bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss ofTbx4Affects Postnatal Lung Development and Predisposes to Pulmonary Hypertension
Authors: Maldonado-Velez Gabriel , Mickler Elizabeth A. , Cook Todd G. , Aldred Micheala A. 
Published: September 2024

AbstractPulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by remodeling of the precapillary pulmonary arteries. Genomic variation within the T-box 4 (TBX4) transcription factor is the second most common genetic cause of PAH, and can also cause severe lung developmental disorders with neonatal PH. Currently, the effect of TBX4 loss-of-function on later stages of lung development and predisposition to lung disease, including PH, is not well understood. Therefore, we have generatedTbx4conditional knockout (Tbx4-CKO) mice in whichCre recombinasedeletes exon 5 ofTbx4within the embryonic lung mesenchyme to create a null allele. We harvested lungs from these mice at various timepoints to examine alveologenesis, vascularization, vascular remodeling, lung cellular composition, and disruption of transcriptional activity compared with control lungs. Right ventricular systolic pressure (RVSP) was measured in six-month-old mice to evaluate for PH.Tbx4-CKOlungs show enlargement of airspaces, as confirmed by an increase in mean linear intercept at P14 (24.9%), P36 (31.5%), and P180 (49.6%). These lungs also show a 39.3% decrease in von Willebrand Factor-positive vessels and a 14.2% increase in vessel wall thickness. Consistent with these results,Tbx4-CKOmice show a statistically significant increase of 15.7% in RVSP and 16.3% in the Fulton index. Bulk-RNA sequencing analysis revealed enrichment of pathways and genes relevant to lung alveologenesis, angiogenesis, and PH. Our results show that disruption ofTbx4expression during early lung development is sufficient to disrupt postnatal lung development and circulation.
Gli2 Overexpression Alters the Differentiation Status of Dedifferentiated Liposarcoma Cells and Results in an Immunosuppressive Myeloid Phenotype in Orthotopic Tumors
Authors: Bennett Natalie E. , Beadle Erik P. , Parker Dominique V. , Coe Erykah J. , Cottam Matthew A. , Baum Jennifer E. , Miller Jade S. , Serrenho Joseph A. , Rhoades Julie A. 
Published: September 2024

AbstractSarcomas are a rare classification of tumor derived from tissues of mesenchymal origin including bone, fat, muscle, cartilage, and blood vessels. These tumors often grow rapidly and have limited treatment options with few significant therapeutic advances in recent years. Liposarcomas (LPSs), the most common type of malignant soft tissue sarcoma, are derived from mesenchymal progenitors that have undergone an adipogenic lineage commitment compared to their multipotent counterparts. Interestingly, the grade of differentiation within LPS can vary highly, and the differentiation status of these tumors can drastically affect prognosis and likelihood of metastasis, making tumor differentiation a potential mechanism to target in liposarcoma development. Here, we show that overexpression of the Hedgehog transcription factor Gli2 in dedifferentiated liposarcoma (DDLPS) cells represses adipogenic differentiation while simultaneously activating markers of osteoblast differentiationin vitro. In addition, we observed marked differences in cytokine expression and secretion, prompting us to perform orthotopic fat pad injections of control and Gli2 overexpressing DDLPS cells. Using flow cytometry, we observed distinct changes in fat pad macrophage populations, with a particular increase in M2-like macrophages. Taken together, we find that overexpression of Gli2 in DDLPS cells alters their differentiation capacity and interactions between tumor cells and macrophages, highlighting a novel role for this developmental transcription factor in liposarcoma pathogenesis.
Complex genomic ancestry in southern regions and drivers of continental-level genetic diversity in the wolves of Asia
Authors: Hennelly Lauren M. , Parreira Barbara R , Noble Ash , Scharff-Olsen Camilla , Kemahlı Aytekin M. Çisel , Şekercioğlu Çağan H. , Kosintsev Pavel , Paule Ladislav , Hulva Pavel , Stenøien Hans K. , Habib Bilal , Fatima Hira , Sarwar Ghulam , El-Haddad Samara P. , Hailer Frank , Sun Xin , Gomes Martins Nuno Filipes , Gilbert M Thomas P , Sinding Mikkel-Holger S. , Sacks Benjamin N , Gopalakrishnan Shyam 
Published: September 2024

