bluuebunny/crossref_metadata_2025 huggingface dataset:
Transmission dynamics of low pathogenicity avian influenza (H2N2) viruses in live bird markets of the Northeast United States of America, 2013–2019
Authors: Chung David H , Torchetti Mia. K , Killian Mary L , Swayne David E , Lee Dong-Hun
Published: February 2022

Live bird market (LBM) surveillance was conducted in the Northeast United States (US) to monitor for the presence of avian influenza viruses (AIV) in domestic poultry and market environments. A total of 384 H2N2 low pathogenicity AIV (LPAIV) isolated from active surveillance efforts in the LBM system of New York, Connecticut, Rhode Island, New Jersey, Pennsylvania, and Maryland during 2013–2019 were included in this analysis. Comparative phylogenetic analysis showed that a wild-bird-origin H2N2 virus may have been introduced into the LBMs in Pennsylvania and independently evolved since March 2012 followed by spread to LBMs in New York City during late 2012–early 2013. LBMs in New York state played a key role in the maintenance and dissemination of the virus to LBMs in the Northeast US including reverse spread to Pennsylvania LBMs. The frequent detections in the domestic ducks and market environment with viral transmissions between birds and environment possibly led to viral adaptation and circulation in domestic gallinaceous poultry in LBMs, suggesting significant roles of domestic ducks and contaminated LBM environment as reservoirs in maintenance and dissemination of H2N2 LPAIV.
The #PedsMatch21 Webinar Series: Coordinated Specialty-Level Communication During the Virtual Residency Application Cycle
Authors: Neelakantan Mekala , Heitkamp Nicholas M. , Blankenburg Rebecca , Frohna John G.
Published: February 2022

Problem

The landscape of pediatric medical education changed significantly in the wake of the COVID-19 pandemic. Fourth-year medical students applying to pediatric residency programs were particularly affected by alterations to traditional away rotations, the inability to conduct in-person visits, and resulting changes in ways of communicating with residency programs. Applicants were concerned about the virtual component of the application cycle and worried as to how to manage the COVID-19-related changes. Program leaders also faced apprehension at how to close communication gaps and effectively use virtual tools to reach applicants.

Approach

Founders of the Twitter-based @FuturePedsRes (FPR) organization recognized these concerns and developed a webinar series during the 2020–2021 academic year to create opportunities for programs and applicants to communicate. Leaders of the Association of Pediatric Program Directors and the Council on Medical Student Education in Pediatrics joined as sponsors and co-hosts. The #PedsMatch21 webinar series consisted of 9 total webinars: 2 overviews, 5 regional, 1 for osteopathic students, and 1 for international medical graduates.

Outcomes

A total of 138 pediatric residency programs across the country participated in the #PedsMatch21 webinar series. Each webinar brought in a mean of 431 attendees, from the United States and several other countries. Follow-up surveys immediately after each webinar and again at the end of the interview season demonstrated that the webinars decreased applicants’ anxiety, provided helpful information on the virtual season, and increased their awareness of programs.

Next Steps

The #PedsMatch21 webinar series demonstrated utility in addressing applicants’ concerns and allowing applicants access to a greater number of programs. Webinar-based strategies should be considered across all medical specialties as a useful method of providing accessible forums for programs and applicants.
Chlamydia trachomatis Infection and Seropositivity in Women Reporting Sexual Contact to a Chlamydia-Infected Partner
Authors: Gupta Kanupriya , Van Der Pol Barbara , Press Christen G. , Geisler William M.
Published: February 2022

Among 73 women presenting to a sexually transmitted infection (STI) clinic in Birmingham, Alabama for reported sexual contact to a chlamydia-infected partner, Chlamydia trachomatis was detected in genital specimens in 24 (32.8%), less often in women reporting prior chlamydial infection (P = 0.001). Most women (93.2%) were C. trachomatis seropositive.
Anatomical Characterization of the Tear Trough and the Lid-Cheek Junction: An Iodine Staining Technique Based on High-Resolution Micro–Computed Tomography
Authors: Chen Shuxiu , Ma Hengyuan , Song Tao , Li Haidong , Wu Di , Wang Yongqian , Yin Ningbei
Published: February 2022

Background:

The literature presents the tear trough and lid-cheek junction’s controversial anatomical explanations. In this study, the authors explored the anatomical characterization of the tear trough deformity and lid-cheek junction.

Methods:

Twelve human cadaver specimens were obtained from the authors’ anatomy department. Iodine staining and high-resolution micro–computed tomography was used to observe the suborbital area’s anatomy. Anatomical studies and histologic evaluation were performed.

Results:

The orbicularis retaining ligament is composed of a main septum right on the rim and multiple fibrous septa in the retro-orbicularis plain. The septum arises from the deep fascia of the palpebral part of the orbicularis oculi at approximately the level of the medial corneoscleral limbus, anchors the muscle to the orbital rim, and continues laterally as the lateral orbital thickening at the lateral canthus. Along the lid-cheek junction, multiple fibrous septa emanating from the deep fascia of the orbital part of the orbicularis oculi converge to the above septum. Using three-dimensional simulation, the skin-insert junction between the pre–palpebral part of the orbicularis oculi and pre–orbicularis oculi fibers precisely corresponded with the tear trough and the lid-cheek groove. Anatomical studies and histologic evaluation confirmed these observations.

