bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-marketing surveillance of encorafenib in combination with binimetinib in Japanese patients with BRAF-mutant melanoma
Authors: Yamazaki Naoya , Sakata Hidenori , Iida Osamu , Katayama Teruaki , Uhara Hisashi 
Published: February 2025

Abstract

Background
A BRAF inhibitor, encorafenib, combined with a MEK inhibitor, binimetinib, was approved in Japan in early 2019 for the treatment of BRAF V600-mutant, unresectable malignant melanoma based on results of the global phase III trial, COLUMBUS, conducted in various countries including Japan. This post-marketing surveillance (PMS) assessed the combination in real-world clinical practice in Japan.

Methods
We performed a prospective, multicentre, 12-month PMS of the safety and effectiveness of encorafenib plus binimetinib for radically unresectable, BRAF-mutant malignant melanoma in Japan.

Results
Among 174 survey forms collected from 85 centres between February 2019 and August 2020, 172 were included for safety and effectiveness analysis. Patients (male [52.3%], median age 62.0 years) had Eastern Cooperative Oncology Group Performance Status 0 or 1 (91.8%) and comorbidities (55.2%). Respective encorafenib and binimetinib median dosages were 450 mg/day and 90 mg/day; median treatment duration, 24.1 and 24.2 weeks, and discontinuation, 71.5% for each, primarily for disease progression (56.9%) and adverse drug reactions (ADRs, 38.2%). Safety assessment ADRs occurred in 99 patients (57.6%), including eye disorders (40.7%), hepatic dysfunction (20.3%), rhabdomyolysis (4.7%), haemorrhage (2.3%), palmar-plantar erythrodysaesthesia syndrome (1.7%), and hypertension (1.7%); 19.8% were grade ≥ 3, none were grade 5, most resolved with/without treatment modification. At 12 months, the objective response rate was 48.8% (95% CI 41.2, 56.6; complete [19.2%], partial [29.7%]), overall survival was 40.1%.

Conclusion
The safety and effectiveness of encorafenib plus binimetinib in Japanese patients with BRAF-mutant malignant melanoma were similar to data reported in COLUMBUS; no new safety concerns were identified.
Fling amplitude inventory of near-fault strong motion recordings in Turkiye
Authors: Adanır Emrecan , Tanırcan Gülüm 
Published: February 2025

Abstract
The fling step, a significant near-field effect, has an adverse impact on long-period engineering structures. Despite early recognition by pioneers, identifying and processing the ground motions containing the fling step remains challenging due to conventional data filtering methods that ignore low-frequency components. This study investigates the recovery of the fling step from near fault records and by modifying and/or adding processing steps to previous methods, proposes a robust processing scheme for strong ground motion recordings in capturing fling amplitude. The proposed scheme’s capability is verified through GNSS-derived displacements from global and Turkiye earthquakes. Subsequently, the method is applied to strong motion recording in the Turkish dataset (Mw ≥ 6 shallow crust earthquakes recorded at RJB≤50 km), resulting in a comprehensive inventory of fling amplitudes across multiple motion components. This inventory serves both engineering and earth sciences research by facilitating the evaluation of existing predictive models. In addition, a Türkiye-specific performance evaluation of existing predictive models is conducted using the presented database. Lastly, a refined fling amplitude prediction model, based on conformity with the presented fling inventory, is proposed. This work addresses critical gaps in strong ground motion analyses, promoting improved seismic resilience through accurate characterization of near-fault effects.
Drivers of energy efficiency in the Portuguese water industry
Authors: Amaral António L. , Martins Rita , Dias Luís C. 
Published: February 2025

Abstract
Identifying service providers with the best performance regarding their main operational indicators is relevant to improve the sustainability of the water sector. It is also critical to determine the corresponding drivers, and understand the interdependences, to enlighten the relevant stakeholders about the best course of action. The energy consumption of the service provider is a major issue, regarding sustainability, both for financial (being one of the largest operating expenses) and environmental (emission of greenhouse gases) reasons. In that regard, a Data Envelopment Analysis—Slacks Based Measure is employed to identify the service providers within the efficiency frontier. Only the efficient providers were considered to determine the main drivers and to model the energy consumption by multilinear regression. The current study identifies the effectively served population and the number of served households as paramount for the estimation of energy consumption at the efficiency frontier in wastewater and drinking water treatment, respectively. Other explanatory factors were also found to be significant, especially regarding normalized (per water intake) energy consumption, including energy certification, wastewater treatment plants typology, mains and sewers grid rehabilitation, wastewater satisfactory treatment, number of septic tanks and drinking water treatment plants and collected water volumes. The proposed methodology can be applied to data from any country to identify the role model SP and the corresponding energy consumption drivers, allowing policy recommendations to be tailored to each specific context.
Spermatozoa centriole quality determined by FRAC may correlate with zygote nucleoli polarization—a pilot study
Authors: Kluczynski Derek F. , Jaiswal Ankit , Xu Min , Nadiminty Nagalakshmi , Saltzman Barbara , Schon Samantha , Avidor-Reiss Tomer 
Published: February 2025

Abstract

Purpose
Spermatozoa centriolar defects can result in abnormal zygote functions. Recently, a method to quantify spermatozoa centriolar defects was developed named Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC). However, whether spermatozoa centriolar defects identified by FRAC can result in abnormal zygote functions was not tested.

