bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empowering Pediatricians With Direct Penicillin Challenges: A Promising Delabeling Strategy
Authors: Park Katherine , Schwartz David J 
Published: September 2024

ABSTRACT

Objective
Current literature supports a multidisciplinary approach to penicillin allergy delabeling. Our study aims to review the success rate of penicillin challenges performed at Walter Reed National Military Medical Center Allergy Clinic and assess the reaction rate associated with a direct oral challenge in low-risk patients.

Materials and Methods
We conducted a retrospective review of the outcomes of pediatric penicillin challenges at the Walter Reed National Military Medical Center Allergy and Immunology clinic from June 2019 to May 2023. A total of 74 challenges were included in this study. Patients were initially screened to assess the date of reaction, nature of reaction, if the reaction was life-threatening, and if the patient was hospitalized or sought emergency medical care for the reported reaction. After completion of the screening questionnaire, a direct graded challenge was performed (without skin testing) if a patient’s history was deemed low risk. Patients with a recent reaction or a history of multiple drug allergies were more likely to be directed to skin prick testing and intra-dermal testing with Pre-pen and Penicillin-G prior to challenge.

Results
All patients passed all challenges. Thus, there was a 100% pass rate for both direct challenges and skin test with oral challenges.

Conclusion
Given the low rate of adverse events in this study, expansion of penicillin delabeling in the primary care setting should be considered in patients deemed to be at low risk. It is important for allergists to empower and educate their peers and push forward a movement to create a multidisciplinary approach to penicillin delabeling.
A targeted gene expression biomarker predicts clinic low-risk meningioma recurrence
Authors: Nguyen Minh P , Morshed Ramin A , Youngblood Mark W , Perlow Haley K , Lucas Calixto-Hope G , Patel Akash J , Palmer Joshua D , Horbinski Craig M , Magill Stephen T , Chen William C , Raleigh David R 
Published: September 2024

Abstract

Background
Despite reassuring clinical and histological features, low-grade meningiomas can recur after surgery. Targeted gene expression profiling improves risk stratification of meningiomas, but the utility of this approach for clinical low-risk meningiomas is incompletely understood.

Methods
This was a multicenter retrospective cohort study of meningiomas from patients who were treated at 4 institutions from 1992 to 2023. Adult patients with newly diagnosed or recurrent World Health Organization (WHO) grade 1 meningiomas that were treated with gross total resection (GTR) or subtotal resection (STR), or newly diagnosed WHO grade 2 meningiomas that were treated with GTR, were included. A 34-gene expression biomarker and gene expression risk score (continuous from 0 to 1) was evaluated in all samples.

Results
The study cohort was comprised of 723 patients, none of which were used for discovery or training of the gene expression biomarker and 265 of which were previously unreported. There were 626 WHO grade 1 meningiomas, 490 with GTR and 126 with STR, and 97 WHO grade 2 meningiomas with GTR. Targeted gene expression profiling classified 51.3% of clinical low-risk meningiomas as molecular intermediate-risk and 9.5% as molecular high-risk. Combining the gene expression biomarker with the extent of resection revealed that 19.8% of clinical low-risk meningiomas had unfavorable local freedom from recurrence (LFFR) and overall survival (OS), including 7.1% of newly diagnosed WHO grade 1 meningiomas with GTR. The risk score was prognostic for LFFR (HR per 0.1 increase in risk score 1.89, 95% CI: 1.58–2.25) across all WHO grades, extents of resection, and newly diagnosed or recurrent presentations.

Conclusions
Targeted gene expression profiling can identify clinical low-risk meningiomas that are likely to recur after surgery.
A phase 1 dose escalation of pritumumab in patients with refractory or recurrent gliomas or brain metastases
Authors: Carrillo Jose , Gill Jaya Mini , Redfern Charles , Babic Ivan , Nomura Natsuko , Shah Dhaval K , Carrick Sean , Kesari Santosh 
Published: September 2024

Abstract

Background
This phase 1 (NCT04396717) open-label, multicenter study, evaluated Pritumumab, a IgG1 monoclonal antibody, in patients with gliomas and brain metastases. The primary objective was to evaluate the safety and/or tolerability and to identify a recommended phase 2 dose (RP2D) of Pritumumab.

Methods
Adult patients with recurrent gliomas or brain metastases were enrolled in the dose cohort that was open at the time of their consent. Study treatment consisted of pritumumab administered intravenously weekly on days 1, 8, 15, and 22 in 28-day cycles. Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated.

