@article{marzook2023nicotinamide,

title = {Nicotinamide riboside kinase-2 regulates metabolic adaptation in the ischemic heart},

author = {Hezlin Marzook and Anamika Gupta and Dhanendra Tomar and Mohamed A. Saleh and Kiran Patil and Mohammad H. Semreen and Rifat Hamoudi and Nelson C. Soares and Rizwan Qaisar and Firdos Ahmad},

url = {https://doi.org/10.1007/s00109-023-02296-6},

doi = {10.1007/s00109-023-02296-6},

issn = {1432-1440},

year  = {2023},

date = {2023-01-01},

journal = {Journal of Molecular Medicine},

volume = {101},

number = {3},

pages = {311–326},

abstract = {Ischemia-induced metabolic remodeling plays a critical role in the pathogenesis of adverse cardiac remodeling and heart failure. However, the underlying molecular mechanism is largely unknown. Here, we assess the potential roles of nicotinamide riboside kinase-2 (NRK-2), a muscle-specific protein, in ischemia-induced metabolic switch and heart failure through employing transcriptomic and metabolomic approaches in ischemic NRK-2 knockout mice. The investigations revealed NRK-2 as a novel regulator of several metabolic processes in the ischemic heart. Cardiac metabolism and mitochondrial function and fibrosis were identified as top dysregulated cellular processes in the KO hearts post-MI. Several genes linked to mitochondrial function, metabolism, and cardiomyocyte structural proteins were severely downregulated in the ischemic NRK-2 KO hearts. Analysis revealed significantly upregulated ECM-related pathways which was accompanied by the upregulation of several key cell signaling pathways including SMAD, MAPK, cGMP, integrin, and Akt in the KO heart post-MI. Metabolomic studies identified profound upregulation of metabolites mevalonic acid, 3,4-dihydroxyphenylglycol, 2-penylbutyric acid, and uridine. However, other metabolites stearic acid, 8,11,14-eicosatrienoic acid, and 2-pyrrolidinone were significantly downregulated in the ischemic KO hearts. Taken together, these findings suggest that NRK-2 promotes metabolic adaptation in the ischemic heart. The aberrant metabolism in the ischemic NRK-2 KO heart is largely driven by dysregulated cGMP and Akt and mitochondrial pathways.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cells12202451,

title = {Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond},

author = {Yauhen Statsenko and Nik V. Kuznetsov and Daria Morozova and Katsiaryna Liaonchyk and Gillian Lylian Simiyu and Darya Smetanina and Aidar Kashapov and Sarah Meribout and Klaus Neidl-Van Gorkom and Rifat Hamoudi and Fatima Ismail and Suraiya Anjum Ansari and Bright Starling Emerald and Milos Ljubisavljevic},

url = {https://www.mdpi.com/2073-4409/12/20/2451},

doi = {10.3390/cells12202451},

issn = {2073-4409},

year  = {2023},

date = {2023-01-01},

journal = {Cells},

volume = {12},

number = {20},

abstract = {Background: Genetic and epigenetic changes, oxidative stress and inflammation influence the rate of aging, which diseases, lifestyle and environmental factors can further accelerate. In accelerated aging (AA), the biological age exceeds the chronological age. Objective: The objective of this study is to reappraise the AA concept critically, considering its weaknesses and limitations. Methods: We reviewed more than 300 recent articles dealing with the physiology of brain aging and neurodegeneration pathophysiology. Results: (1) Application of the AA concept to individual organs outside the brain is challenging as organs of different systems age at different rates. (2) There is a need to consider the deceleration of aging due to the potential use of the individual structure-functional reserves. The latter can be restored by pharmacological and/or cognitive therapy, environment, etc. (3) The AA concept lacks both standardised terminology and methodology. (4) Changes in specific molecular biomarkers (MBM) reflect aging-related processes; however, numerous MBM candidates should be validated to consolidate the AA theory. (5) The exact nature of many potential causal factors, biological outcomes and interactions between the former and the latter remain largely unclear. Conclusions: Although AA is commonly recognised as a perspective theory, it still suffers from a number of gaps and limitations that assume the necessity for an updated AA concept.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.12688/f1000research.130316.1,