Methods
Here, we quantified spermatozoa centriolar defects using FRAC, and zygote centriole function was assessed by imaging Nucleolus Precursor Body (NPB) polarization which was based on the pattern of NPB polarization. Data was analyzed at couple and embryo levels. Subjects were divided into two groups: seven couples and 62 embryos with normal spermatozoa centrioles versus eight couples and 78 embryos with abnormal spermatozoa centrioles (140 embryos from 15 couples in total).

Results
Patterned NPB polarization was statistically significant in both couple- and embryo-level analyses (p < 0.0001 and p = 0.0024). These results suggest that the abnormal spermatozoa centrioles identified by FRAC may correlate with abnormal zygote centrosome function via NPB polarization scoring.

Conclusions
This study provides a foundation for more extensive studies to test for FRAC’s utility in assessing spermatozoa centriole quality.
Analytical modeling of NH3 gas sensing using zigzag graphene nanoscrolls: energy band structure and electrical properties
Authors: Hosseingholipourasl Ali 
Published: February 2025

Abstract
Graphene nanoscrolls (GNSs), a unique nanostructure of graphene, have garnered considerable attention due to their distinctive properties such as a rolled-up papyrus-like structure, adjustable core geometry, increased inner wall area, and enhanced surface-to-volume ratio. These properties make GNS a promising candidate for various nanoelectronic applications, including gas sensing devices. Despite its potential, GNS has been relatively underexplored in the context of gas sensing applications. In this study, we present a series of analytical models to characterize the behavior of zigzag graphene nanoscrolls (ZGNS)-based gas sensors in the presence of NH3 gas. The tight-binding technique, employing nearest neighbor approximation, is utilized to formulate the energy dispersion relation of GNS, incorporating the influence of gas molecule adsorption through parameters such as the hopping integral between GNS and gas and the on-site energy of adsorbed gas molecules. Furthermore, the derived energy equation is employed to establish the conductance relation and explore the impact of gas adsorption on the electrical conductance of GNS. Subsequently, the I-V characteristics of the GNS sensor are formulated, and the variations in current due to NH3 gas exposure are analyzed. The gate voltage is modeled as a function of NH3 concentration, and a sensing parameter is proposed based on current variations across different concentrations. Validation of the model is performed by comparing the obtained results with data extracted from previous studies. The findings demonstrate good agreement, underscoring the effectiveness of the proposed ZGNS-based sensor model for NH3 detection under varying environmental conditions.

Graphical abstract
New Insights into the Composition of Aggregation Pheromones in Polygraphus poligraphus, Polygraphus punctifrons, Polygraphus subopacus and Polygraphus proximus
Authors: Viklund Lina , Bång Joakim , Schroeder Martin , Hedenström Erik 
Published: February 2025

Abstract
Four-eyed bark beetles of the genus Polygraphus have been involved in large bark beetle outbreaks in different parts of the world, resulting in major economic losses. A striking example is the invasive species Polygraphus proximus which is a pest on Abies sibirica in Russia. In Sweden, Polygraphus poligraphus has been involved in bark beetle outbreaks on Norway spruce, Picea abies, together with the European spruce bark beetle Ips typographus. Two related species, Polygraphus punctifrons and Polygraphus subopacus are also present in Sweden. Recently, aggregation pheromones or pheromone components have been identified for these four Polygraphus species. However, questions remain regarding the complete composition of their pheromones, particularly for P. subopacus and P. proximus, whose aggregation pheromones appear to be very similar. In an attempt to better understand the chemical communication of these species, additional studies were conducted on P. poligraphus, P. punctifrons and P. subopacus using solid phase microextraction coupled with gas chromatography and mass spectrometry (SPME–GC–MS), electroantennography (EAG) as well as SPME–GC–MS and GC–MS with electroantennographic detection (EAD). Field experiments were also conducted. In P. punctifrons, some male-specific compounds were found in addition to those previously identified. In EAG and SPME–GC–MS/EAD studies, all three Polygraphus species responded strongly to grandisol. Using a chiral column, GC–MS/EAD revealed that they were able to detect both enantiomers of grandisol. In summary, this work presents our current understanding of the aggregation pheromones in four Polygraphus species and the challenges we have met in identifying species-specific pheromone blends for some of these species.
Eemian snails from Gorzów Wielkopolski palaeolake (NW Poland): malacological and isotopic data and their ecological implications
Authors: Mirosław-Grabowska Joanna , Alexandrowicz Witold Paweł , Stefaniak Krzysztof , Skoczylas-Śniaz Sylwia 
Published: February 2025

