bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic analysis of carboplatin and fluorescein brain permanence following ultrasound-based blood-brain barrier opening
Authors: Habashy Karl J. , Synold Timothy W. , Feng Ye , Gomez Cristal , Amidei Christina , Ward Rachel , VanderMolen Sarah , Zarrieneh Ashkan , Kim Kwang-Soo , Arrieta Victor A. , Fares Jawad , Burdett Kirsten B. , Zhang Hui , Dmello Crismita , Chen Li , Bebawy John F. , Canney Michael , Stupp Roger , Badie Behnam , Portnow Jana , Sonabend Adam M. 
Published: January 2025

AbstractBackgroundThe blood-brain barrier (BBB) impedes the passage of most circulating drugs into the brain. Low-intensity pulsed ultrasound with microbubbles (LIPU/MB) transiently opens the BBB, improving parenchymal drug penetration. Parenchymal drug permanence upon short-lived BBB opening is unknown. We compared the parenchymal permanence of temozolomide, carboplatin, and fluorescein, and investigated the effect of LIPU/MB on the concentration of carboplatin and fluorescein.MethodsWe analyzed four patients who underwent intraoperative LIPU/MB with intravenous administration of carboplatin and fluorescein in theNCT04528680clinical trial. Microdialysis catheters were implanted into sonicated and non-sonicated brain and measured drug levels over 24 hours. Published data from a microdialysis study of temozolomide without LIPU/MB were used for comparison.ResultsLIPU/MB led to sustained elevated parenchymal drug concentrations, achieving 3.1-fold increase in brain-to-plasma AUC for carboplatin and fluorescein (P = 0.03). Compared to non-sonicated brain, sonicated brain had higher concentrations of carboplatin for 11 hours, and fluorescein for 5 hours. Drug levels in the sonicated brain exceeded their plasma concentrations at 21 hours and 7 hours, for carboplatin and fluorescein, respectively. In non-sonicated brain, drug half-life was longest for fluorescein (13.6 ± 11.0 hours), followed by carboplatin (5.1 ± 1.9 hours) and temozolomide (2.9 ± 1.6 hours). Sonication did not affect parenchymal drug half-life.ConclusionFollowing LIPU/MB, BBB-impermeable drugs exhibit sustained elevated parenchymal concentrations surpassing their plasma levels, highlighting the bi-directional restriction of drug passage by the BBB. Future studies are warranted to explore drug trapping and the efficacy of sustained exposure to cytotoxic drugs for the treatment of brain-infiltrating tumors.
From Abstainers to Dependent Drinkers: Alcohol Consumption Patterns and Risk Factors Among Portuguese University Students
Authors: Saldanha Lucas , Crego Alberto , Almeida-Antunes Natália , Rodrigues Rui , Sampaio Adriana , López-Caneda Eduardo 
Published: January 2025

AbstractBackgroundAlcohol is the most widely consumed psychoactive substance worldwide. In Portugal, alcohol consumption is deeply embedded in social and cultural practices, contributing to high prevalence rates among university students, with binge drinking emerging as a predominant consumption pattern. Despite the associations between this drinking behaviour and numerous social, physical, and psychological problems, research on alcohol consumption in Portuguese university populations remains limited. Thus, this study aimed to provide a comprehensive description of alcohol use patterns among a large sample of Portuguese university students, focusing on adolescents and young adults.MethodsA total of 1,746 students, aged 17-24 years, were surveyed using the Alcohol Use Disorders Identification Test (AUDIT) and additional questionnaires regarding socio-demographic information, alcohol and illicit drug use, smoking habits, and alcohol cravings. Students were classified into five drinking groups: Abstainers (16.8%), Moderate Drinkers (35.1%), Hazardous Drinkers (25.8%), Binge Drinkers (20.8%), and Dependent Drinkers (1.5%). Statistical analyses included descriptive statistics, group comparisons, and multinomial logistic regressions to obtain Odds Ratios (ORs) for group membership.ResultsAlcohol consumption was reported by 83.2% of students over the past year. Nearly 47% of students revealed harmful drinking patterns, and 1.5% exhibited symptoms of alcohol dependence. A progressive increase in the severity of alcohol consumption characteristics was observed across the groups, with Dependent Drinkers reporting the highest levels overall. Significant predictors of group membership included polydrug use, standard weekly consumption, earlier drinking onset, and higher levels of alcohol craving. Polydrug use, reported by 27.3% of students, was the strongest predictor for being a Hazardous Drinker (OR = 10.75), Binge Drinker (OR = 13.20), and Dependent Drinker (OR = 21.40). Binge Drinkers displayed standard weekly consumption and craving levels comparable to Dependent Drinkers, while Moderate Drinkers exhibited the least risky patterns, including a later age of onset of drinking. Male students reported significantly greater consumption and craving levels than their female peers.ConclusionsThis study highlights the prevalence of harmful drinking behaviours among Portuguese university students and identifies critical risk factors, such as polydrug use and early drinking onset. These findings underscore the need for prevention programmes focused on delaying the onset of alcohol use, reducing polydrug use, and promoting healthier behaviours within academic settings.
Computationally-designed aptamers targeting RAD51-BRCA2 interaction inhibit RAD51 nuclear recruitment
Authors: Milordini Giulia , Zacco Elsa , Armaos Alexandros , Di Palma Francesco , Masi Mirco , Gilodi Martina , Rupert Jakob , Broglia Laura , Varignani Giulia , Oneto Michele , Scotto Marco , Marotta Roberto , Girotto Stefania , Cavalli Andrea , Tartaglia Gian Gaetano 
Published: January 2025

