bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considerations and expectations for the administration of dispersible arpraziquantel to young children: a landscape analysis
Authors: Kurscheid Johanna , Buhl Andrea , Westenberg Erica , Palmeirim Marta Sólveig , Winkler Andrea Sylvia , Steinmann Peter , Monnier Nora 
Published: December 2024

Abstract
Schistosomiasis is a serious public health problem in many African countries and beyond. Preventive chemotherapy with praziquantel is a successful public health intervention that is recommended for all communities at risk, commonly reached through large-scale mass drug administration campaigns. However, preschool-age children are currently not routinely targeted for treatment due to operational challenges related to dosing and administration with the standard drug formulation. In response to the need for a suitable, child-friendly treatment, the multistakeholder Pediatric Praziquantel Consortium has developed a novel dispersible tablet with improved taste and smaller size. To prepare the introduction and inform future uptake of the novel paediatric formulation in endemic countries, we conducted a landscape analysis to explore perspectives, opinions and experiences of key stakeholders on operational and practical issues in relation to drug dosing and administration. Our findings confirm that child-friendly drug formulations mitigate several operational constraints related to the dosing and administration in young children. The introduction of this novel child health intervention into routine platforms and programs requires solid training and careful communication by engaging with communities, caregivers, healthcare workers and decision-makers to ensure acceptance and future uptake of treatment.
A dataset and benchmark for hospital course summarization with adapted large language models
Authors: Aali Asad , Van Veen Dave , Arefeen Yamin Ishraq , Hom Jason , Bluethgen Christian , Reis Eduardo Pontes , Gatidis Sergios , Clifford Namuun , Daws Joseph , Tehrani Arash S , Kim Jangwon , Chaudhari Akshay S 
Published: December 2024

Abstract

Objective
Brief hospital course (BHC) summaries are clinical documents that summarize a patient’s hospital stay. While large language models (LLMs) depict remarkable capabilities in automating real-world tasks, their capabilities for healthcare applications such as synthesizing BHCs from clinical notes have not been shown. We introduce a novel preprocessed dataset, the MIMIC-IV-BHC, encapsulating clinical note and BHC pairs to adapt LLMs for BHC synthesis. Furthermore, we introduce a benchmark of the summarization performance of 2 general-purpose LLMs and 3 healthcare-adapted LLMs.

Materials and Methods
Using clinical notes as input, we apply prompting-based (using in-context learning) and fine-tuning-based adaptation strategies to 3 open-source LLMs (Clinical-T5-Large, Llama2-13B, and FLAN-UL2) and 2 proprietary LLMs (Generative Pre-trained Transformer [GPT]-3.5 and GPT-4). We evaluate these LLMs across multiple context-length inputs using natural language similarity metrics. We further conduct a clinical study with 5 clinicians, comparing clinician-written and LLM-generated BHCs across 30 samples, focusing on their potential to enhance clinical decision-making through improved summary quality. We compare reader preferences for the original and LLM-generated summary using Wilcoxon signed-rank tests. We further request optional qualitative feedback from clinicians to gain deeper insights into their preferences, and we present the frequency of common themes arising from these comments.

Results
The Llama2-13B fine-tuned LLM outperforms other domain-adapted models given quantitative evaluation metrics of Bilingual Evaluation Understudy (BLEU) and Bidirectional Encoder Representations from Transformers (BERT)-Score. GPT-4 with in-context learning shows more robustness to increasing context lengths of clinical note inputs than fine-tuned Llama2-13B. Despite comparable quantitative metrics, the reader study depicts a significant preference for summaries generated by GPT-4 with in-context learning compared to both Llama2-13B fine-tuned summaries and the original summaries (P&lt;.001), highlighting the need for qualitative clinical evaluation.

Discussion and Conclusion
We release a foundational clinically relevant dataset, the MIMIC-IV-BHC, and present an open-source benchmark of LLM performance in BHC synthesis from clinical notes. We observe high-quality summarization performance for both in-context proprietary and fine-tuned open-source LLMs using both quantitative metrics and a qualitative clinical reader study. Our research effectively integrates elements from the data assimilation pipeline: our methods use (1) clinical data sources to integrate, (2) data translation, and (3) knowledge creation, while our evaluation strategy paves the way for (4) deployment.
Understanding the structural biology of osteomalacia through multiscale 3D X-ray and electron tomographic imaging: a review of X-linked hypophosphatemia, the Hyp mouse model, and imaging methods
Authors: Buss Daniel J , Deering Joseph , Reznikov Natalie , McKee Marc D 
Published: December 2024