AbstractGray wolves (Canis lupus) in Asia encompass most of the species’ global genetic diversity and many endangered populations. However, a clear understanding of the evolutionary history of wolves from many parts of Asia, especially southern regions, is lacking. We used 98 whole genomes of wolves sampled across Eurasia to better resolve their evolutionary history by investigating phylogenetic and gene flow histories across the genome, and to characterize their demographic history and genetic diversity. The strongest barriers to gene flow coincided with boundaries separating the three major extant wolf lineages - Indian, Tibetan, and Holarctic. Wolves in the central Asian mountain ranges belonged to the Holarctic lineage, and despite their geographic adjacency only share minimal ancestry with the Tibetan lineage. In contrast, wolves from eastern Asia share population-wide ancestry with the Tibetan lineage, which may reflect an unsampled lineage similar, but not exactly to, the modern-day Tibetan lineage. Wolves from southwestern Asia also share population-wide ancestry with the Indian lineage, likely due to old (>6kya) admixture events. Long-term historical declines over the last 100,000 years, geographic isolation, and recent inbreeding have resulted in the Indian and Tibetan wolves having some of the lowest levels of genetic diversity and highest realized genetic loads. In contrast, adjacent populations exhibit some of the highest genetic diversity, due in part to admixture along contact zones. Our study illustrates how using multiple approaches that consider heterogenous signals across the genome can more fully resolve the historical and contemporary processes that have led to present-day species’ diversity.
Assessing Aquatic Avian Biodiversity along Hydropower Dam Gradient: Understanding Impacts of Kurichhu Dam-Induced River Fragmentation in Kurrichu River Basin
Authors: Nidup Tshering , Dorji Yonten 
Published: September 2024

AbstractHumans are the dominant ecological and evolutionary force on the planet today, transforming habitats, polluting environments, and changing climates. Obstruction to the passage of flowing rivers has a significant environmental impact on fish. It causes rippling effects on wildlife, food web, and habitat throughout the river ecosystem. However, little is known about how these fragmented habitats impact aquatic avifaunal diversity and composition along the stretch of the river. The Kurichhu hydropower dam has disconnected the continuity of upper and lower portions of the Kurichhu River for over 14 years. To investigate this, avian community data were collected at 51 point-count stations, with 17 plots each: in R (Reservoir), AR (Above Reservoir), and BD (Below Dam) along the Kurichhu hydropower dam gradient. In total, 587 individual birds of 33 species distributed under 14 families were encountered. Shannon-wiener diversity among these three sites was higher for the R pool (H′= 3.04) than AR (H′= 2.74), and the lowest was in BD (H′= 2.44). Menhinicks richness index was higher for AR (D= 2.40) than the R pool (D =1.95) and lowest found in BD (D =1.73). This study recorded two species of birds in vulnerable and another two species of the ordercharadriformesin the near-threatened category. Our findings found that habitats along Kurichhu, around Gyelposhing area, are an important stopover and staging area for migratory waterbird species. In light of these findings, addressing the ecological ramifications of river fragmentation on avian diversity is crucial. The marked variation in species richness and diversity across the river segments highlights the pressing need for targeted conservation strategies. To mitigate adverse impacts, we recommend implementing ecological flow regimes and creating wildlife corridors to reconnect fragmented habitats, enhancing habitat quality and supporting avian biodiversity.
First report ofHexamita nelsoniin blue mussel (Mytilus edulis): morphology, phylogeny, and host-parasite interaction
Authors: Alfjorden Anders , Jerlström Hultqvist Jon , Svärd Staffan , Burki Fabien 
Published: September 2024

