bluuebunny/crossref_metadata_2025 huggingface dataset:
ICT-based fluorescent probes for intracellular pH and biological species detection
Authors: Wu You , Ge Chengyan , Zhang Ying , Wang Yalong , Zhang Deteng
Published: December 2023

Fluorescent probes, typically based on the intramolecular charge transfer (ICT) mechanism, have received considerable research attention in cell detection due to their non-invasiveness, fast response, easy regulation, high sensitivity, and low damage tolerance for in vivo bio-samples. Generally, intracellular pH and biological species such as various gases, metal ions, and anions constitute the foundation of cells and participate in the basic physiological processes, whose abnormal level can lead to poisoning, cardiovascular disease, and cancer in living organisms. Therefore, monitoring of their quantity plays an essential role in understanding the status of organisms and preventing, diagnosing, and treating diseases. In the last decades, remarkable progress has been made in developing ICT probes for the detection of biological elements. In this review, we highlight the recent ICT probes focusing primarily on the detection of intracellular pH, various gases (H2S, CO, H2O2, and NO), metal ions (Cu2+, Hg2+, Pb2+, Zn2+, and Al3+), and anions (ClO−, CN−, SO32−, and F−). In addition, we discuss the issues and limitations of ICT-based fluorescent probes for in vivo detection and explore the clinical translational potential and challenges of these materials, providing valuable guidance and insights for the design of fluorescent materials.
Factors affecting the early establishment of neonatal intestinal flora and its intervention measures
Authors: Ma Guangyu , Shi Yuguo , Meng Lulu , Fan Haolong , Tang Xiaomei , Luo Huijuan , Wang Dongju , Zhou Juan , Xiao Xiaomin
Published: December 2023

In recent years, it has become evident that early-life intestinal flora plays a pivotal role in determining human health. Consequently, it is imperative to explore the establishment of neonatal intestinal flora and its influencing factors. Early neonatal intestinal flora is influenced by a multitude of factors, including maternal and infant-related factors, as well as external environment. This review summarizes the colonization mechanism of intestinal flora in the early life of newborns and discussed their influence on the establishment of neonatal intestinal flora, taking into account factors such as delivery mode, gestational age and feeding mode. Additionally, this review delves into the natural or artificial reconstruction of intestinal flora colonization defects in infants born via cesarean section and premature infants, with the goal of establishing a theoretical foundation for preventing and treating issues related to neonatal intestinal flora colonization and associated diseases.
Language dynamics within adaptive networks: an agent-based approach of nodes and links coevolution
Authors: Charalambous Christos , Sanchez David , Toral Raul
Published: December 2023

Motivated by the dramatic disappearance of endangered languages observed in recent years, a great deal of attention has been given to the modeling of language competition in order to understand the factors that promote the disappearance of a language and its unfolding dynamics. With this in mind, we build on existing network models of language competition in bilingual societies. These models deal with the interplay between the usage of a language (link state) and the preference or attitude of the speakers towards the language (node state). In this work, we allow for the case where agents have the freedom to adapt their local interactions in accordance with their language preference. This is modeled by introducing a local rewiring mechanism triggered by the dissatisfaction of an agent with its usage of a given language. Our numerical simulations show that permitting this freedom to agents likely results in linguistically segregated communities for small network sizes. However, for networks of sufficiently large size, the extinction of one of the languages is the most probable scenario. Furthermore, we analyze how the fraction of minority speakers changes with the system size and we find that this fraction grows as the total population increases, which is consistent with existing data. Overall, the results of this work help us understand the impact of speakers’ preferences and choices in the complex language landscape of bilingual societies.
Heart failure: a prevalence-based and model-based cost analysis
Authors: Mahmoudi Zahra , Chenaghlou Maryam , Zare Hossein , Safaei Naser , Yousefi Mahmood
Published: December 2023

Introduction

Heart failure (HF) imposes a heavy economic burden on patients, their families, and society as a whole. Therefore, it is crucial to quantify the impact and dimensions of the disease in order to prioritize and allocate resources effectively.

Methods

This study utilized a prevalence-based, bottom-up, and incidence-based Markov model to assess the cost of illness. A total of 502 HF patients (classes I–IV) were recruited from Madani Hospital in Tabriz between May and October 2022. Patients were followed up every two months for a minimum of two and a maximum of six months using a person-month measurement approach. The perspective of the study was societal, and both direct and indirect costs were estimated. Indirect costs were calculated using the Human Capital (HC) method. A two-part regression model, consisting of the Generalized Linear Model (GLM) and Probit model, was used to analyze the relationship between HF costs and clinical and demographic variables.

Results

The total cost per patient in one year was 261,409,854.9 Tomans (21,967.21 PPP). Of this amount, 207,147,805.8 Tomans (17,407.38 PPP) (79%) were indirect costs, while 54,262,049.09 Tomans (4,559.84 PPP) (21%) were direct costs. The mean lifetime cost was 2,173,961,178 Tomans. Premature death accounted for the highest share of lifetime costs (48%), while class III HF had the lowest share (2%). Gender, having basic insurance, and disease class significantly influenced the costs of HF, while comorbidity and age did not have a significant impact. The predicted amount closely matched the observed amount, indicating good predictive power.

