bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situ, High-Resolution Quantification of CO2Uptake Rates via Automated Off-Gas Analysis Illuminates Carbon Uptake Dynamics in Cyanobacterial Cultures
Authors: Jones Christopher M. , Innes Sean , Holland Steven , Burch Tyson , Parrish Sydney , Nielsen David R. 
Published: June 2024

AbstractQuantification of CO2fixation rates by cyanobacteria is vital to determining their potential as industrial strains in a circular bioeconomy. Currently, however, CO2fixation rates are most often determined through indirect and/or low-resolution methods, resulting in an incomplete picture of both dynamic behaviors and total carbon fixing potential. To address this, we developed a novel, low-cost system forin situoff-gas analysis which supports the automated acquisition of high-resolution and CO2uptake rates from cyanobacterial cultures. Carbon fixation data obtained via this system was independently verified by elemental analysis of cultivated biomass. UsingSynechococcus sp.PCC 7002 andSynechocystis sp.PCC 6803, we demonstrate that phototrophic CO2uptake rates accelerate linearly to a maximum before then decaying monotonically to cessation by stationary phase. Furthermore, consistent with the expected stoichiometry, we found that strong correlations exist between both the rates and total levels of cell growth and carbon fixation. This system simultaneously provides a high-resolution growth curve, accurate carbon fixation rates, as well as the total amount of carbon fixed in a cyanobacterial batch culture, thus illuminating the parameters with which cyanobacterial researchers can exploit use to realize their full potential in industrial applications.
Tissue resident memory CD8+ T cells are present but not critical for demyelination and neurodegeneration in a mouse model of multiple system atrophy
Authors: Corbin-Stein Nicole J. , Childers Gabrielle M. , Webster Jhodi M. , Zane Asta , Yang Ya-Ting , Ali Md Akkas , Sandoval Ivette M. , Manfredsson Fredric P. , Kordower Jeffrey H. , Tyrrell Daniel J. , Harms Ashley S. 
Published: June 2024

AbstractMultiple system atrophy (MSA) is rare, fast progressing, and fatal synucleinopathy with alpha-synuclein (α-syn) inclusions located within oligodendroglia called glial cytoplasmic inclusions (GCI). Along with GCI pathology there is severe demyelination, neurodegeneration, and neuroinflammation. In post-mortem tissue, there is significant infiltration of CD8+ T cells into the brain parenchyma, however their role in disease progression is unknown. To determine the role of CD8+ T cells, a modified AAV, Olig001-SYN, was used to selectively overexpress α-syn in oligodendrocytes modeling MSA in mice. Four weeks post transduction, we observed significant CD8+ T cell infiltration into the striatum of Olig001-SYN transduced mice recapitulating the CD8+ T cell infiltration observed in post-mortem tissue. To understand the role of CD8+ T cells, a CD8 knockout mice were transduced with Olig001-SYN. Six months post transduction into a mouse lacking CD8+ T cells, demyelination and neurodegeneration were unchanged. Four weeks post transduction, neuroinflammation and demyelination were enhanced in CD8 knockout mice compared to wild type controls. Applying unbiased spectral flow cytometry, CD103+, CD69+, CD44+, CXCR6+, CD8+ T cells were identified when α-syn was present in oligodendrocytes, suggesting the presence of tissue resident memory CD8+ T (Trm) cells during MSA disease progression. This study indicates that CD8+ T cells are not critical in driving MSA pathology but are needed to modulate the neuroinflammation and demyelination response.
Necessity and Impact of Specialization of Large Foundation Model for Medical Segmentation Tasks
Authors: Nguyen Eric , Liu Hengjie , Ruan Dan 
Published: June 2024

