bluuebunny/crossref_metadata_2025_split huggingface dataset:
The intracellular growth of the vacuolar pathogenLegionella pneumophilais dependent on the acyl chain composition of host membranes
Authors: Wilkins Ashley A. , Schwarz Benjamin , Torres-Escobar Ascencion , Castore Reneau , Landry Layne , Latimer Brian , Bohrnsen Eric , Bosio Catharine M. , Dragoi Ana-Maria , Ivanov Stanimir S. 
Published: November 2023

AbstractLegionella pneumophilais an accidental human bacterial pathogen that infects and replicates within alveolar macrophages causing a severe atypical pneumonia known as Legionnaires’ disease. As a prototypical vacuolar pathogenL. pneumophilaestablishes a unique endoplasmic reticulum (ER)-derived organelle within which bacterial replication takes place. Bacteria-derived proteins are deposited in the host cytosol and in the lumen of the pathogen-occupied vacuole via a type IVb (T4bSS) and a type II (T2SS) secretion system respectively. These secretion system effector proteins manipulate multiple host functions to facilitate intracellular survival of the bacteria. Subversion of host membrane glycerophospholipids (GPLs) by the internalized bacteria via distinct mechanisms feature prominently in trafficking and biogenesis of theLegionella-containing vacuole (LCV). Conventional GPLs composed of a glycerol backbone linked to a polar headgroup and esterified with two fatty acids constitute the bulk of membrane lipids in eukaryotic cells. The acyl chain composition of GPLs dictates phase separation of the lipid bilayer and therefore determines the physiochemical properties of biological membranes - such as membrane disorder, fluidity and permeability. In mammalian cells, fatty acids esterified in membrane GPLs are sourced endogenously fromde novosynthesis or via internalization from the exogenous pool of lipids present in serum and other interstitial fluids. Here, we exploited the preferential utilization of exogenous fatty acids for GPL synthesis by macrophages to reprogram the acyl chain composition of host membranes and investigated its impact on LCV homeostasis andL. pneumophilaintracellular replication. Using saturated fatty acids as well ascis- andtrans- isomers of monounsaturated fatty acids we discovered that under conditions promoting lipid packing and membrane rigidificationL. pneumophilaintracellular replication was significantly reduced. Palmitoleic acid – a C16:1 monounsaturated fatty acid – that promotes membrane disorder when enriched in GPLs significantly increased bacterial replication within human and murine macrophages but not in axenic growth assays. Lipidome analysis of infected macrophages showed that treatment with exogenous palmitoleic acid resulted in membrane acyl chain reprogramming in a manner that promotes membrane disorder and live-cell imaging revealed that the consequences of increasing membrane disorder impinge on several LCV homeostasis parameters. Collectively, we provide experimental evidence thatL. pneumophilareplication within its intracellular niche is a function of the lipid bilayer disorder and hydrophobic thickness.
Crossmodal Hierarchical Predictive Coding for Audiovisual Sequences in Human Brain
Authors: Huang Yiyuan Teresa , Wu Chien-Te , Fang Yi-Xin Miranda , Fu Chin-Kun , Koike Shinsuke , Chao Zenas C. 
Published: November 2023

AbstractPredictive-coding theory proposes that the brain actively predicts sensory inputs based on prior knowledge. While this theory has been extensively researched within individual sensory modalities, there is a crucial need for empirical evidence supporting hierarchical predictive processing across different modalities to further generalize the theory. Here, we examine how crossmodal knowledge is represented and learned in the brain by identifying the hierarchical networks underlying crossmodal predictions when information of one sensory modality leads to a prediction in another modality. We record electroencephalogram (EEG) in humans during a crossmodal audiovisual local-global oddball paradigm, in which the predictability of transitions between tones and images are manipulated at two hierarchical levels: stimulus-to-stimulus transition (local level) and multi-stimulus sequence structure (global level). With a model-fitting approach, we decompose the EEG data using three distinct predictive-coding models: one with no audiovisual integration, one with audiovisual integration at the global level, and one with audiovisual integration at both the local and global levels. The best-fitting model demonstrates that audiovisual integration occurs at both levels. This highlights a convergence of auditory and visual information to construct crossmodal predictions, even in the more basic interactions that occur between individual stimuli. Furthermore, we reveal the spatio-spectro-temporal signatures of prediction-error signals across hierarchies and modalities, and show that auditory and visual prediction-error signals are progressively redirected to the central-parietal area of the brain as learning progresses. Our findings unveil a crossmodal predictive coding mechanism, where the unimodal framework is implemented through more distributed brain networks to process hierarchical crossmodal knowledge.
Male germ cell-associated kinase (MAK) is required for axoneme formation during ciliogenesis in zebrafish photoreceptors
Authors: Chiang Hung-Ju , Nishiwaki Yuko , Chiang Wei-Chieh , Masai Ichiro 
Published: November 2023

