bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors influencing voriconazole plasma level in intensive care patients
Authors: Hinze Christopher Alexander , Fuge Jan , Grote-Koska Denis , Brand Korbinian , Slevogt Hortense , Cornberg Markus , Simon Susanne , Joean Oana , Welte Tobias , Rademacher Jessica 
Published: March 2024

Abstract

Background
In clinical routine, voriconazole plasma trough levels (Cmin) out of target range are often observed with little knowledge about predisposing influences.

Objectives
To determine the distribution and influencing factors on voriconazole blood levels of patients treated on intensive- or intermediate care units (ICU/IMC).

Patients and methods
Data were collected retrospectively from patients with at least one voriconazole trough plasma level on ICU/IMC (n = 153) to determine the proportion of sub-, supra- or therapeutic plasma levels. Ordinal logistic regression analysis was used to assess factors hindering patients to reach voriconazole target range.

Results
Of 153 patients, only 71 (46%) reached the target range at the first therapeutic drug monitoring, whereas 66 (43%) patients experienced too-low and 16 (10%) too-high plasma levels. Ordinal logistic regression analysis identified the use of extra corporeal membrane oxygenation (ECMO), low international normalized ratio (INR) and aspartate-aminotransferase (AST) serum levels as predictors for too-low plasma levels.

Conclusion
Our data highlight an association of ECMO, INR and AST levels with voriconazole plasma levels, which should be considered in the care of critically ill patients to optimize antifungal therapy with voriconazole.
An interpretable predictive deep learning platform for pediatric metabolic diseases
Authors: Javidi Hamed , Mariam Arshiya , Alkhaled Lina , Pantalone Kevin M , Rotroff Daniel M 
Published: March 2024

Abstract

Objectives
Metabolic disease in children is increasing worldwide and predisposes a wide array of chronic comorbid conditions with severe impacts on quality of life. Tools for early detection are needed to promptly intervene to prevent or slow the development of these long-term complications.

Materials and Methods
No clinically available tools are currently in widespread use that can predict the onset of metabolic diseases in pediatric patients. Here, we use interpretable deep learning, leveraging longitudinal clinical measurements, demographical data, and diagnosis codes from electronic health record data from a large integrated health system to predict the onset of prediabetes, type 2 diabetes (T2D), and metabolic syndrome in pediatric cohorts.

Results
The cohort included 49 517 children with overweight or obesity aged 2-18 (54.9% male, 73% Caucasian), with a median follow-up time of 7.5 years and mean body mass index (BMI) percentile of 88.6%. Our model demonstrated area under receiver operating characteristic curve (AUC) accuracies up to 0.87, 0.79, and 0.79 for predicting T2D, metabolic syndrome, and prediabetes, respectively. Whereas most risk calculators use only recently available data, incorporating longitudinal data improved AUCs by 13.04%, 11.48%, and 11.67% for T2D, syndrome, and prediabetes, respectively, versus models using the most recent BMI (P &lt; 2.2 × 10–16).

Discussion
Despite most risk calculators using only the most recent data, incorporating longitudinal data improved the model accuracies because utilizing trajectories provides a more comprehensive characterization of the patient’s health history. Our interpretable model indicated that BMI trajectories were consistently identified as one of the most influential features for prediction, highlighting the advantages of incorporating longitudinal data when available.
Leveraging large language models for generating responses to patient messages—a subjective analysis
Authors: Liu Siru , McCoy Allison B , Wright Aileen P , Carew Babatunde , Genkins Julian Z , Huang Sean S , Peterson Josh F , Steitz Bryan , Wright Adam 
Published: March 2024

Abstract

Objective
This study aimed to develop and assess the performance of fine-tuned large language models for generating responses to patient messages sent via an electronic health record patient portal.

Materials and Methods
Utilizing a dataset of messages and responses extracted from the patient portal at a large academic medical center, we developed a model (CLAIR-Short) based on a pre-trained large language model (LLaMA-65B). In addition, we used the OpenAI API to update physician responses from an open-source dataset into a format with informative paragraphs that offered patient education while emphasizing empathy and professionalism. By combining with this dataset, we further fine-tuned our model (CLAIR-Long). To evaluate fine-tuned models, we used 10 representative patient portal questions in primary care to generate responses. We asked primary care physicians to review generated responses from our models and ChatGPT and rated them for empathy, responsiveness, accuracy, and usefulness.