AbstractBackgroundLarge foundation models, such as the Segment Anything Model (SAM), have shown remarkable performance in image segmentation tasks. However, the optimal approach to achieve true utility of these models for domain-specific applications, such as medical image segmentation, remains an open question. Recent studies have released a medical version of the foundation model MedSAM by training on vast medical data, who promised SOTA medical segmentation. Independent community inspection and dissection is needed.PurposeThis study assesses the performance of off-the-shelf medical foundation model MedSAM for the segmentation of anatomical structures in pelvic MR images. We also evaluate the dependency on prompting scheme and demonstrate the gain of further specialized fine-tuning.MethodsMedSAM and its lightweight version LiteMedSAM were evaluated out-of-the-box on a public MR dataset consisting of 589 pelvic images split 80:20 for training and testing. An nnU-Net model was trained from scratch to serve as a benchmark and to provide bounding box prompts for MedSAM. MedSAM was evaluated using different quality bounding boxes, those derived from ground truth labels, those derived from nnU-Net, and those derived from the former two but with 5-pixel isometric expansion. Lastly, LiteMedSAM was refined on the training set and reevaluated on this task.ResultsOut-of-the-box MedSAM and LiteMedSAM both performed poorly across the structure set, especially for disjoint or non-convex structures. Varying prompt with different bounding box inputs had minimal effect. The mean Dice score and mean Hausdorff distances (in mm) for obturator internus using MedSAM and LiteMedSAM were {0.251 ± 0.110, 0.101 ± 0.079} and {34.142 ± 5.196, 33.688 ± 5.306}, respectively. Fine-tuning of LiteMedSAM led to significant performance gain, improving Dice score and Hausdorff distance for the obturator internus to 0.864 ± 0.123 and 5.022 ± 10.684, on par with nnU-Net with no significant difference in evaluation of most structures. All segmentation structures all benefited significantly from specialized refinement, at varying improvement margin.ConclusionOur study alludes to the potential of deep learning models like MedSAM and lite MedSAM for medical segmentation but also highlight the need for specialized refinement and adjudication: it is quite likely that off-the-shelf use of such large foundation models may be suboptimal, and specialized fine-tuning can significantly enhance segmentation accuracy.
Identification of cortical targets for modulating function supported by the human hippocampal network
Authors: Lee Hsin-Ju , Lin Fa-Hsuan 
Published: June 2024

AbstractBackgroundIndividualized transcranial magnetic stimulation (TMS) targeting using functional connectivity analysis of functional magnetic resonance imaging (fMRI) has been demonstrated to be advantageous in inducing neuroplasticity. However, how this approach can benefit modulating the episodic memory function supported by the hippocampal network remains elusive.ObjectiveWe use the resting-state fMRI data from a large cohort to reveal tentative TMS targets at cortical regions within the hippocampal network.MethodsFunctional MRI from 1,133 individuals in the Human Connectome Project was used to analyze the hippocampal network using seed-based functional connectivity.ResultsUsing a weighted sum of time series at the cortex, we identified the average centroids of individualized targets at the medial prefrontal cortex (mPFC) and posterior parietal cortices (PPC) at (-10, 49, 7) and (-40, -67, 30) in the left hemisphere, respectively. The mPFC and PPC coordinate at the right hemispheres are (11, 51, 6) and (48, -59, 24) in the right hemisphere, respectively. These coordinates can be reliably identified (>90% of individuals).ConclusionOur results suggest candidate TMS target coordinates to modulate the hippocampal function.
Amplified DNA Heterogeneity Assessment with Oxford Nanopore Sequencing Applied to Cell Free Expression Templates
Authors: Hejazi Sepehr , Ahsan Afrin , Kashani Mohammad , Reuel Nigel F 
Published: June 2024

AbstractIn this work, Oxford Nanopore sequencing is tested as an accessible method for quantifying heterogeneity of amplified DNA. This method enables rapid quantification of deletions, insertions, and substitutions, the probability of each mutation error, and their locations in the replicated sequences. Amplification techniques tested were conventional polymerase chain reaction (PCR) with varying levels of polymerase fidelity (OneTaq, Phusion, and Q5) as well as rolling circle amplification (RCA) with Phi29 polymerase. Plasmid amplification using bacteria was also assessed. By analyzing the distribution of errors in a large set of sequences for each sample, we examined the heterogeneity and mode of errors in each sample. This analysis revealed that Q5 and Phusion polymerases exhibited the lowest error rates observed in the amplified DNA. As a secondary validation, we analyzed the emission spectra of sfGFP fluorescent proteins synthesized with amplified DNA using cell free expression. Error-prone polymerase chain reactions confirmed the dependency of reporter protein emission spectra peak broadness to DNA error rates. The presented nanopore sequencing methods serve as a roadmap to quantify the accuracy of other gene amplification techniques, as they are discovered, enabling more homogenous cell-free expression of desired proteins.
Effects of Tasks on Functional Brain Connectivity Derived from Inter-Individual Correlations: Insights from Regional Homogeneity of Functional MRI Data
Authors: Di Xin , Jain Pratik , Biswal Bharat B. 
Published: June 2024

