Antibiotic use in tertiary care hospitals in Bangladesh: Revealing the extent through a point prevalence survey.

BACKGROUND: Prevalent use of antibiotics in hospitals results in antimicrobial resistance (AMR), rising mortality, and substantial financial burden. This study assessed the current pattern of antibiotic use among inpatients in tertiary hospitals in Bangladesh. METHODS: Between August and November 2022, we conducted a point prevalence survey in 4 tertiary hospitals in Dhaka, Bangladesh. The World Health Organization-directed point prevalence survey methodology and tools were followed for the data collection. Descriptive and multivariate statistics were performed using Stata version 15. RESULTS: Of 1,063 hospitalized patients, antibiotics were prescribed to 73.5% (781/1063, 95% confidence interval: 70.8-76.1) of patients. A total of 1,164 antibiotics were prescribed, and 49.1% of patients consumed multiple antibiotics. Only 31.4% of patients were prescribed antibiotics based on microbiology results. The reasons for antibiotic prescribing were mentioned only in 19.3% of patients. Infants (adjusted odds ratio: 8.52, P-value: <.001) and neonates (adjusted odds ratio: 4.32, P-value: <.001) were more likely to consume antibiotics compared to adults. Cephalosporins accounted for the majority (54.0%) of antibiotics used in hospitals. None of the hospitals had any antibiotic use guidelines. CONCLUSIONS: Consumption of Watch group antibiotics empirically among all age groups demonstrates irrational antibiotic usage in Bangladeshi hospitals. Implementation of a tailored stewardship program, antibiotic use guidelines, and prescriber-patient awareness could improve the rational use of antibiotics.

YAP induces a neonatal-like pro-renewal niche in the adult heart.

After myocardial infarction (MI), mammalian hearts do not regenerate, and the microenvironment is disrupted. Hippo signaling loss of function with activation of transcriptional co-factor YAP induces heart renewal and rebuilds the post-MI microenvironment. In this study, we investigated adult renewal-competent mouse hearts expressing an active version of YAP, called YAP5SA, in cardiomyocytes (CMs). Spatial transcriptomics and single-cell RNA sequencing revealed a conserved, renewal-competent CM cell state called adult (a)CM2 with high YAP activity. aCM2 co-localized with cardiac fibroblasts (CFs) expressing complement pathway component C3 and macrophages (MPs) expressing C3ar1 receptor to form a cellular triad in YAP5SA hearts and renewal-competent neonatal hearts. Although aCM2 was detected in adult mouse and human hearts, the cellular triad failed to co-localize in these non-renewing hearts. C3 and C3ar1 loss-of-function experiments indicated that C3a signaling between MPs and CFs was required to assemble the pro-renewal aCM2, C3+ CF and C3ar1+ MP cellular triad.

scGIST: gene panel design for spatial transcriptomics with prioritized gene sets.

A critical challenge of single-cell spatial transcriptomics (sc-ST) technologies is their panel size. Being based on fluorescence in situ hybridization, they are typically limited to panels of about a thousand genes. This constrains researchers to build panels from only the marker genes of different cell types and forgo other genes of interest, e.g., genes encoding ligand-receptor complexes or those in specific pathways. We propose scGIST, a constrained feature selection tool that designs sc-ST panels prioritizing user-specified genes without compromising cell type detection accuracy. We demonstrate scGIST's efficacy in diverse use cases, highlighting it as a valuable addition to sc-ST's algorithmic toolbox.

Increased iron uptake by splenic hematopoietic stem cells promotes TET2-dependent erythroid regeneration.

