bluuebunny/crossref_metadata_2025 huggingface dataset:
Supervised Exercise Therapy for Symptomatic Peripheral Artery Disease
Authors: Ehrman Jonathan K. , Gardner Andrew W. , Salisbury Dereck , Lui Karen , Treat-Jacobson Diane
Published: September 2022

Purpose:

This review encompasses several practical components of supervised exercise therapy (SET) for patients with claudication including referral, exercise training, and billing issues. Real-life SET session examples are also provided. SET was approved for reimbursement by the Centers for Medicare & Medicaid Services (CMS) in 2017, and there is continual growth of programs offering SET and in participation. The purpose of this review is to provide useful information for the clinical exercise professionals working with these patients.

Review Methods:

The 2016 ACC/AHA Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease (PAD) provided a class I (highest level) recommendation for the use of SET in those with symptomatic PAD. Since there has been much growth in the literature about the utility of SET, the literature was reviewed (PubMed) to provide information for this article. Topics reviewed include the benefits of exercise training, exercise prescription, billing, referral and participation, and best practices.

SET should be offered to all patients with symptomatic PAD who are not at risk of acute limb ischemia. For optimal results, SET should be implemented several times per week and in a progressive process to increase exercise intensity as tolerated. For best results, programs should recommend patients supplement SET with home exercise. Considerations for utilizing reimbursed sessions should also be discussed because patients have a maximum of 72 sessions/lifetime. Referral practices need refinement, and participation rates remain extremely low and may be influenced by demographics. Research on best practices and home or hybrid training must continue to address issues related to common enrollment and participation barriers.

Condensed abstract:

Supervised exercise training (SET) for symptomatic peripheral artery disease is a class IA recommendation and reimbursable by most insurances. Improvements in walking performance can be dramatic. However, referral and participation in SET remain very low and thus SET is vastly underutilized.
High co-circulation of influenza and SARS-CoV-2
Authors: Kubale John T , Frutos Aaron M , Balmaseda Angel , Saborio Saira , Ojeda Sergio , Barilla Carlos , Sanchez Nery , Shotwell Abigail , Meyers Alyssa , Lopez Roger , Plazaola Miguel , Kuan Guillermina , Gordon Aubree
Published: September 2022

In the first two years of the COVID-19 pandemic, influenza transmission decreased substantially worldwide meaning that health systems were not faced with simultaneous respiratory epidemics. In 2022, however, substantial influenza transmission returned to Nicaragua where it co-circulated with SARS-CoV-2 causing substantial disease burden.
Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function
Authors: Lehmann Sylvain , Schraen-Maschke Susanna , Vidal Jean-Sébastien , Delaby Constance , Blanc Frédéric , Paquet Claire , Allinquant Bernadette , Bombois Stéphanie , Gabelle Audrey , Hanon Olivier
Published: September 2022

Objectives

Plasma P-tau181 is an increasingly established diagnostic marker for Alzheimer’s disease (AD). Further validation in prospective cohorts is still needed, as well as the study of confounding factors that could influence its blood level.

Methods

This study is ancillary to the prospective multicenter BALTAZAR cohort that enrolled participants with mild cognitive impairment (MCI) who were examined for conversion to dementia for up to three years. Plasma Ptau-181 was measured using the ultrasensitive Quanterix HD-X assay.

Results

Among 476 MCI participants, 67% were Aβ+ at baseline and 30% developed dementia. Plasma P-tau181 was higher in the Aβ+ population (3.9 [SD 1.4] vs. 2.6 [SD 1.4] pg/mL) and in MCI that converted to dementia (3.8 [SD 1.5] vs. 2.9 [SD 1.4] pg/mL). The addition of plasma P-tau181 to a logistic regression model combining age, sex, APOEε4 status and mini mental state examination (MMSE) improved predictive performance (AUC 0.691 to 0.744 for conversion and 0.786 to 0.849 for Aβ+). The Kaplan–Meier curve of conversion to dementia, according to the tertiles of plasma P-tau181, revealed a significant predictive value (Log rank P<.0001) with a hazard ratio of 3.8 [95%CI=2.5-5.8]. In addition, patients with plasma P-Tau(181) ≤2.32 pg/mL had a conversion rate of less than 20% over a 3-year period. Using a linear regression approach, chronic kidney disease (CKD), creatinine and glomerular filtration rate (eGFR) were independently associated with plasma P-tau181 concentrations.

Conclusions

Plasma P-tau181 effectively detects Aβ+ status and conversion to dementia, confirming the value of this blood biomarker for the management of AD. However, renal function significantly modifies its levels and may thus induce diagnostic errors if not taken into account.

What is already known on this topic

The clinical use of plasma phosphorylated tau 181 (P-tau181) for Alzheimer’s disease is being considered but further validation and study of confounding factors are still needed.

What this study adds

In our large prospective cohort, P-tau181 predicts brain amyloidopathy and conversion to dementia in patients with mild cognitive impairment, but renal function significantly alters plasma levels and thus may induce diagnostic errors if not taken into account.

