bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic pain is specifically associated with updating working memory: a longitudinal twin study
Authors: Rader Lydia , Wager Tor D. , Friedman Naomi P.
Published: August 2024

Worse executive function (EF) is associated with chronic pain and could mechanistically contribute to pain chronification. It is unclear whether there is overall impairment in EFs or whether there are impairments in specific cognitive domains. Furthermore, the possible genetic risk underlying these associations has not been tested. Participants were from the Colorado Longitudinal Twin study; 786 same-sex twins completed a battery of EF tasks at ages 23 and/or 28 and 634 of these twins self-reported chronic pain at mean age = 28.1; prevalence = 27.76% using the Brief Pain History Questionnaire. The EF tasks were used to define a Common EF factor and 2 factors specific to updating working memory and shifting mental set. We estimated the phenotypic and genetic associations of stable EF variance across ages 23 and 28, as well as EF variance unique to age 28, with pain. With respect to stable EF variance, pain phenotypically correlated with the Updating-specific factor (r = −0.21, P = 0.008) but did not significantly correlate with the Common EF factor (r = −0.06, P = 0.350) nor with the Shifting-specific factor (r = −0.03, P = 0.709). There were no significant phenotypic correlations between pain and EF variance unique to age 28. A twin model indicated that pain and Updating-specific variance share genetic risk (rA = −0.46, P = 0.005) but not environmental risk (rE = 0.05, P = 0.844). Updating working memory shares a phenotypic and genetic relationship with pain in young adults. Impairments in gating or monitoring pain signals may play a mechanistic role in pain development.
Small molecule targeting NaV1.7 via inhibition of CRMP2-Ubc9 interaction reduces pain-related outcomes in a rodent osteoarthritic model
Authors: Hestehave Sara , Allen Heather N. , Gomez Kimberly , Duran Paz , Calderon-Rivera Aida , Loya-López Santiago , Rodríguez-Palma Erick J. , Khanna Rajesh
Published: August 2024

Osteoarthritis (OA) is a highly prevalent and disabling joint disease, characterized by pathological progressive joint deformation and clinical symptoms of pain. Disease-modifying treatments remain unavailable, and pain-mitigation is often suboptimal, but recent studies suggest beneficial effects by inhibition of the voltage-gated sodium channel NaV1.7. We previously identified compound 194 as an indirect inhibitor of NaV1.7 by preventing SUMOylation of the NaV1.7-trafficking protein, collapsin response mediator protein 2. Compound 194 reduces the functional activity of NaV1.7 channels and produces effective analgesia in a variety of acute and neuropathic pain models. However, its effectiveness has not yet been evaluated in models of OA. Here, we explore the effects of 194 on pain-related outcomes in the OA-like monoiodoacetate model using behavioral assessment, biochemistry, novel in vivo fiber photometry, and patch clamp electrophysiology. We found that the monoiodoacetate model induced (1) increased pain-like behaviors and calcium responses of glutamatergic neurons in the parabrachial nucleus after evoked cold and mechanical stimuli, (2) conditioned place aversion to mechanical stimulation, (3) functional weight bearing asymmetry, (4) increased sodium currents in dorsal root ganglia neurons, and (5) increased calcitonin gene–related peptide-release in the spinal cord. Crucially, administration of 194 improved all these pain-related outcomes. Collectively, these findings support indirect inhibition of NaV1.7 as an effective treatment of OA-related pain through the inhibition of collapsin response mediator protein 2-SUMOylation via compound 194.
Disclosure of HIV Status to Sexual Partners Among People With HIV in Singida Regional Referral Hospital of Tanzania: A Cross-Sectional Study
Authors: Alexander Alex Gabagambi , Relf Michael , Bosworth Hayden B. , Mmbaga Blandina T. , Muiruri Charles
Published: August 2024

HIV status nondisclosure to sexual partners remains a major challenge in Tanzania's health system. This hospital-based, descriptive, cross-sectional study design recruited 380 people living with HIV (PLWH) to assess voluntary HIV status disclosure to sexual partners, the associated factors, and outcomes among PLWH in Tanzania. Approximately 78% (n = 297) of the study participants reported disclosing their HIV status to their sexual partners. Adjusted multivariable logistic regression analysis revealed that HIV status disclosure to sexual partners was significantly associated with living with a sexual partner (adjusted odds ratio [AOR] = 3.91, 95% CI [1.43–10.72]), knowledge of HIV disclosure (AOR = 11.71, 95% CI [2.88–47.63]), known serostatus of the sexual partner (AOR = 40.20, 95% CI [15.31–105.56]), and HIV disclosure–related stigma (AOR = 0.92, 95% CI [0.85–0.99]). Addressing these significant factors will maximize the magnitude of voluntary disclosure to sexual partners.
Telemetry discontinuation education for Nurse Practitioners decreases hospital costs—A quality-improvement project
Authors: Rodriguez Christopher , Bianco Nicole , Bucco Theresa , Collum Karen , O'Neill Sharon Patricia , David Daniel
Published: August 2024

Background:

Despite updated American Heart Association guidelines, interventions designed to reduce telemetry misuse are uncommon.

