bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of an evolutionarily conserved TAD boundary compromises spermatogenesis in mice
Authors: Lima Ana C. , Okhovat Mariam , Stendahl Alexandra M. , VanCampen Jake , Nevonen Kimberly A. , Herrera Jarod , Li Weiyu , Harshman Lana , Yang Ran , Fedorov Lev M. , Vigh-Conrad Katinka A. , Ahituv Nadav , Conrad Donald F. , Carbone Lucia 
Published: July 2024

AbstractSpermatogenesis is a complex process that can be disrupted by genetic and epigenetic changes, potentially leading to male infertility. Recent research has rapidly increased the number of protein coding mutations causally linked to impaired spermatogenesis in humans and mice. However, the role of non-coding mutations remains largely unexplored. As a case study to evaluate the effects of non-coding mutations on spermatogenesis, we first identified an evolutionarily conserved topologically associated domain (TAD) boundary near two genes with important roles in mammalian testis function:Dmrtb1andLrp8. We then used CRISPR-Cas9 to generate a mouse line where 26kb of the boundary was removed including a strong and evolutionarily conserved CTCF binding site. ChIP-seq and Hi-C experiments confirmed the removal of the CTCF site and a resulting increase in the DNA-DNA interactions across the domain boundary. Mutant mice displayed significant changes in testis gene expression, abnormal testis histology, a 35% drop in the estimated efficiency of spermatogenesis and a 28% decrease in daily sperm production compared to littermate controls. Despite these quantitative changes in testis function, mutant mice show no significant changes in fertility. This suggests that non-coding deletions affecting testis gene regulation may have smaller effects on fertility compared to coding mutations of the same genes. Our results demonstrate that disruption of a TAD boundary can have a negative impact on sperm production and highlight the importance of considering non-coding mutations in the analysis of patients with male infertility.
Direct Percutaneous Embolization of Head, Neck and Spine Tumors: A Single Center Experience
Authors: Topiwala Karan , Huang Shiwei , Sabal Luke , Kahmeyer Bailey , Grande Andrew , Jagadeesan Bharathi 
Published: July 2024

AbstractIntroductionTransarterial embolization is a well-established adjunct in the management of hypervascular head, neck, and spine tumors. Few case-series have described the role of direct percutaneous embolization (DPE).MethodWe report our experience with DPE (with or without transarterial embolization) in patients with head, neck, and spine tumors treated between 2012-2023. Baseline demographics, angiographic imaging, tumoral pathology, and relevant clinical variables were retrospectively reviewed and descriptively analyzed.ResultA total of 55 patients underwent direct percutaneous embolization (19 of whom also received transarterial embolization either before [n=7] or after [n=12] DPE). The most commonly embolized lesions were malignant carcinomas (n=16), followed by juvenile nasopharyngeal angiofibromas (n=11), paragangliomas (n=8), hemangiomas (n=7), and others (hemangioblastoma, schwannoma, neurofibroma, esthesioneuroblastoma, meningioma and hemangiopericytoma). The most common locations were sinonasal/nasopharyngeal (n=21), followed by scalp/subcutaneous (n=18), carotid body (n=6), spinal/paraspinal (n=4), skull base (n=5), and intracranial (n=1). A median of 4 (interquartile range 4-6) twenty-two-gauge spinal needles were used per embolization with a median fluoroscopy time of 50.5 (23.2-77.8) minutes resulting in median radiation exposure of 3055 (840.5-5053.5) mGy. Seven patients received more than one embolic agent, withn-butyl cyanoacrylate (glue, n=44, 81.5%) being the mostly commonly used embolic, followed by ethylene-vinyl alcohol copolymer (Onyx, n=7, 12.9%), 98% dehydrated ethanol (n=7, 12.9%), sodium tetradecyl sulfate (n=2, 3.7%) and poly-vinyl alcohol particles (n=1, 1.8%). The median volume of embolic agent injected was 5.5(4-7.6) mL resulting in total/near-total (90%-99%) angiographic devascularization in 74.5% cases. The median operative blood-loss was 250(75-700) mL. One patient underwent trans-calavarial DPE for a cerebellar hemangioblastoma and suffered diffuse subarachnoid hemorrhage from profuse tumoral bleeding. One patient had an asymptomatic parent-vessel occlusion from retrograde embolic extension.ConclusionOur single-center study reinforces prior experience that DPE of Sino-nasal carcinomas, angiofibromas and paragangliomas with adhesive and non-adhesive liquid embolic agents is safe, feasible and effective. Further, it suggests that these benefits may also be extended to non-traditional head, neck and spine tumors. Caution must be exercised when applying these techniques to intracranial tumors with robust intratumoral arteriovenous shunting.
Trait genetic architecture and population structure determine model selection for genomic prediction in naturalArabidopsis thalianapopulations
Authors: Gibbs Patrick M. , Paril Jefferson F. , Fournier-level Alexandre 
Published: July 2024

