bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy, tolerability, and safety of teverelix DP in patients with advanced prostate cancer: A multicenter, open‐label, phase 2 trial
Authors: Ulys Albertas , Jankevicus Feliksas , Jievaltas Mindaugas , Venckus Raimundas , Auskalnis Stasys , Kardelis Zygimantas , Barisiene Marija , MacLean Carol M. , van Os Steve , Larsen Finn 
Published: February 2024

AbstractBackgroundTeverelix drug product (DP) is a novel injectable gonadotropin‐releasing hormone antagonist.MethodsAn adaptive phase 2, open‐label, multicenter trial was conducted in patients with advanced prostate cancer to evaluate the efficacy and safety of a combined subcutaneous (SC) and intramuscular (IM) loading dose regimen of teverelix DP of 120 mg SC + 120 mg IM (Group 1; N = 9) or 180 mg SC + 180 mg IM (Group 2; N = 41) administered at a single visit, followed by 6‐weekly SC maintenance doses of 120 mg (Group 1) or 180 mg (Group 2), up to Day 168. The primary endpoint was the proportion of patients achieving castration levels with serum testosterone <0.5 ng/mL at Day 28 with a target castration rate of 90%. Injection sites were inspected by the investigator at every visit and reactions (ISRs) were proactively recorded.ResultsThe target castration rate was reached in Group 2 (97.5%) but not in Group 1 (62.5%). The castration rates were not maintained to Day 42 (Group 2: 82.5%; Group 1: 50.0%). Suppression of testosterone to castrate levels occurred rapidly (median time: 2 days for both groups). Suppression of testosterone, prostate‐specific antigen, follicle‐stimulating hormone, and luteinizing hormone was sustained throughout the treatment period, being more prominent with the higher dose. The adverse event (AE) profile was similar between groups. The most common AEs were injection‐site induration (n = 40: 80.0%), injection‐site erythema (n = 35: 70.0%), and hot flush (n = 21: 42.0%). Most ISRs were Grade 1.ConclusionOverall, the teverelix DP doses were generally well‐tolerated but did not adequately maintain castration levels.
On the relative conservativeness of Bayesian logistic regression method in oncology dose‐finding studies
Authors: Yang Cheng‐Han , Cheng Guanghui , Lin Ruitao 
Published: February 2024

AbstractThe Bayesian logistic regression method (BLRM) is a widely adopted and flexible design for finding the maximum tolerated dose in oncology phase I studies. However, the BLRM design has been criticized in the literature for being overly conservative due to the use of the overdose control rule. Recently, a discussion paper titled “Improving the performance of Bayesian logistic regression model with overall control in oncology dose‐finding studies” in Statistics in Medicine has proposed an overall control rule to address the “excessive conservativeness” of the standard BLRM design. In this short communication, we discuss the relative conservativeness of the standard BLRM design and also suggest a dose‐switching rule to further enhance its performance.
Patient‐based real‐time quality control in medical laboratories: On the design and robustness of the moving average control chart with truncation limits
Authors: Murat Ugur , Testik Murat Caner , Pinar Asli 
Published: February 2024

AbstractQuality is an indispensable requirement in medical laboratories, where controls are performed at different phases of the laboratory processes. In the following, we consider the internal quality control activities during the analytical phase of medical laboratories for verifying the test results prior to their release. To monitor the measurement process for errors in the test results, one approach that is considerably attracting the health professionals is patient‐based real‐time quality control. In this respect, real‐time patient test results are monitored, commonly by implementing the Moving Average (MA) control chart with truncation limits. A usual practice is the use of truncation limits to exclude abnormal patient test results from the MA calculations. However, an open issue in the literature is how to determine the width of the truncation limits and the window size in the MA calculations. Furthermore, the distributions of the test results are often nonnormal and difficult to model by personnel having insufficient training in statistics. Consequently, robustness of the performance of the MA control chart to non‐normal distributions of test results is another open topic in the literature. In this study, a detailed robustness analysis is performed by considering various distributions having different shapes. Performance of several MA control chart designs constructed by altering the truncation limits and window sizes are investigated. Based on our simulation results with selected distributions, we conclude that the truncation limits should not be used and a window size of 20 is recommended. Under such a setting, the MA control chart performs similar to its intended performance in terms of false alarms and in detecting systematic errors, hence being robust to non‐normality of the test results.
Bird‐related non‐fibrotic hypersensitivity pneumonitis with bronchoalveolar lavage fluid eosinophilia that developed after COVID‐19 vaccination: A case report
Authors: Katano Takuma , Ogisu Tomoyuki , Satou Akira , Yonezawa Toshiyuki , Tanaka Hiroyuki , Ito Satoru 
Published: February 2024

