bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Image Augmentation Techniques on Non-Protective Personal Equipment Detection Using YOLOv8
Authors: Park Sungman , Kim Jaejun , Wang Seunghyeon , Kim Juhyung
Published: February 2025

Non-Protective Personal Equipment (PPE) detection is crucial on construction sites. Although deep learning models are adept at identifying such information from on-site cameras, their success relies on large, diverse, and high-quality datasets. Image augmentation offers an alternative for artificially broadening dataset diversity. However, its impact on non-PPE detection in construction environments has not been adequately examined. This study introduces a methodology applying eight distinct augmentation techniques—brightness, contrast, perspective, rotation, scale, shearing, translation, and a combined strategy incorporating all methods. Model performance was assessed by comparing accuracy across different classes and architectures, both with and without augmentation. While most of these augmentations improved accuracy, their effectiveness was found to be task-dependent. Moreover, the most beneficial augmentation varied by non-PPE class and architecture, suggesting that augmentation strategies should be tailored to the unique features of each class and model. Although the primary focus here is on non-PPE, the evaluated techniques could also extend to related tasks on construction sites, such as detecting heavy equipment or identifying hazardous worker behavior.
A Preliminary Study on the Potential of the New Red-Fleshed ‘JB’ Clone Apple for Cider Production
Authors: Lis Zuzanna , Lipińska Edyta , Olewnicki Dawid , Pobiega Katarzyna , Rybak Katarzyna , Przybyłko Sebastian , Latocha Piotr
Published: February 2025

Apples are one of the most widely consumed fruits in the world, resulting in the continuous creation of new cultivars with different properties, both in terms of breeding as well as extended shelf lives and increased bioactive substance contents. This study aimed to determine the potential of a new red-fleshed apple ‘JB’ clone developed at the Warsaw University of Life Sciences to produce high-sensory-quality cider. Fermentation was carried out using the Saccharomyces cerevisiae UCLM S325 yeast strain, commonly used for quality white wines (Fermentis, Lesaffre Polska SA, Warsaw, Poland), at 15 °C for 21 days. The must and the cider were subjected to physicochemical analysis to determine their color, sugar content, total acidity, and polyphenol levels. Additionally, volatile acidity and alcohol content were measured in the cider, followed by an organoleptic evaluation. A red color characterized both the must and the cider, which had total acidities of 8.78 ± 0.05 and 6.61 ± 0.03 g malic acid/L, respectively, as well as polyphenol contents of 307.28 ± 1.29 and 240 ± 7.00 mg chlorogenic acid/L, respectively. Trained panelists evaluated the cider obtained from fermentation. The study’s results indicate that the new ‘JB’ apple clone has strong potential for producing juice and cider with a unique red color and high sensory attributes.
Proteolytic Enzyme Activities of Bromelain, Ficin, and Papain from Fruit By-Products and Potential Applications in Sustainable and Functional Cosmetics for Skincare
Authors: Venetikidou Maria , Lykartsi Eleni , Adamantidi Theodora , Prokopiou Vasileios , Ofrydopoulou Anna , Letsiou Sophia , Tsoupras Alexandros
Published: February 2025

Enzyme peels are an emerging and effective cosmetic technique for controlled skin exfoliation. Naturally occurring proteolytic enzymes such as bromelain, ficin, and papain have gained increasing attention as promising cosmetic and cosmeceutical ingredients due to their exfoliating and skin resurfacing properties. These enzymes catalyze the hydrolysis of keratin protein bonds, facilitate the removal of dead skin cells from the outermost layer of the epidermis, and promote cell turnover. The role of these enzymes in skin care is particularly noteworthy due to their gentle, yet effective, exfoliating action, their ability to improve the penetration of active ingredients, and their contribution to skin renewal and regeneration. While proteolytic enzymes are traditionally extracted from fruit pulp, recent research highlights fruit by-products such as pineapple peels, fig latex, and papaya peels, as sustainable and environmentally friendly sources. These by-products, which are often discarded in the food and agricultural industries, are rich in enzymatic activity and bioactive compounds, making them valuable alternatives for cosmetic applications. Their use is in line with the principles of the circular economy. They contribute to waste prevention while improving the availability of effective enzymatic exfoliants. This review provides a comparative analysis of bromelain, ficin, and papain, highlighting their different biochemical properties, their efficacy in cosmetic formulations, and their common mechanisms of action. In addition, the extraction processes from fruit by-products, their incorporation into skin care formulations, and their potential for sustainable cosmetic applications are examined. The results underline the growing importance of proteolytic enzymes, not only as exfoliating agents, but also as multifunctional bioactive components in next-generation cosmetic products.
Experimental and Analytical Study on Multiscale Cushioning and Energy Absorption of Aluminum Foam at Different Strain Rates
Authors: Qiu Qianzhi , Wang Hongtao , Ma Wentian
Published: February 2025

