bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on the Communication and Governance of Negative Emotions in Major Emergencies Based on Data‐Information‐Intelligence‐Solution Theory
Authors: Wen ZhiQiang , Wang Fei
Published: January 2025

The era of micro‐communication introduces a complex new ecology in the online public opinion surrounding major emergencies. There is an urgent need to explore these new dynamics and develop scientific, reasonable governance strategies to protect public physical and mental health, and maintain social stability and unity. Using the ‘Data‐Information‐Intelligence‐Solution’ (DIIS) think‐tank theory, data was collected from eight different media platforms. An empirical analysis was conducted on ‘emotion, media, region, and group’ (Information). The ‘Driving Force‐State‐Response’ model was utilised to establish a risk assessment system for major emergency online public opinion (Intelligence), followed by the proposal of specific countermeasures and suggestions (Solution). The analysis revealed that anxiety accounts for 88.24% of the negative emotions during major emergencies. The most sought‐after information pertains to the event's development and related large industry groups. Media and event‐related accounts are highly followed, and there is a positive correlation between regional economic levels and anxiety levels. This comprehensive analysis underscores the importance of addressing public anxiety to alleviate negative emotions. The study provides scientific and reasonable strategies based on the DIIS think‐tank theory for government departments to manage the risks of online public opinion during major emergencies.
Macauba (Acrocomia ssp.) fruits: A comprehensive review of nutritional and phytochemical profiles, health benefits, and sustainable oil production
Authors: Sorita Guilherme Dallarmi , Favaro Simone Palma , Gambetta Rossano , Ambrosi Alan , Di Luccio Marco
Published: January 2025

Macauba is an underexplored palm with significant potential for food‐grade vegetable oil production. Its fruits yield two distinct sources of oil, the pulp and the kernel, each with its unique composition, emerging as a potential vegetable oil source with high competitiveness with well‐established conventional oil sources. Besides the oil, macauba fruits are rich in essential nutrients, including proteins, minerals, vitamins, dietary fiber, and phytochemicals, with outstanding health benefits. Macauba processing generates valuable co‐products, including the epicarp, pulp and kernel cakes, and endocarp, which have considerable potential for enhancing the macauba production chain. This review explores the nutritional and phytochemical profile of macauba, its health benefits, and the potential for exploiting its co‐products. Innovative extraction methods and a comprehensive strategy for producing multiple products from macauba co‐products are also highlighted as opportunities to achieve sustainable development goals and a circular economy in macauba fruit processing.
MaxTemp: A Method to Maximise Precision of the Temporal Method for Estimating Ne in Genetic Monitoring Programs
Authors: Waples Robin S. , Masuda Michele M. , LaCava Melanie E. F. , Finger Amanda J.
Published: January 2025

We introduce a new software program, MaxTemp, that increases precision of the temporal method for estimating effective population size (Ne) in genetic monitoring programs, which are increasingly used to systematically track changes in global biodiversity. Scientists and managers are typically most interested in Ne for individual generations, either to match with single‐generation estimates of census size (N) or to evaluate consequences of specific management actions or environmental events. Systematically sampling every generation produces a time series of single‐generation estimates of temporal F (, which can then be used to estimate Ne; however, these estimates have relatively low precision because each reflects just a single episode of genetic drift. Systematic sampling also produces an array of multigenerational temporal estimates that collectively contain a great deal of information about genetic drift that, however, can be difficult to interpret. Here, we show how additional information contained in multigenerational temporal estimates can be leveraged to increase precision of for individual generations. Using information from one additional generation before and after a target generation can reduce the standard deviation of () by up to 50%, which not only tightens confidence intervals around but also reduces the incidence of extreme estimates, including infinite estimates of Ne. Practical application of MaxTemp is illustrated with data for a long‐term genetic monitoring program for California delta smelt. A second feature of MaxTemp, which allows one to estimate Ne in an unsampled generation using a combination of temporal and single‐sample estimates of Ne from sampled generations, is also described and evaluated.
Biogeographical Distribution of River Microbial Communities in Atlantic Catchments
Authors: Goldenberg‐Vilar Alejandra , Morán‐Luis María , Vieites David R. , Álvarez‐Martínez José Manuel , Silió Ana , Mony Cendrine , Varandas Simone , Monteiro Sandra Mariza , Burgess Diane , Cabecinha Edna , Barquín José
Published: January 2025

Microbes inhabit virtually all river ecosystems, influencing energy flow and playing a key role in global sustainability and climate change. Yet, there is uncertainty about how various taxonomic groups respond to large‐scale factors in river networks. We analysed microbial community richness and composition across six European Atlantic catchments using environmental DNA sequencing. Our findings reveal different drivers for diversity and composition: land use is pivotal for eukaryotes, while climate and geology are crucial for prokaryotes. A strong regional influence shapes these communities, with warmer, drier regions (Portugal and France) differing from cooler, wetter ones (Northern Spain, Ireland and the United Kingdom). These patterns suggest potential indicators for global change, such as taxa resistant to temperature increases and water scarcity, or those sensitive to land use changes.
3D Computed Tomography Reconstruction for Pre‐Operative Diagnosis of Anomalous Venous Drainage of the Right Upper Lobe
Authors: Puca Maria Antonietta , Marella Antonio , Marvulli Maria , Rainone Anna , Capasso Francesca , di Filippo Vincenzo , Messina Gaetana , Fiorelli Alfonso
Published: January 2025

