bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between deprivation, and the uptake and use of the common ailments service in community pharmacies in Wales
Authors: Thayer Nick , Mackridge Adam John , White Simon
Published: October 2023

Objectives

Since 2013 community pharmacies in Wales have been commissioned to provide a common ailments service (CAS), providing pharmacy medicine without charge to patients. In the first review of national pharmacy data, this study aimed to describe the relationship between provision of CAS and deprivation.

Methods

A retrospective observational study, using CAS claims data from April 2022 to March 2023 collected as part of routine service delivery. Consultation data were matched to the index of multiple deprivation (IMD) decile of the providing pharmacy. Linear regression was used to describe the correlation between CAS claims data and IMD deciles of the pharmacy postcode.

Key findings

In the study period, 239 028 consultations were recorded. More than twice as many consultations were carried out in pharmacies located in the most deprived decile (33 950) than in pharmacies in the least deprived decile (14 465). Linear regression demonstrated a significant correlation r(10) = −0.927, P < 0.001. There was a strong relationship between greater numbers of consultations and greater deprivation of the pharmacy postcode (R2 = 0.887). This significant correlation with deprivation was also found in the majority of individual conditions. There was no significant correlation between deprivation decile and the number of consultations per patient.

Conclusions

Community pharmacies offer a key resource for tackling health inequalities. Patients in those areas with the greatest need are those most likely to use the CAS in pharmacies and receive the care they need. Commissioning services like this naturally supports deprived communities, through a combination of patient behaviours, location, and accessibility.
Immunoinformatic Approach for Rational Identification of Immunogenic Peptides Against Host Entry and/or Exit Mpox Proteins and Potential Multiepitope Vaccine Construction
Authors: de Araújo Leonardo Pereira , de Melo Santos Natália Cristina , Corsetti Patrícia Paiva , de Almeida Leonardo Augusto
Published: October 2023

COVID-19 has intensified humanity's concern about the emergence of new pandemics. Since 2018, epidemic outbreaks of the mpox virus have become worrisome. In June 2022, the World Health Organization declared the disease a global health emergency, with 14 500 cases reported by the Centers for Disease Control and Prevention in 60 countries. Therefore, the development of a vaccine based on the current virus genome is paramount in combating new cases. In view of this, we hypothesized the obtainment of rational immunogenic peptides predicted from proteins responsible for entry of the mpox virus into the host (A17L, A26L/A30L, A33R, H2R, L1R), exit (A27L, A35R, A36R, C19L), and both (B5R). To achieve this, we aligned the genome sequencing data of mpox virus isolated from an infected individual in the United States in June 2022 (ON674051.1) with the reference genome dated 2001 (NC_003310.1) for conservation analysis. The Immune Epitope Database server was used for the identification and characterization of the epitopes of each protein related to major histocompatibility complex I or II interaction and recognition by B-cell receptors, resulting in 138 epitopes for A17L, 233 for A28L, 48 for A33R, 77 for H2R, 77 for L1R, 270 for A27L, 72 for A35R, A36R, 148 for C19L, and 276 for B5R. These epitopes were tested in silico for antigenicity, physicochemical properties, and allergenicity, resulting in 51, 40, 10, 34, 38, 57, 25, 7, 47, and 53 epitopes, respectively. Additionally, to select an epitope with the highest promiscuity of binding to major histocompatibility complexes and B-cell receptor simultaneously, all epitopes of each protein were aligned, and the most repetitive and antigenic regions were identified. By classifying the results, we obtained 23 epitopes from the entry proteins, 16 from the exit proteins, and 7 from both. Subsequently, 1 epitope from each protein was selected, and all 3 were fused to construct a chimeric protein that has potential as a multiepitope vaccine. The constructed vaccine was then analyzed for its physicochemical, antigenic, and allergenic properties. Protein modeling, molecular dynamics, and molecular docking were performed on Toll-like receptors 2, 4, and 8, followed by in silico immune simulation of the vaccine. Finally, the results indicate an effective, stable, and safe vaccine that can be further tested, especially in vitro and in vivo, to validate the findings demonstrated in silico.
Preanalytical factors influencing the results of ethanol analysis in postmortem specimens
Authors: Olds Maria L , Jones Alan W
Published: October 2023

Excessive drinking and drunkenness are underlying factors in many fatal accidents, which make the quantitative determination of ethanol in postmortem (PM) specimens an essential part of all unnatural death investigations. The same analytical methods are used to determine ethanol in blood taken from living and deceased persons although the interpretation of the results is more complicated in medical examiner cases owing to various preanalytical factors. The biggest problem is that under anaerobic conditions ethanol can be produced naturally in decomposed bodies by microbial activity and fermentation of blood glucose. Ways are needed to differentiate antemortem ingestion of ethanol from PM synthesis. One approach involves the determination of ethanol in alternative specimens, such as bile, cerebrospinal fluid, vitreous humor and/or urine, and comparison of results with blood alcohol concentration (BAC). Another approach involves the analysis of various alcohol biomarkers, such as ethyl glucuronide, ethyl sulfate and/or phosphatidylethanol or the urinary metabolites of serotonin 5-hydroxytryptophol/5-hydroxyindoleacetic acid (5-HTOL/5-HIAA). If ethanol had been produced in the body by microbial activity, the blood samples should also contain other low-molecular volatiles, such as acetaldehyde, n-propanol and/or n-butanol. The inclusion of 1–2% w/v sodium or potassium fluoride, as an enzyme inhibitor, in all PM specimens is essential to diminish the risk of ethanol being generated after sampling, such as during shipment and storage prior to analysis. Furthermore, much might be gained if the analytical cut-off for reporting positive BAC was raised from 0.01 to 0.02 g% when PM blood is analyzed. During putrefaction low BACs are more often produced after death than high BACs. Therefore, when the cadaver is obviously decomposed, a pragmatic approach would be to subtract 0.05 g% from the mean analytical result. Any remaining BAC is expected to give a more reliable indication of whether alcohol had been consumed before death.
Inattention and the Taxation Bias
Authors: Boccanfuso Jérémy , Ferey Antoine
Published: October 2023