Results
The dataset consisted of 499 794 pairs of patient messages and corresponding responses from the patient portal, with 5000 patient messages and ChatGPT-updated responses from an online platform. Four primary care physicians participated in the survey. CLAIR-Short exhibited the ability to generate concise responses similar to provider’s responses. CLAIR-Long responses provided increased patient educational content compared to CLAIR-Short and were rated similarly to ChatGPT’s responses, receiving positive evaluations for responsiveness, empathy, and accuracy, while receiving a neutral rating for usefulness.

Conclusion
This subjective analysis suggests that leveraging large language models to generate responses to patient messages demonstrates significant potential in facilitating communication between patients and healthcare providers.
Levodopa attenuates the feed intake reduction caused by ergot alkaloids in cattle
Authors: Valente Eriton E L , Klotz James L , Markmann Ryana C , Trotta Ronald J , Edwards J Lannett , May John B , Harmon David L 
Published: March 2024

AbstractConsumption of ergot alkaloids from endophyte-infected tall fescue results in losses to the livestock industry in many countries and a means to mitigate these losses is needed. The objective of this study was to evaluate intra-abomasal infusion of the dopamine precursor, levodopa (L-DOPA), on dopamine metabolism, feed intake, and serum metabolites of steers exposed to ergot alkaloids. Twelve Holstein steers (344.9 ± 9.48 kg) fitted with ruminal cannula were housed with a cycle of heat challenge during the daytime (32 °C) and thermoneutral at night (25 °C). The steers received a basal diet of alfalfa cubes containing equal amounts of tall fescue seed composed of a mixture of endophyte-free (E−) or endophyte-infected tall fescue seeds (E+) equivalent to 15 µg ergovaline/kg body weight (BW) for 9 d followed by intra-abomasal infusion of water (L-DOPA−) or levodopa (L-DOPA+; 2 mg/kg BW) for an additional 9 d. Afterward, the steers were pair-fed for 5 d to conduct a glucose tolerance test. The E+ treatment decreased (P = 0.005) prolactin by approximately 50%. However, prolactin increased (P = 0.050) with L-DOPA+. Steers receiving E+ decreased (P &lt; 0.001) dry matter intake (DMI); however, when supplemented with L-DOPA+ the decrease in DMI was less severe (L-DOPA × E, P = 0.003). Also, L-DOPA+ infusion increased eating duration (L-DOPA × E, P = 0.012) when steers were receiving E+. The number of meals, meal duration, and intake rate were not affected (P &gt; 0.05) by E+ or L-DOPA+. The L-DOPA+ infusion increased (P &lt; 0.05) free L-DOPA, free dopamine, total L-DOPA, and total dopamine. Conversely, free epinephrine and free norepinephrine decreased (P &lt; 0.05) with L-DOPA+. Total epinephrine and total norepinephrine were not affected (P &gt; 0.05) by L-DOPA+. Ergot alkaloids did not affect (P &gt; 0.05) circulating free or total L-DOPA, dopamine, or epinephrine. However, free and total norepinephrine decreased (P = 0.046) with E+. Glucose clearance rates at 15 to 30 min after glucose infusion increased with L-DOPA+ (P &lt; 0.001), but not with E+ (P = 0.280). Administration of L-DOPA as an agonist therapy to treat fescue toxicosis provided a moderate increase in DMI and eating time and increased plasma glucose clearance for cattle dosed with E+ seed.
Interactions between γδ T cells and neutrophils in cancer: knowns and unknowns
Authors: Hao Jianlei , Granot Zvi 
Published: March 2024

Abstract
The tumor microenvironment provides a unique opportunity to gain insight into the relationship and crosstalk between different cell types. In this context, little is known about the interaction between γδ T cells and neutrophils, which are innate immune cells abundant in the tumor microenvironment. Interestingly, both γδ T cells and neutrophils are heterogeneous, may play diverse regulatory roles, and have been shown to have both protumor and antitumor functions. In this editorial, we discuss recent advances in the understanding of interplay between γδ T cells and neutrophils in cancer and provide insights and future directions highlighting the role these interactions may play in cancer.
Changing tactics in negotiating refugee assistance policies and practices: A case study of an asylum seeker-led organization in Hong Kong
Authors: Lam Ka Wang Kelvin 
Published: March 2024

