bluuebunny/crossref_metadata_2025 huggingface dataset:
A Potent Pandemic Avian Influenza Virus Vaccine Based on a 4th Generation Fully Deleted Adenoviral Vector
Authors: Qi Yan , Tarbet E Bart , Cull Janae W , Zhang Xianghua , Staerz Uwe D
Published: January 2025

The GreVac system was developed as a fast and flexible plug-and-play vaccine platform based on an architecture of fully deleted (fd) helper virus-independent (hi) adenoviral (Ad) vectors. The present study established the potency of the GreVac technology. It demonstrated that the GreFluVie5 vaccine fully protected mice against lethal challenges with the A/Vietnam/1203/2004 (H5N1) pandemic avian influenza virus. The GreFluVie5 vector delivered a transgene expression cassette for the H5 hemagglutinin and N1 neuramidase influenza genes. Its fd Ad genome was carried in a capsid of the human serotype 5 (Ad5). The efficacies of three different doses and three different administration routes were compared in the mouse model. The vaccine fully protected animals against viral challenges with the wild-type A/Vietnam/1203/2004 virus, whose replication in the recipients' lungs was terminated. It induced strong immune responses. The present experiments also revealed that the intra muscular (i.m.) delivery route of GreFluVie5 was more efficient than sub cutaneous (s.c.) or intra nasal (i.n.) ones. Based on the results of this trial and GreVac's intrinsic versatility and fast development time, we believe that this platform is ideally suited to swiftly deliver powerful vaccines to infectious diseases with high eruption potentials.
Cadmium ingestion does not disrupt the social transmission of the microbiome in juveniles of a subsocial insect
Authors: Cheutin Marie-Charlotte , Honorio Romain , Meunier Joël
Published: January 2025

Symbiotic microbes are essential for host health and fitness. In family-living species, these microbes are often acquired through vertical transmission from parents and horizontal transmission from siblings. However, it is unclear how environmental stressors, such as chemical pollution, influence these contributions to the juvenile microbiome. Here, we tested the independent and interactive effects of social environment and cadmium ingestion - a common heavy metal pollutant - on the microbiome of juvenile European earwigs. We reared juveniles either alone, with siblings or with siblings plus the mother, exposed them to cadmium at 0, 25 or 100mg/L, and analysed their microbiome composition and diversity. Our results showed that both social environment and cadmium independently influenced the phylogenetic beta-diversity of the juvenile microbiome although neither factor nor their interaction affected alpha-diversity. Moreover, we found that observed specific bacterial taxa in the social groups, including the overabundance of putatively pathogenic (Serratia) and mutualistic (Lactobacillus) symbionts were more abundant in juveniles reared with family members than isolated ones. Overall, our findings suggest that while both social environment and cadmium shape the juvenile microbiome, family does not amplify the effects of chemical exposure. This highlights the resilience of microbial transmission within families, even under environmental stress.
Nde1 Promotes Lis1 Binding to Full-Length Autoinhibited Human Dynein-1
Authors: Yang Jun , Zhao Yuanchang , Chai Pengxin , Yildiz Ahmet , Zhang Kai
Published: January 2025

Cytoplasmic dynein-1 (dynein) is the primary motor for the retrograde transport of intracellular cargoes along microtubules. The activation of the dynein transport machinery requires the opening of its autoinhibited Phi conformation by Lis1 and Nde1/Ndel1, but the underlying mechanism remains unclear. Using biochemical reconstitution and cryo-electron microscopy, we show that Nde1 significantly enhances Lis1 binding to autoinhibited dynein and facilitates the opening of Phi. We discover a key intermediate step in the dynein activation pathway where a single Lis1 dimer binds between the Phi-like (PhiL) motor rings of dynein. In this “PhiL-Lis1”, Lis1 interacts with one of the motor domains through its canonical interaction sites at the AAA+ ring and stalk and binds to the newly identified AAA5, AAA6, and linker regions of the other motor domain. Mutagenesis and motility assays confirm the critical role of the PhiL-Lis1 interface. This intermediate state is instantly and efficiently formed in the presence of Nde1, but Nde1 is not part of the PhiL-Lis1. These findings provide key insights into the mechanism of how Nde1 promotes the Lis1-mediated opening of Phi dynein.
D2-expressing neurons of the anterior paraventricular nucleus of the thalamus modulate learned aversive and safety salience
Authors: Miranda Magdalena , Karam Elsa , Tuduri Pola , Vaillant Loic , Drahmani Majda , Ster Jeanne , Perisse Emmanuel , Trouche Stephanie
Published: January 2025

Associative learning provides a mean to learn appropriate valence and salience value signals that animal can later use to make appropriate value-based choices. By generalizing from prior aversive experience and comparing motivational salience signals to a current one, animals can learn the relative aversive (better or worse than) value or relative positive safety between experiences. Yet, how such relative value signals are acquired during learning remain poorly known. The paraventricular nucleus of the thalamus (PVT) is critical for the control of salience and valence signals, therefore it is well-placed to be involved in learning relative aversive value and learned safety. Using a newly-developed conditioned place aversive task, we first uncover specific behavioral signatures associated with learning relative aversive value and learned safety, and related value-based choices. We then show that neurons expressing dopamine D2 receptor (D2+) in the anterior PVT (aPVT) rather than posterior PVT (pPVT), are preferentially recruited by both relative aversive value learning and learned safety. By employing a chemogenetic inactivation strategy, we first demonstrate a role of aPVT D2+ neurons for learning relative aversive value by regulating motivational aversive salience. Finally, we show that the same chemogenetic intervention also increases learned safety salience. Overall, our data are the first to demonstrate that aPVT D2+ neurons modulate the salience of experience independently of valence to compute adapted learned value signals during learning and promote appropriate value-based choices.
Control of limb loading during active horizontal perturbations at moderate and fast trots in rats
Authors: Andrada Emanuel , Fischer Martin S. , Stark Heiko , Arnold Dirk
Published: January 2025

