bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of autologous serum on anin vitrogranuloma model to studyMycobacterium tuberculosisinfection dynamics
Authors: Bourg Chloé , Hodille Elisabeth , Ader Florence , Dumitrescu Oana , Genestet Charlotte 
Published: December 2024

AbstractTuberculosis (TB) remains a global health challenge, withMycobacterium tuberculosis(Mtb) persisting in granulomas, complex immune structures that balance containment and survival of the pathogen.In vitrogranuloma models have advanced TB research but often rely on commercial human serum, which may not fully replicate the native immune environment. Here, we investigated the role of autologous serum, either heat-inactivated or native, in granuloma-like structure (GLS) formation, bacterial dynamics, and immune responses. Using a human PBMC-based model to induce spontaneousin vitrogranuloma formation after infection with Mtb, we found that autologous serum significantly enhanced GLS formation and altered cytokine profiles compared to commercial serum. Native serum also reduced bacterial growth, likely due to active complement system-mediated immune responses. These findings highlight the importance of autologous serum in creating physiologically relevant models, crucial for preclinical evaluation of TB therapies. Incorporating patient-specific serum can improve model accuracy, enabling better exploration of host-pathogen interactions and targeted therapeutic strategies.
Sexually dimorphic ATF4 expression in the fat confers female stress tolerance inDrosophila melanogaster
Authors: Grmai Lydia , Mychalczuk Melissa , Arkalgud Aditya , Vasudevan Deepika 
Published: December 2024

AbstractMetabolic differences between males and females have been well documented across many species. However, the molecular basis of these differences and how they impact tolerance to nutrient deprivation is still under investigation. In this work, we useDrosophila melanogasterto demonstrate that sex-specific differences in fat tissue metabolism are driven, in part, by dimorphic expression of the Integrated Stress Response (ISR) transcription factor, ATF4. We found that female fat tissues have higher ATF4 activity than their male counter parts under homeostatic conditions. This dimorphism was partly due to a female bias in transcript abundance of specificATF4splice isoforms. We found that the canonical sex determinantstransformer(tra) anddoublesex(dsx) drive such dimorphicATF4transcript abundance. These differences persist in a genetic model of nutrient deprivation, where female animals showed greater resistance to lethality than males in an ATF4-dependent manner. These results suggest that higher ATF4 activity confers higher tolerance to stress in females. Together, our data describe a previously unknown facet of ISR signaling wherein sexual identity of adipose tissue confers differential stress tolerance in males and females. Since energy storage mechanisms are known to be dimorphic and have been linked to ATF4 regulation, our studies provide a mechanistic starting point for understanding how sexual identity influences metabolic disease outcomes.
miR-126 modulates neural progenitor cell development
Authors: Bastiaans Jeroen , Glendinning Michael D. , de Marco Garcia Natalia , Stuhlmann Heidi 
Published: December 2024

SummaryNoncoding microRNAs (miRNAs) play important roles in controlling signaling pathways by targeting multiple genes and altering their expression levels. MiR-126 is a known endothelial-specific miRNA that regulates vascular integrity and angiogenesis by enhancing proangiogenic actions of VEGF and FGF. MiR-126 is also expressed in several stem cell compartments, including embryonic stem cell (ESC) and hematopoietic stem/progenitor cells (HSPC) where it regulates cell differentiation and quiescence. Here we show that miR-126 is expressed as well in neural progenitor cells where it regulates cell differentiation by targeting genes of the IGF1R signaling pathway including IRS1, PI3K and AKT. Moreover, Hoxa9 and IGF-1 expression by neural progenitor cells is upregulated when miR-126 expression levels are reduced. Our data, implicating a role for miR-126 in manipulating cell development, could open a window of opportunities for clinical purposes and therapeutic strategies to achieve controlling neural progenitor cell behavior.HighlightsKnockdown of miR-126 in neural progenitor cells increases cell proliferationmiR-126 modulates expression levels of HoxA9 and known target genes involved in the IGF1R signaling pathway in neural progenitor cellsOverexpression of miR-126 results in induced cell differentiation in neural progenitor cellsmiR-126 affects motor neuron development in the thoracic region of the spinal cordKnockdown of miR-126 expression results in increased IGF-1 expression
The association between routine immunisation and COVID-19 vaccination in small island developing states
Authors: Patel Cyra , Bilgin Gizem , Hayen Andrew , Kirk Martyn , Ali Akeem , Dey Aditi , Sargent Ginny , Sheel Meru 
Published: December 2024

