Multi-parametric (ADC/PWI/T2-w) image fusion approach for accurate semi-automatic segmentation of tumorous regions in glioblastoma multiforme.

OBJECT: Glioblastoma multiforme (GBM) brain tumor is heterogeneous in nature, so its quantification depends on how to accurately segment different parts of the tumor, i.e. viable tumor, edema and necrosis. This procedure becomes more effective when metabolic and functional information, provided by physiological magnetic resonance (MR) imaging modalities, like diffusion-weighted-imaging (DWI) and perfusion-weighted-imaging (PWI), is incorporated with the anatomical magnetic resonance imaging (MRI). In this preliminary tumor quantification work, the idea is to characterize different regions of GBM tumors in an MRI-based semi-automatic multi-parametric approach to achieve more accurate characterization of pathogenic regions. MATERIALS AND METHODS: For this purpose, three MR sequences, namely T2-weighted imaging (anatomical MR imaging), PWI and DWI of thirteen GBM patients, were acquired. To enhance the delineation of the boundaries of each pathogenic region (peri-tumoral edema, viable tumor and necrosis), the spatial fuzzy C-means algorithm is combined with the region growing method. RESULTS: The results show that exploiting the multi-parametric approach along with the proposed semi-automatic segmentation method can differentiate various tumorous regions with over 80 % sensitivity, specificity and dice score. CONCLUSION: The proposed MRI-based multi-parametric segmentation approach has the potential to accurately segment tumorous regions, leading to an efficient design of the pre-surgical treatment planning.

Metformin Treatment Leads to Increased HIV Transcription and Gene Expression through Increased CREB Phosphorylation and Recruitment to the HIV LTR Promoter.

Antiretroviral therapy has effectively suppressed HIV infection and replication and prolonged the lifespan of HIV-infected individuals. In the meantime, various complications including type 2 diabetes associated with the long-term antiviral therapy have shown steady increases. Metformin has been the front-line anti-hyperglycemic drug of choice and the most widely prescribed medication for the treatment of type 2 diabetes. However, little is known about the effects of Metformin on HIV infection and replication. In this study, we showed that Metformin treatment enhanced HIV gene expression and transcription in HIV-transfected 293T and HIV-infected Jurkat and human PBMC. Moreover, we demonstrated that Metformin treatment resulted in increased CREB expression and phosphorylation, and TBP expression. Furthermore, we showed that Metformin treatment increased the recruitment of phosphorylated CREB and TBP to the HIV LTR promoter. Lastly, we showed that inhibition of CREB phosphorylation/activation significantly abrogated Metformin-enhanced HIV gene expression. Taken together, these results demonstrated that Metformin treatment increased HIV transcription, gene expression, and production through increased CREB phosphorylation and recruitment to the HIV LTR promoter. These findings may help design the clinical management plan and HIV cure strategy of using Metformin to treat type 2 diabetes, a comorbidity with an increasing prevalence, in people living with HIV.

Infected Ruptured Pseudo-aneurysm in Descending Aorta; a Case Report.

Aortitis is the inflammation of the aortic wall. It can be caused by both infectious and non-infectious etiologies. Mycotic aneurysm is a rare, serious medical condition and typically requires prompt treatment with antibiotics, surgical intervention, or endovascular procedures to prevent rupture and complications. Here we reported, a 66-year-old male patient with a medical history of diabetes and hypertension, who presented to the emergency department (ED) with left-sided hemiplegia. Brain magnetic resonance imaging (MRI) revealed infarction in the right parietooccipital and left occipital lobes, demonstrating an embolic pattern. laboratory analysis revealed elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell (WBC). In order to investigate the possibility of sepsis, a non-contrast chest computed tomography (CT) scan was performed, which showed a soft tissue density surrounded by gas in the posterior mediastinum; for which the rupture of esophagus and infected aorta pseudoaneurysm were among differential diagnoses. To confirm the diagnosis, CT angiography was ordered. The infected ruptured pseudo-aneurysm(s) was confirmed and patient underwent thoracotomy surgery.

Radiofrequency ablation of osteoid osteoma at the base of the coracoid process: Report of two cases.

If you encounter an unexplained case of bone marrow edema in a young patient, consider the possibility of osteoid osteoma (OO). Even in the presence of a nidus near vital structures, RFA can safely be used to treat OO.