To understand how small animals cope with complex, unstructured, and unpredictable substrates, we analyzed the kinetics of rats (n = 10) moving at a fast and at a moderate trot over an unperturbed substrate and a substrate subjected to active horizontal perturbations. Perturbations were active single forwards or backwards displacements of an instrumented platform by amplitudes of 5mm or 10mm in 0.05s. Single leg ground reaction forces (SLGRF) were collected for unperturbed and perturbed locomotion (hindlimbs: 50/102, forelimbs: 45/130, respectively). When negotiating horizontal perturbations, rats displayed gait resetting (braking, accelerating) and non-resetting behaviors. Feedforward strategies differed between the fore- and hindlimbs. In circa 60% of the perturbed trials, forelimbs started the step in acceleration mode, while hindlimbs began the stance mostly in non-resetting mode (∼45%). In about 50% of all perturbed steps, the impulse provided by the SLGRF displayed a change in behavior according to the expected response to the perturbation. The remaining 50% retained the feedforward strategy. Still, most perturbed trials displayed changes in SLGRF patterns that indicated passive and active reactions to platform shifts.

Our results indicate that rats’ sensorimotor control system tunes fore- and hindlimbs differently in expectation of a perturbation. In addition, the tendon-muscle systems of the limbs are recruited to prevent leg collapse at the beginning and end of the stance. At lower speeds, spinal and/or higher center commands have enough time to re-adapt limb behavior. At higher speeds of locomotion, rats rely more on their limbs’ intrinsic stability and on feedforward control.
Osmolarity regulatesC. elegansegg-laying behavior via parallel chemosensory and biophysical mechanisms
Authors: Medrano Emmanuel , Jendrick Karen , McQuirter Julian , Moxham Claire , Rajic Dominique , Rosendorf Lila , Stilman Liraz , Wilright Dontrel , Collins Kevin M.
Published: January 2025

Animals alter their behavior in response to changes in the environment. Upon encountering hyperosmotic conditions, the nematode wormC. elegansinitiates avoidance and cessation of egg-laying behavior. While the sensory pathway for osmotic avoidance is well-understood, less is known about how egg laying is inhibited. We analyzed egg-laying behavior after acute and chronic shifts to and from hyperosmotic media. Animals on 400 mM sorbitol stop laying eggs immediately but then resume ~3 hours later, after accumulating additional eggs in the uterus. Surprisingly, the hyperosmotic cessation of egg laying did not require known osmotic avoidance signaling pathways. Acute hyperosmotic shifts in hyperosmotic-resistant mutants overproducing glycerol also blocked egg laying, but these animals resumed egg laying more quickly than similarly treated wild-type animals. These results suggest that hyperosmotic conditions disrupt a "high-inside" hydrostatic pressure gradient required for egg laying. Consistent with this hypothesis, animals adapted to hyperosmotic conditions laid more eggs after acute shifts back to normosmic conditions. Optogenetic stimulation of the HSN egg-laying command neurons in hyper-osmotic treated animals led to fewer and slower egg-laying events, an effect not seen following direct optogenetic stimulation of the postsynaptic vulval muscles. Hyperosmotic conditions also affected egg-laying circuit activity with the vulval muscles showing reduced Ca2+transient amplitudes and frequency even after egg-laying resumes. Together, these results indicate that hyperosmotic conditions regulate egg-laying via two parallel mechanisms: a sensory pathway that acts to reduce HSN excitability and neurotransmitter release, and a biophysical mechanism where a hydrostatic pressure gradient reports egg accumulation in the uterus.
Neurodegenerative and neurodevelopmental roles for bulk lipid transportersVPS13AandBLTP2in movement disorders
Authors: Neuman Sarah D. , Thakur Rajan S. , Gratz Scott J. , O’Connor-Giles Kate M. , Bashirullah Arash
Published: January 2025

Background

Bridge-like lipid transfer proteins (BLTPs) mediate bulk lipid transport at membrane contact sites. Mutations in BLTPs are linked to both early-onset neurodevelopmental and later-onset neurodegenerative diseases, including movement disorders. The tissue specificity and temporal requirements of BLTPs in disease pathogenesis remain poorly understood.

Objectives

To determine the age-of-onset and tissue-specific roles ofVPS13AandBLTP2in movement disorder pathogenesis usingDrosophilamodels.

Methods

We generated tissue-specific knockdowns of theVPS13Aortholog (Vps13) and theBLTP2ortholog (hobbit) in neurons and muscles ofDrosophila. We analyzed age-dependent locomotor behavior, neurodegeneration, and synapse development and function.