title = {Impact of estrogen and progesterone hormone receptors on the progression of interferon-? sensitized breast cancer cells [version 1; peer review: 1 approved]},

author = {I Shihab and A Bouzid and B Yener and A Altaie and P Manasa Bhamidimarri and M Al Ameri and R Bendardaf and M Hamad and R Hamoudi},

doi = {10.12688/f1000research.130316.1},

year  = {2023},

date = {2023-01-01},

journal = {F1000Research},

volume = {12},

number = {1117},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{CHAMEETTACHAL2023167924,

title = {Understanding Retroviral Life Cycle and its Genomic RNA Packaging},

author = {Akhil Chameettachal and Farah Mustafa and Tahir A. Rizvi},

url = {https://www.sciencedirect.com/science/article/pii/S0022283622005514},

doi = {https://doi.org/10.1016/j.jmb.2022.167924},

issn = {0022-2836},

year  = {2023},

date = {2023-01-01},

journal = {Journal of Molecular Biology},

volume = {435},

number = {3},

pages = {167924},

abstract = {Members of the family Retroviridae are important animal and human pathogens. Being obligate parasites, their replication involves a series of steps during which the virus hijacks the cellular machinery. Additionally, many of the steps of retrovirus replication are unique among viruses, including reverse transcription, integration, and specific packaging of their genomic RNA (gRNA) as a dimer. Progress in retrovirology has helped identify several molecular mechanisms involved in each of these steps, but many are still unknown or remain controversial. This review summarizes our present understanding of the molecular mechanisms involved in various stages of retrovirus replication. Furthermore, it provides a comprehensive analysis of our current understanding of how different retroviruses package their gRNA into the assembling virions. RNA packaging in retroviruses holds a special interest because of the uniqueness of packaging a dimeric genome. Dimerization and packaging are highly regulated and interlinked events, critical for the virus to decide whether its unspliced RNA will be packaged as a “genome” or translated into proteins. Finally, some of the outstanding areas of exploration in the field of RNA packaging are highlighted, such as the role of epitranscriptomics, heterogeneity of transcript start sites, and the necessity of functional polyA sequences. An in-depth knowledge of mechanisms that interplay between viral and cellular factors during virus replication is critical in understanding not only the virus life cycle, but also its pathogenesis, and development of new antiretroviral compounds, vaccines, as well as retroviral-based vectors for human gene therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1073/pnas.2207025120,

title = {White matter plasticity following cataract surgery in congenitally blind patients},

author = {Caterina A. Pedersini and Nathaniel P. Miller and Tapan K. Gandhi and Sharon Gilad-Gutnick and Vidur Mahajan and Pawan Sinha and Bas Rokers},

url = {https://www.pnas.org/doi/abs/10.1073/pnas.2207025120},

doi = {10.1073/pnas.2207025120},

year  = {2023},

date = {2023-01-01},

journal = {Proceedings of the National Academy of Sciences},

volume = {120},

number = {19},

pages = {e2207025120},

abstract = {The visual system develops abnormally when visual input is absent or degraded during a critical period early in life. Restoration of the visual input later in life is generally thought to have limited benefit because the visual system will lack sufficient plasticity to adapt to and utilize the information from the eyes. Recent evidence, however, shows that congenitally blind adolescents can recover both low-level and higher-level visual function following surgery. In this study, we assessed behavioral performance in both a visual acuity and a face perception task alongside longitudinal structural white matter changes in terms of fractional anisotropy (FA) and mean diffusivity (MD). We studied congenitally blind patients with dense bilateral cataracts, who received cataract surgery at different stages of adolescence. Our goal was to differentiate between age- and surgery-related changes in both behavioral performance and structural measures to identify neural correlates which might contribute to recovery of visual function. We observed surgery-related long-term increases of structural integrity of late-visual pathways connecting the occipital regions with ipsilateral fronto-parieto-temporal regions or homotopic contralateral areas. Comparison to a group of age-matched healthy participants indicated that these improvements went beyond the expected changes in FA and MD based on maturation alone. Finally, we found that the extent of behavioral improvement in face perception was mediated by changes in structural integrity in late visual pathways. Our results suggest that sufficient plasticity remains in adolescence to partially overcome abnormal visual development and help localize the sites of neural change underlying sight recovery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{https://doi.org/10.1111/tra.12902,