A rare case report of heterotopic cesarean scar pregnancy in the 8th week of gestation that was managed successfully by exploratory laparotomy with dilation and curettage.

Key Clinical Message: Swift and precise identification of heterotopic cesarean scar pregnancy, coupled with standardized treatment approaches for handling possible serious complications, form an essential component in reaching favorable outcomes for patients experiencing this rare type of pregnancy. Abstract: Heterotopic pregnancy (HP) denotes a form of multiple gestation where intrauterine and ectopic pregnancies coexist. Cesarean scar ectopic pregnancy, on the other hand, involves the implantation of a fetus over the previous cesarean scar. This condition poses a significant risk of uterine rupture, which may lead to serious health complications, and even death. We report a case of a fit 37-year-old woman with two previous cesarean deliveries who was diagnosed with a heterotopic cesarean scar pregnancy at 8 weeks gestation following symptoms of lower abdominal pain and delayed menstruation. Both pregnancies demonstrated cardiac activity and the portion of the myometrium located between the bladder wall and the gestational sac was noted to exhibit considerable thinness. The patient underwent an exploratory laparotomy coupled with dilation and curettage and recovered uneventfully. The proper management of a HCSP requires timely diagnosis through ultrasonography. Early diagnosis allows for immediate intervention to prevent complications such as uterine rupture or potentially lethal bleeding.

Effect of spaceflight experience on human brain structure, microstructure, and function: systematic review of neuroimaging studies.

Spaceflight-induced brain changes have been commonly reported in astronauts. The role of microgravity in the alteration of the brain structure, microstructure, and function can be tested with magnetic resonance imaging (MRI) techniques. Here, we aim to provide a comprehensive overview of Spaceflight studies exploring the potential role of brain alterations identified by MRI in astronauts. We conducted a search on PubMed, Web of Science, and Scopus to find neuroimaging correlates of spaceflight experience using MRI. A total of 20 studies (structural MRI n = 8, diffusion-based MRI n = 2, functional MRI n = 1, structural MRI and diffusion-weighted MRI n = 6, structural MRI and functional MRI n = 3) met our inclusion criteria. Overall, the studies showed that regardless of the MRI techniques, mission duration significantly impacts the human brain, prompting the inclusion of various brain regions as features in the analyses. After spaceflight, notable alterations were also observed in the superior occipital gyrus and the precentral gyrus which show alterations in connectivity and activation during spaceflight. The results provided highlight the alterations in brain structure after spaceflight, the unique patterns of brain remodeling, the challenges in drawing unified conclusions, and the impact of microgravity on intracranial cerebrospinal fluid volume.

Language Abnormalities in Alzheimer's Disease Arise from Reduced Informativeness: A Cross-Linguistic Study in English and Persian.

INTRODUCTION: This research investigates the psycholinguistic origins of language impairments in Alzheimer's Disease (AD), questioning if these impairments result from language-specific structural disruptions or from a universal deficit in generating meaningful content. METHODS: Cross-linguistic analysis was conducted on language samples from 184 English and 52 Persian speakers, comprising both AD patients and healthy controls, to extract various language features. Furthermore, we introduced a machine learning-based metric, Language Informativeness Index (LII), to quantify informativeness. RESULTS: Indicators of AD in English were found to be highly predictive of AD in Persian, with a 92.3% classification accuracy. Additionally, we found robust correlations between the typical linguistic abnormalities of AD and language emptiness (low LII) across both languages. DISCUSSION: Findings suggest AD linguistics impairments are attributed to a core universal difficulty in generating informative messages. Our approach underscores the importance of incorporating biocultural diversity into research, fostering the development of inclusive diagnostic tools.

Theranostics in targeting fibroblast activation protein bearing cells: Progress and challenges.

Cancer cells are surrounded by a complex and highly dynamic tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), a critical component of TME, contribute to cancer cell proliferation as well as metastatic spread. CAFs express a variety of biomarkers, which can be targeted for detection and therapy. Most importantly, CAFs express high levels of fibroblast activation protein (FAP) which contributes to progression of cancer, invasion, metastasis, migration, immunosuppression, and drug resistance. As a consequence, FAP is an attractive theranostic target. In this review, we discuss the latest advancement in targeting FAP in oncology using theranostic biomarkers and imaging modalities such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), computed tomography (CT), fluorescence imaging, and magnetic resonance imaging (MRI).