Results

Neuron-specific loss of theVPS13Aortholog caused neurodegeneration followed by age- onset movement deficits and reduced lifespan, while muscle-specific loss affected only lifespan, revealing neurodegeneration and myopathy as independent comorbidities inVPS13Adisease. In contrast, neuronal loss of theBLTP2ortholog resulted in severe early-onset locomotor defects without neurodegeneration, while muscle loss impaired synaptogenesis and neurotransmission at the neuromuscular junction (NMJ).

Conclusions

VPS13Amaintains neuronal survival, whileBLTP2orchestrates synaptic development.VPS13Afunction in muscle does not play a role in movement defects. The phenotypic specificity of BLTP function provides mechanistic insights into distinct disease trajectories for BLTP-associated movement disorders.
Cryo-EM structure of the conjugation H-pilus reveals the cyclic nature of the TrhA pilin
Authors: Ishimoto Naito , Wong Joshua L C , Singh Nanki , Shirran Sally , He Shan , Seddon Chloe , Wright Olivia , Balsalobre Carlos , Sonani Ravi R , Clements Abigail , Egelman Edward , frankel gad , Beis Konstantinos
Published: January 2025

Conjugation, the major driver of the spread of antimicrobial resistance genes, relies on a conjugation pilus for DNA transfer. Conjugative pili, such as the F–pilus, are dynamic tubular structures, composed of a polymerized pilin, that mediate the initial donor–recipient interactions, a process known as mating pair formation (MPF). IncH are low copy number plasmids, traditionally considered broad host range, which are found in bacteria infecting both humans and animals. The reference IncHI1 plasmid R27, isolated from Salmonella enterica serovar Typhi, encodes the conjugative H–pilus subunit TrhA containing 74 residues after cleavage of the signal sequence. Here, we show that the H–pilus forms long filamentous structures that mediate MPF, and describe its cryo electron–microscopic (cryo–EM) structure at 2.2 Å resolution. Like the F pilus, the H-pilin subunits form helical assemblies with phospholipid molecules at a stochiometric ratio of 1:1. While there were previous reports that the T–pilus from Agrobacterium tumefaciens was composed of cyclic subunits, three recent cryo-EM structures of the T–pilus found no such cyclization. Here, we report that the H–pilin is cyclic, with a covalent bond connecting the peptide backbone between the N– and C–termini. Both the cryo–EM map and mass spectrometry revealed cleavage of the last five residues of the pilin, followed by cyclization via condensation of the amine and carboxylate residues. The cyclic nature of the pilin could stabilize the pilus and may explain the high incidence of IncH plasmid dissemination.
Boosting the detection of enhancer-promoter loops via novel normalization methods for chromatin interaction data
Authors: Wang Xiaotao , Shi Detong , Xue Feiyang , Liu Yunxia , Yang Hongbo , Jiang Linghan
Published: January 2025

Accurately detecting enhancer-promoter loops from genome-wide interaction data, such as Hi-C, is crucial for understanding gene regulation. Current normalization methods, such as Iterative Correction and Eigenvector decomposition (ICE), are commonly used to remove biases in Hi-C data prior to chromatin loop detection. However, while structural or CTCF-associated loop signals are retained, enhancer-promoter interaction signals are often greatly diminished after ICE normalization and similar methods, making these regulatory loops harder to detect. To address this limitation, we developed Raichu, a novel method for normalizing chromatin contact data. Raichu identifies nearly twice as many chromatin loops as ICE, recovering almost all loops detected by ICE and revealing thousands of additional enhancer-promoter loops missed by ICE. With its enhanced sensitivity for regulatory loops, Raichu detects more biologically meaningful differential loops between conditions in the same cell type. Furthermore, Raichu performs consistently across different sequencing depths and platforms, including Hi-C, HiChIP, and single-cell Hi-C, making it a versatile tool for uncovering new insights into three- dimensional (3D) genomic organization and transcriptional regulation.
Deep Learning Identified Extra-Prostatic Extension and Seminal Vesicle Invasion as an MRI Biomarker for Prostate Cancer Outcomes
Authors: Hossain Sajid , Hossain Saeed , Sritharan Durga , Fu Daniel , Nene Aishwarya , Hossain Jahid , Chadha Saahil , Kim Issac , Lin MingDe , Aboian Mariam , Aneja Sanjay
Published: January 2025

Current risk stratification methods for localized prostate cancer (PCa) are reliant on clinical and pathological variables that do not easily account for location of cancer spread. Prostate MRI is a helpful tool to identify anatomic extra-prostatic cancer spread (EPE) and seminal vesicle invasion (SVI) but is subject to radiologist expertise and inter-observer variation. We report deep learning models which provide objective end-to-end evaluation of EPE and SVI on prostate MRI. Both EPE and SVI models demonstrate high discriminatory ability on three held-out test sets spanning different clinical settings, equipment manufacturers, and MRI magnet strengths. Interpretability studies suggest both EPE and SVI models identify clinically-relevant anatomic regions. Lastly, we show that classification of EPE and SVI by our models is independently associated with increased risk of biochemical recurrence (BCR) following localized treatment. Furthermore, we demonstrate that our models can be easily integrated to well-established risk stratification methods (NCCN and UCSF-CAPRA) for improved ability to identify high risk PCa phenotypes.
Detection of Hemagglutinin H5 influenza A virus RNA and model of potential inputs in an urban California sewershed
Authors: Paulos Abigail P. , Hilton Stephen P. , Shelden Bridgette , Duong Dorothea , Boehm Alexandria B. , Wolfe Marlene K.
Published: January 2025

