bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histopathological Evaluation of Bipolar and Microneedle Radiofrequency Energy on the Skin and Fat of the Abdominal Region of the Rat
Authors: Gelbal Caner , Tatar Burak Ergün , Yilmaz Bengi , Uyanikgil Yiğit , Tomruk Canberk , Bozkurt Mehmet 
Published: April 2024

Background:
Radiofrequency-based devices are used frequently in plastic surgery procedures. In the current literature, no comparative experimental study has demonstrated the histologic and immunologic effects of these devices, which are used frequently in the facial area. In this study, the authors investigated the histologic and immunologic effects of bipolar radiofrequency (BodyTite) and microneedle radiofrequency (Morpheus 8) devices in the rat abdominal region.

Methods:
A total of 24 rats were used in this study. The rats were divided into 4 groups: controls (group 1), BodyTite applied to the abdominal region (group 2), Morpheus 8 applied to the abdominal region (group 3), and both Morpheus 8 and BodyTite applied to the abdominal region (group 4). The histologic and immunologic features of the tissues, collagen formation, and desmosome structures were examined using light microscopy.

Results:
Collagens in group 2 were thinner than those in the other groups. In addition, there were fewer vessels in group 3. The collagen scores were as follows: group 2, 1.5; group 3, 2; and group 4, 3. Vascular endothelial growth factor scores were 2.5 in group 2, 2 in group 3, and 3 in group 4. The collagen score in group 2 and vascular endothelial growth factor score in group 3 were significantly lower than in the other groups. In addition, the bonds between desmosomes in group 3 were found to be looser using electron microscopy. Collagen morphology in groups 3 and 4 was found to be similar to that in group 1.

Conclusion:
Radiofrequency-based devices increased tissue regeneration and healing.

Clinical Relevance Statement:
The use of radiofrequency devices has increased in plastic surgery practice over the past 2 decades, particularly emerging as a unique alternative for nonsurgical candidates. There is a lack of experimental studies concerning these devices, which are commonly used in clinical practice.
Reducing False-Positives Due to Urinary Stagnation in the Prostatic Urethra on 18F-DCFPyL PSMA PET/CT With MRI
Authors: Gelikman David G. , Mena Esther , Lindenberg Liza , Azar William S. , Rathi Nityam , Yilmaz Enis C. , Harmon Stephanie A. , Schuppe Kyle C. , Hsueh Jessica Y. , Huth Hannah , Wood Bradford J. , Gurram Sandeep , Choyke Peter L. , Pinto Peter A. , Turkbey Baris 
Published: April 2024

Purpose
Prostate-specific membrane antigen (PSMA)–targeting PET radiotracers reveal physiologic uptake in the urinary system, potentially misrepresenting activity in the prostatic urethra as an intraprostatic lesion. This study examined the correlation between midline 18F-DCFPyL activity in the prostate and hyperintensity on T2-weighted (T2W) MRI as an indication of retained urine in the prostatic urethra.

Patients and Methods
Eighty-five patients who underwent both 18F-DCFPyL PSMA PET/CT and prostate MRI between July 2017 and September 2023 were retrospectively analyzed for midline radiotracer activity and retained urine on postvoid T2W MRIs. Fisher's exact tests and unpaired t tests were used to compare residual urine presence and prostatic urethra measurements between patients with and without midline radiotracer activity. The influence of anatomical factors including prostate volume and urethral curvature on urinary stagnation was also explored.

Results
Midline activity on PSMA PET imaging was seen in 14 patients included in the case group, whereas the remaining 71 with no midline activity constituted the control group. A total of 71.4% (10/14) and 29.6% (21/71) of patients in the case and control groups had urethral hyperintensity on T2W MRI, respectively (P < 0.01). Patients in the case group had significantly larger mean urethral dimensions, larger prostate volumes, and higher incidence of severe urethral curvature compared with the controls.