AbstractGenomic prediction applies to a wide range of agronomically relevant traits, with distinct ontologies and genetic architectures. Selecting the most appropriate model for the distribution of genetic effects and their associated allele frequencies in the training population is crucial. Linear regression models are often preferred for genomic prediction. However, linear models may not suit all genetic architectures and training populations. Machine Learning approaches have been proposed to improve genomic prediction owing to their capacity to capture complex biology including epistasis. However, the applicability of different genomic prediction models, including non-linear/non-parametric approaches, have not been rigorously assessed across a wide variety of plant traits in natural outbreeding populations. This study evaluates genomic prediction sensitivity to trait ontology and the impact of population structure on model selection and prediction accuracy. Examining 36 quantitative traits measured for 1000+ natural genotypes of the model plantArabidopsis thaliana, we assessed the performance of penalised regression, random forest, and multilayer perceptron at producing genomic predictions. Regression models were generally the most accurate, except for biochemical traits where random forest performed best. We link this result to the genetic architecture of each trait – notably that biochemical traits have simpler genetic architecture than macroscopic traits. Moreover, complex macroscopic traits, particularly those related to flowering and yield, were strongly correlated to population structure, while molecular traits were better predicted by fewer, independent markers. This study highlights the relevance of machine learning approaches for simple molecular traits and underscores the need to consider ancestral population history when designing training samples.Article summaryMachine learning and linear models were tested for genomic prediction of multiple traits in the model plantArabidopsis thaliana. We associate the performance of genomic prediction models to trait ontology, finding machine learning approaches applicable to biochemical traits, and linear models best for macroscopic traits. We link this result to the genetic architecture of each trait and patterns of selection in the association panel’s ancestral population, thus underscoring the relevance of these two sensitivities to genomic prediction in plant breeding.
Local genetic adaptation to habitat in wild chimpanzees
Authors: Ostridge Harrison J. , Fontsere Claudia , Lizano Esther , Soto Daniela C. , Schmidt Joshua M. , Saxena Vrishti , Alvarez-Estape Marina , Barratt Christopher D. , Gratton Paolo , Bocksberger Gaëlle , Lester Jack D. , Dieguez Paula , Agbor Anthony , Angedakin Samuel , Assumang Alfred Kwabena , Bailey Emma , Barubiyo Donatienne , Bessone Mattia , Brazzola Gregory , Chancellor Rebecca , Cohen Heather , Coupland Charlotte , Danquah Emmanuel , Deschner Tobias , Dotras Laia , Dupain Jef , Egbe Villard Ebot , Granjon Anne-Céline , Head Josephine , Hedwig Daniela , Hermans Veerle , Hernandez-Aguilar R. Adriana , Jeffery Kathryn J. , Jones Sorrel , Junker Jessica , Kadam Parag , Kaiser Michael , Kalan Ammie K. , Kambere Mbangi , Kienast Ivonne , Kujirakwinja Deo , Langergraber Kevin E. , Lapuente Juan , Larson Bradley , Laudisoit Anne , Lee Kevin C. , Llana Manuel , Maretti Giovanna , Martín Rumen , Meier Amelia , Morgan David , Neil Emily , Nicholl Sonia , Nixon Stuart , Normand Emmanuelle , Orbell Christopher , Ormsby Lucy Jayne , Orume Robinson , Pacheco Liliana , Preece Jodie , Regnaut Sebastien , Robbins Martha M. , Rundus Aaron , Sanz Crickette , Sciaky Lilah , Sommer Volker , Stewart Fiona A. , Tagg Nikki , Tédonzong Luc Roscelin , van Schijndel Joost , Vendras Elleni , Wessling Erin G. , Willie Jacob , Wittig Roman M. , Yuh Yisa Ginath , Yurkiw Kyle , Vigilant Linda , Piel Alex , Boesch Christophe , Kühl Hjalmar S. , Dennis Megan Y. , Marques-Bonet Tomas , Arandjelovic Mimi , Andrés Aida M. 
Published: July 2024

