bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and pharmacodynamics of five distinct commercially available hemp-derived topical cannabidiol products
Authors: Zamarripa C Austin , Tilton Hayleigh E , Lin Spencer , Cone Edward J , Winecker Ruth E , Flegel Ronald R , Kuntz David , Beals Melissa , Jacques Martin , Clark Michael , Welsh Eric R , Wagner Lynn , Bonn-Miller Marcel O , Vandrey Ryan , Spindle Tory R 
Published: January 2024

Abstract
Products containing cannabidiol (CBD) have proliferated after the 2018 Farm Bill legalized hemp (cannabis with ≤0.3% delta-9-tetrahydrocannabinol (Δ9-THC)). CBD-containing topical products have surged in popularity, but controlled clinical studies on them are limited. This study characterized the effects of five commercially available hemp-derived high CBD/low Δ9-THC topical products. Healthy adults (N = 46) received one of six study drugs: a CBD-containing cream (N = 8), lotion (N = 8), patch (N = 7), balm (N = 8), gel (N = 6) or placebo (N = 9; matched to an active formulation). The protocol included three phases conducted over 17 days: (i) an acute drug application laboratory session, (ii) a 9-day outpatient phase with twice daily product application (visits occurred on Days 2, 3, 7 and 10) (iii) a 1-week washout phase. In each phase, whole blood, oral fluid and urine specimens were collected and analyzed via liquid chromatography with tandem mass spectrometry (LC–MS-MS) for CBD, Δ9-THC and primary metabolites of each and pharmacodynamic outcomes (subjective, cognitive/psychomotor and physiological effects) were assessed. Transdermal absorption of CBD was observed for three active products. On average, CBD/metabolite concentrations peaked after 7–10 days of product use and were highest for the lotion, which contained the most CBD and a permeation enhancer (vitamin E). Δ9-THC/metabolites were below the limit of detection in blood for all products, and no urine samples tested “positive” for cannabis using current US federal workplace drug testing criteria (immunoassay cut-off of 50 ng/mL and confirmatory LC–MS-MS cut-off of 15 ng/mL). Unexpectedly, nine participants (seven lotions, one patch and one gel) exhibited Δ9-THC oral fluid concentrations ≥2 ng/mL (current US federal workplace threshold for a “positive” test). Products did not produce discernable pharmacodynamic effects and were well-tolerated. This study provides important initial data on the acute/chronic effects of hemp-derived topical CBD products, but more research is needed given the diversity of products in this market.
Breaking Bad News in Breast Imaging: Keys to Success
Authors: Greenstein Joshua , Green-Walker Aja , Stein Regina , Wang Lilian C , Bhole Sonya 
Published: January 2024

Abstract
The radiologist’s ability to effectively communicate with patients is crucial in breast imaging. Having to tell a patient that she or he requires a biopsy procedure or has a new diagnosis of breast cancer is both a challenging task and a daily reality for many practicing breast radiologists. Despite this, communication in breast imaging is often not formally taught in most training programs, leading many breast radiologists to obtain their skills through on-the-job experience. We discuss the importance of effective communication with patients and a breast imaging–specific method for delivering bad news, adapted from approaches used in medical oncology. A conversation “script” or guide is provided along with the rationale for how to best handle these difficult conversations. Lastly, we review how to teach effective communication to those in training using our breast imaging fellowship program and recent survey results as an example.
The effect of wind barriers on the local wind field on a bridge deck
Authors: Chou Chin-Chen , Chung Cheng-Yang , Chung Kung-Ming 
Published: January 2024

Abstract
The adverse effect of crosswinds on road vehicles on a bridge deck or traffic lanes is of increasing concern. Local flow characteristics depend on the bridge's architecture and wind barriers (WBs) are commonly used to alleviate wind-induced instability for vehicles. Terrain orography is another dominant factor. This study uses a terrain model with a coastal bridge (Chen-Kung Bridge, Penghu, Taiwan). The bridge is located between a reservoir and the Taiwan Strait. Numerous accidents have occurred due to strong monsoon winds in autumn and winter. In wind tunnel experiments, an atmosphere boundary layer is established and the test conditions (wind speed and wind incidence) are taken from local meteorological data. The effect of the height of solid WBs on local wind direction and speed is determined. The results can be used to remodel WBs to increase safety for road vehicles.
Patient’s perception of medication and nonadherence to chronic disease treatments. A population-based study in Brazil
Authors: da Silva Menolli Poliana Vieira , Ivama Brummel Adriana Mitsue , Guidoni Camilo Molino , Girotto Edmarlon 
Published: January 2024

Abstract

Objective
To identify the association between patients’ perception of medication for hypertension, diabetes, and dyslipidemia and nonadherence by regions of Brazil.

