bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual and joint associations of obesity and metabolic health parameters on arterial stiffness: Evidence from the UK Biobank
Authors: Ananda Roshan A. , Solomon Bethlehem , Ray Kausik K.
Published: November 2024

Aims

There is conflicting evidence regarding whether excess adiposity without metabolic abnormalities reflects a truly benign phenotype. This study evaluated the independent and joint associations of the presence of excess adiposity and metabolic abnormalities on arterial stiffness.

Materials and Methods

Participants in UK Biobank with body mass index (BMI) and arterial stiffness index (ASI) recorded between 2006 and 2010, free from cardiovascular diseases and not underweight (BMI <18.5 kg/m2) were included. The primary outcome was severity of ASI analysed using multivariate‐adjusted linear regression.

Results

Of 162 590 participants, 42.5% were overweight and 24.4% were obese. Within the normal BMI strata, 50.7% had ≥1 metabolic abnormality. Compared to individuals with normal BMI and no metabolic abnormality (reference group), increased BMI or metabolic abnormalities were similarly associated with higher ASI: normal BMI with metabolic abnormalities (adjusted β‐coefficient and 95% CI, 0.35; 0.30–0.40); overweight without metabolic abnormalities (0.32; 0.26–0.37). Individuals with obesity and no metabolic abnormality had higher ASI (0.65; 0.57–0.74) but was lower than individuals with overweight and metabolic abnormalities (0.80; 0.75–0.84). Individuals with obesity and metabolic abnormalities had the highest ASI (1.07; 1.02–1.12) among all six metabolic combinations, p < 0.001 for each versus reference group. Sensitivity analysis suggested higher ASI with increasing number of metabolic abnormalities within BMI categories and higher ASI in the presence of abdominal obesity within metabolic categories.

Conclusions

Excess adiposity and metabolic abnormalities are independently associated with increased arterial stiffness to a similar degree, suggesting that metabolically healthy individuals with overweight and obesity are not benign groups. This reinforces the need to prevent excess adiposity and consider primary prevention strategies even before metabolic abnormalities emerge.
Inclisiran versus alirocumab in improving lipid profile parameters: A systematic review and meta‐analysis
Authors: Saad Cleto André , Schirlo João Matheus , Oliveira Gomes Victor Hugo , Julinhaque Beraldo Maria Luiza , Sponholz Neiverth Guinter , Beltrame Mayara , Machozeki Janete , Martins Camila Marinelli
Published: November 2024

Aims

Dyslipidemia is a risk factor for cardiovascular diseases. Some patients are resistant to conventional treatment. In these patients, there is the possibility of using PCSK9 inhibitors. The objective of this systematic review was to compare alirocumab with inclisiran in improving the lipid profile.

Materials and Methods

This study was carried out in accordance with Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols Statement (PRISMA) and registered with PROSPERO (CRD42024563261). The following databases were accessed on 2 July 2024: PubMed, Scopus and Web of Science. Clinical trials that evaluated the lipid profile were included. With these data, meta‐analyses were carried out seeking to evaluate the difference between the baseline and the 12‐ and 24‐week endpoints.

Results

Initially, 1157 studies were found, of which 32 were included. In total, 30 718 patients participated in the included studies. There was a statistically significant difference, favouring alirocumab 75 mg (−51.54%, 95% confidence interval [CI] −53.43%; −49.66%), in relation to inclisiran 300 mg (−41.34%, 95% CI −50.30%; −31.34%) in reducing low‐density lipoprotein cholesterol (LDL‐C) (p = 0.05), in relation to inclisiran 200 and 300 mg in reducing total cholesterol (p < 0.01) (p < 0.01) and triglycerides (p = 0.02) (p = 0.04) in 24 weeks. Furthermore, alirocumab 150 mg was superior to both doses of inclisiran in reducing total cholesterol (p < 0.01) (p < 0.01). There was no statistically significant difference in the reduction of lipoprotein(a) by alirocumab 75 mg (−22.35%, 95% CI −24.67; −20.03) and 150 mg (−25.17%, 95% CI −30.94; −19.41) compared to inclisiran 300 mg (−13.37, 95% CI −28.66; 1.93) (p = 0.26) (p = 0.16).

