bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rise in inappropriate antibiotic prescriptions for Streptococcal Pharyngitis in an era of antibiotic shortages
Authors: Bausley Lauryn , Wozniak Amy , Qureshi Nadia K 
Published: October 2024

Abstract

Background
Group A streptococcal (GAS) pharyngitis is the most common cause of bacterial pharyngitis. It accounts for about a quarter of pharyngitis cases seen in children. The American Academy of Pediatrics (AAP) and Infectious Disease Society of America (IDSA) have issued guidelines for the diagnosis and treatment of GAS pharyngitis. Penicillin is the antibiotic of choice for GAS infections along with Amoxicillin. Based on a previous study at Loyola University Medical Center (LUMC), over 1/3rd of all antibiotics prescribed in our sample of 7000 encounters were considered inappropriate. During our intervention period, there was an increased incidence in GAS infections along with multiple antibiotic shortages from Oct 2022. Our study aimed to 1) Do provider education on evaluation of streptococcal pharyngitis and treatment 2) Evaluation of adherence to the evidence-based protocol 3) Determine frequency of inappropriate testing and antibiotic management 4) Determine the antibiotic when treating GAS at LUMC.

Methods
A retrospective chart review of patients between the ages of 0-18 years presented at LUMC with the pharyngitis diagnoses codes between Jan 2022-Dec 2022 and post-education between Jan 2023-June 2023 was done. LUMC providers were educated via different forums and an evidence-based protocol was shared. Patient-level data extracted from the Electronic Health Record (EHR) included race, gender, age in years, insurance type, drug allergies and encounter type i.e., clinic visit, immediate care (IMC) or emergency department (ED). P-values were calculated with repeated patients’ statement and exchangeable correlation matrix.

Results
Individuals with allergies and individuals who received antibiotics due to secondary diagnoses were excluded. The baseline year of 2022 had a lower incidence of positive GAS cases (5.7%) compared to the 2023 Q1 (27.5%) and Q2 (22.9%). Overall inappropriate prescribing was 19.2% in 2022 and increased to 39.2% and 40.9% in Q1 and Q2 of 2023, respectively. While there was an increased use of Penicillin in post-education period, there was an increase in use of other broad-spectrum antibiotics as well.

Conclusion
This study showed despite provider education, due to a significant increase in GAS cases across the US and national antibiotic shortages (amoxicillin and then penicillin) during our post-education period, there was an increase in inappropriate management of GAS cases. With reduction in antibiotic shortages, and continued provider education, future clinical management for GAS pharyngitis will improve for pediatric patients.

Fig 1. Summary of incorrect prescribing: By Scenario

Fig 2. Trends over time (by month) with reference lines for antibiotic shortages
Table 1. Summary of Testing and Prescribing by Time
Leveraging thePlasmodium falciparum esterase repertoire to design parasite-specific prodrugs
Authors: Sundararaman Sesh A , Kasak Paulina , Daniels Abigail , John Audrey O 
Published: October 2024

Abstract

Background
Antimalarial drug resistance remains a constant threat, highlighting the need to identify new antimalarials with novel modes of action. Unfortunately, new drug development is often hampered by poor drug-like properties of lead compounds. Prodrugging temporarily masks undesirable compound features, improving bioavailability and target penetration. However, many prodrugs are activated by non-specific host enzymes, losing these beneficial features before they reach their target site. Designing prodrugs that are activated by enzymes specific to a target pathogen, “pathogen specific prodrugs,” would allow prodrugs to maintain their beneficial pharmacokinetic and pharmacodynamic effects until they reach their target. We have previously shown that lipophilic ester prodrug modifications substantially increase the potency of antimalarial phosphonates both in vitro and in vivo. However, ester prodrug activation in the malaria parasite, Plasmodium falciparum is poorly understood, as only a single P. falciparum esterase has been characterized.

Methods
In this study, we use a novel fluorogenic ester substrate library, to characterize the substrate specificity of the entire esterase repertoire of P. falciparum. We compare this substrate specificity to that of host erythrocytes, serum, liver and intestinal epithelium. We employ a combination of substrate activity profiling, enzymatic inhibition assays, and liquid chromatography mass spectrometry, to identify the activating enzyme of highly potent antimalarial phosphonate prodrugs.

