bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-Cost, Label-Free Blue Light Cystoscopy through Digital Staining of White Light Cystoscopy Videos
Authors: Chang Shuang , Wintergerst Greyson A , Carlson Camella , Yin Haoli , Scarpato Kristen R. , Luckenbaugh Amy N. , Chang Sam S. , Kolouri Soheil , Bowden Audrey K. 
Published: March 2024

AbstractBladder cancer is 10thmost common malignancy and carries the highest treatment cost among all cancers. The high cost of bladder cancer treatment stems from its high recurrence rate, which necessitates frequent surveillance. White light cystoscopy (WLC), the standard of care surveillance tool to examine the bladder for lesions, has limited sensitivity for early-stage bladder cancer. Blue light cystoscopy (BLC) utilizes a fluorescent dye to induce contrast in cancerous regions, improving the sensitivity of detection by 43%. Nevertheless, the added cost and lengthy administration time of the dye limits the availability of BLC for surveillance. Here, we report the first demonstration of digital staining on clinical endoscopy videos collected with standard-of-care clinical equipment to convert WLC images to accurate BLC-like images. We introduce key pre-processing steps to circumvent color and brightness variations in clinical datasets needed for successful model performance; the results show excellent qualitative and quantitative agreement of the digitally stained WLC (dsWLC) images with ground truth BLC images as measured through staining accuracy analysis and color consistency assessment. In short, dsWLC can provide the fluorescent contrast needed to improve the detection sensitivity of bladder cancer, thereby increasing the accessibility of BLC contrast for bladder cancer surveillance use without the cost and time burden associated with the dye and specialized equipment.
Understanding the impact of antenatal care policies in Georgia (USA) and Scotland (UK): A textual synthesis
Authors: Shim J. , Burnett V. , Vernon M. , Work F. , Uwaifo I. , Ray C. , Reddi P. 
Published: March 2024

AbstractObjectivesThis study aims to (1) understand the role of policy in maternal health outcomes, and (2) establish any differences or similarities between health systems, providing benchmarks for future maternal and infant care policies in Georgia and Scotland.MethodsGuided by JBI methodology, a textual review of policies and public health interventions that have influenced the antenatal care process in both health systems was conducted. Inclusion criteria for this review were classified using the “PCC” mnemonic: Population-Pregnant women and mothers; Concept-Policies and strategies that supports prenatal and maternal health; and Context-Relevant to Scotland and Georgia. Published primary and secondary research, and grey literature (guidelines, reports, and legislation from authoritative sources) were included.ResultsOverall, 60 sources contributed to the report on maternal health system topics. Findings of the textual synthesis presented a regionalized system of maternity care led by physician-provided care models in Georgia compared to the nationalized health system in Scotland with an extended scope for midwife-led care models. On a secondary, organizational level, Scotland also widely operates on protocolized, standardized care informed by clinical guidelines such as NICE. The Georgia health systems also follow national guidelines for care, but extent of standardization may vary based on a mixed system of private and public insurance coverage.Discussion/ConclusionThis is the first study to comprehensively examine maternal health policies in the distinct contexts of Georgia and Scotland, shedding light on the diverse approaches within their respective healthcare systems. These observed variations stem from historical, cultural, and policy contexts unique to each region. As the United States continue to prioritize maternal and child health through public health initiatives, our findings feature crucial considerations for maternal antenatal care policies. Specifically, there is a discernible need to increase access to antenatal care and invest in the maternity care provider workforce, revealing opportunities for targeted improvements in support of maternal health.
Equalizing prognostic disparities in stage III KRAS-mutant NSCLC: addition of durvalumab to combined chemoradiotherapy improves survival
Authors: Eklund Ella A. , Orgard Mathilda , Wallin Delice , Sayin Sama I. , Fagman Henrik , Raghavan Sukanya , Akyürek Levent M , Nyman Jan , Wiel Clotilde , Hallqvist Andreas , Sayin Volkan I. 
Published: March 2024

