bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 Expression in Triple-negative Breast Cancer—a Comparative Study of 3 Different Antibodies
Authors: Vlajnic Tatjana , Baur Fabienne , Soysal Savas D. , Weber Walter P. , Piscuoglio Salvatore , Muenst Simone 
Published: September 2022

Background:
Assessment of programmed death protein-ligand 1 (PD-L1) in triple-negative breast cancer (TNBC) has entered daily practice to identify patients eligible for treatment with immune checkpoint inhibitors. However, different antibodies and different cut-offs for PD-L1 positivity are used, and the interchangeability of these methods is not clear. The aim of our study was to analyze whether different PD-L1 antibodies can be used interchangeably to identify TNBC patients as PD-L1 positive.

Methods:
A tissue microarray encompassing 147 TNBC cases was immunohistochemically analyzed using 3 different antibodies against PD-L1: SP142, SP263, and E1L3N. PD-L1 positivity was determined as ≥1% of positive tumor-associated immune cells. The staining patterns of the 3 antibodies were compared and correlated with clinicopathological data.

Results:
A total of 84 cases were evaluable for PD-L1 analysis with all 3 antibodies. PD-L1 was positive in 50/84 patients (59.5%) with SP263, in 44/84 (52.4%) with E1L3N, and in 29/84 (34.5%) with SP142. There was no statistical difference between the performance of SP263 and E1L3N, but both antibodies stained significantly more cases than the SP142 antibody.

Conclusions:
Our results show that the 3 PD-L1 antibodies identify different TNBC patient subgroups as PD-L1 positive and, therefore cannot be used interchangeably. Additional studies are needed to further investigate the use and impact of different PD-L1 antibody clones for predictive selection of TNBC patients for treatment with immune checkpoint inhibitors.
Modern Low-Field MRI of the Musculoskeletal System
Authors: Khodarahmi Iman , Keerthivasan Mahesh B. , Brinkmann Inge M. , Grodzki David , Fritz Jan 
Published: September 2022

Abstract
Magnetic resonance imaging (MRI) provides essential information for diagnosing and treating musculoskeletal disorders. Although most musculoskeletal MRI examinations are performed at 1.5 and 3.0 T, modern low-field MRI systems offer new opportunities for affordable MRI worldwide. In 2021, a 0.55 T modern low-field, whole-body MRI system with an 80-cm-wide bore was introduced for clinical use in the United States and Europe. Compared with current higher-field-strength MRI systems, the 0.55 T MRI system has a lower total ownership cost, including purchase price, installation, and maintenance. Although signal-to-noise ratios scale with field strength, modern signal transmission and receiver chains improve signal yield compared with older low-field magnetic resonance scanner generations. Advanced radiofrequency coils permit short echo spacing and overall compacter echo trains than previously possible. Deep learning–based advanced image reconstruction algorithms provide substantial improvements in perceived signal-to-noise ratios, contrast, and spatial resolution. Musculoskeletal tissue contrast evolutions behave differently at 0.55 T, which requires careful consideration when designing pulse sequences. Similar to other field strengths, parallel imaging and simultaneous multislice acquisition techniques are vital for efficient musculoskeletal MRI acquisitions. Pliable receiver coils with a more cost-effective design offer a path to more affordable surface coils and improve image quality. Whereas fat suppression is inherently more challenging at lower field strengths, chemical shift selective fat suppression is reliable and homogeneous with modern low-field MRI technology. Dixon-based gradient echo pulse sequences provide efficient and reliable multicontrast options, including postcontrast MRI. Metal artifact reduction MRI benefits substantially from the lower field strength, including slice encoding for metal artifact correction for effective metal artifact reduction of high-susceptibility metallic implants. Wide-bore scanner designs offer exciting opportunities for interventional MRI. This review provides an overview of the economical aspects, signal and image quality considerations, technological components and coils, musculoskeletal tissue relaxation times, and image contrast of modern low-field MRI and discusses the mainstream and new applications, challenges, and opportunities of musculoskeletal MRI.
Synthetic Contrasts in Musculoskeletal MRI
Authors: Hilbert Tom , Omoumi Patrick , Raudner Marcus , Kober Tobias 
Published: September 2022