AbstractA 60‐year‐old man who had been keeping seven budgerigars and four cockatiels in his house for 2 years developed dyspnea and was admitted to our hospital the day after receiving the second dose of the messenger RNA coronavirus disease 2019 vaccination. Chest high resolution computed tomography (HRCT) showed bilateral ground glass opacities without nodules or mosaic attenuation. IgG specific for budgerigars was positive. Although his respiratory symptoms were resolved without corticosteroid therapy, he developed severe dyspnea soon after the discharge to his home. The results of bronchial alveolar lavage fluid obtained at the initial admission and after the provocation challenge showed elevation of lymphocytes (34%) and eosinophils (37%). We finally diagnosed him with non‐fibrotic bird‐related hypersensitivity pneumonitis. His condition and HRCT findings were improved by corticosteroid treatment. All his birds were given away. He has not experienced any recurrence or deterioration of respiratory function even after withdrawal of corticosteroid.
Strategic Design of Hemi‐Isoindigo Polymer for a Highly Sensitive and Selective All‐Printed Flexible Nitrogen Dioxide Chemiresistive Sensor
Authors: Ngai Jenner H. L. , Li Zhao , Wang Jia , He Jinghui , Ding Jianfu , Li Yuning 
Published: February 2024

AbstractThe study has developed two hemi‐isoindigo (HID)‐based polymers for printed flexible resistor‐type nitrogen oxide (NO2) sensors: poly[2‐ethylhexyl 3‐((3′“,4′‐bis(dodecyloxy)‐3,4‐dimethoxy‐[2,2′:5′,2′”‐terthiophen]‐5‐yl)methylene)‐2‐oxoindoline‐1‐carboxylate] (P1) and poly[2‐ethylhexyl 2‐oxo‐3‐((3,3′“,4,4′‐tetrakis(dodecyloxy)‐[2,2′:5′,2′”‐terthiophen]‐5‐yl)methylene)indoline‐1‐carboxylate] (P2). These polymers feature thermally removable carbamate side chains on the HID units, providing solubility and creating molecular cavities after thermal annealing. These cavities enhance NO2 diffusion, and the liberated unsubstituted amide ─C(═O)NH─ groups readily form robust double hydrogen bonds (DHB), as demonstrated by computer simulations. Furthermore, both polymers possess elevated highest occupied molecular orbital (HOMO) energy levels of −4.74 and −4.77 eV, making them highly susceptible to p‐doping by NO2. Gas sensors fabricated from P1 and P2 films, anneal under optimized conditions to partially remove carbamate side chains, exhibit remarkable sensitivities of +1400% ppm−1 and +3844% ppm−1, and low detection limit (LOD) values of 514 ppb and 38.9 ppb toward NO2, respectively. These sensors also demonstrate excellent selectivity for NO2 over other gases.
Bending moments redistribution in two‐span reinforced concrete beams reinforced with FRP bars based on collected data research
Authors: Szczepański Konrad , Kotynia Renata 
Published: February 2024

