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Article ; Online: Deep feature based cross-slide registration.

Awan, Ruqayya / Raza, Shan E Ahmed / Lotz, Johannes / Weiss, Nick / Rajpoot, Nasir

Computerized medical imaging and graphics : the official journal of the Computerized Medical Imaging Society

2022 Volume 104, Page(s) 102162

Abstract: Registration of multiple sections in a tissue block is an important pre-requisite task before any cross-slide image analysis. Non-rigid registration methods are capable of finding correspondence by locally transforming a moving image. These methods often ...

Abstract	Registration of multiple sections in a tissue block is an important pre-requisite task before any cross-slide image analysis. Non-rigid registration methods are capable of finding correspondence by locally transforming a moving image. These methods often rely on an initial guess to roughly align an image pair linearly and globally. This is essential to prevent convergence to a non-optimal minimum. We explore a deep feature based registration (DFBR) method which utilises data-driven descriptors to estimate the global transformation. A multi-stage strategy is adopted for improving the quality of registration. A visualisation tool is developed to view registered pairs of WSIs at different magnifications. With the help of this tool, one can apply a transformation on the fly without the need to generate a transformed moving WSI in a pyramidal form. We compare the performance on our dataset of data-driven descriptors with that of hand-crafted descriptors. Our approach can align the images with only small registration errors. The efficacy of our proposed method is evaluated for a subsequent non-rigid registration step. To this end, the first two steps of the ANHIR winner's framework are replaced with DFBR to register image pairs provided by the challenge. The modified framework produce comparable results to those of the challenge winning team.
MeSH term(s)	Image Processing, Computer-Assisted/methods
Language	English
Publishing date	2022-12-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	639451-6
ISSN	1879-0771 ; 0895-6111
ISSN (online)	1879-0771
ISSN	0895-6111
DOI	10.1016/j.compmedimag.2022.102162
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Book ; Online: Mimicking a Pathologist

Raza, Manahil / Awan, Ruqayya / Bashir, Raja Muhammad Saad / Qaiser, Talha / Rajpoot, Nasir M.

Dual Attention Model for Scoring of Gigapixel Histology Images

2023

Abstract: Some major challenges associated with the automated processing of whole slide images (WSIs) includes their sheer size, different magnification levels and high resolution. Utilizing these images directly in AI frameworks is computationally expensive due ... ...

Abstract	Some major challenges associated with the automated processing of whole slide images (WSIs) includes their sheer size, different magnification levels and high resolution. Utilizing these images directly in AI frameworks is computationally expensive due to memory constraints, while downsampling WSIs incurs information loss and splitting WSIs into tiles and patches results in loss of important contextual information. We propose a novel dual attention approach, consisting of two main components, to mimic visual examination by a pathologist. The first component is a soft attention model which takes as input a high-level view of the WSI to determine various regions of interest. We employ a custom sampling method to extract diverse and spatially distinct image tiles from selected high attention areas. The second component is a hard attention classification model, which further extracts a sequence of multi-resolution glimpses from each tile for classification. Since hard attention is non-differentiable, we train this component using reinforcement learning and predict the location of glimpses without processing all patches of a given tile, thereby aligning with pathologist's way of diagnosis. We train our components both separately and in an end-to-end fashion using a joint loss function to demonstrate the efficacy of our proposed model. We employ our proposed model on two different IHC use cases: HER2 prediction on breast cancer and prediction of Intact/Loss status of two MMR biomarkers, for colorectal cancer. We show that the proposed model achieves accuracy comparable to state-of-the-art methods while only processing a small fraction of the WSI at highest magnification.
Keywords	Electrical Engineering and Systems Science - Image and Video Processing ; Computer Science - Computer Vision and Pattern Recognition
Subject code	006
Publishing date	2023-02-19
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Deciphering the differential expression patterns of yield-related negative regulators in hexaploid wheat cultivars and hybrids at different growth stages.

