bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Nurse Residency Program on Time-to-Fill Nurse Vacancies at the Veterans Health Administration
Authors: Li Yufei , Legler Aaron , Kabdiyeva Aigerim , Nguyen PhiYen , Garrido Melissa , Pizer Steven
Published: July 2024

Background:

The Department of Veterans Affairs (VA) offers a 1-year Post-Baccalaureate-Registered Nurse Residency (PB-RNR) Program. The impact of the PB-RNR program on local RN recruitment was unknown.

Objectives:

We aimed to evaluate the effect of the size of the PB-RNR program at a VA facility on its time-to-fill RN vacancies.

Project Design:

We used an instrumental variable approach with a 2-stage residual inclusion specification.

Subjects:

We included RN filled vacancies in the VA that were posted nationwide between 2020 and 2021.

Measures:

Our independent variable was the facility-year level number of PB-RNR program allocations. The 3 binary outcomes were whether the RN vacancy was filled within 90, 60, or 30 days.

Results:

An increase of one training allocation was significantly associated with a 5.60 percentage point (PP) (95% CI: 2.74–8.46) higher likelihood of filling a vacancy within 90 days, 7.34 PP (95% CI: 4.66–10.03) higher likelihood of filling a vacancy within 60 days, and 5.32 PP (95% CI: 3.18–7.46) higher likelihood of filling a vacancy within 30 days. The impact was significant in both 2020 and 2021 positions, and in facilities located in areas with lower social deprivation scores, higher-quality public schools, or with either no or partial primary care physician shortages.

Conclusions:

We found favorable impacts of the size of the PB-RNR program at a VA facility on filling RN vacancies.
Practices of Physical Therapists Who Assist People With Cerebral Palsy in Brazil: A National Survey
Authors: Furtado Michelle Alexandrina Dos Santos , Longo Egmar , Campos Ana Carolina de , Silva Maiara Aparecida Tino da , Silva Ana Clara de Carvalho , Ayupe Kênnea Martins Almeida , Camargos Ana Cristina Resende , Leite Hércules Ribeiro
Published: July 2024

Purpose:

To describe the practices of pediatric physical therapists (PTs) working with children and adolescents with cerebral palsy (CP) in Brazil.

Methods:

PTs working with children and adolescents with CP were invited to participate via social media and email campaigns to complete an online survey containing 46 questions.

Results:

In total, 373 PTs participated. Most PTs reported searching in scientific databases (96.8%) and on social media (71%). The main barrier to information reported was limited access to full-text articles (44%). Among the PTs, 58.4% and 84% reported using the International Classification of Functioning, Disability and Health (ICF) and family centered practice models, respectively. Regarding tools and interventions, there was little focus on the domains of contextual factors and participation.

Conclusions:

This survey points to some important advances. However, strategies are still needed to promote knowledge translation and evidence-based practices among pediatric PTs in Brazil.
Functional Symmetry Observation Scale, Version 2: Reliability, Construct Validity, and Potential for Clinical Use
Authors: Rahlin Mary , Sarmiento Bernadette
Published: July 2024

Purpose:

To examine the intrarater and interrater reliability and construct validity of the Functional Symmetry Observation Scale, Version 2 (FSOS-V2) in infants with congenital muscular torticollis (CMT).

Methods:

The FSOS-V2 is a video-based measure of postural and movement symmetry in infants with CMT. Four examiners scored 50 participants’ videos twice. Scores obtained by the same rater and across 4 raters were compared to examine intrarater and interrater reliability, respectively. Participants’ habitual head deviation from midline in supine photographs was measured using a protractor. Relationship between the head tilt angles and FSOS-V2 scores was examined to assess construct validity.

Results:

Fifty infants with CMT, age range 1 to 16 months, participated. Results indicated moderate to good intrarater and poor to moderate interrater reliability. The FSOS-V2 construct validity was supported.

Conclusion:

The FSOS-V2 can be used by the same therapist repeatedly to make clinical decisions. Further research will strengthen its psychometric properties.
Impact of Cognitive Intervention on Neurocognitive Development of Schoolchildren Exposed to Lead in a Semi-Urban Community in Mexico
Authors: Cortez-Lugo Marlene , Huanca-Laura Lizeth Ximena , Hernández-Bonilla David , Alamo-Hernández Urinda , Montes Sergio , García-Feregrino Raquel , Velázquez Sara , Tristán-López Luis Antonio
Published: July 2024

Lead exposure is a severe public health issue that can adversely affect children’s neurocognitive development. A semi-urban community in Mexico has been exposed to lead from food cooked in glazed clay pots. A cognitive intervention was conducted from 2015 to 2016 to minimize this negative impact. This intervention aimed to improve the neurocognitive development of the affected children.

Methods

A quasi-experimental study with a control group was conducted in children aged 7 to 12 years from 2 communities in Morelos, Mexico. Blood lead levels were determined, and the neurocognitive function was assessed pre- and postintervention with the Wechsler Intelligence Scale for Children and Children’s Auditory Verbal Learning Test-2. A cognitive intervention was conducted at the school. The difference-in-differences method adjusted for variables known as priori and evaluated the impact of cognitive intervention.

Results

The differences-in-differences models indicated a significant average increase in scores on the Verbal Comprehension Index (9.58 points), Processing Speed Index (5.33 points), intelligence quotient (5.63 points) level of learning (7.66 points), interference trial (10.12 points), immediate memory span (7.98 points), and recognition accuracy (1.18 points) subtests after the cognitive intervention.

