bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of a shared decision making process for severe stroke-a mixed methods study
Authors: Visvanathan Akila , Morton Sarah , Macraild Allan , Black Polly , Gilbert Sophie , Barber Mark , Dennis Martin , O’Brien Richard , Mead Gillian
Published: December 2024

Background

Clinical decisions made early after stroke can make the difference between survival with disability or death. We aimed to develop, implement and evaluate a new Shared decision making (SDM) process for severe stroke into a regional 36 bedded stroke unit.

Methods

We developed the process through four coproduction workshops, attempted its implementation then its impact on death at 6 months, discharge destination and tube feeding. We also explored patients, families and staff views about SDM.

Results

Eleven people (staff and people with lived experience of stroke) attended the first co-production workshop, eight the second, seven the third and six the fourth. The new SDM process incorporated Tailored Talks (a digital platform with information about stroke and its prognosis) and an implementation plan (including staff training). We implemented this process on 1stAugust 2022.

Only 8/1020 patients received Tailored Talks (4 before and 4 after implementation). For the entire group there was no change tube feeding, discharge destination or death. The proportion of people with severe strokes dead at six months was higher before implementation. Twenty-one patients or family members provided views about SDM quality, but the sample size was too small to draw conclusions. Staff interviews suggested that insufficient time, lack of a ‘human touch’ and inadequate leadership explained the lack of implementation.

Conclusion

Our co-produced SDM was not effectively implemented into a stroke unit and there was no change in the use of tube feeding or death in 1020 patients.

Key points

Shared decision making after severe stroke is complex.

A co-produced new process for shared decision making after severe stroke was not effectively implemented into clinical practice.

There was no change in tube feeding, death or institutionalisation.
Origin, pattern of bone metastasis and need for surgery in patients with Metastatic bone disease treated at tertiary hospital in Northern Tanzania. A hospital based cross sectional study
Authors: Ncheye Mathias , Maya Elifuraha , Serventi Furaha , Mandari Faiton , Temu Rogers , Magembe Peter , Massawe Honest
Published: December 2024

Bones are the third most common sites for cancer metastasis after lung and liver. Bone metastasis cause skeletal complications (SRE’s) that affect the quality of life of patients with bone metastasis. Management of these patients depend on the primary tumor and pattern of bone metastasis.

The aim of this study was to describe the origin, distribution pattern of bone metastases, common SRE’s and proportion of patients with bone metastasis that need surgery.

A cross sectional study was conducted among cancer patients with Metastatic bone disease attending KCMC Hospital from November 2022 to April 2023. Data was collected from patient’s files, histopathology and radiology reports by a structured extraction sheet. VAS, SINS and Mirel’s scores was used to document pain severity, spinal instability and fracture risk respectively. The ASIA impairment scale was used for documenting neurological deficits in patients with spine metastasis. Data was entered and analyzed in SPSS version 25.0

A total of 72 participants were enrolled. Their mean age was 69 ± 11 years and (75%) were male. Prostate cancer (65.3%) was the leading cause of metastatic bone disease followed by breast cancer (18.1%). Most of patients with MBD have multiple lesions (91.7%) involving multiple sites but the spine (93.1%) was the mostly affected site. Osteoblastic lesions were the predominant radiological type by 59.7% followed by osteolytic lesions which accounted for 23.6% of the study participants. 30.6% had pathological fractures and half of these occurred in patients with osteolytics lesions. 36.1% of the study participants had an indication for surgical treatment of the bone metastasis.

Most of MBD originate from Prostate and Breast cancer giving multiple lesions involving multiple sites but the spine remains to be the most affected site. Even though about a third of the patients had SRE’s that needed surgical intervention but few are expected to be operated considering the prognosis. This calls for more emphasis on prevention of SRE’s and use of appropriate less invasive therapies to prevent progression of the disease.
Survey of the Landscape of Society Practice Guidelines for Genetic Testing of Neurodevelopmental Disorders
Authors: Srivastava Siddharth , Cole Jordan J. , Cohen Julie S. , Chopra Maya , Smith Hadley Stevens , Deardorff Matthew A. , Pedapati Ernest , Corner Brian , Anixt Julia S. , Jeste Shafali , Sahin Mustafa , Gurnett Christina A. , Campbell Colleen A.
Published: December 2024

Genetic testing of patients with neurodevelopmental disabilities (NDDs) is critical for diagnosis, medical management, and access to precision therapies. Because genetic testing approaches evolve rapidly, professional society practice guidelines serve an essential role in guiding clinical care; however, several challenges exist regarding the creation and equitable implementation of these guidelines. In this scoping review, we assessed the current state of United States professional societies’ guidelines pertaining to genetic testing for unexplained global developmental delay, intellectual disability, autism spectrum disorder, and cerebral palsy. We describe several identified shortcomings and argue the need for a unified, frequently-updated and easily-accessible cross-specialty society guideline.
The Gut Metabolism is altered in patients withCRB1-associated inherited retinal degeneration
Authors: Moekotte Lude , de Boer Joke H. , Hiddingh Sanne , Gerritsen Bram , Lintelmann Jutta , Cecil Alexander , van den Born L. Ingeborgh , Nguyen Xuan-Thanh-An , Boon Camiel J.F. , van Genderen Maria M. , Kuiper Jonas J.W.
Published: December 2024

Purpose

To compare the plasma metabolic profile of patients with aCRB1-associated inherited retinal degeneration (CRB1-IRD) with healthy controls (HCs).

