bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing Indoor Temperature Forecasting through Synthetic Data in Low-Data Regime
Authors: Ruocco Massimiliano , Thiry Zachari , Nocente Alessandro , Spitieris Michail
Published: June 2024

Forecasting indoor temperatures is of paramount importance to achieve efficient control of HVAC systems. In this task, the limited data availability presents a challenge as most of the available data is acquired during standard operation where extreme scenarios and transitory regimes such as major temperature increases or decreases are de-facto excluded. Acquisition of such data requires significant energy consumption and a dedicated facility, hindering the quantity and diversity of available data. To acquire such data, we make use of such a facility referred to as the Test-cell. Cost related constraints however do not allow for continuous year-around acquisition.To address this, we investigate the efficacy of data augmentation techniques, particularly leveraging state-of-the-art AI-based methods for synthetic data generation. Inspired by practical and experimental motivations, we explore fusion strategies of real and synthetic data to improve forecasting models. This approach alleviates the need for continuously acquiring extensive time series data, especially in contexts involving repetitive heating and cooling cycles in buildings. Our evaluation methodology for synthetic data synthesis involves a dual-focused approach: firstly, we assess the performance of synthetic data generators independently, particularly focusing on SoTA AI-based methods; secondly, we measure the utility of incorporating synthetically augmented data in a subsequent downstream tasks (forecasting). In the forecasting tasks, we employ a simple model in two distinct scenarios: 1) we first examine an augmentation technique that combines real and synthetically generated data to expand the training dataset, 2) Second, we delve into utilizing synthetic data to tackle dataset imbalances. Our results highlight the potential of synthetic data augmentation in enhancing forecasting accuracy while mitigating training variance. Through empirical experiments, we show significant improvements achievable by integrating synthetic data, thereby paving the way for more robust forecasting models in low-data regime.
Exploring demonstration pre-training with improved Deep Q-learning
Authors: Pettersson Max , Westphal Florian , Riveiro Maria
Published: June 2024

This study explores the effects of incorporating demonstrations as pre-training of an improved Deep Q-Network (DQN). Inspiration is taken from methods such as Deep Q-learning from Demonstrations (DQfD), but instead of retaining the demonstrations throughout the training, the performance and behavioral effects of the policy when using demonstrations solely as pre-training are studied. A comparative experiment is performed on two game environments, Gymnasium's Car Racing and Atari Space Invaders. While demonstration pre-training in Car Racing shows improved learning efficacy, as indicated by higher evaluation and training rewards, these improvements do not show in Space Invaders, where it instead under-performed. This divergence suggests that the nature of a game's reward structure influences the effectiveness of demonstration pre-training. Interestingly, despite less pronounced quantitative differences, qualitative observations suggested distinctive strategic behaviors, notably in target elimination patterns in Space Invaders. These retained behaviors seem to get forgotten during extended training. The results show that we need to investigate further how exploration functions affect the effectiveness of demonstration pre-training, how behaviors can be retained without explicitly making the agent mimic demonstrations, and how non-optimal demonstrations can be incorporated for more stable learning with demonstrations.
The Social Life of Algorithmic Values: Examining the Impact of Value-Based Frameworks in Everyday Life
Authors: Garnham Ignacio , Smith Rachel
Published: June 2024

Value-based frameworks are widely used to guide the design of algorithms, yet their influence in mediating users’ perception and use of algorithm-driven technologies is vastly understudied. Moreover, there is a need to move research beyond a focus on human-algorithm interaction to account for how the values these frameworks promote – algorithmic values – become socialised outside the boundaries of the (human-algorithm) interaction and how they influence everyday practices that are not algorithmically mediated. This paper traces the entanglement of algorithmic values and everyday life by mapping how residents of the Salvadorian town of El Zonte perceive the top-down transition of the town into "Bitcoin Beach" through value-driven transformations to diverse aspects of their material culture and built environment. This approach advances empirical research on the impact of algorithms by acknowledging the myriad ways in which those who won’t or can’t (afford to) interact with algorithm-driven technologies are impacted by the value-based outcomes of their programming and provides novel insights for critically examining the role of algorithm-driven technologies in shaping sustainable futures.
Machine Learning for Lithology Analysis using a Multi-Modal Approach of Integrating XRF and XCT data
Authors: Neelakantan Suraj , Hansson Alexander , Norell Jesper , Schött Johan , Längkvist Martin , Loutfi Amy
Published: June 2024

We explore the use of various machine learning (ML) models for classifying lithologies utilizing data from X-ray fluorescence (XRF) and X-ray computed tomography (XCT). Typically, lithologies are identified over several meters, which restricts the use of ML models due to limited training data. To address this issue, we augment the original interval dataset, where lithologies are marked over extensive sections, into finer segments of 10cm, to produce a high resolution dataset with vastly increased sample size. Additionally, we examine the impact of adjacent lithologies on building a more generalized ML model. We also demonstrate that combining XRF and XCT data leads to an improved classification accuracy compared to using only XRF data, which is the common practice in current studies, or solely relying on XCT data.
The Bias that Lies Beneath: Qualitative Uncovering of Stereotypes in Large Language Models
Authors: Babonnaud William , Delouche Estelle , Lahlouh Mounir
Published: June 2024

