bluuebunny/crossref_metadata_2025 huggingface dataset:
The perils and promises of fact-checking with large language models
Authors: Quelle Dorian , Bovet Alexandre
Published: February 2024

Automated fact-checking, using machine learning to verify claims, has grown vital as misinformation spreads beyond human fact-checking capacity. Large language models (LLMs) like GPT-4 are increasingly trusted to write academic papers, lawsuits, and news articles and to verify information, emphasizing their role in discerning truth from falsehood and the importance of being able to verify their outputs. Understanding the capacities and limitations of LLMs in fact-checking tasks is therefore essential for ensuring the health of our information ecosystem. Here, we evaluate the use of LLM agents in fact-checking by having them phrase queries, retrieve contextual data, and make decisions. Importantly, in our framework, agents explain their reasoning and cite the relevant sources from the retrieved context. Our results show the enhanced prowess of LLMs when equipped with contextual information. GPT-4 outperforms GPT-3, but accuracy varies based on query language and claim veracity. While LLMs show promise in fact-checking, caution is essential due to inconsistent accuracy. Our investigation calls for further research, fostering a deeper comprehension of when agents succeed and when they fail.
Deleterious effects of free fatty acids and hydrogen peroxide towards the dinoflagellate Gymnodinium catenatum
Authors: Encinas-Yánez Martín Fernando , Band-Schmidt Christine Johanna , Zenteno-Savín Tania , Leyva-Valencia Ignacio , Fernández Herrera Leyberth José , Palacios-Mechetnov Elena
Published: February 2024

Allelopathy refers to biochemical interactions among competing microalgae, it involves a donor species that produces metabolites which can cause inhibitory effects on susceptible species. This phenomenon can participate in the regulation of harmful algal blooms. The dinoflagellate Gymnodinium catenatum is negatively affected by allelopathic interactions with co-occurring microalgae species, like Chattonella marina var. marina, which has been suggested to produce reactive oxygen species (ROS) and free fatty acids (FFA) as nocive and allelopathic agents. This study explored the effect of hydrogen peroxide (H2O2) and the main fatty acids produced by C. marina. An analysis of fatty acids content of C. marina in exponential phase detected 16:0 (12.5 ± 0.01%), 18:4ω-3 (15.4 ± 0.36%) and 20:5ω-3 (35.4 ± 0.71%) as the most abundant. These fatty acids along with H2O2 were used in dose-response bioassays with cultures of G. catenatum in exponential phase. Results suggest that these substances affect cell morphology, including the loss of motility and signs of chlorosis, as well as the chain forming qualities of G. catenatum. Toxicity among these substances varied, suggesting that the polyunsaturated fatty acid 18:4ω-3 can potentially act as a more effective allelochemical (LD50 = 1.7 ± 0.19 mg L-1 at 24 h), followed by 20:5ω-3 (LD50 = 3.6 ± 0.17 mg L-1 at 24 h) and the saturated fatty acid 16:0 (LD50 = 6.2 ± 1.05 at 48 h). Our results suggest these substances can act, at least partially, as allelochemicals, with PUFA being the most effective metabolites. These results contribute in elucidating the potential role of ROS and FFA in allelopathy in marine phytoplankton communities.
Analysis of the gut microbiome in sled dogs reveals glucosamine- and activity-related effects on gut microbial composition
Authors: Wang Dong , Russel William A. , Macdonald Kaitlyn M. , De Leon Valerie M. , Ay Ahmet , Belanger Kenneth D.
Published: February 2024

The composition of the microbiome influences many aspects of physiology and health, and can be altered by environmental factors, including diet and activity. Glucosamine is a dietary supplement often administered to address arthritic symptoms in humans, dogs, and other mammals. To investigate how gut microbial composition varies with glucosamine supplementation, we performed 16S rRNA sequence analysis of fecal samples from 24 Alaskan and Inuit huskies and used mixed effects models to investigate associations with activity, age, and additional factors. Glucosamine ingestion, age, activity, sex, and diet were correlated with differences in alpha-diversity, with diversity decreasing in dogs consuming glucosamine. Beta-diversity analysis revealed clustering of dogs based on glucosamine supplementation status. Glucosamine supplementation and exercise-related activity were associated with greater inter-individual pairwise distances. At the family level, Lactobacillaceae and Anaerovoracaceae relative abundances were lower in supplemented dogs when activity was accounted for. At the genus level, Eubacterium [brachy], Sellimonus, Parvibacter, and an unclassified genus belonging to the same family as Parvibacter (Eggerthellaceae) all were lower in supplemented dogs, but only significantly so post-activity. Our findings suggest that glucosamine supplementation alters microbiome composition in sled dogs, particularly in the context of exercise-related activity.
The Tengmalm’s owl Aegolius funereus (Aves, Strigidae) as the definitive host of Sarcocystis funereus sp. nov. (Apicomplexa)
Authors: Máca Ondřej , Kouba Marek , Langrová Iva , Panská Lucie , Korpimäki Erkki , González-Solís David
Published: February 2024

Background

Owls have been reported as definitive hosts, whereas wild small mammals (naturally and experimentally) as intermediate hosts of several species of Sarcocystis. Recently, dead fledglings were found infected by an unnamed species of Sarcocystis since its intermediate host was unknown. After collecting additional samples of owls and wild small mammals, the present study focused on elucidating the identity, potential intermediate host, and complete life cycle of the found Sarcocystis through experimentally infected rodents. The developmental stages’ morphological and molecular characterizations (28S rRNA gene, ITS1 region) are presented herein.