AbstractVertebrate photoreceptors are highly specialized retinal neurons that have cilium-derived membrane organelles called outer segments (OS), which function as platforms for phototransduction. Male germ cell-associated kinase (MAK) is a cilium-associated serine/threonine kinase, and its genetic mutation causes photoreceptor degeneration in mice and retinitis pigmentosa in humans. However, the role of MAK in photoreceptors is not fully understood. Here, we report that zebrafishmakmutants show rapid photoreceptor degeneration during embryonic development. Inmakmutants, both cone and rod photoreceptors completely lack OSs and undergo apoptosis. Interestingly, zebrafishmakmutants fail to generate axonemes during photoreceptor ciliogenesis, whereas basal bodies are specified. These data suggest that MAK contributes to axoneme development in zebrafish, in contrast to mouseMakmutants, which have elongated photoreceptor axonemes. Furthermore, the kinase activity of MAK is critical in ciliary axoneme development and photoreceptor survival. Thus, MAK is required for ciliogenesis and OS formation in zebrafish photoreceptors to ensure intracellular protein transport and photoreceptor survival.Summary statementMale germ cell-associated kinase (MAK) is a cilium-associated serine/threonine kinase that promotes axoneme development during ciliogenesis in zebrafish photoreceptors to ensure intracellular protein transport and photoreceptor survival.
Speedy and satisfying: Real-time Location System increases Emergency Department efficiency and decreases frustration with finding medical equipment
Authors: LoGalbo Sandhya , Trojanowski Sophia , Slusser Alexandria , Iyeke Lisa , Jordan Lindsay , Richman Mark 
Published: November 2023

ABSTRACTINTRODUCTIONWe evaluated the impact of a real-time locating system on emergency department efficiency and frustration locating mobile otoscope/ophthalmoscope carts.DATA AND METHODSThirty ED providers were selected on-shift, each serving as their own control. Investigators hid two mobile otoscope/ophthalmoscopes carts (with and without the RTLS device) equidistant from the center of a provider’s work area. Providers were timed finding both devices and were queried regarding feelings about the search experience.RESULTSRTLS was associated with statistically-significantly less time locating equipment (average of 25 vs. 92 seconds) and percent of providers requiring 30, 60, 90, and 120 seconds to find the device. Providers felt finding the mobile cart with RTLS was easier; all rated finding the RTLS-tagged cart as easy. Without RTLS, two-thirds of subjects reported either frustration or extreme frustration vs. 3% with RTLS. All differences in comparisons of subjective experience were statistically-significant. Annual time and cost saving with RTLS would be 116.4 hours ($9,135.66).CONCLUSIONRTLS in EDs can decrease time and frustration associated with finding equipment and is cost-effective. Frustration is a common driver behind burnout in Emergency Medicine. Use of RTLS technology might improve the provider experience and, thereby, reduce burnout levels.
Understanding healthcare workers’ experiences of face mask and RPE use in healthcare settings: an interview study
Authors: Carter Holly , Sharp Ashley , Davidson Louise , Foster Clare , McGuire Emma , Brown Colin , Weston Dale 
Published: November 2023