Anatomical variation of the pulmonary vessels poses challenges to thoracoscopic lung resection and may be associated with an increased risk of intraoperative bleeding and damage to pulmonary circulation. Herein, we reported a rare and dangerous variation as the partial anomalous venous drainage of the right upper lobe into the superior vena cava in a patient undergoing thoracoscopic lobectomy for management of lung cancer of right upper lobe. The preoperative identification of such variation by 3D computed tomography scan allowed to plan a safe and accurate resection, and to prepare additional strategies for overcome unexpected intraoperative bleeding. No intraoperative and/or postoperative complications were observed. Chest drainage was removed on postoperative day two and patient discharged the day after. At 3 months follow up, the patient was well without recurrence.
The effect of the type of anaesthesia on long‐term outcomes after cancer resection surgery: a narrative review
Authors: Bezu Lucillia , Rahmani Lua S. , Buggy Donal J.
Published: January 2025

Background

The peri‐operative period may create a biological environment conducive to cancer cell survival and dissemination. Microscopic residual tumours (micrometastases) can be dislodged even with excellent surgical technique. At the same time, the stress response from surgery can temporarily impair immune function and activate inflammatory processes, increasing the risk of tumour proliferation.

Methods

This narrative review investigates how peri‐operative anaesthetic and analgesic interventions may influence cancer recurrence and metastasis by exploring evidence from both experimental and clinical studies. A comprehensive review of the literature was conducted to identify relevant preclinical and clinical studies published.

Results

While surgery remains the best curative option for many cancers, metastasis remains the leading cause of death. Numerous studies have suggested that different anaesthetic drugs and techniques could impact cancer outcomes including volatile anaesthetic agents; total intravenous anaesthesia with propofol; local anaesthetics; regional anaesthesia; and opioids. This review focuses on these five commonly used anaesthetic approaches and evaluates their potential impact on cancer progression.

Discussion

There is a complex interplay between anaesthetic and analgesic techniques and cancer outcomes. Despite promising data from laboratory experimental models, the balance of available clinical trials indicates an equivalent influence of all evaluated anaesthetic techniques on long‐term oncologic outcomes, except, possibly, for peritumoral or intraperitoneal local anaesthetic infiltration.
Systemic anti‐cancer therapy and anaesthesia: a narrative review
Authors: Weaver Jamie M. J. , Patey Susannah J.
Published: January 2025

Introduction

Cancer research has revolutionised the treatment, quality of life and life expectancy of people living with cancer. Systemic anti‐cancer treatments have expanded to involve not only cytotoxic drugs, but targeted drugs and immunotherapy. Although highly effective in many patients, these drugs can cause serious and sometimes life‐threatening adverse reactions. As part of their treatment, many patients living with cancer will be offered both systemic anti‐cancer therapy and surgery, and many patients will undergo recurrent episodes of both with the aims of cure, palliation or prolongation of life expectancy. It is important for anaesthetists to understand the effects of systemic anti‐cancer therapy on their patients.

Methods

An electronic literature search using was conducted in May 2024 for peer‐reviewed articles in English. An initial search of the terms ‘anaesthesia’ and ‘chemotherapy’ revealed that existing review literature was tailored towards the neoadjuvant setting and prompted this review to include the complications of targeted therapies, emergency care and intra‐operative administration of systemic anti‐cancer therapy to reflect this evolving field. A narrative approach was taken to discuss common regimens and their complications.

Results

The review encompasses a wide range of sub‐topics including pharmacology; physiology; peri‐operative medicine; specialist surgery; adverse events; and safety. Data from multicentre trials that form the basis of current treatment regimens and practice were prioritised during the selection process. Smaller studies, case series and case reports were included to illustrate the rarer but clinically significant adverse effects of specific therapies.

Conclusions

It is important for anaesthetists to have a comprehensive understanding of the effects of systemic anti‐cancer therapies, including cytotoxic and immunotherapies. There are many potential toxicities and complications associated with these treatments, particularly in the context of emergency surgery and the administration of cytotoxic drugs within the operating theatre environment.
How do women with Rokitansky syndrome and healthcare professionals reflect on the provision of uterine transplantation? Insights from an interview study in France, Norway, and Sweden
Authors: Carton Isis , Dion Ludivine , Lavoué Vincent , Hofmann Bjorn Morten
Published: January 2025

Introduction

Uterine transplantation is currently intended for women with absolute uterine infertility. Since proof of the concept in 2014, many countries have started research programs and clinical activities. However, access to uterine transplantation remains limited given that only a few hundred transplants have been described worldwide compared with the 1.5 million women of childbearing age who suffer from absolute uterine infertility. The aim of this study was to investigate how limited access to uterine transplantation is perceived by women with Mayer–Rokitansky–Küster–Hauser syndrome and health professionals involved in uterus transplantation programs.

Material and Methods

We conducted a qualitative study with semistructured interviews in France, Norway, and Sweden with women with Mayer–Rokitansky–Küster–Hauser syndrome and health professional involved in uterine transplantation programs. The interviews were analyzed manually using thematic content analysis. The research questions were: How do (a) women with Mayer–Rokitansky–Küster–Hauser syndrome and (b) healthcare professionals involved in uterus transplantation programs perceive uterus transplantation and its accessibility 10 years after proof of concept?

