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103. The Link Between Glycemic Control Measures and Eye Microvascular Complications in a Clinical Cohort of Type 2 Diabetes with MicroRNA-223 Signature

Author

Da'as, Sahar, primary, Ahmed, Ikhlak, additional, Hasan, Waseem, additional, Abdelrahman, Doua, additional, Aliyev, Elbay, additional, Nisar, Sabah, additional, Bhat, Ajaz Ahmed, additional, Joglekar, Mugdha, additional, Hardikar, Anand, additional, Fakhro, Khalid, additional, and Akil, Ammira Al-Shabeeb, additional

Published
2023
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104. Guggulsterone Induces Apoptosis in Multiple Myeloma Cells by Targeting High Mobility Group Box 1 via Janus Activated Kinase/Signal Transducer and Activator of Transcription Pathway

Author

Akhtar, Sabah, primary, Zarif, Lubna, additional, Kuttikrishnan, Shilpa, additional, Prabhu, Kirti S., additional, Patil, Kalyani, additional, Nisar, Sabah, additional, Abou-Saleh, Haissam, additional, Merhi, Maysaloun, additional, Dermime, Said, additional, Bhat, Ajaz A., additional, and Uddin, Shahab, additional

Published
2022
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107. Functional Validation and Network-Based Prioritization of Key Transcriptional Factors of Diabetic Kidney Disease

Author

Ahmed, Ikhlak, Ziab, Mubarak, Da’as, Sahar, Hasan, Waseem H., Jeya, Sujitha P., Aliyev, Elbay, Nisar, Sabah, A. Bhat, Ajaz, Fakhro, Khalid, and Akil, Ammira S. Alshabeeb

Subjects
Biomedical and clinical sciences, Medical biotechnology, FOS: Medical biotechnology
Abstract

Poster by Ikhlak Ahmed (Sidra Medicine), Mubarak Ziab (Sidra Medicine), Sahar Da’as (Sidra Medicine, Hamad Bin Khalifa University), Waseem Hasan (Sidra Medicine), Sujitha P. Jeya (Sidra Medicine), Elbay Aliyev (Sidra Medicine), Sabah Nisar (Sidra Medicine), Ajaz A. Bhat (Sidra Medicine), Khalid Fakhro (Sidra Medicine, Hamad Bin Khalifa University, Weill Cornell Medicine College - Qatar), Ammira S. Alshabeeb Akil (Sidra Medicine) Background: Diabetic nephropathy (DN) is one of the most established microvascular complications of diabetes and a key cause of end-stage renal disease. It is well established that gene susceptibility to DN plays a critical role in disease pathophysiology. Therefore, many genetic studies have been performed to categorize candidate genes in prominent diabetic cohorts, aiming to investigate DN pathogenesis and etiology. Objective: The objective of this study is to identify critical transcriptional factors associated with diabetic nephropathy (DN) progression and validate their role in DN development using a hyperglycemic zebrafish model. Methods: In this study, we performed a meta-analysis on the expression profiles of GSE1009, GSE30122, GSE96804, GSE99340, GSE104948, GSE104954, and GSE111154 to identify critical transcriptional factors associated with DN progression. The analysis was conducted for all individual datasets for each kidney tissue (glomerulus, tubules, and kidney cortex). Results: We identified distinct clusters of susceptibility genes that were dysregulated in a renal compartment- specific pattern. Further, we recognized a small but a closely connected set of these susceptibility genes enriched for podocyte differentiation, several of which were characterized as genes encoding critical transcriptional factors (TFs) involved in DN development and podocyte function. To validate the role of identified TFs in DN progression, we functionally validated the three main TFs (DACH1, LMX1B, and WT1) identified through differential gene expression and network analysis using the hyperglycemic zebrafish model. We report that hyperglycemia-induced altered gene expression of the key TF genes leads to morphological abnormalities in zebrafish glomeruli, pronephric tubules, proximal and distal ducts. Conclusion: This study demonstrated that altered expression of these TF genes could be associated with hyperglycemia-induced nephropathy and, thus, aids in understanding the molecular drivers, essential genes, and pathways that trigger DN initiation and development.

