bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mismatch Between Brain MRIs and 18F-DOPA PET/CT
Authors: Bourbonne Vincent , Dissaux Brieg , Seizeur Romuald , Nguyen Jessica , Querellou Solène 
Published: February 2024

Abstract
After receiving erlotinib for 4 years, a man with advanced lung adenocarcinoma was treated with stereotactic radiotherapy for a left cerebellar brain metastasis. Local relapse of the metastasis was suspected 14 months after and confirmed on 18F-DOPA PET. Three additional uptakes were described with no unequivocal MRI pathological signal. A second radiotherapy course was delivered. One year later, isolated local recurrence was suspected on a 3 T MRI, with a suspicious 18F-DOPA uptake. Five additional 18F-DOPA uptakes were described among which one increased between the 2 PETs. Because of these MRI/PET mismatches, a switch from erlotinib to osimertinib was preferred over surgery.
Multiple Nervous System Involvement of Erdheim-Chester Disease With Responsive Perinephritic Hypermetabolism
Authors: Koç Zehra Pinar , Özcan Pinar Pelin , Tombak Anil , Sönmezoğlu Kerim 
Published: February 2024

Abstract
A 36-year-old man who was at follow-up for histiocytosis had sudden-onset symptoms of unilateral ophthalmic increased pressure. The patient was referred to the FDG PET/CT for determination of involvement with suspicion of Erdheim-Chester disease. The reduction of the FDG uptake in all of the lesions (medial temporal lobes, nasal septum, medulla spinalis in sacral region, as well as perinephritic infiltrations), which were determined by the first PET/CT, was achieved at second imaging.
Unusual Presence of Synchronous Primary Ovarian and Thyroid Extranodal Non-Hodgkin Lymphoma Without Lymph Node Involvement
Authors: Babacan Gündüzalp Buğrahan , Acar Tayyar Merve Nur , Şahin Mehmet Can , Şengiz Erhan Selma , Tamam Müge Öner 
Published: February 2024

Abstract
Extranodal lymphomas without lymph node involvement are rarely observed and create diagnostic challenges. We present the case of a 33-year-old woman who was admitted with abdominal swelling. Ultrasonography findings suggested bilateral ovarian masses. 18F-FDG PET/CT revealed intense uptake on the bilateral pelvic mass and thyroid gland. Following excisional surgery and thyroid fine-needle aspiration biopsy, the patient was diagnosed with diffuse large B-cell lymphoma. This case is exceptionally rare, as it presents 2 synchronous extranodal involvements in the ovaries and the thyroid gland independently while not presenting any lymph node activity, which has not been reported before.
Ultrasound Microbubble-Stimulated miR-145-5p Inhibits Malignant Behaviors of Breast Cancer Cells by Targeting ACTG1
Authors: Ren Liang , Wang Li , Yi Xuelin , Tan Yang , Yi Lingxian , He Jinlan , Li Danping 
Published: February 2024

Abstract
Ultrasound-targeted microbubble destruction (UTMD) technology combines ultrasound with a variety of functional microbubble vectors to enhance the transfection and expression of target genes, and has become a promising noninvasive method for localized gene transfer, which is widely used in gene therapy for cancer. This research aimed to explore the role of UTMD-mediated miR-145-5p on breast cancer (BC) tumorigenesis and the underlying mechanisms. To achieve UTMD-mediated miR-145-5p overexpression, BC cells were cotransfected with microbubbles (MBs) and miR-145-5p mimics. The BC cell malignant phenotypes were assessed through CCK-8, wound healing, and transwell assays. MiR-145-5p and actin gamma 1 (ACTG1) binding relationship was verified through luciferase reporter and RNA pull-down assays. MiR-145-5p and ACTG1 levels in BC cells and tissues were detected through RT-qPCR and Western blotting. ACTG1 was upregulated, whereas miR-145-5p was downregulated in BC cells and tissues. MiR-145-5p targeted ACTG1 and negatively regulated its level in BC cells. Overexpressing miR-145-5p restrained BC cell growth, migration, and invasion. Ultrasound-targeted microbubble destruction improved the overexpression efficiency of miR-145-5p and enhanced the suppressive influence on BC cell malignant phenotypes. In addition, ACTG1 overexpression compromises the repression of UTMD-mediated miR-145-5p on cellular behaviors in BC. Ultrasound-targeted microbubble destruction–delivered miR-145-5p hindered malignant behaviors of BC cells through downregulating ACTG1.
Loss of function inRBBP5results in a syndromic neurodevelopmental disorder associated with microcephaly
Authors: Huang Yue , Jay Kristy L. , Huang Alden Yen-Wen , Wan Jijun , Jangam Sharayu V. , Chorin Odelia , Rothschild Annick , Barel Ortal , Mariani Milena , Iascone Maria , Xue Han ,   Undiagnosed Diseases Network, Huang Jing , Mignot Cyril , Boris Keren , Saillour Virginie , Mah-Som Annelise Y. , Sacharow Stephanie , Rajabi Farrah , Costin Carrie , Yamamoto Shinya , Kanca Oguz , Bellen Hugo J. , Rosenfeld Jill A. , Palmer Christina G S , Nelson Stanley F. , Wangler Michael F. , Martinez-Agosto Julian A 
Published: February 2024