Conclusion

Alirocumab was superior to inclisiran in improving the lipid profile, especially in reducing LDL‐C, total cholesterol and triglycerides.
Growth across Grades and Common Item Grade Alignment in Vertical Scaling Using the Rasch Model
Authors: Student Sanford R. , Briggs Derek C. , Davis Laurie
Published: November 2024

Vertical scales are frequently developed using common item nonequivalent group linking. In this design, one can use upper‐grade, lower‐grade, or mixed‐grade common items to estimate the linking constants that underlie the absolute measurement of growth. Using the Rasch model and a dataset from Curriculum Associates’ i‐Ready Diagnostic in math in grades 3–7, we demonstrate how grade‐to‐grade mean differences in mathematics proficiency appear much larger when upper‐grade linking items are used instead of lower‐grade items, with linkings based on a mixture of items falling in between. We then consider salient properties of the three calibrated scales including invariance of the different sets of common items to student grade and item difficulty reversals. These exploratory analyses suggest that upper‐grade common items in vertical scaling are more subject to threats to score comparability across grades, even though these items also tend to imply the most growth.
Sick leave and homecare need in patients with transient ischaemic attack compared with ischaemic stroke: A nationwide follow‐up study
Authors: Ebbesen Birgitte Hede , Grøntved Simon , Modrau Boris , Rathleff Michael Skovdal , Andreasen Jane , Johnsen Søren Paaske
Published: November 2024

Background and purpose

Emerging evidence indicates lasting impairments in patients with transient ischaemic attack (TIA), which may be unexpected as symptoms per definition recover within 24 h. How these impairments impact return to work or the ability to maintain independence is unknown. The aim of our study was to investigate the need of sick leave or homecare following TIA compared with acute ischaemic stroke (AIS).

Materials and methods

Patients registered with TIA in the Danish Stroke Registry from 2014 to 2021 were included. Information on sick leave benefits and use of homecare was obtained from national registries. The cumulative risk of sick leave or homecare was calculated and compared with AIS. A hazard rate ratio (HRR) for return to work was calculated.

Results

In total, 29,261 TIA and 64,295 AIS events were included. For TIA, 6770 patients paid labour market contribution before TIA, of which 1240 patients (18.3%) received sick leave benefits after 5–12 weeks. For AIS 48.1% (5940 of 12,340) received sick leave benefits. The HRR for return to work was 2.37 (95% confidence interval 2.13–2.64). For patients aged 65–79, a total of 15.4% TIA (175 of 1136) and 30.6% AIS (1443 of 4716) started to receive homecare at 3 months. The HRR was 0.55 (95% confidence interval 0.49–0.62).

Conclusion

Despite the transient event almost one out of five working patients with TIA receive sick leave benefits 5–12 weeks after. Initiation of homecare was required in nearly one out of six patients with TIA aged 65–79 years.
Decrement of choroid vascularization during spontaneous migraine attacks: An optical coherence tomography angiography study
Authors: Romozzi Marina , Trigila Vincenzo , Cuffaro Giovanni , Marcelli Sofia , Iannone Luigi Francesco , Calabresi Paolo , Savino Gustavo , Vollono Catello
Published: November 2024

Objective

This study aimed to analyze the microcirculation of the macula, the optic nerve, and the choroid in patients with migraine by optical coherence tomography angiography (OCTA) during spontaneous migraine attacks, comparing the findings with scans performed in the interictal period in the same subjects and healthy controls (HCs).

