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1. Synthesis and analysis of a novel thermal interface material for DC-DC boost converter

Author

Ali Hamza, Mariam Mahmood, Abasin Ulasyar, Syed Najeeb Ali Kazmi, Sheeraz Iqbal, Yazeed Yasin Ghadi, Ali Saeed Almuflih, and Z. M. S. Elbarbary

Subjects
Power electronics circuits, Boost converter, Thermal management, Thermal interface material, Thermal conductivity, Threshold frequency, Medicine, Science
Abstract

Abstract The rapid evolution of power electronics has triggered an intensified focus on thermal management within electronics circuits, stemming from the critical necessity to mitigate thermal-related failure rates. Thermal management in power electronics circuits relies heavily on efficient heat transfer to prevent overheating of components and ensure their reliable operation, optimal performance, and safety. To facilitate the effective heat transfer, a thermal interface material (TIM) is utilized between switching components such as MOSFETs and heat sinks to improve surface contact, which increases heat transfer. In this research work, a novel thermal interface material (TIM) based on Tungsten-Gallium is introduced and evaluated to enhance thermal properties such as thermal conductivity and viscosity of Gallium-based TIM material with the addition of Tungsten microparticles. The study involves the examination of three distinct TIM samples with varying Tungsten content. Their surface morphology, composition, and topography were analyzed through techniques such as Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) within the context of a DC-DC boost converter. The results indicate that the addition of Tungsten significantly enhances TIM’s viscosity and fluidity, even at high temperatures reaching up to 308 °C, which is crucial for power electronics circuits. In addition, thermal constant analyzer, and DC-DC converter circuit such as boost converter circuit were utilized for thermal and electrical characterization, respectively. These characterization results demonstrate that 10%/wt. addition of Tungsten can increase the thermal conductivity of Gallium from 13.1 to 22.82 W/m.K at room temperature, which represents an overall 74.2% increase in thermal conductivity. Furthermore, when the proposed TIM sample 2 was used in a boost converter circuit, the switching frequency of MOSFET IRF3808 was increased up to 20 kHz while the conduction losses were also lowest compared to other TIM samples.

Published
2024
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4. Mutational landscape of inflammatory breast cancer

Author

Bertucci, François, Lerebours, Florence, Ceccarelli, Michele, Guille, Arnaud, Syed, Najeeb, Finetti, Pascal, Adélaïde, José, Van Laere, Steven, Goncalves, Anthony, Viens, Patrice, Birnbaum, Daniel, Mamessier, Emilie, Callens, Céline, and Bedognetti, Davide

Published
2024
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5. Burden of Mendelian disorders in a large Middle Eastern biobank

Author

Aamer, Waleed, Al-Maraghi, Aljazi, Syed, Najeeb, Gandhi, Geethanjali Devadoss, Aliyev, Elbay, Al-Kurbi, Alya A., Al-Saei, Omayma, Kohailan, Muhammad, Krishnamoorthy, Navaneethakrishnan, Palaniswamy, Sasirekha, Al-Malki, Khulod, Abbasi, Saleha, Agrebi, Nourhen, Abbaszadeh, Fatemeh, Akil, Ammira S. Al-Shabeeb, Badii, Ramin, Ben-Omran, Tawfeg, Lo, Bernice, Mokrab, Younes, and Fakhro, Khalid A.

Published
2024
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6. Colonisation of hospital surfaces from low- and middle-income countries by extended spectrum β-lactamase- and carbapenemase-producing bacteria

Author

Nieto-Rosado, Maria, Sands, Kirsty, Portal, Edward A. R., Thomson, Kathryn M., Carvalho, Maria J., Mathias, Jordan, Milton, Rebecca, Dyer, Calie, Akpulu, Chinenye, Boostrom, Ian, Hogan, Patrick, Saif, Habiba, Sanches Ferreira, Ana D., Hender, Thomas, Portal, Barbra, Andrews, Robert, Watkins, W. John, Zahra, Rabaab, Shirazi, Haider, Muhammad, Adil, Ullah, Syed Najeeb, Jan, Muhammad Hilal, Akif, Shermeen, Iregbu, Kenneth C., Modibbo, Fatima, Uwaezuoke, Stella, Audu, Lamidi, Edwin, Chinago P., Yusuf, Ashiru H., Adeleye, Adeola, Mukkadas, Aisha S., Mazarati, Jean Baptiste, Rucogoza, Aniceth, Gaju, Lucie, Mehtar, Shaheen, Bulabula, Andrew N. H., Whitelaw, Andrew, Roberts, Lauren, Chan, Grace, Bekele, Delayehu, Solomon, Semaria, Abayneh, Mahlet, Metaferia, Gesit, and Walsh, Timothy R.