The rapid growth of Large Language Models (LLMs), such as ChatGPT and Mistral, has raised concerns about their ability to generate inappropriate, toxic and ethically problematic content. This problem is further amplified by LLMs' tendency to reproduce the prejudices and stereotypes present in their training datasets, which include misinformation, hate speech and other unethical content. Traditional methods of automatic bias detection rely on static datasets that are unable to keep up with society's constantly changing prejudices, and so fail to capture the large diversity of biases, especially implicit associations related to demographic characteristics like gender, ethnicity, nationality, and so on. In addition, these approaches frequently use adversarial techniques that force models to generate harmful language. In response, this study proposes a novel qualitative protocol based on prompting techniques to uncover implicit bias in LLM-generated texts without explicitly asking for prejudicial content. Our protocol focuses on biases associated with gender, sexual orientation, nationality, ethnicity and religion, with the aim of raising awareness of the stereotypes perpetuated by LLMs. We include the Tree of Thoughts technique (ToT) in our protocol, enabling a systematic and strategic examination of internal biases. Through extensive prompting experiments, we demonstrate the effectiveness of the protocol in detecting and assessing various types of stereotypes, thus providing a generic and reproducible methodology. Our results provide important insights for the ethical evaluation of LLMs, which is essential in the current climate of rapid advancement and implementation of generative AI technologies across various industries.Warning: This paper contains explicit statements of offensiveor upsetting contents.
How does it feel? An exploration of teaching perceptive sensoriality in hairdressing education
Authors: Öhman Anna , Klope Eva
Published: June 2024

This study explores vocational didactics and embodied knowledge in hairdressing education by studying how perceptive sensoriality is used by teachers and students in creating shared understandings of vocational knowledge. Among multiple actions, touch is distinguished as a central resource in learning the vocation, as it emerges in interaction between teacher and student related to the ongoing teaching and its assignment. The data is based on video-recordings displaying how touch is used in manipulating objects and material, or in assessing qualities and defects. In such instances, touch becomes a  diagnostic criterion (Goodwin, 1997) to investigate how the material worked with can be evaluated and handled. To bridge the gap between individual and collective vocational knowledge, metaphors are of use. The results show two approaches to the teaching of perceptive sensoriality. In order to learn the vocational subject content the teaching need to provide for and practice the individual’s embodied sense of touch as well as the vocation’s verbalised collective feel. This is the core of the didactical challenge.
Member education in three Finnish parliamentary parties
Authors: Pastuhov Annika
Published: June 2024

This study investigates the purposes and corresponding preconditions of member education practices in three Finnish political parties using the theory of practice architectures. To accomplish this, it examines the educational endeavours of three Finnish parliamentary parties—namely, the Centre Party of Finland (Suomen Keskusta), the National Coalition Party (Kansallinen Kokoomus) and the Social Democratic Party of Finland (Suomen sosiaalidemokraattinen puolue). The study draws on the theory of practice architectures, which provides a framework for examining the arrangements comprising the preconditions underlying practices—that is, purposeful endeavours based on established human courses of action. The research questions addressed in this study are as follows. What are the main purposes of education within the studied political parties? What preconditions enable or constrain the educational practices related to those purposes? The findings reveal that the Centre Party of Finland aims to foster expertise among its entire membership in a consistent and impactful manner, emphasising educational planning and supporting political ambition. Moreover, the National Coalition Party’s political education aims to foster members’ expertise and success, as supported by individualisation, while the Social Democratic Party of Finland’s party-political education focuses on engaging members and renewing the party, which are pursued through offering open educational opportunities and considering both local preconditions and historical knowledge. In conclusion, the identified purposes seek a balance between ensuring equality and supporting hierarchy among the party membership, while the identified preconditions indicate understandings of the political party as either a collective actor or an arena in which individual political actors operate.
EMPREEENDEDORISMO, INOVAÇÃO E GERENCIAMENTO EMPRESARIAL: UM ESTUDO SOBRE UTILIZAÇÃO DE TÉCNICAS E FERRAMENTAS DE GESTÃO EM MICRO E PEQUENAS EMPRESAS DO MUNICÍPIO DE CAMPO MOURÃO.
Authors: Souza Adalberto Dias de
Published: June 2024