In 2024, the highly pathogenic avian influenza A H5N1 caused outbreaks in wild birds, poultry, cows, and other mammals in the United States with 61 human cases also reported by the CDC. Detection of influenza A H5 RNA in wastewater has been previously reported in sewersheds in Texas and North Carolina with nearby impacted dairy herds following the emergence of H5N1 in dairy cows. Here, we conduct retrospective testing of total influenza A and H5 hemagglutinin genes in wastewater as well presenting and applying new assays for detection of H1 and H3 genes across a respiratory virus season in an urban California sewershed from September 2023 – May 2024. Total influenza A, H1, and H3 were regularly detected, while H5 was first detected in March. We developed a model that uses Monte Carlo simulations and previously published parameters to estimate numbers of infected people, poultry, wild birds, or liters of H5-contaminated milk required to result in measured H5 concentrations in wastewater. Our findings demonstrate that in this California sewershed, contaminated milk or infected poultry were the most likely sources of H5 to wastewater. We created a publicly available tool to apply the H5 input model in other sewersheds estimate required inputs.

Synopsis

We developed a model to understand potential sources of influenza A H5 RNA in wastewater, enabling interpretation of H5 RNA wastewater detections.

TOC figure
The limit of life at extremely low water activity: Lithium-concentration ponds in a solar saltern (Salar de Atacama, Chile)
Authors: Demergasso C. , Avendaño P , Escuti C. , Veliz R. , Chong G. , Pedrós-Alió C.
Published: January 2025

Extremely hyper-saline ponds from an industrial lithium-concentration process in solar salterns in the Atacama Desert were studied to determine the limits of life at very low water activity. Water activity (aw) of 0.61 is the lowest awvalue for growth of living beings recorded to date. Xerophilic (sometimes called osmophilic) filamentous fungi and yeasts are predominant in high-sugar foods with such low awvalues. Some microorganisms are capable of growth at that water activity level. By contrast, high-salt environments are almost exclusively populated by prokaryotes, notably theHalobacteriaclass and someBacteroidetes, capable of growing in saturated NaCl (aw0.75). The lowest awthat can be achieved by the addition of NaCl is 0.75 (saturation point for NaCl). Crystallizer ponds in Li+concentration plants reach down to water activity levels around 0.1. The aim of this study was to determine how far along the salinity gradient could life be found. Cell counts were attempted by epifluorescence microscopy and qPCR with bacterial and archaeal universal primers. Biomass for DNA extraction was obtained by an optimized protocol involving dialysis of brines previously fixed with ethanol. Prokaryotic diversity was studied by DNA extraction, PCR, qPCR and 16S rRNA amplicon sequencing in different ponds along the salinity gradient. Archaeal DNA was found in the lower salinity ponds, while bacterial DNA was found along the whole gradient. Bacterial cDNA was retrieved from ponds down to an awof 0.2. Moreover, bacteria could be grown in enriched cultures from most ponds.
Acquisition of discrete immune suppressive barriers contributes to the initiation and progression of preinvasive to invasive human lung cancer
Authors: Yoffe Liron , Bhinder Bhavneet , Kang Sung Wook , Zhang Haoran , Singh Arshdeep , Ravichandran Hiranmayi , Markowitz Geoffrey , Martin Mitchell , Kim Junbum , Zhang Chen , Elemento Olivier , Tansey Wesley , Bates Stewart , McGraw Timothy E. , Borczuk Alain , Lee Hyun-Sung , Altorki Nasser K. , Mittal Vivek
Published: January 2025

Computerized chest tomography (CT)-guided screening in populations at risk for lung cancer has increased the detection of preinvasive subsolid nodules, which progress to solid invasive adenocarcinoma. Despite the clinical significance, there is a lack of effective therapies for intercepting the progression of preinvasive to invasive adenocarcinoma. To uncover determinants of early disease emergence and progression, we used integrated single-cell approaches, including scRNA-seq, multiplexed imaging mass cytometry and spatial transcriptomics, to construct the first high-resolution map of the composition, lineage/functional states, developmental trajectories and multicellular crosstalk networks from microdissected non-solid (preinvasive) and solid compartments (invasive) of individual part-solid nodules. We found that early disease initiation and subsequent progression are associated with the evolution of immune-suppressive cellular phenotypes characterized by decreased cytotoxic CD8 T and NK cells, increased T cell exhaustion and accumulation of immunosuppressive regulatory T cells (Tregs) and M2-like macrophages expressing TREM2. Within Tregs, we identified a unique population of 4-1BB+ Treg subset enriched for the IL2-STAT5 suppressive pathway with transcription profiles supporting discrete metabolic alterations. Spatial analysis showed increased density of suppressive immune cells around tumor cells, increased exhaustion phenotype of both CD4 and CD8 T cells expressing chemokine CXCL13, and spatial micro-complex of endothelial and lymphocyte interactions within tertiary lymphoid structures. The single-cell architecture identifies determinants of early disease emergence and progression, which may be developed not only as diagnostic/prognostic biomarkers but also as targets for disease interception. Additionally, our dataset constitutes a valuable resource for the preinvasive lung cancer research community.
CD44 and Ezrin restrict EGF receptor mobility to generate a novel spatial arrangement of cytoskeletal signaling modules driving bleb-based migration
Authors: Jha Ankita , Chandra Ankit , Farahani Payam , Toettcher Jared , Haugh Jason M. , Waterman Clare M.
Published: January 2025