AbstractThis article presents a review of state of the art on nonmetallic reinforcement in terms of bending moment redistribution in double‐span elements. The authors present a summary of existing research programs focused on moment redistribution in FRP (Fiber Reinforced Polymer) reinforced concrete (RC). On this basis authors created a database of concrete elements with all the important construction properties of the elements. Gathered data are presented with quantitative analysis of several variables effecting moment redistribution in published articles. In the following publication authors show a research review which includes an analysis of the influence of variable parameters from the point of view of the database, concerning: degrees of longitudinal reinforcement, ratio between degrees of reinforcement in span and over the support, type of reinforcement (FRP/steel/hybrid), concrete class and transverse reinforcement.
Re‐examining the placement ofHydrostachysusing a large‐scale phylogenetic approach
Authors: Xu Zhun , Folk Ryan A. , Gitzendanner Matthew A. , Hu Guang‐Wan , Soltis Pamela S. , Soltis Douglas E. , Wang Qing‐Feng 
Published: February 2024

AbstractPhylogenetic placement ofHydrostachys(Hydrostachyaceae) has long been enigmatic, the highly divergent morphology ofHydrostachyshaving prevented its confident placement in any clade of angiosperms. Phylogenetic placements using DNA sequence data have varied, with most studies suggesting a placement within Cornales. We conducted a large‐scale phylogenetic analysis based on nuclear and chloroplast datasets to re‐examine the relationships of the genus and assess the data sources and methodological factors that may cause alternative placements.Hydrostachyswas consistently recovered as a member of Cornales in all of our analyses based on 338 single‐copy nuclear genes and 78 chloroplast genes, but the divergentmatKsequences ofHydrostachysavailable in GenBank led to different phylogenetic placements. These highly divergent DNA sequences may make phylogenetic placement problematic, and other factors may also impact the placement, including taxon sampling, long‐branch attraction, incomplete lineage sorting, and potential artifacts (from contaminants, paralogs, or assembly errors) in the datasets.
Radiological and laboratory prognostic parameters for gastric dilation in rabbits (Oryctolagus cuniculus)
Authors: Böttcher Anja , Müller Kerstin 
Published: February 2024

AbstractBackgroundThe aim of this study was to evaluate the radiographical and laboratory findings in pet rabbits with gastric dilation (GD) and identify prognostic parameters.MethodsOne hundred and fifty‐five rabbits with GD were included for the radiographical analyses and 75 for the laboratory analyses. A vertebral stomach score (VSS) was established to determine the extension of the stomach on lateral radiographs. In addition, the caudal limit of gastric distention and the extension and position of gas accumulation in the stomach were recorded.ResultsThe VSS was significantly higher in rabbits with GD than in healthy rabbits (p = 0.001). Extensive amounts of gas accumulation in the stomach (p = 0.001) and a ventral or central location of gas accumulation (p = 0.023) were associated with significantly increased mortality. Azotemia (51%), hyperglycaemia (44%) and hyponatraemia (37%) were the most frequent biochemical alterations in rabbits with GD.LimitationsDue to the retrospective nature of the data, the cause of GD could not be determined in all animals.ConclusionRabbits with GD and severe alterations in glucose, creatinine and sodium concentrations, ventral or central gas accumulations and a large amount of gas in the stomach had a poor prognosis.
Similar long‐term outcomes for venous, bovine pericardial, and polyester patches for primary carotid endarterectomy
Authors: Liesker David J. , Gareb Barzi , Köhlen Bart T. , Donners Simone J.A. , de Borst Gert J. , Zeebregts Clark J. , Saleem Ben R. 
Published: February 2024

AbstractBackgroundCurrently, the type of patch used for carotid endarterectomy closure depends on the preference of the operating surgeon. Various materials are available, including autologous venous patches, bovine pericardial patches (BPP), and synthetic patches. The purpose of this study was to compare the long‐term outcomes.MethodsAll patients who underwent primary carotid endarterectomy with patch angioplasty using a venous, bovine, or polyester patch between 2010 and 2020 at two high‐volume medical centers were included in this retrospective analysis on largely prospectively collected data. Study endpoints included long‐term ipsilateral transient ischemic attack or cerebrovascular accident, restenosis, reintervention, and all‐cause mortality. Cox proportional hazard models were fitted to assess the effect of patch type to each outcome.ResultsIn total, 1481 CEAs were performed with a follow‐up of 32 (13–65) months. Venous patch was used in 309 patients (20.9%), BPP in 1000 patients (67.5%), and polyester patch in 172 patients (11.6%). A preoperative symptomatic carotid artery stenosis of >50% was observed in 91.9% (n = 284) of the patients who received a venous patch, 92.1% (n = 921) of the patients who received BPP, and 90.7% (n = 156) of the patients who received a polyester patch (p = 0.799). Only in selected patients with an asymptomatic stenosis of >70% surgery was considered. Multivariable analyses showed no significant differences between the three patch types regarding long‐term outcomes after adjusting for confounders.ConclusionsIn patients undergoing primary carotid endarterectomy, the use of venous, bovine pericardial, or polyester patches seems equally safe and durable in terms of comparability in long‐term outcomes.
Agonistic interactions and social behaviors in the Saharan Dorcas gazelle (Gazella dorcas neglecta): Using social network analysis to evaluate relationships and social structure in captive male groups
Authors: Cortés Blanca , Fidalgo Ana , Díaz Sergio , Abáigar Teresa 
Published: February 2024