This paper shows that inattention to taxes generates a time-inconsistency problem in the choice of tax policy, leading to higher taxes in equilibrium. These discretionary tax increases are inefficient as they are deviations from the socially optimal commitment policy. We call these deviations a taxation bias. Combining sufficient statistics and structural approaches, we quantify the magnitude of this policy distortion for the U.S. redistributive tax-transfer system. We find that the taxation bias ranges between 3 and 8 percentage points, alters tax-transfer progressivity, and has significant welfare effects. Overall, our findings shed new light on the implications of inattention and misperceptions.
Crime of Aggression against Ukraine
Authors: Grzebyk Patrycja
Published: October 2023

In the discourse around prosecution of perpetrators of the crime of aggression against Ukraine, there is a need to consider the impact of Eastern European regional norms, both treaty-based and customary. This concerns both the interpretation of principles of responsibility for the crime of aggression as well as the modes of prosecution thereof. The article argues that, in Eastern Europe, the crime of aggression is a well-established norm of international and national law, and aggression — as a conduct by a state — is defined based on the principle of first use of force, while political, economic and any other justifications in order to avoid responsibility are disallowed. Individual responsibility for the crime of aggression represents a departure from the International Criminal Court’s Rome Statute standard and is instead based on the International Military Tribunal’s Charter, which limits its scope to responsibility for a war of aggression. At the same time, it does not preclude, for example, prosecution of those responsible for the administration of occupied territories. As a consequence, the leadership clause might be understood as broader in comparison to the Rome Statute standards.
Molecular diagnosis of 5 silkworm strains endemic to South Korea using single-nucleotide polymorphisms selected from whole-genome sequences
Authors: Park Jeong Sun , Kim Seong-Wan , Park Jong Woo , Kim Kee-Young , Kim Seong-Ryul , Kwak Woori , Kim Iksoo
Published: October 2023

The domesticated silkworm, Bombyx mori Linnaeus (Lepidoptera: Bombycidae), often poses a challenge in strain identification due to similarities in morphology and genetic background. In South Korea, around 40 silkworm strains are classified as premium, including 5 endemic tri-molting strains: Goryeosammyeon, Sammyeonhonghoeback, Hansammyeon, Sun7ho, and Sandongsammyeon. These strains have potential for breeding programs in response to emerging industry demands, necessitating a reliable strain identification method. In this study, we established a molecular diagnosis approach for these 5 strains. We selected 2–4 single-nucleotide polymorphisms (SNPs) for each strain from whole-genome sequences of 39 strains, encompassing 37 previously studied and 2 newly added. These SNPs were utilized to construct decision trees for each endemic strain identification. The SNPs can be used to distinguish each target strain from the 38 nontarget strains by the tetra-primer amplification refractory mutation system-polymerase chain reaction, with the exception of HMS which needs the addition of PCR-restriction fragment length polymorphism method at the final step. This decision tree-based method using genomic SNPs, coupled with the 2 typing methods, produced consistent and accurate results, providing 100% accuracy. Additionally, the significant number of remaining SNPs identified in this study could be valuable for future diagnosis of the other strains.
How to Exercise Integrity in Medical Billing: Don’t Distort Prices, Don’t Free-Ride on Other Physicians
Authors: Langston Christopher
Published: October 2023

This paper proposes that billing gamesmanship occurs when physicians free-ride on the billing practices of other physicians. Gamesmanship is non-universalizable and does not exercise a competitive advantage; consequently, it distorts prices and allocates resources inefficiently. This explains why gamesmanship is wrong. This explanation differs from the recent proposal of Heath (2020. Ethical issues in physician billing under fee-for-service plans. J. Med. Philos. 45(1):86–104) that gamesmanship is wrong because of specific features of health care and of health insurance. These features are aggravating factors but do not explain gamesmanship’s primary wrong-making feature, which is to cause diffuse harm not traceable to any particular patient or insurer. This conclusion has important consequences for how medical schools and professional organizations encourage integrity in billing. To avoid free-riding, physicians should ask themselves, “could all physicians bill this way?” and if not, “does the patient benefit from the distinctive service I am providing under this code?” If both answers are “no,” physicians should refrain from the billing practice in question.
The national utilization of nonoperative management for small renal masses over 10 years
Authors: Filipas Dejan K , Beatrici Edoardo , Nolazco Jose I , Qian Zhiyu , Marks Phillip , Labban Muhieddine , Stone Benjamin V , Pierorazio Phillip M , Lipsitz Stuart R , Trinh Quoc-Dien , Chang Steven L , Cole Alexander P
Published: October 2023

Background

Management of small renal masses often involves a nonoperative approach, but there is a paucity of information about the use and associated predictors of such approaches. This study aimed to determine the trends in and predictors of use of nonoperative management of small renal masses.

