bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison between ultrasound-guided intertransverse process and erector spinae plane blocks for breast cancer surgery
Authors: Qian Lulu , Zhang Hongye , Miao Yongsheng , Qu Zongyang , Zhang Yuelun , Hua Bin , Hua Zhen
Published: October 2024

BACKGROUND

Clinical comparisons between intertransverse process block (ITPB) and erector spinae plane block (ESPB) are lacking.

OBJECTIVE

This study aimed to compare their blocking profile and clinical efficacy in breast cancer surgery.

DESIGN

Randomised, blinded, active-controlled superiority trial.

SETTING

A tertiary hospital in China from 20 February to 31 July 2023.

PATIENTS

Sixty-eight females undergoing unilateral breast cancer surgery.

INTERVENTION

Patients were randomised to receive either ITPB performed at T2–6 (5 ml of 0.5% ropivacaine per level) or ESPB at T4 (25 ml of 0.5% ropivacaine). General anaesthesia and postoperative analgesia were standardised.

MAIN OUTCOME MEASURES

The primary outcome was the number of blocked dermatomes at anterior T2–7, assessed 45 min after block completion, with a predefined superiority margin of 1.5 dermatomes. The important secondary outcome was the worst resting pain scores (11-point numerical rating scale) within 30 min in the recovery room, which was tested following a gatekeeping procedure. Other secondary outcomes included resting pain scores at various time points, use of rescue analgesics, opioid consumption, patient satisfaction, recovery quality score, and adverse effects within 24 h postoperatively.

RESULTS

The ITPB group showed a median [q1, q3] of 5 [4, 6] blocked dermatomes at anterior T2–7, whereas the ESPB group had 1 [0, 4], with a median difference of 4 (95% confidence interval (CI), 3 to 4); the lower 95% CI limit exceeded the predefined superiority margin of 1.5 (superiority P < 0.001). Worst resting pain scores within 30 min in the recovery room in the ITPB group were 1 [0, 2] vs. 3 [1, 4] in the ESPB group, with a median difference of −1 (95% CI, −2 to 0; P = 0.004). Patients in the ITPB group required fewer rescue analgesics within 30 min in the recovery room than did those in the ESPB group. No other clinically relevant results were observed in the secondary outcomes.

CONCLUSIONS

Although ITPB demonstrated more consistent anterior dermatomal spread and improved immediate postoperative analgesia compared to ESPB, no additional benefits were identified for breast cancer surgery. Future studies may investigate the potential of ITPB for surgical anaesthesia.

TRIAL REGISTRATION

www.chictr.org.cn (ChiCTR2300068454).
The Effect of Forgiveness Psychoeducation on Death Anxiety, Caregiver Burden, and Forgiveness Tendencies in Caregivers of Patients at the End of Life
Authors: Şahin Merve , Demirkıran Fatma
Published: October 2024

Background

Providing caregivers with the skills and awareness of forgiveness is crucial to help them express their emotions, navigate the grieving process more smoothly, enhance their interaction with the patient, and make the time until the patient’s death more meaningful.

Objective

To examine the effect of forgiveness psychoeducation on death anxiety, caregiver burden, and forgiveness tendencies in caregivers of patients at the end of life.

Methods

A randomized controlled experimental method was used, including a pretest, posttest, 1-month follow-up, and 3-month follow-up. The research sample included 56 caregivers of patients (experimental group = 28, control group = 28) at the end of life. During the study, forgiveness psychoeducation was administered to the experimental group, whereas no intervention was carried out in the control group. Data were collected using the Personal Information Form, Thorson-Powell Death Anxiety Scale, Caregiver Burden Scale, and Heartland Forgiveness Scale.

Results

The average scores of death anxiety and caregiving burden in the posttest and follow-up measurements of caregivers in the experimental group were statistically significantly lower than those of caregivers in the control group (P < .05).

Conclusion

Forgiveness psychoeducation reduces death anxiety and caregiving burdens in caregivers of patients at the end of life. It is recommended to provide psychoeducation on forgiveness.

Implication for Practice

The psychoeducation conducted by Consultation Liaison Psychiatry Nurses aimed at increasing the internal process of forgiveness can positively influence the communication, emotions, and spiritual development of caregivers of patients at the end of life. Thus, improving the quality of care can be achieved through forgiveness.
Live as if
Authors: Ferren Melora D.
Published: October 2024

In this column, Marguerite C. Samms, chief learning officer (CLO) for Intermountain Health, shares her career journey and how nursing practice prepared her for executive leadership.
Clinicopathologic and Genomic Features of Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix Coexisting With High-grade Squamous Intraepithelial Lesion
Authors: Long Xinyuan , Ma Xiaoting , Xiao Wei , Lv Jinghuan
Published: October 2024

