Poor Definition Research Articles

P-2099. A Novel Anaerobic Activity Index to define the “anti-anaerobic” spectrum of antimicrobials

Abstract Background While necessary for the treatment of anaerobic infections, use of antibiotics with anaerobic activity may be associated with poor patient outcomes including graft-versus host disease after bone marrow transplant and mortality in critically ill patients. However, we lack a uniform method to assess the relative anaerobic activity of antibiotics and have poor definitions of what it means for antimicrobials to be “anti-anaerobic”. Methods A PubMed search using terms “microbial sensitivity test”, “anti-bacterial agents” and “bacteria, anaerobic” yielded 575 papers published between January 2013-2024 (Figure 1). Papers with < 100 isolates, non-human isolates, or without antimicrobial susceptibility testing (AST) were excluded. AST for an average of 17,709 anaerobic clinical isolates per antimicrobial from 56 publications were summarized. Anaerobes were categorized into 11 groups based on the literature (Table 1). For 16 commonly used antibiotics, values of 0, 1, or 2 were awarded for each group of anaerobes for average published susceptibility of ≤ 10%, 11-89.4%, and ≥ 89.5%, respectively, and tallied to create a composite score (0-22, Score A). Three alternative scores were created based on different susceptibility cutoffs (Scores B-D; Table 2).Table 1:Groups of anaerobes for which antimicrobial susceptibility was scored Results In Anaerobic Activity Index Score A, scores ranged from 11 for moxifloxacin to 22 for tigecycline, meropenem, and imipenem (Table 2). Anaerobic Activity Index scores were plotted against the Antibiotic Spectrum Coverage (ASC), a previously published antibiotic “broad” spectrum score (Figure 2). Varying susceptibility thresholds affected estimated anaerobic activity for some antibiotics, including clindamycin and vancomycin, but overall, there was good agreement across all scores (A-D). Moxifloxacin had the lowest overall scores due to high rates of resistance across all groups of anaerobes. Conclusion Antibiotic broad-spectrum scores have been proposed, but no valid score exists and no score assessing anaerobic activity has been developed. An Anaerobic Activity Index may improve the definition of “anti-anaerobic” antimicrobials for clinical care and research. Further studies are needed to validate this index as a potential tool to evaluate the effect of anaerobic antibiotic exposure on clinical outcomes. Disclosures Vincent B. Young, MD, PhD, Aimmune: Honoraria|American Society for Microbiology: Board Member|Debiopharm: Advisor/Consultant|Peggy Lillis Foundation: Board Member|University of Oklahoma COBRE: Advisor/Consultant|Vedanta: Advisor/Consultant|Vedanta Bioscience: Advisor/Consultant|Vedanta Bioscience: Grant/Research Support David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support

Selective use of ferumoxytol-enhanced magnetic resonance angiography in patients with renal insufficiency: insights from a pilot study.

The use of conventional contrast agents in computed tomography (CT) and magnetic resonance (MR) imaging is often limited in patients with chronic kidney disease (CKD) due to potential nephrotoxicity. Ferumoxytol, originally developed for iron supplementation, has emerged as a promising alternative MR contrast agent that is safer for patients with CKD. This study aims to present our center's experience with ferumoxytol as a contrast agent in CKD patients. We retrospectively reviewed 24 MR imaging studies of the chest, abdomen, and pelvis performed in CKD patients at our center. All patients were deemed suitable for ferumoxytol administration, receiving a dose of 4mg/kg with post-injection monitoring. The imaging quality of the ascending, descending, suprarenal and infrarenal aortic segments was assessed by three independent observers using a qualitative scoring system (nondiagnostic, poor vascular definition, good vascular definition, and excellent vascular definition). Quantitative analyses, including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and heterogeneity index, were also performed. No adverse reactions to ferumoxytol were observed. Of the 72 vascular segments evaluated, 90.8% of the images were rated as excellent vascular definition, and 9.2% were rated as good vascular definition. Inter-observer agreement was substantial (k = 0.647), with no statistically significant differences in ratings between observers. Ferumoxytol is a safe and effective alternative to conventional contrast agents for MR vascular imaging, particularly in patients with renal insufficiency. These findings support its selective use in appropriate clinical scenarios, offering a reliable imaging option for CKD patients.