Conclusions:

The orbicularis retaining ligament’s subtle anatomical features are clearly seen using the approach described. The tear trough and the lid-cheek junction’s anatomical characterization is defined by a suborbital ligament-fascia system whose description has implications in designing lower eyelid cosmetic surgery.
Virtual Reality Head-Mounted Displays in Medical Education
Authors: Tursø-Finnich Thomas , Jensen Rune Overgaard , Jensen Lasse X. , Konge Lars , Thinggaard Ebbe
Published: February 2022

Summary Statement

Simulation-based training using virtual reality head-mounted displays (VR-HMD) is increasingly being used within the field of medical education. This article systematically reviews and appraises the quality of the literature on the use of VR-HMDs in medical education. A search in the databases PubMed/MEDLINE, Embase, ERIC, Scopus, Web of Science, Cochrane Library, and PsychINFO was carried out. Studies were screened according to predefined exclusion criteria, and quality was assessed using the Medical Education Research Study Quality Instrument. In total, 41 articles were included and thematically divided into 5 groups: anatomy, procedural skills, surgical procedures, communication skills, and clinical decision making. Participants highly appreciated using VR-HMD and rated it better than most other training methods. Virtual reality head-mounted display outperformed traditional methods of learning surgical procedures. Although VR-HMD showed promising results when learning anatomy, it was not considered better than other available study materials. No conclusive findings could be synthesized regarding the remaining 3 groups.
Student Perceptions of Effective Simulation Instructor Teaching
Authors: Pylman Stacey E. , Emery Matthew T.
Published: February 2022

Summary Statement

Twenty-three focus groups were held with 183 first-year medical students to assess student perceptions of effective simulation instructors during preclinical training in a medical school. Qualitative descriptive analysis guided the interpretation of focus group data. Students identified 6 areas of knowledge (schedule, student learning goals, session scenario, tasks and checklists, technique, and session purpose); 5 effective instructor skill categories (setting up the learning environment, teaching at the appropriate level, teaching technique, providing deeper context, and giving effective feedback); and 8 positive instructor attributes (enthusiasm, engaged, prepared, knowledgeable, patient, relational, transparent, and calm) instructors should have. Each category of instructor attributes, skills, and knowledge was also described in detail providing illustrative examples of what effective instruction would look like in practice from the students' perspective. Recommendations for instructor faculty development methods and topics/goals are given.
A predictive flight-altitude model for avoiding future conflicts between an emblematic raptor and wind energy development in the Swiss Alps
Authors: Vignali Sergio , Lörcher Franziska , Hegglin Daniel , Arlettaz Raphaël , Braunisch Veronika
Published: February 2022

Deployment of wind energy is proposed as a mechanism to reduce greenhouse gas emissions. Yet, wind energy and large birds, notably soaring raptors, both depend on suitable wind conditions. Conflicts in airspace use may thus arise due to the risks of collisions of birds with the blades of wind turbines. Using locations of GPS-tagged bearded vultures, a rare scavenging raptor reintroduced into the Alps, we built a spatially explicit model to predict potential areas of conflict with future wind turbine deployments in the Swiss Alps. We modelled the probability of bearded vultures flying within or below the rotor-swept zone of wind turbines as a function of wind and environmental conditions, including food supply. Seventy-four per cent of the GPS positions were collected below 200 m above ground level, i.e. where collisions could occur if wind turbines were present. Flight activity at potential risk of collision is concentrated on south-exposed mountainsides, especially in areas where ibex carcasses have a high occurrence probability, with critical areas covering vast expanses throughout the Swiss Alps. Our model provides a spatially explicit decision tool that will guide authorities and energy companies for planning the deployment of wind farms in a proactive manner to reduce risk to emblematic Alpine wildlife.
Anti-cancer and antimicrobial potential of five soil
Streptomycetes
: a metabolomics-based study
Authors: Osama Nada , Bakeer Walid , Raslan Mai , Soliman Hanan A. , Abdelmohsen Usama Ramadan , Sebak Mohamed
Published: February 2022

Lack of new anti-cancer and anti-infective agents directed the pharmaceutical research to natural products' discovery especially from actinomycetes as one of the major sources of bioactive compounds. Metabolomics- and dereplication-guided approach has been used successfully in chemical profiling of bioactive actinomycetes. We aimed to study the metabolomic profile of five bioactive actinomycetes to investigate the interesting metabolites responsible for their antimicrobial and anti-cancer activities. Three actinomycetes, namely,
Streptomyces
sp. SH8, SH10 and SH13, were found to exhibit broad spectrum of antimicrobial activities, whereas isolate SH4 showed the broadest antimicrobial activity against all tested strains. In addition, isolates SH8, SH10 and SH12 displayed potent cytotoxicity against the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), whereas isolates SH4 and SH12 exhibited potent anti-cancer activity against the hepatoma cell line hepatoma G2 (HepG2) compared with their weak inhibitory properties on the normal breast cells MCF-10A and normal liver cells transformed human liver epithelial-2 (THLE2), respectively. All bioactive isolates were molecularly identified as
Streptomyces
sp. via 16S rRNA gene sequencing. Our actinobacterial dereplication analysis revealed putative identification of several bioactive metabolites including tetracycline, oxytetracycline and a macrolide antibiotic, novamethymycin. Together, chemical profiling of bioactive
Streptomycetes
via dereplication and metabolomics helped in assigning their unique metabolites and predicting the bioactive compounds instigating their diverse bioactivities.
Echo reception in group flight by Japanese horseshoe bats,
Rhinolophus ferrumequinum nippon
Authors: Hase Kazuma , Kadoya Yukimi , Takeuchi Yuki , Kobayasi Kohta I. , Hiryu Shizuko
Published: February 2022

