bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and facilitators for physical activity in people living with chronic pain: a systematic review and combined analysis
Authors: Leese Callum , Gupte Devashri , Christogianni Aikaterini , Higgins Cassie , Adair Pauline , Dall Philippa , Cameron Paul , Smith Blair H. , Colvin Lesley
Published: July 2024

Chronic pain is a prevalent and complex health issue associated with physical, emotional, and social consequences. Management of pain is multifactorial and challenging; however, physical activity (PA) has consistently been shown to be beneficial. Despite this, PA levels among people with chronic pain are low. This study aimed to identify facilitators and barriers to PA among adults with chronic pain and analyse these using the structure of a validated behaviour change model: the capability, opportunity, and motivation behaviour change model (COM-B). We performed a systematic review of 6 databases and subsequent combined analysis including peer-reviewed primary research published in English up to November 15, 2023. Search terms consisted of 3 components: pain, PA, and facilitators/barriers. Quality appraisal of studies was conducted using appropriate tools. The systematic search yielded 40 eligible studies with a total of 2164 participants. The studies represented various chronic pain conditions, locations, and study designs. The key barriers to engagement in PA were the impact of pain severity, comorbidities, lack of knowledge about PA benefits, and time constraints. Key facilitators were a personalised approach, social support, and awareness of the benefits. The findings were categorised according to the COM-B model, allowing for the identification of modifiable factors. Person-centred approaches, education, and accessible environments were identified as important aspects to consider for successful PA promotion among people with chronic pain. Utilising the factors identified in the COM-B model is crucial for successful future interventions to increasing PA uptake and adherence in this population.
Is the relationship between chronic pain and mortality causal? A propensity score analysis
Authors: Ryan Eva , Grol-Prokopczyk Hanna , Dennison Christopher R. , Zajacova Anna , Zimmer Zachary
Published: July 2024

Chronic pain is a serious and prevalent condition that can affect many facets of life. However, uncertainty remains regarding the strength of the association between chronic pain and death and whether the association is causal. We investigate the pain–mortality relationship using data from 19,971 participants aged 51+ years in the 1998 wave of the U.S. Health and Retirement Study. Propensity score matching and inverse probability weighting are combined with Cox proportional hazards models to investigate whether exposure to chronic pain (moderate or severe) has a causal effect on mortality over a 20-year follow-up period. Hazard ratios (HRs) with 95% confidence intervals (CIs) are reported. Before adjusting for confounding, we find a strong association between chronic pain and mortality (HR: 1.32, 95% CI: 1.26-1.38). After adjusting for confounding by sociodemographic and health variables using a range of propensity score methods, the estimated increase in mortality hazard caused by pain is more modest (5%-9%) and the results are often also compatible with no causal effect (95% CIs for HRs narrowly contain 1.0). This attenuation highlights the role of confounders of the pain–mortality relationship as potentially modifiable upstream risk factors for mortality. Posing the depressive symptoms variable as a mediator rather than a confounder of the pain–mortality relationship resulted in stronger evidence of a modest causal effect of pain on mortality (eg, HR: 1.08, 95% CI: 1.01-1.15). Future work is required to model exposure–confounder feedback loops and investigate the potentially cumulative causal effect of chronic pain at multiple time points on mortality.
Sport-specific Differences in Cartilage Treatment
Authors: Allahabadi Sachin , Yazdi Allen A. , Weissman Alexander C. , Meeker Zachary D. , Yanke Adam B. , Cole Brian J.
Published: July 2024

Articular cartilage defects in the knee are common in athletes who have a variety of loading demands across the knee. Athletes of different sports may have different baseline risk of injury. The most studied sports in terms of prevalence and treatment of cartilage injuries include soccer (football), American football, and basketball. At this time, the authors do not specifically treat patients by their sport; however, return to sports timing may be earlier in sports with fewer demands on the knee based on the rehabilitation protocol. If conservative management is unsuccessful, the authors typically perform a staging arthroscopy with chondroplasty, followed by osteochondral allograft transplantation with possible additional concomitant procedures, such as osteotomies or meniscal transplants. Athletes in a variety of sports and at high levels of competition can successfully return to sports with the appropriate considerations and treatment.
Racial Disparities in Treatment and Outcomes of Pediatric Hepatoblastoma
Authors: Billion Taylor , Braaten Marco , Holland Eva , Mishra Anjali , Kashikar Rimzhim , Silberstein Peter , Tauseef Abubakar , Asghar Noureen , DeVrieze Bradley , Mirza Mohsin
Published: July 2024

Pediatric Hepatoblastoma is a rare malignancy of the liver. This study used the National Cancer Database (NCDB) to identify 1068 patients diagnosed with hepatoblastoma from 2004 to 2020. χ2 and Analysis of Variance testing, as well as Kaplan-Meier, Cox Regression, and multinomial logistic regression models were used. Data was analyzed using SPSS version 27, and statistical significance was set at α=0.05. Our results found Black patients experienced a significantly lower median survival rate compared with White patients, a difference which persisted after controlling for covariates. Black patients were also less likely to receive surgery and chemotherapy and more likely to be from low-income households than White patients. White patients had a significantly shorter inpatient hospital stay compared to Black patients and were more likely to receive treatment at more than 1 CoC accredited facility. There was no significant difference in grade, size of tumor, metastasis, or time of diagnosis to surgery. This study showed Black patients experienced inferior overall survival when diagnosed and treated for hepatoblastoma compared to White patients.
Performance of GPT-4 on Chinese Nursing Examination
Authors: Miao Yiqun , Luo Yuan , Zhao Yuhan , Li Jiawei , Liu Mingxuan , Wang Huiying , Chen Yuling , Wu Ying
Published: July 2024

Background:

The performance of GPT-4 in nursing examinations within the Chinese context has not yet been thoroughly evaluated.

