bluuebunny/crossref_metadata_2025 huggingface dataset:
Remodeling of cytoskeleton, chromatin, and gene expression during mechanical rejuvenation of aged human dermal fibroblasts
Authors: Sornapudi Trinadha Rao , Yuan Luezhen , Braunger Jana M. , Uhler Caroline , Shivashankar G.V.
Published: December 2024

Aging is associated with a progressive decline in cellular function. To reset the aged cellular phenotype, various reprogramming approaches, including mechanical routes, have been explored. However, the epigenetic mechanisms underlying cellular rejuvenation are poorly understood. Here, we studied the cytoskeletal, genome-wide chromatin and transcriptional changes in young, aged, and mechanically rejuvenated fibroblasts using immunofluorescence, RNA sequencing, and Hi-C experiments. The mechanically rejuvenated aged fibroblasts, that had partially reset their transcription to a younger cell state, showed a local reorganization of the interchromosomal contacts and lamina-associated domains. Interestingly, the observed chromatin reorganization correlated with the transcriptional changes. Immunofluorescence experiments in the rejuvenated state confirmed increased actomyosin contractility like younger fibroblasts. In addition, the rejuvenated contractile properties were maintained over multiple cell passages. Overall, our results give an overview of how changes in the cytoskeleton, chromatin, and gene activity are connected to aging and rejuvenation.
Impact of working memory training on brain network plasticity and genetic associations: insights from individual differences
Authors: Wu Hang , Chen Xiongying , Li Yinlong , Zhao Wan , Zhang Bofan , Luo Caiying , Zhang Xinyue , Shi Jing , Zhang Qiumei , Li Gao , Li Jun
Published: December 2024

Considerable individual differences in learning ability have long been recognized, yet cognitive learning studies traditionally emphasized group averages while overlooking individual differences. We conducted intersubject similarity of functional connectivity analysis on a month-long randomized controlled trial dataset. Subjects in the training group, together with an additional 66 subjects undergoing the same training, were included to examine the correlations between intersubject similarity of functional connectivity and the intersubject similarity of single nucleotide polymorphisms related to mental disorders (schizophrenia, attention-deficient hyperactivity disorder, and autism spectrum disorder). We also used the Allen Human Brain Atlas to investigate genetic correlations at the gene expression level. Training increased the intersubject similarity of functional connectivity of some brain networks (especially the limbic network–frontoparietal network) across the resting and task states. Furthermore, the change in the intersubject similarity of functional connectivity of the limbic network–frontoparietal network after training seems to have a different genetic basis from its intersubject similarity of functional connectivity at baseline. Allen Human Brain Atlas analysis on the limbic network–frontoparietal network indicated correlations at baseline functional connectivity weights functional connectivity. Working memory training resulted in specific brain changes that differed among individuals, which may be partially due to genetics, especially concerning single nucleotide polymorphisms related to schizophrenia. Our findings emphasize the need to consider individual genetic backgrounds in personalized cognitive training.
Forest fires in cool-temperate and humid-continental forests—an overview
Authors: Ewald Michael , Conedera Marco , Stavros E Nathasha , Fassnacht Fabian Ewald
Published: December 2024

Rising temperatures and an expected increase in the frequency of droughts and heat waves have raised concerns about forest fires in cool-temperate and humid-continental regions. This concern is accompanied by a lack of detailed knowledge of fire behaviour and fire ecology in many of these regions. A special issue ‘Forest fires in cool-temperate and humid-continental forests’ was launched in early 2022 in Forestry to collect studies that address existing knowledge gaps. The featured research papers cover several topics related to remotely-sensed and field-based fuel assessment, flammability of forest fuels, fire behaviour, and fire effects. In this article, we provide an overview of the research papers and their main findings. Based on the results of the special issue and a review of recent literature, we identified major directions for future research that address fire behaviour, fuel characteristics and post-fire forest management.
Withdrawal Signs and Symptoms Among Patients Positive for Fentanyl With and Without Xylazine
Authors: Alexander Ryan , Agwuncha Chinelo , Wilson Christopher , Schrecker Joshua , Holt Andrew , Heltsley Rebecca
Published: December 2024

Background

Xylazine is not approved for human use, yet it has emerged as a common adulterant of illicit fentanyl. It is currently unclear whether there is a withdrawal syndrome associated with xylazine and the potential impact of fentanyl coexposure.

Methods

A retrospective cohort study of patients with opioid use disorder admitted to an inpatient medically monitored withdrawal facility was performed. Patients positive for fentanyl were compared to patients copositive for fentanyl and xylazine. Outcomes were self-directed discharge and completion of treatment. Independent variables included Clinical Opioid Withdrawal Scale (COWS) scores, heart rate, and blood pressure. Associations between individuals with or without xylazine were measured.

Results

Among 71 patients admitted for opioid withdrawal management positive for fentanyl, 51.4% were copositive with xylazine. There was no difference detected in average COWS scores (P = 0.12–0.78) or average heart rate (P = 0.33–0.80) between groups. Xylazine copositive patients had higher average systolic blood pressure on days 1 (129.0 vs 123.0, P = 0.01) and 2 (127.9 vs 116.3, P = 0.04) although unclear if clinically meaningful. Individuals copositive for xylazine were less likely to complete treatment (43.2% vs 55.9%, P = 0.23) and more likely to have self-directed discharge (67.6% vs 44.1%; OR, 2.64; 95% CI, 1.0–6.9) although not statistically significant.

