bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of sugammadex dosing and administration practices on potential cost savings for pharmacy departments
Authors: Linn Dustin D , Renew Johnathan R 
Published: May 2024

Abstract

Purpose
Neuromuscular blocking agents (NMBAs) are commonly used during surgery, and restoring neuromuscular function at the end of surgery is vital in preventing complications of residual paralysis. Recent guidelines from the American Society of Anesthesiology recommend using sugammadex over neostigmine; however, sugammadex is significantly more expensive than neostigmine and may increase drug expenditure for pharmacy departments. This review summarizes evidence evaluating sugammadex dose adjustments and the potential of these dose adjustments to lead to cost savings for pharmacy departments.

Summary
We found evidence suggesting that the manufacturer-recommended sugammadex dose may not be needed in many patients and that dosing based on an adjusted body weight or based on depth of neuromuscular blockade may lead to lower sugammadex usage. Combining sugammadex with neostigmine could also decrease the dose of sugammadex required. We have highlighted the importance of objective neuromuscular monitoring to guide sugammadex dosing and evaluation for residual neuromuscular blockade. Cost savings for pharmacy departments may be realized by these alternative dosing strategies and/or vial-splitting practices.

Conclusion
Implementing practices related to sugammadex vial splitting and dose adjustment based on body weight and depth of neuromuscular blockade shows potential benefits in terms of sugammadex cost savings.
Data-driven selection of analysis decisions in single-cell RNA-seq trajectory inference
Authors: Dong Xiaoru , Leary Jack R , Yang Chuanhao , Brusko Maigan A , Brusko Todd M , Bacher Rhonda 
Published: May 2024

Abstract
Single-cell RNA sequencing (scRNA-seq) experiments have become instrumental in developmental and differentiation studies, enabling the profiling of cells at a single or multiple time-points to uncover subtle variations in expression profiles reflecting underlying biological processes. Benchmarking studies have compared many of the computational methods used to reconstruct cellular dynamics; however, researchers still encounter challenges in their analysis due to uncertainty with respect to selecting the most appropriate methods and parameters. Even among universal data processing steps used by trajectory inference methods such as feature selection and dimension reduction, trajectory methods’ performances are highly dataset-specific. To address these challenges, we developed Escort, a novel framework for evaluating a dataset’s suitability for trajectory inference and quantifying trajectory properties influenced by analysis decisions. Escort evaluates the suitability of trajectory analysis and the combined effects of processing choices using trajectory-specific metrics. Escort navigates single-cell trajectory analysis through these data-driven assessments, reducing uncertainty and much of the decision burden inherent to trajectory inference analyses. Escort is implemented in an accessible R package and R/Shiny application, providing researchers with the necessary tools to make informed decisions during trajectory analysis and enabling new insights into dynamic biological processes at single-cell resolution.
TransPTM: a transformer-based model for non-histone acetylation site prediction
Authors: Meng Lingkuan , Chen Xingjian , Cheng Ke , Chen Nanjun , Zheng Zetian , Wang Fuzhou , Sun Hongyan , Wong Ka-Chun 
Published: May 2024

Abstract
Protein acetylation is one of the extensively studied post-translational modifications (PTMs) due to its significant roles across a myriad of biological processes. Although many computational tools for acetylation site identification have been developed, there is a lack of benchmark dataset and bespoke predictors for non-histone acetylation site prediction. To address these problems, we have contributed to both dataset creation and predictor benchmark in this study. First, we construct a non-histone acetylation site benchmark dataset, namely NHAC, which includes 11 subsets according to the sequence length ranging from 11 to 61 amino acids. There are totally 886 positive samples and 4707 negative samples for each sequence length. Secondly, we propose TransPTM, a transformer-based neural network model for non-histone acetylation site predication. During the data representation phase, per-residue contextualized embeddings are extracted using ProtT5 (an existing pre-trained protein language model). This is followed by the implementation of a graph neural network framework, which consists of three TransformerConv layers for feature extraction and a multilayer perceptron module for classification. The benchmark results reflect that TransPTM has the competitive performance for non-histone acetylation site prediction over three state-of-the-art tools. It improves our comprehension on the PTM mechanism and provides a theoretical basis for developing drug targets for diseases. Moreover, the created PTM datasets fills the gap in non-histone acetylation site datasets and is beneficial to the related communities. The related source code and data utilized by TransPTM are accessible at https://www.github.com/TransPTM/TransPTM.
Treating epidermolytic ichthyosis and ichthyosis with confetti with epidermal autografts cultured from revertant skin
Authors: Tanahashi Kana , Kono Michihiro , Yoshikawa Takenori , Suzuki Yuika , Inoie Masukazu , Kuwatsuka Yachiyo , Kinoshita Fumie , Takeichi Takuya , Akiyama Masashi 
Published: May 2024