Este estudo teve como objetivo realizar um diagnóstico organizacional afim de analisar as práticas gerenciais dos micros e pequenos empreendimentos localizados no município de Campo Mourão, no estado do Paraná, a partir da identificação do grau de utilização de técnicas e ferramentas de apoio à gestão empresarial pelos empreendedores. Para atingir esse objetivo, foi adotada uma abordagem exploratória e descritiva. A operacionalização da pesquisa foi desenvolvida, inicialmente, por meio de um levantamento bibliográfico abrangente, tendo como base, artigos, dissertações, teses e livros sobre os temas de empreendedorismo, gerenciamento empresarial e inovação, para dar suporte ao estudo. Posteriormente, foi conduzido um levantamento empírico por meio de pesquisa do tipo survey por meio de um formulário eletrônico no aplicativo Google Forms. A amostra da pesquisa foi composta por 11 empresas de micro e pequeno porte, selecionadas de forma probabilista, aleatória e por conveniência. A partir das respostas obtidas pelo questionário, foram realizadas observações e análise dos registros de informações e dados da organização. Os resultados revelam, inicialmente, que os empreendedores tendem a utilizar predominantemente ferramentas e técnicas de gestão na área financeira, de compras, recursos humanos e mercadológica. Foi verificado que entre as 11 empresas objetos de estudo, 10 deles utilizam pelo menos uma ferramenta para o gerenciamento destas áreas, contudo ainda há limitações. No entanto, a área de inovação e estratégia demonstraram limitações ainda mais significativas, onde 45,4% das empresas objetos de estudo não utilizam nenhum tipo de instrumento de apoio para o gerenciamento destas áreas, evidenciando uma alta deficiência. Esses resultados apontam para um grande desafio a ser superado pelos empreendedores na condução da gestão de seus negócios, no tocante as práticas gerencias de inovação e estratégia, destacando a necessidade de investimento em capacitação e desenvolvimento dessas áreas, que, hoje, são fatores determinantes para o crescimento e o desempenho empresarial em meio a um mercado cada vez mais competitivo.
Addressing data imbalance in Sim2Real: ImbalSim2Real scheme and its application in finger joint stiffness self-sensing for soft robot-assisted rehabilitation
Authors: Zhou Zhongchao , Lu Yuxi , Tortós Pablo Enrique , Qin Ruian , Kokubu Shota , Matsunaga Fuko , Xie Qiaolian , Yu Wenwei
Published: June 2024

The simulation-to-reality (sim2real) problem is a common issue when deploying simulation-trained models to real-world scenarios, especially given the extremely high imbalance between simulation and real-world data (scarce real-world data). Although the cycle-consistent generative adversarial network (CycleGAN) has demonstrated promise in addressing some sim2real issues, it encounters limitations in situations of data imbalance due to the lower capacity of the discriminator and the indeterminacy of learned sim2real mapping. To overcome such problems, we proposed the imbalanced Sim2Real scheme (ImbalSim2Real). Differing from CycleGAN, the ImbalSim2Real scheme segments the dataset into paired and unpaired data for two-fold training. The unpaired data incorporated discriminator-enhanced samples to further squash the solution space of the discriminator, for enhancing the discriminator’s ability. For paired data, a term targeted regression loss was integrated to ensure specific and quantitative mapping and further minimize the solution space of the generator. The ImbalSim2Real scheme was validated through numerical experiments, demonstrating its superiority over conventional sim2real methods. In addition, as an application of the proposed ImbalSim2Real scheme, we designed a finger joint stiffness self-sensing framework, where the validation loss for estimating real-world finger joint stiffness was reduced by roughly 41% compared to the supervised learning method that was trained with scarce real-world data and by 56% relative to the CycleGAN trained with the imbalanced dataset. Our proposed scheme and framework have potential applicability to bio-signal estimation when facing an imbalanced sim2real problem.
Epigenetic determinants of fusion-driven sarcomas: paradigms and challenges
Authors: Stanton Benjamin Z. , Pomella Silvia
Published: June 2024

We describe exciting recent advances in fusion-driven sarcoma etiology, from an epigenetics perspective. By exploring the current state of the field, we identify and describe the central mechanisms that determine sarcomagenesis. Further, we discuss seminal studies in translational genomics, which enabled epigenetic characterization of fusion-driven sarcomas. Important context for epigenetic mechanisms include, but are not limited to, cell cycle and metabolism, core regulatory circuitry, 3-dimensional chromatin architectural dysregulation, integration with ATP-dependent chromatin remodeling, and translational animal modeling. Paradoxically, while the genetic requirements for oncogenic transformation are highly specific for the fusion partners, the epigenetic mechanisms we as a community have uncovered are categorically very broad. This dichotomy prompts the question of whether the investigation of rare disease epigenomics should prioritize studying individual cell populations, thereby examining whether the mechanisms of chromatin dysregulation are specific to a particular tumor. We review recent advances focusing on rhabdomyosarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, undifferentiated round cell sarcoma, Ewing sarcoma, myxoid/round liposarcoma, epithelioid hemangioendothelioma and desmoplastic round cell tumor. The growing number of groundbreaking discoveries in the field, motivated us to anticipate further exciting advances in the area of mechanistic epigenomics and direct targeting of fusion transcription factors in the years ahead.
A causal reasoning approach for power transformer failure diagnosis
Authors: Jiao Fei , Ma Zhenyuan , Chen Qikun , Zhang Fengda , Zhao Dezong
Published: June 2024

