bluuebunny/crossref_metadata_2025 huggingface dataset:
MAN AND TECHNOLOGY: HISTORY AND MODERNITY
Authors:   Saratov State University, Saratov, Russia, Kalinnikova Marina V. , Romanovskaya Оlga A. ,   Saratov State University, Saratov, Russia
Published: January 2025

Introduction. The article is devoted to the study of the legacy of the outstanding Russian geographer, sociologist, anthropologist, ethnographer and publicist Lev Ilyich Mechnikov. The study of his works today creates fruitful prerequisites for deep interaction between Eastern and Western cultures, contributing to the comprehension of modern societal risks. The aim of this study is sociological reflection of the scientist's scientific heritage in the context of the phenomenon of societal risks.
scientist's scientific heritage in the context of the phenomenon of social solidarity. The analysis of scientific works of modern scientists (historians, sociologists) has shown that the author's interest is focused on the intellectual research of Л. I. Mechnikov in the field of specific laws of social life and the possibility of establishing reliable criteria of social progress. Methods. The paper utilizes the genetic method, comparative-historical and systemic research approaches, which allowed us to reveal the discursive potential of L. I. Mechnikov's theory of social solidarity. Results and Discussion. The authors have characterized several of the most expressive and promising discourses of study, perception and scientific analysis of the phenomenon of social solidarity outlined by Lev Ilyich in his work “Civilization and the Great Historical Rivers. A Geographical Theory of the Development of Modern Societies”. The authors believe that the idea of social solidarity is contextualized through factual projections in the scientific work “The Japanese Empire”. Conclusion. An important aspect of Mechnikov's sociological approach is his belief that social solidarity is the result of both objective historical processes and people's conscious choices. Solidarity, according to Mechnikov, is not just sacrifice, but active participation in the affairs of society, where everyone contributes, realizing that the general well-being depends on it. The conclusions that follow from modern scientific and public reflection of Lev Ilyich Mechnikov's creative heritage can become part of a solid foundation for building a harmonious social worldview of the XXI century, which emphasizes the unity of humanity.
Challenges in designing interventions for food insecure families with food allergy in a Californian latinx cohort
Authors: Albarran Marleni , Brown Emily , Martinez Erin , Chin Andrew R. , Sindher Sayantani B. , Warren Christopher M. , Chinthrajah R. Sharon
Published: January 2025

Food allergy poses substantial social, economic, and quality of life burdens which are even heavier for families that are struggling with food insecurity. In the United States (US), food insecurity disproportionately affects vulnerable and historically marginalized communities, such as Latino/a/x and Black households. Targeting these disparities via our recent Food Equality Initiative (FEI) research intervention was challenging due to the barriers faced by the target underserved populations, which included poor digital literacy, language barriers, and limited access to necessary resources. These barriers hindered our efforts to promote access to nutritious and safe food options for food-insecure families, potentially further exacerbating health disparities. Here we discuss common challenges and opportunities associated with conducting research interventions in underserved communities in the US—leveraging our experiences designing and implementing an intervention to improve food allergy management through supplemental nutrition assistance in a predominantly Spanish-speaking, lower-income neighborhood in Northern California. We also provide recommendations for other researchers regarding how to tailor research strategies to address these challenges, and in so doing reduce health disparities and promote positive health outcomes for vulnerable and historically marginalized communities.
Ningaloo Marine Park management program best practice for whale shark (Rhincodon typus) conservation
Authors: Tyne Julian A. , Raudino Holly , Lester Emily , Francis Gemma , Barnes Peter , Waples Kelly
Published: January 2025

The predictable nature of whale shark (Rhincondon typus) aggregations around the world forms the basis for nature-based tourism. The Ningaloo Marine Park (NMP), Western Australia is one of those locations and a management program has been in place since 1993. Measuring the effectiveness of the management program is important to minimise potential impacts on the whale sharks. In NMP tour operator vessels are equipped with an Electronic Management System (EMS) to collect data during whale shark encounters. Using EMS data and associated images of identified whale sharks from the months of March to July between 2011 to 2019, Generalised Additive Mixed Models (GAMMs) and Generalised Linear Mixed Effect Models (GLMMs) assessed the variation in duration of whale shark encounters. Using EMS data from 2010 to 2023 we mapped the density distribution of all whale shark encounters to identify hotspots. From the 44,017 whale shark encounters between 2011 to 2019, 7585 involved 986 individuals. On average individual sharks were encountered 4.30 times per day (± SD 3.15), with a mean duration of 15.30 mins (± SD 13.17). In Tantabiddi, daily encounters, distance, Southern Oscillation Index (SOI), habitat and vessel were important in predicting the variation in encounter duration, whereas in Coral Bay daily encounters, encounter number, SOI, sex and vessel were important at predicting the variation in encounter duration. There was no evidence to suggest a significant variation in whale shark encounter duration between days after repeated encounters in Tantabiddi or Coral Bay. However, some individuals were repeatedly encountered in a day with a cumulative encounter duration up to 224 minutes. A significant negative relationship between encounter duration and number of daily encounters was identified for Tantabiddi -0.073, p-value < 0.001, Coral Bay -12.3, p-value < 0.001 and for NMP overall -0.083, p-value <0.001. A Gi* statistic identified significant whale shark encounter hotspots where commercial whale shark encounters occur in higher densities. Our findings support the best practice standard of the whale shark management program in the NMP, however the potential pressure of prolonged cumulative whale shark encounter durations, and the high density of the whale shark encounters in some areas warrants further investigation.
Early childhood teachers’ understanding of executive functions and strategies employed to facilitate them
Authors: Madanipour Parian , Garvis Susanne , Cohrssen Caroline , Pendergast Donna
Published: January 2025