Invasive stratified mucin-producing carcinoma (ISMC) is a specific type of adenocarcinoma of the cervix, which is associated with human papillomavirus infection and often coexists with other types of carcinomas. However, given its rarity, understanding of this disease remains insufficient. We present a unique case of ISMC of the cervix coexisting with a high-grade squamous intraepithelial lesion (HSIL). In addition to histologic and immunohistochemical feature observation, genomic profiling of the 2 lesions was performed. Histologically, the ISMC and HSIL lesions were independent of each other. Aside from the typical morphology, various architectural features of ISMC were observed. Immunohistochemically, the ISMC and HSIL lesions were strongly and diffusely positive for p16 and exhibited high Ki-67 expression. The ISMC lesion was also positive for CK7, MUC5AC, and MUC6, while it was negative for PAX-8. The HSIL lesion was positive for CK5/6 and p40. The combined positive score of PD-L1 was 55. The other markers were all negative in both lesions, and the p53 was wild-type. Next-generation sequencing analysis revealed multiple gene mutations in the ISMC and HSIL lesions. A total of 88 gene mutations were identified in the ISMC lesion, while 20 gene mutations were identified in the HSIL lesion. Three mutations (ERBB2, histidine decarboxylase gene [HDC], and BSN) were detected in the ISMC and HSIL lesions. Both lesions had a low tumor mutation burden and microsatellite-stable status. No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.
Sleep and circadian rhythm disturbances as risk and progression factors for multiple chronic overlapping pain conditions: a protocol for a longitudinal study
Authors: Mun Chung Jung , Youngstedt Shawn D. , Petrov Megan E. , Pituch Keenan A. , Elliott Jeffrey A. , George Steven Z. , LoVecchio Frank , Mardian Aram S. , Elam Kit K. , Winsick Nina , Eckert Ryan , Sajith Surabhi , Alperin Kate , Lakhotia Ananya , Kohler Kaylee , Reid Matthew J. , Davis Mary C. , Fillingim Roger B.
Published: October 2024

Introduction:

Chronic overlapping pain conditions (COPCs), such as chronic low back pain (cLBP) and fibromyalgia, frequently cooccur and incur substantial healthcare costs. However, to date, much focus has been placed on individual anatomically based chronic pain conditions, whereas little is known about the mechanisms underlying progression to multiple (more than 1) COPCs. This study aims to address the gap by investigating the role of common and modifiable risk factors, specifically sleep and circadian rhythm disturbances, in the development of multiple COPCs.

Methods:

The study will enroll 300 participants with cLBP, including 200 with cLBP only and 100 with cLBP plus other COPCs (ie, fibromyalgia, temporomandibular disorders, irritable bowel syndrome, and chronic headaches) and follow them up for 12 months. Sleep and circadian rhythms will be assessed using wireless sleep electroencephalography, 24-hour evaluation of the rhythm of urinary 6-sulfatoxymelatonin, actigraphy, and sleep diaries. Pain amplification using quantitative sensory testing, psychological distress using validated self-report measures, and the number of pain sites using a pain body map will also be assessed.

Perspectives:

This research aims to (1) comprehensively characterize sleep/circadian disturbances in individuals with single and multiple COPCs using multimodal in-home assessments; (2) examine the associations between sleep/circadian disturbances, changes in pain amplification, and psychological distress; and (3) investigate the relationship among these factors and the progression in the number of pain sites, a proxy for multiple COPCs. The findings will provide insights into the mechanisms leading to multiple COPCs, potentially informing treatment and prevention strategies for these complex conditions.
Bipolar disorder in people with HIV
Authors: Vollmond Cecilie V. , Tetens Malte M. , Gerstoft Jan , Kronborg Gitte , Johansen Isik S. , Larsen Carsten S. , Porskrog Anders , Dalager-Pedersen Michael , Leth Steffen , Kessing Lars V. , Lebech Anne-Mette , Obel Niels , Omland Lars H.
Published: October 2024

Objectives:

To assess whether bipolar disorders are associated with the risk of HIV infection and whether the risk of bipolar disorders is increased among people with HIV (PWH) and their siblings.

Design:

Nationwide, population-based, combined matched nested case-control and cohort study of PWH of Danish origin (1995–2021), a comparison cohort from the background population, matched on date of birth and sex, and sibling cohorts.

Methods:

Conditional logistic regression and Cox regression was used to calculate adjusted odds ratios (aORs) for HIV infection and hazard ratios among PWH for bipolar disorder and receipt of lithium.

Results:

We included 5322 PWH and 53 220 comparison cohort members. In the case–control study, bipolar disorder was associated with an increased risk of HIV infection [aOR: 1.9, 95% confidence interval (CI): 1.2–3.0], especially when injection drug use was the route of infection (aOR: 7.6, 95% CI: 2.0–28.9). In the cohort study, we observed an increased risk of bipolar disorders among PWH, especially in the first 2 years of observation (hazard ratio: 4.2, 95% CI: 2.4–7.4), whereas the risk of receipt of lithium was lower and the CI crossed 1. The 20-year risk of bipolar disorders for PWH was approximately 1%. Siblings of PWH also had an increased risk of bipolar disorder but not to the same degree as PWH and not of receipt of lithium.