Abstract
This article examines the tactical changes made by the asylum seeker community in Hong Kong in negotiating local refugee assistance policies and practices. The analysis presented in this paper is grounded in my ethnographic fieldwork with an asylum seeker-led organization and supplemented by archival study and informal interviews. In recent years, the asylum seeker community has adopted a pragmatic approach to advocacy, increasingly asking the local community for support in providing humanitarian aid rather than calling for changes to the assistance system, a tactic that this group used in the past. I argue that these tactical changes cannot be separated from the social and political contexts of Hong Kong. The presence of stimulating events, particularly those involving local and global refugee and migrant communities, the space available for voicing dissent, and the level of institutional responsiveness, all affect how the asylum seeker community in Hong Kong participates in policy discussions.
Retractions in arts and humanities: an analysis of the retraction notices
Authors: Heibi Ivan , Peroni Silvio 
Published: March 2024

Abstract
The aim of this work is to understand the retraction phenomenon in the arts and humanities domain through an analysis of the retraction notices—formal documents stating and describing the retraction of a particular publication. The retractions and the corresponding notices are identified using the data provided by Retraction Watch. Our methodology for the analysis combines a metadata analysis and a content analysis (mainly performed using a topic modelling process) of the retraction notices. Considering 343 cases of retraction, we found that many retraction notices are neither identifiable nor findable. In addition, these were not always separated from the original papers, introducing ambiguity in understanding how these notices were perceived by the community (i.e. cited). Also, we noticed that there is no systematic way to write a retraction notice. Indeed, some retraction notices presented a complete discussion of the reasons for retraction, while others tended to be more direct and succinct. We have also reported many notices having similar text while addressing different retractions. We think a further study with a larger collection should be done using the same methodology to confirm and investigate our findings further.
E-XQR-30: The evolution of Mg ii, C ii, and O i across 2 &lt; z &lt; 6
Authors: Sebastian Alma Maria , Ryan-Weber Emma , Davies Rebecca L , Becker George D , Keating Laura C , D’Odorico Valentina , Meyer Romain A , Bosman Sarah E I , Cupani Guido , Kulkarni Girish , Haehnelt Martin G , Lai Samuel , Eilers Anna–Christina , Bischetti Manuela , Gallerani Simona 
Published: March 2024

ABSTRACT
Intervening metal absorbers in quasar spectra at z &gt; 6 can be used as probes to study the chemical enrichment of the Universe during the Epoch of Reionization. This work presents the comoving line densities (dn/dX) of low-ionization absorbers, namely, Mg ii (2796 Å), C ii (1334 Å), and O  i (1302 Å) across 2 &lt; z &lt; 6 using the E-XQR-30 metal absorber catalogue prepared from 42 XSHOOTER quasar spectra at 5.8 &lt; z &lt; 6.6. Here, we analyse 280 Mg ii (1.9 &lt; z &lt; 6.4), 22 C ii (5.2 &lt; z &lt; 6.4), and 10 O i (5.3 &lt; z &lt; 6.4) intervening absorbers, thereby building up on previous studies with improved sensitivity of 50 per cent completeness at an equivalent width of W &gt; 0.03 Å. For the first time, we present the comoving line densities of 131 weak (W &lt; 0.3 Å) intervening Mg ii absorbers at 1.9 &lt; z &lt; 6.4 which exhibit constant evolution with redshift similar to medium (0.3 &lt; W &lt; 1.0 Å) absorbers. However, the cosmic mass density of Mg ii – dominated by strong Mg ii systems – traces the evolution of global star formation history from redshift 1.9 to 5.5. E-XQR-30 also increases the absorption path-length by a factor of 50 per cent for C ii and O i whose line densities show a rising trend towards z &gt; 5, in agreement with previous works. In the context of a decline in the metal enrichment of the Universe at z &gt; 5, the overall evolution in the incidence rates of absorption systems can be explained by a weak – possibly soft fluctuating – ultraviolet background. Our results, thereby, provide evidence for a late reionization continuing to occur in metal-enriched and therefore, biased regions in the Universe.
POLARIS: A phase 2 trial of encorafenib plus binimetinib evaluating high-dose and standard-dose regimens in patients with BRAF V600-mutant melanoma with brain metastasis
Authors: Menzies Alexander M , Long Georgina V , Kohn Amiee , Tawbi Hussein , Weber Jeffrey , Flaherty Keith , McArthur Grant A , Ascierto Paolo A , Pfluger Yanina , Lewis Karl , Tsai Katy K , Hamid Omid , Prenen Hans , Fein Luis , Wang Erjian , Guenzel Carolin , Zhang Fan , Kleha Joseph F , di Pietro Alessandra , Davies Michael A 
Published: March 2024

Abstract

Background
POLARIS (phase 2 [ph2]; NCT03911869) evaluated encorafenib (BRAF inhibitor) in combination with binimetinib (MEK1/2 inhibitor) in BRAF/MEK inhibitor-naïve patients with BRAF V600-mutant melanoma with asymptomatic brain metastases.