AbstractObjectivesUnderstanding the link between routine immunisation (RI) performance and vaccination during an epidemic can provide insights on health systems resilience and investments to strengthen health systems. We examined the relationship between RI performance and COVID-19 vaccination coverage in small island developing states (SIDS).MethodsCOVID-19 vaccination coverage at four timepoints (June 2021, December 2021, June 2022 and December 2022) in 55 SIDS was our primary outcome. We examined associations with coverage of six childhood immunisations (5-year mean annual coverage for 2015–2019), pandemic-related disruptions to RI, new vaccine introductions, health system performance measures, and economic and demographic characteristics. We calculated Spearman correlations for continuous variables and mean COVID-19 vaccination coverage by categorical variables.FindingsWe found COVID-19 vaccination coverage was higher in countries that sustained RI coverage during the pandemic, and where HPV, influenza and measles-containing (second dose) vaccines had been introduced. There were weak correlations (|r|<0.4) between coverage of COVID-19 vaccination and RI, with a few exceptions of moderate correlations with the birth dose of hepatitis B vaccine (June 2022: r=0.421, p=0.007; December 2022: r=0.438, p=0.005) and first dose of measles vaccine (December 2021: r=0.420, p=0.002). COVID-19 vaccination coverage was strongly correlated with the density of physicians (June 2021: 0.897, p<0.001; December 2021: 0.785, p<0.001) and moderately correlated with that of nurses and midwives (June 2021: 0.630, p=0.001; December 2021: 0.605, p=0.002). COVID-19 vaccination coverage was lower in SIDS with lower country income and development status.ConclusionsCountries that achieved high COVID-19 vaccination coverage maintained RI coverage, demonstrating health system resilience. Our findings highlight the importance of having sufficient skilled health professionals and experience in introducing new vaccines targeting different age groups into national programs, particularly in small island settings.
Winter temperature effects in a cold-adapted northern population of a range-expanding spider: survival, energy stores, and differential gene expression
Authors: Ortiz-Movliav Carolina , Wolz Marina , Klockmann Michael , Kuß Andreas , Jensen Lars , Jensen Corinna , Wacker Alexander , Uhl Gabriele 
Published: December 2024

AbstractSpecies expand their spatial distribution when environmental conditions are favorable or when mutations arise that allow them to live in previously unfavorable conditions. The European wasp spider,Argiope bruennichi, is known to have expanded its range poleward faster than climate change would predict. Northern edge populations show higher cold tolerance and are genetically differentiated from core populations, suggesting local adaptation to colder winter conditions. To investigate the degree and limits of plasticity in a cold-adapted population, we exposed overwintering juveniles (spiderlings) from Estonia - the northern edge of the distribution - to three winter regimes: two with a strong difference in day/night temperatures and an overall 10 degrees’ difference (warm and cold treatment) and one with moderate temperatures and less difference between day and night (moderate). We investigated if survival, lipid content, metabolites, and gene expression patterns differ depending on these temperature regimes. The survival probability of the spiderlings and their overall lipid content decreased over winter, with no difference between treatments, suggesting high resilience of the spiderlings towards very different temperature regimes at the edge of the distribution. At the end of winter, the content of saturated and monounsaturated fatty acids per spiderling also did not differ between treatments. However, omega-3 polyunsaturated fatty acids (PUFAs) levels were significantly lower in spiders exposed to the warm winter suggesting increased metabolic activity. We identified 4096 significant differentially expressed genes (DEGs) across the treatments, of which 1389 were specific for the moderate treatment, and 832 specific for the warm treatment, while 69 were unique for the cold treatment, showing a stronger temperature stress response to the moderate and warmer than to the cold treatment. Taken together, our results show thatA. bruennichihas physiological plasticity and the ability to cope with very different winter temperature regimes despite being cold adapted. However, warmer winters might come with metabolic costs that could impact on the spiderlingś survival and foraging success when they emerge from the egg sac in spring.
Towards community-driven visual proteomics with large-scale cryo-electron tomography ofChlamydomonas reinhardtii
Authors: Kelley Ron , Khavnekar Sagar , Righetto Ricardo D. , Heebner Jessica , Obr Martin , Zhang Xianjun , Chakraborty Saikat , Tagiltsev Grigory , Michael Alicia K. , van Dorst Sofie , Waltz Florent , McCafferty Caitlyn L. , Lamm Lorenz , Zufferey Simon , Van der Stappen Philippe , van den Hoek Hugo , Wietrzynski Wojciech , Harar Pavol , Wan William , Briggs John A.G. , Plitzko Jürgen M. , Engel Benjamin D. , Kotecha Abhay 
Published: December 2024