Results
Fifteen patients received Pritumumab in the recurrent setting. Pritumumab was well tolerated, with no serious adverse events related to Pritumumab reported. The most common drug-related toxicities were constipation and fatigue. There were no dose-limiting toxicities observed, and a maximum tolerable dose was not reached. Thus, the maximum feasible dose and recommended phase 2 dose of Pritumumab was established at 16.2 mg/kg weekly. Out of eleven patients evaluated for efficacy, one patient (9.1%) demonstrated partial response based on response assessment in neuro-oncology criteria, and disease stabilization was seen in 3 patients (27.3%).

Conclusions
Pritumumab was well tolerated with no DLTs observed up to 16.2 mg/kg weekly. Further studies are warranted to determine clinical benefit in patients.
Inductive Calculation of Superconformal Indices Based on Giant Graviton Expansion
Authors: Imamura Yosuke , Murayama Shuichi 
Published: September 2024

Abstract
We investigate a simple-sum giant graviton expansion of the superconformal indices of ${\cal N}=2$ superconformal field theories realized on D3-branes probing 7-brane backgrounds with constant axio-dilation field. The expansion is of self-dual type, and imposes strong constraints on the indices. By using the constraints we determine the first few terms in the superconformal indices for arbitrary rank $N$.
Systematic Local Simulations of Fast Neutrino Flavor Conversions with Scattering Effects
Authors: Azari Milad Delfan , Sasaki Hirokazu , Takiwaki Tomoya , Okawa Hirotada 
Published: September 2024

Abstract
We investigate the dynamics of fast neutrino flavor conversions (FFCs) in the one-dimensional (1D) and zero-dimensional (0D) models, in which spatial advection is considered and ignored, respectively. In this study, we employ snapshots obtained by our self-consistent, realistic Boltzmann-neutrino-radiation-hydrodynamics simulations. We show that the FFC growth rate is considerably larger in the 1D model than in the 0D model, as expected from the previous linear analysis results. We find that the momentum space dimension does not significantly influence the neutrino transition probability in 1D models. On the other hand, in the 0D model without collisions, the FFC depends on the momentum space, and the azimuthal angle dependence breaks the periodicity of the FFC. Our study demonstrates that collisional instability can lead to further flavor conversions on a long timescale in 1D models after the asymptotic state of FFC has been reached. Such an effect should be taken into consideration when the fast and collisional flavor instabilities coexist.
Comprehensive Analysis of Impurity Detection in Linear Alkyl Benzene–Based Liquid Scintillators Using Infrared Spectroscopy for Enhanced Neutrino Detection
Authors: Choi Ji Young , Joo Kyung Kwang , Park Jubin , Cheoun Myung-Ki 
Published: September 2024

Abstract
We present a comprehensive analysis of infrared (IR) spectra for linear alkyl benzene (LAB)-based scintillation solutions, focusing on the detection and identification of impurities. Previous research primarily utilized ultraviolet-visible spectroscopy to investigate electronic structures and transitions, whereas our approach emphasizes vibrational transitions and IR spectral characteristics. We specifically examined the presence of common impurities, such as acetone, water, and three impurity compounds (IMP1, IMP2, and IMP3) identified by the JUNO Collaboration. Acetone, a common contaminant from cleaning procedures, was detected by its characteristic absorption peaks at 1200, 1360, and 1700 $\rm {cm}^{-1}$. Water, an inevitable by-product of Gd-loaded LAB using a neutralization reaction process, was identified through distinct O-H stretching and H-O-H bending vibrations at 3200–3600 $\rm {cm}^{-1}$ and 1600 $\rm {cm}^{-1}$, respectively. The IR spectra of IMP1, IMP2, and IMP3 were theoretically calculated, revealing unique absorption bands for key functional groups, including carbonyl (C=O), amide (C-N), sulfoxide (S=O), aryl chloride (Ar-Cl), azo (N=N), and ether (C-O-C) groups. The findings confirm the absence of these impurities in the LAB (+ 2,5-Diphenyloxazole [PPO] + 1,4-Bis(2-methylstyryl)benzene [bis-MSB]) sample, ensuring the high performance and accuracy of neutrino detectors. This study demonstrates the effectiveness of IR spectroscopy as a powerful analytical tool for quality assurance in liquid scintillation solutions, providing a robust framework for enhancing the reliability and precision of neutrino detection experiments.
Progranulin enhances the engraftment of transplanted human iPS cell-derived cerebral neurons
Authors: Yamagami Keitaro , Samata Bumpei , Doi Daisuke , Tsuchimochi Ryosuke , Kikuchi Tetsuhiro , Amimoto Naoya , Ikeda Megumi , Yoshimoto Koji , Takahashi Jun 
Published: September 2024

