bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding a cryptic mechanism of metronidazole resistance among globally disseminated fluoroquinolone-resistant Clostridioides difficile
Authors: Olaitan Abiola O. , Dureja Chetna , Youngblom Madison A. , Topf Madeline A. , Shen Wan-Jou , Gonzales-Luna Anne J. , Deshpande Aditi , Hevener Kirk E. , Freeman Jane , Wilcox Mark H. , Palmer Kelli L. , Garey Kevin W. , Pepperell Caitlin S. , Hurdle Julian G. 
Published: July 2023

AbstractSevere outbreaks and deaths have been linked to the emergence and global spread of fluoroquinolone-resistant Clostridioides difficile over the past two decades. At the same time, metronidazole, a nitro-containing antibiotic, has shown decreasing clinical efficacy in treating C. difficile infection (CDI). Most metronidazole-resistant C. difficile exhibit an unusual resistance phenotype that can only be detected in susceptibility tests using molecularly intact heme. Here, we describe the mechanism underlying this trait. We find that most metronidazole-resistant C. difficile strains carry a T-to-G mutation (which we term PnimBG) in the promoter of gene nimB, resulting in constitutive transcription. Silencing or deleting nimB eliminates metronidazole resistance. NimB is related to Nim proteins that are known to confer resistance to nitroimidazoles. We show that NimB is a heme-dependent flavin enzyme that degrades nitroimidazoles to amines lacking antimicrobial activity. Furthermore, occurrence of the PnimBG mutation is associated with a Thr82Ile substitution in DNA gyrase that confers fluoroquinolone resistance in epidemic strains. Our findings suggest that the pandemic of fluoroquinolone-resistant C. difficile occurring over the past few decades has also been characterized by widespread resistance to metronidazole.
Mesitylated trityl radicals, a platform for doublet emission: symmetry breaking, charge-transfer states and conjugated polymers
Authors: Murto Petri , Chowdhury Rituparno , Gorgon Sebastian , Guo Erjuan , Zeng Weixuan , Li Biwen , Sun Yuqi , Francis Haydn , Friend Richard H. , Bronstein Hugo 
Published: July 2023

AbstractNeutral π-radicals have potential for use as light emitters in optoelectronic devices due to the absence of energetically low-lying non-emissive states. Here, we report a defect-free synthetic methodology via mesityl substitution at the para-positions of tris(2,4,6-trichlorophenyl)methyl radical. These materials reveal a number of novel optoelectronic properties. Firstly, mesityl substituted radicals show strongly enhanced photoluminescence arising from symmetry breaking in the excited state. Secondly, photoexcitation of thin films of 8 wt% radical in 4,4’-bis(carbazol-9-yl)-1,1’-biphenyl host matrix produces long lived (in the order of microseconds) intermolecular charge transfer states, following hole transfer to the host, that can show unexpectedly efficient red-shifted emission. Thirdly, covalent attachment of carbazole into the mesitylated radical gives very high photoluminescence yield of 93% in 4,4’-bis(carbazol-9-yl)-1,1’-biphenyl films and light-emitting diodes with maximum external quantum efficiency of 28% at a wavelength of 689 nm. Fourthly, a main-chain copolymer of the mesitylated radical and 9,9-dioctyl-9H-fluorene shows red-shifted emission beyond 800 nm.
Volcanic evolution of an ultraslow-spreading ridge
Authors: Stubseid H. H. , Bjerga A. , Haflidason H. , Pedersen L. E. R. , Pedersen R. B. 
Published: July 2023

AbstractNearly 30% of ocean crust forms at mid-ocean ridges where the spreading rate is less than 20 mm per year. According to the seafloor spreading paradigm, oceanic crust forms along a narrow axial zone and is transported away from the rift valley. However, because quantitative age data of volcanic eruptions are lacking, constructing geological models for the evolution of ultraslow-spreading crust remains a challenge. In this contribution, we use sediment thicknesses acquired from ~4000 km of sub-bottom profiler data combined with 14C ages from sediment cores to determine the age of the ocean floor of the oblique ultraslow-spreading Mohns Ridge to reveal a systematic pattern of young volcanism outside axial volcanic ridges. Here, we present an age map of the upper lava flows within the rift valley of a mid-ocean ridge and find that nearly half of the rift valley floor has been rejuvenated by volcanic activity during the last 25 Kyr.
Spatial immunophenotypes orchestrate prognosis in triple-negative breast cancer with Miller-Payne grade 4 following neoadjuvant chemotherapy
Authors: Ma Jianli , Deng Yuwei , Chen Dawei , Li Xiaomei , Yu Zhiyong , Wang Haibo , Zhong Lei , Li Yingjie , Wang Chengqin , Li Xiang , Yu Jinming , Zhang Qingyuan 
Published: July 2023