Methods

Using data from the National Cancer Database for localized small renal masses (N0/M0, cT1a) diagnosed between 2010 and 2020, we conducted a cross-sectional study. Nonoperative management was defined as expectant management (active surveillance or watchful waiting) or focal ablation. Adjusted odds ratios (AORs) were calculated using multivariable logistic regression models.

Results

Of the 156 734 patients included, 10.5% underwent expectant management, and 13.9% underwent focal ablation. Later year of diagnosis was associated with a higher likelihood of nonoperative management. In 2020, the odds of receiving expectant management and focal ablation were 90% (AOR = 1.90, 95% confidence interval [CI] = 1.71 to 2.11) and 44% (AOR = 1.44, 95% CI = 1.31 to 1.57) higher, respectively, than in 2010. Black patients had increased odds of expectant management (AOR = 1.47, 95% CI = 1.39 to 1.55) but decreased odds of focal ablation (AOR = 0.93, 95% CI = 0.88 to 0.99).

Conclusion

Over the decade, the use nonoperative management of small renal masses increased, with expectant management more frequently used than focal ablation among Black patients. Possible explanations include race-based differences in physicians' risk assessments and resource allocation. Adjusting for Black race in calculations for glomerular filtration rate could influence the differential uptake of these techniques through deflated glomerular filtration rate calculations. These findings highlight the need for research and policies to ensure equitable use of less invasive treatments in small renal masses.
Neuroepithelial tumor with EWSR1::PATZ1 fusion: A literature review
Authors: Kim Hyunhee , Lee Kwanghoon , Phi Ji Hoon , Paek Sun Ha , Yun Hongseok , Choi Seung Hong , Park Sung-Hye
Published: October 2023

We present the clinicopathological and molecular genetic characteristics of a neuroepithelial tumor (NET), EWSR1::PATZ1 fusion-positive with a literature review. This fusion has recently been discovered in rare central nervous system tumors and soft tissue sarcomas and was not included in the fifth edition of the WHO classifications. We identified this fusion in 2 NETs. The first case involved a 7-year-old girl and the second case occurred in a 53-year-old man; both presented with headaches and vomiting. The pediatric case initially showed an intermediate grade of the tumor, but upon recurrences, it transformed into a high-grade tumor with 2 relapses in 8.3 years. This case exhibited high mitotic activity (20/10 high-power fields), and a high Ki-67 index (21%). The TERT promoter (TERTp) mutation was present in both initial and recurrent tumors. In contrast, the adult case was a low-grade tumor with no mitotic activity or recurrence over 13.5 months after subtotal resection and gamma knife surgery. Interestingly, the pediatric case demonstrated a longer survival time compared to conventional glioblastoma. The TERTp mutation, similar to being a molecular signature in adult-type glioblastoma, could also be an indicator of high-grade behavior in PATZ1 fusion NET.
New international commercial courts: a delocalized approach
Authors: Yates Sean David
Published: October 2023

New international commercial courts can be analysed by examining how their features differ from those of their domestic counterpart courts and from those of international commercial arbitration. This conceptual tool is termed delocalization. Higher and lower levels of featural differences, or delocalization, may affect a new court’s reception, whether local actors can participate in the new court and the new court’s relations with the domestic courts. These factors influence the extent and speed of a new court’s integration into the legal landscape as an institutional transplant. A delocalization analysis can also help track the new and domestic courts’ continuing influence over each other and the adoption, sharing or abandonment of features over time.
Who Will Suffer Most if US AIDS Funding Ends
Authors: Dow Dorothy , Mmbaga Blandina
Published: October 2023

The President's Emergency Plan for AIDS Relief (PEPFAR) is among the most successful US global health programs. It has moved HIV/AIDS from a certain death to a treatable disease. PEPFAR is now in danger of not being renewed. This perspective seeks to highlight the voice of perinatally HIV-infected Tanzanian youth.
The leaf idioblastome of the medicinal plantCatharanthus roseusis associated with stress resistance and alkaloid metabolism
Authors: Guedes Joana G , Ribeiro Rogério , Carqueijeiro Inês , Guimarães Ana Luísa , Bispo Cláudia , Archer John , Azevedo Herlander , Fonseca Nuno A , Sottomayor Mariana
Published: October 2023

Catharanthus roseus leaves produce a range of monoterpenoid indole alkaloids (MIAs) that include low levels of the anticancer drugs vinblastine and vincristine. The MIA pathway displays a complex architecture spanning different subcellular and cell type localizations, and is under complex regulation. As a result, the development of strategies to increase the levels of the anticancer MIAs has remained elusive. The pathway involves mesophyll specialized idioblasts where the late unsolved biosynthetic steps are thought to occur. Here, protoplasts of C. roseus leaf idioblasts were isolated by fluorescence-activated cell sorting, and their differential alkaloid and transcriptomic profiles were characterized. This involved the assembly of an improved C. roseus transcriptome from short- and long-read data, IDIO+. It was observed that C. roseus mesophyll idioblasts possess a distinctive transcriptomic profile associated with protection against biotic and abiotic stresses, and indicative that this cell type is a carbon sink, in contrast to surrounding mesophyll cells. Moreover, it is shown that idioblasts are a hotspot of alkaloid accumulation, suggesting that their transcriptome may hold the key to the in-depth understanding of the MIA pathway and the success of strategies leading to higher levels of the anticancer drugs.
Tracing connections: using network analysis to study trade and movement in the Mediterranean in the 11th to 14th centuries
Authors: Hancock Annabel
Published: October 2023