Design

A case-control study.

Methods

Plasma concentration of 619 metabolites was measured with the MxP®Quant 500 Kit in 30 patients with aCRB1-IRD and 29 HCs. We fitted a linear regression model with adjustments for age and sex based on the concentration of metabolites in µM (µmol/L), or on the sums and ratios of metabolites, to determine differences between patients and controls.

Results

Over-representation of pathways among metabolites associated strongest toCRB1-IRDs (P< 0.05, n = 62) identified amino acid pathways (such as beta-alanine, histidine, and glycine/serine) and bile acid biosynthesis, driven by a decrease in deoxycholic acid derivatives produced by gut microbiota. Enrichment analysis of metabolic classes across the plasma metabolic profile further identified significant positive enrichment for lipid metabolites glycerophospholipids, cholesterol esters, and ceramides, and significant depletion for bile acid metabolites. Further investigation of the sums and ratios (i.e., metabolism indicators) ascertained a significant decrease in intestinal microbial-dependent secondary bile acid classes.

Conclusions

Lipid metabolic alterations and decreased microbiota-related secondary bile acid concentrations indicate significant alterations in gut metabolism in patients with aCRB1-IRD.
Prenatal ochratoxin A exposure, birth outcomes and infant growth in rural Burkina Faso: a human biomonitoring sub-study from the MISAME-III trial
Authors: Bastos-Moreira Yuri , Argaw Alemayehu , Dailey-Chwalibóg Trenton , El-Hafi Jasmin , Ouédraogo Lionel Olivier , Toe Laeticia Celine , De Saeger Sarah , Lachat Carl , De Boevre Marthe
Published: December 2024

Mycotoxin exposure during pregnancy has been associated with adverse birth outcomes and poor infant growth in low- and middle-income countries. We assessed multiple biomarkers and metabolites of exposure to mycotoxins during pregnancy and their associations with birth outcomes and infant growth in 305 pregnant participants, between 30 and 34 completed weeks of gestation, in rural Burkina Faso. In this study, whole blood microsamples were analyzed for mycotoxin concentrations using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Unadjusted and adjusted associations between mycotoxin exposure, and birth outcomes and infant growth at 6 months were estimated using linear regression models for continuous outcomes and linear probability models with robust variance estimation for binary outcomes. Infant growth trajectories from birth to 6 months were compared by exposure status using mixed-effects models with random intercept for the individual infant and random slope for the infant’s age. Ochratoxin A (OTA) exposure was detected in 50.8% of the study participants, with aflatoxin G1, aflatoxin M1, cyclopiazonic acid, deoxynivalenol and T-2-toxin being detected in the range of 0.33% and 2.31% of the population. We found no statistically significant (allp≥ 0.05) associations between OTA exposure, and birth outcomes and infant growth. Despite this, the findings indicate a significant presence of ochratoxin A among pregnant participants. Public health policies and nutrition-sensitive interventions must ensure that OTA exposure is reduced in Burkina Faso.
Zoonotic and environmental sources of infant enteric pathogen infections identified with longitudinal sampling
Authors: Paulos Abigail P. , Mboya John , Lowe Jeremy , Kim Daehyun Daniel , Wharton Hannah C. , Thuita Faith , Flax Valerie L. , Njenga Sammy M. , Harris Angela R. , Pickering Amy J.
Published: December 2024

Enteric pathogen infections in young children can result in diarrhea, malnutrition, and developmental impairments. Many enteric pathogens that infect young children can be zoonotic, yet the exposure risk of domestic animals living in close proximity to young children is poorly understood. We conducted a prospective cohort study with longitudinal microbiological sampling of child stool, animal feces, and the household environment to investigate pathogen transmission between animals and children under two years of age in pastoralist communities in rural Northern Kenya. We generated 28,743 pathogen-sample observations by measuring 33 bacterial, viral, protozoan, and helminth pathogens in the following types of samples (n=871) collected from households at four consecutive visits: child stool, caregiver stool, drinking water, food, child hands, household soil, and feces from ruminant, avian, and canine domesticated animals. Child enteric pathogen burden increased with age from a median of 1 pathogen among children under 3 months to 5 pathogens at 1-2 years old. Of the 20 unique pathogens detected in child stool, 85% were also detected in animal feces. New infections in children were associated with preceding household detection of the same pathogen in soil (Odds ratio: 8.8, 95% confidence interval: 3.3 – 23) and on child hands (Odds ratio: 5.0, 95% confidence interval 1.1 – 17). Network analysis revealed transmission of pathogens from poultry, dog, and ruminant feces to household soil, and between child hands and child stool. Our results indicate child hand contact with soil containing animal feces is a primary transmission route for first infections among children living in close proximity to animals. Our study provides new evidence that domestic animals in the household environment contribute to early-life enteric pathogen exposure, and that child hand hygiene could substantially prevent animal-human enteric pathogen exchange.
Scaling ecological niches from individuals to populations and beyond
Authors: Lu Muyang , Yanco Scott , Carlson Ben , Winner Kevin , Cohen Jeremy , Ellis-Soto Diego , Sharma Shubhi , Rogers Will , Jetz Walter
Published: December 2024

