bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term tree population growth can predict woody encroachment patterns
Authors: Shriver Robert K. , Pletcher Elise , Biondi Franco , Urza Alexandra K. , Weisberg Peter J. 
Published: April 2024

AbstractRecent increases of woody plant density in dryland ecosystems around the world are often attributed to land use changes such as increased livestock grazing and fire suppression, or to climatic trends driven by increasing atmospheric carbon dioxide1,2. While such changes have undoubtedly impacted ecosystem structure and function, the evidence linking them to woody encroachment is mixed and demographic processes underlying changes in woody plant abundance require further consideration3. After examining tree age structures from woodlands across the interior western USA using demographic models, we find little evidence of widespread increases in per-capita tree establishment rates following 19thcentury Euro-American settlement. Woodlands dominated by young trees have often been cited as evidence of woody encroachment driven by a number of anthropogenic processes, but we demonstrate they can also be accurately predicted by a null model including only steady long-term tree population growth. Contrary to common interpretations, we show that tree establishment rates in the last century have mostly declined, rather than increased, and in fact they are currently at their lowest rates since at least 1600 CE.
In humans, insulo-striate structural connectivity is largely biased toward either striosome-like or matrix-like striatal compartments
Authors: Funk AT , Hassan AAO , Waugh JL 
Published: April 2024

AbstractThe insula is an integral component of sensory, motor, limbic, and executive functions, and insular dysfunction is associated with numerous human neuropsychiatric disorders. Insular afferents project widely, but insulo-striate projections are especially numerous. The targets of these insulo-striate projections are organized into tissue compartments, the striosome and matrix. These striatal compartments have distinct embryologic origins, afferent and efferent connectivity, dopamine pharmacology, and susceptibility to injury. Striosome and matrix appear to occupy separate sets of cortico-striato-thalamo-cortical loops, so a bias in insulo-striate projections towards one compartment may also embed an insular subregion in distinct regulatory and functional networks. Compartment-specific mapping of insulo-striate structural connectivity is sparse; the insular subregions are largely unmapped for compartment-specific projections.In 100 healthy adults, we utilized probabilistic diffusion tractography to map and quantify structural connectivity between 19 structurally-defined insular subregions and each striatal compartment. Insulo-striate streamlines that reached striosome-like and matrix-like voxels were concentrated in distinct insular zones (striosome: rostro- and caudoventral; matrix: caudodorsal) and followed different paths to reach the striatum. Though tractography was generated independently in each hemisphere, the spatial distribution and relative bias of striosome-like and matrix-like streamlines were highly similar in the left and right insula. 16 insular subregions were significantly biased towards one compartment: seven toward striosome-like voxels and nine toward matrix-like voxels. Striosome-favoring bundles had significantly higher streamline density, especially from rostroventral insular subregions. The biases in insulo-striate structural connectivity we identified mirrored the compartment-specific biases identified in prior studies that utilized injected tract tracers, cytoarchitecture, or functional MRI. Segregating insulo-striate structural connectivity through either striosome or matrix may be an anatomic substrate for functional specialization among the insular subregions.
Divergence of Grainy head affects chromatin accessibility, gene expression, and embryonic viability inDrosophila melanogaster
Authors: Ertl Henry A. , Bayala Erick X. , Siddiq Mohammad A. , Wittkopp Patricia J. 
Published: April 2024