ABSTRACTPurposeEpigenetic dysregulation has been associated with many inherited disorders.RBBP5encodes a core member of the protein complex that methylates histone 3 lysine-4 (H3K4) and has not been implicated in human disease.MethodsWe identify five unrelated individuals withde novoheterozygous pathogenic variants inRBBP5. Three truncating and two missense variants were identified in probands with neurodevelopmental symptoms including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenicDrosophilamodels.ResultsBoth missense p.T232I and p.E296D variants affect evolutionarily conserved amino acids and are expected to interfere with the interface between RBBP5 and the histones. InDrosophila,ubiquitous overexpression of humanRBBP5is lethal in the larval developmental stage. Loss ofRbbp5leads to a reduction in brain size, and the human reference, p.T232I, or p.E296D variant transgenes fail to rescue loss ofRbbp5.Expression of either missense variant in anRbbp5null background results in a less severe microcephaly phenotype than the human reference, indicating both p.T232I and p.E296D variants are loss-of-function alleles.ConclusionDe novoheterozygous variants inRBBP5are associated with a syndromic neurodevelopmental disorder.Graphical abstract
Large- and Small-Animal Studies of Safety, Pharmacokinetics (PK), and Biodistribution of Inflammasome-Targeting Nanoligomer in the Brain and Other Target Organs
Authors: Risen Sydney , Kusick Breonna , Sharma Sadhana , Gilberto Vincenzo S. , Brindley Stephen , Aguilar Mikayla , Brown Jared M. , McGrath Stephanie , Chatterjee Anushree , Moreno Julie A. , Nagpal Prashant 
Published: February 2024

ABSTRACTImmune malfunction or misrecognition of healthy cells and tissue, termed autoimmune disease, is implicated in more than 80 disease conditions and multiple other secondary pathologies. While pan-immunosuppressive therapies like steroids offer some relief for systemic inflammation for some organs, many patients never achieve remission and such drugs do not cross the blood-brain barrier making them ineffective for tackling neuroinflammation. Especially in the brain, unintended activation of microglia and astrocytes is hypothesized to be directly or indirectly responsible for Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), Parkinson’s Disease (PD), and Alzheimer’s Disease (AD). Recent studies have also shown that targeting inflammasome and specific immune targets can be beneficial for these diseases. Further, our previous studies have shown targeting NF-κB and NLRP3 through brain penetrant Nanoligomer cocktail SB_NI_112 (abbreviated to NI112) can be therapeutic for several neurodegenerative diseases. Here we show safety-toxicity studies, followed by pharmacokinetics (PK) and biodistribution in small- (mice) and large-animal (dog) studies of this inflammasome-targeting Nanoligomer cocktail NI 112. We conducted studies using four different routes of administration: intravenous (IV), subcutaneous (SQ), intraperitoneal (IP), and intranasal (IN), and identified the drug concentration over time using inductively coupled plasma mass spectrometry (ICP-MS) in the blood serum, the brain (including different brain regions), and other target organs like liver, kidney, and colon. Our results indicate the Nanoligomer cocktail has a strong safety profile, and shows high biodistribution (F ∼0.98) and delivery across multiple routes of administration. Further analysis showed high brain bioavailability with a ratio of NI112 in brain tissue to blood serum ∼30%. Our model accurately shows dose scaling, translation between different routes of administration, and interspecies scaling. These results provide an excellent platform for human clinical translation and predicting therapeutic dosage between different routes of administration.
Variability of immune gene expression among different groups within ant colonies show multifaceted response to infection by a non-lethal ectoparasitic fungus
Authors: Orbán-Bakk Kincső , Schultner Eva , Heinze Jürgen , Markó Bálint , Csata Enikő 
Published: February 2024

