bluuebunny/crossref_metadata_2025 huggingface dataset:
Woodland expansion and deer management shape tick abundance and Lyme disease hazard
Authors: Olsthoorn Fanny , Gilbert Lucy , Fonville Manoj , Blache Nolwenn , May Livia , Mondini Flavia , Rotbarth Ronny , Schlierenzauer Corinne , Gandy Sara , Sprong Hein , Ghazoul Jaboury
Published: January 2025

The largest land use change in Europe is woodland expansion, through planting and natural regeneration. Unforeseen consequences of this could include changes in environmental hazards, such as exposure to parasites and pathogens.

Tick‐borne Lyme disease is the most prevalent tick‐borne disease in the northern hemisphere and is often associated with woodlands. Therefore, to inform the planning and management of expanding woodlands, we test how land covers that reflect different types and stages of the woodland expansion process, along with their deer management, impact tick densities and Lyme disease hazard (density of infected nymphs). We also test whether differences in rodent abundance play a mechanistic role in explaining differences in Lyme disease hazard.

In Northwest Scotland, a touristic area undergoing woodland expansion, we recorded deer management, rodent densities, Ixodes ricinus nymph densities, pathogen prevalence and Lyme disease hazard between open moorland, young pine and mature pine, and birch and spruce. These represent pre‐, early and late stage woodland establishments, and the three woodland types in the region.

Rodents, ticks, pathogen prevalence and Lyme disease hazard were generally lowest in moorland and young pine and highest in mature woodland, especially birch, although variability was high. Deer management reduced tick densities and, marginally, Lyme disease hazard. There was insufficient evidence for rodents increasing Lyme disease hazard, but rodents augmented tick densities and the most abundant Lyme disease pathogen was that transmitted by rodents.

Practical implication. woodland expansion could, once mature, eventually lead to higher tick densities, pathogen prevalence and Lyme disease hazard. Importantly, an environmental solution could be to control deer populations.
Crosslinguistic Differences in Grammar
Authors: Hasselgård Hilde
Published: January 2025

This chapter discusses grammar in terms of the levels of unit, structure, class, and system, which may be similar or different across languages. It discusses the concept of
tertium comparationis
in contrastive studies and presents some alternatives relative to the material and methods used in the language comparison. Special attention is given to the use of corpora in crosslinguistic studies, and a variety of case studies are briefly presented which describe crosslinguistic differences in grammar at various levels of language description. Various applications of crosslinguistic grammar knowledge are also outlined.
Peter French
Authors: MacLeod Nicci
Published: January 2025

Peter French (1953–) is one of the world's most experienced practitioners in forensic speech science, having worked in the field for over 30 years and provided forensic speech and audio analysis expertise in over 6,000 cases. He has also frequently appeared as an expert witness in court, both in the United Kingdom and internationally. These court appearances have ranged from Magistrates court trials to appearances at the International War Crimes Tribunal. He holds the positions of Emeritus Professor of Forensic Speech Science at the University of York, Honorary Visiting Professor of Forensic Speech Science at the University of Huddersfield, and Honorary Visiting Professor at York St John University. In 1987, he founded J P French Associates, which is the UK's oldest and largest independent provider of forensic speech and audio analysis for criminal and civil cases. More recently, he was a co‐founder of the Centre for Forensic Phonetics and Acoustics at the University of Zurich, where he was also awarded an honorary doctorate in 2022 in recognition of his achievements in forensic phonetics and acoustics.
Grammar and Discourse
Authors: Dontcheva‐Navratilova Olga
Published: January 2025

Grammar and discourse are interconnected but distinct notions associated with two different aspects of linguistic analysis. While grammar refers to the system of rules and principles underlying the form and meaning of words, phrases, clauses, and sentences, the study of discourse explores how language is used in human interaction to convey meaning in context. Discourse studies of grammar analyze the structure of words, phrases, and sentences in specific communicative contexts in order to explain how they are used in actual communication. This entry offers an overview of the most important aspects of the interface between grammar and discourse. It focuses on functions of grammatical structures in discourse, the emergence of new grammatical forms as a result of grammaticalization and variation in pragmatic functions of discourse markers in different contexts of use. Another aspect of the grammar–discourse interface discussed in this entry concerns information processing and the contribution of grammar to discourse organization, cohesion, and coherence.
Grammar in Language Teaching and Education
Authors: Slater Tammy , Li Jinrong
Published: January 2025

The concept of “grammar” has shifted in meaning from an initial focus on writing to its current reference to the rules of language, or language form. Throughout history, issues have persisted regarding the best approach to teaching and learning grammar, and such issues have been reflected in the various methodological approaches that have been introduced as well as in the research carried out on the ways grammar has been and can be taught. This entry presents a chronology of grammar teaching in second and foreign language education. It also discusses technological innovations that teachers and learners have at their disposal to hone their second and foreign language grammar skills.
Modality
Authors: Boye Kasper
Published: January 2025