AbstractHow populations adapt to their environment is a fundamental question in biology. Yet we know surprisingly little about this process, especially for endangered species such as non-human great apes. Chimpanzees, our closest living relatives, are particularly interesting because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite having wide implications for evolutionary biology and conservation. Using 828 newly generated exomes from wild chimpanzees, we find evidence of fine-scale genetic adaptation to habitat. Notably, adaptation to malaria in forest chimpanzees is mediated by the same genes underlying adaptation to malaria in humans. This work demonstrates the power of non-invasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees.One-Sentence SummaryChimpanzees show evidence of local genetic adaptation to habitat, particularly to pathogens, such as malaria, in forests.
A unique mechanism of snRNP core assembly
Authors: Wang Yingzhi , Chen Xiaoshuang , Kong Xi , Chen Yunfeng , Xiang Zixi , Xiang Yue , Hu Yan , Hou Yan , Zhou Shijie , Shen Congcong , Mu Li , Su Dan , Zhang Rundong 
Published: July 2024

ABSTRACTThe assembly of spliceosomal snRNP cores involves seven Sm proteins (D1/D2/F/E/G/D3/B) forming a ring around each snRNA and typically requires several essential assembly chaperones, particularly the SMN-Gemins complex implicated in spinal muscular atrophy (SMA). Strikingly, in budding yeast, snRNP core assembly only involves Brr1, a nonessential homolog of Gemin2. To unravel this enigma, we systematically investigated snRNP core assembly in budding yeast using biochemical and genetic approaches. We discovered two distinct pathways in budding yeast: chaperone-mediated and direct. The chaperone-mediated pathway involves two proteins, Brr1 and a novel protein, Lot5, but is inefficient. Lot5 binds D1/D2/F/E/G to form a heterohexameric ring (6S). Brr1 binds D1/D2/F/E/G and 6S but cannot displace Lot5 to facilitate assembly. Disruption of both BRR1 and LOT5 genes caused mild growth retardation, but LOT5 overexpression substantially impeded growth. The direct pathway uniquely involves F/E/G as a trimer and a stable D1/D2/F/E/G intermediate complex, explaining the non-essentiality of assembly chaperones. These findings unveil a unique assembly mechanism of snRNP cores, illuminate the evolution of assembly chaperones, and suggest avenues for studying SMA pathophysiology.
Reconstruction and identification of the native PLP synthase complex from Methanosarcina acetivorans lysate
Authors: Agnew Angela , Humm Ethan , Zhou Kang , Gunsalus Robert P. , Zhou Z. Hong 
Published: July 2024

AbstractMany protein-protein interactions behave differently in biochemically purified forms as compared to theirin vivostates. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here we apply the bottom-up structural proteomics method,cryoID, toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through thecryoIDapproach, we successfully reconstructed and identified the nativeMethanosarcina acetivoranspyridoxal 5’-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryoEM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryoEM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37 amino acid insertion present in these prior cases. This study demonstrates the potential of applying thecryoIDworkflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.
Characteristics of Suicide Prevention Apps: A Content Analysis of Apps Available in Canada and the United Kingdom
Authors: Bennett-Poynter Laura , Groves Samantha , Kemp Jessica , Shin Hwayeon Danielle , Sequeira Lydia , Lascelles Karen , Strudwick Gillian 
Published: July 2024

AbstractObjectiveWe aimed to examine the characteristics, features, and content of suicide prevention mobile apps available in app stores in Canada and the United Kingdom.DesignSuicide prevention apps were identified from Apple and Android app stores between March-April 2023. Apps were screened against predefined inclusion criteria, and duplicate apps were removed. Data were then extracted based on descriptive (e.g., genre, app developer), security (e.g., password protection), and design features (e.g., personalization options). Content of apps were assessed using the Essential Features Framework. Extracted data were analyzed using a content analysis approach including narrative frequencies and descriptive statistics.ResultsFifty-two (n=52) suicide prevention apps were included within the review. Most were tailored for the general population and were in English language only. One app had the option to increase app accessibility by offering content presented using sign language. Many apps allowed some form of personalization by adding text content, however most did not facilitate further customization such as the ability to upload photo and audio content. All identified apps included content from at least one of the domains of the Essential Features Framework. The most commonly included domains were sources of suicide prevention support, and information about suicide. The domain least frequently included was screening tools followed by wellness content. No identified apps had the ability to be linked to patient medical records.ConclusionsThe findings of this research present implications for the development of future suicide prevention apps. Development of a co-produced suicide prevention app which is accessible, allows for personalization, and can be integrated into clinical care may present an opportunity to enhance suicide prevention support for individuals experiencing suicidal thoughts and behaviours.Article SummaryStrengths and limitations of this studyThis app review used an established method for systematically identifying and examining suicide prevention apps, which has been successfully used previously.There is potential for overlap between different domains of the Essential Features Framework, which could lead to changes in reporting of percentages relating to app review findings.Only apps available in the UK and Canada in the English language were assessed. Current provision and content of suicide prevention apps may differ across countries, including those available in lower- and middle-income countries.Due to resource and time constraints, the quality of apps were not assessed.
The Safety, Effectiveness and Prognostic Factors of Intravitreal Avastin (Bevacizumab) Injection for the Treatment of Macular Edema at the University of Gondar Tertiary Eye Care and Training Center, NW Ethiopia
Authors: Gizachew Yoseph , Tsegaw Asamere , Wuletaw Tarekegn 
Published: July 2024