AbstractIn situcryo-electron tomography (cryo-ET) has emerged as the method of choice to investigate structures of biomolecules in their native context. However, challenges remain in the efficient production of large-scale cryo-ET datasets, as well as the community sharing of this information-rich data. Here, we applied a cryogenic plasma-based focused ion beam (cryo-PFIB) instrument for high-throughput milling of the green algaChlamydomonas reinhardtii, a useful model organism forin situvisualization of numerous fundamental cellular processes. Combining cryo-PFIB sample preparation with recent advances in cryo-ET data acquisition and processing, we generated a dataset of 1829 reconstructed and annotated tomograms, which we provide as a community resource to drive method development and inspire biological discovery. To assay the quality of this dataset, we performed subtomogram averaging (STA) of both soluble and membrane-bound complexes ranging in size from >3 MDa to ∼200 kDa, including 80S ribosomes, Rubisco, nucleosomes, microtubules, clathrin, photosystem II, and mitochondrial ATP synthase. The majority of these density maps reached sub-nanometer resolution, demonstrating the potential of thisC. reinhardtiidataset, as well as the promise of modern cryo-ET workflows and open data sharing towards visual proteomics.
Decoding primitive endoderm - epiblast interactions using mouse ICM embryoids
Authors: Tan Beatrice F. , Schäffers Olivier J.M. , Merzouk Sarra , Bindels Eric M. , Huylebroeck Danny , Gribnau Joost , Dupont Cathérine 
Published: December 2024

AbstractStem cell-based embryo models are promising alternatives for investigating early embryogenesis. We introduce two distinct models to replicate the dynamics between extra-embryonic endoderm and epiblast during mouse embryonic development. InducibleGata6(iGata6) embryoid bodies (EBs), exclusively derived from iGata6embryonic stem (ES) cells, are valuable for modeling the position-dependent development of the primitive endoderm. Inner cell mass (ICM) embryoids, conversely, efficiently formed by aggregating ‘wild-type’ and iGata6ES cells, accurately and at a comparable pace simulatein vivodevelopment from E3.5 to E7.5. Notably, ICM embryoids model cell sorting and through a rosette-like stage, the transition of the epiblast from naïve to primed pluripotency. Furthermore, the absence of extra-embryonic ectoderm-like cells in this model, directs both the epiblast and visceral endoderm towards an anterior developmental fate. As such, iGata6EBs and ICM embryoids are powerful tools for advancing our understanding of cell fate decisions during early embryonic development in mice.
Oral delivery of semaglutide and tirzepatide using milk-derived small extracellular vesicles
Authors: Zhang Yuefei , Han Jianyi , Wu Wei , Dang Bobo 
Published: December 2024

AbstractTherapeutic proteins and peptides have revolutionized modern biomedicine. However, the large size and complex structure of these macromolecules preclude their oral administration, greatly limiting their applications in patient care. Biochemical degradation in the gastrointestinal tract, mucus, and cellular barrier are the major obstacles to oral development. Small extracellular vesicles (sEVs) are natural nano lipid vesicles serving as essential vehicles for intercellular communication. sEVs are resistant to biochemical degradation, permeable to mucus barriers, and can penetrate cellular barriers. sEVs are thus considered the next-generation vehicles with the potential for oral peptide/protein drug delivery. Herein, we report the use of milk-derived sEVs as delivery vehicles to achieve successful and highly efficient oral delivery of two therapeutic GLP-1 receptor agonists, semaglutide and tirzepatide. We showed that semaglutide and tirzepatide can be efficiently loaded onto sEVs in vitro, and oral gavage of semaglutide-loaded sEVs or tirzepatide-loaded sEVs can effectively lower blood glucose levels in db/db mouse models. This study demonstrates that sEVs is a platform technology for oral peptide drug delivery and opens a new avenue for oral peptide/protein therapeutics delivery.
Migrastatic Therapy as a Potential Game-Changer in Adaptive Cancer Treatment
Authors: Schneider Katharina , Spekking Louise , Azimi Sepinoud , Peltanová Barbora , Rösel Daniel , Brown Joel S. , Gatenby Robert A. , Brábek Jan , Staňková Kateřina 
Published: December 2024