Methods

In total, 21 Tengmalm’s owl carcasses (15 nestlings, 5 fledglings, and 1 adult male) were collected in Kauhava (west-central Finland) and parasitologically examined by wet mounts. Intestinal mucosa scrapings were used to isolate oocysts/sporocysts and employed for experimental infections in dexamethasone-immunosuppressed BALB/cOlaHsd mice. Additionally, sarcocysts were searched in the skeletal muscle of 95 samples from seven wild small mammal species. All these developmental stages were molecularly characterized by the 28S rRNA gene and ITS1 region. Experimental infections were carried out by using immunosuppressed female 8-week-old BALB/cOlaHsd mice, divided into three groups: (1) water with 15 μg/mL of dexamethasone, (2) water with 30 μg/mL of dexamethasone, (3) no dexamethasone treatment. Each group consisted of four individuals. In each group, two mice were infected with 1,000 sporocysts each, and the remaining two with 10,000 sporocysts each. All mice were euthanized on specific days post-infection.

Results

The intestinal mucosa of 11 nestlings and 5 fledglings of the Tengmalm’s owl were positive for Sarcocystis funereus sp. nov. The adult male owl and all owls’ breast and heart muscles were negative for Sarcocystis. Two dexamethasone-immunosuppressed BALB/cOlaHsd mice (group 2) were positive to S. funereus sp. nov. in diaphragm and leg muscles after 22- and 24-day post-infection. Some sarcocysts were found in the wild small mammals. Molecular identification at 28S rRNA revealed sequences from naturally infected Tengmalm’s owls, as well as sarcocysts of dexamethasone-immunosuppressed BALB/cOlaHsd mice were 99.87–100% similar to Sarcocystis sp. isolate Af1 previously found in the Tengmalm’s owl. At the ITS1 region, the S. funereus sp. nov. isolates Af2 haplotype B and Af3 haplotype A were 98.77–100% identical to Sarcocystis sp. isolate Af1. The sequences from sarcocysts of naturally infected wild small mammals were 75.23–90.30% similar at ITS1 region to those of S. funereus sp. nov.

Conclusion

The morphological and molecular characterizations and phylogenetic placement of S. funereus sp. nov. are presented here for the first time and support the erection of the new species.
GPU Adding-Doubling Algorithm for Analysis of Optical Spectral Images
Authors: Milanic Matija , Hren Rok
Published: February 2024

The Adding-Doubling (AD) algorithm is a general analytical solution of the radiative transfer equation (RTE). AD offers a favorable balance between accuracy and computational efficiency, surpassing other RTE solutions, such as Monte Carlo (MC) simulations, in terms of speed while outperforming approximate solutions like the Diffusion Approximation method in accuracy. While AD algorithms have traditionally been implemented on central processing units (CPUs), this study focuses on leveraging the capabilities of graphics processing units (GPUs) to achieve enhanced computational speed. In terms of processing speed, the GPU AD algorithm showed an improvement by a factor of about 5000 to 40,000 compared to the GPU MC method. The optimal number of threads for this algorithm was found to be approximately 3000. To illustrate the utility of the GPU AD algorithm, the Levenberg–Marquardt inverse solution was used to extract object parameters from optical spectral data of human skin under various hemodynamic conditions. With regards to computational efficiency, it took approximately 5 min to process a 220 × 100 × 61 image (x-axis × y-axis × spectral-axis). The development of the GPU AD algorithm presents an advancement in determining tissue properties compared to other RTE solutions. Moreover, the GPU AD method itself holds the potential to expedite machine learning techniques in the analysis of spectral images.
Assessing the Impact of Patient Characteristics on Genetic Clinical Pathways: A Regression Approach
Authors: Alderighi Stefano , Landa Paolo , Tànfani Elena , Testi Angela
Published: February 2024

Molecular genetic techniques allow for the diagnosing of hereditary diseases and congenital abnormalities prenatally. A high variability of treatments exists, engendering an inappropriate clinical response, an inefficient use of resources, and the violation of the principle of the equality of treatment for equal needs. The proposed framework is based on modeling clinical pathways that contribute to identifying major causes of variability in treatments justified by the clinical needs’ variability as well as depending on individual characteristics. An electronic data collection method for high-risk pregnant women addressing genetic facilities and laboratories was implemented. The collected data were analyzed retrospectively with two aims. The first is to identify how the whole activity of genetic services can be broken down into different clinical pathways. This was performed by building a flow chart with the help of doctors. The second aim consists of measuring the variability, within and among, the different paths due to individual characteristics. A set of statistical models was developed to determine the impact of the patient characteristics on the clinical pathway and its length. The results show the importance of considering these characteristics together with the clinical information to define the care pathway and the use of resources.
A Literature Review on Some Trends in Artificial Neural Networks for Modeling and Simulation with Time Series
Authors: Muñoz-Zavala Angel E. , Macías-Díaz Jorge E. , Alba-Cuéllar Daniel , Guerrero-Díaz-de-León José A.
Published: February 2024