Local problem:

There was a systemic failure within the institution to adopt the most recent guidelines, resulting in poor use of resources and downstream costs.

Methods:

Case–control. Pre–post educational intervention, quality-improvement (QI) project in an urban academic cancer institution. Baseline telemetry usage was observed in 2,984 nonintensive inpatients in 21 hospital services over 6 months. Outcome measures were weekly telemetry usage in total minutes and cost savings based on a cost-predicted algorithm. Performance was compared between the intervention group and a control group for 3 months. Measures were compared using QI control charts and inferential statistics.

Intervention:

Three high-using telemetry services primarily staffed by certified nurse practitioners (CNPs) were provided with a telemetry education intervention. The intervention consisted of four ten-minute educational sessions over 2 weeks delivered to the highest three telemetry using services.

Results:

Forty-five providers received the educational intervention (78% CNPs and physician assistants [PAs] and 22% medical doctors [MDs]) and 272 did not (57% CNPs and PAs and 43% MDs). Only the educational intervention group showed measurable decreases shown by shifts in QI control charts. Decreased usage in the intervention group produced greater cost savings per patient when compared with the control group ($71.98 vs. $60.68), resulting in an estimated total annual cost savings of $94,740.

Conclusions:

Educational interventions for inpatient CNPs that reinforce national policies for telemetry discontinuation improve practice efficiency and potentially decrease health care costs.
Behind the Curtain
Authors: Sun Ruichen , Henderson Morgan , Goetschius Leigh , Han Fei , Stockwell Ian
Published: August 2024

Introduction:

Predictive models have proliferated in the health system in recent years and have been used to predict both health services utilization and medical outcomes. Less is known, however, on how these models function and how they might adapt to different contexts. The purpose of the current study is to shed light on the inner workings of a large-scale predictive model deployed in 2 distinct populations, with a particular emphasis on adaptability issues.

Methods:

We compared the performance and functioning of a predictive model of avoidable hospitalization in 2 very different populations: Medicaid and Medicare enrollees in Maryland. Specifically, we assessed characteristics of the risk scores from March 2022 for the 2 populations, the predictive ability of the scores, and the driving risk factors behind the scores. In addition, we created and assessed the performance of an “unadapted” model by applying coefficients from the Medicare model to the Medicaid population.

Results:

The model adapted to, and performed well in, both populations, despite demographic differences in these 2 groups. However, the most salient risk factors and their relative weightings differed, sometimes dramatically, across the 2 populations. The unadapted Medicaid model displayed poor performance relative to the adapted model.

Conclusions:

Our findings speak to the need to “peek behind the curtain” of predictive models that may be applied to different populations, and we caution that risk prediction is not “one size fits all”: for optimal performance, models should be adapted to, and trained on, the target population.
Trajectories of Depressive Symptoms Among Patients Undergoing Chemotherapy for Breast, Gastrointestinal, Gynecological, or Lung Cancer
Authors: Suskin Johanna A. , Paul Steven M. , Stuckey Ashley R. , Conley Yvette P. , Levine Jon D. , Hammer Marilyn J. , Miaskowski Christine , Dunn Laura B.
Published: August 2024

Background

Individuals who undergo chemotherapy for cancer are at elevated risk of developing depressive symptoms, yet substantial interindividual variation exists in trajectories of these symptoms.

Objective

To examine interindividual variations in trajectories of depressive symptoms during 2 cycles of chemotherapy and to evaluate associations between demographic and clinical characteristics, symptom severity scores, psychological adjustment characteristics (eg, stress and coping), and initial levels and trajectories of depressive symptoms.

Methods

Patients (n = 1323) diagnosed with breast, gynecologic, lung, or gastrointestinal cancer completed the Center for Epidemiological Studies—Depression Scale 6 times, over 2 cycles of chemotherapy. At enrollment, patients provided demographic information and completed a broad range of symptom, stress, and coping measures. Hierarchical linear modeling was used to identify characteristics associated with initial levels and trajectories of depressive symptoms.

Results

Interindividual differences in initial levels of depressive symptoms were associated with marital status, functional status, level of comorbidity, chemotherapy toxicity, sleep disturbance, morning fatigue, cognitive function, global and cancer-related stress, and coping characteristics (ie, sense of coherence, venting, behavioral disengagement, and self-blame). Interindividual differences in depression trajectories were associated with education, cancer type, chemotherapy toxicity, sleep disturbance, evening energy, evening fatigue, cognitive function, global and cancer-related stress, and self-blame.

Conclusions

We present new findings concerning the trajectories and predictors of depressive symptoms during chemotherapy.

Implications for Practice

Modifiable risk factors (eg, stress and coping) are important targets for intervening to address depressive symptoms in oncology patients.
Navigating Improper Care Settings: Nurses’ Experiences Assisting Oncological Patients at the End of Life in Surgical Departments
Authors: Bearzot Sara , Ortez Giulia , Cadorin Lucia , Ghirotto Luca , Bressan Valentina
Published: August 2024

Background

Despite the growing preference for end-of-life care at home, numerous oncological patients continue to spend their final moments in surgical wards. This incongruity in settings may contribute to “dysthanasia,” unnecessarily prolonging futile treatments and resulting in undue suffering. As frontline caregivers, nurses frequently bear the brunt of these challenging situations for patients and their families.