This study uses network approaches to study late medieval Mediterranean trade and movement and test the validity of using network methods to investigate the past. Historical literature largely focuses on merchant communities and which cities were most central for trade. In this article, two networks, one created from archaeological finds and the other from the writings of four medieval travellers, are analysed using various Social Network Analysis centrality measures and Complex Systems Science models and are compared to each other in order to explore the importance of various Mediterranean settlements and the ways in which movement occurred around the region, investigating whether they challenge or support current understandings. Network methods are shown to be useful approaches with various potential future developments to more fully explore the late medieval Mediterranean. These networks both support and challenge current historiographical views of Mediterranean trade and movement. Many of the same settlements are identified as central, and the importance of islands for movement is supported. However, some smaller settlements, which are infrequently mentioned in current historical literature are revealed as central. Movement also appears to have relied on small stopping points, rather than following express routes between a few important centres.
Deep learning-based lexical character identification in TV series
Authors: Dalla Torre Paola , Fantozzi Paolo , Naldi Maurizio
Published: October 2023

Automated character identification in movies and TV series has been typically carried out through face detection in video and the association of faces with characters’ names extracted from dialogues or cast lists. We propose a deep learning architecture to identify characters based on subtitles only, precisely through the lexicon those characters employ. The identification task is formalized as a multi-class classification task. We apply our technique to the complete set of episodes in the Gomorrah TV series and achieve an average identification accuracy beyond 94 per cent on the full set of characters.
Coccidioides species antifungal susceptibility testing: Experience from a large healthcare system in the endemic region
Authors: Zangeneh Tirdad T , Lainhart William D , Wiederhold Nathan P , Al-Obaidi Mohanad M
Published: October 2023

The clinical utility of Coccidioides species antifungal susceptibility testing (AST) remains unclear. This study describes the clinical course of eight patients with severe or chronic coccidioidomycosis and subsequent Coccidioides AST. We present the clinical manifestations, antifungal treatment regimens, and clinical outcomes for these patients.
Nannizzia species causing dermatophytosis in cats and dogs: First report of Nannizzia incurvata as an etiological agent in Brazil
Authors: Bescrovaine Jéssica de Oliveira , Warth José Francisco Ghignatti , de Souza Cybelle , Benoni Vanessa Wotkoski , Baja Franciele , Schneider Gabriela Xavier , Vicente Vania Aparecida , de Hoog Gerrits Sybren , Queiroz-Telles Flavio
Published: October 2023

Dermatophytosis is a superficial cutaneous infection, most commonly caused by fungal species such as Microsporum canis, Nannizzia gypsea (Microsporum gypseum), and Trichophyton mentagrophytes in dogs and cats. The zoonotic potential of these species is concerning, as companion animals are increasingly close to their owners. Therefore, the objectives of the study were to evaluate the current prevalence of Nannizzia-causing canine and feline dermatophytosis in Curitiba and Metropolitan Region, as well as perform phenotypic and phylogenetic characterizations of these isolates. Thus, 241 skin and fur samples from 163 dogs and 78 cats were analyzed from 2020 to 2021. The samples were obtained from animals of three sources: Veterinary Hospital of the Federal University of Paraná, animal shelters, and private clinics. The diagnosis was performed through phenotypic characterization and sequencing ITS rDNA region. Among 97 positive samples for dermatophytes, Nannizzia was identified in 14 (14.4%) samples, while other dermatophyte genera were found in the remaining 83 (85.6%) samples. Among the canine samples, nine (90%) were N. gypsea, and one (10%) was N. incurvata. Whereas in feline samples, three (75%) were N. gypsea, and one (25%) was N. incurvata. It was concluded that among 97 animals infected with dermatophytes, dogs (24.4%; 10/41) were significantly more affected by Nannizzia than cats (7.1%; 4/56) (P < .05). According to molecular analyses, the ITS rDNA region provided satisfactory results for species-level identification of Nannizzia, confirming the first report of N. incurvata as an etiological agent of canine and feline dermatophytosis in Brazil.
Evaluating bulk flow estimators for CosmicFlows–4 measurements
Authors: Whitford Abbé M , Howlett Cullan , Davis Tamara M
Published: October 2023

For over a decade there have been contradictory claims in the literature about whether the local bulk flow motion of galaxies is consistent or in tension with the ΛCDM model. While it has become evident that systematics affect bulk flow measurements, systematics in the estimators have not been widely investigated. In this work, we thoroughly evaluate the performance of four estimator variants, including the Kaiser maximum likelihood estimator (MLE) and the minimum variance estimator (MVE). We find that these estimators are unbiased, however their precision may be strongly correlated with the survey geometry. Small biases in the estimators can be present leading to underestimated bulk flows, which we suspect are due to the presence of non-linear peculiar velocities. The uncertainty assigned to the bulk flows from these estimators is typically underestimated, which leads to an overestimate of the tension with ΛCDM. We estimate the bulk flow for the CosmicFlows–4 data and use mocks to ensure the uncertainties are appropriately accounted for. Using the MLE we find a bulk flow amplitude of 408 ± 165 kms−1 at a depth of $49\, \mathrm{Mpc} h^{-1}$, in reasonable agreement with ΛCDM. However using the MVE which can probe greater effective depths, we find an amplitude of 428 ± 108 kms−1 at a depth of $173\, \mathrm{Mpc} h^{-1}$, in tension with the model, having only a 0.11 per cent probability of obtaining a larger χ2. These measurements appear directed towards the Great Attractor region where more data may be needed to resolve tensions.
Rates and properties of Type Ia supernovae in galaxy clusters within the dark energy survey
Authors: Toy M , Wiseman P , Sullivan M , Frohmaier C , Graur O , Palmese A , Popovic B , Davis T M , Galbany L , Kelsey L , Lidman C , Scolnic D , Allam S , Desai S , Abbott T M C , Aguena M , Alves O , Annis J , Bacon D , Bertin E , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Castander F J , Conselice C , da Costa L N , Pereira M E S , De Vicente J , Diehl H T , Doel P , Everett S , Ferrero I , Frieman J , Gerdes D W , Gruen D , Gruendl R A , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kuehn K , Kuropatkin N , Marshall J L , Melchior P , Mena-Fernández J , Menanteau F , Miquel R , Pieres A , Plazas Malagón A A , Romer A K , Sanchez E , Scarpine V , Sevilla-Noarbe I , Smith M , Soares-Santos M , Suchyta E , Tarle G , To C , Weaverdyck N ,   (DES Collaboration)
Published: October 2023

