bluuebunny/crossref_metadata_2025_split huggingface dataset:
Re-evaluating malarial retinopathy to improve its diagnostic accuracy in cerebral malaria
Authors: Wilson Kyle J , Liomba Alice Muiruri , Seydel Karl B , Moxon Christopher A , MacCormick Ian JC , Harding Simon P , Beare Nicholas AV , Taylor Terrie E 
Published: December 2024

AbstractBackgroundPrevious work has identified that malarial retinopathy (MR) has diagnostic value in cerebral malaria (CM). To improve our understanding of MR as a predictor of cerebral parasite sequestration in CM we reviewed data from the Blantyre autopsy study.MethodsWe performed a retrospective analysis of data collected from a consecutive series of patients presenting to the Pediatric Research Ward at Queen Elizabeth Central Hospital in Blantyre, Malawi between 1996 and 2010. We determined the diagnostic accuracy of MR as a predictor of cerebral parasite sequestration in a cohort of children with fatal CM.ResultsOf 84 children included in the study, 65 met the WHO criteria for CM during life. Eighteen (28%) of 65 did not have evidence of cerebral parasite sequestration at autopsy and 17 had an alternative cause of death. MR had a sensitivity of 89% and specificity of 73% to predict sequestration. In a subset of patients with graded retinal assessments, this was improved to 94% and 88% by reclassifying patients with 1-5 hemorrhages in only one eye as retinopathy negative.ConclusionsMR remains the most specific point-of-care test for CM in endemic areas. Its specificity can be improved, without sacrificing sensitivity, by reclassifying patients with less than 5 hemorrhages in one eye only as MR negative.
Deaminase-mediated chromatin accessibility profiling with single-allele resolution
Authors: Yu Tian , Li Zhijian , Gibbs Ellie , Iwase Reina , Francoeur Matthew J , Phan Quang vinh , Zhao Jing , Rosin Jane , Cole Phillip A , Pinello Luca , Sherwood Richard I 
Published: December 2024

AbstractBinding of transcription factors (TFs) at gene regulatory elements controls cellular epigenetic state and gene expression. Current genome-wide chromatin profiling approaches have inherently limited resolution, complicating assessment of TF occupancy and co-occupancy, especially at individual alleles. In this work, we introduce Accessible Chromatin by Cytosine Editing Site Sequencing with ATAC-seq (ACCESS-ATAC), which harnesses a double-stranded DNA cytosine deaminase (Ddd) enzyme to stencil TF binding locations within accessible chromatin regions. We optimize bulk and single-cell ACCESS-ATAC protocols and develop computational methods to show that the increased resolution compared with ATAC-seq improves the accuracy of TF binding site prediction. We use ACCESS-ATAC to perform genome-wide allelic occupancy and co-occupancy imputation for 64 TFs each in HepG2 and K562, revealing that the propensity of a majority of TFs to co-occupy nearby motifs oscillates with a period approximating the helical turn of DNA. Altogether, ACCESS-ATAC expands the resolution and capabilities of bulk and single-cell epigenomic profiling.
Auditory and Visual Thalamocortical Connectivity Alterations in Unmedicated People with Schizophrenia: An Individualized Sensory Thalamic Localization and Resting-State Functional Connectivity Study
Authors: Williams John C. , Tubiolo Philip N. , Gil Roberto B. , Zheng Zu Jie , Silver-Frankel Eilon B. , Haubold Natalka K. , Abeykoon Sameera K. , Pham Dathy T. , Ojeil Najate , Bobchin Kelly , Slifstein Mark , Weinstein Jodi J. , Perlman Greg , Horga Guillermo , Abi-Dargham Anissa , Van Snellenberg Jared X. 
Published: December 2024