The niche is a key concept that unifies ecology and evolutionary biology. However, empirical and theoretical treatments of the niche are mostly performed at the species level, neglecting individuals as important units of ecological and evolutionary processes. So far, a formal mathematical link between individual-level niches and higher organismal-level niches has been lacking, hampering the unification of ecological theories and more accurate forecasts of biodiversity change. To fill in this gap, we propose a bottom-up approach to derive population and higher organismal-level niches from individual niches. We demonstrate the power of our framework by showing that 1) the statistical properties of higher organismal-level niches (e.g. niche breadth, skewness etc.) can be partitioned into individual contributions; 2) the species-level niche shifts can be estimated by tracing the responses of individuals. Our method paves the way for a unifying niche theory and enables mechanistic assessments of organism-environment relationships across organismal scales.
Root-pore interactions, the underestimated driver for rhizosphere structure and rhizosheath development
Authors: Geers-Lucas Maik , Guber Andrey , Kravchenko Alexandra
Published: December 2024

Physical characteristics of rhizosphere are crucial for plant performance; and analyses of rhizosheath, i.e. root-adhering soil, is a common tool in rhizosphere studies. Yet, despite numerous efforts, processes that lead to formation of rhizosphere porosity gradients, as well as their relationships with rhizosheath, remain poorly understood. We used X-ray computed micro-tomography (uCT) to examine rhizosphere porosity and to distinguish between the effect of direct root-induced changes vs. that of preferential root growth patterns on observed rhizosphere macroporosity gradients. We also utilized 14C labeling to evaluate rhizosheath in relation to rhizosphere macroporosity and rhizodeposition. The experiments were conducted in intact soil with inherent structure preserved and in sieved structureless soil. Rhizosphere macroporosity was found to be largely the outcome of root growth preferences, while root-induced changes occurred at <0.1 mm distances from the root surface and primarily in sieved soils. Rhizosheath formation was linked to the roots actively compacting their surrounding and releasing carbon in it, while there was no link between destructively-sampled rhizosheath and intactly uCT-observed rhizosphere. The findings suggest that root-soil interactions, rather than root-induced changes, drive rhizosphere porosity. Rhizosheath development compensates for low soil-root contact, however, traditionally sampled rhizosheath is not representative of the actual rhizosphere.
Loom response in mouse superior colliculus depends on sensorimotor context
Authors: Zucca Stefano , Schulz Auguste , Gonçalves Pedro J. , Macke Jakob H. , Saleem Aman B. , Solomon Samuel G.
Published: December 2024

Visual motion is produced both by an organism’s movement through the world, and by objects moving in the world such as potential predators. Choosing appropriate behaviour therefore requires organisms to distinguish these sources of visual motion. Here we asked how mice integrate self-movement with looming visual motion by combining virtual reality and neural recordings from superior colliculus (SC), a brain area important in visually-guided approach and avoidance behaviours. We first measured locomotion behaviour and neural activity while animals approached an object in virtual reality, and while the same object loomed at them. In both cases, vision dominated activity in superficial layers (SCs), while locomotion had more influence on activity in intermediate layers (SCim). In addition, animals instinctively slowed their locomotion when nearing the object, or when the object neared them. To directly test animals’ ability to distinguish self-from object motion we replayed the visual images generated during object approach. Locomotion behaviour often changed during replay, showing animals are able to establish if visual motion is matched to their self-movement. Further, decoders trained on locomotion behaviour, or on population activity in SC, particularly in SCim, were able to reliably discriminate epochs of replay and object approach. We conclude that both mouse behaviour and SC activity encode whether looming visual motion arises from self-or object movement, with implications for understanding sensorimotor coordination in dynamic environments.

Highlights

We recorded from superficial (SCs) and intermediate (SCim) superior colliculus in VR

Vision dominated SCs, while SCim was modulated by both vision and locomotion

Mice altered behaviour when visual experience did not match that expected from their locomotion

Population activity differed between matched and unmatched visual experiences, particularly in SCim
Efficient High-Throughput DNA Breathing Features Generation Using Jax-EPBD
Authors: Inan Toki Tahmid , Kabir Anowarul , Rasmussen Kim , Shehu Amarda , Usheva Anny , Bishop Alan , Alexandrov Boian , Bhattarai Manish
Published: December 2024

DNA breathing dynamics—transient base-pair opening and closing due to thermal fluctuations—are vital for processes like transcription, replication, and repair. Traditional models, such as the Extended Peyrard-Bishop-Dauxois (EPBD), provide insights into these dynamics but are computationally limited for long sequences. We presentJAX-EPBD, a high-throughput Langevin molecular dynamics framework leveragingJAXfor GPU-accelerated simulations, achieving up to 30x speedup and superior scalability compared to the original C-based EPBD implementation.JAX-EPBDefficiently captures time-dependent behaviors, including bubble lifetimes and base flipping kinetics, enabling genome-scale analyses. Applying it to transcription factor (TF) binding affinity prediction using SELEX datasets, we observed consistent improvements inR2values when incorporating breathing features with sequence data. Validating on the 77-bp AAV P5 promoter,JAX-EPBDrevealed sequence-specific differences in bubble dynamics correlating with transcriptional activity. These findings establishJAX-EPBDas a powerful and scalable tool for understanding DNA breathing dynamics and their role in gene regulation and transcription factor binding.
inVAE: Conditionally invariant representation learning for generating multivariate single-cell reference maps
Authors: Aliee Hananeh , Kapl Ferdinand , Pham Duy , Cakir Batuhan , Jimba Takahiro , Cranley James , Teichmann Sarah A. , Meyer Kerstin B. , Vento-Tormo Roser , Theis Fabian J.
Published: December 2024