AbstractSocial interactions, including agonistic behavior, are very important for the management and welfare of individuals forming groups in captivity. One of the main concerns for the stability and durability of adult male groups is a noticeable level of intraspecific aggression. This study comprises a Social Network Analysis to illustrate social structure in different groups of captive Saharan Dorcas gazelles (Gazella dorcas neglecta). Our main objectives were to examine the relationship between agonistic, affiliative, and association networks and their reciprocity, assessing also whether the agonistic networks can conform to a linear dominance hierarchy. For these purposes, we recorded the behavior of 23 adult males organized in five herds, three composed only of Saharan Dorcas gazelle males and two mixed herds in which there were also Mhorr gazelle males (Nanger dama mohor). Observations were carried out during 295 h through scan sampling. We found no correlation between the affiliative and association networks in any group, although there was a significant correlation between the agonistic and association networks in mixed‐species groups which was not present in single‐species groups. Overall, there was no consistent reciprocity in either affiliative nor agonistic networks and none of the agonistic networks showed a linear structure. These results indicate that affiliative behavior in Saharan Dorcas gazelles offers distinctive and valuable information about the bonds between individuals, however, their dominance structure is far more complex than previously thought. As information provided by affiliative and proximity behaviors is different in this species, we suggest considering affiliative interactions to stablish affinity between individuals. Evaluating different social behaviors and not only agonistic interactions in later studies, is also recommended to develop a more accurately daily management in zoos that guarantee group stability and individuals' welfare, which will improve the conservation of captive populations.
Combining imaging mass spectrometry and immunohistochemistry to analyse the lipidome of spinal cord inflammation
Authors: Calvo Ibai , Montilla Alejandro , Huergo Cristina , Martín-Saiz Lucía , Martín-Allende Javier , Tepavcevic Vanja , Domercq María , Fernández José A. 
Published: February 2024

AbstractInflammation is a complex process that accompanies many pathologies. Actually, dysregulation of the inflammatory process is behind many autoimmune diseases. Thus, treatment of such pathologies may benefit from in-depth knowledge of the metabolic changes associated with inflammation. Here, we developed a strategy to characterize the lipid fingerprint of inflammation in a mouse model of spinal cord injury. Using lipid imaging mass spectrometry (LIMS), we scanned spinal cord sections from nine animals injected with lysophosphatidylcholine, a chemical model of demyelination. The lesions were demonstrated to be highly heterogeneous, and therefore, comparison with immunofluorescence experiments carried out in the same section scanned by LIMS was required to accurately identify the morphology of the lesion. Following this protocol, three main areas were defined: the lesion core, the peri-lesion, which is the front of the lesion and is rich in infiltrating cells, and the uninvolved tissue. Segmentation of the LIMS experiments allowed us to isolate the lipid fingerprint of each area in a precise way, as demonstrated by the analysis using classification models. A clear difference in lipid signature was observed between the lesion front and the epicentre, where the damage was maximized. This study is a first step to unravel the changes in the lipidome associated with inflammation in the context of diverse pathologies, such as multiple sclerosis.
Graphical abstract
Engineering amino acid residues of pentacyclic triterpene synthases for improving the activity
Authors: Guo Hao , Chen Tongtong , Zhu Hanrong , Wang Huiyan , Huo Yi-Xin 
Published: February 2024