This paper reviews the application of artificial neural network (ANN) models to time series prediction tasks. We begin by briefly introducing some basic concepts and terms related to time series analysis, and by outlining some of the most popular ANN architectures considered in the literature for time series forecasting purposes: feedforward neural networks, radial basis function networks, recurrent neural networks, and self-organizing maps. We analyze the strengths and weaknesses of these architectures in the context of time series modeling. We then summarize some recent time series ANN modeling applications found in the literature, focusing mainly on the previously outlined architectures. In our opinion, these summarized techniques constitute a representative sample of the research and development efforts made in this field. We aim to provide the general reader with a good perspective on how ANNs have been employed for time series modeling and forecasting tasks. Finally, we comment on possible new research directions in this area.
Physics-Embedded Deep Learning to Predict Real-Time Flow Parameters in Complex Thermodynamic Machinery
Authors: Lin Zhifu , Xiao Dasheng , Xiao Hong
Published: February 2024

Flow through complex thermodynamic machinery is intricate, incorporating turbulence, compressibility effects, combustion, and solid–fluid interactions, posing a challenge to classical physics. For example, it is not currently possible to simulate a three-dimensional full-field gas flow through the propulsion of an aircraft. In this study, a new approach is presented for predicting the real-time fluid properties of complex flow. This perspective is obtained from deep learning, but it is significant in that the physical context is embedded within the deep learning architecture. Cases of excessive working states are analyzed to validate the effectiveness of the given architecture, and the results align with the experimental data. This study introduces a new and appealing method for predicting real-time fluid properties using complex thermomechanical systems.
Behavioural Synchronisation between Dogs and Humans: Unveiling Interspecific Motor Resonance?
Authors: Lamontagne Angélique , Gaunet Florence
Published: February 2024

Dogs’ behavioural synchronisation with humans is of growing scientific interest. However, studies lack a comprehensive exploration of the neurocognitive foundations of this social cognitive ability. Drawing parallels from the mechanisms underlying behavioural synchronisation in humans, specifically motor resonance and the recruitment of mirror neurons, we hypothesise that dogs’ behavioural synchronisation with humans is underpinned by a similar mechanism, namely interspecific motor resonance. Based on a literature review, we argue that dogs possess the prerequisites for motor resonance, and we suggest that interspecific behavioural synchronisation relies on the activation of both human and canine mirror neurons. Furthermore, interspecific behavioural studies highlight certain characteristics of motor resonance, including motor contagion and its social modulators. While these findings strongly suggest the potential existence of interspecific motor resonance, direct proof remains to be established. Our analysis thus paves the way for future research to confirm the existence of interspecific motor resonance as the neurocognitive foundation for interspecific behavioural synchronisation. Unravelling the neurocognitive mechanisms underlying this behavioural adjustment holds profound implications for understanding the evolutionary dynamics of dogs alongside humans and improving the day-to-day management of dog–human interactions.
Pain Mitigation Strategies for Disbudding in Goat Kids
Authors: Singh Preet , Venkatachalam Dinakaran , Kongara Kavitha , Chambers Paul
Published: February 2024

Pain mitigation strategies for disbudding in goat kids have gained significant attention in recent years because of growing concerns for animal welfare. Disbudding, the removal of horn buds in young goats, is a common practice to enhance safety and manage herd dynamics. However, the procedure will cause pain and distress if not managed effectively. This review covers the array of pain mitigation techniques currently available for disbudding, including the efficacy of these strategies in reducing pain and stress during the disbudding process, with specific attention to the potential toxicity associated with local anesthetics. The current best practice for disbudding on the farm suggests sedation/analgesia with an alpha-2 agonist, the placement of a two-point cornual nerve block, and then an NSAID for postoperative pain. In conclusion, this review offers recommendations for future research directions aimed at enhancing the welfare of young goats subjected to the disbudding procedure. These suggestions hold the promise of fostering significant improvements in the overall well-being of these animals.
Experiences of Interdisciplinary Working from the Perspective of the Society of Master Saddlers Qualified Saddle Fitters
Authors: Nankervis Kathryn , MacKechnie-Guire Russell , Maddock Christy , Pyatt Alison
Published: February 2024