Feasibility of three dimensional and strain transthoracic echocardiography in a single-centre dedicated NHS cardio-oncology clinic

BackgroundFollowing the publication of international cardio-oncology (CO) imaging guidelines, standard echocardiographic monitoring parameters of left ventricular systolic function have been endorsed. Recommendations highlight that either two-dimensional (2D) or three-dimensional (3D) left ventricular ejection fraction (LVEF), alongside global longitudinal strain (GLS) should be routinely performed for surveillance of patients at risk of cancer therapy-related cardiac dysfunction (CTRCD). We studied the feasibility of 3D-LVEF, 2D-GLS and 2D-LVEF in a dedicated CO service.MethodsThis was a single-centre prospective analysis of consecutive all-comer patients (n = 105) referred to an NHS CO clinic. Using a dedicated Philips EPIQ CVx v7.0, with X5-1 3D-transducer and 3DQA software, we sought to acquire and analyse 2D- and 3D-LVEF and 2D-GLS, adhering to the British Society of Echocardiography (BSE) and British Cardio-Oncology Society (BCOS) transthoracic echocardiography protocol.ResultsA total of 105 patients were enrolled in the study; 5 were excluded due to carcinoid heart disease (n = 5). Calculation of 3D-LVEF was achieved in 40% (n = 40), 2D-GLS in 73% (n = 73), and 2D-LVEF in 81% (n = 81). LV quantification was not possible in 19% (n = 19) due to poor myocardial border definition. Strong correlation existed between 2D-LVEF and 3D-LVEF (r = 0.94, p < 0.0001). Bland–Altman plot demonstrated no statistical differences in that the mean deviation between 2D-LVEF and 3D-LVEF were consistent throughout a range of LVEF values. The most persistent obstacle to 3D-LVEF acquisition was insufficient myocardial border tracking (n = 30, 50%).ConclusionThis study demonstrates the high feasibility of 2D-GLS and 2D-LVEF, even in those with challenging echocardiographic windows. The lower feasibility of 3D-LVEF limits its real-world clinical application, even though only a small difference in agreement with 2D-LVEF calculation was found when successfully performed.

Automated Cervical Cancer Screening Using Single-Cell Segmentation and Deep Learning: Enhanced Performance with Liquid-Based Cytology

Cervical cancer (CC) remains a significant health issue, especially in low- and middle-income countries (LMICs). While Pap smears are the standard screening method, they have limitations, like low sensitivity and subjective interpretation. Liquid-based cytology (LBC) offers improvements but still relies on manual analysis. This study explored the potential of deep learning (DL) for automated cervical cell classification using both Pap smears and LBC samples. A novel image segmentation algorithm was employed to extract single-cell patches for training a ResNet-50 model. The model trained on LBC images achieved remarkably high sensitivity (0.981), specificity (0.979), and accuracy (0.980), outperforming previous CNN models. However, the Pap smear dataset model achieved significantly lower performance (0.688 sensitivity, 0.762 specificity, 0.8735 accuracy). This suggests that noisy and poor cell definition in Pap smears pose challenges for automated classification, whereas LBC provides better classifiable cells patches. These findings demonstrate the potential of AI-powered cervical cell classification for improving CC screening, particularly with LBC. The high accuracy and efficiency of DL models combined with effective segmentation can contribute to earlier detection and more timely intervention. Future research should focus on implementing explainable AI models to increase clinician trust and facilitate the adoption of AI-assisted CC screening in LMICs.