How this study might affect research, practice or policy

Our study suggests that measurement of creatinine or estimation of glomerular filtration rate, which are easy and standardizable ways to provide information on renal function, will contribute to optimal interpretation of plasma P-tau181 results in routine clinical practice.
Hospital vulnerability to spread of respiratory infections: close contact data collection and mathematical modelling
Authors: Shirreff George , Huynh Bich-Tram , Duval Audrey , Pereira Lara Cristina , Annane Djillali , Dinh Aurélien , Lambotte Olivier , Bulifon Sophie , Guichardon Magali , Beaune Sebastien , Toubiana Julie , Kermorvant-Duchemin Elsa , Chéron Gerard , Cordel Hugues , Argaud Laurent , Douplat Marion , Abraham Paul , Tazarourte Karim , Martin-Gaujard Géraldine , Vanhems Philippe , Hilliquin Delphine , Nguyen Duc , Chelius Guillaume , Fraboulet Antoine ,   EMEA-MESuRS Working Group on Nosocomial SARS-CoV-2 Modelling, Temime Laura , Opatowski Lulla , Guillemot Didier
Published: September 2022

The transmission risk of SARS-CoV-2 within hospitals can exceed that in the general community because of more frequent close proximity interactions. However, epidemic risk across wards is still poorly described. We measured CPIs directly using wearable sensors given to all those present in a clinical ward over a 36-hour period, across 15 wards in three hospitals in spring 2020. Data were collected from 2114 participants. These data were combined with a simple transmission model describing the arrival of a single index case to the ward to estimate the risk of an outbreak. Estimated epidemic risk ranged four-fold, from 0.12 secondary infections per day in an adult emergency to 0.49 per day in general paediatrics. The risk presented by an index case in a patient varied twenty-fold across wards. Using simulation, we assessed the potential impact on outbreak risk of targeting the most connected individuals for prevention. We found that targeting those with the highest cumulative contact hours was most impactful (20% reduction for 5% of the population targeted), and on average resources were better spent targeting patients. This study reveals patterns of interactions between individuals in hospital during a pandemic and opens new routes for research into airborne nosocomial risk.
Dehumanisation and Datafication: Key stressors of Algorithmic Management: A qualitative analysis of Chinese couriers
Authors: Wei Hua , Shi Huiyue , Kou Yilin , Yu Mengke , Li Shugang , O’Toole Thomas , Armitage Christopher J. , Chandola Tarani , Whelan Pauline , Zhang Yanchun , Xu Yan , van Tongeren Martie
Published: September 2022

Introduction

Technology is an important social determinant of health that has so far been poorly understood. Nevertheless, technologies such as algorithms and artificial intelligence are rapidly changing how work is organised and managed globally. Courier work is one of the most affected occupations due to the common use of digital labour platforms. This study will explore how AM shapes Chinese couriers’ work experience and engenders health inequity.

Method

We conducted 15 in-depth interviews with couriers in May-June 2021 in China. Thematic analysis was completed using Nvivo 12.

Results

AM can introduce new work stressors and interact with existing factors to alleviate or intensify work stress. Couriers’ responses to AM and its effects varied as some felt motivated while others frustrated. Key themes emerged from the interviews included ‘App the “boss”’, ‘Unequal exposure to AM and the role of human support’, ‘New work stressors of AM – Dehumanisation and Datafication’, ‘Job stressors intensified by AM’ and ‘Varying individual response to AM’. App ‘the boss’ described how the couriers felt when managed by algorithms. Employed, gig and agency couriers had different exposure to AM and human support of different quality. Dehumanisation characterizes how algorithmic systems fulfil managerial functions in ways that differ from managers qualitatively or quantitatively. Datafication refers to the conversion of real-world information and user behaviour into data and being input in the system to assist automated decision-making. Couriers also reported that the use of digital methods could intensify some work stressors, e.g. time pressure and customer behaviour. Nevertheless, some couriers reported that AM provided new job resources, e.g. flexible hours, job opportunities, pay transparency, and bypassing office politics.

Conclusion

This paper identified key work stressors of AM and explored how AM interacts with existing work stressors to shape Chinese couriers’ work experience. Dehumanisation could reduce the quality of support and their sense of relatedness to the workplace. Datafication or extraction of data from workers and lack of transparency led to concerns about potential discrimination, workplace unfairness and power imbalance. Couriers’ responses to AM varied and future research should take such heterogeneity into account.
Dynamics-informed deconvolutional neural networks for super-resolution identification of regime changes in epidemiological time series
Authors: Vilar Jose M. G. , Saiz Leonor
Published: September 2022

Inferring the timing and amplitude of perturbations in epidemiological systems from their stochastically spread low-resolution outcomes is as relevant as challenging. It is a requirement for current approaches to overcome the need to know the details of the perturbations to proceed with the analyses. However, the general problem of connecting epidemiological curves with the underlying incidence lacks the highly effective methodology present in other inverse problems, such as super-resolution and dehazing from computer vision. Here, we develop an unsupervised physics-informed convolutional neural network approach in reverse to connect death records with incidence that allows the identification of regime changes at single-day resolution. Applied to COVID-19 data with proper regularization and model-selection criteria, the approach can identify the implementation and removal of lockdowns and other nonpharmaceutical interventions with 0.93-day accuracy over the time span of a year.
Improving estimates of waning immunity rates in stochastic SIRS models with a hierarchical framework
Authors: Alahakoon Punya , McCaw James M. , Taylor Peter G.
Published: September 2022

As most disease causing pathogens require transmission from an infectious individual to a susceptible individual, continued persistence of the pathogen within the population requires the replenishment of susceptibles through births, immigration, or waning immunity.