AbstractSome triple-negative breast cancer (TNBC) patients evaluated as Miller-Payne 4 with ypN0 after neoadjuvant chemotherapy (NACT) who have better prognoses should avoid escalation of therapy. We aim to identify these patients by evaluating pretherapeutic spatial distributions of immunophenotypes. Our retrospective study in patients with TNBC assessed as Miller-Payne grade 4/5 with ypN0 showed that Miller-Payne 4 with ypN0 group had poorer 5-year disease-free survival (DFS, 63.8% vs. 83.0%, p = 0.003) and the 5-year overall survival (OS, 71.0% vs. 85.5%, p = 0.007) than Miller-Payne 5 with ypN0 group. High TILs were significantly associated with better DFS and OS in patients with Miller-Payne 4 and ypN0 (both p = 0.016). Spatially, detected by multiplexed ion beam imaging by the time of flight combined with proteomics, tumors assessed as Miller-Payne 4 and ypN0 with good prognosis exhibited an inflamed phenotype, with dominant CD8+ T cells on tumor center, few scattered CD68+ myeloid-derived cells far away from T cells, and deposit of increased activated molecules of lymphocyte. While those with poor prognoses presented excluded phenotypes, with few CD8+ T cells restricted to invasive margins and a high density of CD14+CD68+CD11c+ myeloid cells. A good classifier model based on 29 spatial immunophenotypes was established by the random forest algorithm (AUC = 0.975), for identifying patients with Miller-Payne 4 and ypN0 who had favorable prognoses. We also observed similar signatures in patients with Miller-Payne 5 and ypN0. Taken together, spatial immunophenotypes may assess the prognosis in TNBC patients with Miller-Payne 4 and ypN0 after NACT.
A framework for individualized splice-switching oligonucleotide therapy
Authors: Kim Jinkuk , Woo Sijae , de Gusmao Claudio M. , Zhao Boxun , Chin Diana H. , DiDonato Renata L. , Nguyen Minh A. , Nakayama Tojo , Hu Chunguang April , Soucy Aubrie , Kuniholm Ashley , Thornton Jennifer Karlin , Riccardi Olivia , Friedman Danielle A. , El Achkar Christelle Moufawad , Dash Zane , Cornelissen Laura , Donado Carolina , Faour Kamli N. W. , Bush Lynn W. , Suslovitch Victoria , Lentucci Claudia , Park Peter J. , Lee Eunjung Alice , Patterson Al , Philippakis Anthony A. , Margus Brad , Berde Charles B. , Yu Timothy W. 
Published: July 2023

AbstractSplice-switching antisense oligonucleotides (ASOs) could be used to treat a subset of individuals with genetic diseases1, but the systematic identification of such individuals remains a challenge. Here we performed whole-genome sequencing analyses to characterize genetic variation in 235 individuals (from 209 families) with ataxia-telangiectasia, a severely debilitating and life-threatening recessive genetic disorder2,3, yielding a complete molecular diagnosis in almost all individuals. We developed a predictive taxonomy to assess the amenability of each individual to splice-switching ASO intervention; 9% and 6% of the individuals had variants that were ‘probably’ or ‘possibly’ amenable to ASO splice modulation, respectively. Most amenable variants were in deep intronic regions that are inaccessible to exon-targeted sequencing. We developed ASOs that successfully rescued mis-splicing and ATM cellular signalling in patient fibroblasts for two recurrent variants. In a pilot clinical study, one of these ASOs was used to treat a child who had been diagnosed with ataxia-telangiectasia soon after birth, and showed good tolerability without serious adverse events for three years. Our study provides a framework for the prospective identification of individuals with genetic diseases who might benefit from a therapeutic approach involving splice-switching ASOs.
Global climate-change trends detected in indicators of ocean ecology
Authors: Cael B. B. , Bisson Kelsey , Boss Emmanuel , Dutkiewicz Stephanie , Henson Stephanie 
Published: July 2023