We identify 66 photometrically classified Type Ia supernovae (SNe Ia) from the Dark Energy Survey (DES) that have occurred within red-sequence selected galaxy clusters. We compare light-curve and host galaxy properties of the cluster SNe to 1024 DES SNe Ia located in field galaxies, the largest comparison of two such samples at high redshift (z > 0.1). We find that cluster SN light curves decline faster than those in the field (97.7 per cent confidence). However, when limiting these samples to host galaxies of similar colour and mass, there is no significant difference in the SN light-curve properties. Motivated by previous detections of a higher-normalized SN Ia delay-time distribution in galaxy clusters, we measure the intrinsic rate of SNe Ia in cluster and field environments. We find the average ratio of the SN Ia rate per galaxy between high-mass ($10\le \log \mathrm{(\mathit{ M}_{*}/{\rm \mathit{ M}}_{\odot })} \le 11.25$) cluster and field galaxies to be 0.594 ± 0.068. This difference is mass-dependent, with the ratio declining with increasing mass, which suggests that the stellar populations in cluster hosts are older than those in field hosts. We show that the mass-normalized rate (or SNe per unit mass) in massive–passive galaxies is consistent between cluster and field environments. Additionally, both of these rates are consistent with rates previously measured in clusters at similar redshifts. We conclude that in massive–passive galaxies, which are the dominant hosts of cluster SNe, the cluster delay-time distribution is comparable to the field.
The APOGEE value-added catalogue of Galactic globular cluster stars
Authors: Schiavon Ricardo P , Phillips Siân G , Myers Natalie , Horta Danny , Minniti Dante , Allende Prieto Carlos , Anguiano Borja , Beaton Rachael L , Beers Timothy C , Brownstein Joel R , Cohen Roger E , Fernández-Trincado José G , Frinchaboy Peter M , Jönsson Henrik , Kisku Shobhit , Lane Richard R , Majewski Steven R , Mason Andrew C , Mészáros Szabolcs , Stringfellow Guy S
Published: October 2023

We introduce the Sloan Digital Sky Survey (SDSS)/ Apache Point Observatory Galactic Evolution Experiment (APOGEE) value-added catalogue of Galactic globular cluster (GC) stars. The catalogue is the result of a critical search of the APOGEE Data Release 17 (DR17) catalogue for candidate members of all known Galactic GCs. Candidate members are assigned to various GCs on the basis of position in the sky, proper motion, and radial velocity. The catalogue contains a total of 7737 entries for 6422 unique stars associated with 72 Galactic GCs. Full APOGEE DR17 information is provided, including radial velocities and abundances for up to 20 elements. Membership probabilities estimated on the basis of precision radial velocities are made available. Comparisons with chemical compositions derived from the GALactic Archaeology with HERMES (GALAH) survey, as well as optical values from the literature, show good agreement. This catalogue represents a significant increase in the public data base of GC star chemical compositions and kinematics, providing a massive homogeneous data set that will enable a variety of studies. The catalogue in fits format is available for public download from the SDSS-IV DR17 value-added catalogue website.
3D global simulations of accretion onto gap-opening planets: implications for circumplanetary disc structures and accretion rates
Authors: Li Ya-Ping , Chen Yi-Xian , Lin Douglas N C
Published: October 2023

We perform a series of 3D simulations to study the accretion of giant planet embedded in protoplanetary discs (PPDs) over gap-opening time-scales. We find that the accretion mass flux mainly comes from the intermediate latitude above the disc mid-plane. The circumplanetary disc (CPD) for a super-thermal planet is rotation-supported up to ∼20–30 per cent of the planet Hill radius. While both mass inflow and outflow exists in the CPD mid-plane, the overall trend is an outflow that forms a meridional circulation with high-latitude inflows. We confirm the absence of accretion outburst from disc eccentricity excited by massive planets in our 3D simulations, contrary to the consensus of previous 2D simulations. This suggests the necessity of 3D simulations of accretion even for super-Jupiters. The accretion rates of planets measured in a steady state can be decomposed into the ‘geometric’ and ‘density depletion’ factors. Through an extensive parameter survey, we identify a power-law scaling for the geometric factor $\propto q_{\rm th}^{2/3}$ for super-thermal planets (qth being the thermal mass ratio), which transform to $\propto q_{\rm th}^{2}$ for less massive cases. The density depletion factor is limited by the disc accretion rate for mildly super-thermal planets and by gap-opening for highly super-thermal ones. Moderate planetary eccentricities can enhance the accretion rates by a factor of 2–3 by making the gap shallower, but it does not impact the flow geometry. We have applied our simulations results to accreting protoplanet system PDS 70 and can satisfactorily explain the accretion rate and CPD size in observations.
Flat patterns in cosmic structure
Authors: Peebles P J E
Published: October 2023