Conclusions

Among 71 patients admitted for medically monitored withdrawal, individuals who were copositive for xylazine at the time of admission had higher average blood pressure and were more likely to have a self-directed discharge. Additional research is needed to determine the impact of xylazine on withdrawal.
A Comprehensive Exploration of Digital Twinning in Spine Surgery
Authors: Lomax Nija , Vinjamuri Shreya , Vinjamuri Sthavir , Franco Daniel , Schroeder Gregory , Harrop James
Published: December 2024

One recent innovation in the health care landscape is the integration of Digital Twin (DT) in the field of spine surgery. DT, first used in 2002 is defined as the replication of physical entities in a virtual environment. It has emerged as a transformative tool for optimizing complex systems. In this review, we delve into the intersection of DT and spine surgery, exploring how this symbiotic relationship is reshaping precision medicine. By creating virtual replicas of the spine and its intricate neural networks, surgeons gain insights into personalized patient care, preoperative planning, and postoperative analysis. This exploration tackles the potential impact of DT on neurosurgical procedures, emphasizing its role in enhancing surgical precision, improving patient outcomes, and pushing the boundaries of innovation in modern health care.
Self-Expandable Versus Balloon-Expandable Transcatheter Aortic Valve Replacement for Treatment of Patients With Small Aortic Annulus: An Updated Meta-Analysis of Reconstructed Individual Patient Data
Authors: Khalefa Basma Badrawy , Yassin Mazen Negmeldin Aly , Gonnah Ahmed R. , Elkasaby Mohamed Hamouda , Hasan Mohammed Tarek , Altobaishat Obieda , Bani-Salame Abdallah , Rashed Mohamed Abdalla , Mansour Mohamed Ahmed , Al Hennawi Hussam , Roberts David Hesketh
Published: December 2024

Transcatheter aortic valve replacement has emerged as an effective alternative to surgery in selected patients with aortic stenosis. It needs to be made clear which type of valve has better results in patients with small aortic annulus. We searched PubMed, Scopus, Embase, Cochrane Library, and Web of Science, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A total of 27 articles were included, including 10,378 patients [5989 in balloon-expanding valve (BEV) and 4389 in the self-expanding valve (SEV) groups] with small aortic annulus. Our meta-analysis demonstrated no significant difference between SEVs and BEVs for 1-year all-cause mortality. There was a statistically significant increased risk of permanent pacemaker implantation (PPI) within 30 days and ischemic stroke at 1 year with SEVs [risk ratio (RR) = 1.69, 95% confidence interval (CI) = 1.18–2.42, P < 0.01, and RR = 1.83, 95% CI = 1.03–3.26, P = 0.04, respectively]. Our meta-analysis showed that SEVs are favored over BEVs in terms of 1-year change from baseline in effective orifice area (mean difference = 0.45, 95% CI = 0.19–0.71, P < 0.01). Moreover, after 1-year follow-up, severe patient-prosthesis mismatch was significantly lower in the SEV group (RR = 0.24, 95% CI = 0.11–0.53, P < 0.01). In conclusion, SEVs were associated with better echocardiographic outcomes from baseline. Patients with SEVs were more likely to develop stroke and require PPI but were less likely to have patient-prosthesis mismatch. The benefit of a larger effective aortic valve area with SEVs has to be balanced against higher PPI and stroke rates.
Assessing Professional Behaviors of Physician Assistant Students in Objective Structured Clinical Examinations: A Scoping Review
Authors: Francis Erika R. , Sapre Kimberly
Published: December 2024

Introduction

Professionalism in physician assistant (PA) students is an essential behavior to assess during formative medical education. Objective structured clinical examinations (OSCEs) provide an opportunity to evaluate PA students performing professional behaviors within simulated clinical settings. This scoping review aims to explore insights the existing literature offers regarding evaluating the professional behaviors of PA students using an OSCE. A secondary objective is to identify gaps in the literature to clarify future research.

Methods

This scoping review was conducted in March 2024. From January 2018 until March 2024, CINAHL, MEDLINE Ultimate, Health Source—Nursing/Education, and PubMed online databases were searched for publications in English. Records included research studying PA or medical students evaluated on professional behaviors using an OSCE or performance-based assessment instrument. Allied health profession students were excluded from the primary search because of their heterogeneous curriculum models outside the population of interest.

Results

This review includes 5 papers. All papers reported communication as a professional behavior measured in an OSCE or performance-based assessment. A consensus or formal definition of professional behavior is a notable absence in this scoping review.

Discussion

More definitive homogenous evidence is needed to assess the professional behaviors of PA students using an OSCE. This limits the guidance and educational standards for future health profession educators. Comprehensive research into professional behaviors among PA students is essential. Scholars must publish their findings on professionalism curriculum design and outcomes to facilitate a broader understanding and improvement in educating future PA professionals.
Disparities among Different Countries in Access for Diagnosis and Treatment of Pediatric Sensorineural Hearing Loss
Authors: DeVries Jacquelyn , Birman Catherine S. , Loundon Natalie , MacAskil Melissa , Távora Nathália Manhães , Tsuji Robinson Koji , Cheung Linea , Kari Elina , Carvalho Daniela
Published: December 2024

Objective

Timely diagnosis and management of pediatric sensorineural hearing loss (SNHL) is essential for best outcomes. This study evaluated the differences of health access among cochlear implant (CI) centers of countries with different health care systems.