Objective:

To assess the performance of GPT-4 on multiple-choice and open-ended questions derived from nursing examinations in the Chinese context.

Methods:

The data sets of the Chinese National Nursing Licensure Examination spanning 2021 to 2023 were used to evaluate the accuracy of GPT-4 in multiple-choice questions. The performance of GPT-4 on open-ended questions was examined using 18 case-based questions.

Results:

For multiple-choice questions, GPT-4 achieved an accuracy of 71.0% (511/720). For open-ended questions, the responses were evaluated for cosine similarity, logical consistency, and information quality, all of which were found to be at a moderate level.

Conclusion:

GPT-4 performed well at addressing queries on basic knowledge. However, it has notable limitations in answering open-ended questions. Nursing educators should weigh the benefits and challenges of GPT-4 for integration into nursing education.
Acute Kidney Injury in Systemic Sclerosis Beyond Scleroderma Renal Crisis
Authors: Wajid Sumbal , Shapiro Lee , Farrukh Larabe , Hu Kurt , Feustel Paul J. , Hongalgi Krishnakumar , Mehta Swati
Published: July 2024

Background and Objectives

Renal involvement in systemic sclerosis remains a significant concern with the focus often centered on scleroderma renal crisis (SRC). However, the broader spectrum of renal manifestations, beyond SRC, remains underrecognized. In our case-control analysis, we describe other causes, risk factors, and renal outcomes of acute kidney injury (AKI) in systemic sclerosis other than SRC.

Methods

Patients diagnosed with SSC, with and without AKI, between 2017 and 2023 at Albany Medical Center, were included in the case-control study using International Classification of Diseases, 10th Revision codes and electronic medical records. Patients with SRC were carefully excluded. Data were collected and compared between AKI and non-AKI groups for patients' demographics, clinical characteristics, and baseline treatment. Additionally, data were collected for baseline, peak, and follow-up creatinine, etiology of AKI, treatment, and outcomes. Statistical analysis was performed using R (version 4.3.0) and Minitab (V19). Categorical variables were presented as frequencies/percentages, and continuous variables as means/standard deviations. Associations between categorical variables were assessed by χ2 test and Fisher exact test. Odds ratios and 95% confidence intervals were calculated using binary logistic regression to separately assess the effect of each independent variable on the odds of AKI. Statistical significance was set at p < 0.05.

Results

A total of 74 cases were identified. Out of these 74 cases, 27 had AKI and 47 did not have AKI. Out of the 27 AKI cases, 4 with SRC were excluded. Advanced age, chronic kidney disease, and heart failure were identified as risk factors for AKI development. The predominant cause of AKI was prerenal etiology, accounting for 47.8% (n = 11) of cases. This was followed by cardiorenal syndrome and acute tubular necrosis, accounting for 21.7% and 17.3% of the cases, respectively. Most of the cases with AKI had complete renal recovery 78% (n = 18), whereas 17% (n = 4) had progression of the underlying chronic kidney disease. One patient progressed to end-stage renal disease requiring hemodialysis.

Conclusions

This analysis highlights the risk factors and variable clinicopathological courses of renal involvement in patients with scleroderma. This may range from mild AKI with good prognosis to life-threatening SRC.
Can narrative help people engage with and understand information without being persuasive? An empirical study
Authors: Freeman Alexandra L. J. , Tanase Lisa-Maria , Schneider Claudia R. , Kerr John
Published: July 2024

Stories have been shown to be engaging and aid the comprehension and retention of information. However, the persuasive power of storytelling is well-recognized. Is this an inherent property? Can a narrative be constructed that helps people engage with information but does not persuade them? We presented participants (
n 
= 1309) with information about a fictional new drug and asked them whether they would license it on the basis of this. All saw the same information, in either a bullet-pointed list or as a ‘process narrative’—a journalist’s ‘journey of discovery’, designed to avoid persuasive language. Participants rated the narrative format a little more engaging than the non-narrative (
p
= 0.033,
d
= 0.12) and remembered the information in it slightly better (
p
 = 0.040,
d
= 0.11). They did not rate the narrative version as more persuasive, but those reading it were on average more opposed to licensing the drug than those reading the non-narrative (
p
< 0.001,
d
= 0.18). Based on participants’ responses to other questions, we speculate this may be owing to the increased salience of risks of the drug, arising from subtle differences in wording. Thus, while narratives may have useful properties, they must be carefully constructed to avoid unintentional effects.
One-factor sex determination evolves without linkage between feminizing and masculinizing mutations
Authors: Scott Michael F. , Immler Simone
Published: July 2024