Single-cell data is driving new insights into the spatiotemporal dynamics of cells and individual disease susceptibility. However, accurately identifying cell states across diverse cohorts remains challenging, as both biological variation and technical biases cause distributional shifts in the data. Separating these effects is crucial for capturing cellular heterogeneity and ensuring interpretability. To address this, we developedinVAE, a conditionally invariant deep generative model based on variational autoencoders. inVAE models the latent space as a combination of invariant variables, encoding true biological signals, and spurious variables, capturing technical biases. By conditioning the prior distribution of cells on biological covariates, such as disease variants, inVAE identifies high-resolution cell states in the invariant representation. Enforcing independence between the two representations disentangles biological signals from noise, enabling a more interpretable and generalizable model with a causal semantic. inVAE outperformed existing methods across four human cellular atlases of the human heart and lung, while uncovering novel cell states. It precisely stratified cell atlas donors based on the genetic impact of pathogenic variants, and excelled in predicting cell types and disease in unseen data, proving its generalizability as a reference model for label transfer. Furthermore, inVAE accurately identified temporal cell states and trajectories from developmental datasets, and captured spatial cell states in a spatially-resolved atlas. In summary, inVAE provides a powerful method for integrating multivariate single-cell transcriptomics data. By leveraging prior knowledge such as metadata, it effectively accounts for biological variation and improves latent space interpretability by disentangling biological and technical sources of variation. These capabilities enable deeper insights into cellular heterogeneity and its role in disease progression.
Variant Set Distillation
Authors: Christ Ryan , Kang Chul Joo , Aslett Louis J.M. , Lam Daniel , Savitski Maria Faelth , Stitziel Nathan , Steinsaltz David , Hall Ira
Published: December 2024

Allelic heterogeneity – the presence of multiple causal variants at a given locus – has been widely observed across human traits. Combining the association signals across these distinct causal variants at a given locus presents an opportunity for empowering gene discovery. This opportunity is growing with the increasing population diversity and sequencing depth of emerging genomic datasets. However, the rapidly increasing number of null (non-causal) variants within these datasets makes leveraging allelic heterogeneity increasingly difficult for existing testing approaches. We recently-proposed a general theoretical framework for sparse signal problems, Stable Distillation (SD). Here we present a SD-based methodvsdistill, which overcomes several major shortcomings in the simple SD procedures we initially proposed and introduces many innovations aimed at maximizing power in the context of genomics. We show via simulations thatvsdistillprovides a significant power boost over the popular STAAR method.vsdistillis available in our new R package gdistill, with core routines implemented in C. We also show our method scales readily to large datasets by performing an association analysis with height in the UK Biobank.
Hypocretin receptor 1 blockade early in abstinence reduces future demand for cocaine
Authors: Samels Shanna B. , Shaw Jessica K. , Alonso Pamela , Black Emily M. , España Rodrigo A.
Published: December 2024

Relapse to cocaine use after abstinence remains a significant challenge for treating cocaine use disorder. While the mechanisms of relapse are still under investigation, adaptations in mesolimbic dopamine systems may contribute to cocaine craving and propensity for relapse. Current pharmacological treatments targeting dopamine systems are often intolerable and may have abuse potential. Therefore, identifying novel pharmacological targets for cocaine use disorder is crucial. The hypocretin/orexin system has been shown to regulate cocaine-associated behavior and dopamine transmission. Our previous studies indicated that the hypocretin receptor 1 antagonist, RTIOX-276, reduced motivation for cocaine and attenuated dopamine responses to cocaine. Importantly, the effects of RTIOX-276 on dopamine transmission persisted for at least 24 hours, suggesting lasting effects of hypocretin receptor antagonism. Here, we hypothesized that a single RTIOX-276 treatment would reduce motivation for cocaine and normalize dopamine transmission after abstinence. Rats were pre-assessed for cocaine consumption and motivation using a within-session threshold schedule before intermittent access exposure to cocaine. Rats were subsequently treated with RTIOX-276 on the first day of a 7-day abstinence period, after which they were reassessed for cocaine consumption and motivation or examined for dopamine transmission using fast-scan cyclic voltammetry in nucleus accumbens core slices. We found that a single treatment with RTIOX-276 on the first day of abstinence reduced motivation for cocaine and normalized aberrant dopamine uptake observed following intermittent access to cocaine. These findings suggest that hypocretin receptor 1 may be a viable target for reducing motivation for cocaine through alterations in dopamine transmission in the nucleus accumbens.
Small Extracellular Vesicles Isolated from Cardiac Tissue Matrix or Plasma Display Distinct Aging-Related Changes in Cargo Contributing to Chronic Cardiovascular Disease
Authors: Ronan George , Yang Jun , Zorlutuna Pinar
Published: December 2024

