bluuebunny/crossref_metadata_2025 huggingface dataset:
Time restricted feeding with or without ketosis influences metabolism-related gene expression in a tissue-specific manner in aged rats
Authors: Ding Sarah , Banerjee Anisha , Burke Sara N. , Hernandez Abbi R.
Published: December 2024

Many of the ‘hallmarks of aging’ involve alterations in cellular and organismal metabolism. One pathway with the potential to impact several traditional markers of impaired function with aging is the PI3K/AKT metabolic pathway. Regulation of this pathway includes many aspects of cellular function, including protein synthesis, proliferation and survival, as well as many downstream targets, including mTOR and FOXOs. Importantly, this pathway is pivotal to the function of every organ system in the human body. Thus, we investigated the expression of several genes along this pathway in multiple organs, including the brain, liver and skeletal muscle, in aged subjects that had been on different experimental diets to regulate metabolic function since mid-life. Specifically, rats were fed a control ad lib diet (AL), a time restricted feeding diet (cTRF), or a time restricted feeding diet with ketogenic macronutrients (kTRF) for the majority of their adult lives (from 8-25 months). We previously reported that regardless of macronutrient ratio, TRF-fed rats in both macronutrient groups required significantly less training to acquire a biconditional association task than their ad lib fed counterparts. The current experiments expand on this work by quantifying metabolism-related gene expression across tissues and interrogating for potential relationships with cognitive performance. AKT expression was significantly reduced in kTRF fed rats within liver and muscle tissue. However, AKT expression within the perirhinal cortex (PER) was higher in kTRF rats with the best cognitive performance. Within CA3, higher levels of FOXO1 gene expression correlated with poorer cognitive performance in ad libitum fed rats. Together, these data demonstrate diet- and tissue-specific alterations in metabolism-related gene expression and their correlation with cognitive status.
Female Olfactory Sensitivity Is Temporally Asynchronous with Male Courtship in a Butterfly
Authors: Murphy Matthew J. , Ter Yi Ting , Riddington Ian M. , Joshi Neelendra K. , Westerman Erica L.
Published: December 2024

Signal efficacy is crucial to communicative behaviours. To be effective, a signal once broadcast must be capable of being received and interpreted by a receiver or receivers. In addition to maximizing the amount that a signal stimulates receptive organs, optimally the timing of when a signal is broadcast would synchronize with a receiver’s peak receptivity. Here, we investigated whether peak timing of male courtship, which includes release of a pheromone required for copulation to occur, is synchronized with female pheromone sensitivity in the butterflyBicyclus anynana(Lepidoptera: Nymphalidae). To do this, we performed behavioural and electrophysiological assays at dawn, noon, and dusk. We also investigated the circadian rhythmicity of antennae gene expression by performing RNA-Sequencing on antennal tissues collected at dawn, noon and dusk. We found that although males court most often near dusk, females are more sensitive to odorants in the morning. Furthermore, antennae exhibited differential and diurnally rhythmic expression of odorant receptors and genes associated with learning and sexual receptivity, as well as gene ontology (GO) terms related to fatty acid metabolism and trehalose biosynthesis, supporting our circadian electrophysiological results. Previous literature indicates females form both positive and negative mate preference associations with male pheromones in the morning, regardless of whether males court females. Thus, this asynchrony may enable femaleB. anynanato learn mate preferences before they are courted by conspecific (or potentially heterospecific) males.

MaleBicyclus anynanabutterflies court more at dusk while females are more sensitive to odorants in the morning. Patterns of antenna gene expression also suggest circadian rhythmicity of odorant sensitivity.
Mitochondrial ACSS1 regulates the oncometabolite 2-hydroxyglutarate and De Novo Pyrimidine biosynthesis under nutrient-deprived conditions in lymphoma
Authors: Basappa Johnvesly , Goldman Aaron , Lobello Cosimo , Wang Shengchun , Rushmore David , Melnikova Olga , Sen Neil , Mallikarjuna Vinay , Jain Priyanka , Edalati Masoud , Cai Kathy , Lu Pin , Nejati Reza , Borghaei Hossein , Wellen Kathryn , Wasik Mariusz
Published: December 2024

The mitochondrial Acetyl-CoA synthetase short-chain family member 1 (ACSS1) converts acetate, an energy source in nutrient-deprived conditions1,2, to mitochondrial acetyl-CoA. However, the specific mechanism behind this process remains unknown. Here, we show that ACSS1 is overexpressed in patients with mantle cell lymphoma (MCL), diffuse large B cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), and Ibrutinib (IBR)-resistant cell lines. The mitochondrial stress test showed reduced oxygen consumption in ACSS1 knockdown (KD) cell lines. 13C-acetate stable isotope tracing revealed that ACSS1 knockdown (KD) in MCL cell lines attenuates the flux of mitochondrial acetate to acetyl-CoA, acetylcarnitine, and TCA cycle intermediates, including glutamine and aspartate, which are precursors for de novo pyrimidine synthesis. Consistently, there was a decrease in the labeling of glutamate, aspartate, dihydroorotate, and orotate pools in KD cell lines. Pathway analysis revealed the enrichment of de novo pyrimidine synthesis metabolites and depleting ACSS1 impaired cell growth and potential vulnerability of IBR-resistant MCL cells. Further, we discovered that acetate was used to synthesize 2-hydroxyglutarate in an ACSS1-dependent manner. These results highlight a metabolic phenotype in MCL cells, showing their ability to metabolize acetate in nutrient-deprived conditions and provide new insights into the role of ACSS1 in cancer metabolism.
Towards the implementation and interpretation of masked ICA for identifying signatures of autonomic activation in the brainstem with resting-state BOLD fMRI
Authors: Miedema Mary , Pattinson Kyle T.S. , Mitsis Georgios D.
Published: December 2024