Awan, Muhammad Jawad Akbar / Farooq, Muhammad Awais / Naqvi, Rubab Zahra / Karamat, Umer / Bukhari, Sayyad Ali Raza / Waqas, Muhammad Abu Bakar / Mahmood, Muhammad Arslan / Buzdar, Muhammad Ismail / Rasheed, Awais / Amin, Imran / Saeed, Nasir A / Mansoor, Shahid

Molecular biology reports

2024 Volume 51, Issue 1, Page(s) 537

Abstract: Background: Hexaploid bread wheat underwent a series of polyploidization events through interspecific hybridizations that conferred adaptive plasticity and resulted in duplication and neofunctionalization of major agronomic genes. The genetic ... ...

Abstract	Background: Hexaploid bread wheat underwent a series of polyploidization events through interspecific hybridizations that conferred adaptive plasticity and resulted in duplication and neofunctionalization of major agronomic genes. The genetic architecture of polyploid wheat not only confers adaptive plasticity but also offers huge genetic diversity. However, the contribution of different gene copies (homeologs) encoded from different subgenomes (A, B, D) at different growth stages remained unexplored. Methods: In this study, hybrid of elite cultivars of wheat were developed via reciprocal crosses (cytoplasm swapping) and phenotypically evaluated. We assessed differential expression profiles of yield-related negative regulators in these cultivars and their F1 hybrids and identified various cis-regulatory signatures by employing bioinformatics tools. Furthermore, the preferential expression patterns of the syntenic triads encoded from A, B, and D subgenomes were assessed to decipher their functional redundancy at six different growth stages. Results: Hybrid progenies showed better heterosis such as up to 17% increase in the average number of grains and up to 50% increase in average thousand grains weight as compared to mid-parents. Based on the expression profiling, our results indicated significant dynamic transcriptional expression patterns, portraying the different homeolog-dominance at the same stage in the different cultivars and their hybrids. Albeit belonging to same syntenic triads, a dynamic trend was observed in the regulatory signatures of these genes that might be influencing their expression profiles. Conclusion: These findings can substantially contribute and provide insights for the selective introduction of better cultivars into traditional and hybrid breeding programs which can be harnessed for the improvement of future wheat.
MeSH term(s)	Triticum/genetics ; Plant Breeding ; Hybridization, Genetic ; Hybrid Vigor/genetics
Language	English
Publishing date	2024-04-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-024-09454-0
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Book ; Online: Deep Feature based Cross-slide Registration

Awan, Ruqayya / Raza, Shan E Ahmed / Lotz, Johannes / Weiss, Nick / Rajpoot, Nasir

2022

Abstract: Cross-slide image analysis provides additional information by analysing the expression of different biomarkers as compared to a single slide analysis. These biomarker stained slides are analysed side by side, revealing unknown relations between them. ... ...

Abstract	Cross-slide image analysis provides additional information by analysing the expression of different biomarkers as compared to a single slide analysis. These biomarker stained slides are analysed side by side, revealing unknown relations between them. During the slide preparation, a tissue section may be placed at an arbitrary orientation as compared to other sections of the same tissue block. The problem is compounded by the fact that tissue contents are likely to change from one section to the next and there may be unique artefacts on some of the slides. This makes registration of each section to a reference section of the same tissue block an important pre-requisite task before any cross-slide analysis. We propose a deep feature based registration (DFBR) method which utilises data-driven features to estimate the rigid transformation. We adopted a multi-stage strategy for improving the quality of registration. We also developed a visualisation tool to view registered pairs of WSIs at different magnifications. With the help of this tool, one can apply a transformation on the fly without the need to generate transformed source WSI in a pyramidal form. We compared the performance of data-driven features with that of hand-crafted features on the COMET dataset. Our approach can align the images with low registration errors. Generally, the success of non-rigid registration is dependent on the quality of rigid registration. To evaluate the efficacy of the DFBR method, the first two steps of the ANHIR winner's framework are replaced with our DFBR to register challenge provided image pairs. The modified framework produces comparable results to that of challenge winning team.
Keywords	Electrical Engineering and Systems Science - Image and Video Processing ; Computer Science - Computer Vision and Pattern Recognition
Subject code	004
Publishing date	2022-02-20
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Deep Learning based Prediction of MSI using MMR Markers in Colorectal Cancer