Functional localization of the human auditory and visual thalamus using a thalamic localizer functional magnetic resonance imaging task

Abstract Functional magnetic resonance imaging (fMRI) of the auditory and visual sensory systems of the human brain is an active area of investigation in the study of human health and disease. The medial geniculate nucleus (MGN) and lateral geniculate nucleus (LGN) are key thalamic nuclei involved in the processing and relay of auditory and visual information, respectively, and are the subject of blood-oxygen-level-dependent (BOLD) fMRI studies of neural activation and functional connectivity in human participants. However, localization of BOLD fMRI signal originating from neural activity in MGN and LGN remains a technical challenge, due, in part, to the poor definition of boundaries of these thalamic nuclei in standard T1-weighted and T2-weighted magnetic resonance imaging sequences. Here, we report the development and evaluation of an auditory and visual sensory thalamic localizer (TL) fMRI task that produces participant-specific functionally-defined regions of interest (fROIs) of both MGN and LGN, using 3 Tesla multiband fMRI and a clustered-sparse temporal acquisition sequence, in less than 16 minutes of scan time. We demonstrate the use of MGN and LGN fROIs obtained from the TL fMRI task in standard resting-state functional connectivity (RSFC) fMRI analyses in the same participants. In RSFC analyses, we validated the specificity of MGN and LGN fROIs for signals obtained from primary auditory and visual cortex, respectively, and benchmarked their performance against alternative atlas- and segmentation-based localization methods. The TL fMRI task and analysis code (written in Presentation and MATLAB, respectively) have been made freely available to the wider research community.

Reflexiones sobre la vinculación con el medio y el concepto de territorio en el marco de la educación superior: el caso de Chile

The purpose of this article is to reflect on a complex conception of the concept of territory within the framework of the link with the environment of Chilean state universities. To achieve this purpose, the institutional policies of the area of the 18 universities of the State of Chile, the Higher Education Law and the Law of State Universities were reviewed, as well as the reference framework of linkage with the environment of the Consortium of Universities of the State of Chile. The results indicate that in the documents analyzed there is a poor definition of the concept of territory, and its mention is mainly geographical, which deprives a critical sense of a highly relevant university function for the development of society.

University teachers' perspectives on synchronous in-person and distance teaching and learning (SynPaD hybrid)

Although most teaching in higher education may still involve either in-person teaching or online distance teaching, various forms of hybrid teaching are becoming more common. Maturity of hybrid teaching has been limited by the lack of research-based development and poor definition of teaching practices in the literature. This article is about a particular variant of hybrid teaching (SynPaD hybrid) involving learners in the physical presence of one or more teachers with other learners attending synchronously via videoconferencing, in situations where all participants can, or should be able to, interact both verbally and visually with all other participants. The article applies a recognised qualitative research approach to gather potentially important insights into the perspectives of university teachers in capacities as teachers and as learners about SynPaD hybrid teaching, and interprets its findings using self-determination theory. Notable insights from this research suggest that university teachers in the role of learners are able to appreciate SynPaD hybrid and may insist that university teachers tasked with supporting learning in this context should rise to the challenges of teaching in this way. University teachers, acting in the role of teacher, may question the practicality of teaching in SynPaD hybrid and their motivation to teach in this way. This article describes and comments on the difficult decisions faced by higher education institutions as SynPaD hybrid emerges as an alternative to more orthodox in-person and online teaching situations.