Results

The interviews enabled us to highlight a number of themes addressed by doctors and women with Mayer–Rokitansky–Küster–Hauser syndrome, the main ones being the hope raised by this technique and the disappointment for those who do not have access to it, the lack of perception of the risks associated with the technique, and finally, an inequity of access and the training difficulties this entails for the teams.

Conclusions

Access to uterine transplantation varies widely across Europe owing to legislative restrictions and limited access due to resources or competence. The result is a feeling of injustice/misunderstanding and despair for these women who had planned to become parents and cannot benefit from a transplant. They appear to be poorly supported. Women who are ultimately unable to access a transplant program should perhaps be given psychological support to deal with this disappointment, whereas the minority who finally have had access to transplant programs are supervised by well‐trained multidisciplinary teams.
Effects of dietary supplementation of myristic acid on jejunal mucosa‐associated microbiota, mucosal immunity, and growth performance of nursery pigs
Authors: Choi Hyunjun , Rocha Gabriel Cipriano , Kim Sung Woo
Published: January 2025

The objective of this study was to investigate the effects of myristic acid on jejunal mucosal microbiota, mucosal immunity, and growth performance of nursery pigs. Thirty‐six pigs (6.6 ± 0.4 kg of body weight) were assigned to three treatments (n = 12) for 35 d in three phases: (NC) basal diet; (PC) NC + bacitracin; and (MA) NC + myristic acid compound. Pigs were euthanized to collect jejunal mucosa, jejunal tissues, and ileal digesta. The PC increased (p < 0.05) the relative abundance (RA) of Lactobacillus spp., and Bifidobacterium boum than the NC group. The MA increased (p < 0.05) RA of Bifidobacterium dentium and Megasphaera spp. than the NC group. The PC tended to decrease IL‐8 (p = 0.053) and protein carbonyl (p = 0.075) whereas IgG (p = 0.051) and IL‐8 (p = 0.090) in jejunal mucosa were decreased by the MA. The PC increased (p < 0.05) the villus height to crypt depth ratio than the NC group. Both bacitracin and myristic acid improved the intestinal health and growth performance of nursery pigs. Effects of bacitracin were rather immediate whereas the effects of myristic acid were obtained after a 3‐week feeding.
Cancer drug applications to the EMA and the FDA: A comparison of new drugs and extension of indication in terms of approval decisions and time in review
Authors: Cramer Allan , Sørup Freja Karuna Hemmingsen , Christensen Hanne Rolighed , Petersen Tonny Studsgaard , Karstoft Kristian
Published: January 2025

Aims

The aim of this study was to compare the final approval decision and time from submission to final decision for new drug applications and applications for extension of indications to the EMA and the FDA within cancer drugs.

Methods

We performed a retrospective analysis on antineoplastic drug applications with a final decision in both the EMA and the FDA from January 1, 2018, to December 31, 2022. For each included drug application, we collected data from the EMA website and the Drugs@FDA database.

Results

A total of 48 new drug applications and 94 applications for extension were included. Agreement in the final decision between the EMA and the FDA was found in 94% of new drug applications and 96% of applications for extension. For new drug applications, the time from submission to approval in the EMA and the FDA were median (interquartile range, IQR) 424 (394–481) days and 216 (169–243) days, respectively. For extensions, the median time from submission to approval in the EMA and the FDA were 295 (245–348) days and 176 (140–183) days, respectively.

Conclusions

We found a high agreement in final approval decisions for cancer drug applications between the EMA and the FDA both for new drug applications and applications for extension. The time from submission to the final decision was markedly shorter in the FDA than in the EMA, albeit the difference was smaller for extensions than for new drug applications. The results indicate that the longer time from submission to decision in the EMA than in the FDA has limited influence on the final approval decisions.
Venetoclax therapy in chronic lymphocytic leukaemia patients relapsed after allogeneic haematopoietic stem cell transplantation
Authors: Perutelli Francesca , Boccellato Elia , Montalbano Maria Chiara , Catania Gioacchino , Deodato Marina , Frustaci Anna Maria , Innocenti Idanna , Moia Riccardo , Quaglia Francesca Maria , Quaresmini Giulia , Rivela Paolo , Gaidano Gianluca , Krampera Mauro , Laurenti Luca , Rambaldi Alessandro , Bruno Benedetto , Vitale Candida , Coscia Marta
Published: January 2025

Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains an option for young and fit chronic lymphocytic leukaemia (CLL) patients with high‐risk disease features. However, allotransplanted patients are generally excluded from clinical trials, making data regarding the use of venetoclax after alloHSCT extremely rare. We report data from 7 CLL patients who received venetoclax after alloHSCT among 53 Italian centers. These patients underwent alloHSCT between 2006 and 2021 after failing chemoimmunotherapy (7/7), ibrutinib (5/7) and/or idelalisib (1/7). Of note, 3/7 patients had already received venetoclax‐based therapy before alloHSCT. Post‐allo HSCT venetoclax treatment resulted safe, with adverse events not different from what reported in clinical trials. Importantly, no meaningful impact on graft versus host disease (GvHD) course was observed: 4/7 patients with pre‐existing chronic GvHD had no exacerbation after venetoclax start, and only one patient developed GvHD during venetoclax therapy, that was managed as per standard clinical practice. Concerning efficacy, 5/7 patients presented a clinical response to venetoclax, with two patients achieving an undetectable minimal residual disease. To our knowledge, this is the largest reported series of CLL patients treated with venetoclax after alloHSCT. In these heavily pretreated and high‐risk patients, previous alloHSCT did not compromise the feasibility of venetoclax therapy, that lacked unexpected toxicities and did not exacerbate GvHD.
Carbonic anhydrase IX inhibition as a path to treat neuroblastoma
Authors: Petrosiute Agne , Zakšauskas Audrius , Lučiūnaitė Asta , Petrauskas Vytautas , Baranauskienė Lina , Kvietkauskaitė Agnė , Ščerbavičienė Alvilė , Tamošiūnaitė Marta , Musvicaitė Justina , Jankūnaitė Alberta , Žvinys Gediminas , Stančaitis Laimonas , Čapkauskaitė Edita , Mickevičiūtė Aurelija , Juozapaitienė Vaida , Dudutienė Virginija , Zubrienė Asta , Grincevičienė Švitrigailė , Bukelskienė Virginija , Schiöth Helgi B. , Matulienė Jurgita , Matulis Daumantas
Published: January 2025

Background and Purpose

Tumour hypoxia frequently presents a major challenge in the treatment of neuroblastoma (NBL). The neuroblastoma cells produce carbonic anhydrase IX (CA IX), an enzyme crucial for the survival of cancer cells in low‐oxygen environments.

Experimental Approach

We designed and synthesised a novel high‐affinity inhibitor of CA IX. The highest to‐date. The affinities were determined for all human catalytically active CA isozymes showing significant selectivity for CA IX over other isozymes. The inhibitor effect on neuroblastoma cancer cell growth was determined in vitro and in vivo via a mice xenograft model.

Key Results

The novel designed inhibitor effectively mitigated the acidification induced by CA IX and reduced spheroid growth under hypoxic conditions in the SK‐N‐AS cell line. It also diminished the secretion of pro‐tumour chemokines IL‐8 (CXCL2) and CCL2. When we combined this novel CA IX inhibitor with a compound that inhibits the chemokine receptor CCR2 protein activity, we observed a reduction in mouse tumour growth. The combined treatment also prompted tumours to exhibit adaptive resistance by producing higher levels of vascular endothelial growth factor receptors (VEGFR) and other compensatory signals.

Conclusions and Implications

This research underscores the pivotal role of CA IX in cancer and the potential of a novel CA IX inhibitor‐based combination intervention therapy for neuroblastoma treatment.
CYP24A1 Binding to FUS Maintains Tumor Properties by Regulating the miR‐200c/ZEB1/EMT Axis
Authors: Wang Ping , Xu Jiming , You Weijing , Li Jie , Yu Jing , Jiang Fei , Zhang Zengli , Hu Wentao , Li Bingyan
Published: January 2025

The active vitamin D‐degrading enzyme (CYP24A1) is commonly overexpressed in various types of cancer, which is associated with poor prognosis in cancer patients. Recent studies highlight the antagonism of CYP24A1 toward the anticancer role of active vitamin D. However, the impact of CYP24A1 on tumorigenesis and its underlying mechanisms largely remains unexplored. This study also found that high CYP24A1 mRNA expressions were associated with poor prognosis in ovarian cancer and lung adenocarcinoma (LUAD) patients. Moreover, we demonstrated that the overexpression of CYP24A1 accelerated the proliferation, migration, and invasion of ovarian cancer and LUAD cancer cells in vitro. Furthermore, knockdown of CYP24A1 displayed an anticancer effector both in vitro and in vivo. Mechanically, 87–297 amino acid motif of CYP24A1 bound specifically to FUS protein, consequentially reducing FUS affinity for miR‐200c. Considering FUS promotes gene silencing by binding to microRNA targets, a decrease in miR‐200c levels led to a notable activation of its target ZEB1, resulting in the promotion of the epithelial‐mesenchymal transition (EMT) process. In conclusion, FUS binding specifically by CYP24A1 impaired miR‐200c‐mediated ZEB1 silencing, thereby augmenting EMT progression and tumorigenesis. These findings elucidate a fundamental mechanism by which CYP24A1 operates as an oncogene, offering potential targets for therapeutic interventions in cancer treatment.
Enhancing pashmina fabric aesthetics: Assessing the dyeing efficacy of indigenous wild underutilised plants
Authors: Mushtaq Irtizah , Singh Amerjeet , Sofi Asif H. , Sofi P. A. , Khan P. A. , Bhat G. M. , Malik A. R. , Jalal Heena , Jeelani Iqbal , Bilal Tuybia , Benatul‐Behar  , Shabir Sufiya
Published: January 2025