AbstractSocial insect colonies are known to be targeted by a wide variety of different parasites and pathogens because of their high host abundance. However, within a colony, the level of risk to exposure could vary among individuals depending on their role. Unlike many known parasites, which mostly target specific groups of individuals, e.g. foragers, the myrmecoparasitic fungusRickia wasmanniiinfects entire ant colonies, being linked to subtle changes in physiology, morphology and behaviour. We investigated how different groups within the colonies respond to being exposed to the fungus by measuring the expression of the genesdefensin 1andprophenoloxidase, both vital components of ant immunity. We found that workers, queens and broods varied in their immune response. Workers displayed diverse profiles, with variable responses to infection: in same-age workers, bothprophenoloxidaseanddefensin 1levels exhibited increases in correlation with pathogen loads. Queens exhibited a more pronounced immune response. Highly infected queens had a heightened immune response. Larvae did not show a discernible response. Morphological and physiological characteristics had limited effects on gene expression, except in the case of queens, where larger individuals displayed higherdefensin 1expression. Our study shows that these divergent responses likely stem from the differing physiological needs and priorities of various groups within the colony.HighlightsIn same-age workers,prophenoloxidaseanddefensin 1levels increased with pathogen loads.Body size affecteddefensin 1expression in a caste-specific manner: larger queens displayed higher expression.Infection did not elicit any specific response in larvae.The diverse response to infection likely arise from distinct physiological needs and priorities within colony groups.
Functional genomic screening inKomagataella phaffiienabled by high-activity CRISPR-Cas9 library
Authors: Tafrishi Aida , Trivedi Varun , Xing Zenan , Li Mengwan , Mewalal Ritesh , Culter Sean , Blaby Ian , Wheeldon Ian 
Published: February 2024

AbstractCRISPR-based high-throughput genome-wide loss-of-function screens are a valuable approach to functional genetics and strain engineering. The yeastKomagataella phaffiiis a host of particular interest in the biopharmaceutical industry and as a metabolic engineering host for proteins and metabolites. Here, we design and validate a highly active 6-fold coverage genome-wide sgRNA library for this biotechnologically important yeast containing 30,848 active sgRNAs targeting over 99% of its coding sequences. Conducting fitness screens in the absence of functional non-homologous end joining (NHEJ), the dominant DNA repair mechanism inK. phaffii, provides a quantitative means to assess the activity of each sgRNA in the library. This approach allows for the experimental validation of each guide’s targeting activity, leading to more precise screening outcomes. We used this approach to conduct growth screens with glucose as the sole carbon source and identify essential genes. Comparative analysis of the called gene sets identified a core set ofK. phaffiiessential genes, many of which relate to protein production, secretion, and glycosylation. The high activity, genome-wide CRISPR library developed here enables functional genomic screening inK. phaffii, applied here to gene essentiality classification, and promises to enable other genetic screens.HighlightsDesigned and validated a high activity genome-wide CRISPR-Cas9 library forK. phaffiiDisabling NHEJ DNA repair enables the generation of genome-wide guide activity profilesActivity-corrected fitness screens identify a high confidence set of essential genes inK. phaffiiProtein production, secretion, and glycosylation pathways are essential inK. phaffiibut not in other yeasts
Innate floral object identification in the generalist solitary hoverfly pollinatorEristalinus aeneus
Authors: Mishra Aditi , Jain Anupreksha , Iyer Padmapriya S , Suryanarayanan Ashwin , Nordström Karin , Olsson Shannon B. 
Published: February 2024