Impact of Region-of-Interest Delineation on Stability and Reproducibility of Liver SNR Measurements in 68 Ga-PSMA PET/CT.

Objective This study aims to assess the impact of various regions of interest (ROIs) and volumes of interest (VOIs) delineations on the reproducibility of liver signal-to-noise-ratio (SNRliver) measurements, as well as to find the most reproducible way to estimate it in gallium-68 positron emission tomography ( 68 Ga-PET) imaging. We also investigated the SNRliver-weight relationship for these ROIs and VOIs delineations. Methods A cohort of 40 patients (40 males; mean weight: 76.5 kg [58-115 kg]) with prostate cancer were included. 68 Ga-PET/CT imaging (mean injected activity: 91.4 MBq [51.2 MBq to 134.1 MBq] was performed on a 5-ring bismuth germanium oxide-based Discovery IQ PET/CT using ordered subset expectation maximization image reconstruction algorithm. Afterward, circular ROIs and spherical VOIs with two different diameters of 30 and 40 mm were drawn on the right lobe of the livers. The performance of the various defined regions was evaluated by the average standardized uptake value (SUV mean ), standard deviation (SD) of the SUV (SUV SD ), SNR liver , and SD of the SNR liver metrics. Results There were no significant differences in SUV mean among the various ROIs and VOIs ( p > 0.05). On the other hand, the lower SUV SD was obtained by spherical VOI with diameter of 30 mm. The largest SNR liver was obtained by ROI (30 mm). The SD of SNR liver with ROI (30 mm) was also the largest, while the lowest SD of SNR liver was observed for VOI (40 mm). There is a higher correlation coefficient between the patient-dependent parameter of weight and the image quality parameter of SNRliver for both VOI (30 mm) and VOI (40 mm) compared to the ROIs. Conclusion Our results indicate that SNR liver measurements are affected by the size and shape of the respective ROIs and VOIs. The spherical VOI with a 40 mm diameter leads to more stable and reproducible SNR measurement in the liver.

Correction: Identifying connectivity for two sympatric carnivores in human-dominated landscapes in central Iran.

[This corrects the article DOI: 10.1371/journal.pone.0269179.].

A review of caracal and jungle cat diets across their geographical ranges during 1842-2021.

Co-occurring carnivore species that are phylogenetically related or of similar size, morphology, and ecological needs often reduce competition by partitioning shared resources through temporal, spatial, and dietary niche segregation via behavioral adaptations. Caracals (Caracal caracal) and jungle cats (Felis chaus) co-occur in portions of their geographical ranges and are expected to display resource segregation in these ranges. We compiled scat, stomach content, and prey remains found data from published and unpublished sources to summarize information on the diets of caracals and jungle cats across their geographical ranges during 1842-2021. We obtained 63 sources from 26 countries in Europe, Asia, and Africa, in which caracal diet included 151 species while jungle cat diet included 61 species. We found that caracals and jungle cats did not exhibit dietary niche partitioning and had greater dietary similarities in areas of range overlap. We also found that caracals consumed more diverse prey species including prey with greater average body mass compared to jungle cats. Our results suggest that greater prey diversity in areas of range overlap, caracal predation on wide range of prey, and opportunistic feeding behavior that facilitates consumption of more diverse prey species compared to jungle cats, may facilitate co-occurrence between these two felid species.

Machine learning applied to functional magnetic resonance imaging in anxiety disorders.