This study explores the use of dyes extracted from Berberis aristata and Bistorta amplexicaulis for dyeing pashmina fabric. The effectiveness of these plant‐derived dyes was evaluated based on colour strength, absorption efficiency and fastness properties including washing, light and rubbing. Results indicate that both Berberis aristata and Bistorta amplexicaulis dyes significantly enhance the colour quality of pashmina fabric, with simultaneous mordanting yielding the highest colour strength and fastness properties, followed by premordanting. Berberis aristata exhibited poor light fastness (1), but showed excellent rubbing and washing fastness (5), while Bistorta amplexicaulis demonstrated good light fastness (4) and (4/5), as well as excellent performance in rubbing and washing fastness (5). Dye concentrations positively impacted colour strength, with higher concentrations resulting in deeper shades. The percentage absorption of the dye into the fabric was notably high, reflecting effective dye uptake. Mordant enhanced the colour quality of the fabric because of the increased efficiency in absorption, colour strength, colour coordinates and fastness grades in terms of washing, light and rubbing, respectively. These findings suggest that dyes from Berberis aristata and Bistorta amplexicaulis are promising for textile applications, offering vibrant, durable colours and adaptable dyeing methods.
White Depressed Areas and Tumor Infiltrating Lymphocytes: The Cancer Cure That Lies Within?
Authors: Murphy George F.
Published: January 2025

This brief overview is inspired by seminal contributions by the late Dr. Martin C. Mihm, Jr. who provided a basis for recognition and better understanding of interactions between lymphocytes (tumor‐infiltrating lymphocytes [TILs]) that home to and permeate cancers. In primary melanomas, this phenomenon may produce what Dr. Mihm called white depressed areas, prescient clues to what would fuel future attempts at harnessing anticancer immunity. The critical and sequential TIL attributes of antigenic stimulation, homing, and effector–target cell apoptotic injury herein are briefly reviewed in light of more recent advances in the field of immuno‐oncology. The intent is to emphasize how fundamental clinical and histopathological observations, as forged by Dr. Mihm and his associates, have led to critically important prognostic paradigms as well as to translational insights that now have become transformative in the field of cancer immunotherapy.
Long‐term health benefit and economic return of time in range (TIR) improvement in individuals with type 2 diabetes
Authors: Alkhuzam Khalid , Li Piaopiao , Abuloha Sumaya , Xue Qiaochu , Shi Lizheng , Fonseca Vivian , Zhang Yongkang , Shao Hui
Published: January 2025

Objective

Time in range (TIR) is an important metric to measure variability of blood glucose levels. The aim is to quantify the long‐term health benefits and economic return associated with improved TIR for individuals with type 2 diabetes (T2D).

Method

A Markov model with three states (T2D, T2D with cardiovascular disease (CVD) and death) estimated 20‐year medical costs, quality‐adjusted life‐years (QALY) gained and CVD risk under four TIR scenarios: >85%, 71%–85%, 51%–70% and ≤50%. The T2D population was identified using the National Health and Nutrition Examination Survey, and model parameters were sourced from literature. Costs were estimated from a healthcare sector perspective and standardized to 2021 US dollars. Cost ceilings were determined using three willingness‐to‐pay (WTP) thresholds: $100 000/QALY, $50 000/QALY and $0/QALY (cost‐saving).

Results

Compared to TIR <50%, improving TIR to 51%–70% resulted in a 0.79 QALY increase and 4.91% CVD risk reduction; to 71%–85%, a 0.95 QALY increase and 6.24% CVD risk reduction; to >85%, a 1.18 QALY increase and 8.75% CVD risk reduction. To be cost‐effective at $100 000/QALY, annual costs for TIR improvements from <50% to 51%–70%, 71%–85% and >85% should be <$1148, $4200 and $7252, respectively. To be cost‐saving, these costs should be <$612, $2816 and $5021.

Conclusion

Improving TIR yields significant health benefits. We calculated feasible medical cost allocations for TIR improvements, informing the implementation of interventions like continuous glucose monitoring devices.
MicroRNA‐mediated Ets1 repression in retinal endothelial cells: A novel anti‐angiogenic mechanism in nonproliferative diabetic retinopathy
Authors: Zhao Jianyu , Sun Zewen , Li Zimeng , Xu Mengyu , Tian Aowen , An Zhengwen , Guo Wenbo , He Chang , Dong Ying , Wen Jianping , Yang Jianli , Wang Qing , Chen Peng
Published: January 2025

Aims

This study aimed to discover the regulatory mechanisms contributing to angiogenesis in nonproliferative diabetic retinopathy (NPDR).

Materials and Methods

This study employed a case–control design involving type 2 diabetes patients with and without NPDR. We utilised microRNA sequencing to analyse plasma and retina samples from T2D patients, to identify both existing and novel microRNAs relevant to retinal health. An integrative approach combining single‐cell sequencing data from mouse and rat models was used to explore the molecular mechanism in retinal cells under diabetes condition.

Results

We identified a specific set of circulating microRNAs with strong predictive potential for distinguishing NPDR patients. In addition, a novel microRNA targeting the ETS proto‐oncogene 1 (Ets1), a key regulator of microvascular angiogenesis, was found to be upregulated in the plasma of NPDR patients. Analysis of single‐cell sequencing data suggested that Ets1 expression was downregulated in diabetic endothelial cells and was associated with the repression of Angiopoietin‐1 and phosphoinositide 3‐kinase‐Akt (PI3K‐Akt) signalling pathways, indicating an anti‐angiogenic mechanism in NPDR.