Conclusion

This study revealed that HF places a significant economic burden on patients in terms of both direct and indirect costs. The substantial contribution of indirect costs, which reflect the impact of the disease on other sectors of the economy, highlights the importance of unpaid work. Given the significant variation in HF costs among assessed variables, social and financial support systems should consider these variations to provide efficient and fair support to HF patients.
Cusp-overlap view reduces conduction disturbances and permanent pacemaker implantation after transcatheter aortic valve replacement even with balloon-expandable and mechanically-expandable heart valves
Authors: Stephan Tilman , Krohn-Grimberghe Marvin , von Lindeiner genannt von Wildau Annika , Buck Christoph , Baumhardt Michael , Mörike Johannes , Gonska Birgid , Rottbauer Wolfgang , Buckert Dominik
Published: December 2023

Background

Conduction disturbances demanding permanent pacemaker implantation (PPI) remain a common complication after transcatheter aortic valve replacement (TAVR). Optimization of the implantation depth (ID) by introducing the cusp-overlap projection (COP) technique led to a reduced rate of PPI when self-expanding valves were used.

Objectives

The aim of the present study was to determine if using the novel COP view is applicable for all types of TAVR prosthesis and results in a higher ID and reduced incidence of new conduction disturbances and PPI.

Methods

In this prospective case-control study 586 consecutive patients undergoing TAVR with either balloon-expandable Edwards SAPIEN S3 (n = 280; 47.8%), or mechanically expandable Boston LOTUS Edge heart valve prostheses (n = 306; 52.2%) were included. ID as well as rates of periprocedural PPI and left bundle branch block (LBBB) were compared between the conventional three-cusp coplanar (TCC) projection and the COP view for implantation.

Results

Of 586 patients, 282 (48.1%) underwent TAVR using COP, whereas in 304 patients (51.9%) the TCC view was applied. Using COP a significantly higher ID was achieved in Edwards SAPIEN S3 TAVR procedures (ID mean difference −1.0 mm, 95%−CI −1.9 to −0.1 mm;P = 0.029), whereas the final platform position did not differ significantly between both techniques when a Boston LOTUS Edge valve was used (ID mean difference −0.1 mm, 95%-CI −1.1 to +0.9 mm;P = 0.890). In Edwards SAPIEN S3 valves, higher ID was associated with a numerically lower post-procedural PPI incidence (4.9% vs. 7.3%;P = 0.464). Moreover, ID was significantly deeper in patients requiring PPI post TAVR compared to those without PPI [8.7 mm (6.8–10.6 mm) vs. 6.5 mm (6.1–7.0 mm);P = 0.005]. In Boston LOTUS Edge devices, COP view significantly decreased the incidence of LBBB post procedure (28.1% vs. 47.9%;P < 0.001), while PPI rates were similar in both groups (21.6% vs. 25.7%;P = 0.396).

Conclusion

The present study demonstrates the safety, efficacy and reproducibility of the cusp-overlap view even in balloon-expandable and mechanically-expandable TAVR procedures. Application of COP leads to significantly less LBBB in repositionable Boston LOTUS Edge valves and a numerically lower PPI rate in Edwards SAPIEN S3 valves post TAVR compared to the standard TCC projection. The results should encourage to apply the COP view more widely in clinical practice.
Digital literacy in university students of education degrees in Ecuador
Authors: Pegalajar Palomino Maria del Carmen , Rodríguez Torres Ángel F.
Published: December 2023

Digital technologies have transformed the social and, consequently, educational context. Given this situation, it is worth highlighting the importance of promoting digital literacy to actively participate in the society in which it develops. This work analyzes the level of mastery of digital skills of the university students in Ecuador. To do this, a descriptive methodology has been used, based on the survey technique, based on a questionnaire (n = 778). Results reveal how the students give priority to research and information management, presenting difficulties in the development and adaptation of technological materials, as well as in the creation and adaptation of digital content. It even highlights how male university education students claim to have better digital skills, while the same situation is not the case for those others who study Intercultural Bilingual Education. This analysis enables Higher Education institutions to make decisions for planning, developing and acquiring digital skills in the university students of Education in Ecuador, in favor of better teaching professional development.
Driving the career readiness agenda in Hong Kong higher education
Authors: Chan Benjamin Tak Yuen
Published: December 2023

The concept of “career readiness” can trace its origin to earlier studies about learning and employability in higher education as well as management of student life cycle. Since then, career readiness has evolved into a major concern for public funders and regulators of higher education. Policy researchers contend that following the expansion of higher education and subsequent institutional commitment to ensuring student success, the current stage is about emphasizing employability as the primary indicator of graduate outcomes. This policy shift projects the university-employer interface into the spotlight and creates a favorable condition for promoting work-based experiential learning in higher education. While all postsecondary education institutions in Hong Kong give due regard to graduate employment as a measure of successful “university to work transition,” most of them however do not offer structured courses to train their students in skills for lifetime employability. This leads to the question of whether the status quo is desirable and what would be an effective lever for effecting change. Should coaching students for career readiness remain the responsibility of career development office or can academic staff also have a role to play in supporting it? What are the different approaches for teaching about “work life” in the crowded undergraduate curriculum space? Answers to the above would depend on how much the higher education sector in Hong Kong is prepared to embark on a “whole-of-life” approach to develop “work conscious” and not just “work ready” graduates. The new direction will help to generate a positive effect on higher education institutions in Hong Kong for them to compete through curricular and pedagogical innovations in support of the career-readiness agenda.
Intestinal permeability is associated with aggravated inflammation and myofibroblast accumulation in Graves’ orbitopathy: the MicroGO study
Authors: Fenneman Aline C. , van der Spek Anne H. , Hartstra Annick , Havik Stefan , Salonen Anne , de Vos Willem M. , Soeters Maarten R. , Saeed Peeroz , Nieuwdorp Max , Rampanelli Elena
Published: December 2023