ABSTRACTPioneer factors are critical for gene regulation and development because they bind chromatin and make DNA more accessible for binding by other transcription factors. The pioneer factor Grainy head (Grh) is present across metazoans and has been shown to retain a role in epithelium development in fruit flies, nematodes, and mice despite extensive divergence in both amino acid sequence and length. Here, we investigate the evolution of Grh function by comparing the effects of the fly (Drosophila melanogaster) and worm (Caenorhabditis elegans) Grh orthologs on chromatin accessibility, gene expression, embryonic development, and viability in transgenicD. melanogaster. We found that theCaenorhabditis elegansortholog rescued cuticle development but not full embryonic viability inDrosophila melanogaster grhnull mutants. At the molecular level, theC. elegansortholog only partially rescued chromatin accessibility and gene expression. Divergence in the disordered N-terminus of the Grh protein contributes to these differences in embryonic viability and molecular phenotypes. These data show how pioneer factors can diverge in sequence and function at the molecular level while retaining conserved developmental functions at the organismal level.SUMMARY STATEMENTDespite divergence in a disordered region that affects function at both molecular and organismal levels, theCaenorhabditis elegansGrainy head (Grh) protein rescued cuticle morphology inD. melanogasterembryos.
Assessing Cognitive Functions Remotely Using a Music-Game-Like Program
Authors: Perron Maxime , Imran Ashna , Alain Rebecca , Alain Claude , Sakaki Yayoi 
Published: April 2024

AbstractThere is a growing need to develop ways of assessing cognitive functions remotely and providing interventions using a web-based approach. The Ipsilon Test is a music-based cognitive assessment and training tablet application. On each trial, it presents simplified musical notation with colours, spatial cues, and gestural references so that users can translate spatial information into motor actions by tapping on the screen. In this study, we examined the correlation between the performance of a group of healthy older adults on the Ipsilon test and standard measures of cognitive function—a total of 30 participants aged 58 and over were recruited for the study. Before and after one week of training using the web-based program Ipsilon, all participants completed an online version of the Montreal Cognitive Assessment (MoCA) and the visual Stroop task. Of the participants recruited, 22 participants completed the Ipsilon training and cognitive testing. In our sample, performance on the Ipsilon test was generally high, with all participants scoring above the chance level. Importantly, we found a correlation between Ipsilon test performance and pre-Ipsilon MoCA scores. In addition, participants who scored higher on the Ipsilon test also showed improvement in the visual Stroop task after Ipsilon training, particularly in the ability to inhibit irrelevant information. These results suggest the Ipsilon test is a practical web-based cognitive assessment and training tool. Future research will explore its relationship with other cognitive tests and its diagnostic power for differentiating individuals with normal cognition from those with cognitive disorders.
Flynotyper 2.0: An updated tool for rapid quantitative assessment ofDrosophilaeye phenotypes
Authors: Ray Johnathan , Banerjee Deepro , Wang Qingyu , Girirajan Santhosh 
Published: April 2024

AbstractAbout two-thirds of the genes in theDrosophila melanogastergenome are also involved in its eye development, making theDrosophilaeye an ideal system for genetic studies. We previously developed Flynotyper, a software that uses image processing operations to identify and quantify the degree of roughness by measuring disorderliness of ommatidial arrangement in the fly eye. This software has enabled researchers to quantify morphological defects of thousands of eye images caused by genetic perturbations. Here, we present Flynotyper 2.0, a software that has an updated computer vision library, improved performance, and a streamlined pipeline for high-throughput analysis of multiple eye images. We also tested several batches ofDrosophilaeye images to ensure robustness and reproducibility of the updated Flynotyper 2.0 software.Availability and implementationThe source code for Flynotyper 2.0 can be downloaded and installed fromhttps://github.com/girirajanlab/flynotyper-desktop-application.
Role of Mutual Information Profile Shifts in Assessing the Pathogenicity of Mutations on Protein Functions: The Case of Pyrin Variants Associated with Familial Mediterranean Fever
Authors: Hacisuleyman Aysima , Gul Ahmet , Erman Burak 
Published: April 2024

