bluuebunny/crossref_metadata_2025 huggingface dataset:
A Large‐Scale Serological Survey in Pets From October 2020 Through June 2021 in France Shows Significantly Higher Exposure to SARS‐CoV‐2 in Cats Compared to Dogs
Authors: Fritz Matthieu , Elguero Eric , Becquart Pierre , De Riols de Fonclare Daphné , Garcia Déborah , Beurlet Stephanie , Denolly Solène , Boson Bertrand , Rosolen Serge G. , Cosset François‐Loïc , Briend‐Marchal Alexandra , Legros Vincent , Leroy Eric M.
Published: December 2024

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has the potential to infect various animals, including domestic pets like dogs and cats. Many studies have documented infection in companion animals by molecular and serological methods. However, only a few have compared seroprevalence in cats and dogs from the general population, and these studies were limited by small sample sizes and collections over short periods. Our aim was to obtain a more accurate evaluation of seroprevalence in companion animals in France and to determine whether cats and dogs differ in their exposure to SARS‐CoV‐2.

Methods

We conducted an extensive serological survey of SARS‐CoV‐2, collecting blood samples from 2036 cats and 3577 dogs during routine veterinary medical examinations across different regions of metropolitan France from October 2020 to June 2021. This period encompassed the peaks and onset of two waves, as well as the emergence of the first variants. A microsphere immunoassay targeting the receptor‐binding domain and trimeric spike protein was used to detect anti‐SARS‐CoV‐2 antibodies. A subset of 308 seropositive samples was tested for the presence of neutralising antibodies.

Results

We determined an overall seroprevalence of anti‐SARS‐CoV‐2 antibodies of 7.1% (95% confidence interval [CI]: 6.4%–7.8%) among the sampled pets. Cats exhibited a significantly higher seroprevalence (9.3%; 95% CI: 8.1%–10.1%) compared to dogs (5.9%; 95% CI: 5.2%–6.8%). Among the subset of seropositive samples, 81 (26.3%; 95% CI: 21.5%–31.6%) displayed neutralizing antibodies. Furthermore, seroprevalence in both species was lower in older animals and was not associated with sex. Finally, unlike cats, seroprevalence in dogs was found to be correlated with the date of sampling.

Conclusions

The large sample size enhances the reliability and statistical robustness of our estimates regarding pet exposure to SARS‐CoV‐2. This study on SARS‐CoV‐2 reaffirms the crucial importance of adopting a One Health approach incorporating domestic animals when managing an epidemic caused by a zoonotic virus.
Zoonotic Surveillance of Bartonella spp.: Exploring the Public Health Risks in Human Settlements
Authors: Thakur Mukesh , Dolker Stanzin , Wangmo Lenrik K. , Ghosh Avijit , Dhankhar Nikhil , Singh Vinaya K. , Shukla Malay , Rameshkumar Anandhan , Biswal Manisha , Banerjee Dhriti , Joshi Bheem Dutt , Sharma Lalit K.
Published: December 2024

Introduction

Urban rodents are reservoirs of zoonotic pathogens, including Bartonella spp., which are transmitted by ectoparasites such as fleas. Zoonotic diseases caused by Bartonella often go undocumented due to confusing or subtle clinical symptoms, lack of awareness and poor diagnosis. This study aimed to assess the prevalence and diversity of Bartonella spp. by screening free‐ranging rodents and their ectoparasites in the unique ecological settings of Alipore Railway Station, Kolkata, India. The station's high passenger traffic and proximity to food stalls create favourable conditions for rodents and fleas to thrive, increasing the risk of zoonotic transmission.

Methods

Rodents and fleas were identified by morphological features and DNA sequencing. Detection of Bartonella was carried out by DNA sequencing of citrate synthase (gltA) gene. Phylogenetic relationships among the obtained sequences were inferred through phylogenetic tree and haplotype network analyses. Q‐PCR testing from human samples from the surrounding area was performed to confirm the zoonotic transfer potential.

Results

Of 60 rodents, identified as Bandicota indica 28 (46.7%) and Bandicota bengalensis 32 (53.3%), and 110 fleas (Xenopsylla cheopis) were collected. The prevalence of Bartonella infection varied across three different hosts, that is, 32/60 rodents (53.33%), 87/110 fleas (79.1%) and 4/25 human (16%). Phylogenetic analysis revealed four distinct Bartonella lineages comprising 11 novel haplotypes (H1–H11), with haplotype H4 shared between rodents, fleas and humans, indicating active and cross species transmission of Bartonella spp. Haplotype H10, identified as B. rochalimae, was a phylogenetically diverged lineage exclusively found in fleas, suggesting a potentially novel lineage.