Published
2024
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7. Copolymerization of ethylene and isoprene initiated by metallocene catalyst

Author

Amjad Ali, Muhammad Nadeem, Ahmad Naveed, Jamile Mohammadi Moradian, Syed Najeeb-Uz-Zaman Haider, Shahid Khan, Adnan Murad Bhayo, Jianwei Lu, Rai Nauman Ali, Naushad Ahmad, Fan Zhiqiang, and Li Guo

Subjects
Metallocene, Olefin, Catalyst, Cocatalyst, Isoprene, Ethylene, Chemistry, QD1-999
Abstract

In this study, we explore the dynamic nature of metallocene catalysts during ethylene/isoprene E/IP) copolymerization, with a focus on the influence of various reaction parameters. Challenges, why do olefinic catalysts show lower activity and molecular weight (Mw) at higher temperatures and low activity with higher diene content? Firstly, we investigate the observed phenomena of decreased catalyst activity and Mw at elevated temperatures using 1.25 μmole of the metallocene. Notably, a substantial increase in active sites from 30 °C to 40 °C, reaching a peak of 89 %. Surprisingly, further temperature increments lead to a noticeable decline in active sites. At 30 °C, the active site primarily engages in the insertion of IP through 3,4 connections, with no detectable cis-1,4 or trans-1,4 connections, which suggests a lack of stereoselectivity at this temperature. At 40–50°C, cis/trans-1,4 connections and active sites are approaching a higher level. This implies a reduction in chain transfer reactions, making catalytic active sites more favorable to cis/trans-1,4 connections. Secondly, we observe a remarkable impact of IP concentration in the E/IP copolymers, active centers, and activity show stability when the amount of IP was 0.116–0.48 mol/L and then started to decline when the amount of IP 0.96 mol/L, indicating a threshold beyond which deactivation occurs. Increasing IP concentration not only reduces activity and active sites but also fails to reactivate dormant polyethylene sites. The Mw and active centers of copolymers progressively decrease with elevated IP concentration, suggesting a faster chain transfer reaction with IP compared to E.

Published
2024
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8. An integrated tumor, immune and microbiome atlas of colon cancer.

Author

Roelands, Jessica, Kuppen, Peter, Ahmed, Eiman, Mall, Raghvendra, Masoodi, Tariq, Singh, Parul, Monaco, Gianni, Raynaud, Christophe, de Miranda, Noel, Ferraro, Luigi, Carneiro-Lobo, Tatiana, Syed, Najeeb, Rawat, Arun, Awad, Amany, Decock, Julie, Mifsud, William, Miller, Lance, Sherif, Shimaa, Mohamed, Mahmoud, Rinchai, Darawan, Van den Eynde, Marc, Sayaman, Rosalyn, Ziv, Elad, Bertucci, Francois, Petkar, Mahir, Lorenz, Stephan, Mathew, Lisa, Wang, Kun, Murugesan, Selvasankar, Chaussabel, Damien, Vahrmeijer, Alexander, Wang, Ena, Ceccarelli, Anna, Fakhro, Khalid, Zoppoli, Gabriele, Ballestrero, Alberto, Tollenaar, Rob, Marincola, Francesco, Galon, Jérôme, Khodor, Souhaila, Ceccarelli, Michele, Hendrickx, Wouter, and Bedognetti, Davide

Subjects
Humans, Cohort Studies, Biomarkers, Tumor, Colonic Neoplasms, Transcriptome, Tumor Microenvironment
Abstract

The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

Published
2023

9. Colonisation of hospital surfaces from low- and middle-income countries by extended spectrum β-lactamase- and carbapenemase-producing bacteria

Author

Maria Nieto-Rosado, Kirsty Sands, Edward A. R. Portal, Kathryn M. Thomson, Maria J. Carvalho, Jordan Mathias, Rebecca Milton, Calie Dyer, Chinenye Akpulu, Ian Boostrom, Patrick Hogan, Habiba Saif, Ana D. Sanches Ferreira, Thomas Hender, Barbra Portal, Robert Andrews, W. John Watkins, Rabaab Zahra, Haider Shirazi, Adil Muhammad, Syed Najeeb Ullah, Muhammad Hilal Jan, Shermeen Akif, Kenneth C. Iregbu, Fatima Modibbo, Stella Uwaezuoke, Lamidi Audu, Chinago P. Edwin, Ashiru H. Yusuf, Adeola Adeleye, Aisha S. Mukkadas, Jean Baptiste Mazarati, Aniceth Rucogoza, Lucie Gaju, Shaheen Mehtar, Andrew N. H. Bulabula, Andrew Whitelaw, Lauren Roberts, Grace Chan, Delayehu Bekele, Semaria Solomon, Mahlet Abayneh, Gesit Metaferia, Group BARNARDS, and Timothy R. Walsh

Subjects
Science
Abstract

Abstract Hospital surfaces can harbour bacterial pathogens, which may disseminate and cause nosocomial infections, contributing towards mortality in low- and middle-income countries (LMICs). During the BARNARDS study, hospital surfaces from neonatal wards were sampled to assess the degree of environmental surface and patient care equipment colonisation by Gram-negative bacteria (GNB) carrying antibiotic resistance genes (ARGs). Here, we perform PCR screening for extended-spectrum β-lactamases (bla CTX-M-15) and carbapenemases (bla NDM, bla OXA-48-like and bla KPC), MALDI-TOF MS identification of GNB carrying ARGs, and further analysis by whole genome sequencing of bacterial isolates. We determine presence of consistently dominant clones and their relatedness to strains causing neonatal sepsis. Higher prevalence of carbapenemases is observed in Pakistan, Bangladesh, and Ethiopia, compared to other countries, and are mostly found in surfaces near the sink drain. Klebsiella pneumoniae, Enterobacter hormaechei, Acinetobacter baumannii, Serratia marcescens and Leclercia adecarboxylata are dominant; ST15 K. pneumoniae is identified from the same ward on multiple occasions suggesting clonal persistence within the same environment, and is found to be identical to isolates causing neonatal sepsis in Pakistan over similar time periods. Our data suggests persistence of dominant clones across multiple time points, highlighting the need for assessment of Infection Prevention and Control guidelines.