It is natural to wonder how far the flat pattern in the distribution of galaxies and clusters of galaxies around the de Vaucoueurs Local Supercluster extends, and whether there are other similarly extended flat patterns in the large-scale structure of the Universe. I present evidence of two extended flat and thin sheet-like patterns in the distributions of galaxies and clusters detected at redshift z < 0.021. Sheet A contains our position and is tilted 11° from the supergalactic pole, meaning the Local Supercluster is a moderately bent part of the more extended Sheet A. The continuation of this sheet is detected in the disjoint sample of galaxies at redshifts 0.021 < z < 0.041 and again in the disjoint samples of galaxies and clusters of galaxies at 0.042 < z < 0.085. Sheet B is 15 Mpc from us at its closest point. It is detected at z < 0.021 and at 0.021 < z < 0.041. These results make a serious case for the reality of signatures of close to flat and thin extended sheet-like patterns in cosmic structure, and an interesting challenge for the lambda-cold dark matter cosmology.
fried v2: a new grid of mass-loss rates for externally irradiated protoplanetary discs
Authors: Haworth Thomas J , Coleman Gavin A L , Qiao Lin , Sellek Andrew D , Askari Kanaar
Published: October 2023

We present a new fried grid of mass-loss rates for externally far-ultraviolet (FUV) irradiated protoplanetary discs. As a precursor to the new grid, we also explore the microphysics of external photoevaporation, determining the impact of polycyclic aromatic hydrocarbon (PAH) abundance, metallicity, coolant depletion (via freeze out and radial drift), and grain growth (depletion of small dust in the outer disc) on disc mass-loss rates. We find that metallicity variations typically have a small effect on the mass-loss rate, since the impact of changes in heating, cooling and optical depth to the disc approximately cancel out. The new fried grid therefore focuses on (i) expanding the basic physical parameter space (disc mass, radius, UV field, stellar mass), (ii) on enabling variation of the the PAH abundance, and (iii) including an option for grain growth to have occurred or not in the disc. What we suggest is the fiducial model is comparable to the original fried grid. When the PAH-to-dust ratio is lower, or the dust in the wind more abundant, the mass-loss rate can be substantially lower. We demonstrate with a small set of illustrative disc evolutionary calculations that this in turn can have a significant impact on the disc mass/radius/ evolution and lifetime.
Formation of misaligned second-generation discs through fly-by encounters
Authors: Smallwood Jeremy L , Nealon Rebecca , Cuello Nicolás , Dong Ruobing , Booth Richard A
Published: October 2023

Observations reveal protoplanetary discs being perturbed by fly-by candidates. We simulate a scenario where an unbound perturber, i.e. a fly-by, undergoes an inclined grazing encounter, capturing material and forming a second-generation protoplanetary disc. We run N-body and three-dimensional hydrodynamical simulations of a parabolic fly-by grazing a particle disc and a gas-rich protoplanetary disc, respectively. In both our N-body and hydrodynamic simulations, we find that the captured, second-generation disc forms at a tilt twice the initial fly-by tilt. This relationship is robust to variations in the fly-by’s tilt, position angle, periastron, and mass. We extend this concept by also simulating the case where the fly-by has a disc of material prior to the encounter but we do not find the same trend. An inclined disc with respect to the primary disc around a misaligned fly-by is tilted by a few degrees, remaining close to its initial disc tilt. Therefore, if a disc is present around the fly-by before the encounter, the disc may not tilt up to twice the perturber tilt depending on the balance between the angular momentum of the circumsecondary disc and captured particles. In the case where the perturber has no initial disc, analysing the orientation of these second-generation discs can give information about the orbital properties of the fly-by encounter.
Effect of the extended dosing interval of anti-TNF-α NANOBODY® compound ozoralizumab in patients with low disease activity rheumatoid arthritis
Authors: Takeuchi Tsutomu , Nakanishi Megumi , Kawanishi Masafumi , Yamasaki Hironori , Tanaka Yoshiya
Published: October 2023

Objectives

This article aims to evaluate the effect of the extended dosing interval on the efficacy and safety of ozoralizumab in patients with rheumatoid arthritis (RA).

Methods

In a long-term extension study (HOSHIZORA trial) for patients who had completed a phase II/III study with methotrexate or a phase III study without methotrexate, the dosing interval of ozoralizumab was allowed to extend from every 4 weeks (Q4W) to every 8 weeks (Q8W), at the physician’s discretion, for patients who had maintained a 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) <3.2 at the last two time points. The continuation rate, efficacy, and safety were examined in patients who had completed 24 weeks after the change in the dosing interval by the data cut-off point.

Results

Of the 32 patients who maintained DAS28-ESR <3.2 and changed the interval from Q4W to Q8W, 28 (87.5%) remained on Q8W for 24 weeks. At Week 24, the percentages of patients who remained on Q8W and achieved DAS28-ESR <2.6 and <3.2 were 71.9% and 84.4%, respectively. No safety concerns were observed for 24 weeks in the Q8W group.