Hematopoietic stem cells (HSCs) are capable of regenerating the blood system, but the instructive cues that direct HSCs to regenerate particular lineages lost to the injury remain elusive. Here, we show that iron is increasingly taken up by HSCs during anemia and induces erythroid gene expression and regeneration in a Tet2-dependent manner. Lineage tracing of HSCs reveals that HSCs respond to hemolytic anemia by increasing erythroid output. The number of HSCs in the spleen, but not bone marrow, increases upon anemia and these HSCs exhibit enhanced proliferation, erythroid differentiation, iron uptake, and TET2 protein expression. Increased iron in HSCs promotes DNA demethylation and expression of erythroid genes. Suppressing iron uptake or TET2 expression impairs erythroid genes expression and erythroid differentiation of HSCs; iron supplementation, however, augments these processes. These results establish that the physiological level of iron taken up by HSCs has an instructive role in promoting erythroid-biased differentiation of HSCs.

Endothelial cells adopt a pro-reparative immune responsive signature during cardiac injury.

Modulation of the heart's immune microenvironment is crucial for recovery after ischemic events such as myocardial infarction (MI). Endothelial cells (ECs) can have immune regulatory functions; however, interactions between ECs and the immune environment in the heart after MI remain poorly understood. We identified an EC-specific IFN responsive and immune regulatory gene signature in adult and pediatric heart failure (HF) tissues. Single-cell transcriptomic analysis of murine hearts subjected to MI uncovered an EC population (IFN-ECs) with immunologic gene signatures similar to those in human HF. IFN-ECs were enriched in regenerative-stage mouse hearts and expressed genes encoding immune responsive transcription factors (Irf7, Batf2, and Stat1). Single-cell chromatin accessibility studies revealed an enrichment of these TF motifs at IFN-EC signature genes. Expression of immune regulatory ligand genes by IFN-ECs suggests bidirectional signaling between IFN-ECs and macrophages in regenerative-stage hearts. Our data suggest that ECs may adopt immune regulatory signatures after cardiac injury to accompany the reparative response. The presence of these signatures in human HF and murine MI models suggests a potential role for EC-mediated immune regulation in responding to stress induced by acute injury in MI and chronic adverse remodeling in HF.

ScribbleDom: using scribble-annotated histology images to identify domains in spatial transcriptomics data.

MOTIVATION: Spatial domain identification is a very important problem in the field of spatial transcriptomics. The state-of-the-art solutions to this problem focus on unsupervised methods, as there is lack of data for a supervised learning formulation. The results obtained from these methods highlight significant opportunities for improvement. RESULTS: In this article, we propose a potential avenue for enhancement through the development of a semi-supervised convolutional neural network based approach. Named "ScribbleDom", our method leverages human expert's input as a form of semi-supervision, thereby seamlessly combines the cognitive abilities of human experts with the computational power of machines. ScribbleDom incorporates a loss function that integrates two crucial components: similarity in gene expression profiles and adherence to the valuable input of a human annotator through scribbles on histology images, providing prior knowledge about spot labels. The spatial continuity of the tissue domains is taken into account by extracting information on the spot microenvironment through convolution filters of varying sizes, in the form of "Inception" blocks. By leveraging this semi-supervised approach, ScribbleDom significantly improves the quality of spatial domains, yielding superior results both quantitatively and qualitatively. Our experiments on several benchmark datasets demonstrate the clear edge of ScribbleDom over state-of-the-art methods-between 1.82% to 169.38% improvements in adjusted Rand index for 9 of the 12 human dorsolateral prefrontal cortex samples, and 15.54% improvement in the melanoma cancer dataset. Notably, when the expert input is absent, ScribbleDom can still operate, in a fully unsupervised manner like the state-of-the-art methods, and produces results that remain competitive. AVAILABILITY AND IMPLEMENTATION: Source code is available at Github (https://github.com/1alnoman/ScribbleDom) and Zenodo (https://zenodo.org/badge/latestdoi/681572669).

Structural underpinnings of mutation rate variations in the human genome.