Consider the introduction of an unknown infectious disease into a fully susceptible population where it is not known how long immunity is conferred once an individual recovers from infection. If, initially, the prevalence of disease increases (that is, the infection takes off), the number of infectives will usually decrease to a low level after the first major outbreak. During this post-outbreak period, the disease dynamics may be influenced by stochastic effects and there is a non-zero probability that the epidemic will die out. Die out in this period following the first major outbreak is known as an epidemic fade-out. If the disease does not die out, the susceptible population may be replenished by the waning of immunity, and a second wave may start.

In this study, we investigate if the rate of waning immunity (and other epidemiological parameters) can be reliably estimated from multiple outbreak data, in which some outbreaks display epidemic fade-out and others do not. We generated synthetic outbreak data from independent simulations of stochasticSIRSmodels in multiple communities. Some outbreaks faded-out and some did not. We conducted Bayesian parameter estimation under two alternative approaches: independently on each outbreak and under a hierarchical framework. When conducting independent estimation, the waning immunity rate was poorly estimated and biased towards zero when an epidemic fade-out was observed. However, under a hierarchical approach, we obtained more accurate and precise posterior estimates for the rate of waning immunity and other epidemiological parameters. The greatest improvement in estimates was obtained for those communities in which epidemic fade-out was observed. Our findings demonstrate the feasibility and value of adopting a Bayesian hierarchical approach for parameter inference for stochastic epidemic models.
Genetic Disruption of System xc- Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat
Authors: Hess Evan M. , Kassel Sara , Simandl Gregory , Raddatz Nicholas J. , Maunze Brian , Hurley Matthew M. , Grzybowski Michael , Klotz Jason , Geurts Aron M. , Liu Qing-song , Choi SuJean , Twining Robert C. , Baker David A.
Published: September 2022

The impact of CNS disorders is exacerbated by the difficulty in developing safe, effective glutamatergic therapeutics. Synaptic glutamate transmission is vital for neural physiology throughout the brain, which contributes to the vast therapeutic potential and safety risk of glutamatergic therapeutics. Here, we created a genetically modified rat (MSxc) to survey the range of brain functions impacted by the loss of glutamate release from astrocytes involving system xc- (Sxc). Eliminating Sxc activity was not lethal and did not alter growth patterns, activity states, novel object recognition or performance of other simple tasks. In contrast, MSxc rats differed from WT in Pavlovian Conditioned Approach and cocaine self-administration/reinstatement paradigms. Both WT and MSxc rats readily learned that a cue predicted food delivery during Pavlovian Conditioned Approach training. However, WT rats were more likely to approach the food tray (i.e., goal tracking) whereas MSxc rats were more likely to approach the food-predicted cue (i.e., sign tracking) even when this behavior was punished. In the self-administration/reinstatement paradigm, MSxc rats had higher levels of cocaine-primed drug seeking in the absence of altered extinction or cocaine self-administration. These data demonstrate that Sxc-mediated glutamate release from astrocytes regulates non-reinforced and negative-outcome behaviors without altering simple learning or other forms of basic brain function.
ortho_seqs: A Python tool for sequence analysis and higher order sequence–phenotype mapping
Authors: Nafees Saba , Pranathi Vemuri Venkata Naga , Woollacott Miles , Solak Ahmet Can , Logan Phoenix , McGeever Aaron , Yoo Olivia , Rice Sean H.
Published: September 2022

Motivation

An important goal in sequence analysis is to understand how parts of DNA, RNA, or protein sequences interact with each other and to predict how these interactions result in given phenotypes. Mapping phenotypes onto underlying sequence space at first- and higher order levels in order to independently quantify the impact of given nucleotides or residues along a sequence is critical to understanding sequence–phenotype relationships.

Results

We developed a Python software tool, ortho_seqs, that quantifies higher order sequence-phenotype interactions based on our previously published method of applying multivariate tensor-based orthogonal polynomials to biological sequences. Using this method, nucleotide or amino acid sequence information is converted to vectors, which are then used to build and compute the first- and higher order tensor-based orthogonal polynomials. We derived a more complete version of the mathematical method that includes projections that not only quantify effects of given nucleotides at a particular site, but also identify the effects of nucleotide substitutions. We show proof of concept of this method, provide a use case example as applied to synthetic antibody sequences, and demonstrate the application of ortho_seqs to other other sequence–phenotype datasets.