Study Design

Retrospective.

Setting

Multicenter, tertiary pediatric CI referral center in four different countries: United States (USA), France (FR), Australia (AUS), and Brazil (BR).

Patients

Pediatric (age 0–21 years (0–16 years AUS)) patients receiving CI between January 2017 and December 2019.

Intervention(s)

CI.

Main Outcome Measure(s)

Primary outcome measures included age at milestones in CI process and age at implantation.

Results

There were 1,673 patients who underwent CI surgery at four multinational designated institutions were identified (n = 143 AUS; 153 BRA; 1,158 FR; and 219 USA). Median age at time of hearing loss diagnosis (p < 0.0001), median age at hearing aid (HA) fitting (p < 0.0001), and CI evaluation (p < 0.0001) differed between countries. However, age at CI surgery was not significantly different between countries. Time from diagnosis to HA fitting was impacted by country (p < 0.0001) and language (p = 0.01) but not by private compared with public insurance. There were 512 children with available data regarding onset of hearing loss as prelingual n = 358 (70%) and postlingual n = 154 (30%). In patients with prelingual severe to profound hearing loss, country and race/ethnic origin affected age at diagnosis (p < 0.0001, p = 0.001), HA fitting (p < 0.0001, p < 0.001), candidacy evaluation (p = 0.0001, p = 0.02), and CI surgery (p = 0.0027, p = 0.001).

Conclusions

Age at pediatric CI was comparable across the CI centers compared in the four countries. This is encouraging given the effect of neuroplasticity on pediatric CI outcomes, despite different health care expenditures and delivery systems in the four countries. Improvement in care access for certain populations may decrease disparities in pediatric CI access worldwide.
Individual- and Community-Level Social Determinant Associations With Acoustic Neuroma Disparities in the United States
Authors: Fei-Zhang David J. , Sethia Rishabh , Abrahamson Cyrus W. , Sosnoski Olivia K. , Sheyn Anthony M. , D'Souza Jill N. , Chelius Daniel C. , Rastatter Jeffrey C.
Published: December 2024

Objective

This investigation aims to determine whether community-level social determinants of health (SDoH) influenced acoustic neuroma outcomes more profoundly than individual-level SDoH through the use of multivariate models and census-level socioeconomic status (SES) measures.

Study Design

Observational, retrospective cohort study. Setting: Specially Authorized Head–Neck SEER 2020 Dataset.

Patients

23,330 adult (20+ yr) patients diagnosed with acoustic neuroma from 2010 to 2018.

Main outcome measures

Age-adjusted multivariate regressions and hazard models were performed for individual level (sex, race–ethnicity) and community-level factors (Yost Index–SES, rurality–urbanicity) to assess for differences in acoustic neuroma treatment, including delay of intervention, treatment receipt, and overall survival.

Results

Lower Yost–SES/community-level SES had a markedly positive association with an increase in all-cause mortality (HR, 1.55; 95% CI, 1.41–1.71) and negative association with stereotactic radiotherapy treatment (OR, 0.93; 95% CI, 0.86–0.99; p = 0.040). Patients with poor Yost–SES had a significantly positive association with receipt of surgical resection (OR, 1.13; 95% CI, 1.07–1.20; p < 0.001).

Conclusions

Data generated from this investigation suggest that community-level SDoH, particularly Yost–SES, have more detrimental care and prognostic disparities in acoustic neuroma treatment compared with individual-level factors.
Advance Directives for Adolescents and Young Adults Living With Neuromuscular Disease
Authors: Battista Vanessa , Baker Deborah J. , Trimarchi Tara , Stoney Sarah , D'Aoust Rita
Published: December 2024

The literature shows that adolescents and young adults (AYAs) living with neuromuscular disease want to have discussions about goals of care and want them sooner. Conversations about goals of care and advance directives are not common practice in the neuromuscular clinic setting. This nurse practitioner–led project used a conversation tool as a 1-time intervention to guide conversations about participants' goals and wishes, comparing the number of participants with advance directives before and after the use of the intervention, and their satisfaction with having had a conversation about goals of care using this tool was measured. A total of 14 AYAs with genetically confirmed neuromuscular disease were enrolled in this project. There was a 92.9% increase in the number of AYAs with an advance directive demonstrating clinical meaningfulness. Most project participants were either quite a bit satisfied (21.4%) or very much satisfied (57.1%) with having used the intervention to discuss goals of care. This quality improvement project demonstrated that, if asked, AYAs with neuromuscular disease willingly agreed to discuss their goals of care and found satisfaction in using the intervention to complete an advance directive. Advanced Practice Registered Nurses should consider systematic processes to include these discussions as a part of routine practice.
Internal Jugular Vein Fenestration and Duplication
Authors: Triantafyllou George , Vassiou Katerina , Olewnik Łukasz , Duparc Fabrice , Tsakotos George , Vlychou Marianna , Zielinska Nicol , Piagkou Maria
Published: December 2024