Single nucleotide mutation rates have critical implications for human evolution and genetic diseases. Importantly, the rates vary substantially across the genome and the principles underlying such variations remain poorly understood. A recent model explained much of this variation by considering higher-order nucleotide interactions in the 7-mer sequence context around mutated nucleotides. This model's success implicates a connection between DNA shape and mutation rates. DNA shape, i.e. structural properties like helical twist and tilt, is known to capture interactions between nucleotides within a local context. Thus, we hypothesized that changes in DNA shape features at and around mutated positions can explain mutation rate variations in the human genome. Indeed, DNA shape-based models of mutation rates showed similar or improved performance over current nucleotide sequence-based models. These models accurately characterized mutation hotspots in the human genome and revealed the shape features whose interactions underlie mutation rate variations. DNA shape also impacts mutation rates within putative functional regions like transcription factor binding sites where we find a strong association between DNA shape and position-specific mutation rates. This work demonstrates the structural underpinnings of nucleotide mutations in the human genome and lays the groundwork for future models of genetic variations to incorporate DNA shape.

Noncanonical binding of transcription factors: time to revisit specificity?

Transcription factors (TFs) are one of the most studied classes of DNA-binding proteins that have a direct functional impact on gene transcription and thus, on human physiology and disease. The mechanisms that TFs use for recognizing target DNA binding sites have been studied for nearly five decades, yet they remain poorly understood. It is classically assumed that a TF recognizes a specific sequence pattern, or motif, as its binding sites. However, recent studies are consistently finding examples of noncanonical binding, that is, TFs binding at sites that do not resemble their sequence motifs. Here we review the current literature on four major types of noncanonical TF binding, namely binding based on DNA shape readout, at Guanine-quadruplex structures, at repeat sequences, and bispecific binding. These examples point to a critical need for studies to unify our current observations, many of which are at odds with the "one TF, one motif" view, into a more comprehensive definition of the DNA-binding specificity of TFs.

NoVaTeST: identifying genes with location-dependent noise variance in spatial transcriptomics data.

MOTIVATION: Spatial transcriptomics (ST) can reveal the existence and extent of spatial variation of gene expression in complex tissues. Such analyses could help identify spatially localized processes underlying a tissue's function. Existing tools to detect spatially variable genes assume a constant noise variance across spatial locations. This assumption might miss important biological signals when the variance can change across locations. RESULTS: In this article, we propose NoVaTeST, a framework to identify genes with location-dependent noise variance in ST data. NoVaTeST models gene expression as a function of spatial location and allows the noise to vary spatially. NoVaTeST then statistically compares this model to one with constant noise and detects genes showing significant spatial noise variation. We refer to these genes as "noisy genes." In tumor samples, the noisy genes detected by NoVaTeST are largely independent of the spatially variable genes detected by existing tools that assume constant noise, and provide important biological insights into tumor microenvironments. AVAILABILITY AND IMPLEMENTATION: An implementation of the NoVaTeST framework in Python along with instructions for running the pipeline is available at https://github.com/abidabrar-bracu/NoVaTeST.

Approach to Quantify Eye Movements to Augment Stroke Diagnosis With a Non-Calibrated Eye-Tracker.

Automated eye-tracking technology could enhance diagnosis for many neurological diseases, including stroke. Current literature focuses on gaze estimation through a form of calibration. However, patients with neuro-ocular abnormalities may have difficulty completing a calibration procedure due to inattention or other neurological deficits. OBJECTIVE: We investigated 1) the need for calibration to measure eye movement symmetry in healthy controls and 2) the potential of eye movement symmetry to distinguish between healthy controls and patients. METHODS: We analyzed fixations, smooth pursuits, saccades, and conjugacy measured by a Spearman correlation coefficient and utilized a linear mixed-effects model to estimate the effect of calibration. RESULTS: Healthy participants (n = 18) did not differ in correlations between calibrated and non-calibrated conditions for all tests. The calibration condition did not improve the linear mixed effects model (log-likelihood ratio test p = 0.426) in predicting correlation coefficients. Interestingly, the patient group (n = 17) differed in correlations for the DOT (0.844 [95% CI 0.602, 0.920] vs. 0.98 [95% CI 0.976, 0.985]), H (0.903 [95% CI 0.746, 0.958] vs. 0.979 [95% CI 0.971, 0.986]), and OKN (0.898 [95% CI 0.785, 0.958] vs. 0.993 [95% CI 0.987, 0.996]) tests compared to healthy controls along the x-axis. These differences were not observed along the y-axis. SIGNIFICANCE: This study suggests that automated eye tracking can be deployed without calibration to measure eye movement symmetry. It may be a good discriminator between normal and abnormal eye movement symmetry. Validation of these findings in larger populations is required.