The evolution of separate sexes from cosexuality requires at least two mutations: a feminizing allele to cause female development and a masculinizing allele to cause male development. Classically, the double mutant is assumed to be sterile, which leads to two-factor sex determination where male and female sex chromosomes differ at two loci. However, several species appear to have one-factor sex determination where sexual development depends on variation at a single locus. We show that one-factor sex determination evolves when the double mutant develops as a male or a female. The feminizing allele fixes when the double mutant is male, and the masculinizing allele fixes when the double mutant is female. The other locus then gives XY or ZW sex determination based on dominance: for example, a dominant masculinizer becomes a Y chromosome. Although the resulting sex determination system differs, the conditions required for feminizers and masculinizers to spread are the same as in classical models, with the important difference that the two alleles do not need to be linked. Thus, we reveal alternative pathways for the evolution of sex determination and discuss how they can be distinguished using new data on the genetics of sex determination.
Heart rate monitoring reveals differential seasonal energetic trade-offs in male noctule bats
Authors: Keicher Lara , Shipley J. Ryan , Dietzer Melina T. , Wikelski Martin , Dechmann Dina K. N.
Published: July 2024

Understanding how animals meet their daily energy requirements is critical in our rapidly changing world. Small organisms with high metabolic rates can conserve stored energy when food availability is low or increase energy intake when energetic requirements are high, but how they balance this in the wild remains largely unknown. Using miniaturized heart rate transmitters, we continuously quantified energy expenditure, torpor use and foraging behaviour of free-ranging male bats (
Nyctalus noctula
) in spring and summer. In spring, bats used torpor extensively, characterized by lowered heart rates and consequently low energy expenditures. In contrast, in summer, bats consistently avoided torpor, even though they could have used this low-energy mode. As a consequence, daytime heart rates in summer were three times as high compared with the heart rates in spring. Daily energy use increased by 42% during summer, despite lower thermogenesis costs at higher ambient temperatures. Likely, as a consequence, bats nearly doubled their foraging duration. Overall, our results indicate that summer torpor avoidance, beneficial for sperm production and self-maintenance, comes with a high energetic cost. The ability to identify and monitor such vulnerable energetic life-history stages is particularly important to predict how species will deal with increasing temperatures and changes in their resource landscapes.
Torpor use in the wild by one of the world’s largest bats
Authors: Turbill Christopher , Walker Melissa , Boardman Wayne , Martin John M. , McKeown Adam , Meade Jessica , Welbergen Justin A.
Published: July 2024

Torpor is widespread among bats presumably because most species are small, and torpor greatly reduces their high mass-specific resting energy expenditure, especially in the cold. Torpor has not been recorded in any bat species larger than 50 g, yet in theory could be beneficial even in the world’s largest bats (flying-foxes;
Pteropus
spp.) that are exposed to adverse environmental conditions causing energy bottlenecks. We used temperature telemetry to measure body temperature in wild-living adult male grey-headed flying-foxes (
P. poliocephalus
; 799 g) during winter in southern Australia. We found that all individuals used torpor while day-roosting, with minimum body temperature reaching 27°C. Torpor was recorded following a period of cool, wet and windy weather, and on a day with the coldest maximum air temperature, suggesting it is an adaptation to reduce energy expenditure during periods of increased thermoregulatory costs and depleted body energy stores. A capacity for torpor among flying-foxes has implications for understanding their distribution, behavioural ecology and life history. Furthermore, our discovery increases the body mass of bats known to use torpor by more than tenfold and extends the documented use of this energy-saving strategy under wild conditions to all bat superfamilies, with implications for the evolutionary maintenance of torpor among bats and other mammals.
Precise tactile localization on the human fingernail
Authors: Longo Matthew R.
Published: July 2024

Fingernails are specialized features of the primate hand, which are believed to contribute to manual dexterity. The sensorimotor functions of fingernails, however, remain poorly understood. This study investigates the ability of humans to precisely localize touches applied to the fingernail plate. Nine different locations on the fingernail were touched and participants judged the location by clicking a mouse cursor on a photograph of their finger. Performance in this condition was compared with stimuli applied to the skin of the fingertip. The results showed that participants are able to localize touch on the fingernails at substantially higher than chance levels. Moreover, the precision of this ability is not appreciably lower than that of the fingertips. These results show that the fingernail is a highly sensitive sensory organ, which is capable of providing rich spatial information about tactile stimuli.
GWarrange: a pre- and post- genome-wide association studies pipeline for detecting phenotype-associated genome rearrangement events
Authors: Tam Yi Ling , Cameron Sarah , Preston Andrew , Cowley Lauren
Published: July 2024

The use of k-mers to capture genetic variation in bacterial genome-wide association studies (bGWAS) has demonstrated its effectiveness in overcoming the plasticity of bacterial genomes by providing a comprehensive array of genetic variants in a genome set that is not confined to a single reference genome. However, little attempt has been made to interpret k-mers in the context of genome rearrangements, partly due to challenges in the exhaustive and high-throughput identification of genome structure and individual rearrangement events. Here, we present GWarrange, a pre- and post-bGWAS processing methodology that leverages the unique properties of k-mers to facilitate bGWAS for genome rearrangements. Repeat sequences are common instigators of genome rearrangements through intragenomic homologous recombination, and they are commonly found at rearrangement boundaries. Using whole-genome sequences, repeat sequences are replaced by short placeholder sequences, allowing the regions flanking repeats to be incorporated into relatively short k-mers. Then, locations of flanking regions in significant k-mers are mapped back to complete genome sequences to visualise genome rearrangements. Four case studies based on two bacterial species (Bordetella pertussis and Enterococcus faecium) and a simulated genome set are presented to demonstrate the ability to identify phenotype-associated rearrangements. GWarrange is available at https://github.com/DorothyTamYiLing/GWarrange.
Reinforcement learning guides single-cell sequencing in decoding lineage and cell fate decisions
Authors: Fu Zeyu , Wang Song , Sun Kangfu , Xu Baichuan , Ye Xianpeng , Wen Zhaoyang , Shen Mingqiang , Chen Mo , Chen Fang , Xu Yang , Deng Youcai , Wang Junping , Chen Shilei
Published: July 2024