Methods
This is a cross-sectional study using open data from the urban population-based survey National Survey on Access, Use and Promotion of Rational Use of Medicines in Brazil (PNAUM), conducted from September 2013 to February 2014. Patients’ self-reported perceptions recorded on each of the medicines for hypertension, diabetes, and dyslipidaemia were used for analysis. The dependent variable was nonadherence to treatment, and the patient’s perceptions about medication were the independent variable. Logistic regression was performed to calculate the crude and adjusted odds ratios.

Key findings
Nonadherence was observed in 6.6% of the 16 491 drugs, with missed doses (84.5%) being the main cause. In the adjusted analysis, perception of medication effectiveness considered regular or poor (OR 3.025; 95% CI 1.672–5.473), perception that caused discomfort (OR 2.731; 95% CI 1.464–5.092), and medicines used for &lt;6 months (OR 1.557; 95% CI 1.089–2.227) had higher chances of nonadherence in Brazil (all regions).

Conclusion
Patient perception of the effectiveness, safety, and time of use of medications are key factors associated with nonadherence and can contribute to building medication beliefs that may affect current and future adherence.
Physiological adaptation to irradiance in duckweeds is species and accession specific and depends on light habitat niche
Authors: Smith Kellie E , Cowan Laura , Taylor Beth , McAusland Lorna , Heatley Matthew , Yant Levi , Murchie Erik H 
Published: January 2024

Abstract
Duckweeds span 36 species of free-floating aquatic organisms with body sizes ranging from 2 mm to 10 mm, where each plant body plan is reduced to a largely leaf-like structure. As an emerging crop, their fast growth rates offer potential for cultivation in closed systems. We describe a novel UK collection derived from low light (dLL) or high light (dHL) habitats, profiled for growth, photosynthesis, and photoprotection (non-photochemical quenching, NPQ) responses. Twenty-three accessions of three Lemna species and one Spirodela polyrhiza were grown under relatively low light (LL: 100 μmol m–2 s–1) and high light (HL: 350 μmol m–2 s–1) intensities. We observed broad within- and between-species level variation in photosynthesis acclimation. Duckweeds grown under HL exhibited a lower growth rate, biomass, chlorophyll, and quantum yield of photosynthesis. In HL compared with LL, carotenoid de-epoxidation state and NPQ were higher, whilst PSII efficiency (φPSII) and Chl a:b ratios were unchanged. The dLL plants showed relatively stronger acclimation to HL compared with dHL plants, especially Lemna japonica accessions. These achieved faster growth in HL with concurrent higher carotenoid levels and NPQ, and less degradation of chlorophyll. We conclude that these data support local adaptation to the light environment in duckweed affecting acclimation in controlled conditions.
Structural insights into the Smirnoff–Wheeler pathway for vitamin C production in the Amazon fruit camu-camu
Authors: Vargas Jhon A , Sculaccio Susana A , Pinto Andressa P A , Pereira Humberto D’Muniz , Mendes Luis F S , Flores Jhoao F , Cobos Marianela , Castro Juan C , Garratt Richard C , Leonardo Diego A 
Published: January 2024

Abstract
l-Ascorbic acid (AsA, vitamin C) is a pivotal dietary nutrient with multifaceted importance in living organisms. In plants, the Smirnoff–Wheeler pathway is the primary route for AsA biosynthesis, and understanding the mechanistic details behind its component enzymes has implications for plant biology, nutritional science, and biotechnology. As part of an initiative to determine the structures of all six core enzymes of the pathway, the present study focuses on three of them in the model species Myrciaria dubia (camu-camu): GDP-d-mannose 3',5'-epimerase (GME), l-galactose dehydrogenase (l-GalDH), and l-galactono-1,4-lactone dehydrogenase (l-GalLDH). We provide insights into substrate and cofactor binding and the conformational changes they induce. The MdGME structure reveals a distorted substrate in the active site, pertinent to the catalytic mechanism. Mdl-GalDH shows that the way in which NAD+ association affects loop structure over the active site is not conserved when compared with its homologue in spinach. Finally, the structure of Mdl-GalLDH is described for the first time. This allows for the rationalization of previously identified residues which play important roles in the active site or in the formation of the covalent bond with FAD. In conclusion, this study enhances our understanding of AsA biosynthesis in plants, and the information provided should prove useful for biotechnological applications.
Simultaneous multicolour transit photometry of hot Jupiters HAT-P-19b, HAT-P-51b, HAT-P-55b, and HAT-P-65b
Authors: Kang H , Chen G , Pallé E , Murgas F , García N Abreu , de Leon J , Enoc G , Esparza-Borges E , Fukuda I , Fukui A , Galán D , Hayashi Y , Isogai K , Kagetani T , Kawauchi K , Korth J , Livingston J H , Luque R , Ma Y , Madrigal-Aguado A , Meni P , Rodriguez P Montañes , Mori M , Torres S Muñoz , Narita N , Orell-Miquel J , Parviainen H , Peláez-Torres A , Stangret M , Tamura M , Watanabe N 
Published: January 2024