DeepBend: An interpretable model of DNA bendability.

The bendability of genomic DNA impacts chromatin packaging and protein-DNA binding. However, we do not have a comprehensive understanding of the motifs influencing DNA bendability. Recent high-throughput technologies such as Loop-Seq offer an opportunity to address this gap but the lack of accurate and interpretable machine learning models still remains. Here we introduce DeepBend, a convolutional neural network model with convolutions designed to directly capture the motifs underlying DNA bendability and their periodic occurrences or relative arrangements that modulate bendability. DeepBend consistently performs on par with alternative models while giving an extra edge through mechanistic interpretations. Besides confirming the known motifs of DNA bendability, DeepBend also revealed several novel motifs and showed how the spatial patterns of motif occurrences influence bendability. DeepBend's genome-wide prediction of bendability further showed how bendability is linked to chromatin conformation and revealed the motifs controlling the bendability of topologically associated domains and their boundaries.

Outersphere Approach to Increasing the Persistance of Oxygen-Sensitive Europium(II)-Containing Contrast Agents for Magnetic Resonance Imaging with Perfluorocarbon Nanoemulsions toward Imaging of Hypoxia.

Radiographic mapping of hypoxia is needed to study a wide range of diseases. Complexes of Eu(II) are a promising class of molecules to fit this need, but they are generally limited by their rapid oxidation rates in vivo. Here, a perfluorocarbon-nanoemulsion perfused with N2 , forms an interface with aqueous layers to hinder oxidation of a new perfluorocarbon-soluble complex of Eu(II). Conversion of the perfluorocarbon solution of Eu(II) into nanoemulsions results in observable differences between reduced and oxidized forms by magnetic resonance imaging both in vitro and in vivo. Oxidation in vivo occurrs over a period of ≈30 min compared to <5 min for a comparable Eu(II)-containing complex without nanoparticle interfaces. These results represent a critical step toward delivery of Eu(II)-containing complexes in vivo for the study of hypoxia.

Uptake of Influenza Vaccine and Factors Associated with Influenza Vaccination among Healthcare Workers in Tertiary Care Hospitals in Bangladesh: A Multicenter Cross-Sectional Study.

Influenza, highly contagious in hospital settings, imposes a substantial disease burden globally, and influenza vaccination is critical for healthcare workers (HCWs) to prevent this illness. This study assessed influenza vaccine uptake, including its associated factors among HCWs of tertiary care hospitals in Bangladesh. Between September and December 2020, this multicenter study included 2046 HCWs from 11 hospitals. Face-to-face interviews were conducted using a semi-structured questionnaire to collect data from physicians, nurses, and cleaning and administrative staff for the survey. Only 13.8% (283/2046) of HCWs received the influenza vaccine, of which the majority (76.7%, 217/283) received it for free from the hospital. Nurses had the highest (20.0%, 187/934) influenza vaccine coverage, followed by physicians at 13.5% (71/526), whereas cleaning staff had the lowest at 6.0% (19/318). Among unvaccinated HCWs, the desire to get vaccinated was high (86.2%), with half of the respondents even being willing to pay for it. The HCWs who were aware of the influenza vaccine were over five times more likely to get the vaccine (OR 5.63; 95% CI: 1.04, 1.88) compared to those who were not. HCWs in Bangladesh were vaccinated against influenza at a very low rate. Free and mandatory influenza vaccination programs should be initiated to optimize vaccine coverage among HCWs.