Conclusion

The results suggest that cognitive intervention improves neurocognitive development in schoolchildren exposed to Pb.
Combating Disparities in a Pandemic: Increasing Dissemination of Coronavirus Disease 2019 Resources in Spanish
Authors: Barral Romina L. , Clark Nicholas A. , Zapata Fernando , Vargas Collado Lines M. , Cuevas July Jean , Fernandez Cristina
Published: July 2024

Introduction:

Disparities exist in access to coronavirus disease 2019 (COVID-19)-related health information. We aimed to close a gap in online traffic between English and Spanish COVID-19-related health information on our institution’s publicly-facing website by 50% within ten months.

Methods:

We used A3 improvement methodology. Outcome measures were the mean monthly difference between English and Spanish COVID-19 online traffic vis-a-vis (1) total webpage views and (2) unique webpage visits. Process measures were stratification of outcome measures by language. Plan-Do-Study-Act cycles included: Recurring advertisements on a local Spanish television station disseminating up-to-date COVID-19 information, including our institution’s Spanish COVID-19 online resources, incorporation of QR codes into clinic discharge paperwork linking to institutional Spanish COVID-19 resources, and leveraging social media to expand reach. Control charts assessed impact over time.

Results:

There were 1,226,196 total webpage views (369,983 Spanish; 856,213 English) and 1,065,536 unique webpage visits (350,518 Spanish; 715,018 English). Both outcome measures displayed sustained, special cause improvement from a mean monthly difference of 25,397 to 11,321 webpage views (55.4% reduction, June 2021) and 25,066 to 7080 unique webpage visits (71.8% reduction, February 2021) corresponding to special cause improvements in process measures. Improvements were not temporally associated with an intervention but coincided with emergency use approval of the COVID-19 vaccine for children aged 12–15 years (May 2021).

Conclusions:

Although our interventions did not directly show improvements in our measures, we noted increased page views of Spanish COVID-19-related health information on our institution’s publicly-facing website in times of high demand for linguistically appropriate services, including pediatric vaccine roll-out.
Islet Isolation Outcomes in Patients Undergoing Total Pancreatectomy With Islet Autotransplantation in the POST Consortium
Authors: Mattke Jordan , Eaton Anne , Wijkstrom Martin , Witkowski Piotr , Trikudanathan Guru , Singh Vikesh K. , Schwarzenberg Sarah J. , Ramanathan Karthik , Pruett Timothy L. , Posselt Andrew , Nathan Jaimie D. , Morgan Katherine , Mokshagundam Sri Prakash , Lara Luis , Gardner Timothy B. , Freeman Martin , Downs Elissa , Chinnakotla Srinath , Beilman Gregory J. , Ahmad Syed , Adams David , Abu-El-Haija Maisam , Naziruddin Bashoo , Bellin Melena D.
Published: July 2024

Background.

In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes.

Methods.

We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 μm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses.

Results.

In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures (P < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity (P = 0.002) or overweight status pre-TPIAT (P < 0.001) and lower with non-White race (P = 0.03), genetic pancreatitis (P = 0.02), history of lateral pancreaticojejunostomy (P = 0.03), and presence of atrophy (P = 0.006) or ductal changes (P = 0.014) on imaging. IEQ/kg was higher in females (P = 0.01) and Hispanic participants (P = 0.046) and generally lower with older age (nonlinear association, P < 0.001) and pancreatic atrophy (P < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively.

Conclusions.

Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results.
Habitat structural complexity predicts cognitive performance and behaviour in western mosquitofish
Authors: Irwin Kyndal , Aspbury Andrea S. , Bonner Timothy , Gabor Caitlin R.
Published: July 2024

Urban stream syndrome alters stream habitat complexity. We define habitat complexity as the degree of variation in physical habitat structure, with increasing variation equating to higher complexity. Habitat complexity affects species composition and shapes animal ecology, physiology, behaviour and cognition. We used a delayed detour test to measure whether cognitive processes (motor self-regulation) and behaviour (risk-taking) of female Western mosquitofish,
Gambusia affinis,
varied with habitat structural complexity (low, moderate and high) that was quantified visually for nine populations. We predicted that motor self-regulation and risk-taking behaviour would increase with increasing habitat complexity, yet we found support for the opposite. Lower complexity habitats offer less refuge potentially leading to higher predation pressure and selecting for greater risk-taking by fish with higher motor self-regulation. Our findings provide insight into how habitat complexity can shape cognitive processes and behaviour and offers a broader understanding of why some species may tolerate conditions of urbanized environments.
A new pseudosuchian from the Favret Formation of Nevada reveals that archosauriforms occupied coastal regions globally during the Middle Triassic
Authors: Smith Nathan D. , Klein Nicole , Sander P. Martin , Schmitz Lars
Published: July 2024