The ability to detect behaviourally relevant sensory information is crucial for survival. Especially when active-sensing animals behave in proximity, mutual interferences may occur. The aim of this study was to examine how active-sensing animals deal with mutual interferences. Echolocation pulses and returning echoes were compared in spaces of various sizes (wide and narrow) in
Rhinolophus ferrumequinum nippon
flying alone or in a group of three bats. We found that in the narrow space, the group-flying bats increased the duration and bandwidth of the terminal frequency-modulated component of their vocalizations. By contrast, the frequency of the returning echoes did not differ in the presence of conspecifics. We found that their own echo frequencies were compensated within the narrow frequency ranges by Doppler shift compensation. By contrast, the estimated frequencies of the received pulses emitted by the other bats were much more broadly distributed than their echoes. Our results suggest that the bat auditory systems are sharply tuned to a narrow frequency to filter spectral interference from other bats.
Improving transcatheter aortic valve interventional predictability via fluid–structure interaction modelling using patient-specific anatomy
Authors: Govindarajan Vijay , Kolanjiyil Arun , Johnson Nils P. , Kim Hyunggun , Chandran Krishnan B. , McPherson David D.
Published: February 2022

Transcatheter aortic valve replacement (TAVR) is now a standard treatment for high-surgical-risk patients with severe aortic valve stenosis. TAVR is being explored for broader indications including degenerated bioprosthetic valves, bicuspid valves and for aortic valve (AV) insufficiency. It is, however, challenging to predict whether the chosen valve size, design or its orientation would produce the most-optimal haemodynamics in the patient. Here, we present a novel patient-specific evaluation framework to realistically predict the patient's AV performance with a high-fidelity fluid–structure interaction analysis that included the patient's left ventricle and ascending aorta (AAo). We retrospectively evaluated the pre- and post-TAVR dynamics of a patient who underwent a 23 mm TAVR and evaluated against the patient's virtually de-calcified AV serving as a hypothetical benchmark. Our model predictions were consistent with clinical data. Stenosed AV produced a turbulent flow during peak-systole, while aortic flow with TAVR and de-calcified AV were both in the laminar-to-turbulent transitional regime with an estimated fivefold reduction in viscous dissipation. For TAVR, dissipation was highest during early systole when valve deformation was the greatest, suggesting that an efficient valve opening may reduce energy loss. Our study demonstrates that such patient-specific modelling frameworks can be used to improve predictability and in the planning of AV interventions.
Viscous froth model applied to the motion and topological transformations of two-dimensional bubbles in a channel: three-bubble case
Authors: Torres-Ulloa C. , Grassia P.
Published: February 2022

The viscous froth model is used to predict rheological behaviour of a two-dimensional (2D) liquid-foam system. The model incorporates three physical phenomena: the viscous drag force, the pressure difference across foam films and the surface tension acting along them with curvature. In the so-called infinite staircase structure, the system does not undergo topological bubble neighbour-exchange transformations for any imposed driving back pressure. Bubbles then flow out of the channel of transport in the same order in which they entered it. By contrast, in a simple single bubble staircase or so-called lens system, topological transformations do occur for high enough imposed back pressures. The three-bubble case interpolates between the infinite staircase and simple staircase/lens. To determine at which driving pressures and at which velocities topological transformations might occur, and how the bubble areas influence their occurrence, steady-state propagating three-bubble solutions are obtained for a range of bubble sizes and imposed back pressures. As an imposed back pressure increases quasi-statically from equilibrium, complex dynamics are exhibited as the systems undergo either topological transformations, reach saddle-node bifurcation points, or asymptote to a geometrically invariant structure which ceases to change as the back pressure is further increased.
New results in the theory of plane strain flexure of incompressible isotropic hyperelastic materials
Authors: Anssari-Benam Afshin , Horgan Cornelius O.
Published: February 2022

New results on the classical problem of bending by end moments for incompressible isotropic hyperelastic materials within the framework of nonlinear elasticity are investigated and presented in this paper. The particular results of concern here include (i) the adaptation of Rivlin's standard analysis to the case whereone endof the beam isfixedand the other end is subjected to a bending moment; and (ii) results on the finite bending of (infinitesimally)thinisotropic hyperelastic plates which are valid forlarge deformations, extending the classical results from the linear elasticity theory which are restricted to small deformations. An interesting feature observed in this context is that a flexed thin plate develops an oscillatory surface along the circular arc near the free end, due to local (small)deviationsof the radius of curvature. A potential application to the bending of a biological soft tissue, namely the aortic valve leaflet, is briefly described by way of an example. Finally, some new results are obtained for finite bending of hyperelastic materials that exhibit limiting chain extensibility at the molecular level and involve constraints on the deformation. The amount of bending that such materials can sustain is limited by the constraint. On using a limiting chain extensibility model, closed-form solutions for the Cauchy stress components, the bending moment and the normal out-of-plane force required to sustain the bending deformation are derived.
Fast active thermal cloaking through PDE-constrained optimization and reduced-order modelling
Authors: Sinigaglia Carlo , Quadrelli Davide E. , Manzoni Andrea , Braghin Francesco
Published: February 2022

