bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isavuconazole as prophylaxis and therapy for invasive fungal diseases: a real-life observational study
Authors: Ergün Mehmet , Jansen Anouk M E , Hilbrands Luuk B , de Kort Elizabeth , Kunst Henricus , Reijers Monique H E , Schouten Jeroen A , Verweij Paul E , Brüggemann Roger J M 
Published: June 2024

Abstract

Background
Isavuconazole is a relatively new antifungal agent indicated for the management of various invasive fungal diseases (IFDs), including invasive aspergillosis. Information on real-world experience with isavuconazole is scarce. This retrospective observational study aimed to describe the usage of isavuconazole in clinical practice with an in-depth evaluation of individual isavuconazole exposure.

Methods
Patients treated with isavuconazole were evaluated based on retrospective data, including therapeutic drug monitoring (TDM) data and efficacy and safety data. Additionally, we calculated the individual isavuconazole exposure described by the average AUC24 over the first 7 days of treatment by means of non-linear mixed-effects modelling and compared this with the currently desired lower target AUC of 60 mg·h/L.

Results
Ninety-nine patients treated with isavuconazole were evaluated. In our real-life cohort, isavuconazole was often deployed off-label in patients with non-classical host factors and infections with non-Aspergillus and non-Mucorales species. Isavuconazole was most often chosen for its safety profile, even after prior triazole treatment with manifestations of toxicity. TDM and subsequent dosage adjustments were frequently performed. The individual average AUC24 over 7 days was above 60 mg·h/L in 29 out of 77 (37.7%) patients.

Conclusions
This overview provides practical insights that can aid clinicians in the management of their patients with IFD. Our study shows that isavuconazole was used in a diverse patient population and was well tolerated overall. Individual isavuconazole exposure reflected by the average AUC24 over the first 7 days of treatment was generally low and variable. Dosage adjustments following TDM were frequently performed. Our experience shows that isavuconazole is a feasible alternative after prior azole treatment.
Stratifying heart failure patients with graph neural network and transformer using Electronic Health Records to optimize drug response prediction
Authors: Chowdhury Shaika , Chen Yongbin , Li Pengyang , Rajaganapathy Sivaraman , Wen Andrew , Ma Xiao , Dai Qiying , Yu Yue , Fu Sunyang , Jiang Xiaoqian , He Zhe , Sohn Sunghwan , Liu Xiaoke , Bielinski Suzette J , Chamberlain Alanna M , Cerhan James R , Zong Nansu 
Published: June 2024

Abstract

Objectives
Heart failure (HF) impacts millions of patients worldwide, yet the variability in treatment responses remains a major challenge for healthcare professionals. The current treatment strategies, largely derived from population based evidence, often fail to consider the unique characteristics of individual patients, resulting in suboptimal outcomes. This study aims to develop computational models that are patient-specific in predicting treatment outcomes, by utilizing a large Electronic Health Records (EHR) database. The goal is to improve drug response predictions by identifying specific HF patient subgroups that are likely to benefit from existing HF medications.

Materials and Methods
A novel, graph-based model capable of predicting treatment responses, combining Graph Neural Network and Transformer was developed. This method differs from conventional approaches by transforming a patient's EHR data into a graph structure. By defining patient subgroups based on this representation via K-Means Clustering, we were able to enhance the performance of drug response predictions.

Results
Leveraging EHR data from 11 627 Mayo Clinic HF patients, our model significantly outperformed traditional models in predicting drug response using NT-proBNP as a HF biomarker across five medication categories (best RMSE of 0.0043). Four distinct patient subgroups were identified with differential characteristics and outcomes, demonstrating superior predictive capabilities over existing HF subtypes (best mean RMSE of 0.0032).

Discussion
These results highlight the power of graph-based modeling of EHR in improving HF treatment strategies. The stratification of patients sheds light on particular patient segments that could benefit more significantly from tailored response predictions.

Conclusions
Longitudinal EHR data have the potential to enhance personalized prognostic predictions through the application of graph-based AI techniques.
Automatic uncovering of patient primary concerns in portal messages using a fusion framework of pretrained language models
Authors: Ren Yang , Wu Yuqi , Fan Jungwei W , Khurana Aditya , Fu Sunyang , Wu Dezhi , Liu Hongfang , Huang Ming 
Published: June 2024

Abstract

Objectives
The surge in patient portal messages (PPMs) with increasing needs and workloads for efficient PPM triage in healthcare settings has spurred the exploration of AI-driven solutions to streamline the healthcare workflow processes, ensuring timely responses to patients to satisfy their healthcare needs. However, there has been less focus on isolating and understanding patient primary concerns in PPMs—a practice which holds the potential to yield more nuanced insights and enhances the quality of healthcare delivery and patient-centered care.