Conclusions

The identification of a novel microRNA involved in the anti‐angiogenic mechanism in NPDR provides new insights into the molecular underpinnings of endothelial dysfunction in diabetic retinopathy. Our retina‐specific circulating microRNA panel has potential utility in risk assessment and early detection of NPDR.
Pedagogical and Methodological Principles for the Development of Artistry of Vocal Performance in the Context of Distance Learning
Authors: Liu Aizhen
Published: January 2025

The objective of this study was to investigate the influence of contemporary pedagogical principles of distance learning on the quality of acquiring artistic skills in the field of vocal arts. The research was conducted based on a sample of 750 first‐year students from the School of Literature and Journalism (Zhengzhou Business University), utilising a random sampling method. The research entailed the implementation of a case study method to facilitate an in‐depth examination of the impact of modern pedagogical principles of distance learning on the quality of acquiring artistic skills in the realm of vocal arts. Pedagogical observation materials were employed in two experimental groups of students for empirical investigation purposes. To obtain statistical data, the method of qualitative analysis was employed and experimental online sessions were conducted from February to April 2023. It has been ascertained that, based on preliminary surveys, the average performance scores for the three groups, as per the mental principle, did not exceed 3.8 points; as per the physical principle, 4.3 points; and as per the aesthetic principle, 4.4 points. This equates to a low and borderline average level of knowledge and signifies the low efficacy of the methodological principles.
The Role of Lifestyle and Environmental Factors in the Pathogenesis of Multiple Myeloma
Authors: Suska Anna , Tyczyńska Agata , Zaucha Jan Maciej , Kopińska Anna , Helbig Grzegorz , Markiewicz Mirosław , Warzybok Katarzyna , Leder Ewa , Grosicki Sebastian , Machaliński Bogusław , Baumert Bartłomiej , Bator Michał , Usnarska‐Zubkiewicz Lidia , Fornagiel Szymon , Ciepłuch Hanna , Waszczuk‐Gajda Anna , Kruczkowska‐Tarantowicz Kamila , Rzepecki Piotr , Hus Marek , Morawska‐Krekora Anna , Raźny Małgorzata , Charliński Grzegorz , Puła Anna , Nita Ewa , Wojciechowska Małgorzata , Krawczyk‐Kuliś Małgorzata , Goldberg Joanna , Woźny Tomasz , Rodzaj Marek , Olejarz Dariusz , Gronau‐Dziurkowska Marlena , Skalniak Ewa , Krzysztoń Janusz , Niezabitowska Karolina , Jurczyszyn Artur
Published: January 2025

Objectives

The study evaluated the impact of lifestyle and environmental exposure on the etiology of multiple myeloma (MM).

Methods

A multicenter case–control study was conducted in 20 hematology centers and in 5 outpatient clinics in Poland. The questionnaire on exposure to potential risk factors including sociodemographic data, lifestyle, and environmental factors was completed.

Results

A total of 274 patients with newly diagnosed MM and 208 patients from primary healthcare centers in the control group were enrolled in the study. Regarding lifestyle, sports practiced systematically for at least half a year play a protective role in the development of myeloma (OR = 0.40, 95% CI, 0.28–0.58, p < 0.001). Among environmental factors harmful exposures that increase the likelihood of the development of MM include pesticides (OR = 3.29, p < 0.001), asphalt (OR = 2.42, p = 0.026), coal dust (OR = 2.27, p = 0.004), organic vapors (OR = 2.11, p = 0.001), metal dust (OR = 2.07, p = 0.023), exhaust fumes (OR = 2.03, p < 0.01), and chemicals (OR = 1.80, p < 0.01).

Conclusions

The pathogenesis of MM is complex with the impact of modifiable factors. Lifestyle, with physical activity, seems to play a key role.
Delineating the genetic landscape of Charcot–Marie–tooth disease in Türkiye: Distinct distribution, rare phenotypes, and novel variants
Authors: Cakar Arman , Candayan Ayse , Bagırova Gulandam , Uyguner Zehra Oya , Ceylaner Serdar , Durmus Hacer , Battaloglu Esra , Parman Yesim
Published: January 2025

Background

Charcot–Marie‐Tooth (CMT) disease is the most common inherited neuropathy. In this study, we aimed to analyze the genetic spectrum and describe phenotypic features in a large cohort from Türkiye.

Methods

Demographic and clinical findings were recorded. Patients were initially screened for PMP22 duplication. Targeted sequencing or whole‐exome sequencing was performed in duplication‐negative patients.

Results

Overall, 311 patients from 265 families were included. Demyelinating CMT (67.4%) was more common than axonal (20.5%) and intermediate subtypes (11.7%). PMP22 duplication was the most frequent mutation, followed by pathogenic variants in GJB1, MFN2, SH3TC2, and GDAP1 genes. MPZ‐neuropathy was rare in our cohort (3.0%). Interestingly, CMT4 is the second most common type after CMT1. Lower extremity weakness and foot deformities were the most frequent presenting complaints. Striking clinical features included a high frequency of scoliosis in SH3TC2, peripheral hyperexcitability in HINT1, and central nervous system findings in GJB1. Autosomal recessive CMT subtypes had higher CMTESv2 scores when compared to autosomal dominant ones (12.39 ± 4.81 vs. 8.36 ± 4.15, p: 0.023). Twenty‐one patients used wheelchairs during their last examination. Among them, 16 had an autosomal recessive subtype. Causative variants were identified in 31 genes, including 28 novel pathogenic or likely pathogenic changes.