Conclusion:

Bipolar disorders are associated with the risk of HIV infection, and PWH have increased risk of bipolar disorder and receipt of lithium beyond what familial factors could explain.
Molecular correlates of swarming behaviour in
Aedes aegypti
males
Authors: Devilliers Julien , Marshall Hollie , Warren Ben , Kyriacou Charalambos P. , Araripe Luciana O. , Bruno Rafaela V. , Rosato Ezio , Feuda Roberto
Published: October 2024

Mosquitoes are the deadliest vectors of diseases. They impose a huge health burden on human populations spreading parasites as disparate as protozoans (malaria), viruses (yellow fever and more) and nematodes (filariasis) that cause life-threatening conditions. In recent years, mating has been proposed as a putative target for population control. Mosquitoes mate mid-air, in swarms initiated by males and triggered by a combination of internal and external stimuli. As the number of females in a swarm is limited, there is intense competition among males, and they ‘retune’ their physiology for this demanding behaviour. There is limited knowledge on the ‘genetic reprogramming’ required to enable swarming. Interestingly, recent evidence indicates that the upregulation of circadian clock genes may be involved in the swarming of malaria mosquitoes of the genus
Anopheles
. Here, we use whole-head RNA-seq to identify gene expression changes in
Aedes aegypti
males that are engaged in swarming in a laboratory setting. Our results suggest that in preparation to swarming, males tend to lower some housekeeping functions while increasing remodelling of the cytoskeleton and neuronal connectivity; the transcription of circadian clock genes is unaffected.
A brief review of non-avian dinosaur biogeography: state-of-the-art and prospectus
Authors: Upchurch Paul , Chiarenza Alfio Alessandro
Published: October 2024

Dinosaurs potentially originated in the mid-palaeolatitudes of Gondwana 245–235 million years ago (Ma) and may have been restricted to cooler, humid areas by low-latitude arid zones until climatic amelioration made northern dispersals feasible
ca
215 Ma. However, this scenario is challenged by new Carnian Laurasian fossils and evidence that even the earliest dinosaurs had adaptations for arid conditions. After becoming globally distributed in the Early–Middle Jurassic (200–160 Ma), dinosaurs experienced vicariance driven by Pangaean fragmentation. Regional extinctions and trans-oceanic dispersals also played a role, and the formation of ephemeral land connections meant that older vicariance patterns were repeatedly overprinted by younger ones, creating a reticulate biogeographic history. Palaeoclimates shaped dispersal barriers and corridors, including filters that had differential effects on different types of dinosaurs. Dinosaurian biogeographic research faces many challenges, not the least of which is the patchiness of the fossil record. However, new fossils, extensive databasing and improved analytical methods help distinguish signal from noise and generate fresh perspectives. In the future, developing techniques for quantifying and ameliorating sampling biases and modelling the dispersal capacities of dinosaurs are likely to be two of the key components in our modern research programme.
New lessons from biology for economics and business: a systems approach to non-market environments
Authors: Lee YunHee , Mayer Colin , Snower Dennis , Noble Denis
Published: October 2024

Drawing on recent advances in biology, this paper describes a systems approach, ‘Systems Public Affairs’ (SPA), to integrate non-market strategies in corporate purposes and strategies. Just as the environment of organisms affects and is affected by their development and evolution, so individuals and businesses adjust to and can shape their non-market environment, which we define as ‘a historically formed national and social sphere, including laws, regulations, and policies, which supports, maintains and restrains the operation and preservation of markets’. The paper uses cases from South Korea to illustrate this approach. Emergent ideas in biology have great relevance for micro-foundations of business. Traditionally, economic activities are outcomes of individualistic decision-makers, each promoting their distinct objectives within economic markets. In the SPA approach, decision makers in the domains of business, policy and civil society collaborate in shaping non-market environments to align business objectives with public interest. This requires agency to rise to higher levels than that of businesses, policymakers and civil society through collaboration and experimentation in the presence of stochasticity and radical uncertainty. Analogous to the advancement of organism evolution through emergence of nervous systems and learning, so alignment of organizations with their non-market environments accelerates economic and social development.
Long-term tracing of individual human neural cells using multiphoton microscopy and photoconvertible polymer capsules
Authors: Smirnov Ivan V. , Usatova Veronika S. , Berestovoy Mikhail A. , Fedotov Andrei B. , Lanin Aleksandr A. , Belousov Vsevolod V. , Sukhorukov Gleb B.
Published: October 2024

The study of human neural cells, their behaviour and migration are important areas of research in the biomedical field, particularly for potential therapeutic applications. The safety of using neural cells in therapy is still a concern due to a lack of information on long-term changes that may occur. While current methods of cell tracing explore gene manipulations, we elaborate approaches to cell marking with no genetic interference. In this study, we present a novel method for labelling and tracking neural cells using cell-impregnatable photoconvertible polyelectrolyte microcapsules. These capsules demonstrated low cytotoxicity with no effect on the differentiation ability of the neural cells, maintained a high level of fluorescent signal and ability for tracing individual neural cells for over 7 days. The capsules modified with rhodamine- and fluorescein-based dyes were demonstrated to undergo photoconversion by both one- and two-photon lasers while being internalized by neural cells. The finding gives the possibility to select individual capsules inside multicellular structures like spheroids and tissues and alternate their fluorescent appearance. Thus, we can track individual cell paths in complex systems. This new method offers a promising alternative for studying neural cells’ long-term behaviour and migration in complex systems such as three-dimensional cellular populations.
Emergence of synchronized growth oscillations in filamentous fungi
Authors: Prakash Praneet , Jiang Xue , Richards Luke , Schofield Zoe , Schäfer Patrick , Polin Marco , Soyer Orkun S. , Asally Munehiro
Published: October 2024