Introduction

Adult-child interactions have a noteworthy influence over how executive functions develop. However, despite recognising the importance of executive functions in a child’s success, little research has been undertaken to explore the role of early childhood teachers in facilitating the development of executive functions in children through their teaching practice. The current study thus explored what understanding early childhood teachers have of executive functions and what pedagogical practices they use to contribute to the development of executive functions in 3 to 5-year-old children within preschool settings.

Methods

Data were collected through an online questionnaire completed by 58 early childhood teachers across Victoria, Australia. The questionnaire included both closed and open-ended questions, aiming to explore participants’ understanding of executive functions and the specific pedagogical practices they employed to facilitate the development of these skills in their classroom. Qualitative data from open-ended responses were analysed thematically to identify recurring practices and perceptions.

Results

The results reveal that some early childhood teachers reported strong pedagogical understanding of executive functions. Further, they reported implementing practices in the everyday classroom intended to promote executive functions. Thematic analysis of qualitative data reveals that these early childhood teachers apply five pedagogical practices intended to facilitate executive functions: environment and activity structuring, supporting autonomous behaviours, enacting purposeful classroom organisation, encouraging sustained shared thinking, and conducting activities that support executive functions.

Discussion

The self-reported data in this study suggest that some early childhood teachers know much about evidence-based pedagogical practices that facilitate children’s executive functions. The reported pedagogical practices employed by such teachers aligned closely with practices recommended in the literature. However, participants’ pedagogical understanding was reported to have been gained through experience, drawing attention to the need for a stronger focus on executive functions during initial teacher education courses. As such, this study highlights the need for Australian early childhood initial teacher education courses to ensure that executive functions and executive functions-supportive pedagogical practices are explicitly addressed. The insights revealed here should inform initiatives that raise awareness and understanding of executive functions among early childhood teachers to forefront executive functions during their time spent with preschoolers.
Citrate: a key signalling molecule and therapeutic target for bone remodeling disorder
Authors: Liu Qichang , Xue Yuchuan , Guo Junzhe , Tao Lin , Zhu Yue
Published: January 2025

Bone remodeling is a continuous cyclic process that maintains and regulates bone structure and strength. The disturbance of bone remodeling leads to a series of bone metabolic diseases. Recent studies have shown that citrate, an intermediate metabolite of the tricarboxylic acid (TCA) cycle, plays an important role in bone remodeling. But the exact mechanism is still unclear. In this study, we focused on the systemic regulatory mechanism of citrate on bone remodeling, and found that citrate is involved in bone remodeling in multiple ways. The participation of citrate in oxidative phosphorylation (OXPHOS) facilitates the generation of ATP, thereby providing substantial energy for bone formation and resorption. Osteoclast-mediated bone resorption releases citrate from bone mineral salts, which is subsequently released as an energy source to activate the osteogenic differentiation of stem cells. Finally, the differentiated osteoblasts secrete into the bone matrix and participate in bone mineral salts formation. As a substrate of histone acetylation, citrate regulates the expression of genes related to bone formation and bone reabsorption. Citrate is also a key intermediate in the metabolism and synthesis of glucose, fatty acids and amino acids, which are three major nutrients in the organism. Citrate can also be used as a biomarker to monitor bone mass transformation and plays an important role in the diagnosis and therapeutic evaluation of bone remodeling disorders. Citrate imbalance due to citrate transporter could result in the supression of osteoblast/OC function through histone acetylation, thereby contributing to disorders in bone remodeling. Therefore, designing drugs targeting citrate-related proteins to regulate bone citrate content provides a new direction for the drug treatment of diseases related to bone remodeling disorders.
Male bluegill vary in color and behavior relative to their position in a lek
Authors: Peroš Matthew , Vij Lakshita , Anavian Elana , Almeida Arteaga Kevin , Haruna Fatima Iya , Siegman Aliza , Fang Wei , Alvarado Sebastian Gaston
Published: January 2025

Animals organize into social groups to increase collective fitness. These groups use behavior and morphological traits like color to communicate social status. Male bluegill (Lepomis macrochirus) form breeding collectives during the reproductive months. However, whether these colonies generate resource-stratified social hierarchies to manage intrasexual competition is unknown. We hypothesize that territorial position within the colony results in different body colors and behavioral profiles. To test this hypothesis, we quantified color patterns in wild communities of bluegill using computer vision, scored the behavior of lek occupying parental males, and categorically classified lek position as a function of neighboring males. From these data, we show that body coloration and behavior vary with lek position, suggesting a division of labor in the construction and maintenance of grouped territories where courtship and sexual selection take place. Collectively, these data underline the importance of male-specific morphological plasticity and its impacts on social organization.
The use of BirdNET embeddings as a fast solution to find novel sound classes in audio recordings
Authors: Allen-Ankins Slade , Hoefer Sebastian , Bartholomew Jacopo , Brodie Sheryn , Schwarzkopf Lin
Published: January 2025