ABSTRACT
Accurate physical parameters of exoplanet systems are essential for further exploration of planetary internal structure, atmospheres, and formation history. We aim to use simultaneous multicolour transit photometry to improve the estimation of transit parameters, to search for transit timing variations (TTVs), and to establish which of our targets should be prioritized for follow-up transmission spectroscopy. We performed time series photometric observations of 12 transits for the hot Jupiters HAT-P-19b, HAT-P-51b, HAT-P-55b, and HAT-P-65b using the simultaneous four-colour camera MuSCAT2 on the Telescopio Carlos Sánchez. We collected 56 additional transit light curves from TESS photometry. To derive transit parameters, we modelled the MuSCAT2 light curves with Gaussian processes to account for correlated noise. To derive physical parameters, we performed EXOFASTv2 global fits to the available transit and radial velocity data sets, together with the Gaia DR3 parallax, isochrones, and spectral energy distributions. To assess the potential for atmospheric characterization, we compared the multicolour transit depths with a flat line and a clear atmosphere model. We consistently refined the transit and physical parameters. We improved the orbital period and ephemeris estimates, and found no evidence for TTVs or orbital decay. The MuSCAT2 broad-band transmission spectra of HAT-P-19b and HAT-P-65b are consistent with previously published low-resolution transmission spectra. We also found that, except for HAT-P-65b, the assumption of a planetary atmosphere can improve the fit to the MuSCAT2 data. In particular, we identified HAT-P-55b as a priority target among these four planets for further atmospheric studies using transmission spectroscopy.
Reflecting on naked singularities: iron line fitting as a probe of the cosmic censorship conjecture
Authors: Mummery Andrew , Ingram Adam 
Published: January 2024

ABSTRACT
We demonstrate that the X-ray iron line fitting technique can be leveraged as a powerful probe of the cosmic censorship conjecture. We do this by extending existing emission line models to arbitrary spin parameters of the Kerr metric, no longer restricted to black hole metrics with |a•| &lt; 1. We show that the emission lines from naked singularity metrics (|a•| &gt; 1) show significant differences to their black hole counterparts, even for those metrics with identical locations of the innermost stable circular orbit, i.e. emission line fitting does not suffer from the degeneracy which affects continuum fitting approaches. These differences are entirely attributable to the disappearance of the event horizon for |a•| &gt; 1. We highlight some novel emission line features of naked singularity metrics, such as ‘inverted’ emission lines (with sharp red wings and extended blue wings) and ‘triple lines’. The lack of detection of any of these novel features provides support of the cosmic censorship conjecture. We publicly release xspec packages skline and skconv which can now be used to probe the cosmic censorship conjecture in Galactic X-ray binaries and active galactic nuclei. The inclusion of super-extremal space–times can be alternatively posed as a way of stress testing conventional models of accretion.
Accurate halo mass functions from the simplest excursion set theory
Authors: Delos M Sten 
Published: January 2024

ABSTRACT
Excursion set theory is a powerful and widely used tool for describing the distribution of dark matter haloes, but it is normally applied with simplifying approximations. We use numerical sampling methods to study the mass functions predicted by the theory without approximations. With a spherical top-hat window and a constant δ = 1.5 threshold, the theory accurately predicts mass functions with the M200 mass definition, both unconditional and conditional, in simulations of a range of matter-dominated cosmologies. For Λ cold dark matter at the present epoch, predictions lie between the M200m and M200c mass functions. In contrast, with the same window function, a non-constant threshold based on ellipsoidal collapse predicts uniformly too few haloes. This work indicates a new way to simply and accurately evaluate halo mass functions, clustering bias, and assembly histories for a range of cosmologies. We provide a fitting function that accurately represents the predictions of the theory for a wide range of parameters.
Streptococcal toxic shock syndrome due to Streptococcus dysgalactiae subsp. equisimilis from retroperitoneal panniculitis during the treatment with anti-IL-6 receptor antibody: A case report
Authors: Fujimoto Sho , Eriguchi Yoshihiro , Nakamura Rinto , Kamikawa Sota , Yonekawa Akiko , Miyake Noriko , Ono Nobuyuki , Niiro Hiroaki 
Published: January 2024