Availability

https://github.com/snafees/ortho_seqs & documentation https://ortho-seqs.readthedocs.io/
Neuroprotective tissue adaptation induced by IL-12 attenuates CNS inflammation
Authors: Andreadou Myrto , Ingelfinger Florian , De Feo Donatella , Friebel Ekaterina , Tuzlak Selma , Cramer Teresa M.L. , Schreiner Bettina , Eede Pascale , Schneeberger Shirin , Geesdorf Maria , Ridder Frederike , Welsh Christina , Kirschenbaum Daniel , Tyagarajan Shiva K. , Greter Melanie , Heppner Frank L. , Mundt Sarah , Becher Burkhard
Published: September 2022

IL-12 is a well-established driver of type 1 immune responses. Paradoxically, in several autoimmune conditions including neuroinflammation, IL-12 reduces pathology and exhibits regulatory properties. Yet, the mechanism and the involved cellular players behind this immune regulation remain elusive. To identify the IL-12-responsive elements which prevent immunopathology, we generated mouse models lacking a functional IL-12 receptor either in all cells or in specific populations within the immune or central nervous system (CNS) compartments, and induced experimental autoimmune encephalomyelitis (EAE), which models human Multiple Sclerosis (MS). This revealed that the CNS tissue-protective features of IL-12 are mediated by cells of the neuroectoderm, and not immune cells. Importantly, sections of brain from patients with MS show comparable patterns of expression, indicating parallel mechanisms in humans. By combining spectral flow cytometry, bulk and single-nucleus RNA sequencing, we uncovered an IL-12-induced neuroprotective adaption of the neuroectoderm critically involved in maintaining CNS tissue integrity during inflammation.
Unique potential of immature adult-born neurons for the remodeling of CA3 spatial maps
Authors: Mugnaini Matías , Trinchero Mariela F. , Schinder Alejandro F. , Piatti Verónica C. , Kropff Emilio
Published: September 2022

Mammalian hippocampal circuits undergo extensive remodeling through adult neurogenesis. While this process has been widely studied, the specific contribution of adult-born granule cells (aGCs) to spatial operations in the hippocampus remains unknown. Here we show that optogenetic activation of 4-week-old (young) aGCs in free-foraging mice produces a non- reversible reconfiguration of spatial maps in proximal CA3, while rarely evoking neural activity. Stimulation of the same neuronal cohort on subsequent days recruits CA3 neurons with increased efficacy but fails to induce further remapping. In contrast, stimulation of 8- week-old (mature) aGCs can reliably activate CA3 cells but produce no alterations in spatial maps. Our results reveal a unique role of young aGCs in remodeling CA3 representations, a potential that can be depleted and is lost with maturation. This ability could contribute to generate orthogonalized downstream codes supporting pattern separation.
Non-invasive temporal interference electrical stimulation of the human hippocampus
Authors: Violante Ines R. , Alania Ketevan , Cassarà Antonino M. , Neufeld Esra , Acerbo Emma , Carron Romain , Williamson Adam , Kurtin Danielle L. , Rhodes Edward , Hampshire Adam , Kuster Niels , Boyden Edward S. , Pascual-Leone Alvaro , Grossman Nir
Published: September 2022

Deep brain stimulation (DBS) via implanted electrodes is used worldwide to treat patients with severe neurological and psychiatric disorders however its invasiveness precludes widespread clinical use and deployment in research. Temporal interference (TI) is a strategy for non-invasive steerable DBS using multiple kHz-range electric fields with a difference frequency within the range of neural activity. Here we report the validation of the non-invasive DBS concept in humans. We used electric field modelling and measurements in a human cadaver to verify that the locus of the transcranial TI stimulation can be steerably focused in the hippocampus with minimal exposure to the overlying cortex. We then used functional magnetic resonance imaging (fMRI) and behaviour experiments to show that TI stimulation can focally modulate hippocampal activity and enhance the accuracy of episodic memories in healthy humans. Our results demonstrate targeted, non-invasive electrical stimulation of deep structures in the human brain.
Parafoveal and foveal N400 effects in natural reading: A timeline of semantic processing from fixation-related potentials
Authors: Li Nan , Wang Suiping , Kornrumpf Florian , Sommer Werner , Dimigen Olaf
Published: September 2022

The depth at which parafoveal words are processed during reading is an ongoing topic of debate. Recent studies using RSVP-with-flanker paradigms have shown that implausible words within sentences elicit N400 components while they are still in parafoveal vision, suggesting that the semantics of parafoveal words can be accessed to rapidly update the sentence representation. To study this effect in natural reading, we combined the co-registration of eye movements and EEG with the deconvolution modeling of fixation-related potentials (FRPs) to test whether semantic plausibility is processed parafoveally during Chinese sentence reading. For one target word per sentence, both its parafoveal and foveal plausibility were orthogonally manipulated using the boundary paradigm. Consistent with previous eye movement studies, we observed a delayed effect of parafoveal plausibility on fixation durations that only emerged on the foveal word. Crucially, in FRPs aligned to the pre-target fixation, a clear N400 effect emerged already based on parafoveal plausibility, with more negative voltages for implausible previews. Once participants fixated the target, we again observed an N400 effect of foveal plausibility. Interestingly, this foveal N400 was absent whenever the preview had been implausible, indicating that when a word’s (im)plausibility is already processed in parafoveal vision, this information is not revised anymore upon direct fixation. Implausible words also elicited a late positive complex (LPC), but exclusively in foveal vision. Our results provide convergent neural and behavioral evidence for the parafoveal uptake of semantic information, but also indicate different contributions of parafoveal versus foveal information towards higher-level sentence processing.
Combining historical agricultural and climate datasets sheds new light on early 20thcentury barley performance
Authors: Raymond Joanna , Mackay Ian , Penfield Steven , Lovett Andrew , Philpott Haidee , Dorling Stephen
Published: September 2022