The brainstem is the site of key exchanges between the autonomic and central nervous systems but has historically presented a challenging target for study with BOLD fMRI. A potentially powerful although under-characterized approach to identifying nucleic activation within the brainstem is masked independent component analysis (mICA), which restricts signal decomposition to the brainstem itself, thus aiming to reduce the strong effect of physiological noise in nearby regions such as ventricles and large arteries. In this study, we systematically investigate the use of mICA to uncover signatures of autonomic activation in the brainstem at rest. We apply mICA on 40 subjects in a high-resolution resting state 7T dataset following different strategies for dimensionality selection, denoising, and component classification. We show that among the noise mitigation techniques investigated, cerebrospinal fluid denoising makes the largest impact in terms of mICA outcomes. We further demonstrate that across preprocessing pipelines and previously reported results the majority of components are spatially reproducible, but temporal outcomes differ widely depending on denoising strategy. Evaluating both hand-labelling and whole-brain specificity criteria, we develop an intuitive framework for mICA classifications. Finally, we make a comparison between mICA and atlas-based segmentations of brainstem nuclei, finding little consistency between these two approaches. Based on our evaluation of the effects of methodology on mICA and its relationship to other signals of interest in the brainstem, we provide recommendations for future uses of mICA to identify autonomically-relevant BOLD fluctuations in subcortical structures.
Postnatal Sensory Experience and Barrel Cortex Alterations Anticipate Autistic Traits in a Mouse Model of Cdkl5 Deficiency Disorder
Authors: Raspanti Alessandra , Pizzo Riccardo , Gurgone Antonia , Giraudo Cecilia , Sagona Giulia , Macioce Andrea , Battaglia Anthony , Katsanou Lamprini , Medici Giorgio , Ferrini Francesco , Pizzorusso Tommaso , Ciani Elisabetta , Giustetto Maurizio
Published: December 2024

Autistic traits may arise from atypical sensory experience during postnatal life, but whether there is a causal link between defects in cortical circuitry in the brain, altered sensory processing and social behavior remains unknown. Here, we studied tactile stimuli processing in the barrel cortex (BC) and social interactions in juvenile male mice lacking Cyclin-dependent kinase-like 5 (CDKL5), a model of a severe neurodevelopmental disease showing autistic traits and sensory impairments. We identified in these mice defects of whisker-dependent postnatal sensorimotor reflexes, NMDA receptors-dependent signaling, and dendritic orientation in thalamic inputs-receiving spiny stellate neurons. We also found that CDKL5 is required for mapping and processing whisker-derived tactile stimuli in the BC. Intriguingly, KO mice show autistic traits at p21 that are rescued by neonatal CDKL5 replacement in the BC. Our data suggest that CDKL5 is required to link tactile processing in the BC to the onset of social interaction abilities.
Identification of strain-specific cues that regulate biofilm formation inBacteroides thetaiotaomicron
Authors: Glowacki Robert W.P. , Engelhart Morgan J. , Till Jessica M. , Kadam Anagha , Nemet Ina , Sangwan Naseer , Ahern Philip P.
Published: December 2024

Members of the gut microbiome encounter a barrage of host- and microbe-derived microbiocidal factors that must be overcome to maintain fitness in the intestine. The long-term stability of many gut microbiome strains within the microbiome suggests the existence of strain-specific strategies that have evolved to foster resilience to such insults. Despite this, little is known about the mechanisms that mediate this resistance. Biofilm formation represents one commonly employed defense strategy against stressors like those found in the intestine. Here, we demonstrate strain-level variation in the capacity of the gut symbiontBacteroides thetaiotaomicronto form biofilms. Despite the potent induction of biofilm formation by purified bile in most strains, we show that the specific bile acid species driving biofilm formation differ among strains, and uncover that a secondary bile-acid, lithocholic acid, and its conjugated forms, potently induce biofilm formation in a strain-specific manner. Additionally, we found that the short-chain fatty acid, acetic acid, could suppress biofilm formation. Thus, our data defines the molecular components of bile that promote biofilm formation inB. thetaiotaomicronand reveals that distinct molecular cues trigger the induction or inhibition of this process. Moreover, we uncover strain-level variation in these responses, thus identifying that both shared and strain-specific determinants govern biofilm formation in this species.