AbstractBackgroundConverging evidence from clinical neuroimaging and animal models has strongly implicated dysfunction of thalamocortical circuits in the pathophysiology of schizophrenia. Preclinical models of genetic risk for schizophrenia have shown reduced synaptic transmission from auditory thalamus to primary auditory cortex, which may represent a correlate of auditory disturbances such as hallucinations. Human neuroimaging studies, however, have found a generalized increase in resting state functional connectivity (RSFC) between whole thalamus and sensorimotor cortex in people with schizophrenia (PSZ). We aimed to more directly translate preclinical findings by specifically localizing auditory and visual thalamic nuclei in unmedicated PSZ and measuring RSFC to primary sensory cortices.MethodsIn this case-control study, 82 unmedicated PSZ and 55 matched healthy controls (HC) completed RSFC functional magnetic resonance imaging (fMRI). Auditory and visual thalamic nuclei were localized for 55 unmedicated PSZ and 46 HC who additionally completed a sensory thalamic nuclei localizer fMRI task (N = 101). Using localized nuclei as RSFC seeds we assessed group differences in auditory and visual thalamocortical connectivity and associations with positive symptom severity.ResultsAuditory thalamocortical connectivity was not significantly different between PSZ and HC, but hyperconnectivity was associated with greater positive symptom severity in bilateral superior temporal gyrus. Visual thalamocortical connectivity was significantly greater in PSZ relative to HC in secondary and higher-order visual cortex, but not predictive of positive symptom severity.ConclusionThese results indicate that visual thalamocortical hyperconnectivity is a generalized marker of schizophrenia, while hyperconnectivity in auditory thalamocortical circuits relates more specifically to positive symptom severity.
Hemodynamic Mechanisms Underlying Orthostatic Hypotension in Stroke Survivors: A Cross-Sectional Study
Authors: Oyake Kazuaki , Mochida Ayumi , Terashi Masakiyo , Hasegawa Mahiro , Saito Akari , Kondo Kunitsugu , Otaka Yohei , Momose Kimito 
Published: December 2024

AbstractBackgroundOrthostatic hypotension is an important consideration for stroke survivors, given its association with adverse outcomes, such as cardiovascular diseases and falls. Understanding the hemodynamic mechanisms underlying orthostatic hypotension is essential for selecting the appropriate treatment based on individual hemodynamic patterns. However, the relative contribution of changes in cardiac output and total peripheral resistance to orthostatic hypotension remains unclear in stroke survivors.ObjectiveTo determine whether orthostatic hypotension is more strongly associated with a marked decrease in cardiac output or an impaired increase in total peripheral resistance among individuals with stroke.MethodsThis cross-sectional study included 23 individuals with stroke (13 males, mean [SD] age 63.7 [12.1] years, mean time since stroke 85.1 [34.1] days) recruited from an intensive inpatient rehabilitation ward between June 2022 and November 2023. Participants underwent a head-up tilt test to assess orthostatic hypotension and associated changes in cardiac and total peripheral resistance indices. The head-up tilt test protocol consisted of a 5-min period in the supine position followed by a 5-min period with a 70° head-up tilt. Orthostatic hypotension was defined as a reduction in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg during the test.ResultsOrthostatic hypotension was identified in five participants (22%). During the head-up tilt test, these individuals demonstrated a significantly greater increase in the cardiac index (p = 0.023) and decrease in the total peripheral resistance index (p = 0.002) than those without orthostatic hypotension.ConclusionsOur results suggest that an impaired increase in total peripheral resistance upon standing mainly contributes to orthostatic hypotension in individuals with stroke. These findings advance the understanding of the hemodynamic mechanisms underlying orthostatic hypotension in the stroke population and may guide the implementation of targeted therapeutic strategies.HighlightsOrthostatic hypotension is associated with a higher risk of adverse outcomes.Mechanisms of orthostatic hypotension were examined in stroke survivors.Orthostatic hypotension may be associated with impaired vasoconstriction.Findings may aid in managing orthostatic hypotension during stroke rehabilitation.
The Effects of Climate Hazards on Personal Hygiene Practices among People with Disabilities in Bangladesh: A Qualitative Study
Authors: Nawaz Shahpara , Upoma Tasnia Alam , Goshami Arka , Podder Bithy , Akter Jarin , Hasan Mehedi , Shoaib Dewan Muhammad , D’Mello-Guyett Lauren , Kovats Sari , Alam Mahbub-Ul , Wilbur Jane 
Published: December 2024