Published
2023
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111. Effect of Metric Variation in Object Shapes and Colours on Cross-Situational Word Learning in Adults

Author

Bhat, Ajaz, Spencer, John, and Samuelson, Larissa

Abstract

Cross-situational word learning (CSWL) is the ability to overcome ambiguity in individually ambiguous scenarios by tracking word-object co-occurrence statistics over multiple such naming scenarios to learn correct word-object mappings. Force choice tests of adults in lab experiments on CSWL has demonstrated adults’ ability to learn words under referential uncertainty (Trueswell, Medina, Hafri, & Gleitman, 2013). Furthermore, eye-tracking data in these and other studies (Yu, Zhong, & Fricker, 2012) demonstrate that participants who are better at learning such words spend more time looking at the target object when named, indicating that eye-movements are a fair reflection of learning accuracy in such tasks. These looking behaviours may, however, be influenced by the perceived characteristics of the object, prior knowledge of the word referent pairs, familiarity with words, and the competition due to other distractors (Yu et al., 2012). In particular, while there is strong evidence to suggest that object properties (like colour and shape) directly affect object categorisation and learning their names (Jiang & Chun, 2001; Landau, Smith, & Jones, 1988; Smith, Jones, Landau, Gershkoff-Stowe, & Samuelson, 2002), the effect has never been demonstrated in cross-situational word learning with systemic property variations. Therefore, in this experiment we plan to use object stimuli of systematic variations in colour and shape properties in a cross-situational learning task and employ eye-tracking to understand the effect of these metric variations on real-time attention and word learning. To assess the metric effects, we will control the difference between the object properties on each training trial to create two conditions: The ‘Near’ condition where the two objects on each learning trial are very similar either in shape or in colour. The ‘’Far condition where the objects presented within a learning trial are very different in shape and colour. Critically, the same objects are used in both conditions: it’s just the pairing that creates metric conflict in the moment. Importantly, in the ‘Near’ condition, there is always similarity in one of the feature dimensions.

Published
2022
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112. Understanding the Role of GLUT2 in Dysglycemia Associated with Fanconi–Bickel Syndrome

Author

Sharari, Sanaa, primary, Kabeer, Basirudeen, additional, Mohammed, Idris, additional, Haris, Basma, additional, Pavlovski, Igor, additional, Hawari, Iman, additional, Bhat, Ajaz Ahmad, additional, Toufiq, Mohammed, additional, Tomei, Sara, additional, Mathew, Rebecca, additional, Syed, Najeeb, additional, Nisar, Sabah, additional, Maacha, Selma, additional, Grivel, Jean-Charles, additional, Chaussabel, Damien, additional, Ericsson, Johan, additional, and Hussain, Khalid, additional

Published
2022
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115. Minimally invasive calcaneal fracture fixation by using two-point distractor - A Prospective Observational Cohort Study.

Author

Wani, Iftikhar H., Khan, Jawaher Mehmood, Nisar, Rouf un, Ahamd, Mushtaq, Gani, Naseem ul, and Bhat, Ajaz Ahmad

Subjects
HEEL bone fractures, FRACTURE fixation, COMPLEX regional pain syndromes, INJURY complications, SUBTALAR joint, MINIMALLY invasive procedures
Abstract