Conclusions

The results highlight the significant public health risks posed by Bartonella spp. in densely populated urban areas, particularly in environments like railway stations where human–rodent interactions are frequent. This study underscores the necessity of integrated pest management and surveillance strategies, using molecular tools such as Q‐PCR, to mitigate the risk of zoonotic disease transmission in urban settings.
The prevalence of motility-related genes within the human oral microbiota
Authors: Rocha Sofia T. , Shah Dhara D. , Zhu Qiyun , Shrivastava Abhishek
Published: December 2024

The human oral and nasal microbiota contains approximately 770 cultivable bacterial species. More than 2,000 genome sequences of these bacteria can be found in the expanded Human Oral Microbiome Database (eHOMD). We developed HOMDscrape, a freely available Python software tool to programmatically retrieve and process amino acid sequences and sequence identifiers from BLAST results acquired from the eHOMD website. Using the data obtained through HOMDscrape, the phylogeny of proteins involved in bacterial type 9 secretion system (T9SS)-driven gliding motility, flagellar motility, and type IV pilus-driven twitching motility was constructed. A comprehensive phylogenetic analysis was conducted for all components of the rotary T9SS, a machinery responsible for secreting various enzymes, virulence factors, and enabling bacterial gliding motility. Results revealed that the T9SS outer membrane β-barrel protein SprA of human oral bacteria underwent horizontal evolution. Overall, we catalog motile bacteria that inhabit the human oral microbiota and document their evolutionary connections. These results will serve as a guide for further studies exploring the impact of motility on the shaping of the human oral microbiota.

IMPORTANCE

The human oral microbiota has been extensively studied, and many of the isolated bacteria have genome sequences stored on the human oral microbiome database (eHOMD). Spatial distribution and polymicrobial biofilms are observed in the oral microbiota, but little is understood on how they are influenced by motility. To bridge this gap, we developed a software tool to identify motile bacteria from eHOMD. The results enabled the cataloging of motile bacteria present in the oral microbiota but also provided insight into their evolutionary relationships. This information can guide future research to better understand how bacterial motility shapes the human oral microbiota.
The Impact of Imported Timber Price Fluctuations on the Margins of Wood Forest Product Exports: Empirical Evidence from Provincial-Level Data in China
Authors: shi zhenghuang , hou fangmiao
Published: December 2024

This paper adopts a comprehensive approach to integrating the wood forest product trade of China's provinces with the global market, utilizing over four million records of trade data from the Chinese Customs database and the United Nations Trade and Commerce database, creating a three-dimensional panel dataset structured by year—province—importing country. The paper decomposes the export trade share into extensive margin, quantity margin, and price margin, collectively referred to as the ternary margins of export, to analyze the impact of imported timber price fluctuations on these export margins of wood forest products. The findings indicate that fluctuations in imported timber prices increase uncertainty, thereby suppressing the growth of China's wood forest product export share, extensive margin, and quantity margin while increasing the price margin. Heterogeneity tests further reveal that the impact of imported timber price fluctuations is more pronounced for southern forest regions, labor-intensive wood products, and countries without a free trade agreement. Mechanism tests suggest that increasing forestry fixed asset investment intensity and enhancing timber supply capacity can help mitigate the uncertainty effects associated with imported timber price fluctuations. The paper proposes policy implications, including enhancing local timber supply resilience, strengthening government support for forestry, and reinforcing the supply chain.
The Connectivity and Fault Diameter of Strong Product Graph of n Paths
Authors: Yue Yuxiang , Li Feng
Published: December 2024

Fault diameter is an important parameter to measure the reliability and efficiency of interconnection networks. Strong product is an efficient method to construct large graphs from small graphs. In this paper, we study the fault diameter of strong product graph of [Formula: see text] paths. By recursion and mathematical induction, combined with the connectivity of the strong product graph of complete graph and connected graph, the connectivity of the strong product graph of [Formula: see text] paths is determined. By defining two [Formula: see text]-dimensional vectors [Formula: see text] and [Formula: see text] to construct internally vertex disjoint paths between any two vertices, the fault diameter of the strong product graph of [Formula: see text] paths is determined.
Conditional Edge Fault Hamiltonicity of Exchanged Hypercube
Authors: Wang Chen , Wang Shiying
Published: December 2024

The exchanged hypercube is regarded as an attractive alternative to the hypercube. In this paper, we investigate the Hamiltonicity of the exchanged hypercube [Formula: see text] [Formula: see text]. We further show the conditional edge fault Hamiltonicity of the exchanged hypercube.
Separation and Dynamic Binding Mechanism of 3D Model Animation by Integrating Improved Genetic Algorithm and WebAR
Authors: Yang Shu , Lin Wei
Published: December 2024

With the development of the economy, the demand for 3D model animation in fields such as games, film and television, and education is constantly increasing. At present, many 3D model animations are built based on genetic algorithm. However, due to the slow convergence speed and poor local search ability of genetic algorithm, this model still has many shortcomings. Therefore, a cellular automaton is used to optimize the genetic algorithm, and a cellular genetic algorithm is proposed. It is integrated with WebAR technology, which has the characteristics of lightweight and low cost, aiming to improve the separation and dynamic binding mechanism of 3D model animation. Experimental analysis showed that when the number of chromosome genes was 90, the vertex gene value of the research algorithm was the highest, ranging from 281 to 501, and the convergence was the highest. The file size of the model dataset based on the research method was reduced by 50% compared with before. The FPDT based on the animation separation and dynamic binding mechanism was decreased by 15.2 s on average. To sum up, it can be seen that the designed 3D model animation is more detailed and the animation dynamic is also the best. This research method can significantly improve the separation and dynamic binding mechanism of 3D model animation. This research will improve the integration of genetic algorithm and WebAR technology, which can not only effectively deal with complex 3D models and animations, but also has broad application prospects.
The Pannonian Stage: stratigraphy and geoenergy resources
Authors: Magyar Imre , Botka Dániel , Katona Lajos , Harangi Szabolcs , Lukács Réka , Šujan Michal
Published: December 2024