The internal jugular vein (IJV) is considered one of the prominent veins of the neck. It corresponds to the continuation of the sigmoid sinus and joins the subclavian vein to form the brachiocephalic vein. A retrospective study of 200 computed tomography angiographies was performed at the Larissa University Hospital Radiology Department, where the IJV variant morphology was investigated. Three unilateral cases of IJV duplication were observed (0.75%) in three patients (2 on the left and 1 on the right side). One case of IJV fenestration was identified (0.25%) in one patient on the left side. IJV duplication and fenestration are rare aberrations reported in several case reports, while their incidence has been barely reported. Knowledge of IJV variant anatomy (common and uncommon morphological variants) is paramount for head and neck surgeons and anesthesiologists to avoid iatrogenic injury.
The emergence of nonlinear evolutionary trade-offs and the maintenance of genetic polymorphisms
Authors: Hulse Samuel V. , Bruns Emily L.
Published: December 2024

Evolutionary models of quantitative traits often assume trade-offs between beneficial and detrimental traits, requiring modellers to specify a function linking trait values. The choice of trade-off function can be consequential; functions that assume diminishing returns (accelerating costs) typically lead to single equilibrium genotypes, while decelerating costs often lead to genetic polymorphisms. Despite their importance, our current theory has little to say on which trade-off functions are the most biologically plausible. To address this gap, we explored how the genetic determination of quantitative traits can lead to different trade-off functions, using resistance to infectious diseases as an example trait. We developed a model where alleles at separate loci pleiotropically increase resistance while decreasing fecundity. We then used this model to generate genotype landscapes and investigate how epistasis effects the trade-off function. Regardless of the strength of epistasis, our model consistently led to accelerating costs. We then incorporated our genotype model into an eco-evolutionary model of disease resistance. Unlike other models with accelerating costs, our approach often led to genetic polymorphisms. Our results suggest that accelerating costs are a strong null model for evolutionary trade-offs and that the eco-evolutionary conditions required for polymorphism may be more nuanced than previously thought.
Collective movement increases initial accuracy and path efficiency in talitrid amphipod orientation
Authors: Phillips Magdalena L. , Granger Jesse N. , Johnsen Sönke
Published: December 2024

Talitrid amphipods are an extensively studied system for navigation due to their robust ability to navigate back to the optimal burrowing zone after foraging and could be a model system in which to study the impacts of collective behaviour on short-distance navigation and orientation. We investigated whether talitrid amphipods (
Megalorchestia pugettensis
) differ in their orientation abilities when released individually versus in a group. When released individually, the amphipods took longer to start moving (
p
< 0.001), travelled longer paths (
p
= 0.003), moved faster (
p
= 0.016), had a different initial bearing (
p
= 0.003) and exhibited more spread in their initial bearing (
p
= 0.009) than when released in groups. There was no difference between individuals and groups in terms of their trial time nor in the direction or spread of their final orientation. This study introduces a tractable, invertebrate species in which to study the impacts of collective movement and reveals previously unexamined differences in orientation abilities for talitrid amphipods released independently versus in a group that have implications for experimental design in this system.
Soft tissue can absorb surprising amounts of energy during knee exoskeleton use
Authors: Barrutia W. Sebastian , Yumiceva Ada , Thompson Mai-Ly , Ferris Daniel P.
Published: December 2024

Soft tissue at the human–exoskeleton interface can deform under load to absorb, return and dissipate the mechanical energy generated by the exoskeleton. These soft tissue effects are often not accounted for and may mislead researchers on the actual joint assistance an exoskeleton provides. We assessed the effects of soft tissue by quantifying the performance and energy distribution of a knee exoskeleton under different assistance strategies using a synthetic lower limb phantom. The phantom emulated knee kinematics and soft tissue deformation at the exoskeleton interface. We loaded the exoskeleton on the phantom under six different spring stiffness conditions. Motion capture marker and load cell data from the phantom–exoskeleton assembly allowed us to estimate the moments, stiffness and energy contributions of the exoskeleton and physical interface. We found that soft tissue caused interface power to increase and exoskeleton power to decrease with increasing spring stiffness. Despite similar joint kinematics, our findings show that increasing exoskeleton assistance did not notably change power transfer to the targeted joint, as soft tissue compressed under high forces. Our methodology improves exoskeleton design process by estimating energy distribution and transfer for exoskeletons while accounting for the effects of soft tissue deformation before human testing.
A global cross-cultural analysis of string figures reveals evidence of deep transmission and innovation
Authors: Kaaronen Roope O. , Walsh Matthew J. , Henrich Allison K. , Wisher Isobel , Miu Elena , Manninen Mikael A. , Eronen Jussi T. , Riede Felix
Published: December 2024