AbstractResearch on brain functional connectivity often relies on intra-individual moment-to-moment correlations of functional brain activity, typically using techniques like functional MRI (fMRI). Inter-individual correlations are also employed on data from fMRI and positron emission tomography (PET). Many past studies have not specified tasks for participants, keeping them in an implicit “resting” condition. This lack of task specificity raises questions about how different tasks impact inter-individual correlation estimates. In our analysis of fMRI data from 100 unrelated participants, scanned during seven task conditions and in a resting state, we calculated Regional Homogeneity (ReHo) for each task as a regional measure of brain functions. We found that changes in ReHo due to different tasks were relatively small compared with the variations across brain regions. Cross-region variations of ReHo were highly correlated between different tasks. Similarly, whole-brain inter-individual correlation patterns were remarkably consistent across the tasks, showing correlations greater than 0.78. Changes in inter-individual correlations between tasks were primarily driven by connectivity in the visual, somatomotor, default mode network, and the interactions between them. The subtle yet statistically significant differences in functional connectivity may be linked to specific brain regions associated with the studied tasks. Future studies should consider task design when exploring inter-individual connectivity in specific brain systems.
Reactivation-dependent transfer of fear memory between contexts requires M1 muscarinic receptor stimulation in dorsal hippocampus
Authors: Abouelnaga Karim H. , Huff Andrew E. , Jardine Kristen H. , O’Neill Olivia S. , Winters Boyer D. 
Published: June 2024

AbstractBackgroundMemory updating is essential for integrating new information into existing representations. However, this process could become maladaptive in conditions like post-traumatic stress disorder (PTSD), when fear memories generalize to neutral contexts. Previously, we have shown that contextual fear memory malleability in rats requires activation of M1 muscarinic acetylcholine receptors in the dorsal hippocampus. Here, we investigated the involvement of this mechanism in transfer of contextual fear memories to other contexts using a novel fear memory updating paradigm.MethodsFollowing brief re-exposure to a previously fear conditioned context, male rats (n=8-10/group) were placed into a neutral context to evaluate the transfer of fear memory. We also infused the selective M1 receptor antagonist pirenzepine into the dorsal hippocampus prior to memory reactivation to try to block this effect.ResultsResults support the hypothesis that fear memory can be updated with novel contextual information, but only if rats are re-exposed to the originally trained context relatively recently prior to the neutral context; evidence for transfer was not seen if the fear memory reactivation was omitted or if it occurred 6h prior to neutral context exposure. The transferred fear persisted for four weeks, and the effect was blocked by M1 antagonism.ConclusionsThese findings strongly suggest that fear transfer requires reactivation and destabilization of the original fear memory. Specific parameters likely dictate similar generalization in disorders like PTSD. The novel preclinical model introduced here, and its implication of muscarinic receptors in this process, should inform therapeutic strategies in this area.
Cognitive ability in offspring conscripts and cardiovascular disease risk in extended family members: assessing the impact of modifiable risk factors on familial risk
Authors: Vinueza-Veloz María Fernanda , Jones Paul Remy , Råberg Kjøllesdal Marte Karoline , Thu Huong , Carslake David , Næss Øyvind 
Published: June 2024