Results
We find that structurally similar substrates exhibit varying degrees of activation by human and parasite esterases. We identify a group of long unbranched alkyl substrates that are specifically activated by P. falciparum esterases, suggesting an important structure activity relationship. We also identify an erythrocyte serine hydrolase (APEH), which is imported by the parasite and activates multiple antimalarial phosphonate prodrugs.

Conclusion
This study identifies ester prodrug modifications that are specifically activated by P. falciparum, and highlights candidate enzymes responsible for their activation. Our data reveals that an imported human esterase is involved in the activation of antimalarial phosphonate ester prodrugs. Our method can be applied to other organisms or genetic mutants to rapidly characterize esterase activity. Ongoing work will use recombinantly expressed enzymes to specifically characterize their substrate specificities, allowing for the identification of substrates and prodrugs targeted towards those enzymes.
In vitro and in vivo performance of amorphous solid dispersions of ursolic acid as a function of polymer type and excipient addition
Authors: Zhao Tingting , Gu Chenming , Qi Jianbo , Liu Jingwen , Wang Yajun , Chen Xiaojing , Guo Fujiang , Li Yiming 
Published: October 2024

Abstract

Objectives
The objective of this research was to enhance the bioavailability of ursolic acid (UA) by preparing multielement amorphous solid dispersion (ASD) systems comprising excipients.

Methods
The ASDs were prepared via the solvent evaporation method, characterized by a range of techniques, and investigated with respect to permeability of human colorectal adenocarcinoma cell line (Caco-2) cells monolayers and pharmacokinetics, with comparisons made to the physical mixture and the pure drug.

Key findings
The (UA-choline)-Polyethylcaprolactam—polyvinyl acetate—polyethylene glycol grafted copolymer (Soluplus)-Vitamin E polyethylene glycol succinate (TPGS) ASD demonstrated superior dissolution properties compared to the corresponding binary solid dispersions and ternary solid dispersions (P&lt; .05). The permeability studies of Caco-2 cell monolayers revealed that the ASD exhibited moderate permeability, with an efflux rate that was significantly lower than that of the UA raw material (P&lt; .05). Pharmacokinetic studies in rats demonstrated that the oral bioavailability of the ASD was 19.0 times higher than that of UA (P&lt; .01).

Conclusions
The research indicated that the multielement ASD could be employed as an efficacious drug delivery system for UA. Furthermore, the Soluplus/TPGS/choline combination represents a promising candidate for the fabrication of ASDs that can load weakly acidic and poorly soluble drugs.
Repulsion, chaos, and equilibrium in mixture models
Authors: Cremaschi Andrea , Wertz Timothy M , De Iorio Maria 
Published: October 2024

Abstract
Mixture models are commonly used in applications with heterogeneity and overdispersion in the population, as they allow the identification of subpopulations. In the Bayesian framework, this entails the specification of suitable prior distributions for the weights and locations of the mixture. Despite their popularity, the flexibility of these models often does not translate into the interpretability of the clusters. To overcome this issue, repulsive mixture models have been recently proposed. The basic idea is to include a repulsive term in the distribution of the atoms of the mixture, favouring mixture locations far apart. This approach induces well-separated clusters, aiding the interpretation of the results. However, these models are usually not easy to handle due to unknown normalizing constants. We exploit results from equilibrium statistical mechanics, where the molecular chaos hypothesis implies that nearby particles spread out over time. In particular, we exploit the connection between random matrix theory and statistical mechanics and propose a novel class of repulsive prior distributions based on Gibbs measures associated with joint distributions of eigenvalues of random matrices. The proposed framework greatly simplifies computations thanks to the availability of the normalizing constant in closed form. We investigate the theoretical properties and clustering performance of the proposed distributions.
Correction of lower limb deformity in an adult patient with Ellis-van Creveld syndrome: a rare case report
Authors: Metoki Yukie , Iwase Dai , Ota Ryo , Aikawa Jun , Mukai Manabu , Fukushima Kensuke , Inoue Gen , Takaso Masashi 
Published: October 2024