BACKGROUND: Brain functional abnormalities have been commonly reported in anxiety disorders, including generalized anxiety disorder, social anxiety disorder, panic disorder, agoraphobia, and specific phobias. The role of functional abnormalities in the discrimination of these disorders can be tested with machine learning (ML) techniques. Here, we aim to provide a comprehensive overview of ML studies exploring the potential discriminating role of functional brain alterations identified by functional magnetic resonance imaging (fMRI) in anxiety disorders. METHODS: We conducted a search on PubMed, Web of Science, and Scopus of ML investigations using fMRI as features in patients with anxiety disorders. A total of 12 studies (resting-state fMRI n = 5, task-based fMRI n = 6, resting-state and task-based fMRI n=1) met our inclusion criteria. RESULTS: Overall, the studies showed that, regardless of the classifiers, alterations in functional connectivity and aberrant neural activation involving the amygdala, anterior cingulate cortex, hippocampus, insula, orbitofrontal cortex, temporal pole, cerebellum, default mode network, dorsal attention network, sensory network, and affective network were able to discriminate patients with anxiety from controls, with accuracies spanning from 36 % to 94 %. LIMITATIONS: The small sample size, different ML approaches and heterogeneity in the selection of regions included in the multivariate pattern analyses limit the conclusions of the present review. CONCLUSIONS: ML methods using fMRI as features can distinguish patients with anxiety disorders from healthy controls, indicating that these techniques could be used as a helpful tool for the diagnosis and the development of more targeted treatments for these disorders.

PI3K/Akt signaling in urological cancers: Tumorigenesis function, therapeutic potential, and therapy response regulation.

In addition to environmental conditions, lifestyle factors, and chemical exposure, aberrant gene expression and mutations involve in the beginning and development of urological tumors. Even in Western nations, urological malignancies are among the top causes of patient death, and their prevalence appears to be gender dependent. The prognosis for individuals with urological malignancies remains dismal and unfavorable due to the ineffectiveness of conventional treatment methods. PI3K/Akt is a popular biochemical mechanism that is activated in tumor cells as a result of PTEN loss. PI3K/Akt escalates growth and metastasis. Moreover, due to the increase in tumor cell viability caused by PI3K/Akt activation, cancer cells may acquire resistance to treatment. This review article examines the function of PI3K/Akt in major urological tumors including bladder, prostate, and renal tumors. In prostate, bladder, and kidney tumors, the level of PI3K and Akt are notably elevated. In addition, the activation of PI3K/Akt enhances the levels of Bcl-2 and XIAP, hence increasing the tumor cell survival rate. PI3K/Akt ] upregulates EMT pathways and matrix metalloproteinase expression to increase urological cancer metastasis. Furthermore, stimulation of PI3K/Akt results in drug- and radio-resistant cancers, but its suppression by anti-tumor drugs impedes the tumorigenesis.

Long non-coding RNAs (lncRNAs) in hepatocellular carcinoma progression: Biological functions and new therapeutic targets.

Liver is an important organ in body that performs vital functions such as detoxification. Liver is susceptible to development of cancers, and hepatocellular carcinoma (HCC) is among them. 75-85% of liver cancer cases are related to HCC. Therefore, much attention has been directed towards understanding factors mediating HCC progression. LncRNAs are epigenetic factors with more than 200 nucleotides in length located in both nucleus and cytoplasm and they are promising candidates in cancer therapy. Directing studies towards understanding function of lncRNAs in HCC is of importance. LncRNAs regulate cell cycle progression and growth of HCC cells, and they can also induce/inhibit apoptosis in tumor cells. LncRNAs affect invasion and metastasis in HCC mainly by epithelial-mesenchymal transition (EMT) mechanism. Revealing the association between lncRNAs and downstream signaling pathways in HCC is discussed in the current manuscript. Infectious diseases can affect lncRNA expression in mediating HCC development and then, altered expression level of lncRNA is associated with drug resistance and radio-resistance. Biomarker application of lncRNAs and their role in prognosis and diagnosis of HCC are also discussed to pave the way for treatment of HCC patients.

Progress in targeting PTEN/PI3K/Akt axis in glioblastoma therapy: Revisiting molecular interactions.