The youngest regional chronostratigraphic unit of the Central Paratethys, the Pannonian Stage, is benchmarked by the deposits of Lake Pannon, containing a highly endemic, Caspian-type biota, and the sediments of adjacent deltas and fluvial plains. The Pannonian Stage also includes various freshwater lake deposits and vast volcanic formations, especially in the northern and eastern margins of the Pannonian Basin system. The Pannonian correlates with the Tortonian, Messinian, Zanclean and Piacenzian Stages, thus representing 9 Myr between 11.6 and 2.6 Ma. The Pannonian is divided into biochronostratigraphic units by the application of mollusc and dinoflagellate biochronozones in the Lake Pannon deposits and mammal biozones in the freshwater sediments. The Pannonian Stage is a leading geoenergy provider in terms of hydrocarbons and lignite. Prolific oil and gas reservoirs occur in both the deep-water and deltaic sand bodies in the central part of the Pannonian Basin, which is a highly mature exploration area. The practically inexhaustible lignite resource of the Pannonian Stage has been mined or is still being mined in the basin margins in all ten countries of the Pannonian Basin system.
Towards Automated Model Design on Recommender Systems
Authors: Zhang Tunhou , Cheng Dehua , He Yuchen , Chen Zhengxing , Dai Xiaoliang , Xiong Liang , Liu Yudong , Cheng Feng , Cao Yufan , Yan Feng , Li Hai , Chen Yiran , Wen Wei
Published: December 2024

The increasing popularity of deep learning models has created new opportunities for developing AI-based recommender systems. Designing recommender systems using deep neural networks requires careful architecture design, and further optimization demands extensive co-design efforts on jointly optimizing model architecture and hardware. Design automation, such as Automated Machine Learning (AutoML), is necessary to fully exploit the potential of recommender model design, including model choices and model-hardware co-design strategies. We introduce a novel paradigm that utilizes weight sharing to explore abundant solution spaces. Our paradigm creates a large supernet to search for optimal architectures and co-design strategies to address the challenges of data multi-modality and heterogeneity in the recommendation domain. From a model perspective, the supernet includes a variety of operators, dense connectivity, and dimension search options. From a co-design perspective, it encompasses versatile Processing-In-Memory (PIM) configurations to produce hardware-efficient models. Our solution space’s scale, heterogeneity, and complexity pose several challenges, which we address by proposing various techniques for training and evaluating the supernet. Our crafted models show promising results on three Click-Through Rates (CTR) prediction benchmarks, outperforming both manually designed and AutoML-crafted models with state-of-the-art performance when focusing solely on architecture search. From a co-design perspective, we achieve 2 × FLOPs efficiency, 1.8 × energy efficiency, and 1.5 × performance improvements in recommender models.
What Could Possibly Go Wrong: Undesirable Patterns in Collective Development
Authors: Evtikhiev Mikhail , Koshchenko Ekaterina , Kovalenko Vladimir
Published: December 2024

Software development, often perceived as a technical endeavor, is fundamentally a social activity requiring collaboration among team members. Acknowledging this, the software development community has devised strategies to address possible collaboration-related shortcomings. Various studies have attempted to capture the social dynamics within software engineering. These studies developed methods to identify numerous teamwork issues and proposed various approaches to address them. However, there is a need for a comprehensive bottom-up exploration from practitioner’s perceptions to common patterns. This article introduces the concept of undesirable patterns in collective development, referring to potential teamwork problems that may escalate if unaddressed. Through 38 in-depth exploratory interviews, we identify and classify 42 patterns, revealing their origins and consequences. To the best of our knowledge, some patterns, like
Teamwork pipeline bottleneck
, were never reported before. Subsequent surveys, 436 and 968 participants each, explore the significance and frequency of the undesirable patterns and evaluate potential tools and features to manage these patterns. The study contributes a nuanced understanding of undesirable patterns, evaluating their impact and proposing pragmatic tools and features for industrial application. The findings provide a valuable foundation for further in-depth studies and the development of tools to enhance collaborative software engineering practices.
Towards Improving the Efficiency of Drug Repurposing by Leveraging Node Promiscuity in Biomedical Knowledge Graphs
Authors: Korn Daniel , Hou Pei-Yu , Schatz Kara , Beasley Jon-Michael , Tropsha Alexander , Chirkova Rada
Published: December 2024

To accelerate the time- and labor-intensive processes of drug discovery and repurposing, it is increasingly common to mine knowledge sources for connections between diseases and the drugs that can treat them. In this article we address the scalability challenge in the connection mining, by introducing algorithms that can be used to find plausible mechanistic connections between drugs and the potentially associated diseases in biomedical knowledge graphs. These connections are then presented to biomedical experts as candidate hypotheses for further studies of whether the drugs can be repurposed to treat the diseases.