Biomimetic and soft lab-on-a-chip platform based on enzymatic-crosslinked silk fibroin hydrogel for 3D cell co-culture

Integrating biological material within soft microfluidic systems made of hydrogels offers countless possibilities in biomedical research to overcome the intrinsic limitations of traditional microfluidics based on solid, non-biodegradable, and non-biocompatible materials. Hydrogel-based microfluidic technologies have the potential to transformin vitrocell/tissue culture and modeling. However, most hydrogel-based microfluidic platforms are associated with device deformation, poor structural definition, reduced stability/reproducibility due to swelling, and a limited range in rigidity, which threatens their applicability. Herein, we describe a new methodological approach for developing a soft cell-laden microfluidic device based on enzymatically-crosslinked silk fibroin (SF) hydrogels. Its unique mechano-chemical properties and high structural fidelity, make this platform especially suited forin vitrodisease modelling, as demonstrated by reproducing the native dynamic 3D microenvironment of colorectal cancer and its response to chemotherapeutics in a simplistic way. Results show that from all the tested concentrations, 14 wt% enzymatically-crosslinked SF microfluidic platform has outstanding structural stability and the ability to perfuse fluid while displayingin vivo-like biological responses. Overall, this work shows a novel technique to obtain an enzymatically-crosslinked SF microfluidic platform that can be employed for developing soft lab-on-a-chipin vitromodels.

Functional Localization of the Human Auditory and Visual Thalamus Using a Thalamic Localizer Functional Magnetic Resonance Imaging Task.

Functional magnetic resonance imaging (fMRI) of the auditory and visual sensory systems of the human brain is an active area of investigation in the study of human health and disease. The medial geniculate nucleus (MGN) and lateral geniculate nucleus (LGN) are key thalamic nuclei involved in the processing and relay of auditory and visual information, respectively, and are the subject of blood-oxygen-level-dependent (BOLD) fMRI studies of neural activation and functional connectivity in human participants. However, localization of BOLD fMRI signal originating from neural activity in MGN and LGN remains a technical challenge, due in part to the poor definition of boundaries of these thalamic nuclei in standard T1-weighted and T2-weighted magnetic resonance imaging sequences. Here, we report the development and evaluation of an auditory and visual sensory thalamic localizer (TL) fMRI task that produces participant-specific functionally-defined regions of interest (fROIs) of both MGN and LGN, using 3 Tesla multiband fMRI and a clustered-sparse temporal acquisition sequence, in less than 16 minutes of scan time. We demonstrate the use of MGN and LGN fROIs obtained from the TL fMRI task in standard resting-state functional connectivity (RSFC) fMRI analyses in the same participants. In RSFC analyses, we validated the specificity of MGN and LGN fROIs for signals obtained from primary auditory and visual cortex, respectively, and benchmark their performance against alternative atlas- and segmentation-based localization methods. The TL fMRI task and analysis code (written in Presentation and MATLAB, respectively) have been made freely available to the wider research community.

Mie metasurfaces for enhancing photon outcoupling from single embedded quantum emitters

Abstract Solid-state quantum emitters (QE) can produce single photons required for quantum information processing. However, their emission properties often exhibit poor directivity and polarisation definition resulting in considerable loss of generated photons. Here we propose and numerically evaluate Mie metasurface designs for outcoupling photons from an embedded and randomly-positioned QE. These Mie metasurface designs can provide over one order of magnitude enhancement in photon outcoupling with only several percent of photons being lost. Importantly, the Mie metasurfaces provide the enhancement in photon outcoupling without the need for strict QE position alignment and without affecting the intrinsic QE emission rate (Purcell enhancement). Electric dipole modes are key for achieving the enhancement and they offer a path for selective outcoupling for photons emitted with specific polarisation, including the out-of-plane polarisation. Mie metasurfaces can provide an efficient, polarisation-selective and scalable platform for QEs.

Radiomic detection of abnormal brain regions in tuberous sclerosis complex.