AbstractIntroductionStage III non-small cell lung cancer (NSCLC) is heterogeneous and identification of subgroups with differential responses is crucial to optimize treatment. Addition of durvalumab to concurrent chemoradiotherapy (cCRT) has previously been shown to improve survival outcomes. Meanwhile, subgroups harboring KRAS mutations have been shown to have worse prognosis. We investigated whether KRAS mutational status may affect survival outcomes after adjuvant durvalumab following cCRT in stage III NSCLC.MethodsIn this retrospective study, we present a real-world dataset of all stage III NSCLC patients treated with cCRT with a curative intent and molecularly assessed between 2016-2021 in West Sweden. Primary study outcomes were overall survival (OS) and progression free survival (PFS).ResultsWe identified 145 patients receiving cCRT with a curative intent, 32% harbored an activating mutation in the KRAS gene (KRASMUT). Compared to KRAS wild-type (KRASWT), KRASMUThad a worse OS (p=0.047) and PFS (p=0.038). The finding persisted on multivariate analysis with OS (HR 1.703, 95%CI 1.074-2.702,p= 0.024) and PFS (HR 1.628, 95% CI 1.081-2.453,p= 0.020). After the addition of durvalumab to cCRT, there were no longer any significant differences between KRASWTand KRASMUTin OS or PFS.ConclusionsKRASmutations are a negative prognostic factor after cCRT in stage III NSCLC, and the addition of durvalumab equalizes the negative impact of harboring this mutation.
Long non-coding RNAs direct the SWI/SNF complex to cell-specific enhancers
Authors: Oo James A. , Warwick Timothy , Pálfi Katalin , McNicoll Francois , Cao Can , Prieto-Garcia Cristian , Zhou Yinuo , Gavrilov Alexey A. , Razin Sergey V. , Lam Frederike , Günther Stefan , Cabrera-Orefice Alfredo , Wittig Ilka , Pullamsetti Soni Savai , Kurian Leo , Gilsbach Ralf , Schulz Marcel H. , Dikic Ivan , Müller-McNicoll Michaela , Brandes Ralf P. , Leisegang Matthias S. 
Published: March 2024

AbstractThe coordination of chromatin remodeling is essential for DNA accessibility and gene expression control1. The highly conserved and ubiquitously expressed SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays a central role in cell type- and context-dependent gene expression2. Despite the absence of a defined DNA recognition motif, SWI/SNF binds lineage specific enhancers genome-wide where it actively maintains open chromatin state2–5. It does so while retaining the ability to respond dynamically to cellular signals4. However, the mechanisms that guide SWI/SNF to specific genomic targets have remained elusive. Here we demonstrate thattrans-acting long non-coding RNAs (lncRNAs) direct the SWI/SNF complex to cell type-specific enhancers. SWI/SNF preferentially binds lncRNAs and these predominantly bind DNA targets intrans. Together they localize to enhancers, many of which are cell type-specific. Knockdown of SWI/SNF- and enhancer-bound lncRNAs causes the genome-wide redistribution of SWI/SNF away from enhancers and a concomitant differential expression of spatially connected target genes. These lncRNA-SWI/SNF-enhancer networks support an enhancer hub model of SWI/SNF genomic targeting. Our findings reveal a competitive recruitment of SWI/SNF by lncRNAs which provide a specific and dynamic layer of control in chromatin accessibility and gene expression.
Base composition at the start of the coding sequence controls the balance between translation initiation and mRNA degradation inE. coli
Authors: Lipońska Anna , Monlezun Laura , Wilkins Isaac , Ngo Saravuth , Oïffer Thomas , Bouchachi Cylia , Hunt John F. , Aalberts Daniel P. , Boël Grégory 
Published: March 2024

AbstractProtein synthesis efficiency is highly dependent on mRNA coding sequence. Furthermore, there is extensive evidence of a correlation between mRNA stability and protein expression level, though the mechanistic determinants remain unclear. Using yellow fluorescent protein (YFP) as a reporter gene, we herein demonstrate that adenosine (A) abundance in the first six codons is a critical determinant for achieving high protein synthesis inE. coli. Increasing A and/or decreasing guanosine (G) content in this region results in substantial increases in protein expression level bothin vivoandin vitrothat are correlated with steady-state mRNA concentrationin vivo, and this effect is attributable to changes in the stability of the mRNA that are directly coupled to its translation efficiency. Increasing A content promotes mRNA incorporation into the functional 70S ribosomal initiation complex without altering its affinity for the 30S ribosomal subunit. These results support a model in which base composition in the first six codons modulates local mRNA folding energy to control the balance between productive translation initiationversusdegradation of mRNAs bound to the 30S ribosomal subunit. Based on these findings, we developed a short N-terminal coding sequence that optimizes translation initiation efficiency for protein production inE. coli.
Loss of KIF13B causes time-dependent changes in ciliary polycystin-2 levels and extracellular vesicle release
Authors: Rezi Csenge K. , Frei Alina , Campestre Fabiola , Berggreen Christina R. , Laplace Julie , Sicot Aurelien , Li Geyi , Johansen Søren L. , Sørensen Julie K. T. , Berchtold Martin W. , Chamlali Mohamed , Christensen Søren T. , Boldt Karsten , Anvarian Zeinab , May-Simera Helen L. , Pedersen Lotte B. 
Published: March 2024