Published
2024
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13. Mapping the genetic landscape of treatable inherited metabolic disorders in a large Middle Eastern biobank

Author

Ismail, Said I., Al-Muftah, Wadha, Badji, Radja, Mbarek, Hamdi, Darwish, Dima, Fadl, Tasnim, Yasin, Heba, Ennaifar, Maryem, Abdellatif, Rania, Alkuwari, Fatima, Alvi, Muhammad, Al-Sarraj, Yasser, Saad, Chadi, Althani, Asmaa, Fethnou, Eleni, Qafoud, Fatima, Alkhayat, Eiman, Afifi, Nahla, Tomei, Sara, Liu, Wei, Lorenz, Stephan, Syed, Najeeb, Almabrazi, Hakeem, Vempalli, Fazulur Rehaman, Temanni, Ramzi, Saqri, Tariq Abu, Khatib, Mohammedhusen, Hamza, Mehshad, Zaid, Tariq Abu, El Khouly, Ahmed, Pathare, Tushar, Poolat, Shafeeq, Al-Ali, Rashid, Albagha, Omar, Al-Khodor, Souhaila, Alshafai, Mashael, Badii, Ramin, Chouchane, Lotfi, Estivill, Xavier, Fakhro, Khalid A., Mokrab, Younes, Puthen, Jithesh V., Suhre, Karsten, Tatari, Zohreh, Devadoss Gandhi, Geethanjali, Aliyev, Elbay, Al-Saei, Omayma, Al-Maraghi, Aljazi, Abdi, Mona, Krishnamoorthy, Navaneethakrishnan, Akil, Ammira A., and Ben-Omran, Tawfeg

Published
2024
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16. Genomic architecture of autism spectrum disorder in Qatar: The BARAKA-Qatar Study

Author

Abdi, Mona, Aliyev, Elbay, Trost, Brett, Kohailan, Muhammad, Aamer, Waleed, Syed, Najeeb, Shaath, Rulan, Gandhi, Geethanjali Devadoss, Engchuan, Worrawat, Howe, Jennifer, Thiruvahindrapuram, Bhooma, Geng, Melissa, Whitney, Joe, Syed, Amira, Lakshmi, Jyothi, Hussein, Sura, Albashir, Najwa, Hussein, Amal, Poggiolini, Ilaria, Elhag, Saba F., Palaniswamy, Sasirekha, Kambouris, Marios, de Fatima Janjua, Maria, Tahir, Mohamed O. El, Nazeer, Ahsan, Shahwar, Durre, Azeem, Muhammad Waqar, Mokrab, Younes, Aati, Nazim Abdel, Akil, Ammira, Scherer, Stephen W., Kamal, Madeeha, and Fakhro, Khalid A.

Published
2023
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19. Germline genetic contribution to the immune landscape of cancer.

Author

Sayaman, Rosalyn W, Saad, Mohamad, Thorsson, Vésteinn, Hu, Donglei, Hendrickx, Wouter, Roelands, Jessica, Porta-Pardo, Eduard, Mokrab, Younes, Farshidfar, Farshad, Kirchhoff, Tomas, Sweis, Randy F, Bathe, Oliver F, Heimann, Carolina, Campbell, Michael J, Stretch, Cynthia, Huntsman, Scott, Graff, Rebecca E, Syed, Najeeb, Radvanyi, Laszlo, Shelley, Simon, Wolf, Denise, Marincola, Francesco M, Ceccarelli, Michele, Galon, Jérôme, Ziv, Elad, and Bedognetti, Davide

Subjects
Killer Cells, Natural, T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Humans, Neoplasms, Interferons, Immunotherapy, Signal Transduction, Gene Expression Regulation, Neoplastic, Quantitative Trait, Heritable, Germ-Line Mutation, Genes, BRCA1, Databases, Genetic, Middle Aged, Female, Male, Retinoblastoma-Like Protein p107, Wnt Proteins, beta Catenin, Genome-Wide Association Study, Cancer immunotherapy, GWAS, Immune subtypes, TCGA, cancer immune landscape, cancer immunity, germline genetics, heritability, iATLAS, rare variant analysis, Genetics, Human Genome, Cancer, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Immunology
Abstract

Understanding the contribution of the host's genetic background to cancer immunity may lead to improved stratification for immunotherapy and to the identification of novel therapeutic targets. We investigated the effect of common and rare germline variants on 139 well-defined immune traits in ∼9000 cancer patients enrolled in TCGA. High heritability was observed for estimates of NK cell and T cell subset infiltration and for interferon signaling. Common variants of IFIH1, TMEM173 (STING1), and TMEM108 were associated with differential interferon signaling and variants mapping to RBL1 correlated with T cell subset abundance. Pathogenic or likely pathogenic variants in BRCA1 and in genes involved in telomere stabilization and Wnt-β-catenin also acted as immune modulators. Our findings provide evidence for the impact of germline genetics on the composition and functional orientation of the tumor immune microenvironment. The curated datasets, variants, and genes identified provide a resource toward further understanding of tumor-immune interactions.