Background

Graves’ disease (GD) and Graves’ orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital pre-adipocytes and fibroblasts also express the TSH receptor, resulting in expanded retro-orbital tissue and causing exophthalmos and limited eye movement. Recent studies have shown that GD/GO patients have a disturbed gut microbiome composition, which has been associated with increased intestinal permeability. This study hypothesizes that enhanced intestinal permeability may aggravate orbital inflammation and, thus, increase myofibroblast differentiation and the degree of fibrosis.

Methods

Two distinct cohorts of GO patients were studied, one of which was a unique cohort consisting of blood, fecal, and retro-orbital tissue samples. Intestinal permeability was assessed by measuring serum lipopolysaccharide-binding protein (LBP), zonulin, TLR5, and TLR9 ligands. The influx of macrophages and accumulation of T-cells and myofibroblast were quantified in orbital connective tissue. The NanoString immune-oncology RNA targets panel was used to determine the transcriptional profile of active fibrotic areas within orbital sections.

Results

GO patients displayed significantly higher LBP serum concentrations than healthy controls. Within the MicroGO cohort, patients with high serum LBP levels also showed higher levels of zonulin and TLR5 and TLR9 ligands in their circulation. The increased intestinal permeability was accompanied by augmented expression of genes marking immune cell infiltration and encoding key proteins for immune cell adhesion, antigen presentation, and cytokine signaling in the orbital tissue. Macrophage influx was positively linked to the extent of T cell influx and fibroblast activation within GO-affected orbital tissues. Moreover, serum LBP levels significantly correlated with the abundance of specific Gram-negative gut bacteria, linking the gut to local orbital inflammation.

Conclusion

These results indicate that GO patients have enhanced intestinal permeability. The subsequent translocation of bacterial compounds to the systemic circulation may aggravate inflammatory processes within the orbital tissue and, as a consequence, augment the proportion of activated myofibroblasts, which actively secrete extracellular matrix leading to retro-orbital tissue expansion. These findings warrant further exploration to assess the correlation between specific inflammatory pathways in the orbital tissue and the gut microbiota composition and may pave the way for new microbiota-targeting therapies.
Total bilirubin and bilirubin-to-triglycerides ratio predict changes in glycated hemoglobin in healthy children
Authors: Puerto-Carranza Elsa , Nuevo-Casals Silvia , Roca-Portella Berta , Mas-Parés Berta , Gómez-Vilarrubla Ariadna , Carreras-Badosa Gemma , Niubó Maria , Prats-Puig Anna , de Zegher Francis , Ibáñez Lourdes , Bassols Judit , López-Bermejo Abel
Published: December 2023

Objective

Bilirubin and triglycerides can regulate insulin secretion and glucose uptake. The aim of our study is to analyze associations between total bilirubin (TB) and the bilirubin-to-triglycerides ratio (BTR) with metabolic markers in healthy prepubertal children.

Methods

Subjects were 246 healthy children (mean age 8), of whom 142 (58%) were reevaluated 4 years later (mean age 12). The subjects were stratified according to age into three groups (<7.8 years; 7.8-9.6 years; and >9.6 years; n=82 each) at baseline and into two groups (<12.9 years and ≥12.9 years; n=71 each) at follow-up. Anthropometrics and laboratory parameters [TB and its fractions (direct and indirect bilirubin), triglycerides, HDL-cholesterol, glucose, insulin, HOMA-IR, HOMA-B and glycated hemoglobin (HbA1c)] were assessed at both baseline and follow-up.

Results

TB and BTR showed independent and negative association with baseline and follow-up HbA1c. These associations were stronger for BTR and in the highest age group. No independent associations were observed with HOMA-IR or HOMA-B.

Conclusion

TB and BTR are independently associated with HbA1c and predict its changes over time in healthy children. Our results indicate that TB and BTR may be useful parameters in studies of glucose tolerance in healthy children.
Why a feminist ethics of care and socio-ecological justice lens matter for global, interdisciplinary research on water security
Authors: Narayanaswamy Lata , Ferritto Robert , Hillesland Marya , Anker Victoria , Singhal Shivani , Maysels Rachael Marjorie , Bantider Amare , Charles Katrina , Doss Cheryl , Kumar Ashok , Mdee Anna , Neo Sau-Mei , Pinzón Federico , Mengistu Bamlaku T.
Published: December 2023