Abstract
This review summarizes the existing techniques and methods used to generate synthetic contrasts from magnetic resonance imaging data focusing on musculoskeletal magnetic resonance imaging. To that end, the different approaches were categorized into 3 different methodological groups: mathematical image transformation, physics-based, and data-driven approaches. Each group is characterized, followed by examples and a brief overview of their clinical validation, if present. Finally, we will discuss the advantages, disadvantages, and caveats of synthetic contrasts, focusing on the preservation of image information, validation, and aspects of the clinical workflow.
Blood Perfusion Characteristics of Renal Cell Carcinoma in the Process of Tumor Growth: Monitored With Multiple Sonographic Modalities
Authors: Li Cui-Xian , Lu Qing , Li Cong , Wang Wen-Ping , Huang Bei-Jian 
Published: September 2022

Abstract
Tumor angiogenesis is an essential factor for tumor growth and antiangiogenic therapy. To simulate the blood perfusion characteristics of human renal cell carcinoma (RCC) longitudinally in the process of tumor growth, multimodal ultrasound examination was performed on 40 orthotopic xenograft RCC mouse models. According to tumor maximum diameter (d), tumor growth progress was divided into 3 steps: d ≤ 5 mm, 5 mm < d ≤ 10 mm, and d > 10 mm. Color Doppler flow imaging (CDFI), superb microvascular imaging (SMI), and contrast-enhanced ultrasound were administered to monitor tumor perfusion characteristics. The abundance of tumor vascularity on CDFI and SMI was divided into grades 0 to III in ascending order, and their distribution range was categorized into types I to IV. As a result, heterogeneous echogenicity and irregular shape were more common in tumors d > 10 mm than those d < 10 mm (P < 0.001 for both). Tumor perfusion grade and type on both CDFI and SMI made statistic difference among different growth steps, with higher ratio of hypervascular characteristic in bigger ones (all P < 0.05). Tumor in the same growth step had a higher perfusion grade on SMI than that on CDFI (P < 0.001). On contrast-enhanced ultrasound, heterogeneous enhancement was more common in those >10 mm (P < 0.001). It can be concluded that the blood perfusion characteristics of RCC keep on changing during its growth process. In addition, SMI is more sensitive in evaluating tumor perfusion than CDFI.
Mechanism of acteoside-activated let-7g-5P attenuating Aβ-induced increased permeability and apoptosis of brain microvascular endothelial cells based on experimental and network pharmacology
Authors: Wu Meijun , Gao Yue , Chen Bin 
Published: September 2022

Objectives
Amyloid β-protein (Aβ)-induced apoptosis and oxidative stress of human brain microvascular endothelial cells(BMECs) are contributors to the development of Alzheimer’s disease (AD). Acteoside has shown its therapeutic potential for AD treatment. Therefore, this study investigated the effect of acteoside on Aβ-induced blood–brain barrier damage, oxidative stress and apoptosis as well as to explore the underlying mechanisms through network pharmacology.

Methods
The study used Aβ to induce human BMECs to construct an in-vitro injury model. Following treatment with acteoside, transendothelial electrical resistance (TEER), RT-qPCR and Western blot were used to evaluate the permeability of BMECs. The apoptosis level was detected by TUNEL and Western blot, ROS assay kit was used for the detection of reactive oxygen species (ROS) expression. The let-7g-5p expression level was detected by RT-qPCR. After additional treatment with let-7g-5p inhibitor, corresponding assays were performed again. Finally, network pharmacology was used to verify the mechanism.

Results
Acteoside decreased the permeability, oxidative stress and cell apoptosis of Aβ-stimulated cells. More importantly, acteoside-activated let-7g-5p and additional treatment with let-7g-5p inhibitor abated the effects of acteoside on Aβ-induced permeability, oxidative stress and apoptosis of Aβ-stimulated BMECs. According to network pharmacology, 233 targeted genes of acteoside and 122 potential targets of let-7g-5p were determined by screening several databases, and two targets called Casp-3 and ITGB3 were obtained after taking the intersection.