Assigning pathogenicity for TAB2 variants using a novel scalable functional assay and expanding TAB2 disease spectrum.

Haploinsufficiency of TGF-beta-activated kinase 1 (MAP3K7) binding protein 2 (TAB2) has been associated with congenital heart disease and more recently multiorgan structural abnormalities. Missense variant represents a major proportion of non-synonymous TAB2 variants reported in gnomAD (295/576) and Clinvar (16/73), most of which are variants of uncertain significance (VUSs). However, interpretation of TAB2 missense variants remains challenging because of lack of functional assays. To address this issue, we established a cell-based luciferase assay that enables high-throughput screening of TAB2 variants to assess the functional consequence for predicting variant pathogenicity. Using this platform, we screened 47 TAB2 variants including five pathogenic controls and one benign control, and the results showed that the transcriptional activity of activator protein 1 (AP-1) but not nuclear factor kappa B predicts the TAB2 variant pathogenicity. This assay provides accurate functional readout for both loss-of-function (LOF) and gain-of-function variants, which are associated with distinct phenotypes. In all, 22 out of 32 tested VUSs were reclassified. Genotype-Phenotype association showed that most patients with partial LOF variants do not exhibit congenital heart disease but high frequency of developmental delay, hypotonia and dysmorphic features, which suggests that genetic testing for TAB2 is needed for a broader spectrum of patients with more diverse phenotypes. Molecular modeling with Npl4 zinc finger (NZF) domain variants revealed that the stability of the NZF domain in TAB2 protein is crucial for AP-1 activation. In conclusion, we developed a highly effective functional assay for TAB2 variant prediction and interpretation.

Hippo-deficient cardiac fibroblasts differentiate into osteochondroprogenitors.

Cardiac fibrosis, a common pathophysiology associated with various heart diseases, occurs from the excess deposition of extracellular matrix (ECM) 1 . Cardiac fibroblasts (CFs) are the primary cells that produce, degrade, and remodel ECM during homeostasis and tissue repair 2 . Upon injury, CFs gain plasticity to differentiate into myofibroblasts 3 and adipocyte-like 4,5 and osteoblast-like 6 cells, promoting fibrosis and impairing heart function 7 . How CFs maintain their cell state during homeostasis and adapt plasticity upon injury are not well defined. Recent studies have shown that Hippo signalling in CFs regulates cardiac fibrosis and inflammation 8-11 . Here, we used single-nucleus RNA sequencing (snRNA-seq) and spatially resolved transcriptomic profiling (ST) to investigate how the cell state was altered in the absence of Hippo signaling and how Hippo-deficient CFs interact with macrophages during cardiac fibrosis. We found that Hippo-deficient CFs differentiate into osteochondroprogenitors (OCPs), suggesting that Hippo restricts CF plasticity. Furthermore, Hippo-deficient CFs colocalized with macrophages, suggesting their intercellular communications. Indeed, we identified several ligand-receptor pairs between the Hippo-deficient CFs and macrophages. Blocking the Hippo-deficient CF-induced CSF1 signaling abolished macrophage expansion. Interestingly, blocking macrophage expansion also reduced OCP differentiation of Hippo-deficient CFs, indicating that macrophages promote CF plasticity.

Hospitalization and Mortality by Vaccination Status among COVID-19 Patients Aged ≥ 25 Years in Bangladesh: Results from a Multicenter Cross-Sectional Study.