One challenge that has to be addressed in this effort is the processing of
promiscuous
knowledge-graph nodes, that is, nodes associated with numerous relationships that may not be unique or indicative of the node properties. As it turns out, the multiplicity of relationships involving promiscuous graph nodes may prevent the aforementioned path-finding algorithms from aiding in drug repurposing. To address the promiscuous-node challenge, we introduce
promiscuity scores
for nodes and paths in knowledge graphs, and incorporate the scores in the proposed path-finding algorithms. We report experimental results that indicate that paths with low-promiscuity scores could be meaningful and of interest to biomedical experts in drug repurposing.
Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity
Authors: Sowton Alice P. , Holzner Lorenz M. W. , Krause Fynn N. , Baxter Ruby , Mocciaro Gabriele , Krzyzanska Dominika K. , Minnion Magdalena , O’Brien Katie A. , Harrop Matthew C. , Darwin Paula M. , Thackray Benjamin D. , Vacca Michele , Feelisch Martin , Griffin Julian L. , Murray Andrew J.
Published: December 2024

Inorganic nitrate has been suggested to be of therapeutic benefit in obesity-related conditions, as it increases nitric oxide bioavailability, enhances mitochondrial β-oxidation, and reverses metabolic syndrome in eNOS−/− mice. However, we here show that over 12 months nitrate was ineffective in preventing metabolic consequences in high fat, high sucrose-fed mice and worsened aspects of metabolic health, impairing cholesterol handling, increasing cardiac fibrosis, and exacerbating steatotic liver disease progression, with acceleration to hepatocellular carcinoma.
Spatial Distribution Patterns of Pleural Dissemination in Patients With Thymoma and Survival Analysis
Authors: Chang Hao , Li Gaiyan , He Dongjie , Zhu Siying , Jing Yong , Liu Honggang , Li Junting , Wu Peiwen , Shao Qiuju
Published: December 2024

Background: Thymoma is a common malignancy with low incidence, and pleural metastases are common pattern of recurrence. It is necessary that the spatial location of pleural metastatic lesions be analyzed. This study aimed to analyze the spatial distribution patterns of pleural dissemination in patients with thymoma and evaluate the variables that influence the survival of pleural metastasis in this population.

Methods: This retrospective study investigated hospital admissions of patients diagnosed with pleural metastasis from thymoma. The spatial distribution pattern and visualization of the pleural metastases were analyzed after establishing a coordinate system. We further analyzed the survival and influencing factors in patients with pleural metastases from thymoma.

Results: The analysis included 56 patients with a cumulative count of 365 pleural metastases, with 351 metastases from Zones 1–5 finally included in the analysis. The spatial distribution of the 285 initially diagnosed pleural metastases was significantly concentrated in Zones 3 and 4 near the lateral half of the spine (56.5%), followed by Zone 5 (17.5%). Collectively, these two components accounted for 74.0% (211/285) of all initial metastatic lesions. The survival rates at 5 years for those who underwent surgery versus nonsurgical treatment were 68.3% and 37.1%, respectively (p = 0.015). Univariate Cox regression analysis showed that surgical intervention reduced the risk of death by 61%.

Conclusions: The distribution of pleural metastatic lesions exhibited a nonuniform pattern, primarily concentrated on the spinal aspect below the aortic arch of the costal pleura and the spinal aspect of the diaphragmatic pleura.
Giant Gastric Trichobezoar: Unveiling the Complexity of a 14‐Year‐Old’s Abdominal Pain
Authors: Iqbal Aiza , Faraz Fatima , Bano Bazigha , Atta Alishba , Azeem Ayesha , Shahzad Faizan , Jabeen Nimrah , Shami Besher
Published: December 2024

Trichobezoars are accumulations of undigested hair. Usually, this disorder follows a psychiatric etiology; however, sometimes a nonpsychiatric etiology, such as pica, can also be suspected. Rapunzel syndrome is a rare type of trichobezoar in which the hair is usually confined to the stomach and small intestine. The authors present a rare case of trichobezoar in a young female without any psychiatric symptoms. Trichobezoar results in nonspecific GI symptoms and this causes delays in its diagnosis. It should always be considered a differential in a young female with nonspecific GI symptoms, especially in those with evidence of iron deficiency anemia.
Care Convoys and Solitary Vessels: Navigating Family Care for Older Adults Living With Dementia in Arctic Norway
Authors: Blix Bodil H. , Ågotnes Gudmund
Published: December 2024

Drawing on the metaphor of “care convoys,” this study explores the experiences and strategies of family caregivers of older adults with dementia in rural areas of Northern Norway. The study is part of a broader project that investigates how these older adults and their caregivers use or do not use municipal health and care services. We conducted qualitative in‐depth interviews with 11 family caregivers in rural municipalities. The thematic analysis of the interview data yielded three main themes: Delaying the transition to long‐term care amid evolving needs, facilitating knowledge transition, and navigating divergent expectations about involvement. In addition, a fourth theme, caregiving in the rural Arctic, was identified as cross‐cutting, reflecting the unique rural Arctic context that was a backdrop across all themes. In navigating the caregiving journey, family caregivers assume various roles within care convoys. They may act as solitary vessels, as an integral part of a larger care convoy, or as the main ship guiding the convoy. At times, family caregivers serve as vessels called upon by the convoy when needed. Difficulties in assembling an adequate or robust care convoy were exacerbated by the context of the Artic North, which represents treacherous waters for the convoy to navigate, primarily due to two factors: first, many of the smaller ships (other family members) were not present or had to travel great distances to join the convoy and second, the lengthy journeys (long travel distances), and particularly in the winter time, made the convoys susceptible to loosing ships along the way.
Exogenous Application of Oxidized Glutathione During the Seedling Stage Promotes Root Growth After Transplantation and Potentially Increases Panicles in Rice
Authors: Mohri Taku , Uekita Ken , Saito Hiroshi , Shiraiwa Tatsuhiko , Nojiri Masutoshi
Published: December 2024