As a term relating to linguistic categories, modality is used in its most narrow sense to refer to categories that can be defined in terms of the notions of necessity and possibility. A number of broader uses are also common, however. For instance, the term is used also for categories that have to do with the indication of degree of certainty and possibly the indication of information source (a notion associated with the category of evidentiality). Some use it in an even broader sense as related to mood (including notions like indicative, subjunctive, imperative, declarative, and interrogative), or for linguistic elements that have to do with the indication of speakers' attitude or stance toward what they describe. Narrow‐sense modality may be seen as organized in three dimensions. (a) Modal strength basically covers a distinction between necessity (strong) and possibility (weak). (b) Modal source concerns a distinction between necessities and possibilities originating within the entity for which something is necessary or possible, and necessities originating outside this entity. (c) Modality type covers a distinction between, among other things, “dynamic” (physical), “deontic” (social), and “epistemic” (reasoning‐related) necessities and possibilities.
Qualitative Corpus Analysis
Authors: Hasko Victoria
Published: January 2025

The article offers a brief overview of qualitative approaches to corpus analysis. Qualitative corpus analysis is introduced as a methodology for pursuing in‐depth investigations of authentic language use representative of purposefully selected communicative situations that are digitally captured, documented as to their origins and ecology, stored as electronic language corpora, annotated as needed, and made available for digital access, retrieval, and analysis grounded in theory‐informed descriptive and explanatory accounts of the language samples under analysis. The article notes the evolution of both qualitative and quantitative approaches to corpus analysis and the emerging importance of the latter to a range of professional fields. Methodological foundations of conducting qualitative corpus analysis are reviewed, with a particular focus on the deliberate and specialized corpus markup, annotation, retrieval, and interpretation that are required for the in‐depth and grounded investigations carried out by linguists interested in qualitative approaches to corpus studies.
Sociopragmatics
Authors: Eslami Zohreh R. , Guo Weiqi
Published: January 2025

The term “sociopragmatics” was initially proposed by Leech (1983) to describe (the study of) how pragmatic meanings reflect “specific ‘local’ conditions on language use” (p. 10). Emphasizing the social side of pragmatics (sociopragmatics), compared to its linguistic side (pragmalinguistics), indicates the primacy of speakers over utterances. Focusing on interlocutors in the process of interaction relates to social identities, positioning of interlocutors, and the role of agency during interaction as participants shape their identities and positionality dynamically and strategically as members of a speech community. In this entry, we first discuss the distinction between pragmalinguistics and sociopragmatics based on Leech's (1983) perspective. Next, context as an important defining aspect of sociopragmatics is discussed to clarify where the boundaries of context can be placed in relation to sociopragmatics. We then discuss how the conceptual foundations of this distinction can clarify research related to issues such as pragmatic transfer and pragmatic failure and teaching of L2 pragmatics. In the last section, remarks related to future areas of research and inquiries will be shared.
Common European Framework of Reference
Authors: Huhta Ari
Published: January 2025

This chapter focuses on the
Common European Framework of Reference for Languages: Learning, teaching, assessment
(CEFR) by the Council of Europe (CoE) and gives an account of how the new version of the CEFR (CEFR—Companion Volume, or CEFR/CV) published in 2020 updates and expands the original version. The CEFR/CV focuses on providing both conceptual and practical tools that can be applied in the classroom and in teacher education in order to increase the application of the framework in those areas of language education where the influence of the original CEFR was quite modest compared with its impact on assessment. To achieve this, the CEFR/CV includes significant new content such as validated scales for mediation, plurilingual language use, online language use, and for sign language. The CEFR/CV also aims to improve the clarity and usefulness of the framework by providing metatext and summaries to guide the reader and by removing some of the previous content to an online source. In fact, the CEFR comprises not only the main document but also a considerable number of additional sources via a dedicated website that assists in applying the framework in new contexts.
Communicative Grammar and Communicative Competence
Authors: Kern Richard , Kramsch Claire
Published: January 2025

This chapter explores grammar from multiple perspectives: as an abstract set of mental rules that shape language performance, or conversely, as a by‐product of discourse, or as a dynamic interaction among message, code, and context (which we refer to as “communicative grammar”). It then considers implications of these different views of grammar for the ways we conceive of communicative competence and educational goals for language learners. The evolution of the notion of communicative competence is traced from the 1970s to the present, with emphasis on the influence of cross‐cultural pragmatics, conversational analysis, discourse studies, and critical discourse analysis. These influences have led to an ecological grammar of language use that operates on multiple scales—from the microcosm of individual conversational encounters to larger geopolitical exchanges between collective entities and their political representatives. Our understandings of communicative competence are further complicated by the Internet, racial and gendered identity claims, political power struggles, and the use of digital algorithms to manipulate information and behavior. Notions such as
translanguaging
,
multimodality
,
inclusive and non‐binary language
,
algorithmic awareness
, and
symbolic competence
have now become central to knowing how to communicate with people from different languages and cultures. The third section of the chapter presents implications for educational practice, tracing movements from a pedagogy of correctness to a pedagogy of discourse/context relations that puts linguistic structures in relation with social and cultural discourses and beliefs, social and historical events in relation with their representations in various modalities, and discourse genres in relation with one another.
Process Research Screen Capture
Authors: Mroz Aurore P.
Published: January 2025