Conclusions
Stagnated urine within the prostatic urethra is a potential confounding factor on PSMA PET scans. Integrating PET imaging with T2W MRI can mitigate false-positive calls, especially as PSMA PET/CT continues to gain traction in diagnosing localized prostate cancer.
Activity-driven trafficking of endogenous synaptic proteins through proximity labeling
Authors: Pascual-Caro Carlos , de Juan-Sanz Jaime 
Published: April 2024

AbstractTo enable transmission of information in the brain, synaptic vesicles fuse to presynaptic membranes, liberating their content and exposing transiently a myriad of vesicular transmembrane proteins. However, versatile methods for quantifying the synaptic translocation of endogenous proteins during neuronal activity remain unavailable, as the fast dynamics of synaptic vesicle cycling difficult specific isolation trafficking proteins during such a transient surface exposure. Here we developed a novel approach using synaptic cleft proximity labeling to capture and quantify activity-driven trafficking of endogenous synaptic proteins at the synapse. We show that accelerating cleft biotinylation times to match the fast dynamics of vesicle exocytosis allows capturing endogenous proteins transiently exposed at the synaptic surface during neural activity, enabling for the first time the study of the translocation of nearly every endogenous synaptic protein. As proof-of-concept, we further applied this technology to obtain direct evidence of the surface translocation of non-canonical trafficking proteins, such as ATG9A and NPTX1, which had been proposed to traffic during activity but for which direct proof had not yet been shown. The technological advancement presented here will facilitate future studies dissecting the molecular identity of proteins exocytosed at the synapse during activity, helping to define the molecular machinery that sustains neurotransmission in the mammalian brain.Significance statementSynaptic trafficking is critical for neurons to communicate and sustain brain function. Pascual-Caro and de Juan-Sanz develop a pioneering method to enable the study of the activity-driven translocation of any endogenous synaptic protein. Coordinating neuronal activity and proximity labeling at synaptic clefts during just a few seconds, the authors visualize the trafficking of endogenous synaptic vesicle proteins and non-canonical trafficking proteins at the synapse. This work provides a technological framework to uncover the complex molecular choreography of translocation events occurring within firing synapses, enabling a deeper study of the molecular control of neuronal communication and circuit physiology in the brain.
LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironment
Authors: Reina Jeffrey , Vallmajo-Martin Queralt , Ning Jia , Michi Aubrey N. , Yeung Kay , Wahl Geoffrey M. , Hunter Tony 
Published: April 2024

AbstractTriple-negative breast cancer (TNBC) is a highly aggressive and metastatic form of breast cancer that lacks an effective targeted therapy. To identify new therapeutic targets, we investigated the phosphohistidine phosphatase, LHPP, which has been implicated in the development of several types of cancer. However, the full significance of LHPP in cancer progression remains unclear due to our limited understanding of its molecular mechanism. We found that levels of the LHPP phosphohistidine phosphatase were significantly increased in human breast cancer patients compared to normal adjacent tissues, with the highest levels in the TNBC subtype. When LHPP was knocked out in the MDA-MB-231 human TNBC cell line, cell proliferation, wound healing capacity, and invasion were significantly reduced. However, LHPP knockout in TNBC cells did not affect the phosphohistidine protein levels. Interestingly, LHPP knockout in MDA-MB-231 cells delayed tumor growth and reduced metastasis when orthotopically transplanted into mouse mammary glands. To investigate LHPP’s role in breast cancer progression, we used next-generation sequencing and proximity-labeling proteomics, and found that LHPP regulates gene expression in chemokine-mediated signaling and actin cytoskeleton organization. Depletion of LHPP reduced the presence of tumor-infiltrating macrophages in mouse xenografts. Our results uncover a new tumor promoter role for LHPP phosphohistidine phosphatase in TNBC and suggest that targeting LHPP phosphatase could be a potential therapeutic strategy for TNBC.
No evidence that visual impulses enhance the readout of retrieved long-term memory contents from EEG activity
Authors: van Bree Sander , Mackenzie Abbie Sarah , Wimber Maria 
Published: April 2024