AbstractStrong natural variability has been thought to mask possible climate-change-driven trends in phytoplankton populations from Earth-observing satellites. More than 30 years of continuous data were thought to be needed to detect a trend driven by climate change1. Here we show that climate-change trends emerge more rapidly in ocean colour (remote-sensing reflectance, Rrs), because Rrs is multivariate and some wavebands have low interannual variability. We analyse a 20-year Rrs time series from the Moderate Resolution Imaging Spectroradiometer (MODIS) aboard the Aqua satellite, and find significant trends in Rrs for 40% of the global surface ocean. The climate-change signal in Rrs emerges after 20 years in similar regions covering a similar fraction of the ocean in a state-of-the-art ecosystem model2, which suggests that our observed trends indicate shifts in ocean colour—and, by extension, in surface-ocean ecosystems—that are driven by climate change. On the whole, low-latitude oceans have become greener in the past 20 years.
Transcriptomic and lipidomic profiling of subcutaneous and visceral adipose tissues in 15 vertebrates
Authors: Liu Pengliang , Li Diyan , Zhang Jiaman , He Mengnan , Li Yan , Liu Rui , Li Mingzhou 
Published: July 2023

AbstractThe storage of lipids as energy in adipose tissue (AT) has been conserved over the course of evolution. However, substantial differences in ATs physiological activities were reported among species. Hence, establishing the mechanisms shaping evolutionarily divergence in ATs transcriptomes could provide a deeper understanding of AT regulation and its roles in obesity-related diseases. While previous studies performed anatomical, physiological and morphological comparisons between ATs across different species, little is currently understood at the molecular phenotypic levels. Here, we characterized transcriptional and lipidomic profiles of available subcutaneous and visceral ATs samples across 15 vertebrate species, spanning more than 300 million years of evolution, including placental mammals, birds and reptiles. We provide detailed descriptions of the datasets produced in this study and report gene expression and lipid profiles across samples. We demonstrate these data are robust and reveal the AT transcriptome and lipidome vary greater among species than within the same species. These datasets may serve as a resource for future studies on the functional differences among ATs in vertebrate species.
Broadband high-efficiency 3-bit coding metasurface in transmission mode based on the polarization conversion technique
Authors: Karimipour Majid , Heydari Mohammad Bagher , Aryanian Iman 
Published: July 2023

AbstractThe main drawback of the transmissive focusing metasurface (TFM) is its low operational bandwidth and aperture efficiency. Increasing both of these radiation characteristics simultaneously is a major challenge for these structures. This paper introduces a novel multi-state coding metasurface that utilizes system-level and element-level synthesis approaches to enhance frequency bandwidth and aperture efficiency. Unlike most of the TFMs proposed in this field, the proposed novel element consists of only two dielectric layers. The multi-frequency phase synthesis (MFPS) approach, a well-established broadband technique, is utilized for the system-level synthesis approach. An optimization algorithm is utilized to balance the phase error in the whole band in terms of gain variations and aperture efficiency. At the element design level, a PCT-based wideband technology is utilized and implemented by a subwavelength non-resonant element. The element is composed of three C-shaped metallic patterns, and the metal layers are printed on both sides of two identical dielectric layers without using any metalized via in the configuration. By simply changing the angle of arc curves in all layers, eight states of phase quantization are achieved. The amplitude of the transmitted wave with rotated polarization is larger than 0.9 from 12.3 to 16.5 GHz, except for state 4, which has an amplitude greater than 0.5 at the beginning of the band. A 25 $$\times $$
×
25-element TFM was designed, fabricated, and tested using the aforementioned broadband technique (MFPS along with PCT-based wideband technology). The measurement results show that the 1-dB gain bandwidth of the antenna is 12.3–16.5 GHz, which is equivalent to 29%. The maximum measured aperture efficiency is 53.6%, occurring at 12.8 GHz. The proposed metasurface is classified in the group of broadband high-efficiency TFMs.
Sleep quality is a predictor of muscle mass, strength, quality of life, anxiety and depression in older adults with obesity
Authors: Genario Rafael , Gil Saulo , Oliveira-Júnior Gersiel , Leitão Alice Erwig , Franco Tathiane , dos Santos Sales Ruan Célio , Ferriolli Eduardo , Busse Alexandre Leopold , Filho Wilson Jacob , Gualano Bruno , Roschel Hamilton 
Published: July 2023