Cells under high confinement form highly polarized hydrostatic pressure-driven, stable leader blebs that enable efficient migration in low adhesion, environments. Here we investigated the basis of the polarized bleb morphology of metastatic melanoma cells migrating in non-adhesive confinement. Using high-resolution time-lapse imaging and specific molecular perturbations, we found that EGF signaling via PI3K stabilizes and maintains a polarized leader bleb. Protein activity biosensors revealed a unique EGFR/PI3K activity gradient decreasing from rear-to-front, promoting PIP3 and Rac1-GTP accumulation at the bleb rear, with its antagonists PIP2 and RhoA-GTP concentrated at the bleb tip, opposite to the front-to-rear organization of these signaling modules in integrin-mediated mesenchymal migration. Optogenetic experiments showed that disrupting this gradient caused bleb retraction, underscoring the role of this signaling gradient in bleb stability. Mathematical modeling and experiments identified a mechanism where, as the bleb initiates, CD44 and ERM proteins restrict EGFR mobility in a membrane-apposed cortical actin meshwork in the bleb rear, establishing a rear-to-front EGFR-PI3K-Rac activity gradient. Thus, our study reveals the biophysical and molecular underpinnings of cell polarity in bleb-based migration of metastatic cells in non-adhesive confinement, and underscores how alternative spatial arrangements of migration signaling modules can mediate different migration modes according to the local microenvironment.
Evidence for distinct networks underlying symptom clusters of posttraumatic stress disorder
Authors: Hauner Katherina K. , Chau Aileen , Krueger Frank , Gordon Barry , Grafman Jordan
Published: January 2025

Background

Clinical and psychometric evidence has long supported a multidimensional model of PTSD, with symptom subcategories derived from factor analytic methods. Although research on the biological bases of PTSD as a unitary construct is profuse, comparatively few studies have examined the neural mechanisms underlying subcategories of PTSD symptoms. The present study aimed to provide the first evidence of causal relationships between brain structure and PTSD symptom subcategories, using a lesion-behavior mapping approach.

Methods

Using a group of male combat veterans with focal penetrating traumatic brain injuries (n= 177), we determined the effects of focal damage on the PTSD symptom subcategories of hyperarousal, avoidance, and re-experiencing.

Results

Our findings revealed two distinct networks that underlie symptom subcategories of PTSD: (1) an amygdala-ventromedial prefrontal cortex network underlying hyperarousal and avoidance symptoms, in which amygdala damage acts as a risk factor for the development of these symptoms, while vmPFC damage acts as a protective factor against the same symptoms; and (2) a hippocampal network underlying re-experiencing and avoidance, in which hippocampal damage acts as a protective factor against these symptoms.

Conclusions

The present study provides novel insights regarding the causal role of key brain regions in the heterogeneous expression of PTSD symptoms. Results not only contribute to a more complete picture of the neural mechanisms underlying PTSD, but may also aid in the future development of individualized therapeutic strategies that target specific symptom profiles.
Meaningful organizational routines in primary healthcare: influencing factors and their consequences for routine enactment
Authors: Jacobsson Mattias , Näsholm Malin
Published: January 2025

Purpose

Based on the well-known risks associated with deviating from established routines in primary healthcare and the positive consequences of upholding them, the purpose of this study is to increase the understanding of the role of meaningfulness in the enactment of organizational routines.

Design/methodology/approach

The study is based on 24 semi-structured interviews with three different professional categories in primary healthcare in Sweden. The data were analyzed using thematic analysis on a latent level, combined with a two-factor model as sensitizing concepts.

Findings

Differences are identified between factors that reduce meaninglessness (called “sufficiency factors”) and those that enable meaningfulness (called “meaningfulness factors”). Nine sufficiency factors and six meaningfulness factors explain what makes organizational routines perceived as meaningful by the different professional groups. A two-factor matrix is developed that highlights the intricate challenges associated with routine enactment based on these factors.

Originality/value

The study is unique in that it is the first to integrate research on organizational routines and meaningfulness. However, understanding meaningful organizational routines is not only essential because it is an overlooked area in both of these two streams of research but also because of its clear, practical relevance in the primary healthcare setting.
P2Y2 Inhibition Modifies the Anabolic Response to Exercise in Adult Mice
Authors: Chougule Amit , Zhang Chunbin , Denbow Jordan , Vinokurov Nickolas , Mendez Devin , Vojtisek Elizabeth , Gardinier Joseph
Published: January 2025

As the aging population continues to grow, the incidence of osteoporotic fractures increases and is compounded by our lack of therapeutic strategies that increase bone formation. Although exercise and physical activity play a key role in maintaining bone mass throughout our lives, the loads and exertion required to elicit an anabolic response becomes exceedingly difficult to achieve with age. Based on previous work, the P2Y2 receptor offers a unique therapeutic target to increasing bone mass by modifying the mechanotransduction. Others have also shown P2Y2 to have a negative effect on osteoblast function. However, the extent to which inhibiting P2Y2 pharmaceutically improves bone mass or the mechanotransduction of bone remains unknown. Our central hypothesis for this study states that inhibiting P2Y2 activity can enhance the anabolic response to loading in an aging population. To test this hypothesis, the anabolic response to exercise was examined by treating adult mice, which typically display a minimal response, with the P2Y2 inhibitor AR‐C118925XX (ARC). Our findings from this study demonstrate that ARC treatment of adult mice increases periosteal bone formation in response to exercise. The enhanced response to exercise was characterized by a reduction in osteocytes' induction of osteoclast activity. Endocortical bone formation also increased with treatment independently of exercise, providing gains in mechanical strength and tissue level properties. Overall, inhibiting P2Y2 activation has a beneficial effect on bone formation and the anabolic response to loading, namely by limiting osteoclast activation.
How Does Humanoid Virtual Influencers' Appearance Convey Social Presence? The Underlying Process and Path to Purchase Intention
Authors: Zourrig Haithem , Park Jeongsoo , Becheur Imene
Published: January 2025