Horse owners seek the advice and support of a number of equestrian professionals in carrying out their duty of care for their animal. In some instances, these professionals form a multi-disciplinary team (MDT). The aim of this study was to explore the experiences of the Society of Master Saddlers’ qualified saddle fitters (SMSQSFs) working with other professionals and to understand the nature of inter-disciplinary working from an SMSQSF perspective. Semi-structured, one-to-one online interviews with fourteen SMSQSFs were completed. Areas explored included the nature of the participant’s client base; the frequency and nature of their interactions with other professionals; their perceptions of horse owner expectations of an MDT approach; and any benefits, challenges, and barriers to an MDT approach within an equestrian setting. Interviews were video and audio recorded (MS Teams), transcribed verbatim (Otter ai), and imported into qualitative data analysis software (NVivo, version 12). Data were analysed using thematic analysis. Six themes were identified: (1) effective communication; (2) multidisciplinary expectations; (3) horse welfare; (4) professionalism; (5) relationships; (6) working together. Communication was recognised as a crucial component of an effective MDT. Most participants valued and desired an MDT approach. They felt they had a key role to play within the equestrian MDT, not only in the prevention of deterioration in horse welfare but also in improving the functionality and performance of the horse–rider partnership. Effective MDT working was also seen as having benefits to SMSQSFs and other professional stakeholders alike, although time and financial constraints were identified as barriers to MTD working. The role of the horse owner within the MDT was unclear and potentially complex, and this and other factors such as the professional identity of the SMSQSF, personal relationships, and input from others outside of the MDT team were identified as challenges to effective MDT working. This present study found that SMSQSFs experience similar benefits and challenges to an MDT approach as seen in human healthcare settings. The role of the horse owner, communication, and professional recognition are indicated as pivotal to MDT effectiveness in achieving optimal saddle fit.
Analysis of Genetic Diversity in Romanian Carpatina Goats Using SNP Genotyping Data
Authors: Vlaic Bogdan Alin , Vlaic Augustin , Russo Isa-Rita , Colli Licia , Bruford Michael William , Odagiu Antonia , Orozco-terWengel Pablo ,   CLIMGEN Consortium
Published: February 2024

Animal husbandry is one of man’s oldest occupations. It began with the domestication of animals and developed continuously, in parallel with the evolution of human society. The selection and improvement of goats in Romania was not a clearly defined objective until around 1980. In recent years, with the increasing economic value given to goats, breeding programs are becoming established. In Romania, a few goat genetic studies using microsatellites and mtDNA have been carried out; however, a systematic characterization of the country’s goat genomic resources remains missing. In this study, we analyzed the genetic variability of Carpatina goats from four distinct geographical areas (northern, north-eastern, eastern and southern Romania), using the Illumina OvineSNP60 (RefSeq ARS1) high-density chip for 67 goats. Heterozygosity values, inbreeding coefficients and effective population size across all autosomes were calculated for those populations that inhabit high- and low-altitude and high- and low-temperature environments. Diversity, as measured by expected heterozygosity (HE), ranged from 0.413 in the group from a low-temperature environment to 0.420 in the group from a high-temperature environment. Within studied groups, the HT (high temperature) goats were the only group with a positive but low average inbreeding coefficient value, which was 0.009. After quality control (QC) analysis, 46,965 SNPs remained for analysis (MAF < 0.01). LD was calculated for each chromosome separately. The Ne has been declining since the time of domestication, having recently reached 123, 125, 185 and 92 for the HA (high altitude), LA (low altitude), HT (high temperature) and LT (low temperature) group, respectively. Our study revealed a low impact of inbreeding in the Carpatina population, and the Ne trend also indicated a steep decline in the last hundred years. These results will contribute to the genetic improvement of the Carpatina breed.
Assessment and Prediction of Future Climate Change in the Kaidu River Basin of Xinjiang under Shared Socioeconomic Pathway Scenarios
Authors: Cao Chenglin , Wang Yi , Fan Lei , Ding Junwei , Chen Wen
Published: February 2024

Xinjiang, located in the arid region of the northwest, is one of the areas most sensitive to global changes. The Kaidu River Basin, situated in the heart of Xinjiang, is one of the sources of China’s largest inland river—the Tarim River. The Kaidu River not only bears the responsibility for supplying water for industrial use and agricultural production and people’s daily life in the basin, but also plays a crucial role in ecological water supply to the Tarim River. Studying and analyzing the characteristics and trends of meteorological condition in the future under climate change can provide important references and a basis for a deeper understanding of changes in the hydrological process and water resources in the basin. Therefore, this paper selects seven precipitation bias correction methods and four temperature bias correction methods to adjust the precipitation and temperature output data of eight general circulation models of the Sixth Coupled Model Intercomparison Project (CMIP6) within the Kaidu River Basin. The applicability of different bias correction methods in the study area is evaluated, and based on the corrected future meteorological data and calculated extreme meteorological index, the trends of meteorological data (precipitation, temperature) in the future period (2025–2050) under four SSP scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0, SSP5-8.5) in the Kaidu River Basin are analyzed. The results show that: (1) Different types of bias correction methods have different correction focus and effects; their reflections on evaluation indicators are also different. (2) In the future period (2025–2050), the annual precipitation and average temperature in the Kaidu River Basin are higher than those in the historical period (1975–2014). The average annual temperature shows an upward trend in the future, but the annual precipitation shows a downward trend in the future except for the SSP2-4.5 scenario. (3) Compared with the historical period, the extreme precipitation in the future period under the SSP1-2.6, SSP2-4.5, and SSP5-8.5 scenarios is higher than that in the historical period, and the number of rainless days decreases. In the future, under the SSP1-2.6 and SSP5-8.5 scenarios, the probability of meteorological drought events occurring due to high temperatures in the basin may further increase, while under the SSP2-4.5 scenario, the situation of high temperatures and heavy rain in the basin may continue to increase.
Metrological Evaluation of the Building Influence on Air Temperature Measurements
Authors: Garcia Izquierdo Carmen , Coppa Graziano , Hernández Sonia , Merlone Andrea
Published: February 2024