Passive acoustic monitoring has emerged as a useful technique for monitoring vocal species and contributing to biodiversity monitoring goals. However, finding target sounds for species without pre-existing recognisers still proves challenging. Here, we demonstrate how the embeddings from the large acoustic model BirdNET can be used to quickly and easily find new sound classes outside the original model’s training set. We outline the general workflow, and present three case studies covering a range of ecological use cases that we believe are common requirements in research and management: monitoring invasive species, generating species lists, and detecting threatened species. In all cases, a minimal amount of target class examples and validation effort was required to obtain results applicable to the desired application. The demonstrated success of this method across different datasets and different taxonomic groups suggests a wide applicability of BirdNET embeddings for finding novel sound classes. We anticipate this method will allow easy and rapid detection of sound classes for which no current recognisers exist, contributing to both monitoring and conservation goals.
A comparison of sex-specific senescence patterns in a long-lived marine mammal
Authors: Macdonald Kaitlin R. , Rotella Jay J. , Link William A.
Published: January 2025

The lifetime fitness of an individual is determined by the integrated results of survival and reproduction. Improving our understanding of variation in survival senescence within and between species will therefore provide greater insight into the evolution of different life history strategies. Survival is influenced by multiple factors, consequently, variation in patterns of senescence is expected between individuals and sexes and across mating systems and the continuum of life history strategies. To date there is little consensus regarding the mechanisms driving the evolution of sex differences in actuarial senescence, necessitating the need for studies of sex-specific senescence for species across a wide range of life histories. The Weddell seal is a species of long-lived mammal that displays moderate polygyny and little sexual size dimorphism, which makes it an unusual species compared to other long-lived mammals that share the polygynous mating system. Here we used 37 years of data for 1,879 female and 1,474 male Weddell seals from Erebus Bay, Antarctica, to estimate and compare sex-specific patterns of survival rates using basis splines which allow flexible modeling of age-specific patterns. We found that males had lower rates of survival throughout life and higher rates of actuarial senescence after early adulthood compared to females. These results add to our understanding of sex-specific survival rates in the species and contribute information for a long-lived, polygynous species that should aid in achieving a broader understanding of aging between sexes and across the tree of life.
Immune dynamics throughout life in relation to sex hormones and perspectives gained from gender-affirming hormone therapy
Authors: Yalcinkaya Ahmet , Yalcinkaya Rumeysa , Sardh Fabian , Landegren Nils
Published: January 2025

Biological sex is closely associated with the properties and extent of the immune response, with males and females showing different susceptibilities to diseases and variations in immunity. Androgens, predominantly in males, generally suppress immune responses, while estrogens, more abundant in females, tend to enhance immunity. It is also established that sex hormones at least partially explain sex biases in different diseases, particularly autoimmune diseases in females. These differences are influenced by hormonal, genetic, and environmental factors, and vary throughout life stages. The advent of gender-affirming hormone therapy offers a novel opportunity to study the immunological effects of sex hormones. Despite the limited studies on this topic, available research has revealed that testosterone therapy in transgender men may suppress certain immune functions, such as type I interferon responses, while increasing inflammation markers like TNF-α. Transgender women on estrogen therapy also experience alterations in coagulation-related and inflammatory characteristics. Furthermore, other possible alterations in immune regulation can be inferred from the assessment of inflammatory and autoimmune markers in transgender individuals receiving hormone therapy. Understanding the complex interactions between sex hormones and the immune system, particularly through the unique perspective offered by gender-affirming hormone therapies, may facilitate the development of targeted therapies for infections and autoimmune diseases while also improving healthcare outcomes for transgender individuals. Here we review immune dynamics throughout life in both sexes and provide a summary of novel findings drawn from studies exploring gender-affirming hormone therapy.
Evaluation of de novo donor specific antibodies after kidney transplantation in the era of donor-derived cell-free DNA
Authors: Tian Yuan , Frischknecht Lukas , Mallone Anna , Rössler Fabian , Schachtner Thomas , Nilsson Jakob
Published: January 2025

Background

Donor-derived cell-free DNA (dd-cfDNA) is a promising non-invasive biomarker for detecting graft injury in solid organ transplant recipients. Elevated dd-cfDNA levels are strongly associated with rejection and graft injury, especially antibody-mediated rejection (ABMR). While de novo donor-specific antibodies (dnDSA) are crucial in ABMR, the relationship between dd-cfDNA levels and dnDSA features, such as DSA category, MFI and HLA target loci, remains unclear.

Methods

We analyzed dd-cfDNA levels in 75 kidney transplant recipients who developed dnDSA post-transplant. dnDSA were categorized as “true”, “possible”, or “false” based on bead reactivity patterns and HLA typing. dd-cfDNA was assessed alongside dnDSA detection and sequential follow-up samples in a subgroup.