AbstractThe polycystic kidney disease gene product polycystin-2 (PC2) localizes to and is released from primary cilia in extracellular vesicles (EVs). We report that KIF13B regulates ciliary EV release and PC2 levels in kidney epithelial cells in a time-dependent manner and show that KIF13B itself is released from the ciliary tip. In early stages of ciliation,Kif13b-/-cells displayed excessive ciliary accumulation of PC2 and initially released fewer small EVs than control cells. Over time, ciliatedKif13b-/-cells increased their small EV release rate to control levels, however proteomic analysis identified >50 proteins depleted from mutant EV samples. These included the ubiquitin E3 ligase ITCH and palmitoyl transferase ZDHHC5, which localized to primary cilia. MatureKif13b-/-cilia exhibited aberrant membrane bulges and decreased PC2 and ALIX, an ITCH substrate that negatively regulated ciliary PC2 levels. Our work provides new insight into the mechanisms of ciliary EV release, which is important for regulating ciliary membrane homeostasis and signalling function.
Inhibition of eukaryotic translation initiation factor 1A (eIF1A) and 3B (eIF3B) diminishes the psoriatic phenotype in two mouse models and human 3D model samples
Authors: Golob-Schwarzl Nicole , Pilic Johannes , Vrebo Azelma , Bordag Natalie , Shirsath Nitesh , Müller Christin-Therese , El-Heliebi Amin , Wolf Peter 
Published: March 2024

AbstractBackgroundPsoriasis is a systemic inflammatory disease for which new topical treatments are required. Psoriatic inflammation is associated with overexpression of eukaryotic translation initiation factors (eIFs), which critically regulate gene expression in many important cellular processes, including proliferation, apoptosis, and differentiation. However, the exact link between overexpression of eIF and psoriasis is unknown. Here, we investigated the role of eIFs, particularly eIF1A and eIF3B, and the impact of their inhibition on the pathophysiology of psoriasis.MethodsWe used two mouse models reflecting the pathophysiology of psoriasis: (i) BALB/c mice topically treated with the immune activator imiquimod (IMQ) and (ii) K5.TGFβ transgenic mice. eIF1A and eIF3B were inhibited by either topical or systemic application of specific small interfering RNA (siRNA). In addition, we employed commercial human 3D psoriatic skin model samples. Importantly,in situmRNA detection-based padlock probes against transcript variants of eIF1A und eIF3B was performed.ResultsTopical and systemic inhibition of eIF1A and eIF3B inhibited inflammation in both imiquimod and TGFß mouse models as well as in a human 3D psoriasis model. Downregulation of eIF1A and eIF3B was associated with normalization of cell proliferation, restoration of the inflammatory milieu and epidermal hyperplasia of psoriasis, and normalization of levels of proinflammatory cytokines (e.g., TNFα, IL-1b, IL-17, and IL-22) and keratinocyte differentiation markers (e.g., KRT16 and FLG).ConclusionThese results reveal an imbalance in translation and emphasize the crucial role of eIF1A and eIF3B in the pathophysiology of psoriasis. Targeting eIFs opens new avenues for the development of novel therapeutic treatment strategies against psoriasis.
Cell class-specific long-range axonal projections of neurons in mouse whisker-related somatosensory cortices
Authors: Liu Yanqi , Bech Pol , Tamura Keita , Délez Lucas T. , Crochet Sylvain , Petersen Carl C.H. 
Published: March 2024