Aging is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and numerous other diseases, but the mechanisms of these aging-related effects remain elusive. Chronic changes in the microenvironment and paracrine signaling behaviors have been implicated, but remain understudied. Here, for the first time, we directly compare extracellular vesicles obtained from young and aged patients to identify therapeutic or disease-associated agents, and directly compare vesicles isolated from heart tissue matrix (TEVs) or plasma (PEVs). While young EVs showed notable overlap of miRNA cargo, aged EVs differed substantially, indicating differential age-related changes between TEVs and PEVs. TEVs overall were uniquely enriched in miRNAs which directly or indirectly demonstrate cardioprotective effects, with 45 potential therapeutic agents implicated in our analysis. Both populations also showed increased predisposition to disease with aging, though through different mechanisms. PEVs were largely correlated with chronic systemic inflammation, while TEVs were more related to cardiac homeostasis and local inflammation. From this, 17 protein targets unique to TEVs were implicated as aging-related changes which likely contribute to the development of cardiovascular disease.
Development of a Real-Time Neural Controller using an EMG-Driven Musculoskeletal Model
Authors: Thomas Joel Biju , Laschowski Brokoslaw
Published: December 2024

Here we present our development of a novel real-time neural controller based on an EMG-driven musculoskeletal model, designed for volitional control of robots and computers. Our controller uniquely enables motion control during both isometric and non-isometric muscle contractions. We address several key challenges in EMG control system design, including accuracy, latency, and robustness. Our approach combines EMG signal processing, neural activation dynamics, and Hill-type muscle modeling to translate neural commands into muscle forces, which can enhance robustness against electrode variability and signal noise. Additionally, we integrate muscle activation dynamics with impedance control, inspired by the human motor control system, for smooth and adaptive interactions. As an initial proof of concept, we demonstrated that our system could control a robot actuator across a range of movements, both static and dynamic, and at different operating speeds, achieving high reference tracking performance and state-of-the-art processing times of 2.9 ms, important for real-time embedded computing. This research helps lay the groundwork for next-generation neural-machine interfaces that are fast, accurate, and adaptable to diverse users and control applications.
Triggered Temptations: A New Procedure to Compare Reward-Seeking Behaviour Induced by Discriminative and Conditioned Stimuli in Rats
Authors: LeCocq Mandy Rita , Najafipashaki Shaghayegh , Casale Domiziana , Laplante Isabel , Samaha Anne-Noël
Published: December 2024

Rationale

Environmental cues guide animals towards resources vital for survival but can also drive maladaptive reward-seeking behaviours, as in gambling and eating disorders. While conditioned stimuli (CSs) are paired with reward delivery after reward-seeking actions, discriminative stimuli (DSs) signal reward availability independent of behaviour.

Objective

We introduce a procedure to compare CS and DS effects on reward-seeking behaviour, in the same subjects within a single session.

Methods

Female and male Sprague-Dawley rats learned to self-administer sucrose. During each session, DS+ trials signaled that lever pressing would produce sucrose paired with a CS+, and DS−trials signaled no sucrose and a CS−. Next, in the absence of sucrose, we assessed the ability of the cues toi)reinforce lever pressing andii)increase sucrose seeking when presented response-independently. We also assessed the effects of the mGlu2/3receptor agonist LY379268 and d-amphetamine on cue-induced sucrose seeking.

Results

By the end of self-administration training, lever pressing peaked during DS+ trials and dropped during DS−trials. The DS+ was a conditioned reinforcer of sucrose seeking in both sexes, whereas the CS+ was more effective in males. Response-independent presentations of the DS+ invigorated sucrose seeking in both sexes, whereas the CS+ was effective only in males. LY379268 suppressed DS+-triggered sucrose seeking in females, with no effect in males. D-amphetamine enhanced sucrose seeking non-specifically across cue conditions in males, with no effect in females.

Conclusions

Our new trial-based procedure can be used to identify unique and similar mechanisms underlying DS and CS influences on appetitive behaviour.
Pathway Thermodynamic Analysis Postulates Change in Glutamate Metabolism as a Key Factor in Modulating Immune Responses
Authors: Malla Sunayana , Saha Rajib
Published: December 2024

Background

Temperature, as seen during fever, plays a pivotal role in modulating immune responses and maintaining cellular homeostasis. Shifts in temperature influence the thermodynamic feasibility of metabolic reactions, with Gibbs free energy (ΔG) serving as a key indicator of the spontaneity of reactions under specific conditions. By altering ΔG in response to temperature changes across various metabolite concentrations and cell types, we can gain insights into the thermodynamic properties of metabolic pathways and identify critical factors involved in metabolism and immune function. Using Max-Min Driving Force (MDF) analysis, we can assess changes in ΔG by varying temperature and metabolite concentrations, allowing for a detailed examination of thermodynamic feasibility at both the pathway and individual reaction levels.

Results

In this study, MDF analysis is applied to measure the changes in the driving force of pathways and the ΔG of each reaction at normal human core temperature (310.15 K) and elevated temperatures (up to 315.15 K). Additionally, we explore how shifts in the thermodynamic feasibility of reactions under immune activation, compared to normal physiological conditions, highlight key metabolic intermediates—such as fructose-1,6-bisphosphate, glucose-6-phosphate, and several steps in glutamate metabolism—as important regulators of metabolic processes and immune responses.