Glioblastoma (GBM) is one of the most malignant cancers of central nervous system and due to its sensitive location, surgical resection has high risk and therefore, chemotherapy and radiotherapy are utilized for its treatment. However, chemoresistance and radio-resistance are other problems in GBM treatment. Hence, new therapies based on genes are recommended for treatment of GBM. PTEN is a tumor-suppressor operator in cancer that inhibits PI3K/Akt/mTOR axis in diminishing growth, metastasis and drug resistance. In the current review, the function of PTEN/PI3K/Akt axis in GBM progression is evaluated. Mutation or depletion of PTEN leads to increase in GBM progression. Low expression level of PTEN mediates poor prognosis in GBM and by increasing proliferation and invasion, promotes malignancy of tumor cells. Moreover, loss of PTEN signaling can result in therapy resistance in GBM. Activation of PTEN signaling impairs GBM metabolism via glycolysis inhibition. In contrast to PTEN, PI3K/Akt signaling has oncogenic function and during tumor progression, expression level of PI3K/Akt enhances. PI3K/Akt signaling shows positive association with oncogenic pathways and its expression similar to PTEN signaling, is regulated by non-coding RNAs. PTEN upregulation and PI3K/Akt signaling inhibition by anti-cancer agents can be beneficial in interfering GBM progression. This review emphasizes on the signaling networks related to PTEN/PI3K/Akt and provides new insights for targeting this axis in effective GBM treatment.

Combining multiscale niche modeling, landscape connectivity, and gap analysis to prioritize habitats for conservation of striped hyaena (Hyaena hyaena).

Identifying spatial gaps in conservation networks requires information on species-environment relationships, and prioritization of habitats and corridors. We combined multi-extent niche modeling, landscape connectivity, and gap analysis to investigate scale-dependent environmental relationships, and identify core habitats and corridors for a little-known carnivore in Iran, the striped hyaena (Hyaena hyaena). This species is threatened in Iran by road vehicle collisions and direct killing. Therefore, understanding the factors that affect its habitat suitability, spatial pattern of distribution, and connectivity among them are prerequisite steps to delineate strategies aiming at human-striped hyaena co-existence. The results showed that the highest predictive power and extent of habitats was obtained at the extent sizes of 4 and 2 km, respectively. Also, connectivity analysis revealed that the extent and number of core habitats and corridors changed with increasing dispersal distance, and approximately 21% of the landscape was found to support corridors. The results of gap analysis showed that 15-17% of the core habitats overlapped with conservation areas. Given the body size of the species, its mobility, and lack of significant habitat specialization we conclude that this species would be more strongly influenced by changes in habitat amount rather than landscape configuration. Our approach showed that the scale of variables and dispersal ability must be accounted for in conservation efforts to prioritize habitats and corridors, and designing conservation areas. Our results could facilitate the conservation of striped hyaena through the identification and prioritization of habitats, establishment of conservation areas, and mitigating conflicts in corridors.

Identifying connectivity for two sympatric carnivores in human-dominated landscapes in central Iran.

Central Iran supports a diversity of carnivores, most of which are threatened by habitat loss and fragmentation. Carnivore conservation requires the identification and preservation of core habitats and ensuring connectivity between them. In the present study, we used species distribution modeling to predict habitat suitability and connectivity modeling to predict linkage (resistant kernel and factorial least-cost path analyses) for grey wolf and golden jackal in central Iran. For grey wolf, elevation, topographic ruggedness, and distance to Conservation Areas (CAs) were the strongest predictors; for golden jackal, distance to human settlements, dump sites and topographic ruggedness were the most influential variables in predicting the occurrence of this species. Our results also indicated a high potential for large parts of the landscape to support the occurrence of these two canid species. The largest and the most crucial core habitats and corridor paths for the conservation of both species are located in the southern part of the study landscape. We found a small overlap between golden jackal corridor paths and core habitats with CAs, which has important implications for conservation and future viability of the golden jackal populations. Some sections of core areas are bisected by roads, where most vehicle collisions with grey wolf and golden jackal occurred. To minimize mortality risk, we propose that successful conservation of both species will necessitate integrated landscape-level management, as well as conservation of core areas and corridors and development of mitigation strategies to reduce vehicle collisions.

Tip110/SART3-Mediated Regulation of NF-κB Activity by Targeting IκBα Stability Through USP15.