Results

“True” dnDSA showed significantly higher dd-cfDNA levels compared to “possible” and “false” groups. None of the dd-cfDNA values in the “false” group exceeded 0.6%, and only a small fraction of the “possible” group had values slightly above 0.6%. dd-cfDNA levels were not significantly affected by dnDSA target loci or number. A strong correlation between cumulative dnDSA MFI and dd-cfDNA levels was observed, especially in patients with “true” HLA-DQ-directed dnDSA. Sequential dd-cfDNA analysis showed dynamic changes in 25% of patients, all from the “true” dnDSA group, which tended to align with shifts in cumulative MFI over time.

Conclusion

These findings highlight the correlation between cumulative dnDSA MFI and dd-cfDNA levels, particularly in HLA-DQ-directed dnDSA, and suggest graft injury is dynamic in dnDSA-positive patients. Integrated monitoring of dnDSA and dd-cfDNA offers a promising non-invasive approach for assessing graft injury and alloimmunity, potentially enhancing post-transplant care.
From ecological to anthropogenic factors: unraveling the drivers of blue crab Callinectes sapidus occurrence along the Mediterranean coasts
Authors: Gavioli Anna , Castaldelli Giuseppe , Eggleston David B. , Christian Robert R.
Published: January 2025

Introduction

Non-native species are widely recognized as threats to biodiversity, ecosystems, and the services they provide to humans. The Mediterranean Sea has a high biodiversity of endemic species and is a hot spot of biological invasions. One of the most recent threats to Mediterranean ecosystems is the invasion of the Atlantic blue crab Callinectes sapidus.

Methods

The occurrences of the crab throughout the Mediterranean coastline were indexed from citizen science through the Global Biodiversity Information Facility. Using spatial analysis and linear mixed models, we investigated geomorphology (i.e., water depth and coastal wetlands extension), water physical variables (i.e., salinity and winter and summer water temperature), water quality variables (i.e., chlorophyll-a, nitrate and orthophosphate) and anthropogenic factors (i.e., ship density and population size) potentially affecting the blue crab occurrence along the coast.

Results

Our results showed that nitrate, as an indicator of riverine nutrient loading, and water depth, as an indicator of slope of the bottom, were the most influential variables in explaining the occurrences of blue crabs. Water temperature and salinity had lesser impacts; anthropogenic factors, such as the density of commercial marine traffic and human population size had no effect on blue crab occurrence.

Discussion

These results sug gest that benthic primary production and shallow water drive blue crab occurrences along the Mediterranean coasts. Even considering data limitations and gaps, our large-scale findings contribute to a broader understanding of the factors that drive blue crab invasion success which, in turn, can inform management actions and outline research needs.
Treatment of neovascular age-related macular degeneration: one year real-life results with intravitreal Brolucizumab
Authors: Rossi Settimio , Gesualdo Carlo , Marano Ernesto , Perrotta Raffaele , Trotta Maria Consiglia , Del Giudice Antonio , Simonelli Francesca
Published: January 2025

Background

Age-related macular degeneration (AMD) is a prevalent cause of irreversible vision loss worldwide, particularly among the elderly population. Two forms of late AMD are described: neovascular AMD (nAMD), characterized by abnormal choroidal blood vessel growth, and atrophic (dry) AMD, involving retinal cell degeneration. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have transformed nAMD treatment, with Brolucizumab emerging as a promising therapy. The aim of this study is to provide the real-life anatomical-functional and safety results, after 1 year of treatment experience with Brolucizumab.

Methods

This is a retrospective observational real-life study in which 44 patients (44 eyes) diagnosed with nAMD and treated with Brolucizumab were enrolled. We identified two groups: group 1 (24 treatment-naïve eyes) that received a loading dose of 3 monthly intravitreal injections of Broluciziumab 6 mg (0.05 mL solution) + Q8w/Q12w regimen, and a Group 2 (20 non-naïve eyes) which performed 1 injection + ProReNata (PRN) scheme. Monthly, all participants underwent comprehensive ophthalmological evaluation until 12 months follow-up.

Results

We observed a significant improvement in best corrected visual acuity (39 ± 15 L vs. 30 ± 17 L; p < 0.01) and central retinal thickness (265 ± 89 μ vs. 360 ± 129 μ; p < 0.0001) at the end of follow-up without any differences between treatment-naïve and non-naïve patients. These results were obtained with a low number of injections (3.7 ± 1.9) with only one case of intraocular drug-related adverse event. Finally, the presence of subretinal hyperreflective material correlates with lower visual recovery.