Recent studies suggest that both stem- and crown-group Archosauria encompassed high ecological diversity during their initial Triassic radiation. We describe a new pseudosuchian archosaur,
Benggwigwishingasuchus eremicarminis
gen. et sp. nov., from the Anisian (Middle Triassic) Fossil Hill Member of the Favret Formation (Nevada, USA), a pelagic setting in the eastern Panthalassan Ocean characterized by the presence of abundant ammonoids and large-bodied ichthyosaurs. Coupled with archosauriforms from the eastern and western Tethys Ocean,
Benggwigwishingasuchus
reveals that pseudosuchians were also components of Panthalassan ocean coastal settings, establishing that the group occupied these habitats globally during the Middle Triassic. However,
Benggwigwishingasuchus
,
Qianosuchus
, and
Ticinosuchus
(two other pseudosuchians known from marine sediments) are not recovered in a monophyletic group, demonstrating that a nearshore marine lifestyle occurred widely across Archosauriformes during this time.
Benggwigwishingasuchus
is recovered as part of an expanded Poposauroidea, including several taxa (e.g.
Mandasuchus
,
Mambawakalae
) from the Middle Triassic Manda Beds of Tanzania among its basally branching members. This implies a greater undiscovered diversity of poposauroids during the Early Triassic, and supports that the group, and pseudosuchians more broadly, diversified rapidly following the End-Permian mass extinction.
Sailfish generate foraging opportunities for seabirds in multi-species predator aggregations
Authors: Licht M. , Burns A. L. , Pacher K. , Krause S. , Bartashevich P. , Romanczuk P. , Hansen M. J. , Then A. Y. , Krause J.
Published: July 2024

While various marine predators form associations, the most commonly studied are those between subsurface predators and seabirds, with gulls, shearwaters or terns frequently co-occurring with dolphins, billfish or tuna. However, the mechanisms underlying these associations remain poorly understood. Three hypotheses have been proposed to explain the prevalence of these associations: (1) subsurface predators herd prey to the surface and make prey accessible to birds, (2) subsurface predators damage prey close to the surface and thereby provide food scraps to birds, and (3) attacks of underwater predators lower the cohesion of prey groups and thereby their collective defences making the prey easier to be captured by birds. Using drone footage, we investigated the interaction between Indo-Pacific sailfish (
Istiophorus platypterus
) and terns (
Onychoprion
sp
.
) preying on schooling fish off the eastern coast of the Malaysian peninsula. Through spatio-temporal analysis of the hunting behaviour of the two predatory species and direct measures of prey cohesion we showed that terns attacked when school cohesion was low, and that this decrease in cohesion was frequently caused by sailfish attacks. Therefore, we propose that sailfish created a by-product benefit for the bird species, lending support to the hypothesis that lowering cohesion can facilitate associations between subsurface predators and seabirds.
Assessment of ten-year cardiovascular disease risk in Bangladesh: A comparative analysis of laboratory and non-laboratory-based WHO risk prediction models
Authors: Monower Md Mostafa , Abid Shehab Uddin Al , Bhuiyan Mahfuzur Rahman , Mamun Mohammad Abdullah Al , Choudhury Sohel Reza
Published: July 2024

Objectives

This study aimed to estimate the 10-year cardiovascular diseases (CVD) risk in Bangladeshi adults using updated 2019 WHO laboratory-based and non-laboratory-based models, identify key CVD risk determinants, and assess the agreement between two models.

Methods

We conducted a cross-sectional analysis of nationally representative Bangladesh STEPS 2018 survey data, involving 2767 adults aged 40-69 years without prior CVDs, using both versions of the updated 2019 WHO 10-year CVD risk prediction models. Logistic regression identified determinants and model agreement was assessed using Bland-Altman Plot, concordance, and Kappa statistics with STATA version 17.

Results

In the laboratory-based model, 10.32% (95% CI: 8.78-12.11) of the population was at elevated risk (≥10%), while the non-laboratory-based model showed 9.25% (95% CI: 7.7-11.08). Males had significantly higher risk than females in both models (p<0.0001). Elevated 10-year CVD risk was associated with age increments of five years (OR=4.29, 95% CI: 3.48-5.30), being female (OR=0.31, 95% CI: 0.18-0.53), urban residence (OR=1.82, 95% CI: 1.20-2.74), residing in Dhaka division (OR=2.44, 95% CI: 1.26-4.73), and higher education (OR=2.42, 95% CI: 1.06-5.51). Key metabolic factors included high waist-hip ratio (OR=2.08, 95% CI: 1.22-3.52) and elevated triglycerides (OR=2.70, 95% CI: 1.65-4.41). Comparing models, Bland-Altman plots showed limit of agreement (-3.16, 3.52) with mean difference of 0.18, proportional bias (males: y=-0.43 + 1.11x; females: y=-0.43 + 1.16x), Lin’s Concordance Correlation Coefficient (LCCC) 0.90 (95% CI: 0.89-0.91), and a Kappa statistic of 0.69 (95%CI: 0.67-0.72).

Conclusion

A substantial portion of the adult Bangladeshi population is at elevated risk of a cardiovascular event within the next decade, with males at higher risk per both models. Sociodemographic, and metabolic factors indicating potential target groups for intervention. The non-laboratory-based model generally shows agreement with the laboratory-based model and can serve as an alternative in settings with limited laboratory resources, though caution is advised for high-risk individuals.
Tattoo ink exposure is associated with lymphoma and skin cancers – a Danish study of twins
Authors: Clemmensen Signe B. , Mengel-From Jonas , Kaprio Jaakko , Frederiksen Henrik , Hjelmborg Jacob vB.
Published: July 2024

We aim to study the possible association between tattoo ink exposure and development of certain cancers in the recently established Danish Twin Tattoo Cohort.