ABSTRACTThe interaction between RAD51 and BRCA2 plays a key role in homologous recombination (HR), a critical DNA repair mechanism essential for the survival of cancer cells. Disrupting this interaction increases the sensitivity of cancer cells to chemotherapeutic agents. Here, we employedin silicomethods to design a novel class of aptamers—customized single-stranded oligonucleotides—specifically engineered to bind RAD51. These aptamers were developed with the aim of selectively modulating RAD51’s nuclear recruitment and its role in DNA repair processes. The leading candidate displays high affinity for RAD51, competing with BRCA2 for the same interaction sitein vitro, as confirmed through biolayer interferometry (BLI) and fluorescence lifetime imaging microscopy (FLIM). We tested the efficacy of the leading aptamer in pancreatic cancer cells and observed that it significantly impedes RAD51 nuclear localization, reduces homologous recombination (HR) efficiency, and increases DNA damage. Critically, our aptamer potentiates the cytotoxicity of the PARP inhibitor olaparib, exploiting synthetic lethality (SL) to induce cancer cell death. Our study showcases an aptamer-based approach for selectively targeting protein interactions within DNA repair pathways, introducing a promising avenue for SL-based treatments applicable to a wide range of cancers.
A formal model of anxiety disorders based on the neural circuit dynamics of the fear and extinction circuits
Authors: Rubin Alan Lawrence , Walth Mark 
Published: January 2025

AbstractThe pathophysiology of anxiety disorders is the outcome of an imbalance of the fear-anxiety circuit and the extinction circuit. We present a formal model using nonlinear dynamics and network theory, which captures the dynamic interactions of the key nodes of the anxiety and extinction networks. This rudimentary model can be modified by newer data. These core nodes consist of the cells of the paraventricular nucleus of the thalamus coding negative valence, the neurons of the basal-lateral amygdala coding negative valence (Rspo2+), the anterior cingulate cortex, the ventral hippocampus neurons coding fear memories, the somatostatin expressing cells of the lateral segment of the central amygdala, the medial segment of the central nucleus of the amygdala-bed nucleus of the stria terminalis and their target nodes. The extinction network consists primarily of the paraventricular thalamic cells coding positive valence, (Ppp1r1b+) cells of the basolateral amygdala coding positive valence, the ventromedial prefrontal cortex, the PKCδ cells of the lateral segment of the central amygdala, and the intercalated cells.Human and non-human animal genetic and epigenetic studies point to deficiencies in brain-derived neurotrophic factor and neurotrophic receptor kinase tyrosine 2 production in key nodes causing reduced plasticity extinction network plasticity and leading to a weakened extinction response.We rely primarily on the neurophysiological studies of non-human animal models since nodes generating fear/anxiety and extinction responses are highly conserved across species and equivalent nodes are present within analogous circuits of the human brain. The results are confirmed, where possible by human functional magnetic resonance imaging studies.We believe this simplified model is of heurist value and can lead to a more consistent focus on physiologically based pathophysiology. This would lead to treatments to reverse the pathologic physiology produced by genetic and epigenetic abnormalities, and greater efforts to directly correct pathologic circuit activity through direct interventions such as transcranial magnetic stimulation.SignificanceWe believe this simplified model is of heurist value and can lead to a more consistent focus on physiologically based pathophysiology. This would lead to treatments to reverse the pathologic physiology produced by genetic and epigenetic abnormalities, and greater efforts to directly correct pathologic circuit activity through direct interventions such as transcranial magnetic stimulation.
Postnatal interaction of size and shape in the human endocranium and brain structures
Authors: Takagi Kuranosuke , Kondo Osamu 
Published: January 2025