In this conceptual analysis, we set out some of the negotiations and tensions that emerge when we try to build a shared understanding of water (in)security through the dual lenses of a feminist ethics of care and socio-ecological justice. We further reflect on how these theoretical lenses shape our work in practice—how do we actualise them in an international, interdisciplinary partnership? We actively seek to engage all our colleagues in how we understand the function of power and inequality in relation to the distribution of water resources and the ways in which intersectional inequalities shape access to, and availability of, water. We conclude that our international partnership will only add value to our understanding of water (in)security if we are able to identify not just how intersectional inequalities circumscribe differential access to water itself in a range of diverse contexts, but the ways socio-ecological justice and a feminist ethics of care are understood and in turn shape how we work together to achieve greater water security across diverse contexts.
Lipid compartments and lipid metabolism as therapeutic targets against coronavirus
Authors: Cesar-Silva Daniella , Pereira-Dutra Filipe S. , Giannini Ana Lucia Moraes , Maya-Monteiro Clarissa M. , de Almeida Cecília Jacques G.
Published: December 2023

Lipids perform a series of cellular functions, establishing cell and organelles’ boundaries, organizing signaling platforms, and creating compartments where specific reactions occur. Moreover, lipids store energy and act as secondary messengers whose distribution is tightly regulated. Disruption of lipid metabolism is associated with many diseases, including those caused by viruses. In this scenario, lipids can favor virus replication and are not solely used as pathogens’ energy source. In contrast, cells can counteract viruses using lipids as weapons. In this review, we discuss the available data on how coronaviruses profit from cellular lipid compartments and why targeting lipid metabolism may be a powerful strategy to fight these cellular parasites. We also provide a formidable collection of data on the pharmacological approaches targeting lipid metabolism to impair and treat coronavirus infection.
Dermatophagoides farinae microRNAs released to external environments via exosomes regulate inflammation-related gene expression in human bronchial epithelial cells
Authors: He Kaiyue , Yang Ting , Yu Jinyan , Zang Xiao , Jiang Shangde , Xu Shuyue , Liu Jiaxi , Xu Zuyu , Wang Wei , Hong Shanchao
Published: December 2023

Background

Dermatophagoides farinae (DFA) is an important species of house dust mites (HDMs) that causes allergic diseases. Previous studies have focused on allergens with protein components to explain the allergic effect of HDMs; however, there is little knowledge on the role of microRNAs (miRNAs) in the allergic effect of HDMs. This study aimed to unravel the new mechanism of dust mite sensitization from the perspective of cross-species transport of extracellular vesicles-encapsulated miRNAs from HDMs.

Methods

Small RNA (sRNA) sequencing was performed to detect miRNAs expression profiles from DFA, DFA-derived exosomes and DFA culture supernatants. A quantitative fluorescent real-time PCR (qPCR) assay was used to detect miRNAs expression in dust specimens. BEAS-2B cells endocytosed exosomes were modeled in vitro to detect miRNAs from DFA and the expression of related inflammatory factors. Representative dfa-miR-276-3p and dfa-novel-miR2 were transfected into BEAS-2B cells, and then differentially expressed genes (DEGs) were analyzed by RNA sequencing. Protein-protein interaction (PPI) network analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment analyses were performed on the first 300 nodes of DEGs.

Results

sRNA sequencing identified 42 conserved miRNAs and 66 novel miRNAs in DFA, DFA-derived exosomes, and DFA culture supernatants. A homology analysis was performed on the top 18 conserved miRNAs with high expression levels. The presence of dust mites and miRNAs from HDMs in living environment were also validated. Following uptake of DFA-derived exosomes by BEAS-2B cells, exosomes transported miRNAs from DFA to target cells and produced pro-inflammatory effects in corresponding cells. RNA sequencing identified DEGs in dfa-miR-276-3p and dfa-novel-miR2 transfected BEAS-2B cells. GO and KEGG enrichment analyses revealed the role of exosomes with cross-species transporting of DFA miRNAs in inflammatory signaling pathways, such as JAK-STAT signaling pathway, PI3K/AKT signaling pathway and IL-6-mediated signaling pathway.

Conclusion

Our findings demonstrate the miRNAs expression profiles in DFA for the first time. The DFA miRNAs are delivered into living environments via exosomes, and engulfed by human bronchial epithelial cells, and cross-species regulation may contribute to inflammation-related processes.
The multi-faceted role of NADPH in regulating inflammation in activated myeloid cells
Authors: Ting Kenneth K. Y. , Jongstra-Bilen Jenny , Cybulsky Myron I.
Published: December 2023

Recent advances in the immunometabolism field have demonstrated the importance of metabolites in fine-tuning the inflammatory responses in myeloid cells. Cofactors, which are metabolites comprised of inorganic ions and organic molecules, may tightly or loosely bind to distinct sites of enzymes to catalyze a specific reaction. Since many enzymes that mediate inflammatory and anti-inflammatory processes require the same cofactors to function, this raises the possibility that under conditions where the abundance of these cofactors is limited, inflammatory and anti-inflammatory enzymes must compete with each other for the consumption of cofactors. Thus, this competition may reflect a naturally evolved mechanism to efficiently co-regulate inflammatory versus anti-inflammatory pathways, fine-tuning the extent of an inflammatory response. The role of NADPH, the reduced form of nicotinamide adenine dinucleotide phosphate (NADP+), in mediating inflammatory and anti-inflammatory responses in activated myeloid cells has been well-established in the past decades. However, how the dynamic of NADPH consumption mediates the co-regulation between individual inflammatory and anti-inflammatory pathways is only beginning to be appreciated. In this review, we will summarize the established roles of NADPH in supporting inflammatory and anti-inflammatory pathways, as well as highlight how the competition for NADPH consumption by these opposing pathways fine-tunes the inflammatory response in activated myeloid cells.
Adeno-associated virus vectors for retinal gene therapy in basic research and clinical studies
Authors: Xia Xue , Guo Xinzheng
Published: December 2023