In this research, the compressive behavior of closed-cell aluminum foam was examined across a broad strain rate spectrum, spanning from 0.005 s⁻1 to 2000 s⁻1. Utilizing an enhanced Hopkinson bar apparatus, the deformation and fracture mechanisms of the foam were captured through high-speed videography. Additionally, a microscale finite element model was developed to elucidate the dynamic deformation characteristics of aluminum foam at multiple scales. The findings indicate that the material’s response is highly strain rate-dependent, with both stress levels and energy absorption efficiency escalating as the strain rate rises. Moreover, the damage progression in aluminum foam manifests as a progressive collapse pattern.
Medical 3D Printing Using Material Jetting: Technology Overview, Medical Applications, and Challenges
Authors: Chokshi Shivum , Gangatirkar Raghav , Kandi Anish , DeLeonibus Maria , Kamel Mohamed , Chadalavada Seetharam , Gupta Rajul , Munigala Harshitha , Tappa Karthik , Kondor Shayne , Burch Michael B. , Ravi Prashanth
Published: February 2025

Material Jetting (MJT) 3D printing (3DP) is a specific technology that deposits photocurable droplets of material and colored inks to fabricate objects layer-by-layer. The high resolution and full color capability render MJT 3DP an ideal technology for 3DP in medicine as evidenced by the 3DP literature. The technology has been adopted globally across the Americas, Europe, Asia, and Australia. While MJT 3D printers can be expensive, their ability to fabricate highly accurate and multi-color parts provides a lucrative opportunity in the creation of advanced prototypes and medical models. The literature on MJT 3DP has expanded greatly as of late, in part aided by the lowering costs of the technology, and this report is the first review to document the applications of MJT in medicine. Additionally, this report portrays the technological information behind MJT 3DP, cases involving fabricated MJT 3DP models from the University of Cincinnati 3DP lab, as well as the challenges of MJT in a clinical setting, including cost, expertise in managing the machines, and scalability issues. It is expected that MJT 3DP, as imaging and segmentation technologies undergo future improvement, will be best poised with representing the voxel-level-variations captured by radiologic-image-sets due to its capacity for voxel-level-control.
Evolution of the PE_PGRS Proteins of Mycobacteria: Are All Equal or Are Some More Equal than Others?
Authors: Chen Bei , Bajramović Belmin , Vriesendorp Bastienne , Spaink Herman Pieter
Published: February 2025

PE_PGRS domain proteins represent a family of proteins found in pathogenic and non-pathogenic mycobacteria such as M. smegmatis. This conserved family is characterized by two distinct regions denoted as the variable PGRS domain defined by glycine-rich repeats, and a PE domain consisting of two antiparallel alpha-helices. There are many indications that PE_PGRS proteins are involved in immunopathogenesis and virulence by evading or triggering the host immune response. However, there is not yet any information on their degree of specialization or redundancy. Computational analysis and structural annotation using AlphaFold3 combined with other tools reveals an exceptionally powerful and unprecedented ability to undergo phase separation by the PGRS domain. This suggests that PGRS’s glycine-rich, multivalent, low-complexity composition supports phase separation while adopting a structured conformation, contrary to the disordered nature typical of such domains. While previously never reported, the hypothesized role of PGRS in virulence indicates a novel window into the seemingly ubiquitous role of phase separation in cellular compartmentalization and molecular dynamics. This review aims to summarize the current understanding of the PE_PGRS family and its various biological roles in the context of bioinformatic analyses of some interesting representatives of M. marinum that are under control by host sterols. Based on the structural bioinformatics analysis, we discuss future approaches to uncover the mechanistic role of this intriguing family of mycobacterial proteins in both pathogenic and non-pathogenic mycobacteria.
Soil Moisture Is the Key Factor Facilitating Giant Ragweed Invasions in Grasslands of the Yili Vally, China
Authors: Chen Xinyi , Song Zhanli , Chen Baoxiong , Yu Wanli , Dong Hegan
Published: February 2025

Giant ragweed (GR; Ambrosia trifida L.), an invasive alien species, causes significant harm to grassland ecosystems and farmlands in some areas but is challenging to control. GR has invaded the hilly grasslands of Yili Valley, China, since 2013, and preliminary observations have shown that GR populations on the lower slopes of hills are more successful than those on the middle or upper slopes. To clarify the factors determining GR’s invasion success, we compared GR population distributions among slope positions and the relationship between non-biotic factors and the invasion of GR. Of the soil physicochemical properties, only soil moisture differed significantly among slope positions, with the wettest soils found on the lower slopes. GR biomass increased with the soil water content, irrespective of native plant diversity. In our experiment, when the annual average soil volume moisture content exceeded 20.3% and 25.3%, GR could reduce the biomass of native herbs by more than 50% and 80%. Therefore, water is the determining factor of a successful GR invasion in the grasslands of the Yili Valley. On a global scale, it was discovered for the first time that GR can invade temperate grasslands, but also has risks of invading other grasslands that share similar conditions. So, GR invasions of temperate grasslands must be closely monitored, particularly in low-lying areas or those with increasing precipitation.
IL-1 Receptor Antagonist Anakinra Inhibits the Effect of IL-1β- Mediated Osteoclast Formation by Periodontal Ligament Fibroblasts
Authors: Steemers Elizabeth , Talbi Wael M. I. , Hogervorst Jolanda M. A. , Schoenmaker Ton , de Vries Teun J.
Published: February 2025