Barley (Hordeum vulgare ssp. vulgare) is cultivated globally across a wide range of environments, both in highly productive agricultural systems and in subsistence agriculture and provides valuable feedstock for the animal feed and malting industries. However, as the climate changes there is an urgent need to identify adapted spring barley varieties that will consistently yield highly under increased environmental stresses. In this research we combined recently released historical weather data with published early 20thcentury Irish spring barley trials data for two heritage varieties:ArcherandGoldthorpe, following an analysis first published by Student in 1923. Using linear mixed models, we show that interannual variation in observed spring barley yields can be partially explained by recorded weather variability. We find that whilstArcherlargely yields more highly,Goldthorpeis more stable under wetter growing conditions, highlighting the importance of considering growing climate in variety selection. Furthermore, this study demonstrates the benefits of access to historical trials and climatic data and the importance of incorporating climate data in modern day breeding programmes to improve climate resilience of future varieties.
Determinants of survival and dispersal along the range expansion of a biological invasion
Authors: Edeline Eric , Starck Agnès , Bennevault Yoann , Paillisson Jean-Marc , Petit Eric J.
Published: September 2022

Projecting and managing the future response of biological systems to global change requires a mechanistic understanding of how climate and ecology jointly drive species demography and range dynamics. Such knowledge is particularly crucial when it comes to invasive species, which expansion may have far-reaching consequences for recipient ecosystems. Here, we use mark recapture in replicated outdoor mesocosms to examine how survival and dispersal, two key drivers of population and range dynamics, respond to climate and ecology in the invasive red swamp crayfish (Procambarus clarkii) along an invasion gradient. We show that crayfish survival probability increased with (i) increasing body size at high (but not low) crayfish density and (ii) with warmer temperatures, and decreased (i) with increasing body condition and (ii) under higher crayfish density. Overland dispersal probability by crayfish increased with increasing (i) body-size, (ii) body condition and (iii) temperatures. In contrast, crayfish from range-edge and range-core habitats had similar survival and overland dispersal probabilities, suggesting no evolution of the crayfish expansion potential along the invasion gradient. Our results highlight that species population dynamics and range shifts in a changing world are driven by joint contributions from both climate and ecology. InP. clarkii, global warming will simultaneously promote both a demographic increase and a geographic range expansion, especially in populations dominated by large-bodied individuals. In already-invaded ecosystems, selective harvesting of large-bodied crayfish can potentially reduce the dispersal potential of populations and, after a few generations, might further induce an evolutionary decline in fitness traits that is desirable from a management perspective.

Open research statement

Upon acceptance of this manuscript, data and codes will be made publicly available online on the INRAE data repository (https://entrepot.recherche.data.gouv.fr/dataverse/inrae).
Hybridization led to a rewired pluripotency network in the allotetraploid Xenopus laevis
Authors: Phelps Wesley A. , Hurton Matthew D. , Ayers Taylor N. , Carlson Anne E. , Rosenbaum Joel C. , Lee Miler T.
Published: September 2022

After fertilization, maternally contributed factors to the egg initiate the transition to pluripotency to give rise to embryonic stem cells, in large part by activating de novo transcription from the embryonic genome. Diverse mechanisms coordinate this transition across animals, suggesting that pervasive regulatory remodeling has shaped the earliest stages of development. Here, we show that maternal homologs of mammalian pluripotency reprogramming factors OCT4 and SOX2 divergently activate the two subgenomes of Xenopus laevis, an allotetraploid that arose from hybridization of two diploid species ~18 million years ago. Although most genes have been retained as two homeologous copies, we find that a majority of them undergo asymmetric activation in the early embryo. Chromatin accessibility profiling and CUT&RUN for modified histones and transcription factor binding reveal extensive differences in enhancer architecture between the subgenomes, which likely arose through genomic disruptions as a consequence of allotetraploidy. However, comparison with diploid X. tropicalis and zebrafish shows broad conservation of embryonic gene expression levels when divergent homeolog contributions are combined, implying strong selection to maintain dosage in the core vertebrate pluripotency transcriptional program, amid genomic instability following hybridization.
An island “endemic” born out of hybridization between introduced lineages
Authors: Salter Jessie F. , Brumfield Robb T. , Faircloth Brant C.
Published: September 2022