Abstract
Cerebral organoids (COs) in cell replacement therapy offer a viable approach to reconstructing neural circuits for individuals suffering from stroke or traumatic brain injuries. Successful transplantation relies on effective engraftment and neurite extension from the grafts. Earlier research has validated the effectiveness of delaying the transplantation procedure by 1 week. Here, we hypothesized that brain tissues 1 week following a traumatic brain injury possess a more favorable environment for cell transplantation when compared to immediately after injury. We performed a transcriptomic comparison to differentiate gene expression between these 2 temporal states. In controlled in vitro conditions, recombinant human progranulin (rhPGRN) bolstered the survival rate of dissociated neurons sourced from human induced pluripotent stem cell-derived COs (hiPSC-COs) under conditions of enhanced oxidative stress. This increase in viability was attributable to a reduction in apoptosis via Akt phosphorylation. In addition, rhPGRN pretreatment before in vivo transplantation experiments augmented the engraftment efficiency of hiPSC-COs considerably and facilitated neurite elongation along the host brain’s corticospinal tracts. Subsequent histological assessments at 3 months post-transplantation revealed an elevated presence of graft-derived subcerebral projection neurons—crucial elements for reconstituting neural circuits—in the rhPGRN-treated group. These outcomes highlight the potential of PGRN as a neurotrophic factor suitable for incorporation into hiPSC-CO-based cell therapies.
SheepEye: a based-web app for real-time diagnosis of sheep anemia
Authors: Freitas Luara A , da Rocha Naila C , Barbosa Abner M P , Dorea Joao R R , Paz Claudia C P , Rosa Guilherme J M 
Published: September 2024

Abstract
Haemonchus contortus is an extremely harmful blood-feeding nematode affecting small ruminants, leading to anemia, weight loss, and, in severe cases, animal death. Traditional methods of monitoring anemia in sheep, such as regular physical examinations by veterinarians and laboratory tests, can be expensive and time-consuming. In this work, we propose an anemia monitoring system that uses a web-based app. The methodology for the SheepEye app is based on deep learning algorithms, including the U-net model for segmentation and the VGG19 model for classification. All learning algorithms, as well as the development of the app, were implemented in Python. The SheepEye web-based app is a promising technology that can facilitate and improve the diagnosis of parasitic infections in sheep and enhance sheep productivity. By using the app, farmers can detect anemia in their flocks and implement target selective treatment, which reduces the use of anthelmintics and consequently minimizes the risk of parasitic resistance. The SheepEye app is still in a prototype stage, but its prospective is extremely promising and our goal is to further develop it so that it can be made available for producers to use.
Factors Associated With Successful Withdrawal of Biologic Agents in Children With Colchicine-Resistant Familial Mediterranean Fever
Authors: Taş Özen , Aydın Fatma , Sezer Müge , Çelikel Acar Banu , Bahçeci Onur , Çakar Nilgün , Dumlupınar Ebru , Özçakar Zeynep Birsin 
Published: September 2024

Background
Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease, and colchicine is the mainstay of treatment. Approximately 5%–10% of patients may respond inadequately to colchicine, and anti–interleukin-1 (anti-IL-1) agents are important treatment options in these patients. The aim of this study was to see whether there is any factor associated with the withdrawal of these anti-IL-1 agents and to investigate the characteristics of colchicine-resistant FMF patients who needed biological therapy.

Methods
Demographic, clinical characteristics, and disease severity of patients, at 2 referral centers, between 2012 and 2022, in whom anti-IL-1 treatment was continued and discontinued, were compared in this study. The international severity scoring system for FMF (ISSF) was used for disease severity assessment.