Rheumatoid arthritis and periodontitis are comorbidities that share mutual pathways. IL-1β is a pro-inflammatory cytokine that plays a crucial role in both diseases. One of the treatment options for rheumatoid arthritis is the use of an IL-1 receptor antagonist (IL-1RA) such as anakinra. Anakinra tempers the disease by decreasing bone resorption and it could possibly stimulate bone formation. Here, we investigate the effect of anakinra in a periodontal disease setting on osteoclastogenesis by co-culturing periodontal ligament fibroblasts (PDLFs) and peripheral blood mononuclear cells (PBMCs) that contain monocytes, a source of osteoclast precursors, as well as by culturing PBMCs alone. The effect of anakinra on PDLF-mediated osteogenesis was studied under mineralization conditions. To mimic a chronic infection such as that prevalent in periodontitis, 10 ng/mL of IL-1β was added either alone or with 10 µg/mL of anakinra. Osteoclastogenesis experiments were performed using co-cultures of PDLF and PBMCs and PBMCs only. Osteoclastogenesis was determined through the formation of multinucleated cells in co-cultures of PDLF and PBMCs, as well as PBMCs alone, at day 21, and gene expression through qPCR at day 14. Osteogenesis was determined by measuring alkaline phosphatase activity (ALP) per cell at day 14. Anakinra is effective in downregulating IL-1β mediated leukocyte clustering and osteoclastogenesis in the co-cultures of both PDLF and PMBCs and PBMCs alone. Gene expression analysis shows that IL-1β increases the expression of the osteoclastogenic marker RANKL and its own expression. This higher expression of IL-1β at the RNA level is reduced by anakinra. Moreover, IL-1β downregulates OPG expression, which is upregulated by anakinra. No effects of anakinra on osteogenesis were seen. Clinically, these findings suggest that anakinra could have a beneficial systemic effect on periodontal breakdown in rheumatoid arthritis patients taking anakinra.
Hypertrophic Cardiomyopathy Through the Lens of Mitochondria
Authors: Kirichenko Tatiana V. , Zhivodernikov Ivan V. , Kozlova Maria A. , Markin Alexander M. , Sinyov Vasily V. , Markina Yuliya V.
Published: February 2025

The mechanisms of pathogenesis of hypertrophic cardiomyopathy are associated with mutations in the sarcomere genes of cardiomyocytes and metabolic disorders of the cell, including mitochondrial dysfunction. Mitochondria are characterized by the presence of their own DNA and enzyme complexes involved in oxidative reactions, which cause damage to mitochondrial protein structures and membranes by reactive oxygen species. Mitochondrial dysfunctions can also be associated with mutations in the genes encoding mitochondrial proteins and lead to a violation of protective functions such as mitophagy, mitochondrial fusion, and fission. Mutations in myofibril proteins can negatively affect mitochondria through increased oxidative stress due to an increased need for ATP. Mitochondrial dysfunction is associated with impaired ATP synthesis and cardiac contractility, leading to clinical manifestations of hypertrophic cardiomyopathy. The current review was designed to characterize the role of mitochondria in the pathogenesis of hypertrophic cardiomyopathy based on published data; the search for publications was based on the analysis of articles including the keywords “hypertrophic cardiomyopathy, mitochondria, dysfunction” in the PubMed and Scopus databases up to January 2025.
CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca2+ Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer Mice
Authors: Yuan Ziyan , Liu Huanhuan , Diao Zhijun , Yuan Wei , Wu Yuwei , Xue Simeng , Gao Xinyan , Qiao Haifa
Published: February 2025

Background: Referred pain frequently co-exists with visceral pain. However, the exact mechanism governing referred somatic hyperalgesia remains elusive. Methods: By injecting 20% acetic acid into the stomach, we established a mouse model of gastric ulcer (GU). Hematoxylin and eosin (H&E) staining was used as the evaluation criterion for the gastric ulcer model. Evan’s blue (EB) and von Frey tests detected the somatic sensitized area. The DRG neurons distributed among the spinal segments of the sensitized area were prepared for biochemical and electrophysiological experiments. The CCR2 antagonist was intraperitoneally (i.p.) injected into GU mice to test the effect of blocking CCR2 on somatic neurogenic inflammation. Results: GU not only instigated neurogenic plasma extravasation and referred somatic allodynia in the upper back regions spanning the T9 to T11 segments but also augmented the co-expression of T-type Ca2+ channels and CCR2 and led to the gating properties of T-type Ca2+ channel alteration in T9–T11 small-diameter DRG neurons. Moreover, the administration of the CCR2 antagonist inhibited the T-type Ca2+ channel activation, consequently mitigating neurogenic inflammation and referred somatic hyperalgesia. The application of the CCR2 agonist to normal T9–T11 small-diameter DRG neurons simulates the changes in the gating properties of T-type Ca2+ channel that occur in the GU group. Conclusions: Therefore, these findings indicate that CCR2 may function as a critical regulator in the generation of neurogenic inflammation and mechanical allodynia by modulating the gating properties of the T-type Ca2+ channels.
Tracking Changes in Corticospinal Excitability During Visuomotor Paired Associative Stimulation to Predict Motor Resonance Rewriting
Authors: Guidali Giacomo , Bolognini Nadia
Published: February 2025