Abstract
Pentacyclic triterpenoids exhibit a wide range of biological activities which have wide applications in the food, cosmetics, and pharmaceutical industries. High-performance chassis strains have been developed for the production of various pentacyclic triterpenoids, e.g., lupane-type and oleanane-type triterpenoids. The production of common pentacyclic triterpenes and their derivatives is limited by the poor activity of typical pentacyclic triterpene synthases (PTSs). However, a general strategy applicable to typical PTSs is still lacking. As typical pentacyclic triterpenes are derived from the baccharenyl cation, engineering the non-active-site residues in the MXXXXR motif might be beneficial for the catalytic efficiencies of typical PTSs by the stabilization of the baccharenyl cation. Here, we develop a general strategy for improving the activity of typical PTSs. As a proof of concept, the activity of three PTSs such as lupeol synthase, β-amyrin synthase, and α-amyrin synthases was significantly increased up to 7.3-fold by site-directed saturation mutagenesis. This strategy could be applied to improve the activity of various typical PTSs.

Key points
• The strategy could be applied to typical PTSs for improving the activity.
• The catalytic activity of typical PTSs was significantly increased.
CRISPR/Cas9-based toolkit for rapid marker recycling and combinatorial libraries in Komagataella phaffii
Authors: Zhou Wei , Li Yuanyi , Liu Guosong , Qin Weichuang , Wei Dongzhi , Wang Fengqing , Gao Bei 
Published: February 2024

Abstract
Komagataella phaffii, a nonconventional yeast, is increasingly attractive to researchers owing to its posttranslational modification ability, strict methanol regulatory mechanism, and lack of Crabtree effect. Although CRISPR-based gene editing systems have been established in K. phaffii, there are still some inadequacies compared to the model organism Saccharomyces cerevisiae. In this study, a redesigned gRNA plasmid carrying red and green fluorescent proteins facilitated plasmid construction and marker recycling, respectively, making marker recycling more convenient and reliable. Subsequently, based on the knockdown of Ku70 and DNA ligase IV, we experimented with integrating multiple DNA fragments at a single locus. A 26.5-kb-long DNA fragment divided into 11 expression cassettes for lycopene synthesis could be successfully integrated into a single locus at one time with a success rate of 57%. A 27-kb-long DNA fragment could also be precisely knocked out with a 50% positive rate in K. phaffii by introducing two DSBs simultaneously. Finally, to explore the feasibility of rapidly balancing the expression intensity of multiple genes in a metabolic pathway, a yeast combinatorial library was successfully constructed in K. phaffii using lycopene as an indicator, and an optimal combination of the metabolic pathway was identified by screening, with a yield titer of up to 182.73 mg/L in shake flask fermentation.

Key points
• Rapid marker recycling based on the visualization of a green fluorescent protein
• One-step multifragment integration and large fragment knockout in the genome
• A random assembly of multiple DNA elements to create yeast libraries in K. phaffii

Graphical Abstract
Online algorithms for ambulance routing in disaster response with time-varying victim conditions
Authors: Shiri Davood , Akbari Vahid , Salman F. Sibel 
Published: February 2024

AbstractWe present a novel online optimization approach to tackle the ambulance routing problem on a road network, specifically designed to handle uncertainties in travel times, triage levels, required treatment times of victims, and potential changes in victim conditions in post-disaster scenarios. We assume that this information can be learned incrementally online while the ambulances get to the scene. We analyze this problem using the competitive ratio criterion and demonstrate that, when faced with a worst-case instance of this problem, neither deterministic nor randomized online solutions can attain a finite competitive ratio. Subsequently, we present a variety of innovative online heuristics to address this problem which can operate with very low computational running times. We assess the effectiveness of our online solutions by comparing them with each other and with offline solutions derived from complete information. Our analysis involves examining instances from existing literature as well as newly generated large-sized instances. One of our algorithms demonstrates superior performance when compared to the others, achieving experimental competitive ratios that closely approach the optimal ratio of one.