Ultime 50 pubblicazioni PubMed

  • Enabling uncertainty estimation in neural networks through weight perturbation for improved Alzheimer's disease classification
    on 21 Febbraio 2024

    CONCLUSION: We believe that being able to estimate the uncertainty of a prediction, along with tools that can modulate the behavior of the network to a degree of confidence that the user is informed about (and comfortable with), can represent a crucial step in the direction of user compliance and easier integration of deep learning tools into everyday tasks currently performed by human operators.

  • Concomitant transthyretin cardiac amyloidosis in patients undergoing TAVR for aortic stenosis: A systemic review and meta-analysis
    on 17 Febbraio 2024

    CONCLUSION: The overall pooled TTRCA-AS prevalence was reported to be 13.3% in AS patients who underwent TAVR. Furthermore, transthyretin-associated CA was found to be associated with an increased risk of mortality and hospitalization. Large patient population studies are required to assess the safety and efficacy of TAVR in TTRCA-AS patients, as current research report data from small patient cohorts.

  • COVID-19 Testing Trend: A Retrospective Analysis of the Three Major Pandemic Waves in Punjab, Pakistan
    on 15 Febbraio 2024

    CONCLUSION: In this study, there is convincing evidence of COVID-19 under-testing and thus under-reporting. This study also suggests that fear-based interventions may be counterproductive; however, economic factors such as education, employment, and traveling are significant in guiding the behavior for infectious disease prevention and management.

  • Salivary Galectin 3 Levels in Schizophrenia Patients
    on 11 Febbraio 2024

    CONCLUSION: Galectin 3 levels are raised in the saliva of schizophrenia patients and these levels are positively correlated with levels of galectin 3 in the serum of schizophrenia patients. Galectin 3 levels in the saliva can be an effective indicator in diagnostic confirmation of clinically suspected schizophrenia patients.

  • Echo state networks for the recognition of type 1 Brugada syndrome from conventional 12-LEAD ECG
    on 9 Febbraio 2024

    Artificial Intelligence (AI) applications and Machine Learning (ML) methods have gained much attention in recent years for their ability to automatically detect patterns in data without being explicitly taught rules. Specific features characterise the ECGs of patients with Brugada Syndrome (BrS); however, there is still ambiguity regarding the correct diagnosis of BrS and its differentiation from other pathologies. This work presents an application of Echo State Networks (ESN) in the Recurrent...

  • Identifying cortical structure markers of resilience to adversity in young people using surface-based morphometry
    on 30 Gennaio 2024

    Previous research on the neurobiological bases of resilience in youth has largely used categorical definitions of resilience and voxel-based morphometry methods that assess gray matter volume. However, it is important to consider brain structure more broadly as different cortical properties have distinct developmental trajectories. To address these limitations, we used surface-based morphometry and data-driven, continuous resilience scores to examine associations between resilience and cortical...

  • Optimized two-stage time-truncated control chart for Weibull distribution
    on 24 Gennaio 2024

    In this article, an attribute control chart is proposed when the lifetime of a product follows a Weibull distribution in two-stage sampling, which is based on the number of failures from a truncated life test. The coefficients of the proposed double sampling attribute control chart and the test duration are determined so that the average run length when the process is in control is close to the target value. An overview is reported on how double sampling np control charts work. Tables reporting...

  • Predicting the Length of Stay of Cardiac Patients Based on Pre-Operative Variables-Bayesian Models vs. Machine Learning Models
    on 23 Gennaio 2024

    Length of stay (LoS) prediction is deemed important for a medical institution's operational and logistical efficiency. Sound estimates of a patient's stay increase clinical preparedness and reduce aberrations. Various statistical methods and techniques are used to quantify and predict the LoS of a patient based on pre-operative clinical features. This study evaluates and compares the results of Bayesian (simple Bayesian regression and hierarchical Bayesian regression) models and machine learning...

  • Whole-genome analysis and evolutionary characterization of cervical and oral human papillomavirus 16
    on 10 Gennaio 2024

    High-throughput genome-wide sequencing has revealed high genomic variability of HPV16 in different geographic regions which is the most predominant genotype in human papillomavirus (HPV)-associated malignancies. Analysis of the HPV16 by whole-genome sequence (WGS) is an advanced method for the identification of mutations in the genome. There is limited information about HPV16 diversity in Pakistan, especially at the genomic level. Till now, WGS for HPV16 has not been previously reported in...