Drawing on the stimulus‐organism‐response (S‐O‐R) framework, the current work contends that the interplay between Humanoid Virtual Influencer (HVI) traits acts as a stimulus that shapes consumers' sense of social presence and perception of HVI's attractiveness, which in turn influences their willingness to follow HVI's recommendations and purchase intention. Four online survey studies were conducted among Instagram users in Japan. The results from Study 1 show that animism partially mediates the impact of HVI anthropomorphism on social presence. Moreover, Study 2 reveals that warmth and competence dimensions, as stereotypical evaluations, partially mediate the influence of anthropomorphism and animism on social presence. Unexpectedly, Study 3 found that HVI attractiveness does not mediate the linkage between social presence and consumers' disposition to follow HVI recommendations. However, Study 4 reveals that the disposition to follow HVI recommendations acts as a mediating factor in the pathway between attractiveness and the intention to make a purchase. This research expands the existing literature by considering animism as an additional characteristic of HVIs and examining its influence on stereotypical evaluations. These insights provide practical implications for retail marketers who collaborate with HVIs in their advertising efforts.
Exploring the competencies of nephrology nurses: A comprehensive scoping review
Authors: Andreoli Desirèe , Morales Palomares Sara , Mancin Stefano , Parozzi Mauro , Gazineo Domenica , Palmisano Addolorata , Angileri Salvatore Alessio , Ricco Mattia , Anastasi Giuliano , Savini Serenella , Cangelosi Giovanni , Godino Lea , Sguanci Marco
Published: January 2025

Background

Chronic kidney disease (CKD) presents a significant global health challenge. Nephrology nurses, possessing specialized competencies, play an essential role in providing high‐quality care to CKD patients.

Aim

This scoping review aims to comprehensively map and synthesize literature on the competencies of nephrology nurses worldwide.

Methods

A scoping review was reported using the PRISMA‐ScR framework and aligned with the Joanna Briggs Institute (JBI) methodology. The population, concept, and context (PCC) model was employed to formulate the research question. The search was conducted between June and July 2023 across five databases:Medline, Scopus, Cochrane Library, ASSIA, and CINAHL, with additional consultation of gray literature sources. Screening of articles, data extraction, and quality appraisal were independently performed by two authors. Critical appraisal was conducted using JBI critical appraisal tools. Data were analyzed using descriptive analysis.

Results

Of the 8786 records identified, 25 were included. The included articles predominantly consisted of position papers published between 2000 and 2022, with studies conducted across all continents. Core competencies for nephrology nurses were identified, along with advanced competencies encompassing advanced clinical practice, education, leadership and management, and research.

Conclusion

The review of competencies among nephrology nurses worldwide reveals a comprehensive and diverse set of skills required to address the complexities of CKD. As the field of nephrology continues to evolve, ongoing efforts should be directed toward refining and expanding the competencies of nephrology nurses in individual national contexts as well as defining, in the light of a systematic mapping of skills, homogeneous training paths.

Implications for nursing

This scoping review aims to synthesize global literature on nephrology nurses' core and advanced skills, providing a foundation for defining competencies at both national and institutional levels.
Hot‐Air‐Assisted Infrared Drying for Marinated Anchovy: Effects of Spice Blends on Drying Characteristics and Quality
Authors: Neethu K. C. , Aniesrani Delfiya D. S. , Remya S. , Murali S. , Ninan George
Published: January 2025

This study examined the drying characteristics and quality of raw and marinated anchovy using a hot‐air‐assisted pilot‐scale infrared (IR) dryer. Anchovy was marinated with various Indian spice blends and dried for 3 h under controlled conditions. Four marinade formulations were tested: M1 (0.5% salt, 0.25% red chili powder, 0.25% turmeric powder), M2 (1% salt, 0.25% red chili powder, 0.25% turmeric powder), M3 (1% salt, 0.5% red chili powder, 0.5% turmeric powder), and M4 (0.5% salt, 0.5% red chili powder, 0.5% turmeric powder), along with a control. Both marination and drying time significantly affected the final moisture content (p ≤ 0.001). The highest drying rate was observed for M3 (1.442 g/g dry matter/h) and the lowest for raw anchovy (1.389 g/g dry matter/h). Tukey's analysis revealed significant differences in drying rates between M3 and other marinated samples, as well as between raw and certain marinated samples, highlighting the effect of marination on drying efficiency. The diffusion approach model worked best with M3 anchovy. Effective moisture diffusivity values ranged from 7.003 × 10−9 to 8.913 × 10−9 m2/s, with a highest value reported for M3. The results signify the opportunities to improve the hot‐air‐assisted infrared (IR‐HA) drying process and potentially reduce drying time and certainly energy usage. The findings emphasize that spice blends influence both drying characteristics and sensory attributes, offering valuable insights for refining marination strategies to enhance flavor, consistency, and product quality. Marinating before drying is recommended as a method to add the value to anchovy. The economic analysis revealed that the payback period for the IR‐HA dryer when used to dry marinated anchovy is 0.88 years.
Global Burden, Trends, and Inequalities of Gallbladder and Biliary Tract Cancer, 1990–2021: A Decomposition and Age–Period–Cohort Analysis
Authors: Lei Sen , Huang Guizhong , Li Xiaohui , Xi Pu , Yao Zehui , Lin Xiaojun
Published: January 2025

Background

Gallbladder and biliary tract cancer (GBTC) increasingly aggravates the global malignancy burden. This study aimed to evaluate the updated condition of GBTC temporal burden trends and inequalities from 1990 to 2021.