Abstract
Biomineralization in bones and teeth is a highly regulated extracellular event. In the skeleton, mineralization at the tissue level is controlled within the collagenous extracellular matrix by both circulating and local factors. While systemic regulation of mineral ion homeostasis has been well-studied over many decades, much less is known about the regulation of mineralization at the local level directly within the extracellular matrix. Some local regulators have been identified, such as tissue-nonspecific alkaline phosphatase (TNAP), phosphate-regulating endopeptidase homolog X-linked (PHEX), pyrophosphate, and osteopontin, and others are currently under investigation. Dysregulation of the actions of enzyme-inhibitor substrate pairs engaged in mineralization (as we describe by the Stenciling Principle for extracellular matrix mineralization) leads to osteomalacic “soft bone” diseases, such as hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). This review addresses how advances in 3D imaging tools and software now allow contextual and correlative viewing and interpretation of mineralized tissue structure across most length scales. Contextualized and integrated 3D multiscale data obtained from these imaging modalities have afforded an unprecedented structural biology view of bone from the macroscale to the nanoscale. Such correlated volume imaging data is highly quantitative, providing not only an integrated view of the skeleton in health, but also a means to observe alterations that occur in disease. In the context of the many hierarchical levels of skeletal organization, here we summarize structural features of bone over multiple length scales, with a focus on nano- and microscale features as viewed by X-ray and electron tomography imaging methods (submicron μCT and FIB-SEM). We additionally summarize structural changes observed after dysregulation of the mineralization pathway, focusing here on the Hyp mouse model for XLH. More specifically, we summarize how mineral patterns/packs at the microscale (3D crossfibrillar mineral tessellation), and how this is defective in Hyp mouse bone and Hyp enthesis fibrocartilage.
Allometric equations for estimating above- and below-ground biomass of reed (Phragmites australis) marshes
Authors: Jin Xianglong , Lou Yanjing , Zhang Peng , Tang Haoran , Zhang Qiyao , Smith Pete 
Published: December 2024

Abstract
Accurate estimate of vegetation biomass is a critical component for estimating terrestrial ecosystem carbon stocks. However, knowledge of vegetation biomass estimation for herbaceous marsh is scant. Here, 270 paired above-ground biomass (AGB) and trait data on reed marshes in Northeast China were sampled to estimate AGB, and 70 paired AGB and below-ground biomass (BGB) data from global papers to estimate BGB. The results showed that dividing reed marshes into salt and freshwater marshes greatly improved the fit of the models (R2 of classification vs overall: above 0.50 vs 0.31 and above 0.50 vs 0.10 for AGB and BGB estimation, respectively). A power-law allometric model with plant height alone as a predictor was appropriate for AGB estimation, and inclusion of plant density did not markedly improve prediction accuracy. The power function also fitted well with the relationship between AGB and BGB, with a scaling exponent of 1.13 and 0.60 for salt and freshwater marshes, respectively. Our results indicate that salt and freshwater marsh classification is necessary for estimating wetland vegetation carbon. These findings provide a profound insight into the prediction performance of carbon dynamics in wetland ecosystem.
Solar radiation shapes the spatial pattern of spring phenology on the Qinghai-Tibetan Plateau
Authors: Meng Fandong , Yan Yanzi , Li Lili , Zhang Lirong , Guo Bixi , Yang Zhiyong , Dorji Tsechoe 
Published: December 2024

Abstract
Spatial pattern of phenology reflects long-term plant adaptation to local environments, yet the drivers of these patterns remain understudied. Using satellite data from 2001-2018, this study employed the Normalized Difference Vegetation Index (NDVI) for vegetation structural greenness and Solar-Induced Chlorophyll Fluorescence (SIF) for vegetation functional photosynthesis to analyze spring phenology on the Qinghai-Tibetan Plateau (hereafter, QTP). A machine learning method, Boosted Regression Trees (BRT), was applied to evaluate the contributions of 19 abiotic and biotic factors to the spring phenology. Studies showed that both the spring leaf phenology (SOSNDVI) and photosynthesis phenology (SOSCISF) exhibited a delayed trend decreasing from east to west across the QTP. BRT analysis demonstrated shortwave radiation or/and elevation as key drivers, with higher radiation or elevation associated with more delayed spring phenology spatially, likely due to the constraints of extreme radiation and elevations on spring phenology. Furthermore, we also noted that plants were acclimated to strong radiation to some extent with elevation increasing, namely declined negative effect of radiation/elevation on spring phenology. This acclimation likely enhances plants fitness in QTP's harsh environments. Our study provides novel insights into plant phenology researches on the QTP, and highlight the importance of coupling spatial and temporal analysis on phenology to improve the localization of phenology models.
Exploring Evolution to Uncover Insights Into Protein Mutational Stability
Authors: Hermans Pauline , Tsishyn Matsvei , Schwersensky Martin , Rooman Marianne , Pucci Fabrizio 
Published: December 2024