Discussion

Our findings highlight the efficacy of Brolucizumab in managing wet-AMD and suggest its role for long-term efficacy in stabilizing retinal exudation and fluid accumulation, resulting in improved visual prognosis.
Does the audiogram shape influence the intracochlear recording of Electrocochleography during and after cochlear implantation?
Authors: Haumann Sabine , Timm Max E. , Büchner Andreas , Lenarz Thomas , Salcher Rolf B.
Published: January 2025

During cochlear implant (CI) surgery, it is desirable to perform intraoperative measurements such as Electrocochleography (ECochG) to monitor the inner ear function and thereby to support the preservation of residual hearing. However, a significant challenge arises as the recording location of intracochlear ECochG via the CI electrode changes during electrode insertion. This study aimed to investigate the relationships between intracochlear ECochG recordings, the position of the recording contact within the cochlea relative to its anatomy, and the implications for frequency and residual hearing preservation. Intraoperative ECochG recordings were conducted using the CI electrode (MED-EL) during the insertion of hearing preservation electrodes and after the insertion process. Recordings were continuously conducted using the most apical electrode (contact 1) during insertion. After insertion, the recordings were performed on all different electrode contacts. The electrode location in the cochlea during insertion was estimated using mathematical models and preoperative clinical imaging, while the postoperative electrode position was determined using postoperative clinical imaging. The study involved 10 adult CI recipients. In those with good low-frequency hearing, an increase in signal amplitude was observed, with the highest amplitudes closest to the stimulation frequency generators, and no phase change was observed. Conversely, patients with flat hearing loss exhibited a second peak with an opposite phase in the medial area of the cochlea. This study is the first to suggest that the pattern of the preoperative audiogram may influence the ECochG outcomes measured intraoperatively. Specifically, the ECochG responses during insertion appeared to behave as expected with good low-frequency hearing, while with flat hearing loss there appear to be further effects. These findings indicate that this approach can provide valuable information for the interpretation of intracochlearly recorded ECochG signals.
Analysis of physical activity levels and influencing factors in cancer survivors after pancreaticoduodenectomy
Authors: Tian Qiuju , Xue Meiqin , Chen Leying , Zhang Min , Zhu Weiyi , Wu Beiwen
Published: January 2025

Introduction

Physical activity is becoming more important in cancer patient care. However, there are limited studies investigating physical activity levels in cancer survivors after pancreaticoduodenectomy. This study aims to assess the present status of physical activity levels in cancer survivors after pancreaticoduodenectomy and whether perioperative metrics and length of follow-up have an impact on physical activity levels in survivorship.

Methods

This is a cross-sectional study. The study included cancer survivors who were treated at a tertiary general teaching hospital for pancreaticoduodenectomy from December 2019 to January 2022 following surgery. We quantified physical activity frequency, duration, and intensity using the International Physical Activity Questionnaire-Short Form. Patient demographic and clinical characteristics were obtained via an electronic medical record system. Postoperative complication data were obtained from our survival cohort. Variables univariately associated with the physical activity level at an alpha level of less than 0.1 were included in the logistic regression analysis of factors influencing physical activity in cancer survivors after pancreaticoduodenectomy.

Results

A total of 223 patients who met the eligibility criteria completed a telephone survey. The main form of physical exercise is walking, 69.5% of participants’ physical activity belongs to the active category, but only 16.6% of participants met the aerobic guideline. Logistic regression showed that cancer survivors without pancreatic fistula were 2.453 times more likely to perform active physical activity in survival than those with pancreatic leakage (p = 0.041). For a one-unit increase in operation duration, there is approximately a 0.5% reduction in the level of active physical activity participation among cancer survivors after pancreaticoduodenectomy (p = 0.015). For each unit increase in follow-up time, post-pancreaticoduodenectomy patients were 1.046 times more likely to participate in active physical activity (p = 0.030).

Conclusion

Although half of the cancer survivors after pancreaticoduodenectomy experienced active physical activity, only a small percentage of individuals met the guideline-recommended level of aerobic exercise. More physical activity support should be provided to cancer survivors after pancreaticoduodenectomy. Moreover, operation duration, postoperative pancreatic fistula, and follow-up time should be taken into consideration when giving exercise instructions to postoperative survivors of pancreaticoduodenectomy.
Application value of 18F-FDG PET/CT in soft tissue metastasis of intrahepatic cholangiocarcinoma: a case report and literature review
Authors: Liu Siwen , Sun Xiaohui , Liu Yu , Shi Ning , Zhang Xiaoli , Yu Yuechao
Published: January 2025

Intrahepatic cholangiocarcinoma (ICC)originates from the epithelial cells of the intrahepatic bile ducts, with insidious onset and strong invasiveness, and most of the cases are found in the advanced stage, with extremely poor prognosis. In advanced stages, distant metastases to the lungs, bones, and brain are common, but distant soft tissue (subcutaneous and skeletal muscle) and breast metastases are rare, and simultaneous metastases to all three rare sites had not been reported. We report a 69-year-old woman with right upper abdominal pain who underwent a plain and enhanced CT scan of the upper abdomen, which revealed an intrahepatic space-occupying lesion, as well as subcutaneous and peritoneal nodules in the abdomen. To further evaluate the presence of other metastases, an 18F-FDG PET/CT scan was performed, which showed abnormal FDG uptake in the liver, peritoneum, left upper femur, right breast, subcutaneous tissues of the thoracic and abdominal regions, and skeletal muscle, while the corresponding CT densities of part of the skeletal muscle and the left upper femur did not show any significant abnormality. Pathologic confirmation of ICC with multiple metastases was obtained by puncture biopsy of the liver and subcutaneous nodes. This case demonstrates the advantages of 18F-FDG PET/CT in comprehensively evaluating systemic metastasis of ICC and detecting occult metastases, which is of great significance in its clinical diagnosis and staging.
Pooled safety analysis of two phase 3 studies investigating trifluridine/tipiracil plus bevacizumab in patients with metastatic colorectal cancer
Authors: Taieb Julien , Fakih Marwan , Liposits Gabor , Prager Gerald W. , Van Cutsem Eric , Ciardiello Fortunato , Amellal Nadia , Calleja Elizabeth , Liu Mei , Roby Lucas , Tabernero Josep , André Thierry
Published: January 2025