Materials and Methods
We propose a fusion framework to leverage pretrained language models (LMs) with different language advantages via a Convolution Neural Network for precise identification of patient primary concerns via multi-class classification. We examined 3 traditional machine learning models, 9 BERT-based language models, 6 fusion models, and 2 ensemble models.

Results
The outcomes of our experimentation underscore the superior performance achieved by BERT-based models in comparison to traditional machine learning models. Remarkably, our fusion model emerges as the top-performing solution, delivering a notably improved accuracy score of 77.67 ± 2.74% and an F1 score of 74.37 ± 3.70% in macro-average.

Discussion
This study highlights the feasibility and effectiveness of multi-class classification for patient primary concern detection and the proposed fusion framework for enhancing primary concern detection.

Conclusions
The use of multi-class classification enhanced by a fusion of multiple pretrained LMs not only improves the accuracy and efficiency of patient primary concern identification in PPMs but also aids in managing the rising volume of PPMs in healthcare, ensuring critical patient communications are addressed promptly and accurately.
Validation and Collaborative Studies of Headspace Gas Chromatography-Mass Spectrometry for Determination of 1,4-Dioxane in Cosmetic Samples
Authors: Lusianti Erita , Zannah Nenden Solihatul , Purwaningsih Sri , Kusuma Hasti , Hastuti Agustina A M B , Windarsih Anjar , Cheah Nuan Ping , Thongprakaisang Siriporn , Rohman Abdul 
Published: June 2024

Abstract

Background
1,4-Dioxane (1,4-D) is a byproduct of the synthesis of surfactants, typically found in some cosmetics products such as shampoo, toothpaste, and soap. The presence of 1,4-D in cosmetics products is limited to a certain amount since 1,4-D is classified as a probable human carcinogen.

Objective
This present study was intended to validate static headspace gas chromatography-mass spectrometry (HS GC-MS) for the determination of 1,4-D in cosmetics products.

Methods
The condition of HS and GC-MS was optimized to get the best condition for analysis of 1,4-D using 1,4-dioxane-d8 (1,4-D-d8) as internal standard (IS). The developed method was validated by evaluating the key performance characteristics, including specificity, linearity, limit of detection (LoD), limit of quantification (LoQ), accuracy, and precision.

Results
The results showed that HS GC-MS was specific since the peaks of the selected ion monitoring (SIM) mode could be separated and confirmed at m/z 88 and m/z 96 for 1,4-D and 1,4-D-d8, respectively. The method was linear over the concentration range of 0.1287–1.2875 µg/mL, with R2 &gt; 0.999 and RSD residuals &lt;2.0. A collaborative study was conducted on this method, with 10 participating laboratories from four countries. The outcome of this study was found to be accurate and precise, as evidenced by the excellent recoveries ranging from 94.6% to 102.1%, and with good reproducibility with RSD values ranging from 0.2 to 1.1%. The collaborative studies exhibited that all data reported by 10 participating laboratories in four countries were inliers without any extreme values observed either in mean or RSD values

Conclusions
HS GC-MS is found to be fit and suitable for the determination of trace level of 1,4-D in cosmetics products.

Highlights
The HS GC-MS method could be proposed as a standard method for quantitative analysis of 1,4-D in cosmetics products since the collaborative studies indicated that the developed method meet the requirement in “Guidelines for Collaborative Study Procedures to Validate Characteristics of a Method of Analysis.”
First report of resistance in Spodoptera frugiperda (Lepidoptera: Noctuidae) to lambda-cyhalothrin from Pakistan: baseline susceptibility, selection, occurrence of cross-resistance, realized heritability, and inheritance mode of resistance
Authors: Zaidi Sayed Wasif Naseer , Saddiq Bushra , Afzal Muhammad Babar Shahzad , Banazeer Ansa , Serrão José Eduardo , Farooq Umar , Baloch Muhammad Affan Zahid 
Published: June 2024