title = {Genetic disruption of mammalian endoplasmic reticulum-associated protein degradation: Human phenotypes and animal and cellular disease models},

author = {Sally Badawi and Feda E. Mohamed and Divya Saro Varghese and Bassam R. Ali},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/tra.12902},

doi = {https://doi.org/10.1111/tra.12902},

year  = {2023},

date = {2023-01-01},

journal = {Traffic},

volume = {24},

number = {8},

pages = {312-333},

abstract = {Abstract Endoplasmic reticulum-associated protein degradation (ERAD) is a stringent quality control mechanism through which misfolded, unassembled and some native proteins are targeted for degradation to maintain appropriate cellular and organelle homeostasis. Several in vitro and in vivo ERAD-related studies have provided mechanistic insights into ERAD pathway activation and its consequent events; however, a majority of these have investigated the effect of ERAD substrates and their consequent diseases affecting the degradation process. In this review, we present all reported human single-gene disorders caused by genetic variation in genes that encode ERAD components rather than their substrates. Additionally, after extensive literature survey, we present various genetically manipulated higher cellular and mammalian animal models that lack specific components involved in various stages of the ERAD pathway.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{https://doi.org/10.1002/rmv.2449,

title = {Differentially-regulated miRNAs in COVID-19: A systematic review},

author = {Waqar Ahmad and Bushra Gull and Jasmin Baby and Neena G. Panicker and Thanumol A. Khader and Shaima Akhlaq and Tahir A. Rizvi and Farah Mustafa},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/rmv.2449},

doi = {https://doi.org/10.1002/rmv.2449},

year  = {2023},

date = {2023-01-01},

journal = {Reviews in Medical Virology},

volume = {33},

number = {4},

pages = {e2449},

abstract = {Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for coronavirus disease of 2019 (COVID-19) that infected more than 760 million people worldwide with over 6.8 million deaths to date. COVID-19 is one of the most challenging diseases of our times due to the nature of its spread, its effect on multiple organs, and an inability to predict disease prognosis, ranging from being completely asymptomatic to death. Upon infection, SARS-CoV-2 alters the host immune response by changing host-transcriptional machinery. MicroRNAs (miRNAs) are regarded as post-transcriptional regulators of gene expression that can be perturbed by invading viruses. Several in vitro and in vivo studies have reported such dysregulation of host miRNA expression upon SARS-CoV-2 infection. Some of this could occur as an anti-viral response of the host to the viral infection. Viruses themselves can counteract that response by mounting their own pro-viral response that facilitates virus infection, an aspect which may cause pathogenesis. Thus, miRNAs could serve as possible disease biomarkers in infected people. In the current review, we have summarised and analysed the existing data about miRNA dysregulation in patients infected with SARS-CoV-2 to determine their concordance between studies, and identified those that could serve as potential biomarkers during infection, disease progression, and death, even in people with other co-morbidities. Having such biomarkers can be vital in not only predicting COVID-19 prognosis, but also the development of novel miRNA-based anti-virals and therapeutics which can become invaluable in case of the emergence of new viral variants with pandemic potential in the future.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nu15112477,

title = {The Role of Vitamin D Supplementation on Airway Remodeling in Asthma: A Systematic Review},

author = {Laila Salameh and Walid Mahmood and Rifat Hamoudi and Khulood Almazrouei and Mahesh Lochanan and Suheyl Seyhoglu and Bassam Mahboub},