In teaching, learning, and research that focus on a mediated process, screen capture has become a key instrument. Consisting in the recording of multiple channels of information happening simultaneously in‐ and off‐screen (e.g., typing, clicking, navigating, speaking, ambient noises, gestures, eye movements, and props used), screen capture provides a rich multimodal audiovisual rendering of an unfolding event. Once restricted to computer‐based interactions, screen capture is now available on most mobile devices and on virtual or augmented reality headsets. Originally used for step‐by‐step tutorial videos, screen capture has since become an important tool to create pedagogical materials, support asynchronous teaching, or help learners revisit their own learning strategies. Research‐wise, it primarily serves process‐oriented studies by providing access to hidden learning events, allowing to reconstruct a sequence of events, and documenting the multimodality of mediated interactions. Although predominantly employed to investigate text‐based computer‐mediated processes (reading and writing), its use has more recently expanded to also examine oral, aural, and nonverbal activities (eye‐tracking and gesture studies more specifically). Particularly well suited for research grounded in task‐based, ecological, or complex dynamic systems theory approaches, screen capture can be employed for quantitative, qualitative, or mixed methods studies. The greatest challenge of its use resides in the analysis and representation of data due to the sheer volume and richness of information contained in the recordings, requiring overt methodological decisions anchored in theory, and a systematic annotation and transcription system.
Individual Differences in Bilingual Language Experience: Overview and Assessment
Authors: Kałamała Patrycja , Castro Sofía , Wodniecka Zofia
Published: January 2025

“Bilingualism” is an umbrella construct that encompasses individuals with different language experiences. The diversity of these experiences generates the need for a paradigm shift from testing group effects to studying individual differences within and between different bilingual communities. In this entry, we discuss the most recognized dimensions of bilingual language experience, the most common methods of their measurement, and the current methodological challenges faced by researchers who aim to describe and understand the language variation of bilinguals. While recent calls to consider individual differences in language experience have already greatly advanced our understanding of the bilingualism phenomenon, this line of research is only gaining momentum. Ultimately, collaborative research efforts to develop a comprehensive measurement toolkit and trace the relationships between different language dimensions should help to determine how individual language experiences translate into bilingual profiles within and across different bilingual communities.
Multimodal Processing in Bilingualism and Second Language Acquisition
Authors: Morett Laura M.
Published: January 2025

This entry provides an overview of how multimodal processing benefits communication between L2 and L1 speakers and bilinguals. The impacts of text, images, facial cues, and hand gestures are considered in combination with speech, as are hand and air writing. Thus, this entry reviews multimodal L2 processing across the auditory, visual, and haptic modalities, providing insight into how it can be conjointly leveraged by bilinguals, L2 learners, and their L1 interlocutors to communicate effectively.
Engineered IL‐21‐Expressing Nanovesicles for Co‐Delivery of GOX and Ferrocene to Induce Synergistic Anti‐Tumor Effects
Authors: Li Chao , Zhou Mengyang , Li Yang , Jia Haojie , Huang Lin
Published: January 2025

Glucose oxidase (GOX)‐induced starvation is a safe treatment for tumor. However, the non‐specific targeting of GOX and the plasticity of tumor metabolism lead to toxic side effects and low tumor mortality. Thus, it is necessary to develop a synergistic strategy with high tumor targeting specificity to enhance the mortality of GOX. In this study, a genetically engineered CD44 targeting peptide (CP) and IL‐21 fusion protein‐displaying nanovesicles platform (mCP@IL21‐Fc‐GOX) are designed to efficiently encapsulate GOX and ferrocene (Fc). After reaching the tumor site, IL‐21 can be precisely released and targeted to NK cells through the cleavage of MMP‐2, thus achieving precise anti‐tumor immunotherapy of IL‐21. Second, the exposed CP enable mCP‐Fc‐GOX to be further targeted to tumor cells, completing the synergistic anti‐cancer effects of starvation and chemodynamic therapy (CDT) triggered by GOX and Fc. In situ breast cancer models, the results show that mCP@IL21‐Fc‐GOX not only enhances NK and T cells aggregation in tumor tissue but also achieves precise nutrition deprivation and abundant reactive oxygen species production, thus significantly inhibits tumor growth based on the synergistic function of the immunotherapy, starvation and CDT. Therefore, this work provides a smart nanovesicle platform for achieving precise and safe synergistic anti‐tumor therapy.
Arrhenius Activation Energy Impact on 3D Unsteady Carreau Nanofluid Flow with Joule Heating and Nonlinear Thermal Radiation by Taylor Wavelet
Authors: Preetham M. P. , Kumbinarasaiah S.
Published: January 2025

This investigation focuses on the unsteady 3D electrically conducting Carreau nanofluid (CNF) flow over a bilateral nonlinear stretching sheet. In this study, a new mathematical model is developed that includes the effects of Arrhenius activation energy, nonlinear thermal radiation, and Joule heating, analyzed using the Taylor wavelet series collocation method (TWSCM). An appropriate similarity transformation is applied to transform the governing partial differential equations (PDEs) into nonlinear coupled ordinary differential equations (ODEs). These ODEs are tackled using TWSCM to explore the physical parameters' impact on fluids demonstrating shear thinning (SThin) and shear thickening (SThick) behavior. The investigation's findings indicate that the activation energy parameter and thermal Biot number amplify the concentration field. Furthermore, it is observed that the Nusselt number intensifies for the temperature ratio and thermal Biot parameters while it declines for the thermophoresis parameter and Eckert number.
Rbfox3 Promotes Transformation of MDSC‐Like Tumor Cells to Shape Immunosuppressive Microenvironment
Authors: Li Zhiyang , Feng Zhuangzhuang , Chen Mengzhan , Shi Xinxiu , Cui Bijia , Sun Yujie , Zhang Heng , Li Yinan , Chen Caihong , Feng Yiqian , Han Jingxia , Xing Xuewu , Liu Huijuan , Sun Tao
Published: January 2025