AbstractWhilst healthcare workers (HCWs) are at high risk of contracting COVID-19, measures can be put in place to reduce the spread of COVID-19 and other respiratory infections in healthcare settings. These currently include the use of masks: fluid-resistant surgical masks and respiratory protective equipment. However, for mask policies to be effective, compliance with their use must be high. This study interviewed 12 HCWs from a variety of backgrounds to understand their experiences of mask use. We explored factors associated with compliance with mask use and potential impacts on HCW wellbeing. Overall, participants reported good understanding of the benefits of masks and high compliance levels with policy. However, factors that reduced their compliance with mask policy and impacted their ability to carry out their role were highlighted. These included wearing masks for longer durations, policy being perceived as out of proportion with risk, communication challenges, and discomfort. This study highlights the importance of clear communication of guidance, particularly when it has changed, ensuring staff are familiar with up-to-date research on efficacy of masks, and ensuring guidance aligns with risk. Furthermore, this study highlights the importance of masks being required for an appropriate duration (based on risk).
Management and outcomes of fractures over cranial venous sinuses: A scoping review protocol
Authors: Takoutsing Berjo D. , Njineck Ubraine Wunde , Wah Praise Senyuy , Sebopelo Lorraine , Tchoffo Josiane Ngouanfo , Bah Ella Shiynyuy , Esene Ignatius 
Published: November 2023

ABSTRACTIntroductionFractures over venous sinuses (FOVS) are associated with difficulties in diagnosis, and treatment resulting in a high level of morbidity, and mortality. Despite its importance, there is limited aggregate data to guide the management of these fractures ultimately inflicting a major challenge to neurosurgeons. This protocol describes the methodology of a scoping review that aims to synthesise contemporary evidence on the management and outcomes of FOVS.Methods and analysisThe proposed study will be conducted in accordance with the Arksey and O’Malley’s framework for scoping reviews. The research question, eligibility criteria and search strategy were developed based on the Population, Intervention, Comparator, Outcome strategy. The following electronic bibliographic databases will be searched without restrictions on language, and date of publication: PubMed, WHO Global Index Medicus, African Journals Online, SCOPUS, Embase. All peer-reviewed studies of primary data reporting on the management and outcomes of FOVS will be included. The data extracted from included articles will be presented through descriptive statistics, pooled statistics, and a narrative description.Ethics and disseminationBecause this study did not directly involve human individuals, ethical approval was not necessary. Dissemination strategies will include publication in a peer-reviewed journal, oral and poster presentations at local, regional, national and international conferences and promotion over social media.ARTICLE SUMMARYStrengths and limitations of this studyTo our knowledge this is the first scoping review focusing on the management and outcomes of fractures over the venous sinusesThis protocol will ensure transparency in the methodology of the proposed review, thus will reduce the likelihood of reviewing bias.The search strategy will be conducted in five electronic databases commonly used across both high- and low-income countries.There will be no restrictions on language, location, or publication date during the screening process.Unpublished studies will not be sought.There will be no formal assessment on the quality of the included studies.
Increased Severity of New-onset Type 1 Diabetes in Children and Adolescents during the COVID-19 Pandemic: Experience from a Tertiary Care Center in Serbia
Authors: Jovanovic Damjan , Blagojevic Jelena , Stanisavljevic Dejana , Jesic Maja 
Published: November 2023

AbstractBackground and objectivesPublic health measures, parental fear of infection, and redeployment of medical resources in response to the COVID-19 pandemic might have led to a decrease in pediatric healthcare access. As a result, a delay in type 1 diabetes diagnosis might have occurred, leading to the worsening of its clinical presentation in the pediatric population. This study aimed to examine the clinical and biochemical features of new-onset DM1 in children and adolescents during the COVID-19 pandemic, comparing it to the pre-pandemic period.Materials and methodsThe clinical and biochemical features of diabetes observed during the COVID-19 period from April 1, 2020, until December 31, 2022, were compared with the period from April 1, 2017, until December 31, 2019. In the COVID-19 pandemic group, the clinical and biochemical features were compared between children with and without SARS-CoV-2 infection at diagnosis or before the diagnosis of DM1.ResultsDuring the COVID-19 pandemic, observed frequencies of DKA and severe DKA at diagnosis were 47.6% and 20.7%, both significantly higher than during the pre-pandemic period (an absolute increase of 15% and 11.3%, respectively). In the COVID-19 group, blood pH levels were significantly lower than in the pre-pandemic group, while HbA1c levels were higher. Clinical and biochemical features of diabetes in children with SARS-CoV-2 infection at or before the diagnosis were not significantly different compared to children without an infection.ConclusionWe report a significant worsening of the clinical presentation of new-onset type 1 diabetes and an increase in the frequency of DKA and severe DKA at diagnosis during the COVID-19 pandemic. Further studies are necessary to gain quantitative insight into pediatric healthcare availability in Serbia.
Exploring the thermally-controlled fentanyl transdermal therapy to provide constant drug delivery by physics-based digital twins
Authors: Bahrami Flora , Psikuta Agnes , Rossi René Michel , Dommann Alex , Defraeye Thijs 
Published: November 2023