Importance

In order to thrive within the intestine, it is imperative that gut microbes resist the multitude of insults derived from the host immune system and other microbiome members. As such, they have evolved strategies that ensure their survival within the intestine. We investigated one such strategy, biofilm formation, inBacteroides thetaiotaomicron, a common member of the human microbiome. We uncovered significant variation in natural biofilm formation in the absence of an overt stimulus among differentBacteroides thetaiotaomicronstrains, and revealed that different strains adopted a biofilm lifestyle in response to distinct molecular stimuli. Thus our studies provide novel insights into factors mediating gut symbiont resiliency, revealing strain-specific and shared strategies in these responses. Collectively, our findings underscore the prevalence of strain-level differences that should be factored into our understanding of gut microbiome functions.
Circuit-Level Dynamics of Slow Wave Activity and Propagation During the Awakening Process
Authors: Pazienti Antonio , Müller Mariel , Bosman Conrado A. , Olcese Umberto , Mattia Maurizio
Published: December 2024

Slow-wave activity (SWA) is a hallmark of the loss of consciousness in non-REM sleep and anesthesia. The mechanistic underpinnings of SWA, and its evolution when transitioning towards the conscious brain state is poorly understood. We address this topic by recording multi-area and laminar activity in posterior parietal (PPC) and primary visual (V1) cortices of mice spontaneously awakening from isoflurane anesthesia. Spectral power is stronger in PPC (especially in superficial layers) during deep unconsciousness, but stronger in V1 when awakening. Rostro-caudal (feedback-like) propagation of SWA also shows state-dependent modulation, particularly in layer 5. The excitability of layer 2/3 neurons, hindered at high isoflurane, recovers during awakening, when V1 and the feedforward pathway reacquire a strong role. Detailing the hierarchical and laminar properties of spontaneous traveling oscillations, we provide evidence that SWA is a multiscale phenomenon. Explicating the functional role of these processes is critical to understand the neuronal mechanisms of consciousness.
Increased cerebrospinal fluid and plasma apoE glycosylation is associated with reduced levels of Alzheimer’s disease biomarkers
Authors: Nedelkov Dobrin , Tsokolas Zoe E. , Rodrigues Matheus Scarpatto , Sible Isabel , Han S. Duke , Kerman Bilal E. , Renteln Michael , Mack Wendy J. , Pascoal Tharick A. , Yassine Hussein N ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2024

The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD). ApoE is glycosylated with an O-linked Core-1 sialylated glycan at several sites, yet the impact and function of this glycosylation on AD biomarkers remains unclear. We examined apoE glycosylation in a cohort of cerebrospinal fluid (CSF, n=181) and plasma (n= 178) samples from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) stratified into 4 groups: cognitively normal (CN), Mild Cognitive Impairment (MCI), progressors and non-progressors based on delayed word recall performance over 4 years. We observed decreasing glycosylation from apoE2 > apoE3 > apoE4 in CSF, and in plasma (apoE3 > apoE4). ApoE glycosylation was reduced in the MCI compared with CN groups, and in progressors compared to non-progressors. In CSF, higher apoE glycosylation associated cross-sectionally with lower total tau (t-tau), p-tau181, and with higher Aβ1-42. Similar associations of apoE glycosylation with higher Aβ1-42were observed in plasma. In CSF, greater apoE4 glycosylation was associated with lower t-tau and p-tau181. Over a 6-year period, higher baseline levels of CSF apoE glycosylation predicted lower rates of increase in CSF t-tau and p-tau181 and lower rates of decrease in CSF Aβ1-42. These results indicate strong associations of apoE glycosylation with biomarkers of AD pathology independent of apoE genotype, warranting a deeper understanding of the functional role of apoE glycosylation on AD tau pathology.
Online interference of declarative memory on fast and slow adaptive processes in force field motor learning
Authors: Rudolph J. L. , Selen L. P. J. , Medendorp W. P.
Published: December 2024

Error-based motor adaptation is currently understood as a dual-rate process involving a fast adaptive process that learns quickly but also decays rapidly and a slow process that learns slowly but has good retention. While the fast process is typically categorized as procedural learning, recent evidence suggests that it relies on the declarative memory system. To test this hypothesis, we investigated in what manner a declarative memory task interferes with two processes that supposedly underly force field adaptation in reaching. This declarative memory task, which involved learning of a list of words, was assessed through either recognition or recall, and was compared to a non-declarative, vowel counting task, using a within-subject design (n=32). We employed a Bayesian hierarchical dual-rate process model to capture the observed force compensation across trials, expecting that the parameters of the fast process would be affected by the declarative memory task. We examined the 95% highest density interval of the posterior distribution of the difference between the experimental and control condition for each parameter. While most parameters remained unaffected by the declarative memory task, the retention rate of the fast process showed a hint of reduction, suggesting a complex interplay between declarative memory and ongoing motor adaptation processes.
Use of Genome Scale Metabolic Reconstructions of Avian PathogenicEscherichia coli(APEC) phylogroups for the identification of lineage-specific metabolic pathways
Authors: Long Huijun , Mehat Jai W. , Wu HuiHai , van Vliet Arnoud H. M. , La Ragione Roberto M.
Published: December 2024