Abstract
Ellis-van Creveld syndrome (EVC) is a rare disorder with marked valgus knee deformity, and orthopedic surgeons may experience challenges with lower limb treatment. Most previous reports have focused on EVC in childhood and few on its treatment in adulthood. Our patient was a 23-year-old woman with bilateral knee pain and gait abnormalities, with no history of orthopedic treatment. Valgus knee deformities with anterolateral depression of the lateral tibial plateaus and external rotation deformities of the lower legs were observed on radiography. We performed extra-articular osteotomy of the femurs and tibias and soft tissue release. Although the correction of each femur and tibia was good, mild valgus deformity of the lower limbs remained. This may be because the depression of the lateral tibial plateau was not repaired, and no postoperative remodeling was performed. However, 10 years post-surgery, no recurrence of the deformity was observed and walking was stable without pain.
The Hague Convention on the Recognition of Divorces and Legal Separations 1970: an effective mechanism for regulating divorce as between the UK and the EU post-Brexit?
Authors: Ní Shúilleabháin Máire , Trimmings Katarina 
Published: October 2024

Abstract
This article examines the potential of the 1970 Hague Convention on the Recognition of Divorces and Legal Separations to act as a replacement for Brussels IIa in regulating international divorce as between the UK and the EU. The article proceeds in two steps: first, there is a doctrinal analysis of the 1970 Hague Convention and of its merits and demerits by comparison with Brussels IIa, and secondly, there is a discussion of empirical research undertaken at the University of Aberdeen in conjunction with partner universities in six EU Member States, examining the practical utility of the Convention in Contracting States, and the treatment of international divorce in non-Contracting States. Insofar, as the 1970 Hague Convention is currently applicable in only 12 out of the 27 EU Member States, the article also discusses the likelihood of EU-wide adoption of the Convention. The article concludes that the 1970 Hague Convention has aged relatively well and, on the whole, offers a satisfactory alternative mechanism for the regulation of international divorce in the UK-EU context; however, the article also acknowledges the liberalism of many existing national laws on divorce recognition, suggesting that EU-wide adoption (if it occurs) might not have a very significant impact.
Feasibility Assessment of Rapid Response EEG in the Identification of Nonconvulsive Seizures During Military Medical Air Transport
Authors: Luster Joshua D , Hoffman William R , Jordan Morgan , Cacic Kelsey , Tchopev Zahari N , Anderson Jess , Gissendanner William , Miranda Elijah , Yuan Tony , Willis Adam 
Published: October 2024

ABSTRACT

Introduction
Traumatic brain injury often requires neurologic care and specialized equipment, not often found downrange. Nonconvulsive seizures (NCSs) and nonconvulsive status epilepticus (NCSE) occur in up to 30% of patients with moderate or severe traumatic brain injury and is associated with a 39% morbidity and an 18% mortality. It remains difficult to identify at bedside because of the heterogeneous clinical manifestations. The primary diagnostic tool is an electroencephalogram (EEG) which is large, requires an external power source, and requires a specialized technician and neurologist to collect and interpret the data. Rapid response EEG (rr-EEG) is an FDA-approved device that is pocket sized and battery powered and uses a disposable 10-electrode headset. Prior studies have demonstrated the noninferiority of rr-EEG in the identification of NCSE and NCS as compared to conventional EEG in hospitals. An unanswered question is whether rr-EEG could be used in the identification of NCSE and NCS by medics.

Materials and Methods
In conjunction with the Critical Care Air Transport (CCAT) team, a simulation was created and implemented on a CCAT training mission. The simulation team included a neurology resident, who oversaw the simulation, a pulmonary critical care fellow, an intensive care unit nurse, and a respiratory therapy. A survey was provided before and after the simulation. The team was expected to review the rr-EEG to make clinical decisions during ground transport, takeoff, and landing. The neurology resident monitored and recorded the team’s ability to distinguish between NCS and a normal EEG. In between, the neurology resident monitored the quality of the EEG for potential interference and loss of quality.