Results
In 64 colchicine-resistant FMF patients, the median (interquartile range) duration of biological treatment was 39 (45) months. Treatment of 26 patients (40.6%) was started with anakinra and 38 (59.4%) with canakinumab. During follow-up, anti-IL-1 treatment was discontinued in 23 patients (35.9%). High ISSF scores before biological treatment, presence of exertional leg pain, subclinical inflammation, and comorbidities were found to be statistically more frequent in the group whose biological therapy could not be discontinued (p = 0.009, p = 0.006, p = 0.026, p = 0.001, respectively).

Conclusions
Low ISSF scores before biological treatment with no accompanying exertional leg pain, subclinical inflammation, and comorbidities may be stated as an associated factors in terms of the discontinuation of biological agents in colchicine-resistant pediatric FMF patients.
Characterisation of virulence ofPuccinia coronataf. sp.avenaein Australia in the 2023 growing season
Authors: Nguyen Duong T. , Henningsen Eva C. , Lewis David , Mago Rohit , Sperschneider Jana , Stone Eric , Dodds Peter N. , Figueroa Melania 
Published: September 2024

AbstractCrown rust caused by the basidiomycete fungusPuccinia coronataf. sp.avenae(Pca) results in significant crop losses worldwide. Genetic solutions to protect against this disease require disease resistance gene discovery and introduction of resistance genes into elite germplasm by breeders. To inform disease resistance breeding activities, it is paramount to monitor changes of virulence in thePcapopulation and link those to genotypes of the pathogen. In 2023, a collection of 37Pcaisolates from diverse regions in Australia were gathered and their infection types across a commonly used set of oat differential lines determined to assign virulence pathotypes. We compared those virulence phenotypes to data collected in previous collections. While some of the virulence phenotypes had been reported in 2022, our analysis detected new virulence or an increase in frequency for virulence on some resistance genes. Notably, some of the frequency increases in virulence were recorded in Western Australia (WA), a region of interest due to its role in oat production for milling.
Trial-level factors affecting accrual rate of systemic sclerosis randomized clinical trials over 20 years
Authors: Russo Barbara , Chirică Iulia-Simona , Courvoisier Delphine Sophie , Iudici Michele 
Published: September 2024

AbstractObjectivesTo estimate the average time to complete patient enrollment and identify factors associated with accrual rates in systemic sclerosis (SSc) randomized controlled trials (RCTs).MethodsWe searched published SSc-RCTs indexed in PubMed from 2000 to 2024, selecting those with recruitment completed before the COVID-19 pandemic. We recorded key trial features (country, phase, randomization ratio, intervention, blinding, funding source, outcome type) and enrollment year(s). We measured enrollment duration and accrual rate (participants per month). A multivariable negative binomial generalized linear model was used to identify factors associated with accrual rate.ResultsWe included 80 studies, mostly single-country (75.0%) and industry-funded (57.5%), mainly recruiting in Europe (36.2%) and North America (22.5%). In 65% of studies, both limited and diffuse SSc patients were enrolled. The median sample size was 40.5 patients, with 20% of RCTs enrolling ≥100 patients. The median recruitment time was 15 months (IQR 9.9 – 30.0), with a median accrual rate of 3.1 (IQR 1.6 - 5.5) participants per month. Recruitment rates varied over time, with faster accrual early in the 2000s and after 2012, and a slower period in between. Multivariable analysis showed that accrual rate was positively associated with skewed randomization, non-industry funding, international recruitment, and inclusion of both SSc subsets, especially compared to studies involving only dcSSc patients.ConclusionsRecruiting SSc patients for RCTs has been challenging, with generally slow accrual over the past 20 years and no significant improvement over time.
Nuclear Type I Myosins are Essential for Life and Genome Organization
Authors: Peng Audrey Yi Tyan , Li Jianhui , Freeman Brian C. 
Published: September 2024

AbstractThe active transport of large biomolecules within a cell is critical for homeostasis. While the cytoplasmic process is well-studied, how the spacing of nucleoplasmic cargo is coordinated is poorly understood. We investigated the impact of myosin motors in the nucleus of budding yeast. We found that life requires a nuclear type I myosin whereas the essential type II or V myosins were not requisite in the nucleus. Nuclear depletion of type I myosins triggered 3D genome disorganization, nucleolar disruption, broad gene expression changes, and nuclear membrane morphology collapse. Genome disorganization occurred first supporting a model where type I myosins actively maintain genome architecture that scaffolds nuclear membrane and nucleolar morphologies. Overall, nuclear myosin is critical for the form and function of the nucleus.
Use it or lose it: A four-year follow-up to assess whether engagement with physical activity close to one’s physical capacity may protect against decline in physical functioning among older adults
Authors: Löppönen Antti , Lindeman Katja , Palmberg Lotta , Van Roie Evelien , Delecluse Christophe , Portegijs Erja , Rantanen Taina , Rantalainen Timo , Karavirta Laura 
Published: September 2024