Abstract
Determining the impact of mutations on the thermodynamic stability of proteins is essential for a wide range of applications such as rational protein design and genetic variant interpretation. Since protein stability is a major driver of evolution, evolutionary data are often used to guide stability predictions. Many state-of-the-art stability predictors extract evolutionary information from multiple sequence alignments of proteins homologous to a query protein, and leverage it to predict the effects of mutations on protein stability. To evaluate the power and the limitations of such methods, we used the massive amount of stability data recently obtained by deep mutational scanning to study how best to construct multiple sequence alignments and optimally extract evolutionary information from them. We tested different evolutionary models and found that, unexpectedly, independent-site models achieve similar accuracy to more complex epistatic models. A detailed analysis of the latter models suggests that their inference often results in noisy couplings, which do not appear to add predictive power over the independent-site contribution, at least in the context of stability prediction. Interestingly, by combining any of the evolutionary features with a simple structural feature, the relative solvent accessibility of the mutated residue, we achieved similar prediction accuracy to supervised, machine learning-based, protein stability change predictors. Our results provide new insights into the relationship between protein evolution and stability, and show how evolutionary information can be exploited to improve the performance of mutational stability prediction.
Animal and vegetal materials of mouse oocytes segregate at first zygotic cleavage: a simple mechanism that makes the two-cell blastomeres differ reciprocally from the start
Authors: Nolte Thomas , Halabian Reza , Israel Steffen , Suzuki Yutaka , Avelar Roberto A , Palmer Daniel , Fuellen Georg , Makalowski Wojciech , Boiani Michele 
Published: December 2024

Abstract
Recent advances in embryology have shown that the sister blastomeres of two-cell mouse and human embryos differ reciprocally in potency. An open question is whether the blastomeres became different as opposed to originating as different. Here we wanted to test two relevant but conflicting models: one proposing that each blastomere contains both animal and vegetal materials in balanced proportions because the plane of first cleavage runs close to the animal–vegetal axis of the fertilized oocyte (meridional cleavage); and the other model proposing that each blastomere contains variable proportions of animal and vegetal materials because the plane of the first cleavage can vary – up to an equatorial orientation – depending on the topology of fertilization. Therefore, we imposed the fertilization site in three distinct regions of mouse oocytes (animal pole, vegetal pole, equator) via ICSI. After the first zygotic cleavage, the sister blastomeres were dissociated and subjected to single-cell transcriptome analysis, keeping track of the original pair associations. Non-supervised hierarchical clustering revealed that the frequency of correct pair matches varied with the fertilization site (vegetal pole &gt; animal pole &gt; equator), thereby, challenging the first model of balanced partitioning. However, the inter-blastomere differences had similar signatures of gene ontology across the three groups, thereby, also challenging the competing model of variable partitioning. These conflicting observations could be reconciled if animal and vegetal materials were partitioned at the first cleavage: an event considered improbable and possibly deleterious in mammals. We tested this occurrence by keeping the fertilized oocytes immobilized from the time of ICSI until the first cleavage. Image analysis revealed that cleavage took place preferentially along the short (i.e. equatorial) diameter of the oocyte, thereby partitioning the animal and vegetal materials into the two-cell blastomeres. Our results point to a simple mechanism by which the two sister blastomeres start out as different, rather than becoming different.
Mastering Mālikī Law: A Moroccan Case Study
Authors: Sayeed Asma , Qaouar Nour-Eddine 
Published: December 2024

Abstract
Pedagogical canons, loosely defined as frameworks and instructional content to impart disciplinary literacy, can be vital sources for understanding stability and transformation in diverse historical contexts. This article documents and contextualizes the curriculum of fiqh and uṣūl al-fiqh during a period of far-reaching reform at Dar El hadith El Hassania, a Moroccan institute for training elite ʿulamāʾ. The balance of pre-modern canonical material with more recent sources anchors the institution in a centuries-long tradition of Mālikī fiqh while facilitating adaptation to political, social, and economic transformations.
BpMYB06 acts as a positive regulatory factor in saline–alkaline stress resistance by binding to two novel elements
Authors: Zhou Xuemei , Ren Ruyi , Sun Hu , Wang Luyao , He Wenjie , Guo Huiyan 
Published: December 2024