Awan, Ruqayya / Nimir, Mohammed / Raza, Shan E Ahmed / Bilal, Mohsin / Lotz, Johannes / Snead, David / Robinson, Andrew / Rajpoot, Nasir

2022

Abstract: The accurate diagnosis and molecular profiling of colorectal cancers are critical for planning the best treatment options for patients. Microsatellite instability (MSI) or mismatch repair (MMR) status plays a vital role in appropriate treatment selection, ...

Abstract	The accurate diagnosis and molecular profiling of colorectal cancers are critical for planning the best treatment options for patients. Microsatellite instability (MSI) or mismatch repair (MMR) status plays a vital role in appropriate treatment selection, has prognostic implications and is used to investigate the possibility of patients having underlying genetic disorders (Lynch syndrome). NICE recommends that all CRC patients should be offered MMR/MSI testing. Immunohistochemistry is commonly used to assess MMR status with subsequent molecular testing performed as required. This incurs significant extra costs and requires additional resources. The introduction of automated methods that can predict MSI or MMR status from a target image could substantially reduce the cost associated with MMR testing. Unlike previous studies on MSI prediction involving training a CNN using coarse labels (MSI vs Microsatellite Stable (MSS)), we have utilised fine-grain MMR labels for training purposes. In this paper, we present our work on predicting MSI status in a two-stage process using a single target slide either stained with CK8/18 or H&E. First, we trained a multi-headed convolutional neural network model where each head was responsible for predicting one of the MMR protein expressions. To this end, we performed the registration of MMR stained slides to the target slide as a pre-processing step. In the second stage, statistical features computed from the MMR prediction maps were used for the final MSI prediction. Our results demonstrated that MSI classification can be improved by incorporating fine-grained MMR labels in comparison to the previous approaches in which only coarse labels were utilised.
Keywords	Quantitative Biology - Quantitative Methods ; Computer Science - Computer Vision and Pattern Recognition ; Electrical Engineering and Systems Science - Image and Video Processing
Subject code	006
Publishing date	2022-02-24
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Clinical and Economic Burden of Percutaneous Coronary Intervention in Hospitalized Young Adults in the United States, 2004-2018.

Minhas, Abdul Mannan Khan / Awan, Muhammad Umer / Raza, Munis / Virani, Salim S / Sharma, Garima / Blankstein, Ron / Blaha, Michael J / Al-Kindi, Sadeer G / Kaluksi, Edo / Nasir, Khurram / Khan, Safi U

Current problems in cardiology

2021 Volume 47, Issue 11, Page(s) 101070

Abstract: The clinical and economic burden of percutaneous coronary intervention (PCI) in young adults (18-45 years) is understudied. We used the National Inpatient Sample database between 2004 and 2018 to study trends in PCI volume, in-hospital mortality, length ... ...

