bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the global burden of mesothelioma: trends, socioeconomic influences, and asbestos exposure – a retrospective cohort study
Authors: Zhao Ziran , Li Jiagen , Tan Fengwei , Xue Qi , Gao Shugeng , He Jie 
Published: July 2024

Introduction:
Mesothelioma is an uncommon type of cancer that has received little attention. This study aims to evaluate the global disease burden, trends of mesothelioma by age, sex, and geographic locations, and its risk factors at the population level.

Methods:
The Global Cancer Observatory in 2022 and 2019 Global Burden of Disease were accessed for mesothelioma incidence and its risk factors worldwide. Multivariable linear regression analyses were conducted to explore the associations between mesothelioma incidence and key predictors, including Human Development Index (HDI), Gross Domestic Product (GDP) per capita, and occupational asbestos exposure, adjusting for age and sex across global regions.

Results:
This study identified 30 870 global cases of mesothelioma in 2022, with a higher age-standardized incidence rate in males (0.25 per 100 000) compared to females (0.39 per 100 000). Geographical analysis indicated the highest disease burden in Northern Europe, with particular prevalence in more developed regions. The incidence was also significantly associated with a higher HDI, with a β coefficient of 0.133 overall, and GDP per capita, with a β coefficient of 0.101. These socioeconomic factors exhibited stronger associations in the elderly population, especially with HDI (β=0.512) and GDP (β=0.389), than in adults. Additionally, occupational exposure to asbestos remained a significant risk factor across all groups, except for the younger adult population, with an overall β of 0.122 for incidence. The temporal trend analysis revealed a general decrease in mesothelioma incidence, particularly in the 15–49 years age group.

Conclusions:
The analysis indicates a higher mesothelioma incidence in males and in developed regions, with marked disparities noted particularly in Northern Europe. Significant correlations with socioeconomic indicators – HDI and GDP – and occupational asbestos exposure were identified, particularly affecting the elderly. Despite a decline in global incidence, especially among younger individuals, persistent cases in females highlight the need for continued public health measures addressing both occupational and environmental exposures.
Comparative study between aquatic therapy and land-based exercises in hemiplegic patients after stroke: a randomized controlled trial
Authors: Iatridou Georgia , Stergiou Alexandra N. , Varvarousis Dimitrios N. , Theodorou Areti , Doulgeri Sofia , Pelidou Henrietta-Syngliti , Dimakopoulos George , Ploumis Avraam 
Published: July 2024

ABSTRACT

Objective
This study aimed to assess the effects of aquatic therapy in individuals with hemiplegia compared to those of a conventional land-based exercise program.

Design
This was a blinded, randomized controlled study of chronic stroke patients with hemiplegia. The participants were randomized in to aquatic therapy (experimental) or conventional therapy (control) groups. The aquatic therapy group conducted the exercise program in a swimming pool, and the conventional therapy group performed to an exercise on the land environment three times per week for six weeks. Both interventions focused on posture, balance, and weight-bearing exercises. Outcomes included the Berg Balance Scale, Brunnstrom scale, Motricity Index, muscle strength tests, Modified Ashworth Scale, Postural Assessment Scale for Stroke, Trunk Control Test and Functional Independence Measure. Also, postural sway was evaluated by using the variables of center of pressure displacements in the mediolateral and anteroposterior directions.

Results
The findings of the present study show that the experimental group (26 patients) exhibited significant improvements in spasticity compared to the control group (25 patients) (p = 0.01). The conventional therapy group also achieved significant improvements (p < 0.05) in anteroposterior deviation, mediolateral velocity, and total velocity of center of pressure in a sitting position with eyes closed.