Few cultural practices beyond language are as widespread as string figure games. Their global distribution and potential to yield insights into cultural transmission and cognition have long been noted. Yet, it remains unknown how or when this behaviour originated and to what extent shared motifs are signals of repeated innovations or deep cultural transmission. Here, we combined a global cross-cultural inventory of string figures with a novel methodology based on knot theory, which enables the unequivocal numerical coding of string figures. We performed a computational analysis of a sample of 826 figures from 92 societies around the world. Across these societies, we found 83 recurring string figure designs, some of which are regionally restricted while others display a global distribution. The cognitively opaque nature of string figure designs and their clear geographic distribution reveal processes of cultural transmission, innovation, and convergent evolution. Most strikingly, the global distribution of some figures raises the possibility of shared ancient origins.
A hybrid tau-leap for simulating chemical kinetics with applications to parameter estimation
Authors: Trigo Trindade Thomas , Zygalakis Konstantinos C.
Published: December 2024

We consider the problem of efficiently simulating stochastic models of chemical kinetics. The Gillespie stochastic simulation algorithm (SSA) is often used to simulate these models; however, in many scenarios of interest, the computational cost quickly becomes prohibitive. This is further exacerbated in the Bayesian inference context when estimating parameters of chemical models, as the intractability of the likelihood requires multiple simulations of the underlying system. To deal with issues of computational complexity in this paper, we propose a novel hybrid τ-leap algorithm for simulating well-mixed chemical systems. In particular, the algorithm uses τ-leap when appropriate (high population densities), and SSA when necessary (low population densities, when discrete effects become non-negligible). In the intermediate regime, a combination of the two methods, which uses the properties of the underlying Poisson formulation, is employed. As illustrated through a number of numerical experiments, the hybrid τ offers significant computational savings when compared with SSA without, however, sacrificing the overall accuracy. This feature is particularly welcomed in the Bayesian inference context, as it allows for parameter estimation of stochastic chemical kinetics at reduced computational cost.
Seasonal diversity, daily use and behaviour of birds using a green roof in a Mediterranean city
Authors: Luna Álvaro , Blanch Estel
Published: December 2024

Urban green roofs offer environmental and social benefits and provide resources for urban wildlife; however, how birds use green roofs remains poorly studied in Mediterranean cities. Here, we develop a 1-year study in Madrid, Spain, recording the birds that use both an urban green roof and the adjacent conventional roofs throughout the four seasons. We recorded a total of 17 bird species in the area, of which 8 use the green roof surveyed. The most common species detected in both types of roofs was the feral pigeon (
Columba livia
), which exploited the green roof permanently, in contrast with the other species observed, which only appeared occasionally. We also found that more species visited the green roof in the central hours of the day and a higher richness of species in the spring. Moreover, we detect that most of the species were residents all year in the area and have granivorous or granivorous–omnivorous feeding habits. The main behaviour observed in the green roof was feeding, while no reproduction of any species was confirmed. We conclude that green roofs offer birds much-needed resources in metropolitan areas, promoting greener, more connected and more biodiverse cities.
Self-dual electromagnetic fields
Authors: Lekner John
Published: December 2024

Self-dual electromagnetic fields are shown to be maximally chiral. Monochromatic self-dual beams have electric and magnetic fields that are eigenstates of curl. The chiral density and chiral current of self-dual monochromatic beams are proportional to the energy and momentum densities. Their energy and momentum densities do not oscillate in time. Self-dual pulses based on an oscillatory solution of the wave equation lack the oscillations of non-self-dual pulses based on the same wave function. All of these properties could be significant in physical applications, but few self-dual fields seem to have been studied experimentally.
A novel multiscale model for micro-structured electromagnetic media
Authors: Blanco P. J. , Pinheiro F. A. , Novotny A. A.
Published: December 2024

We present a novel multiscale formalism to characterize complex phenomena in electromagnetic media featuring micro-structures. By contrast to the conventional homogenization approaches, the proposed model is based on the variational framework given by the Method of Multiscale Virtual Power applied to Maxwell’s equations, which ensures energetic consistency between the macro- and micro-scales. From a set of well-defined minimal assumptions on the primal variables, the electromagnetic field and its curl, the formulation yields not only the micro-cell problem to be solved but also the homogenization formulae of the dual entities, as well as the homogenization of tangent operators that characterize, for instance, the effective electric permittivity and magnetic permeability. The proposed multiscale model is not restricted to periodic media, although it accounts for the periodicity assumption as a specific case. We apply the method in different cases of interest that range from low-frequency to high-frequency regimes to demonstrate the predictive and descriptive capabilities of the model in terms of effective electromagnetic properties.
Expanding the Stenotrophomonas maltophilia complex: phylogenomic insights, proposal of Stenotrophomonas forensis sp. nov. and reclassification of two Pseudomonas species
Authors: Nguyen Scott V. , Edwards Denise , Vaughn Eric L. , Escobar Vicktor , Ali Shahin , Doss Janis H. , Steyer Joel T. , Scott Sarah , Bchara Wadih , Bruns Nathan , Zelaya Elizabeth , Tran Anthony , Payne David , Hauser Jocelyn R.
Published: December 2024