AbstractPeople with disabilities experience unique challenges in practising good hygiene, and climate hazards exacerbate those challenges. This study investigates the effects of climate hazards on personal hygiene practices (handwashing, bathing, laundry, and menstrual health) among people with disabilities and their caregivers in cyclone-affected Satkhira and flood-affected Gaibandha of Bangladesh.A phenomenological qualitative study was conducted in rural Satkhira and Gaibandha. We applied purposive sampling to select 39 people with disabilities and 16 caregivers who experienced cyclones or floods between 2018 and 2023. Data were collected through in-depth interviews, photovoice and ranking, and observations. We thematically analysed findings using Nvivo 14.During Cyclone Amphan in Satkhira and recurrent floods in Gaibandha, handwashing practices remained unchanged. However, water-logged muddy paths led participants to refrain from bathing for days in Satkhira, causing dissatisfaction about cleanliness. Flooded water points and surroundings in Gaibandha forced participants to bathe and do laundry in contaminated floodwaters, resulting in people reporting increased rashes, skin infections, and fevers. In both districts, the need for bathing and laundering soiled clothes and bedding among people with disabilities experiencing incontinence remained unmet. Additionally, caregivers struggled to provide dignified hygiene support. Women with disabilities could not wash menstrual materials during cyclone in Satkhira. In Gaibandha, contaminated floodwater was used to wash menstrual materials, and individuals living in temporary shelters expressed privacy concerns. Disposal practices were disrupted, with used materials stored indoors or thrown into floodwaters. These challenges adversely affected the health and well-being of people with disabilities and the emotional well-being of the caregivers.People with disabilities face more complex challenges in maintaining personal hygiene during floods and cyclones due to impairments, gender-specific biological needs, additional health requirements, and dependency on caregivers. To prevent worsening inequalities in a changing climate, it is crucial to systematically include people with disabilities in climate-resilient hygiene initiatives.
Aberrant Neuronal Synchronization Associated with Cognitive Deficits in a Rodent Model of Childhood Cranial Irradiation
Authors: Barrientos Sebastian A. , Konradsson Elise , Ceberg Crister , Petersson Per 
Published: December 2024

AbstractCranial radiation can be a life-saving intervention in pediatric brain cancer therapy but often results in debilitating cognitive decline. To clarify the underlying mechanisms of these side-effects we have here recorded neurophysiological activity in distributed brain networks involved in decision-making and memory functions in adult rats exposed to cranial irradiation on postnatal day 21. Multi-structure local field potential (LFP) recordings revealed decreased power in irradiated animals in the 4-9 Hz frequency band. Additionally, a distinct slowing of the oscillatory activity was observed preceding erroneous choice in a decision-making task. Moreover, irradiated rats showed reduced dynamics and a fragmented pattern of inter-structural coherence across different phases of the task. Our results suggest that the cognitive deficits and reduced processing speed following irradiation of the juvenile brain arise as a consequence of changes in long-range functional connectivity, including thalamocortical circuits, causing abnormally slow and spatially fractionated patterns of coordinating LFP activity.
A Toolbox for Generating Multidimensional 3-D Objects with Fine-Controlled Feature Space: Quaddle 2.0
Authors: Wen Xuan , Malchin Leo , Womelsdorf Thilo 
Published: December 2024