Conclusion

The goal of this study is to underscore the value of thermodynamic parameters such as ΔG, concentration, and temperature in identifying potential therapeutic targets, with the aim of mitigating the detrimental effects of fever while preserving its beneficial aspects.
Acute Flaccid Paralysis Surveillance System Evaluation, Ho Municipality, Volta Region, Ghana, 2022
Authors: Kijera Bakalilu , Alhasan Abdul Nasir , Jarjusey Sarja , Bobb Mary , Manjang Lamin F , Ameme Donne , Noora Charles Lwanga , Bandoh Delia , Kenu Ernest
Published: December 2024

Background

Ghana reported the last native Wild Poliovirus that causes poliomyelitis in 1999. However, Ghana experienced another outbreak when cases were imported into the country in 2003 and 2004. The decade-long polio-free status ended in 2019 following the detection of circulatory Vaccine-Derived Polio Virus type 2 (cVDPV2) through Environmental Health Surveillance (EHS). Ghana is currently free from cVDPV2 but is at risk of potential outbreaks. This evaluation describes the usefulness and attributes of an Acute Flaccid Paralysis (AFP) surveillance system and whether the system meets its objectives.

Methods

A descriptive evaluation of the AFP surveillance system from January 2017 to December 2021 was conducted in Ho Municipality, Volta Region. Interviews of health workers and key stakeholders, observations, records review, and administration of semi-structured questionnaires were made. The Centres for Disease Control and Prevention Updated guidelines for evaluating public health surveillance systems were used as a reference for developing a checklist. The quantitative data was analyzed using summary statistics and presented in percentages and frequencies. The qualitative interviews were audio recorded, transcribed, and narratively analyzed.

Results

Ten AFP cases were reported from January 2017 to December 2021. Six of these (28.57%) were detected based on actions taken on AFP surveillance data. The average NP-AFP was 2.14/100,000 with a minimum of 1.09/100,000 and a maximum of 4.12/100,000 under 15 population. One (10.0%) of the specimens reached the reference lab within 72 hours and an overall completeness of 68.04%. Three (30.0%) cases were follow-up after 60 days from the onset of the paralysis.

Conclusion

The AFP surveillance system in Ho municipality is partially meeting its objectives. It is useful, partially stable, and sensitive. The system is acceptable, representative, flexible, and accurate but poor in timeliness. The District Health Management Team should ensure specimens are sent to the reference laboratory within 72 hours after the case investigation.
TrackingHelicoverpa zea(Lepidoptera: Noctuidae) flight behavior with infrared camera around pheromone trap
Authors: Duplais Christophe , Roh Chris
Published: December 2024

Understanding the flight behavior of nocturnal insect pests is essential for designing effective trapping systems and improving integrated pest management (IPM). This study used infrared (IR) reflectance and IR camera to analyze the flight behavior of corn earworm (Helicoverpa zea) around Scentry Heliothis pheromone trap, focusing on approach, escape, and capture rates. Video analysis revealed low average catch rate of 25% for a total of 48 approaches from 7 p.m. to 4 a.m., as many moths approached the lure but escaped without being trapped. The study identified critical behavioral patterns, such as upwind approach, downwind horizontal escape, or vertical ascending leading to capture. These findings suggest that positioning lure closer to the trap entrance could significantly improve the effectiveness of Scentry Heliothis trap. Additionally, the study highlights the importance of developing a comprehensive database of nocturnal insect behavior around trapping systems. This knowledge can be used to refine trap design for specific insect pest and to update catch count thresholds to improve the effectiveness of insecticide spray programs in precision agriculture. This work demonstrates the potential of IR cameras as a simple, commercially available, and affordable tool for studying nocturnal insect pest activity and flight behavior, with the potential to enhance pest management strategies in agriculture.
Multimodal single-cell analyses reveal molecular markers of neuronal senescence in human drug-resistant epilepsy
Authors: Ge Qianqian , Yang Jiachao , Huang Fei , Dai Xinyue , Chen Chao , Guo Jinxin , Wang Mi , Zhu Mengyue , Shao Yijie , Xia Yuxian , Zhou Yu , Peng Jieqiao , Deng Suixin , Shi Jiachen , Hu Yiqi , Zhang Huiying , Wang Yi , Wang Xiaoqun , Li Xiao-Ming , Chen Zhong , Shu Yousheng , Zhu Jun-Ming , Zhang Jianmin , Shen Ying , Duan Shumin , Xu Shengjin , Shen Li , Chen Jiadong
Published: December 2024