AbstractBackground and aimPrevious studies have demonstrated an inverse association between cognitive ability (CA) and risk of cardiovascular diseases (CVD). This study aims to investigate the associations between CA in offspring and CVD mortality in relatives of the parental generation (i.e., parents, aunts/uncles (A/U), and A/U partners), and assess the role of modifiable risk factors on these associations.MethodsThis longitudinal study included nearly 3 million adults who were followed up from age 45 until death. Data for participants were obtained through the linkage of various Norwegian surveys and registries. Hazard ratios (HR) for CVD mortality among the parental generation in relation to offspring CA were estimated using Cox proportional hazard regression.ResultsOne standard deviation (SD) unit increase in CA was associated with a reduction in CVD mortality among mothers (HR: 0.77, 95%CI [0.74, 0.81]); fathers (0.83, [0.81, 0.86]); A/U (0.91, [0.87, 0.94]); and A/U partners (0.91, [0.89, 0.94]). Adjusting the models for CVD risk factors in the parental generation attenuated all associations (mothers-HR: 0.91, 95%CI [0.87, 0.96]; fathers: 0.93, [0.91, 0.96]; A/U: 0.99, [0.96, 1.03]; A/U partners: 0.98, [0.95, 1.01]).ConclusionsWe observed an inverse association between offspring CA and CVD and all-cause mortality in various familial relationships. Our findings suggest the existence of factors shared among relatives that explain familial risk to suffer lower CA and higher CVD mortality. A significant portion of the association between CA and CVD mortality in all familial relationships was explained by modifiable risk factors in relatives of the older generation.HighlightsA lower cognitive ability might drive inequalities in cardiovascular disease (CVD).Shared environments explain most of the association between cognitive ability and CVD.The role of genetic factors in this relationship has probably been overestimated.
Prevalence of indications of alcohol and drug use among patients treated for injurious falls by Emergency Medical Services
Authors: Itzkowitz Nicole G. , Burford Kathryn G. , Crowe Remle P. , Wang Henry E. , Lo Alexander X. , Rundle Andrew G. 
Published: June 2024

AbstractObjectiveTo describe the distribution of alcohol and drug involvement in injurious falls by location and subtype of fall.MethodsUsing the 2019 National Emergency Medical Services Information System (NEMSIS) dataset we identified 1,854,909 patients injured from falls requiring an Emergency Medical Services (EMS) response and determined the fall location (e.g. indoors or on street/sidewalk) and the EMS clinician’s notation of alcohol or drug involvement. We analyzed substance involvement by fall subtype, location of fall and patient demographics.ResultsOverall, for 7.4% of injurious falls there was a notation of substance use: 6.5% for alcohol alone, 0.6% for drugs and 0.3% for alcohol and drugs. 21.2% of falls that occurred on a street or sidewalk had a notation of substance use; alcohol use alone for 18.5% of falls, drugs alone for 1.7% of falls and alcohol and drugs for 0.9% of falls. Substance use prevalence was highest, at 30.3%, in the age group 21 to 64 years, for falls occurring on streets and sidewalks, without syncope or heat illness as contributing factors; alcohol use alone for 26.3%, drugs alone for 2.6%, and alcohol and drugs for 1.4%. Reported substance use involvement was more frequent for men compared to women for each location type.ConclusionsOverall, 1-in-5 injurious falls on streets and sidewalks and requiring EMS attention involved substance use, and these numbers likely underestimate the true burden. As cities seek to expand nightlife districts, design strategies to protect pedestrians from falls should be enacted.
Estimated global and regional incidence and prevalence of herpes simplex virus infections and genital ulcer disease in 2020: Mathematical modeling analyses
Authors: Harfouche Manale , AlMukdad Sawsan , Alareeki Asalah , Osman Aisha M. M. , Gottlieb Sami L. , Rowley Jane , Abu-Raddad Laith J. , Looker Katharine J. 
Published: June 2024