In this paper, we show how to efficiently achieve thermal cloaking from a computational standpoint in several virtual scenarios by controlling a distribution of active heat sources. We frame this problem in the setting of PDE-constrained optimization, where the reference field is the solution of the time-dependent heat equation in the absence of the object to cloak. The optimal control problem then aims at actuating the space–time control field so that the thermal field outside the obstacle is indistinguishable from the reference field. In particular, we consider multiple scenarios where material’s thermal diffusivity, source intensity and obstacle’s temperature are allowed to vary within a user-defined range. To tackle the thermal cloaking problem in a rapid and reliable way, we rely on a parametrized reduced order model built through the reduced basis method, thus entailing huge computational speedups compared with a high-fidelity, full-order model exploiting the finite-element method while dealing both with complex target shapes and disconnected control domains.
Certain implementations in fractional calculus operators involving Mittag-Leffler-confluent hypergeometric functions
Authors: Ghanim Firas , Bendak Salaheddine , Al Hawarneh Alaa
Published: February 2022

The Mittag-Leffler function and confluent hypergeometric functions were created to approximate interpolation in exponential functions. The researchers noted that Prabhakar’s integral transformation, which involves extended multi-parameter Mittag-Leffler functions, may be used to create and explore different fractional calculus models. This four-parameter function is further illustrated in graphs using MATLAB. With classical (Riemann–Liouville) fractional integrals, the research shows a set of formulations for these fractional differintegral operators. Moreover, using AB Model results of Prabhakar and the generalized Prabhakar models, the authors use a series of formulae to come up with new results. This paper demonstrates how this series formula may be used to provide simple alternative evidence for numerous well-known effects of Prabhakar differintegrals.
Relationship between capillaries, mitochondria and maximum power of the heart: a meta-study from shrew to elephant
Authors: Horrell Heidi D. , Lindeque Anika , Farrell Anthony P. , Seymour Roger S. , White Craig R. , Kruger Kayla M. , Snelling Edward P.
Published: February 2022

This meta-study uses phylogenetic scaling models across more than 30 species, spanning five orders of magnitude in body mass, to show that cardiac capillary numerical density and mitochondrial volume density decrease with body mass raised to the –0.07 ± 0.03 and –0.04 ± 0.01 exponents, respectively. Thus, while an average 10 g mammal has a cardiac capillary density of approximately 4150 mm−2and a mitochondrial density of 33%, a 1 t mammal has considerably lower corresponding values of 1850 mm−2and 21%. These similar scaling trajectories suggest quantitative matching for the primary oxygen supply and oxygen consuming structures of the heart, supporting economic design at the cellular level of the oxygen cascade in this aerobic organ. These scaling trajectories are nonetheless somewhat shallower than the exponent of –0.11 calculated for the maximum external mechanical power of the cardiac tissue, under conditions of heavy exercise, when oxygen flow between capillaries and mitochondria is probably fully exploited. This mismatch, if substantiated, implies a declining external mechanical efficiency of the heart with increasing body mass, whereby larger individuals put more energy in but get less energy out, a scenario with implications for cardiovascular design, aerobic capacity and limits of body size.
Characterizing ontogeny of quantity discrimination in zebrafish
Authors: Sheardown Eva , Torres-Perez Jose Vicente , Anagianni Sofia , Fraser Scott E. , Vallortigara Giorgio , Butterworth Brian , Miletto-Petrazzini Maria Elena , Brennan Caroline H.
Published: February 2022

A sense of non-symbolic numerical magnitudes is widespread in the animal kingdom and has been documented in adult zebrafish. Here, we investigated the ontogeny of this ability using a group size preference (GSP) task in juvenile zebrafish. Fish showed GSP from 21 days post-fertilization and reliably chose the larger group when presented with discriminations of between 1 versus 3, 2 versus 5 and 2 versus 3 conspecifics but not 2 versus 4 conspecifics. When the ratio between the number of conspecifics in each group was maintained at 1 : 2, fish could discriminate between 1 versus 2 individuals and 3 versus 6, but again, not when given a choice between 2 versus 4 individuals. These findings are in agreement with studies in other species, suggesting the systems involved in quantity representation do not operate separately from other cognitive mechanisms. Rather they suggest quantity processing in fishes may be the result of an interplay between attentional, cognitive and memory-related mechanisms as in humans and other animals. Our results emphasize the potential of the use of zebrafish to explore the genetic and neural processes underlying the ontogeny and function of number cognition.
First isolation and genomic characterization of bovine parechovirus from faecal samples of cattle in Japan
Authors: Oba Mami , Sakaguchi Shoichi , Wu Hong , Fujioka Yoshihiko , Takemae Hitoshi , Oki Hisako , Kawai Megumi , Shiokawa Mai , Aoki Hiroshi , Fukase Yuka , Madarame Hiroo , Nakano Takashi , Mizutani Tetsuya , Nagai Makoto
Published: February 2022

