The role of microRNAs (miRNAs) in cellular processes such as growth, apoptosis, differentiation and proliferation verifies the importance of miRNAs in carcinogenesis. Moreover, levels of miRNAs are dysregulated in cancer cells, so they could be used as novel classes of biomarkers for diagnosing cancer. The oncogenic role of miR-106a and its increased expression have been demonstrated in some cancers. In contrast, there is no consensus for miR-9 expression rate in different cancers. Therefore, this study was done to investigate the role of miR-106a and miR-9 in gastric cancer (GC). METHODS: The current study was performed on 31 GC tissues as case, and 31 healthy adjacent tissues as a control group. Quantitative reverse transcriptase (q-RT) PCR was used for studying the expression rate of both miR-106a and miR-9. RESULTS: The expression rate of both miRNAs in cancerous tissues was significantly higher than healthy adjacent tissues (≈10 folds) (P<0.05). CONCLUSIONS: The results showed that the expression rate of both markers was significantly increased in cancerous tissues. Therefore, they can be suggested as potential biomarkers for cancer diagnosis and prognosis as well as targets for therapy.

Evaluation of miR-22 and miR-20a as diagnostic biomarkers for gastric cancer.

BACKGROUND: Gastric cancer (GC) is the fourth most common cancers and the second reason for cancer-related death around the world, particularly in East Asian countries. Diagnosing GC in its early stages is followed by more successful treatment. Unfortunately, there is no accurate method for GC diagnosis in its early stages. Recently, miRNAs have been investigated in the most cancer researches which have demonstrated that they have been dysregulated in many cancers. METHODS: This case-control study aims to investigate the expression rate of miR-22 and miR-20a in 32 cancerous tissues as well as 32 healthy adjacent tissues. Quantitative reverse transcriptase PCR (q-RT PCR) was used for investigating the expression rate of these miRNAs. RESULTS: The expression rate of miR-20a in cancerous tissues was significantly increased (8.9 times) in comparison with their healthy tissues (P<0.001), while the expression rate of miR-22 in cancerous tissues was significantly decreased (1.9 times) (P<0.05). CONCLUSIONS: The obtained results suggest miR-22 and miR-20a as good diagnostic biomarkers for early detection of GC. However more research is needed to investigate their efficacy.

The effect of age and clinical circumstances on the outcome of red blood cell transfusion in critically ill patients.

INTRODUCTION: Whether red blood cell (RBC) transfusion is beneficial remains controversial. In both retrospective and prospective evaluations, transfusion has been associated with adverse, neutral, or protective effects. These varying results likely stem from a complex interplay between transfusion, patient characteristics, and clinical context. The objective was to test whether age, comorbidities, and clinical context modulate the effect of transfusion on survival. METHODS: By using the multiparameter intelligent monitoring in intensive care II database (v. 2.6), a retrospective analysis of 9,809 critically ill patients, we evaluated the effect of RBC transfusion on 30-day and 1-year mortality. Propensity score modeling and logistic regression adjusted for known confounding and assessed the independent effect of transfusion on 30-day and 1-year mortality. Sensitivity analysis was performed by using 3,164 transfused and non-transfused pairs, matched according the previously validated propensity model for RBC transfusion. RESULTS: RBC transfusion did not affect 30-day or 1-year mortality in the overall cohort. Patients younger than 55 years had increased odds of mortality (OR, 1.71; P < 0.01) with transfusion. Patients older than 75 years had lower odds of 30-day and 1-year mortality (OR, 0.70; P < 0.01) with transfusion. Transfusion was associated with worse outcome among patients undergoing cardiac surgery (OR, 2.1; P < 0.01). The propensity-matched population corroborated findings identified by regression adjustment. CONCLUSION: A complex relation exists between RBC transfusion and clinical outcome. Our results show that transfusion is associated with improved outcomes in some cohorts and worse outcome in others, depending on comorbidities and patient characteristics. As such, future investigations and clinical decisions evaluating the value of transfusion should account for variations in baseline characteristics and clinical context.

Myocarditis complicating Plasmodium vivax malaria.