Introduction: A displaced fracture of calcaneum is serious and disabling injury. Treatment options have evolved from conservative to open surgical alternatives and include a variety of minimally invasive techniques also. We hypothesise that minimally invasive surgery of calcaneal fractures by using a distractor achieves a good clinical and functional outcome with minimum wound complications. Aims and objectives: The aim of our study was to assess the functional outcome of minimally invasive surgery in the management of calcaneal fractures and the subsequent complication rate in the management of displaced intra-articular fractures. Methods: Between April 2018 and March 2021, patients with unilateral or bilateral closed calcaneal fractures, treated operatively with minimally invasive technique using distractor were included in the study. 64 patients with 60 calcaneal fractures were included in the study. Pre operatively CT scan evaluation was done and fractures were classified as per Sander's classification. Only type II and type III were included in the study. Pre operatively both Bohler's and Gissane's angles were measured. Maryland foot and ankle score was used for evaluation and effectiveness of intervention. Results: The average operative time in our study was 45± 11.2 minutes. No major wound complications were reported in our study. Screw prominence was seen in three patients. Complex regional pain syndrome was seen in seven of our patients. Both Gissane and Bohlers angles were restored in 94% of our patients. Maryland foot and ankle score was excellent in 20 % (11) of patients, Good in 60% (33), Fair in 15% and Poor in 5%. Conclusion:We concluded that management of calcaneal fractures with the use of distractor helps to restore the articular congruity of subtalar joint with minimum soft tissue complications. [ABSTRACT FROM AUTHOR]

Published
2023

117. Cytokine‐ and chemokine‐induced inflammatory colorectal tumor microenvironment: Emerging avenue for targeted therapy

Author

Bhat, Ajaz A., primary, Nisar, Sabah, additional, Singh, Mayank, additional, Ashraf, Bazella, additional, Masoodi, Tariq, additional, Prasad, Chandra P., additional, Sharma, Atul, additional, Maacha, Selma, additional, Karedath, Thasni, additional, Hashem, Sheema, additional, Yasin, Syed Besina, additional, Bagga, Puneet, additional, Reddy, Ravinder, additional, Frennaux, Michael P., additional, Uddin, Shahab, additional, Dhawan, Punita, additional, Haris, Mohammad, additional, and Macha, Muzafar A., additional

Published
2022
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119. Bioinformatics Analysis Reveals FOXM1/BUB1B Signaling Pathway as a Key Target of Neosetophomone B in Human Leukemic Cells: A Gene Network-Based Microarray Analysis

Author

Kuttikrishnan, Shilpa, primary, Masoodi, Tariq, additional, Sher, Gulab, additional, Bhat, Ajaz A., additional, Patil, Kalyani, additional, El-Elimat, Tamam, additional, Oberlies, Nicholas H., additional, Pearce, Cedric J., additional, Haris, Mohmmad, additional, Ahmad, Aamir, additional, Alali, Feras Q., additional, and Uddin, Shahab, additional

Published
2022
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120. Activation of NOTCH signaling via DLL1 is mediated by APE1-redox-dependent NF-κB activation in oesophageal adenocarcinoma

Author

Chen, Lei, primary, Lu, Heng, additional, Peng, Dunfa, additional, Cao, Long Long, additional, Ballout, Farah, additional, Srirmajayam, Kannappan, additional, Chen, Zheng, additional, Bhat, Ajaz, additional, Wang, Timothy C, additional, Capobianco, Anthony, additional, Que, Jianwen, additional, McDonald, Oliver Gene, additional, Zaika, Alexander, additional, Zhang, Shutian, additional, and El-Rifai, Wael, additional

Published
2022
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121. Abstract 6221: Tandem use of multi-omics and artificial intelligence identified novel prognostic and therapeutic biomarkers for head and neck squamous cell carcinoma

Author

Bhat, Ajaz A., primary, Masoodi, Tariq, additional, Mishra, Deepika, additional, Singh, Mayank, additional, Nisar, Sabah, additional, Hashem, Sheema, additional, Baba, Sana K., additional, Bagga, Puneet, additional, Reddy, Ravinder, additional, Bedognetti, Davide, additional, Uddin, Shahab, additional, El-Rifai, Wael, additional, Macha, Muzafar A., additional, and Haris, Mohammad, additional

Published
2022
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123. Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents

Author

Hashem, Sheema, primary, Ali, Tayyiba Akbar, additional, Akhtar, Sabah, additional, Nisar, Sabah, additional, Sageena, Geetanjali, additional, Ali, Shahid, additional, Al-Mannai, Sharefa, additional, Therachiyil, Lubna, additional, Mir, Rashid, additional, Elfaki, Imadeldin, additional, Mir, Mohammad Muzaffar, additional, Jamal, Farrukh, additional, Masoodi, Tariq, additional, Uddin, Shahab, additional, Singh, Mayank, additional, Haris, Mohammad, additional, Macha, Muzafar, additional, and Bhat, Ajaz A., additional

Published
2022
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124. Understanding the Mechanism of Dysglycemia in a Fanconi-Bickel Syndrome Patient

Author

Sharari, Sanaa, primary, Aouida, Mustapha, additional, Mohammed, Idris, additional, Haris, Basma, additional, Bhat, Ajaz Ahmad, additional, Hawari, Iman, additional, Nisar, Sabah, additional, Pavlovski, Igor, additional, Biswas, Kabir H., additional, Syed, Najeeb, additional, Maacha, Selma, additional, Grivel, Jean-Charles, additional, Saifaldeen, Maryam, additional, Ericsson, Johan, additional, and Hussain, Khalid, additional

Published
2022
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125. Sa1078: CLOCK-LIKE SBS5 MUTATATIONAL SIGNATURE IS AN INDEPENDENT PREDICTOR OF METASTASIS AND OVERALL SURVIVAL IN COLORECTAL CANCER

Author

Bhat, Ajaz A., primary, Masoodi, Tariq, additional, Mishra, Deepika, additional, Singh, Mayank, additional, Nisar, Sabah, additional, Hashem, Sheema, additional, Chauhan, Ravi, additional, Akobeng, Anthony, additional, Mifsud, William, additional, Bagga, Puneet, additional, Reddy, Ravinder, additional, Dhawan, Punita, additional, Bedognetti, Davide, additional, El-Rifai, Wael, additional, Macha, Muzafar A., additional, and Haris, Mohammad, additional

Published
2022
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126. Activation of NOTCH signaling via DLL1 is mediated by APE1-redox-dependent NF-κB activation in oesophageal adenocarcinoma.

Author

Lei Chen, Heng Lu, Dunfa Peng, Long Long Cao, Ballout, Farah, Srirmajayam, Kannappan, Zheng Chen, Bhat, Ajaz, Wang, Timothy C., Capobianco, Anthony, Que, Jianwen, McDonald, Oliver Gene, Zaika, Alexander, Shutian Zhang, and El-Rifai, Wael

Subjects
DNA ligases, CARCINOGENS, TRANSCRIPTION factors, ADENOCARCINOMA, SMALL molecules, ESOPHAGEAL cancer, BARRETT'S esophagus, HEARTBURN
Published
2023
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127. miRNAs as novel immunoregulators in cancer

Author

Lone, Saife N., primary, Bhat, Ajaz A., additional, Wani, Nissar A., additional, Karedath, Thasni, additional, Hashem, Sheema, additional, Nisar, Sabah, additional, Singh, Mayank, additional, Bagga, Puneet, additional, Das, Bhudev Chandra, additional, Bedognetti, Davide, additional, Reddy, Ravinder, additional, Frenneaux, Michael P., additional, El-Rifai, Wael, additional, Siddiqi, Mushtaq A., additional, Haris, Mohammad, additional, and Macha, Muzafar A., additional

Published
2022
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130. Development of a Critical Appraisal Tool (AIMRDA) for the Peer-Review of Studies Assessing the Anticancer Activity of Natural Products: A Step towards Reproducibility

Author

Ahmad, Rizwan, primary, Riaz, Muhammad, additional, Aldholmi, Mohammed, additional, Qureshi, Muhammad Asif, additional, Uddin, Shahab, additional, Bhat, Ajaz, additional, Poyil, Pratheeshkumar, additional, Baig, Mukhtiar, additional, Pourahmad, Jalal, additional, Ganesan, Trivadi, additional, Khan, Abdul, additional, Siddiqui, Zainab, additional, El-Demellawy, Maha, additional, Gholamalizadeh, Maryam, additional, Purnomosari, Dewajani, additional, Salim, Elsayed, additional, Mousavi Jarrahi, Seyedeh Zahra, additional, Zhang, Jian-ye, additional, Mohammad Nejad, Samad, additional, and Jarrahi, Alireza, additional