Abstract

Background
No efficient treatment has yet been established for epidermolytic ichthyosis (EI), which is caused by pathogenic variants of KRT1 or KRT10. Patients with ichthyosis with confetti (IWC) have multiple normal-appearing spots, caused by the revertant somatic recombination of pathogenic variants that occurs at each spot independently. Additionally, some patients with EI have large areas of normal skin due to revertant postzygotic mosaicism.

Objectives
To assess the feasibility of transplanting cultured epidermal autografts (CEAs) produced from revertant epidermal keratinocytes in patients with EI and IWC.

Methods
We performed a clinical trial of treatment with CEAs produced from each patient’s own revertant epidermal keratinocytes as a proof-of-concept study. This was a single-arm, open, unmasked, uncontrolled, single-assignment, treatment-purpose study. The primary outcome was the percentage area that lacked recurrence of ichthyosis lesions 4 weeks after the final transplant. The secondary outcome was the percentage area lacking recurrence of ichthyosis lesions 24 weeks after the initial transplantation. The trial was registered with the Japan Registry of Clinical Trials (jRCTb041190097).

Results
We successfully produced CEAs from genetically confirmed revertant skin from two patients with mosaic EI and from one patient with IWC and confirmed by amplicon sequencing and droplet digital polymerase chain reaction analysis that the CEAs mainly consisted of revertant wild-type cells. Single-cell RNA sequencing analysis confirmed the normal proliferation and safety profiling of CEAs. CEAs were transplanted onto desquamated lesional sites in the patients. Four weeks post-transplantation, the percentage area lacking recurrence of ichthyosis lesions in the three patients was 40%, 100% and 100% respectively, although recurrence of ichthyosis lesions was seen at the site of CEA transplantation in all three patients at 24 weeks post-transplantation.

Conclusions
CEAs from normal skin have the potential to be a safe and local treatment option for EI and IWC.
Stability-Indicating HPLC Method for Determination of Ibuprofen and Famotidine Degradation Products
Authors: Atilgan Nurdan , Tabansiz Gizem , Turkes Ezgi , Sarracoglu Nagehan , Doganay Asuman Aybey , Pinarbasli Onur 
Published: May 2024

Abstract
A new stability-indicating high-performance liquid chromatographic method for the quantitative determination of ibuprofen and famotidine degradation products in combined pharmaceutical products was developed and validated. The current aim of this study is to develop a rapid, accurate and robust analytical stability indicating impurity method that can separate ibuprofen, famotidine and their related impurities by using a reversed-phase high-performance liquid chromatography. A Zorbax SB-Phenyl column (4.6 × 150 mm2, 5-μm particle size) with mobile phase containing phosphate buffer solution with a pH value of 3.0 and acetonitrile was used. The flow rate was 0.8 mL/min and the analytes were detected by UV detector at 265 nm. The retention times of ibuprofen and famotidine were 18.43 and 5.14 min, respectively. This method was validated to confirm specificity, linearity, sensitivity (limit of detection and limit of quantitation), precision, accuracy, robustness and sample stability according to the International Conference on Harmonization guidelines. Studies have been completed and reported with two active substances in the combined dosage form and seven impurities in total. There is no method in the literature that simultaneously distinguishes and quantitatively analyzes both active substances and degradation products.
Empagliflozin inhibits increased Na influx in atrial cardiomyocytes of patients with HFpEF
Authors: Trum Maximilian , Riechel Johannes , Schollmeier Elisa , Lebek Simon , Hegner Philipp , Reuthner Kathrin , Heers Silvia , Keller Karoline , Wester Michael , Klatt Susanne , Hamdani Nazha , Provaznik Zdenek , Schmid Christof , Maier Lars , Arzt Michael , Wagner Stefan 
Published: May 2024

Abstract

Aims
Heart failure with preserved ejection fraction (HFpEF) causes substantial morbidity and mortality. Importantly, atrial remodelling and atrial fibrillation are frequently observed in HFpEF. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have recently been shown to improve clinical outcomes in HFpEF, and post-hoc analyses suggest atrial anti-arrhythmic effects. We tested if isolated human atrial cardiomyocytes from patients with HFpEF exhibit an increased Na influx, which is known to cause atrial arrhythmias, and if that is responsive to treatment with the SGTL2i empagliflozin.