This paper describes the metrological procedure carried out for the evaluation of the building influence on air temperature measurements. This evaluation aims to produce reliable conclusions, information, and data to contribute to the WMO siting classification schemes for air temperature measurements. For this purpose, a field experiment was designed, deployed, and carried out. As a result, one-year-lasting air temperature measurements were collected and analyzed. In this field experiment, a 200 m wide building is the unique artificial heat source and the unique object projecting shades over a flat surface (no discernible slope) in an open space bigger than 40,000 m2, covered with short grass. Eight calibrated thermometers, equipped with the same model of artificially ventilated radiation shields, were set up at a height of 1.5 m from the ground and at different distances from a 200 m wide building. This configuration provides the observation of the horizontal air temperature radially distributed from the building and, as a conclusion, it enables the quantification of the building influences on air temperature measurements at different distances from the building. This document describes the field experiment, the analysis procedure, the evolution of the building influence on air temperature measurements along the day, and the impact of other meteorological parameters on this building effect. Two different building effects are observed: the positive building effect, where the air temperature decreases with the distance to the building, and the negative building effect, where the air temperature increases with the distance to the building. It is also noticed that the building influence is higher on clear days and the daily maximum building influence values are directly linked with the corresponding maximum solar irradiance. The influence of wind on the building effect is also analyzed, reaching the conclusion that due to characteristic of local winds, in terms of low speed and direction, the wind impact could be considered as negligible. The maximum values of building influence on air temperature measurements, the associated uncertainty analysis, and the conclusions are presented in this paper. All these points have been addressed using metrological principles with the purpose of giving consistency and robustness to the evidence presented here.
Lower Limb Cross-Over Effects on Postural Control: Impact of Proximal and Distal Muscle Fatigue
Authors: Farivar Morteza , Harris Sara , Agana Anton , King Adam C.
Published: February 2024

The purpose of this study was to examine the cross-over influence of lower limb fatigue on postural control. Using two experiments, cross-over fatigue was investigated using a proximal (Experiment 1—single-leg squat) and distal (Experiment 2—calf raise) muscle group. In Experiment 1, 15 healthy young participants underwent a single-leg standing task on both the right and left leg, with variations of having eyes open or closed and on stable or unstable surfaces, performing each task for 30 s. For Experiment 2, 20 individuals performed single-leg balance testing for the right and left leg and stable and unstable surfaces. Center-of-pressure data were collected during the balance tasks and were analyzed with linear (standard deviation) and nonlinear (detrended fluctuation analysis) metrics. The results lacked significant differences (p > 0.05) for cross-over fatigue effects on the non-exercised limb, which exhibited similar levels of postural sway between the pre- and post-fatigue balance tests. These tasks may have lacked an appropriate level of duration or intensity to cause a significant effect of central fatigue on the nervous system. The findings underscore the need to better understand how a specific fatiguing task during unilateral rehabilitation may alter postural control.
Social Brain Perspectives on the Social and Evolutionary Neuroscience of Human Language
Authors: Oesch Nathan
Published: February 2024

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. Nonetheless, an emerging view suggests an alternative perspective. Drawing on the theoretical underpinnings of the social brain hypothesis (thesis of the evolution of brain size and intelligence), the social complexity hypothesis (thesis of the evolution of communication), and empirical research from comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language, it is argued that social cognition and language are two significantly interconnected capacities of the human species. Here, evidence in support of this view reviews (1) recent developmental studies on language learning in infants and young children, pointing to the important crucial benefits associated with social stimulation for youngsters, including the quality and quantity of incoming linguistic information, dyadic infant/child-to-parent non-verbal and verbal interactions, and other important social cues integral for facilitating language learning and social bonding; (2) studies of the adult human brain, suggesting a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting that the function of these neural areas may connect social cognition with language and social bonding; (3) developmental deficits in language and social cognition, including autism spectrum disorder (ASD), illustrating a unique developmental profile, further linking language, social cognition, and social bonding; and (4) neural biomarkers that may help to identify early developmental disorders of language and social cognition. In effect, the social brain and social complexity hypotheses may jointly help to describe how neurotypical children and adults acquire language, why autistic children and adults exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other organisms with significant computational capacities cannot learn language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain.
Particle Boards from Forest Residues and Bio-Based Adhesive
Authors: Krumins Janis Andris , Vamza Ilze , Dzalbs Arnis , Blumberga Dagnija
Published: February 2024