Background/Objectives. Mirror properties of the action observation network (AON) can be modulated through Hebbian-like associative plasticity using paired associative stimulation (PAS). We recently introduced a visuomotor protocol (mirror–PAS, m-PAS) that pairs transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) with visual stimuli of ipsilateral (to TMS) movements, leading to atypical corticospinal excitability (CSE) facilitation (i.e., motor resonance) during PAS-conditioned action observation. While m-PAS aftereffects are robust, little is known about markers of associative plasticity during its administration and their predictive value for subsequent motor resonance rewriting. The present study aims to fill this gap by investigating CSE modulations during m-PAS and their relationship with the protocol’s aftereffects. Methods. We analyzed CSE dynamics in 81 healthy participants undergoing the m-PAS before and after passively observing left- or right-hand index finger movements. Here, typical and PAS-conditioned motor resonance was assessed with TMS over the right M1. We examined CSE changes during the m-PAS and used linear regression models to explore their relationship with motor resonance modulations. Results. m-PAS transiently reshaped both typical and PAS-induced motor resonance. Importantly, we found a gradual increase in CSE during m-PAS, which predicted the loss of typical motor resonance but not the emergence of atypical responses after the protocol’s administration. Conclusions. Our results suggest that the motor resonance reshaping induced by the m-PAS is not entirely predictable by CSE online modulations. Likely, this rewriting is the product of a large-scale reorganization of the AON rather than a phenomenon restricted to the PAS-stimulated motor cortex. This study underlines that monitoring CSE during non-invasive brain stimulation protocols could provide valuable insight into some but not all plastic outcomes.
How Anxiety State Influences Speech Parameters: A Network Analysis Study from a Real Stressed Scenario
Authors: Wang Qingyi , Xu Feifei , Wang Xianyang , Wu Shengjun , Ren Lei , Liu Xufeng
Published: February 2025

Background/Objectives: Voice analysis has shown promise in anxiety assessment, yet traditional approaches examining isolated acoustic features yield inconsistent results. This study aimed to explore the relationship between anxiety states and vocal parameters from a network perspective in ecologically valid settings. Methods: A cross-sectional study was conducted with 316 undergraduate students (191 males, 125 females; mean age 20.3 ± 0.85 years) who completed a standardized picture description task while their speech was recorded. Participants were categorized into low-anxiety (n = 119) and high-anxiety (n=197) groups based on self-reported anxiety ratings. Five acoustic parameters—jitter, fundamental frequency (F0), formant frequencies (F1/F2), intensity, and speech rate—were analyzed using network analysis. Results: Network analysis revealed a robust negative relationship between jitter and state anxiety, with jitter as the sole speech parameter consistently linked to state anxiety in the total group. Additionally, higher anxiety levels were associated with a coupling between intensity and F1/F2, whereas the low-anxiety network displayed a sparser organization without intensity and F1/F2 connection. Conclusions: Anxiety could be recognized by speech parameter networks in ecological settings. The distinct pattern with the negative jitter-anxiety relationship in the total network and the connection between intensity and F1/2 in high-anxiety states suggest potential speech markers for anxiety assessment. These findings suggest that state anxiety may directly influence jitter and fundamentally restructure the relationships among speech features, highlighting the importance of examining jitter and speech parameter interactions rather than isolated values in speech detection of anxiety.
Emotional Valence, Interdependence, and Job Autonomy as Predictors of Creativity Through Perspective-Taking: An Integrative Model
Authors: Han Kyueun , Kim You Jin
Published: February 2025

This study examines the underexplored intersection of emotional valence and perspective-taking in workplace creativity, and how job characteristics like interdependence and autonomy moderate these relationships. Participants (N = 307; 41% women) recruited through Amazon’s Mechanical Turk platform and employed across various U.S. companies completed an experimental study where they were randomly assigned to recall either positive or negative workplace relationships. Through this manipulation, the participants identified specific colleagues with whom they had direct working experience and reported their emotional valence toward these relationships before completing questionnaires on perspective-taking, creativity, autonomy, and interdependence. Integrating emotional valence and perspective-taking into a moderated mediation model yielded insights into how these variables shape creativity within organizations. The findings demonstrate that positive emotional states significantly enhance creativity through perspective-taking, especially in environments that promote collaboration and independent decision-making. This research broadens workplace dynamics by illuminating the roles of emotional and contextual factors in fostering creativity. It provides practical implications for organizations, recommending positive emotional climates and roles that balance interdependence with autonomy to maximize employee creativity. This study’s comprehensive approach provides a holistic understanding of conditions that foster creativity in organizational environments, expanding on existing frameworks.
Effects of Vertical Irregularity on Transverse Reinforcement Spacing in Reinforced Concrete Columns to Avoid Shear Failure Subjected to Seismic Behavior
Authors: Chang Hak-Jong , Cho Jae-Hyun , Kim Mun-Gi , Kim Jun-Hee
Published: February 2025