Conclusion
Land-based exercises were more beneficial in the spasticity of chronic stroke patients.
Revisiting Perdeck's massive avian migration experiments debunks alternative social interpretations
Authors: Pot Morrison T. , Visser Marcel E. , Helm Barbara , von Rönn Jan A. C. , van der Jeugd Henk P. 
Published: July 2024

Whether avian migrants can adapt to their changing world depends on the relative importance of genetic and environmental variation for the timing and direction of migration. In
the
classic series of field experiments on avian migration, A. C. Perdeck discovered that translocated juveniles failed to reach goal areas, whereas translocated adults performed ‘true-goal navigation’. His translocations of > 14 000 common starlings (
Sturnus vulgaris
) suggested that genetic mechanisms guide juveniles into a population-specific direction, i.e. ‘vector navigation’. However, alternative explanations involving social learning after release in juveniles could not be excluded. By adding historical data from translocation sites, data that was unavailable in Perdeck's days, and by integrated analyses including the original data, we could not explain juvenile migrations from possible social information upon release. Despite their highly social behaviour, our findings are consistent with the idea that juvenile starlings follow inherited information and independently reach their winter quarters. Similar to more solitarily migrating songbirds, starlings would require genetic change to adjust the migration route in response to global change.
Analysis of direct traffic at the transport protocol level in the WiMax-1/2 cluster oriented to offload the smart city's wireless ecosystem
Authors: Kovtun Viacheslav , Grochla Krzysztof , Aldosary Saad , Al-Maitah Mohammed 
Published: July 2024

Rerouting of direct information traffic under the WiMax-1/2 technology control in the case of licensed frequency spectrum overload ensures communication continuity in the smart city's critical infrastructure. The support of such a process in the WiMax-1/2 cluster has its specificity, worthy of analytical formalization. The article presents a mathematical apparatus that allows the average service duration of an information message during its transfer from the terminal to the WiMax-1/2 base station to be estimated. Unlike analogues, the presented concept adequately describes the investigated process for any number of terminals, taking into account both the queuing effect on their side and the functioning of the cumulative query transmission mechanism inherent in WiMax-1/2 technology. Therefore, the proposed mathematical apparatus, describing the process of servicing an information message, takes into account both the average duration accompanied by potential collisions in the process of sending a request for the allocation of communication resources for its transmission to the base station, and the average duration of the information message's stay in the terminal queue. Experimental studies demonstrated the adequacy of the proposed mathematical apparatus for describing the investigated process. The experimental section also formulates the optimization problem of the investigated process resulting from the management of competitive access parameters.
Physiological state matching in a pair bonded poison frog
Authors: Nowicki Jessica P. , Rodríguez Camilo , Lee Julia C. , Goolsby Billie C. , Yang Chen , Cleland Thomas A. , O'Connell Lauren A. 
Published: July 2024

More than a century ago, Charles Darwin hypothesized that the empathy-like phenotype is a phylogenetically widespread phenomenon. This idea remains contentious, due to the challenges of empirically examining emotions, and few investigations among non-mammalian vertebrates. We provide support for Darwin's hypothesis by discovering partial evidence for the most ancestral form of empathy, emotional contagion (i.e. matching another individual's emotional state), in the pair bonding mimetic poison frog,
Ranitomeya imitator
. We found that male corticosterone, a physiological biomarker of stress, positively correlates with female partners in experimental and semi-natural conditions. This does not appear to coincide with behavioural state-matching. However, it is specific to female partners relative to familiar female non-partners, and is independent of effects that commonly confound studies on emotional contagion. Furthermore, this physiological state-matching is irrespective of partnership longevity or lifetime reproductive output. These results physiologically indicate socially selective emotional contagion in a monogamous amphibian, and paradigms that elicit coinciding neural and behavioural indicators and morphogenic co-variation are needed for further corroboration. Further studies on ancestral forms of empathy in non-mammalian vertebrates are warranted.
IGF-1 Peptide Mimetic-functionalized Hydrogels Enhance MSC Survival and Immunomodulatory Activity
Authors: Tan Xiaohong , Jing Liufang , Neal Sydney M. , Gupta Munish C. , Buchowski Jacob M. , Setton Lori A. , Huebsch Nathaniel 
Published: July 2024