The rapid development of single-cell sequencing provides unparalleled opportunity for delineating the heterogeneous characteristics of individual cells, while current methodologies fall short in accurately deciphering the origins of cellular heterogeneity and pinpointing the states of cell fate decisions. In this study, we introduce a novel approach termed Single-cell Reinforcement Learning (scRL) by integrating a framework of reinforcement learning into single-cell data analysis with the assistance of an actor-critic architecture. scRL reveals that the intensity of fate decisions precedes the maximum potential of lineage differentiation and actual gene expression, which enables the forecasting and perturbation of cellular fate in an earlier stage. The superiority of scRL in assessing fate decisions is confirmed in several different patterns of single-cell datasets. By using scRL, we disclose a distinct role ofDapp1in myeloid lineage decision during hematopoietic stem cells (HSCs) differentiation and uncover the priority of erythroid fate decision occurring post irradiation exposure.
S. cerevisiaeserves as keystone species for spoilage resistance in experimental synthetic wine yeast communities
Authors: Leale Alanna M. , Pourcelot Eléonore , Guezenec Stéphane , Sicard Delphine , Nidelet Thibault
Published: July 2024

Species diversity is a commonly stated contributor to the fate of an invader, and thus community resistance, in both microbial and non-microbial communities. Termed the “diversity-invasion hypothesis”, a positive relationship between diversity and resistance to invasion is observed when an introduced species exhibits lower levels of survival in resident communities with higher species richness. The diversity-invasion hypothesis is an attractive perspective with convincing theory and examples, yet an “invasion paradox” of contrasting results means that a positive role of diversity against invasion is still not a certainty and under debate. In this study we investigated the relationship between resistance to invasion and resident community species richness versus species identity (i.e., keystone species). Using synthetic communities comprised of combinations of four wine yeasts (Saccharomyces cerevisiae, Lachancea thermotolerans, Torulaspora delbrueckii, Starmerella bacillaris), we tracked over 21 days the presence of introducedBrettanomyces bruxellensisspoilage yeast andLactiplantibacillus plantarumlactic acid bacteria to ask the following: 1. Does yeast community species richness impact the establishment ofB. bruxellensisyeast andL. plantarumbacteria during wine fermentation? 2. How does yeast species identity influence such establishment? We found that species identity rather than richness drove the prevention of establishment ofB. bruxellensisandL. plantarum, withS. cerevisiaeplaying a critical keystone species role. Aside from spoilage prevention byS. cerevisiae, the four resident yeast species demonstrated a strict dominance ranking of competitive exclusion regardless of background community composition. Our research lends evidence against the commonly predicted positive relationship between species richness and resistance to invasion. Furthermore, as spontaneously fermented natural wines and diverse starter cultures gain popularity, our findings support a remaining importance ofS. cerevisiaein preventingB. bruxellensisspoilage..
AI-driven high-throughput droplet screening of cell-free gene expression
Authors: Zhu Jiawei , Meng Yaru , Gao Wenli , Yang Shuo , Zhu Wenjie , Ji Xiangyang , Zhai Xuanpei , Liu Wan-Qiu , Luo Yuan , Ling Shengjie , Li Jian , Liu Yifan
Published: July 2024

Cell-free gene expression (CFE) systems enable transcription and translation using crude cellular extracts, offering a versatile platform for synthetic biology by eliminating the need to maintain living cells. This allows direct manipulation of molecular components and the focused synthesis of specific products. However, the optimization of CFE systems is constrained by cumbersome composition, high costs, and limited yields due to numerous additional components required to maintain biocatalytic efficiency. While optimizing such complicated systems is daunting for existing high-throughput screening means, we introduce DropAI, a droplet-based, AI-driven screening strategy designed to optimize CFE systems with high throughput and economic efficiency. DropAI employs microfluidics to generate picoliter reactors and utilizes a fluorescent color-based coding-decoding system to address and screen a vast array of additive combinations. The in-droplet screening is complemented by in silico optimization, where experimental results train a machine-learning model to estimate the contribution of the components and predict high-yield combinations, which are then validated in vitro. Applying DropAI to anEscherichia coli-based CFE system, we simplified a set of 12 additives to only 3 essential components. Through further optimization, we achieved a 2.1-fold cost reduction and a 1.9-fold increase in yield for the expression of superfolder green fluorescent protein (sfGFP). This optimized formulation was further validated across 12 different proteins. Notably, the establishedE. colimodel is successfully adapted to aBacillus subtilis-based system through transfer learning, leading to doubled yield through prediction. DropAI thus offers a generalizable and scalable method for optimizing CFE systems, enhancing their potential for biochemical engineering and biomanufacturing applications.
White matter microglia morphological changes with aging in guinea pig offspring born growth restricted
Authors: Nunes Timothy B. , Nygard Karen L. , Courchesne Marc C.J. , Whitehead Shawn N. , Richardson Bryan S. , Regnault Timothy R.H.
Published: July 2024

Fetal growth restriction is implicated in the programming of later-life neurodegeneration. We hypothesized that growth restricted offspring would show accelerated changes to microglial white matter morphology, relative to controls.