AbstractWe aimed to investigate associations between sleep quality with selected quantitative and qualitative parameters of health in older individuals with obesity. Cross-sectional assessment (n = 95 men/women; ≥ 65 years; BMI ≥ 30 kg/m2) of sleep quality, body composition, handgrip strength, quality-of-life, anxiety/depression. Mean PSQI score was 6.3. Poor sleepers (n = 49) presented lower appendicular lean mass (ALM) (16.2 vs 17.8 kg; p = 0.0273), ALM/BMI (0.47 vs 0.53 kg/BMI; p = 0.0085), fat mass (48.6 vs 46.6%; p = 0.0464), handgrip strength (19.7 vs 22.0 kgf; p = 0.0542) and handgrip/BMI (0.57 vs 0.66 kgf/BMI; p = 0.0242) than good sleepers. They also had higher anxiety (8.6 vs 5.6; p = 0.0100) and depression (4.8 vs 3.2; p = 0.0197) scores, worse health-related quality-of-life and lower scores in mental (62.8 vs 73.0; p = 0.0223) and physical (52.9 vs 67.3; p = 0.0015) domains. Adjusted models showed that PSQI was negatively associated with ALM (β = − 0.13, 95% CI − 0.25; − 0.01) and health-related quality of life on physical (β = − 2.76, 95% CI − 3.82; − 1.70) and mental (β = − 2.25, 95% CI − 3.38; − 1.12) domains, and positively associated with anxiety (β = 0.57; 95% CI 0.26; 0.87) and depression (β = 0.31; 95% CI 0.13; 0.49). Poor sleep quality associates with impaired selected quantitative and qualitative parameters of health. Additionally, sleep quality was shown as an independent predictor of ALM, health-related quality-of-life, anxiety and depression in older individuals with obesity.
PhysVENeT: a physiologically-informed deep learning-based framework for the synthesis of 3D hyperpolarized gas MRI ventilation
Authors: Astley Joshua R. , Biancardi Alberto M. , Marshall Helen , Smith Laurie J. , Hughes Paul J. C. , Collier Guilhem J. , Saunders Laura C. , Norquay Graham , Tofan Malina-Maria , Hatton Matthew Q. , Hughes Rod , Wild Jim M. , Tahir Bilal A. 
Published: July 2023

AbstractFunctional lung imaging modalities such as hyperpolarized gas MRI ventilation enable visualization and quantification of regional lung ventilation; however, these techniques require specialized equipment and exogenous contrast, limiting clinical adoption. Physiologically-informed techniques to map proton (1H)-MRI ventilation have been proposed. These approaches have demonstrated moderate correlation with hyperpolarized gas MRI. Recently, deep learning (DL) has been used for image synthesis applications, including functional lung image synthesis. Here, we propose a 3D multi-channel convolutional neural network that employs physiologically-informed ventilation mapping and multi-inflation structural 1H-MRI to synthesize 3D ventilation surrogates (PhysVENeT). The dataset comprised paired inspiratory and expiratory 1H-MRI scans and corresponding hyperpolarized gas MRI scans from 170 participants with various pulmonary pathologies. We performed fivefold cross-validation on 150 of these participants and used 20 participants with a previously unseen pathology (post COVID-19) for external validation. Synthetic ventilation surrogates were evaluated using voxel-wise correlation and structural similarity metrics; the proposed PhysVENeT framework significantly outperformed conventional 1H-MRI ventilation mapping and other DL approaches which did not utilize structural imaging and ventilation mapping. PhysVENeT can accurately reflect ventilation defects and exhibits minimal overfitting on external validation data compared to DL approaches that do not integrate physiologically-informed mapping.
Cytoskeletal disarray increases arrhythmogenic vulnerability during sympathetic stimulation in a model of hypertrophic cardiomyopathy
Authors: Cserne Szappanos Henrietta , Viola Helena M. , Ito Danica W. , Lim Seakcheng , Mangala Melissa , Holliday Mira , Barratt Ross Samantha , Semsarian Christopher , Hill Adam , Dixon Rose E. , Hool Livia C. 
Published: July 2023