AbstractTransdermal drug delivery is suitable for low-molecular-weight drugs with specific lipophilicity, like fentanyl, which is widely used for cancer-induced pain management. However, fentanyl’s transdermal therapy displays high intra-individual variability. Factors like skin characteristics at application sites and ambient temperature contribute to this variation. In this study, we developed a physics-based digital twin of the human body to cope with this variability and propose better adapted setups. This twin includes anin-silicoskin model for drug penetration, a pharmacokinetic model, and a pharmacodynamic model. Based on the results of our simulations, applying the patch on the flank (side abdominal area) showed a 15.3% higher maximum fentanyl concentration in the plasma than on the chest. Additionally, the time to reach this maximum concentration when delivered through the flank was 19.8 h, which was 10.3 h earlier than via the upper arm. Finally, this variation led to an 18% lower minimum pain intensity for delivery via the flank than the chest. Moreover, the impact of seasonal changes on ambient temperature and skin temperature by considering the activity level was investigated. Based on our result, the fentanyl uptake flux by capillaries increased by up to 11.8% from an inactive state in winter to an active state in summer. We also evaluated the effect of controlling fentanyl delivery by adjusting the temperature of the patch to alleviate the pain to reach a mild pain intensity (rated three on the VAS scale). By implementing this strategy, the average pain intensity decreased by 1.1 points, and the standard deviation for fentanyl concentration in plasma and average pain intensity reduced by 37.5% and 33.3%, respectively. Therefore, our digital twin demonstrated the efficacy of controlled drug release through temperature regulation, ensuring the therapy toward the intended target outcome and reducing therapy out-come variability. This holds promise as a potentially useful tool for physicians.Graphical Abstract(Created withBioRender.comandwww.flaticon.com)
Estimating the optimal age for infant measles vaccination
Authors: Goult Elizabeth , Barrero Guevara Laura Andrea , Briga Michael , Domenech de Cellès Matthieu 
Published: November 2023

AbstractThe persistence of measles in many regions demonstrates large immunity gaps, resulting from incomplete or ineffective immunization with measles-containing vaccines (MCVs). A key factor affecting MCV impact is age, with infants receiving dose 1 (MCV1) at older ages having a reduced risk of vaccine failure, but also an increased risk of contracting infection before vaccination. Here, we designed a new method—based on a transmission model incorporating realistic vaccination delays and age variations in MCV1 effectiveness—to capture this risk trade-off and estimate the optimal age for recommending MCV1. We predict a large heterogeneity in the optimal ages (range: 6–20 months), contrasting the homogeneity of observed recommendations worldwide. Furthermore, we show that the optimal age depends on the local epidemiology of measles, with a lower optimal age predicted in populations suffering higher transmission. Overall, our results suggest the scope for public health authorities to tailor the recommended schedule for better measles control.
Quality of systematic reviews on physiotherapy interventions for musculoskeletal disorders is critically low: a meta-epidemiological study
Authors: Ferri Nicola , Ravizzotti Elisa , Bracci Alessandro , Carreras Giulia , Pillastrini Paolo , Di Bari Mauro 
Published: November 2023