Control guinea pig sows were fedad libitum, while maternal nutrient restriction sows received 70% of control diet switched to 90% from mid-gestation. Offspring were sacrificed at ∼26 days (neonate) or ∼110 days (adult) postpartum. Coronal brain sections from the frontal cortex were subject to IBA1-staining for microglial detection and analyzed by machine learning software.

At birth, total body weight of growth restricted offspring was reduced relative to control (p<0.0001) with postnatal catch-up growth observed. Microglial density was reduced in the corpus callosum of control (p<0.05) and growth restricted (p=0.13) adults, relative to neonates. Adults from both groups showed greater IBA1-positive area in the cingulum and periventricular white matter (p<0.05) and increased microglial fractal dimension in the corpus callosum (p<0.10) and periventricular white matter (p<0.05), relative to neonates.

At the timepoints studied, we report age-related changes in white matter microglial morphology. However, maternal nutrient restriction leading to fetal growth restriction in guinea pigs does not appear to exacerbate these white matter microglia morphological changes as a marker for later-life neurodegeneration.
Interpretable variational encoding of genotypes identifies comprehensive clonality and lineages in single cells geometrically
Authors: Chung Hoi Man , Huang Yuanhua
Published: July 2024

Clone assignment in single-cell genomics remains a challenge due to its diverse mutation macrostructures and many missing signals. Existing statistical methods, for the sake of numerical convergence, pose strong constraints on the form of predicted mutation patterns, so they easily identify sub-optimally fitted clones that overlook weak and rare mutations. To solve this problem, we developed SNPmanifold, a Python package that learns flexible mutation patterns using a shallow binomial variational autoencoder. The latent space of SNPmanifold can effectively represent and visualize complex mutations of SNPs (single-nucleotide polymorphisms) in the form of geometrical manifolds. Based on nuclear or mitochondrial SNPs, we demonstrated that SNPmanifold can effectively identify a large number of multiplexed donors of origin (k = 18) that all existing unsupervised methods fail and lineages of somatic clones with promising biological interpretation. Therefore, SNPmanifold can reveal insights into single-cell SNPs more comprehensively than other existing methods, especially in complex datasets.
Fish predation induces drifting and emergence in an experimental stream mesocosm system
Authors: Vermiert Anna-Maria , Pimentel Iris Madge , Rehsen Philipp M. , Meisner Jonathan , Horstmann Martin , Beermann Arne J. , Leese Florian , Weiss Linda C. , Tollrian Ralph
Published: July 2024

Predator-prey interactions are important drivers of adaptation in aquatic communities, shaping the behaviour of invertebrates with cascading effects on community dynamics. Behavioural responses, such as moving with the downstream current (drift) or altering the timing of emergence, can be initiated and reduces the risk of encountering predators. This study aimed to examine the effects of indirect and direct predation pressure on drift behaviour and emergence patterns of aquatic invertebrates. Using an experimental mesocosm setup (ExStream), we analysed how the number of drifting and emerging invertebrates changed with elevated levels of chemical cues from fish (indirect predation,Gasterosteus aculeatusandCottus rhenanus) and subsequent additional direct predation byCottus rhenanusover a 9-day period. Our findings show that most of the analysed invertebrate groups displayed noticeable responses to either indirect, direct, or both forms of predation. Furthermore, our study revealed a significant impact of predation on emergence patterns, reducing the number and the size of emergent invertebrates. Given the importance of drift and emergence in dispersion and in facilitating resource flows into terrestrial systems, our findings indicate a strong effect of predation on the communities.
Behavioral and neural correlates of social hierarchy formation in a sex-changing fish
Authors: Quertermous Haylee M , Kamstra Kaj , van der Burg Chloé A , Muncaster Simon , Todd Erica V , Jasoni Christine L , Brown Culum , Gemmell Neil J
Published: July 2024

Social hierarchies in sex-changing fish determine which fish will change sex, yet little is known about how these hierarchies are formed at the neurobehavioral level. Here, we investigate the formation of social hierarchies within groups of the New Zealand spotty wrasse (spotty), integrating both behavioral observations of social activity with neural activation patterns upon social disruption. We find that dominance hierarchies form rapidly and linearly based on size, with larger fish displaying more aggressive or dominant behaviors (such as monopolizing the shelter) and smaller fish displaying more submissive behaviors (such as escape behavior). Disruption of the social hierarchy induced rapid behavioral changes, particularly in the second-ranked fish, highlighting that second ranked spotty will opportunistically adopt a dominant position in the hierarchy upon removal of the most dominant fish. Neural activation patterns reveal that the social decision-making network is deeply involved in the establishment of dominance, with the fish attaining dominance showing significant differences to all other ranked fish. This study underscores the complexity of social relationships and their neural underpinnings in the spotty wrasse, providing a foundation for further research into the cellular and molecular mechanisms of socially-controlled sex change. Overall, we demonstrate that disruption of social hierarchy triggers rapid changes in behavior and brain regions associated with social decision-making.
Age-related differences in working memory subprocesses decomposed by the reference-back paradigm
Authors: Gaál Zsófia Anna , Nagy Boglárka , Czigler István , Csizmadia Petra , Petró Béla , Kojouharova Petia
Published: July 2024

We used a data-driven approach to study the electrophysiological correlates of the working memory subprocesses revealed by the reference-back paradigm. In the absence of prior research, we focused on how aging affects the four subprocesses:updating,substitution,gate opening, andgate closing.