Methods

Data on GBTC were extracted from the Global Burden of Disease (GBD) 2021 study. Incidence, deaths, and disability‐adjusted life years (DALYs) and their age‐standardised rates (ASR) were quantified from 1990 to 2021, stratified by sex, age and sociodemographic index (SDI). The age–period–cohort (APC) model was used to elucidate the effects of age, period, and cohort. Decomposition analysis and cross‐country inequality evaluation were performed to assess the contributing factors and disease imbalance, respectively. Bayesian APC analysis was used to estimate the future burden.

Results

In 2021, the global incident cases of GBTC were 216 768, with 171 961 deaths and 3 732 121 DALYs lost. From 1990 to 2021, the ASR of incidence, mortality, and DALYs decreased slightly. Males showed a slight increase in ASR of incidence, while females experienced a significant decrease. High‐income regions, particularly in Asia Pacific and Latin America, exhibited a higher burden, while Western Sub‐Saharan Africa had the lowest. Low and low‐middle SDI regions showed a gradual rise in all metrics despite lower absolute numbers. The APC analysis indicated that the global incidence of GBTC tended to rise with age, but gender differences existed. Besides, a deteriorating cohort effect was detected amongst individuals born between 1907 and 1917. Decomposition analysis revealed that population growth was the primary driver of the increased GBTC burden globally. Significant disparities in GBTC burden by SDI were observed, with a notable decline in inequality over time. Projections indicated a slow decline in the global ASR through 2040, with a more pronounced decrease in females.

Conclusions

There are significant regional and gender differences in the global burden of GBTC. Population growth remains a major contributor to the burden. Despite the overall decline, the increasing incidence in low and lower‐middle SDI regions and the persistent male burden highlight the need for targeted interventions. Future efforts should focus on addressing socio‐economic inequalities and reducing risk factors, particularly in vulnerable populations.
Effectiveness of Neighborhood Care Volunteer Training Programs: A Mixed‐Methods Study
Authors: Kung Pen‐Chen , Sung Ya‐Li , Wong May‐Kuen Alice , Liao Yen‐Ting , Chou Yen‐Fang , Huang Huei‐Ling
Published: January 2025

Objective

To develop and implement a tiered training model for neighborhood caregiving volunteers and to evaluate its impact on participants’ knowledge, behaviors, and attitudes toward caregiving services.

Design and Methods

We employed a mixed‐methods research design. Participants included 32 neighborhood care volunteers and six seed volunteers. The neighborhood volunteer training program comprised three phases: Development (establishing the tiered training structure), Testing (conducting a pilot study), and Promotion (refining the training curriculum and service model, followed by community practice).d This study primarily evaluated the training outcomes of participants in the promotion phase, with additional qualitative interviews to capture the volunteers’ experiences.

Results

Quantitative data analysis showed that graded healthcare training significantly improved volunteers’ caregiving knowledge, self‐efficacy, and perceptual behavior. Course satisfaction was highest with advanced caregiver training, followed by basic caregiver and volunteer caregiver‐instructor training. Qualitative analysis revealed three themes: (1) improved volunteer role effectiveness, (2) positive service experience, and (3) positive, personal understanding of health.

Conclusions

Providing progressive training and adequate support for volunteers is crucial. Volunteer trainers or management units should emphasize creating positive experiences for volunteers, fostering their abilities, and promoting their willingness to remain engaged in community health services.
Modeling Student Problem Solving for Improving Project-Based Learning
Authors: Lauren Fogg  , Mary Fendley
Published: January 2025

Project-Based Learning courses are widespread in engineering curriculums worldwide. As such, understanding how students problem-solve in these settings benefits curriculum designers, educators, and future learners. The objective of this research was to employ a human factors approach of modeling and error analysis to develop and apply a cognitive model to illustrate how students make decisions and problem-solve in a Project-Based Learning course. In addition, the Systematic Human Error Reduction and Prediction (SHERPA) was applied to identify errors in the process illustrated through the model. Data was collected from direct observations of 84 students in the classroom over two terms, along with qualitative reflection surveys and individual interviews to understand the project's impact on their problem-solving skills during their studies. The final model can be extended to other PBL courses to allow the targeted design of course materials to fit the student problem-solving processes, improve the project, and thereby improve learning outcomes. One main finding of this study was that students consistently failed to predict consequences, and predominately relied on each other as well as course PowerPoints to solve any problems that arose, illustrating the value in developing processes for improved materials.
Book Review: Instructional Scaffolding in STEM Education – Strategies and Efficacy Evidence
Authors: Ibrahim Mohamad Syahrul Nizam , Julius Avelinah
Published: January 2025