Retinal degenerative diseases, including glaucoma, age-related macular degeneration, diabetic retinopathy, and a broad range of inherited retinal diseases, are leading causes of irreversible vision loss and blindness. Gene therapy is a promising and fast-growing strategy to treat both monogenic and multifactorial retinal disorders. Vectors for gene delivery are crucial for efficient and specific transfer of therapeutic gene(s) into target cells. AAV vectors are ideal for retinal gene therapy due to their inherent advantages in safety, gene expression stability, and amenability for directional engineering. The eye is a highly compartmentalized organ composed of multiple disease-related cell types. To determine a suitable AAV vector for a specific cell type, the route of administration and choice of AAV variant must be considered together. Here, we provide a brief overview of AAV vectors for gene transfer into important ocular cell types, including retinal pigment epithelium cells, photoreceptors, retinal ganglion cells, Müller glial cells, ciliary epithelial cells, trabecular meshwork cells, vascular endothelial cells, and pericytes, via distinct injection methods. By listing suitable AAV vectors in basic research and (pre)clinical studies, we aim to highlight the progress and unmet needs of AAV vectors in retinal gene therapy.
Tracking the contamination sources of microbial population and characterizing Listeria monocytogenes in a chicken slaughterhouse by using culture-dependent and -independent methods
Authors: Jeong Jiyeon , Song Hyokeun , Kim Woo-Hyun , Chae Myeongju , Lee Ji-Youn , Kwon Yong-Kuk , Cho Seongbeom
Published: December 2023

Listeria monocytogenes is the etiologic agent of listeriosis, a foodborne disease that poses a threat to public health globally. Chicken meat exhibits heightened susceptibility to L. monocytogenes contamination during butchery. The persistence of this pathogen in the slaughterhouse environment enables recurring contamination of meat products. This study aimed at identifying the sources and transmission routes of L. monocytogenes contamination within an abattoir where it was consistently detected for three consecutive years (2019–2021). Furthermore, the environmental factors aiding contamination along chicken processing lines were determined by surveying the microbiome within the facility. Samples collected in 2019 to 2021 were subjected to culture-dependent analysis to assess the prevalence, serotypes, and multi-locus sequence typing (MLST) of L. monocytogenes. Additionally, the specimens collected in 2021 underwent culture-independent analysis via real-time quantitative polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing to identify the contamination sources and characterize the entire microbial community within the slaughterhouse. L. monocytogenes was isolated only from the clean zone, where the final slaughtering stage occurs. Most strains isolated from the final carcasses showed the same genetic cluster as the isolate in the chilling water and were assigned to MLST profile ST3. Culture-independent qPCR confirmed L. monocytogenes contamination in all samples, excluding post-scalding carcasses, prewashed post-evisceration carcasses, and the bleeding areas. Consequently, qPCR enabled more comprehensive identification of L. monocytogenes contamination points than culture-dependent approaches. Moreover, 16S rRNA gene amplicon sequencing demonstrated that psychro-tolerant and spoilage-related bacteria with L. monocytogenes-like attributes exhibited enhanced viability in the clean zone and immersion-chilling water. Metagenomics-based source tracking analysis further revealed that the shackles and chilling waters represent predominant sources of cross-contamination between different slaughterhouse zones, whereas the grading and packaging workstations and chilling water in the clean zone were deemed crucial sources affecting final carcass contamination. Collectively, these findings demonstrate through culture-dependent and -independent methods that L. monocytogenes spreads along the slaughter line, contaminating the slaughterhouse. Moreover, by investigating changes in microbial community and bacterial flow along the slaughter line within the facility, the sources influencing carcass contamination can be effectively traced.
Profiling the autoantibody repertoire reveals autoantibodies associated with mild cognitive impairment and dementia
Authors: Ehtewish Hanan , Mesleh Areej , Ponirakis Georgios , Lennard Katie , Al Hamad Hanadi , Chandran Mani , Parray Aijaz , Abdesselem Houari , Wijten Patrick , Decock Julie , Alajez Nehad M. , Ramadan Marwan , Khan Shafi , Ayadathil Raheem , Own Ahmed , Elsotouhy Ahmed , Albagha Omar , Arredouani Abdelilah , Blackburn Jonathan M. , Malik Rayaz A. , El-Agnaf Omar M. A.
Published: December 2023

Background

Dementia is a debilitating neurological disease affecting millions of people worldwide. The exact mechanisms underlying the initiation and progression of the disease remain to be fully defined. There is an increasing body of evidence for the role of immune dysregulation in the pathogenesis of dementia, where blood-borne autoimmune antibodies have been studied as potential markers associated with pathological mechanisms of dementia.