Objective

To investigate the experiences of nurses providing care to terminally ill oncological patients inappropriately admitted to surgical departments.

Methods

We adopted a phenomenological descriptive study. Nurses purposefully selected from 7 distinct surgical units at a University Hospital in Northeast Italy were recruited. Data collection took place through open-ended semistructured interviews. The interview content was analyzed using Colaizzi’s framework.

Results

The study with 26 participants revealed emotional challenges, especially for less-experienced nurses. Diverse perspectives among nurses emphasized the need for better palliative care knowledge. Despite the commitment to quality care, collaboration challenges and discordant goals with physicians impacted comprehensive care delivery.

Conclusions

Dysthanasia relates to participants’ challenges in caring for oncological patients in inappropriate settings, hindering transparent communication and exacerbating discordance with doctors.

Implications for Practice

Communication and collaboration among healthcare professionals, particularly nurses, and surgeons are crucial. Ongoing education in end-of-life care, coupled with advance care planning, empowers patients, aligns treatment choices, and prevents dysthanasia across diverse healthcare settings.
Experiences of Exercise-Related Worry Among Chinese Childhood Cancer Survivors and Their Carers
Authors: Gu Yujing , Xu Xiaomin , Fan Juhong , Wu Feifei , Fan Shujun , Xie Jun
Published: August 2024

Background

The low levels of physical activity in childhood cancer survivors have increasingly garnered attention from nursing scholars. Exercise-related worry is a prominent barrier, yet the understanding of such experiences among childhood cancer survivors and their primary caregivers remains scarce.

Objective

The aim of this study was to further understand the factors contributing to exercise-related worry from the perspective of childhood cancer survivors and their primary caregivers.

Methods

In this qualitative study, we conducted face-to-face semistructured interviews with childhood cancer survivors (n = 20) and carers (n = 20) in 2 hospitals in China. The interviews were analyzed according to thematic analysis.

Results

Two main themes and 8 subthemes emerged: (1) internal factors: changes in the perception of physical activity (threat perception from the disease, active avoidance of stressful events, lack of safety due to past experiences), and (2) external factors: weak support system (limited peer support, family strength, feeling abandoned by the tumor team, reintegration into school, external environmental constraints). In summary, exercise-related worry is from internal factors and can be influenced by external factors.

Conclusion

There are various factors contributing to the concerns of exercise in childhood cancer survivors, which may be a key factor for their significantly lower levels of physical activity compared to guideline recommendations.

Implications for Practice

The findings of this study call for healthcare professionals to provide additional assistance for childhood cancer survivors with exercise-related worry and establish personalized mechanisms for supporting physical activity in pediatric cancer survivors within the Chinese healthcare system.
Feeling Valued as a Mid-Career Nurse
Authors: Crossen Emily M. , Hunter Revell Susan M.
Published: August 2024

Retaining mid-career nurses is a priority to address the nursing shortage exacerbated by COVID-19. Nurses are more likely to stay if they feel valued. This scoping review revealed a variety of intrapersonal, interpersonal, and external factors that influence how mid-career nurses feel valued. Nursing professional development practitioners can influence satisfaction and retention by implementing mentoring and professional development programs for nurses and managers. More research is needed to understand the impact of the mid-career nurse–nurse manager relationship.
99mTc-PYP and 68Ga-FAPI PET/CT Images of Hereditary Transthyretin Amyloidosis With Cardiac Involvement
Authors: Kibar Ali , Sahin Kubra , Ikitimur Baris , Sager Sait , Sayman Haluk Burcak
Published: August 2024

Amyloidosis is a protein misfolding disorder characterized by the extracellular deposition of insoluble amyloid fibrils, derived from abnormally folded proteins. These fibrils disrupt tissue structure and function, leading to organ dysfunction. The condition encompasses various subtypes, each associated with distinct precursor proteins and clinical manifestations. 99mTc-PYP scintigraphy is used widely and holds significant importance for diagnosis. 68Ga-FAPI is also a promising radiotracer for various diseases. To our knowledge, this is the first case of a patient with hereditary transthyretin amyloidosis with cardiac involvement, which FAPI PET showed diffuse increased myocardial uptake.
The Application Value of Using Semiquantitative and Quantitative Parameters in Multimodal Ultrasound to Distinguish Between Benign and Malignant BI-RADS 4 Lesions
Authors: Dai Xi , Zhou Xiao-Yu , Chen Piao-Fei , Gong Zhe-Li , Wang Zhi-Ping , Wang Di
Published: August 2024