Abstract
The results of isotope and malacological investigations of mollusc shells from the Eemian Interglacial (MIS 5e) and Vistulian (Weichselian, MIS 5a-d - MIS 4) lake sediments in Gorzów Wielkopolski (NW Poland) are presented. The palaeolake in Gorzów Wielkoposki is the newest paleontological site with the skeleton of the Eemian rhinoceros. The analyzed sediments contained numerous mollusc shells representing 29 species. The dominant species in the malacofauna are Valvata piscinalis and Bithynia tentaculata. Two types of mollusc assemblages have been distinguished, indicating the changes in the lake environment. Carbon and oxygen isotope compositions (δ13C and δ18O) were measured in the shells of Valvata piscinalis and in the opercula of Bithynia tentaculata. The δ18O values of the Eemian snail shells changed from − 6.0 to − 3.8‰, and are higher than the bulk carbonate data. The δ13C values oscillated between − 8.6 and − 1.8‰ in the Eemian shells and are lower than the bulk carbonate data. Environmental changes occurring in the immediate vicinity of the rhinoceros skeleton likely influenced the isotope composition of shells, resulting in different δ13C and δ18O values. The malacological and isotope data aided in distinguishing six phases of lake development. In the first phase (M-1, Early Eemian), a progressive increase in the water level was noted. Then (M-2, Middle Eemian), a significant shallowing of the lake took place. The next phase (M-3, Middle Eemian) was characterized by high water levels and stable hydrological conditions. In the M-4 phase (Late Eemian), a gradual lowering of the water level was observed, leading to the complete disappearance of the lake at the end of the Eemian. During the Vistulian, the lake reemerged. Initially (M-5), it was a permanent lake with a relatively high water level. In the highest part of the profile (M-6, Vistulian), its significant shallowing occurred, and this lake disappeared.
The governance of the coastal region: evolutionary changes in the conceptualisation and integration of landscape in Portuguese coastal planning institutions
Authors: Gonçalves Carla , Pinho Paulo 
Published: February 2025

Abstract

Context
Coastal landscapes are unique and fragile socio-ecological systems, yet despite political and scientific efforts toward integrated coastal governance, challenges such as fragmented approaches, multiple boundaries, and inadequate policy integration persist. While landscape governance offers significant potential for rethinking coastal governance by emphasising the integrative power of landscapes, many scientific discussions still employ a binary perspective, limiting its full potential. Additionally, research on how the conceptualisation and integration of landscape has evolved in European coastal planning institutions remains scarce.

Objectives
This article aims to advance coastal landscape governance research by examining the evolution of the conceptualisation and integration of landscape in Portuguese coastal planning institutions, assessing whether the narrow view found in national laws is reflected at the policy instrument level.

Methods
We used multiple explanatory case study research to explore the evolution of the conceptualisation and integration of landscape within Portuguese coastal planning institutions from 1978 to 2021, employing qualitative content analysis.

Results
Findings indicate that coastal plans have increasingly failed to use the integrative potential of landscapes fully. This decline is accompanied by a growing tendency to associate landscape valuation with Nature Protected Areas.
Furthermore, the analysed instruments revealed an increase in references to the landscape over time. However, differing conceptualisations of the landscape emerged, with the unexpected finding that a holistic conceptualisation did not always correspond to high levels of integration. Instead, landscape integration primarily focused on aspects such as multifunctionality, connectivity, and fragmentation.

Conclusions
Our research underscores the urgent need for more empirical research in coastal landscape governance. From a broader perspective, such research could demonstrate the benefits of leveraging the integrative power of landscapes in coastal governance, potentially contributing to a paradigm shift towards coastal landscape governance.
Self-referring as self-directed action
Authors: Orbán Krisztina 
Published: February 2025

Abstract
I propose that examining pointing and, especially, self-pointing helps us to better understand Self-Referring (knowingly and intentionally self-referring). I explain basic features of pointing and self-pointing, such as referring, reference-fixing and the subject’s knowledge of the referent. I propose to treat Self-Referring as a self-directed action. Self-pointing makes it explicit how Self-Referring is a self-directed action produced for intentionally expressing something about the agent of the self-directed action. My project is an attempt to naturalize the capacity for Self-Reference. The capacity for self-directed action predates and enables the acquisition of Self-Referring. The structure of self-pointing reveals how the referent of ‘I’ is fixed in such way that we can begin to see how it supports the cognitive significance of Self-Referring expressions. In arguing for my proposal, I reflect on findings from developmental and comparative psychology and analyze Self-Reference in both spoken and sign-languages.
A new technology for a novel clinical approach in a dog with a complex vascular anomaly: the “extended reality”
Authors: Cupido Simone , Valeri Federica , Nicoli Stefano , Bargellini Paolo , Caivano Domenico , Birettoni Francesco , Bortolotti Andrea , Rishniw Mark , Porciello Francesco 
Published: February 2025