Radiomics refers to the extraction of quantitative information from medical images and is most commonly utilized in oncology to provide ancillary information for solid tumor diagnosis, prognosis, and treatment response. The traditional radiomic pipeline involves segmentation of volumes of interest with comparison to normal brain. In other neurologic disorders, such as epilepsy, lesion delineation may be difficult or impossible due to poor anatomic definition, small size, and multifocal or diffuse distribution. Tuberous sclerosis complex (TSC) is a rare genetic disease in which brain magnetic resonance imaging (MRI) demonstrates multifocal abnormalities with variable imaging and epileptogenic features. The purpose of this study was to develop a radiomic workflow for identification of abnormal brain regions in TSC, using a whole-brain atlas-based approach with generation of heatmaps based on signal deviation from normal controls. This was a retrospective pilot study utilizing high-resolution whole-brain 3D FLAIR MRI datasets from retrospective enrollment of tuberous sclerosis complex (TSC) patients and normal controls. Subjects underwent MRI including high-resolution 3D FLAIR sequences. Preprocessing included skull stripping, coregistration, and intensity normalization. Using the Brainnetome and Harvard-Oxford atlases, brain regions were parcellated into 318 discrete regions. Expert neuroradiologists spatially labeled all tubers in TSC patients using ITK-SNAP. The pyradiomics toolbox was used to extract 88 radiomic features based on IBSI guidelines, comparing tuber-affected and non-tuber-affected parenchyma in TSC patients, as well as normal brain tissue in control patients. For model training and validation, regions with tubers from 20 TSC patients and 30 normal control subjects were randomly divided into two training sets (80%) and two validation sets (20%). Additional model testing was performed on a separate group of 20 healthy controls. LASSO (least absolute shrinkage and selection operator) was used to perform variable selection and regularization to identify regions containing tubers. Relevant radiomic features selected by LASSO were combined to produce a radiomic score ω, defined as the sum of squared differences from average control group values. Region-specific ω scores were converted to heat maps and spatially coregistered with brain MRI to reflect overall radiomic deviation from normal. The proposed radiomic workflow allows for quantification of deviation from normal in 318 regions of the brain with the use of a summative radiomic score ω. This score can be used to generate spatially registered heatmaps to identify brain regions with radiomic abnormalities. The pilot study of TSC showed radiomic scores ω that were statistically different in regions containing tubers from regions without tubers/normal brain (p<0.0001). Our model exhibits an AUC of 0.81 (95% confidence interval: 0.78-0.84) on the testing set, and the best threshold obtained on the training set, when applied to the testing set, allows us to identify regions with tubers with a specificity of 0.91 and a sensitivity of 0.60. We describe a whole-brain atlas-based radiomic approach to identify abnormal brain regions in TSC patients. This approach may be helpful for identifying specific regions of interest based on relatively greater signal deviation, particularly in clinical scenarios with numerous or poorly defined anatomic lesions.

Personalized interpretable prediction of perceived sleep quality: Models with meaningful cardiovascular and behavioral features.

Understanding a person's perceived quality of sleep is an important problem, but hard due to its poor definition and high intra- as well as inter-individual variation. In the short term, sleep quality has an established impact on cognitive function during the following day as well as on fatigue. In the long term, good quality sleep is essential for mental and physical health and contributes to quality of life. Despite the need to better understand sleep quality as an early indicator for sleep disorders, perceived sleep quality has been rarely modeled for multiple consecutive days using biosignals. In this paper, we present novel insights on the association of cardiac activity and perceived sleep quality using an interpretable modeling approach utilizing the publicly available intensive-longitudinal study M2Sleep. Our method takes as input signals from commodity wearable devices, including motion and blood volume pulses. Despite processing only simple and clearly interpretable features, we achieve an accuracy of up to 70% with an AUC of 0.76 and reduce the error by up to 36% compared to related work. We further argue that collected biosignals and sleep quality labels should be normalized per-participant to enable a medically insightful analysis. Coupled with explainable models, this allows for the interpretations of effects on perceived sleep quality. Analysis revealed that besides higher skin temperature and sufficient sleep duration, especially higher average heart rate while awake and lower minimal activity of the parasympathetic and sympathetic nervous system while asleep increased the chances of higher sleep quality.