Abstract	The clinical and economic burden of percutaneous coronary intervention (PCI) in young adults (18-45 years) is understudied. We used the National Inpatient Sample database between 2004 and 2018 to study trends in PCI volume, in-hospital mortality, length of stay (LOS), and health care expenditure among adults aged 18-45 years who underwent PCI. The data were weighted to explore national estimates of the entire US hospitalized population. We identified 558,611 PCI cases, equivalent to 31.4 per 1,000,000 person-years; 25.4% were women, and 69.5% were White adults. Overall, annual PCI volume significantly decreased from 41.6 per 100,000 in 2004 to 21.9 per 100,000 in 2018, mainly due to 83% volume reduction in non-myocardial infarction (MI) cases. The prevalence of cardiometabolic comorbidities, smoking, and drug abuse increased. Overall, in-hospital mortality was 0.87%; women had higher mortality than men (1.12% vs 0.78%; P = 0.01). The crude and risk-adjusted in-hospital mortality significantly increased between 2004 and 2018. Women, STEMI, NSTEMI, drug abuse, heart failure, peripheral vascular disease, and renal failure were associated with higher odds of in-hospital mortality. Inflation-adjusted cost significantly increased over time ($21,567 to $24,173). We noted reduction in PCI volumes but increasing mortality and clinical comorbidities among young patients undergoing PCI. Demographic disparities existed with women having higher in-hospital mortality than men.
MeSH term(s)	Female ; Financial Stress ; Hospital Mortality ; Humans ; Male ; Non-ST Elevated Myocardial Infarction ; Percutaneous Coronary Intervention ; Risk Factors ; ST Elevation Myocardial Infarction ; Treatment Outcome ; United States/epidemiology ; Young Adult
Language	English
Publishing date	2021-11-26
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	441230-8
ISSN	1535-6280 ; 0146-2806
ISSN (online)	1535-6280
ISSN	0146-2806
DOI	10.1016/j.cpcardiol.2021.101070
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Article: Neurodegenerative diseases and effective drug delivery: A review of challenges and novel therapeutics

Akhtar, Amna / Andleeb, Anisa / Waris, Tayyba Sher / Bazzar, Masoomeh / Moradi, Ali-Reza / Awan, Nasir Raza / Yar, Muhammad

Journal of controlled release. 2021 Feb. 10, v. 330

2021

Abstract: The central nervous system (CNS) encompasses the brain and spinal cord and is considered the processing center and the most vital part of human body. The central nervous system (CNS) barriers are crucial interfaces between the CNS and the periphery. ... ...

Abstract	The central nervous system (CNS) encompasses the brain and spinal cord and is considered the processing center and the most vital part of human body. The central nervous system (CNS) barriers are crucial interfaces between the CNS and the periphery. Among all these biological barriers, the blood-brain barrier (BBB) strongly impede hurdle for drug transport to brain. It is a semi-permeable diffusion barrier against the noxious chemicals and harmful substances present in the blood stream and regulates the nutrients delivery to the brain for its proper functioning. Neurological diseases owing to the existence of the BBB and the blood-spinal cord barrier have been terrible and threatening challenges all over the world and can rarely be directly mediated. In fact, drug delivery to brain remained a challenge in the treatment of neurodegenerative (ND) disorders, for these different approaches have been proposed. Nano-fabricated smart drug delivery systems and implantable drug loaded biomaterials for brain repair are among some of these latest approaches. In current review, modern approaches developed to deal with the challenges associated with transporting drugs to the CNS are included. Recent studies on neural drug discovery and injectable hydrogels provide a potential new treatment option for neurological disorders. Moreover, induced pluripotent stem cells used to model ND diseases are discussed to evaluate drug efficacy. These protocols and recent developments will enable discovery of more effective drug delivery systems for brain.
Keywords	biocompatible materials ; blood flow ; blood-brain barrier ; brain ; drug delivery systems ; drugs ; humans ; hydrogels ; induced pluripotent stem cells ; models ; neurodegenerative diseases ; nutrients ; spinal cord
Language	English
Dates of publication	2021-0210
Size	p. 1152-1167.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2020.11.021
Database	NAL-Catalogue (AGRICOLA)

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Article: Selenium and Salt Interactions in Black Gram (

Jawad Hassan, Muhammad / Ali Raza, Muhammad / Khan, Imran / Ahmad Meraj, Tehseen / Ahmed, Mukhtar / Abbas Shah, Ghulam / Ansar, Muhammad / Awan, Samrah Afzal / Khan, Nanak / Iqbal, Nasir / Peng, Yan / Li, Zhou

Plants (Basel, Switzerland)

2020 Volume 9, Issue 4

Abstract: Salinity is a major abiotic stress which limits crop production, especially under rainfed conditions. Selenium (Se), as an important micronutrient, plays a vital role in mitigating detrimental effects of different abiotic stresses. The objective of this ... ...