AbstractAdaptive therapy, which anticipates and counters the evolution of resistance in cancer cells, has gained significant traction, especially following the success of the Zhang et al.’s protocol in treating metastatic castrate-resistant prostate cancer. While several adaptive therapies have now advanced to clinical trials, none currently incorporates migrastatics, i.e. treatments designed to inhibit cancer cell metastasis.In this study, we propose integrating migrastatics into adaptive therapy protocols and evaluate the potential benefits of using a game-theoretic spatial model. Our results demonstrate that combining adaptive therapy with migrastatics effectively delays the onset of metastasis and reduces both the number and size of metastases across most cancer scenarios analyzed. This approach not only extends the time to the first metastasis but also enhances the overall efficacy of adaptive therapies. Our findings suggest a promising new direction for cancer treatment, where adaptive therapy, in combination with migrastatic agents, can target both the evolution of resistance and the metastatic spread of cancer cells.
A Non-Pharmacological, Nociceutical Formulation Lessens Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients
Authors: Servitja Sonia , Castro-Henriques Maria , Álvarez-Busto Iñaki , Díez-Franco Carlota , Medina-Castillo Alba , Algarra-García Maria Asunción , López-Miranda Elena , Lario-Martínez Margaret , Luengo-Alcázar Maria Isabel , Borregón Miguel , Davó Ana , Gassull-Delgado Anna , Roque-García Sara , Gonzaga-López Ana , Poveda-Ferriols Jesus Manuel , Pascal Severine , Ferrándiz-Huertas Clotilde , Mitroi-Marinescu Ana María , García-Escolano Marta , Fernández-Carvajal Asia , Ferrer-Montiel Antonio 
Published: December 2024

AbstractPurposeUp to 80% of patients undergoing taxanes or platinum-based chemotherapy (CT) develop a disturbing peripheral polyneuropathy referred to as CIPN, that affects their treatment compliance to CT and long-term quality of life (QoL). Cumulative evidence shows that taxanes and platinum agents sensitize epidermal nociceptive terminals by potentiating the activity of nociceptor thermosensitive channels. Our aim was to evaluate the efficacy and safety of a non-pharmacological nociceutical formulation acting on epidermal nociceptive endings preventing, delaying and/or lessening CIPN sensory symptoms during CT.MethodsWe designed a proof-of-concept, double-blind, randomized, two-arms multicenter clinical study (NCT06733545). Participants started a daily topical application of the assigned formulation in hands (moisturizing or nociceutical). Upon appearance of neuropathic symptoms in hands and/or feet, they applied the creams twice daily in hands and feet. Diagnosis and follow up of CIPN grade and adverse effects were conducted by study investigators, as well as a QoL questionnaire.ResultsA cohort of 142 patients treated with taxanes and/or platinum agents were randomly assigned to the two groups. Withdrawals were similar in both arms (9 and 14), leading to a balanced number of patients per group (61 moisturizing vs 58 nociceutical). Overall, a similar number of participants developed a peripheral neuropathy in both arms (73% moisturizing vs 67% nociceutical, p=0.1). A lower CIPN incidence in hands was observed in the nociceutical arm (32% vs 13%, p=0.03). Furthermore, the nociceutical formulation delayed the appearance of neuropathic symptoms as compared to the moisturizing cream (6 vs 8 cycle, p=0.009). The Leonard scale questionnaire revealed that the nociceutical formulation attenuated the severity of patients’ neuropathic symptoms from extremely to hardly any (58% vs. 35%, p<0.0017), increasing patient QoL.ConclusionThis pilot study suggests that topical protection of nociceptive epidermal terminals with a topical nociceutical formulation reduced the incidence of CIPN in hands, delayed its onset and increased the QoL of patients. These findings provide solid evidence for a larger, confirmatory clinical study.
Influences on rural HPV vaccine hesitancy: A multi-level mixed methods study
Authors: Gorin Sherri Sheinfeld , Klugas Arturas , Stack Matthew , Chuisano Samantha , Knoll Hannah , Jamison Cornelius D. , McGrady Angela , Chen Dongru , Hyman Rebecca , DeJonckheere Melissa 
Published: December 2024