Methods

This study included plasma from 50 cognitively normal individuals, 55 subjects with MCI (mild cognitive impairment), and 22 subjects with dementia. Autoantibody profiling for more than 1,600 antigens was performed using a high throughput microarray platform to identify differentially expressed autoantibodies in MCI and dementia.

Results

The differential expression analysis identified 33 significantly altered autoantibodies in the plasma of patients with dementia compared to cognitively normal subjects, and 38 significantly altered autoantibodies in the plasma of patients with dementia compared to subjects with MCI. And 20 proteins had significantly altered autoantibody responses in MCI compared to cognitively normal individuals. Five autoantibodies were commonly dysregulated in both dementia and MCI, including anti-CAMK2A, CKS1B, ETS2, MAP4, and NUDT2. Plasma levels of anti-ODF3, E6, S100P, and ARHGDIG correlated negatively with the cognitive performance scores (MoCA) (r2 –0.56 to −0.42, value of p < 0.001). Additionally, several proteins targeted by autoantibodies dysregulated in dementia were significantly enriched in the neurotrophin signaling pathway, axon guidance, cholinergic synapse, long-term potentiation, apoptosis, glycolysis and gluconeogenesis.

Conclusion

We have shown multiple dysregulated autoantibodies in the plasma of subjects with MCI and dementia. The corresponding proteins for these autoantibodies are involved in neurodegenerative pathways, suggesting a potential impact of autoimmunity on the etiology of dementia and the possible benefit for future therapeutic approaches. Further investigations are warranted to validate our findings.
Overnight exposure to pink noise could jeopardize sleep-dependent insight and pattern detection
Authors: Vickrey Beverly , Lerner Itamar
Published: December 2023

Accumulated evidence from the past decades suggests that sleep plays a crucial role in memory consolidation and the facilitation of higher-level cognitive processes such as abstraction and gist extraction. In addition, recent studies show that applying pink noise during sleep can further enhance sleep-dependent memory consolidation, potentially by modulating sleep physiology through stochastic resonance. However, whether this enhancement extends to higher cognitive processes remains untested. In this study, we investigated how the application of open-loop pink noise during sleep influences the gain of insight into hidden patterns. Seventy-two participants were assigned to three groups: daytime-wake, silent sleep, and sleep with pink noise. Each group completed the number reduction task, an established insight paradigm known to be influenced by sleep, over two sessions with a 12-h interval. Sleep groups were monitored by the DREEM 3 headband in home settings. Contrary to our prediction, pink noise did not induce an increase in insight compared to silent sleep and was statistically more similar to the wake condition despite evidence for its typical influence on sleep physiology. Particularly, we found that pink noise limited the time spent in the initial cycle of N1 just after sleep onset, while time spent in N1 positively predicted insight. These results echo recent suggestions that the time in the initial cycle of N1 plays a critical role in insight formation. Overall, our results suggest that open-loop pink noise during sleep may be detrimental to insight formation and creativity due to the alterations it causes to normal sleep architecture.
Translating single-neuron axonal reconstructions into meso-scale connectivity statistics in the mouse somatosensory thalamus
Authors: Timonidis Nestor , Bakker Rembrandt , Rubio-Teves Mario , Alonso-Martínez Carmen , Garcia-Amado Maria , Clascá Francisco , Tiesinga Paul H. E.
Published: December 2023

Characterizing the connectomic and morphological diversity of thalamic neurons is key for better understanding how the thalamus relays sensory inputs to the cortex. The recent public release of complete single-neuron morphological reconstructions enables the analysis of previously inaccessible connectivity patterns from individual neurons. Here we focus on the Ventral Posteromedial (VPM) nucleus and characterize the full diversity of 257 VPM neurons, obtained by combining data from the MouseLight and Braintell projects. Neurons were clustered according to their most dominantly targeted cortical area and further subdivided by their jointly targeted areas. We obtained a 2D embedding of morphological diversity using the dissimilarity between all pairs of axonal trees. The curved shape of the embedding allowed us to characterize neurons by a 1-dimensional coordinate. The coordinate values were aligned both with the progression of soma position along the dorsal-ventral and lateral-medial axes and with that of axonal terminals along the posterior-anterior and medial-lateral axes, as well as with an increase in the number of branching points, distance from soma and branching width. Taken together, we have developed a novel workflow for linking three challenging aspects of connectomics, namely the topography, higher order connectivity patterns and morphological diversity, with VPM as a test-case. The workflow is linked to a unified access portal that contains the morphologies and integrated with 2D cortical flatmap and subcortical visualization tools. The workflow and resulting processed data have been made available in Python, and can thus be used for modeling and experimentally validating new hypotheses on thalamocortical connectivity.
Research status of elderly-care robots and safe human-robot interaction methods
Authors: Zhao Donghui , Sun Xingwang , Shan Bo , Yang Zihao , Yang Junyou , Liu Houde , Jiang Yinlai , Hiroshi Yokoi
Published: December 2023