ABSTRACTQuestionHow good is the quality of systematic reviews on the effectiveness of physiotherapy for musculoskeletal conditions? Are there any factors associated with quality?DesignThis is a meta-epidemiological study on systematic reviews with meta-analysis (SR-MA) of randomised controlled trials (RCT).MethodsMEDLINE, Cochrane Database of Systematic Reviews (CDSR), CINAHL, and PEDro were searched for SR-MA of RCT on physiotherapy in musculoskeletal disorders in the last ten years. Two independent researchers screened and extracted the records and analysed the full-texts. The quality of SR-MA was quantified with AMSTAR-2 tool on a sample of 100 studies, randomly selected from the records retrieved. Disagreements were solved by consensus.ResultsThe number of eligible publications increased over the past ten years. However, the methodological quality was critically low in as many as 90% of the studies retrieved and did not increase with time. The last author’s H-index was the only quality predictor among the variables analysed.ConclusionThe methodological quality of the SR-MA of RCT is unacceptably low. Given the frequent application of physiotherapy in musculoskeletal disorders, there is an urgent need to improve secondary research by adopting more rigorous methods.RegistrationOpen Science Framework (https://osf.io/bc8zw/)
Deep Learning Approach to Measure Alveolar Bone Loss After COVID-19
Authors: Lee Sang Won , Huz Kateryna , Gorelick Kayla , Bina Thomas , Matsumura Satoko , Yin Noah , Zhang Nicholas , Naa Ardua Anang Yvonne , Li Jackie , Servin-DeMarrais Helena I. , McMahon Donald J , Yin Michael T. , Wadhwa Sunil , Lu Helen H. 
Published: November 2023

AbstractSeverity of periodontal disease may be determined by measurement of alveolar crestal height (ACH) on dental bitewing radiographs; however, the prevailing method of assessment is through visualization which is time consuming and not a direct measure. The primary objective of this manuscript is to create and validate a deep learning technique for precise evaluation of alveolar bone loss in bitewing radiographs. Additionally, surveys were conducted with dental professionals to determine accuracy of visualized measures of ACH for severe periodontal disease versus the deep learning program and to determine the acceptability of utility of the program among diverse dental professionals. Lastly, the deep learning program was utilized in research to evaluate the role of COVID on periodontal disease through longitudinal measures of bitewing radiograph ACH from patients during the: "pre-pandemic" (Feb 2017 - Feb 2020) and "post-pandemic" (Feb 2020 - Feb 2023) periods. The pre-pandemic group had a mean percentage loss of ACH of -1.74 + 16.5%, representing a gain in alveolar bone. In contrast, the post-pandemic group had a gain in ACH of 2.46 + 14.6%, representing a loss in alveolar bone. There remained a trend for greater annualized percent change in ACH in the post-pandemic vs pre-pandemic group (1.33 + 11.9% vs -0.94 + 12.5%, p=0.07), after accounting for differences in duration between xrays. Overall, this study demonstrates the successful training and validation of a deep learning program for ACH measurement as well as its utility and acceptability among dental professionals for clinical and research.
High radiosensitivity in Norway spruce (Picea abies) is rendered by less comprehensive mobilisation of protection, repair and stress responses compared to the radiotolerantArabidopsis thaliana
Authors: Bhattacharjee Payel , Blagojevic Dajana , Lee YeonKyeong , Gillard Gareth B , Grønvold Lars , Hvidsten Torgeir Rhoden , Sandve Simen Rød , Lind Ole Christian , Salbu Brit , Brede Dag Anders , Olsen Jorunn E. 
Published: November 2023

SummaryRisk assessment and protection of plant communities in contaminated ecosystems require in-depth understanding of differential sensitivity to chronic ionising radiation in plants. However, the contributing molecular factors are poorly understood.We compared early molecular events associated with protection, repair, and stress responses, by analysing growth, organelle and DNA damage, and the dynamics of transcriptome and DNA damage repair (DDR) gene expression in gamma-irradiated seedlings of the radiosensitive conifer Norway spruce (Picea abies) and the radiotolerantArabidopsis thaliana.Norway spruce showed reduced growth at 290 mGy h-1and severe organelle damage, especially in mitochondria, at ≥ 1 mGy h-1whereasA. thalianashowed unaffected development, minor organelle damage at ≥ 100 mGy h-1and significantly less DNA damage, after 48-h of gamma exposure. Comparative transcriptomics revealed thatA. thalianashowed massive activation of genes related to DDR, antioxidants, and other stress responses at ≥ 1 mGy h-1while Norway spruce mobilized transcription of such pathways only at ≥ 40 mGy h-1.The transcriptional activation of repair and protection responses at higher gamma dose-rates only and its absence in lower dose-rates, corelates with high radiosensitivity of Norway spruce, compared to the massive transcriptional activation from low dose-rates in the radiotolerantA. thaliana.