Extensive research validates the effectiveness of employing Dissolved Gas Analysis (DGA) for diagnosing electric power transformer failures. However, a significant portion of existing research focuses on static data for classifying failure types, lacking a thorough exploration of causality. This study proposes an approach integrating causality and the DGA framework to infer power transformer failures. Validation through 96 historical samples from diverse transformers demonstrates the capability of this method to identify probable abnormal failures of the power transformer accurately. The proposed causal reasoning method is able to diagnose all common transformer states, accounting for the level of severity in both electrical and thermal failures, and with an accuracy of 95.8%.
Unlocking the potential of pyroptosis in tumor immunotherapy: a new horizon in cancer treatment
Authors: Yin Qinan , Song Si-Yuan , Bian Yuan , Wang Yiping , Deng Anchen , Lv Jianzhen , Wang Yi
Published: June 2024

Background

The interaction between pyroptosis—a form of programmed cell death—and tumor immunity represents a burgeoning field of interest. Pyroptosis exhibits a dual role in cancer: it can both promote tumor development and counteract it by activating immune responses that inhibit tumor evasion and encourage cell death. Current tumor immunotherapy strategies, notably CAR-T cell therapy and immune checkpoint inhibitors (ICIs), alongside the potential of certain traditional Chinese medicinal compounds, highlight the intricate relationship between pyroptosis and cancer immunity. As research delves deeper into pyroptosis mechanisms within tumor therapy, its application in enhancing tumor immune responses emerges as a novel research avenue.

Purpose

This review aims to elucidate the mechanisms underlying pyroptosis, its impact on tumor biology, and the advancements in tumor immunotherapy research.

Methods

A comprehensive literature review was conducted across PubMed, Embase, CNKI, and Wanfang Database from the inception of the study until August 22, 2023. The search employed keywords such as “pyroptosis”, “cancer”, “tumor”, “mechanism”, “immunity”, “gasdermin”, “ICB”, “CAR-T”, “PD-1”, “PD-L1”, “herbal medicine”, “botanical medicine”, “Chinese medicine”, “traditional Chinese medicine”, “immunotherapy”, linked by AND/OR, to capture the latest findings in pyroptosis and tumor immunotherapy.

Results

Pyroptosis is governed by a complex mechanism, with the Gasdermin family playing a pivotal role. While promising for tumor immunotherapy application, research into pyroptosis’s effect on tumor immunity is still evolving. Notably, certain traditional Chinese medicine ingredients have been identified as potential pyroptosis inducers, meriting further exploration.

Conclusion

This review consolidates current knowledge on pyroptosis’s role in tumor immunotherapy. It reveals pyroptosis as a beneficial factor in the immunotherapeutic landscape, suggesting that leveraging pyroptosis for developing novel cancer treatment strategies, including those involving traditional Chinese medicine, represents a forward-looking approach in oncology.
Vaccines for Streptococcus agalactiae: current status and future perspectives
Authors: Pena João Matheus Sobral , Lannes-Costa Pamella Silva , Nagao Prescilla Emy
Published: June 2024

A maternal vaccine to protect newborns against invasive Streptococcus agalactiae infection is a developing medical need. The vaccine should be offered during the third trimester of pregnancy and induce strong immune responses and placental transfer of protective antibodies. Polysaccharide vaccines against S. agalactiae conjugated to protein carriers are in advanced stages of development. Additionally, protein-based vaccines are also in development, showing great promise as they can provide protection regardless of serotype. Furthermore, safety concerns regarding a new vaccine are the main barriers identified. Here, we present vaccines in development and identified safety, cost, and efficacy concerns, especially in high-need, low-income countries.
Incentive diversity is key to the more effective and equitable governance of marine protected areas
Authors: Jones Peter J. S. , Stafford Richard , Hesse Isabel , Khuu Duong T.
Published: June 2024