AbstractThis paper presents a novel method to assess the pathogenicity of Pyrin protein mutations by using mutual information (MI) as a measure to quantify the correlation between residue motions or fluctuations and associated changes affecting the phenotype. The concept of MI profile shift is presented to quantify changes in MI upon mutation, revealing insights into residue-residue interactions at critical positions. We apply this method to the Pyrin protein variants, which are associated with an autosomal recessively inherited disease called familial Mediterranean fever (FMF) since the available tools do not help predict the pathogenicity of the most penetrant variants. We demonstrate the utility of MI profile shifts in assessing the effects of mutations on protein stability, function, and disease phenotype. The importance of MI shifts, for the pyrin example the negative shifts, as indicators of severe functional effects is emphasized, along with exploring potential compensatory mechanisms indicated by positive MI shifts, which are otherwise random and inconsequential. The paper also discusses challenges in relating MI profile changes to disease severity and advocates for comprehensive analysis considering genetic, environmental, and stochastic factors. Overall, this study provides insights into the molecular mechanisms underlying the pathogenesis of FMF and offers a framework for identifying potential therapeutic targets based on MI profile changes induced by mutations.
Parallel Trends in an Unparalleled Pandemic Difference-in-differences for infectious disease policy evaluation
Authors: Feng Shuo , Bilinski Alyssa 
Published: April 2024

Researchers frequently employ difference-in-differences (DiD) to study the impact of public health interventions on infectious disease outcomes. DiD assumes that treatment and non-experimental comparison groups would have moved in parallel in expectation, absent the intervention (“parallel trends assumption”). However, the plausibility of parallel trends assumption in the context of infectious disease transmission is not well-understood. Our work bridges this gap by formalizing epidemiological assumptions required for common DiD specifications, positing an underlying Susceptible-Infectious-Recovered (SIR) data-generating process. We demonstrate that popular specifications can encode strict epidemiological assumptions. For example, DiD modeling incident case numbers or rates as outcomes will produce biased treatment effect estimates unless untreated potential outcomes for treatment and comparison groups come from a data-generating process with the same initial infection and equal transmission rates at each time step. Applying a log transformation or modeling log growth allows for different initial infection rates under an “infinite susceptible population” assumption, but invokes conditions on transmission parameters. We then propose alternative DiD specifications based on epidemiological parameters – the effective reproduction number and the effective contact rate – that are both more robust to differences between treatment and comparison groups and can be extended to complex transmission dynamics. With minimal power difference incidence and log incidence models, we recommend a default of the more robust log specification. Our alternative specifications have lower power than incidence or log incidence models, but have higher power than log growth models. We illustrate implications of our work by re-analyzing published studies of COVID-19 mask policies.Significance StatementDifference-in-differences is a popular observational study design for policy evaluation. However, it may not perform well when modeling infectious disease outcomes. Although many COVID-19 DiD studies in the medical literature have used incident case numbers or rates as the outcome variable, we demonstrate that this and other common model specifications may encode strict epidemiological assumptions as a result of non-linear infectious disease transmission. We unpack the assumptions embedded in popular DiD specifications assuming a Susceptible-Infected-Recovered data-generating process and propose more robust alternatives, modeling the effective reproduction number and effective contact rate.
Factors shaping vaginal microbiota long-term community dynamics in young adult women
Authors: Kamiya Tsukushi , Tessandier Nicolas , Elie Baptiste , Bernat Claire , Boué Vanina , Grasset Sophie , Groc Soraya , Rahmoun Massilva , Selinger Christian , Humphrys Michael S. , Bonneau Marine , Graf Christelle , Foulongne Vincent , Reynes Jacques , Tribout Vincent , Segondy Michel , Boulle Nathalie , Ravel Jacques , Murall Carmen Lía , Alizon Samuel 
Published: April 2024