We conducted our experiment with 25 younger adults (M=20.17±1.47) and 23 older adults (M=67.35±4.01) using the reference-back paradigm. Significant reaction time costs were observed for all four subprocesses, but age-related differences were found only insubstitution, which was larger in older than younger adults, indicating it as being the most vulnerable subprocess in aging.

Using difference waves, we identified event-related potential components that characterize the subprocesses we studied. Regardingupdating:three occipital negativities between 80-180 ms, 300-400 ms, and 400-1,000 ms were observed, with only the latter range showing age group differences. Source analysis showed larger activity differences in the right frontal and temporal areas for younger adults. Regardingsubstitution: a frontal positivity between 250-600 ms emerged in younger adults, while a posterior positivity between 550-750 ms was found in older adults indicating different underlying processes supported by sLORETA results. Regardinggate opening:three parieto-occipital components were identified: a negativity between 150-250 ms, a positivity between 300-500 ms, and a positivity between 500-700 ms, all showing age-related differences. Regardinggate closing: we found an occipital negativity between 150-300 ms and a frontal positivity between 300-600 ms, neither of which changed between the age groups.

From our findings, we conclude that the process of protecting information (gate closing) remains stable with age, despite older adults’ sensitivity to interference. Conversely,gate openingis sensitive to age-related changes, likely to be resulting in different brain activity patterns duringsubstitutionbeing the updating of working memory with new information.
Differentiation Success of Reprogrammed Cells is HeterogenousIn Vivoand Modulated by Somatic Cell Identity Memory
Authors: Zikmund Tomas , Fiorentino Jonathan , Penfold Chris , Stock Marco , Shpudeiko Polina , Agarwal Gaurav , Langfeld Larissa , Petrova Kseniya , Peshkin Leonid , Hamperl Stephan , Scialdone Antonio , Hoermanseder Eva
Published: July 2024

Nuclear reprogramming can change cellular fates. Yet, reprogramming efficiency is low and the resulting cell types are often not functional. Here, we used nuclear transfer to eggs to follow single cells during reprogrammingin vivo. We show that the differentiation success of reprogrammed cells varies across cell types and depends on the expression of genes specific to the previous cellular identity. We find subsets of reprogramming resistant cells that fail to form functional cell types, undergo cell death, or disrupt normal body patterning. Reducing expression levels of genes specific to the cell-type of origin leads to better reprogramming and improved differentiation trajectories. Thus, our work demonstrates that failing to reprogramin vivois cell-type specific and emphasises the necessity of minimising aberrant transcripts of the previous somatic identity for improving reprogramming.
Structured neural fluctuations can generate noise invariance and inter-areal gating at distinct timescales
Authors: Montijn Jorrit S. , Heimel J. Alexander
Published: July 2024

The brain processes, computes, and categorizes sensory input. But even in sensory brain areas, the relationship between input signals and neuronal spiking activity is complex and non-linear. Fast subsecond fluctuations in neuronal population responses dominate the temporal dynamics of neural circuits. Traditional approaches have treated this activity as “noise” that can be averaged away by taking the mean spiking rate over wide time bins or over multiple trial repetitions, but this ignores much of the temporal dynamics that naturally occur in neural systems. We find that subsecond flares of increased population activity are layer– and cell-type specific, and large-scale computational modelling suggests they may serve as an inter-areal gating mechanism. Moreover, we find that most of the neural variability is restricted to a population-gain axis. This observation explains why neural systems can function in the presence of excessive variability: population-level spiking dynamics generate invariance to the majority of neural noise.
Physiologically refined cell culture conditions uncover oncogene-dependent metabolic signatures in Ewing sarcoma spheroids
Authors: Ceranski A. Katharina , Carreño-Gonzalez Martha J. , Ehlers Anna C. , Kolodynska Zuzanna , Vinca Endrit , Faehling Tobias , Hanssen Kimberley M. , Poeller Philipp , Ohmura Shunya , Cidre-Aranaz Florencia , Schulze Almut , Grünewald Thomas G. P.
Published: July 2024

Ewing sarcoma (EwS) cell line culture largely relies on standard techniques, which do not recapitulate physiological conditions. Here, we report on a physiologically improved, feasible, and cost-efficient EwS cell culture technique employing an advanced medium composition, reduced fetal calf serum, and spheroidal growth. Functionalin vitroassays and transcriptome profiling demonstrated that these refined conditions better recapitulate proliferation rates of patient tumors as well as hypoxic conditions relevant for EwS pathophysiology. Moreover, transcriptional signatures associated with the oncogenic activity of the EwS-specific FET::ETS fusion transcription factors in the refined culture conditions were shifted from proliferative towards metabolic gene signatures. The herein presented optimized physiological EwS cell culture technique provides a broadly applicable approach for enhancedin vitromodeling relevant to advancing EwS research and the validity of experimental results.