A novel picornavirus was isolated from the faeces of a diarrhoeic cow using MA-104 cells at the third blind passage. This virus, named Den1/2021/JPN, was completely sequenced using total RNA from the cell culture supernatant by deep sequencing. The genome of Den1/2021/JPN had a standard picornavirus genome organisation with conserved picornaviral motifs. The 5′ untranslated region harboured a type-II internal ribosomal entry site. Den1/2021/JPN was most closely related to a bovine parechovirus (Bo_ParV) named cow/2018/4, which has been recently identified in publicly available databases. Phylogenetic analyses and pairwise sequence comparison revealed that Den1/2021/JPN and Bo_ParV cow/2018/4 clustered with parechoviruses and were most closely related to Parechovirus E identified in birds of prey, exhibiting nucleotide sequence similarity of 64.2–64.5 %, 58.6–59.7 % and 66.3–66.4 % in the polyprotein, P1 and 2C+3 CD coding regions, respectively. This study presents the first report on the isolation of Bo_ParV. Den1/2021/JPN and Bo_ParV cow/2018/4, which are candidates for a novel species in the genus Parechovirus.
Category-specific fMRI correlates of picture naming: A study with Arabs and Filipinos
Authors: Tayeb Haythum O. , Alghamdi Jamaan , Ahmed Naushad , Alsawwaf Yousef , Alsafi Khalid , Baduwailan Abrar , Yaghmoor Bassam , Elyas Tariq , Mudarris Mohammed , Weisholtz Daniel S.
Published: February 2022

Cross cultural neuroimaging work has demonstrated differences in neural correlates of some cognitive processes between individuals from different cultures, often comparing American and Chinese subjects. In contrast, a limited number of studies examined Arab and/or Filipino participants. This fMRI study aimed to demonstrate neural activations during animal and tool picture naming by 18 healthy Arabs and 18 healthy Filipino participants. In animal naming contrasted with tool naming, Arabs preferentially activated regions in the right lateral occipital and fusiform cortices, whereas Filipinos recruited bilateral visual areas. Cross-group comparisons of animal naming revealed that Arabs recruited right visual areas more than Filipinos, who in turn recruited the cerebellum more than Arabs. In tool naming, Arabs preferentially activated a predominantly left frontoparietal network, whereas no regions were identified in Filipinos, and no differences in activation between groups were found. Using a low-demand picture-naming task, this study revealed category-specific neural activations during picture naming by Arabs and Filipinos, as well as between-group differences in animal naming. The results suggest that Arabs and Filipinos may have culture-specific differences in processing animate and inanimate pictures, and caution against generalizing findings from the more commonly studied populations, especially in verbal tasks such as picture naming.

HIGHLIGHTS

▪

The neural correlates of animal and tool picture naming in Arabs and Filipinos are category specific.

▪

Animal naming by Arabs tended to preferentially activate the nondominant ventral visual stream.

▪

Animal naming by Filipinos activated bilateral visual areas, and the cerebellum.

▪

Tool naming by Arabs activated dominant frontoparietal areas related to praxis.

▪

Results suggest that Arabs and Filipinos have culture-specific differences in visual processing.
Neural decoding from surface high-density EMG signals: influence of anatomy and synchronization on the number of identified motor units
Authors: de Oliveira Daniela Souza , Casolo Andrea , Balshaw Thomas G. , Maeo Sumiaki , Lanza Marcel Bahia , Martin Neil R.W. , Maffulli Nicola , Kinfe Thomas Mehari , Eskofier Björn , Folland Jonathan P. , Farina Dario , Del Vecchio Alessandro
Published: February 2022

Objective

High-density surface electromyography (HD-sEMG) allows the reliable identification of individual motor unit (MU) action potentials. Despite the accuracy in decomposition, there is a large variability in the number of identified MUs across individuals and exerted forces. Here we present a systematic investigation of the anatomical and neural factors that determine this variability.

Approach

We investigated factors of influence on HD-sEMG decomposition, such as synchronization of MU discharges, distribution of MU territories, muscle-electrode distance (MED - subcutaneous fat thickness), maximum anatomical cross-sectional area (ACSAmax), and fiber CSA. For this purpose, we recorded HD-sEMG signals, ultrasound, magnetic resonance imaging, and muscle biopsy of the biceps brachii muscle from two groups of participants – untrained-controls (UT=14) and strength-trained (>3 years of training, ST=16) – while they performed isometric ramp contractions with elbow flexors (at 15, 35, 50 and 70% maximum voluntary torque - MVT). We assessed the correlation between the number of accurately detected MUs by HD-sEMG decomposition and each measured parameter, for each target force level. Multiple regression analysis was then applied.