ABSTRACTBivalve diseases caused by protozoan parasitic infection are monitored by coordinated surveillance programs across European member countries. These routine monitorings of bivalve health, however, only survey a few relatively well known parasites, which may leave undetected a range of lesser known opportunistic protozoan agents. Under increased stress, for example due to shifting environmental conditions affecting water quality and nutrient access, these opportunistic parasites may develop pathogenicity impacting reproduction or growth and therefore decreasing the success and future development of aquaculture or wild population sustainability. During routine histopathological surveillance of blue mussels in Sweden, we noticed cryptic lesions in the adductor muscle in high prevalence over a period ranging from 2017 to 2022. These lesions suggested cell infiltration and degenerative changes in the muscle tissues. In this study, we report on the isolation, identification, and culture of the protistan cells likely responsible for at least some of these lesions. Using histology and cytology, molecular phylogeny, and catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH), we show that the cells correspond to theH. nelsonisequence initially isolated from oysters. We also reveal the presence ofH. nelsoniin the digestive glands and mantel, and that this parasite might be horizontally transmitted from adult to larvae via infections within gonads, ovaries. This study represents the first report ofH. nelsoniin blue mussel.
Adaptive Nesting Strategies of Dusky Crag Martins in desert ecoregions: Implications for Conservation and Bioinspired Innovations
Authors: Mukherjee Manasi , Pant Aali , Sankhala Kirti , Sandeep Devavrath , Mukerji Mitali 
Published: September 2024

AbstractUnderstanding the adaptive strategies of species in extreme environments is crucial for biodiversity conservation. This study is the first to explore the nesting behavior of the Dusky Crag MartinPtyonoprogne concolorin the Thar Desert, Rajasthan. It examined the bird’s site selection, nesting frequency, and construction methods. Soil samples from nest sites and source locations were analyzed to identify structural and elemental properties.The bird adopts several strategies, such as aligning its nesting period with the monsoon, reusing nests, and utilizing both macro and micro-level additive construction techniques. Detailed analysis revealed a preference for cohesionless sand with low moisture and higher Soil Organic Carbon (SOC) content. The bird strategically alternates light and dark soil layers in its nest. Structural and elemental analyses using optical microscopy and Scanning Electron Microscopy (SEM), and X-ray Fluorescence (XRF), shows the light layers is rich in calcium oxide and fibrous material, and dark layers containing higher iron oxide and partially decomposed litter fromProsopis cineraria.The study concludes that alternating calcium-rich and iron-rich layers enhances energy efficiency, structural integrity, and pathogen resistance in nest construction. his behavior underscores the evolutionary adaptations ofP. concolorto the extreme desert environment. These findings highlight the importance of conserving desert habitats and provide bio-inspired insights for sustainable building and agricultural practices in arid regions.
Investigating the use of novel blood processing methods to boost the identification of biomarkers of non-small cell lung cancer
Authors: McMahon Rosalee , Lucas Natasha , Hill Cameron , Pascovici Dana , Herbert Ben , Karsten Elisabeth 
Published: September 2024

1.AbstractBackground and objectivesDiagnosis of non-small cell lung cancer (NSCLC) currently relies on imaging and in-clinic visits, however these methods are not effective at detecting early-stage disease. The investigation into blood-based biomarkers aims to simplify the diagnostic process and has the potential for identifying disease-associated changes before they can be seen using imaging techniques.Methods and designIn this study, plasma and frozen whole blood cell pellets from patients with NSCLC and healthy controls were processed using both classical as well as novel techniques to produce a unique set of 4 sample types from a single blood draw. Samples were analysed using 12 commercially available immunoassay kits in addition to liquid chromatography mass spectrometry using a Q Exactive HF-X Orbitrap to collectively screen 3974 proteins as potential biomarkers.Results and conclusionsAnalysis of all sample types produced a set of 522 differentially expressed proteins, with conventional blood analysis (proteomic analysis of plasma) accounting for only 7 of that total. Boosted regression tree analysis of the differentially expressed proteins produced a panel of 13 proteins that were able to discriminate between controls and NSCLC patients with an area under the ROC curve (AUC) of 0.864 for the set. Our rapid and reproducible blood preparation and analysis methods enable the production of high-quality data from small aliquots of complex samples that are typically seen as requiring significant fractionation prior to proteomic analysis.
Secondary brain injury after parenchymal cerebral hemorrhage in humans: the role of oxidative stress and Endothelin-1
Authors: De Michele M. , Amisano P. , Schiavo O.G. , Carnevale R. , Cammisotto V. , Ciacciarelli A. , Berto I. , Angeloni U. , Pugliese S. , Toni D. , Lorenzano S. 
Published: September 2024

