bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical hyoid bone repositioning effects on mandibular advancement and upper airway collapsibility
Authors: Tannous Hiba J , Samaha Corine J , Chami Hassan A , Ghafari Joseph G , Amatoury Jason 
Published: September 2024

AbstractMandibular advancement serves as a treatment option for obstructive sleep apnea (OSA), but its effectiveness differs among patients. The position of the hyoid bone is crucial for maintaining upper airway patency and may influence mandibular advancement outcomes. This study aimed to assess the impact of surgical hyoid re-positioning on mandibular advancement-induced changes in upper airway collapsibility in an animal model.MethodsTwelve anesthetized male New Zealand White rabbits underwent mandibular advancement (0-4mm), combined with hyoid repositioning in various directions (anterior, cranial, caudal, anterior-cranial, anterior-caudal) and increments (0- 4mm). Upper airway collapsibility was quantified as the negative pressure required to close the airway (Pclose) at various mandibular and hyoid positions.ResultsIncreasing mandibular advancement alone led to a progressive reduction in Pclose, indicating a decrease in upper airway collapsibility. Similarly, anterior hyoid repositioning alone resulted in incremental reductions in Pclose, with similar outcomes observed for anterior-cranial and anterior-caudal directions. When mandibular advancement was combined with anterior-based hyoid repositioning directions, a further decrease in Pclose was observed compared to when either intervention was applied alone. Cranial and caudal hyoid repositioning had no direct effect on Pclose or on mandibular advancement outcomes.ConclusionsIn summary, decreases in upper airway collapsibility induced by mandibular advancement are dependent on both hyoid repositioning direction and increment. The findings suggest that combining mandibular advancement with anterior-based hyoid repositioning may enhance the effectiveness of mandibular advancement in treating OSA.
MHC class I / II restricted T cell epitopes from clinical isolate ofMycobacterium tuberculosis: A potential candidate for vaccine development for Tuberculosis
Authors: Sharma Niharika , Sharma Bhawna , Joshi Beenu , Kumar Santosh , Mohanty Keshar Kunja , Prakash Hridayesh 
Published: September 2024

AbstractTuberculosis is major challenge to the health care system with TB associated death rates increasing annually. Optimum management of TB (particularly latent or MDR cases) warrants use of immunological approaches like subunit or peptide-based vaccination for tailoring effector immunity in patients. Since MHC class I is a potent enhancer element of host immunity and effective in clearing large variety of intracellular pathogens or tumors. In this context, we explore whether MHC-I restricted peptides from clinical isolates ofM. tuberculosiscan be used as an adjuvant for augmenting host immune responses. In the present study, we have synthesized various peptides from clinical isolates ofM. tuberculosiswhich were having high affinity for Class I MHC molecules as potential immune enhancer for T cell or iNKT cell populations. We have evaluated the immunogenic potential of various MHC class I restricted epitopes (Rv2588c, Rv1357, Rv0148, Rv2973, Rv2557 and Rv2445) which were derived from clinical isolates ofM. tuberculosison increased proliferation of T or iNKT cells, release of IFN gamma secreted by T cells as well as NO as indicative parameters of immuno-stimulation. As expected, FACS and ELISA data clearly revealed that these peptides were potentially immunogenic for PBMCs from both healthy as well as 10 HC PTB patients. Our data clearly demonstrated a significant immune response in the PBMC from w PTB patients over healthy individuals which mimicked booster response. Our cytokine and nitric oxide data further revealed the influence of these peptides on sensitizing innate immune response as well.SignificanceOur study demonstrates the significance of MHC class I restricted peptides fromM. tuberculosisfor inducing potential immunogenic responses in host that may qualify them as potent vaccine candidate. To the best of our knowledge this is the first immune monitoring protocol describing the impact of synthetic novel MHC class I restricted T-cell epitope (Rv2588c, Rv0148) on cell mediated and innate immune response in PBMC populations and suggests their potential as vaccine candidate
The late onset Alzheimer’s disease risk factor iRhom2/RHBDF2 is a modifier of microglial TREM2 proteolysis
Authors: Jocher Georg , Müller Stephan A. , Hsia Hung-En , Lastra Osua Miranda , Özcelik Gözde , Hofmann Laura I. , Aßfalg Marlene , Dinkel Lina , Feng Xiao , Schlepckow Kai , Willem Michael , Haass Christian , Tahirovic Sabina , Blobel Carl P. , Lichtenthaler Stefan F. 
Published: September 2024