url = {https://www.mdpi.com/2072-6643/15/11/2477},

doi = {10.3390/nu15112477},

issn = {2072-6643},

year  = {2023},

date = {2023-01-01},

journal = {Nutrients},

volume = {15},

number = {11},

abstract = {Asthma is a common chronic respiratory disease that affects millions of people worldwide, and its prevalence continues to increase. Vitamin D has been proposed as a potential environmental factor in asthma pathogenesis, due to its immunomodulatory effects. This systematic review aimed to evaluate the effect of vitamin D supplementation in order to prevent airway remodeling in asthmatic patients. Four electronic databases, namely PubMed, Embase, Clinical trails.gov, and CINAHL, were thoroughly searched to conduct a comprehensive literature review. The International Prospective Register of Systematic Reviews (CRD42023413798) contains a record of the registered protocol. We identified 9447 studies during the initial search; 9 studies (0.1%) met the inclusion criteria and were included in the systematic review. All included studies were experimental studies that investigated the impact of vitamin D supplementation on airway remodeling in asthma. The studies included in this review suggest that vitamin D inhibits airway smooth muscle cell contraction and remodeling, reduces inflammation, regulates collagen synthesis in the airways, and modulates the action of bronchial fibroblasts. However, one study suggests that TGF-β1 can impair vitamin D-induced and constitutive airway epithelial host defense mechanisms. Overall, vitamin D appears to have a potential role in the prevention and management of asthma.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Statsenkoe068608,

title = {Multimodal diagnostics in multiple sclerosis: predicting disability and conversion from relapsing-remitting to secondary progressive disease course – protocol for systematic review and meta-analysis},

author = {Yauhen Statsenko and Darya Smetanina and Teresa Arora and Linda Östlundh and Tetiana Habuza and Gillian Lylian Simiyu and Sarah Meribout and Tatsiana Talako and Fransina Christina King and Iryna Makhnevych and Juri George Gelovani and Karuna M Das and Klaus Neidl-Van Gorkom and Taleb M Almansoori and Fatmah Al Zahmi and Mikl'os Sz'olics and Fatima Ismail and Milos Ljubisavljevic},

url = {https://bmjopen.bmj.com/content/13/7/e068608},

doi = {10.1136/bmjopen-2022-068608},

issn = {2044-6055},

year  = {2023},

date = {2023-01-01},

journal = {BMJ Open},

volume = {13},

number = {7},

publisher = {British Medical Journal Publishing Group},

abstract = {Background The number of patients diagnosed with multiple sclerosis (MS) has increased significantly over the last decade. The challenge is to identify the transition from relapsing-remitting to secondary progressive MS. Since available methods to examine patients with MS are limited, both the diagnostics and prognostication of disease progression would benefit from the multimodal approach. The latter combines the evidence obtained from disparate radiologic modalities, neurophysiological evaluation, cognitive assessment and molecular diagnostics. In this systematic review we will analyse the advantages of multimodal studies in predicting the risk of conversion to secondary progressive MS.Methods and analysis We will use peer-reviewed publications available in Web of Science, Medline/PubMed, Scopus, Embase and CINAHL databases. In vivo studies reporting the predictive value of diagnostic methods will be considered. Selected publications will be processed through Covidence software for automatic deduplication and blind screening. Two reviewers will use a predefined template to extract the data from eligible studies. We will analyse the performance metrics (1) for the classification models reflecting the risk of secondary progression: sensitivity, specificity, accuracy, area under the receiver operating characteristic curve, positive and negative predictive values; (2) for the regression models forecasting disability scores: the ratio of mean absolute error to the range of values. Then, we will create ranking charts representing performance of the algorithms for calculating disability level and MS progression. Finally, we will compare the predictive power of radiological and radiomical correlates of clinical disability and cognitive impairment in patients with MS.Ethics and dissemination The study does not require ethical approval because we will analyse publicly available literature. The project results will be published in a peer-review journal and presented at scientific conferences.PROSPERO registration number CRD42022354179.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{genes14010204,

title = {KIBRA Gene Variant Is Associated with Ability in Chess and Science},

author = {Ildus I. Ahmetov and Elena V. Valeeva and Meruert B. Yerdenova and Gaukhar K. Datkhabayeva and Amal Bouzid and Poorna Manasa Bhamidimarri and Liliya M. Sharafetdinova and Emiliya S. Egorova and Ekaterina A. Semenova and Leysan J. Gabdrakhmanova and Rinat A. Yusupov and Andrey K. Larin and Nikolay A. Kulemin and Edward V. Generozov and Rifat Hamoudi and Almira M. Kustubayeva and Tim Rees},