A novel Stenotrophomonas species was isolated as a contaminant in viral transport media at the District of Columbia Department of Forensic Sciences Public Health Laboratory. Phylogenomic and biochemical analyses of the isolate determined that it represented a novel species within Stenotrophomonas. Related strains in public genome databases suggested that this novel species is associated with clinically acquired infections, similar to closely related Stenotrophomonas maltophilia. The name Stenotrophomonas forensis sp. nov. is proposed. Comparative genomic and phylogenetic analyses of the S. maltophilia complex reveal that Stenotrophomonas africana is an independent species and is not a later heterotypic synonym of S. maltophilia. We also propose the transfer of two misclassified Pseudomonas species into Stenotrophomonas as Stenotrophomonas beteli comb. nov. and Stenotrophomonas hibiscicola comb. nov. The type strain for S. forensis sp. nov. is DFS-20110405T (=ATCC TSD-272T=NCTC 14893T).
Comparison of the bacterial microbiome in the pharynx and nasal cavity of persistent, intermittent carriers and non-carriers of Staphylococcus aureus
Authors: González-García Samuel , Hamdan-Partida Aida , Pérez-Ramos Julia , Aguirre-Garrido José Félix , Bustos-Hamdan Anaíd , Bustos-Martínez Jaime
Published: December 2024

Introduction.
Staphylococcus aureus is a bacterium that colonizes various human sites. The pharynx has been considered as a site of little clinical relevance and little studied. Recently, it has been reported that S. aureus can colonize more the pharynx than the nose. In addition, S. aureus can persist in these sites for prolonged periods of time.

Hypothesis. The composition of the pharyngeal and nasal microbiome will differ between persistent, intermittent carriers and non-carriers of S. aureus.

Aim. Determine whether the pharyngeal and nasal microbiome is different between carriers and non-carriers of S. aureus.

Methodology.
S. aureus carriers were monitored by means of pharyngeal and nasal exudates of apparently healthy adult university students for 3 months. Samples from individuals of the same carrier type were pooled, and DNA was extracted and the 16S rRNA was sequenced. The sequences were analysed in MOTHUR v.1.48.0 software, by analysing the percentages of relative abundance in the STAMP 2.1.3 program, in addition to the predictive analysis of metabolic pathways in PICRUSt2.

Results. A greater colonization of S. aureus was found in the pharynx than in the nose. The microbiomes of S. aureus carriers and non-carriers do not show significant differences. The main microbiome difference found was between pharyngeal and nasal microbiomes. No significant differences were found in the abundance of the genus Staphylococcus in pharyngeal and nasal S. aureus carriers and non-carriers. The nasal microbiome was found to have more variation compared to the pharyngeal microbiome, which appears to be more stable between individuals and pools. Predictive analysis of metabolic pathways showed a greater presence of Staphylococcus-associated pathways in the nose than in the pharynx.

Conclusion.
S. aureus can colonize and persist in the pharynx in equal or greater proportion than in the nose. No statistically significant differences were found in the microbiome of the pharyngeal and nasal carriers and non-carriers of S. aureus, but the pharyngeal and nasal microbiomes are different independent of the type of S. aureus carrier or non-carrier. Therefore, the microbiome apparently does not influence the persistence of S. aureus.
Susceptibility of Gram-negative bacteria from blood cultures assessed by a rapid antimicrobial susceptibility assay, the VITEK® Reveal™: a preliminary study
Authors: Bonetti Cristina , Radaelli Giovanni Mario , De Francesco Maria Antonia
Published: December 2024

The timely administration of the effective therapy is an important factor for the favourable outcome of patients with sepsis. In this study, we evaluated a new rapid antimicrobial susceptibility testing (AST) method, the Vitek®Reveal™ system, to determine the antibiotic susceptibility of 44 Gram-negative bacteria randomly isolated from blood. The results show a mean turnaround time of 5.42 h. The overall agreement with the reference method was >90%, except for piperacillin/tazobactam and cefepime (90.4%). The study, therefore, suggests that the assay decreases the time for obtaining AST with the potential to have a positive impact on patient care. However, further studies are needed to extend and confirm these preliminary findings, particularly the assay performance for some drugs and eventually for Gram-positive micro-organisms.
Influence of mould growth and outdoor exposure on the efficacy of attractive targeted sugar baits in western kenya
Authors: Yalla Nick , Kosgei Jackline , Mechan Frank , McDermott Daniel P. , Polo Brian , Omondi Seline , Omukunda Elizabeth , Ochomo Eric
Published: December 2024

Introduction

Attractive targeted sugar baits (ATSBs) are effective againstAnophelesmosquitoes in semiarid climates with low humidity. High humidity, however, promotes growth of moulds on the surface of ATSBs. The impact of mould on ATSB efficacy against malaria vectors remains unknown. This study explored how mould growth affects the performance of ATSB version 1.2 by comparing mouldy stations from exposed environments to non-mouldy stations from protected settings through laboratory bioassays with the local malaria vector,Anopheles arabiensis.

Methods

One hundred ATSB stations were deployed in Asembo, Rarieda-Subcounty, Siaya County, with six samples (three mouldy from exposed locations and three non-mouldy from protected locations) collected monthly for laboratory bioassays. These were tested alongside three new laboratory-kept ATSBs and two negative controls (water only and 77% sugar solution with water) to assess mosquito feeding and mortality over 48 hours.