Many species of soil fungi grow in the form of branched networks that enable long-range communication and mass flow of nutrient. These networks play important roles in the soil ecosystem as a major decomposer of organic materials. While there have been investigations on the branching of the fungal networks, their long-term growth dynamics in space and time is still not very well understood. In this study, we monitor the spatio-temporal growth dynamics of the plant-promoting filamentous fungus
Serendipita indica
for several days in a controlled environment within a microfluidic chamber. We find that
S. indica
cells display synchronized growth oscillations with the onset of sporulation and at a period of 3 h. Quantifying this experimental synchronization of oscillatory dynamics, we show that the synchronization can be recapitulated by the nearest neighbour Kuramoto model with a millimetre-scale cell–cell coupling. The microfluidic set-up presented in this work may aid the future characterization of the molecular mechanisms of the cell–cell communication, which could lead to biophysical approaches for controlling fungi growth and reproductive sporulation in soil and plant health management.
Sex as a biological variable in ageing: insights and perspectives on the molecular and cellular hallmarks
Authors: Fritz García José Héctor Gibrán , Keller Valsecchi Claudia Isabelle , Basilicata M. Felicia
Published: October 2024

Sex-specific differences in lifespan and ageing are observed in various species. In humans, women generally live longer but are frailer and suffer from different age-related diseases compared to men. The hallmarks of ageing, such as genomic instability, telomere attrition or loss of proteostasis, exhibit sex-specific patterns. Sex chromosomes and sex hormones, as well as the epigenetic regulation of the inactive X chromosome, have been shown to affect lifespan and age-related diseases. Here we review the current knowledge on the biological basis of sex-biased ageing. While our review is focused on humans, we also discuss examples of model organisms such as the mouse, fruit fly or the killifish. Understanding these molecular differences is crucial as the elderly population is expected to double worldwide by 2050, making sex-specific approaches in the diagnosis, treatment, therapeutic development and prevention of age-related diseases a pressing need.
Novel image-analytic approach reveals new insights in fine-tuning of slime mould network adaptation
Authors: Rosina Philipp , Grube Martin
Published: October 2024

This study introduces a novel methodology to explore the network dynamics of
Physarum polycephalum
, an organism celebrated for its remarkable adaptive capabilities. We used two innovative techniques to analyse its growth behaviour and network modifications under stress conditions, including starvation and differential epinephrine exposures. The first method provided a quantitative assessment of growth and exploration over time. The second method provided a detailed examination of vein diameter and contraction patterns, illuminating the physiological adjustments
P. polycephalum
undergoes in response to environmental challenges. By integrating these approaches, we were able to estimate the total network volume of the organism, with a focus on the normalized estimated volume, unveiling insightful aspects of its structural adaptations. While starvation reduced the volume, indicating a significant structural compromise, low and high epinephrine concentrations maintained a volume-to-area ratio comparable with the control. Determining the fractal dimension of the networks over time revealed a fine-tuning of the network complexity in response to environmental conditions, with significant reductions under stress indicating a constrained network adaptation strategy. These methods, novel in their application to
P. polycephalum
, provide a framework for future studies and a basis for exploring complex network behaviours with potential applications in bioengineering and adaptive network design.
‘IT FROM BIT’: How does information shape the structures in the Universe?
Authors: Davatolhagh S. , Sheykhi A. , Zarei M. H.
Published: October 2024

Based on a synthesis of three main ingredients: (i) the Shannon information in non-equilibrium systems, (ii) the semiclassical energy-time quantization rule and (iii) the quasi-static information-energy correspondence, a new general rule for the quantization of quasi-static information states supported by an environment away from equilibrium is introduced if the history of the environment is known as a function of time in terms of its thermodynamic potential for information

T
(
t
)

Δ

S
(
t
)

that is a free energy measuring the distance from equilibrium

Δ

S
(
t
)

, and

T
(
t
)

is the mean temperature of the environment at time

t

. This all new quasi-static information-time quantization rule is applied to the expanding Universe using a phenomenological thermodynamic potential for information in the matter-dominated era in order to find the eigen-information of the persistent structures that are supported by the universe (or the local environments therein) at any given epoch, thus providing an information–theoretic foundation for formation of structures and rise of complexity with time that embodies the cosmic evolution as epitomized by the late Wheeler’s famous conjecture ‘it from bit’. This theoretical procedure must also open new avenues for further research into the quantum theory of information and complexity in non-equilibrium thermodynamics.
Bi-Hamiltonian structures of WDVV-type
Authors: Opanasenko S. , Vitolo R.
Published: October 2024

We study a class of nonlinear partial differential equations (PDEs) that admit the same bi-Hamiltonian structure as the Witten–Dijkgraaf–Verlinde–Verlinde (WDVV) equations: a Ferapontov-type first-order Hamiltonian operator and a homogeneous third-order Hamiltonian operator in a canonical Doyle–Potëmin form, which are compatible. Using various equivalence groups, we classify such equations in two-component and three-component cases. In a four-component case we add further evidence to the conjecture that there exists only one integrable system of the above type. Finally, we give an example of the six-component system with required bi-Hamiltonian structure. To streamline the symbolic computation, we develop an algorithm to find the aforementioned Hamiltonian operators, which includes putting forward a conjecture on the structure of the metric parameterizing the first-order Hamiltonian operator.
Phylogenomics supports a single origin of terrestriality in isopods
Authors: Thomas Thorpe Jessica A.
Published: October 2024