AbstractThe application of multivariate pattern analysis (MVPA) to electroencephalography (EEG) data allows neuroscientists to track neural representations at temporally fine-grained scales. This approach has been leveraged to study the locus and evolution of long-term memory contents in the brain, but a limiting factor is that decoding performance remains low. A key reason for this is that processes like encoding and retrieval are intrinsically dynamic across trials and participants, and this runs in tension with MVPA and other techniques that rely on consistently unfolding neural codes to generate predictions about memory contents. The presentation of visually perturbing stimuli may experimentally regularize brain dynamics, making neural codes more stable across measurements to enhance representational readouts. Such enhancements, which have repeatedly been demonstrated in working memory contexts, remain to our knowledge unexplored in long-term memory tasks. In this study, we evaluated whether visual perturbations—orpings—improve our ability to predict the category of retrieved images from EEG activity during cued recall. Overall, our findings suggest that while pings evoked a prominent neural response, they did not reliably produce improvements in MVPA-based classification across several analyses. We discuss possibilities that could explain these results, including the role of experimental and analysis parameter choices and mechanistic differences between working and long-term memory.
Structural visualisation of the dynamics of DNA unwinding by a replicative helicase
Authors: Shahid Taha , Tehseen Muhammad , Alhudhali Lubna , Clark Alice , Savva Christos G. , Hamdan Samir M. , De Biasio Alfredo 
Published: April 2024

AbstractRing-shaped hexameric helicases are nucleotide hydrolases that unwind double-stranded DNA into single strands, a necessary step in DNA replication. Two main questions are critical to understanding their function: the location of DNA strand separation within the helicase, and the precise dynamic linkage between nucleotide hydrolysis and DNA translocation. We explore these questions by employing cryo-EM to visualize the translocation mechanics of a AAA+ helicase, the SV40 Large Tumor Antigen (LTag), on forked DNA. We find the DNA fork nexus is positioned deep within the core helicase domain, with each DNA-binding loop from the six subunits securing the tracking strand by forming a paired staircase spiral that substitutes the passive strand. This structure forges an internal separation wedge, channeling the passive strand through a gap in the subunit C-tiers at the back of the helicase. Via cryo-EM continuous heterogeneity analysis we capture, and exhaustively model, a seamless spectrum of conformations of translocating LTag at high resolution. ATP hydrolysis at the tightest inter-subunit interface operates like an ‘entropy switch’, triggering coordinated rigid-body rotations of the subunit C-tiers and DNA-binding loops, resulting in directional escorting of the tracking strand through the central channel, concomitantly setting preparatory steps for cycle restart. Overall, we demonstrate a dynamic model for hydrolysis-coupled translocation and DNA unwinding by a model helicase active in replication, with implications for origin unwinding. High structural conservation of core helicase regions suggests this mechanism is applicable to hexameric helicases across domains.
Blocking uncertain mispriming errors of PCR
Authors: Takahashi Takumi , Aoyanagi Hiroyuki , Pigolotti Simone , Toyabe Shoichi 
Published: April 2024

The polymerase chain reaction (PCR) plays a central role in genetic engineering and is routinely used in various applications, from biological and medical research to the diagnosis of viral infections. PCR is an extremely sensitive method for detecting target DNA sequences, but it is substantially error-prone. In particular, the mishybridization of primers to contaminating sequences can result in false positives for virus tests. The blocker method, also called the clamping method, has been developed to suppress mishybridization errors. However, its application is limited by the requirement that the contaminating template sequence must be known in advance. Here, we demonstrate that a mixture of multiple blocker sequences effectively suppresses the amplification of contaminating sequences even in the presence of uncertainty. The blocking effect was characterized by a simple model validated by experiments. Furthermore, the modeling allowed us to minimize the errors by optimizing the blocker concentrations. The results highlighted an inherent robustness of the blocker method, in that fine-tuning of the blocker concentrations is not necessary. Our method extends the applicability of PCR and other hybridization-based techniques, including genome editing, RNA interference, and DNA nanotechnology, by improving their fidelity.SignificanceThe applications of PCR are increasing day by day, and there is a need to suppress PCR errors to improve the accuracy of PCR-based techniques and broaden their applicability. The blocker method has been developed to substantially suppress mispriming. However, the method requires prior knowledge of the contaminating sequence, which limits its applicability. We successfully demonstrate that adding a combination of multiple blocker sequences can substantially suppress PCR errors, even when we have only partial information about the contaminating sequences. We also construct a biophysical model of the blocking effect, which allows us to find the optimal blocker combinations that minimize the PCR error. Since the method targets hybridization, it is readily applicable to a wide range of biotechnologies.
Antigen affinity and site of immunization dictate B cell recall responses
Authors: Termote M. , Marques R. C. , Hyllner E. , Guryleva M. V. , Henskens M. , Brutscher A. , Baken I.J.L. , Dopico X. Castro , Gasull A. Dalmau , Murrell B. , Stamatatos L. , Westerberg L. S. , Dosenovic P. 
Published: April 2024