Abstract
Fall armyworm (FAW) Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is a global pest causing damage to several crops. However, its management using chemical control is a challenge due to its capacity to evolve resistance to insecticides. After 6 generations of selection with lambda-cyhalothrin, the LC50 for the insecticide-resistant strain (Lambda-Sel) was 486 ppm, higher than that of the field strain (FAW-MUL) (7.5 ppm), susceptible laboratory strain (Lab-PK) (0.46 ppm), and laboratory unselected strain (UNSEL) (5.26 ppm). Laboratory selection with lambda-cyhalothrin increased resistance from 16.3- to 1056.52-fold and 1.43- to 92.4-fold to lambda-cyhalothrin compared to Lab-PK and UNSEL strains, respectively. The selected strain of S. frugiperda (Lambda-Sel) presented low cross-resistance to chlorpyrifos, moderate to deltamethrin and indoxacarb, very low to spinosad, and no cross-resistance to emamectin benzoate. The realized heritability (h2) of lambda-cyhalothrin resistance in the Lambda-Sel strain was very high (0.88). The reciprocal cross progenies of F1 (Lambda-Sel ♀ × Lab-PK ♂), F1ʹ (Lambda-Sel ♂ × Lab-PK ♀), BC1 (F1 ♀ × Lambda-Sel ♂), and BC2 (F1 ♀ × Lab-PK ♂) showed high resistance ratios of 545.64-, 396.52-, 181.18-, and 146.54-fold, respectively compared to Lab-PK. The degree of dominance values for lambda-cyhalothrin in F1 and F1ʹ indicates incompletely dominant resistance. The difference between observed and expected mortality in backcross populations (BC1 and BC2) revealed a polygenic resistance. In conclusion, the resistance to lambda-cyhalothrin was autosomal, incompletely dominant, and polygenic. These findings provide new insights for insect resistance management strategies to mitigate the occurrence of resistance in this global pest.
Novel transinfections of Rickettsiella do not affect insecticide tolerance in Myzus persicae, Rhopalosiphum padi, or Diuraphis noxia (Hemiptera: Aphididae)
Authors: Dorai Ashritha Prithiv Sivaji , Umina Paul A , Chirgwin Evatt , Yang Qiong , Gu Xinyue , Thia Joshua , Hoffmann Ary 
Published: June 2024

Abstract
Aphids (Hemiptera: Aphidoidea) are economically important crop pests worldwide. Because of growing issues with insecticide resistance and environmental contamination by insecticides, alternate methods are being explored to provide aphid control. Aphids contain endosymbiotic bacteria that affect host fitness and could be targeted as potential biocontrol agents, but such novel strategies should not impact the effectiveness of traditional chemical control. In this work, we used a novel endosymbiont transinfection to examine the impact of the endosymbiont Rickettsiella viridis on chemical tolerance in 3 important agricultural pest species of aphid: Myzus persicae (Sulzer) (Hemiptera: Aphididae), Rhopalosiphum padi (Linnaeus) (Hemiptera: Aphididae), and Diuraphis noxia (Mordvilko ex Kurdjumov) (Hemiptera: Aphididae). We tested tolerance to the commonly used insecticides alpha-cypermethrin, bifenthrin, and pirimicarb using a leaf-dip bioassay. We found no observed effect of this novel endosymbiont transinfection on chemical tolerance, suggesting that the strain of Rickettsiella tested here could be used as a biocontrol agent without affecting sensitivity to insecticides. This may allow Rickettsiella transinfections to be used in combination with chemical applications for pest control. The impacts of other endosymbionts on insecticide tolerance should be considered, along with tests on multiple aphid clones with different inherent levels of chemical tolerance.
Eliminating explanations for Maladera formosae (Coleoptera: Scarabaeidae) preponderance in sandy soil
Authors: Pekarcik Adrian J , Ranger Christopher M , Long Elizabeth Y , Tilmon Kelley J 
Published: June 2024