  • A translational MRI approach to validate acute axonal damage detection as an early event in multiple sclerosis
    on 9 Gennaio 2024

    Axonal degeneration is a central pathological feature of multiple sclerosis and is closely associated with irreversible clinical disability. Current noninvasive methods to detect axonal damage in vivo are limited in their specificity and clinical applicability, and by the lack of proper validation. We aimed to validate an MRI framework based on multicompartment modeling of the diffusion signal (AxCaliber) in rats in the presence of axonal pathology, achieved through injection of a neurotoxin...

  • Effects of transcranial magnetic stimulation on reactive response inhibition
    on 9 Gennaio 2024

    Reactive response inhibition cancels impending actions to enable adaptive behavior in ever-changing environments and has wide neuropsychiatric implications. A canonical paradigm to measure the covert inhibition latency is the stop-signal task (SST). To probe the cortico-subcortical network underlying motor inhibition, transcranial magnetic stimulation (TMS) has been applied over central nodes to modulate SST performance, especially to the right inferior frontal cortex and the presupplementary...

  • Adult Para Testicular Spindle Cell Rhabdomyosarcoma: A Case Report From Pakistan
    on 8 Gennaio 2024

    Para testicular or intra-scrotal Rhabdomyosarcomas (RMS) are rare. The spindle cell variant of rhabdomyosarcoma is the least common variant among embryonal subtypes. They are mostly seen in childhood but rarely reported in adults. We present a case of a 56-year-old man who presented with a three-year history of painless left inguinoscrotal swelling, which he initially ignored and misinterpreted as an Inguinal hernia but later sought medical help upon a progressive increase in the size of the...

  • A machine learning approach to assess Sustainable Development Goals food performances: The Italian case
    on 2 Gennaio 2024

    In this study, we introduce an innovative application of clustering algorithms to assess and appraise Italy's alignment with respect to the Sustainable Development Goals (SDGs), focusing on those related to climate change and the agrifood market. Specifically, we examined SDG 02: Zero Hunger, SDG 12: Responsible Consumption and Production, and SDG 13: Climate Change, to evaluate Italy's performance in one of its most critical economic sectors. Beyond performance analysis, we administered a...

  • Bench to Bedside Development of [18F]Fluoromethyl-(1,2-2H4)choline ([18F]D4-FCH)
    on 23 Dicembre 2023

    Malignant transformation is characterised by aberrant phospholipid metabolism of cancers, associated with the upregulation of choline kinase alpha (CHKα). Due to the metabolic instability of choline radiotracers and the increasing use of late-imaging protocols, we developed a more stable choline radiotracer, [^(18)F]fluoromethyl-[1,2-²H(4)]choline ([^(18)F]D4-FCH). [^(18)F]D4-FCH has improved protection against choline oxidase, the key choline catabolic enzyme, via a ¹H/²D isotope effect,...

  • Shake It Up Baby Now: The Changing Focus on TWIST1 and Epithelial to Mesenchymal Transition in Cancer and Other Diseases
    on 23 Dicembre 2023

    TWIST1 is a transcription factor that is necessary for healthy neural crest migration, mesoderm development, and gastrulation. It functions as a key regulator of epithelial-to-mesenchymal transition (EMT), a process by which cells lose their polarity and gain the ability to migrate. EMT is often reactivated in cancers, where it is strongly associated with tumor cell invasion and metastasis. Early work on TWIST1 in adult tissues focused on its transcriptional targets and how EMT gave rise to...

  • The ISMRM Open Science Initiative for Perfusion Imaging (OSIPI): Results from the OSIPI-Dynamic Contrast-Enhanced challenge
    on 20 Dicembre 2023

    CONCLUSIONS: This study reports results from the OSIPI-DCE challenge and highlights the high inter-software variability within K trans $$ {K}^{\mathrm{trans}} $$ estimation, providing a framework for ongoing benchmarking against the scores presented. Through this challenge, the participating teams were ranked based on the performance of their software tools in the particular setting of this challenge. In a real-world clinical setting, many of these tools may perform differently with...