Main results

ST subjects showed lower MED (UT: 4.8 ± 1.4 vs. ST: 3.7 ± 0.8 mm) associated to a greater number of identified motor units (UT: 21.3 ± 10.2 vs. ST: 29.2 ± 11.8 MUs/subject). Both groups showed a negative correlation between MED and the number of identified MUs at low forces (r= −0.6, p=0.002 at 15% MVT). Moreover, the number of identified MUs was positively correlated to the distribution of MU territories (r=0.56, p=0.01) and ACSAmax (r=0.48, p=0.03) at 15% MVT. By accounting for all anatomical parameters, we were able to partly predict the number of decomposed MUs at low but not at high forces.

Significance

Our results confirmed the influence of subcutaneous tissue on the quality of HD-sEMG signals and demonstrated that MU spatial distribution and ACSAmax are also relevant parameters of influence for current decomposition algorithms.
NMNAT2 in cortical glutamatergic neurons exerts both cell and non-cell autonomous influences to shape cortical development and to maintain neuronal health
Authors: Niou ZhenXian , Yang Sen , Sri Anoosha , Rodriquez Hugo , Gilley Jonathan , Coleman Michael P. , Lu Hui-Chen
Published: February 2022

Here we show that deleting NMNAT2 from cortical glutamatergic neurons (NMNAT2 cKO) results in progressive axonal loss, neuroinflammation, small hippocampi and enlarged ventricles. Interestingly, dramatic neuroinflammation responses were observed around the long-range axonal tracts of NMNAT2 cKO cortical neurons. In addition to the neurodegenerative-like phenotype, we also found the absence of whisker-representation patterns “barrels” in the primary somatosensory cortex of NMNAT2 cKO mice. These observations suggest that NMNAT2 is required in developing cortical circuits and in maintaining the health of cortical neurons. Unbiased transcriptomic analysis suggests that NMNAT2 loss in cortical neurons after axonal outgrowth phase upregulates mitochondria function while greatly reducing synaptogenesis pathways. Complete loss of Sarm1 function in NMNAT2 cKO mice restores barrel map formation and axonal integrity and abolishes the inflammatory response. Interestingly, reducing Sarm1 function in NMNAT2 cKO mice by deleting only one copy of Sarm1 restores barrel map formation but did not diminish the neurodegenerative-like phenotype. Only complete loss of Sarm1 prevents neurodegeneration and inflammatory responses.
Accelerated cognitive decline in obese mouse model of Alzheimer’s disease is linked to sialic acid-driven immune deregulation
Authors: Suzzi Stefano , Croese Tommaso , Ravid Adi , Gold Or , Clark Abbe R. , Medina Sedi , Kitsberg Daniel , Adam Miriam , Vernon Katherine A. , Kohnert Eva , Shapira Inbar , Malitsky Sergey , Itkin Maxim , Colaiuta Sarah P. , Cahalon Liora , Slyper Michal , Greka Anna , Habib Naomi , Schwartz Michal
Published: February 2022

Systemic immunity supports healthy brain homeostasis. Accordingly, conditions causing systemic immune deregulation may accelerate onset of neurodegeneration in predisposed individuals. Here we show that, in the 5xFAD mouse model of Alzheimer’s disease (AD), high-fat diet-induced obesity accelerated cognitive decline, which was associated with immune deviations comprising increased splenic frequencies of exhausted CD4+T effector memory cells and CD4+FOXP3+regulatory T cells (Tregs). Non-targeted plasma metabolomics identifiedN-acetylneuraminic acid (NANA), the predominant sialic acid, as the major obesity-induced metabolite in 5xFAD mice, the levels of which directly correlated with Tregs abundance and inversely correlated with cognitive performance. Visceral adipose tissue macrophages were identified by sNuc-Seq as one potential source of NANA. Exposure to NANA led to immune deregulation in middle-aged wild-type mice, andex vivoin human T cells. Our study identified diet-induced immune deregulation, potentially via sialic acid, as a previously unrecognized link between obesity and AD.
Neural responses to broadband visual flicker in marmoset primary visual cortex
Authors: Schwenk Jakob C. B. , Hagan Maureen A. , Cloherty Shaun L. , Zavitz Elizabeth , Morris Adam P. , Price Nicholas S. C. , Rosa Marcello G. P. , Bremmer Frank
Published: February 2022

Temporal information is ubiquitous in natural vision and must be represented accurately in the brain to allow us to interact with a constantly changing world. Recent studies have employed a random stimulation paradigm to map the temporal response function (TRF) to luminance changes in the human EEG. This approach has revealed that the visual system, when presented with broadband visual input, actively selects distinct temporal frequencies, and retains their phase-information for prolonged periods of time. This non-linear response likely originates in primary visual cortex (V1), yet, so far it has not been investigated on a neural level. Here, we characterize the steady-state response to random broadband visual flicker in marmoset V1. In two experiments, we recorded from i) marmosets passively stimulated under general anesthesia, and ii) awake marmosets, under free viewing conditions. Our results show that LFP coupling to the stimulus was broadband and unselective under anesthesia, whereas in awake animals, it was restricted to two distinct frequency components, in the alpha and beta range. Within these frequency bands, coupling adhered to the receptive field (RF) boundaries of the local populations. The responses outside the RF did not provide evidence for a propagation of stimulus information across the cortex, contrary to results in human EEG studies. This result may be explained by short fixation durations, warranting further investigation. In summary, our findings show that during awake behavior V1 neural responses to broadband information are selective for distinct frequency bands, and that this selectivity is likely controlled actively by top-down mechanisms.
Aging clocks, entropy, and the limits of age-reversal
Authors: Tarkhov Andrei E. , Denisov Kirill A. , Fedichev Peter O.
Published: February 2022