Conclusion
In conclusion, these results reveal that acteoside-activated let-7g-5p attenuating Aβ-induced increased permeability and apoptosis of human BMECs.
A LITERATURE REVIEW ON COMPLEMENTARY THERAPIES IN AUTISM CHILDREN: A NURSING SCIENCE PHILOSOPHY
Authors: Alfiyanti Dera , Pandin Moses Glorino Rumambo , Rahayuningtyas Imelda Rizky 
Published: September 2022

ABSTRACTIntroductionAutism is a neurodevelopmental disorder that can cause repetitive behavior, limited activity, and a lack of ability to communicate and socialize. The purpose of this literature review is to identify the effectiveness of Complementary mind-body-spirit therapies, manipulative and body-based therapies, and energy therapies in children with autism.MethodLiterature search method using ProQuest, PubMed, and Science Direct databases with include the keywords Complementary therapy in children with autism or Complementary therapy in children with autism. The search was limited to publication criteria in the 2018-2022 timeframe, full-text articles, and not review articles.ResultsOf the study showe that Complementary therapies are effective in improving development in children with autism consisting of mind-body-spirit therapies (music, yoga, Qur’an Murrotal Audio) effective in improving: communication and social skills also brain connectivity, the concentration, and attention span, and sleep quality, manipulative and body based therapies (physical activity, Tai Chi Chuan, massage) are effective in improving social interaction and communication skills, reducing stereotyped behavior, and preventing the risk of autism, energy therapies (reflexology, hypnotherapy, and healing touch) are effective in reducing the symptoms of autism and constipation and overcome hyperactive behavior.ConclusionComplementary mind-body-spirit therapies, manipulative and body-based therapies, and energy therapies are effective in improving the development of children with autism.
Identifying Genes with Location Dependent Noise Variance in Spatial Transcriptomics Data
Authors: Abrar Mohammed Abid , Kaykobad M. , Rahman M. Saifur , Samee Md. Abul Hassan 
Published: September 2022

ABSTRACTSpatial transcriptomics (ST) holds the promise to identify the existence and extent of spatial variation of gene expression in complex tissues. Such analyses could help identify gene expression signatures that distinguish between healthy and disease samples. Existing tools to detect spatially variable genes assume a constant noise variance across location. This assumption might miss important biological signals when the variance could change across spatial locations, e.g., in the tumor microenvironment. In this paper, we proposeNoVaTeST, a framework to identify genes with location-dependent noise variance in ST data. NoVaTeST can model gene expression as a function of spatial location with a spatially variable noise. We then compare the model to one with constant noise to detect genes that show significant spatial variation in noise. Our results show genes detected by NoVaTeST provide complimentary information to existing tools while providing important biological insights.
Thalamic volume and functional connectivity are associated with nicotine dependence severity and craving
Authors: Lor Cindy Sumaly , Haugg Amelie , Zhang Mengfan , Schneider Letitia M. , Herdener Marcus , Quednow Boris B. , Golestani Narly , Scharnowski Frank 
Published: September 2022

AbstractTobacco smoking is associated with deleterious health outcomes. Most smokers want to quit smoking, yet relapse rates are high. Understanding neural differences associated with tobacco use may help generate novel treatment options. Several animal studies have recently highlighted the central role of the thalamus in substance use disorders, but this research focus has been understudied in human smokers. Here, we investigated associations between structural and functional magnetic resonance imaging measures of the thalamus and its subnuclei to distinct smoking characteristics. We acquired anatomical scans of 32 smokers as well as functional resting-state scans before and after a cue-reactivity task. Thalamic functional connectivity was associated with craving and dependence severity, whereas the volume of the thalamus was associated with dependence severity only. Craving, which fluctuates rapidly, was best characterized by differences in brain function, whereas the rather persistent syndrome of dependence severity was associated with both brain structural differences and function. Our study supports the notion that functional versus structural measures tend to be associated with behavioral measures that evolve at faster versus slower temporal scales, respectively. It confirms the importance of the thalamus to understand mechanisms of addiction and highlights it as a potential target for brain-based interventions to support smoking cessation, such as brain stimulation and neurofeedback.
Feasibility Analyses and Experimental Confirmation of Dove Prism Based Dual-fiberscope Rotary Joint
Authors: Liu Yuehan , Park Hyeon-Cheol , Zhang Haolin , Li Xingde 
Published: September 2022