  • Unlocking the anti-diabetic potential of Gymnema sylvestre, Trigonella foenum-graecum, and their combination thereof: An in-vivo evaluation
    on 18 Dicembre 2023

    The current study aimed to explore the anti-diabetic effect of aqueous extracts of Gymnema sylvestre, Trigonella foenum-graecum and mixture of both the plants in alloxan-induced diabetic rabbits. A total of 30 rabbits were grouped into six equal groups as: normal control, diabetic control, diabetic treated with 300 mg/kg body weight (bw) G. sylvestre, diabetic treated with 300 mg/kg bw T. foenum-graecum, diabetic treated with 300 mg/kg bw mixture of both the plants and diabetic treated with 500...

  • Beyond multilayer perceptrons: Investigating complex topologies in neural networks
    on 14 Dicembre 2023

    This study delves into the crucial aspect of network topology in artificial neural networks (NNs) and its impact on model performance. Addressing the need to comprehend how network structures influence learning capabilities, the research contrasts traditional multilayer perceptrons (MLPs) with models built on various complex topologies using novel network generation techniques. Drawing insights from synthetic datasets, the study reveals the remarkable accuracy of complex NNs, particularly in...

  • Seeding the meiotic DNA break machinery and initiating recombination on chromosome axes
    on 11 Dicembre 2023

    Programmed DNA double-strand break (DSB) formation is a unique meiotic feature that initiates recombination-mediated linking of homologous chromosomes, thereby enabling chromosome number halving in meiosis. DSBs are generated on chromosome axes by heterooligomeric focal clusters of DSB-factors. Whereas DNA-driven protein condensation is thought to assemble the DSB-machinery, its targeting to chromosome axes is poorly understood. We discovered in mice that efficient biogenesis of DSB-machinery...

  • Cohort profile: the Pregnancy Risk Infant Surveillance and Measurement Alliance (PRISMA) - Pakistan
    on 10 Dicembre 2023

    PURPOSE: Pakistan has disproportionately high maternal and neonatal morbidity and mortality. There is a lack of detailed, population-representative data to provide evidence for risk factors, morbidities and mortality among pregnant women and their newborns. The Pregnancy Risk, Infant Surveillance and Measurement Alliance (PRISMA) is a multicountry open cohort that aims to collect high-dimensional, standardised data across five South Asian and African countries for estimating risk and developing...

  • The age-specific comorbidity burden of mild cognitive impairment: a US claims database study
    on 7 Dicembre 2023

    CONCLUSIONS: The comorbidity burden of MCI relative to non-MCI is age-dependent. A model based on comorbidities alone predicted an MCI diagnosis with reasonable accuracy.

  • Interception of vertically approaching objects: temporal recruitment of the internal model of gravity and contribution of optical information
    on 4 Dicembre 2023

    Introduction: Recent views posit that precise control of the interceptive timing can be achieved by combining on-line processing of visual information with predictions based on prior experience. Indeed, for interception of free-falling objects under gravity's effects, experimental evidence shows that time-to-contact predictions can be derived from an internal gravity representation in the vestibular cortex. However, whether the internal gravity model is fully engaged at the target motion outset...

  • Association between e-cigarette use and myocardial infarction: a systematic review and meta-analysis
    on 30 Novembre 2023

    CONCLUSIONS: Dual use is associated with an increased risk of MI than e-cigarette use only. Similarly, dual and solely e-cigarette consumption patterns of nicotine delivery are at a higher risk of MI than non-smokers.

  • Seroprevalence and haemato-biochemical effects of bovine leucosis in buffalo, Punjab, Pakistan
    on 29 Novembre 2023

    Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a Deltaretrovirus belonging to the family Retroviridae. BLV causes huge economic losses to the dairy industry in the form of decreased milk production, premature culling, and poor reproductive performance of the animals. The aim of the present study was to determine the seroprevalence of BLV infection in buffalo in two districts of Punjab, Pakistan. A total of 384 samples were collected and analysed using a commercial indirect...