Conclusions

In patients with RA and maintained DAS28-ESR <3.2 with ozoralizumab, efficacy was sustained and well tolerated after the dosing interval was extended from Q4W to Q8W.
Copper isotope ratios in serum do not track cancerous tumor evolution, but organ failure
Authors: Miaou Emily , Tissot François L H
Published: October 2023

Relative to healthy controls, lighter copper isotopic compositions have been observed in the serum of breast cancer and end-stage liver disease patients, raising the possibility that Cu isotope ratios could be used as a tracer for disease progression. Here, we assess the potential of natural Cu isotopic variations (expressed as δ65Cu) as diagnostic tools for cancer progression and/or liver failure by performing a first-order analysis of Cu isotopic cycling in the human body. Using a box model, we simulate the kinetics of Cu mass transfer throughout significant reservoirs in the body, allowing isotopic fractionation to occur during Cu uptake/release from these reservoirs. With this model, we determine under which conditions the serum δ65Cu values would reflect perturbation related to cancer growth and/or liver failure at a level resolvable with modern mass spectrometry. We find that tumor growth alone is unable to explain the light isotopic signature observed in serum. Instead, we find that metabolic changes to the liver function resulting in a ∼1‰ isotope fractionation during Cu uptake from the blood into the liver can readily explain the long-term serum isotopic shift of ∼0.2‰ observed in cancer patients. A similar fractionation (∼1.3‰) during Cu uptake into the liver also readily explains the −1.2‰ shift observed in the serum of cirrhosis patients with ascites, suggesting a potentially common driver of isotopic fractionation in both cases. Using this model, we then test hypotheses put forward by previous studies and begin to probe the mechanisms behind the measured isotopic compositions.
Efficacy and Safety of Cefmetazole for Bacteremia Caused by Extended-Spectrum β-Lactamase–Producing Enterobacterales vs Carbapenems: A Retrospective Study
Authors: Kashihara Eriko , Sada Ryuichi Minoda , Tsugihashi Yukio , Obayashi Hitoshi , Nakamura Akihiro , Abe Noriyuki , Miyake Hirofumi , Akebo Hiroyuki
Published: October 2023

Background

Extended-spectrum β-lactamase (ESBL)–producing Enterobacterales have become a global concern owing to increased infections, high mortality, and limited antibiotic treatment options. Carbapenems (CPMs) are effective against ESBL-producing Enterobacterales, but their overuse leads to the emergence of multidrug-resistant bacteria. Cefmetazole (CMZ) is effective in vitro; however, its clinical efficacy remains unclear.

Methods

We retrospectively reviewed patients who were treated with CMZ or CPMs for bacteremia caused by ESBL-producing Enterobacterales between 1 April 2014 and 31 September 2022 at Tenri Hospital. The primary outcome measure was 90-day mortality. We also evaluated resistance genes and sequence types of ESBL-producing Enterobacterales.

Results

In total, 156 patients were enrolled in this study. Ninety patients (58%) received CMZ therapy. Patients in the CMZ group were significantly older than those in the CPM group (median [IQR], 79 years [71–86] vs 74 years [64–83]; P = .001). The severity of the Pitt bacteremia score of the CMZ group was lower than that in the CPM group (0 [0–2] vs 2 [0–2], P = .042). Six patients (7%) in the CMZ group and 10 (15%) in the CPM group died by day 90 (P = .110). Charlson Comorbidity Index and prevalence of sequence 131 between the groups were statistically insignificant.

Conclusions

Our findings suggest that CMZ is a well-tolerated alternative to CPM for treating bacteremia caused by ESBL-producing Enterobacterales.
Use of Ceftriaxone and Benzylpenicillin in Outpatient Parenteral Antimicrobial Therapy: Spectrum vs Cost
Authors: Kalatharan L , Ferman M , Kumar S , Rajendra S , Pripanapong S , Wu Y , Richards H , Rogers B A
Published: October 2023

Background

The application of antimicrobial stewardship (AMS) principles may entail increased cost to allow for narrower-spectrum therapy. Prescribing benzylpenicillin (BP) and ceftriaxone (CRO) for outpatient parenteral antimicrobial therapy (OPAT) demonstrates the complex challenge of this principle. The aim of this study is to analyze the use of BP and CRO in our OPAT program, including indications and relative cost.

Methods

We analyzed all adult patients in our OPAT program who received intravenous BP or CRO over 1 year. We identified a “crossover group” of patients who could have received either agent. Economic comparison was based on acquisition cost of the therapy (drug, infuser, and preparation costs).

Results

Of 105 eligible patients, 54 (51%) and 51 (49%) received BP and CRO, respectively. Forty (38%) patients were suitable for either agent; of these, the majority (n = 31, 78%) were treated with BP. Economic analysis demonstrated that the average daily cost of BP therapy was $93.76/d (AUD) vs $1.23/d for CRO. Thus, across our OPAT programs, we had an additional average cost of $92.53/patient/d to use BP instead of CRO. Program-wide the annual additional cost of using BP and thus applying this AMS strategy was $68 386.12.