Avian PathogenicEscherichia coli(APEC) are a genetically diverse pathotype primarily associated with extra-intestinal infections in birds. APEC lineages are predicted to have unique metabolic capabilities contributing to virulence and survival in the host environment. Here we present a genome-scale metabolic model for the APEC pathotype based on 114 APEC genome sequences, and lineage-specific models for the phylogroups B2, C and G based on a representative isolate for each phylogroup. A total of 1,848 metabolic reactions were predicted in the 114 APEC isolates before gap filling and manual correction. Of these, 89% represented core reactions, whilst the 11% accessory reactions were mostly associated with carbon and nitrogen metabolism. Predictions of auxotrophy were confirmed by inactivation of the conditionally essentiallysAand the non-essentialpotEgenes. The APEC metabolic model outperformed theE. coliK-12iJO1366 model in the Biolog Phenotypic Array platform. Sub-models specific for phylogroups B2, C and G predicted differences in the metabolism of 3-hydroxyphenylacetate (3-HPAA), a phenolic acid derived from the flavonoid quercetin, which is commonly added to poultry feed. Two 3-HPAA associated reactions/genes distinguished APEC phylogroup C from APEC phylogroups B2 and G, and 3-HPAA supported the growth of APEC phylogroup C in minimal media, but not phylogroups B2 and G. In conclusion, we have constructed genome-scale metabolic models for the three major APEC phylogroups B2, C and G, and have identified a metabolic pathway distinguishing phylogroup C APEC. This demonstrates the importance of lineage- and pathotype-specific metabolic models when investigating genetically diverse microbial pathogens.

IMPACT STATEMENT

Avian PathogenicEscherichia coli(APEC) are the cause of colibacillosis in poultry, which results in a significant economic burden to the poultry industry, and strongly affects the health and welfare of flocks. APEC isolates show a high level of genetic diversity, which complicates diagnostics, epidemiology and the design of prevention and treatment strategies. In this study we have used genome sequences derived from 114 APEC isolates to investigate their metabolic capabilities, and define the metabolic diversity of APEC within a generalised APEC metabolic model, and lineage-specific metabolic models. These models have been interrogated to find unique pathways that can be targeted for the development of anti-APEC treatments, and one such metabolic pathway was identified as a proof of principle. This approach shows great promise for the design of future strategies to prevent and deal with APEC infections, and can be adapted to other genetically diverse microbial pathogens.
Proteome-scale quantification of the interactions driving condensate formation of intrinsically disordered proteins
Authors: Norrild Rasmus K. , von Bülow Sören , Halldórsson Einar , Lindorff-Larsen Kresten , Rogers Joseph M. , Buell Alexander K.
Published: December 2024

The formation of biomolecular condensates is involved in compartmentalisation, regulation, and signalling across most living organisms. Condensation can be driven by phase separation of proteins, and involves highly dynamic, multivalent, and weak interactions of their intrinsically disordered regions (IDRs). Understanding these interactions has been limited by the lack of large-scale experimental methods capable of generating thermodynamic data. Here, we develop and use Condensate Partitioning by mRNA-Display (CPmD) to directly measure the energetics of the partitioning of almost 100,000 peptides of 14 to 40 amino acid length into condensates formed by an IDR, that of the germ granule protein Dead-box helicase 4 (DDX4). This large set of peptides contained many that were derived from DDX4 itself, as well as a tiling library of a significant fraction of all experimentally characterised IDRs. We show that the results of such large scale partitioning studies yield a uniquely quantitative picture of the driving forces that govern IDR condensate formation of DDX4, as well as partitioning of other sequences into its condensates. Furthermore, we demonstrate that the derived set of interactions is also able to quantitatively explain condensate formation of unrelated sequences.
Transcriptional regulation of the piRNA pathway by Ovo in animal ovarian germ cells
Authors: Alizada Azad , Hannon Gregory J. , Nicholson Benjamin Czech
Published: December 2024

The gene-regulatory mechanisms controlling the expression of the germline PIWI-interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female germline piRNA pathway remains a mystery. Here, usingDrosophilaas a model, we combined multiple genomics approaches to reveal the transcription factor Ovo as regulator of the germline piRNA pathway in ovarian germ cells. Ectopic expression of Ovo in ovarian somatic cells activates germline piRNA pathway components, including the ping-pong factors Aubergine, Argonaute-3, and Vasa, leading to assembly of perinuclear cellular structures resembling nuage bodies of germ cells. We found that in ovarian somatic cells, transcription ofovois repressed byl(3)mbt, thus preventing expression of germline piRNA pathway genes in the soma. Cross-species ChIP-seq and motif analyses demonstrate that Ovo is binding to genomic CCGTTA motifs within the promoters of germline piRNA pathway genes, suggesting a regulation by Ovo in ovaries analogous to that of A-MYB in testes. Our results also show consistent engagement of the Ovo transcription factor family at ovarian piRNA clusters across metazoan species, reflecting a deep evolutionary conservation of this regulatory paradigm from insects to humans.
Do career competencies optimize individual work performance? Evidence from Indian HR professionals
Authors: Shrivastava Neha , Mishra Pavan
Published: December 2024

Purpose

This paper aims to synergize the Job Demands-Resources (JD-R) theory with the Intelligent Career theory (ICT) to identify the potential influence of career competencies (CCs) on individual work performance.

Design/methodology/approach

We explore a motivational process within JD-R theory, where CCs such as knowing-why, knowing-how, and knowing-whom serve as personal resources to optimize contextual performance (CP), task performance (TP), and reduce counterproductive work behavior (CWB). The study comprises two phases with samples of human resource (HR) professionals in India. Phase-1 (N = 107) involves adapting measurement instruments through exploratory factor analysis, while phase-2 (N = 396) tests the model using structural equation modeling. We applied the confirmatory factor analysis marker technique, with “conflict avoidance” as the non-ideal marker variable.