ABSTRACTAll animals must locate and identify food for their survival. Most insects are solitary. Newly emerged solitary insects must therefore employ innate identification of food cues to locate relevant nutritive objects from a distance. Innate preferences for food cues should be both specific enough to allow discrimination between food and non-food objects and general enough to allow for the variety of food objects relevant to each species’ ecology. How insects with small nervous systems are able to encode these cues innately is an area of intense study for ecologists and neuroscientists alike. Here, we used the solitary generalist pollinatorEristalinus aeneusto understand how the innate search template used to identify multiple floral species can arise through a small number of sensory cues spanning multiple modalities. We found that innate floral choices of the hoverflyE. aeneusare a product of contextual integration of broad, plant-based olfactory cues and visual cues, where a combination of radial symmetry and reflection in the 500-700 nm wavelength range was particularly important. Our study, therefore, shows how tiny brains can efficiently encode multimodal cues to identify multiple relevant objects without prior experience.
Program Directors’ Perspectives on Duty Hours Following the Physicians’ Work Style Reforms in Japan
Authors: Shikino Kiyoshi , Nishizaki Yuji , Nagasaki Kazuya , Kobayashi Hiroyuki , Kataoka Koshi , Shimizu Taro , Tokuda Yasuharu 
Published: February 2024

ABSTRACTBackgroundIn anticipation of Japan’s physician work style reforms scheduled for April 2024, which will restrict physicians’ overtime duty hours to under 960 (Level A) or 1920 (Level C-1) hours per year, this study evaluates the potential impact on clinical resident physicians’ training environments through the lens of residency program directors.MethodsA cross-sectional survey was administered to program directors from 701 facilities associated with the 2023 General Medicine-In Training Examination (GM-ITE), capturing responses regarding their planned level of overtime, perceptions of optimal working hours for training efficacy, and items considered as duty hours.ResultsOut of the 701 facilities, 254 responded (36.2% response rate), with a predominant inclination towards adopting Level A (83.5%). A consensus emerged favoring 40 overtime duty hours per month as optimal, significantly lower than previous suggestions of 60–65 hours per week. The study also delineated the classification of activities as duty hours, with patient procedures and mandatory educational sessions identified as such, while self-improvement was largely not considered duty.DiscussionThe findings indicate a substantial shift from previously recommended optimal duty hours towards a more conservative approach. This shift may reflect a proactive adaptation to upcoming regulatory changes and raises questions about the potential impact on the quality of clinical training. The distinction between educational activities and duty hours underscores the need for clarity within the impending work style reforms.
Fine-grained neural coding of bodies and body parts in human visual cortex
Authors: Garcia Ramirez Jesus , Vanhoyland Michael , Apurva Murty Ratan N. , Decramer Thomas , Van Paesschen Wim , Bracci Stefania , Op de Beeck Hans , Kanwisher Nancy , Janssen Peter , Theys Tom 
Published: February 2024

AbstractThe visual image of a human body provides a valuable source of socially relevant information. However, our understanding of the neuronal mechanisms underlying body perception in humans remains limited given the spatiotemporal constraints of functional imaging. Here we recorded multi-unit spiking activity in two neurosurgical patients in or near the extrastriate body area (EBA), a critical region for body perception. Our recordings revealed a strong preference for human bodies over a large range of control stimuli. Notably, this preference was driven by a distinct selectivity for body parts. Moreover, the observed body selectivity generalized to non-photographic depictions of bodies such as silhouettes and stick figures. Overall, our study provides an unprecedented access into the representation of bodies in the human visual cortex to bridge the gap between human neuroimaging and macaque electrophysiology studies, and form a solid basis for computational models of human body processing.
Antiviral effect of betacyanins from red pitahaya (Hylocereus polyrhizus) against influenza A virus
Authors: Lim Chie Min , Lal Sunil Kumar , Isa Nurulfiza Mat , Omar Abdul Rahman , Choo Wee Sim 
Published: February 2024