AbstractTwo-photon fluorescence microscopy has enjoyed its wide adoption in neuroscience. Head-mounted miniaturized fiberscopes offered an exciting opportunity for enabling neural imaging in freely-behaving animals with high 3D resolution. Here we propose a dual-fiberscope rotary joint based on a Dove prism, for enabling simultaneous two-photon imaging of two brain regions with two fiberscopes in freely-walking/rotating mice. Analytic proof has confirmed the key properties of a Dove prism. Feasibility analyses and proof-of-concept experimental results have demonstrated the feasibility of such a rotary joint for allowing two fiberscopes to rotate simultaneously while maintaining an excellent single-mode fiber-to-fiber coupling for the excitation femtosecond laser. Fiberscopes with a dual-probe rotary joint offer an exciting opportunity to explore neural network dynamics of multiple interconnected brain regions in freely-walking rotating animals.
AF2-multimer guided high accuracy prediction of typical and atypical ATG8 binding motifs
Authors: Ibrahim Tarhan , Khandare Virendrasinh , Mirkin Federico Gabriel , Tumtas Yasin , Bubeck Doryen , Bozkurt Tolga O. 
Published: September 2022

AbstractMacroautophagy/autophagy is an intracellular degradation process central to cellular homeostasis and defense against pathogens in eukaryotic cells. Regulation of autophagy relies on hierarchical binding of autophagy cargo receptors and adaptors to ATG8/LC3 protein family members. Interactions with ATG8/LC3 are typically facilitated by a conserved, short linear sequence, referred to as the ATG8/LC3 interacting motif/region (AIM/LIR), present in autophagy adaptors and receptors as well as pathogen virulence factors targeting host autophagy machinery. Since the canonical AIM/LIR sequence can be found in many proteins, identifying functional AIM/LIR motifs has proven challenging. Here we show that protein modelling using Alphafold-Multimer (AF2-multimer) identifies both canonical and atypical AIM/LIR motifs with a high level of accuracy. AF2-multimer can be modified to detect additional functional AIM/LIR motifs by using protein sequences with mutations in primary AIM/LIR residues. By combining protein modelling data from AF2-multimer with phylogenetic analysis of protein sequences and protein-protein interaction assays, we demonstrate that AF2-multimer predicts the physiologically relevant AIM motif in the ATG8-interacting protein 2 (ATI-2) as well as the previously uncharacterized non-canonical AIM motif in ATG3 from potato (Solanum tuberosum). AF2-multimer also identified the AIM/LIR motifs in pathogen-encoded virulence factors that target ATG8 members in their plant and human hosts, revealing that cross-kingdom ATG8-LIR/AIM associations can also be predicted by AF2-multimer. We conclude that the AF2-guided discovery of autophagy adaptors/receptors will substantially accelerate our understanding of the molecular basis of autophagy in all biological kingdoms.
Rapid reductions in population size drive evolutionary divergence in diatoms
Authors: Walworth Nathan G. , Espinoza Josh L. , Argyle Phoebe A. , Hinners Jana , Levine Naomi M. , Doblin Martina A. , Dupont Chris L. , Collins Sinéad 
Published: September 2022