Wood chipboard, common in interior spaces for applications ranging from furniture to decorative panelling, often falls short due to the presence of toxic adhesives, posing risks to both human health and the environment. This research delves into the potential transformation of wood chipboard into a 100% bio-based product. Previous research has shown the possibility of the partial replacement of petrochemical-based adhesives with bio-based adhesives. Hence, previous results do not reach the policy ambitions of the Green Deal of making the Green Transition to a bio-based economy. For chipboard production, logging residues from Latvian State Forests were systematically gathered within two months post-logging, comprising primarily Picea abies and Pinus sylvestris biomass, including branches, needles, bark, and various particles. A custom chipper and Vibrotehnik PM-120 hammer mill were employed for particle size separation into three fractions via sieving: <2.8 mm, 2.8–8 mm, and 8.0–10.0 mm, and combined with binders and hot-pressed into board samples. As a result, particle boards containing 100% bio-based carbon were achieved, demonstrating the possibility of excluding petroleum adhesives from chipboard production, paving the way for new research exploring bio-based binders and conifer bark.
Comprehensive Examination of Cholangiocarcinoma Patients Treated with Novel Targeted Therapies after Extended Molecular Profiling on Liquid Biopsies
Authors: Mahmood Umair , Muhamad Faizul Elisya , Howlett Sarah , Amin Zahir , Hochhauser Daniel , Shiu Kai-Keen , Bridgewater John , Khan Khurum
Published: February 2024

Background: Cholangiocarcinoma (CCA) is associated with poor outcomes and limited treatment options, leading to increased use of targeted therapies for its management. Here, we performed one of the largest single-centre reviews evaluating outcomes following personalised targeted agents in CCA patients. Methods: All consecutive CCA patients receiving systemic therapy between January 2010 and April 2023 at UCLH were included. The primary objective of this study was to evaluate treatment response, survival outcomes and predictors of clinical benefit in CCA patients treated with molecularly guided therapies. Patient demographic factors, disease characteristics and survival outcomes were evaluated using the Kaplan–Meier method and Cox proportional-hazards models. Results: Of the 227 consecutive CCA patients, 162 (71%) had molecular profiling, of whom 56 (35%) were eligible and 55 received molecular-targeted treatment. CCA histological classifications comprised intrahepatic (N = 32), extrahepatic (N = 11), hilar (N = 4) and unknown (N = 9) subtypes. Most patients received targeted agents based on genomic profiling in a second treatment line setting (N = 34). Frequently observed genomic alterations occurred in the FGFR2 (N = 21), IDH1 (N = 7) and BRCA2 (N = 6) genes. Median progression-free survival (PFS) following first-, second- and third-line systemic therapy and overall survival (OS) were 8.44 (95% CI, 7.49–12.78), 5.65 (95% CI, 3.71–7.13), 5.55 (2.79–12.58) and 29.01 (24.21–42.91) months, respectively. CCA subtype and FGFR/BRCA molecular aberration status were not associated with PFS or OS. However, a prior CCA-related surgical history was predictive of OS (p = 0.02). Stratification by best overall response to second-line targeted agents demonstrated an association with PFS (p = 0.002) and OS (p = 0.02). Duration of treatment with second-line targeted therapy was associated with OS (p < 0.001). Conclusions: Patients receiving targeted therapeutics achieved promising outcomes, especially those attaining a favourable treatment response and those receiving targeted agents for longer periods. Liquid biopsies can reliably provide information on extended molecular profiling to aid patient selection for personalised therapies.
Systematic Review of Preoperative Prognostic Biomarkers in Perihilar Cholangiocarcinoma
Authors: Pawaskar Rishaan , Huang Kevin Zhang , Pham Helen , Nagrial Adnan , Wong Mark , O’Neill Siobhan , Pleass Henry , Yuen Lawrence , Lam Vincent W. T. , Richardson Arthur , Pang Tony , Nahm Christopher B.
Published: February 2024

Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery for pCCA are not well-established currently. This systematic review aimed to identify and summarise preoperative biomarkers associated with survival in pCCA, thereby potentially improving treatment decision-making. The Embase, Medline, and Cochrane databases were searched, and a systematic review was performed using the PRISMA guidelines. English-language studies examining the association between serum and/or tissue-derived biomarkers in pCCA and overall and/or disease-free survival were included. Our systematic review identified 64 biomarkers across 48 relevant studies. Raised serum CA19-9, bilirubin, CEA, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and tumour MMP9, and low serum albumin were most associated with poorer survival; however, the cutoff values used widely varied. Several promising molecular markers with prognostic significance were also identified, including tumour HMGA2, MUC5AC/6, IDH1, PIWIL2, and DNA index. In conclusion, several biomarkers have been identified in serum and tumour specimens that prognosticate overall and disease-free survival after pCCA resection. These, however, require external validation in large cohort studies and/or in preoperatively obtained specimens, especially tissue biopsy, to recommend their use.
Mechanisms of Resistance and Therapeutic Perspectives in Immunotherapy for Advanced Head and Neck Cancers
Authors: Meci Andrew , Goyal Neerav , Slonimsky Guy
Published: February 2024