Brian R. Belland's Instructional Scaffolding in STEM Education: Strategies and Efficacy Evidence provides an in-depth analysis of instructional scaffolding's role in enhancing student learning within STEM disciplines. The book focuses on the efficacy of computer-based scaffolding, exploring its potential to support students engaged in problem-centered instructional approaches such as project-based and inquiry-based learning. Belland meticulously reviews the theoretical foundations of scaffolding and presents findings from a meta-analysis of 144 studies, identifying scaffolding strategies that most effectively promote higher-order thinking, problem-solving, and deep content knowledge. The book also addresses the customization of scaffolding, stressing the importance of adapting support to meet individual learner needs. Key themes include the integration of conceptual, strategic, and motivational scaffolding, as well as their impact on cognitive outcomes. This review highlights the book’s relevance to educators, researchers, and curriculum developers, offering practical insights for integrating scaffolding into STEM education to foster more engaged and capable learners.
Physical Parameter Screening of Feather Protein Hydrolysate Production by Aspergillus terreus UniMAP AA-1 using Submerged Fermentation
Authors: Ahmad Zaki Siti Nazeera , Mahmad Puzi Syazwani , Tompang Mohamad  Fahrurrazi , Abdullah Nurul Ain Harmiza , Zainul Kamal Syazni , Zakaria Zarina , Hassan Huzairy , Adnan Sinar Arzuria , Ahmad Zaidi Nur Hidayah , Mohamed  Idris Zulkarnain , Mahmad Rozi Siti Khalijah , Wan Azelee Nur Izyan , Jamaludin Mohd Nasrul Izzani
Published: January 2025

Feathers, a significant by-product of the poultry industry, pose considerable waste management challenges due to their abundance and resistance to degradation. This study explores the potential of utilizing chicken feather waste as a sustainable protein source through microbial fermentation. We employed Aspergillus terreus UniMAP AA-1, a keratinolytic fungus for fermentation aimed at degrading feather keratin. Various fermentation conditions, including initial pH, fermentation time, and inoculum size were tested using a fractional factorial design to optimize protein yield. The highest protein hydrolysate concentration achieved was 5.92 mg/mL, obtained with an inoculum size of 5%, a fermentation duration of 10 days, and an initial pH of 10.0. These results underscore the effectiveness of Aspergillus terreus UniMAP AA-1 in transforming feather waste into valuable protein hydrolysate. This research contributes to the advancement of eco-friendly and economically viable methods for valorizing poultry by-products, addressing environmental issues while providing innovative protein sources for livestock feed formulations.
Carbohydrate Extraction from Brown Algae using Green Technology Approach - Ultrasonic Assisted Extraction (UAE)
Authors: Chee Hui Fen , Waslee Nur Nadhirah , Mohd Jusoh Yanti Maslina , Zainan Nur Hidayah
Published: January 2025

Over the past decade, conventional methods have been widely employed for extracting carbohydrate from brown algae, involving significant quantities of acid and alkaline chemicals, lengthy processing times, and high energy requirements. However, in line with the current global emphasis on environmental friendliness, the focus has shifted towards green technologies in the extraction process. Green technologies usually refer to non-conventional methods, with Ultrasonic-Assisted Extraction (UAE) being one of the most commonly utilized techniques. This research paper focuses on the extraction of carbohydrates from brown algae using a green technology approach, specifically UAE. Central composite design (CCD) was used in this study with different combinations of parameters such as temperature (30-60 °C), time (15-45 min) and material to solvent ratio (1:15-1:35). The best operating parameters that obtained the highest carbohydrate yield are the material-to-solvent ratio of 1:35 g/mL, extraction time of 30 min, and extraction temperature of 45 °C. The highest yield of carbohydrate obtained was 7.73 mg/g. These findings will contribute to the development of sustainable and efficient methods for carbohydrate extraction from brown algae using green technology approaches.
Optimisation of Flour Composition Ratio, Baking Temperature and Time on Papaya Biscuit Production and Evaluation of Biscuit Stability during Storage
Authors: Chong Chee Han , A. Aziz Azni , Salehuddin Mohd Harfiz , Md Lazim Nurul Asmak , Zainan Nur Hidayah , Hashim Zanariah , Abang Zaidel Dayang Norulfairuz , Mohd Jusoh Yanti Maslina
Published: January 2025

The underutilized papaya from agroindustry can cause adverse impact towards economy and environment. Papaya is a highly nutritious fruit however it is prone to decay and injury during storage. Thus, it is important to find solutions for this underutilised papaya. One of the solutions is to convert fresh papaya into papaya powder, and used as functional ingredient in food and beverage. The objectives of this study were to optimize the flour composition ratio, baking temperature and time for biscuit production, and evaluate the stability of physicochemical properties of optimized papaya biscuit during storage. The optimized condition with desirability of 0.537 produced biscuits with moisture content of 3.83 ± 0.08%, antioxidant activity of 85.95 ± 0.86%, hardness of 1256.33 ± 93.11 N, 43.52 ± 0.57 of L* value, 19.91 ± 0.27 of a* value, and 21.47 ± 0.63 of b* value. Flour composition ratio, baking temperature and time have significant impacts on the properties studied. Kinetic studies show that the optimized papaya biscuit was more stable during storage since the kinetic rate constants of the antioxidant, moisture content, hardness and color were lower than the control biscuit.