Published
2021

22. Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Author

Saha, Samir, Islam, Maksuda, Bin-Ahmed, Zabed, Ahmed, Wazir, Begum, Taslima, Chowdhury, Mitu, Sharmin, Shaila, Rani Dey, Chumki, Uttam, Matin, Abdul, Chakraborty, Sowmitra Ranjan, Tasmin, Sadia, Rema, Dipa, Khatun, Rashida, Nath, Liza, Balkachew, Nigatu, Bekele, Delayehu, Schaughency, Katherine, Solomon, Semaria, Gebreyohanes, Zenebe, Ambachew, Rozina, Odumade, Oludare, Haileselassie, Misgana, Chan, Grace, Russo, Abigail, Workneh, Redeat, Metaferia, Gesit, Abayneh, Mahlet, Mohammed, Yahya Zekaria, Biteye, Tefera, Teklu, Alula, Gezahegn, Wendimagegn, Chakravorty, Partha Sarathi, Mukherjee, Anuradha, Nandy, Ranjan Kumar, Roy, Samarpan, Sinha, Anuradha, Naha, Sharmi, Malakar, Sukla Saha, Bose, Siddhartha, Majhi, Monaki, Sahoo, Subhasree, Mukherjee, Putul, Routa, Sumitra Kumari, Nandi, Chaitali, Basu, Sulagna, Saha, Bijan, Chattopadhyay, Pinaki, Modibbo, Fatima Zara Isa, Uwaezuoke, Stella, Meduekwe, Dilichukwu, Muhammad, Khairiyya, Nsude, Queen, Ukeh, Ifeoma, Okenu, Mary-Joe, Chinenye, Akpulu, Yakubu, Samuel, Asunugwo, Vivian, Aina, Folake, Issy, Isibong, Adekeye, Dolapo, Eunice, Adiele, Amina, Abdulmlik, Oyewole, R, Oloton, I, Nnaji, BC, Umejiego, M, Anoke, PN, Adebayo, S, Abegunrin, GO, Omotosho, OB, Ibrahim, R, Igwe, B, Abroko, M, Balami, K, Bayem, L, Anyanwu, C, Haruna, H, Okike, J, Goroh, K, Boi-Sunday, M, Ugafor, Augusta, Makama, Maryam, Ndukwe, Kaniba, Odama, Anastesia, Yusuf, Hadiza, Wachukwu, Patience, Yahaya, Kachalla, Kalade Colsons, Titus, Kura, Mercy, Orebiyi, Damilola, Iregbu, Kenneth C., Mmadueke, Chukwuemeka, Audu, Lamidi, Idris, Nura, Gambo, Safiya, Ibrahim, Jamila, Precious, Edwin, Hassan, Ashiru, Gwadabe, Shamsudden, Adeleye Falola, Adeola, Aliyu, Muhammad, Ibrahim, Amina, Mukaddas, Aisha Sani, Khalid, Rashida Yakubu, Alkali, Fatima Ibrahim, Muhammad, Maryam Yahaya, Tukur, Fatima Mohammad, Muhammad, Surayya Mustapha, Shittu, Adeola, Bello, Murjanatu, Hassan, Muhammad Abubakar, Sa ad, Fatima Habib, Kassim, Aishatu, Shirazi, Haider, Muhammad, Adil, Zahra, Rabaab, Ullah, Syed Najeeb, Hilal Jan, Muhammad, Kamran, Rubina, Sajana, Saeed, Jazba, Maqsood, Noreen, Zafar, Maria, Sadiq, Saraeen, Ahsan, Sumble, Tariq, Madiha, Sajid, Sidra, Mustafa, Hasma, Rehman, Anees-ur, Muhammad, Atif, Mehmood, Gahssan, Nisar, Mahnoor, Akif, Shermeen, Yasmeen, Tahira, Nawaz, Sabir, Atta, Anam Shanal, Laiq-ur-Rehman, Mian, Kousar, Robina, Bibi, Kalsoom, Waheed, Kosar, Majeed, Zainab, Jalil, Ayesha, Kajibwami, Espoir, Rucogoza, Aniceth, Nzabahimana, Innocent, Jean-Baptiste, Mazarati, Gaju, Lucie, Riziki, Kankundiye, Uwamahoro, Brigette, Uwera, Rachel, Nyiratuza, Eugenie, Muzungu, Kumwami, Uwitonze, Violette, Horanimpundu, Marie C, Nzeyimana, Francine, Mitima, Prince, Dramowski, Angela, Whitelaw, Andrew, Paterson, Lauren, Frans, Mary, Johnson, Marvina, Swanepoel, Eveline, Bojana, Zoleka, du Preez, Mieme, Mehtar, Shaheen, Bulabula, Andre, Liu, Feiyan, van Hasselt, Johan GC, Walsh, Timothy, Sands, Kirsty, Carvalho, Maria, Milton, Rebecca, Thomson, Kathryn, Portal, Edward, Mathias, Jordan, Dyer, Calie, Ferreira, Ana, Andrews, Robert, Watkins, John, Gillespie, David, Hood, Kerry, Taiyai, Katie, Kirby, Nigel, Nieto, Maria, Hender, Thomas, Hogan, Patrick, Saif, Habiba, Hassan, Brekhna, Jones, Ellis, Barrell, Matthew, Boostrom, Ian, Frayne, Francis, Rees, Jessica, Jones, Lim, Dunachie, Susanna, Spiller, Brad, Parkhill, Julian, Thomson, Kathryn M, Carvalho, Maria J, Farzana, Refath, Chan, Grace J, Mahlet, Abayneh, Nandy, Ranjan K, Iregbu, Kenneth, Modibbo, Fatima, Syed, Najeeb U, Mazarati, Jean-Baptiste, Bulabula, Andre N H, van Hasselt, Johan G C, and Walsh, Timothy R

