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Hameed, S.

Publications and source records attributed to Hameed, S..

8 recordsLinked to original sources

Cumulative Transfer Function for Assessment of MRI-Induced RF Heating Risk in Pediatric Patients Implanted with Bifurcated Leads

PurposeRF-induced heating remains a major barrier to MRI access for patients with epicardial cardiac implantable electronic devices (CIEDs). Although ISO/TS 10974 Tier-3 transfer function (TF) methods are established for unbranched leads, no analogous framework exists for bifurcated leads, in which branch asymmetry and inter-branch coupling may substantially alter heating. We developed and validated a cumulative transfer function (cTF) framework to address this gap. MethodsFollowing ISO/TS 10974 Tier-3 formalism, we measured, calibrated, and validated cTFs for a commercial 35 cm bipolar epicardial lead at 1.5 T. The framework explicitly accounts for branch-specific response and cross-branch coupling. Validation was performed with 24 canonical lead configurations in a homogeneous phantom and, without recalibration, in a heterogeneous anthropomorphic pediatric phantom with clinically derived trajectories. A single-branch TF approximation served as a comparator. The validated cTF was applied to predict RF heating across adult and pediatric human models at multiple imaging landmarks. ResultsCompared with the single-branch TF approximation, the cTF reduced prediction error by nearly 70% in the primary validation dataset. In secondary validation, the cTF maintained low error across clinically relevant trajectories and imaging landmarks. In human models, the framework revealed marked anatomy- and landmark-dependent variation in predicted heating for the tested 35 cm lead, with low predicted heating in pediatric models and substantially higher heating in selected adult chest and upper abdominal imaging scenarios. ConclusionThe cTF provides a validated framework for RF-heating assessment of bifurcated leads and substantially improves prediction accuracy over single-branch TF approximations that neglect branch coupling.

bioengineering↗

Task-Based Spinal fMRI using a Median Nerve Stimulation Reveals Functional Alterations in Degenerative Cervical Myelopathy

Functional spinal cord MRI (fMRI) is an emerging technique for evaluating sensorimotor responses in both healthy and disease states. However, degenerative cervical myelopathy (DCM), a non-traumatic, age-related pathology characterized by spinal cord compression, often leads to motor and sensory impairments that make standard task-based fMRI paradigms challenging to perform or execute. To overcome this, we implemented an fMRI paradigm using direct electrical stimulation to the median nerve to evoke neural responses in both motor and sub-motor spinal cord pathways. In this study, 23 DCM and 23 aged-matched healthy controls (HC) underwent two task-based spinal cord fMRI sessions with direct, median nerve stimulation to the right upper limb. Motor thresholds were determined on an individual basis by a thumb/finger twitching, and sub-motor thresholds were set to be 15% underneath motor with no visible twitching. Blood Oxygenation Level Depended (BOLD) signals were analyzed across the C5-C8 cervical spinal cord segments. HCs demonstrated increased activation during motor vs sub-motor stimulation (1155 vs 496 voxels; +7.1%), whereas DCM patients showed reduction in activation with higher stimulation (1028 vs 1220 voxels; -2.2%). This activation pattern was consistent across the cervical spinal segments, with HCs peaking at C7 (sub-motor: 328 voxels, motor: 608 voxels), which is consistent with median nerve input for forearm and hand. While DCM responses were altered, with sub-motor differentially maximized at C6 (406 voxels) and abnormal recruitment at C5 (112 voxels) and C8 (198 voxels). Spatially, HC responses were focused in the gray matter (GM) and bilateral, whereas DCM responses showed reduced GM localization and were more ipsilateral. Furthermore, we saw spikes in sub-motor DCM deactivation at the overall (3032 voxels) and C6 root level (1500 voxels) that were greater than the other conditions. This study demonstrates the feasibility and effectiveness of median nerve stimulation as a task-based paradigm for assessing spinal cord function in those with spinal cord compression. Group level differences between DCM patients and age-matched HCs showed spatial and quantitatively distinct patterns across stimulation thresholds and spinal segments. Our findings suggest disrupted sub-motor and motor activation in the DCM group, highlighting the use of this approach as a functional biomarker to capture disease specific alterations.