Immunotherapy is emerging as an effective treatment for advanced head and neck cancers and interest in this treatment modality has led to rapid expansion of this research. Pembrolizumab and nivolumab, monoclonal antibodies directed against the programmed cell death-1 (PD-1) receptor, are US Food and Drug Administration (FDA)- and European Medical Agency (EMA)-approved immunotherapies for head and neck squamous cell carcinoma (HNSCC). Resistance to immunotherapy is common, with about 60% of patients with recurrent or metastatic HNSCC not responding to immunotherapy and only 20–30% of patients without disease progression in the long term. Overcoming resistance to immunotherapy is therefore essential for augmenting the effectiveness of immunotherapy in HNSCC. This review details the innate and adaptive mechanisms by which head and neck cancers can become resistant to immunotherapeutic agents, biomarkers that can be used for immunotherapy patient selection, as well as other factors of the tumor microenvironment correlated with therapeutic response and prognosis. Numerous combinations and novel immunotherapies are currently being trialed, based on better understood immune evasion mechanisms. These potential treatments hold the promise of overcoming resistance to immunotherapy in head and neck cancers.
The Value of Local Therapies in Advanced Adrenocortical Carcinoma
Authors: Kimpel Otilia , Altieri Barbara , Laganà Marta , Vogl Thomas J. , Adwan Hamzah , Dusek Tina , Basile Vittoria , Pittaway James , Dischinger Ulrich , Quinkler Marcus , Kroiss Matthias , Puglisi Soraya , Cosentini Deborah , Kickuth Ralph , Kastelan Darko , Fassnacht Martin
Published: February 2024

International guidelines recommend local therapies (LTs) such as local thermal ablation (LTA; radiofrequency, microwave, cryoablation), transarterial (chemo)embolisation (TA(C)E), and transarterial radioembolisation (TARE) as therapeutic options for advanced adrenocortical carcinoma (ACC). However, the evidence for these recommendations is scarce. We retrospectively analysed patients receiving LTs for advanced ACC. Time to progression of the treated lesion (tTTP) was the primary endpoint. The secondary endpoints were best objective response, overall progression-free survival, overall survival, adverse events, and the establishment of predictive factors by multivariate Cox analyses. A total of 132 tumoural lesions in 66 patients were treated with LTA (n = 84), TA(C)E (n = 40), and TARE (n = 8). Complete response was achieved in 27 lesions (20.5%; all of them achieved by LTA), partial response in 27 (20.5%), and stable disease in 38 (28.8%). For the LTA group, the median tTTP was not reached, whereas it was reached 8.3 months after TA(C)E and 8.2 months after TARE (p < 0.001). The median time interval from primary diagnosis to LT was >47 months. Fewer than four prior therapies and mitotane plasma levels of >14 mg/L positively influenced the tTTP. In summary, this is one of the largest studies on LTs in advanced ACC, and it demonstrates a very high local disease control rate. Thus, it clearly supports the guideline recommendations for LTs in these patients.
CXCL13 Positive Cells Localization Predict Response to Anti-PD-1/PD-L1 in Pulmonary Non-Small Cell Carcinoma
Authors: Vahidian Fatemeh , Lamaze Fabien C. , Bouffard Cédrik , Coulombe François , Gagné Andréanne , Blais Florence , Tonneau Marion , Orain Michèle , Routy Bertrand , Manem Venkata S. K. , Joubert Philippe
Published: February 2024

Background: Immune checkpoint inhibitors (ICIs) have revolutionized non-small cell lung cancers (NSCLCs) treatment, but only 20–30% of patients benefit from these treatments. Currently, PD-L1 expression in tumor cells is the only clinically approved predictor of ICI response in lung cancer, but concerns arise due to its low negative and positive predictive value. Recent studies suggest that CXCL13+ T cells in the tumor microenvironment (TME) may be a good predictor of response. We aimed to assess if CXCL13+ cell localization within the TME can predict ICI response in advanced NSCLC patients. Methods: This retrospective study included 65 advanced NSCLC patients treated with Nivolumab/Pembrolizumab at IUCPQ or CHUM and for whom a pretreatment surgical specimen was available. Good responders were defined as having a complete radiologic response at 1 year, and bad responders were defined as showing cancer progression at 1 year. IHC staining for CXCL13 was carried out on a representative slide from a resection specimen, and CXCL13+ cell density was evaluated in tumor (T), invasive margin (IM), non-tumor (NT), and tertiary lymphoid structure (TLS) compartments. Cox models were used to analyze progression-free survival (PFS) and overall survival (OS) probability, while the Mann–Whitney test was used to compare CXCL13+ cell density between responders and non-responders. Results: We showed that CXCL13+ cell density localization within the TME is associated with ICI efficacy. An increased density of CXCL13+ cells across all compartments was associated with a poorer prognostic (OS; HR = 1.22; 95%CI = 1.04–1.42; p = 0.01, PFS; HR = 1.16; p = 0.02), or a better prognostic when colocalized within TLSs (PFS; HR = 0.84, p = 0.03). Conclusion: Our results support the role of CXCL13+ cells in advanced NSCLC patients, with favorable prognosis when localized within TLSs and unfavorable prognosis when present elsewhere. The concomitant proximity of CXCL13+ and CD20+ cells within TLSs may favor antigen presentation to T cells, thus enhancing the effect of PD-1/PD-L1 axis inhibition. Further validation is warranted to confirm the potential relevance of this biomarker in a clinical setting.
Role of Epiregulin in Lung Tumorigenesis and Therapeutic Resistance
Authors: Sunaga Noriaki , Miura Yosuke , Masuda Tomomi , Sakurai Reiko
Published: February 2024