url = {https://www.mdpi.com/2073-4425/14/1/204},

doi = {10.3390/genes14010204},

issn = {2073-4425},

year  = {2023},

date = {2023-01-01},

journal = {Genes},

volume = {14},

number = {1},

abstract = {The kidney and brain expressed protein (KIBRA) plays an important role in synaptic plasticity. Carriers of the T allele of the KIBRA (WWC1) gene rs17070145 C/T polymorphism have been reported to have enhanced spatial ability and to outperform individuals with the CC genotype in working memory tasks. Since ability in chess and science is directly related to spatial ability and working memory, we hypothesized that the KIBRA T allele would be positively associated with chess player status and PhD status in science. We tested this hypothesis in a study involving 2479 individuals (194 chess players, 119 PhD degree holders in STEM fields, and 2166 controls; 1417 males and 1062 females) from three ethnicities (236 Kazakhs, 1583 Russians, 660 Tatars). We found that frequencies of the T allele were significantly higher in Kazakh (66.9 vs. 55.1%; p = 0.024), Russian (44.8 vs. 32.0%; p = 0.0027), and Tatar (51.5 vs. 41.8%; p = 0.035) chess players compared with ethnically matched controls (meta-analysis for CT/TT vs. CC: OR = 2.05},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cancers15082258,

title = {Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer},

author = {Rama Alsabbagh and Munazza Ahmed and Mohammad A. Y. Alqudah and Rifat Hamoudi and Rania Harati},

url = {https://www.mdpi.com/2072-6694/15/8/2258},

doi = {10.3390/cancers15082258},

issn = {2072-6694},

year  = {2023},

date = {2023-01-01},

journal = {Cancers},

volume = {15},

number = {8},

abstract = {Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and its incidence is increasing. Brain metastasis occurs through a multi-step cascade where cancer cells spread from the primary tumor site to the brain. The extravasation of tumor cells through the blood-brain barrier (BBB) is a critical step in brain metastasis. During extravasation, circulating cancer cells roll along the brain endothelium (BE), adhere to it, then induce alterations in the endothelial barrier to transmigrate through the BBB and enter the brain. Rolling and adhesion are generally mediated by selectins and adhesion molecules induced by inflammatory mediators, while alterations in the endothelial barrier are mediated by proteolytic enzymes, including matrix metalloproteinase, and the transmigration step mediated by factors, including chemokines. However, the molecular mechanisms mediating extravasation are not yet fully understood. A better understanding of these mechanisms is essential as it may serve as the basis for the development of therapeutic strategies for the prevention or treatment of brain metastases. In this review, we summarize the molecular events that occur during the extravasation of cancer cells through the blood-brain barrier in three types of cancer most likely to develop brain metastasis: breast cancer, melanoma, and lung cancer. Common molecular mechanisms driving extravasation in these different tumors are discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{biomedicines11071999,

title = {Unraveling Lifelong Brain Morphometric Dynamics: A Protocol for Systematic Review and Meta-Analysis in Healthy Neurodevelopment and Ageing},

author = {Yauhen Statsenko and Tetiana Habuza and Darya Smetanina and Gillian Lylian Simiyu and Sarah Meribout and Fransina Christina King and Juri G. Gelovani and Karuna M. Das and Klaus N. -V. Gorkom and Kornelia Zaręba and Taleb M. Almansoori and Miklós Szólics and Fatima Ismail and Milos Ljubisavljevic},

url = {https://www.mdpi.com/2227-9059/11/7/1999},

doi = {10.3390/biomedicines11071999},

issn = {2227-9059},

year  = {2023},

date = {2023-01-01},

journal = {Biomedicines},

volume = {11},

number = {7},

abstract = {A high incidence and prevalence of neurodegenerative diseases and neurodevelopmental disorders justify the necessity of well-defined criteria for diagnosing these pathologies from brain imaging findings. No easy-to-apply quantitative markers of abnormal brain development and ageing are available. We aim to find the characteristic features of non-pathological development and degeneration in distinct brain structures and to work out a precise descriptive model of brain morphometry in age groups. We will use four biomedical databases to acquire original peer-reviewed publications on brain structural changes occurring throughout the human life-span. Selected publications will be uploaded to Covidence systematic review software for automatic deduplication and blinded screening. Afterwards, we will manually review the titles, abstracts, and full texts to identify the papers matching eligibility criteria. The relevant data will be extracted to a ‘Summary of findings’ table. This will allow us to calculate the annual rate of change in the volume or thickness of brain structures and to model the lifelong dynamics in the morphometry data. Finally, we will adjust the loss of weight/thickness in specific brain areas to the total intracranial volume. The systematic review will synthesise knowledge on structural brain change across the life-span.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.3389/fonc.2023.1128753,