AbstractThe cell surface receptor TREM2 is a key genetic risk factor and drug target in Alzheimer’s disease (AD). In the brain, TREM2 is expressed in microglia, where it undergoes proteolytic cleavage, linked to AD risk, but the responsible protease in microglia is still unknown. Another microglia-expressed AD risk factor is catalytically inactive rhomboid 2 (iRhom2, RHBDF2), which binds to and acts as a non-catalytic subunit of the metalloprotease ADAM17. A potential role in TREM2 proteolysis is not yet known. Using microglial-like BV2 cells, bone marrow-derived macrophages and primary murine microglia, we identify iRhom2 as a modifier of ADAM17-mediated TREM2 shedding. Loss of iRhom2 increased TREM2 in cell lysates and at the cell surface and enhanced TREM2 signaling and microglial phagocytosis of the amyloid β-peptide (Aβ). This study establishes ADAM17 as a physiological TREM2 protease in microglia, and suggests iRhom2 as a potential drug target for modulating TREM2 proteolysis in AD.
Mitochondrial superoxide acts in the intestine to extend longevity
Authors: Liontis Thomas , Senchuk Megan M. , Zhu Shusen , Jacob-Tomas Suleima , Anglas Ulrich , Traa Annika , Soo Sonja K. , Van Raamsdonk Jeremy M. 
Published: September 2024

AbstractReactive oxygen species (ROS) are highly reactive oxygen containing molecules that are generated by normal metabolism. While ROS can cause damage to the building blocks that make up cells, these molecules can also act as intracellular signals that promote longevity. The levels of ROS within the cell can be regulated by antioxidant enzymes, such as superoxide dismutase (SOD), which converts superoxide to hydrogen peroxide. Interestingly, our previous work has shown that disruption of the mitochondrial SOD genesod-2results in increased lifespan, indicating that elevating levels of mitochondrial superoxide can promote longevity. To explore the molecular mechanisms involved, we determined the tissues in which disruption ofsod-2is necessary for lifespan extension and the tissues in which disruption ofsod-2is sufficient to extend lifespan. We found that tissue-specific restoration of SOD-2 expression in worms lacking SOD-2 could partially revert changes in fertility, embryonic lethality and resistance to stress, but did not inhibit the effects ofsod-2deletion on lifespan. Knocking downsod-2expression using RNA interference specifically in the intestine, but not other tissues, was sufficient to extend longevity. Intestine-specific knockdown ofsod-2also increased resistance to heat stress and while decreasing resistance to oxidative stress. Combined, these results indicate that disruption ofsod-2in neurons, intestine, germline, or muscle is not required for lifespan extension, but that decreasingsod-2expression in just the intestine extends lifespan. This work defines the conditions required for elevated mitochondrial superoxide to increase longevity.
Comprehensive mapping of the Interaction of levodopa and iron metabolism in Parkinson’s disease
Authors: Wang Jian , Ekambaram Srinivasan , Huang Xuemei , Mailman Richard B. , Proctor Elizabeth A. , Dokholyan Nikolay V. 
Published: September 2024

AbstractLevodopa remains the primary treatment for Parkinson’s disease (PD), yet its long-term use has been associated with iron accumulation in the brain, a phenomenon linked to neurodegeneration. We utilize deep machine learning to determine plausible molecular mechanisms that may underlie the effects of levodopa on iron metabolism. Using the DRIFT platform, we performed a proteome-wide target identification of levodopa and uncovered significant interactions potentially involved in cellular iron transport. Pathway analysis revealed that levodopa may influence critical iron-related pathways, including the response of EIF2AK1 to heme deficiency, heme signaling, and ABC-family protein-mediated transport. These findings suggest that levodopa may contribute to iron dysregulation in PD by interacting with iron transporters and modulating iron-related pathways. Because levodopa is used at relatively high doses in PD, our findings provide new insight into secondary effects unrelated to being a precursor of dopamine. This highlights the need for careful consideration of its effects on iron metabolism as a consequence of use in the long-term management of PD. Further experimental validation is required to confirm these interactions, and also to explore potential strategies to mitigate iron-related side effects while preserving therapeutic efficacy.
A workflow for microclimate sensor networks: integrating geographic tools, statistics, and local knowledge
Authors: Klinges David H. , Lembrechts Jonas J. , Van de Vondel Stijn , Greenlee Eric , Hayles-Cotton Kian , Senior Rebecca A. 
Published: September 2024