Myeloid‐derived suppressor cells (MDSCs) within the tumor microenvironment (TME) contribute to the malignant progression of tumors by exerting immunosuppressive effects. Bacterial lipopolysaccharides (LPS) have been widely demonstrated in various types of solid tumors. LPS can promote the malignant progression of tumors, which mechanism has not yet been fully elucidated. In this study, a type of MDSC‐like tumor cells (MLTCs) is found in tumor tissues induced by low‐dose and long‐term LPS stimulation. MLTCs can simultaneously express tumor cell and MDSCs markers. Similar to MDSCs, MLTCs can produce arginine, nitric oxide, and reactive oxygen species and inhibit the activity of NK and T cells to promote the formation of an immunosuppressive microenvironment. MLTCs can also promote tumor cell proliferation and vasculogenic mimicry formation. CRISPR‐Cas9 activity screening studies identified RNA‐binding Fox‐1 homolog 3 (Rbfox3) as a critical protein for MLTCs formation after LPS treatment. Rbfox3 can transcriptionally regulate the expression of Ass1 in the form of phase‐separated particles. Crocin can inhibit the generation of MLTCs by disrupting phase‐separated particles of Rbfox3 and enhance the anti‐tumor effects of immune checkpoint inhibitors (ICIs).
AAVR Expression is Essential for AAV Vector Transduction in Sensory Hair Cells
Authors: Wu Fan , Chen Guisheng , Hu Rui , Liu Peiwen , Lou Jintao , Zhao Wenji , He Zuhong , Sha Suhua , Zheng Yiqing
Published: January 2025

Adeno‐associated virus (AAV) vectors are a leading platform for gene therapy. Recently, AAV‐mediated gene therapy in the inner ear has progressed from laboratory use to clinical trials, but the lower transduction rates in outer hair cells (OHCs) in the organ of Corti and in vestibular hair cells in adult mice still pose a challenge. OHCs are particularly vulnerable to inner ear insults. In this study, we demonstrated that expression of a key AAV receptor (AAVR, Kiaa0319l, or Au040320) in OHCs and vestibular hair cells decreases significantly in mature mice and AAV particles directly interact with AAVR by forming complexes. Consequently, antibody blockage of AAVR significantly inhibits AAV transduction in sensory hair cells in cochlear explants. Moreover, use of AAVR knockout mice confirms inhibition of AAV transduction in sensory hair cells in vivo. Finally, conditional overexpression of AAVR in sensory hair cells of adult mice successfully restores AAV transduction efficiency in OHCs and vestibular hair cells. In conclusion, this strong evidence that AAVR is essential for AAV transduction in sensory hair cells will help to increase the efficacy of future gene therapy in inner ear.
Defining Structure‐Function Relationships of Amphiphilic Excipients Enables Rational Design of Ultra‐Stable Biopharmaceuticals
Authors: Prossnitz Alexander N. , Nguyen Leslee T. , Eckman Noah , Borkar Suraj , Tetef Samantha , Autzen Anton A. A. , Fuller Gerald G. , Appel Eric A.
Published: January 2025

Biopharmaceuticals are the fastest‐growing class of drugs in the healthcare industry, but their global reach is severely limited by their propensity for rapid aggregation. Currently, surfactant excipients such as polysorbates and poloxamers are used to prevent protein aggregation, which significantly extends shelf‐life. Unfortunately, these excipients are themselves unstable, oxidizing rapidly into 100s of distinct compounds, some of which cause severe adverse events in patients. Here, the highly stable, well‐defined, and modular nature of amphiphilic polyacrylamide‐derived excipients is leveraged to isolate the key mechanisms responsible for excipient‐mediated protein stabilization. With a library of compositionally identical but structurally distinct amphiphilic excipients, a new property is quantified, compositional dispersity, that is key to excipient performance and utilized this property to rationally design new ultra‐stable surfactant excipients that increase the stability of a notoriously unstable biopharmaceutical, monomeric insulin, by an order of magnitude. This comprehensive and generalizable understanding of excipient structure‐function relationships represents a paradigm shift for the formulation of biopharmaceuticals, moving away from trial‐and‐error screening approaches toward rational design.
Wearable Fluidic Fabric with Excellent Heat Transfer Performance for Sports Recovery
Authors: Yang Jing , Xiong Ying , Piao Jinli , Leung Manyui , Liu Guosai , Zhu Mingyue , Tang Shengyang , Zhang Lisha , Tao Xiaoming
Published: January 2025