Findings

Our research indicates that CCs positively influence TP based on statistical and substantive significance. However, their influence on CP and CWB lacks substantive significance.

Research limitations/implications

This study enhances the JD-R theory by highlighting individual performance as a key outcome of personal resources, like CCs, within the theory’s motivational process.

Practical implications

Organizations can structure skill development programs to align with specific CCs and desired outcomes, using them as benchmarks to assess effectiveness.

Originality/value

To our knowledge, this is the first attempt to apply both JD-R theory and ICT in a work context, specifically among Indian HR professionals, which remains an unexplored area. Additionally, we assume that CCs may initiate motivation independently, even in the absence of job resources.
Dynamic capabilities and firm performance: moderated mediation model with product innovation as mediator and technology uncertainty as moderator
Authors: Zehir Cemal , Vural Sümeyye Çiçek
Published: December 2024

Purpose

This study aims to explain the relationships between dynamic capabilities, product innovation, firm performance and technology uncertainty.

Design/methodology/approach

The quantitative research method was the preferred approach. Data were collected through a questionnaire from managers working in different sectors. The study’s sample consists of 619 managers from 226 different firms.

Findings

The findings show that there is a positive relationship between dynamic capabilities and product innovation and that dynamic capabilities have a positive relationship with firm performance. In addition, the findings indicate a significant positive mediating effect of product innovation on the relationship between dynamic capabilities and firm performance. Another key finding is the positive moderation effect of technology uncertainty on the relationship between product innovation and firm performance.

Research limitations/implications

Using a single sample (country) limits generalizability due to differences in economic structure and market dynamics. Furthermore, by focusing only on product innovation, the role of other types of innovation is not considered.

Practical implications

This study emphasizes that, especially in environments with high technology uncertainty, it is important to develop dynamic capabilities for better firm performance as well as turn these capabilities into tangible outputs such as product innovation.

Originality/value

This study examines the relationship between dynamic capabilities and firm performance, which is frequently discussed and extremely important for the literature, from different perspectives within the context of an emerging economy. In addition to the direct relationship between dynamic capabilities and firm performance, the contribution of dynamic capabilities to performance through product innovation, which is an ordinary capability, (together with the moderating effect of technological uncertainty) was investigated.
A Geometric Morphometric Study on the Rat Mandible
Authors: Gürbüz İftar , Demiraslan Yasin
Published: December 2024

The aim of the study was to investigate the shape of the mandible in Wistar albino rats using the geometric morphometric method. However, ‘Is the shape of the mandible different in rats depending on gender?’ the question formed the hypothesis of the study. For this purpose, a total of 52 rat mandibles, 31 female and 21 male rats, were used in the study. The right mandible was photographed from the lateral aspect. A total of 16 landmarks were marked on the photographs. In the study, principal component analysis (PCA) and discriminant function analysis were performed with the MorphoJ program. As a result of the study, 28 principal components (PC) were calculated. The values of variance of the first three PC were explained as 54.887% of the total shape difference. Principal component analysis showed the shape changes were more in mandibular ramus. However, no shape change was observed, especially the most top point of the ventral edge of the mandible at the rostral side. In the graph of PCA, the groups according to gender did not show a clear distinction. According to cross‐validation scores, 24 females and 17 males showed correct grouping. In the study, the shape characteristics of the rat mandible from the lateral aspect were revealed. However, it was determined that the most difference in shape by gender was in the condylar process, coronoid process and angular process. As a result, despite the formal differences, when all the data were evaluated, it was concluded that gender discrimination could be made mostly (77% female, 80% male) according to shape of the rat mandible.
Examining the Effects of Different Exertion Levels and Reference Standards on the Diagnostic Accuracy of Exercise ECG for Detecting Coronary Artery Disease — A Pilot Study
Authors: Heimann Julius , Schramm Thomas , Grauduszus Martin , Joisten Christine
Published: December 2024

Background

Exercise electrocardiogram (ECG) is frequently used for evaluating patients with suspected coronary artery disease (CAD). However, it has been downgraded in international guidelines due to a limited sensitivity and specificity, compared with other non‐invasive tests.

Methods

We hypothesized, that a sufficient exertion going beyond 85% of the age predicted maximal heart rate (APMHR), by considering the achieved level of workload can improve sensitivity and specificity of the exercise ECG. Secondly, the performance of exercise ECG, when evaluated against a functional reference standard has barely been investigated, although an improved diagnostic accuracy has been reported for other non‐invasive tests in this case. Therefore, in this pilot study, a total of 147 patients without known CAD who underwent exercise ECG followed by coronary angiography within 90 days were retrospectively evaluated.

Results

The combined end point of 85% of APMHR and 75% of the predicted workload showed a slight but not statistically significant benefit over APMHR alone (66.7% vs. 58.1%; p = 0.545). The sensitivity of ST‐segment depression was 51.3% for detecting anatomically defined CAD and 62.5% for functionally relevant CAD (p = 0.378).

