bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vidian Canal in Chiari Type I Malformation: A Computed Tomography Study
Authors: Kilinç Mustafa Cemil , Zaimoglu Murat , Eroglu Umit , Özpişkin Ömer Mert , Erdin Engin , Güngör Berkay , Beger Orhan 
Published: August 2024

Objective:
To evaluate the position and dimension of the Vidian canal (VC) in Chiari type I malformation (CIM).

Materials and Methods:
Radiologic views of 49 CIM (mean age: 23.58±15.62 y, sex: 23 males/26 females) and 51 healthy subjects (mean age: 42.50±20.12 y, sex: 21 males/30 females) were included in this computed tomography study.

Results:
In comparison with controls, the VC angle and the distance of the round foramen to VC were greater in CIM, but VC length and the distances of the superior wall of the bony sphenoidal sinus, midsagittal plane, and vomerine crest to VC were smaller in CIM. Relative to the sphenoid bone, the position of VC in CIM was determined as type 1 (59.2%) >type 2 (28.6%) >type 3 (12.2%), whereas in controls as type 1 (54.9%) >type 3 (25.5%) >type 2 (19.6%). Relative to the medial pterygoid plate, the position of VC in CIM was determined as type A (63.3%) >type B (20.4%) >type C (16.3%), while in controls as type B (43.1%) >type A (40.2%) >type C (16.7%).

Conclusion:
VC size and position correlated with CIM. Compared with controls, CIM patients had more partially protruded VC into the bony sphenoidal sinus and more medially located VC according to the medial pterygoid plate.
Discovery of Novel, Potent and Orally Bioavailable SMARCA2 PROTACs with Synergistic Anti-tumor Activity in Combination with KRAS G12C Inhibitors
Authors: Kotagiri Sasikumar , Wang Yawen , Han Yanyan , Liang Xiaobing , Blazanin Nicholas , Nguyen Phuong Kieu , Jiang Yongying , Lissanu Yonathan 
Published: August 2024

ABSTRACTCancer genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex includingSMARCA4in non-small cell lung cancer with a frequency of up to 33% in advanced stage disease, making it the most frequently mutated complex in lung cancer. We and others have identifiedSMARCA2to be synthetic lethal toSMARCA4,indicating SMARCA2 is a high value therapeutic target. Here, we disclose the discovery and characterization of potent, selective and orally bioavailable Cereblon-based SMARCA2 PROTACs. Biochemically, YDR1 and YD54 are potent SMARCA2 degraders with an average DC50of 7.7nM and 3.5nM respectively inSMARCA4mutant lung cancer cells. Phenotypically, both YDR1 and YD54 selectively inhibited growth ofSMARCA4mutant cancer cells. Further, we showed anti-tumor growth inhibitory activity of YDR1 and YD54 inSMARCA4mutant xenograft models of lung cancer. Finally, we show that YDR1 and YD54 synergize with the KRAS G12C inhibitor sotorasib to inhibit growth ofSMARCA4andKRAS G12Cco-mutant lung cancer cells. These findings provide additional evidence for the utility of single agent or combination regimens containing SMARCA2 PROTACs as synthetic lethal therapeutics againstSMARCA4mutant cancers.
Playtime for Cephalopods: Understanding the Significance of Play Behavior in Octopus bimaculoides
Authors: Jarmoluk Katarina , Pelled Galit 
Published: August 2024

AbstractPlay is considered to be an essential part of development that supports learning, memory, and the development of flexible behavioral strategies. An increasing amount of non-mammalian species have been discovered to engage in play behavior, but there has been little research into play behavior in cephalopods specifically. Here we studied play behavior of wild-caught, laboratory-housed California Two-Spot Octopuses,Octopus bimaculoides. The behavior observed in these animals is consistent with established criteria of play behavior in animals. The evidence of play inO. bimaculoidesprovides further insight into the evolutionary development of play behavior as a whole, the characteristics of play in an under-studied species, and also has the potential to be used as a factor in determining the welfare state of octopuses to improve their management in captivity.
Cluster Buster: A Machine Learning Algorithm for Genotyping SNPs from Raw Data
Authors: Martin Jessica , Kuznetsov Nicole , Levine Kristin , Koretsky Mathew J. , Hong Samantha , Nalls Mike A. , Vitale Dan 
Published: August 2024