Methods

In this case‐crossover design study, patients diagnosed with migraine who underwent an OCTA during a migraine attack were enrolled. A cohort of HCs was recruited for comparison. Data from ocular and orthotic examinations and clinical and demographical information were collected. All subjects were imaged with Solix full range OCT, recording the following parameters: macular vessel density (VD), inside disc VD, peripapillary VD, disc whole image VD, fovea choriocapillaris VD, fovea VD, parafovea VD, peripapillary thickness, fovea thickness, parafovea thickness, macular full retinal thickness, and foveal avascular zone (FAZ).

Results

Thirteen patients (26 eyes individually assessed) with a diagnosis of migraine were included (9 without aura [69.2%] and 4 with aura [30.7%], with a mean age of 25.2 ± 3.4 years) and scanned during the ictal and interictal phase. Fifteen age‐matched HCs (30 eyes individually assessed) were included. The foveal choriocapillaris VD was significantly lower in the ictal phase (63.3 ± 2.47%) compared to the interictal phase in the same patients (64.9 ± 2.79%) (p = 0.0019). Comparing the ictal scans from migraine patients and HCs, the FAZ area was significantly larger, and the inside disc, fovea, and fovea choriocapillaris VDs were significantly lower.

Conclusion

The study demonstrated a dynamic decrement in choroidal vascularization in migraine patients during spontaneous migraine attacks.
Flexible Distribution Approaches to Enhance Regression and Deep Topic Modelling Techniques
Authors: Koochemeshkian Pantea , Bouguila Nizar
Published: November 2024

This paper presents an extension of the Dirichlet multinomial regression (DMR) and deep Dirichlet multinomial regression (dDMR) topic modelling approaches by incorporating the generalised Dirichlet (GD) and Beta‐Liouville (BL) distributions using collapsed Gibbs sampling for parameter inference. The DMR and dDMR approaches have been shown to be effective in discovering latent topics in text corpora. However, these approaches have limitations when it comes to handling complex data structures and overfitting issues. To address these limitations, we introduce the GD and BL distributions, which have more flexibility in modelling complex data structures and handling sparse data. Additionally, we use collapsed Gibbs sampling to estimate the model parameters, which provides a computationally efficient method for inference. Experimental results on benchmark datasets demonstrate the effectiveness of the proposed approach in improving topic modelling performance, particularly in handling complex data structures and reducing overfitting. The proposed models also exhibit good interpretability of the learned topics, making them suitable for various applications in natural language processing and machine learning.
Limited Evidence Base for Determining Impacts (Or Not) of Offshore Wind Energy Developments on Commercial Fisheries Species
Authors: Gill Andrew B. , Bremner Julie , Vanstaen Karen , Blake Sylvia , Mynott Frances , Lincoln Susana
Published: November 2024

The coexistence between offshore wind and fisheries has raised questions about potential impacts on species that are fished. We systematically evaluated the offshore wind farm (OWF) literature for evidence of effects leading to impacts on commercial fisheries species. First, we collated evidence of environmental effects of OWFs on fisheries species and then determined whether these could be interpreted as impacts using fishery‐scale and organism‐scale parameters for pelagic finfish, demersal and reef‐associated roundfish, demersal flatfish, elasmobranchs and shellfish. We appraised consistency and level of agreement of direct evidence and explored the body of indirect evidence. A total of 1268 documents featured evidence of OWF effects on fisheries species, with only 60 documents (274 species records) providing direct evidence. Evidence on finfish far outweighed that for shellfish. Demersal and reef‐associated roundfish were the best‐studied group, while elasmobranchs were poorly evidenced. Most studies considered population rather than stock parameters. There was limited evidence of impacts, owing to inconclusive results and inconsistent effects within the parameters assessed—illustrating the importance of looking across the evidence base rather than focussing on individual studies. Hence, there is currently insufficient direct evidence to confidently determine OWF impacts on fisheries species. Overwhelmingly, the evidence deals with indirect effects, although these should not be disregarded as they can highlight plausible impacts on fisheries species, which could guide research and monitoring targeted at understanding the impacts of OWF—a pressing concern given the increased policy commitment of many nations to these two marine sectors sharing marine space.
Chronic low back pain and decreased physical activity are associated with social frailty incidence among community‐dwelling older adults
Authors: Matsuda Soichiro , Doi Takehiko , Katayama Osamu , Sakimoto Fumio , Makino Keitaro , Sudo Motoki , Yamashiro Yukari , Takayanagi Naoto , Shimada Hiroyuki
Published: November 2024