Results
The CCAT team was able to efficiently set up the rr-EEG on a patient manikin, correctly identify visual EEG wave forms of a patient in NCS, and utilize the proprietary audio program of a simulated patient in NCS. The team reported that the device was easily set up in the environment, and the data were interpretable despite vibration, aircraft auditory and electrical noise, and the ergonomics of the aircraft medical section.

Conclusions
This pilot study has validated a potentially revolutionary technology in medical transport. The rr-EEG technology is measurably user-friendly and will improve patient outcomes. This device and simulation can reduce time to an EEG by hours to days allowing for immediate treatment and intervention, which can significantly reduce morbidity and mortality.
Comparing dark matter and MOND hyphotheses from the distribution function of A, F, early-G stars in the solar neighbourhood
Authors: Syaifudin M A , Arifyanto M I , Wulandari H R T , Mulki F A M 
Published: October 2024

ABSTRACT
Dark matter is hypothetical matter assumed to address the historically known as missing mass problem in galaxies. However, alternative theories, such as Modified Newtonian Dynamics (MOND), have been notably successful in explaining the missing mass problem in various astrophysical systems. The vertical distribution function of stars in the solar neighbourhood serves as a proxy to constrain galactic dynamics in accordance to its contents. We employ both the vertical positional and velocity distribution of stars in cylindrical coordinates with a radius of 150 pc and a half-height of 200 pc from the galactic plane. Our tracers consist of main-sequence A, F, and early-G stars from the GAIA, RAVE, APOGEE, GALAH, and LAMOST catalogues. We attempt to solve the missing mass in the solar neighbourhood, interpreting it as either dark matter or MOND. Subsequently, we compare both hypotheses Newtonian gravity with dark matter and MOND, using the Bayes factor (BF) to determine which one is more favoured by the data. We found that the inferred dark matter in the solar neighbourhood is in range of $\sim (0.01 \!-\! 0.07) \, \textrm {M}_{\odot } \, \textrm {pc}^{-3}$. The wide range of inferred dark matter density is caused by the peculiar behaviour of F-type stars, which could be a sign of dynamical disequilibrium. We also determine that the MOND hypothesis’s acceleration parameter $a_0$ is $(1.26 \pm 0.13) \times 10^{-10} \, \textrm {m} \, \textrm {s}^{-2}$ for simple interpolating function. The average of BF for all tracers between the two hypotheses is $\log \textrm {BF}\sim 0.1$, meaning no strong evidence in favour of either the dark matter or MOND hypotheses.
BEBOP VI. Enabling the detection of circumbinary planets orbiting double-lined binaries with the DOLBY method of radial–velocity extraction
Authors: Sairam Lalitha , Baycroft Thomas A , Boisse Isabelle , Heidari Neda , Santerne Alexandre , Triaud Amaury H M J , Coleman Gavin A L , Davis Yasmin T , Deleuil Magali , Hébrard Guillaume , Martin David V , Maxted Pierre F L , Nelson Richard P , Sebastian Daniel , Scutt Owen J , Standing Matthew R 
Published: October 2024

ABSTRACT
Circumbinary planets, orbiting both stars in a binary system, offer the opportunity to study planet formation and orbital migration in an environment different from that around single stars. However, despite the fact that $\gt 90~\% $ of binary systems in the solar neighbourhood are spectrally resolved double-lined binaries, there has been only one detection of a circumbinary planet orbiting a double-lined binary using the radial velocity method so far. Spectrally disentangling binary components is challenging due to blending of spectral lines and inaccuracies in spectral modelling. These inaccuracies add scatter to the measurements, which can hide the weak radial velocity signature of circumbinary exoplanets. We have obtained new high signal-to-noise, high-resolution spectra with the SOPHIE spectrograph, mounted on the 193 cm telescope at Observatoire de Haute-Provence (OHP), for six bright, double-lined binaries for which circumbinary exoplanet detection has been attempted in the past. To extract radial velocities, we use the DOLBY code, a recent method of spectral disentangling using Gaussian processes to model the time-varying components. We analyse the resulting radial velocities with a diffusive nested sampler to seek planets, and compute sensitivity limits. We do not detect any new circumbinary planet. However, we show that the combination of new data, new radial velocity extraction methods, and improved statistical methods to determine a data set’s sensitivity to planets leads to an approximately one order of magnitude improvement compared to previous results. This improvement brings us into the range of known circumbinary exoplanets and paves the way for future observation campaigns targeting double-lined binaries.
Early-type galaxy speciation: elliptical (E) and ellicular (ES) galaxies in the Mbh–M*,sph diagram, and a merger-driven explanation for the origin of ES galaxies, antitruncated stellar discs in lenticular (S0) galaxies, and the Sérsicification of E galaxy light profiles
Authors: Graham Alister W 
Published: October 2024