Faced with the increasingly severe global aging population with fewer children, the research, development, and application of elderly-care robots are expected to provide some technical means to solve the problems of elderly care, disability and semi-disability nursing, and rehabilitation. Elderly-care robots involve biomechanics, computer science, automatic control, ethics, and other fields of knowledge, which is one of the most challenging and most concerned research fields of robotics. Unlike other robots, elderly-care robots work for the frail elderly. There is information exchange and energy exchange between people and robots, and the safe human-robot interaction methods are the research core and key technology. The states of the art of elderly-care robots and their various nursing modes and safe interaction methods are introduced and discussed in this paper. To conclude, considering the disparity between current elderly care robots and their anticipated objectives, we offer a comprehensive overview of the critical technologies and research trends that impact and enhance the feasibility and acceptance of elderly care robots. These areas encompass the collaborative assistance of diverse assistive robots, the establishment of a novel smart home care model for elderly individuals using sensor networks, the optimization of robot design for improved flexibility, and the enhancement of robot acceptability.
Influence of treatment-related lymphopenia on the efficacy of immune checkpoint inhibitors in lung cancer: a meta-analysis
Authors: Zhang Ye , Huang Cheng , Li Shanqing
Published: December 2023

Background

Treatment-related lymphopenia (TRL) is common in patients with lung cancer, particularly in those with radiotherapy. However, the influence of TRL on the efficacy of immune checkpoint inhibitors (ICIs) for patients with lung cancer remains poorly understood. We performed a systematic review and meta-analysis to investigate the influence of TRL on survival of lung cancer patients on ICIs.

Methods

In order to accomplish the aim of the meta-analysis, a comprehensive search was conducted on databases including PubMed, Embase, Cochrane Library, and the Web of Science to identify observational studies with longitudinal follow-up. The Cochrane Q test was employed to evaluate heterogeneity among the included studies, while the I2 statistic was estimated. Random-effects models were utilized to merge the results, considering the potential impact of heterogeneity.

Results

Ten cohort studies with 1130 lung cancer patients who were treated with ICIs were included. Among them, 427 (37.8%) had TRL. Pooled results showed that compared to patients without TRL, patients with TRL were associated with poor progression-free survival (hazard ratio [HR]: 2.05, 95% confidence interval [CI]: 1.62 to 2.60, p < 0.001; I2 = 22%) and overall survival (HR: 2.69, 95% CI: 2.10 to 3.43, p < 0.001; I2 = 0%). Sensitivity analysis limited to patients with non-small cell lung cancer showed similar results (HR: 2.66 and 2.62, both p < 0.05). Moreover, subgroup analyses according to the diagnostic criteria of TRL, regression analysis model (univariate or multivariate), and indications of ICIs (for locally advanced or advanced lung cancer) showed consistent results (p for subgroup difference all > 0.05).

Conclusion

TRL was associated with poor survival of lung cancer patients who were treated with ICIs.
The regulatory role and mechanism of exosomes in hepatic fibrosis
Authors: Yao Youli , Chen Da , Yue Zengchang
Published: December 2023

Globally, the prevalence and fatality rates of liver disorders are on the rise. Among chronic liver conditions, hepatic fibrosis stands out as a central pathological process. Despite this, approved treatments for hepatic fibrosis are currently lacking. Exosomes, small extracellular vesicles secreted by various cell types, play a significant role in intercellular communication and have emerged as essential mediators in liver fibrosis. In this regard, this review compiles the mechanisms through which exosomes regulate hepatic fibrosis, encompassing diverse targets and signaling pathways. Furthermore, it delves into the regulatory impact of exosomes modulated by natural plant-derived, endogenous, and synthetic compounds as potential therapeutic strategies for addressing hepatic fibrosis.
Development and validation of PAMPA-BBB QSAR model to predict brain penetration potential of novel drug candidates
Authors: Kato Rintaro , Zeng Wenyu , Siramshetty Vishal B. , Williams Jordan , Kabir Md , Hagen Natalie , Padilha Elias C. , Wang Amy Q. , Mathé Ewy A. , Xu Xin , Shah Pranav
Published: December 2023

Efficiently circumventing the blood-brain barrier (BBB) poses a major hurdle in the development of drugs that target the central nervous system. Although there are several methods to determine BBB permeability of small molecules, the Parallel Artificial Membrane Permeability Assay (PAMPA) is one of the most common assays in drug discovery due to its robust and high-throughput nature. Drug discovery is a long and costly venture, thus, any advances to streamline this process are beneficial. In this study, ∼2,000 compounds from over 60 NCATS projects were screened in the PAMPA-BBB assay to develop a quantitative structure-activity relationship model to predict BBB permeability of small molecules. After analyzing both state-of-the-art and latest machine learning methods, we found that random forest based on RDKit descriptors as additional features provided the best training balanced accuracy (0.70 ± 0.015) and a message-passing variant of graph convolutional neural network that uses RDKit descriptors provided the highest balanced accuracy (0.72) on a prospective validation set. Finally, we correlated in vitro PAMPA-BBB data with in vivo brain permeation data in rodents to observe a categorical correlation of 77%, suggesting that models developed using data from PAMPA-BBB can forecast in vivo brain permeability. Given that majority of prior research has relied on in vitro or in vivo data for assessing BBB permeability, our model, developed using the largest PAMPA-BBB dataset to date, offers an orthogonal means to estimate BBB permeability of small molecules. We deposited a subset of our data into PubChem bioassay database (AID: 1845228) and deployed the best performing model on the NCATS Open Data ADME portal (https://opendata.ncats.nih.gov/adme/). These initiatives were undertaken with the aim of providing valuable resources for the drug discovery community.
Examining the mediating effects of motivation between job insecurity and innovative behavior using a variable-centered and a person-centered approach
Authors: Ma Bing , Zhou Yarong , Lassleben Hermann , Ma Guimei , Yang Rong
Published: December 2023

Introduction

The fierce market competition environment makes employees feel insecure at work. While it is difficult for enterprises to provide employees with a sense of security, they have to rely on employees’ innovative behavior to seek competitive advantage. Therefore, this study focuses on how employees engage in innovative behavior when they face job insecurity.