Tattoo ink is known to transfer from skin to blood stream and accumulate in regional lymph nodes. We are concerned that tattoo ink induce inflammation at deposit site that may eventually become chronic and increase risk of abnormal cell proliferation, especially skin cancer and lymphoma.

We conducted two designs of study in twins in order to improve confounder control: A cohort study of 2,367 randomly selected twins and a case-control study of 316 twins born in the period 1960-1996. Cancer diagnoses (ICD-10) were retrieved from the Danish Cancer Registry and tattoo ink exposure from the Danish Twin Tattoo survey from 2021. The analysis addressed effects of time-varying exposure.

In the case-control study, individual level analysis resulted in a hazard of skin cancer (of any type except basal cell carcinoma) that was 1.62 times higher among tattooed (95% CI: 1.08-2.41). Twin-matched analysis of 14 twin pairs discordant for tattoo ink exposure and skin cancer show HR=1.33 (95% CI: 0.46-3.84). For skin cancer and lymphoma, increased hazards were found for tattoos larger than the palm of a hand: HR=2.37 (95% CI: 1.11-5.06) and HR=2.73 (95% CI: 1.33-5.60), respectively. In the cohort study design, individual level analysis resulted in a hazard ratio of 3.91 (95% CI: 1.42-10.8) for skin cancer and 2.83 (95% CI: 1.30-6.16) for basal cell carcinoma.

In conclusion, we are very concerned that tattoo ink interacting with surrounding cells may have severe consequences. Further studies are needed beneficial to public health – the sooner the better.
Airway smooth muscle tone curbs hyperresponsiveness in experimental asthma
Authors: Gazzola Morgan , Boucher Magali , Henry Cyndi , Rojas-Ruiz Andrés , Marsolais David , Bossé Ynuk
Published: July 2024

Background & Objectives

A sustained contraction of airway smooth muscle, hereinafter called tone, increases the response to methacholine in healthy mice and humans. However, the effect of tone in the context of an active inflammation remains to be investigated. The objective of the present study was to test the effect of tone on thein vivoresponse to methacholine in mice during an active inflammatory phase of experimental asthma.

Methods

Male BALB/c mice were exposed once-daily to either intranasal saline or house dust mite for 10 consecutive days to induce experimental asthma. They then underwent one of two methacholine challenges 24 h after the last exposure. While the same cumulative dose was administered in both challenges, one was preceded by a 20-min period of tone induced by nebulizing low doses of methacholine at 5-min intervals. Respiratory mechanics were monitored before and throughout the methacholine challenge by oscillometry. Bronchoalveolar lavages (BAL) and histology were also performed.

Results

BAL inflammation and histological alterations were consistent with experimental asthma. In accordance with previous studies, tone potentiated the response to methacholine in control mice, mainly by stiffening the lung periphery. The lung was even stiffer upon methacholine challenge during an active phase of inflammation in mice with experimental asthma, but this was not further potentiated by tone. In fact, in mice with experimental asthma, tone mitigated hyperresponsiveness by preventing further airway narrowing and, more importantly, small airway narrowing heterogeneity and closure.

Conclusion

During an active inflammatory phase of experimental asthma, tone protects against hyperresponsiveness.

Take-home message

The effect of airway smooth muscle tone on the methacholine response was investigated in mice with or without experimental asthma. While tone potentiated the methacholine response in control mice, it mitigated hyperresponsiveness in experimental asthma. These results unveiled a protective role of the airway smooth muscle in experimental asthma.
Optimization and model averaging of histogram-based place cell firing rate maps using the point process framework
Authors: Okatan Murat
Published: July 2024

Background

The firing rate of hippocampal place cells depends on the spatial position of the organism in an environment. This position dependence is often quantified by constructing spike-in-location and time-in-location histograms, the ratio of which yields a firing rate map.

New Method

The purpose of this study is to present a new method for optimizing the spatial resolution of histogram-based firing rate maps.

Results

It is pointed out that histogram-based firing rate maps are conditional intensity functions of inhomogeneous Poisson process models of neural spike trains, and, as such, they can be optimized through model selection within the point process framework.

Results

The point process framework is used here for optimizing the size and the aspect ratio of the histogram bins using the Akaike Information Criterion (AIC). It is also used for model averaging using Akaike weights, when maps of various bin sizes provide comparable fits. Application of the method is illustrated on data from real rat hippocampal place cells.

Comparison with existing methods

Existing methods do not optimize the number of bins used in each dimension of the firing rate map.

Conclusion

The proposed approach allows for the construction of the AIC-best histogram-based firing rate map for each individual place cell.
Evolutionary dynamics in the decades preceding acute myeloid leukaemia
Authors: Watson Caroline J. , Poon Gladys Y. P. , MacGregor Hamish A.J. , Fonseca Adriana V.A. , Apostolidou Sophia , Gentry-Maharaj Aleksandra , Menon Usha , Blundell Jamie R.
Published: July 2024