A target to conserve 30% of oceans by designating marine protected areas (MPAs) has been agreed, yet the effectiveness of existing MPAs is often low, with few weakly implemented restrictions on impacting uses. Drawing on coevolutionary governance and social-ecological systems concepts, we hypothesize that (1) effective governance frameworks for MPAs rely on various combinations of diverse incentives, which encourage people (actors) to behave in a manner that reduces the impacts of their uses and thereby more effectively achieves conservation objectives; (2) effective MPAs will tend to employ a higher diversity of governance incentives, creating resilient MPAs analogous to resilient ecosystems with higher species diversity. This multiple case study empirical analysis of the governance of 50 MPAs supports these hypotheses and demonstrates that: (a) there is strong correlation between the effectiveness of MPAs and the number of governance incentives used; (b) combinations of economic, legal, communication, knowledge and participatory incentives are shown to be employed in effective MPAs and mostly needed in less effective MPAs; (c) whilst some incentives are frequently identified as being important to promote effectiveness, no particular ‘magic wand’ incentive or ‘best practice’ combinations of incentives guarantee this. These findings show that effectiveness is not determined by any specific governance approaches or incentives, but rather the combination of a diversity of functionally integrated incentives, which interact with and support one another to promote MPA effectiveness and resilience, i.e. diversity is the key to resilience, both of species in ecosystems and incentives in governance systems.
Purse-string suture with nylon cords and metal clips for the treatment of duodenal fistulae under the endoscope: a case report
Authors: Wang Lei , Zhang Ruiya , Wang Bochu , Zhou Guoxiong , Zhou Xiaorong , Meng Run
Published: June 2024

Purse-string suture with nylon cords and metal clips under the endoscope is a novel therapeutic technique which is minimally invasive and it is particularly indicated for the closure and repair of gastrointestinal fistula or perforations such as duodenal fistulae. Duodenal fistulae are often caused by medical manipulation, disease progression or trauma. Once this occurs, it leads to a series of pathophysiologic changes and a variety of complications. In most cases, these complications will exacerbate the damage to the organism, and the complications are difficult to treat and can lead to infections, nutrient loss, multi-organ dysfunction and many other adverse effects. In this case report, the use of endoscopic nylon cords combined with purse-string suture and metal clips in the treatment of duodenal fistula is presented and discussed. The patient was treated with endoscopic purse-string suture and the duodenal fistula was significantly improved. The results indicate that endoscopic purse-string suture is an effective strategy for the treatment of duodenal fistulae.
Cross-talk of MLST and transcriptome unveiling antibiotic resistance mechanism of carbapenem resistance Acinetobacter baumannii clinical strains isolated in Guiyang, China
Authors: Qiu Zhilang , Yuan Kexin , Cao Huijun , Chen Sufang , Chen Feifei , Mo Fei , Guo Guo , Peng Jian
Published: June 2024

Introduction

Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing nosocomial infection in the clinic. The occurrence rate of antibiotic resistance is increasing year by year, resulting in a highly serious situation of bacterial resistance.

Methods

To better understand the local epidemiology of multidrug-resistant A. baumannii, an investigation was conducted on the antibiotic resistance of different types of A. baumannii and its relationship with the genes of A. baumannii. Furthermore, the molecular mechanism underlying antibiotic resistance in A. baumannii was investigated through transcriptome analysis.

Results

These results showed that a total of 9 STs were detected. It was found that 99% of the strains isolated in the hospital belonged to the same STs, and the clone complex CC208 was widely distributed in various departments and all kinds of samples. Furthermore, these A. baumannii strains showed high resistance to ertapenem, biapenem, meropenem, and imipenem, among which the resistance to ertapenem was the strongest. The detection rate of blaOXA–51 gene in these carbapenem resistance A. baumannii (CRAB) reached 100%; Additionally, the transcriptome results showed that the resistance genes were up-regulated in resistance strains, and these genes involved in biofilm formation, efflux pumps, peptidoglycan biosynthesis, and chaperonin synthesis.

Discussion

These results suggest that the CC208 STs were the main clonal complex, and showed high carbapenem antibiotic resistance. All these resistant strains were distributed in various departments, but most of them were distributed in intensive care units (ICU). The blaOXA–23 was the main antibiotic resistance genotype; In summary, the epidemic trend of clinical A. baumannii in Guiyang, China was analyzed from the molecular level, and the resistance mechanism of A. baumannii to carbapenem antibiotics was analyzed with transcriptome, which provided a theoretical basis for better control of A. baumannii.
Salinity affects microbial function genes related to nutrient cycling in arid regions
Authors: Li Yan , Li Wenjing , Jiang Lamei , Li Eryang , Yang Xiaodong , Yang Jianjun
Published: June 2024

Introduction

Salinization damages soil system health and influences microbial communities structure and function. The response of microbial functions involved in the nutrient cycle to soil salinization is a valuable scientific question. However, our knowledge of the microbial metabolism functions in salinized soil and their response to salinity in arid desert environments is inadequate.

Methods

Here, we applied metagenomics technology to investigate the response of microbial carbon (C), nitrogen (N), phosphorus (P), and sulfur (S) cycling and the key genes to salinity, and discuss the effects of edaphic variables on microbial functions.