SummaryProtective antibodies against HIV-1 require unusually high levels of somatic hypermutations (SHMs) introduced in germinal centers (GCs). To achieve this, a sequential vaccination approach was proposed. Using HIV-1 antibody knock-in mice with fate-mapping genes, we examined if antigen affinity affects the outcome of the B cell recall response. Compared to high affinity boost, low affinity boost resulted in decreased numbers of memory-derived B cells in secondary GCs, but with higher average SHM, indicating an affinity threshold for memory B cells to enter secondary GCs. Upon boosting local LNs, numbers of residual GC B cells increased independent on antigen affinity, while average SHM decreased. Our results demonstrate that antigen affinity and location of the boost affect the outcome of the B cell recall response. These results can help guide the design of vaccine immunogens aiming to selectively engage specific B cell clones for further SHM diversification.
Evolving antibody response to SARS-CoV-2 antigenic shift from XBB to JN.1
Authors: Jian Fanchong , Wang Jing , Yisimayi Ayijiang , Song Weiliang , Xu Yanli , Chen Xiaosu , Niu Xiao , Yang Sijie , Yu Yuanling , Wang Peng , Sun Haiyan , Yu Lingling , Wang Jing , Wang Yao , An Ran , Wang Wenjing , Ma Miaomiao , Xiao Tianhe , Gu Qingqing , Shao Fei , Wang Youchun , Shen Zhongyang , Jin Ronghua , Cao Yunlong 
Published: April 2024

AbstractThe continuous evolution of SARS-CoV-2, particularly the emergence of the BA.2.86/JN.1 lineage replacing XBB lineages, necessitates re-evaluation of current vaccine compositions. Here, we provide a comprehensive analysis of the humoral immune response to XBB and JN.1 human exposures, emphasizing the need for JN.1-lineage-based boosters. We demonstrate the antigenic distinctiveness of XBB and JN.1 lineages in SARS-CoV-2-naive individuals but not in those with prior vaccinations or infections, and JN.1 infection elicits superior plasma neutralization titers against its subvariants. We highlight the strong immune evasion and receptor binding capability of KP.3, supporting its foreseeable prevalence. Extensive analysis of the BCR repertoire, isolating ∼2000 RBD-specific monoclonal antibodies (mAbs) with their targeting epitopes characterized by deep mutational scanning (DMS), underscores the systematic superiority of JN.1-elicited memory B cells (MBCs). Notably, Class 1 IGHV3-53/3-66-derived neutralizing antibodies (NAbs) contribute majorly within wildtype (WT)-reactive NAbs against JN.1. However, KP.2 and KP.3 evade a substantial subset of them, even those induced by JN.1, advocating for booster updates to KP.3 for optimized enrichment. JN.1-induced Omicron-specific antibodies also demonstrate high potency across all Omicron lineages. Escape hotspots of these NAbs have mainly been mutated in Omicron RBD, resulting in higher immune barrier to escape, considering the probable recovery of previously escaped NAbs. Additionally, the prevalence of broadly reactive IGHV3-53/3-66- encoding antibodies and MBCs, and their capability of competing with all Omicron-specific NAbs suggests their inhibitory role on the de novo activation of Omicron-specific naive B cells, potentially explaining the heavy immune imprinting in mRNA-vaccinated individuals. These findings delineate the evolving antibody response to Omicron antigenic shift from XBB to JN.1, and highlight the importance of developing JN.1 lineage, especially KP.3-based vaccine boosters, to enhance humoral immunity against current and future SARS-CoV-2 variants.
A disease similarity approach identifies short-lived Niemann-Pick type C disease mice with accelerated brain aging as a novel mouse model for Alzheimer’s disease and aging research
Authors: Gujjala Vikas Anil , Klimek Isaiah , Abyadeh Morteza , Tyshkovskiy Alexander , Oz Naci , Castro José Pedro , Gladyshev Vadim N. , Newton Jason , Kaya Alaattin 
Published: April 2024