Somatic evolution in ageing tissues underlies many cancers. However, our quantitive understanding of the rules governing this pre-cancerous evolution remains incomplete. Here we exploit a unique collection of serial blood samples collected annually up to 15 years prior to diagnosis of acute myeloid leukaemia (AML) to provide a quantitative description of pre-cancerous evolutionary dynamics. Using deep duplex sequencing and evolutionary theory, we quantify the acquisition ages and fitness effects of the key driver events in AML development. The first driver mutations are typically acquired in the first few decades of life when the blood remains highly polyclonal. These early slow-growing clones subsequently acquire multiple further driver mutations which confer selective advantages up to 100-fold larger than the early drivers. These faster-growing clones harbouring multiple driver mutations can cause complete somatic sweeps of the blood decades before diagnosis, a feature strongly associated with future AML. Once established in the blood, the dynamics of driver mutations are highly predictable. Trajectories are shaped by strong clonal competition between lineages with limited evidence of other extrinsic factors playing a major role. Our data show that the clonal dynamics of blood are consistent with a set of remarkably simple evolutionary rules which strike a balance between chance and determinism.
Chemogenetic control of GABAergic activity within the interpeduncular nucleus reveals dissociable behavioral components of the nicotine withdrawal phenotype
Authors: Miguelez Fernández Anabel M. M. , Netherton Shana , Niladhuri Seshadri B. , Rivera Patricia , Tseng Kuei Y. , Peters Christian J.
Published: July 2024

Chronic exposure to nicotine results in the development of a dependent state such that a withdrawal syndrome is elicited upon cessation of nicotine. The habenulo-interpeduncular (Hb-IPN) circuit contains a high concentration of nAChRs and has been identified as a main circuit involved in nicotine withdrawal. Here we investigated the contribution of two distinct subpopulations of IPN GABAergic neurons to nicotine withdrawal behaviors. Using a chemogenetic approach to specifically target Amigo1-expressing or Epyc-expressing neurons within the IPN, we found that activity of the Amigo1 and not the Epyc subpopulation of GABAergic neurons is critical for anxiety-like behaviors both in naïve mice and in those undergoing nicotine withdrawal. Moreover, data revealed that stimulation of Amigo1 neurons in nicotine-naïve mice elicits opposite effects on affective and somatic signs of withdrawal. Taken together, these results suggest that somatic and affective behaviors constitute dissociable components of the nicotine withdrawal phenotype and are likely supported by distinct subpopulations of neurons within the IPN.
Origin of division of labor is decoupled from polymorphism in colonial animals
Authors: Leventhal Sarah , Edie Stewart M. , Morrison Rebecca , Simpson Carl
Published: July 2024

Division of labor, the specialization of sometimes phenotypically divergent cell types or group members, is often associated with ecological success in eukaryotic colonial organisms. Despite its many independent evolutionary origins, how division of labor originates remains unclear. Conventional hypotheses tend towards an “economic” model, so that biological division of labor may reflect a partitioning of pre-existing tasks and morphologies into specialized colony members. Here, we present an alternative model of the origin of division of labor, which can explain the evolution of new functions within a colony. We show that in colonies of the Cretaceous aged (103-96 Ma) fossil bryozoan of the genusWilbertopora, the first cheilostome bryozoan to evolve polymorphism, new member morphologies were not a simple partitioning of pre-existing morphologies, but instead expanded into novel morphospace as they lost functions, specifically feeding. This expansion into new morphologies occurred primarily during two pulses of heightened morphological disparity, suggesting that the evolution of polymorphism corresponded to relaxed constraints on morphology and perhaps to the exploration of novel functions. Using a simple model of physiological connections, we show that regardless of the functionality of these new colony members, all non-feeding members could have been supported by neighboring feeding members. This suggests that the geometric constraints and physiological connectedness could be prerequisites for evolving both polymorphism and division of labor in modular organisms, and that a classic partitioning model of specialization cannot be broadly applied to biological systems.

One Sentence summary

In cheilostome bryozoans, polymorphism evolved through the loss of preexisting functions, rather than the gain of new functions, suggesting that polymorphism can evolve through drift rather than division of labor.
A NovelEx VivoApproach for Investigating Profibrotic Macrophage Polarization Using Murine Precision-Cut Lung Slices
Authors: Vierhout Megan , Ayoub Anmar , Ali Pareesa , Kumaran Vaishnavi , Naiel Safaa , Isshiki Takuma , Koenig Joshua F. , Kolb Martin R.J. , Ask Kjetil
Published: July 2024

Idiopathic pulmonary fibrosis (IPF) is fatal interstitial lung disease characterized by excessive scarring of the lung tissue and declining respiratory function. Given its short prognosis and limited treatment options, novel strategies to investigate emerging experimental treatments are urgently needed. Macrophages, as the most abundant immune cell in the lung, have key implications in wound healing and lung fibrosis. However, they are highly plastic and adaptive to their surrounding microenvironment, and thus to maximize translation of research to lung disease, there is a need to study macrophages in multifaceted, complex systems that are representative of the lung. Precision-cut lung slices (PCLS) are living tissue preparations derived from the lung that are culturedex vivo,which bypass the need for artificial recapitulation of the lung milieu and architecture. Our objective was to establish and validate a moderate-throughput, biologically- translational, viable model to study profibrotic polarization of macrophages in the lung using murine PCLS. To achieve this, we used a polarization cocktail (PC), consisting of IL-4, IL-13, and IL-6, over a 72-hour time course. We first demonstrated no adverse effects of the PC on PCLS viability and architecture. Next, we showed that multiple markers of macrophage profibrotic polarization, including Arginase-1, CD206, YM1, and CCL17 were induced in PCLS following PC treatment. Through tissue microarray-based histological assessments, we directly visualized and quantified Arginase-1 and CD206 staining in PCLS in a moderate-throughput manner. We further delineated phenotype of polarized macrophages, and using high-plex immunolabelling with the Iterative Bleaching Extends Multiplexity (IBEX) method, showed that the PC effects both interstitial and alveolar macrophages. Substantiating the profibrotic properties of the system, we also showed expression of extracellular matrix components and fibrotic markers in stimulated PCLS. Finally, we demonstrated that clodronate treatment diminishes the PC effects on profibrotic macrophage readouts. Overall, our findings support a suitable complex model for studying ex vivo profibrotic macrophage programming in the lung, with future capacity for investigating experimental therapeutic candidates and disease mechanisms in pulmonary fibrosis.
Metagenome-assembled genomes of Estonian Microbiome cohort reveal novel species and their links with prevalent diseases
Authors: Pantiukh Kateryna , Aasmets Oliver , Krigul Kertu Liis , Org Elin
Published: July 2024