Humans have profoundly impacted the distribution of plant and animal species over thousands of years. The most direct example of these effects is human-mediated movement of individuals, either through translocation of individuals within their range or the introduction of species to new habitats. While human involvement may be suspected in species with obvious range disjunctions, it can be difficult to detect natural versus human-mediated dispersal events for populations at the edge of a species’ range, and this uncertainty muddles how we understand the evolutionary history of populations and broad biogeographic patterns. Studies combining genetic data with archeological, linguistic, and historical evidence have confirmed prehistoric examples of human-mediated dispersal; however, it is unclear whether these methods can disentangle recent dispersal events, such as species translocated by European colonizers during the past 500 years. We use genomic DNA from historical specimens and historical records to evaluate three hypotheses regarding the timing and origin of Northern Bobwhites (Colinus virginianus) in Cuba, whose status as an endemic or introduced population has long been debated. We discovered that bobwhites from southern Mexico arrived in Cuba between the 12th and 16th centuries, followed by the subsequent introduction of bobwhites from the southeastern USA to Cuba between the 18th and 20th centuries. These dates suggest the introduction of bobwhites to Cuba was human-mediated and concomitant with Spanish colonial shipping routes between Veracruz, Mexico and Havana, Cuba during this period. Our results identify endemic Cuban bobwhites as a genetically distinct population born of hybridization between divergent, introduced lineages.
All-Aqueous Printing of Viscoelastic Droplets in Yield-Stress Fluids
Authors: Zhu Jinchang , Cai Li-Heng
Published: September 2022

All-aqueous printing of viscoelastic droplets (aaPVD) in yield-stress fluids is the core of an emerging voxelated bioprinting technology that enables the digital assembly of spherical bio-ink particles (DASP) to create functional tissue mimics. However, the mechanism of aaPVD is largely unknown. Here, by quantifying the dynamics of the whole printing process in real-time, we identify two parameters critical to aaPVD: (1) acceleration of print nozzle, and (2) droplet/nozzle diameter ratio. Moreover, we distinguish three stages associated with aaPVD: droplet generation, detachment, and relaxation. To generate a droplet of good roundness, the ink should be a highly viscous shear-thinning fluid. Using particle image velocimetry and scaling theory, we establish a universal description for the droplet displacements at various printing conditions. Along the direction of nozzle movement, the droplet displacement is determined by the detachment number, a dimensionless parameter defined as the ratio between the dragging force from the nozzle and the confinement force from the supporting matrix. Perpendicular to the direction of nozzle movement, the droplet displacement is determined by the Oldroyd number, a dimensionless parameter that describes the yielded area of the supporting matrix near the print nozzle. For a relaxed droplet, the droplet tail length is independent of droplet/nozzle diameter ratio but determined by the nozzle acceleration. We conclude that printing droplets of good fidelity requires a relatively large droplet/nozzle diameter ratio and intermediate nozzle accelerations. These ensure that the droplet is more solid-like to not flow with the nozzle to form a tadpole-like morphology and that the confinement force from the yield-stress fluid is large enough to prevent large droplet displacement. Our results provide the knowledge and tools forin situgenerating and depositing highly viscoelastic droplets of good roundness at prescribed locations in 3D space, which help establish the foundational science for voxelated bioprinting.

Statement of Significance

Analogues of pixels to two-dimensional (2D) pictures, voxels – in the form of small cubes or spheres – are the basic units of three-dimensional (3D) objects. All-aqueous printing of viscoelastic droplets (aaPVD) is the core of voxelated bioprinting, an emerging technology that uses spherical bio-ink voxels as building blocks to create 3D tissue mimics. By quantifying the dynamics of the whole printing process in real-time, we distinguish the stages associated with aaPVD, identify parameters critical to aaPVD, and develop a universal understanding forin situgenerating and depositing viscoelastic droplets of good roundness at prescribed locations in 3D space. Our results help establish the foundational science for voxelated bioprinting and provide a general approach for precisely manipulating viscoelastic voxels in 3D space.
Perception and Memory Retrieval States are Reflected in Distributed Patterns of Background Functional Connectivity
Authors: Li Y. Peeta , Wang Yida , Turk-Browne Nicholas B. , Kuhl Brice A. , Hutchinson J. Benjamin
Published: September 2022

The same visual input can serve as the target of perception or as a trigger for memory retrieval depending on whether cognitive processing is externally oriented (perception) or internally oriented (memory retrieval). While numerous human neuroimaging studies have characterized how visual stimuli are differentially processed during perception versus memory retrieval, perception and memory retrieval may also be associated with distinct neural states that are independent of stimulus-evoked neural activity. Here, we combined human fMRI with full correlation matrix analysis (FCMA) to reveal potential differences in “background” functional connectivity across perception and memory retrieval states. We found that perception and retrieval states could be discriminated with high accuracy based on patterns of connectivity across (1) the control network, (2) the default mode network (DMN), and (3) retrosplenial cortex (RSC). In particular, clusters in the control network increased connectivity with each other during the perception state, whereas clusters in the DMN were more strongly coupled during the retrieval state. Interestingly, RSC switched its coupling between networks as the cognitive state shifted from retrieval to perception. Finally, we show that background connectivity 1) was fully independent from stimulus-related variance in the signal and, further, 2) captured distinct aspects of cognitive states compared to traditional classification of stimulus-evoked responses. Together, our results reveal that perception and memory retrieval are associated with sustained cognitive states that manifest as distinct patterns of connectivity among large-scale brain networks.
Tactile stimulation restores inhibited stretch reflex attributable to attenuation of la afferents during surprise landing
Authors: Konishi Yu , Yoshii Ryo , Takeshita Daisuke
Published: September 2022

Purpose

Arthrogenic muscle inhibition(AMI) is induced by pathological knee conditions. The present study aimed to investigate the effect of tactile stimulation on reflex changes induced by simulated AMI during unpredictable landing performances.