Results

We found that carbon fixation dominated the carbon cycle. Nitrogen fixation, denitrification, assimilatory nitrate reduction (ANRA), and nitrogen degradation were commonly identified as the most abundant processes in the nitrogen cycle. Organic phosphorus dissolution and phosphorus absorption/transport were the most enriched P metabolic functions, while sulfur metabolism was dominated by assimilatory sulfate reduction (ASR), organic sulfur transformation, and linkages between inorganic and organic sulfur transformation. Increasing salinity inhibited carbon degradation, nitrogen fixation, nitrogen degradation, anammox, ANRA, phosphorus absorption and transport, and the majority of processes in sulfur metabolism. However, some of the metabolic pathway and key genes showed a positive response to salinization, such as carbon fixation (facA, pccA, korAB), denitrification (narG, nirK, norBC, nosZ), ANRA (nasA, nirA), and organic phosphorus dissolution processes (pstABCS, phnCD, ugpAB). High salinity reduced the network complexity in the soil communities. Even so, the saline microbial community presented highly cooperative interactions. The soil water content had significantly correlations with C metabolic genes. The SOC, N, and P contents were significantly correlated with C, N, P, and S network complexity and functional genes. AP, NH4+, and NO3− directly promote carbon fixation, denitrification, nitrogen degradation, organic P solubilization and mineralization, P uptake and transport, ASR, and organic sulfur transformation processes.

Conclusion

Soil salinity in arid region inhibited multiple metabolic functions, but prompted the function of carbon fixation, denitrification, ANRA, and organic phosphorus dissolution. Soil salinity was the most important factor driving microbial functions, and nutrient availability also played important roles in regulating nutrient cycling.
Tetrandrine inhibits aldosterone synthesis by covalently targeting CYP11A1 to attenuate hypertension
Authors: Chu Simeng , Yang Wei , Lu Yujie , Li Junjie , Peng Jiamin , Liu Wenjuan , Jiang Min , Bai Gang
Published: June 2024

Introduction

Tetrandrine (Tet) is the main pharmacological component of Stephania tetrandra S. Moore, which is a well-documented traditional Chinese medicine known for its diuretic and antihypertensive properties. Unraveling the specific targets and mechanisms of Tet involved in inducing diuresis and mitigating hypertension can provide valuable insights into its therapeutic effects. This study aimed to explore the diuretic and antihypertensive targets and mechanisms of Tet using chemical biology coupled with activity analyses in vivo and in vitro.

Methods

The diuretic effects of Tet were evaluated using a water-loaded mouse model. The direct target proteins for the diuretic and antihypertensive effects of Tet were determined using chemical biology. Furthermore, the molecular mechanism of Tet binding to target proteins was analyzed using a multidisciplinary approach based on the structure and function of the proteins. Finally, the effects of the Tet-targeted protein on downstream signaling pathways and blood pressure were evaluated in hypertensive model rats.

Results

Tet exhibited significant antihypertensive and potassium-preserving diuretic effects. The mechanism underlying these effects involves the modulation of the enzyme activity by covalent binding of Tet to Cys423 of CYP11A1. This interaction alters the stability of heme within CYP11A1, subsequently impeding electron transfer and inhibiting aldosterone biosynthesis.

Discussion

This study not only revealed the mechanism of the diuretic and antihypertensive effects of Tet but also discovered a novel covalent inhibitor of CYP11A1. These findings contribute significantly to our understanding of the therapeutic potential of Tet and provide a foundation for future research in the development of targeted treatments for hypertension.
Capecitabine-associated gastrointestinal ulceration, haemorrhage, and obstruction: a pharmacovigilance analysis based on the FAERS
Authors: Wang Yuwei , Meng Long , Liu Xiao
Published: June 2024

Background

Capecitabine has been reported to be associated with severe gastrointestinal (GI) adverse drug reactions (gastrointestinal ulceration, haemorrhage, and obstruction). However, statistical correlations have not been demonstrated, and specific GI adverse drug reactions, such as GI obstruction, are not listed on its label.

Aim

We aimed to determine the associations between capecitabine and GI ulceration, haemorrhage, or obstruction among patients with breast cancer by examining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods

We performed disproportionality analysis of GI ulceration, haemorrhage, and obstruction by evaluating the reporting odds ratio (ROR) and the information component (IC) with their 95% confidence intervals (CIs).

Results

We identified 279 patients with capecitabine-associated GI ulceration, haemorrhage, or obstruction reported between 1 January 2004 and 31 December 2020. One-fourth of the cases of GI ulceration, haemorrhage, or obstruction resulted in death. Capecitabine as a drug class had disproportionately high reporting rates for GI ulceration [ROR 1.94 (1.71–2.21); IC 0.80 (0.60–0.99)], haemorrhage [ROR 2.27 (1.86–2.76); IC 0.99 (0.69–1.28)], and obstruction [ROR 2.19 (1.63–2.95); IC 0.96 (0.51–1.40)].