Deep metagenomic data from population studies enables genome recovery and construction of population-specific references, including new species and uncovering microbial diversity that global references might miss. We constructed an Estonian population-specific reference of metagenome-assembled genomes (MAGs) from 1,878 stool samples of the EstMB-deep cohort. We assembled 84,762 MAGs, representing 2,257 species, including 353 potentially novel species (15.6%). Additionally, 607 species (26.9%) were not present in the global Unified Human Gastrointestinal Genome (UHGG) reference database and may therefore be population-specific. We further demonstrated the value ofde novoassembly of bacterial genomes by analysing associations with 33 prevalent diseases and detected 44 significant associations for 15 diseases, including with 10 potentially new species and 5 species absent from UHGG. The correlations, especially with new species, demonstrate thatde novobacterial genome assembly from population cohorts can provide significant novel insights linking the microbiome with prevalent diseases and uncovering population-specific differences.
Nemacounter: A user-friendly software to accurately phenotype SCN cysts
Authors: Mejias Joffrey , Kozlowski Djampa K. L. , Goshon Jackson , Maier Thomas R. , Baum Thomas J.
Published: July 2024

The soybean-cyst nematode (SCN;Heterodera glycines) is one of the most destructive pests affecting soybean crops. Effective management of SCN is imperative for the sustainability of soybean agriculture. A promising approach to achieving this goal is the development and breeding of new resistant soybean varieties. Researchers and breeders typically employ exploratory methods such as Genome-Wide Association Studies or Quantitative Trait Loci mapping to identify genes linked to resistance. These methods depend on extensive phenotypic screening. The primary phenotypic measure for assessing SCN resistance is often the number of cysts that form on a plant’s root system. Manual counting hundreds of cysts on a given root system is not only laborious but also subject to variability due to individual assessor differences. Additionally, while measuring cyst size could provide valuable insights due to its correlation with cyst development, this aspect is frequently overlooked because it demands even more hands-on work. To address these challenges, we have created Nemacounter, an intuitive software designed to detect, count, and measure the size of cysts autonomously. Nemacounter boasts a user-friendly graphical interface, simplifying the process for users to obtain reliable results. It enhances productivity by delivering annotated images and compiling data into csv files for easy analysis and reporting.
A negative correlation between the rate coefficient of repair after photoinhibition of cold acclimated plants and the mean annual temperature of the habitats ofArabidopsis thalianaecotypes
Authors: Oguchi Riichi , Nagano Soichiro , Pfleger Ana , Ozaki Hiroshi , Hikosaka Kouki , Osmond Barry , Chow Wah Soon
Published: July 2024

Both the activity of photosynthesis and the repair of damaged photosystems decline in cold environments, which may increase the extent of the damage of photosynthetic machinery by light, namely photoinhibition. We hypothesized that plants in colder habitats may possess greater tolerance to photoinhibition, especially in low temperature conditions.

We measured the rate of photoinhibition, rate of photoinhibition repair and other thylakoid activities in cold environments using 298Arabidopsis thalianaecotypes and studied the relationships among the indicators of photoinhibition tolerance and climatic data of the habitat of each ecotype. The plants acclimated to cold conditions (12°C) for three days showed a negative correlation between the rate of photoinhibition repair at 5°C and the mean annual temperature of habitats, although we could not see this correlation with the control plants grown in 22°C. This result would indicate that the acclimation capacity of photoinhibition tolerance in cold conditions can affect the distribution of plants especially in colder regions.
Detecting somatic variants in purified brain DNA obtained from surgically implanted depth electrodes in epilepsy
Authors: Mascarenhas Rumika , Merrikh Daria , Khanbabaei Maryam , Kaur Navprabhjot , Ghaderi Navid , Maroilley Tatiana , Liu Yiping , Soule Tyler , Appendino Juan Pablo , Jacobs Julia , Wiebe Samuel ,   The Calgary Comprehensive Epilepsy Program Collaborators, Hader Walter , Pfeffer Gerald , Tarailo-Graovac Maja , Klein Karl Martin
Published: July 2024