AbstractWireless environmental sensors have become integral tools in environmental and conservation research, offering diverse data streams that complement traditional inventory-based surveys. Despite advancements in sensor technology, the ad-hoc nature of site selection for sensor deployment often limits the potential of collected data. In this paper, we argue for the importance of informed site selection to capture environmental variation effectively. We introduce a comprehensive step-by-step practical guide for environmental sensor site selection and network deployment, drawing on experiences from diverse geographic locations and focusing on microclimate monitoring as a representative environmental variable. The workflow integrates Geographic Information Systems (GIS) tools, local community-based knowledge, and statistical methods to provide adaptive and iterative guidelines for both new and expanded sensor deployments. We demonstrate the workflow’s applicability across three distinct settings: arid montane deserts in Oman, urban and rural gardens in Belgium, and humid forested landscapes in Madagascar. To facilitate the workflow’s implementation and reproducibility worldwide, we provide a modular software supplement with flexible user input for robust, data-driven and interactive site selection. Critically, our workflow underscores the importance of equitable collaboration with local stakeholders, addresses challenges in sensor deployment, and offers a practical tool to enhance the effectiveness and efficiency of environmental sensing across disciplines including ecology, meteorology, agriculture, and landscape design.
Plasma exosomes from individuals with type 2 diabetes drive breast cancer aggression in patient-derived organoids
Authors: Ennis Christina S. , Seen Michael , Chen Andrew , Kang Heejoo , Ilinski Adrian , Mahdaviani Kiana , Ko Naomi , Monti Stefano , Denis Gerald V. 
Published: September 2024

AbstractWomen with obesity-driven diabetes are predisposed to more aggressive breast cancers. However, patient metabolic status does not fully inform the current standard of care. We previously identified plasma exosomes as functionally critical actors in intercellular communication and drivers of tumor progression. Here, we generated patient-derived organoids (PDOs) from breast tumor resections to model signaling within the tumor microenvironment (TME). Novel techniques and a short (1-week) culture preserved native tumor-infiltrating lymphocytes for the first time in breast tumor PDOs. After 3-day exosome treatment, we measured the impact of exosomal signaling on PDOs via single-cell RNA sequencing. Exosomes derived from Type 2 diabetic patient plasma significantly upregulated pathways associated with epithelial-to-mesenchymal transition, invasiveness, and cancer stemness, compared to non-diabetic exosome controls. Intratumoral heterogeneity and immune evasion increased in the diabetic context, consistent with enhanced tumor aggressiveness and metastatic potential of these PDOs. Our model of systemic metabolic dysregulation and perturbed transcriptional networks enhances understanding of dynamic interactions within the TME in obesity-driven diabetes and offers new insights into novel exosomal communication.
Ancient DNA reveals historical demographic decline and genetic erosion in the Atlantic bluefin tuna
Authors: Andrews Adam Jon , Eriksen Emma Falkeid , Star Bastiaan , Præbel Kim , Natale Antonio Di , Malca Estrella , Zapfe Glenn , Onar Vedat , Aniceti Veronica , Carenti Gabriele , Piquès Gäel , Nielsen Svein Vatsvåg , Persson Per , Piattoni Federica , Fontani Francesco , Atmore Lane M. , Kersten Oliver , Tinti Fausto , Cilli Elisabetta , Cariani Alessia 
Published: September 2024