  • [11C]-PBR28 positron emission tomography signal as an imaging marker of joint inflammation in knee osteoarthritis
    on 28 Novembre 2023

    Although inflammation is known to play a role in knee osteoarthritis (KOA), inflammation-specific imaging is not routinely performed. In this article, we evaluate the role of joint inflammation, measured using [11C]-PBR28, a radioligand for the inflammatory marker 18-kDa translocator protein (TSPO), in KOA. Twenty-one KOA patients and 11 healthy controls (HC) underwent positron emission tomography/magnetic resonance imaging (PET/MRI) knee imaging with the TSPO ligand [11C]-PBR28. Standardized...

  • Incidence of aflatoxin M1 in cows' milk in Pakistan, effects on milk quality and evaluation of therapeutic management in dairy animals
    on 20 Novembre 2023

    The present study was aimed at measuring the concentration of aflatoxin M(1) (AFM(1)) in the milk of Holstein Friesian cows, its effect on the milk quality and seasonal trends, as well as to investigate the efficacy of a commercial clay-based toxin binder. For this purpose, milk samples from dairy cows (n = 72) were collected and assayed for AFM(1) before employing a clay-based toxin binder. The milk samples (n = 72) were collected from selected animals, revealing that 69.4% of the milk samples...

  • Microsatellite-based diversity analysis and the development of core-set germplasm in Pakistani barley lines
    on 13 Novembre 2023

    Illustrating the population structure and genetic diversity in selected germplasm resources (after three year multi locations trials) plays a key role which directly utilize the selection of lines in a population for accumulative trait breeding in crops. In order to further understand, the structure of population and genetic variability, we explored 100 selected lines, cultivated for three consecutive years (2016-2019) in swat, University of Malakand, Khyber Pakhtunkhwa Pakistan and Provinces of...

  • Influence of scan duration on dynamic contrast -enhanced magnetic resonance imaging pharmacokinetic parameters for brain lesions
    on 8 Novembre 2023

    CONCLUSION: K(ep) and V(e) were time-dependent in brain tumors, so a longer scan time is needed to obtain reliable parameter values. K^(trans) was found to be time-independent, as it remains the same in all 6 acquisition times and is the only reliable parameter with short acquisition times.

  • Radiomics-based decision support tool assists radiologists in small lung nodule classification and improves lung cancer early diagnosis
    on 6 Novembre 2023

    CONCLUSIONS: SN-RPV may provide net-benefit in terms of earlier cancer diagnosis.

  • Minimal residual disease status is the prognostic determinant following high-dose treatment for patients with multiple myeloma
    on 3 Novembre 2023

    CONCLUSIONS: Our results indicate that being MRD- is a more crucial prognostic factor for the 3-year PFS and OS than the presence of high-risk cytogenetic markers or undergoing maintenance treatment. The latter appears insufficient, particularly for MRD+ patients following ASCT in the second-line setting, suggesting that these patients may require a more intensive treatment approach.

  • Molecular Epidemiology, Seasonality and Phylogenetic Investigations of Anaplasma ovis in Small Ruminants from Diverse Agro-Climatic Regions of Punjab, Pakistan
    on 28 Ottobre 2023

    Anaplasma (A.) ovis is the most important cause of anaplasmosis in small ruminants. The current study was planned to estimate the molecular prevalence, risk factors, and phylogenetic analysis of A. ovis infection in sheep and goats from different agro-climatic regions of Central and Southern Punjab, Pakistan. A total of 400 jugular blood samples were collected from asymptomatic goats (n = 200) and sheep (n = 200) from the Jhang and Dera Ghazi Khan districts from January 2021 to February, 2023....

  • Preliminary Evidence of the Differential Expression of Human Endogenous Retroviruses in Kawasaki Disease and SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children
    on 28 Ottobre 2023

    Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with some clinical features overlapping with Kawasaki disease (KD). Our research group and others have highlighted that the spike protein of SARS-CoV-2 can trigger the activation of human endogenous retroviruses (HERVs), which in turn induces inflammatory and immune reactions, suggesting HERVs as contributing factors in COVID-19 immunopathology. With...

  • MRI and Clinical Biomarkers Overlap between Glaucoma and Alzheimer's Disease
    on 14 Ottobre 2023

    Glaucoma is the leading cause of blindness worldwide. It is classically associated with structural and functional changes in the optic nerve head and retinal nerve fiber layer, but the damage is not limited to the eye. The involvement of the central visual pathways and disruption of brain network organization have been reported using advanced neuroimaging techniques. The brain structural changes at the level of the areas implied in processing visual information could justify the discrepancy...