Somatic variants causing epilepsy are challenging to detect as they are only present in a subset of brain cells (e.g., mosaic) resulting in low variant allele frequencies. Traditional methods that rely on surgically resected brain tissue are limited to patients undergoing brain surgery. We developed an improved protocol to detect somatic variants using DNA from stereo- electroencephalography (SEEG) depth electrodes, enabling access to a larger patient cohort and diverse brain regions. This protocol mitigates issues of cell contamination and low yields by purifying neuronal nuclei using fluorescence-activated nuclei sorting. Furthermore, we employed advanced amplification techniques, stringent quality control and an optimized bioinformatic workflow to decrease false positives. Using digital droplet polymerase chain reaction, we confirmed all four selected candidate somatic variants. Our approach enhances the reliability and applicability of SEEG-derived DNA for epilepsy, offering insights into its molecular basis, facilitating identification of the epileptogenic zone and other advancements in precision medicine.
From forests to farming: identification of photosynthetic limitations in breadfruit across diverse environments
Authors: Dow Graham J. , Lincoln Noa Kekuewa , Autufuga Dolly , Paull Robert
Published: July 2024

Breadfruit (Artocarpus altilis) is a prolific tropical tree producing highly nutritious and voluminous carbohydrate-rich fruits. Already recognized as an underutilized crop, breadfruit could ameliorate food insecurity and protect against climate-related productivity shocks in undernourished equatorial regions. However, a lack of fundamental knowledge impedes widespread agricultural adoption, from modern agroforestry to plantation schemes. Here, we used a multi-environment breadfruit variety trial across the Hawaiian Islands to determine photosynthetic limitations, understand the role of site conditions or varietal features, and define their contributions to agronomic efficiency. Photosynthetic rates were dependent on location and variety, and strongly correlated with fruit yield (r2=0.80, p<0.001). Photochemistry was suitable to full-sunlight conditions, with a saturation point of 1545 PAR,Vcmaxof 151 μmol m-2s-1, andJmaxof 128 μmol m-2s-1, which are high-end compared to other tropical and temperate tree crops. However, limitations on CO2assimilation were imposed by stomatal characteristics, including stomatal density (p<0.05) and diurnal oscillations of stomatal conductance (>50% reductions from daily maxima). These constraints on CO2diffusion are likely to limit maximum productivity more than photochemistry. Our results comprise the first comprehensive analysis of breadfruit photosynthesis, successfully links ecophysiology with fruit yield, and identifies vital traits for future research and management optimization.
Early Embryonic Development of the German CockroachBlattella germanica
Authors: Bar-Lev Viterbo Ariel , Wexler Judith R. , Mayost Lev-Ari Orel , Chipman Ariel D.
Published: July 2024

Background

Early embryogenesis is characterized by dramatic cell proliferation and movement. In most insects, early embryogenesis includes a phase called the uniform blastoderm, during which cells evenly cover the entirety of the egg. However, the embryo of the German cockroach,Blattella germanica, like those of many insects within the super order Polyneoptera, does not have a uniform blastoderm; instead, its first cells condense rapidly at the site of a future germband. We investigated early development in this species in order to understand how early gene expression is or is not conserved in these insect embryos with distinct early cell behaviors.

Results

We present a detailed time series of nuclear division and distribution from fertilization through germband formation and report patterns of expression for the early patterning geneshunchback,caudal, and twist in order to understand early polarization and mesoderm formation. We show a detailed time course of the spatial expression of two genes involved in the segmentation cascade,hedgehogandeven-skipped,and demonstrate two distinct dynamics of the segmentation process.

Conclusions

Despite dramatic differences in cell distribution between the blastoderms of many Polyneopteran insects and those of more well-studied developmental models, expression patterns of early patterning genes are mostly similar. Genes associated with axis determination in other insects are activated relatively late and are probably not maternally deposited. The two phases of segmentation – simultaneous and sequential – might indicate a broadly conserved mode of morphological differentiation. The developmental time course we present here should be of value for further investigation into the causes of this distinct blastoderm type.
Ovarian cancer cells exhibit diverse migration strategies on stiff collagenous substrata
Authors: S Madhumitha , Bhat Ramray
Published: July 2024

In homoeostasis, the shape of epithelial cells and their sessility, i.e. lack of movement are intricately linked together. Alterations in this relationship as a result of malignant transformation and variations, thereof by the mechanical microenvironments that cancer cells encounter as they migrate are as yet ill-understood. Here we explore the interdependency of such traits in two morphologically distinct but invasive ovarian cancer cell lines (OVCAR-3 and SK-OV-3) under mechanically variant contexts. To do so, we came up with a minimal metric toolkit consisting of velocity, local and global turning angles, persistence of migration, major axis dynamics, morphomigrational angle, and elongation dynamics, and rigorously measured their variation using a Shannon entropic distribution to map heterogeneity in behavior between, and across, trajectories of migration. Two stiffness conditions on polymerized Collagen I with Youngs moduli of 0.5 (soft) and 20 (stiff) kPa were chosen. Both the epithelioid OVCAR-3 and mesenchymal SK-OV-3 cells on soft substrata migrated slowly and in an undirected manner. On stiff substrata, SK-OV-3 showed a persistent directed motion with higher velocity. Surprisingly, OVCAR-3 cells on higher stiffness moved at a velocity higher than SK-OV-3 cells and showed a distinct angular motion. The polarity of SK-OV-3 cells on stiff substrata was well-correlated with their movement, whereas for OVCAR-3, we observed an unusual slip behavior, where the axes of cell shape and movement were poorly correlated. An examination of their deformability showed that OVCAR-3 and SKOV-3 on softer substrata were relatively rigid but showed greater shape variation (especially OVCAR-3) on stiffer substrata. Therefore, a rigorous quantification using the above metric toolkit reveals how an interplay between intrinsic deformability and the mechanical microenvironment on pathotypic matrix substrata allow distinct migratory dynamics of epithelioid and mesenchymal ovarian cancer cells.
An avidity-driven mechanism of extracellular BMP regulation by Twisted gastrulation
Authors: Moore Gareth , Revici Raluca , Forbes Beadle Lauren , Birchenough Holly , Baldock Clair , Ashe Hilary L
Published: July 2024