AbstractOverexploitation has depleted fish stocks during the past century, nonetheless its genomic consequences remain poorly understood. Characterising the spatiotemporal patterns of these consequences may provide baseline estimates of past diversity and productivity to aid management targets, help predict future dynamics, and facilitate the identification of evolutionary factors limiting fish population recovery. Here, we evaluate human impacts on the evolution of the iconic Atlantic bluefin tuna (Thunnus thynnus), one of the longest and most intensely exploited marine fishes, with a tremendous cultural and economic importance. We sequenced whole genomes from modern (n=49) and ancient (n=41) specimens dating up to 5000 years ago, uncovering several novel findings. First, we identify temporally stable patterns of population admixture, as bluefin tuna caught off Norway and in the eastern Mediterranean share a greater degree of ancestry with Gulf of Mexico bluefin tuna than western and central Mediterranean bluefin tuna. This suggests that Atlantic spawning areas are important mixing grounds for the genetic diversity of Mediterranean bluefin tuna. We model effective population size to show that Mediterranean bluefin tuna began to undergo a demographic decline by the year 1900 to an extent not observed across the previous millennia. Coinciding with this, we found that heterozygosity and nucleotide diversity was significantly lower in modern (2013-2020), than ancient (pre-1941) Mediterranean bluefin tuna, suggesting bluefin tuna underwent a genetic bottleneck. With this work we show how ancient DNA provides novel perspectives on ecological complexity with the potential to inform the management and conservation of fishes.SignificanceAchieving the aim of the current UN Ocean Decade to “protect and restore ecosystems and biodiversity” is stymied by a lack of historical knowledge on how human exploitation has impacted and therefore what should be restored. Here, we sequence DNA in ancient fish bones to evaluate the historical diversity of the Atlantic bluefin tuna; which has been of great commercial importance for centuries. We find that bluefin tuna began to undergo demographic decline by 1900, 70 years earlier than currently recognised. Correspondingly, we find modern bluefin tuna had lower levels of genetic diversity than historical ones. This suggests that human impacts on the diversity of marine fishes are likely to have begun earlier and be more complex than previously thought.
Cnes2bRegulates Host Resistance, Inflammatory Responses and Tissue Damage FollowingCryptococcus deneoformansInfection
Authors: Angers Isabelle , Beauchamp Annie , El Sheikh Marwa , Kaufmann Eva , Vinh Donald C. , Qureshi Salman T. 
Published: September 2024

AbstractThe 32.1 MbCnes2chromosome 17 interval was shown to confer resistance to progressiveCryptococcus deneoformans52D infection. To refine the location ofCnes2host resistance genes, a subcongenic mouse strain (B6.CBA-Cnes2b) that contains 8.7 Mb from the telomeric region ofCnes2was created. At 28 days postinfection B6.CBA-Cnes2bmice had a lower lung fungal burden, increased lung injury, as well as mortality compared to C57BL/6N. B6.CBA-Cnes2bmice had increased pulmonary production of pro-inflammatory mediators, chemokines and Th1-type cytokines as well as increased recruitment of monocytes and neutrophils to the lungs.Cnes2balso regulated several elements of the host response toC. deneoformans52D infection in a sex-dependent manner. Specifically, male B6.CBA-Cnes2bmice had a lower lung fungal burden, increased brain injury and mortality relative to females. Taken together these findings demonstrate thatCnes2bregulates host inflammation in a manner that controls fungal burden and increases tissue damage. Precise identification of the genes encoded byCnes2bcould reveal key mechanisms of cryptococcal host resistance and immune reconstitution or postinfectious inflammatory syndromes.ImportanceThe 32.1 MbCnes2congenic interval from chromosome 17 of resistant CBA/J mice regulates host resistance toC. deneoformans52D infection. This study characterizes the host response of B6.CBA-Cnes2bmice that carry an 8.7 Mb sub-congenic interval derived fromCnes2followingC. deneoformans52D infection. B6.CBA-Cnes2bmice had reduced lung fungal burden, increased lung and brain injury, and mortality. The effects ofCnes2bdiffered between male and female subcongenic mice and are consistent with known sex differences in human cryptococcal disease. The host response of B6.CBA-Cnes2bmice reflects a crucial balance between effective control of fungal burden and potentially deleterious consequences of enhanced inflammation during cryptococcal infection as predicted by the damage response framework. Further analysis of theCnes2bsub-congenic interval will lead to definitive identification of genes that confer resistance to progressive cryptococcal infection and/or contribute to deleterious inflammatory responses. Defining key mechanisms that regulate the immune response toCryptococcus sp.is an important step towards the development of host-directed therapeutics that could improve disease outcomes.
Variation in Biosynthetic Gene Clusters Among Lifestyles Across Kingdom Fungi
Authors: Allen Brooke M. , Drott Milton , Nickles Grant R , Hoeksema Jason D. 
Published: September 2024