Dispelling the Myths of Isotretinoin and Implications for Rhinoplasty

Summary: Despite concerns from 1980s case reports, oral isotretinoin, a derivative of Vitamin A, has largely proven to be safe in surgical procedures with the exception of deep skin resurfacing. Isotretinoin modulates thinning skin and internal scarring in select rhinoplasty patients who may otherwise have poor definition and excessive scarring. A review of patients undergoing surgical interventions including rhinoplasty in the setting of concomitant isotretinoin was performed to examine safety and therapeutic potential. Forty-nine studies were reviewed. Isotretinoin use appears to be safe in a wide variety of surgical procedures relying on internal scar formation. In rhinoplasty, studies utilized oral isotretinoin to thin skin and improve appearance, patient and surgeon satisfaction. As such, the clinical potential for using oral isotretinoin in select rhinoplasty candidates such as those with thick glaborous sebaceous skin, ethnic, male, and/or revision patients, could mitigate internal scarring processes. Further studies examining the optimal dosing regimen and long-term benefits are warranted.

Intimate Partner Violence, Femicide, and General Theories: Issues for Research and Policy From the View of Modern Control Theory

Intimate partner violence (IPV), including intimate partner homicide (IPH) and femicide, raises issues for general theories of crime, such as control and opportunity theories, that see close relationships among friends and family as barriers to interpersonal crimes. Crime-specific studies of both correlates and trends in IPV, including recent interrupted trend studies that examine the effects of COVID restrictions, often test opportunity theories absent considerations of theoretically driven images of actors. Review of empirical research on IPV and IPH reveals strong compatibility between the predictions of modern control theory and consistent findings from trend data. Barriers to understanding of the explanatory power of general theories of crime (including, for example, control theories and feminist perspectives) in contemporary research include use of poor definitions of intimacy, misspecification of age effects, failure to consider the versatility of offending behavior, neglecting the importance of trends in analogous behaviors, neglecting the role of situational factors in violence, and the limitations in the measurement of repetitive victimization. Theories such as routine activity and situational crime prevention that fail to explicitly include characteristics of actors can go only a limited way in providing meaningful policy. Research supports the potential policy effects of investments in early childhood and attention to situational barriers (including limitations on alcohol use and firearm availability) to reduce IPV. Although modern control theory is used to illustrate these issues, other general theories, like feminist theories, can make similar arguments.

Preparation of Simple Bicyclic Carboxylate-Rich Alicyclic Molecules for the Investigation of Dissolved Organic Matter.

Dissolved organic matter (DOM) is a vast and complex chemical mixture that plays a key role in the mediation of the global carbon cycle. Fundamental understanding of the source and fate of oceanic organic matter is obscured due to poor definition of the key molecular contributors to DOM, which limits accurate sample analysis and prediction of the Earth's carbon cycle. Previous work has attempted to define the components of the DOM through a variety of chromatographic and spectral techniques. However, modern preparative and analytical methods have not isolated or unambiguously identified molecules from DOM. Therefore, previously proposed structures are based solely on the mixture's aggregate properties and do not accurately describe any true individual molecular component. In addition to this, there is a lack of appropriate analogues of the individual chemical classes within DOM, limiting the scope of experiments that probe the physical, chemical, and biological contributions from each class. To address these problems, we synthesized a series of analogues of carboxylate-rich alicyclic molecules (CRAM), a molecular class hypothesized to exist as a major contributor to DOM. Key analytical features of the synthetic CRAMs were consistent with marine DOM, supporting their suitability as chemical substitutes for CRAM. This new approach provides access to a molecular toolkit that will enable previously inaccessible experiments to test many unproven hypotheses surrounding the ever-enigmatic DOM.