Aim

Nearly half of older adults with frailty experience chronic pain. Chronic pain contributes to activity restrictions. Decreased physical activity with chronic pain is associated not only with physical dysfunction but also with reduced engagement in social activities. We aimed to verify the hypothesis that chronic pain and decreased physical activity are associated with social frailty incidence.

Methods

The study included 1198 community‐dwelling older adults (aged 70.2 ± 6.3 years) without social frailty at baseline. Chronic pain, physical activity and basic information were assessed at baseline. The participants were divided into two groups based on the presence (yes, n = 167) or absence (no, n = 1031) of chronic low back pain. The incidence of social frailty was investigated during the follow‐up examination after 2.5 years.

Results

Binomial logistic regression analysis showed that older adults with chronic low back pain and low step counts had a higher odds ratio for the development of incident social frailty than older adults without chronic low back pain and high step counts (odds ratio 1.89, 95% confidence interval 1.03–3.46).

Conclusion

Our results suggest that a combination of chronic low back pain and low step counts is associated with the incidence of social frailty. Further research is required to establish intervention methods for pain and decreased physical activity to prevent social frailty. Geriatr Gerontol Int 2025; 25: 25–30.
Possible negative impact of polypharmacy on surgical outcomes in older patients with lumbar spinal stenosis
Authors: Kawabata Soya , Michikawa Takehiro , Nagai Sota , Akaike Yuki , Imai Takaya , Ito Kei , Takeda Hiroki , Ikeda Daiki , Kaneko Shinjiro , Fujita Nobuyuki
Published: November 2024

Aim

Older patients with lumbar spinal stenosis (LSS) have a higher incidence of polypharmacy attributed to comorbidities and the use of pain relief medications. This study aimed to explore the effect of polypharmacy and hyperpolypharmacy on surgical outcomes in older patients with LSS based on health‐related quality of life (HRQOL) and locomotive syndrome.

Methods

Consecutive patients aged ≥65 years who underwent lumbar spinal surgery for LSS were retrospectively reviewed. We assessed the preoperative and 1‐ and 2‐year postoperative scores of three common HRQOL tools and the 25‐question Geriatric Locomotive Function Scale. The patients were classified into the hyperpolypharmacy group (those taking ≥10 medications), polypharmacy group (those taking 6–9 medications) and non‐polypharmacy group (those taking ≤5 medications).

Results

In total, 148 participants were evaluated. Among them, 35 were included in the non‐polypharmacy group. There were no significant changes in the HRQOL and locomotive syndrome stage at baseline, even with polypharmacy progression. However, the HRQOL and locomotive syndrome stage worsened postoperatively with polypharmacy progression. When surgical efficacy was directly examined, results showed that the surgical outcomes were significantly associated with polypharmacy progression in older patients with LSS, even after adjusting for potential confounders.

Conclusions

Polypharmacy, especially hyperpolypharmacy, had a negative impact on surgical outcomes in older patients with LSS. The number of prescription drugs should be taken into consideration before surgery in this patient group. Geriatr Gerontol Int 2025; 25: 31–37.
Rock climbing sites as locations for geoheritage and geoscience engagement in mountains
Authors: Knight Jasper , Bollati Irene Maria
Published: November 2024