Methods
The safety lead-in (SLI) assessed tolerability for high-dose encorafenib 300 mg twice daily (BID) plus binimetinib 45 mg BID. If the high dose was tolerable in ph2, patients would be randomized to receive high or standard dose (encorafenib 450 mg once daily [QD] plus binimetinib 45 mg BID). Otherwise, standard dose was evaluated as the recommended ph2 dose (RP2D). Patients who tolerated standard dosing during Cycle 1 could be dose escalated to encorafenib 600 mg QD plus binimetinib 45 mg BID in Cycle 2. Safety, efficacy, and pharmacokinetics were examined.

Results
RP2D was standard encorafenib dosing, as &gt;33% of evaluable SLI patients (3/9) had dose-limiting toxicities. Overall, of 13 safety-evaluable patients (10 SLI, 3 ph2), 9 had prior immunotherapy. There were 9 treatment-related adverse events in the SLI and 3 in ph2. Of the SLI efficacy-evaluable patients (n = 10), 1 achieved complete response and 5 achieved partial responses (PR); the brain metastasis response rate (BMRR) was 60% (95% CI: 26.2, 87.8). In ph2, 2 of 3 patients achieved PR (BMRR, 67% [95% CI: 9.4, 99.2]). Repeated encorafenib 300 mg BID dosing did not increase steady-state exposure compared with historical 450 mg QD data.

Conclusions
Despite small patient numbers due to early trial termination, BMRR appeared similar between the SLI and ph2, and the ph2 safety profile appeared consistent with previous reports of standard-dose encorafenib in combination with binimetinib.
Developmental outcomes of preschool children requiring craniosynostosis surgery in Manitoba: a cohort study
Authors: Ripstein Yael , Pylypjuk Christy , Conway Alexandra , Ricci M Florencia 
Published: March 2024

Abstract
Craniosynostosis is a congenital abnormality resulting in the premature fusion of one or more cranial sutures and usually requires surgical correction in the first year of life. While the majority of craniosynostosis cases represent isolated, nonsyndromic defects, approximately 25% are linked to a genetic diagnosis. Craniosynostosis has been associated with developmental delay. Therefore, historically in Manitoba, all children with surgically managed craniosynostosis were referred to the Child Development Clinic (CDC) for developmental assessment. There are currently prolonged wait times for neurodevelopmental assessments at CDC, leading to the need to better prioritize children who require neurodevelopmental assessment. The aim of the study was then to determine the developmental outcomes of preschool children requiring craniosynostosis surgery in Manitoba from July 1, 2016 through December 1, 2021. In this retrospective cohort study, clinical records were reviewed to evaluate the developmental outcomes of patients who were assessed at CDC for surgically managed craniosynostosis. Out of 67 children included in this study, 18% demonstrated global developmental delay, 24% demonstrated mild developmental delay, and 58% were developmentally appropriate across all levels. The presence of a genetic syndrome, multisutural craniosynostosis, and parental socioeconomic status were associated with risk of global developmental delay. The findings of this study suggest that while not all children with craniosynostosis present with developmental delay, those with suspected or confirmed syndromic involvement, multisutural cranyosinostosis, and/or low SES, should be referred for neurodevelopmental evaluation.
Scaling laws for lattice distortions: Application to high entropy alloys
Authors: Wang Zhaowei , Pattamatta A S L Subrahmanyam , Han Jian , Srolovitz David J 
Published: March 2024