Conclusions

Although the results of this pilot study lack statistical significance, the numeric differences clearly justify further research on this topic.
Surgical Outcomes of Multiple Robot‐Assisted Hysterectomies in a Single Workday by the Same Surgeon
Authors: Nozaki Takahiro , Matsuda Kosuke , Hosaka Ayaka , Ito Yoshihiko , Kagami Keiko , Sakamoto Ikuko
Published: December 2024

Introduction

Due to the growing medical need for gynecologic robotic surgery, several robotic surgeries may be performed in a single day at high‐volume centers. This study evaluated the safety of performing multiple robot‐assisted hysterectomies (RAHs) per day by the same surgeon.

Methods

We reviewed the clinical data of patients who underwent robotic surgery from April 2018 to September 2024 at the Department of Gynecology, Yamanashi Central Hospital, and also examined the surgical type, order, and surgeon for each procedure.

Results

A total of 352 RAHs performed by the same surgeon were included. Among them, 267 were the first and second cases performed on the same day (Group A), and 85 were the third to fifth cases (Group B). There were no statistically significant differences between the two groups regarding age, body mass index, uterine weight, surgical indication, and history of abdominal surgery. The median operative time of 68 (35–179) min in Group A and 66 (37–187) min in Group B was similar (p = 0.141). Both groups also had similar estimated blood loss (p = 0.744). Each group had two perioperative complications, and no patient underwent conversion to open or laparoscopic surgery.

Conclusion

Performing multiple RAHs by the same surgeon in a single day may be a safe procedure with no negative impact on operative time, blood loss, or perioperative complications. Hence, it could be a useful treatment option for high‐volume centers.
Trait responsiveness to verbal suggestions predicts nocebo responding: A meta‐analysis
Authors: Stein Madeline V. , Heller Monika , Chapman Sarah , Rubin G. James , Terhune Devin B.
Published: December 2024

Background

Nocebo responding involves the experience of adverse health outcomes in response to contextual cues. These deleterious responses impact numerous features of mental and physical health but are characterized by pronounced heterogeneity. Suggestion is widely recognized as a contributing factor to nocebo responding but the moderating role of trait responsiveness to verbal suggestions (suggestibility) in nocebo responding remains poorly understood.

Objective

We conducted a pre‐registered meta‐analysis (PROSPERO registration number CRD42023425605) to quantitatively synthesize available research on the relationship between suggestibility and nocebo responding.

Methods

Four electronic databases were searched for original studies involving both the assessment of suggestibility and symptom reports in response to an inactive stimulus.

Results

Of 7729 search results, 10 articles presenting 13 correlations between suggestibility and nocebo responding were analysed. A random‐effects meta‐analysis revealed a significant, albeit weak, positive correlation, r = .21 [95% CI: .04, .37], between suggestibility and nocebo responses, such that more highly suggestible individuals displayed larger responses. Sensitivity and meta‐regression analyses demonstrated that studies of higher methodological quality, including those that maintained experimenter blinding, exhibited stronger effect sizes.

Conclusion

These results corroborate proposals that trait responsiveness to verbal suggestions confers greater response to nocebos and warrants renewed attention to the role of suggestibility in symptom induction and perception.
Simulated Impacts of Harvesting Chamaedorea linearis and C. pinnatifrons (Arecaceae): Implications for Their Conservation
Authors: Cepeda Paula , Balslev Henrik , Isaza Carolina
Published: December 2024

Palms are important sources of nontimber forest products. One of their most common uses is as ornamentals, which often involves harvesting whole individuals or plant parts from wild populations. Chamaedorea linearis and Chamaedorea pinnatifrons are still not excessively harvested, but they have substantial ornamental potential, and their populations are decreasing. The use of a wild species can contribute to its conservation if the use is governed by adequate harvest rates. We simulated harvest impacts on the population dynamics of C. linearis and C. pinnatifrons in an Andean montane forest in Parque Natural Chicaque, Colombia, using integral projection models (IPMs) over the period 2019–2021. We projected management scenarios including the harvest of juveniles, as well as leaves and fruits of adults. In our model, the finite growth rate of C. linearis decreased (λ = 0.76–0.91) whereas in C. pinnatifrons it remained stable (λ = 0.98–1.04). The simulations of the harvest of juveniles and leaves suggested negative impacts on the populations' sizes and in the transient growth rate (λ20) in the long term when compared to no harvest. Fruits harvest had no considerable effects under 20% of removal once per year in both of the populations, but had a decrease in populations under 20% of removal twice and four times a year. We conclude that sustainable use strategies should focus on protecting juveniles in both populations. Fruit harvest for propagation can be promoted as a sustainable use strategy that does not endanger their conservation.
Intraoperative Cardiac Arrests in Asian Recipients of Liver Transplantation—Second Report After Learning Curve
Authors: Choi Jisun , Lee SangHyun , Ko Justin Sangwook , Gwak Mi Sook , Kim Gaab Soo
Published: December 2024

Background

Although surgical competency and anesthesia for liver transplantation (LT) have evolved significantly in the past decades, intraoperative cardiac arrest (ICA) is still an event that brings a poor prognosis to the recipient. We report a second‐decade experience of ICA as a follow‐up study of our first report at our institution.