AbstractThe vaginal microbiota is known to affect women’s health. Yet, there is a notable paucity of high-resolution follow-up studies lasting several months, which would be required to interrogate the long-term dynamics and associations with demographic and behavioural covariates. Here, we present a high-resolution longitudinal cohort of 125 women followed for a median duration of 8.6 months, providing 11 samples per woman. Using a hierarchical Bayesian Markov model, we characterised the patterns of vaginal microbiota community persistence and transition, simultaneously estimated the impact of 16 covariates and quantified individual variability among women. We showed that ‘optimal’ (Community State Type (CST) I, II, and V) and ‘sub-optimal’ (CST III) communities are more stable over time than ‘non-optimal’ (CST IV) ones. Furthermore, we found that some covariates — most notably alcohol consumption — impacted the probability of shifting from one CST to another. We performed counterfactual simulations to confirm that alterations of key covariates, such as alcohol consumption, could shape the prevalence of different microbiota communities in the population. Finally, our analyses indicated that there is a relatively canalised pathway leading to the deterioration of vaginal microbiota communities, whereas the paths to recovery can be highly individualised among women. In addition to providing one of the first insights into vaginal microbiota dynamics over a year, our study showcases a novel application of a hierarchical Bayesian Markov model to clinical cohort data with many covariates. Our findings pave the way for an improved mechanistic understanding of microbial dynamics in the vaginal environment and the development of novel preventative and therapeutic strategies to improve vaginal health.
Telehealth versus face-to-face delivery of speech language pathology services: a systematic review and meta-analysis
Authors: Scott Anna Mae , Clark Justin , Cardona Magnolia , Atkins Tiffany , Peiris Ruwani , Greenwood Hannah , Wenke Rachel , Cardell Elizabeth , Glasziou Paul 
Published: April 2024

ABSTRACTBackgroundThere is an increasing demand for the provision of speech language pathology (SLP) services via telehealth. Therefore, we systematically reviewed randomized controlled trials comparing telehealth to face-to-face provision of SLP services.MethodsWe searched Medline, Embase, and Cochrane, clinical trial registries, and conducted a citation analysis to identify trials. We included randomized trials comparing similar care delivered live via telehealth (phone or video), to face-to-face. Primary outcomes included: % syllables stuttered (%SS) (for individuals who stutter); change in sound pressure levels monologue (for individuals with Parkinson’s disease); and key function scores (for other areas). Where data were sufficient, mean differences were calculated.ResultsNine randomized controlled trials were included; 8 evaluated video and 1 evaluated phone telehealth. Risk of bias was generally low or unclear, excepting blinding. There were no significant differences at any time-point up to 18 months for %SS (mean difference, MD 0.1, 95% CI –0.4 to 0.6, p=0.70). For people with Parkinson’s disease, there was no difference between groups in change in sound pressure levels (monologue) (MD 0.6, 95% CI –1.2 to 2.5, p=0.49). Four trials investigated interventions for speech sound disorder, voice disorder, and post-stroke dysphagia and aphasia; they found no differences between telehealth service delivery and face-to-face delivery.ConclusionsEvidence suggests that the telehealth provision of SLP services may be a viable alternative to their provision face-to-face, particularly to people who stutter and people with Parkinson’s disease. The key limitation is the small number of randomized controlled trials, as well as evidence on the quality of life, well-being and satisfaction, and economic outcomes.
Disability patterns in multiple sclerosis: a meta-analysis on PIRA and RAW in the real world context
Authors: Prosperini Luca , Ruggieri Serena , Haggiag Shalom , Tortorella Carla , Gasperini Claudio 
Published: April 2024

ABSTRACTBackgroundThe confirmed disability accrual (CDA) due to multiple sclerosis (MS) is driven by two factors: relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). However, accurate estimations of these phenomena in the real-world setting are lacking. This study aims at summarizing current evidence on RAW and PIRA, including associated factors, through a quantitative synthesis of real-world studies.MethodsScientific databases were searched to identify real-world studies published until December 31, 2023, reporting how many patients experienced RAW and PIRA (events of interest). Random-effects meta-analyses, subgroup analyses and meta-regression models were ran to provide pooled estimates of RAW and PIRA events, and to identify their potential moderators (PROSPERO registration: CRD42024503895).ResultsEighteen articles met the eligibility criteria, with a pooled sample size of 52,667 patients followed for 2.4 to 12.1 years (415,825 patient-years). Pooled event rates for RAW and PIRA were 1.6 and 3.1 per 100 patient-years, respectively. Less RAW events were found in patient cohorts under high-efficacy disease-modifying treatments (β=–0.031, p=0.007), while PIRA events were directly related to older age (β=0.397, p=0.027), predicting ≥6 PIRA events per 100 patient-years at an age ≥54 years. Additionally, we found significant differences in PIRA event rates according to the criteria adopted to define CDA.DiscussionPIRA accounts for most CDA events in the real-world setting, even at the earlier disease stages, whereas RAW represents a less frequent phenomenon, likely due to effective treatments. However, the detection and statistical analysis of PIRA outcomes pose challenges, raising the risk of biased interpretation.What is already known on this topicIrreversible accumulation of disability in multiple sclerosis stems from two distinct yet not mutually exclusive phenomena: relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA).What this study addsIn this meta-analysis including data of 52,667 patients followed for 2.4 to 12.1 years, the pooled event rates were 1.6 and 3.1 per 100 patient-years for RAW and PIRA, respectively. High-efficacy treatment strongly suppresses RAW but not PIRA, which is instead associated with age and definition criteria.How this study might affect research, practice or policyAlthough PIRA accounts for most disability events in MS, its detection in real-world setting is necessarily inaccurate and its statistical analysis is challenging.
NeoCoMM: Neocortical Computational Microscale Model
Authors: Al Harrach M. , Yochum M. , Wendling F. 
Published: April 2024