Rapid temperature contrast hydrotherapy by water immersion has been utilized by athletes for effective sports recovery. However, its application at some training or competition venues is limited by high water consumption, bucky size, personal hygiene, and inconvenience. Here, a novel portable system equipped with highly effective, lightweight, and hygienic wearable fluidic fabric device is reported, that replaces direct water immersion. The measured heat transfer coefficient between the skin and the fabric is 98.5 W m−2 K−1, which is 92% of that in direct water immersion at 10 °C and significantly higher than that by previously reported cooling garments. The core layer, a flexible heat transfer panel (FHTP), can switch between cold and hot modes (5–40 °C) over an area of 0.3 m2. The contact condition between skin and the deformable FHTP has been considered in a new verified heat transfer model. Optimization of the parameters has resulted in excellent heat transfer performance. This fluidic fabric also holds potential in diverse applications, such as enhancing thermal safety and comfort in extreme environments (e.g., personal thermal management systems and fire‐protection suits), supporting cryotherapy and thermotherapy in rehabilitation and healthcare, and simulation of total tactile sensations in virtual reality.
Late anastomotic complication after laparoscopic surgery for clinical stage I low rectal cancers located within 5 cm of the anal verge: Sub‐analysis of the ultimate trial
Authors: Shimomura Manabu , Yoshimitsu Masanori , Tsukada Yuichiro , Ohdan Hideki , Watanabe Jun , Fukunaga Yosuke , Hirano Yasumitsu , Sakamoto Kazuhiro , Hamamoto Hiroki , Horie Hisanaga , Matsuhashi Nobuhisa , Kuriu Yoshiaki , Nagai Shuntaro , Hamada Madoka , Yoshioka Shinichi , Ohnuma Shinobu , Hayama Tamuro , Otsuka Koki , Inoue Yusuke , Ueda Kazuki , Toiyama Yuji , Maruyama Satoshi , Yamaguchi Shigeki , Tanaka Keitaro , Suzuki Motoko , Misumi Toshihiro , Naitoh Takeshi , Watanabe Masahiko , Ito Masaaki ,   Ultimate Trial Group
Published: January 2025

Background

Although extensive research has been conducted on early anastomotic leakage (AL) after sphincter‐sparing surgery, the status of late anastomotic complications (post‐30 days) has received limited attention. These late complications significantly affect a patient's quality of life and often lead to permanent stoma creation.

Methods

This study conducted a sub‐analysis of a phase II trial assessing the outcomes of laparoscopic surgery for cStage I lower rectal adenocarcinoma (the ultimate trial). This study included 278 patients who underwent intestinal anastomosis and investigated the frequency, timing, and risk factors of late anastomotic complications (stenosis, fistula, and intestinal prolapse).

Results

Anastomotic stenosis occurred in 27 patients (9.7%), and the median time of occurrence was 274 days (range, 70–1226 days). Only early AL (p = 0.004) was identified as an independent risk factor. A late anastomotic fistula was observed in five patients (1.8%), and 18 patients (6.4%) requiring permanent stomas. A short distance from the lower tumor margin to the anal verge (AV) (p = 0.004) and the presence of stenosis or fistula (p < 0.0001) were independent risk factors.

Intestinal prolapse occurred in eight cases (3%), with a median occurrence of 221 days (range, 122–725 days). Intersphincteric resection (ISR) (p = 0.02) and splenic flexure takedown (p < 0.0001) were independent risk factors.

Conclusion

Anastomotic stenosis and late fistula formation frequently emerge as secondary consequences of early AL and represent significant complications linked to permanent stoma creation, often proving resistant to treatment. Intestinal prolapse is a characteristic anastomotic complication of ISR that can be caused by excessive intestinal mobilization.
Breaking the Bone Marrow Barrier: Peripheral Blood as a Gateway to Measurable Residual Disease Detection in Acute Myelogenous Leukemia
Authors: Butler John T. , Yashar William M. , Swords Ronan
Published: January 2025

Acute myeloid leukemia (AML) is a genetically heterogeneous disease with high rates of relapse after initial treatment. Identifying measurable residual disease (MRD) following initial therapy is essential to assess response, predict patient outcomes, and identify those in need of additional intervention. Currently, MRD analysis relies on invasive, serial bone marrow (BM) biopsies, which complicate sample availability and processing time and negatively impact patient experience. Additionally, finding a positive result can generate more questions than answers, causing anxiety for both the patient and the provider. Peripheral blood (PB) evaluation has shown promise in detecting MRD and is now recommended by the European Leukemia Net for AML for certain genetic abnormalities. PB‐based sampling allows for more frequent testing intervals and better temporal resolution of malignant expansion while sparing patients additional invasive procedures. In this review, we will discuss the current state of PB testing for MRD evaluation with a focus on next‐generation sequencing methodologies that are capable of MRD detection across AML subtypes.
Secondary Metabolites from Tripterygium wilfordii Hook. f.‐Associated Endophytes: Producing Microbes, Structures, and Bioactivities
Authors: Chen Cuili , Lu Shan , Zou Yanmin , Mao Di , Kakeya Hideaki
Published: January 2025

Endophytes have been recognized as important sources for discovering novel bioactive natural products with diverse structures and biological activities. This review focuses on the endophytes of Tripterygium wilfordii Hook. f. (T. wilfordii), a famous traditional medicinal plant, and summarizes the producing microbes, chemical diversities, and bioactivities of the metabolites discovered from the T. wilfordii ‐associated endophytes over the past thirty years (1995–2024). One hundred and one metabolites together with their bioactivities from twelve endophytes are systematically reviewed. A comprehensive comparison of the 101 metabolites with those isolated from T. wilfordii reveals that the T. wilfordii‐associated endophytes produce structurally distinct metabolites with diverse biological activities. To the best of our knowledge, this is the first holistic overview of the T. wilfordii‐associated endophytes and their secondary metabolites.
Anaesthetic management of a large multi‐nodular goitre with dynamic bilateral carotid artery compression
Authors: Milder D. A. , Zaklama R. , Wang K. , Harrison J. , Sandler G.
Published: January 2025