Results

This study found that after 12 months of outdoor exposure, the mouldiest ATSBs from exposed locations showed a non-significant reduction inAnopheles arabiensisfeeding rates compared to the least mouldy ATSBs from protected locations 57.42% (95% CI: 45.64-68.85) vs. 74.40% (95% CI: 64.56-82.50), respectively (P =0.062). Mosquito mortality significantly declined on mouldy ATSBs compared to laboratory controls (95% CI: 92.23-97.48) vs. 98.70% (95% CI: 97.87-99.30) respectively (P = 0.002). In contrast, protected (non-mouldy) ATSBs showed only a slight reduction in mortality compared to controls 95.94% (95% CI: 90.42-97.46) vs. 98.91% (95% CI: 97.67-99.60) respectively (P = 0.009).

Conclusion

This study provides evidence that environmental exposure post-deployment slightly reduced the efficacy of ATSBs in controllingAnopheles arabiensis, particularly beyond the recommended 6-month period. Although mould may have contributed to this reduction over 12 months, no significant difference was found between mouldy and non-mouldy ATSBs. However, mould invasion and community concerns highlight the need to replace mouldy stations to maintain effectiveness and safety.
Leukemia-mutated proteins PHF6 and PHIP form a chromatin complex that represses acute myeloid leukemia stemness
Authors: Pawar Aishwarya S. , Somers Patrick , Alex Aleena , George Subin S. , Antony Charles , Verner Roman , White-Brown Sanese K. , Khera Mohit , Mendoza-Figueroa María Saraí , Liu Kathy Fange , Morrissette Jennifer J. D. , Paralkar Vikram R.
Published: December 2024

Myeloid leukemias are heterogeneous cancers with diverse mutations, sometimes in genes with unclear roles and unknown functional partners. PHF6 and PHIP are two poorly-understood chromatin-binding proteins recurrently mutated in acute myeloid leukemia (AML).PHF6mutations are associated with poorer outcomes, whilePHIPwas recently identified as the most common selective mutation in Black patients in AML. Here, we show that PHF6 is a transcriptional repressor that suppresses a stemness gene network, and that PHF6 missense mutations, classified by current clinical algorithms as variants of unknown significance, produce unstable or non-functional protein. We present multiple lines of evidence converging on a critical mechanistic connection between PHF6 and PHIP. We show that PHIP loss phenocopies PHF6 loss, and that PHF6 requires PHIP to occupy chromatin and exert its downstream transcriptional program. Our work unifies PHF6 and PHIP, two disparate leukemia-mutated proteins, into a common functional complex that suppresses AML stemness.
Single-cell spatial atlas of high-grade serous ovarian cancer unveils MHC class II as a key driver of spatial tumor ecosystems and clinical outcomes
Authors: Perez-Villatoro Fernando , van Wagensveld Lilian , Shabanova Aleksandra , Junquera Ada , Kang Ziqi , Niemiec Iga , Falco Matias M , Anttila Ella , Casado Julia , Marcus Eric , Kahelin Essi , Chamchougia Foteini , Salko Matilda , Shah Saundarya , Russo Salvatore , Chiaro Jacopo , Grönholm Mikaela , Sonke Gabe S. , Van de Vijver Koen K. , Kruitwagen Rutgerus FPM , Avan der Aa Maaike , Virtanen Anni , Cerullo Vincenzo , Vähärautio Anna , Sorger Peter K. , Horlings Hugo M. , Färkkilä Anniina
Published: December 2024

The tumor microenvironment (TME) is a complex network of interactions between malignant and host cells, yet its orchestration in advanced high-grade serous ovarian carcinoma (HGSC) remains poorly understood. We present a comprehensive single-cell spatial atlas of 280 metastatic HGSCs, integrating high-dimensional imaging, genomics, and transcriptomics. Using 929 single-cell maps, we identify distinct spatial domains associated with phenotypically heterogeneous cellular compositions, and demonstrate that immune cell co-infiltration at the tumor-stroma interface significantly influences clinical outcomes. To uncover the key drivers of the tumor ecosystem, we developed CEFIIRA (Cell Feature Importance Identification by RAndom forest), which identified tumor cell-intrinsic MHC-II expression as a critical predictor of prolonged survival, independent of clinicomolecular profiles. Validation with external datasets confirmed that MHC-II-expressing cancer cells drive immune infiltration and orchestrate spatial tumor-immune interactions. Our atlas offers novel insights into immune surveillance mechanisms across HGSC clinicomolecular groups, paving the way for improved therapeutic strategies and patient stratification.
A universal of speech timing: Intonation units form low frequency rhythms and balance cross-linguistic syllable rate variability
Authors: Inbar Maya , Grossman Eitan , Landau Ayelet N.
Published: December 2024

Intonation units (IUs) are a universal building-block of human speech. They are found cross-linguistically and are tied to important language functions such as the pacing of information in discourse and swift turn-taking. We study the rate of IUs in 48 languages from every continent and from 27 distinct language families. Using a novel analytic method to annotate natural speech recordings, we identify a low-frequency rate of IUs across the sample, with a peak at 0.6 Hz, and little variation between sexes or across the life span. We find that IU rate is only weakly related to speech rate quantified at the syllable level (SR), and crucially, that cross-linguistic variation in IU rate is smaller than cross-linguistic variation in SR. Since SR was shown to be inversely related to information density quantified at the syllable level, we suggest that across languages, IUs are more balanced than syllables in their information content.
Integrated Database of Force-Field Parameters, Experimental Measurements and Molecular Dynamics Simulations
Authors: Banáš Pavel , Mlýnský Vojtěch , Číž David , Furmánek Radek , Pilat Nestor , Pauw Viktoria , Hachinger Stephan , Šponer Jiří , Martinovič Jan , Otyepka Michal
Published: December 2024