MOTIVATION

Cell culture remains the main platform to model EwS for research purposes. Yet, concerns exist about the limitations of standardin vitrotechniques to adequately reflect physiological conditions. In this study, we refined EwS cell culture methods to increase modeling capacity while ensuring a practical and cost-effective handling, thereby broadening their applicability within the scientific community.
Combinations of Insecticide-Treated Nets and Indoor Residual Spraying for Insecticide Resistance Management: A Modelling Exploration
Authors: Hobbs Neil Philip , Hastings Ian Michael
Published: July 2024

Insecticides are heavily used for the control of vectors of disease. Malaria control has been reliant on insecticide treated nets (ITNs) and indoor residual spraying (IRS). There are concerns insecticide resistance will impede malaria control. The use of insecticide resistance management (IRM) strategies is recommended. One proposed IRM strategy is the combination of ITNs and IRS. Using a mathematical model of polygenic insecticide resistance evolution, this combination strategy is evaluated. First, combinations are evaluated against ITNs alone to determine if and when combinations may be beneficial in slowing resistance evolution to the pyrethroid on the ITN. Second combinations where multiple IRS insecticides are available are compared against full-dose mixture ITNs. Results of the simulations indicate the addition of IRS to ITNs may be beneficial, providing coverage of both interventions is high. The greater number IRS insecticides available for rotation the better, however even when combinations rotate three different IRS insecticides this is still a less potent IRM strategy than deploying full-dose mixtures. In conclusion the combination of ITNs and IRS appears to offer limited benefit over full-dose mixture ITNs for an IRM perspective
Gut microbiota regulates food intake in a rodent model of binge-eating disorder
Authors: Demangeat Thomas , Loison Léa , Huré Marion , Jean-Luc do Rego , Déchelotte Pierre , Achamrah Najate , Coëffier Moïse , Ribet David
Published: July 2024

Objective

Binge-eating disorder is characterized by recurrent episodes of consumption of large amounts of food within a short period of time, without compensatory behaviours. This disease is a major public health issue since it decreases patients quality of life and is associated with numerous comorbidities, encompassing anxiety, depression and complications associated with obesity. The pathophysiology of binge-eating disorder is complex and involves both endogenous, environmental and sociocultural factors. The gut microbiota has been proposed to be an important player in the onset or maintenance of eating disorders. Here, we aim to better delineate the potential role of the gut microbiota in binge-eating disorder.

Method

We used a model of binge-eating disorder where eight-weeks-old C57Bl/6 female mice had access during 2 hours, every 2 days over a 10-day period, to a highly palatable and high-calorie diet. Half of the animals received antibiotics to deplete their gut microbiota. Eating behaviour and other behavioural parameters were compared between groups.

Results

We observed an increase in food intake in mouse exposed to high-fat high-sucrose diet, as well as tachyphagia and craving for food during binge-eating episodes. We demonstrate the gut microbiota depletion further increases food intake, specifically during binge-eating episodes.

Discussion

These results show that the gut microbiota is involved in the control of food intake during episodes of binge-eating. This strengthens the potential role of the gut bacteria in binge-eating disorder and open the way for future therapeutic strategies aiming at targeting patients’ gut microbiota.
Unbiased multiplex antigen screening of Cerebrospinal Fluid detects microbial and autoantigenic epitopes associated with Multiple Sclerosis
Authors: Barton Nathaniel J. , Tran Khanh , Olson Meagan N. , Deshpande Mugdha , Radu Irina , Francis Nimmy , Kurban Mariana , Orszulak Adrian R. , Chigas Samantha M. , Sundstrom Jonathan , Dawes Pepper , Murray Liam F. , Ionete Carolina , Lim Elaine T. , Hemond Christopher C. , Chan Yingleong
Published: July 2024

To comprehensively investigate the intrathecal antibody profile of multiple sclerosis (MS), we examined the cerebrospinal fluid of 195 patients (92 MS and 103 non-MS) for antibodies using a multiplex unbiased bacteria peptide library. We first tested against Epstein-Barr nuclear antigen 1 (EBNA1) for epitope sites enriched in MS and found a significant enrichment at position 407-419. We then used the data to perform a high-throughput screen against a library of 129 viruses known to infect humans. We discovered several additional epitopes from viruses such as Hantaan virus, Human Herpesvirus 6A and Human respiratory syncytial virus B associated with MS. Besides viral epitopes, we also screened for potential autoantigens of the central nervous system (CNS). We discovered several autoantigenic epitopes in proteins such as ADRB3, HTR3A and MPO that were significantly enriched for MS. Because of previous associations of Toxoplasma gondii infection with MS, we also performed a Toxoplasma gondii specific analysis and discovered additional epitopes enriched for MS. We further assessed epitope-epitope correlations within the patient samples and found distinct patterns of association between these microbial and autoantigenic epitopes. Finally, we performed machine-learning to determine if these epitopes are predictive for MS and found that the model incorporating all the epitopes could most effectively discriminate between MS and non-MS (ROC-AUC score = 0.91). Our results demonstrate the effectiveness of multiplex unbiased screens to detect the identity of potentially cross-reactive antibodies targeting MS CNS epitopes and they can also be used as effective biomarkers for MS.