The histopathological neurons in the brain tissue of drug-resistant epilepsy exhibit aberrant cytoarchitecture and imbalanced synaptic circuit function. However, the gene expression changes of these neurons remain unknown, making it difficult for the diagnosis or to dissect the mechanism of drug-resistant epilepsy. By integrating whole-cell patch clamp recording and single-cell RNA sequencing approaches, we identified a transcriptionally distinct subset of cortical pyramidal neurons. These neurons highly expressed genesCDKN1A(P21),CCL2andNFKBIAthat associated with mTOR pathway, inflammatory response and cellular senescence. We confirmed the expression of senescent marker genes in a subpopulation of cortical pyramidal neurons with enlarged soma size in the brain tissue of drug-resistant epilepsy. We further revealed the expression of senescent cell markers P21, P53, COX2, γ-H2AX, β-Gal and reduction of nuclear integrity marker Lamin B1 in histopathological neurons in the brain tissue of drug-resistant epilepsy patients with different pathologies, but not in control brain tissue with no history of epilepsy. Additionally, chronic, but not acute, epileptic seizures induced senescent markers expression in cortical neurons in mouse models of drug-resistant epilepsy. These results provide important molecular markers for histopathological neurons and new insights into the pathophysiological mechanisms of drug-resistant epilepsy.
Identification of Differentially Expressed Genes and Proteins Related to Diapause inLymantria dispar: Insights for the Mechanism of Diapause from Transcriptome and Proteome Analyses
Authors: Xie Qing , Ma Xiaofan , Li Yafei , Ji Wenzhuai , Dou Fengrui , Zhu Xiue , Shi Juan , Cao Yixia
Published: December 2024

Spongy moth (Lymantria disparLinnaeus) is a globally recognized quarantine leaf-eating pest. Spongy moths typically enter diapause after completing embryonic development and overwinter in the egg stage. They spend three-quarters of their life cycle (approximately nine months) in the egg stage, which requires a period of low-temperature stimulation to break diapause and continue growth and development. In this study, we explored the molecular mechanism underlying the diapause process in spongy moth. We performed bioinformatics analysis on four Asian populations of spongy moth and one Asian–European hybrid population through a transcriptome analysis combined with proteomics. The results revealed that 1,842 genes were differentially expressed upon diapause initiation, while 264 genes were identified upon diapause termination. Eight diapause-related genes were screened out from the three-level pathways that were significantly enriched by differentially expressed genes at the time of diapause and diapause termination, and the phylogenetic tree and protein three-dimensional structure model were constructed. This study elucidates the diapause mechanism of spongy moth at the gene and protein levels, providing theoretical insights into the early and precise prevention and control of spongy moth. This study can facilitate the development of an efficient, environmentally friendly control system for managing spongy moth populations in the field.
scPDA: Denoising Protein Expression in Droplet-Based Single-Cell Data
Authors: Zhu Ouyang , Li Jun
Published: December 2024

Droplet-based profiling techniques such as CITE-seq measure the surface protein abundance of single cells, providing crucial information for cell-type identification. How-ever, these measurements are often significantly contaminated by technical noise, which lowers the efficiency of using the gating strategy to identify cell types. Current computational denoising methods have serious limitations, including a strong reliance on often-unavailable empty droplets or null controls, insufficient efficiency due to the ignoring of protein-protein interactions, and a heavy computational load. Here, we introduce scPDA, a new probabilistic model that employs a variational autoencoder to achieve high computational efficiency. scPDA completely eliminates the use of empty droplets, and it shares information across proteins to increase denoising efficiency. Compared to currently available methods, scPDA has removed noise much more thoroughly while preserving biological signals, and it has substantially improved the efficiency of gating-strategy-based cell-type identification, marking a clear advancement in the computational denoising of the protein modality.
Sexual size dimorphism correlates with the number of androgen response in mammals, but only in small-bodied species
Authors: Ghione Caleb R. , Dean Matthew D.
Published: December 2024

Sexual size dimorphism (SSD) is common throughout the animal kingdom. “Rensch’s Rule” was proposed nearly 80 years ago, named for the observation that the magnitude of SSD in male-larger species increased with average body size. Here we re-examine this trend across 268 mammalian species with full genome assemblies and annotations, and place the evolution of SSD in the context of androgen response elements or estrogen response elements, the DNA motifs to which sex hormone receptors bind. Hormone receptors provide intuitive mechanisms for sex-specific regulation of the genome and could greatly impact SSD. We find that the three relatively large-bodied lineages (orders Carnivora, Cetartiodactyla, and Primates) follow Rensch’s Rule, and SSD does not correlate with the number of receptor elements. In contrast, SSD in small-bodied lineages (Chiroptera and Rodentia) correlates with the number of androgen response elements, but SSD does not correlate with overall body size. One hypothesis to unify our observations is that small-bodied organisms like bats and rodents tend to reach peak reproductive fitness quickly and are more reliant on hormonal signaling to achieve SSD over relatively short time periods. Our study uncovers a previously unappreciated relationship between SSD, body size, and hormone signaling that likely varies in ways related to life history.
Developmentally Incomplete Barb Rami Increased the Morphological Diversity of Early Feathers
Authors: Zhang Yanyun , Tang Jiawei , Wang Ying , Wang Shuo
Published: December 2024

Recent studies have significantly advanced our understanding of the evolutionary processes and developmental mechanisms behind feather branching patterns. However, little attention has been given to the tissue differentiation of branches associate with this process. Here, we describe eight feathers preserved in Burmese ambers, characterized by ribbon-like barb rami composed solely of cortex, lacking a medulla. These feathers are categorized into three morphotypes based on the details of their barb rami morphologies. For each morphotype, potential developmental scenarios were proposed through inference of barb development in chickens, suggesting limited tissue differentiation of barb rami in these early feathers. Functional simulations indicate that the configuration of modern barb rami is aerodynamically more stable than those of early feathers, indicating that flexural stiffness may have been a crucial factor driving the evolution of feather branches toward modern configurations. The discovery of developmentally incomplete barb rami in Burmite feathers implies that, while the three-level hierarchical branching pattern of modern feathers had evolved by the Jurassic period, tissue differentiation patterns of feather branches may not have fully stabilized by the Late Cretaceous. This instability likely contributes to the morphological diversity of early feathers, resulting in forms not seen in modern birds.
Exercise-induced differential transcriptional output of AMPK signalling improves axon regeneration and functional recovery
Authors: Behera Sibaram , Ghosh Roy Anindya
Published: December 2024