Dynamic carotid compression arising from a change in patient position is a rare complication of goitre, with the potential for cerebral ischaemia and infarction. In this report, a 37‐year‐old woman presented with a multi‐nodular goitre with clinical features concerning for transient cerebral ischaemia. The anaesthetic management and neurological monitoring used to mitigate the risk of cerebral ischaemia during thyroidectomy is described and the literature surrounding this rare complication is explored.
Irrigation Expansion and Rural Transformation in China: Evidence of Provincial Data in 1978–2018
Authors: Shi Pengfei , Huang Jikun
Published: January 2025

The role of irrigation expansion in facilitating rural transformation has been widely documented, yet quantitative studies remain rather limited. Based on the statistical data from 27 provinces in China, this paper analyses the correlation between irrigation expansion and rural transformation over the period of 1978–2018. The econometric results indicate a positive relationship between irrigation expansion and high‐value agriculture. However, from a dynamic perspective, for each percentage point increase in the share of cultivated land with irrigation, the share of high‐value agriculture decreases by 0.09 percentage points in the early stage, but increases by 0.07 and 0.12 percentage points in the subsequent middle and later stages, respectively. Likewise, the relationship between irrigation expansion and non‐farm employment of rural labourers is not always negative. Specifically, an additional one percentage point increase in the share of cultivated land with irrigation is associated with a 0.09 percentage points decline in the share of rural labour non‐farm employment in the early stage. This reduction moderates to a 0.05 percentage points in the middle stage, but there is a 0.08 percentage points increase in the later stage. This paper further concludes with several implications for policymakers and academic research.
Antioxidant activity, phytochemical composition, and antitumor capacity of Amazonian fruits taperebá (Spondias mombin) and murici (Byrsonima crassifolia)
Authors: Lima Thuane Passos Barbosa , Coimbra Pedro Paulo Saldanha , da Silva Antonio Ananda , Pereira Henrique Marcelo Gualberto , da Silva Giovana Ramalho Patrizi , da Veiga‐Junior Valdir Florêncio , Silva Otniel Freitas , Felzenszwalb Israel , Araujo‐Lima Carlos Fernando , Teodoro Anderson Junger
Published: January 2025

The Amazon rainforest is renowned for its biodiversity and as a reservoir of edible and medicinal plants. The phytochemicals in murici and taperebá fruits serve as natural antioxidants, contributing to cultural preservation, ecosystem protection, and economic opportunities. However, limited scientific research on their composition and health benefits hinders their recognition as functional foods. This study aimed to evaluate the antioxidant activity, carotenoid content, phenolic compounds, and antitumor effects of murici and taperebá fruit pulps. Four antioxidant tests (2,2‐Diphenyl‐1‐picrylhydrazylradical scavenging activity, 2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) method, 2,2′‐azino‐bis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) method, oxygen radical absorbance capacity) were conducted, and total phenolics were quantified (Folin‐Ciocalteu). Phenolics were identified using UHPLC‐HRMS, and carotenoids by high‐performance liquid chromatography (HPLC). The impact on breast cancer cell viability (MCF‐7, MDA‐MB‐231) was assessed via water‐soluble tetrazolium (WST) assay. Both fruits showed high antioxidant activity and phenolic content, with murici leading. HPLC revealed five carotenoids per fruit, with taperebá showing higher concentrations. UHPLC‐HRMS identified 23 phenolic compounds: 16 in murici aqueous extract, 18 in murici ethanolic extract, and 15 in each taperebá extract. WST assay demonstrated that both fruits exerted a significant impact on breast cancer cells, reducing their viability in a dose‐dependent manner. These findings underscore the potential of murici and taperebá as sources of phytochemical antioxidants and antiproliferative agents with promising health applications.
Triple exponentially weighted moving average controller optimization using deep reinforcement learning in semiconductor manufacturing process
Authors: Pan Tianhong , Jin Biao , Ma Zhu , Fang Liandi
Published: January 2025

The triple exponentially weighted moving average (TriEWMA) controller integrates three distinct EWMAs to mitigate process dynamics and disturbances, enhancing system stability in the semiconductor manufacturing process. However, the performance of TriEWMA is highly dependent on its weight parameters, which are challenging to optimize manually. This work develops a composite strategy utilizing deep reinforcement learning to autonomously optimize these weights. Specifically, the weight adjustment process is modeled as a Markov decision process. Furthermore, the deep deterministic policy gradient (DDPG) algorithm is employed for optimization. The DDPG agent acts as an auxiliary controller to generate the ideal weights of TriEWMA, while the TriEWMA acts as the primary controller to generate appropriate recipes after obtaining the optimal combination of weights. Finally, the proposed algorithm demonstrates superior performance in handling process dynamics and disturbance rejection, as evidence in simulations of a chemical mechanical polishing process.
Development of a Novel Synchronous Spectrofluorimetric Method Coupled With Chemometric Modelling for Ultrasensitive Analysis of Tenofovir and Dolutegravir With Implication for Pharmacokinetic Studies
Authors: Alnemari Reem M. , Alaqel Saleh I. , Abduljabbar Maram H. , Almalki Atiah H. , Serag Ahmed
Published: January 2025