Background

Trifluridine/tipiracil (FTD/TPI) is approved as monotherapy and in combination with bevacizumab for the treatment of patients with refractory metastatic colorectal cancer (mCRC). FTD/TPI plus bevacizumab showed good tolerability in the phase 3 SOLSTICE (first-line) and SUNLIGHT (later-line) trials. This pooled analysis was performed to further characterize the safety of FTD/TPI plus bevacizumab and to compare safety in untreated and previously treated patients with mCRC.

Methods

Patients must have received at least one dose of FTD/TPI plus bevacizumab in SOLSTICE (NCT03869892) or SUNLIGHT (NCT04737187). Treatment-emergent adverse events (TEAEs) in SOLSTICE and SUNLIGHT were graded per Common Terminology Criteria for Adverse Events versions 4.03 and 5.0, respectively. Times to onset/resolution of grade ≥3 hematologic TEAEs were assessed using Kaplan–Meier methodology. Treatment-related adverse events (TRAEs) were analyzed by age and Eastern Cooperative Oncology Group performance status (ECOG PS).

Results

The pooled safety population comprised 669 patients (SOLSTICE, n = 423; and SUNLIGHT, n = 246). Grade ≥3 TEAEs were reported more frequently in SOLSTICE than in SUNLIGHT (86.8% vs. 72.4%), the most common being neutropenia and anemia. Overall, granulocyte colony-stimulating factor was used in 30.6% of patients. Median time to resolution of grade ≥3 hematologic adverse events/neutropenia to grade ≤2 was 8 days. Grade ≥3 TRAEs were more frequent in patients aged ≥75 years and those with an ECOG PS of 0 versus 1 or 2.

Conclusions

FTD/TPI plus bevacizumab showed a consistent and manageable safety profile across first- and later-line mCRC treatment, including in vulnerable patients. Hematologic TEAEs were mostly reversible with appropriate management.
Exosomal lncRNAs as diagnostic and therapeutic targets in multiple myeloma
Authors: Yan Hong , Jiang Nan , Li Xiaoying , Lin Chenyang , Wang Fang , Zhang Juan , Chen Lijuan , Li Dan
Published: January 2025

Multiple Myeloma (MM) is the second most common malignancy of the hematopoietic system, accounting for approximately 10% of all hematological malignancies, and currently, there is no complete cure. Existing research indicates that exosomal long non-coding RNAs (lncRNAs) play a crucial regulatory role in the initiation and progression of tumors, involving various interactions such as lncRNA-miRNA, lncRNA-mRNA, and lncRNA-RNA binding proteins (RBP). Despite the significant clinical application potential of exosomal lncRNAs, research in this area still faces challenges due to their low abundance and technical limitations. To our knowledge, this review is the first to comprehensively integrate and elucidate the three mechanisms of action of exosomal lncRNAs in MM, and to propose potential therapeutic targets and clinical cases based on these mechanisms. We highlight the latest advancements in the potential of exosomal lncRNAs as biomarkers and therapeutic targets, offering not only a comprehensive analysis of the role of exosomal lncRNAs in MM but also new perspectives and methods for future clinical diagnosis and treatment of multiple myeloma.
Impact of using time-averaged exposure metrics on binary endpoints in exposure-response analyses
Authors: Lin Yu-Wei , Largajolli Anna , Edwards A. Yin , Cheung S. Y. Amy , Patel Kashyap , Hennig Stefanie
Published: January 2025

Exposure-response (ER) analyses are routinely performed as part of model-informed drug development to evaluate the risk-to-benefit ratio for dose selection, justification, and confirmation. For logistic regression analyses with binary endpoints, several exposure metrics are investigated, based on pharmacological plausibility, including time-averaged concentration to event (CavTE). CavTE is informative because it accounts for dose interruptions, modifications, and reductions and is therefore often compared against ER relationships identified using steady-state exposures. However, its derivation requires consideration in a logistic regression framework for time-invariant ER analysis because it has the potential to introduce bias. This study evaluated different approaches to derive CavTE for subjects whom did not have an event by the end of treatment (EoT) and assessed their impact on the ER relationship. Here we used a modified model based on a real data example for simulating exposures and events (safety) in different virtual population sizes (n = 50, 100, or 200) and drug effect magnitudes (0.5, 0.75, or 1). Events were generated using a proportional odds model with Markov components. For subjects whom did not experience an event, CavTE was derived at EoT, EoT+7 days, +14 days, +21 days, +28 days. The derivation of CavTE at different time points demonstrated significant impact on trends detected in logistic ER relationships that could bias subsequent event projection, dose selection and Go/No-Go decisions. CavTE in censored subjects must therefore be carefully derived to avoid potentially making false positive or negative conclusions. Overall, CavTE can be a useful exposure metrics in an ER analysis, when considered along with physiological or biological plausibility, the drug’s pharmacokinetic, and mechanism of action. Biological plausibility and different analysis factors (e.g., the time of the events with respect to observational period, the level of dose reduction/interruption) should be considered in the choice of the exposure metric. It is recognized that although time-invariant logistic regression is relatively fast and efficient, it overlooks recurring events and does not take into account the exposure and response time course with the potential drawback of ignoring important elements of the analysis like onset or duration of the effect. Care should be taken when ER relationships with other exposure metrics do not identify any statistically significant trends.
Analysis of stomatal characteristics of maize hybrids and their parental inbred lines during critical reproductive periods
Authors: Zhang Changyu , Jin Yu , Wang Jinglu , Zhang Ying , Zhao Yanxin , Lu Xianju , Song Wei , Guo Xinyu
Published: January 2025