Unaligned Hip Radiograph Assessment Utilizing Convolutional Neural Networks for the Assessment of Developmental Dysplasia of the Hip

Abstract Developmental dysplasia of the hip (DDH) is a condition in which the acetabular socket inadequately contains the femoral head (FH). If left untreated, DDH can result in degenerative changes in the hip joint. Several imaging techniques are used for DDH assessment. In radiographs, the acetabular index (ACIN), center-edge angle, Sharp's angle (SA), and migration percentage (MP) metrics are used to assess DDH. Determining these metrics is time-consuming and repetitive. This study uses a convolutional neural network (CNN) to identify radiographic measurements and improve traditional methods of identifying DDH. The dataset consisted of 60 subject radiographs rotated along the craniocaudal and mediolateral axes 25 times, generating 1500 images. A CNN detection algorithm was used to identify key radiographic metrics for the diagnosis of DDH. The algorithm was able to detect the metrics with reasonable accuracy in comparison to the manually computed metrics. The CNN performed well on images with high contrast margins between bone and soft tissues. In comparison, the CNN was not able to identify some critical points for metric calculation on a few images that had poor definition due to low contrast between bone and soft tissues. This study shows that CNNs can efficiently measure clinical parameters to assess DDH on radiographs with high contrast margins between bone and soft tissues with purposeful rotation away from an ideal image. Results from this study could help inform and broaden the existing bank of information on using CNNs for radiographic measurement and medical condition prediction.

Alpha-180 spin-echo-based line-scanning method for high-resolution laminar-specific fMRI in animals

Abstract Laminar-specific functional magnetic resonance imaging (fMRI) has been widely used to study circuit-specific neuronal activity by mapping spatiotemporal fMRI response patterns across cortical layers. Hemodynamic responses reflect indirect neuronal activity given the limitation of spatial and temporal resolution. Previously, a gradient-echo-based line-scanning fMRI (GELINE) method was proposed with high temporal (50 ms) and spatial (50 µm) resolution to better characterize the fMRI onset time across cortical layers by employing two saturation RF pulses. However, the imperfect RF saturation performance led to poor boundary definition of the reduced region of interest (ROI) and aliasing problems outside of the ROI. Here, we propose an α (alpha)-180 spin-echo-based line-scanning fMRI (SELINE) method in animals to resolve this issue by employing a refocusing 180˚ RF pulse perpendicular to the excitation slice (without any saturation RF pulse) and also achieve high spatiotemporal resolution. In contrast to GELINE signals which peaked at the superficial layer, we detected varied peaks of laminar-specific BOLD signals across deeper cortical layers using the SELINE method, indicating the well-defined exclusion of the large draining-vein effect using the spin-echo sequence. Furthermore, we applied the SELINE method with a 200 ms repetition time (TR) to sample the fast hemodynamic changes across cortical layers with a less draining vein effect. In summary, this SELINE method provides a novel acquisition scheme to identify microvascular-sensitive laminar-specific BOLD responses across cortical depth.

Energy poverty assessment: Indicators and implications for developing and developed countries

Energy poverty represents a considerable challenge that is difficult to quantify, monitor, and effectively address through policy measures. Efforts to tackle this problem have proven unsatisfactory for many reasons, including insufficient data on who is experiencing energy poverty to a poor definition of what this concept entails. This study examines methods for measuring energy poverty considering spatial, household preferences, home standards, and cultural differences among countries. The focus is on two commonly used indicators to communicate energy poverty issues at the local, national, and global levels: single indicators and multidimensional indices. The advantages and disadvantages of these indicators will be thoroughly examined. A dedicated study is provided to investigate the mechanism through which energy poverty affects the quality of life. The analysis reveals the limitations of single indicators in capturing the nuances of energy poverty across diverse contexts. Multidimensional indices offer a more comprehensive approach but require careful design and data availability. A framework is proposed for selecting appropriate indicators considering local needs and cultural specificities. By integrating insights from quality-of-life studies, the recommendations guide policymakers in designing effective interventions and targeting resources to maximize the impact on populations experiencing energy poverty.

Adaptive Laboratory Evolution of Probiotics toward Oxidative Stress Using a Microfluidic-Based Platform.