As a result of the 2017 Pohang earthquake, numerous piloti-type structures incurred damage, and the cause was attributed to the wide spacing of transverse reinforcement. Improper spacing of transverse reinforcement can lead to brittle failure of columns, potentially causing the collapse of buildings. This study aimed to analyze the failure mode of columns where load and displacement are concentrated due to vertical irregularity, and to quantify the spacing of shear reinforcement according to the degree of vertical irregularity to prevent shear failure of the column. First, a vertically irregular frame with vertical irregularity and an RC moment frame with the same upper and lower structural systems was modeled, and the failure mode of the column was analyzed. In this paper, the failure modes were classified into shear failure, flexure–shear failure, and flexural failure based on the shear capacity ratio. The analysis results showed that in the case of vertical irregularity, the shear demand of the column was evaluated as high due to the high flexural stiffness of the horizontal members, and the failure mode of the column was classified as shear failure. The impact of the spacing of shear reinforcement on the shear strength of the structure was also examined. Next, an analysis was performed according to the degree of vertical irregularity by adjusting the thickness of the first-floor shear wall, and as a result, the proportion of the entire columns classified as shear failure increased as the vertical irregularity increased. It was confirmed that the minimum spacing of shear reinforcement of 150 mm specified in Korean standards becomes inadequate when the degree of vertical irregularity exceeds 2.6. At a vertical irregularity of 8.3, the spacing required to prevent shear failure decreased to 136 mm, which is 9.33% less than the minimum specified by the Korean standards. This indicates that even if the code’s minimum spacing is adhered to, shear failure can still occur in columns. In order to prevent shear failure of the column, the spacing of the shear reinforcement should be designed smaller, because the shear force increases as the vertical irregularity increases. For piloti-type structures with high horizontal irregularity, there is a need to design shear reinforcement narrower than the minimum standard to prevent shear failure of the column.
Resilient House Evaluation Matrix: Attributes and Quality Indicators for Social Housing
Authors: Villa Simone Barbosa , Bortoli Karen Carrer Ruman de , Oliveira Lamonise Vasconcelos
Published: February 2025

Background: This study explores resilience in Brazilian social housing (SH), focusing on single-family, one-story housing units within the “Minha Casa, Minha Vida” (MCMV) program. Despite reducing the housing deficit by delivering 7.7 million units since 2009, the program’s projects often lack resilience, contributing to social, physical, and environmental vulnerabilities. Resilience is defined as the built environment’s ability to respond, absorb, and adapt to impacts and demands, addressing vulnerability and adaptive capacity. Methods: This study developed the Resilient House Evaluation Matrix (RHEM), piloted in two MCMV developments in Uberlândia, MG, Brazil. Data were collected using performance and post-occupancy evaluation tools, focusing on attributes such as thermal comfort, energy efficiency, flexibility, and accessibility for the elderly. Indicators and sub-indicators were defined to measure resilience. Results: The RHEM attributes proved useful in improving housing quality and resilience, while evaluation tools identified key impacts and residents’ perceptions. The Resilience Ruler (RR) assessed resilience levels, supporting the development of design strategies to enhance resilience in SH. These findings align with Sustainable Development Goal (SDG) 11, contributing to resilient communities. Conclusions: This study emphasizes the importance of resilient SH design to address vulnerabilities and enhance adaptability. The RHEM provides a valuable framework for advancing housing resilience.
Characterizing Cardiotoxicity of FDA-Approved Soft Tissue Sarcoma Targeted Therapies and Immune Checkpoint Inhibitors: A Systematic Review
Authors: Houmsse Mustafa , Muskara Andrew , Pasca Damaris , Roy Arnab , Sughra Sana , Ghazi Sanam , Addison Daniel , Husain Marium
Published: February 2025

Background: Soft tissue sarcomas (STS) are aggressive cancers that show increasing response to novel targeted-therapies and immune-checkpoint-inhibitors. Despite anecdotal reports of cardiovascular adverse events (AEs) and major adverse cardiovascular events (MACE) potentially hindering their utility, the true cardiotoxic profile of these novel-therapies in STS has been largely understudied. Methods: We assessed the incidence and severity of AEs and MACE of contemporary FDA-approved targeted and immune-based therapies for STS, using data from landmark clinical trials supporting FDA-approval. We also analyzed data from the FDA adverse-event-reporting-system-(FAERS) for FDA-approved STS targeted and immune-based therapies for comparative real-world validation. Results: Overall, 12 clinical trials supporting FDA-approval of STS targeted-therapies and immune-checkpoint-inhibitors, incorporating 1249 patients, were identified. These clinical trials revealed 751 AEs including, hypertension (382, 50.87%), atrial fibrillation (3, 0.40%), myocardial infarction (2, 0.27%), cardiac failure (congestive included) (9, 1.20%), and cardiac failure (heart failure included) (7, 0.93%). Compared to placebo, those treated saw higher MACE (OR: 3.27, p < 0.001). The FAERS data showed 489 reported AEs including hypertension (275, 56.24%), atrial fibrillation (31, 6.34%), myocardial infarction (15, 3.07%), and cardiac failure (congestive included) (30, 6.13%). Programmed death-ligand 1 (PD-L1) inhibitors had the highest probability of AEs (0.65, 1.17), followed by tyrosine kinase inhibitors (0.66, 0.11), tropomyosin receptor kinase inhibitors (0.25, 0.13), mammalian target of rapamycin inhibitors (0.21, 0.09), and enhancer of zeste homologue 2 inhibitors (0.11, 0.06). Proportions were calculated from the samples in clinical trials supporting FDA-approval and FAERS, respectively. Conclusions: In this investigation, contemporary FDA-approved therapies for STS are associated with increased risk of AEs
Quality-of-Life and Oncological Outcomes in Male Breast Cancer: Insights from an Extensive 20-Year Experience
Authors: Ferrucci Massimo , Milardi Francesco , Passeri Daniele , Pozzerle Maria , Cagol Matteo , Saibene Tania , Michieletto Silvia , Toffanin Mariacristina , Del Bianco Paola , Marchet Alberto
Published: February 2025