AbstractIntroductionThe current management of macular edema (ME) is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs and this represents an important advance in the treatment of ME.Studies done in the western eye care settings have confirmed that intravitreal injection of Avastin is effective for the treatment of ME. However, data on this drug’s efficacy and safety in African eye care settings are very scarce.ObjectiveTo assess the Safety and Effectiveness of intravitreal Bevacizumab (Avastin) injection for the treatment of Macular Edema (ME) due to retina vascular diseases at university of Gondar tertiary eye care and training center, NW Ethiopia.MethodA retrospective study was done on patients who were given intravitreal avastin (IVA) for the treatment of diabetic macular edema (DME), retinal vein occlusion (RVO) and Neovascular Age related macular degeneration (AMD). The main outcome measure was visual acuity (VA) and central macular thickness (CMT) measured by spectral domain OCT.ResultsMedical records of 50 patients (66 eyes) were reviewed of which 46 (69.7%) were males and mean age of 54.2 years (range 20-80). The means of baseline VA and CMT were 1.0logMAR and 379.4 µm respectively. At the end of follow up and after mean injection of 2.5 times per eye, the mean VA improved to 0.7 logMAR (p=0.001) and the mean CMT reduced to 295 µm (p=0.0001). Baseline mean VA was significant prognostic factor for VA improvement (p=0.0001). Baseline mean CMT (P=0.007), number of injection (P=0.009) and diffuse macular edema (P=0.03) were significant factors for CMT reduction.ConclusionsIVA injection for ME edema due to retinal vascular diseases resulted in a significant improvement in mean VA (p=0.001) and CMT (p=0.0001) at the end of follow up. There was no any ocular or systemic complication of IVA injection.
Environmental differences impactAcinetobacter baumanniiphage isolation and infectivity
Authors: Alseth Ellinor O , Roush Carli , Irby Iris , Kopylov Mykhailo , Bobe Daija , Nguyen Kristy , Xu Huaijin , Bryksin Anton V , Rather Philip N 
Published: July 2024

AbstractWith the global rise of antimicrobial resistance, phage therapy is increasingly re-gaining traction as a strategy to treat bacterial infections. For phage therapy to be successful however, we first need to isolate appropriate candidate phages for both clinical and experimental research. Acinetobacter baumanniiis an opportunistic pathogen known for its ability to rapidly evolve resistance to antibiotics, making it a prime target for phage therapy. Yet phage isolation is often hampered byA. baumannii’s ability to rapidly switch between capsular states. Here, we report the discovery and structural characterisation of a novel lytic phage, Mystique. This phage was initially isolated against the wild-type AB5075: a commonly used clinical model strain against which no phage has previously been readily available for the capsulated form. When screening Mystique on 103 highly diverse isolates ofA. baumannii, we found that it has a broad host range, being able to infect 85.4% of all tested strains when tested on bacterial lawns – a host range which expanded to 91.3% when tested in liquid culture. This variation between solid and liquid environments on phage infectivity was also observed for several other phages in our collection that were assumed unable to infect AB5075, and capsule negative mutants that initially seemed completely resistant to Mystique proved susceptible when assayed in liquid. Overall, through the discovery of a novel phage we demonstrate how environmental differences can drastically impact phage infectivity with important consequences for phage isolation and characterisation efforts.Author summaryBacterial infections caused byAcinetobacter baumanniiare a major global health concern due to high antibiotic resistance, earning it a critical priority pathogen ranking by the WHO. Phage therapy is resurging as a treatment option, with some success againstA. baumannii. However, the wild-type clinical model strain used to assess new therapies lacks an available phage, and isolating phages forA. baumanniiis challenging due to its complex capsule. Here, we report the discovery of a novel lytic phage, Mystique, which exhibits a broad host range, infecting 94 out of 103 testedA. baumanniistrains. We conducted genomic sequencing and structural analysis to fully characterise Mystique. Additionally, we found that the testing environment significantly impacts results; some phages that do not form plaques on bacterial lawns can still infect and amplify in liquid cultures of the same strain. Moreover, mutants resistant to Mystique based on plaque assays were susceptible in liquid culture assays. This work underscores the necessity of a multifaceted approach for phage isolation and characterisation, as traditional phage assays may not be sufficient for studying bacteria-phage dynamics in certain bacteria such asA. baumannii.