Methods and results
Cardiomyocytes were isolated from atrial biopsies of 124 patients (82 with HFpEF) undergoing elective cardiac surgery. Na influx was measured with the Na-dye Asante Natrium Green–2 AM (ANG-2). Compared to patients without heart failure (NF), Na influx was doubled in HFpEF patients (NF vs. HFpEF: 0.21 ± 0.02 vs. 0.38 ± 0.04 mmol/L/min (N = 7 vs. 18); P = 0.0078). Moreover, late INa (measured via whole-cell patch clamp) was significantly increased in HFpEF compared to NF. Western blot and HDAC4 pulldown assay indicated a significant increase in CaMKII expression, CaMKII autophosphorylation, CaMKII activity, and CaMKII-dependent NaV1.5 phosphorylation in HFpEF compared to NF, whereas NaV1.5 protein and mRNA abundance remained unchanged. Consistently, increased Na influx was significantly reduced by treatment not only with the CaMKII inhibitor autocamtide-2-related inhibitory peptide (AIP), late INa inhibitor tetrodotoxin (TTX) but also with sodium/hydrogen exchanger 1 (NHE1) inhibitor cariporide. Importantly, empagliflozin abolished both increased Na influx and late INa in HFpEF. Multivariate linear regression analysis, adjusting for important clinical confounders, revealed HFpEF to be an independent predictor for changes in Na handling in atrial cardiomyocytes.

Conclusion
We show for the first time increased Na influx in human atrial cardiomyocytes from HFpEF patients, partly due to increased late INa and enhanced NHE1-mediated Na influx. Empagliflozin inhibits Na influx and late INa, which could contribute to anti-arrhythmic effects in patients with HFpEF.
Influence of prey availability on the movement pattern of breeding saker falcons (Falco cherrug) in Mongolia
Authors: Bold Batbayar , Rahman Lutfor , Purev-Ochir Gankhuyag , Saruul Amarsaikhan , Zhan Xiangjiang , Dixon Andrew 
Published: May 2024

Abstract
As an apex predator in arid steppe, saker falcon plays a crucial role in maintaining ecosystem balance. Understanding their movement patterns concerning conspecific competition and prey availability is important for their conservation. We aim to understand how movement pattern of breeding saker falcons relates to prey availability. Twelve adult sakers were tracked during the breeding seasons, using satellite transmitters. Throughout the breeding season, sakers exhibited territorial behavior, with minimal overlap in range use among neighboring conspecifics. Males occupied larger areas (mean = 2,397 ha, median = 1,221 ha), compared to females (mean = 1,241 ha, median = 554 ha), and it remained consistent throughout breeding season. Female home range size increased notably during a late nestling stage and post-fledging dependence periods, indicating release from brooding constraints. Notably, we found a negative relationship between male home range size and prey availability. In high rodent density areas, males occupied smaller areas (mean = 1,135 ha, median = 1,034 ha), contrasting with low rodent density areas (mean = 6,815 ha, median = 6,516 ha). However, no significant relationship was observed between female home range size and prey availability. We also noted instances of nest abandonment and early dispersal behavior in some females, potentially influenced by a handicapping effect of tagging. Our findings offer valuable insight into how prey availability shapes saker falcon space use and defines their spatial requirements for successful breeding. This knowledge is crucial for the conservation and management of globally endangered saker falcons, informing targeted habitat protection and resource management strategies.
Racial/Ethnic Disparities in Hospital Readmission and Frequent Hospitalizations Among Medicare Beneficiaries With Alzheimer’s Disease and Related Dementia: Traditional Medicare Versus Medicare Advantage
Authors: Mahmoudi Elham , Margosian Sara , Lin Paul 
Published: May 2024

Abstract

Objectives
Examine racial/ethnic disparities in 30-day readmission and frequent hospitalizations among Medicare beneficiaries with dementia in traditional Medicare (TM) versus Medicare Advantage (MA).