AbstractThe uniqueness of human brain growth and development has been considered promising to understand the advanced cognitive ability of humans. Compared with that of chimpanzees, the human endocranium undergoes several characteristic shape changes immediately after birth, which has been termed “endocranial globularization.” However, how the brain structures and surrounding neurocranium interact with each other during early development in the context of brain–neurocranium integration remains to be investigated. We observed shape changes in the human brain and endocranium during postnatal development using magnetic resonance imaging, and analyzed spatial constraints and interactions among subdivisions of the brain influencing endocranial morphology. Our results suggest that during postnatal development, the relative size changes of supratentorial and infratentorial regions and the cranial base largely constrain brain and endocranium shape. Specifically, a disproportionate increase in the size of the cerebellum relative to the cranial base affects infratentorial spatial packing constraints in neonates, causing inferoposterior expansion of the posterior cranial fossa and coronal reorientation of the petrous bone without lateral opening of the tentorium cerebelli. The dramatic size increase of the cerebellum relative to the cranial base immediately after birth is inferred to be characteristic of human development, which corresponds to previously observed bony shape changes.
Neuropeptidergic circuit modulation of developmental sleep inDrosophila
Authors: Hemmi Chikayo , Ishii Kenichi , Motoyoshi Mana , Tsuji Masato , Emoto Kazuo 
Published: January 2025

AbstractSleep-wakefulness regulation dynamically evolves along development in flies, fish, and humans. While the mechanisms regulating sleep in adults are relatively well understood, little is known about their counterparts in early developmental stages. Here, we report a neuropeptidergic circuitry that modulates sleep in developingDrosophilalarvae. Through an unbiased screen, we identified the neuropeptide Hugin and its receptor PK2-R1 as critical regulators of larval sleep. Our data suggest that HugPC neurons secrete Hugin peptides to activate insulin-producing cells (IPCs), which express a Hugin receptor PK2-R1. IPCs, in turn, releaseDrosophilainsulin-like peptides (Dilps) to regulate sleep. We further show that the Hugin/PK2-R1 axis is dispensable for adult sleep control. Our findings thus reveal the neuromodulatory circuitry regulating larval sleep, highlighting differential impacts of the same modulatory axis on developmental sleep and adult sleep.
Lysosomal Glucocerebrosidase is needed for ciliary Hedgehog signaling: A convergent pathway to Parkinson’s disease
Authors: Nair Sreeja V. , Jaimon Ebsy , Adhikari Ayan , Nikoloff Jonas , Pfeffer Suzanne R. 
Published: January 2025

SUMMARYMutations inLRRK2andGBA1are the most common genetic causes of familial Parkinson’s disease. Previously, we showed that pathogenicLRRK2mutations inhibit primary cilia formation in rare interneurons and astrocytes of the mouse and human dorsal striatum. This blocks Hedgehog signaling and reduces synthesis of neuroprotective GDNF and NRTN, which support neurons vulnerable in PD. Here we show thatGBA1mutations also impair Hedgehog signaling through a distinct mechanism. Loss ofGBA1activity decreases accessible cholesterol in primary cilia of cultured cells, thereby disrupting Hedgehog signaling. In the mouse striatum,Gba1mutations result in reduced Hedgehog-inducedGdnfRNA expression in cholinergic interneurons, despite having no detectable impact on cilia formation. Also, bothLrrk2andGba1mutations suppress Hedgehog-inducedBdnfexpression in striatal astrocytes. These findings underscore the role of Hedgehog signaling in the nigrostriatal circuit and reveal a convergent mechanism by which distinct mutations may contribute to PD pathogenesis.
Low-temperature state in strontium titanate microcrystals using
in situ
multireflection Bragg coherent x-ray diffraction imaging
Authors: Yang David , Suzana Ana F. , Wu Longlong , Ha Sung Soo , Choi Sungwook , Ngo Hieu Minh , Nawaz Muhammad Mahmood , Kim Hyunjung , Liu Jialun , Treuherz Daniel , Zhang Nan , An Zheyi , Nisbet Gareth , Porter Daniel G. , Robinson Ian K. 
Published: January 2025