Abstract
Most field corn in the United States receives a neonicotinoid seed treatment for the management of early-season, soil-dwelling insect pests. Grubs of Maladera formosae (Brenske) (Coleoptera: Scarabaeidae) have been reported feeding on young field corn with both low and high rates of clothianidin seed treatments in Indiana, Michigan, and Ohio. Anecdotally, these infestations are restricted to sandy soils in the region. The purpose of this study was to (1) evaluate whether grub populations in corn are restricted to sandy soils, (2) assess whether soil type influences M. formosae survival, and (3) determine whether soil type affects clothianidin uptake by the plant, possibly explaining the observed differences in M. formosae abundance by soil type. We observed nearly 10-times more grubs in sand (&gt;80% sand content) than loam (&lt;80% sand content) soil within a single corn field. Grub survival to adult was not influenced by soil type. We then compared the concentrations of clothianidin seed treatment in the roots and shoots of corn seedlings grown in either sand or loam soil over time. Similar amounts of the active ingredient were found in the roots and shoots of corn grown in both soil types. Within 2 week, the clothianidin concentrations in both soil types had significantly declined in roots and shoots and were no different from the no-insecticide control. These findings suggest that factors other than insecticide exposure contribute to the higher abundance of M. formosae larvae in sand relative to loam soils, even within the same field.
A correspondence theorem for interpretability logic with respect to Verbrugge semantics
Authors: Horvat Sebastijan , Perkov Tin 
Published: June 2024

AbstractInterpretability logic is a modal logic that can be used to describe relative interpretability between extensions of a given first-order arithmetical theory. Verbrugge semantics is a generalization of the basic semantics for interpretability logic. Bisimulation is the basic equivalence between models for modal logic. The Van Benthem Correspondence Theorem establishes modal logic as the bisimulation invariant fragment of first-order logic. In this paper we show that a special type of bisimulations, the so-called w-bisimulations, enable an analogue of the Van Benthem Theorem for interpretability logic w.r.t. Verbrugge semantics.
A review of molt in mammals, with an emphasis on marmots (Rodentia: Sciuridae: Marmota)
Authors: Mills Kendall K , Brandler Oleg V , Olson Link E 
Published: June 2024

Abstract
Molting is an evolutionarily ancient trait in which the outermost layer of an organism is replenished, usually according to a regular circannual rhythm. It is a metabolically costly process and, in vertebrates, is generally timed around other energetically demanding events such as reproduction and migration. In mammals, molting involves replacement of the fur coat—one of the most distinct innovations of the mammalian lineage. Despite the obvious importance of hair to mammalian fitness, our knowledge of hair growth cycles, circannual molting patterns, and hair structure remains largely restricted to marine and domesticated mammals, and our ability to identify explicit adaptive advantages of molting strategies in any mammal is therefore limited. In this review, we summarize what is known of these topics in wild, terrestrial mammals with a particular emphasis on marmots (Marmota spp.). Marmots are the largest extant ground squirrels and are well adapted to seasonally cold environments. Molting may be particularly relevant to fitness in marmots given the presumed importance of a healthy, insulative coat for metabolic efficiency in cold environments. Moreover, marmots hibernate for 7 to 8 months each year, meaning the annual molt and all other energetically demanding life-history events (such as parturition, lactation, fat accumulation, and dispersal) are constrained to an active period of only 4 to 5 months. Because the energetics of hibernation, fat accumulation, reproduction, and social behavior are already well studied, examining how molt is timed with respect to other important events and how it is influenced by local conditions may inform how molting is prioritized and how molting strategies evolve under specific selective pressures.
Therapeutic effects of Tanshinone IIA and Tetramethylpyrazine nanoemulsions on cognitive impairment and neuronal damage in Alzheimer’s disease rat models
Authors: Fang Liang , Cheng Hongyan , Chen Weidong , Peng Can , Liu Yuanxu , Zhang Caiyun 
Published: June 2024

Abstract

Objectives
The aim of this study was to investigate the therapeutic effects and related mechanisms of Tanshinone IIA and Tetramethylpyrazine O/W composite nanoemulsions on Alzheimer’s disease (AD) rats.

Methods
The therapeutic effect of TSN/TMP O/W NEs on AD rats was evaluated by behavioral tests, H&E, Nissl, and Immunohistochemistry staining. ELISA and Western blot were used to analyze the mechanism.

Key findings
The results showed that TSN/TMP O/W NEs could down-regulate the expression of Bax and Caspase-3 proteins, decrease the level of MDA, increase the expression of SOD and GSH-Px, and alleviate cognitive impairment in AD rats.