Molecular Dynamic (MD) simulation is a vital theoretical tool for exploring nucleic acids (RNA, DNA), proteins and other (bio)molecular systems, generating vast amounts of data daily. Efficient storage and possible reuse of this data is a persistent challenge. Here, we introduce IDA (Integrated DAtabase of force fields and datasets from experiments and MD simulations), an innovative database scheme for datasets from various types of MD simulations. IDA supports outputs from different MD approaches, i.e., standard MD simulations, importance sampling techniques, simulated annealing, and other enhanced sampling methods including replica-exchange simulations. IDA also houses a collection of molecule-specific force fields (FFs) and experimental datasets. Uploaded MD outputs, FFs, and experimental data are integrated in a standardized format, allowing efficient data mining and extraction of valuable insights from the extensive data generated by diverse MD simulations. With the data and metadata holdings of IDA, and the prospective assignment of persistent identifiers, our work aims to make key steps towards making MD data FAIR (findable, accessible, interoperable, reusable).
An investigation of the effects of α and β-frequency neural entrainment using tACS on phase-aligned TMS-evoked corticospinal excitability
Authors: Gialopsou Aikaterini , Jackson Stephen R.
Published: December 2024

Deep brain stimulation [DBS] is an effective treatment for many brain disorders (e.g., Parkinson’s disease), has a favourable adverse effect profile, and can be particularly effective for individuals with treatment resistant symptoms. DBS is, however, inaccessible for most individuals, is extremely expensive, and is not considered suitable for children and adolescents. For these reasons, non-invasive alternatives to DBS, such as transcranial magnetic stimulation [TMS], are increasingly being sought to treat brain health conditions. Unfortunately, current TMS approaches exhibit large intra- and inter-subject variability in their efficacy, which limits their use clinically. One likely reason for this is that TMS is invariably delivered without reference to ongoing brain activity (i.e., open loop). We propose that the efficacy of stimulation might be improved, and the variability of its effects reduced, if stimulation could be synchronised with ongoing brain activity. To investigate this, we used transcranial alternating current stimulation (tACS) to induce entrainment of brain activity at two frequencies (α=10 Hz and β=20 Hz), and we delivered single pulse TMS that was temporally aligned with the phase of each tACS oscillation. To investigate the effects of tACS-phase-aligned TMS we measured motor-evoked potentials (MEPs). Our findings confirm that for α-tACS and β-tACS both corticospinal excitability and inter-trial variability varied as a function of tACS phase. Importantly, however, the tACS phase angle that produced maximum TMS-evoked excitability was different for α-tACS and β-tACS; coinciding with the negative peak (trough) for α-tACS and the positive peak (peak) for β-tACS. These findings confirm that aligning non-invasive brain stimulation to ongoing brain activity may increase the efficacy of TMS and reduce the variability of its effects. However, our results illustrate that the optimal phase of the tACS cycle at which to deliver TMS may vary for different tACS frequencies.
Plant electrophysiological reactions to specific environmental conditions
Authors: Wilkening Soren H.P.
Published: December 2024

Plant cells exhibit as much electrical activity as aninmal cells but the nature of these electrical variations is not always well understood, especially at the organism level. Damaging a plant, transitions from darkness to light and back, mechanical shocks, temperature shocks and pathogen attacks have been shown to elecit changes in plant electrical patterns at the organism level under laboratory conditions, but plant electrical behavior in the wild is comparatively less well studied. Here we show that by using simple extracellular voltage measurements across a number of wild plant species it is possible to identify associations between very specific environmental conditions and patterns of electrical variation on the scale of seconds to hours in the plants exposed to them. This work has potential applications in using plants as environmental sensors.
Differential transcriptional activity of ΔNp63β is encoded by an isoform-specific C-terminus
Authors: McCann Abby A. , Sammons Morgan A.
Published: December 2024

p63 is a clinically-relevant transcription factor heavily involved in development and disease. Mutations in the p63 DNA-binding domain lead to severe developmental defects and overexpression of p63 plays a role in the progression of epithelial-associated cancers. Unraveling the specific biochemical mechanisms underlying these phenotypes is made challenging by the presence of multiple p63 isoforms and their shared and unique contributions to development and disease. Here, we explore the function of the p63 isoforms ΔNp63ɑ and ΔNp63β to determine the contribution of C-terminal splice variants on known and unique molecular and biochemical activities. Using RNA-seq and ChIP-seq on isoform-specific cell lines, we show that ΔNp63β regulates both canonical ΔNp63ɑ targets and a unique set of genes with varying biological functions. We demonstrate that the majority of genomic binding sites are shared, however the enhancer-associated histone modification H3K27ac is highly enriched at ΔNp63β binding sites relative to ΔNp63ɑ. An array of ΔNp63β C-terminal mutants demonstrates the importance of isoform-specific C-terminal domains in regulating these unique activities. Our results provide novel insight into differential activities of p63 C-terminal isoforms and suggest future directions for dissecting the functional relevance of these and other transcription factor isoforms in development and disease.