Methods

Twenty participants performed six unilateral landing tasks: 15cm normal landing (15NL), 30cm normal landing(30NL), surprise landing(SL), 30cm normal landing following vibration (30NLV), surprise landing following vibration(SLV), and surprise landing following vibration with Kinesiology-tape(SLK). For the surprise landing tasks, the solid landing platform(15cm) was removed and replaced by a false plate platform. Since the false plate dislodged easily under load, participants unpredictably fell through the plate to the actual landing surface 15cm below. After completing 15NL, 30NL, SL, vibration stimulation was applied to participants’ knees to induce neurological changes similar to AMI. After vibration stimulation, participants performed 30NLV, SLV and SLK in a random order. EMG in the post-landing short latency(31–60 ms) and medium latency(61–90 ms) periods were examined. EMG signals from the vastus lateralis(VL), vastus medialis(VM), and lateral hamstrings(LH) were recorded and compared between tasks.

Results

EMG of all muscles were significantly enhanced in the medium latency period. Enhanced EMG were suppressed by vibration stimulation in the VL, but the suppressed EMG were restored after cutaneous stimulation(p<0.01).

Conclusion

Our findings suggest that AMI could alter motor control patterns during unpredictable landing, and that tactile stimulation could restore the altered motor control to a normal state. The use of tactile stimulation may help maintain normal motor control patterns in injured individuals.
Efficient coding of natural images in the mouse visual cortex
Authors: Bolaños Federico , Orlandi Javier G. , Aoki Ryo , Jagadeesh Akshay V. , Gardner Justin L. , Benucci Andrea
Published: September 2022

How communication between neurons gives rise to natural vision remains a matter of intense investigation. The mid-level visual areas along the ventral stream, as studies in primates have shown, are selective to a common class of natural images—textures—but a circuit-level understanding of this selectivity and its link to perception remain unclear. We addressed these questions in mice, first showing that they can perceptually discriminate between texture types and statistically simpler spectrally matched stimuli. Then, at the neural level, we found that the secondary visual area (LM), more than the primary one (V1), was selective for the higher-order statistics of textures, both at the mesoscopic and single-cell levels. At the circuit level, textures were encoded in neural activity subspaces whose relative distances correlated with the statistical complexity of the images and with the mice’s ability to discriminate between them. These dependencies were more significant in LM, in which the texture-related subspaces were smaller and closer to each other, enabling better stimulus decoding in this area. Together, our results demonstrate texture vision in mice, finding a linking framework between stimulus statistics, neural representations, and perceptual sensitivity—a distinct hallmark of efficient coding computations.
Rapid and fully automated blood vasculature analysis in 3D light-sheet image volumes of different organs
Authors: Spangenberg Philippa , Hagemann Nina , Squire Anthony , Förster Nils , Krauß Sascha D. , Qi Yachao , Yusuf Ayan Mohamud , Wang Jing , Grüneboom Anika , Kowitz Lennart , Korste Sebastian , Totzeck Matthias , Cibir Zülal , Tuz Ali Ata , Singh Vikramjeet , Siemes Devon , Struensee Laura , Engel Daniel R. , Ludewig Peter , Melo Luiza Martins Nascentes , Helfrich Iris , Chen Jianxu , Gunzer Matthias , Hermann Dirk M. , Mosig Axel
Published: September 2022

Blood vasculature represents a complex network of vessels with varying lengths and diameters that are precisely organized in space to allow proper tissue function. Light-sheet fluorescence microscopy (LSFM) is very useful to generate tomograms of tissue vasculature with high spatial accuracy. Yet, quantitative LSFM analysis is still cumbersome and available methods are restricted to single organs and advanced computing hardware. Here, we introduce VesselExpress, an automated software that reliably analyzes six characteristic vascular network parameters including vessel diameter in LSFM data on average computing hardware. VesselExpress is ~100 times faster than other existing vessel analysis tools, requires no user interaction, integrates batch processing, and parallelization. Employing an innovative dual Frangi filter approach we show that obesity induces a large-scale modulation of brain vasculature in mice and that seven other major organs differ strongly in their 3D vascular makeup. Hence, VesselExpress transforms LSFM from an observational to an analytical working tool.
A new high-resolution three-dimensional retinal implant: System design and preliminary human results
Authors: Yanovitch Leonid , Raz-Prag Dorit , Hanein Yael
Published: September 2022