AbstractThe extensive long-range axonal projections of diverse classes of neocortical excitatory neurons are thought to contribute importantly to the highly integrative brain-wide interactions underlying the processing of sensory, cognitive and motor signals. Here, we investigated the long-range axonal output of various classes of genetically-defined projection neurons with cell bodies located in the whisker-related somatosensory cortices of the mouse through brain-wide light-sheet imaging of fluorescently-labeled axons segmented by specifically-trained convolutional networks quantified within the Allen Mouse Brain Atlas Common Coordinate Framework. We injected Cre-dependent virus to express GFP or tdTomato in the posterior primary somatosensory barrel cortex and the posterior supplemental somatosensory cortex, which contain the representations of the large posterior mystacial whiskers. We investigated the six following transgenic mouse lines which preferentially express Cre in different glutamatergic neocortical cell classes: Rasgrf2-dCre for layer 2/3 intratelencephalic projection neurons, Scnn1a-Cre for layer 4 intratelencephalic projection neurons, Tlx3-Cre for layer 5 intratelencephalic projection neurons, Sim1-Cre for layer 5 pyramidal tract projection neurons, Rbp4-Cre for layer 5 projection neurons and Ntsr1-Cre for layer 6 corticothalamic neurons. We found long-range axonal projections in many diverse downstream brain areas with largely similar output from primary and secondary cortices, but with genetically-defined cell classes showing distinct innervation patterns, with Rbp4-Cre mice showing the broadest innervation targets, subsets of which were innervated in the other mouse lines. To test whether the revealed axonal projections might underpin functional circuits, we compared the spatial organization of the axonal innervation with functional connectivity maps obtained from optogenetic stimulation of sensory cortex and wide-field imaging of the activity propagation to frontal cortices. Both methods indicated that neurons located more laterally in somatosensory cortex topographically signaled to more anteriorly located regions in motor cortex. The current methodology therefore appears to quantify brain-wide axonal innervation patterns supporting brain-wide signaling, and, together with further technological advances, this will help provide increasingly detailed connectivity information of the mouse brain, essential for understanding the complex neuronal circuitry underlying even simple goal-directed behaviors.
Translational impacts of enzymes that modify ribosomal RNA around the peptidyl transferase centre
Authors: Bao Letian , Liljeruhm Josefine , Crespo Blanco Rubén , Brandis Gerrit , Remme Jaanus , Forster Anthony C. 
Published: March 2024

AbstractLarge ribosomal RNAs (rRNAs) are modified heavily post-transcriptionally in functionally-important regions but, paradoxically, individual knockouts (KOs) of the modification enzymes have minimal impact onEscherichia coligrowth. Furthermore, we recently constructed a strain with combined KOs of five modification enzymes (RluC, RlmKL, RlmN, RlmM and RluE) of the “critical region” of the peptidyl transferase center (PTC) in 23S rRNA that exhibited only a minor growth defect at 37°C (although major at 20°C). However, our combined KO of modification enzymes RluC and RlmE resulted in conditional lethality (at 20°C). Although the growth rates for both multiple-KO strains were characterized, the molecular explanations for such deficits remain unclear. Here, we pinpoint biochemical defects in these strains.In vitrofast kinetics at 20 and 37°C with ribosomes purified from both strains revealed, counterintuitively, the slowing of translocation, not peptide bond formation or peptidyl release. Rates of protein synthesisin vivo, as judged by the kinetics of β-galactosidase induction, were also slowed. For the five-KO strain, the biggest deficit at 37°C was in 70S ribosome assembly, as judged by a dominant 50S peak in ribosome sucrose gradient profiles at 5 mM Mg2+. Reconstitution of this 50S subunit from purified five-KO rRNA and ribosomal proteins supported a direct role in ribosome biogenesis of the PTC region modificationsper se, rather than of the modification enzymes. These results clarify the importance and roles of the enigmatic rRNA modifications.
The gases H2and O2in open-culture reactors influence the performance and microbiota of chain elongation inton-caproate andn-caprylate
Authors: Spirito Catherine M. , Lucas Timo N. , Patz Sascha , Jeon Byoung Seung , Werner Jeffrey J. , Trondsen Lauren H. , Guzman Juan J. , Huson Daniel H. , Angenent Largus T. 
Published: March 2024