AbstractBackgroundGenital herpes simplex virus (HSV) type 1 and 2 infections are lifelong and can cause symptomatic genital ulcer disease (GUD). HSV-2 almost always causes sexually transmitted genital infection, while HSV-1 mainly causes oral infection but can be sexually transmitted to cause genital infection. This study estimated genital infection with both HSV types and associated GUD globally in 2020, breaking down the data by World Health Organization (WHO) region and sex for females and males.MethodsA calibrated mathematical model was employed to generate estimates for the incidence and prevalence of HSV-2 infection, genital HSV-1 infection, and GUD caused by both HSV types. Estimates for non-genital infections caused by HSV-1 were also generated. Model input was derived from a comprehensive systematic review and meta-analyses of HSV prevalence data for all WHO regions.ResultsGlobally in 2020 there were 25.6 million (95% uncertainty interval (UI): 23.1-29.4 million) people aged 15 to 49 years with new HSV-2 infections and 519.5 million (95% UI: 464.3-611.3 million), or 13.3% (95% UI: 11.9-15.6%), with existing (prevalent) HSV-2 infections. In addition, there were 16.8 million (95% UI: 10.6-22.4 million) people aged 15-49 years with new genital HSV-1 infections and 376.2 million (95% UI: 235.6-483.5 million), or 10.2% (95% UI: 6.4-13.1%), with prevalent genital HSV-1 infections. The estimated number of people aged 15 to 49 years with at least one episode of HSV-attributable genital ulcer disease in 2020 was 187.9 million (95% UI: 116.0-291.8 million) for HSV-2 and 16.7 million (95% UI: 9.3-25.2 million) for HSV-1, totaling 204.6 million (95% UI: 132.3-306.5).ConclusionGenital HSV infections have a high incidence and prevalence worldwide, contributing to a significant GUD disease burden. New prevention and treatment measures, such as prophylactic and therapeutic HSV vaccines, are critically needed to control HSV infections and reduce the associated disease burden.
Viral load monitoring practices and correlates of viral non-suppression among children and young adolescents living with HIV in level five hospitals in Kiambu county, Kenya
Authors: Gachoka Lilian N. , Njoroge Anne 
Published: June 2024

AbstractBackgroundHIV has been a major global public health issue among children and young adolescents living with HIV (CYALHIV), their viral suppression rates being lower compared to adults. Follow up through viral load monitoring may influence their health outcomes.ObjectiveIn a cross-sectional study we determined viral load monitoring practices and correlates of viral non-suppression of all CYALHIV in three level five hospitals in Kiambu county, KenyaMethodsWe abstracted data from electronic and paper medical records. Multivariable log binomial regression was used to estimate prevalence ratios (PR) and assess correlates of non-suppression. Adherence to viral load testing guidelines was assessed. Viral non-suppression was defined as a VL >1000c/ml.ResultsOf the 252 CYALHIV, the median age was 11 (IQR: 7-13) years. Fourteen had non-suppression at last assessment. Correlates of non-suppression included having previously had TB [aPR=4.25; 95% CI=1.41-12.8; p=0.01], ART side effects [aPR=3.01; 95% CI=1.37-6.62 p=0.006] and having received enhanced adherence counselling [aPR =5.32; 95% CI=2.00-14.15; p=0.001]. Being on Dolutegravir was significantly associated with a lower likelihood of non-suppression (aPR=0.35; CI:0.15-0.85: p = 0.021). Timing of baseline VL tests improved through the years though there were gaps in routine VL monitoring and follow-up on unsuppressed results.ConclusionAt most current VL, 14% children were non-suppressed, higher than the 5% UNAIDS 2030 target. Special strategies on assessing and addressing corelates of non-suppression are essential for ART programs. Routine VL monitoring as per the guidelines was suboptimal despite increased access to VL testing, suggesting other barriers to VL monitoring.
Nonlinear spatial integration allows the retina to detect the sign of defocus in natural scenes
Authors: Goethals Sarah , Louboutin Awen , Hamlaoui Samy , Quetu Tom , Virgili Samuele , Goldin Matias A. , Baranton Konogan , Marre Olivier 
Published: June 2024

AbstractEye growth is regulated by the visual input. Many studies suggest that the retina can detect if a visual image is focused in front or behind the back of the eye, and modulate eye growth to bring it back to focus. How can the retina distinguish between these two types of defocus? Here we simulated how eye optics transform natural images and recorded how the isolated retina responds to different types of simulated defocus. We found that some ganglion cell types could distinguish between an image focussed in front or behind the retina, by estimating spatial contrast. Aberrations in the eye optics made spatial contrast, but not luminance, a reliable cue to distinguish these two types of defocus. Our results suggest a mechanism for how the retina can estimate the sign of defocus and provide an explanation for several results aiming at mitigating strong myopia by slowing down eye growth.