The NR600 retinal prosthetic device is a unique newly developed implant intended to restore visual perception to people who lost their vision due to retinal degenerative diseases. The miniature implant captures the visual image in place of the damaged photoreceptor cells and creates the electrical stimulation required to activate the preserved retinal cell layers. The NR600 system transduces visual signal into electrical signals that are delivered to the retina via an array of needle shaped electrodes to minimize electrical activation levels and improve stimulation localization. NR600 consists of two components: A miniature implantable chip and eyeglasses set worn by the patient. The eyeglasses deliver power and control the implantable device. In this report, we present the NR600 system design, its optical, electrical, and electro-chemical characteristics, and preliminary results from human subjects.
P3HT-GRAPHENE DEVICE FOR THE RESTORATION OF VISUAL PROPERTIES IN A RAT MODEL OF RETINITIS PIGMENTOSA
Authors: Francia Simona , Marco Stefano Di , DiFrancesco Mattia L. , Ferrari Davide V. , Shmal Dmytro , Cavalli Alessio , Pertile Grazia , Attanasio Marcella , Maya-Vetencourt José Fernando , Manfredi Giovanni , Lanzani Guglielmo , Benfenati Fabio , Colombo Elisabetta
Published: September 2022

Retinal degeneration is one of the prevalent causes of blindness worldwide, for which no effective treatment has yet been identified. Inorganic photovoltaic devices have been investigated for visual restoration in advanced stage Retinitis pigmentosa (RP), although lack of implant flexibility and foreign-object reactions have limited their application. Organic photoactive retinal prostheses may overcome these limitations, being biomimetic and tissue friendly. Inspired by organic photovoltaic strategies involving graphene, a hybrid retinal prosthesis was recently engineered consisting of a dual poly-3-hexylthiophene (P3HT) and graphene layer onto a flexible substrate. Here, this hybrid prosthesis was subretinally implanted in vivo in 5-month-old Royal College of Surgeons (RCS) rats, a rodent model of RP. Implanted dystrophic rats restored visual performances at both subcortical and cortical levels in response to light stimuli, in the absence of marked inflammatory responses. Moreover, the analysis of the physical-mechanical properties after prolonged permanence in the eye showed excellent biocompatibility and robustness of the device. Overall, the results demonstrate that graphene-enhanced organic photovoltaic devices can be suitably employed for the rescue of retinal dystrophies and supports the translation of the organic strategy into the medical practice.

TABLE OF CONTENTS

Inspired by organic photovoltaic, a hybrid retinal prosthesis consisting of poly-3-hexylthiophene (P3HT) and graphene on a flexible substrate was subretinally implanted in vivo in Royal College of Surgeons (RCS) rats, a model of Retinitis pigmentosa. Implanted dystrophic rats restored visual performances at both subcortical and cortical levels in response to light stimuli, in the absence of marked inflammatory responses.
Adaptive Optical Coherent Raman Imaging of Axons through Mouse Cranial Bone
Authors: Lim Jong Min , Yoon Seokchan , Kim Seho , Choi Youngjin , Hong Jin Hee , Choi Wonshik , Cho Minhaeng
Published: September 2022

Coherent Raman scattering imaging has provided inherent chemical information of biomolecules without the need for any external labels.1–3 However, its working depth in deep-tissue imaging is extremely shallow because both the intrinsic scattering cross-section and image contrast are so small that even weak perturbation of the pump and Stokes beam focusing by the complex tissue causes the loss of the resolving power.4,5 Here, we propose a deep-tissue coherent Raman scattering (CRS) microscopy equipped with an advanced adaptive optics (AO) system measuring complex tissue aberration from elastic backscattering. Using this label-free AO-CRS microscopy, we demonstrate the vibrational imaging of lipid-rich substances such as myelin inside the mouse brain even through the thick and opaque cranial bones.
Comparison of Transcriptomic Changes in Younger and Older Multiple Myeloma Patients from the MMRF-CoMMpass Study RNA-Seq Data
Authors: Keskin Merve
Published: September 2022

Background

Age-related differences in Multiple Myeloma (MM) are studied in clinical and genomic context, however, transcriptome changes have not yet been determined. The aim of this study is to identify the genes that are expressed differently in young and old patient groups and to examine the relationship of these genes with biological pathways and the drugs that can be used.

Methods

The MMRF CoMMpass cohort RNA-Seq data (n=634) was used to analyze differentially expressed genes between young and old patients. GO term and KEGG gene-set enrichment analysis were conducted using R packages. Drug-gene interactions were detected using DGIdb.

Results

Globally, 523 genes (366 upregulated, 157 downregulated) were differentially expressed (p < 0.05) in young patients. Totally 220 GO terms, mostly related to immune regulation pathways were enriched. “Cytokine-cytokine receptor interaction” gene-set was enriched in KEGG GSEA. Among the highest expression difference, genes involved in immune regulation (FCGR1A, FCER1G, TLR2), known proto-oncogenic genes (BCL2, FGR) and genes under investigation for association with various cancers (RGL4, MT-RNR1, ETS2, ENPP3, FUT7, NTNG2, PRAM1) were identified. Drugs associated with the pathways affected by these genes were identified.

Conclusions

Further investigation of differentially expressed genes in young patients may shed light on new treatment options.