AbstractHuman mesenchymal stem cells (MSCs) have demonstrated promise when delivered to damaged tissue or tissue defects for their cytokine secretion and inflammation modulation behaviors that can promote repair. Insulin-like growth factor 1 (IGF-1) has been shown to augment MSCs’ viability and survival and promote their secretion of cytokines that signal to endogenous cells, in the treatment of myocardial infarction, wound healing, and age-related diseases. Biomaterial cell carriers can be functionalized with growth factor-mimetic peptides to enhance MSC function while promoting cell retention and minimizing off-target effects seen with direct administration of soluble growth factors. Here, we functionalized alginate hydrogels with three distinct IGF-1 peptide mimetics and the integrin-binding peptide, cyclic RGD. One IGF-1 peptide mimetic (IGM-3) was found to activate Akt signaling and support survival of serum-deprived MSCs. MSCs encapsulated in alginate hydrogels that presented both IGM-3 and cRGD showed a significant reduction in pro-inflammatory cytokine secretion when challenged with interleukin-1β. Finally, MSCs cultured within the cRGD/IGM-3 hydrogels were able to blunt pro-inflammatory gene expression of human primary cells from degenerated intervertebral discs. These studies indicate the potential to leverage cell adhesive and IGF-1 growth factor peptide mimetics together to control therapeutic secretory behavior of MSCs.Significance StatementInsulin-like growth factor 1 (IGF-1) plays a multifaceted role in stem cell biology and may promote proliferation, survival, migration, and immunomodulation for MSCs. In this study, we functionalized alginate hydrogels with integrin-binding and IGF-1 peptide mimetics to investigate their impact on MSC function. Embedding MSCs in these hydrogels enhanced their ability to reduce inflammatory cytokine production and promote anti-inflammatory gene expression in cells from degenerative human intervertebral discs exposed to proteins secreted by the MSC. This approach suggests a new way to retain and augment MSC functionality using IGF-1 peptide mimetics, offering an alternative to co-delivery of cells and high dose soluble growth factors for tissue repair and immune- system modulation.
Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets
Authors: Kendsersky Nathan M. , Odrobina Michal , Mabe Nathaniel W. , Farrel Alvin , Grossmann Liron , Tsang Matthew , Groff David , Wolpaw Adam J. , Zammarchi Francesca , van Berkel Patrick H. , Dang Chi V. , Mossé Yaël P. , Stegmaier Kimberly , Maris John M. 
Published: July 2024

AbstractBackgroundNeuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.MethodsWe characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES- dominant to define subtype-specific and pan-neuroblastoma gene sets. Targets were validated with ChIP- sequencing, immunoblotting, and flow cytometry in neuroblastoma cell lines and isogenic ADRN-to-MES transition cell line models. Finally, we evaluated the activity of MES-specific agentsin vivoandin vitro.ResultsMost immunotherapeutic targets being developed for neuroblastoma showed significantly higher expression in the ADRN subtype with limited expression in MES-like tumor cells. In contrast,CD276(B7-H3) andL1CAMmaintained expression across both ADRN and MES states. We identified several receptor tyrosine kinases (RTKs) enriched in MES-dominant samples and showed that AXL targeting with ADCT-601 was potently cytotoxic in MES-dominant cell lines and showed specific anti-tumor activity in a MES cell line-derived xenograft.ConclusionsImmunotherapeutic strategies for neuroblastoma must address the potential of epigenetic downregulation of antigen density as a mechanism for immune evasion. We identified several RTKs as candidate MES-specific immunotherapeutic target proteins for the elimination of therapy-resistant cells. We hypothesize that the phenomena of immune escape will be less likely when targeting pan-neuroblastoma cell surface proteins such as B7-H3 and L1CAM, and/or dual targeting strategies that consider both the ADRN- and MES-cell states.Key PointsCellular plasticity influences the abundance of immunotherapeutic targets.Subtype-specific targets may be susceptible to epigenetically-mediated downregulation.Immunotherapeutic targets in development, B7-H3 and L1CAM, show “pan-subtype” expression.Importance of StudyNeuroblastoma is a lethal childhood malignancy that shows cellular plasticity in response to anti-cancer therapies. Several plasma membrane proteins are being developed as immunotherapeutic targets in this disease. Here we define which cell surface proteins are susceptible to epigenetically regulated downregulation during an adrenergic to mesenchymal cell state switch and propose immunotherapeutic strategies to anticipate and circumvent acquired immunotherapeutic resistance.
A comparative analysis across species of maternal mRNA regulation in embryos using QUANTA
Authors: Tawil Mazal , Alcalay Dina , Greenberg Pnina , Har-Sheffer Shirel , Fishman Lior , Rabani Michal 
Published: July 2024