One Sentence Summary

We performed an unbiased multiplex bacteria peptide antibody library screen on cerebrospinal fluid samples of patients with multiple sclerosis (MS) as well as non-MS controls and detected multiple viral and autoantigenic epitopes that are significantly enriched in MS patient samples.
Activation of two noncanonical R proteins by an insect effector confers plant immunity to aphid infestation
Authors: Lei Kang , Tian Dong , Shao Yutao , Wang Faming , Chang Jinhua , Char Si Nian , Li Guangwei , Dong Zhenying , Zhang Jianping , Cui Jiang-Hui , Zhao Songmin , Li Jingjing , Liu Hua , Liu Guo-Qing , Lv Peng , Wei Mingshu , Jin Xiaohuan , Song Qisheng , Yang Bing , Zhang Kunpu , Wu Di , Wang Dao Wen
Published: July 2024

Molecular characterization of resistance genes is crucial for efficiently understanding and fortifying plant immunity against insect herbivores. Here we report that RMES1A and RMES1B proteins confer resistance to the sorghum aphidMelanaphis sorghiwhen activated by an insect effector MsEF1. Map-based cloning plus genetic analysis of knockout mutants confirm that RMES1A and RMES1B are both required for aphid resistance. Upon aphid attack, RMES1A and RMES1B expression is elevated in the sclerenchyma cells and vascular bundles of leaves; the two proteins interact with MsEF1 in the exocysts, thus upregulating key defense processes such as reactive oxygen species burst. Structural modeling predicts that RMES1A and RMES1B each carry an ATP binding site and two leucine-rich-repeat domains but lack coiled-coil or Toll/Interleukin-1 receptor/resistance domain, thus likely representing a new type of resistance controlling proteins in plants. Our work reveals new genes and mechanisms for further deciphering and improving plant immunity to insect pests.
Antimicrobial mechanism ofin-situplasma activated water treatment of pathogenicEscherichia coliandStaphylococcus aureusbiofilms
Authors: Xia Binbin , Vyas Heema Kumari Nilesh , Rice Scott A. , Newsome Timothy P. , Cullen Patrick J. , Mai-Prochnow Anne
Published: July 2024

Aims

This study investigated the efficacy and mechanisms of inactivation of againstEscherichia coliUTI89 andStaphylococcus aureusNCTC8325 through anin-situplasma-activated water (PAW) treatment.

Methods and Results

PAW was prepared by discharging atmospheric pressure cold plasma beneath the surface of sterile distilled water. The study investigated the inactivation of biofilm cells and biofilm matrix. A complete killing of biofilm cells was achieved on both ofE. coli(6.76 ± 0.01 log CFU/mL) andS. aureus(6.82 ± 0.02 log CFU/mL). This process happened earlier inS. aureus. Simultaneously, PAW treatment disrupted the biofilm structure, inducing a significant reduction in general biofilm biomass and extracellular polymer substances (EPS) matrix. With the disruption of EPS, PAW was enabled to further interact with the bacterial membrane, causing a significant increase in membrane permeability and disrupted membrane structure. Finally, PAW treatment led to a significant accumulation of intracellular reactive oxygen and nitrogen species within the biofilm cells.

Conclusions

Collectively, these findings indicate that PAW effectively inactivates biofilms by mechanically targeting the biofilm EPS matrix and biofilm cells in both gram-negative and gram-positive bacteria.

Impact statement

This study contributes novel insights into plasma-activated water’s mechanisms of action, particularly its impact on the biofilm extracellular polymeric substances matrix (exopolysaccharides, extracellular DNA, and protein), cell membrane permeability, depolarization, and intracellular ROS and RNS accumulation in both of Gram-positive and Gram-negative species. These findings highlight PAW-based treatments against biofilm-related challenges in antimicrobial development and water system decontamination.
Genome-wide mapping of autonomously replicating sequences in the marine diatomPhaeodactylum tricornutum
Authors: Yun Hyun-Sik , Yoneda Kohei , Sugasawa Takehito , Suzuki Iwane , Maeda Yoshiaki
Published: July 2024

Autonomously replicating sequences (ARSs) are important accessories in episomal vectors that allow them to be replicated and stably maintained within transformants. Despite their importance, no information on ARSs in diatoms have been reported. Therefore, we attempted to identify ARS candidates in the model diatom,Phaeodactylum tricornutum, via chromatin immunoprecipitation sequencing. In this study, subunits of the origin recognition complex (ORC), ORC2 and ORC4, were used to screen for ARS candidates. ORC2 and ORC4 bound to 355 sites on theP. tricornutumgenome, of which 69 were constantly screened after multiple attempts. The screened ARS candidates had an AT-richness of approximately 50% (44.39–52.92%) and did not have conserved sequences. In addition, ARS candidates were distributed randomly but had a dense distribution pattern at several sites. Their positions tended to overlap with those of the genetic region (73.91%). Compared to the ARSs of several other eukaryotic organisms, the characteristics of the screened ARS candidates are complex. Thus, our findings suggest that the diatom has a distinct and unique native ARSs.