AbstractBackground and aimsPerihematomal hypoperfusion may lead to ischemic damage during intraparenchymal cerebral hemorrhage (ICH), resulting in worse prognosis. We aimed to (1) investigate the relationship between serum biomarkers related to oxidative stress and vasoactive substances and the occurrence of hypoperfusion and ischemic perihematomal lesions in ICH, (2) to evaluate their correlation with the volumetric evolution of the hematoma and perihematomal edema.MethodsWe enrolled 28 patients affected by ICH. Blood samples were collected at timepoint T0 (admission to Emergency-Room), T1 (12-24hs from symptoms onset), T2 (48- 72hs from onset), to measure Endothelin-1 (ET-1), nitrites/nitrates (NO), NADPH oxidase-2 (NOX-2), metalloproteinase-12 (MMP12) and asymmetric dimethylarginine (ADMA). Patients underwent brain MRI with perfusion study at T1 and MRI without perfusion at T2.Results12 patients had ischemic perihematomal lesions at T1. A higher NOX-2 concentration at T0 was observed in patients with ischemic perihematomal lesions compared to those without, (34.9 pg/ml vs 22.4 pg/ml, p=0.051) and with a more severe perihematomal edema at T2 (37.99 pg/ml vs. 19.17 pg/ml, p=0.011). The ischemic perihematomal lesions development was also associated with an increased hematoma volume (p<0.005), perilesional edema (p=0.046), greater midline shift (p=0.036). ET-1 values at T1 inversely correlated with hemorrhage volume at T2 (ρ=-0.717, p=0.030).ConclusionsNOX-2 seems to have a role in the development of ischemic perihematomal lesions. The association between higher ET-1 values and a lower hemorrhage volume could be related to the ET-1 vasoconstriction action on the ruptured vessel wall.
Proteomic profiling of peripheral blood mononuclear cells reveals immune dysregulation and metabolic alterations in kidney transplant recipients with COVID-19
Authors: Leite Giuseppe G. F. , Sousa Mônica Bragança , Rodrigues Larissa de Oliveira C. P. , Brunialti Milena Karina Colo , Medina-Pestana José , Butler Joe M. , Peters-Sengers Hessel , Requião-Moura Lúcio , Salomão Reinaldo 
Published: September 2024

AbstractThe emergence of the Coronavirus disease 2019 (COVID-19) pandemic in 2020 has profoundly impacted global health systems, particularly affecting vulnerable populations like kidney transplant recipients (KTRs).We prospectively collected blood samples from 17 PCR-confirmed COVID-19 KTR patients and 10 non-COVID-19 KTRs between May and September 2020. Using tandem mass tag-based quantitative proteomics, we characterized peripheral blood mononuclear cells (PBMCs) from KTRs alongside plasma protein biomarkers and lymphocyte counts, followed by bioinformatics analyses. Our study revealed significant proteomic alterations within PBMCs of SARS-CoV-2 infected KTRs, particularly in pathways associated with glycolysis, glucose metabolism, and neutrophil degranulation. Additionally, we observed an altered immune response marked by elevated cytokines and inflammatory mediators, coupled with decreased lymphocyte counts. Notably, patients with acute kidney injury (AKI) exhibited worse outcomes, including higher rates of ICU transfer and mechanical ventilation. Comparison of PBMC proteomic profiles between AKI and non-AKI patients highlighted distinct immune-related pathways, with AKI patients showing pronounced alterations in innate immune responses, particularly in neutrophil degranulation. Moreover, our analysis unveiled a negative correlation between T cell counts and neutrophil degranulation, suggesting potential implications for immune dysregulation in COVID-19. Our findings shed light on the complex proteomic landscape and immune responses in COVID-19-infected KTRs, emphasizing the critical need for studies focused on this population, especially in individuals with AKI. Furthermore, our observations provide valuable insights for further exploration of therapeutic interventions targeting immune dysregulation pathways in this vulnerable population.
Clinical stratification of Major Depressive Disorder in the UK Biobank: A gene-environment-brain Topological Data Analysis
Authors: Tassi Emma , Pigoni Alessandro , Turtulici Nunzio , Colombo Federica , Fortaner-Uyà Lidia , Bianchi Anna Maria , Benedetti Francesco , Fabbri Chiara , Vai Benedetta , Brambilla Paolo , Maggioni Eleonora 
Published: September 2024