Abstract
Lattice distortions are intrinsic features of all solid solution alloys associated with varying atomic radii; this phenomenon facilitates the formation of single-phase solid solutions. Using high-entropy alloys (HEAs), as an example, we investigate the influence of variations in inter-atomic separations for stabilizing and controlling their structural, mechanical, and thermodynamic properties. This is done through a combination of statistical mechanics analysis and molecular dynamics simulations on simplified 2D systems, as well as a 3D crystals with harmonic and anharmonic inter-atomic bonds with varying natural inter-atomic separations. We demonstrate that the impact of this inter-atomic length disorder (representing static lattice distortion) and temperature fluctuations (representing dynamic lattice distortion) on fundamental and universal thermodynamic, structural, and elastic characteristics are similar and can be unified through effective temperature; i.e. a scaling law for HEAs that establishes a relationship between these factors. This scaling law reveals that different HEAs (i.e. varying degrees of local lattice distortions) collapse onto a single curve when plotted against the effective temperature. We demonstrate that lattice distortion significantly enhances the stability of solid solution alloys (relative to phase separation or ordering by effectively increasing the temperature of the system; this stabilization effect is particularly pronounced in HEAs).
Boundedness of Differential Transforms for Poisson Semigroups Generated by Bessel Operators
Authors: Zhang Chao 
Published: March 2024

Abstract
In this paper we analyze the convergence of the following type of series: $$ T_N \,\,f(x)=\sum_{j=N_1}^{N_2} v_j\Big({\mathcal P}_{a_{j+1}} \,\,f(x)-{\mathcal P}_{a_{j}} \,\,f(x)\Big),\quad x\in \mathbb R_+, $$ where $\{{\mathcal P}_{t} \}_{t\gt0}$ is the Poisson semigroup associated with the Bessel operator $\displaystyle \Delta_\lambda:=-{d^2\over dx^2}-{2\lambda\over x}{d\over dx}$, with λ being a positive constant, $N=(N_1, N_2)\in \mathbb Z^2$ with $N_1 \lt N_2,$ $\{v_j\}_{j\in \mathbb Z}$ is a bounded real sequence and $\{a_j\}_{j\in \mathbb Z}$ is an increasing real sequence. Our analysis will consist in the boundedness, in $L^p(\mathbb{R}_+)$ and in $BMO(\mathbb{R}_+)$, of the operators TN and its maximal operator $\displaystyle T^*\,\,f(x)= \sup_N \left\vert T_N \,\,f(x)\right\vert.$ It is also shown that the local size of the maximal differential transform operators is the same with the order of a singular integral for functions f having local support.
Poly(ADP‐ribose) mediates bioenergetic defects and redox imbalance in neurons following oxygen and glucose deprivation
Authors: Hossain M. Iqbal , Lee Jun Hee , Gagné Jean‐Philippe , Khan Junaid , Poirier Guy G. , King Peter H. , Dawson Valina L. , Dawson Ted M. , Andrabi Shaida A. 
Published: March 2024

AbstractPARP‐1 over‐activation results in cell death via excessive PAR generation in different cell types, including neurons following brain ischemia. Glycolysis, mitochondrial function, and redox balance are key cellular processes altered in brain ischemia. Studies show that PAR generated after PARP‐1 over‐activation can bind hexokinase‐1 (HK‐1) and result in glycolytic defects and subsequent mitochondrial dysfunction. HK‐1 is the neuronal hexokinase and catalyzes the first reaction of glycolysis, converting glucose to glucose‐6‐phosphate (G6P), a common substrate for glycolysis, and the pentose phosphate pathway (PPP). PPP is critical in maintaining NADPH and GSH levels via G6P dehydrogenase activity. Therefore, defects in HK‐1 will not only decrease cellular bioenergetics but will also cause redox imbalance due to the depletion of GSH. In brain ischemia, whether PAR‐mediated inhibition of HK‐1 results in bioenergetics defects and redox imbalance is not known. We used oxygen–glucose deprivation (OGD) in mouse cortical neurons to mimic brain ischemia in neuronal cultures and observed that PARP‐1 activation via PAR formation alters glycolysis, mitochondrial function, and redox homeostasis in neurons. We used pharmacological inhibition of PARP‐1 and adenoviral‐mediated overexpression of wild‐type HK‐1 (wtHK‐1) and PAR‐binding mutant HK‐1 (pbmHK‐1). Our data show that PAR inhibition or overexpression of HK‐1 significantly improves glycolysis, mitochondrial function, redox homeostasis, and cell survival in mouse cortical neurons exposed to OGD. These results suggest that PAR binding and inhibition of HK‐1 during OGD drive bioenergetic defects in neurons due to inhibition of glycolysis and impairment of mitochondrial function.