Background/Objectives: Male breast cancer (MBC) is a rare malignancy with a globally rising incidence. Due to the paucity of specific evidence, therapeutic strategies are often extrapolated from female breast cancer guidelines. The quality of life (QoL) among MBC patients remains underexplored. Methods: This single-institution retrospective study analyzed male patients who underwent surgery for newly diagnosed breast cancer at our institution from 1998 to 2020. The primary aim was to assess QoL after surgical and medical treatments using a newly developed 12-item dedicated questionnaire. Clinicopathological features were recorded, and oncological and survival outcomes were evaluated, with a specific focus on identifying factors influencing QoL. Results: A total of 109 consecutive MBC patients who underwent surgery were included, with 96.3% undergoing total mastectomy. The median global QoL score was 28.5 out of 36, where scores above 24 indicated a low impact of BC treatments on QoL. Multivariate analyses identified adjuvant chemotherapy (p < 0.001) and postoperative complications (p < 0.001) as significant predictors of poorer QoL. Patients reported significantly lower scores on medical treatment-related items compared to surgery-related items (p < 0.001). The 10-year overall survival rate was 79.1%, with a 10-year BC-specific mortality of 3.5%. Advanced age, higher stage disease, and receiving adjuvant chemotherapy were independently associated with poorer overall survival. Conclusions: Despite elevated mastectomy rates, MBC patients self-reported high levels of satisfaction with their treatment outcomes. Medical therapies showed a more pronounced negative impact on QoL than surgery. These findings provide novel insights into the QoL of MBC patients, highlighting the need for future prospective studies and tailored treatments.
Proteogenomic Profiling of Treatment-Naïve Metastatic Malignant Melanoma
Authors: Kuras Magdalena , Betancourt Lazaro Hiram , Hong Runyu , Szadai Leticia , Rodriguez Jimmy , Horvatovich Peter , Pla Indira , Eriksson Jonatan , Szeitz Beáta , Deszcz Bartłomiej , Welinder Charlotte , Sugihara Yutaka , Ekedahl Henrik , Baldetorp Bo , Ingvar Christian , Lundgren Lotta , Lindberg Henrik , Oskolas Henriett , Horvath Zsolt , Rezeli Melinda , Gil Jeovanis , Appelqvist Roger , Kemény Lajos V. , Malm Johan , Sanchez Aniel , Szasz Attila Marcell , Pawłowski Krzysztof , Wieslander Elisabet , Fenyö David , Nemeth Istvan Balazs , Marko-Varga György
Published: February 2025

Background: Melanoma is a highly heterogeneous disease, and a deeper molecular classification is essential for improving patient stratification and treatment approaches. Here, we describe the histopathology-driven proteogenomic landscape of 142 treatment-naïve metastatic melanoma samples to uncover molecular subtypes and clinically relevant biomarkers. Methods: We performed an integrative proteogenomic analysis to identify proteomic subtypes, assess the impact of BRAF V600 mutations, and study the molecular profiles and cellular composition of the tumor microenvironment. Clinical and histopathological data were used to support findings related to tissue morphology, disease progression, and patient outcomes. Results: Our analysis revealed five distinct proteomic subtypes that integrate immune and stromal microenvironment components and correlate with clinical and histopathological parameters. We demonstrated that BRAF V600-mutated melanomas exhibit biological heterogeneity, where an oncogene-induced senescence-like phenotype is associated with improved survival. This led to a proposed mortality risk-based stratification that may contribute to more personalized treatment strategies. Furthermore, tumor microenvironment composition strongly correlated with disease progression and patient outcomes, highlighting a histopathological connective tissue-to-tumor ratio assessment as a potential decision-making tool. We identified a melanoma-associated SAAV signature linked to extracellular matrix remodeling and SAAV-derived neoantigens as potential targets for anti-tumor immune responses. Conclusions: This study provides a comprehensive stratification of metastatic melanoma, integrating proteogenomic insights with histopathological features. The findings may aid in the development of tailored diagnostic and therapeutic strategies, improving patient management and outcomes.
Prognostic Significance of Sarcopenia in Patients Undergoing Surgery for Perihilar Cholangiocarcinoma: A Systematic Review and Meta-Analysis
Authors: Efstathiou Anastasia , Suarez Benitez Pablo , Hajibandeh Shahin , Hajibandeh Shahab , Satyadas Thomas
Published: February 2025