This study introduces a novel synchronous spectrofluorimetry coupled with chemometric tools for the determination of tenofovir and dolutegravir antiretroviral drugs. Utilizing partial least squares regression (PLS) fine‐tuned by genetic algorithm as variable selection tool, the developed models demonstrate greater sensitivity, cost‐effectiveness, and reduced environmental impact compared to traditional HPLC methods. The model's validation was further confirmed using external validation in addition to QC samples as per ICH M10 guidelines, which yielded high accuracy ranged between 94.78% and 102.48% for tenofovir and 94.56% and 103.31% for dolutegravir, respectively. Additionally, the %CV values for within‐run precision were below 4%, while those for between‐run precision stayed under 6%, for tenofovir and dolutegravir, respectively. Hence, the developed models were adeptly applied to pharmacokinetic studies in a rat model, revealing slight changes in the tenofovir and dolutegravir plasma concentration profiles and half‐lives when administered in combination, highlighting possible drug interactions. Greenness analysis of this spectrofluorimetric approach using the AGREE tool further substantiates its advantages over conventional chromatographic techniques. Hence, this simple, rapid, and environmentally friendly analytical methodology presents a promising alternative for therapeutic drug monitoring and pharmacokinetic studies of tenofovir and dolutegravir antiretroviral drugs.
Building a teaching method for “clinical molecular biology testing technology” guided by the cultivation of thinking skills
Authors: Deng Xin , Ma Nuoya , Hu Xinwen , Li Yong , He Junyu , Zou Guoying
Published: January 2025

The knowledge of “clinical molecular biology testing technology” is complex, conceptual expressions are abstract and difficult to understand, and the student's interest in learning is low. This study aimed to evaluate the effectiveness of a cyclic teaching method based on case analysis combined with an exploratory teaching method using mind mapping as an assignment. Students from the 2019 cohort of medical laboratory technology at Hunan University of Chinese Medicine served as the control group and received conventional lecture‐based teaching methods. Students from the 2021 cohort served as the test group and were undergoing teaching methods that focused on developing critical thinking skills. Course regular grades, exam scores, teaching evaluations, and questionnaires were used to evaluate the teaching effect. The test group had higher scores than the control group. It is also better in terms of memorization ability and comprehensive analytical ability. However, there were no differences between the two groups in terms of understanding and application ability. The test group showed higher satisfaction in improving knowledge mastery, cultivating learning interest, enhancing logical thinking ability, and utilizing post‐class assignments in the form of mind mapping for better knowledge consolidation and expansion than did the control group. The survey results from the test group indicate that a teaching method focused on developing thinking skills has significant effects on stimulating learning interest, improving cognitive ability, and helping to address clinical issues. Combining the cyclic teaching method based on case analysis with the exploratory teaching method using mind mapping as assignments can enhance learning motivation, facilitate knowledge acquisition, and is suitable for teaching in the discipline of “clinical molecular biology testing technology”.
How Climate Change Anxiety Enhances Sustainable Trust and Consumption Behavior: Evidence From Vietnam and Italy
Authors: Nguyen Khoi Minh , Nguyen Ngan Thanh , Ngo Tra Linh , Le Thuy Thu
Published: January 2025

This study explores the intricate associations between climate change anxiety, sustainable trust and three aspects of sustainable consumption behaviors (quality of life, care for environment and care for future generations) among consumers in Vietnam and Italy, with a focus on the moderating role of nature connectedness and hyperopia psychology. Employing an exploratory sequential mixed‐methods approach that integrates both qualitative and quantitative techniques, the study initially conducted 20 in‐depth interviews to gain insights into the interplay between climate change‐related factors, trust, and sustainable consumer behaviors, which helped to formulate the quantitative research framework. Subsequently, a quantitative approach was utilized, gathering 681 online surveys from Vietnamese and Italian consumers, with the data assessed through structural equation modeling using SmartPLS software. This study is the first to reveal crucial theoretical insights into how climate change anxiety and sustainable trust, affected by climate change risk perception and climate change knowledge, impact three aspects of sustainable consumption behaviors: quality of life, care for the environment, and care for future generations. These effects are positively moderated by hyperopia and nature connectedness, providing profound understanding of consumer behavior between the two regions within sustainable consumption amid the urgent global climate change crisis. Scholars benefit from an enriched understanding of consumer behaviors amidst climate change anxiety, while policymakers, businesses, and advocates gain actionable insights to drive effective climate mitigation and adaptation strategies, which contributes to advancing the United Nations' Sustainable Development Goals.
Identification of significant single‐nucleotide polymorphisms associated with breast cancer recurrence and metastasis using GWAS
Authors: Sun Shujuan , Yin Sha , Huang Jie , Zhou Dongdong , Tan Qiaorui , Man Xiaochu , Wang Wen , Zhang Jiale , Li Huihui
Published: January 2025

Background

Identification of risk genes and loci associated with the recurrence and metastasis of breast cancer (BC) is of utmost importance. Genome‐wide association studies (GWASs) represent valuable tools for identifying the disease risk associated with a given single‐nucleotide polymorphism (SNP); they offer significant insights into the disease progression mechanism by analyzing SNP information of the entire genome. Though GWAS has already identified several genetic susceptibility SNPs for BC, their significance in the recurrence and metastasis of this cancer remains unclear. Here, we used a GWAS approach to identify SNPs specifically associated with the risk of BC recurrence and metastasis.