This study aims to explore the value of real-time strain elastography (RTE) and contrast-enhanced ultrasonography (CEUS) in the diagnosis of breast BI-RADS 4 lesions. It collected 85 cases (totaling 85 lesions) diagnosed with breast BI-RADS 4 through routine ultrasound from October 2020 to December 2022 in Huangshan City People's Hospital. All lesions underwent RTE and CEUS examination before surgery, and the ImageJ software was used to measure the periphery of lesion images in the enhancement peak mode and grayscale mode to calculate the contrast-enhanced ultrasound area ratio. The diagnostic capabilities of single-modal and multimodal ultrasound examination for the malignancy of breast BI-RADS 4 lesions were compared using the receiver operating characteristic curve; the Spearman correlation analysis was adopted to evaluate the correlation between multimodal ultrasound and CEUS area ratio. As a result, among the 85 lesions, 51 were benign, and 34 were malignant. The areas under the curve (AUCs) of routine ultrasound (US), US + RTE, US + CEUS, and US + RTE + CEUS were 0.816, 0.928, 0.953, and 0.967, respectively, with the combined method showing a higher AUC than the single application. The AUC of the CEUS area ratio diagnosing breast lesions was 0.888. There was a strong positive correlation (r = 0.819, P < 0.001) between the diagnostic performance of US + RTE + CEUS and the CEUS area ratio. In conclusion, based on routine ultrasound, the combination of RTE and CEUS can further improve the differential diagnosis of benign and malignant lesions in breast BI-RADS 4.
Chronic Lung Allograft Dysfunction: Clinical Manifestations and Immunologic Mechanisms
Authors: Bery Amit I. , Belousova Natalia , Hachem Ramsey R. , Roux Antoine , Kreisel Daniel
Published: August 2024

The term “chronic lung allograft dysfunction” has emerged to describe the clinical syndrome of progressive, largely irreversible dysfunction of pulmonary allografts. This umbrella term comprises 2 major clinical phenotypes: bronchiolitis obliterans syndrome and restrictive allograft syndrome. Here, we discuss the clinical manifestations, diagnostic challenges, and potential therapeutic avenues to address this major barrier to improved long-term outcomes. In addition, we review the immunologic mechanisms thought to propagate each phenotype of chronic lung allograft dysfunction, discuss the various models used to study this process, describe potential therapeutic targets, and identify key unknowns that must be evaluated by future research strategies.
Liver Retransplantation Using Living Donor Grafts: A Feasible Approach for Chronic Allograft Failure
Authors: Tanaka Kosuke , Ito Takashi , Uchida Yoichiro , Masano Yuki , Okumura Shinya , Hirata Masaaki , Kageyama Shoichi , Anazawa Takayuki , Koyama Yukinori , Ogiso Satoshi , Ishii Takamichi , Nagai Kazuyuki , Hatano Etsuro
Published: August 2024

Background.

The indication of living donor liver retransplantation (re-LDLT) for retransplant candidates with chronic allograft failure (CAF) is increasing because of the high mortality rate of patients on the waiting list. However, evidence supporting re-LDLT for CAF remains scarce because of technical difficulties. We aimed to examine the feasibility based on our significant case experience.

Methods.

A total of 95 retransplant cases (adult: 53, pediatric: 42) between 2000 and 2020 were retrospectively reviewed. Graft survival after re-LDLT and deceased donor liver retransplantation (re-DDLT) was compared among recipients with CAF and acute allograft failure (AAF).

Results.

Re-LDLTs for CAF were performed in 58 (61.1%) cases, re-DDLTs for CAF in 16 (16.8%) cases, re-LDLTs for AAF in 13 (13.7%) cases, and re-DDLTs for AAF in 8 (8.4%) cases. Re-DDLTs have become increasingly prevalent over time. Retransplantation for AAF results in lower graft survival than that for CAF in both adult and pediatric cases. All adult recipients who underwent re-LDLT for AAF died within 1 y after retransplantation. The 5-y graft survival between re-LDLT and re-DDLT for CAF was not significantly different (73.8% versus 75.0%, P = 0.84). Operation time and blood loss were not significantly different.

Conclusions.

The survival rate of re-LDLT for recipients with CAF is permissible. Re-LDLT may be another treatment option for recipients with CAF.
Reliable biogeography requires fossils: insights from a new species-level phylogeny of extinct and living carnivores
Authors: Faurby Søren , Silvestro Daniele , Werdelin Lars , Antonelli Alexandre
Published: August 2024

A central objective of historical biogeography is to understand where clades originated and how they moved across space and over time. However, given the dynamic history of ecosystem changes in response to climate change and geological events, the manifold long-distance dispersals over evolutionary timescales, and regional and global extinctions, it remains uncertain how reliable inferences based solely on extant taxa can be achieved. Using a novel species-level phylogeny of all known extant and extinct species of the mammalian order Carnivora and related extinct groups, we show that far more precise and accurate ancestral areas can be estimated by fully integrating extinct species into the analyses, rather than solely relying on extant species or identifying ancestral areas only based on the geography of the oldest fossils. Through a series of simulations, we further show that this conclusion is robust under realistic scenarios in which the unknown extinct taxa represent a biased subset of all extinct species. Our results highlight the importance of integrating fossil taxa into a phylogenetic framework to further improve our understanding of historical biogeography and reveal the dynamic dispersal and diversification history of carnivores.
Effects of the maternal social environment on the mating signals and mate preferences of adult offspring in
Enchenopa
treehoppers
Authors: Little Drew W. , Lindemann Kirsten J. , Rodríguez Rafael L.
Published: August 2024