To date, there are a small number of nuclear-restricted proteins that have been reported to play a role in NF-κB signaling. However, the exact molecular mechanisms are not fully understood. Tip110 is a nuclear protein that has been implicated in multiple biological processes. In a previous study, we have shown that Tip110 interacts with oncogenic ubiquitin specific peptidase 15 (USP15) and that ectopic expression of Tip110 leads to re-distribution of USP15 from the cytoplasm to the nucleus. USP15 is known to regulate NF-κB activity through several mechanisms including modulation of IκBα ubiquitination. These findings prompted us to investigate the role of Tip110 in the NF-κB signaling pathway. We showed that Tip110 regulates NF-κB activity. The expression of Tip110 potentiated TNF-α-induced NF-κB activity and deletion of the nuclear localization domain in Tip110 abrogated this potentiation activity. We then demonstrated that Tip110 altered IκBα phosphorylation and stability in the presence of TNF-α. Moreover, we found that Tip110 and USP15 opposingly regulated NF-κB activity by targeting IκBα protein stability. We further showed that Tip110 altered the expression of NF-κB-dependent proinflammatory cytokines. Lastly, by using whole-transcriptome analysis of Tip110 knockout mouse embryonic stem cells, we found several NF-κB and NF-κB-related pathways were dysregulated. Taken together, these findings add to the nuclear regulation of NF-κB activity by Tip110 through IκBα stabilization and provide new evidence to support the role of Tip110 in controlling cellular processes such as cancers that involve proinflammatory responses.

The effect of eight weeks of moderate and high intensity aerobic training on the gene expression of Mir-145, Wnt3a and Dab2 in the heart tissue of type 2 diabetic rats.

PURPOSE: Pathological hypertrophy of heart tissue has been attributed to changes in some microRNAs and their target genes in heart tissue. This study intended to study the effects of eight weeks of moderate and high intensity aerobic training (MIT&HIT) on the mRNA of Mir-145, Wnt3a, and Dab2 in heart tissue of type 2 diabetic rats. METHODS: To implement this experimental research, 60 male Wistar rats were randomly divided into 6 groups, including Healthy-control (HC), Diabetic-control (DC), Moderate intensity training (MIT), Diabetes-MIT (DMIT), high intensity training (HIT) and Diabetes-HIT (DHIT). The aerobic training was conducted with moderate (50-60% VO2max) and high (85-90% VO2max) intensity, 5 days a week, for 8 weeks. The Mir-145, Wnt3a and Dab2 gene expression in the heart tissue samples was measured by Real Time PCR. Data were analyzed by one-way ANOVA and Tukey post hoc test at the P < 0.05. RESULTS: Moderate and high intensity aerobic training was associated with non-significant increase in Mir-145 mRNA of Heart tissue in type 2 diabetic rats than the diabetic control group(P < 0.05). Moderate and high intensity aerobic training was associated with significant increase in Wnt3a mRNA (P = 0.001) and significant decrease in Dab-2 mRNA (P = 0.001) of Heart tissue in type 2 diabetic rats than the diabetic control group. The Dab-2 mRNA was significantly lower of heart tissue in the diabetes- high intensity training group than the diabetes- moderate intensity training group (P = 0.001). CONCLUSION: It seems that moderate and high intensity aerobic exercise can help regulate the genes of the physiological hypertrophy pathway of the heart tissue in diabetes.

Effects of Prenatal Methamphetamine Exposure on the Developing Human Brain: A Systematic Review of Neuroimaging Studies.

Methamphetamine (MA) can cross the placenta in pregnant women and cause placental abruption and developmental alterations in offspring. Previous studies have found prenatal MA exposure effects on the social and cognitive performance of children. Recent studies reported some alterations in structural and functional magnetic resonance imaging (MRI) of prenatal MA-exposed offspring. In this study, we aimed to investigate the effect of prenatal MA exposure on brain development using recently published structural, metabolic, and functional MRI studies. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed and SCOPUS databases for articles that used each brain imaging modality in prenatal MA-exposed children. Seventeen studies were included in this study. We investigated brain imaging alterations using 17 articles with four different modalities, including structural MRI, diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), and functional MRI (fMRI). The participants' age range was from infancy to 15 years. Our findings demonstrated that prenatal MA exposure is associated with macrostructural, microstructural, metabolic, and functional deficits in both cortical and subcortical areas. However, the most affected regions were the striatum, frontal lobe, thalamus and the limbic system, and white matter (WM) fibers connecting these regions. The findings from our study might have valuable implications for targeted treatment of neurocognitive and behavioral deficits in children with prenatal MA exposure. Even so, our results should be interpreted cautiously due to the heterogeneity of the included studies in terms of study populations and methods of analysis.