The COVID-19 pandemic has inflicted a massive disease burden globally, involving 623 million confirmed cases with 6.55 million deaths, and in Bangladesh, over 2.02 million clinically confirmed cases of COVID-19, with 29,371 deaths, have been reported. Evidence showed that vaccines significantly reduced infection, severity, and mortality across a wide age range of populations. This study investigated the hospitalization and mortality by vaccination status among COVID-19 patients in Bangladesh and identified the vaccine's effectiveness against severe outcomes in real-world settings. Between August and December 2021, we conducted this cross-sectional survey among 783 RT-PCR-confirmed COVID-19 hospitalized patients admitted to three dedicated COVID-19 hospitals in Bangladesh. The study used a semi-structured questionnaire to collect information. We reviewed the patient's records and gathered COVID-19 immunization status from the study participants or their caregivers. Patients with incomplete or partial data from the record were excluded from enrollment. Logistic regression analyses were performed to determine the association between key variables with a patient's vaccination status and mortality. The study revealed that overall hospitalization, severity, and morality were significantly high among unvaccinated study participants. Only one-fourth (25%) of hospitalized patients were found COVID-19 vaccinated. Morality among unvaccinated COVID-19 study participants was significantly higher (AOR: 7.17) than the vaccinated (11.17% vs. 1.53%). Severity was found to be seven times higher among unvaccinated patients. Vaccination coverage was higher in urban areas (29.8%) compared to rural parts (20.8%), and vaccine uptake was lower among female study participants (22.7%) than male (27.6%). The study highlighted the importance of COVID-19 vaccines in reducing mortality, hospitalization, and other severe consequences. We found a gap in vaccination coverage between urban and rural settings. The findings would encourage the entire population toward immunization and aid the policymakers in the ground reality so that more initiatives are taken to improve vaccination coverage among the pocket population.

Infection prevention and control in tertiary care hospitals of Bangladesh: results from WHO infection prevention and control assessment framework (IPCAF).

INTRODUCTION: Infection prevention and control (IPC) in healthcare settings is imperative for the safety of patients as well as healthcare providers. To measure current IPC activities, resources, and gaps at the facility level, WHO has developed the Infection Prevention and Control Assessment Framework (IPCAF). This study aimed to assess the existing IPC level of selected tertiary care hospitals in Bangladesh during the COVID-19 pandemic using IPCAF to explore their strengths and deficits. METHODS: Between September and December 2020, we assessed 11 tertiary-care hospitals across Bangladesh. We collected the information from IPC focal person and/or hospital administrator from each hospital using the IPCAF assessment tool.. The score was calculated based on eight core components and was used to categorize the hospitals into four distinct IPC levels- Inadequate, Basic, Intermediate, and Advanced. Key performance metrics were summarized within and between hospitals. RESULTS: The overall median IPCAF score was 355.0 (IQR: 252.5-397.5) out of 800. The majority (73%) of hospitals scored as 'Basic' IPC level, while only 18% of hospitals were categorized as 'Intermediate'. Most hospitals had IPC guidelines as well as environments, materials and equipments. Although 64% of hospitals had IPC orientation and training program for new employees, only 30% of hospitals had regular IPC training program for the staff. None of the hospitals had an IPC surveillance system with standard surveillance case definitions to track HAIs. Around 90% of hospitals did not have an active IPC monitoring and audit system. Half of the hospitals had inadequate staffing considering the workload. Bed occupancy of one patient per bed in all units was found in 55% of hospitals. About 73% of hospitals had functional hand hygiene stations, but sufficient toilets were available in only 37% of hospitals. CONCLUSION: The majority of sampled tertiary care hospitals demonstrate inadequate IPC level to ensure the safety of healthcare workers, patients, and visitors. Quality improvement programs and feedback mechanisms should be implemented to strengthen all IPC core components, particularly IPC surveillance, monitoring, education, and training, to improve healthcare safety and resilience.

Rationale and guidance for strengthening infection prevention and control measures and antimicrobial stewardship programs in Bangladesh: a study protocol.