ABSTRACT
In a recent series of papers, supermassive black holes were used to discern pathways in galaxy evolution. By considering the black holes’ coupling with their host galaxy’s bulge/spheroid, the progression of mass within each component has shed light on the chronological sequence of galaxy speciation. Offsets between the galaxy-morphology-dependent $M_{\rm bh}$–$M_{\rm \star ,sph}$ scaling relations trace a pattern of ‘punctuated equilibrium’ arising from merger-driven transitions between galaxy types, such as from spirals to dust-rich lenticulars and further to ‘ellicular’ and elliptical galaxies. This study delves deeper into the distinction between the ellicular galaxies – characterised by their intermediate-scale discs – and elliptical galaxies. Along the way, it is shown how some antitruncated large-scale discs in lenticular galaxies can arise from the coexistence of a steep intermediate-scale disc and a relatively shallow large-scale disc. This observation undermines application of the popular exponential-disc plus Sérsic-bulge model for lenticular galaxies and suggests some past bulge mass measurements have been overestimated. Furthermore, it is discussed how merger-driven disc-heating and blending likely leads to the spheroidalisation of discs and the conglomeration of multiple discs leads to the (high-n) Sérsicification of light profiles. The ellicular and elliptical galaxy distribution in the $M_{\rm bh}$–$M_{\rm \star ,sph}$ diagram is explored relative to major-merger-built lenticular galaxies and brightest cluster galaxies. The super-quadratic $M_{\rm bh}$–$M_{\rm \star }$ relations, presented herein, for merger-built systems should aid studies of massive black hole collisions and the gravitational wave background. Finally, connections to dwarf compact elliptical and ultracompact dwarf galaxies, with their 100–1000 times higher $M_{\rm bh}/M_{\rm \star ,sph}$ ratios, are presented.
Stochastic and secular anomalies in pulsar braking indices
Authors: Vargas Andrés F , Melatos Andrew 
Published: October 2024

ABSTRACT
Stochastic and secular variations in the spin frequency $\nu$ of a rotation-powered pulsar complicate the interpretation of the measured braking index, n, in terms of a power-law spin-down torque $\propto \nu ^{n_{\rm pl}}$. Both categories of variation can lead to anomalous braking indices, with $\vert n \vert = \vert \nu \ddot{\nu } / \dot{\nu }^2 \vert \gg 1$, where the overdot symbolizes a derivative with respect to time. Here, we quantify the combined effect of stochastic and secular deviations from pure power-law spin-down on measurements of n. Through analytical calculations, Monte Carlo simulations involving synthetic data, and modern Bayesian timing techniques, it is shown that the variance of n satisfies the predictive, falsifiable formula $\langle n^{2} \rangle = (n_{\rm pl}+\dot{K}_{\rm dim})^{2}+\sigma _{\rm dim}^{2}$, where $\dot{K}_{\rm dim}$ is inversely proportional to the time-scale $\tau _K$ over which the proportionality constant of the power-law spin-down torque varies, $\sigma _{\rm dim}$ is proportional to the timing noise amplitude and inversely proportional to the square root of the total observing time, and the average is over an ensemble of random realizations of the timing noise process. The anomalous regime $\langle n^2 \rangle \gg 1$ occurs for $\dot{K}_{\rm dim} \gg 1$, $\sigma _{\rm dim} \gg 1$, or both. The sign of n depends in part on the sign of $\dot{K}_{\rm dim}$, so it is possible to measure unequal numbers of positive and negative n values in a large sample of pulsars. The distinguishable impact of stochastic and secular anomalies on phase residuals is quantified to prepare for extending the analysis of synthetic data to real pulsars.