Abstract	Salinity is a major abiotic stress which limits crop production, especially under rainfed conditions. Selenium (Se), as an important micronutrient, plays a vital role in mitigating detrimental effects of different abiotic stresses. The objective of this research was to examine the effect of Se fertilization on black gram (
Language	English
Publishing date	2020-04-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704341-1
ISSN	2223-7747
ISSN	2223-7747
DOI	10.3390/plants9040467
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Article ; Online: Neurodegenerative diseases and effective drug delivery: A review of challenges and novel therapeutics.

Akhtar, Amna / Andleeb, Anisa / Waris, Tayyba Sher / Bazzar, Masoomeh / Moradi, Ali-Reza / Awan, Nasir Raza / Yar, Muhammad

Journal of controlled release : official journal of the Controlled Release Society

2020 Volume 330, Page(s) 1152–1167

Abstract	The central nervous system (CNS) encompasses the brain and spinal cord and is considered the processing center and the most vital part of human body. The central nervous system (CNS) barriers are crucial interfaces between the CNS and the periphery. Among all these biological barriers, the blood-brain barrier (BBB) strongly impede hurdle for drug transport to brain. It is a semi-permeable diffusion barrier against the noxious chemicals and harmful substances present in the blood stream and regulates the nutrients delivery to the brain for its proper functioning. Neurological diseases owing to the existence of the BBB and the blood-spinal cord barrier have been terrible and threatening challenges all over the world and can rarely be directly mediated. In fact, drug delivery to brain remained a challenge in the treatment of neurodegenerative (ND) disorders, for these different approaches have been proposed. Nano-fabricated smart drug delivery systems and implantable drug loaded biomaterials for brain repair are among some of these latest approaches. In current review, modern approaches developed to deal with the challenges associated with transporting drugs to the CNS are included. Recent studies on neural drug discovery and injectable hydrogels provide a potential new treatment option for neurological disorders. Moreover, induced pluripotent stem cells used to model ND diseases are discussed to evaluate drug efficacy. These protocols and recent developments will enable discovery of more effective drug delivery systems for brain.
MeSH term(s)	Blood-Brain Barrier ; Brain ; Central Nervous System ; Drug Delivery Systems ; Humans ; Neurodegenerative Diseases/drug therapy
Language	English
Publishing date	2020-11-13
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	632533-6
ISSN	1873-4995 ; 0168-3659
ISSN (online)	1873-4995
ISSN	0168-3659
DOI	10.1016/j.jconrel.2020.11.021
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Article ; Online: Identification of a Novel Homozygous Missense (c.443A>T:p.N148I) Mutation in

Ali, Ghazanfar / Sadia / Foo, Jia Nee / Nasir, Abdul / Chang, Chu-Hua / Chew, Elaine GuoYan / Latif, Zahid / Azeem, Zahid / Ain-Ul-Batool, Syeda / Kazmi, Syed Akif Raza / Awan, Naheed Bashir / Khan, Abdul Hameed / Rehman, Fazal-Ur- / Khalid, Madiha / Wali, Abdul / Sarwar, Samina / Akhtar, Wasim / Ahmed Abbasi, Ansar / Nisar, Rameez

BioMed research international

2021 Volume 2021, Page(s) 6626015

Abstract: Background: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease- ... ...

Abstract	Background: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. Methods: The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. Results: WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the Conclusion: Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.
MeSH term(s)	Adult ; Amino Acid Substitution ; Bardet-Biedl Syndrome/metabolism ; Bardet-Biedl Syndrome/pathology ; Female ; Homozygote ; Humans ; India ; Male ; Mutation, Missense ; Pedigree ; Proteins/genetics
Chemical Substances	Bbs2 protein, human ; Proteins
Language	English
Publishing date	2021-02-23
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2021/6626015
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