AbstractSince its first description in 1906 by Dr. Alois Alzheimer, Alzheimer’s disease (AD) has been the most common type of dementia. Initially thought to be caused by age-associated accumulation of plaques, in recent years, research has increasingly associated AD with lysosomal storage and metabolic disorders, and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions. However, the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined. Here, we applied a disease similarity approach to identify unknown molecular targets of AD by using transcriptomic data from congenital diseases known to increase AD risk, namely Down Syndrome, Niemann Pick Disease Type C (NPC), and Mucopolysaccharidoses I. We uncovered common pathways, hub genes, and miRNAs acrossin vitroandin vivomodels of these diseases as potential molecular targets for neuroprotection and amelioration of AD pathology, many of which have never been associated with AD. We then investigated common molecular alterations in brain samples from an NPC disease mouse model by juxtaposing them with brain samples of both human and mouse models of AD. Detailed phenotypic and molecular analyses revealed that the NPCmutmouse model can serve as a potential short-livedin vivomodel for AD research and for understanding molecular factors affecting brain aging. This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on AD research while highlighting shortcomings and lack of correlation in diversein vitromodels. Considering the lack of an AD mouse model that recapitulates the physiological hallmarks of brain aging, the characterization of a short-lived NPC mouse model will further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of AD from a perspective of accelerated brain aging.
Improving genomic selection in hexaploid wheat with sub-genome additive and epistatic models
Authors: Tessele Augusto , González-Diéguez David O. , Crossa Jose , Johnson Blaine E. , Morris Geoffrey P. , Fritz Allan K. 
Published: April 2024

AbstractThe goal of wheat breeding is the development of superior cultivars tailored to specific environments, and the identification of promising crosses is crucial for the success of breeding programs. Although genomic estimated breeding values were developed to estimate additive effects of genotypes before testing as parents, application has focused on predicting performance of candidate lines, ignoring non-additive genetic effects. However, non-additive genetic effects are hypothesized to be especially importance in allopolyploid species due to the interaction between homeologous genes. The objectives of this study were to model additive and additive-by-additive epistatic effects to better delineate the genetic architecture of grain yield in wheat and to the improve accuracy of genomewide predictions. The dataset utilized consisted of 3740 F5:6experimental lines tested in the K-State wheat breeding program across the years 2016 and 2018. Covariance matrices were calculated based on whole and sub-genome marker data and the natural and orthogonal interaction approach (NOIA) was used to estimate variance components for additive and additive-by-additive epistatic effects. Incorporating epistatic effects in additive models resulted in non-orthogonal partitioning of genetic effects but increased total genetic variance and reduced deviance information criteria. Estimation of sub-genome effects indicated that genotypes with the greatest whole genome effects often combine sub-genomes with intermediate to high effects, suggesting potential for crossing parental lines which have complementary sub-genome effects. Modeling epistasis in either whole-genome or sub-genome models led to a marginal (3%) but significant improvement in genomic prediction accuracy, which could result in significant genetic gains across multiple cycles of breeding.
InsulatedpiggyBacand FRT vectors for engineering transgenic homozygous and heterozygous eHAP cells
Authors: Minard Annabel Y , Winistorfer Stanley , Piper Robert C 
Published: April 2024

AbstractTransgene expression in eHAP cells, a haploid cell line popularly used to generate gene knockouts, is difficult owing to its low transfection efficiency and propensity for silencing integrated transgenes. To simplify transgene expression, we engineered insulated integrating plasmids that sustain high levels of transgene expression in eHAP cells, and that can be used in other cell lines. These vectors are compatible with FLP-FRT andpiggyBacintegration, they flank a gene-of interest bilaterally with tandem cHS4 core insulators, and co-express nuclear-localized blue fluorescent protein for identification of high expressing cells. We further demonstrate that transgenic haploid eHAP cells can be fused to form transgenic heterozygous diploid cells. This method creates diploid cells carrying the transgenic material of the haploid progenitors and could also be used to create heterozygous cells of defined genotypes. These tools expand the repertoire of experiments that can be performed in eHAP cells and other cultured cells.