title = {Identification of p53-target genes in human papillomavirus-associated head and neck cancer by integrative bioinformatics analysis},

author = {Amal Bouzid and Muwaffaq Al Ani and David Fuente and Zainab Mohamed Al Shareef and Asif Quadri and Rifat Hamoudi and Natheer Al-Rawi},

url = {https://www.frontiersin.org/articles/10.3389/fonc.2023.1128753},

doi = {10.3389/fonc.2023.1128753},

issn = {2234-943X},

year  = {2023},

date = {2023-01-01},

journal = {Frontiers in Oncology},

volume = {13},

abstract = {IntroductionHead and neck cancer (HNC) is a highly prevalent and heterogeneous malignancy. Although extensive efforts have been made to advance its treatment, the prognosis remained poor with increased mortality. Human papillomaviruses (HPV) have been associated with high risk in HNC. TP53, a tumor suppressor, is the most frequently altered gene in HNC, therefore, investigating its target genes for the identification of novel biomarkers or therapeutic targets in HPV-related HNC progression is highly recommended.MethodsTranscriptomic profiles from three independent gene expression omnibus (GEO) datasets, including 44 HPV+ and 70 HPV- HNC patients, were subjected to integrative statistical and Bioinformatics analyses. For the top-selected marker, further in-silico validation in TCGA and GTEx databases and experimental validation in 65 (51 HPV- and 14 HPV+) subjects with histologically confirmed head and neck squamous cell carcinoma (HNSCC) have been performed.ResultsA total of 498 differentially expressed genes (DEGs) were identified including 291 up-regulated genes and 207 down-regulated genes in HPV+ compared to HPV- HNSCC patients. Functional annotations and gene set enrichment analysis (GSEA) showed that the up-regulated genes were significantly involved in p53-related pathways. The integrative analysis between the Hub-genes identified in the complex protein-protein network and the top frequent genes resulting from GSEA showed an intriguing correlation with five biomarkers which are EZH2, MDM2, PCNA, STAT5A and TYMS. Importantly, the MDM2 gene showed the highest gene expression difference between HPV+ and HPV- HNSCC (Average log2FC = 1.89). Further in-silico validation in a large HNSCC cohort from TCGA and GTEx databases confirmed the over-expression of MDM2 in HPV+ compared to HPV- HNSCC patients (p = 2.39E-05). IHC scoring showed that MDM2 protein expression was significantly higher in HPV+ compared to HPV- HNSCC patients (p = 0.031).DiscussionOur findings showed evidence that over-expression of MDM2, proto-oncogene, may affect the occurrence and proliferation of HPV-associated HNSCC by disturbing the p53-target genes and consequently the p53-related pathways.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.3389/fnagi.2022.943566,

title = {Patterns of structure-function association in normal aging and in Alzheimer's disease: Screening for mild cognitive impairment and dementia with ML regression and classification models},

author = {Yauhen Statsenko and Sarah Meribout and Tetiana Habuza and Taleb M. Almansoori and Klaus Neidl-Van Gorkom and Juri G. Gelovani and Milos Ljubisavljevic},