Myocarditis complicating Plasmodium vivax malaria is an extremely rare complication. We report this development in a young girl who was diagnosed to have P. vivax malaria on the basis of peripheral smear. While undergoing antimalarial treatment, she developed respiratory distress requiring invasive mechanical ventilation and inotropic support due to cardiogenic shock secondary to myocarditis. Cardiovascular complications are well recognized with Plasmodium falciparum malaria. Nevertheless, a high index of suspicion should be maintained for the same in Plasmodium vivax infection especially if symptoms of heart failure develop in a young patient.

Pseudomonas necrotizing fasciitis in an otherwise healthy infant.

Necrotizing fasciitis is an uncommon rapidly progressing infection of soft tissue characterized by a severe inflammation of the fascia and soft tissue. The disease is associated with necrosis and subcutaneous gangrene of the inflamed tissue with systemic toxicity that carries a significant mortality unless timely diagnosed and aggressively treated. Monomicrobial necrotizing fasciitis caused by Pseudomonas aeruginosa is an exceptionally uncommon condition with only few cases reported in the literature so far. We are reporting a six-month-old female infant who was previously healthy and who presented with necrotizing fasciitis and isolates Pseudomonas aeruginosa both from the blood and tissue. The child improved after the intensive treatment.

Good knowledge about hypertension is linked to better control of hypertension; a multicentre cross sectional study in Karachi, Pakistan.

BACKGROUND: According to the National Health survey only 3% of the population has controlled hypertension. This study was designed to elucidate the knowledge about hypertension in hypertensive patients at three tertiary care centers in Karachi. Secondly we sought to compare the knowledge of those with uncontrolled hypertension and controlled hypertension. METHODS: It was a cross-sectional study conducted at The Aga Khan University hospital (AKUH), Ziauddin Hospital (ZH) and Civil hospital, Karachi (CHK. All diagnosed Hypertensive patients (both inpatients and outpatients) coming to a tertiary care hospital in Pakistan aged > 18 years were included. Patients were categorized into 2 groups: controlled and uncontrolled hypertension based on their initial BP readings on presentation Uncontrolled Hypertension was defined as average BP ≥ 140/90 mm Hg in patients on treatment. Controlled Hypertension (HTN) was defined as average BP <140/90 mm Hg in patients on treatment. Standardized methods were used to record BP in the sitting position. Knowledge was recorded as a15 item question. Primary outcome was knowledge about hypertension. RESULTS: A total of 650 participants were approached and consented 447 were found eligible. 284(63.5%) were from Aga Khan University, 101(22.6) from Dow University of health sciences and 62(13.9) were from Ziauddin University. Mean (SD) age of participants was 57.7(12) years, 50.1(224) were men. Controlled hypertension was present in 323(72.3) and uncontrolled hypertension was present in 124(27.4). The total mean (SD) Knowledge score was 20.97(4.93) out of a maximum score of 38. On comparison of questions related to knowledge between uncontrolled and controlled hypertension, there was statistically significant different in; meaning of hypertension (p <0.001), target SBP(p0.001), target DBP(p 0.001), importance of SBP versus DBP, improvement of health with lowering of blood pressure (p 0.002), high blood pressure being asymptomatic (p <0.001), changing lifestyle improves blood pressure(p 0.003),hypertension being a lifelong disease (<0.001), lifelong treatment with antihypertensives(<0.001) and high blood pressure being part of aging(<0.001). On comparison of knowledge as a composite score between uncontrolled and controlled hypertensive; Mean (SD) score was 21.85(4.74) v18.67 (4.70) (p value: < 0.001). On multivariate analysis; gender ß (95% CI) 1.67(0.75, 2.59) p <0.001, uncontrolled blood pressure; -2.70(-3.76,-1.67) p <0.001, Sindhi ethnicity; -1.79(-3.25,-3.27) p 0.01 and pukhtoon ethnicity; -2.72(-4.13,-1.32) p <0.001 were significantly associated with knowledge score. CONCLUSION: Knowledge about hypertension in hypertensive patients is not adequate and is alarmingly poor in patients with uncontrolled hypertension. More emphasis needs to be made on target blood pressure and need for taking antihypertensives for life to patients by physicians.

Knowledge, Attitude and Practice of Vitamin Supplementation among Patients visiting Out-Patient Physicians in a Teaching Hospital in Karachi.