Methods

This study adopted a two‐stage GWAS approach. In the first stage, 97 pairs of BC patients with or without recurrence and metastasis, treated at the Shandong Cancer Hospital and Institute from November 2013 to April 2014, were identified using propensity score matching. DNA extracted from the patient peripheral blood was then subjected to Illumina ASA chip analysis for genome‐wide SNP detection. In the second stage, the findings were verified in a validation set of 854 BC patients recruited at the same hospital from May 2014 to June 2015. SNP genotyping was performed using time‐of‐flight mass spectrometry. The SNP loci and their corresponding genes and pathways were analyzed using the DAVID (https://david.ncifcrf.gov/) online enrichment analysis tool.

Results

Based on the GWAS results, 191 SNP‐related genes significantly associated with BC recurrence and metastasis were identified as expression quantitivative trait loci (p < 0.001). Functional and pathway enrichment analyses subsequently revealed the potential involvement of glutamatergic synaptic transmission, calcium signaling, and insulin secretion pathways in BC recurrence and metastasis. Based on genotype correlation and database expression levels, rs10108514, rs12920540, rs4273077, and rs4730155 were found to be significantly associated with the risk of BC recurrence and metastasis.

Conclusion

Our study suggests that the SNPs rs10108514, rs12920540, rs4273077, and rs4730155 are correlated with the risk of BC recurrence and metastasis, potentially by being implicated in glutamatergic synaptic transmission, calcium signaling, and insulin secretion pathways.
Fronto‐Orbital Osteoblastoma With Unilateral Exophthalmos: A Rare Presentation and Review of Diagnostic Challenges
Authors: Khorraminejad‐Shirazi Mohammadhossein , Nabavizadeh Ali , Bojnoordi Anita , Firouzabadi Dena , Rakhsha Abbas , Hosseini Seyed Ali , Dehghanian Amirreza
Published: January 2025

Osteoblastoma is an uncommon benign bone tumor rarely involving the craniofacial skeleton. Manifestations in the fronto‐orbital region are exceptionally rare. A 19‐year‐old man presented with persistent headache, nausea, vomiting, right eye pain, and longstanding right exophthalmos. Imaging revealed a heterogeneous enhancing lesion located in the right anterior cranial fossa‐orbital apex junction causing pressure on the orbital roof. Differential diagnoses included fibrous dysplasia and meningioma. The tumor was resected via frontal craniotomy. Definitive diagnosis of osteoblastoma was achieved postoperatively through histopathological examination and IHC studies. Craniofacial osteoblastomas, especially in the fronto‐orbital region, are exceptionally rare and may present radiological features similar to other bone pathologies. Accurate diagnosis hinges on histopathological evaluation. A multidisciplinary approach is pivotal for successful diagnosis and treatment of such challenging cases.
Impact of Sotorasib, a KRAS G12C Inhibitor, on the Pharmacokinetics and Therapeutic Window of Digoxin, a P‐Glycoprotein Substrate
Authors: Cardona Panli , Houk Brett
Published: January 2025

Sotorasib is a small‐molecule Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C inhibitor indicated for the treatment of KRAS G12C‐driven cancers. KRAS G12C is a common mutation in solid tumors, including non‐small cell lung cancer. In vitro studies suggested that sotorasib is a weak inhibitor of P‐glycoprotein transporter. Digoxin is a known substrate for P‐glycoprotein. The primary objective of this study was to assess the impact of sotorasib on digoxin pharmacokinetics in healthy subjects. This Phase 1, open‐label, fixed‐sequence study enrolled 14 healthy subjects. Each subject received 0.5 mg of digoxin on Day 1 and 960 mg of sotorasib followed by 0.5 mg of digoxin on Day 7. Blood samples for digoxin pharmacokinetics were collected before dosing and up to 144 hours after the digoxin dose. Digoxin median time to maximum observed plasma concentration and mean terminal half‐life were similar following coadministration of digoxin with sotorasib compared with those of digoxin alone. Geometric mean digoxin area under the concentration‐time curve from time 0 extrapolated to infinity following coadministration of digoxin with sotorasib (40.3 h•ng/mL) was similar to that of digoxin alone (33.2 h•ng/mL). Geometric mean digoxin maximum observed plasma concentration following coadministration of digoxin with sotorasib (3.64 ng/mL) was higher compared with that of digoxin alone (1.90 ng/mL). Coadministration of digoxin and sotorasib did not impact sotorasib exposure. Single doses of 0.5 mg of digoxin were safe and well tolerated when administered alone or coadministered with 960 mg of sotorasib. Coadministration of digoxin with a single dose of sotorasib increased digoxin area under the concentration‐time curve from time 0 extrapolated to infinity and maximum observed plasma concentration by factors of 1.21 and 1.91, respectively, compared with digoxin alone.