Various stresses, such as transplanting damage, inhibit the initial growth of rice (Oryza sativa) seedlings to varying extents. Oxidized glutathione (GSSG) is involved in stress responses and metabolic activation in plants. In this study, we performed three experiments that investigated whether GSSG application affects root development in seedlings following transplanting and the number of panicles at maturity. In Experiment 1, “Koshihikari” seedlings were cultivated in a nursery bed and received 4 mM GSSG, ammonium sulfate, or amino acids, or left untreated 1 week before transplanting. In Experiment 2, “Koshihikari” and “Akitakomachi” seedlings received either 4 or 12 mM GSSG. Finally, in Experiment 3, “Haenuki” seedlings received 4 mM GSSG. In Experiment 1, the number of emerging roots and total root surface area in the 4 mM GSSG group were higher than those in the ammonium sulfate group, whereas the aboveground plant growth did not differ between treatments. In Experiment 2, the number of panicles of “Koshihikari” treated with GSSG increased by 10% compared to the control. Similar results were obtained for “Akitakomachi,” with a 4%–26% increase in panicle number. In Experiment 3, the number of emerging roots and tillers in the 4 mM GSSG group were higher than those in the control group. GSSG application had no negative effects on plant performance, indicating that GSSG application at the seedling stage can promote the emergence of crown roots after transplanting, which contributes to an increase in panicle number.
Inclusion of Inverse Terms in Design of Experiments for Mixtures Applied to Wood Plastic Composites
Authors: Cruz-Salgado Javier , Romero Sergio Alonso , Ruelas-Santoyo Edgar Augusto , Jiménez-García José Alfredo , López Roxana Zaricell Bautista
Published: December 2024

Wood–plastic composites (WPCs) are materials that combine a polymeric phase with a filler, typically wood powder or fiber. This common practice significantly enhances certain mechanical properties of WPCs, such as tensile, compressive, and flexural strength, especially when coupling agents are added. Polyethylene terephthalate (PET) is a thermoplastic commonly used due to its high stiffness, mechanical strength, and chemical resistance. However, the increasing demand for PET has led to a rise in plastic waste accumulation, posing an environmental challenge. Therefore, recycling and promoting a circular economy are considered key strategies to reduce environmental impact and achieve sustainable development. The main challenge in WPC production lies in its formulation—specifically, determining the appropriate proportion of thermoplastic polymer, wood filler, and coupling agent. To optimize the mechanical properties of WPCs, it is necessary to vary these component proportions and understand how these changes affect the composite properties. This article describes a statistical approach for optimizing the mechanical properties of a WPC with PET as the polymer matrix. It is assumed that the mechanical properties of the WPC are a function of the proportions of the components that make up the mixture, so the optimization consists of determining these proportions in a way that maximizes the mechanical properties. With the experimental design, three models with inverse terms were fitted, which modeled the relationship between the component proportions and the flexural, compression, and tensile strength. The optimal formulation for maximizing flexural strength was found to be 58% PET, 39% wood, and 3% E‐GMA. The optimal formulation for maximizing compressive strength was found to be 58% PET, 40% wood, and 2% E‐GMA. The optimal formulation for maximizing tensile strength was found to be 86% PET, 11% wood, and 3% E‐GMA. The results are validated through analysis of variance of the mixture experimental design for mixtures. Finally, three response surface plots are presented for each mechanical property, which graphically describe the relationship between the different proportions of the mixture components and the mechanical properties.
Indigenous Knowledge, Habitat, and Nest Characterization of Stingless Bee (Meliponula beccarii) in West Arsi Zone of Oromia, Ethiopia
Authors: Beyene Taye , Woldetsadik Mekonen , Abi Desta , Ararso Hora Zewdu
Published: December 2024