OBJECTIVE: To determine the knowledge, attitude and practices regarding the use of vitamin supplements among patients visiting Out-Patient clinics of a teaching hospital. METHODS: Four hundred patients were interviewed during the period of July to September 2008, at the Out-patient clinics, Aga Khan University hospital, Karachi. A pre-tested and structured questionnaire was used to collect information. It consisted of questions regarding demographics, awareness of vitamin supplements and its consumption, reasons for usage and its effects. The purpose of the study was explained and assurance of confidentiality was given. After obtaining written consent, eligible individuals were interviewed. Statistical Package for the Social Sciences version 19.0 was used to analyze the data. RESULTS: The results revealed that 98% of the respondents were aware of vitamin supplements. The most known vitamin was found to be Vitamin C (16.9%) with Vitamin K being the least well-known (0.4%); while 51.8% of the respondents were unaware of the harmful effects of vitamin supplements. The results also showed that 84.8% of the study population had taken vitamin supplements, and 79% of the participants considered that vitamin supplements to be helpful. Taking vitamin supplements as a compensation for the deficiencies in the body was the most frequently chosen answer (17.7%) as the reason for use of vitamin supplements. On the other hand, a majority of the population was unaware of the indications for use of vitamin supplements. CONCLUSION: This study highlights a very significant yet ignored issue of vitamin supplementation in Pakistan. A need exists to inform the general population about the use of vitamin supplementation. The media and the medical community are required to play their role in this regard. Short/ refresher training courses are needed for doctors to update and disseminate adequate knowledge of vitamin supplementation to their patients.

Knowledge of asthma management by general practitioners in Karachi, Pakistan: comparison with international guidelines.

BACKGROUND: Suboptimal management of asthma by general practitioners (GPs) can lead to poor health outcomes AIMS: To assess the management of common asthma presentations by GPs using the Global Initiative for Asthma (GINA) guidelines as a comparative tool. METHODS: A cross-sectional survey was conducted in Karachi, Pakistan. Of 250 GPs approached, 192 completed a self-administered questionnaire regarding pathology, key history points, risk factors, diagnosis, and management of asthma. RESULTS: Overall, 28.6% of GPs had adequate knowledge of the core concepts of asthma, while only 10.4% had adequate practice in asthma management. About 78% of GPs had inadequate knowledge of pathology, about 90% had inadequate knowledge of medications to be used, and 63% had inadequate knowledge regarding diet restrictions. Knowledge regarding symptoms not usually associated with asthma was adequate, as was knowledge regarding non-pharmacological management (79% each). Practices regarding asthma diagnosis were good (99.0%). However, practices regarding acute exacerbations and patients who wish to exercise were inadequate in 85.9% and 82.8% of GPs, respectively. CONCLUSIONS: The majority of GPs had poor knowledge and practice of asthma. We recommend initiation of programmes to improve their knowledge and practices.

Correlation of circulating omentin-1 with bone mineral density in multiple sclerosis: the crosstalk between bone and adipose tissue.

BACKGROUND: Patients with multiple sclerosis (MS) are at increased risk of osteoporosis and fractures. Adipose tissue-derived adipokines may play important roles in the osteoimmunology of MS. In order to determine whether omentin-1 and vaspin may be related to bone health in MS patients, we compared circulating levels of these recently identified adipokines, between MS patients and healthy controls. METHODS: A total of 35 ambulatory MS patients with relapsing-remitting courses were compared with 38 age- and sex-matched healthy controls. Bone mineral density (BMD) was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy x-ray absorptiometry. Circulating omentin-1, vaspin, osteocalcin, osteopontin, osteoprotegerin, the receptor activator of nuclear factor-κB ligand, matrix metalloproteinase 9, C-reactive protein and 25-hydroxy vitamin D levels were evaluated by highly specific enzyme-linked immunosorbent assay methods. RESULTS: There was no significant difference between the two groups regarding bone-related cytokines, adipocytokines, and the BMD measurements of patients with MS and the healthy controls. However, in multiple regression analysis, serum omentin-1 levels were positively correlated with BMD at the femoral neck (ß = 0.49, p = 0.016), total hip (ß = 0.42, p = 0.035), osteopontin (ß = 0.42, p = 0.030) and osteocalcin (ß = 0.53, p = 0.004) in MS patients. No correlations were found between vaspin, biochemical, and BMD measures in both groups. CONCLUSIONS: Elevated omentin-1 serum levels are correlated with BMD at the femoral neck and the serum levels of osteocalcin and osteopontin in MS patients. Therefore, there is crosstalk between adipose tissue and bone in MS.