Methods

Using a variable-centered approach, this study aims to examine the mediating effects of intrinsic and impression management motivation in the relationship between quantitative and qualitative job insecurity and innovative behavior, including proactive and reactive innovative behavior. In addition, a person-centered approach is used to investigate whether it is possible to distinguish different combinations of quantitative and qualitative job insecurity, and examine the effect of these job insecurity profiles on motivation and innovative behavior. We used 503 data sets collected via the Credamo platform in China into the data analysis.

Results

The study found that quantitative job insecurity affects proactive and reactive innovative behavior through impression management motivation and that qualitative job insecurity affects proactive and reactive innovative behavior through intrinsic and impression management motivation. In addition, three job insecurity profiles were identified: balanced high job insecurity, balanced low job insecurity, and a profile dominated by high quantitative job insecurity, all of which have significantly different effects on motivation and innovative behavior.

Discussion

This study contributes to provide new insights into the relationship between job insecurity and innovative behavior and compensate for the limitation of the traditional variable-centered approach that cannot capture heterogeneity within the workforce.
Mechanism and application of Lactobacillus in type 2 diabetes-associated periodontitis
Authors: Chen Sisi , Zhang Yuhan
Published: December 2023

Type 2 diabetes mellitus (T2DM) accelerates the progression of periodontitis through diverse pathways. Abnormal immune responses, excessive activation of inflammation, increased levels of advanced glycation end products, and oxidative stress have defined roles in the pathophysiological process of T2DM-associated periodontitis. Furthermore, in the periodontium of diabetic individuals, there are high levels of advanced glycation end-products and glucose. Meanwhile, progress in microbiomics has revealed that dysbacteriosis caused by T2DM also contributes to the progression of periodontitis. Lactobacillus, owing to its fine-tuning function in the local microbiota, has sparked tremendous interest in this field. Accumulating research on Lactobacillus has detailed its beneficial role in both diabetes and oral diseases. In this study, we summarize the newly discovered mechanisms underlying Lactobacillus-mediated improvement of T2DM-associated periodontitis and propose the application of Lactobacillus in the clinic.
The efficacy of mindfulness-based interventions on mental health among university students: a systematic review and meta-analysis
Authors: Zuo Xinyi , Tang Yong , Chen Yifang , Zhou Zhimiao
Published: December 2023

Introduction

We aimed to estimate the effect of mindfulness therapy on mental health.

Methods

Two researchers searched 12 databases to identify relevant trials that were published from 1 January 2018 to 1 May 2023. We performed a meta-analysis to determine the effect of mindfulness therapy on depression, which was measured by the Beck Depression Inventory (BDI), Patient Health Questionnaire-9 (PHQ-9), Quick Inventory of Depressive Symptomatology (QIDS), Hamilton Depression Rating Scale (HDRS), Patient-Reported Outcomes Measurement Information System (PROMIS), Hospital Anxiety and Depression Scale (HADS), and Depression Anxiety Stress Scales (DASS); anxiety, which was measured by the Beck Anxiety Inventory (BAI), PROMIS, and DASS, Generalized Anxiety Disorder-7 (GAD-7); stress, which was measured by the Perceived Stress Scale (PSS), DASS, and GAD-7; mindfulness, which was measured by the GAD-7, Five Facet Mindfulness Questionnaire (FFMQ), Mindful Attention Awareness Scale (MAAS), Short Form-12 Mental Component Score (SF-12 MCS) and Short Form-12 Physical Component Score (SF-12 PCS); and sleep quality, which was measured by the Pittsburgh Sleep Quality Index (PSQI). After screening studies based on the inclusion and exclusion criteria, 11 randomized controlled trials (RCTs) involving 1,824 participants were ultimately included.

Results

All these studies demonstrated positive effects of mindfulness therapy on depression (SMD = −0.33, 95% CI: [−0.44, −0.22], p < 0.00001, I2 = 29%), anxiety (SMD = −0.35, 95% CI: [−0.46, −0.25], p < 0.00001, I2 = 40%), stress (SMD = −0.39, 95% CI: [−0.48, −0.29], p < 0.00001, I2 = 69%) and sleep quality scores (SMD = −0.81, 95% CI: [−1.54, −0.09], p = 0.03, I2 = 0%). However, there was no significant difference in mindfulness (SMD = −0.12, 95% CI: [−0.36, −0.12], p = 0.34, I2 = 34%) between the mindfulness therapy group and the control group.

Discussion

In future studies, it is necessary to consider the investigation on whether the strategies of improving the mindfulness therapy in adherence and fidelity can work on the improvement of the outcomes in mental health.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42023469301].