Terrestriality, the adaptation to life on land, is one of the key evolutionary transitions, occurring numerous times across the tree of life. Within Arthropoda, there have been several independent transitions: in hexapods, myriapods, arachnids and isopods. Isopoda is a morphologically diverse order within Crustacea, with species adapted to almost every environment on Earth. The order is divided into 11 suborders with the most speciose, Oniscidea, including terrestrial isopods such as woodlice and sea-slaters. Recent molecular phylogenetic studies have challenged traditional isopod morphological taxonomy, suggesting that several well-accepted suborders, including Oniscidea, may be non-monophyletic. This implies that terrestriality may have evolved multiple times. Current molecular hypotheses, however, are based on limited sequence data. Here, I collate available genome and transcriptome datasets for 36 isopods and four peracarid crustaceans from public sources, generate assemblies and use 970 single-copy orthologues to estimate isopod relationships and divergence times with molecular dating. The resulting phylogenetic analyses support monophyly of terrestrial isopods and suggest conflicting relationships based on nuclear ribosomal RNA sequences may be caused by long-branch attraction. Dating analyses suggest a Permo-Carboniferous origin of isopod terrestriality, much more recently than other terrestrial arthropods.
Adaptive human behaviour modulates the impact of immune life history and vaccination on long-term epidemic dynamics
Authors: Espinoza Baltazar , Saad-Roy Chadi M. , Grenfell Bryan T. , Levin Simon A. , Marathe Madhav
Published: October 2024

The multiple immunity responses exhibited in the population and co-circulating variants documented during pandemics show a high potential to generate diverse long-term epidemiological scenarios. Transmission variability, immune uncertainties and human behaviour are crucial features for the predictability and implementation of effective mitigation strategies. Nonetheless, the effects of individual health incentives on disease dynamics are not well understood. We use a behavioural-immuno-epidemiological model to study the joint evolution of human behaviour and epidemic dynamics for different immunity scenarios. Our results reveal a trade-off between the individuals’ immunity levels and the behavioural responses produced. We find that adaptive human behaviour can avoid dynamical resonance by avoiding large outbreaks, producing subsequent uniform outbreaks. Our forward-looking behaviour model shows an optimal planning horizon that minimizes the epidemic burden by balancing the individual risk–benefit trade-off. We find that adaptive human behaviour can compensate for differential immunity levels, equalizing the epidemic dynamics for scenarios with diverse underlying immunity landscapes. Our model can adequately capture complex empirical behavioural dynamics observed during pandemics. We tested our model for different US states during the COVID-19 pandemic. Finally, we explored extensions of our modelling framework that incorporate the effects of lockdowns, the emergence of a novel variant, prosocial attitudes and pandemic fatigue.
Ecological shifts underlie parallels between ontogenetic and evolutionary allometries in parrotfishes
Authors: Neves Mayara P. , Hugi April , Chan Howan , Arnold Kaleigh , Titus Kara , Westneat Mark W. , Zelditch Miriam L. , Brandl Simon , Evans Kory M.
Published: October 2024

During ontogeny, animals often undergo significant shape and size changes, coinciding with ecological shifts. This is evident in parrotfishes (Eupercaria: Labridae), which experience notable ecological shifts during development, transitioning from carnivorous diets as larvae and juveniles to herbivorous and omnivorous diets as adults, using robust beaks and skulls for feeding on coral skeletons and other hard substrates. These ontogenetic shifts mirror their evolutionary history, as parrotfishes are known to have evolved from carnivorous wrasse ancestors. Parallel shifts at ontogenetic and phylogenetic levels may have resulted in similar evolutionary and ontogenetic allometric trajectories within parrotfishes. To test this hypothesis, using micro-computed tomography (μCT) scanning and three-dimensional geometric morphometrics, we analyse the effects of size on the skull shape of the striped parrotfish
Scarus iseri
and compare its ontogenetic allometry to the evolutionary allometries of 57 parrotfishes and 162 non-parrotfish wrasses. The young
S. iseri
have skull shapes resembling non-parrotfish wrasses and grow towards typical adult parrotfish forms as they mature. There was a significant relationship between size and skull shapes and strong evidence for parallel ontogenetic and evolutionary slopes in parrotfishes. Our findings suggest that morphological changes associated with the ecological shift characterizing interspecific parrotfish evolution are conserved in their intraspecific ontogenies.
Democratizing Virtual Patient Case Creation: A Proof-of-concept Technical Framework for Clinicians
Authors: Tsaftaridis Nikolaos , Koulas Ioannis , Zafeiropoulos Stefanos , Saint-Joy Veauthyelau , Ilali Marwa , Ibrahim Michel , Brice Taina , Haynes Norrisa
Published: October 2024

Objective

Virtual patient cases are a scalable and engaging tool for training medical professionals. Strategies and frameworks for their implementation in teaching and training settings are few, technically complicated and/or expensive. We developed and evaluated open source and free virtual patient cases to test knowledge acquisition during an echocardiography training program for internal medicine trainees in Haiti. The objective of this paper is to describe the technical aspects of the GMENEcho virtual patient cases implementation and motivate similar work by resource-constrained teams.