Adaptive laboratory evolution (ALE) can be used to make bacteria less susceptible to oxidative stress. An alternative to large batch scale ALE cultures is to use microfluidic platforms, which are often more economical and more efficient. Microfluidic ALE platforms have shown promise, but many have suffered from subpar cell passaging mechanisms and poor spatial definition. A new approach is presented using a microfluidic Evolution on a Chip (EVoc) design which progressively drives microbial cells from areas of lower H2O2 concentration to areas of higher concentration. Prolonged exposure, up to 72h, revealed the survival of adaptive strains of Lacticaseibacillus rhamnosus GG, a beneficial probiotic often included in food products. After performing ALE on this microfluidic platform, the bacteria persisted under high H2O2 concentrations in repeated trials. After two progressive exposures, the ability of L. rhamnosus to grow in the presence of H2O2 increased from 1mm H2O2 after a lag time of 31h to 1mm after 21h, 2mm after 28h, and 3mm after 42h. The adaptive strains have different morphology, and gene expression compared to wild type, and genome sequencing revealed a potentially meaningful single nucleotide mutation in the protein omega-amidase.

Natural history of mitochondrial optic neuropathies

Mitochondrial optic neuropathies (MON) may occur as a single organ disease (non‐syndromic MON) or in the context of a multisystem mitochondrial disorder (syndromic MON). By far the most frequent MON are Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA). LHON is in most cases caused by mitochondrial DNA (mtDNA) mutations m.11778G&gt;A, m.3460G&gt;A or m.14484T&gt;C, while ADOA is most frequently due to mutations in the OPA1 gene. As therapy trials have been performed, are ongoing or are planned for LHON and ADOA, it is important to know about the natural history of these disorders which may help to design trials or may serve as an external comparator.In LHON, an international observational retrospective registry (REALITY) analysed the visual course and outcome in 44 LHON patients, and found (after an average follow‐up time of 32.5 months) the mean best‐corrected visual acuity (BCVA) to be 1.46 LogMAR in m.11778G&gt;A, 1.52 LogMAR in m.3460G&gt;A, and 0.97 LogMAR in m.14484T&gt;C mutations carriers. In line with previous findings, children below age 12 years at onset had the best visual prognosis. Since 25 of the 44 patients had taken idebenone at some point, this work does not qualify as a natural history study, though.A meta‐analysis of 12 retrospective and 3 prospective studies included data from 695 LHON patients with the m.11778G&gt;A mutation. This meta‐analysis was hampered by the poor and variable definition of recovery among studies, and by the fact that idebenone use could not always be excluded. Main findings were some degree of recovery in 14.4% of patients, and 11.3% in those above age 15 years. Final BCVA of better than 1.0 logMAR was rare.In an own study of 83 LHON patients (73.5% with m.11778G&gt;A mutation), BCVA at last observation was better than 1.0 logMAR in 18.1%, between 1.0 and 1.68 logMAR in 33.7% and worse than 1,68 logMAR (off‐chart) in 48.2%. Spontaneous recovery by at least 0.2 logMAR occurred in 16.3% of patients.In OPA1‐ADOA, a retrospective analysis of data from 64 affected patients showed a mean age at visual failure onset of 7.0 years (range 1.0–16.0 years), and a mean BCVA at last observation of 1.02 LogMAR. Longitudinal data in 43 OPA1 patients with a mean follow‐up duration of 18.0 years showed on average a slow visual decline of 0.032 LogMAR/year, but some patients deteriorated much faster (range 0–0.171 LogMAR/year).In conclusion, currently available data on the natural history of MON are hampered by retrospective analysis, low sample sizes, unsystematic phenotyping, variable definitions of key outcomes (eg, recovery) and often incomplete information on the administration of idebenone or other drugs. Large multicenter studies on natural history are needed but are more and more difficult to perform with the advent and sometimes even approval of disease‐modifying treatments.