Methods
In this case-control study, we used 2018–2019 TM and MA claims data. Participants included individuals 65+ with 2 years of continuous enrollment, diagnosis of dementia, a minimum of 4 office visits in 2018, and at least 1 hospitalization in 2019, (cases: TM [n = 36,656]; controls: MA [n = 29,366]). We conducted matching based on health-need variables and applied generalized linear models adjusting for demographics, health-related variables, and healthcare encounters.

Results
TM was associated with higher odds of 30-day readmission (OR = 1.07 [CI: 1.02 to 1.12]) and frequent hospitalizations (OR = 1.10 [CI: 1.06 to 1.14]) compared to MA. Hispanic and Black enrollees in TM had higher odds of frequent hospitalizations compared with Hispanic and Black enrollees in MA, respectively (OR = 1.35 [CI: 1.19 to 1.54]) and (OR = 1.26 [CI: 1.13 to 1.40]). MA was associated with lower Hispanic–White and Black–White disparities in frequent hospitalizations by 5.8 (CI: −0.09 to −0.03) and 4.4 percentage points (PP; CI: −0.07 to −0.02), respectively. For 30-day readmission, there was no significant difference between Black enrollees in TM and MA (OR = 1.04 [CI: 0.92 to 1.18]), but Hispanic enrollees in TM had higher odds of readmission than Hispanics in MA (OR = 1.23 [CI: 1.06 to 1.43]). MA was associated with a lower Hispanic–White disparity in readmission by 1.9 PP (CI: −0.004 to −0.01).

Discussion
MA versus TM was associated with lower risks of 30-day readmission and frequent hospitalizations. Moreover, MA substantially reduced Hispanic–White and Black–White disparities in frequent hospitalizations compared with TM.
PE (Prickly Eggplant) encoding a cytokinin-activating enzyme responsible for the formation of prickles in eggplant
Authors: Zhang Lei , Zhang Runzhi , Yan Ping , Zeng Liqian , Zhao Weiwei , Feng Huiqian , Mu Ruyu , Hou Wenqian 
Published: May 2024

Abstract
Eggplant is one of the most important vegetables worldwide, with some varieties displaying prickles. These prickles, present on the leaves, stems, and fruit calyxes, posing challenges during cultivation, harvesting, and transportation, making them an undesirable agronomic trait. However, the genetic mechanisms underlying prickle morphogenesis in eggplant remain poorly understood, impeding genetic improvements. In this study, genetic analyses revealed that prickle morphogenesis is governed by a single dominant nuclear gene, termed PE (Prickly Eggplant). Subsequent bulk segregant RNA-sequencing (BSR-seq) and linkage analysis preliminarily mapped PE to chromosome 6. This locus was then fine mapped to a 9233 bp interval in a segregating population of 1109 plants, harboring only one candidate gene, SmLOG1, which encodes a LONELY GUY (LOG)-family cytokinin biosynthetic enzyme. Expression analyses via transcriptome and qRT-PCR demonstrate that SmLOG1 is predominantly expressed in immature prickles. CRISPR-Cas9 knockout experiments targeting SmLOG1 in prickly parental line ‘PI 381159’ abolished prickles across all tissues, confirming its critical role in prickle morphogenesis. Sequence analysis of SmLOG1 pinpointed variations solely within the non-coding region. We developed a cleaved amplified polymorphic sequences (CAPS) marker from a distinct SNP located at −735-bp within the SmLOG1 promoter, finding significant association with prickle variation in 190 eggplant germplasms. These findings enhance our understanding of the molecular mechanisms governing prickle development in eggplant and facilitate the use of marker-assisted selection (MAS) for breeding prickleless cultivars.
Phenotypic Convergence Is Stronger and More Frequent in Herbivorous Fishes
Authors: Kolmann M A , Poulin E , Rosen J , Hemraj-Naraine D , Burns M D 
Published: May 2024