ABSTRACT
A 53-year-old man with adult-onset Still’s disease developed severe streptococcal toxic shock syndrome (STSS) due to Streptococcus dysgalactiae subsp. equisimilis (SDSE), following retroperitoneal panniculitis. He was receiving tocilizumab (TCZ), an interleukin-6 receptor inhibitor. The modifying effect of TCZ on the immune response and the pathophysiology of SDSE infection may have led to retroperitoneal panniculitis and atypical STSS with delayed shock and flare of soft tissue inflammation.
Target DNA-dependent activation mechanism of the prokaryotic immune system SPARTA
Authors: Finocchio Giada , Koopal Balwina , Potocnik Ana , Heijstek Clint , Westphal Adrie H , Jinek Martin , Swarts Daan C 
Published: January 2024

Abstract
In both prokaryotic and eukaryotic innate immune systems, TIR domains function as NADases that degrade the key metabolite NAD+ or generate signaling molecules. Catalytic activation of TIR domains requires oligomerization, but how this is achieved varies in distinct immune systems. In the Short prokaryotic Argonaute (pAgo)/TIR-APAZ (SPARTA) immune system, TIR NADase activity is triggered upon guide RNA-mediated recognition of invading DNA by an unknown mechanism. Here, we describe cryo-EM structures of SPARTA in the inactive monomeric and target DNA-activated tetrameric states. The monomeric SPARTA structure reveals that in the absence of target DNA, a C-terminal tail of TIR-APAZ occupies the nucleic acid binding cleft formed by the pAgo and TIR-APAZ subunits, inhibiting SPARTA activation. In the active tetrameric SPARTA complex, guide RNA-mediated target DNA binding displaces the C-terminal tail and induces conformational changes in pAgo that facilitate SPARTA-SPARTA dimerization. Concurrent release and rotation of one TIR domain allow it to form a composite NADase catalytic site with the other TIR domain within the dimer, and generate a self-complementary interface that mediates cooperative tetramerization. Combined, this study provides critical insights into the structural architecture of SPARTA and the molecular mechanism underlying target DNA-dependent oligomerization and catalytic activation.
STIM1 translocation to the nucleus protects cells from DNA damage
Authors: Sanchez-Lopez Irene , Orantos-Aguilera Yolanda , Pozo-Guisado Eulalia , Alvarez-Barrientos Alberto , Lilla Sergio , Zanivan Sara , Lachaud Christophe , Martin-Romero Francisco Javier 
Published: January 2024

Abstract
DNA damage represents a challenge for cells, as this damage must be eliminated to preserve cell viability and the transmission of genetic information. To reduce or eliminate unscheduled chemical modifications in genomic DNA, an extensive signaling network, known as the DNA damage response (DDR) pathway, ensures this repair. In this work, and by means of a proteomic analysis aimed at studying the STIM1 protein interactome, we have found that STIM1 is closely related to the protection from endogenous DNA damage, replicative stress, as well as to the response to interstrand crosslinks (ICLs). Here we show that STIM1 has a nuclear localization signal that mediates its translocation to the nucleus, and that this translocation and the association of STIM1 to chromatin increases in response to mitomycin-C (MMC), an ICL-inducing agent. Consequently, STIM1-deficient cell lines show higher levels of basal DNA damage, replicative stress, and increased sensitivity to MMC. We show that STIM1 normalizes FANCD2 protein levels in the nucleus, which explains the increased sensitivity of STIM1-KO cells to MMC. This study not only unveils a previously unknown nuclear function for the endoplasmic reticulum protein STIM1 but also expands our understanding of the genes involved in DNA repair.
Site-specific acetylation of polynucleotide kinase 3′-phosphatase regulates its distinct role in DNA repair pathways
Authors: Islam Azharul , Chakraborty Anirban , Sarker Altaf H , Aryal Uma K , Pan Lang , Sharma Gulshan , Boldogh Istvan , Hazra Tapas 
Published: January 2024