Conclusions
TSN/TMP O/W NEs can inhibit MAPK/ERK/CREB signaling pathway and effectively alleviate cognitive impairment, oxidative stress injury, and neuronal apoptosis in AD rats.
Why you should avoid using multiple Fine–Gray models: insights from (attempts at) simulating proportional subdistribution hazards data
Authors: Bonneville Edouard F , de Wreede Liesbeth C , Putter Hein 
Published: June 2024

Abstract
Studies considering competing risks will often aim to estimate the cumulative incidence functions conditional on an individual’s baseline characteristics. While the Fine–Gray subdistribution hazard model is tailor-made for analysing only one of the competing events, it may still be used in settings where multiple competing events are of scientific interest, where it is specified for each cause in turn. In this work, we provide an overview of data-generating mechanisms where proportional subdistribution hazards hold for at least one cause. We use these to motivate why the use of multiple Fine–Gray models should be avoided in favour of better alternatives such as cause-specific hazard models.
Capitalizing on genebank core collections for rare and novel disease resistance loci to enhance barley resilience
Authors: Yuan Zhihui , Rembe Maximilian , Mascher Martin , Stein Nils , Jayakodi Murukarthick , Börner Andreas , Oldach Klaus , Jahoor Ahmed , Jensen Jens Due , Rudloff Julia , Dohrendorf Viktoria-Elisabeth , Kuhfus Luisa Pauline , Dyrszka Emmanuelle , Conte Matthieu , Hinz Frederik , Trouchaud Salim , Reif Jochen C , El Hanafi Samira 
Published: June 2024

Abstract
In the realm of agricultural sustainability, the utilization of plant genetic resources for enhanced disease resistance is paramount. Preservation efforts in genebanks are justified by their potential contributions to future crop improvement. To capitalize on the potential of plant genetic resources, we focused on a barley core collection from the German ex situ genebank and contrasted it with a European elite collection. The phenotypic assessment included 812 plant genetic resources and 298 elites, with a particular emphasis on four disease traits (Puccinia hordei, Blumeria graminis hordei, Ramularia collo-cygni, and Rhynchosporium commune). An integrated genome-wide association study, employing both Bayesian-information and linkage-disequilibrium iteratively nested keyway (BLINK) and a linear mixed model, was performed to unravel the genetic underpinnings of disease resistance. A total of 932 marker–trait associations were identified and assigned to 49 quantitative trait loci. The accumulation of novel and rare resistance alleles significantly bolstered the overall resistance level in plant genetic resources. Three plant genetic resources donors with high counts of novel/rare alleles and exhibiting exceptional resistance to leaf rust and powdery mildew were identified, offering promise for targeted pre-breeding goals and enhanced resilience in future varieties. Our findings underscore the critical contribution of plant genetic resources to strengthening crop resilience and advancing sustainable agricultural practices.
Oral microbiota in aging and diseases
Authors: Ren Ya , Chen Mingxu , Wang Ziyang , Han Jing-Dong J 
Published: June 2024

Abstract
Human microbiomes are microbial populations that form a symbiotic relationship with humans. There are up to 1000 species on the surface of human skin and mucosal system, among which gut microbiota attracts the most interest. As the beginning of the digestive tract, oral cavity is also an important microbial habitat in the human body which is the first line of defense against pathogens entering the body. Many studies have revealed that oral microbial dysbiosis could not only contribute to oral diseases but also whole-body systemic diseases and health status. Oral microorganisms can enter the gastrointestinal tract with saliva and food, or enter the blood circulation through mouth breakage, thus causing systemic inflammation and aging-related diseases including some causal links to Alzheimer’s disease. A series of changes take place in oral microbial composition during development, with different age stages marked by different dominant microbial species. Despite a lack of comprehensive studies on aging oral microbiota, through systemic inflammation, oral pathogenic microbes are likely to contribute inflammatory aging. As inflammaging is a key signature and one of the causes for accelerated aging, improving the structure of oral microbiome may be not only a new strategy for disease prevention and treatment, but also for aging intervention.
Functional Outcomes Following Internal Fixation versus Hemiarthroplasty for Displaced Intracapsular Neck of Femur Fractures
Authors: Naqvi Ali Z. , Pearse Michael 
Published: June 2024

Abstract
Hip fractures are a common injury requiring input from orthopaedic surgeons throughout the world. Surgical management is important in reducing the risk of disability, increased dependence, and morbidity and mortality. The method of surgical intervention has been guided by surgeon choice and patient factors, and the question that arises is whether to “fix or replace.” This chapter will analyze a prospective randomized controlled trial comparing functional outcomes following two surgical options: internal fixation vs. hemiarthroplasty with a two-year follow-up. With validated functional outcome scores being used as primary outcome measures, this chapter will explore which of these interventions results in improved patient-reported functional outcomes and therefore decreased disability following this life-changing injury.