We analyze aging signatures of DNA methylation and longitudinal electronic medical records from the UK Biobank datasets and observe that aging is driven by a large number of independent and infrequent transitions between metastable states in a vast configuration space. The compound effect of configuration changes can be captured by a single stochastic variable, thermodynamic biological age (tBA), tracking entropy produced, and hence information lost during aging. We show that tBA increases with age, causes the linear and irreversible drift of physiological state variables, reduces resilience, and drives the exponential acceleration of chronic disease incidence and death risks. The entropic character of aging drift sets severe constraints on the possibilities of age reversal. However, we highlight the universal features of configuration transitions, suggest practical ways of suppressing the rate of aging in humans, and speculate on the possibility of achieving negligible senescence.
Clinical and Economic Impact of COVID-19 on Plantation Workers: Preliminary Results from the Guatemala Agricultural Workers and Respiratory Illness Impact (AGRI) Study
Authors: Olson Daniel , Calvimontes Diva M. , Lamb Molly M. , Guzman Gerber , Barrios Edgar , Chacon Andrea , Rojop Neudy , Arias Kareen , Gomez Melissa , Bolanos Guillermo Antonio , Monzon Jose , Chard Anna N. , Iwamoto Chelsea , Duca Lindsey M. , Vuong Nga , Fineman Melissa , Lesteberg Kelsey , Beckham David , Santiago Mario L. , Quicke Kendra , Ebel Gregory , Gutierrez Emily Zielinski , Azziz-Baumgartner Eduardo , Hayden Frederick G. , Mansour Hani , Edwards Kathryn , Newman Lee S. , Asturias Edwin J.
Published: February 2022

We evaluated the clinical and socioeconomic burdens of respiratory disease in a cohort of Guatemalan banana plantation workers. All eligible workers were offered enrollment from June 15–December 30, 2020, and annually, then followed for influenza-like illnesses (ILI) through: 1) self-reporting to study nurses, 2) sentinel surveillance at health posts, and 3) absenteeism. Workers with ILI submitted nasopharyngeal swabs for influenza, RSV, and SARS-CoV-2 testing, then completed surveys at days 0, 7, and 28. Through October 10, 2021, 1,833 workers developed 169 ILIs (12.0/100 person-years) and 43 (25.4%) of these ILIs were laboratory-confirmed SARS-CoV-2 (3.1/100 person-years). Workers with SARS-CoV-2-positive ILI reported more anosmia (p<0.01), dysgeusia (p<0.01), difficulty concentrating (p=0.01), and irritability (p=0.01), and greater clinical and well-being severity scores (Flu-iiQ) than test-negative ILIs; they also had greater absenteeism (p<0.01) and lost income (median US$127.1, p<0.01). These results support the prioritization of Guatemalan farm workers for COVID-19 vaccination.
Influence of human activity on gut microbiota and immune responses of Darwin’s finches in the Galápagos Islands
Authors: Bygrave Jada N. , Zylberberg Maxine , Addesso Alyssa , Knutie Sarah A.
Published: February 2022

Urbanization can influence animal traits, including immunity and gut microbiota. Over the past several decades, the Galápagos Islands have seen rapid resident human population growth and tourist activity, leading to varying levels of human activity across Islands. Consequently, diet, gut microbiota, and immunity of endemic animals, such as Darwin’s finches, may have changed. The goal of this study was to determine the effect of land use on the immune response, gut microbiota, and body measurements of Darwin’s finches in 2008, at a time of rapidly increasing human activity in the Islands. Specifically, we compared proxies of immunity (lysozyme activity, and haptoglobin, complement antibody, and natural antibody levels), gut microbiota (bacterial diversity, community structure and membership, and relative abundance of bacterial taxa), and body measurements (body mass, tarsus length, and scaled mass index) across undeveloped, agricultural, and urban areas for medium ground finches (Geospiza fortis) and small ground finches (G. fuliginosa). We found that lysozyme activity was lower and observed bacterial species richness was higher in urban areas compared to non-urban areas across both finch species. For small ground finches, relative abundances of three bacterial genera (Pseudoxanthomonas, Cloacibacterium, andDietzia spp.) were higher in urban areas compared to non-urban areas, but this pattern was not observed in medium ground finches. Medium ground finches were smaller in undeveloped areas compared to the other two areas, but body measurements of small ground finches did not differ across areas. Our results suggest that human activity can impact immune measures and gut microbiota of Darwin’s finches.
Fast and accurate protein structure search with Foldseek
Authors: van Kempen Michel , Kim Stephanie S. , Tumescheit Charlotte , Mirdita Milot , Lee Jeongjae , Gilchrist Cameron L.M. , Söding Johannes , Steinegger Martin
Published: February 2022