AbstractThe post-transcriptional regulation of mRNAs greatly impacts gene expression dynamics, but the underlying regulatory kinetics and sequence rules and how they change between organisms remain elusive. Thousands of pre-loaded maternal transcripts are post-transcriptionally regulated within metazoan embryos, making it an ideal system to investigate mRNA regulation. We present QUANTA, a computational strategy to distinguish transcriptionally silent genes and analyze their regulation. QUANTA uses kinetic models to compare total and polyA+ expression patterns, and dissect quantitative rates of mRNA polyadenylation and degradation. QUANTA analysis of maternally provided mRNAs in zebrafish, frog, mouse and human embryos shows that widespread polyadenylation precedes their degradation. Degradation rates are proportional to the developmental pace of organisms and diverge between orthologs. Rates also scale by adjusting developmental pace of zebrafish with external temperature. Finally, we implement a massively parallel reporter assay that is compatible with QUANTA analysis in zebrafish embryos, and analyze the effects of 3’UTR sequences on mRNA kinetics. We pinpoint potential regulatory signals in 3’UTRs of each organism. These reveal signals to accelerate maternal degradation in fast-developing organisms, while in slow-developing organisms signals enhance mRNA stability. Our work provides a general strategy to quantify post-transcriptional mRNA kinetics and investigate its sequence-based rules.
Glycation of alpha-synuclein enhances aggregation and neuroinflammatory responses
Authors: Vasili Eftychia , König Annekatrin , Al-Azzani Mohammed , Bosbach Clara , Gatzemeier Luisa Maria , Chegão Ana , Miranda Hugo Vicente , Erskine Daniel , Outeiro Tiago F. 
Published: July 2024

AbstractThe risk of developing Parkinson’s disease (PD) is elevated in people with type 2 diabetes, but the precise molecular pathways underlying this connection are still unclear. One hypothesis is that glycation, a non-enzymatic family of reactions between glycating agents, such as reducing sugars or reactive dicarbonyls, and specific amino acids, such as lysines and arginines, may alter proteostasis and trigger pathological alterations. Glycation of alpha-synuclein (aSyn), a central player in PD pathology, causes profound changes in the aggregation process of aSyn. Methylglyoxal (MGO), a strong glycating agent, induces the formation of pathological inclusions enriched in phosphorylated aSyn on serine 129 (pS129). In addition, we found that neuroinflammatory responses are enhanced by MGO-mediated aSyn glycation. Using novel polyclonal antibodies developed towards specific MGO-glycated aSyn residues, we confirmed the occurrence of glycated aSyn bothin vitroas well as in animal and in human brain tissue. In total, our findings shed light into the interplay between glycation, PD, and type 2 diabetes, potentially paving the way for the development of novel therapeutic strategies targeting these intertwined conditions.
TCRfinder: Improved TCR virtual screening for novel antigenic peptides with tailored language models
Authors: Li Yang , Zhang Chaoting , Zhang Xi , Zhang Yang 
Published: July 2024

AbstractAccurate modeling of T-cell receptor (TCR) and peptide interactions is essential for immunoreaction elucidation and T-cell-based immunotherapeutic developments. We developed TCRfinder, a novel deep-learning architecture for TCR-peptide binding prediction and virtual screening. Large-scale benchmark experiments demonstrated a robust capability of TCRfinder in distinguishing interacting and non-interacting TCRs for unseen peptides, with accuracy significantly beyond current state-of-the-art methods. Furthermore, TCRfinder recognizes tumor neoantigen mutations from wild-type antigens of given TCRs, with a success rate nearly 50% higher than the best of existing methods. Detailed data analyses showed that the major advantage of TCRfinder lies in the specially trained TCR and peptide language models tailored with iterative attention network architecture, which can precisely reveal physical interaction patterns of cross-chain atoms and substantially enhance the precision of TCR-peptide interaction predictions. The open-source TCRfinder program can help facilitate large-scale deployment of high-quality TCR and neoantigen virtual screening, offering exciting potential for personalized TCR-based immunotherapies.
circPCMTD1: A protein-coding circular RNA that regulates DNA damage response inBCR/ABL-positive leukemias
Authors: Papaioannou Dimitrios , Urs Amog P. , Buisson Rémi , Petri Andreas , Kulkarni Rohan , Nicolet Deedra , Woodward Lauren , Goda Chinmayee , Mrózek Krzysztof , Behbehani Gregory K. , Kauppinen Sakari , Eisfeld Ann-Kathrin , Aifantis Iannis , Singh Guramrit , Dorrance Adrienne M. , Garzon Ramiro 
Published: July 2024