AbstractBiosynthetic gene clusters (BGCs) produce secondary metabolites, many of which are involved in trophic interactions and carbon acquisition lifestyles of fungi. As such, BGCs are hypothesized to exhibit evolutionary diversification across those lifestyles. We tested this hypothesis by analyzing predicted BGCs in more than 1000 fungal genomes, and their variation among fungal lineages and across putative fungal lifestyles (trophic modes). Analyses revealed that specific BGC classes, such as PKSI, RiPPs, and terpenes, exhibit significant phylogenetic signals, whereas others, like NRPS and PKS-NRPS Hybrids, do not. BGC abundance was associated with fungal lifestyles: pathotrophs generally had lower BGC abundance, while combined lifestyles such as saprotroph-symbiotrophs had higher BGC abundances. These findings suggest that both phylogenetic history and ecological strategies drive BGC distribution, highlighting their roles in fungal biochemical diversification. Understanding these patterns provides insights into fungal community ecology and the evolutionary processes shaping their biosynthetic potential.
Federated Multiple Imputation for Variables that Are Missing Not At Random in Distributed Electronic Health Records
Authors: Lian Yi , Jiang Xiaoqian , Long Qi 
Published: September 2024

AbstractLarge electronic health records (EHR) have been widely implemented and are available for research activities. The magnitude of such databases often requires storage and computing infrastructure that are distributed at different sites. Restrictions on data-sharing due to privacy concerns have been another driving force behind the development of a large class of distributed and/or federated machine learning methods. While missing data problem is also present in distributed EHRs, albeit potentially more complex, distributed multiple imputation (MI) methods have not received as much attention. An important advantage of distributed MI, as well as distributed analysis, is that it allows researchers to borrow information across data sites, mitigating potential fairness issues for minority groups that do not have enough volume at certain sites. In this paper, we propose a communication-efficient and privacy-preserving distributed MI algorithms for variables that are missing not at random.
Antibodies against the capsid induced after intracranial AAV administration limits second administration in a dose dependent manner
Authors: Xu Yuge , Bai Xiaoni , Lin Jianhua , Lu Kang , Weng Shihan , Wu Yiying , Liu Shanggong , Li Houlin , Chen Gong , Li Wen 
Published: September 2024

AbstractRecombinant adeno-associated virus (rAAV) is a widely used viral vector for gene therapy. However, a limitation of AAV-mediated gene therapy is that patients are typically dosed only once. In this study, we investigated the possiblility to deliver multiple rounds of AAV through intracerebral injections in the mouse brain. We discovered a dose-dependent modulation of the second round AAV infection by the first round AAV injection in the brain-wide scales besides the injection region. High-dose AAV infection increases chemokines CXCL9 and CXCL10 to recruit the parenchymal infiltration of lymphocytes. Surprisingly, the blood-brain-barrier was relatively intact. Brain-wide dissection discovered the likely rountes of the infiltrated lymphocytes through perivascular space and ventricles. Further analysis using B-cell depleted mice revealed that B lymphocytes, but not T lymphocytes, played a critical role in inhibiting the second round AAV infection. Strategies against neutralizing antibodies had limited effects, while reducing the dosage for the first injection or switching the second AAV to a different serotype appeared to be more effective in antagonizing the first round AAV inhibition. Together, these results suggest that mammalian brains are not immunoprivileged for AAV infection, but multiple rounds of AAV gene therapy are still possible if designed carefully with proper doses and serotypes.