Much is known about how the maternal environment can shape offspring traits via intergenerational effects. It is less clear, however, whether such effects may reach adult offspring sexual traits, with potential consequences for sexual selection and speciation. Here, we report effects of adult female aggregation density on the mating signals and mate preferences of their offspring in an insect that communicates via plant-borne vibrational signals. We experimentally manipulated the density of aggregations experienced by egg-laying mothers, reared the offspring in standard densities, and tested for corresponding differences in their signals and preferences. We detected a strong effect in male signals, with sons of mothers that experienced low aggregation density signalling more. We also detected a weak effect on female mate preferences, with daughters of mothers that experienced low aggregation density being less selective. These adjustments may help males and females find mates and secure matings in low densities, if the conditions they encounter correspond to those their mothers experienced. Our results thus extend theory regarding adjustments to the social environment to the scale of intergenerational effects, with maternal social environments influencing the expression of the sexual traits of adult offspring.
Mapping Kappa Opioid Receptor Binding in Titi Monkeys with11C-GR103545 PET
Authors: Almeida Alita Jesal D , Hobson Brad A. , Savidge Logan E. , Manca Claudia , Paulus John P. , Bales Karen L. , Chaudhari Abhijit J.
Published: August 2024

Purpose

The kappa opioid receptor (KOR) plays a pivotal role in stress- and anxiety-related behaviors, especially in social separation and bonding. However, KOR modulations in these social contexts are not fully characterized. The coppery titi monkey (Plecturocebus cupreus) has been utilized as a translational animal model for studying the neurobiology of attachment, as they form socially monogamous adult pair bonds. While the PET radiotracer11C-GR103545 has shown the ability to track KOR activity in other species, it has not been utilized in titi monkeys. This study assessed11C-GR103545 PET for characterizing KOR activityin vivoand its pharmacological blockade in titi monkeys.

Methods

Adult titi monkeys (N=6) underwent11C-GR103545 PET brain scans at baseline, followed by repeat scans upon administration of a KOR antagonist (CERC-501) and a KOR agonist (U50,488). Region-specific, non-displaceable binding potential (BPND) was calculated, with the cerebellum as the reference region, focusing on 14 brain volumes of interest (VOIs) implicated in social bonding.

Results

Baseline11C-GR103545 uptake characteristics across VOIs were consistent with previous reports in humans and other monkey models. CERC-501 pretreatment led to a significant reduction in BPND(average 55.99%) across several, but not all brain VOIs, with the most notable reduction in the superior frontal gyrus (76.25%). In contrast, U50,488 pretreatment resulted in no significant BPNDchanges across the VOIs analyzed.

Conclusions

This study demonstrates the utility of11C-GR103545 to assess KOR binding dynamics in a monkey model of social bonding. Region-specific blockade of KOR was observed after pretreatment by CERC-501, while blockade by the KOR agonist U50,488 did not change11C-GR103545 binding.
Phylogenomics resolve the systematics and biogeography of the ant tribe Myrmicini and tribal relationships within the hyperdiverse ant subfamily Myrmicinae
Authors: Prebus Matthew , Rabeling Christian
Published: August 2024

Ants are a globally distributed and highly diverse group of eusocial animals, playing key ecological roles in most of the world’s terrestrial ecosystems. Our understanding of the processes involved in the evolution this diverse family is contingent upon our knowledge of the phylogeny of the ants. While relationships among most subfamilies have come into resolution recently, several of the tribal relationships within the hyperdiverse subfamily Myrmicinae persistently conflict between or within studies, mirroring the controversial relationships of the Leptanillinae and Martialinae to the remaining ant subfamilies. Another persistent issue of debate in ant phylogenetics is the timing of major evolutionary events as inferred via divergence dating. Here, we test the topology of the myrmicine tribes using genome scale data, inspect gene tree-species tree concordance, and use posterior predictive checks and tests of compositional heterogeneity to infer sequence characteristics which potentially introduce systematic bias in myrmicine tribal topology. Furthermore, we test the placement of the fossil †Manica andrannaeby integrating phylogenomic and morphological data from nearly all species within the genusManica,and a broad sampling of its sister genusMyrmica.Subsequently, we demonstrate the effect of fossil placement on overall divergence times in the Myrmicinae. We then re-evaluate the historical biogeography of the Myrmicini and Pogonomyrmecini considering newly generated genetic data and insights from our phylogenomic results. We find that our current understanding of tribal topology in the Myrmicinae is strongly supported, but this topology is highly sensitive to compositional heterogeneity and gene-tree species-tree conflict. Our fossil placement analyses strongly suggest that †Manica andrannaeis a stemManicaspecies, and that placement of this fossil in the crown group affects not only divergence dates within the tribe Myrmicini, but also has broad implications for divergence times throughout the formicoid clade. The results of our biogeographic reconstructions indicate a South American origin for the Pogonomyrmecini + Myrmicini, with the MRCA ofMyrmicainhabiting the western Nearctic in the early Miocene prior to repeated dispersal across Beringia throughout the Miocene and Pliocene. The MRCA ofManica, on the other hand, was inferred to have a Holarctic range prior to vicariance during the Pliocene. Unexpectedly, we found strong support in the Pogonomyrmecini for three coordinated dispersal events from South to Central America during the early Miocene, which has been previously proposed as an early biotic interchange event prior to the more commonly accepted 3.5 Ma closure of the Isthmus of Panama.
Model selection for spectral parameterization
Authors: Wilson Luc E. , Castanheira Jason da Silva , Kinder Benjamin Lévesque , Baillet Sylvain
Published: August 2024