BACKGROUND: Hospital-acquired infections (HAIs) and antimicrobial resistance (AMR) are major global health challenges. Drug-resistant infectious diseases continue to rise in developing countries, driven by shortfalls in infection control measures, antibiotic misuse, and scarcity of reliable diagnostics. These escalating global challenges have highlighted the importance of strengthening fundamental infection prevention and control (IPC) measures and implementing effective antimicrobial stewardship programs (ASP). This study aims to present a framework for enhancing IPC measures and ASP efforts to reduce the HAI and AMR burden in Bangladesh. METHODS: This implementation approach will employ a mixed-methods strategy, combining both quantitative and qualitative data from 12 tertiary hospitals in Bangladesh. A baseline assessment will be conducted using the Infection Prevention and Control Assessment Framework (IPCAF) developed by the WHO. We will record IPC practices through direct observations of hand hygiene, personal protective equipment (PPE) utilization, and hospital ward IPC infrastructure. Additionally, data on healthcare providers' knowledge, attitudes, and practices regarding IPC and antibiotic prescribing will be collected using both structured questionnaires and qualitative interviews. We will also assist the hospital leadership with establishing and/or strengthening IPC and ASP committees. Based on baseline assessments of each healthcare facility, tailored interventions and quality improvement projects will be designed and implemented. An end-line assessment will also be conducted after 12 months of intervention using the same assessment tools. The findings will be compared with the baseline to determine changes in IPC and antibiotic stewardship practices. DISCUSSION: Comprehensive assessments of healthcare facilities in low-resource settings are crucial for strengthening IPC measures and ASP activities,. This approach to assessing existing IPC and ASP activities will provide policy-relevant data for addressing current shortfalls. Moreover, this framework proposes identifying institutionally-tailored solutions, which will ensure that response activities are appropriately contextualized, aligned with stakeholder priorities, and offer sustainable solutions. CONCLUSION: Findings from this study can guide the design and implementation of feasible and sustainable interventions in resource-constrained healthcare settings to address gaps in existing IPC and ASP activities. Therefore, this protocol will be applicable across a broad range of settings to improve IPC and ASP and reduce the burden of hospital-acquired infections and AMR.

Multinomial Convolutions for Joint Modeling of Regulatory Motifs and Sequence Activity Readouts.

A common goal in the convolutional neural network (CNN) modeling of genomic data is to discover specific sequence motifs. Post hoc analysis methods aid in this task but are dependent on parameters whose optimal values are unclear and applying the discovered motifs to new genomic data is not straightforward. As an alternative, we propose to learn convolutions as multinomial distributions, thus streamlining interpretable motif discovery with CNN model fitting. We developed MuSeAM (Multinomial CNNs for Sequence Activity Modeling) by implementing multinomial convolutions in a CNN model. Through benchmarking, we demonstrate the efficacy of MuSeAM in accurately modeling genomic data while fitting multinomial convolutions that recapitulate known transcription factor motifs.

Dual-Mode Tumor Imaging Using Probes That Are Responsive to Hypoxia-Induced Pathological Conditions.

Hypoxia in solid tumors is associated with poor prognosis, increased aggressiveness, and strong resistance to therapeutics, making accurate monitoring of hypoxia important. Several imaging modalities have been used to study hypoxia, but each modality has inherent limitations. The use of a second modality can compensate for the limitations and validate the results of any single imaging modality. In this review, we describe dual-mode imaging systems for the detection of hypoxia that have been reported since the start of the 21st century. First, we provide a brief overview of the hallmarks of hypoxia used for imaging and the imaging modalities used to detect hypoxia, including optical imaging, ultrasound imaging, photoacoustic imaging, single-photon emission tomography, X-ray computed tomography, positron emission tomography, Cerenkov radiation energy transfer imaging, magnetic resonance imaging, electron paramagnetic resonance imaging, magnetic particle imaging, and surface-enhanced Raman spectroscopy, and mass spectrometric imaging. These overviews are followed by examples of hypoxia-relevant imaging using a mixture of probes for complementary single-mode imaging techniques. Then, we describe dual-mode molecular switches that are responsive in multiple imaging modalities to at least one hypoxia-induced pathological change. Finally, we offer future perspectives toward dual-mode imaging of hypoxia and hypoxia-induced pathophysiological changes in tumor microenvironments.