Epidermal growth factor (EGF) signaling regulates multiple cellular processes and plays an essential role in tumorigenesis. Epiregulin (EREG), a member of the EGF family, binds to the epidermal growth factor receptor (EGFR) and ErbB4, and it stimulates EGFR-related downstream pathways. Increasing evidence indicates that both the aberrant expression and oncogenic function of EREG play pivotal roles in tumor development in many human cancers, including non-small cell lung cancer (NSCLC). EREG overexpression is induced by activating mutations in the EGFR, KRAS, and BRAF and contributes to the aggressive phenotypes of NSCLC with oncogenic drivers. Recent studies have elucidated the roles of EREG in a tumor microenvironment, including the epithelial–mesenchymal transition, angiogenesis, immune evasion, and resistance to anticancer therapy. In this review, we summarized the current understanding of EREG as an oncogene and discussed its oncogenic role in lung tumorigenesis and therapeutic resistance.
A Smooth Muscle Cell-Based Ferroptosis Model to Evaluate Iron-Chelating Molecules for Cardiovascular Disease Treatment
Authors: El Hajj Sarah , Canabady-Rochelle Laetitia , Fries-Raeth Isabelle , Gaucher Caroline
Published: February 2024

Dysregulation of iron homeostasis causes iron-mediated cell death, recently described as ferroptosis. Ferroptosis is reported in many chronic diseases, such as hepatic cancer, renal, and cardiovascular diseases (heart failure, atherosclerosis). However, there is a notable scarcity of research studies in the existing literature that explore treatments capable of preventing ferroptosis. Additionally, as far as the author is aware, there is currently no established model for studying ferroptosis within cardiovascular cells, which would be essential for assessing metal-chelating molecules with the potential ability to inhibit ferroptosis and their application in the treatment of cardiovascular diseases. In this study, a smooth muscle cell-based ferroptosis model is developed upon the inhibition of the system Xc− transporter by erastin associated or not with Fe(III) overload, and its rescue upon the introduction of well-known iron chelators, deferoxamine and deferiprone. We showed that erastin alone decreased the intracellular concentration of glutathione (GSH) without affecting peroxidized lipid concentrations. Erastin with ferric citrate was able to decrease intracellular GSH and induce lipid peroxidation after overnight incubation. Only deferiprone was able to rescue the cells from ferroptosis by decreasing lipid peroxidation via iron ion chelation in a 3:1 molar ratio.
Lateral Track Buckling in Sweden: Insights from Operators and Infrastructure Managers
Authors: Mirzanamadi Raheb , Nyberg Erik , Torstensson Peter , Andersson-Sköld Yvonne
Published: February 2024

Rail transport is expected to become a key component in the development of a long-term sustainable transport system. The planning, construction, operation, and maintenance of railway infrastructure are crucial in this effort. Hence, it is essential to ascertain that the railway infrastructure withstands and is adapted to extreme weather conditions and climate change. This study focuses on evaluating climate adaptation measures for lateral track buckling in Sweden. Through a literature review and interview with an expert at Swedish Transport Administration, it is highlighted that the maintenance status of railway infrastructure plays a significant role in the occurrence of lateral track buckling. According to the expert, inadequate track maintenance is the primary cause of lateral track buckling rather than weather variables like air temperature. The interview also clarifies that the chain of events related to the handling of track buckling is mainly initiated by the observation of a discrete lateral irregularity by a train driver, whereupon the train dispatcher at the traffic management center stops traffic until the location in the track has been inspected by a track entrepreneur. During the inspection, up to half of the observed cases of track buckling turn out to be false.
Artificial Neural Network Models for Determining the Load-Bearing Capacity of Eccentrically Compressed Short Concrete-Filled Steel Tubular Columns
Authors: Chepurnenko Anton , Turina Vasilina , Akopyan Vladimir
Published: February 2024

Artificial neural networks (ANN) have a great promise in predicting the load-bearing capacity of building structures. The purpose of this work was to develop ANN models to determine the ultimate load of eccentrically compressed concrete-filled steel tubular (CFST) columns of circular cross-sections, which operated on the widest possible range of input parameters. Short columns were considered for which the amount of deflection does not affect the bending moment. A feedforward network was selected as the neural network type. The input parameters of the neural networks were the outer diameter of the columns, the thickness of the pipe wall, the yield strength of steel, the compressive strength of concrete and the relative eccentricity. Artificial neural networks were trained on synthetic data generated based on a theoretical model of the limit equilibrium of CFST columns. Two ANN models were created. When training the first model, the ultimate loads were determined at a given eccentricity of the axial force without taking into account additional random eccentricity. When training the second model, additional random eccentricity was taken into account. The total volume of the training dataset was 179,025 samples. Such a large training dataset size has never been used before. The training dataset covers a wide range of changes in the characteristics of the pipe metal and concrete of the core, pipe diameters and wall thicknesses, as well as eccentricities of the axial force. The trained models are characterized by high mean square error (MSE) scores. The correlation coefficients between the predicted and target values are very close to 1. The ANN models were tested on experimental data for 81 eccentrically compressed samples presented in five different works and 265 centrally compressed samples presented in twenty-six papers.