AbstractMultidimensional 3D-rendered objects are an important component of vision research and video- gaming applications, but it has remained challenging to parametrically control and efficiently generate those objects. Here, we describe a toolbox for controlling and efficiently generating 3D rendered objects composed of ten separate visual feature dimensions that can be fine-adjusted using python scripts. The toolbox defines objects as multi-dimensional feature vectors with primary dimensions (object body related features), secondary dimensions (head related features) and accessory dimensions (including arms, ears, or beaks). The toolkit interfaces with the freely available Blender software to create objects. The toolbox allows to gradually morph features of multiple feature dimensions, determine the desired feature similarity among objects, and automatize the generation of multiple objects in 3D object and 2D image formats. We document the use of multidimensional objects in a sequence learning task that embeds objects in a 3D- rendered augmented reality environment controlled by the gaming engine unity. Taken together, the toolbox enables the efficient generation of multidimensional objects with fine control of low- level features and higher-level object similarity useful for visual cognitive research and immersive visual environments.
Transcriptional control ofC. elegansmale tail tip morphogenesis by DMD-3
Authors: Fernandez Porfirio , Ercan Sevinç , Kiontke Karin C. , Fitch David H. A. 
Published: December 2024

AbstractSexual dimorphic morphogenesis is governed by DM-domain transcription factors (TFs) in many animals, but how these transcriptional control links to the morphogenetic mechanisms is insufficiently known. The DM-domain TF DMD-3 inC. elegansis the master regulator of a male-specific development that changes the shape of the tail tip from long and pointed in larvae to short and round in adults. This tail tip morphogenesis (TTM) requires cell-shape changes, cell migration and fusion. To understand how transcriptional regulation by DMD-3 governs TTM, we used male-specific ChIP-seq to identify its direct targets. We found 1,755 DMD-3 bound sites. We identify a DMD-3 associated binding motif and validate its function in TTM. This motif is similar to the binding motif of EOR-1, and we suggest that DMD-3 acts cooperatively with EOR-1 and possibly other TFs. DMD-3 targets 270 genes that play a role in TTM. These genes include other TFs but also effectors and components of morphogenetic mechanisms. By deleting the DMD-3 bound region endogenously and observing changes in reporter expression and tail tip phenotypes, we identify tissue specific enhancers in the cis-regulatory region offos-1, pan-1, nmy-2andhmr-1that play a role in TTM. Forfos-1, we propose that a feed-forward loop is responsible for tail-tip specific increase of gene-expression. This study provides insights into the architecture of the genetic regulatory network controlling a morphogenetic process.Article SummaryDM domain transcription factors are often responsible for sexually dimorphic morphogenesis, but how they connect to morphogenetic mechanisms is insufficiently known. Here, we use ChIP-seq to determine the direct targets of DMD-3, which is the master regulator of male-specific tail tip morphogenesis (TTM) inC. elegans. We find that DMD-3 targets 270 TTM genes which include other transcription factors but also effectors and components of morphogenetic mechanisms. This study provides insights into the architecture of the genetic regulatory network controlling a morphogenetic process.
ScPectral: Spectrally Clustering Hypergraph Representations of Transcription Networks to Identify Developmental Pathways
Authors: Bersenev Dennis 
Published: December 2024

AbstractTranscription Networks, otherwise known as Gene Regulatory Networks (GRNs), are models of biological systems centred on Transcription Factor (TF) interactions. These models equip experimentalists with a powerful computational tool to predict the effects of different genetic perturbations. GRNs are canonically modelled using a digraph, wherein the arcs indicate activation or repression between each pair of nodes to represent the relationships among the TFs. However, gene regulation is accomplished by groups of TFs working in concert, a biological reality the pairwise model neglects. In addition to the paucity of GRN representations incorporating this known TF biology, a persisting challenge to inference of the networks themselves is in accounting for the latent dynamics of gene interactions. In considering this second point, the advent of single-cell RNA sequencing technologies, provides the high resolution data needed to begin effectively inferring temporally-aware models. Despite this, utilisation of temporally-aware statistical metrics to do so has been limited. In addressing these shortcomings to GRN inference, scPectral is introduced as a method to infer a robust dynamic representation of a common GRN motif, the cascade, in the form of a hypergraph. ScPectral is applied to the identification of developmental pathways for known processes to validate its efficacy. Given scPectral’s modest success in finding key constituents of developmental pathways, and its ability to do so in a manner requiring no input or annotation of known biology, through further improvement it may develop to become a technique able to aid experimentalists exploring novel development processes. ScPectral is made available at:https://github.com/Dennis-Bersenev/scPectral.
Development of an H&E on-block staining technique for collagen detection in cryo-fluorescence tomography imaging of frozen breast tissue samples
Authors: Snoddy Erin P. , Tang Tien T. , Fowlkes Natalie , Huynh Thomas , Brewer Savannah Kari J. , Contreras Alejandro , Reece Gregory , Brock Kristy K. 
Published: December 2024