Published
2021
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24. A population study of clinically actionable genetic variation affecting drug response from the Middle East

Author

Jithesh, Puthen Veettil, Abuhaliqa, Mohammed, Syed, Najeeb, Ahmed, Ikhlak, El Anbari, Mohammed, Bastaki, Kholoud, Sherif, Shimaa, Umlai, Umm-Kulthum, Jan, Zainab, Gandhi, Geethanjali, Manickam, Chidambaram, Selvaraj, Senthil, George, Chinnu, Bangarusamy, Dhinoth, Abdel-latif, Rania, Al-Shafai, Mashael, Tatari-Calderone, Zohreh, Estivill, Xavier, and Pirmohamed, Munir

Published
2022
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26. The QChip1 knowledgebase and microarray for precision medicine in Qatar

Author

Rodriguez-Flores, Juan L., Messai-Badji, Radja, Robay, Amal, Temanni, Ramzi, Syed, Najeeb, Markovic, Monika, Al-khayat, Eiman, Qafoud, Fatima, Nawaz, Zafar, Badii, Ramin, Al-Sarraj, Yasser, Mbarek, Hamdi, Al-Muftah, Wadha, Alvi, Muhammad, Rostami, Mahboubeh R., Cruzado, Juan Carlos Martinez, Mezey, Jason G., Shakaki, Alya Al, Malek, Joel A., Greenblatt, Matthew B., Fakhro, Khalid A., Machaca, Khaled, Al-Nabet, Ajayeb, Afifi, Nahla, Brooks, Andrew, Ismail, Said I., Althani, Asmaa, and Crystal, Ronald G.

Published
2022
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27. Genetic predisposition to cancer across people of different ancestries in Qatar: a population-based, cohort study

Author

Ismail, Said I, Al-Muftah, Wadha, Badji, Radja, Mbarek, Hamdi, Darwish, Dima, Fadl, Tasnim, Yasin, Heba, Ennaifar, Maryem, Abdellatif, Rania, Alkuwari, Fatima, Alvi, Muhammad, Al-Sarraj, Yasser, Saad, Chadi, Fethnou, Eleni, Qafoud, Fatima, Alkhayat, Eiman, Afifi, Nahla, Tomei, Sara, Liu, Wei, Lorenz, Stephan, Syed, Najeeb, Almabrazi, Hakeem, Vempalli, Fazulur R, Temanni, Ramzi, Abu Saqri, Tariq, Khatib, Mohammedhusen, Hamza, Mehshad, Abu Zaid, Tariq, El Khouly, Ahmed, Pathare, Tushar, Poolat, Shafeeq, Al-Ali, Rashid, Albagha, Omar, Al-Khodor, Souhaila, Alshafai, Mashael, Badii, Ramin, Chouchane, Lotfi, Estivill, Xavier, Fakhro, Khalid, Mokrab, Younes, Puthen, Jithesh V, Suhre, Karsten, Tatari, Zohreh, Saad, Mohamad, Halabi, Najeeb, Shan, Jingxuan, Razali, Rozaimi, Kunji, Khalid, Subramanian, Murugan, Ceccarelli, Michele, Rafii Tabrizi, Arash, and Bedognetti, Davide

Published
2022
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28. Whole-exome profiles of inflammatory breast cancer and pathological response to neoadjuvant chemotherapy.

Author

Bertucci, François, Guille, Arnaud, Lerebours, Florence, Ceccarelli, Michele, Syed, Najeeb, Adélaïde, José, Finetti, Pascal, Ueno, Naoto T., Van Laere, Steven, Viens, Patrice, De Nonneville, Alexandre, Goncalves, Anthony, Birnbaum, Daniel, Callens, Céline, Bedognetti, Davide, and Mamessier, Emilie