Stingless bees are eusocial insects that play vital roles as pollinators of many flowering plants and high value products. However, information on their nesting habitats and nest characteristics is scarce in West Arsi Zone of Oromia, Ethiopia. This study was conducted to characterize indigenous knowledge, habitat, and nest of stingless bees. Data were collected using semistructured questionnaire, observations, and ground nest component measurement. The questionnaire survey was administered to 36 stingless bee honey hunters. The study result revealed that the stingless bee honey is considered important in treatment of cough and cold, asthma, tuberculosis, malaria, diabetes, and sore throat. Habitat loss and fragmentation, unwise use of agrochemicals, stingless bee enemies, destructive harvesting methods, lack of improved technologies for meliponiculture, and lack of government attention were the dominant threats to stingless bee hunting in the study area. Ground‐nesting stingless bees’ colonies are affected by several natural enemies, including ants, honey badgers, wasps, termites, snakes, and foxes. The eight nests of Meliponula beccarii (M. beccarii) were found under the ground at an average depth of 54.38 ± 17.25 cm in three different soil types. The nests of M. beccarii were protected with an average of 6.42 ± 2.82 guard bees/nest entrance that ranges from 2 to 9/colony. Moreover, the average value of honey volume per pot and per nest of M. beccarii was 20.38 ± 6.88 mL and 1.24 ± 427.28 L, respectively. The similarity of nesting substrates, nest architecture, and nesting environment with stingless bees in other regions and the unique indigenous knowledge of stingless bee honey hunters in the area aid in the direct adoption of stingless bee technologies to rescue the areas’ ever‐decreasing populations. Thus, based on these findings, adopting stingless bee colony domestication technology is critical for maintaining and improving productivity and conserving the species.
Fat‐Free Mass Is Positively Associated With Urine Specific Gravity in Athletes and Active Adults: A Quantitative Review
Authors: Wilson Patrick B. , Winter Ian P.
Published: December 2024

Background: Urine specific gravity (USG) is a commonly used assessment method to estimate the prevalence of hypohydration, typically based on a common threshold of ≥ 1.020. Some research has shown that USG can vary based on body size and composition, but the evidence to date is limited. This review examined whether an association between fat‐free mass (FFM), a component of body composition, and USG could be detected among published articles that have reported these variables in athletes and physically active individuals.

Methods: By searching Google Scholar, the authors identified a large number of published articles (n = 161) reporting anthropometrics and USG. Only articles reporting data on adult samples of athletes or physically active individuals were included. Given differences in body composition and FFM between men and women, articles that did not report data separately for each sex were excluded. Spearman’s rank correlation coefficient (ρ) was used to assess the association between variables.

Results: In men, FFM showed a significant, weak‐sized positive association with USG (ρ = 0.36, p < 0.001). Among women, FFM showed a significant, moderate‐sized positive association with USG (ρ = 0.57, p = 0.006). When results were combined independent of sex, the association between FFM and USG remained significant (ρ = 0.38, p  < 0.001).

Conclusion: Athletes with larger amounts of FFM are more likely to have elevated USG. Protein and muscle metabolites such as creatinine, urea, and uric acid likely play some role in the observed relationships. If USG continues to be utilized in sport settings, more research is needed to determine if development of FFM‐specific USG thresholds may be more appropriate for determining hydration status.
SEMA3G-NRP1 Signaling Functions as an Immune Checkpoint that Enables Tumor Immune Evasion by Impairing T Cell Cytotoxicity
Authors: Chi Hao , Deng Shouyan , Xu Ke , Zhang Yibo , Song Teng , Yu Jianghong , Wang Yiting , Liu Jiayang , Zhang Yuan , Shi Jiawei , Wang Yungang , Xu Jie
Published: December 2024

T cells within the tumor microenvironment frequently exhibit dysfunctional characteristics that compromise their ability to elicit both innate and therapeutic-induced immune responses. Regulators of immune dysfunction represent therapeutic targets to activate anti-tumor immunity. In this study, we identified semaphorin 3G (SEMA3G) as a key regulator of immune responses in cancer. SEMA3G was widely upregulated in diverse human cancers, and its expression was positively correlated with tumor progression. SEMA3G acted as a ligand that inhibited the activation and functionality of T cells. A comprehensive receptor screening approach demonstrated that SEMA3G exhibited a significantly stronger affinity for neuropilin NRP1 compared to NRP2. Furthermore, SEMA3G primarily impeded T-cell functions via NRP1. Disruption of SEMA3G using CRISPR/Cas9 technology or blockade with a neutralizing antibody effectively restored the cytotoxicity of CD8+ T cells and inhibited the growth of tumors in vivo. This research underscores the role of SEMA3G in T-cell dysfunction within tumors and proposes a targeting SEMA3G as a cancer immunotherapeutic strategy.
Abstract A004: Broad and synergistic anti-tumor effects of small-molecule inhibitors of hypoxia inducible factors when paired with immune checkpoint blockade
Authors: Salman Shaima , Huang Tina Y. , Hwang Yousang , Kumar Anmol , Dordai Dominic , MacKerell Alexander D. , Semenza Gregg L.
Published: December 2024

Motivation: Hypoxia inducible factors (HIFs) are critical transcriptional regulators that play fundamental roles in adaptive responses to low oxygen, both in normal and disease conditions. Dysregulated activation of HIFs has been implicated in a variety of cancers due to their role in mediating a broad range of key processes including angiogenesis, glycolysis, cell survival, cancer stem cell specification, and metastasis. Methods: In this study, we utilized virtual and cell-based high-throughput screening approaches to identify compounds that disrupt the binding of HIF-1α and HIF-2α to HIF-1β, leading to the suppression of HIF target gene expression. Results: In syngeneic animal models, we observed significant tumor regression when HIF inhibitors are combined with immunotherapy agents in multiple tumor models. The combined treatment enhanced the infiltration of natural killer (NK) cells into the tumor microenvironment. Conclusion: This study highlights the anti-tumor effects of HIF inhibitors and the immune response resulting in sustained tumor regression. The promising outcomes warrant further exploration of these inhibitors as potential cancer treatment agents.