Conclusions

Our findings provided robust data regarding the genetic distribution of CMT in Türkiye, which may pave the path for building population‐specific diagnostic gene panels. Rare autosomal recessive subtypes were relatively frequent in our cohort. By analyzing genotype–phenotype correlations, our data may provide clinical clues for clinicians.
Identification and characterisation of temporal abundance of microRNAs in synovial fluid from an experimental equine model of osteoarthritis
Authors: Walters Marie , Skovgaard Kerstin , Heegaard Peter M. H. , Fang Yongxiang , Kharaz Yalda A. , Bundgaard Louise , Skovgaard Lene T. , Jensen Henrik E. , Andersen Pia H. , Peffers Mandy J. , Jacobsen Stine
Published: January 2025

Background

MicroRNAs, a class of small noncoding RNAs, serve as post‐transcriptional regulators of gene expression and are present in a stable and quantifiable form in biological fluids. MicroRNAs may influence intra‐articular responses and the course of disease, but very little is known about their temporal changes in osteoarthritis.

Objectives

To identify miRNAs and characterise the temporal changes in their abundance in SF from horses with experimentally induced osteoarthritis. We hypothesised that the abundance of miRNA would change during disease progression.

Study design

In vivo experiments.

Methods

RNA extracted from synovial fluid obtained sequentially (Day 0, 28 and 70) from nine horses with experimentally induced osteoarthritis was subjected to small RNA sequencing using the Illumina Hiseq 4000 sequencing platform. Differentially abundant miRNAs underwent further validation and mapping of temporal abundance (Day 0, 14, 17, 21, 28, 35, 42, 49, 56, 63 and 70 days after osteoarthritis induction) by microfluidic reverse transcription quantitative real‐time PCR. Bioinformatic analyses were performed to predict potential biological associations and target genes of the differentially abundant microRNAs.

Results

Small RNA sequencing revealed 61 differentially abundant microRNAs at an early osteoarthritis stage (Day 28), and subsequent reverse transcription quantitative real‐time PCR analysis validated 20 of these. Significant biological functions of the differentially abundant microRNAs were apoptosis, necrosis, cell proliferation and cell invasion. Following validation, four microRNAs (miRNA‐199b‐3p, miRNA‐139‐5p, miRNA‐1839 and miRNA‐151‐5p) were detected in more than 50% of the synovial fluid samples and had higher abundance in osteoarthritic than in control joints.

Main limitations

Limited sample size.

Conclusion

This is the first study to determine longitudinal changes in synovial fluid microRNA abundance in an equine model of osteoarthritis. Larger studies are needed in naturally occurring osteoarthritis to interrogate putative changes identified by this study.
Inflammation and response to bacterial infection as potential drivers of equine odontoclastic tooth resorption and hypercementosis: A proteomics insight
Authors: Jensen Anders , Clarke Emily J. , Nugent Zoe , Paice Emily , Gringel Iris , Yamamoto Kazuhiro , Rocchigiani Guido , Peffers Andrew J. , Cooper Lee , Peffers Mandy J.
Published: January 2025

Background

Equine dental diseases significantly impact a horse's overall health, performance and quality of life. They can result in secondary infections and digestive disturbances, potentially leading to colic. A recently described disease affecting the incisors of horses is equine odontoclastic tooth resorption and hypercementosis (EOTRH). Understanding EOTRH is crucial for early diagnosis, effective management and prevention of its severe consequences.

Objectives

To determine proteomic differences in incisor cementum in horses with and without clinical EOTRH.

Study design

Comparative and observational clinical study.

Methods

Teeth were extracted (N = 5) and cementum was isolated using a diamond wire. Proteins were extracted using an optimised sequential workflow, and trypsin was digested for mass spectrometry. Protein identification and label‐free quantification were undertaken.

Results

In total 1149 unique proteins were detected in cementum across all samples. We identified four proteins exclusively in EOTRH‐affected cementum. EOTRH samples showed a higher heterogeneity than healthy samples. In total, 54 proteins were increased in EOTRH, and 64 proteins were reduced (adjusted p‐value <0.05). Inflammatory proteins, such as cathepsin G (p = 0.004), neutrophil elastase (p = 0.003), bactericidal permeability‐increasing protein (p = 0.002), azurocidin (p = 0.003) and lactotransferrin (p = 0.002) were all increased in EOTRH. Pathway analysis revealed that antimicrobial peptides (Z score 2.65, p = 1.93E−09) and neutrophil degranulation (Z‐score 1.89, p = 1.7E−04) were commonly up‐regulated canonical pathways.

Main limitations

The sample size was limited. Lack of age‐matched healthy controls.

Conclusion

EOTRH leads to biochemical changes within the cementum proteome, which are important in explaining the physiological changes occurring in disease. Differentially abundant proteins may represent promising biomarkers for earlier disease detection and the establishment of a cell‐based model could provide further insight into the role these proteins play in hypercementosis and resorption.
Responses of Benthic Carbon Flows in Scandinavian Lakes to Atmospheric Sulphur and Nitrogen Depositions: Potential Influence of Nutrient Limitation
Authors: Belle Simon , Fölster Jens , Goedkoop Willem , Johnson Richard K.
Published: January 2025

Paleolimnological reconstructions of past changes in carbon stable isotopic composition of chironomid head capsules (δ13CHC) were used to quantify the impacts of atmospheric sulphur and nitrogen depositions on carbon processing at the base of lake food webs.