Neurophysiological brain activity comprises rhythmic (periodic) and arrhythmic (aperiodic) signal elements, which are increasingly studied in relation to behavioral traits and clinical symptoms. Current methods for spectral parameterization of neural recordings rely on user-dependent parameter selection, which challenges the replicability and robustness of findings. Here, we introduce a principled approach to model selection, relying on Bayesian information criterion, for static and time-resolved spectral parameterization of neurophysiological data. We present extensive tests of the approach with ground-truth and empirical magnetoencephalography recordings. Data-driven model selection enhances both the specificity and sensitivity of spectral and spectrogram decompositions, even in non-stationary contexts. Overall, the proposed spectral decomposition with data-driven model selection minimizes the reliance on user expertise and subjective choices, enabling more robust, reproducible, and interpretable research findings.

Lay summary

Brain activity is composed of rhythmic patterns that repeat over time and arrhythmic elements that are less structured. Recent advances in brain signal analysis have improved our ability to distinguish between these two types of components, enhancing our understanding of brain signals. However, current methods require users to adjust several parameters manually to obtain their results. The outcomes of the analyses therefore depend on each user’s decisions and expertise. To improve the replicability of research findings, the authors propose a new, automated method to streamline the analysis of brain signal contents. They developed a new algorithm that defines the parameters of the analytical pipeline informed by the data. The effectiveness of this new method is demonstrated with both synthesized and real-world data. The new approach is made available to all researchers as a free, open-source app, observing best practices for neuroscience research.
Understanding the Sport Viewership Experience using Functional Near-Infrared Spectroscopy
Authors: Potwarka Luke R. , Safati Adrian B. , Pappas Adam T. , Ramchandani Girish , Naraine Michael L. , Gurbez Nur , Hall Peter A.
Published: August 2024

Subjective evaluation of a sport event in real time is normally assessed using self-report measures, but neural indices of evaluative processing may provide new insights. The extent of evaluative processing of a sporting event at the neural level may depend on the degree of emotional investment by the viewer, as well as the key moment of the game play being observed. Those with high ego involvement might show more activation within evaluative processing nodes, and this pattern may be most pronounced during critical moments of game play. In the current study, we examined neural activations within the medial and lateral prefrontal cortex during game play as a function of ego-involvement, using video clips featuring key moments in a European league ice hockey game. A total of 343 participants were pre-screened to identify 20 high and low ego-involved individuals. These subgroups then viewed a game segment containing 12 key play moments, while undergoing neuroimaging using fNIRS. Findings indicated more engagement of the dmPFC throughout all key moments for high ego-involved participants, but particularly during critical game moments. Overall, findings suggest that neural indices of evaluative processing might contribute meaningfully to understanding when emotionally invested individuals are most engaged in an action sequence during a sporting event.
Genetics of Cardiac Aging Implicate Organ-Specific Variation
Authors: Brundage James , Barrios Joshua P. , Tison Geoffrey H. , Pirruccello James P.
Published: August 2024

Heart structure and function change with age, and the notion that the heart may age faster for some individuals than for others has driven interest in estimating cardiac age acceleration. However, current approaches have limited feature richness (heart measurements; radiomics) or capture extraneous data and therefore lack cardiac specificity (deep learning [DL] on unmasked chest MRI). These technical limitations have been a barrier to efforts to understand genetic contributions to age acceleration. We hypothesized that a video-based DL model provided with heart-masked MRI data would capture a rich yet cardiac-specific representation of cardiac aging.

In 61,691 UK Biobank participants, we excluded noncardiac pixels from cardiac MRI and trained a video-based DL model to predict age from one cardiac cycle in the 4-chamber view. We then computed cardiac age acceleration as the bias-corrected prediction of heart age minus the calendar age. Predicted heart age explained 71.1% of variance in calendar age, with a mean absolute error of 3.3 years. Cardiac age acceleration was linked to unfavorable cardiac geometry and systolic and diastolic dysfunction. We also observed links between cardiac age acceleration and diet, decreased physical activity, increased alcohol and tobacco use, and altered levels of 239 serum proteins, as well as adverse brain MRI characteristics.