Published
2021
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137. Activation of NOTCH signaling via DLL1 is mediated by APE1-redox-dependent NF-κB activation in oesophageal adenocarcinoma

Author

Chen, Lei, Lu, Heng, Peng, Dunfa, Cao, Long Long, Ballout, Farah, Srirmajayam, Kannappan, Chen, Zheng, Bhat, Ajaz, Wang, Timothy C, Capobianco, Anthony, Que, Jianwen, McDonald, Oliver Gene, Zaika, Alexander, Zhang, Shutian, and El-Rifai, Wael

Abstract

ObjectiveOesophageal adenocarcinoma (EAC) arises in the setting of Barrett’s oesophagus, an intestinal metaplastic precursor lesion that can develop in patients with chronic GERD. Here, we investigated the role of acidic bile salts, the mimicry of reflux, in activation of NOTCH signaling in EAC.DesignThis study used public databases, EAC cell line models, L2-IL1β transgenic mouse model and human EAC tissue samples to identify mechanisms of NOTCH activation under reflux conditions.ResultsAnalysis of public databases demonstrated significant upregulation of NOTCH signaling components in EAC. In vitro studies demonstrated nuclear accumulation of active NOTCH1 cleaved fragment (NOTCH intracellular domain) and upregulation of NOTCH targets in EAC cells in response to reflux conditions. Additional investigations identified DLL1 as the predominant ligand contributing to NOTCH1 activation under reflux conditions. We discovered a novel crosstalk between APE1 redox function, reflux-induced inflammation and DLL1 upregulation where NF-κB can directly bind to and induce the expression of DLL1. The APE1 redox function was crucial for activation of the APE1-NF-κB-NOTCH axis and promoting cancer cell stem-like properties in response to reflux conditions. Overexpression of APE1 and DLL1 was detected in gastro-oesophageal junctions of the L2-IL1ß transgenic mouse model and human EAC tissue microarrays. DLL1 high levels were associated with poor overall survival in patients with EAC.ConclusionThese findings underscore a unique mechanism that links redox balance, inflammation and embryonic development (NOTCH) into a common pro-tumorigenic pathway that is intrinsic to EAC cells.

Published
2023
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138. Word-Object Learning via Visual Exploration in Space (WOLVES): A Neural Process Model of Cross-Situational Word Learning.

Author

Bhat, Ajaz A., Spencer, John P., and Samuelson, Larissa K.

Subjects
*VISUAL learning, *SPACE exploration, *AKAIKE information criterion, *ASSOCIATIVE learning
Abstract

Infants, children, and adults have been shown to track co-occurrence across ambiguous naming situations to infer the referents of new words. The extensive literature on this cross-situational word learning (CSWL) ability has produced support for two theoretical accounts--associative learning (AL) and hypothesis testing (HT)--but no comprehensive model of the behavior. We propose Word-Object Learning via Visual Exploration in Space (WOLVES), an implementation-level account of CSWL grounded in real-time psychological processes of memory and attention that explicitly models the dynamics of looking at a moment-to-moment scale and learning across trials. We use WOLVES to capture data from 12 studies of CSWL with adults and children, thereby providing a comprehensive account of data purported to support both AL and HT accounts. Direct model comparison shows that WOLVES performs well relative to two competitor models. In particular, WOLVES captures more data than the competitor models (132 vs. 69 data values) and fits the data better than the competitor models (e.g., lower percent error scores for 12 of 17 conditions). Moreover, WOLVES generalizes more accurately to three "held-out" experiments, although a model by Kachergis et al. (2012) fares better on another metric of generalization (Akaike Information Criterion [AIC]/Bayesian Information Criterion [BIC]). Critically, we offer the first developmental account of CSWL, providing insights into how memory processes change from infancy through adulthood. WOLVES shows that visual exploration and selective attention in CSWL are both dependent on and indicative of learning within a task-specific context. Furthermore, learning is driven by real-time synchrony of words and gaze and constrained by memory processes over multiple timescales. [ABSTRACT FROM AUTHOR]