AbstractFamilial hypertrophic cardiomyopathy (FHC) patients are advised to avoid strenuous exercise due to increased risk of arrhythmias. Mice expressing the human FHC-causing mutation R403Q in the myosin heavy chain gene (MYH6) recapitulate the human phenotype, including cytoskeletal disarray and increased arrhythmia susceptibility. Following in vivo administration of isoproterenol, mutant mice exhibited tachyarrhythmias, poor recovery and fatigue. Arrhythmias were attenuated with the β-blocker atenolol and protein kinase A inhibitor PKI. Mutant cardiac myocytes had significantly prolonged action potentials and triggered automaticity due to reduced repolarization reserve and connexin 43 expression. Isoproterenol shortened cycle length, and escalated electrical instability. Surprisingly isoproterenol did not increase CaV1.2 current. We found alterations in CaV1.2-β1 adrenergic receptor colocalization assessed using super-resolution nanoscopy, and increased CaV1.2 phosphorylation in mutant hearts. Our results reveal for the first time that altered ion channel expression, co-localization and β-adrenergic receptor signaling associated with myocyte disarray contribute to electrical instability in the R403Q mutant heart.
Multilayer 3D bioprinting and complex mechanical properties of alginate-gelatin mesostructures
Authors: Ahmadi Soufivand Anahita , Faber Jessica , Hinrichsen Jan , Budday Silvia 
Published: July 2023

AbstractIn the biomedical field, extrusion-based 3D bioprinting has emerged as a promising technique to fabricate tissue replacements. However, a main challenge is to find suitable bioinks and reproducible procedures that ensure good printability and generate final printed constructs with high shape fidelity, similarity to the designed model, and controllable mechanical properties. In this study, our main goal is to 3D print multilayered structures from alginate-gelatin (AG) hydrogels and to quantify their complex mechanical properties with particular focus on the effects of the extrusion process and geometrical parameters, i.e. different mesostructures and macroporosities. We first introduce a procedure including a pre-cooling step and optimized printing parameters to control and improve the printability of AG hydrogels based on rheological tests and printability studies. Through this procedure, we significantly improve the printability and flow stability of AG hydrogels and successfully fabricate well-defined constructs similar to our design models. Our subsequent complex mechanical analyses highlight that the extrusion process and the mesostructure, characterized by pore size, layer height and filament diameter, significantly change the complex mechanical response of printed constructs. The presented approach and the corresponding results have important implications for future 3D bioprinting applications when aiming to produce replacements with good structural integrity and defined mechanical properties similar to the native tissue, especially in soft tissue engineering. The approach is also applicable to the printing of gelatin-based hydrogels with different accompanying materials, concentrations, or cells.
The effect of single dose albendazole (400 mg) treatment on the human gut microbiome of hookworm-infected Ghanaian individuals
Authors: Appiah-Twum Francis , Akorli Jewelna , Okyere Lydia , Sagoe Kate , Osabutey Dickson , Cappello Michael , Wilson Michael D. 
Published: July 2023

AbstractMicrobes play a key role in human gut homeostasis, metabolic, immunologic and physiopathology of the body. A longitudinal study conducted during 2018–2021 in the Kintampo North Municipality in Ghana demonstrated low hookworm infection cure rates following treatment with a single dose of 400 mg albendazole in some communities. To investigate associations between hookworm infection and the gut microbiome, we examined stool samples from consented participants who were either cured or remained infected after treatment. At each time point, stool was collected prior to and 10–14 days after albendazole treatment. We used 16S rRNA amplicon sequencing of DNA extracted from stool samples to investigate the composition and diversity of the gut microbiota and to identify potential microbial biomarkers associated with treatment outcomes. Hookworm infection was associated with increased species richness (p = 0.0093). Among treated individuals, there was also a significant variation in microbiota composition at 10–14 days following single-dose albendazole treatment. Individuals cured of hookworm infection after treatment showed a significant reduction in microbiota composition when compared to their pre-treatment state (ANOSIM; p = 0.02), whilst individuals who failed to clear the infection showed no change in microbiota composition (ANOSIM; p = 0.35). Uninfected individuals and those who were successfully treated were similar in their microbial composition and structure. We also found that the abundance of Clostridia spp. was increased in infected individuals pre- or post-treatment. Predictive functional profiling revealed the enrichment of two pyruvate ferredoxin oxidoreductase subunit pathways in individuals who remained infected after treatment (p < 0.05), alluding to an upturn of strictly anaerobic commensal bacteria such as Clostridia spp. This study suggests a relationship between human gut microbiome dysbiosis and albendazole therapy outcomes of hookworm infection. Future studies will further characterize specific biomarkers identified within this study to establish their potential for assessment of pharmacological responses to anthelminthic therapies, as well as explore the possibility of using probiotic supplementation as an adjunct treatment to increase albendazole effectiveness against hookworm.