neuroscience↗

Hypoxia induced lipid alterations in iPSC-derived human glial progenitor cells revealed by Matrix assisted laser desorption ionization mass spectrometry based cellular fingerprinting

BackgroundIncreasing evidence suggests that the development of highly aggressive form of brain tumor "glioblastoma" contain cancer stem cells that closely resemble glial progenitor cells. The hypoxic microenvironment of tumors leads to metabolic reprogramming of cells, driving them towards more aggressive and treatment resistant state. To identify better targets for the effective removal of hypoxia adaptive cells, it is crucial to understand how these cells alter metabolism in hypoxic conditions. MethodsWe have used confocal microscopy to visualize mitochondrial morphology which confirmed hypoxia, and matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) to decipher lipid metabolic changes in iPSC-derived human glial progenitor cells induced by that hypoxia. ResultsOur findings revealed that hypoxia induced changes in mitochondrial morphology, interaction of mitochondria with lysosomes, and the expression of oxidized lipid species in iPSC-derived human glial progenitor cells. Hypoxic cells showed elongated mitochondria that resembled strings. MALDI-MSI based finger printing showed upregulation of oxidized phosphatidylethanolamine (PE): m/z 716.484 PE(33:1)+O, m/z 730.01 PE(34:1)+O, m/z 766.497 PE(37:5)+O, m/z 768.510 PE(37:4)+O, and oxidized phosphatidylcholine (PC): m/z 742.500 PC(32:2)+O, m/z 744.513 PC(33:2)+O, m/z 770.531 PC(34:2)+O), m/z 794.534 PC(34:1)+O, m/z 888.523 PC(42:11)+OH, and oxidized phosphatidic acid (PA): m/z 673.444 PA(33:2)+O, m/z 699.466 PA(35:3)+OH, m/z 725.531 PA(37:4)+OH in hypoxic cells. ConclusionsGiven the importance of glial progenitor cells in the central nervous system, as a precursor of glioblastoma, and their structural reliance on lipids, the molecular perturbations in the cell as a result of oxygen deficiency (hypoxia) remains unclear. The change in mitochondrial morphology showed that the cells were under hypoxic stress and mass spectrometry imaging unveiled important lipid metabolic changes in hypoxic iPSC-derived human glial progenitor cells as byproducts of oxidative stress, and provided insights that could lead to better treatment strategies for hypoxia-resistant cells. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/672639v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@873267org.highwire.dtl.DTLVardef@1fe4810org.highwire.dtl.DTLVardef@12d1aa3org.highwire.dtl.DTLVardef@30048f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG Graphical abstract was created in BioRender https://app.biorender.com/illustrations/6822efb6aadd8c37669dd403

biochemistry↗

From Shadows to Data: A Robust Population Assessment of Snow Leopards in the Highland Crossroads

The snow leopard (Panthera uncia) is a flagship species of the greater Himalayan region - referred to as the Third Pole - and symbolizes integrity of this ecological system. Within the greater Himalayas, Pakistan holds special significance as the north of the country represents a confluence of four major mountain ranges (Hindu Kush, Pamir, Karakoram, and Himalaya). However, robustly surveying and monitoring elusive, low-density species such as snow leopards has historically been difficult in the region. As a result, our understanding of the spatial patterns in density and overall population size of snow leopards has remained conjectural in the highland crossroads of northern Pakistan. This lack of objective information is an obstacle to realizing effective conservation planning for the species in Pakistan, as well as the broader ecosystem within which it plays a key role. This study aimed to empirically derive population estimates for snow leopards in Pakistan, based on robust camera trapping. Extensive camera trapping was conducted covering about 39% of the snow leopard range in Pakistan from 2010 to 2019, spread across the four major mountain ranges in the north of the country. A total of 828 cameras were placed over 26,540 trap days, resulting in 4,712 photos of snow leopards obtained from 65 different locations. Among the 53 unique individuals identified, the majority (53%) were detected only once, with an overall recapture frequency of 2.28 times per individual. Spatial capture-recapture (SCR) was employed for population and density estimation. Model selection strongly favored a model in which density was positively associated with elevation, and camera type influenced baseline encounter rates. The estimated population size for snow leopards in this highland crossroads was 127 (95% CI 88-182) adult animals, with a mean density of 0.13 (95% CI 0.09-0.19) animals per 100 km{superscript 2}. Examination of the density predictions revealed that higher density areas were associated with protected areas and greater prey biomass, highlighting the importance of these two key factors. This research provides the first robust population estimate for snow leopards in this region, establishing a foundation for long-term population monitoring and assessing the effectiveness of conservation measures. We recommend the integration of complementary approaches, such as non-invasive genetic methods, to validate and refine population estimates.