Published
2022
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139. Chemokine-Cytokine Networks in the Head and Neck Tumor Microenvironment

Author

Nisar, Sabah, primary, Yousuf, Parvaiz, additional, Masoodi, Tariq, additional, Wani, Nissar A., additional, Hashem, Sheema, additional, Singh, Mayank, additional, Sageena, Geetanjali, additional, Mishra, Deepika, additional, Kumar, Rakesh, additional, Haris, Mohammad, additional, Bhat, Ajaz A., additional, and Macha, Muzafar A., additional

Published
2021
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140. Insights Into the Role of CircRNAs: Biogenesis, Characterization, Functional, and Clinical Impact in Human Malignancies

Author

Nisar, Sabah, primary, Bhat, Ajaz A., additional, Singh, Mayank, additional, Karedath, Thasni, additional, Rizwan, Arshi, additional, Hashem, Sheema, additional, Bagga, Puneet, additional, Reddy, Ravinder, additional, Jamal, Farrukh, additional, Uddin, Shahab, additional, Chand, Gyan, additional, Bedognetti, Davide, additional, El-Rifai, Wael, additional, Frenneaux, Michael P., additional, Macha, Muzafar A., additional, Ahmed, Ikhlak, additional, and Haris, Mohammad, additional

Published
2021
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142. Causal Learning by a Robot with Semantic-Episodic Memory in an Aesop's Fable Experiment

Author

Bhat, Ajaz A. and Mohan, Vishwanathan

Subjects
FOS: Computer and information sciences, Computer Science - Robotics, Artificial Intelligence (cs.AI), Computer Science - Artificial Intelligence, I.2.6, Robotics (cs.RO)
Abstract

Corvids, apes, and children solve The Crow and The Pitcher task (from Aesop's Fables) indicating a causal understanding of the task. By cumulatively interacting with different objects, how can cognitive agents abstract the underlying cause-effect relations to predict affordances of novel objects? We address this question by re-enacting the Aesop's Fable task on a robot and present a) a brain-guided neural model of semantic-episodic memory; with b) four task-agnostic learning rules that compare expectations from recalled past episodes with the current scenario to progressively extract the hidden causal relations. The ensuing robot behaviours illustrate causal learning; and predictions for novel objects converge to Archimedes' principle, independent of both the objects explored during learning and the order of their cumulative exploration., To appear in ICLR 2020 4 pages For associated videos, see https://www.youtube.com/playlist?list=PLIfoHEM1gr24EniCzBuUxZ2tqNpQA8QQm

Published
2020

149. Exploring Dysregulated Signaling Pathways in Cancer

Author

Nisar, Sabah, primary, Hashem, Sheema, additional, Macha, Muzafar A., additional, Yadav, Santosh K., additional, Muralitharan, Sankavi, additional, Therachiyil, Lubna, additional, Sageena, Geetanjali, additional, Al-Naemi, Hamda, additional, Haris, Mohammad, additional, and Bhat, Ajaz A., additional

Published
2020
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150. Brain microstructural changes support cognitive deficits in HIV uninfected children born to HIV infected mothers

Author

Yadav, Santosh K., primary, Gupta, Rakesh K., additional, Hashem, Sheema, additional, Nisar, Sabah, additional, Azeem, Taha, additional, Bhat, Ajaz A., additional, Syed, Najeeb, additional, Garg, Ravindra K., additional, Venkatesh, Vimala, additional, Kamal, Madeeha, additional, Fakhro, Khalid, additional, Frenneaux, Michael P., additional, and Haris, Mohammad, additional

Published
2020
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