url = {https://www.frontiersin.org/articles/10.3389/fnagi.2022.943566},

doi = {10.3389/fnagi.2022.943566},

issn = {1663-4365},

year  = {2023},

date = {2023-01-01},

journal = {Frontiers in Aging Neuroscience},

volume = {14},

abstract = {BackgroundThe combined analysis of imaging and functional modalities is supposed to improve diagnostics of neurodegenerative diseases with advanced data science techniques.ObjectiveTo get an insight into normal and accelerated brain aging by developing the machine learning models that predict individual performance in neuropsychological and cognitive tests from brain MRI. With these models we endeavor to look for patterns of brain structure-function association (SFA) indicative of mild cognitive impairment (MCI) and Alzheimer's dementia.Materials and methodsWe explored the age-related variability of cognitive and neuropsychological test scores in normal and accelerated aging and constructed regression models predicting functional performance in cognitive tests from brain radiomics data. The models were trained on the three study cohorts from ADNI dataset—cognitively normal individuals, patients with MCI or dementia—separately. We also looked for significant correlations between cortical parcellation volumes and test scores in the cohorts to investigate neuroanatomical differences in relation to cognitive status. Finally, we worked out an approach for the classification of the examinees according to the pattern of structure-function associations into the cohorts of the cognitively normal elderly and patients with MCI or dementia.ResultsIn the healthy population, the global cognitive functioning slightly changes with age. It also remains stable across the disease course in the majority of cases. In healthy adults and patients with MCI or dementia, the trendlines of performance in digit symbol substitution test and trail making test converge at the approximated point of 100 years of age. According to the SFA pattern, we distinguish three cohorts: the cognitively normal elderly, patients with MCI, and dementia. The highest accuracy is achieved with the model trained to predict the mini-mental state examination score from voxel-based morphometry data. The application of the majority voting technique to models predicting results in cognitive tests improved the classification performance up to 91.95% true positive rate for healthy participants, 86.21%—for MCI and 80.18%—for dementia cases.ConclusionThe machine learning model, when trained on the cases of this of that group, describes a disease-specific SFA pattern. The pattern serves as a “stamp” of the disease reflected by the model.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.3389/fimmu.2023.978236,

title = {DKK3’s protective role in prostate cancer is partly due to the modulation of immune-related pathways},

author = {Zainab Al Shareef and Mahmood Y. Hachim and Iman M. Talaat and Poorna Manasa Bhamidimarri and Mai Nidal Asad Ershaid and Burcu Yener Ilce and Thenmozhi Venkatachalam and Abdulla Eltayeb and Rifat Hamoudi and Ibrahim Y. Hachim},

url = {https://www.frontiersin.org/articles/10.3389/fimmu.2023.978236},

doi = {10.3389/fimmu.2023.978236},

issn = {1664-3224},

year  = {2023},

date = {2023-01-01},

journal = {Frontiers in Immunology},

volume = {14},

abstract = {While it is considered one of the most common cancers and the leading cause of death in men worldwide, prognostic stratification and treatment modalities are still limited for patients with prostate cancer (PCa). Recently, the introduction of genomic profiling and the use of new techniques like next-generation sequencing (NGS) in many cancers provide novel tools for the discovery of new molecular targets that might improve our understanding of the genomic aberrations in PCa and the discovery of novel prognostic and therapeutic targets. In this study, we investigated the possible mechanisms through which Dickkopf-3 (DKK3) produces its possible protective role in PCa using NGS in both the DKK3 overexpression PCa cell line (PC3) model and our patient cohort consisting of nine PCa and five benign prostatic hyperplasia. Interestingly, our results have shown that DKK3 transfection-modulated genes are involved in the regulation of cell motility, senescence-associated secretory phenotype (SASP), and cytokine signaling in the immune system, as well as in the regulation of adaptive immune response. Further analysis of our NGS using our in vitro model revealed the presence of 36 differentially expressed genes (DEGs) between DKK3 transfected cells and PC3 empty vector. In addition, both CP and ACE2 genes were differentially expressed not only between the transfected and empty groups but also between the transfected and Mock cells. The top common DEGs between the DKK3 overexpression cell line and our patient cohort are the following: IL32, IRAK1, RIOK1, HIST1H2BB, SNORA31, AKR1B1, ACE2, and CP. The upregulated genes including IL32, HIST1H2BB, and SNORA31 showed tumor suppressor functions in various cancers including PCa. On the other hand, both IRAK1 and RIOK1 were downregulated and involved in tumor initiation, tumor progression, poor outcome, and radiotherapy resistance. Together, our results highlighted the possible role of the DKK3-related genes in protecting against PCa initiation and progression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}