We hypothesised that the impacts of atmospheric nitrogen deposition on carbon flows through food webs are influenced by nutrient limitation, as increasing nitrogen inputs are expected to drive higher primary producer biomass in nitrogen‐limited lakes, thus increasing its availability for benthic consumers.

The δ13CHC values showed significant changes before/after 1960, corresponding to the time of early impacts of atmospheric deposition on water chemistry and biological communities in Scandinavian lakes. These results suggest that atmospheric deposition was a key driver of change in carbon flows through benthic food webs. Furthermore, our study showed that lakes responded differently to atmospheric deposition and that differences in δ13CHC values were largely explained by a combination of nutrient limitation, latitude and water transparency.

Overall, results support the hypothesis that the response of carbon flows through benthic food webs to changes in atmospheric nitrogen deposition differs partly depending on lake nutrient limitation. However, the observed strong collinearity between the explanatory variables complicates the interpretation of the relationships between the temporal changes in benthic carbon flows in response to atmospheric deposition and nutrient limitation.
Threonine and tyrosine kinase (TTK) mRNA and protein expression in breast cancer; prognostic significance in the neoadjuvant setting
Authors: Ashi Abrar , Awaji Aeshah A , Bond Jacquelyn , Johnson Colin A , Shaaban Abeer M , Bell Sandra M
Published: January 2025

Aims

Threonine and tyrosine kinase (TTK) is up‐regulated in triple‐negative breast cancer (TNBC), yet its expression in patients undergoing neoadjuvant chemotherapy (NACT) remains unexplored. This investigation aims to assess TTK protein expression in treatment‐naïve pre‐treatment cores and paired pre‐ and post‐NACT breast cancer (BC) cohorts, as well as its correlation with microcephaly 1 (MCPH1) protein expression.

Methods and results

Transcriptomic data were sourced from the Gene Expression Omnibus microarray database for mRNA expression analysis. TTK protein expression was evaluated using immunohistochemistry staining, employing receiver operating characteristic curve analysis to determine an optimal TTK expression cut‐off point. The association between TTK expression, clinicopathological parameters and survival outcomes was examined. Additionally, MCPH1 protein expression was assessed in a pilot study. Analysis revealed a significantly elevated TTK mRNA expression in BC tissue compared to normal breast tissue, with high TTK mRNA levels predicting reduced overall survival. Notably, TTK protein expression increased significantly post‐NACT in a paired cohort. Conversely, decreased TTK protein expression pre‐NACT was correlated with improved overall survival.

Conclusions

High TTK and low MCPH1 protein expression was significantly correlated, highlighting TTK's potential as a biomarker for BC and a therapeutic target for MCPH1‐deficient cancer cells.
Temperature dependent scaling behavior and evolution of domain dynamics in low temperature sintered PZN–PZT ceramics
Authors: Baby Anagha , N. Shara Sowmya , N. S. Reshma , S. Susanth , E. K. Sunny , V. Priyadarshini , Thangavelu Karthik
Published: January 2025

A comprehensive investigation into the dynamic hysteresis behavior of the low temperature sintered 0.4PZN–0.6PZT ceramics across a wide range of electric field frequency, and temperature was carried out in the present study. Our findings from the electric field and frequency dependent scaling analysis at 303 K revealed distinct domain dynamics having three stages of polarization reversal mechanism with a breakdown frequency (fb) of 5 Hz. Temperature dependent scaling analysis till 503 K showcased the influence of thermal energy especially in the stage‐I and stage‐II of the polarization reversal mechanism resulting in enhanced domain wall mobility with reduced switching time at a lower electric field. The power‐law temperature scaling relations for hysteresis area 〈A〉, remanent polarization (Pr), and coercivity (EC) took the form of A ∝ T 0.1468, Pr ∝ T −0.5577, and EC ∝ T −0.68272, respectively. The decay of the derived exponent values with temperature corresponding to 〈A〉, Pr, and EC was minimal as compared to the other reported soft PZT and lead‐free systems. This study provided information on the influence of temperature toward domain wall motion, domain nucleation, and domain switching, and it will be useful for designing devices that demand high reliability and thermal stability.
Impact of sintering parameters on the microstructure of homogeneous U1‐xCexO2+δ ceramics
Authors: Clavier Nicolas , Massonnet Malvina , Claparede Laurent , Podor Renaud , Imbert Paul‐Henri , Martinez Julien , Dacheux Nicolas
Published: January 2025

The effects of atmosphere and cerium content on the densification and the final microstructure of homogeneous U1‐xCexO2+δ solid solutions (x = 0.10; 0.25; 0.50) were investigated. Dilatometric studies first revealed that while the cerium content only slightly modifies sintering under an Ar/H2 atmosphere, a change of the gas to argon dramatically modifies densification kinetics. As a result, samples prepared under Ar/H2 exhibit a dense microstructure with micrometric grains. Conversely, samples sintered under argon appeared to be less densified but with larger grains. These changes were correlated with the variation of the final O/M stoichiometry (M = U+Ce) and illustrated by the construction of sintering maps. Finally, grain growth was found to be driven by grain boundary motion when the O/M ratio remained close to 2.00, while usual power laws did not apply for most hyper‐stoichiometric samples. The first values of activation energy for the sintering of U1‐xCexO2+δ solid solutions under an Ar/H2 atmosphere were also determined.