Abstract

Background: Neoadjuvant chemotherapy (NACT) became a standard treatment strategy for patients with inflammatory breast cancer (IBC) because of high disease aggressiveness. However, given the heterogeneity of IBC, no molecular feature reliably predicts the response to chemotherapy. Whole-exome sequencing (WES) of clinical tumor samples provides an opportunity to identify genomic alterations associated with chemosensitivity. Methods: We retrospectively applied WES to 44 untreated IBC primary tumor samples and matched normal DNA. The pathological response to NACT, assessed on operative specimen, distinguished the patients with versus without pathological complete response (pCR versus no-pCR respectively). We compared the mutational profiles, spectra and signatures, pathway mutations, copy number alterations (CNAs), HRD, and heterogeneity scores between pCR versus no-pCR patients. Results: The TMB, HRD, and mutational spectra were not different between the complete (N = 13) versus non-complete (N = 31) responders. The two most frequently mutated genes were TP53 and PIK3CA. They were more frequently mutated in the complete responders, but the difference was not significant. Only two genes, NLRP3 and SLC9B1, were significantly more frequently mutated in the complete responders (23% vs. 0%). By contrast, several biological pathways involved in protein translation, PI3K pathway, and signal transduction showed significantly higher mutation frequency in the patients with pCR. We observed a higher abundance of COSMIC signature 7 (due to ultraviolet light exposure) in tumors from complete responders. The comparison of CNAs of the 3808 genes included in the GISTIC regions between both patients' groups identified 234 genes as differentially altered. The CIN signatures were not differentially represented between the complete versus non-complete responders. Based on the H-index, the patients with heterogeneous tumors displayed a lower pCR rate (11%) than those with less heterogeneous tumors (35%). Conclusions: This is the first study aiming at identifying correlations between the WES data of IBC samples and the achievement of pCR to NACT. Our results, obtained in this 44-sample series, suggest a few subtle genomic alterations associated with pathological response. Additional investigations are required in larger series. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Genetic architecture of congenital hypogonadotropic hypogonadism: insights from analysis of a Portuguese cohort.

Author

Carriço, Josianne Nunes, Gonçalves, Catarina Inês, Al-Naama, Asma, Syed, Najeeb, Aragüés, José Maria, Bastos, Margarida, Fonseca, Fernando, Borges, Teresa, Pereira, Bernardo Dias, Pignatelli, Duarte, Carvalho, Davide, Cunha, Filipe, Saavedra, Ana, Rodrigues, Elisabete, Saraiva, Joana, Ruas, Luisa, Vicente, Nuno, Martins, João Martin, Lages, Adriana De Sousa, and Oliveira, Maria João

Subjects
HEREDITY, DNA copy number variations, GENETIC testing, PORTUGUESE people, GENE frequency, KALLMANN syndrome
Abstract

STUDY QUESTION What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)? SUMMARY ANSWER Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included. WHAT IS KNOWN ALREADY CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility. STUDY DESIGN, SIZE, DURATION Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls. PARTICIPANTS/MATERIALS, SETTING, METHODS The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS). MAIN RESULTS AND THE ROLE OF CHANCE A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were GNRHR , FGFR1 , ANOS1 , and CHD7. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken. WIDER IMPLICATIONS OF THE FINDINGS This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Portuguese Foundation for Science and Technology (grant numbers PTDC/SAU-GMG/098419/2008, UIDB/00709/2020, CEECINST/00016/2021/CP2828/CT0002, and 2020.04924.BD) and by Sidra Medicine—a member of the Qatar Foundation (grant number SDR400038). The authors declare no competing interests. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Clinical features, epidemiology, autoantibody status, HLA haplotypes and genetic mechanisms of type 1 diabetes mellitus among children in Qatar

Author

Haris, Basma, Ahmed, Ikhlak, Syed, Najeeb, Almabrazi, Hakeem, Saraswathi, Saras, Al-Khawaga, Sara, Saeed, Amira, Mundekkadan, Shihab, Mohammed, Idris, Sharari, Sanaa, Hawari, Iman, Hamed, Noor, Afyouni, Houda, Abdel-Karim, Tasneem, Mohammed, Shayma, Khalifa, Amel, Al-Maadheed, Maryam, Zyoud, Mahmoud, Shamekh, Ahmed, Elawwa, Ahmed, Karim, Mohammed Y., Al-Khalaf, Fawziya, Tatari-Calderone, Zohreh, Petrovski, Goran, and Hussain, Khalid

Published
2021
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38. Colonisation of extended spectrum β-lactamase- and carbapenemase-producing bacteria on hospital surfaces from low-/middle-income countries

Author

Nieto-Rosado, Maria, primary, Sands, Kirsty, additional, Portal, Edward, additional, Thomson, Katy, additional, Carvalho, Maria, additional, Mathias, Jordan, additional, Milton, Rebecca, additional, Dyer, Calie, additional, Akpulu, Chinenye, additional, Boostrom, Ian, additional, Hogan, Patrick, additional, Saif, Habiba, additional, Ferreira, Ana Sanches, additional, Hender, Thomas, additional, Portal, Barbra, additional, Andrews, Robert, additional, Watkins, W, additional, Zahra, Rabaab, additional, Shirazi, Haider, additional, Muhammad, Adil, additional, Ullah, Syed Najeeb, additional, Jan, Muhammad Hilal, additional, Akif, Shermeen, additional, Iregbu, Kenneth, additional, Modibbo, Fatima, additional, Uwaezuoke, Stella, additional, Audu, Lamidi, additional, Edwin, Chinago, additional, Yusuf, Ashiru, additional, Adeleye, Adeola, additional, Mukkadas, Aisha, additional, Mazarati, Jean Baptiste, additional, Rucogoza, Aniceth, additional, Gaju, Lucie, additional, Mehtar, Shaheen, additional, Bulabula, Andrew, additional, Whitelaw, Andrew, additional, Roberts, Lauren, additional, Chan, Grace, additional, Bekele, Delayehu, additional, Solomon, Semaria, additional, Abayneh, Mahlet, additional, Metaferia, Gesit, additional, BARNARDS, Group, additional, and Walsh, Timothy, additional