Aim: The aim of this study was to determine the impact of sarcopenia on outcomes in patients undergoing curative resection for perihilar cholangiocarcinoma. Methods: A systematic review and meta-analysis following PRISMA standards were conducted, searching for studies comparing patients with and without sarcopenia undergoing surgery for perihilar cholangiocarcinoma. The outcomes included postoperative mortality, Clavien–Dindo ≥ 3 complications, intraoperative blood loss, need for blood transfusion, length of hospital stay, and overall survival (OS) (time-to-event). The odds ratio (OR), mean difference (MD), and adjusted hazard ratio (HR) were calculated as summary measures using random effect modelling. Risk of bias was assessed with the Quality in Prognosis Studies tool. Results: Five studies featuring 1304 patients were included. There was no significant difference in postoperative mortality (OR 1.85, 95% CI 0.75–4.57, p = 0.18), Clavien–Dindo ≥ 3 complications (OR 1.44, 95% CI 0.92–2.25, p = 0.11), length of hospital stay (MD 2.13 days, 95% CI −0.89–5.15, p = 0.17) or OS (adjusted HR 1.48, 95% CI, 0.97–2.28, p = 0.07) between the patients with and without sarcopenia. Sarcopenia increased intraoperative blood loss (MD 388.00 mL, 95% CI, 114.99–683.01, p = 0.006) and the need for blood transfusion (OR 2.27, 95% CI, 1.66, 3.10, p < 0.00001). Conclusions: Sarcopenia may increase the risk of bleeding during the resection of perihilar cholangiocarcinoma (low certainty); however, this may not translate into a higher risk of postoperative morbidity or mortality (moderate certainty). Our findings regarding the OS may be subject to type 2 error; hence, the effect of sarcopenia on long-term outcomes after the resection of perihilar cholangiocarcinoma remains unknown and requires further research.
Management Based on Pretreatment PSMA PET of Patients with Localized High-Risk Prostate Cancer Part 2: Prediction of Recurrence—A Systematic Review and Meta-Analysis
Authors: Hoffmann Manuela Andrea , Soydal Cigdem , Virgolini Irene , Tuncel Murat , Kairemo Kalevi , Kapp Daniel S. , von Eyben Finn Edler
Published: February 2025

Background and objectives: For patients with prostate cancer (PCa), PSMA PET better diagnose metastases than conventional imaging. In a systematic review and meta-analysis (INPLASY register, 2024311004), we aimed to summarize findings with pretreatment PSMA PET in patients with PCa that was localized according to conventional imaging and summarize how pretreatment PSMA PET had influence on biochemical recurrence (BCR)-free survival and overall survival (OS). Methods: We searched for publications in Pubmed, Google Scholar, ClinicalTrials.gov, and reference lists between 2016 and February 2025. We summarized biochemical recurrence-free survival in Forest plots. Results: Nine publications reported 1908 patients and showed that pretreatment PSMA PET was associated with survival. Three publications reported that pretreatment PSMA PET gave better 3–5-year BCR-free survival than conventional imaging (74% versus 57%). Two publications reported PSMA PET-risk for 389 patients. Those with PSMA PET-low-risk lived 5 years longer often than those with PSMA PET high-risk (84% versus 20%). Conclusions: Pretreatment PSMA PET is widely used in the real world. Pretreatment PSMA PET supports personalized treatment and may explain why pretreatment PSMA PET improved BCR-free survival and OS. It is believed that pretreatment PSMA PET may facilitate future progress in care of patients with high-risk PCa.
Catalysis in Biofuel Production and Biomass Valorization: Trends, Challenges, and Innovations Through a Bibliometric Analysis
Authors: Alazaiza Motasem Y. D. , Alzghoul Tharaa M. , Ramu Madhusudhan Bangalore , Nassani Dia Eddin
Published: February 2025

Biomass valorization and biofuel production are essential strategies for converting renewable organic materials into sustainable energy, addressing the urgent need for alternatives to fossil fuels. This study conducts a bibliometric analysis of 1657 publications from the Scopus database, covering the period from 2010 to December 2024, revealing significant trends in this field. The number of published articles reached 318 in 2024, peaking at 163 articles in 2020, which garnered 7302 citations, indicating robust global interest. China leads the research landscape with 550 publications and 17,577 citations, followed by the United States with 160 publications and 9359 citations. Key journals include “ACS Sustainable Chemistry and Engineering” and “Chemsuschem”, highlighting important contributions to the field. The analysis identifies four clusters: the role of lignin and heterogeneous catalysis in biomass conversion; pyrolysis and waste valorization techniques; key chemical intermediates from biomass; and advanced reactions like hydrogenolysis for enhancing product value. The study emphasizes the need for innovative strategies and interdisciplinary collaboration to improve biomass utilization and biofuel production. Future research should focus on developing integrated systems that promote a circular economy, optimize reaction conditions, and explore new biomass feedstocks. Overall, this research significantly advances the understanding of biomass conversion processes and supports the transition to renewable energy solutions, underscoring the critical role of biomass in achieving sustainability goals.
Statins as an Adjunctive Antithrombotic Agent in Thrombotic Antiphospholipid Syndrome: Mechanisms and Clinical Implications
Authors: Bucci Tommaso , Menichelli Danilo , Palumbo Ilaria Maria , Pastori Daniele , Ames Paul R. J. , Lip Gregory Y. H. , Pignatelli Pasquale
Published: February 2025