Conclusion

Pharmacovigilance research on the FAERS has revealed a slight increase in reports of GI ulceration, haemorrhage, and obstruction in capecitabine users, which may cause serious or deadly consequences. In addition to the adverse reactions described in the package insert, close attention should be paid to GI obstruction to avoid discontinuation or life-threatening outcomes.
Fluid shear stress-induced changes in megalin trafficking enhance endocytic capacity in proximal tubule cells
Authors: Lackner Emily M. , Cowan Isabella A. , Long Kimberly R. , Weisz Ora A. , Shipman Katherine E.
Published: June 2024

Proximal tubule (PT) cells maintain a high-capacity apical endocytic pathway to recover essentially all proteins that escape the glomerular filtration barrier. The multi ligand receptors megalin and cubilin play pivotal roles in the endocytic uptake of normally filtered proteins in PT cells but also contribute to the uptake of nephrotoxic drugs, including aminoglycosides. We previously demonstrated that opossum kidney (OK) cells cultured under continuous fluid shear stress (FSS) are superior to cells cultured under static conditions in recapitulating essential functional properties of PT cells in vivo. To identify drivers of the high-capacity, efficient endocytic pathway in the PT, we compared FSS-cultured OK cells with less endocytically active static-cultured OK cells. Megalin and cubilin expression are increased, and endocytic uptake of albumin in FSS-cultured cells is > 5-fold higher compared with cells cultured under static conditions. To understand how differences in receptor expression, distribution, and trafficking rates contribute to increased uptake, we used biochemical, morphological, and mathematical modeling approaches to compare megalin traffic in FSS- versus static-cultured OK cells. Our model predicts that culturing cells under FSS increases the rates of all steps in megalin trafficking. Importantly, the model explains why, despite seemingly counterintuitive observations (a reduced fraction of megalin at the cell surface, higher colocalization with lysosomes, and a shorter half-life of surface-tagged megalin in FSS-cultured cells), uptake of albumin is dramatically increased compared with static-grown cells. We also show that FSS-cultured OK cells more accurately exhibit the mechanisms that mediate uptake of nephrotoxic drugs in vivo compared with static-grown cells. This culture model thus provides a useful platform to understand drug uptake mechanisms, with implications for developing interventions in nephrotoxic injury prevention.
Genomic incongruence accompanies the evolution of flower symmetry in Eudicots: a case study in the poppy family (Papaveraceae, Ranunculales)
Authors: Pokorny Lisa , Pellicer Jaume , Woudstra Yannick , Christenhusz Maarten J. M. , Garnatje Teresa , Palazzesi Luis , Johnson Matthew G. , Maurin Olivier , Françoso Elaine , Roy Shyamali , Leitch Ilia J. , Forest Félix , Baker William J. , Hidalgo Oriane
Published: June 2024

Reconstructing evolutionary trajectories and transitions that have shaped floral diversity relies heavily on the phylogenetic framework on which traits are modelled. In this study, we focus on the angiosperm order Ranunculales, sister to all other eudicots, to unravel higher-level relationships, especially those tied to evolutionary transitions in flower symmetry within the family Papaveraceae. This family presents an astonishing array of floral diversity, with actinomorphic, disymmetric (two perpendicular symmetry axes), and zygomorphic flowers. We generated nuclear and plastid datasets using the Angiosperms353 universal probe set for target capture sequencing (of 353 single-copy nuclear ortholog genes), together with publicly available transcriptome and plastome data mined from open-access online repositories. We relied on the fossil record of the order Ranunculales to date our phylogenies and to establish a timeline of events. Our phylogenomic workflow shows that nuclear-plastid incongruence accompanies topological uncertainties in Ranunculales. A cocktail of incomplete lineage sorting, post-hybridization introgression, and extinction following rapid speciation most likely explain the observed knots in the topology. These knots coincide with major floral symmetry transitions and thus obscure the order of evolutionary events.
Effects of oilseed rape green manure on phosphorus availability of red soil and rice yield in rice–green manure rotation system
Authors: Gu Chi-ming , Li Yin-shui , Yang Lu , Dai Jing , Hu Wenshi , Yu Chang-bing , Brooks Margot , Liao Xing , Qin Lu
Published: June 2024

Improving the nutrient content of red soils in southern China is a priority for efficient rice production there. To assess the effectiveness of oilseed rape as green manure for the improvement of soil phosphorus nutrient supply and rice yield in red soil areas, a long-term field plot experiment was conducted comparing two species of rape, Brassica napus (BN) and Brassica juncea (BJ). The effects of returning oilseed rape on soil phosphorus availability, phosphorus absorption, and yield of subsequent rice under rice–green manure rotation mode were analyzed, using data from the seasons of 2020 to 2021. The study found that compared with winter fallow treatment (WT) and no-tillage treatment (NT), the soil available phosphorus content of BN was increased, and that of BJ was significantly increased. The content of water-soluble inorganic phosphorus of BJ increased, and that of BN increased substantially. Compared with the WT, the soil organic matter content and soil total phosphorus content of BN significantly increased, as did the soil available potassium content of BJ, and the soil total phosphorus content of BJ was significantly increased compared with NT. The soil particulate phosphorus content of BJ and BN was significantly increased by 14.00% and 16.00%, respectively. Compared with the WT, the phosphorus activation coefficient of BJ was significantly increased by 11.41%. The rice plant tiller number under the green manure returning treatment was significantly increased by 43.16% compared with the winter fallow treatment. The green manure returning measures increased rice grain yield by promoting rice tiller numbers; BN increased rice grain yield by 9.91% and BJ by 11.68%. Based on these results, returning oilseed rape green manure could augment the phosphorus nutrients of red soil and promote phosphorus availability. Rice–oilseed rape green manure rotation could increase rice grain yield.
A causal relationship between particulate matter 2.5 and obesity and its related indicators: a Mendelian randomization study of European ancestry
Authors: Wu Tian qiang , Han Xinyu , Liu Chun yan , Zhao Na , Ma Jian
Published: June 2024