AbstractSeasonal influenza affects millions of lives worldwide, with influenza A virus (IAV) responsible for pandemics and annual epidemics, causing the most severe illnesses resulting in patient hospitalizations or death. With IAV threatening the next global influenza pandemic, it is a race against time to search for antiviral drugs. Betacyanins are unique nitrogen-containing and water-soluble reddish-violet pigments that have been reported to possess antiviral properties against dengue virus. The objective of this study was to examine the antiviral effect of betacyanins from red pitahaya (Hylocereus polyrhizus) on IAV-infected lung epithelial A549 cells. HPLC and LC-MS analysis of extracted betacyanin showed four betacyanins in the betacyanin fraction, namely phyllocactin, hylocerenin, betanin, and isobetanin. Cytotoxicity assay showed that betacyanin fractions were not cytotoxic to A549 cells at concentrations below 100 µg/mL. Betacyanin fraction concentrations of 12.5, 25.0, and 50.0 µg/mL prevented the formation of viral cytopathic effect and reduced virus titer in IAV-infected cells up to 72 h. A downregulation of protein and mRNA nucleoprotein expression levels was observed after treatment with 25.0 and 50.0 µg/mL of betacyanin fraction after 24 h, thereby providing evidence for the anti-viral activity of betacyanin from red pitahaya against IAVin vitro.
Human color constancy in cast shadows
Authors: Morimoto Takuma , Sato Masayuki , Sunaga Shoji , Uchikawa Keiji 
Published: February 2024

AbstractMost natural scenes contain cast shadows to a varying extent. Illuminant conditions inside and outside the shadow typically differ largely both in intensity and in chromaticity. Nevertheless, our daily experiences suggest that colored materials appear to have the same color in shadows even though the reflected light from the material might be very different. Two experiments were conducted to reveal mechanisms that support human color constancy in cast shadows. In all experiments we built a real scene that consisted of colored hexagons illuminated by two independent liquid crystal projectors simulating “sunlight” and “skylight”, respectively. A part of the scene included a cast shadow under which observers were instructed to change the luminance and the chromaticity of a test field so that it appeared as a full-white paper under the shadow. The color of the skylight was manipulated, testing if our visual system uses a prior that the skylight is typically bluish or yellowish to achieve color constancy. We also created a condition where a cast shadow is not recognized as a shadow. Results showed that color constancy generally holds well in shadows and changing skylight color had little effect. Recognizing a cast shadow as a shadow also had no effect. Overall, these results are consistent with our daily experiences that we stably judge objects’ color even in shadows, providing a key step to reveal mechanisms of color perception in real-world scenes where lighting conditions spatially vary.
Characterization of the common genetic variation in the Spanish population of Navarre
Authors: Maillo Alberto , Huergo Estefania , Apellániz-Ruiz María , UrruDa Edurne , Miranda María , Salgado Josefa , Pasalodos-Sánchez Sara , Delgado-Mora Luna , Teijido Óscar , Goicoechea Ibai , Carmona Rosario , Perez-Florido Javier , Aquino Virginia , Lopez-Lopez Daniel , Peña-Chilet María , Beltrán Sergi , Dopazo Joaquín , Lasa Iñigo , Beloqui Juan José ,   NAGEN-scheme, Alonso Ángel , Gomez-Cabrero David 
Published: February 2024

ABSTRACTPurposeLarge-scale genomic studies have significantly increased our knowledge of genetic variability across populations. Regional genetic profiling is essential for distinguishing common benign variants from disease-causing ones. To this end, we conducted a comprehensive characterization of exonic variants in the population of Navarre (Spain).MethodsGenome sequencing data from 358 unrelated individuals of Spanish origin from the Navarrese population were used.ResultsOur analysis revealed 61,410 biallelic exonic single nucleotide variants (SNV) within the Navarrese cohort, with 35% classified as common (MAF > 1%). By comparing allele frequency data from 1000 Genome Project (excluding the Iberian cohort of Spain, IBS), Genome Aggregation Database, and a Spanish cohort (including IBS individuals and data from Medical Genome Project), we identified 1,069 SNVs common in Navarre but rare (MAF ≤ 1%) in all other populations. We further corroborated this observation with a second regional cohort of 239 unrelated exomes, which confirmed 676 of the 1,069 SNVs as common in Navarre.ConclusionThis study highlights the importance of population-specific characterization of genetic variation to improve allele frequency filtering in sequencing data analysis to identify disease-causing variants.