Citation Format: Shaima Salman, Tina Y. Huang, Yousang Hwang, Anmol Kumar, Dominic Dordai, Alexander D. MacKerell, Gregg L. Semenza. Broad and synergistic anti-tumor effects of small-molecule inhibitors of hypoxia inducible factors when paired with immune checkpoint blockade [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A004.
Abstract A022: Discovery of conformationally constrained ALK2 inhibitors for the treatment of Diffuse Intrinsic Pontine Glioma (DIPG)
Authors: Smil David , González-Álvarez Héctor , Ensan Deeba , Wong Jong Fu , Cros Julien , Hoffer Laurent , Kiyota Taira , Wilson Brian J. , Zepeda-Velázquez Carlos A. , Aman Ahmed , Isaac Methvin B. , Xin Tao , Bullock Alex N. , Sampson Peter B. , Al-awar Rima
Published: December 2024

Despite considerable research on new therapeutics to treat DIPG, a universally fatal grade IV pediatric CNS tumor located in the pons region of the brainstem, there has been minimal progress. Somatic missense mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1 gene encoding activin receptor-like kinase-2 (ALK2) are present in approximately 33% of children with DIPG, prompting our initial efforts towards the development of M4K2009, a 3,5-diphenylpyridine ALK2 inhibitor. Looking to improve potency, selectivity, and brain penetration, we subsequently designed, synthesized, and evaluated a first-in-class set of 5- to 7-member ether-linked and 7-member amine-linked conformationally constrained ALK2 inhibitors including M4K2308, M4K2281, M4K2304 and M4K2306. Overall, these new compounds are highly potent (ALK2 IC50 < 10 nM, nanoBRET ALK2 IC50 < 20 nM), selective (>100-fold over ALK5), brain-penetrant (Cbrain,4h/Cplasma,4h > 3, 10 mg/kg, NOD-SCID male mice) and show in vivo exposure (Cplasma,6h = 1−2 µM, 25 mg/kg, NOD-SCID male mice). In particular, M4K2308 displayed a good balance of potency and DMPK properties and is currently undergoing preclinical evaluation by M4K Pharma.

Citation Format: David Smil, Héctor González-Álvarez, Deeba Ensan, Jong Fu Wong, Julien Cros, Laurent Hoffer, Taira Kiyota, Brian J. Wilson, Carlos A. Zepeda-Velázquez, Ahmed Aman, Methvin B. Isaac, Tao Xin, Alex N. Bullock, Peter B. Sampson, Rima Al-awar. Discovery of conformationally constrained ALK2 inhibitors for the treatment of Diffuse Intrinsic Pontine Glioma (DIPG) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Optimizing Therapeutic Efficacy and Tolerability through Cancer Chemistry; 2024 Dec 9-11; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(12_Suppl):Abstract nr A022.
The Crossroads of Clonal Evolution, Differentiation Hierarchy, and Ontogeny in Leukemia Development
Authors: Sturgeon Christopher M. , Wagenblast Elvin , Izzo Franco , Papapetrou Eirini P.
Published: December 2024

Transformative technologies to sequence tumor genomes at large scale and single-cell resolution have exposed the repertoire of genetic alterations that are present in leukemia genomes, the timing of their acquisition, and patterns of their co-occurrence. In parallel, single-cell multiomics technologies are allowing us to map the differentiation paths and hierarchical structures of malignant cells and giving us a glimpse into hematopoietic development in prenatal life. We propose that interrogating how the genetic evolution, differentiation hierarchy, and ontogeny of malignant myeloid cells intersect with each other, using new experimental systems and multimodal technologies, will fuel the next generation of research breakthroughs.

Significance:

In recent years, remarkable technological advances have illuminated aspects of the pathogenesis of myeloid malignancies—yet outcomes for patients with these devastating diseases have not significantly improved. We posit that a synthesized view of the three dimensions through which hematopoietic cells transit during their healthy and diseased life—clonal evolution, stem cell hierarchy, and ontogeny—promises high yields in new insights into disease pathogenesis and new therapeutic avenues.
Low-Grade Adenosquamous Carcinoma of the Breast: A Case Report
Authors: Ogawa Rikako , Sugiura Hiroshi , Hato Yukari , Kawahara Hikaru , Shiraki Norio , Ito Yukashi , Ando Yoshiaki , Ishikawa Misao
Published: December 2024

Introduction: Low-grade adenosquamous carcinoma (LGASC) is categorized as a metaplastic carcinoma but differs from other types of metaplastic carcinoma in having a more favorable prognosis. Due to its rarity and unusual and inconsistent presentation, there is little information available regarding its characteristics, making correct diagnosis a challenge. Case Presentation: We report herein the case of a 54-year-old Japanese woman who presented with a lump in her left breast. She was found to have a benign lesion which continually relapsed, necessitating repeated excisions, ultimately leading to the diagnosis of LGASC after the third excision. Guidelines for the treatment of LGASC emphasize complete tumor excision, with adjuvant therapies only considered in cases with positive lymph node metastasis. Consequently, the patient underwent total mastectomy but postoperative chemotherapy was not administered, and the patient was followed up with regular observation. By 20 months postoperatively, there was no sign of recurrence. Conclusion: LGASC has distinctive pathological features of the intimate admixture of well-developed glands and solid squamous cell nests within a fibrotic or cellular spindle stroma. It is difficult to determine preoperatively with cytology or needle biopsy because LGASC mimics benign tumors. It is typically triple-negative, but it has an indolent behavior. Adjuvant therapy after surgery is considered unnecessary for triple-negative status, but there is no clear evidence. We aimed to provide more data on the disease characteristics, presentation, and treatment outcome. Accumulation of further evidence is warranted to refine diagnostic and therapeutic strategies of LGASC.
Diagnostic yield and complications of ultrasoundguided trans-thoracic biopsies by pulmonologists: a single-centre retrospective study of lesions with pleural contact
Authors: Lovato Jean-Baptiste , Amari Lyria , Tronchetti Julie , Coiffard Benjamin , Laroumagne Sophie , Astoul Philippe , Dutau Hervé
Published: December 2024