Methods

We used an open source engine for text-based games (Twine) since it provides the necessary interaction mechanics and is usable out-of-the-box. The case code was written in SugarCube 2.30.0 notation and the tweego-generated .html file was hosted on Github Pages for continuous integration and deployment, making iterations by the clinical team seamless. Data from completed tests were reported back via email through a third party integration.

Results

The technical work was completed in two weeks by a team member with a clinical background and minimal computer programming experience. The virtual patient cases were deployed for a pretest (November 2023) and a second time unaltered for a posttest (June 2024) after the interim hands-on and theoretical training had been completed. Qualitative feedback was positive or neutral. The overall score in the posttest was significantly higher with a large effect size (mean absolute improvement 15.26%, p < 0.001; Cohen’s d: 1.398), similarly to the diagnostic score (mean absolute difference 16.09%, p < 0.001; Cohen’s d: 1.402). Management performance missed statistical significance by a small margin. The System Usability Scale (SUS) score was 74.6 (“Excellent”).There was reduced inter-trainee variability across metrics in the posttest, including the SUS score.

Discussion

This proof-of-concept methodology can be applied to create clinical patient cases for use within a class or a clinical training setting, through a friendly graphical user interface. A more complex software stack can allow for remote or larger scale implementations with additional features.

Conclusion

The rapid development time and positive qualitative and quantitative feedback highlight the potential of this approach for clinical education in resource-constrained settings. It can serve as a template for more streamlined adaptations of case-based learning in diverse healthcare settings.
Capturing longitudinal change in cerebellar ataxia: Context-sensitive analysis of real-life walking increases patient relevance and effect size
Authors: Seemann Jens , Beyme Theresa , John Natalie , Harmuth Florian , Giese Martin , Schöls Ludger , Timmann Dagmar , Synofzik Matthis , Ilg Winfried
Published: October 2024

OBJECTIVES

With disease-modifying drugs for degenerative ataxias on the horizon, ecologically valid measures of motor performance that can detect patient-relevant changes in short, trial-like time frames are highly warranted.

In this 2-year longitudinal study, we aimed to unravel and evaluate measures of ataxic gait which are sensitive to longitudinal changes in patients’ real life by using wearable sensors.

METHODS

We assessed longitudinal gait changes of 26 participants with degenerative cerebellar disease (SARA:9.4±4.1) at baseline, 1-year and 2-year follow-up assessment using 3 body-worn inertial sensors in two conditions: (1) laboratory-based walking (LBW); (2) real-life walking (RLW) during everyday living. In the RLW condition, a context-sensitive analysis was performed by selecting comparable walking bouts according to macroscopic gait characteristics, namely bout length and number of turns within a two-minute time interval. Movement analysis focussed on measures of spatio-temporal variability, in particular stride length variability, lateral step deviation, and a compound measure of spatial variability (SPCmp).

RESULTS

Gait variability measures showed high test-retest reliability in both walking conditions (ICC > 0.82). Cross-sectional analyses revealed high correlations of gait measures with ataxia severity (SARA, effect size ρ≥0.75); and in particular with patients’ subjective balance confidence (ABC score, ρ≥0.71), here achieving higher effect sizes for real-life than lab-based gait measures (e.g.SPCmp: RLW ρ=0.81 vs LBW ρ=0.71).

While the clinician-reported outcome SARA showed longitudinal changes only after two years, the gait measureSPCmprevealed changes already after one year with high effect size (rprb=0.80). In the subgroup with spinocerebellar ataxia type 1, 2 or 3 (SCA1/2/3), the effect size was even higher (rprb=0.86). Based on these effect sizes, sample size estimation for the gait measureSPCmpshowed a required cohort size of n=42 participants (n=38 for SCA1/2/3subgroup) for detecting a 50% reduction of natural progression after one year by a hypothetical intervention, compared to n=254 for the SARA.

CONCLUSIONS

Gait variability measures revealed high reliability and sensitivity to longitudinal change in both laboratory-based constrained walking as well as in real-life walking. Due to their ecological validity and larger effect sizes, characteristics of real-life gait recordings are promising motor performance measures as outcomes for future treatment trials.
Impact of a low-threshold exercise and protein supplementation intervention to optimise physical function and target frailty in people experiencing homelessness and addiction: The LEAP II trial
Authors: Kennedy Fiona , Ní Cheallaigh Clíona , Romero-Ortuno Roman , Murray Deirdre , Broderick Julie
Published: October 2024

Objective

Frailty is a state of physiological vulnerability and associated with adverse outcomes. People experiencing homelessness and addiction have a higher burden of frailty than the general population. This study’s aim was to test the feasibility and impact of an exercise intervention with protein supplementation to target low physical functioning and frailty in this population, which was flexibly delivered over 12 weeks, with exercise options three days per week.

Methods

The primary outcome of feasibility was measured by recruitment, retention, adherence, acceptability and adverse events. Secondary outcomes were physical function, pain, frailty and nutritional status, and self-reported health.