ecology↗

Next-generation snow leopard population assessment tool: multiplex-PCR SNP panel for individual identification from feces

Snow leopards, Panthera uncia, are under threat from numerous pressures and are the focus of a great deal of conservation efforts. However, their elusive nature makes it difficult to estimate population sizes. Current methods used to monitor local population sizes include visually identifying individuals from camera trap photos and genetically identifying individuals from fecal samples using microsatellite loci. Here, we present a new method for identifying snow leopard individuals from fecal samples using a multiplex PCR single nucleotide polymorphism (SNP) panel method. The SNP panel we present consists of 144 SNPs and utilizes next-generation sequencing technology, making it cheaper and easier than current microsatellite methods. We validate our SNP panel with paired tissue and fecal samples from zoo individuals, showing a minimum of 96.7% accuracy in allele calls per run. We then generate SNP data from 235 field-collected fecal samples from across Pakistan to show that the panel can reliably identify individuals from low-quality fecal samples of unknown age and is robust to contamination. We also show that our SNP panel has the capability to identify first-order relatives and provides insights into the geographic origin of samples. This SNP panel will empower the snow leopard research community in their efforts to assess local and global snow leopard population sizes. More broadly, we present a method for developing a SNP panel that utilizes open source software for SNP selection and primer design, Illumina sequencing technology, and a streamlined lab and bioinformatics protocol which can be used to create similar SNP panels for any species of interest for which adequate genomic reference data is available.

genetics↗

Spatial proteomics and transcriptomics of placenta accreta spectrum

In severe Placenta Accreta Spectrum (PAS), trophoblasts gain deep access in the myometrium (placenta increta). This study investigated alterations at the fetal-maternal interface in PAS cases using a systems biology approach consisting of immunohistochemistry, spatial transcriptomics and proteomics. We identified spatial variation in the distribution of CD4+, CD3+ and CD8+ T-cells at the maternal-interface in placenta increta cases. Spatial transcriptomics identified transcription factors involved in promotion of trophoblast invasion such as AP-1 subunits ATF-3 and JUN, and NFKB were upregulated in regions with deep myometrial invasion. Pathway analysis of differentially expressed genes demonstrated that degradation of extracellular matrix (ECM) and class 1 MHC protein were increased in increta regions, suggesting local tissue injury and immune suppression. Spatial proteomics demonstrated that increta regions were characterised by excessive trophoblastic proliferation in an immunosuppressive environment. Expression of inhibitors of apoptosis such as BCL-2 and fibronectin were increased, while CTLA-4 was decreased and increased expression of PD-L1, PD-L2 and CD14 macrophages. Additionally, CD44, which is a ligand of fibronectin that promotes trophoblast invasion and cell adhesion was also increased in increta regions. We subsequently examined ligand receptor interactions enriched in increta regions, with interactions with ITG{beta}1, including with fibronectin and ADAMS, emerging as central in increta. These ITG{beta}1 ligand interactions are involved in activation of epithelial-mesenchymal transition and remodelling of ECM suggesting a more invasive trophoblast phenotype. In PAS, we suggest this is driven by fibronectin via AP-1 signalling, likely as a secondary response to myometrial scarring. Overall, this study suggests the biological processes leading to deep trophoblast invasion in the myometrium in placenta increta are as a result of upregulation of transcription factors and subsequent genes and proteins which promote trophoblast invasion. This occurs in a locally immune suppressed environment, with increased ECM degradation suggesting these findings are secondary to iatrogenic uterine injury. Significance statementPlacenta Accreta Spectrum (PAS) is a rare pregnancy complication, where the placenta fails to separate from the womb resulting in severe bleeding, which is associated with significant maternal morbidity and mortality. As Caesarean section rates increase, the incidence of PAS is increasing. The underlying pathophysiology of PAS is poorly understood. Here, we apply a spatial multi-omic approach to explore the biologic changes at the maternal-fetal interface in severe PAS (placenta increta). Using spatial transcriptomics and proteomics, we identified genes and proteins that are dysregulated in severe PAS involving processes such as extracellular matrix degradation, local immune suppression and promotion of epithelial-mesenchymal transition. This study provides new insights into the biological changes and underlying pathophysiology leading to placenta increta.