AbstractThe Neocortical Computational Microscale model (NeoCoMM) is a unique neurophysiologically-inspired software. It offers a friendly graphical user interface that allows for the simulation of the intracellular and extracellular neural activity of a neocortical column. This software provides a realistic framework that can portray the neural activity and underlying cellular mechanisms related to different brain pathologies such as epilepsy. NeoCoMM is capable of (1) simulating the cortical tissue of three different species, (2) visualizing individual cell responses to external stimulation, (3) visualizing the corresponding local field potential, (4) studying the impact of the recording electrode features on simulated signals, and (5) testing various physiological and pathological hypotheses. While NeoCoMM was primarily developed for simulating epileptiform activity, it can also generate healthy brain rhythms or be adapted to other brain disorders.
Modeling CSF circulation and the glymphatic system during infusion using subject specific intracranial pressures and brain geometries
Authors: Dreyer Lars Willas , Eklund Anders , Rognes Marie Elisabeth , Malm Jan , Qvarlander Sara , Støverud Karen-Helene , Mardal Kent-Andre , Vinje Vegard 
Published: April 2024

ABSTRACTBackgroundInfusion testing is an established method for assessing CSF resistance in patients with idiopathic normal pressure hydrocephalus (iNPH). To what extent the increased resistance is related to the glymphatic system is an open question. Here we introduce a computational model that includes the glymphatic system and enables us to determine the importance of 1) brain geometry, 2) intracranial pressure and 3) physiological parameters on the outcome of and response to an infusion test.MethodsWe implemented a seven-compartment multiple network porous medium model with subject specific geometries from MR images. The model consists of the arterial, capillary and venous blood vessels, their corresponding perivascular spaces, and the extracellular space (ECS). Both subject specific brain geometries and subject specific infusion tests were used in the modeling of both healthy adults and iNPH patients. Furthermore, we performed a systematic study of the effect of variations in model parameters.ResultsBoth the iNPH group and the control group reached a similar steady state solution when subject specific geometries under identical boundary conditions was used in simulation. The difference in terms of average fluid pressure and velocity between the iNPH and control groups, was found to be less than 6 % during all stages of infusion in all compartments. With subject specific boundary conditions, the largest computed difference was a 75 % greater fluid speed in the arterial perivascular space (PVS) in the iNPH group compared to the control group. Changes to material parameters changed fluid speeds by several orders of magnitude in some scenarios. A considerable amount of the CSF pass through the glymphatic pathway in our models during infusion, i.e., 28% and 38% in the healthy and iNPH patients, respectively.ConclusionsUsing computational models, we have found the relative importance of subject specific geometries to be less important than individual differences in terms of fluid pressure and flow rate during infusion. Model parameters such as permeabilities and inter-compartment transfer parameters are uncertain but important and have large impact on the simulation results. The computations predicts that a considerable amount of the infused volume pass through the brain either through the perivascular spaces or the extracellular space.