AbstractGenotyping single nucleotide polymorphisms (SNPs) is fundamental to disease research, as researchers seek to establish links between genetic variation and disease. Although significant advances in genome technology have been made with the development of bead-based SNP genotyping and Genome Studio software, some SNPs still fail to be genotyped, resulting in “no-calls” that impede downstream analyses. To recover these genotypes, we introduce Cluster Buster, a genotyping neural network and visual inspection system designed to improve the quality of neurodegenerative disease (NDD) research. Concordance analysis with whole genome sequencing (WGS) and imputed genotypes validated the reliability of predicted genotypes, with dozens of high-performing SNPs acrossLRRK2, APOE, andGBAloci achieving at least 90% concordance per SNP location. Further analysis of concordance between Genome Studio genotypes and imputed and WGS genotypes revealed discrepancies between the genotyping technologies, highlighting the need for selective application of Cluster Buster on SNP locations based on concordance rates. Cluster Buster’s implementation significantly reduces manual labor for recovering no-call SNPs, refining genotype quality for the Global Parkinson’s Genetics Program (GP2). This system facilitates better imputation and GWAS outcomes, ultimately contributing to a deeper understanding of genetic factors in NDDs.
Single-molecule diffusivity quantification inXenopusegg extracts elucidates physicochemical properties of the cytoplasm
Authors: Choi Alexander A. , Zhou Coral Y. , Tabo Ayana , Heald Rebecca , Xu Ke 
Published: August 2024

AbstractThe living cell creates a unique internal molecular environment that is challenging to characterize. By combining single-molecule displacement/diffusivity mapping (SMdM) with physiologically active extracts prepared fromXenopus laeviseggs, we sought to elucidate molecular properties of the cytoplasm. Quantification of the diffusion coefficients of 15 diverse proteins in extract showed that, compared to in water, negatively charged proteins diffused ∼50% slower, while diffusion of positively charged proteins was reduced by ∼80-90%. Adding increasing concentrations of salt progressively alleviated the suppressed diffusion observed for positively charged proteins, signifying electrostatic interactions within a predominately negatively charged macromolecular environment. To investigate the contribution of RNA, an abundant, negatively charged component of cytoplasm, extracts were treated with ribonuclease, which resulted in low diffusivity domains indicative of aggregation, likely due to the liberation of positively charged RNA-binding proteins such as ribosomal proteins, since this effect could be mimicked by adding positively charged polypeptides. Interestingly, negatively charged proteins of different sizes showed similar diffusivity suppression in extract, which are typically prepared under conditions that inhibit actin polymerization. Restoring or enhancing actin polymerization progressively suppressed the diffusion of larger proteins, recapitulating behaviors observed in cells. Together, these results indicate that molecular interactions in the crowded cell are defined by an overwhelmingly negatively charged macromolecular environment containing cytoskeletal networks.Significance StatementThe complex intracellular molecular environment is notably challenging to elucidate and recapitulate.Xenopusegg extracts provide a native yet manipulatable cytoplasm model. Through single-molecule microscopy, here we decipher the cytoplasmic environment and molecular interactions by examining the diffusion patterns of diverse proteins inXenopusegg extracts with strategic manipulations. These experiments reveal an overwhelmingly negatively charged macromolecular environment with crosslinked meshworks, offering new insight into the inner workings of the cell.
Improvement of Spontaneous Locomotor Activity in a Murine Model of Duchenne Muscular Dystrophy by N-Acetylglucosamine Alone and in Combination with Prednisolone
Authors: Satoh Masahiko. S. , St-Pierre Guillaume , Rancourt Ann , Fillion Maude , Sato Sachiko 
Published: August 2024