In adulthood, the regenerative capacity of the injured brain circuit is poor preventing functional restoration. Rehabilitative physical exercise is a promising approach to overcome such functional impairment and the metabolic sensor AMPK has emerged to be a critical mediator for this. However, the mechanistic understanding of upstream and downstream components of AMPK signalling in the physical exercise-mediated enhancement of axon regeneration is not clear. We combined swimming exercise with laser axotomy of posterior lateral microtubule (PLM) neurons ofCaenorhabditis elegansto address this question. We found that direct activation of AMPK through AICAR treatment is sufficient to improve axon regeneration and functional recovery. The PAR-4/Liver kinase B1 (LKB1) acts upstream of AMPK to enhance functional recovery following swimming exercise. Using genetics, tissue-specific RNAi, and AICAR treatment, we found that the transcriptional regulators DAF-16 and MDT-15 act downstream of AMPK in mediating the positive effects of swimming. We found that MDT-15 acts in neuron to mediate the benefit of AMPK activation in axon regeneration, whereas DAF-16 acts both in neuron and muscle to promote regrowth downstream to AMPK. We also showed that swimming exercise induces nuclear localization of DAF-16 in an AMPK-dependent manner. Our results showed that neuronal and non-neuronal arms of AMPK signalling play an integrative role in response to physical exercise to promote functional recovery after axon injury.

Significance statement

Finding ways to promote functional recovery after accidental damage to the nervous system has been challenging as adult neurons lose the capability to regenerate. Rehabilitation therapy is the most promising approach to improve the health condition of patients with nervous system injury. Even in the roundwormC. elegans, axon regeneration could be enhanced through swimming exercise, which is mediated by the metabolic energy sensor AMP Kinase. In this study, using sensory neurons in worm, we found that PAR-4/ Liver kinase B1 acts upstream of AMPK. Whereas, the transcription factor DAF-16/ FOXO and the transcriptional co-regulator MDT-15 act as downstream signalling arms in muscle and neuron tissues. Excitingly, both of these arms could be harnessed through agonist-mediated activation of AMPK to promote functional recovery in adulthood.
Relationship between Brain and Body Temperature in Anesthetized Animals Measured by Ultralocal Thermometry
Authors: Osypov A.A. , Krokhaleva V.K. , Romshin A.M. , Popova I. Yu
Published: December 2024

Temperature is one of the least studied biophysical characteristics of the brain, although both the rate of biochemical reactions and the electrical activity of nervous tissue directly depend on it. The purpose of this study was to analyze the relationship between brain and body temperatures in anesthetized animals. Simultaneous measurement of brain and body temperature (rectally) was carried out at ambient temperature controlled with a thermal mat. The temperature of the deep layers of the somatosensory cortex was measured by ultralocal thermometry using a diamond thermometer. Under anesthesia, the body and brain temperature dropped to 27 C (4 degrees above ambient temperature). When the thermal mat was turned on, the brain and body began to heat up synchronously. The brain initially lagged behind, but when the critical temperature was reached, it began to release heat in quantities exceeding the influx from the blood, reaching physiological values of 37C. A reverse experiment with decreasing the temperature of the thermal mat showed a similar picture: a synchronous start of the decrease, but with reverse dynamics. Thus, we can distinguish two phases of the brain’s reaction to external heating: passive - when neuronal activity is decreased, and active - after internal regulatory mechanisms are triggered, which, in its turn, slows down the temperature drop. In general, the data obtained in the present work indicate that the temperature of neural tissue is not linearly related to body temperature.
The heterogeneity of dermal mesenchymal cells reproduced in skin equivalents regulate barrier function and elasticity
Authors: Kimura Shun , Sekiya Sachiko , Yamashiro Sawa , Kikuchi Tetsutaro , Haga Masatoshi , Shimizu Tatsuya
Published: December 2024

The heterogeneity of dermal mesenchymal cells, including perivascular mesenchymal cells and papillary and reticular fibroblasts, plays critical roles in skin homeostasis. Here, we present human skin equivalents (HSEs) in which pericytes, papillary fibroblasts, and reticular fibroblasts are spatially organized through autonomous three-cell interactions among epidermal keratinocytes, dermal fibroblasts, and vascular endothelial cells. The replication of dermal mesenchymal cell heterogeneity enhances skin functions, including epithelialization, epidermal barrier formation, and dermal elasticity, enabling thein vitroevaluation of drug efficacy using methodologies identical to those used in human clinical studies. Furthermore, we found that ascorbic acid-induced epidermal turnover and well-aligned extracellular matrix synthesis via perivascular niche cells play crucial roles in improving skin aging phenotypes. HSEs with heterogeneous dermal mesenchymal cells will improve our understanding of the mechanisms underlying skin homeostasis through cell-to-cell communication and serve as an alternative model to animal experiments for the development of precision medicine.