The thrombotic physiopathology of antiphospholipid syndrome (APS) is complex, heterogeneous, and dynamic. While venous thromboembolism (VTE) is the most common initial presentation, arterial thrombotic events (ATE) become more frequent in advanced stages and are associated with high morbidity and mortality. Despite the use of oral anticoagulants (OACs), thrombotic APS remains associated with a high risk of recurrent thrombosis. Given their potential antithrombotic effects capable of reducing the risk of both VTE and ATE, statins have been proposed as an adjunctive therapy to OACs for patients with APS and recurrent thrombosis. However, this recommendation is primarily based on studies not specifically conducted in APS populations, with only preclinical data or evidence from retrospective observational studies available from APS patients cohorts. For these reasons, this narrative review aims to synthesise the studies evaluating the potential antithrombotic effects of statins in patients with APS, highlighting the progress made and identifying areas for future research.
Inflammatory Stimuli and Fecal Microbiota Transplantation Accelerate Pancreatic Carcinogenesis in Transgenic Mice, Accompanied by Changes in the Microbiota Composition
Authors: Świdnicka-Siergiejko Agnieszka , Daniluk Jarosław , Miniewska Katarzyna , Daniluk Urszula , Guzińska-Ustymowicz Katarzyna , Pryczynicz Anna , Dąbrowska Milena , Rusak Małgorzata , Ciborowski Michał , Dąbrowski Andrzej
Published: February 2025

An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota–PDAC interactions and towards more personalized and effective cancer therapies.
Chronic Oral D-Galactose Induces Oxidative Stress but Not Overt Organ Dysfunction in Male Wistar Rats
Authors: Martinovic Jelena , Gusevac Stojanovic Ivana , Nesic Sladjan , Todorovic Ana , Bobic Katarina , Stankovic Sanja , Drakulic Dunja
Published: February 2025

D-galactose (d-gal) plays numerous roles in the organism as an energy-providing nutrient and also an important constituent of the complex glycoconjugates. However, excessive amounts of d-gal activate alternative metabolic pathways that can lead to the development of a pro-oxidative environment. This feature is used in numerous aging studies which implied intraperitoneal (i.p.) or subcutaneous (s.c.) administration of d-gal for a prolonged time. The present study aims to investigate the systemic effects of orally administered d-gal (200 mg/kg and 500 mg/kg, dissolved in tap water, for 6 weeks) by analyzing oxidative stress parameters in the liver, kidney, and heart. For comparison with natural aging, the effects were studied in rats aged 12, 18, 24, and 30 months. In addition, histopathologic analyzes and serum biochemical measurements were performed to investigate the potential structural and functional organ damage induced by d-gal administration. Our findings show that chronic oral administration of d-gal induces oxidative stress in rat organs and mimics some aspects of natural aging similar to those of 30-month-old rats. Consistent with its primary role in galactose metabolism, the liver exhibited the most pronounced oxidative damage. However, despite the increased oxidative stress, only minor histopathological changes were observed, while organ function remained largely unaffected. Oral intake of d-gal was found to have milder effects compared to i.p. or s.c. injections, suggesting that this model may induce some features of natural aging but without overt organ dysfunction.
Coalition Formation with Cooperation-Enhancing Transfers When Players Are Heterogeneous and Inequality-Averse
Authors: Rogna Marco , Vogt Carla
Published: February 2025

Obtaining significant levels of cooperation in public goods and environmental games, under the assumption of players being purely selfish, is usually prevented by the problem of free riding. Coalitions, in fact, generally fail to be internally stable, and this causes a serious under-provision of the public good, together with a significant welfare loss. The assumption of relational preferences, capable of better explaining economic behaviours in laboratory experiments, helps to foster cooperation, but, without adequate transfer scheme, no substantial improvements are reached. The present paper proposes a cooperation-enhancing transfer scheme under the assumption of players having Fehr and Schmidt utility functions, whose objectives are to guarantee internal stability and to maximize the sum of the utilities of coalition members. The transfer scheme is tested on a public goods contribution game parameterized on the data provided by the RICE model and benchmarked with other popular transfer schemes in environmental economics. The proposed scheme outperforms its benchmarking counterparts in stabilizing coalitions, and sensibly increases cooperation compared to the absence of transfers. Furthermore, for high but not extreme values of the parameter governing the intensity of dis-utility from disadvantageous inequality, it manages to support very large coalitions.