AbstractN-acetylglucosamine (GlcNAc) is an endogenous compound whose intracellular concentration is closely associated with the biosynthesis of acetyllactosamine-rich N-linked oligosaccharides. These oligosaccharides interact with mammalian lectin galectin-3, mediating cell surface receptor dynamics as well as cell-to-cell and cell-to-extracellular matrix interactions. Our previous and recent studies suggest that GlcNAc, in conjunction with galectin-3, augments muscle regenerationin vitro. We have also demonstrated that intraperitoneal GlcNAc administration improves muscle strength in a murine model of Duchenne muscular dystrophy (DMD) (mdxmice). Here, we show that oral administration of GlcNAc significantly improves the spontaneous locomotor activity of mdx mice. Administering GlcNAc at concentrations of 0.6, 1.2, 1.8, and 2.4 g/kg body weight per day for 35 days significantly improved nocturnal spontaneous locomotor activity at all those doses, with the 1.2 g/kg body weight dose reducing damages of extensor digitorum longus muscle by nearly 50%. While consecutive forced exercises, including horizontal and downhill treadmill running, reduced GlcNAc-promoted locomotor activity, treatment with 0.6 and 1.2 g/kg body weight treatment results in increased spontaneous locomotor activity. These results suggest that GlcNAc enhances overall muscle health, likely through promoting muscle repair/regeneration rather than preventing damage formation. Notably, co-administration of GlcNAc with prednisolone, a corticosteroid commonly used in DMD patients, further enhanced spontaneous locomotor improvement inmdxmice compared to prednisolone alone. These findings suggest that GlcNAc has the potential to improve the clinical status of DMD patients, either as a monotherapy or in combination with corticosteroids.
Simultaneous GCaMP imaging and focal recording of tonic and phasic synapses: Probing short-term plasticity within a defined microenvironment
Authors: Xing Xiaomin , Wu Chun-Fang 
Published: August 2024

AbstractKey point summaryWe developed a protocol for stable simultaneous focal recording and GCaMP imaging on identified motor synaptic boutons in theDrosophilaneuromuscular preparation with minimized muscular movements in extended concentration ranges of extracellular Ca2+and Sr2+.This approach directly demonstrated temporal correlation between the dynamics of cytosolic residual Ca2+and activity-dependent synaptic plasticity in tonic and phasic synapses.Our data demonstrated presynaptic GCaMP signals markedly lagged behind and poorly correlated with the concurrent transmitter release, but reliably indicated the immediate states of short-term plasticity. GCaMP’sphysical-chemicalproperties allow information extraction on cytosolic Ca2+levels during facilitation and depression phases.The decay phase of GCaMP signal often coincided with lingering vesicular releases after stimulation, more pronounced in phasic than tonic synapses and exaggerated in Sr2+-containing saline. Lingering releases were coupled with the tendency of asynchronous transmission.GCaMP fluorescence has been widely used to monitor intracellular Ca2+. However, the physiological significance of the GCaMP signal in presynaptic terminals remains to be further elucidated. We investigated how the dynamics of GCaMP signals correlates with the activity dependence of short-term plasticity in synaptic transmission. We devised a local manipulation protocol that minimizes interference from muscular contraction during simultaneous Ca2+imaging and focal recording at theDrosophilalarval neuromuscular junction (NMJ), where the tonic and phasic excitatory synapses can be compared side-by-side. By confining the local ionic microenvironment, this protocol enabled stable measurements across extended concentration ranges of Ca2+or Sr2+in saline. Compared to tonic synapses, phasic synapses displayed stronger GCaMP signals, along with faster facilitation and more severe depression. Upon repetitive stimulation (40 Hz), facilitation of transmission occurred during or immediately prior to the early rising phase (0.25 s) of the GCaMP signal, which could subsequently convert into a depression phase of transmission decline, most evident during a steeper and longer rise of GCaMP signals in higher Ca2+saline. Typically, deepest depression occurred when GCaMP signals rose to a plateau. Phasic synapses with stronger GCaMP signal and deeper depression, more often exhibited lingering post-stimulation releases. In both tonic and phasic synapses, replacing Ca2+with Sr2+induced extreme asynchronous transmission coupled with post-stimulation lingering releases during the decay of GCaMP signals. Further applications of this focal recording-local manipulation protocol may help to probe additional mechanisms underlying synaptic transmission and plasticity.
Proteome structuring of crown-of-thorns starfish
Authors: Yunchi Zhu , Zuhong Lu 
Published: August 2024

AbstractThis data report presents the proteome structuring of the crown-of-thorns starfish (COTS,Acanthaster planci) using the ColabFold system. The resulting dataset includes 31,743 predicted protein structures, covering 60.4% of residues with confident predictions and 35.5% with very high confidence. A preliminary structural bioinformatics analysis was conducted using post-AlphaFold methods, including fast structure clustering, ligand transplanting, and structure-based Gene Ontology (GO) annotation, which identified potential functions for previously uncharacterized proteins. These findings contribute to a deeper understanding of COTS biology and provide valuable data for developing biocontrol methods to mitigate the impact of COTS outbreaks on coral reefs.
Actin Polymerization Status Regulates Tendon Homeostasis through Myocardin-Related Transcription Factor-A
Authors: West Valerie C. , Owen Kaelyn , Inguito Kameron L. , Ebron Karl Matthew M. , Reiner Tori , Mirack Chloe E. , Le Christian , Marqueti Rita de Cassia , Snipes Steven , Mousavizadeh Rouhollah , Elliott Dawn M. , Parreno Justin 
Published: August 2024