AbstractUnicellular photosynthetic marine microbes, or phytoplankton, make up the base of marine food webs and drive global nutrient cycles. Despite their key roles in ecology and biogeochemistry, we have a limited understanding of how the basic features of their demographics along with dynamic environments affect trait evolution. A key feature of diatom ecology is frequent extreme reductions in population size, both as part of their bloom-and-bust growth dynamics, and as a result of living within ocean currents. Here, we use experimental evolution to understand which metabolic pathways and functions readily diversify in diatom populations following population bottleneck events. We subjected replicate populations of six genetically distinct diatom strains to population bottlenecks and then subsequently allowed them to evolve as large populations in the absence of environmental change. Phylogenies and global expression of orthologs were generally strain-specific, indicating that vertical (inherited) evolutionary constraints largely determine the occupation of specific locations in the transcriptional landscape (i.e. tran-scape). Following bottlenecks and subsequent evolution as large populations, transcriptional networks of most populations returned to those of the ancestral population. However, at least one replicate population per lineage migrated in the tran-scape, demonstrating that evolutionary changes in gene expression patterns and transcriptional relationships can be driven by population bottlenecks even in the absence of environmental change. Importantly, the orthologs dominating transcriptional diversification resided in common, central metabolic pathways. These data advance our understanding of constraints and patterns of transcriptional relationships underlying trait evolution in microbes that drive global food webs and elemental cycles.
Recombination rate variation shapes genomic variability of phylogeographic structure in a widespread North American songbird (Aves:Certhia americana)
Authors: Manthey Joseph D. , Spellman Garth M. 
Published: September 2022

ABSTRACTThe nonrandom distribution of chromosomal characteristics and functional elements—genomic architecture—impacts the relative strengths and impacts of population genetic processes across the genome. Due to this relationship, genomic architecture has the potential to shape variation in population genetic structure across the genome. Population genetic structure has been shown to vary across the genome in a variety of taxa, but this body of work has largely focused on pairwise population genomic comparisons between closely related taxa. Here, we used whole genome sequencing of seven phylogeographically structured populations of a North American songbird, the Brown Creeper (Certhia americana), to determine the impacts of genomic architecture on phylogeographic structure variation across the genome. Using multiple methods to infer phylogeographic structure—ordination, clustering, and phylogenetic methods— we found that recombination rate variation explained a large proportion of phylogeographic structure variation. Genomic regions with low recombination showed phylogeographic structure consistent with the genome-wide pattern. In regions with high recombination, we found strong phylogeographic structure, but with discordant patterns relative to the genome-wide pattern. In regions with high recombination rate, we found that populations with small effective population sizes evolve relatively more rapidly than larger populations, leading to discordant signatures of phylogeographic structure. These results suggest that the interplay between recombination rate variation and effective population sizes shape the relative impacts of linked selection and genetic drift in different parts of the genome. Overall, the combined interactions of population genetic processes, genomic architecture, and effective population sizes shape patterns of variability in phylogeographic structure across the genome of the Brown Creeper.
The genetic overlap between Alzheimer’s disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease
Authors: Wightman Douglas P. , Savage Jeanne E. , Tissink Elleke , Romero Cato , Jansen Iris E. , Posthuma Danielle 
Published: September 2022

AbstractNeurodegenerative diseases are a group of disorders characterised by neuronal cell death causing a variety of physical and mental problems. While these disorders can be characterised by their phenotypic presentation within the nervous system, their aetiologies differ to varying degrees. Some disorders, such as Lewy body dementia and Parkinson’s disease, show overlap in the major proteins found in aggregates, and some diseases, like Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease, are influenced by the same non-neuronal cell types (microglia), suggesting partly shared aetiologies. The identification of shared genetic risk factors common to many neurodegenerative diseases may highlight fundamental biological processes involved in neurodegeneration and provide promising targets for treatment and drug repurposing. The majority of genetic evidence for overlap between neurodegenerative diseases has been pairwise, with little genetic evidence for genes or biological processes found across more than two neurodegenerative diseases. In this study, we aimed to identify overlap between the four investigated neurodegenerative disorders (Alzheimer’s disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease) at the variant, gene, genomic locus, gene-set, cell, or tissue level, with specific interest in overlap between three or more diseases. Using local genetic correlation, we found that the TMEM175 locus was a shared locus between amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease, and the HLA region was shared between Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. We also highlighted genes, genomic loci, gene-sets, cell types, and tissue types which may be important to two or more disorders by analysing the association of variants with a common factor estimated from the four disorders. Our study successfully highlighted genetic loci and tissues associated with two or more neurodegenerative diseases.