Introduction
Ultrasound-guided trans-thoracic needle biopsy (US-TTNB) is a method of choice for the diagnostic management of peripheral lung lesions and pleural masses for pulmonologists. If complication risk factors and diagnostic yield have been well reported for CT-guided biopsies, publications for US-TTNB in this field are very scarce.

Methods
The primary objective of this study was to describe the diagnostic yield of US-TTNB carried out by pulmonologists defined by a definitive histopathological diagnosis
Secondary objectives were to identify factors that may influence diagnostic yield and to describe complications of this procedure.
Between September 2015 and December 2022, charts of consecutive patients presenting peripheral lesion with pleural contact and having undergone US-TTNB were retrospectively analyses.
ROC curves were performed to assess the probability of having a contributing biopsy (definitive histology) depending on scannographic measurements and the number of punctures. Univariate and then multivariate analysis were performed to look for variables associated with complications.

Results
One hundred and fifty nine patients were enrolled in this study. Among them, diagnosis was obtained for 140 patients (88% success rate). The histology was in favor of a neoplastic process in 96% of cases (135/140). Analysis of the ROC curves showed that the depth of the lesion (AUC 75%; CI95% 65-85; cut-off 3.0cm), the width of the lesion (AUC 73%; CI95% 63-86; cut-off 3.9cm), the pleural contact (AUC 68%; CI95% 57-80; cut-off 3.8cm) and the number of biopsies (AUC 70%; CI95% 59-81; cut-off 3 biopsies) were the variables associated with diagnostic yield.
Complications occurred for 27 patients (17%) mainly pneumothorax (6%), hemoptysis (6%), and sepsis (6%)
Univariate analysis showed a significant association between pneumothorax and lesion depth (OR 0.68; 95% CI 0.65-0.92; p = 0.03) with a predicted probability > 5% for a depth < 4cm according to general linear model analysis. Univariate and multivariate analysis revealed a significant association between the number of biopsies and the risk of sepsis (OR 1.90; 95% CI 1.19-3.26; p = 0.01) with a predicted probability > 5% for more than 4 biopsies.

Conclusion
US-TTNB is a reliable diagnostic procedure that can be performed by pulmonologists. The depth, width, pleural contact of the lesion and the number of biopsies are key variables associated with diagnostic yield. The depth of the lesion is associated with the risk of pneumothorax, and the number of biopsies with the risk of pulmonary sepsis.
A Novel Premature Termination Codon Mutation in TRAPPC2 is associated with X-linked Spondyloepiphyseal Dysplasia Tarda
Authors: Yasar Deniz , Güleray Lafcı Naz , Karacan Küçükali Gülin , Araslı Yılmaz Aslıhan , Özkaya Dönmez Beyhan , Yazar Burak Tahir , Uçan Berna , Okur İclal , Sarıkaya Özdemir Behiye , Kurnaz Erdal , Keskin Meliksah , Savaş Erdeve Şenay
Published: December 2024

Introduction: Spondyloepiphyseal dysplasia tarda (SEDT) is an inherited disorder that is typically diagnosed in childhood or adolescence. It is characterized by disproportionate short stature and premature osteoarthritis, and it frequently affects males. Here, we described a novel nonsense mutation, c.406A>T; p(Lys136Ter), in TRAPPC2 (NM_001011658.4) in a Turkish patient with X-linked SEDT.

Case Presentation: A 15-year-old boy, born to non-consanguineous Turkish parents, exhibited a decline in height velocity over three years and complained of back pain despite minimal physical activity. Growth and development were normal until adolescence, with the patient's weight at 35 kg (SDS -3.85), height at 134 cm (SDS -5.44), and a predicted adult height of 137.6 cm. Dysmorphic facial features, microtia, synophrys, hypotelorism, and barrel chest were noted. Radiological examination revealed osteopenic bone structure, hypoplastic odontoid process, platyspondyly, scoliosis, short femoral necks, and coxa vara. Genetic analysis identified a hemizygous novel stop codon mutation (c.406A>T; pLys136Ter) in TRAPPC2, also detected as heterozygous in the patient's mother.

Conclusion: In adolescence or childhood, X-linked SEDT should be considered in cases of disproportionate short stature, short trunk, osteoarthritis, and a family history that is appropriate for X-linked inheritance. Skeletal survey should be performed to suspect to SEDT and radiological findings may be supported to diagnosis.