bioinformatics↗

A study on packed cell volume for deducing hemoglobin: Cholistani camels in perspective

In human medical practice, a hematological rule of three has been validated for healthy human populations. One such formula is estimating hemoglobin (Hb) levels as 1/3rd of Packed Cell Volume (PCV). However, no such hematological formulae have been devised and validated for veterinary medical practice. The present study was devised with an aim to evaluate the relationship between hemoglobin (Hb) concentration and Packed Cell Volume (PCV) in camels (n=215) being reared under pastoralism, and to devise a simple pen-side hematological formula for estimation of Hb from PCV. The PCV was determined through microhematocrit method whereas Hb estimation by cyanmethaemoglobin method (HbD). The Hb was also calculated as 1/3rd of PCV and was dubbed as calculated Hb (HbC). Overall HbD and HbC were significantly (P[≥]0.05) different. Similar results were attained for all study groups i.e. males (n=94) and females (n=121), and young (n=85) and adult (n=130) camels. The corrected Hb (CHb) was deduced through regression prediction equation attained from linear regression model. Scatter-plots were drawn, linear regression was carried out, and Bland Altman chart was built for agreement of both methods of Hb estimation. A non-significant (P[≥]0.05) difference was noticed between HbD and CHb. Bland Altman chart revealed good agreement between HbD and CHb and there was no proportional bias on the distribution of data around the mean difference line (Mean= 0.1436, 95% CI= 3.00, -2.72). We accordingly recommend a simplified pen-side hematological formula for deducing Hb concentration from PCV viz. Hb concentration (g/dL)=0.18(PCV)+5.4 for all age and gender groups of camels instead of its calculation as one-third of PCV.

physiology↗

Identifying Priority Landscapes for Conservation of Snow Leopards in Pakistan

Pakistans total estimated snow leopard habitat is about 80,000 km2 of which about half is considered prime. However, this preliminary demarcation was not always in close agreement with the actual distribution--the discrepancy may be huge at the local and regional level. Recent technological developments like camera trapping and molecular genetics allow for collecting reliable presence records that could be used to construct realistic species distribution based on empirical data and advanced mathematical approaches like MaxEnt. Current study followed this approach to construct accurate distribution of the species in Pakistan. Moreover, movement corridors, among different landscapes, were also identified through the circuit theory. The habitat suitability map, generated from 384 presence points and 28 environmental variables, scored the snow leopards assumed range in Pakistan, from 0 to 0.97. A large shear of previously known range represented low-quality habitat, including areas in lower Chitral, Swat, Astore and Kashmir. Conversely, Khunjerab, Misgar, Chapursan, Qurumber, Broghil, and Central Karakoram represented high-quality habitats. Variables with higher contribution in the MaxEnt model were precipitation of driest month (34%), annual mean temperature (19.5%), mean diurnal range of temperature (9.8%), annual precipitation (9.4%) and river density (9.2). The validation texts suggest a good model fit, and strong prediction power. The connectivity analysis revealed that the population in the Hindukush landscape appears to be more connected with the population in Afghanistan as compared to other populations in Pakistan. Similarly, the Pamir-Karakoram population is better connected with China and Tajikistan, while the Himalayan population was with the population in India. Current study allows for proposing three model landscapes to be considered under GSLEP agenda as regional priority areas, to safeguard safeguard future of the species in the long run. These landsacpes fall in mountain ranges of the Himalaya, Hindu Kush and Karakoram-Pamir, respectively. We also identified gaps in existing protected areas network, and suggest new protected areas in Chitral and Gilgit-Baltistan to protect critical habitats of snow leopard in Pakistan.

zoology↗