Abstract
Saline–alkaline salinity is recognized as one of the most severe abiotic stress factors, limiting plant growth and resulting in significant yield losses. MYB transcription factors (TFs) are crucial for plant tolerance to abiotic stress. However, the roles and regulatory mechanism of MYB TFs underlying saline–alkaline stress tolerance have not yet been investigated in Betula platyphylla. In this report, BpMYB06, an R2R3-MYB TF, is induced in response to saline–alkaline stress in B. platyphylla. This protein functions as a nuclear-localized transcriptional activator. Both gain- and loss-of-function analyses indicate that the transcript level of BpMYB06 is positively correlated with saline–alkaline stress tolerance, primarily through the enhancement of reactive oxygen species scavenging and the regulation of osmotic and ionic balance. Additionally, BpMYB06 is implicated in the control of stomatal aperture. Quantitative real-time PCR results show that BpMYB06 regulates the expression of genes associated with stress tolerance. Furthermore, TF-centered Y1H and chromatin immunoprecipitation assays reveal that BpMYB06 binds to two novel core sequences ([A/C]CGG and TAG[C/A]), thereby inducing the expression of stress-related genes. Our findings provide new insights into the role of BpMYB06 in B. platyphylla under soda saline–alkaline stress and suggest that it could serve as a potential target gene for developing saline–alkaline stress-tolerant B. platyphylla plants.
Endogenous C-type natriuretic peptide offsets the pathogenesis of steatohepatitis, hepatic fibrosis, and portal hypertension
Authors: Perez-Ternero Cristina , Li Wenhao , Aubdool Aisah A , Goldin Robert D , Loy John , Devalia Kalpana , Alazawi William , Hobbs Adrian J 
Published: December 2024

Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), hepatic fibrosis, and portal hypertension constitute an increasing public health problem due to the growing prevalence of obesity and diabetes. C-type natriuretic peptide (CNP) is an endogenous regulator of cardiovascular homeostasis, immune cell reactivity, and fibrotic disease. Thus, we investigated a role for CNP in the pathogenesis of MASLD. Wild-type (WT), global CNP (gbCNP−/−), and natriuretic peptide receptor-C (NPR-C−/−) knockout mice were fed a choline-deficient defined amino acid diet or administered CCl4. Liver damage was assessed by histological and biochemical analyses, with steatosis and portal vein size determined by ultrasound. Portal vein pressure and reactivity were measured in vivo and ex vivo, respectively. Pharmacological CNP delivery was used to evaluate prospective therapeutic benefit, and plasma CNP concentration was compared in controls and patients with cirrhosis. Circulating CNP concentration was lower in patients with cirrhosis compared with controls. gbCNP−/− mice were more susceptible, versus WT, to advanced steatohepatitis and hepatic fibrosis, characterized by increased immune cell infiltration, fibrosis, ballooning, plasma alanine aminotransferase concentration, and up-regulation of markers driving these processes. gbCNP−/− mice had increased portal vein diameter and pressure, underpinned by CNP insensitivity. NPR-C−/− animals recapitulated, comparatively, the exaggerated pathogenic phenotype in gbCNP−/− mice, whereas CNP reduced hepatic stellate cell proliferation via NPR-B-dependent inhibition of extracellular signal-related kinase 1/2. Administration of CNP reversed many aspects of disease severity. These data define a new intrinsic role for CNP in offsetting the pathogenesis of MASLD, hepatic fibrosis, and portal hypertension and the potential for targeting CNP signaling for treating these disorders.
A randomized, clinical trial of intravenous N-acetylcysteine as an antioxidant therapy in acute organophosphorus pesticide poisoning
Authors: Mohammed Sarah S , Zaaqoq Ayman , Talaat Shimaa , Abdelkader Salma I 
Published: December 2024

Abstract
The incidence of acute organophosphate (OP) poisoning has steadily increased in developing countries. Many studies showed that oxidative stress could have a significant role in its mechanism. The current study aimed to evaluate the role of N acetylcysteine (NAC) as an antioxidant in acute OP poisoned. A randomized, controlled, parallel-group trial was conducted in the period from the beginning of January 2022 to the end of June 2022. The study included 56 acute OP poisoned patients admitted to the intensive care unit (ICU) at the Poison Control Center of Ain Shams University Hospitals within 6 h after the exposure. The patients were randomly allocated in two equal groups; group (A): received the standard treatment plus NAC in a total dose of 300 mg/kg administered intravenously (IV) while group (B) received the standard treatment. Then both groups were compared as regards clinical parameters, laboratory investigations, ECG, and outcomes. Baseline parameters were comparable between the groups. However, NAC treatment significantly elevated concentrations of both serum catalase and glutathione peroxidase levels at 24 h, it did not significantly affect the total dose of atropine required, duration of atropine and oximes treatment or need for mechanical ventilation, and length of hospital stay. Mortality was lower in the NAC group (2 out of 28) than the standard treatment-only group (5 out of 28) but the difference was not statistically significant. This trial found that NAC improved antioxidant enzyme levels including serum CAT and GPX but did not affect clinically relevant outcomes.