Results

Forty-three participants enrolled. Overall retention was 69.8%, with higher retention observed in subgroups (women and older adults). Programme adherence and acceptability was reported in 93% and 100% of participants, respectively. No adverse events occurred. At baseline, sub-normative values were demonstrated for limb strength and balance; pain was prevalent in 34.8%; 23% had poor nutritional health between 32.5% and 72.1% lived with some degree of frailty. Significant improvements were demonstrated for lower limb strength, gait speed, pain, nutritional status and frailty, (p<0.05).

Conclusions

This novel intervention delivered to this hard-to-reach population was shown to be feasible and impactful, indicating proof of concept.
Individual Patient Data Analysis of Liver Lesion Dynamics: A Pan Cancer Analysis
Authors: Dickinson Jake , Huber Heinrich J. , Mistry Hitesh B.
Published: October 2024

There are now several databases available that enable the exploration of individual patient data from past Oncology clinical trials. These databases provide researchers with the opportunity to investigate the dynamics of individual lesions across various tumour sites within a patient and compare them across different patients. In this report, we specifically focus on liver metastases and examine the dynamics of individual lesions across different treatment and tumour types. Our findings reveal that when a lesion progresses early on, the rate of growth is significantly higher for liver lesions compared to other types of lesions, regardless of the treatment modality (chemotherapy, targeted therapy, or combination of both). These results indicate the need for further basic research on tumours and their microenvironment specifically within liver metastases. This analysis demonstrates how analysing open trial data can uncover new research prospects at the fundamental science level, thereby bridging the gap between laboratory research and clinical applications.
Reducing Racial Disparities in HTN Control using an Equity-Centered Approach
Authors: Kioko Susan Mwikali , Council Christina , Tomori Cecilia
Published: October 2024

Black Americans have the highest prevalence of hypertension among all racial or ethnic groups in the United States. They are 40% more likely to have uncontrolled blood pressure and are five times more likely to die from hypertension compared to non-Hispanic whites. Experiences of discrimination in healthcare, clinician and institutional bias, and socioeconomic and environmental inequities driven by structural racism contribute to uncontrolled hypertension in this population. Multicomponent interventions have effectively improved blood pressure control among Black Americans but remain inadequately implemented in the clinical setting. Using a one group pre/posttest design, we examined the effect of an innovative, evidence-based 12-week intervention on blood pressure among Black Americans with uncontrolled hypertension aged 18 and older in the primary care setting. Intervention components included remote blood pressure monitoring, weekly phone coaching with culturally congruent care, medication intensification, and a standardized hypertension protocol. The average age of the participants (n=35) was 64 years, and two thirds (n=23) were female (66%). The mean difference in systolic blood pressure from pre to post intervention decreased significantly (M=23, SD=14.0), t(34)= −9.7, p < .001. A significant reduction in the mean difference in diastolic blood pressure from pre to post intervention was also observed (M=11, SD=11.8), t(34)= −5.5, p < .001. At 12 weeks, 87% of participants had achieved blood pressure control. The intervention also improved medication adherence and hypertension knowledge (p <.001). A multicomponent, culturally congruent quality improvement intervention significantly improved blood pressure among Black Americans.
Membrane oscillations driven by Arp2/3 constrict the intercellular bridge during neural stem cell divisions
Authors: LaFoya Bryce , Prehoda Kenneth E.
Published: October 2024

After the first furrowing step of animal cell division, the nascent sibling cells remain connected by a thin intercellular bridge (ICB). In isolated cells nascent siblings migrate away from each other to generate tension and constrict the ICB, but less is known about how cells complete cytokinesis when constrained within tissues. We examined the ICBs formed byDrosophilalarval brain neural stem cell (NSC) asymmetric divisions and find that they rely on constriction focused at the central midbody region rather than the flanking arms of isolated cell ICBs. Super-resolution, full volume imaging revealed unexpected oscillatory waves in plasma membrane sheets surrounding the ICB pore during its formation and constriction. We find that these membrane dynamics are driven by Arp2/3-dependent branched actin networks. Inhibition of Arp2/3 complex activity blocks membrane oscillations and prevents ICB formation and constriction. Our results identify a previously unrecognized role for localized membrane oscillations in ICB function when cells cannot generate tension through migration.
Are we testing for triple elimination? A review of national guidelines on preventing mother-to-child transmission of HIV, syphilis, and hepatitis B in the African region
Authors: List Kellie , Monroe-Wise Aliza , Banks Margaret , Barr-DiChiara Magdalena , Chetty Agnes , Newman-Owiredu Morkor , Lesi Olufunmilayo , Johnson Cheryl Case , Drake Alison L.
Published: October 2024

Introduction

World Health Organization (WHO) updated guidelines for maternal HIV, syphilis and hepatitis B virus (HBV) testing for pregnant women, and advised on using dual HIV/syphilis rapid diagnostic tests (RDTs). We reviewed national testing guidelines to assess political support in alignment with WHO guidance and triple elimination of mother-to-child transmission (MTCT) priorities.