AbstractMajor depressive disorder (MDD) is a leading cause of disability worldwide, affecting over 300 million people and posing a significant burden on healthcare systems. MDD is highly heterogeneous, with variations in symptoms, treatment response, and comorbidities that could be determined by diverse etiologic mechanisms, including genetic and neural substrates, and societal factors.Characterizing MDD subtypes with distinct clinical manifestations could improve patient care through targeted personalized interventions. Recently, Topological Data Analysis (TDA) has emerged as a promising tool for identifying homogeneous subgroups of diverse medical conditions and key disease markers, reducing complex data into comprehensible representations and capturing essential dataset features.Our study applied TDA to data from the UK Biobank MDD subcohort composed of 3052 samples, leveraging genetic, environmental, and neuroimaging data to stratify MDD into clinically meaningful subtypes. TDA graphs were built from unimodal and multimodal feature sets and quantitatively compared based on their capability to predict depression severity, physical comorbidities, and treatment response outcomes.Our findings showed a key role of the environment in determining the severity of depressive symptoms. Comorbid medical conditions of MDD were best predicted by brain imaging characteristics, while brain functional patterns resulted the best predictors of treatment response profiles.Our results suggest that considering genetic, environmental, and brain characteristics is essential to characterize the heterogeneity of MDD, providing avenues for the definition of robust markers of health outcomes in MDD.
Molecular Detection of Multi-drug resistant tuberculosis in clinical isolates from two urban centres in Malawi
Authors: Sikwese Tionge , Msosa Takondwa , Twabi Hussein , Dzunda Samuel , Chaima David , Banda Billy , Kanamazina Yusuf , Nyenje Mirriam , Musopole Alinune , Nliwasa Marriott , Ndhlovu Victor 
Published: September 2024

AbstractIntroductionSuboptimal chemotherapy allowsMycobacterium tuberculosisto develop drug resistance owing to development of resistant mutants in the mycobacterial population. Early diagnosis of TB and identification of drug-resistance is of particular importance in human immunodeficiency virus (HIV)-infected individuals, as delay of therapy and subsequent development of drug-resistant TB can be devastating due to compromised immune systems.MethodologyWe conducted a cross-sectional evaluation study using presumptiveM. tuberculosispositive clinical isolates at two urban sites in Malawi (Blantyre and Lilongwe) to assess the presence of mutant genes on first and second line TB drugs using Line Probe Assay (LPA) and the gold standard drug susceptibility test (DST)ResultsFor the Lilongwe site, the incidence of MDR-TB by Line Probe Assay (LPA) was found to be 14.06% (95% CI: 8%-20%) whereas that for Rif mono-resistance was 6.25% (95% CI: 2%-10%). Contrastingly, MDR-TB by DST was 23.44% (95 CI:16% - 21%) while mono-resistance was 6.25% (95% CI:2% -10). There was a substantial agreement on the detection of MDR-TB (kappa statistic was 0.75 with 95% CI of 0.62-0.88). Blantyre site, at 9.5% confidence interval, the point estimate for MDR-TB was 0% while for INH mono-resistance TB was 3.3%.ConclusionsThere is high incidence of MDR-TB among patients whose samples are sent to the Lilongwe site than previously thought. A short turnaround time to diagnosis, and the ability to simultaneously detect rifampicin and isoniazid resistance, makes LPA a reliable tool for the early detection of multidrug-resistant tuberculosis.