Conclusions

BP is often selected over CRO by clinicians, where possible, as recommended by the Australian guidelines; however, BP is associated with higher daily acquisition costs. More broadly, a number of narrower-spectrum agents may involve significantly higher costs than comparators; as such, the $92.53/d to prevent CRO exposure can be considered when applying other antimicrobial-substitution AMS interventions in an acute health care setting.
Transcriptional activation by WRKY23 and derepression by removal of bHLH041 coordinately establish callus pluripotency in Arabidopsis regeneration
Authors: Xu Chongyi , Chang Pengjie , Guo Shiqi , Yang Xiaona , Liu Xinchun , Sui Baofeng , Yu Dongxue , Xin Wei , Hu Yuxin
Published: October 2023

Induction of the pluripotent cell mass termed callus from detached organs or tissues is an initial step in typical in vitro plant regeneration, during which auxin-induced ectopic activation of root stem cell factors is required for subsequent de novo shoot regeneration. While Arabidopsis (Arabidopsis thaliana) AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 and their downstream transcription factors LATERAL ORGAN BOUNDARIES DOMAIN (LBD) are known to play key roles in directing callus formation, the molecules responsible for activation of root stem cell factors and thus establishment of callus pluripotency are unclear. Here, we identified Arabidopsis WRKY23 and BASIC HELIX-LOOP-HELIX 041 (bHLH041) as a transcriptional activator and repressor, respectively, of root stem cell factors during establishment of auxin-induced callus pluripotency. We show that auxin-induced WRKY23 downstream of ARF7 and ARF19 directly activates the transcription of PLETHORA 3 (PLT3) and PLT7 and thus that of the downstream genes PLT1, PLT2, and WUSCHEL-RELATED HOMEOBOX 5 (WOX5), while LBD-induced removal of bHLH041 derepresses the transcription of PLT1, PLT2, and WOX5. We provide evidence that transcriptional activation by WRKY23 and loss of bHLH041-imposed repression act synergistically in conferring shoot-regenerating capability on callus cells. Our findings thus disclose a transcriptional mechanism underlying auxin-induced cellular reprogramming, which, together with previous studies, outlines the molecular framework of auxin-induced pluripotent callus formation for in vitro plant regeneration programs.
Cell layer–specific expression of the homeotic MADS-box transcription factor PhDEF contributes to modular petal morphogenesis in petunia
Authors: Chopy Mathilde , Cavallini-Speisser Quentin , Chambrier Pierre , Morel Patrice , Just Jérémy , Hugouvieux Véronique , Rodrigues Bento Suzanne , Zubieta Chloe , Vandenbussche Michiel , Monniaux Marie
Published: October 2023

Floral homeotic MADS-box transcription factors ensure the correct morphogenesis of floral organs, which are organized in different cell layers deriving from distinct meristematic layers. How cells from these distinct layers acquire their respective identities and coordinate their growth to ensure normal floral organ morphogenesis is unresolved. Here, we studied petunia (Petunia × hybrida) petals that form a limb and tube through congenital fusion. We identified petunia mutants (periclinal chimeras) expressing the B-class MADS-box gene DEFICIENS in the petal epidermis or in the petal mesophyll, called wico and star, respectively. Strikingly, wico flowers form a strongly reduced tube while their limbs are almost normal, while star flowers form a normal tube but greatly reduced and unpigmented limbs, showing that petunia petal morphogenesis is highly modular. These mutants highlight the layer-specific roles of PhDEF during petal development. We explored the link between PhDEF and petal pigmentation, a well-characterized limb epidermal trait. The anthocyanin biosynthesis pathway was strongly downregulated in star petals, including its major regulator ANTHOCYANIN2 (AN2). We established that PhDEF directly binds to the AN2 terminator in vitro and in vivo, suggesting that PhDEF might regulate AN2 expression and therefore petal epidermis pigmentation. Altogether, we show that cell layer–specific homeotic activity in petunia petals differently impacts tube and limb development, revealing the relative importance of the different cell layers in the modular architecture of petunia petals.
NTRC and thioredoxinsm1/m2 underpin the light acclimation of plants on proteome and metabolome levels
Authors: Dziubek Dejan , Poeker Louis , Siemitkowska Beata , Graf Alexander , Marino Giada , Alseekh Saleh , Arrivault Stéphanie , Fernie Alisdair R , Armbruster Ute , Geigenberger Peter
Published: October 2023

During photosynthesis, plants must manage strong fluctuations in light availability on different time scales, leading to long-term acclimation and short-term responses. However, little is known about the regulation and coordination of these processes and the modulators involved. In this study, we used proteomics, metabolomics, and reverse genetics to investigate how different light environmental factors, such as intensity or variability, affect long-term and short-term acclimation responses of Arabidopsis (Arabidopsis thaliana) and the importance of the chloroplast redox network in their regulation. In the wild type, high light, but not fluctuating light, led to large quantitative changes in the proteome and metabolome, accompanied by increased photosynthetic dynamics and plant growth. This finding supports light intensity as a stronger driver for acclimation than variability. Deficiencies in NADPH-thioredoxin reductase C (NTRC) or thioredoxins m1/m2, but not thioredoxin f1, almost completely suppressed the re-engineering of the proteome and metabolome, with both the induction of proteins involved in stress and redox responses and the repression of those involved in cytosolic and plastid protein synthesis and translation being strongly attenuated. Moreover, the correlations of protein or metabolite levels with light intensity were severely disturbed, suggesting a general defect in the light-dependent acclimation response, resulting in impaired photosynthetic dynamics. These results indicate a previously unknown role of NTRC and thioredoxins m1/m2 in modulating light acclimation at proteome and metabolome levels to control dynamic light responses. NTRC, but not thioredoxins m1/m2 or f1, also improves short-term photosynthetic responses by balancing the Calvin–Benson cycle in fluctuating light.