Methods

We reviewed national HIV-related guidelines from 46 African countries after 2010, including guidelines on prevention MTCT, HIV testing/self-testing, HIV antiretroviral treatment, and/or HIV pre-exposure prophylaxis. Data was extracted data on recommendations for maternal testing for HIV (frequency and timing), syphilis (any test/test type); and HBV. Testing recommendations for all three infections in the most recent country guidelines were compared to WHO guidelines.

Results

Testing policies on HIV, syphilis, or HBV during pregnancy and/or postpartum from 38 (83%) countries were identified; 18 (47%) had policies updated after 2019 and 11 (29%) were high HIV burden. All 38 countries with HIV testing guidelines addressed maternal HIV retesting, while 68% had guidelines recommending syphilis testing (46% of which recommended the dual RDT), and 58% had HBV testing guidelines. Maternal HIV retesting was more frequent than recommended by WHO in 2019 in 9/11 (82%) and 7/27 (26%) of high and low HIV burden countries, respectively. Half of countries had triple elimination of MTCT focused policies, and 10 (26%) had maternal HIV retesting as well as syphilis and/or HBV testing guidance.

Conclusions

Half of countries had guidelines to test for all three infections; policy evaluations to measure implementation and impact are needed.
Induction of cell death in U2OS human cancer cells by Ta3N5
Authors: Nozaki Tomoatsu , Watanabe Kazuto , Watanabe Tomoaki , Nakamura Takahiro J.
Published: October 2024

Photocatalysts are widely used in modern society, with their applications extending into the field of medicine. Ultraviolet irradiation is used for photocatalysis to generate reactive oxygen species (ROS). Ta3N5has attracted attention as a next-generation photocatalyst because it produces ROS upon exposure to visible light. Although ROS generation using visible light irradiation is useful in the field of life sciences, the toxicity of Ta3N5remains unknown. In the present study, we evaluated the cytotoxicity of Ta3N5using U2OS cells in terms of the intensity, irradiation time, and wavelength of light and Ta3N5dose. We also investigated the mode and mechanism of cell death induced by Ta3N5. Cytotoxicity increased with increasing light intensity, irradiation time, and Ta3N5dose. In contrast, high-intensity blue light irradiation induced cytotoxicity with or without Ta3N5, indicating that irradiation to green and red lights, which can selectively toxify Ta3N5-treated cells, is more useful than irradiation to blue light. Moreover, Ta3N5induced secondary necrotic death of U2OS cells. These results suggest that Ta3N5can be used as a photocatalyst in medical and life science fields.
Transcranial Brain-Wide Functional Ultrasound and Ultrasound Localization Microscopy in Mice using Multilinear Probes
Authors: Vert Mathis , Zhang Ge , Bertolo Adrien , Ialy-Radio Nathalie , Pezet Sophie , Osmanski Bruno , Deffieux Thomas , Nouhoum Mohamed , Tanter Mickael
Published: October 2024

Functional ultrasound imaging (fUS) and ultrasound localization microscopy (ULM) are advanced ultrasound imaging modalities for assessing both functional and anatomical characteristics of the brain. However, the application of these techniques at a whole-brain scale has been limited by technological challenges. While conventional linear acoustic probes provide a narrow 2D field of view and matrix probes lack sufficient sensitivity for 3D transcranial fUS, multilinear probes have been developed to combine high sensitivity to blood flow with fast 3D acquisitions. In this study, we present a novel approach the combined implementation of transcranial whole-brain fUS and ULM in mice using a motorized multilinear probe. This technique provides high-resolution, non-invasive imaging of neurovascular dynamics across the entire brain. Our findings reveal a significant correlation between absolute cerebral blood volume (ΔCBV) increases and microbubble velocity, indicating vessel-level dependency of the evoked response. However, the lack of correlation with relative CBV (rCBV) suggests that fUS cannot distinguish functional responses alterations across different arterial vascular compartments. This methodology holds promise for advancing our understanding of neurovascular coupling and could be applied in brain disease diagnostics and therapeutic monitoring.
Carbon nanodots as a red emissive fluorescent probe for the super-resolution microscopy of DNA dynamics during paclitaxel treatment
Authors: Garg Richa , Kaushik Kush , Salam Abdul , Kundu Runmi , Chandra Shilpa , Nandi Chayan Kanti
Published: October 2024

Paclitaxel is a commonly used frontline chemotherapeutic drug for cancer treatment. It is known to be functional by arresting the microtubule disassembly during mitosis. Recently, a non-mitotic pathway has been evolving and thus contemplating the mitotic mechanism. Here, using super-resolution microscopy (SRM), we directly visualized the nuclear dynamics and unveiled the mechanism of paclitaxel treatment. A new class of non-toxic, biocompatible and highly fluorescent carbon nanodots (CNDs) were used as a fluorescent probe that were highly capable to directly stain the nuclear DNA, capture the SRM imaging of chromosome and the chromatin structures. Apart from SRM imaging of chromosomes during all stages of normal mitotic cell division, CNDs successfully visualized the formation of lagging, mis-segregated and bridging chromosomes which leads to the multi-micronucleus formation upon paclitaxel treatment. A detailed chromatin remodelling analysis suggested that heterochromatin played an important role in the formation of condensed multi-micronucleus, ultimately leading to cell death.

Graphical Abstract