Methods

This is a retrospective observational study of the medical records and the Liver Transplant Program database of our institution. LT from January 2011 to June 2023 were included. Of the 1735 LT cases, a total of 1730 cases were included, excluding three non‐Asian and two simultaneous heart and liver transplants (1598 adult LT, 132 pediatric LT).

Results

The ICA incidence during adult LT was 0.7% (11/1598) which is significantly lower compared to our first report (1.5%; 14/919) (p = 0.042). ICA occurred only in adult recipients. Post‐reperfusion syndrome (PRS, six cases) and bleeding (four cases) were the primary causes in most cases and most ICA occurred after reperfusion (10/11). The mortality rates within 24 h, 30 days, and 1 year were 27.3%, 45.5%, and 54.5%, respectively. The survival curve did not show a significant difference from our first report (p = 0.570), and the survival rate of the ICA group was significantly lower compared to the non‐ICA group. (p = 0.000)

Conclusion

The incidence of ICA has decreased, but the main causes of ICA as PRS and bleeding after reperfusion have not changed. Additionally, there was no significant difference in the survival curves from the first report. Because ICA is still fatal, efforts to reduce its incidence should be continued.
Mitral Regurgitation Evaluation in Modern Echocardiography: Bridging Standard Techniques and Advanced Tools for Enhanced Assessment
Authors: Leo Laura Anna , Viani Giacomo , Schlossbauer Susanne , Bertola Sebastiano , Valotta Amabile , Crosio Stephanie , Pasini Matteo , Caretta Alessandro
Published: December 2024

Mitral regurgitation (MR) is one of the most common valvular heart diseases worldwide. Echocardiography remains the first line and most effective imaging modality for the diagnosis of mitral valve (MV) pathology and quantitative assessment of MR. The advent of three‐dimensional echocardiography has significantly enhanced the evaluation of MV anatomy and function. Furthermore, recent advancements in cardiovascular imaging software have emerged as step‐forward tools, providing a powerful support for acquisition, analysis, and interpretation of cardiac ultrasound images in the context of MR. This review aims to provide an overview of the contemporary workflow for echocardiographic assessment of MR, encompassing standard echocardiographic techniques and the integration of semiautomated and automated ultrasound solutions. These novel approaches include advancements in segmentation, phenotyping, morphological quantification, functional grading, and chamber quantification.
Dorsolateral pontine lesions produce distinct ocular motor abnormalities with anatomical correlations
Authors: Kim Hyun Sung , Choi Jae‐Hwan , Oh Eun Hye , Choi Seo Young , Choi Kwang‐Dong
Published: December 2024

Background and Purpose

The dorsolateral portion of the caudal pons contains the vestibular nucleus (VN) and inferior cerebellar peduncle (ICP) that play important roles in conveying and processing vestibular and ocular motor signals. This study aimed to characterize ocular motor abnormalities along with their anatomical correlations in dorsolateral pons (DLP) lesions.

Methods

We analyzed clinical features, and results of neuro‐otological evaluations and neuroimaging of 18 patients with unilateral DLP lesions (17 with DLP infarction and 1 with cavernous malformation) from among 506 patients with pontine infarction in a stroke registry.

Results

Most of the patients (n = 16) presented with isolated acute vestibular syndrome (AVS). The involved structures within the DLP were the ICP in four patients and the VN in the remaining 14. The unilateral ICP lesions were associated with consistent abnormalities in vestibular and ocular motor tests, including ipsilesional nystagmus without gaze‐evoked nystagmus (GEN), and normal head impulse tests (HITs) and caloric response. In contrast, lesions of the VN were associated with a broader range of eye‐movement abnormalities, including ipsi‐ or contralesional nystagmus with GEN, positive HITs, normal or abnormal caloric responses, and fixation nystagmus. Initial diffusion‐weighted magnetic resonance imaging (within 48 h) was falsely negative in 41% (n = 7) of the DLP infarction cases.

Conclusions

This study demonstrates that unilateral DLP lesions frequently present with isolated AVS and diverse ocular motor abnormalities. These characteristics may be due to the complex involvement of afferent or efferent fibers to and from the VN.
Co‐Investments in Private Equity: Do Investor Types Matter?
Authors: Flor Christian Riis , Jensen Emil Tilgaard , Schandlbauer Alexander
Published: December 2024

This paper utilizes detailed data from a Northern European private equity fund‐of‐funds to examine the determinants of co‐investments. Unlike prior studies, we differentiate between two distinct types of co‐investors: sidecar co‐investors and direct co‐investors. This distinction matters. Both types are more likely to participate in larger deals, but the effect is notably stronger for sidecar co‐investments. Furthermore, if the internal funds available to a general partner (GP) are less than the initial capital used for the acquisition, a GP is more inclined to seek sidecar co‐investors, while lower uncalled capital reduces the likelihood of co‐investment offers.
Bacterial purine metabolism modulates C. elegans development and stress tolerance via DAF‐16
Authors: Feng Min , Gao Baizhen , Garcia L. Rene , Sun Qing
Published: December 2024