AbstractThe actin cytoskeleton is a potent regulator of tenocyte homeostasis. However, the mechanisms by which actin regulates tendon homeostasis are not entirely known. This study examined the regulation of tenocyte molecule expression by actin polymerization via the globular (G-) actin-binding transcription factor, myocardin-related transcription factor-a (MRTF). We determined that decreasing the proportion of G-actin in tenocytes by treatment with TGFβ1 increases nuclear MRTF. These alterations in actin polymerization and MRTF localization coincided with favorable alterations to tenocyte gene expression. In contrast, latrunculin A increases the proportion of G-actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis-like phenotype. To parse out the effects of F-actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Similar to latrunculin A treatment, exposure of cells to cytochalasin D increases the proportion of G-actin in tenocytes. However, unlike latrunculin A treatment, cytochalasin D increases nuclear MRTF. Compared to latrunculin A treatment, cytochalasin D led to opposing effects on the expression of a subset of genes. The differential regulation of genes by latrunculin A and cytochalasin D suggests that actin signals through MRTF to regulate a specific subset of genes. By targeting the deactivation of MRTF through the inhibitor CCG1423, we verify that MRTF regulates Type I Collagen, Tenascin C, Scleraxis, and α-smooth muscle actin in tenocytes. Actin polymerization status is a potent regulator of tenocyte homeostasis through the modulation of several downstream pathways, including MRTF. Understanding the regulation of tenocyte homeostasis by actin may lead to new therapeutic interventions against tendinopathies, such as tendinosis.
Sustainablein situextraction of microalgae-derived terpenoids using functionalized silica microparticles
Authors: Overmans Sebastian , Gallo Adair , Mishra Himanshu , Lauersen Kyle J. 
Published: August 2024

AbstractChlamydomonas reinhardtiiis a green microalga that has been genetically engineered to produce heterologous terpenoid metabolites. While this green biochemical approach for producing high-value chemicals holds tremendous potential, the currentin situextraction methods, utilizing traditional solvents such as dodecane and perfluorinated chemicals, present separation challenges, unfavorable economics, and risk of cell toxicity. Here, we develop a low-cost solvent-free approach based on silanized silica particles to fill the technology gap. We determine the feasibility and specificity of three differently coated (C11, C16, C18) silica particles to extract nine terpenoid metabolites fromC. reinhardtiicultures during cultivation. The results reveal that the extraction efficiencies of functionalized particles, particularly those coated with C18, demonstrated high potential as an alternative to traditional extraction methods. While the extraction efficiencies of coated microparticles are for most compounds lower than those observed for dodecane-based extractions, it holds higher potential for larger-scale cultivations where the use of dodecane is restricted due to its flammability and tendency to form emulsions. In addition, the present study provides insights into the optimization of particle-to-culture volume ratio, particle saturation, and the required number of product elution steps, and proves the feasibility of an upscaled extraction of the sesquiterpenoid patchoulol as a representative metabolite in 5 L hanging bag reactors. This study paves the way for a circular bioprocess where product capture with traditional solvent overlays is impractical due to the formation of emulsions, and at the same time allows for an easy product recovery (solid-liquid separation) and reuse of functionalized particles over numerous cycles.
Women’s experiences and acceptability of self-administered, home delivered, intravaginal 5-Fluorouracil cream for cervical precancer treatment in Kenya
Authors: Adewumi Konyin , Kachoria Aparna Ghosh , Adoyo Everlyn , Rop Mercy , Owaya Antony , Tang Jennifer H , Rahangdale Lisa , Mungo Chemtai 
Published: August 2024