Published
2023
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40. A new state of charge estimation technique of lithium-ion battery using adaptive extended Kalman filter and artificial neural network

Author

Syed Najeeb Ali Kazmi, Abasin Ulasyar, Abraiz Khattak, and Haris Sheh Zad

Subjects
Instrumentation
Abstract

Due to rapid rise in climate change, world is seeing a major technology shift from conventional vehicles to electric vehicles (EVs). Battery’s state of charge (SOC) is a critical parameter in EVs whose accuracy affects not only the battery management system but can also influence the driving range estimation for an EV. In this paper, a simulation-based hybrid technique is presented, that combines both adaptive extended Kalman filter (AEKF) and artificial neural network (ANN) for SOC estimation of lithium-ion battery. The proposed hybrid technique is validated using five different EV driving cycles, that is, LA92, US06, urban dynamometer driving schedule (UDDS), highway fuel economy test (HWFET) and a mixed driving cycle at four different temperature values, that is, 0°C, 10°C, 25°C and 40°C. To facilitate the potential EV users, a real-time SOC estimator is also implemented. The real-time SOC estimated through open circuit voltage method and Coulomb counting method is further used for reservation of a charging slot in a nearby charging station. Moreover, to monitor the charging status of a potential EV from a remote location, a cloud-based Internet of things (IoT) platform, that is, ThingSpeak, is used. This results into the reduction of waiting time for an EV user at a charging station. In addition to this, a comparative analysis is carried out between proposed hybrid method and existing methods. It is demonstrated that our hybrid technique achieves lower root mean square error and higher accuracy as compared to existing methods at different operating conditions.

Published
2022

42. A variant in sperm‐specific glycolytic enzyme enolase 4 (ENO4) causes human male infertility.

Author

Nawaz, Shoaib, Hussain, Shabir, Bilal, Muhammad, Syed, Najeeb, Liaqat, Khurram, Ullah, Imran, Akil, Ammira Al‐Shabeeb, Fakhro, Khalid A., and Ahmad, Wasim

Abstract

Background: Although defects in sperm morphology and physiology lead to male infertility, in many instances, the exact disruption of molecular pathways in a given patient is often unknown. The glycolytic pathway is an essential process to supply energy in sperm cell motility. Enolase 4 (ENO4) is crucial for the glycolytic process, which provides the energy for sperm cells in motility. ENO4 is located in the sperm principal piece and is essential for the motility and organization of the sperm flagellum. In the present study, we characterized a family with asthenozoospermia and abnormal sperm morphology as a result of a variant in the enolase 4 (ENO4) gene. Methods: Computer‐assisted semen analysis, papanicolaou smear staining and scanning electron microscopy were used to examine sperm motility and morphology for semen analysis in patients. For genetic analysis, whole‐exome sequencing followed by Sanger sequencing was performed. Results: Two brothers in a consanguineous family were being clinically investigated for sperm motility and morphology issues. Genetic analysis by whole‐exome sequencing revealed a homozygous variant [c.293A>G, p.(Lys98Arg)] in the ENO4 gene that segregated with infertility in the family, shared by affected but not controls. Conclusions: In view of the association of asthenozoospermia and abnormal sperm morphology in Eno4 knockout mice, we consider this to be the first report describing the involvement of ENO4 gene in human male infertility. We also explore the possible involvement of another variant in explaining other phenotypic features in this family. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Author

Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian'an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O'Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Ismail, Said I., Al-Muftah, Wadha, Badji, Radja, Mbarek, Hamdi, Darwish, Dima, Fadl, Tasnim, Yasin, Heba, Ennaifar, Maryem, Abdellatif, Rania, Alkuwari, Fatima, Alvi, Muhammad, Al-Sarraj, Yasser, Saad, Chadi, Althani, Asmaa, Fethnou, Eleni, Qafoud, Fatima, Alkhayat, Eiman, Afifi, Nahla, Tomei, Sara, Liu, Wei, Lorenz, Stephan, Syed, Najeeb, Almabrazi, Hakeem, Vempalli, Fazulur Rehaman, Temanni, Ramzi, Abu Saqri, Tariq, Khatib, Mohammedhusen, Hamza, Mehshad, Abu Zaid, Tariq, El Khouly, Ahmed, Pathare, Tushar, Poolat, Shafeeq, Al-Ali, Rashid, Al-Khodor, Souhaila, Alshafai, Mashael, Badii, Ramin, Chouchane, Lotfi, Estivill, Xavier, Fakhro, Khalid, Mokrab, Younes, Puthen, Jithesh, V, Tatari, Zohreh, Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimaki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietilainen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josee, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., Tobin, Martin, Shrine, Nick, Izquierdo, Abril G., Chen, Jing, Packer, Richard, Hall, Robert J., Guyatt, Anna L., Batini, Chiara, Thompson, Rebecca J., Pavuluri, Chandan, Malik, Vidhi, Hobbs, Brian D., Moll, Matthew, Kim, Wonji, Tal-Singer, Ruth, Bakke, Per, Fawcett, Katherine A., John, Catherine, Coley, Kayesha, Piga, Noemi Nicole, Pozarickij, Alfred, Lin, Kuang, Millwood, Iona Y., Chen, Zhengming, Li, Liming, Wijnant, Sara R. A., Lahousse, Lies, Brusselle, Guy, Uitterlinden, Andre G., Manichaikul, Ani, Oelsner, Elizabeth C., Rich, Stephen S., Barr, R. Graham, Kerr, Shona M., Vitart, Veronique, Brown, Michael R., Wielscher, Matthias, Imboden, Medea, Jeong, Ayoung, Bartz, Traci M., Gharib, Sina A., Flexeder, Claudia, Karrasch, Stefan, Gieger, Christian, Peters, Annette, Stubbe, Beate, Hu, Xiaowei, Ortega, Victor E., Meyers, Deborah A., Bleecker, Eugene R., Gabriel, Stacey B., Gupta, Namrata, Smith, Albert Vernon, Luan, Jian'an, Zhao, Jing-Hua, Hansen, Ailin F., Langhammer, Arnulf, Willer, Cristen, Bhatta, Laxmi, Porteous, David, Smith, Blair H., Campbell, Archie, Sofer, Tamar, Lee, Jiwon, Daviglus, Martha L., Yu, Bing, Lim, Elise, Xu, Hanfei, O'Connor, George T., Thareja, Gaurav, Albagha, Omar M. E., Ismail, Said I., Al-Muftah, Wadha, Badji, Radja, Mbarek, Hamdi, Darwish, Dima, Fadl, Tasnim, Yasin, Heba, Ennaifar, Maryem, Abdellatif, Rania, Alkuwari, Fatima, Alvi, Muhammad, Al-Sarraj, Yasser, Saad, Chadi, Althani, Asmaa, Fethnou, Eleni, Qafoud, Fatima, Alkhayat, Eiman, Afifi, Nahla, Tomei, Sara, Liu, Wei, Lorenz, Stephan, Syed, Najeeb, Almabrazi, Hakeem, Vempalli, Fazulur Rehaman, Temanni, Ramzi, Abu Saqri, Tariq, Khatib, Mohammedhusen, Hamza, Mehshad, Abu Zaid, Tariq, El Khouly, Ahmed, Pathare, Tushar, Poolat, Shafeeq, Al-Ali, Rashid, Al-Khodor, Souhaila, Alshafai, Mashael, Badii, Ramin, Chouchane, Lotfi, Estivill, Xavier, Fakhro, Khalid, Mokrab, Younes, Puthen, Jithesh, V, Tatari, Zohreh, Suhre, Karsten, Granell, Raquel, Faquih, Tariq O., Hiemstra, Pieter S., Slats, Annelies M., Mullin, Benjamin H., Hui, Jennie, James, Alan, Beilby, John, Patasova, Karina, Hysi, Pirro, Koskela, Jukka T., Wyss, Annah B., Jin, Jianping, Sikdar, Sinjini, Lee, Mikyeong, May-Wilson, Sebastian, Pirastu, Nicola, Kentistou, Katherine A., Joshi, Peter K., Timmers, Paul R. H. J., Williams, Alexander T., Free, Robert C., Wang, Xueyang, Morrison, John L., Gilliland, Frank D., Chen, Zhanghua, Wang, Carol A., Foong, Rachel E., Harris, Sarah E., Taylor, Adele, Redmond, Paul, Cook, James P., Mahajan, Anubha, Lind, Lars, Palviainen, Teemu, Lehtimaki, Terho, Raitakari, Olli T., Kaprio, Jaakko, Rantanen, Taina, Pietilainen, Kirsi H., Cox, Simon R., Pennell, Craig E., Hall, Graham L., Gauderman, W. James, Brightling, Chris, Wilson, James F., Vasankari, Tuula, Laitinen, Tarja, Salomaa, Veikko, Mook-Kanamori, Dennis O., Timpson, Nicholas J., Zeggini, Eleftheria, Dupuis, Josee, Hayward, Caroline, Brumpton, Ben, Langenberg, Claudia, Weiss, Stefan, Homuth, Georg, Schmidt, Carsten Oliver, Probst-Hensch, Nicole, Jarvelin, Marjo-Riitta, Morrison, Alanna C., Polasek, Ozren, Rudan, Igor, Lee, Joo-Hyeon, Sayers, Ian, Rawlins, Emma L., Dudbridge, Frank, Silverman, Edwin K., Strachan, David P., Walters, Robin G., Morris, Andrew P., London, Stephanie J., Cho, Michael H., Wain, Louise V., Hall, Ian P., and Tobin, Martin

Abstract

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.

Published
2023
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47. Co-Movement of Digital Currencies and Asian Stock Indexes: A Wavelets Based Multiresolution Analysis

Author

Laraib, Muhammad, Siddiqui, Ammar Ahmed, Kaiser, Syed Najeeb Ullah, Laraib, Muhammad, Siddiqui, Ammar Ahmed, and Kaiser, Syed Najeeb Ullah

Abstract

The paper examines the co-movement relationship between Cryptocurrency and Asian major indices through Wavelet Coherence multiresolution technique and the Granger causality for result robustness. The indices data of Singapore and Japan stock market was used from January 2018 to December 2022, the outcome of our study shows great of co-relationship in the movement between Asian two major listed equity market indices and Cryptocurrencies investments. Moreover, the study shows that Japan stock market found to be more positively correlated with existing cryptocurrencies in comparison to Singapore stock market.

Published
2023

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