The purine metabolism is crucial for cellular function and is a conserved metabolic network from prokaryotes to humans. While extensively studied in microorganisms like yeast and bacteria, the impact of perturbing dietary intermediates from the purine biosynthesis on animal development and growth remains poorly understood. We utilized Caenorhabditis elegans as the metazoan model to investigate the mechanisms underlying this deficiency. Through a high‐throughput screening of an Escherichia coli mutant library Keio collection, we identified 34 E. coli mutants that delay C. elegans development. Among these mutants, we found that E. coli purE gene is an essential genetic component that promotes host development in a dose‐dependent manner. Further metabolites supplementation suggests that bacterial purE downstream metabolite 5‐aminoimidazole‐4‐carboxamide ribotide (AICAR) can inhibit worm growth. Additionally, we found the FoxO transcription factor DAF‐16 is indispensable in worm development delay induced by purE mutation, and observed increased nuclear accumulation of DAF‐16 when fed E. coli purE‐ mutants, suggesting the role of DAF‐16 in response to purE mutation. RNA‐seq analysis and phenotypic assays revealed that worms fed the E. coli purE mutant exhibited elevated lifespan, thermotolerance, and pathogen resistance. These findings collectively suggest that certain intermediates in the bacterial purine biosynthesis can serve as a cue to modulate development and activate the defense response in the nematode C. elegans through DAF‐16.
Evidence for corrin biosynthesis in the last universal common ancestor
Authors: Modjewski Luca D. , Karavaeva Val , Mrnjavac Natalia , Knopp Michael , Martin William F. , Sousa Filipa L.
Published: December 2024

Corrinoids are cobalt‐containing tetrapyrroles. They include adenosylcobalamin (vitamin B12) and cobamides that function as cofactors and coenzymes for methyl transfer, radical‐dependent and redox reactions. Though cobamides are the most complex cofactors in nature, they are essential in the acetyl‐CoA pathway, thought to be the most ancient CO2‐fixation pathway, where they perform a pterin‐to‐cobalt‐to‐nickel methyl transfer reaction catalyzed by the corrinoid iron–sulphur protein (CoFeS). CoFeS occurs in H2‐dependent archaeal methanogens, the oldest microbial lineage by measure of physiology and carbon isotope data, dating corrinoids to ca. 3.5 billion years. However, CoFeS and cobamides are also essential in the acetyl‐CoA pathway of H2‐dependent bacterial acetogens. To determine whether corrin biosynthesis was established before archaea and bacteria diverged, whether the pathways arose independently or whether cobamide biosynthesis was transferred from the archaeal to the bacterial lineage (or vice versa) during evolution, we investigated phylogenies and structural data for 26 enzymes of corrin ring and lower ligand biosynthesis. The data trace cobamide synthesis to the common ancestor of bacteria and archaea, placing it in the last universal common ancestor of all lifeforms (LUCA), while pterin‐dependent methyl synthesis pathways likely arose independently post‐LUCA in the lineages leading to bacteria and archaea. Enzymes of corrin biosynthesis were recruited from preexisting ancient pathways. Evolutionary forerunners of CoFeS function were likely Fe‐, Ni‐ and Co‐containing solid‐state surfaces, which, in the laboratory, catalyze the reactions of the acetyl‐CoA pathway from CO2 to pyruvate under serpentinizing hydrothermal conditions. The data suggest that enzymatic corrin biosynthesis replaced insoluble solid‐state catalysts that tethered primordial CO2 assimilation to the Earth's crust, suggesting a role for corrin synthesis in the origin of free‐living cells.
Strategies to Guide Paediatric Type 1 Diabetes Management and Transition of Care: A State‐Of‐The‐Art Review
Authors: Pehr‐Szeliga Danielle , Rutkowski Aneta , Neuman Michelle , Amer Kim , Webber‐Ritchey Kashica J.
Published: December 2024

Aim

The aim of the study was to synthesise current evidence on the transition of type 1 diabetes management responsibility from caregiver to child.

Design

A state‐of‐the‐art review was conducted.

Methods

Using Rayyan software, two authors independently performed the study selection.

Data Sources

CINAHL, PubMed and Web of Science databases were searched to identify relevant articles that focused on children ages 1–19 who were transitioning care of paediatric type 1 diabetes. The last search was performed on 17 October 2023.

Results

Thirty‐seven studies conducted in four different countries were included following abstract screening, full‐text review and assessment for risk of bias—23 quantitative, 13 qualitative and one mixed method. One study examined early childhood transition, five studies examined middle childhood and 31 studies examined transition strategies utilised in later childhood. Themes in clinician and caregiver transition interventions were identified.

Conclusion

Findings can inform the development and refinement of transition interventions to help clinicians and caregivers ensure a successful transition of type 1 diabetes management to the paediatric patient.

Implications for the Profession and Patient Care

A rigorous investigation to validate strategies for different age groups is needed. To support this process and improve type 1 diabetes mellitus outcomes for paediatric patients, research and recommendations should be further reviewed to assist in tailoring interventions accordingly.

Impact Statement

Effective transition management strategies to shift responsibility from caregiver to child are increasingly important to ensuring safe self‐management of paediatric type 1 diabetes. Reviews on type 1 diabetes transition management strategies for youth are needed. In this systematic review, we highlight transition strategies for children ages 1–19 who were transitioning care of paediatric type 1 diabetes. Findings offer insight on long‐term diabetes management to improve patient outcomes in paediatric patients with type 1 diabetes.

Reporting Method

We adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines.

Patient or Public Contribution

No patient or public contribution was required in this review.