AbstractBackgroundHematoxylin and eosin (H&E) staining is widely considered to be the gold-standard diagnostic tool for histopathology evaluation. However, the fatty nature of some tissue types, such as breast tissue, presents challenges with cryo-sectioning, often resulting in artifacts that can make histopathologic interpretation and correlation with other imaging modalities virtually impossible. We present an optimized on-block H&E staining technique that improves contrast for identifying collagenous stroma during cryo-fluorescence tomography (CFT) sectioning.ApproachIn this prospective study, we embedded four breast specimens with confirmed ligaments from a bilateral mastopexy in an optimal cutting temperature block. Two of the samples were processed on a CFT imager and stained with our on-block staining protocol. In this protocol, hematoxylin was applied to the block face before being washed with deionized water. Eosin was then applied and washed with 95% ethanol. We then applied mounting medium and acquired images with a stereo-dissecting microscope and camera. Prior to staining, GFP fluorescence and white-light images were acquired with the CFT system to serve as a validation metric. The other two samples were sectioned on a standard cryostat and stained according to gold-standard H&E protocol. The resulting microscope slides were imaged with a digital slide scanner and viewed with Leica Imagescope software. An experienced pathologist evaluated both sets of images for qualitative comparisons.ResultsPathologist evaluation confirmed that striations from on-block staining were qualitatively comparable with collagen tracks identified in gold-standard histology images. Furthermore, GFP images captured collagen autofluorescence, which aligned with the same structures identified by our on-block staining protocol.ConclusionOur on-block staining technique shows comparable visualization of collagenous structures at the mesoscopic level for fresh breast tissue samples. This technique improves tissue contrast and region of interest selection for histology during CFT imaging for analysis of the stromal architecture of the breast.
Digital Spatial Profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer
Authors: Eickelschulte Samaneh , Kaczorowski Adam , Janke Florian , Riediger Anja Lisa , Lazareva Olga , Böning Sarah , Kristiansen Glen , Schwab Constantin , Stenzinger Albrecht , Sültmann Holger , Duensing Stefan , Duensing Anette , Görtz Magdalena 
Published: December 2024

AbstractBackgroundProstate cancer (PCa) is a highly heterogeneous disease, with cases ranging from indolent to highly aggressive forms. Ongoing research focuses on identifying new biomarkers to improve early risk stratification in PCa, addressing current limitations to accurately evaluate disease progression. A promising new approach to aid PCa risk stratification is digital spatial profiling (DSP) of PCa tissue.MethodsA total of 94 regions of interest from 38 PCa patients at first diagnosis were analyzed for the expression of 44 proteins, including components of the PI3K-AKT, MAPK, and cell death signaling pathways as well as immune cell markers. An additional validation cohort consisting of 154 PCa patients with long-term follow-up data was analyzed using immunohistochemistry (IHC) to assess the consistency of the identified biomarkers across a larger sample set.ResultsDSP identified proliferation marker Ki-67 and phospho-c-Jun N-terminal protein kinase (p-JNK), a member of the MAPK signaling pathway, as significantly upregulated proteins in aggressive PCa (Gleason scores 4 and 5) compared to indolent disease (Gleason score 3). The upregulation of p-JNK was confirmed through IHC. High p-JNK expression was associated with a shorter time to biochemical recurrence (log-rank, p=0.1).ConclusionOur results indicate that p-JNK may contribute to PCa progression and serve as an early biomarker for aggressive PCa stratification. Identifying this biomarker through DSP could be crucial in advancing disease management and addressing the critical unmet need for more targeted therapies in the treatment of aggressive PCa. Further studies are recommended to evaluate the role of p-JNK in PCa progression.