AbstractHuman Papillomavirus (HPV) is the most common sexually transmitted infection and the leading cause of cervical and oropharyngeal cancers. Vaccination can prevent over 90% of HPV- attributed cancers among those aged 9-26. Rural populations are less likely to receive the complete HPV protocol than urban. The purpose of this convergent mixed methods study was to explore in depth the perspectives that influence hesitancy for HPV vaccination among rural youth, caregivers, and primary care providers in rural Michigan. A mixed methods analysis was conducted to integrate quantitative (cross-sectional PCP survey) and qualitative data (youth, parent focus groups) in a joint display table. Youths and parents reported limited unbiased HPV vaccine information; yet, all responding physicians reported educating their patients about the HPV vaccine. Inductive descriptive analyses revealed that youth wanted a greater role in decision-making about the HPV vaccine, while parents were the PCPs primary focus.Integrative analyses of both qualitative and quantitative data identified parental out-of-pocket costs as significant predictors of lower HPV vaccine uptake. Clinic structural supports were significantly associated with higher HPV vaccine uptake. Adapting evidence-based dissemination approaches to rural primary care physicians could decrease HPV vaccine hesitancy. Youths could be engaged as HPV vaccine champions. Accessing community resources could increase access.
Exploring Digital Health Solutions: Personalised Medicine and N-of-1 Trials in Ghana: A Scoping Review
Authors: Sackey Godsway , Owoyele Babajide , Baiden Frank , Konigorski Stefan 
Published: December 2024

AbstractBackgroundDigital health solutions and personalised medicine are rapidly evolving fields that offer significant potential for enhancing healthcare delivery, particularly in low-resource settings. N-of-1 trials, a personalised experimental approach, hold particular promise for individualised patient care and empowerment. This scoping review aims to explore the current landscape of these innovations in the context of Ghana.ObjectivesThis review seeks to map existing literature on digital health solutions, personalised medicine, and N-of-1 trials in Ghana. It also aims to identify key themes, trends, and gaps in the literature while discussing the current role and potential of N-of-1 trials in this context as an important knowledge base for future exploration of personalised medicine and digital N-of-1 trials in low resource settings like Ghana.MethodsA comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Google Scholar; from year 2000 to April 2024, to identify relevant studies. Inclusion criteria were studies focusing on digital health, personalised medicine, and N-of-1 trials within Ghana or similar low-resource settings. Data were extracted and analysed to identify common themes, trends, and gaps in the existing literature.ResultsThe scoping review included 40 publications, that is, only very few studies have been published in this field that fit our objectives. The studies revealed a predominant focus on digital health solutions in Ghana, particularly mobile health (mHealth) interventions, which account for 60% of the interventions reviewed. These solutions include mobile applications for clinical decision support, patient monitoring, and health education, and have been effective in enhancing healthcare delivery, especially in remote and underserved areas. Introducing electronic health records (EHRs) represent 24% of the interventions and have shown promise in improving data management and patient care coordination. However, challenges such as poor network infrastructure and resistance to change need to be addressed. Personalised medicine, though less represented in the reviewed literature (7.5%), shows promise in providing tailored treatments based on individual genetic profiles. The review did not identify any studies specifically focused on N-of-1 trials, highlighting the innovative potential for future research in this area.ConclusionThe findings underscore the need for robust digital infrastructure, training for healthcare providers, and policy frameworks to support the adoption of digital health solutions, personalised medicine, and N-of-1 trials in Ghana. Addressing these gaps requires concerted efforts to enhance digital infrastructure, provider education, and supportive policies. N-of-1 trials offer substantial potential for personalised care but necessitate further exploration and integration into the healthcare system.