The stomatal phenotype is a crucial microscopic characteristic of the leaf surface, and modulating the stomata of maize leaves can enhance photosynthetic carbon assimilation and water use efficiency, thereby playing a vital role in maize yield formation. The evolving imaging and image processing technologies offer effective tools for precise analysis of stomatal phenotypes. This study employed Jingnongke 728 and its parental inbred to capture stomatal images from various leaf positions and abaxial surfaces during key reproductive stages using rapid scanning electron microscopy. We uesd a target detection and image segmentation approach based on YOLOv5s and Unet to efficiently obtain 11 phenotypic traits encompassing stomatal count, shape, and distribution. Manual validation revealed high detection accuracies for stomatal density, width, and length, with R2 values of 0.92, 0.97, and 0.95, respectively. Phenotypic analyses indicated a significant positive correlation between stomatal density and the percentage of guard cells and pore area (r=0.36), and a negative correlation with stomatal area and subsidiary cell area (r=-0.34 and -0.46). Additionally, stomatal traits exhibited notable variations with reproductive stages and leaf layers. Specifically, at the monocot scale, stomatal density increased from 74.35 to 87.19 Counts/mm2 from lower to upper leaf layers. Concurrently, the stomatal shape shifted from sub-circular (stomatal roundness = 0.64) to narrow and elongated (stomatal roundness = 0.63). Throughout the growth cycle, stomatal density remained stable during vegetative growth, decreased during reproductive growth with smaller size and narrower shape, and continued to decline while increasing in size and tending towards a rounded shape during senescence. Remarkably, hybrid 728 differed notably from its parents in stomatal phenotype, particularly during senescence. Moreover, the stomatal density of the hybrids showed negative super parental heterosis (heterosis rate = -0.09), whereas stomatal dimensions exhibited positive super parental heterosis, generally resembling the parent MC01. This investigation unveils the dynamic variations in maize stomatal phenotypes, bolstering genetic analyses and targeted improvements in maize, and presenting a novel technological instrument for plant phenotype studies.
Microalgae and microbial inoculant as partial substitutes for chemical fertilizer enhance Polygala tenuifolia yield and quality by improving soil microorganisms
Authors: Su Yuying , Ren Ying , Wang Gang , Li Jinfeng , Zhang Hui , Yang Yumeng , Pang Xiaohui , Han Jianping
Published: January 2025

Excessive utilization of chemical fertilizers degrades the quality of medicinal plants and soil. Bio-organic fertilizers (BOFs) including microbial inoculants and microalgae have garnered considerable attention as potential substitutes for chemical fertilizer to enhance yield. In this study, a field experiment was conducted to investigate the effects of BOF partially substituting chemical fertilizer on the growth and quality of medicinal plant Polygala tenuifolia. The growth parameters, bioactive component contents, soil properties and composition of rhizosphere microorganisms were measured. The results indicated that substituting 40% of chemical fertilizer with microalgae showed the most pronounced growth-promoting effect, leading to a 29.30% increase in underground biomass and a 19.72% increase in 3,6’-disinapoylsucrose (DISS) content. Substituting 20% of chemical fertilizer with microalgae improved soil quality, significantly increasing soil organic matter content by 15.68% (p<0.05). Microalgae addition significantly affected the rhizosphere bacterial community composition of P. tenuifolia, reducing the relative abundance of Cladosporium by 33.33% and 57.93%, while increasing the relative abundance of Chloroflexi by 31.06% and 38.27%, under 20% and 40% chemical fertilizer reduction, respectively. The relative abundance of Chloroflexi positively correlated with both the underground biomass and DISS content (p<0.05), indicating that microalgae may stimulate Chloroflexi species associated with carbon cycling, thereby enhancing soil fertility, nutrient absorption, and ultimately leading to increased biomass accumulation and production of bioactive components in P. tenuifolia. In addition, there was no significant difference in underground growth and bioactive component contents between reduced chemical fertilizer dosage combined with solid microbial inoculant (SMI) and polyglutamic microbial inoculant (PMI), compared with 100% chemical fertilizer. Correlation analysis revealed that PMI could increase soil phosphorus availability through Streptomyces recruitment. In conclusion, our findings demonstrated that bio-organic fertilizers can partially substitute chemical fertilizer to improve soil properties and microorganisms, enhancing the growth and quality of P. tenuifolia. This provides a theoretical basis for increasing medicinal plant productivity under chemical fertilizer reduction.
Expression and localization of two β-carbonic anhydrases in Bienertia, a single-cell C4 plant
Authors: Nguyen Tho , Lee Nakyoung , Frömling Fabian J. , Meister Toni L. , Kim Jung Sun , Offermann Sascha , Hwang Inhwan
Published: January 2025