ABSTRACTBACKGROUNDInnovative strategies are essential to meet the World Health Organization’s 90/70/90 cervical cancer elimination targets, aiming for 90% access to precancer treatment globally by 2030. In low-and middle-income countries (LMICs) where most cervical cancer cases occur, access to precancer treatment is severely limited. Scalable solutions like self-administered topical therapies can help close this gap. In a recent Phase I trial (ClinicalTrials.govNCT05362955), we demonstrated safety and adherence to self-administered intravaginal 5% 5-Fluorouracil (5FU) cream as an adjuvant therapy for cervical precancer among women living with HIV (WLWH) in rural Kenya. To understand women’s experiences with self-administered 5FU, we evaluated the acceptability of this intervention among trial participants.METHODSAll 12 participants from the Phase I trial completed a structured questionnaire and in-depth semi-structured interviews in their preferred language, focusing on their experiences with 5FU self-administration, challenges faced, and overall acceptability of the intervention, including whether they would use it again or recommend it to someone who needed it. Quantitative data were analyzed using descriptive statistics. In the qualitative study, acceptability was defined as “the perception that a given treatment is agreeable, palatable, or satisfactory.” A thematic analysis was conducted using five dimensions of acceptability: content, complexity, comfort, delivery, and credibility.RESULTSThe mean age was 43.9 years (SD 4.4), and seven (58%) had primary education or less. While some participants reported feelings of uncertainty when they started using 5FU, at the end of the study, all 12 participants strongly agreed that the cream was safe and were confident they used it correctly. Most participants (91.7%) experienced no discomfort with the vaginal applicator, and most reported using tampons overnight after 5FU use, as recommended. Qualitative findings revealed that favorable perceptions of self-administered 5FU were driven by its ease of use, the discrete nature of the treatment, and the comfort of home application. The main challenges included correctly measuring the study drug, finding a private place at home to self-administer, and the need to use condoms during treatment. Compared to their previous ablation or excision treatments, participants found 5FU to be less painful, and all would prefer a self-administered treatment instead of a procedure if it were an option.CONCLUSIONSelf-administered intravaginal 5FU as an adjuvant treatment for cervical precancer among women living with HIV in Kenya was highly acceptable. Randomized studies of 5FU and other topical therapies in LMICs are needed to evaluate their use in closing the current precancer treatment gaps in these settings.
Cross-Institutional European Evaluation and Validation of Automated Multilabel Segmentation for Acute Intracerebral Hemorrhage and Complications
Authors: Nawabi Jawed , Baumgärtner Georg Lukas , Schulze-Weddige Sophia , Dell’Orco Andrea , Morotti Andrea , Mazzacane Federico , Kniep Helge , Schlunk Frieder , Böhmer Maik FH , Akkurt Burak Han , Orth Tobias , Sofie Weissflog Jana , Schumann Maik , Sporns Peter B. , Scheel Michael , Hanning Uta , Fiehler Jens , Penzkofer Tobias 
Published: August 2024

AbstractPurposeTo evaluate a nnU-Net-based deep learning for automated segmentation of intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and perihematomal edema (PHE) on noncontrast CT scans.Materials and MethodsRetrospective data from acute ICH patients admitted at four European stroke centers (2017-2019), along healthy controls (2022-2023), were analyzed. nnU-Net was trained (n=775) using a 5-fold cross-valiadtion approach, tested (n=189), and seperatly validated on internal (n=121), external (n=169), and diverse ICH etiologies (n=175) datasets. Interrater-validated ground truth served as the reference standard. Lesion detection, segmentation, and volumetric accuracy were measured, alongside time efficiency versus manual segmentation.ResultsTest set results revealed high nnU-Net accuracy (median Dice Similartiy Coefficient (DSC): ICH 0.91, IVH 0.76, PHE 0.71) and volumetric correlation (ICH, IVH: r=0.99; PHE: r=0.92). Sensitivities were high (ICH, PHE: 99%; IVH: 97%), with IVH detection specificities and sensitivities >90% for volumes up to 0.2 ml. Anatomical-specific metrics showed higher performance for lobar and deep hemorrhages (median DSC 0.90 and 0.92, respectively) and lower for brainstem (median DSC 0.70). Concurrent hemorrhages did not affect accuracy, p> 0.05. Across validation sets, segmentation precision was consistent, especially for ICH (median DSC 0.85-0.90), with PHE slightly lower (median DSC 0.61-0.66) and IVH best in the second and third set (median DSC 0.80). Average processing time was 18.2 seconds versus 18.01 minutes manually.ConclusionThe nnU-Net provides reliable, time-efficient ICH, IVH, and PHE segmentation, validated across various clinical settings, with excellent anatomical-specific performance for lobar and deep hemorrhages. It shows promise for enhancing clinical workflow and research initiatives.