As structure prediction methods are generating millions of publicly available protein structures, searching these databases is becoming a bottleneck. Foldseek aligns the structure of a query protein against a database by describing the amino acid backbone of proteins as sequences over a structural alphabet. Foldseek decreases computation times by four to five orders of magnitude with 86%, 88% and 133% of the sensitivities of DALI, TM-align and CE, respectively.
IMPACT OF PHYLLOSPHERE METHYLOBACTERIUM ON HOST RICE LANDRACES
Authors: Sanjenbam Pratibha , Shivaprasad P V , Agashe Deepa
Published: February 2022

The genus Methylobacterium includes widespread plant-associated bacteria that dominate the plant phyllosphere (occupying leaf surfaces), consume plant-secreted methanol, and can produce plant growth promoting metabolites. However, despite the potential to increase agricultural productivity, their impact on host fitness in the natural environment is relatively poorly understood. Here, we conducted field experiments with three traditionally cultivated rice landraces from north eastern India. We inoculated seedlings with native vs. non-native phyllosphere Methylobacterium strains, finding significant impacts on plant growth and grain yield. However, these effects were variable: whereas some Methylobacterium isolates were beneficial for their host, others had no impact or were no more beneficial than the bacterial growth medium. Host plant benefits were not consistently associated with Methylobacterium colonization, altered phyllosphere microbiome composition, changes in early expression of plant stress response pathways, or bacterial auxin production. We provide the first clear demonstration of the benefits of phyllosphere Methylobacterium for rice yield under field conditions, and highlight the need for further analysis to understand the mechanisms underlying these benefits. Given that the host landrace-Methylobacterium relationship is not generalizable, future agricultural applications will require careful testing to identify coevolved host- bacterium pairs that may enhance the productivity of high-value rice varieties.
A comprehensive phenotypic screening strategy to identify modulators of cargo translocation by the bacterial Type IVB secretion system
Authors: Cheng Eric , Dorjsuren Dorjbal , Lehman Stephanie , Larson Charles L. , Titus Steven A. , Sun Hongmao , Zakharov Alexey , Rai Ganesha , Heinzen Robert A. , Simeonov Anton , Machner Matthias P.
Published: February 2022

Bacterial type IV secretion systems (T4SSs) are macromolecular machines that translocate effector proteins across multiple membranes into infected host cells. Loss of function mutations in genes encoding protein components of the T4SS render bacteria avirulent, highlighting the attractiveness of T4SSs as drug targets. Here, we designed an automated high-throughput screening approach for the identification of compounds that interfere with the delivery of a reporter-effector fusion protein from Legionella pneumophila into RAW264.7 mouse macrophages. Using a fluorescence resonance energy transfer (FRET)-based detection assay in a bacteria/macrophage co-culture format, we screened a library of over 18,000 compounds and, upon vetting compound candidates in a variety of in vitro and cell-based secondary screens, isolated several hits that efficiently interfered with biological processes that depend on a functional T4SS, such as intracellular bacterial proliferation or lysosomal avoidance, but had no detectable effect on L. pneumophila growth in culture medium, conditions under which the T4SS is dispensable. Notably, the same hit compounds also attenuated, to varying degrees, effector delivery by the closely related T4SS from Coxiella burnetii, notably without impacting growth of this organism within synthetic media. Together, these results support the idea that interference with T4SS function is a possible therapeutic intervention strategy, and the emerging compounds provide tools to interrogate at a molecular level the regulation and dynamics of these virulence-critical translocation machines.

Importance

Multi-drug-resistant pathogens are an emerging threat to human health. Since conventional antibiotics target not only the pathogen but also eradicate the beneficial microbiota, they often cause additional clinical complications. Thus, there is an urgent need for the development of “smarter” therapeutics that selectively target pathogens without affecting beneficial commensals. The bacterial type IV secretion system (T4SS) is essential for the virulence of a variety of pathogens but dispensable for bacterial viability in general and can, thus, be considered a pathogen’s Achilles heel. By identifying small molecules that interfere with cargo delivery by the T4SS from two important human pathogens, Legionella pneumophila and Coxiella burnetii, our study represents the first step in our pursuit towards precision medicine by developing pathogen-selective therapeutics capable of treating the infections without causing harm to commensal bacteria.
Live cell biosensors based on the fluorescence lifetime of environment-sensing dyes
Authors: Mehl Brian P. , Li Li , Hinde Elizabeth , Liu Bei , MacNevin Christopher J. , Hsu Chia-Wen , Gratton Enrico , Hahn Klaus M.
Published: February 2022

Most biosensors used with fluorescence lifetime imaging (FLIM) have been based on fluorescence resonance energy transfer (FRET). Here we examined the capabilities of FLIM biosensors based on environment-sensing dyes. We screened merocyanine dyes to find an optimal combination of environment-induced FLIM changes, photostability and brightness at wavelengths suitable for live cell imaging. A biosensor reporting conformational changes of endogenous Cdc42 protein was tested in vitro and in live cells. In addition to the known advantages of FLIM (quantitation independent of photobleaching, intracellular biosensor distribution, and excitation intensity), the spectral properties of the merocyanine-FLIM biosensor (mcFLIM) provided enhanced sensitivity at low activation levels (<10%) where FRET is typically least sensitive. We leveraged these properties and the phasor representation of FLIM to determine the specific concentration of activated Cdc42 across the cell.