Abstract
Extended reality includes both virtual and augmented realities. In virtual reality objects are rendered in an artificial environment where the user can move and interact with a head mounted display. In augmented reality virtual objects are superimposed to real environment enriching it via a head mounted display. In human medicine these technologies have been already used for educational surgical purposes, but remain relatively unknown in veterinary medicine. We report a case of a 1-year-old, female, French bulldog presented for exercise intolerance and dyspnea. Echocardiography showed signs of left ventricular enlargement with reduced fractional shortening and turbulent flow distal to the pulmonary artery bifurcation. Computed tomography revealed a complex vascular network comprising the descending aorta and left pulmonary artery resembling a patent ductus arteriosus. Virtual reality was used for the surgical planning and a left thoracotomy was performed to close the abnormal vessel at the level of the entrance in the left pulmonary artery with augmented reality assistance. No complications were reported during or after the surgery and the dog completely recovered. Echocardiographic findings 3 days, 1 month and 18 months after the surgery demonstrated absence of residual flow and improving ventricular dimensions. To our knowledge this report documents the first use of extended reality for the visualization, planning and execution of the surgical correction of a complex vascular defect in veterinary medicine.
Production of aromatic amino acids and their derivatives by Escherichia coli and Corynebacterium glutamicum
Authors: Hirasawa Takashi , Satoh Yasuharu , Koma Daisuke 
Published: February 2025

Abstract
Demand for aromatic amino acids (AAAs), such as L-phenylalanine, L-tyrosine, and L-tryptophan, has been increasing as they are used in animal feed and as precursors in the synthesis of industrial and pharmaceutical compounds. These AAAs are biosynthesized through the shikimate pathway in microorganisms and plants, and the reactions in the AAA biosynthesis pathways are strictly regulated at the levels of both gene expression and enzyme activity. Various attempts have been made to produce AAAs and their derivatives using microbial cells and to optimize production. In this review, we summarize the metabolic pathways involved in the biosynthesis of AAAs and their regulation and review recent research on AAA production using industrial bacteria, such as Escherichia coli and Corynebacterium glutamicum. Studies on fermentative production of AAA derivatives, including L-3,4-dihydroxyphenylalanine, tyrosol, and 3-hydroxytyrosol, are also discussed.
The role of salivary metabolomics in chronic periodontitis: bridging oral and systemic diseases
Authors: Albahri Jawaher , Allison Heather , Whitehead Kathryn A. , Muhamadali Howbeer 
Published: February 2025

Abstract

Background
Chronic periodontitis is a condition impacting approximately 50% of the world’s population. As chronic periodontitis progresses, the bacteria in the oral cavity change resulting in new microbial interactions which in turn influence metabolite production. Chronic periodontitis manifests with inflammation of the periodontal tissues, which is progressively developed due to bacterial infection and prolonged bacterial interaction with the host immune response. The bi-directional relationship between periodontitis and systemic diseases has been reported in many previous studies. Traditional diagnostic methods for chronic periodontitis and systemic diseases such as chronic kidney diseases (CKD) have limitations due to their invasiveness, requiring practised individuals for sample collection, frequent blood collection, and long waiting times for the results. More rapid methods are required to detect such systemic diseases, however, the metabolic profiles of the oral cavity first need to be determined.

Aim of review
In this review, we explored metabolomics studies that have investigated salivary metabolic profiles associated with chronic periodontitis and systemic illnesses including CKD, oral cancer, Alzheimer’s disease, Parkinsons’s disease, and diabetes to highlight the most recent methodologies that have been applied in this field.

Key scientific concepts of the review
Of the rapid, high throughput techniques for metabolite profiling, Nuclear magnetic resonance (NMR) spectroscopy was the most applied technique, followed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Furthermore, Raman spectroscopy was the most used vibrational spectroscopic technique for comparison of the saliva from periodontitis patients to healthy individuals, whilst Fourier Transform Infra-Red Spectroscopy (FT-IR) was not utilised as much in this field. A recommendation for cultivating periodontal bacteria in a synthetic medium designed to replicate the conditions and composition of saliva in the oral environment is suggested to facilitate the identification of their metabolites. This approach is instrumental in assessing the potential of these metabolites as biomarkers for systemic illnesses.