We found cardiac age acceleration to be heritable (h2g 26.6%); a genome-wide association study identified 8 loci related to linked to cardiomyopathy (nearTTN, TNS1, LSM3, PALLD, DSP, PLEC, ANKRD1andMYO18B) and an additional 16 loci (nearMECOM, NPR3, KLHL3, HDGFL1, CDKN1A, ELN, SLC25A37, PI15, AP3M1, HMGA2, ADPRHL1, PGAP3, WNT9B, UHRF1 and DOK5). Of the discovered loci, 21 were not previously associated with cardiac age acceleration. Mendelian randomization revealed that lower genetically mediated levels of 6 circulating proteins (MSRA most strongly), as well as greater levels of 5 proteins (LXN most strongly) were associated with cardiac age acceleration, as were greater blood pressure and Lp(a). A polygenic score for cardiac age acceleration predicted earlier onset of arrhythmia, heart failure, myocardial infarction, and mortality.

These findings provide a thematic understanding of cardiac age acceleration and suggest that heart- and vascular-specific factors are key to cardiac age acceleration, predominating over a more global aging program.
Environmental and molecular noise buffering by the cyanobacterial clock in individual cells
Authors: Eremina Aleksandra , Schwall Christian , Saez Teresa , Witting Lennart , Kohlheyer Dietrich , Martins Bruno M.C. , Thomas Philipp , Locke James C.W.
Published: August 2024

Circadian clocks enable organisms to anticipate daily cycles, while being robust to molecular and environmental noise. Here, we show how the cyanobacterial clock buffers genetic and environmental perturbations through its core phosphorylation loop. We first characterise single-cell clock dynamics in clock mutants using a microfluidics device that allows precise control of the microenvironment. We find known clock regulators are dispensable for clock robustness, whilst perturbations of the core clock reveal that the wild-type operates at a noise optimum that we can reproduce in a stochastic model of just the core phosphorylation loop. We then examine how the clock responds to noisy environments, including natural light conditions. The model accurately predicts how the clock filters out environmental noise, including fast light fluctuations, to keep time while remaining responsive to environmental shifts. Our findings illustrate how a simple clock network can exhibit complex noise filtering properties, advancing our understanding of how biological circuits can perform accurately in natural environments.
Methodology for the identification and analysis of species associations in biological communities using statistical distributions
Authors: Seleznev Dmitriy G. , Prokin Alexander A. , Kurina Ekaterina M.
Published: August 2024

A methodology for identifying pairs of mutually associated and mutually incompatible species pairs based on qualitative ecological data in the ‘species-samples’ format is described. Statistical criteria for assessing the direction and strength of species associations using discrete hypergeometric and binomial distributions are provided. Additionally, there are proposed methods for visualising selected associations using undirected graphs, combining associated species into groups, and analysing them. An open access web application implementing the described methodology is also presented. The methodology is illustrated with data on 37 alien macrozoobenthic species from 255 samples collected in the Volga River reservoirs.
Seeing or believing in hyperplexed spatial proteomics via antibodies. New and old biases for an image-based technology
Authors: Bolognesi Maddalena M , Dall’Olio Lorenzo , Maerten Amy , Borghesi Simone , Castellani Gastone , Cattoretti Giorgio
Published: August 2024

Hyperplexed in-situ targeted proteomics via antibody immunodetection (i.e. > 15 markers) is changing how we classify cells and tissues. Differently from other high-dimensional single-cell assays (flow cytometry, single cell RNA sequencing), the human eye is a necessary component in multiple procedural steps: image segmentation, signal thresholding, antibody validation and iconographic rendering. Established methods complement the human image evaluation, but may carry undisclosed biases in such a new context, therefore we re-evaluate all the steps in hyperplexed proteomics. We found that the human eye can discriminate less than 64 out of 256 gray levels and has limitations in discriminating luminance levels in conventional histology images. Furthermore, only images containing visible signals are selected and eye-guided digital thresholding separates signal from noise. BRAQUE, a hyperplexed proteomic tool, can extract, in a marker-agnostic fashion, granular information from markers which have a very low signal-to-noise ratio and therefore are not visualized by traditional visual rendering. By analyzing a public human lymph node dataset, we also found unpredicted staining results by validated antibodies, which highlight the need to upgrade the definition of antibody specificity in hyperplexed immunostaining. Spatially hyperplexed methods upgrade and supplant traditional image-based analysis of tissue immunostaining, beyond the human eye contribution.

IMPACT STATEMENT

Staining with multiple biomarkers a single tissue section, multiplex staining, is changing how we examine in-situ normalcy, pathology and the interrelationship of good and bad biological actors. Bioinformatic pipelines developed to deal with high-dimensional datasets such as single cell RNA sequencing or multiparameter flow-cytometry have been adapted to analogous types of data derived from tissue, and co-exist with conventional image analysis tools and human eye-guided image evaluation. We wanted to evaluate if multiplex staining with more than 15 markers (hyperplexed) has comparable sensitivity to conventional image analysis and if these latter analysis tools carry undisclosed biases and should not be used together with hyperplexed staining. We found that the human eye has a reduced discriminative power for grayscale and luminance levels compared to the 8-bit available spectrum, affecting positive signal recognition above the noise. We also found that the granular analytical power of recent bioinformatic pipelines can extract information from images which defy human eye perception and deliver information unattainable with existing image analysis tools for single-stain images.
Evaluating permutation-based inference for partial least squares analysis of neuroimaging data
Authors: Danyluik Matthew , Zeighami Yashar , Mukora Alice , Lepage Martin , Shah Jai , Joober Ridha , Misic Bratislav , Iturria-Medina Yasser , Chakravarty M. Mallar
Published: August 2024