Background

In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM2.5) on obesity, but their relationship remains ambiguous.

Methods

Utilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM2.5 exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings.

Results

The UVMR analysis demonstrated a significant association between PM2.5 exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881–21.968; PFDR = 0.005). Additionally, PM2.5 concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244–2.776; PFDR = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092–5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106–2.841; PFDR = 0.019). Furthermore, PM2.5 exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269–3.022; PFDR = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34–4.649; PFDR = 0.007). Finally, a significant negative association was observed between PM2.5 concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025–0.89; PFDR = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM2.5 levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21.

Conclusion

Our MR study demonstrates conclusively that higher PM2.5 concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.
A study on the falls factors among the older adult with cognitive impairment based on large-sample data
Authors: Wang Changying , Zhang Yunwei , Wang Jin , Wan Lingshan , Li Bo , Ding Hansheng
Published: June 2024

Introduction

This study explored the correlative factors of falls among the older adult with cognitive impairment, to provide distinct evidence for preventing falls in the older adult with cognitive impairment compared with the general older adult population.

Methods

This study was based on a cross-sectional survey, with an older adult population of 124,124 was included. The data was sourced from the Elderly Care Unified Needs Assessment for Long-Term Care Insurance in Shanghai. Binary and multivariable logistic regression analyses were conducted sequentially on the correlative factors of falls. Multivariable logistic regression was performed on variables that were significant, stratified by cognitive function levels.

Results

The incidence of fall in the past 90 days was 17.67% in this study. Specific variables such as gender (male), advanced age (≥80), residence with a elevator (or lift), mild or moderate disability, quality of sleep (acceptable/poor) were negatively correlated with falls, while higher education level, living alone, residence with indoor steps, unclean and untidy living environment, MCI or dementia, chronic diseases, restricted joints, impaired vision, and the use of diaper were positively correlative factors of falls. Comparing with older adult with normal cognitive functions, older adult with dementia faced a higher risk of falling due to accessibility barrier in the residence. For general older adults, less frequency of going outside and poor social interactions were positively correlated with falls, while for older adult with cognitive impairments, going outside moderately (sometimes) was found positively correlated with falls. Older adults with cognitive impairments have increased fall risks associated with chronic diseases, restricted joints, and the use of diaper. The risk of falling escalated with the greater number of chronic diseases.

Discussion

For older adult with cognitive impairments, it is advisable to live with others. Additionally, creating an accessible living environment and maintaining the cleanness and tidiness can effectively reduce the risk of falls, particularly for those with MCI or dementia. Optimal outdoor activity plans should be developed separately based on the cognitive function of older adults. Older adult with dementia who have comorbidities should be paid special attention in fall prevention compared to the general older adult population.
Implications of intracochlear decomposition gas formation in non-putrefied cadavers
Authors: Mittmann Philipp , Ernst Arne , Seidl Rainer , Lauer Gina , Gölz Leonie , Mutze Sven , Windgassen Marc , Buschmann Claas
Published: June 2024

Introduction

Postmortem computed tomography (pmCT) prior to forensic autopsy has become increasingly important in recent decades, especially in forensic documentation of single injuries, injury patterns, and causes of death. Postmortem decomposition gas formation can also be detected in pmCT scans, which might affect cochlear implant research in postmortem human temporal bones (TBs).

Material and methods

Fifty non-putrefied hanging fatalities within a 2-year period (January 2017 to December 2019) were included with 100 TBs. Each body underwent whole-body pmCT prior to forensic autopsy. PmCT scans were analyzed with respect to the presence of intracochlear gas despite the lack of putrefaction at autopsy by an experienced fellow neurotologist.

Results

PmCT revealed gas formation in two individuals despite the lack of head trauma and putrefaction at postmortem examination and autopsy. Both individuals showed enclosed gas in the vestibule and the cochlea on both sides.

Discussion

Intracochlear gas formation, most likely related to decomposition, may occur despite the lack of putrefaction at postmortem examination and autopsy and can be detected by pmCT. This finding seems to be rather rare in non-traumatic death cases but might affect cochlear pressure research in postmortem human TB.