AbstractMedium-chain carboxylates are used in various industrial applications. These chemicals are typically extracted from palm oil, which is deemed not sustainable. Recent research has focused on microbial chain elongation using reactors to produce medium-chain carboxylates, such asn-caproate (C6) andn-caprylate (C8), from organic substrates such as wastes. Even though the production ofn-caproate is relatively well-characterized, bacteria and metabolic pathways that are responsible forn-caprylate production are not. Here, three 5-L reactors with continuous membrane-based liquid-liquid extraction (i.e., pertraction) were fed ethanol and acetate and operated for an operating period of 234 days with different operating conditions. Metagenomic and metaproteomic analyses were employed.n-Caprylate production rates and reactor microbiomes differed between reactors even when operated similarly due to differences in H2and O2between the reactors. The complete reverse β-oxidation pathway was present and expressed by several bacterial species in theClostridiaclass. SeveralOscillibacterspp., includingOscillibacter valericigenes, were positively correlated withn-caprylate production rates, whileClostridium kluyveriwas positively correlated withn-caproate production.Pseudoclavibacter caeni, which is a strictly aerobic bacterium, was abundant across all the operating periods, regardless ofn-caprylate production rates. This study provides insight into microbiota that are associated withn-caprylate production in open-culture reactors and provides ideas for further work.ImportanceMicrobial chain elongation pathways in open-culture biotechnology systems can be utilized to convert organic waste and industrial side streams into valuable industrial chemicals. Here, we investigated the microbiota and metabolic pathways that produce medium-chain carboxylates, includingn-caproate (C6) andn-caprylate (C8), in reactors with in-line product extraction. Although the reactors in this study were operated similarly, different microbial communities dominated and were responsible for chain elongation. We found that different microbiota were responsible forn-caproate orn-caprylate production, and this can inform engineers on how to operate the systems better. We also observed which changes in operating conditions steered the production toward and away fromn-caprylate, but more work is necessary to ascertain a mechanistic understanding that could be predictive. This study provides pertinent research questions for future work.
Adherens junctions limit the extent of the septate junctions inDrosophilamidgut enterocytes but are not required for apical-basal polarity
Authors: Carvalho Cátia A. , Tame Mihoko , St Johnston Daniel 
Published: March 2024

AbstractAdherens junctions formed by E-cadherin adhesion complexes play central roles in the organisation and apical-basal polarisation of both mammalian and insect epithelia. Here we investigate the function of the components of the E-cadherin adhesion complex in theDrosophilamidgut epithelium, which establishes polarity by a different mechanism from other fly epithelia and has an inverted junctional arrangement, in which the adherens junctions lie below the septate junctions. Unlike other epithelial tissues, loss of E-cadherin, Armadillo (β-catenin) or α-catenin has no effect on the polarity or organisation of the adult midgut epithelium. This is not due to redundancy with N-cadherin, providing further evidence that the midgut polarises in distinct way from other epithelia. However,E-cadherin(shg) andarmadillomutants have an expanded septate junction domain and a smaller lateral domain below the septate junctions. Thus, E-cadherin adhesion complexes limit the basal extent of the septate junctions. This function does not appear to depend on the linkage of E-cadherin to the actin cytoskeleton because α-catenin mutants do not significantly perturb the relative sizes of the septate and sub-septate junction domains.
Phase transition kinetics revealed by
in situ
x-ray diffraction in laser-heated dynamic diamond anvil cells
Authors: Ricks Matthew , Gleason Arianna E. , Miozzi Francesca , Yang Hong , Chariton Stella , Prakapenka Vitali B. , Sinogeikin Stanislav V. , Sandberg Richard L. , Mao Wendy L. , Pandolfi Silvia 
Published: March 2024

We report successful coupling of dynamic loading in a diamond anvil cell and stable laser heating, which enables compression rates up to 500 GPa/s along high-temperature isotherms. Dynamic loading in a diamond-anvil cell allows exploration of a wider range of pathways in the pressure-temperature space compared to conventional dynamic compression techniques. By x-ray diffraction, we are able to characterize and monitor the structural transitions with the appropriate time resolution i.e., millisecond timescales. Using this method, we investigate the γ−ε phase transition of iron under dynamic compression, reaching compression rates of hundreds of GPa/s and temperatures of 2000 K. Our results demonstrate a distinct response of the γ−ε and α−ε transitions to the high compression rates achieved, possibly due to the different transition mechanisms. These findings open up new avenues to study tailored dynamic compression pathways in the pressure-temperature space and highlight the potential of this platform to capture kinetic effects (over ms time scales) in a diamond anvil cell.

Published by the American Physical Society
2024