AbstractCircular RNAs are a novel class of RNA transcripts, which regulate important cellular functions in health and disease. Herein, we report on the functional relevance of thecircPCMTD1transcript in acute leukemias. In screening experiments, we found thatcircPCMTD1depletion strongly inhibited the proliferative capacity of leukemic cells withBCR-ABLtranslocations. Mass cytometry experiments identified the aberrant activation of the DNA damage response as an early downstream event ofcircPCMTD1depletion. Inin vivoexperiments,circPCMTD1targeting prolonged the survival of mice engrafted with leukemic blasts harboring the Philadelphia chromosome. Mechanistically, we found thatcircPCMTD1was enriched in the cytoplasm and associated with the ribosomes of the leukemic cells. We detected a cryptic open reading frame within thecircPCMTD1sequence and found thatcircPCMTD1could generate a peptide product. ThecircPCMTD1-derived peptide interacted with proteins of the BTR complex and enhanced BTR complex formation, thereby increasing tolerance to genotoxic stress.
spatialGE: A user-friendly web application to democratize spatial transcriptomics analysis
Authors: Ospina Oscar E. , Manjarres-Betancur Roberto , Gonzalez-Calderon Guillermo , Soupir Alex C. , Smalley Inna , Tsai Kenneth , Markowitz Joseph , Vallebuona Ethan , Berglund Anders , Eschrich Steven , Yu Xiaoqing , Fridley Brooke L. 
Published: July 2024

AbstractSpatial transcriptomics (ST) is a powerful tool for understanding tissue biology and disease mechanisms. However, its potential is often underutilized due to the advanced data analysis and programming skills required. To address this, we present spatialGE, a web application that simplifies the analysis of ST data. The application spatialGE provides a user-friendly interface that guides users without programming expertise through various analysis pipelines, including quality control, normalization, domain detection, phenotyping, and multiple spatial analyses. It also enables comparative analysis among samples and supports various ST technologies. We demonstrate the utility of spatialGE through its application in studying the tumor microenvironment of melanoma brain metastasis and Merkel cell carcinoma. Our results highlight the ability of spatialGE to identify spatial gene expression patterns and enrichments, providing valuable insights into the tumor microenvironment and its utility in democratizing ST data analysis for the wider scientific community.
Reward integration in prefrontal-cortical and ventral-hippocampal nucleus accumbens inputs cooperatively modulates engagement
Authors: Iyer Eshaan S. , Vitaro Peter , Wu Serena , Muir Jessie , Tse Yiu Chung , Cvetkovska Vedrana , Bagot Rosemary C. 
Published: July 2024

AbstractThe NAc, a highly integrative brain region controlling motivated behavior, is thought to receive distinct information from various glutamatergic inputs yet strong evidence of functional specialization of inputs is lacking. While circuit neuroscience commonly seeks specific functions for specific circuits, redundancy can be highly adaptive and is a critical motif in circuit organization. Using dual-site fiber photometry in an operant reward task, we simultaneously recorded from two NAc glutamatergic afferents to assess circuit specialization. We identify a common neural motif that integrates reward history in medial prefrontal cortex (mPFC) and ventral hippocampus (vHip) inputs to NAc. Then, by systematically degrading task complexity, dissociating reward from choice and action, we identify key circuit-specificity in the behavioral conditions that recruit encoding. While mPFC-NAc invariantly encodes reward, vHip-NAc encoding is uniquely anchored to loss. Ultimately, using optogenetic stimulation we demonstrate that both inputs co-operatively modulate task engagement. We illustrate how similar encoding, with differential gating by behavioral state, supports state-sensitive tuning of reward-motivated behavior.