Strontium titanate is a classic quantum paraelectric oxide material that has been widely studied in bulk and thin films. It exhibits a well-known cubic-to-tetragonal antiferrodistortive phase transition at 105 K, characterized by the rotation of oxygen octahedra. A possible second phase transition at lower temperature is suppressed by quantum fluctuations, preventing the onset of ferroelectric order. However, recent studies have shown that ferroelectric order can be established at low temperatures by inducing strain and other means. Here, we used multireflection Bragg coherent x-ray diffraction imaging to measure the strain and rotation tensors for two strontium titanate microcrystals at low temperature. We observe strains induced by dislocations and inclusion-like impurities in the microcrystals. Based on radial magnitude plots, these strains increase in magnitude and spread as the temperature decreases. Pearson's correlation heat maps show a structural transition at 50 K, which could possibly be the formation of a low-temperature ferroelectric phase in the presence of strain. We do not observe any change in local strains associated with the tetragonal phase transition at 105 K.

Published by the American Physical Society
2025
Bridging correlation and spectroscopy measurements to access the hadron interaction behind molecular states: The case of the
Ξ(1620)
and
Ξ(1690)
in the
K−Λ
system
Authors: Feijoo A. , Sarti V. Mantovani , Nieves J. , Ramos A. , Vidaña I. 
Published: January 2025

We study the compatibility between the K−Λ correlation function, recently measured by the ALICE collaboration, and the LHCb K−Λ invariant mass distribution obtained in the Ξb−→J/ψΛK− decay. The K−Λ invariant mass distribution associated with the Ξb− decay has been calculated within the framework of unitary effective field theories using two models, one of them constrained by the K−Λ correlation function. We consider two degenerate pentaquark Pcs states in the J/ψΛ scattering amplitude which allows us to investigate their impact on both the K−Λ and J/ψΛ mass distributions assuming different spin-parity quantum numbers and multiplicity. Without any fitting procedure, the K−Λ model is able to better reproduce the experimental K−Λ mass spectrum in the energy region above 1680 MeV as compared to previous unitarized scattering amplitudes constrained to a large amount of experimental data in the neutral S=−1 meson-baryon sector. We observe a tension between our model and the LHCb K−Λ distribution in the region close to threshold, largely dominated by the presence of the still poorly known Ξ(1620) state. We discuss in detail the different production mechanisms probed via femtoscopy and spectroscopy that could provide valid explanations for such disagreement, indicating the necessity to employ future correlation data in other S=−2 channels such as πΞ and K¯Σ.

Published by the American Physical Society
2025
Low-loss on-chip superconducting microwave circulator assisted by shunting capacitors
Authors: Kumar N. Pradeep , Le Dat Thanh , Pakkiam Prasanna , Stace Thomas M. , Fedorov Arkady 
Published: January 2025

Ferrite-free circulators that are passive and readily integratable on a chip are highly sought-after in quantum technologies based on superconducting circuits. In our previous work, we implemented such a circulator using a three-Josephson-junction loop that exhibited unambiguous nonreciprocity and signal circulation, but required junction energies to be within 1% of design values. This tolerance is tighter than standard junction fabrication methods provide, so we propose and demonstrate a design improvement that relaxes the required junction fabrication precision, allowing for higher device performance and fabrication yield. Specifically, we introduce large direct capacitive couplings between the waveguides, which based on the modeling we describe here, requires less stringent junction fabrication tolerance. We implement the design, and measure enhanced “circulation fidelity” above 97%, with optimized on-resonance insertion loss of 0.2 dB, isolation of 18 dB, and power reflectance of −15dB, in good agreement with model calculations.