Bone Morphogenetic Protein (BMP) signalling is tightly regulated extracellularly by specific protein-protein interactions. During dorsoventral patterning of vertebrate and invertebrate embryos, the conserved regulator Twisted gastrulation (Tsg) precisely modulates BMP signalling by binding Chordin/Short gastrulation (Sog) to promote formation of the inhibitory Tsg-Sog/Chordin-BMP ternary complex. Here we elucidate the mechanism by which Tsg interacts with Sog/Chordin to modulate BMP signalling extracellularly. Using AlphaFold predictions, we identify a Chordin binding epitope in the Tsg C-terminal domain, which we validate usingin vitrobinding studies with targeted point mutants. Introduction of the equivalent point mutation intoDrosophilaTsg, to disrupt Tsg-Sog interaction, results in an unexpectedly mild perturbation to embryonic dorsoventral patterningin vivo, in the form of a shallower BMP gradient. Using binding assays, we provide a molecular explanation for this mild phenotype by showing that the BMP ligand can partially rescue ternary complex formation when the Tsg-Sog interaction is disrupted. Additionally, we show that an evolutionary divergent Tsg C-terminal extension is essential for full Tsg function inDrosophilaembryos. Based on these findings we propose that Tsg promotes formation of a Tsg-Sog/Chordin-BMP complex by an avidity-driven mechanism, which will be relevant to a broad range of developmental contexts.
Rapid evolution of gene expression patterns in flowering plants
Authors: Schuster Christoph , Gabel Alexander , Drost Hajk-Georg , Grosse Ivo , Leyser Ottoline , Meyerowitz Elliot M.
Published: July 2024

Phenotypic differences between species are largely driven by changes in both protein-coding sequence and gene expression1. The evolutionary history of angiosperms (flowering plants) is characterised by a highly accelerated rate of diversification, which Darwin referred to as an “abominable mystery”2. Here we show, by analysing the transcriptomes from eight organs across seven species, that angiosperm protein-coding gene expression patterns evolve rapidly: within 45 million years, expression levels of orthologous genes diverged so strongly that they are more similar between different organs within a species than between what are considered homologous organs from different species. This finding differs from previous observations in mammals, which demonstrated that organ-dependent gene expression levels are largely conserved3, 4, 5. Among the angiosperm organs, meristems and leaves show the highest degree of expression conservation, whereas stamen and pollen transcriptomes diverge rapidly. Examining changes in the expression level of functionally related genes, we found low rates for those involved in key cellular, metabolic and developmental processes. In contrast, particularly high rates were observed for genes that are involved in the response to endogenous and external stimuli, presumably reflecting an adaptive response of flowering plants to ever-changing environments. Our work reveals that the evolution of gene expression progresses at different rates in angiosperms and mammals, and provides a comprehensive resource to perform cross-kingdom comparative studies of transcriptome evolution.
Proteomic Aging Clocks and the Risk of Mortality among Longer-Term Cancer Survivors in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wang Shuo , Rao Zexi , Blaes Anne H. , Coresh Josef , Joshu Corinne E. , Pankow James S. , Thyagarajan Bharat , Ganz Peter , Guan Weihua , Platz Elizabeth A. , Prizment Anna
Published: July 2024

Background

We constructed a new proteomic aging clock (PAC) and computed the published Lehallier’s PAC to estimate biological age. We tested PACs’ associations with mortality in longer-term cancer survivors and cancer-free participants.

Methods

ARIC measured 4,712 proteins using SomaScan in plasma samples collected at multiple visits, including Visit 5 (2011-13), from 806 cancer survivors and 3,699 cancer-free participants (aged 66-90). In the training set (N=2,466 randomly selected cancer-free participants), we developed the new PAC using elastic net regression and computed Lehallier’s PAC. Age acceleration was calculated as residuals after regressing each PAC on chronological age after excluding the training set. We used multivariable-adjusted Cox proportional hazards regression to examine the associations of age acceleration with all-cause, cardiovascular disease (CVD), and cancer mortality.

Results

Both PACs were correlated with chronological age [r=0.70-0.75]. Age acceleration for these two PACs was similarly associated with all-cause mortality in cancer survivors [hazard ratios (HRs) per 1 SD=1.40-1.42, p<0.01]. The associations with all-cause mortality were similar in cancer survivors and cancer-free participants for both PACs [p-interactions=0.20-0.62]. There were also associations with all-cause mortality in breast cancer survivors for both PACs [HRs=1.54-1.72, p<0.01] and colorectal cancer survivors for the new PAC [HR=1.96, p=0.03]. Additionally, the new PAC was associated with cancer mortality in all cancer survivors. Finally, HRs=1.42-1.61 [p<0.01] for CVD mortality in cancer-free participants for two PACs but the association was insignificant in cancer survivors perhaps due to a limited number of outcomes.

Conclusion

PACs hold promise as potential biomarkers for premature mortality in cancer survivors.