ABSTRACTPURPOSEPhysical activity (PA) is distinct from physical capacity (PC), even though they are correlated in old age. PC defines the limits for PA, while activities in daily life typically remain submaximal. Individuals whose intensity of daily activities is close to physical capacity may be better protected from future decline in physical function compared to those who do not, although prospective research to support this hypothesis is lacking. Therefore, this study compared changes in physical function over a four-year follow-up between community-dwelling older adults categorized based on their combined baseline PC and PA.METHODSThis was a four-year longitudinal follow-up study of older adults aged 75-85 years at baseline (N = 312, 60% women). Baseline PC was determined based on 5-second Mean Amplitude Deviation (MAD) epoch value during the maximal 10-meter walking test, and PA was determined based on the peak 75-minutes MAD intensity threshold from thigh-worn accelerometer monitoring over 3-7 days. Baseline values of PA and PC were categorized into lowPC-lowPA, lowPC-highPA, highPC-lowPA, and highPC-highPA profiles. Physical function was evaluated using the Short Physical Performance Battery (SPPB) at baseline and at the follow-up, with total score and 5 x Sit-To-Stand (5xSTS) test time as the primary outcomes. Nonparametric tests and generalized estimating equations were used for analyses.RESULTSFrom baseline to follow-up, statistically significant changes in the SPPB total score and 5xSTS test time were observed in all profiles (p<0.05) except the low PC-high PA profile. Over the follow-up period, the decrease was greater for low versus high PA profiles within both PC profiles for SPPB total score (high PC: B -0.61, SE 0.24, 95% CI -1.08, -0.15; low PC: B -0.96, SE 0.35, 95% CI -1.62, -0.32), but not for 5xSTS time. No statistically significant difference was observed in the change in 5xSTS test time between the low and high PA profiles for either PC profile.CONCLUSIONSThe findings suggest that engaging in demanding PA regardless of baseline PC may help to protect against a decline in physical functioning in old age. Consequently, older adults should be encouraged to engage in physically demanding activities that could potentially enhance their functional capacity.
Lipid Trajectories Improve Risk Models for Alzheimer’s Disease and Mild Cognitive Impairment
Authors: Chase Bruce A. , Frigerio Roberta , Yucus Chad J. , Patel Smita , Maraganore Demetrius , Sanders Alan R. , Duan Jubao , Markopoulou Katerina 
Published: September 2024

AbstractTo assess the relationship between lipids and cognitive dysfunction, we retrospectively analyzed blood-lipid levels in clinically well-characterized individuals with stable mild cognitive impairment (MCI) or Alzheimer’s disease (AD) over the decade prior to first cognitive symptoms. In this case/control cohort study, AD and MCI cases were diagnosed using DSM-IV criteria; MCI cases had not progressed to dementia for ≥5 years; and controls were propensity matched to cases at age of symptom onset (MCI: 116 cases, 435 controls; AD: 215 cases, 483 controls). Participants were grouped based on longitudinal trajectories and quintile of variability independent of the mean (VIM) for total cholesterol, HDL-C, LDL-C, non-HDL-C and ln(triglycerides). Models for the risk of cognitive dysfunction evaluated trajectory and VIM groups,APOEgenotype, polygenic risk scores (PRS) for AD and lipid levels, age, comorbidities, and longitudinal correlates of blood-lipid concentrations. Lower HDL-C trajectories (OR = 3.8, 95% CI = 1.3–11.3) and the lowest VIM quintile of non-HDL-C (OR = 2.2, 95% CI = 1.3–3.0) were associated with higher MCI risk. Lower HDL-C trajectories (OR = 3.0, 95% CI = 1.6–5.7) and the lowest VIM quintile of total cholesterol (OR = 2.4, 95% CI = 1.5–3.9) were associated with higher AD risk. The inclusion of lipid-trajectory and VIM groups improved risk-model predictive performance independent ofAPOEgenotype or PRS for AD and lipid levels. These results provide an important real-world perspective on the influence of lipid metabolism and blood-lipid levels on the development of stable MCI and AD.