Published by the American Physical Society
2025
Literacy beyond the early years: teaching complex texts, sustaining joy
Authors: French Ruth 
Published: January 2025

PurposeThe aim of this paper is to explain key aspects of teaching and learning relevant to sustaining literacy development beyond the early years of schooling, including effective teaching of more complex texts. The paper takes as its point of departure Touchstone 9 of the Foundation Touchstones promoted by the Foundation of Learning and Literacy: “Effective literacy teaching and learning need to continue beyond the early years as literacy learning and texts become more complex”.Design/methodology/approachThis essay adopts a general narrative review approach, canvassing a range of relevant research and examples, along with implications for teaching practice.FindingsResearch shows that beyond the early years of school, literacy development involves learners responding to a range of new demands – demands for which foundational literacy skills are a necessary but not sufficient resource. Effective teaching recognises and draws learners’ attention to how language works in different discipline areas while concurrently supporting learning of content knowledge. The sustaining of enjoyment in literate activity is also identified as an important dimension of ongoing literacy development.Originality/valueThis paper distils scholarship of teaching and learning as well as insights from educational linguistics to outline some important ways in which teachers can support learners in expanding their literacy repertoires across the school years.
Anterior segment optical coherence tomography (AS‐OCT) assisted analysis of characteristics of graft dehiscence after Descemet membrane endothelial keratoplasty (DMEK) for failed penetrating keratoplasty
Authors: Vishwakarma Pratima , Mestanoglu Mert , Welge‐Lüßen Veronika , Schlereth Simona , Cursiefen Claus , Bachmann Björn 
Published: January 2025

AbstractPurposeTo analyse anterior segment optical coherence tomography (AS‐OCT) parameters of graft dehiscence after Descemet membrane endothelial keratoplasty (DMEK) for graft failure post penetrating keratoplasty (PK).MethodsRetrospective evaluation of AS‐OCT images of 142 dehiscences post‐DMEK in 75 eyes. Dehiscences' size, depth, location, correlation with graft‐host interface (GHI) override and step at GHI were assessed.ResultsThe majority of patients were male (58.7%) and mean age was 67 ± 13.6 years. Multiple dehiscences were observed in 49.3% eyes. Rebubbling was required once in 72% and multiple times in 24% eyes. Among 142 dehiscences, crossing over GHI was noted in 53.5%. The median distance of peripheral edge of dehiscences from GHI was 0.21 mm. Steps at GHI were noted in 41.5% where 22.5% dehiscences with step crossed the GHI. For dehiscences crossing versus not crossing GHI, no significant difference was noted in median depth (p = 0.268) and size (p = 0.206). For dehiscences crossing over GHI with presence versus absence of step, median depth (p = 0.23) and size (p = 0.196) showed no significant difference. No significant difference was noted in dehiscences' median depth (p = 0.16) and size (p = 0.926) among different step sizes. Incidence of dehiscence with or without steps (p = 0.8853) and graded as per size of steps, showed no significant difference.ConclusionSize and depth of dehiscence were not influenced by their crossing over GHI or the presence and size of steps. Dehiscences typically occurred in close vicinity to GHI, suggesting that DMEK graft should be placed 0.25 mm centrally from the prior PK interface, independent of GHI irregularities.
Investigation of Cannabidiol's Protective Effects on Cadmium‐Induced Toxicity in Mice
Authors: Sahin Serkan , Mortas Tulay , Muderrisoglu Ahmet , Turksoy Vugar Ali 
Published: January 2025

ABSTRACTCurrent chelation treatments used for cadmium poisoning may cause some serious side effects. Thus, safer novel treatments could be promising for clinical use. This study evaluated the effects of cannabidiol on Cd toxicity. Four groups of 10 mice were formed: Groups I and III were cadmium‐free, while groups II and IV received 50 mg/L cadmium in drinking water. Groups III and IV received daily cannabidiol (25 mg/kg) via intragastric gavage. After 30 days, the animals were killed, and blood and tissue samples were collected. Oxidative stress and inflammation markers, including glutathione, catalase, myeloperoxidase, TNF‐α, IL‐1β and IL‐6, were analysed using ELISA. Additionally, histological evaluations of the liver, kidney and testis were performed. Cadmium exposure reduced glutathione and catalase levels in the blood, liver, kidney and testis, while increasing myeloperoxidase. Cannabidiol mitigated these effects on oxidative stress markers. Cannabidiol also reduced the increase in proinflammatory cytokines. Histopathological analysis revealed reduced liver and kidney damage in cannabidiol‐treated groups compared to cadmium‐only groups. In addition, histopathological evaluation showed CBD had no protective effect on the testicular tissue against Cd toxicity. Our results indicate that cannabidiol protects against some toxic effects of cadmium. If confirmed by future studies, cannabidiol may be proposed as a novel treatment for cadmium toxicity.