  • Causal influence of brainstem response to transcutaneous vagus nerve stimulation on cardiovagal outflow
    on 12 Ottobre 2023

    CONCLUSION: Our causal approach allowed us to noninvasively evaluate directional interactions between fMRI BOLD signals from brainstem nuclei and cardiovagal outflow.

  • Robust process capability indices Cpm and Cpmk using Weibull process
    on 9 Ottobre 2023

    Process Capability Indices (PCIs) are very helpful to measure the manufacturing capability and production quality of the products in many manufacturing processes. These PCIs are calculated by using a relationship between process mean and standard deviation, provided that process follows a normal distribution. In case of non-normal processes many researchers recommended the use of robust PCIs by modifying the classical PCIs. In case of robust PCIs most of the work is reported on first- and...

  • Comparison of Marginal Fracture Between Conventional and Bonded Amalgam Restorations in Posterior Permanent Molar Teeth
    on 2 Ottobre 2023

    Background/objectives Dental amalgam has been a successful restoration for over a century. However, restoration failures due to secondary caries, fractured teeth or restorations, marginal deficiencies, tooth wear, and secondary caries remain significant concerns. Amalgam-bond, known for its ability to bond amalgam to the tooth structure and prevent percolation, forms a strong bond with vital dentin. This study aimed to compare the outcome of marginal fractures in bonded amalgam and conventional...

  • Corrigendum: Sero-epidemiological study of zoonotic bacterial abortifacient agents in small ruminants
    on 2 Ottobre 2023

    [This corrects the article DOI: 10.3389/fvets.2023.1195274.].

  • Detection and Phylogenetic Analysis of Extended-Spectrum β-Lactamase (ESBL)-Genetic Determinants in Gram-Negative Fecal-Microbiota of Wild Birds and Chicken Originated at Trimmu Barrage
    on 28 Settembre 2023

    Extended-spectrum β-lactamases (ESBL) give rise to resistance against penicillin and cephalosporin antibiotics in multiple bacterial species. The present study was conducted to map genetic determinants and related attributes of ESBL-producing bacteria in three wild aquatic bird species and chickens at the "Trimmu Barrage" in district Jhang, Punjab province, Pakistan. To study the prevalence of ESBL-producing bacteria, a total of 280 representative samples were collected from wild bird species;...

  • Model of shrimp pond-mediated spatiotemporal dynamic distribution of antibiotic resistance genes in the mangrove habitat of a subtropical gulf
    on 21 Settembre 2023

    Aquacultures are the main reason for the environmental selection of antibiotic resistance genes (ARGs), resulting in the enrichment of ARGs. As a filter, a marine mangrove ecosystem can reduce antimicrobial resistance (AMR) or eliminate ARGs; however, its elimination mechanism remains unclear. This study investigated the spatiotemporal dynamic distribution of ARGs in two different types of mangrove habitats (shrimp ponds and virgin forests), within a subtropical gulf located in the Beibu Gulf,...

  • Effect of ammonium stress on phosphorus solubilization of a novel marine mangrove microorganism Bacillus aryabhattai NM1-A2 as revealed by integrated omics analysis
    on 18 Settembre 2023

    CONCLUSIONS: The accumulation of 2-OG and the inhibition of GS/GOGAT pathway played a key role in ammonium detoxification. The secretion of protons, formic acid and acetic acid was related to PS. Our work provides new insights into the PS mechanism, which will provide theoretical guidance for the application of PSMs.

  • Molecular identification and infection pathology of Mycobacterium spp. in captive wild animals in Pakistan
    on 12 Settembre 2023

    CONCLUSIONS: The study showed that animal tuberculosis is prevalent among wildlife in Pakistan and it may pose serious public health concerns to the people visiting these zoos and wildlife parks.