Synopsis
Constraints on phenotypic evolution can lead to patterns of convergent evolution, by limiting the “pool” of potential phenotypes in the face of endogenous (functional, developmental) or exogenous (competition, predation) selective pressures. Evaluation of convergence depends on integrating ecological and morphological data within a robust, comparative phylogenetic context. The staggering diversity of teleost fishes offers a multitude of lineages adapted for similar ecological roles and, therefore, offers numerous replicated evolutionary experiments for exploring phenotypic convergence. However, our understanding of fish feeding systems has been primarily shaped by marine species, with the monolithic exception of freshwater cichlids. Here we use piranhas and pacus (Serrasalmidae) to explore the evolution of different feeding ecologies and their morphological proxies in Neotropical freshwater environments. Specifically, we explore whether convergence is more widespread among plant-eating fishes, arising from strong constraints on phenotypic evolution in herbivores. Using osteological micro-computed tomographic imaging (μCT), we describe the major axes of morphological variation in pacus and piranhas, regarding their diet and feeding behaviors. Next, we evaluated whether herbivorous niches are less labile than other dietary guilds and whether herbivorous species’ phenotypes evolve at a slower evolutionary rate than other taxa. We then assess how convergent herbivorous taxa are, using three different suites of morphological characters (dental, jaw, and abdominal morphometrics). Ecologically, herbivory is not a dead end, exhibiting similar observed transition rates as those between carnivores and omnivores. However, we documented widespread convergence in herbivores and that herbivores have slower rates of phenotypic evolution than carnivores. Most instances of convergence are found in herbivorous taxa, specifically in frugivores and folivores. Moreover, instances of “complete” convergence, indicated by positive convergence metrics observed in more than one morphometric dataset, were only found in herbivores. Herbivores do appear to evolve under constrained circumstances, but this has not limited their ecological ability.
Extension of the geographical range of the primary burrowing crayfish Cambarus strigosus Hobbs, 1981 (Decapoda: Astacidea: Cambaridae) in South Carolina
Authors: Barnett Zanethia C , Bland Mickey R , Myers Gregory , Loughman Zachary J 
Published: May 2024

Abstract
Knowledge of the geographical distribution for many primary burrowing crayfishes is often limited to information presented in species descriptions or field notes associated with epigean crayfish surveys. Cambarus strigosusHobbs, 1981, a rare primary burrowing crayfish, was collected as part of a survey of the Sumter National Forest, South Carolina (SC), USA. Prior to this discovery, C. strigosus appeared to be endemic to mid-reaches of the Broad River Drainage in Georgia (GA). We conducted additional field sampling in SC and GA and used mitochondrial DNA (mtDNA) to compare the relative genetic distance between individuals across all populations in an effort to determine the identity of the specimens collected. Genetic data indicated that the crayfish collected in SC was C. strigosus, with one shared haplotype between SC and GA populations. Our genetic results exhibited geographic structuring and indicated that SC populations have a specific haplotype unique to them, providing strong evidence that SC populations are not introduced. Two additional SC records of C. strigosus from 1983 housed in the US National Museum were examined and determined to be C. strigosus. With these records, we hypothesized that like in GA, the distribution of C. strigosus in SC is limited to riparian habitats associated with the Savannah River Drainage. While the range of this species has been extended, it is still limited to small portions of this drainage. Thus, further sampling to determine the true extent of C. strigosus distribution within SC along with conservation efforts are needed to protect this globally rare species.
Development of a sterile insect technique as a control strategy for the Asian citrus psyllid: establishing the effect of sterilizing X-rays on fecundity, fertility, and survival
Authors: Ferrater Jedeliza B , Gómez-Marco Francesc , Yoshimoto Andrew K , Greene Thomas D , Simmons Gregory S , Daugherty Matthew P , Rugman-Jones Paul F 
Published: May 2024

Abstract
The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is a major pest of citrus due to its role as the vector of the bacterium that causes huanglongbing. In commercial citrus, ACP control currently relies on the application of insecticides, which may not be sustainable long-term, nor practical in urban areas. The sterile insect technique (SIT) is an alternative strategy in which large numbers of pests are reared, sterilized using radiation, and then released into the field to compete with wild individuals for matings, suppressing population growth. As a fundamental step toward the development of SIT for ACP, this study sought to identify the optimum radiation dose required to sterilize ACP without affecting their survival and mating capacity. Virgin adult ACP of both sexes were subjected to doses of X-ray irradiation ranging from 40 to 480 Gy, then paired with a nonirradiated mate and allowed to produce offspring. Fecundity was estimated as the number of eggs laid, and fertility as the proportion of those eggs that hatched. Females were more radio-sensitive than males, exhibiting a major drop in fecundity at even the lowest dose and 100% sterility at 80 Gy. In contrast, a fivefold higher dose (400 Gy) did not achieve complete sterility in males, with around 5% offspring survival. However, F1 progeny of males exposed to 320 Gy or higher were subsequently found to be 100% sterile. This confirmation of inherited sterility suggests that balancing the sterilizing effects of radiation against its mortality-inducing effects may warrant further evaluation.