Abstract
Mammalian polynucleotide kinase 3′-phosphatase (PNKP), a DNA end-processing enzyme with 3′-phosphatase and 5′-kinase activities, is involved in multiple DNA repair pathways, including base excision (BER), single-strand break (SSBR), and double-strand break repair (DSBR). However, little is known as to how PNKP functions in such diverse repair processes. Here we report that PNKP is acetylated at K142 (AcK142) by p300 constitutively but at K226 (AcK226) by CBP, only after DSB induction. Co-immunoprecipitation analysis using AcK142 or AcK226 PNKP-specific antibodies showed that AcK142-PNKP associates only with BER/SSBR, and AcK226 PNKP with DSBR proteins. Despite the modest effect of acetylation on PNKP’s enzymatic activity in vitro, cells expressing non-acetylable PNKP (K142R or K226R) accumulated DNA damage in transcribed genes. Intriguingly, in striatal neuronal cells of a Huntington's Disease (HD)-based mouse model, K142, but not K226, was acetylated. This is consistent with the reported degradation of CBP, but not p300, in HD cells. Moreover, transcribed genomes of HD cells progressively accumulated DSBs. Chromatin-immunoprecipitation analysis demonstrated the association of Ac-PNKP with the transcribed genes, consistent with PNKP’s role in transcription-coupled repair. Thus, our findings demonstrate that acetylation at two lysine residues, located in different domains of PNKP, regulates its distinct role in BER/SSBR versus DSBR.
Nucleolar detention of NONO shields DNA double-strand breaks from aberrant transcripts
Authors: Trifault Barbara , Mamontova Victoria , Cossa Giacomo , Ganskih Sabina , Wei Yuanjie , Hofstetter Julia , Bhandare Pranjali , Baluapuri Apoorva , Nieto Blanca , Solvie Daniel , Ade Carsten P , Gallant Peter , Wolf Elmar , Larsen Dorthe H , Munschauer Mathias , Burger Kaspar 
Published: January 2024

Abstract
RNA-binding proteins emerge as effectors of the DNA damage response (DDR). The multifunctional non-POU domain-containing octamer-binding protein NONO/p54nrb marks nuclear paraspeckles in unperturbed cells, but also undergoes re-localization to the nucleolus upon induction of DNA double-strand breaks (DSBs). However, NONO nucleolar re-localization is poorly understood. Here we show that the topoisomerase II inhibitor etoposide stimulates the production of RNA polymerase II-dependent, DNA damage-inducible antisense intergenic non-coding RNA (asincRNA) in human cancer cells. Such transcripts originate from distinct nucleolar intergenic spacer regions and form DNA–RNA hybrids to tether NONO to the nucleolus in an RNA recognition motif 1 domain-dependent manner. NONO occupancy at protein-coding gene promoters is reduced by etoposide, which attenuates pre-mRNA synthesis, enhances NONO binding to pre-mRNA transcripts and is accompanied by nucleolar detention of a subset of such transcripts. The depletion or mutation of NONO interferes with detention and prolongs DSB signalling. Together, we describe a nucleolar DDR pathway that shields NONO and aberrant transcripts from DSBs to promote DNA repair.
Electrospun PCL/gelatin/arbutin nanofiber membranes as potent reactive oxygen species scavengers to accelerate cutaneous wound healing
Authors: Du Mindong , Liu Shuhan , Lan Nihan , Liang Ruiming , Liang Shengde , Lan Maoqiang , Feng Disen , Zheng Li , Wei Qingjun , Ma Ke 
Published: January 2024

Abstract
The presence of excessive reactive oxygen species (ROS) at a skin wound site is an important factor affecting wound healing. ROS scavenging, which regulates the ROS microenvironment, is essential for wound healing. In this study, we used novel electrospun PCL/gelatin/arbutin (PCL/G/A) nanofibrous membranes as wound dressings, with PCL/gelatin (PCL/G) as the backbone, and plant-derived arbutin (hydroquinone-β-d-glucopyranoside, ARB) as an effective antioxidant that scavenges ROS and inhibits bacterial infection in wounds. The loading of ARB increased the mechanical strength of the nanofibres, with a water vapour transmission rate of more than 2500 g/(m2 × 24 h), and the water contact angle decreased, indicating that hydrophilicity and air permeability were significantly improved. Drug release and degradation experiments showed that the nanofibre membrane controlled the drug release and exhibited favourable degradability. Haemolysis experiments showed that the PCL/G/A nanofibre membranes were biocompatible, and DPPH and ABTS+ radical scavenging experiments indicated that PCL/G/A could effectively scavenge ROS to reflect the antioxidant activity. In addition, haemostasis experiments showed that PCL/G/A had good haemostatic effects in vitro and in vivo. In vivo animal wound closure and histological staining experiments demonstrated that PCL/G/A increased collagen deposition and remodelled epithelial tissue regeneration while showing good in vivo biocompatibility and non-toxicity. In conclusion, we successfully prepared a multifunctional wound dressing, PCL/G/A, for skin wound healing and investigated its potential role in wound healing, which is beneficial for the clinical translational application of phytomedicines.