Carbonic anhydrases (CAs) are ubiquitous enzymes that catalyze reversibly both the hydration and dehydration reactions of CO2 and HCO3-, respectively. Higher plants contain many different isoforms of CAs that can be classified into α-, β- and γ-type subfamilies. β-type CAs play a key role in the CO2-concentrating mechanism, thereby contributing to efficient photosynthesis in the C4 plants in addition to many other biochemical reactions in plant metabolism. Here, we characterized at the molecular, cellular and biochemical levels two β-type CAs in Bienertia sinuspersici, a plant that operates a C4 carbon concentrating mechanism within individual cells without the Kranz anatomy. These two β-type CAs (BsCAβs), named BsCAβ1 and BsCAβ2, in Bienertia were strongly induced along with maturation of leaves. Both BsCAβ1 and BsCAβ2 existed as a dimeric form in vivo but showed differential localization. BsCAβ2 was localized exclusively to the plasma membrane in Bienertia and when expressed heterologously in the C3 Arabidopsis. In contrast, BsCAβ1 largely localized to the cytosol together with a portion to the plasma membrane (PM) in both plants. BsCAβ2 had two cysteine residues at the N-terminal region for palmitoylation and their substitution with serine residues led to a change in the localization from the plasma membrane (PM) to the cytosol. Thus, we propose that BsCAβ2 localizes to the PM using a lipid moiety added posttranslationally plays a role in conversion of cytosolic CO2 into HCO3- as part of the CO2-concentrating mechanism, thereby contributing to the single-cell C4 photosynthesis in Bienertia.
GmWRKY33a is a hub gene responsive to brassinosteroid signaling that suppresses nodulation in soybean (Glycine max)
Authors: Yang Mingliang , Lei Chengjun , Ma Chao , Hou Xiuming , Yao Mingming , Mi Liang , Liu Enliang , Xu Linli , Wang Shukun , Liu Chunyan , Chen Qingshan , Xin Dawei , Xu Chang , Wang Jinhui
Published: January 2025

Brassinosteroids (BRs) are key phytohormones influencing soybean development, yet their role in symbiosis remains unclear. Here, the RNA-Seq was used to identify important gene associated with BRs and symbiotic nitrogen fixation, and the function of candidate gene was verified by transgenic hairy roots. The result shows that the RNA-Seq analysis was conducted in which BR signaling was found to suppress nodule formation and many DEGs enriched in immunity-related pathways. WGCNA analyses led to the identification of GmWRKY33a as being responsive to BR signaling in the context of symbiosis establishment. Transgenic hairy roots analyses indicated that GmWRKY33a served as a negative regulator of the establishment of symbiosis. The qRT-PCR analysis confirmed that BR signaling upregulates GmWRKY33a, leading to nodulation suppression and activation of soybean immune responses. In summary, our research revealed that BR suppresses root nodule formation by modulating the immune signaling pathway in soybean roots. We further identified that GmWRKY33a, a crucial transcription factor in BR signaling, plays a negative role in the symbiotic establishment.
Genome-wide identification of the wall-associated kinase gene family and their expression patterns under various abiotic stresses in soybean (Glycine max (L.) Merr)
Authors: Li Xiangnan , Qi Sifei , Meng Lingzhi , Su Peisen , Sun Yongwang , Li Nan , Wang Dan , Fan Yinglun , Song Yong
Published: January 2025

The wall-associated kinase (WAK) gene family encodes functional cell wall-related proteins. These genes are widely presented in plants and serve as the receptors of plant cell membranes, which perceive the external environment changes and activate signaling pathways to participate in plant growth, development, defense, and stress response. However, the WAK gene family and the encoded proteins in soybean (Glycine max (L.) Merr) have not been systematically investigated. In this study, the soybean WAK genes (GmWAK) were identified based on genome-wide sequence information, the basic characteristics, chromosome location, gene replication, expression pattern, and responses to stress were comprehensively analyzed. A total of 74 GmWAK genes were identified and mapped to 19 different chromosomes in the soybean genome. Seventy-four GmWAK genes were divided into four groups, and GmWAK genes in the same group shared similar gene structures and conserved motifs. Thirty-seven duplicate pairs were identified in 74 GmWAK genes. Segmental duplication (SD) was critical in soybean WAK gene family expansion, and purification selection occurred during evolution. The promoter cis-element analysis displayed many hormone- and stress-related response elements in the promoter regions of GmWAK genes. GmWAK genes were diversely expressed in different organs and tissues, with most actively responding to cold, heat, salt, drought, and heavy metal stresses, suggesting that GmWAK genes could exhibit relevant roles in various bioprocesses.