Partial least squares (PLS) is actively leveraged in neuroimaging work, typically to map latent variables (LVs) representing brain-behaviour associations. LVs are considered statistically significant if they tend to capture more covariance than LVs derived from permuted data, with a Procrustes rotation applied to map each set of permuted LVs to the space defined by the originals, creating an “apples to apples” comparison. Yet, it has not been established whether applying the rotation makes the permutation test more sensitive to whether true LVs are present in a dataset, and it is unclear if significance alone is sufficient to fully characterize a PLS decomposition, given that complementary metrics like strength and split-half stability may offer non-redundant information about the LVs. Accordingly, we performed PLS analyses across a range of simulated datasets with known latent effects, observing that the Procrustes rotation systematically weakened the null distributions for the first LV. By extension, the first LV was nearly always significant, regardless of whether the effect was weak, undersampled, noisy, or simulated at all. But, if no rotation was applied, all possible LVs tended to be significant as we increased the sample size of UK Biobank datasets. Meanwhile, LV strength and stability metrics accurately tracked our confidence that effects were present in simulated data, and allowed for a more nuanced assessment of which LVs may be relevant in the UK Biobank. We end by presenting a list of considerations for researchers implementing PLS permutation testing, and by discussing promising alternative tests which may alleviate the concerns raised by our findings.
Sequences within and upstream of the mouse Ets1 gene drive high level expression in B cells, but are not sufficient for consistent expression in T cells
Authors: Kearly Alyssa , Saelee Prontip , Bard Jonathan , Sinha Satrajit , Satterthwaite Anne , Garrett-Sinha Lee Ann
Published: August 2024

The levels of transcription factor Ets1 are high in resting B and T cells, but are downregulated by signaling through antigen receptors and Toll-like receptors (TLRs). Loss of Ets1 in mice leads to excessive immune cell activation and development of an autoimmune syndrome and reduced Ets1 expression has been observed in human PBMCs in the context of autoimmune diseases. In B cells, Ets1 serves to prevent premature activation and differentiation to antibody-secreting cells. Given these important roles for Ets1 in the immune response, stringent control ofEts1gene expression levels is required for homeostasis. However, the genetic regulatory elements that control expression of theEts1gene remain relatively unknown. Here we identify a topologically-associating domain (TAD) in the chromatin of B cells that includes the mouseEts1gene locus and describe an interaction hub that extends over 100 kb upstream and into the gene body. Additionally, we compile epigenetic datasets to find several putative regulatory elements within the interaction hub by identifying regions of high DNA accessibility and enrichment of active enhancer histone marks. Using reporter constructs, we determine that DNA sequences within this interaction hub are sufficient to direct reporter gene expression in lymphoid tissues of transgenic mice. Further analysis indicates that the reporter construct drives faithful expression of the reporter gene in mouse B cells, but variegated expression in T cells, suggesting the existence of T cell regulatory elements outside this region. To investigate how the downregulation of Ets1 transcription is associated with alterations in the epigenetic landscape of stimulated B cells, we performed ATAC-seq in resting and BCR-stimulated primary B cells and identified four regions within and upstream of theEts1locus that undergo changes in chromatin accessibility that correlate toEts1gene expression. Interestingly, functional analysis of several putative Ets1 regulatory elements using luciferase constructs suggested a high level of functional redundancy. Taken together our studies reveal a complex network of regulatory elements and transcription factors that coordinate the B cell-specific expression ofEts1.
Octopus can use odor plumes to find food
Authors: Weertman Willem Lee , Gopal Venkatesh , Sivitilli Dominic M. , Scheel David , Gire David H.
Published: August 2024

Odor-plume-guided navigation, tracking an odor plume to its source, is a primordial behavior used by most animals to search beyond the visual range. Here we report the first laboratory observations of octopuses performing this behavior, demonstrating that they can use odor plumes to find food. In a three-station discrimination task carried out in the dark, octopus showed a strong preference to move upstream towards the food-baited target, supporting the hypothesis that they are performing odor-guided search. When seeking a single baited target, also in the dark, octopuses not only preferred to move upstream towards the food source, but they also displayed characteristic motions associated with odor-gated rheotaxis, a commonly used odor tracking strategy used by many animals, which includes pausing, switchbacks, and across-stream redirections to the bait. Additionally, when approaching single baited stations the octopus often made reactive fast lunging motions. The observation of these fastarm-alignedmotions (FAAM), taken together with the observation that the octopus did not have a characteristic body axis orientation to the bait, as would be expected if bilaterally symmetric organs such as the olfactory pits guided this behavior, supports the hypothesis that the suckers are the primary chemosensory organs driving octopus odor-guided behaviors.