  • The proper interplay between the expression of Spo11 splice isoforms and the structure of the pseudoautosomal region promotes XY chromosomes recombination
    on 8 Settembre 2023

    XY chromosome missegregation is relatively common in humans and can lead to sterility or the generation of aneuploid spermatozoa. A leading cause of XY missegregation in mammals is the lack of formation of double-strand breaks (DSBs) in the pseudoautosomal region (PAR), a defect that may occur in mice due to faulty expression of Spo11 splice isoforms. Using a knock-in (ki) mouse that expresses only the single Spo11β splice isoform, here we demonstrate that by varying the genetic background of...

  • Multishell diffusion MRI reveals whole-brain white matter changes in HIV
    on 30 Agosto 2023

    Diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) have been previously used to explore white matter related to human immunodeficiency virus (HIV) infection. While DTI and DKI suffer from low specificity, the Combined Hindered and Restricted Model of Diffusion (CHARMED) provides additional microstructural specificity. We used these three models to evaluate microstructural differences between 35 HIV-positive patients without neurological impairment and 20 healthy controls who...

  • Deciphering equity style returns: An analysis of size and value anomalies in the Pakistani stock exchange
    on 28 Agosto 2023

    This study aims to identify the underlying causes of variation in the time series and cross-sectional equity style returns in the emerging stock market of Pakistan. We use asset pricing models and incorporate variables reflecting business cycle fluctuations to assess the time-varying size and value premiums. The methodology of this paper involves constructing style portfolios based on firm-specific characteristics such as market capitalization, price to earnings ratio, book-to-market equity...

  • Frequency and Types of Periapical Radiographic Lesions Associated With Pulpitis in a Tertiary Care Hospital
    on 28 Agosto 2023

    Objective This cross-sectional study aimed to determine the frequency and types of periapical radiographic lesions (PARLs) associated with pulpitis in patients visiting a tertiary care hospital. Methodology A sample of patients diagnosed with pulpitis, aged 18 years or older, was recruited following a convenient sampling technique. Clinical examinations were conducted to confirm the diagnosis, and radiographic evaluations, including periapical (PA), occlusal, orthopantomogram (OPG), and cone...

  • Efficacy of anti-CD3 monoclonal antibodies in delaying the progression of recent-onset type 1 diabetes mellitus: A systematic review, meta-analyses and meta-regression
    on 15 Agosto 2023

    CONCLUSION: The findings of this review suggest that anti-CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow-up, to validate the generalizability of these findings further.

  • Sero-epidemiological study of zoonotic bacterial abortifacient agents in small ruminants
    on 14 Agosto 2023

    Abortion is one of the leading causes of economic losses in the livestock industry worldwide. Chlamydia abortus, Coxiella burnetii, and Brucella spp. are the leading cause of late fetal loss in small ruminants. This study determined the seroprevalence of these agents in small ruminants in district Jhang. A total of 385 serum samples were taken from the sheep and goats from different flocks with a history of abortion and subjected to i-ELISA. Further, samples were analysed for liver enzymes and...

  • A MYC-controlled redox switch protects B lymphoma cells from EGR1-dependent apoptosis
    on 10 Agosto 2023

    Refractory and relapsed B cell lymphomas are often driven by the difficult-to-target oncogene MYC. Here, we report that high MYC expression stimulates proliferation and protects B lymphoma cells from apoptosis under normal oxidative stress levels and that compounds including N-acetylcysteine (NAC) and vitamin C (VitC) induce apoptosis by reducing oxidative stress. NAC and VitC injections effectively reduce tumor growth in lymphoma cells with high MYC expression but not in those with low MYC...

  • Triple gallbladder: radiological review
    on 10 Agosto 2023

    Triple gallbladder represents a rare congenital anatomical abnormality that can be a diagnostic challenge in reason to its rarity and consequential difficulties with diagnosis and identification. A systematic review of all published literature between 1958 and 2022 was performed. We identified 20 previous studies that provided 20 cases of triple gallbladder; our case was also included in the analysis, making a total of 21 patients. All patients underwent on diagnostic imaging examinations. After...

  • Feasibility of [18F]fluoropivalate hybrid PET/MRI for imaging lower and higher grade glioma: a prospective first-in-patient pilot study
    on 25 Luglio 2023

    CONCLUSION: Tumoural FPIA PET uptake is higher in HGG compared to LGG. This study supports further investigation of FPIA PET/MRI for brain tumour imaging in a larger patient population.


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