Outdoor activities including trekking and hiking are commonly undertaken in mountains and in other environments where bedrock surfaces or bedrock‐controlled landforms are present and where users can enjoy the fresh air and the physical landscape. Information boards and leaflets are often used by scientists and environmental managers in these environments to communicate geoscience issues to the general public along hiking and trekking trails. Rock climbing sites are also prime locations where rock surfaces are exposed and where specific user groups interact with the physical landscape. Here, we describe the relationship between rock climbing and the nature of rock outcrops and the opportunity that this affords for more innovative ways of communicating geoscience information to a physically active and engaged public. As such, rock climbing sites can be considered geoheritage sites, where they represent sites of importance for people and communities (cultural heritage) as well as for their geological and educational value (geological heritage). The characteristics of rock climbing sites as geoheritage sites are discussed in this feature, as are the potential threats to the integrity of these sites.
Associations between gestational exposure to neighbourhood socioeconomic deprivation and early childhood weight status
Authors: Neally Sam J. , Widen Elizabeth M. , Hoyo Cathrine , Martin Chantel L.
Published: November 2024

Objective

This study aimed to examine associations between prenatal neighbourhood socioeconomic deprivation (NSD) with early offspring weight status and to assess potential modification by race and ethnicity.

Methods

We used data from the Newborn Epigenetics STudy (NEST) cohort. Gestational NSD was assessed as neighbourhood deprivation index (NDI) tertiles. Offspring height and weight were assessed at 6 months (N = 1023), 1 year (N = 1268), 2 years (N = 1033) and 3 years (N = 1038). Multilevel logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for the relationship of NDI with overweight or obesity and rapid infant weight gain, adjusting for gestational parent age, race/ethnicity, marital status and educational attainment. Models were estimated in the total sample and also stratified by race and ethnicity.

Results

Children exposed to NDI in the highest (compared to the lowest) tertile had increased odds of having overweight/obesity at 1 year (OR = 1.53, 95%CI = 1.09–2.15). In stratified models, children of NH Black gestational parents residing in the highest tertile of NDI (compared to the lowest) had increased odds of having overweight/obesity at 1 year (OR = 1.67, 95%CI = 1.00–2.77).

Conclusions

This findings suggest that higher gestational exposure to NSD may play a role in early childhood weight status, which has important implications for later development and health.
Sinomenine Ameliorated Microglial Activation and Neuropathic Pain After Chronic Constriction Injury Via TGF‐β1/ALK5/Smad3 Signalling Pathway
Authors: Ling Ling , Luo Min , Yin Haolin , Tian Yunyun , Wang Tao , Zhang Bangjian , Yin Li , Zhang Yuehui , Bian Jiang
Published: November 2024

Sinomenine (SIN), a bioactive isoquinoline alkaloid extracted from the roots and stems of Sinomenium acutum, is efficacious against various chronic pain conditions. Inhibition of microglial activation at the spinal level contributes to the analgesic effects of SIN. Microglial activation in the spinal dorsal horn is key to sensitising neuropathic pain. Consequently, this study aimed to investigate whether the antinociceptive effects of SIN in neuropathic pain are induced through microglial inhibition and the underlying mechanisms. In this study, we observed that SIN alleviated chronic constriction injury (CCI)–induced pain hypersensitivity, spinal microglial activation and neuroinflammation. Consistently, SIN evoked the upregulation of transforming growth factor‐beta1 (TGF‐β1) and phosphorylated Smad3 in the L4–6 ipsilateral spinal dorsal horn of CCI mice. Intrathecal injection of TGF‐β1 siRNA and an activin receptor‐like receptor (ALK5) inhibitor reversed SIN's antinociceptive and antimicroglial effects on CCI mice. Moreover, targeting Smad3 in vitro with siRNA dampened the inhibitory effect of TGF‐β1 on lipopolysaccharide‐induced microglial activation. Finally, targeting Smad3 abrogated SIN‐induced pain relief and microglial inhibition in CCI mice. These findings indicate that the TGF‐β1/ALK5/Smad3 axis plays a key role in the antinociceptive effects of SIN on neuropathic pain, indicating its suppressive ability on microglia.
Deep Learning and Single‐Cell Sequencing Analyses Unveiling Key Molecular Features in the Progression of Carotid Atherosclerotic Plaque
Authors: Zhang Han , Wang Yixian , Liu Mingyu , Qi Yao , Shen Shikai , Gang Qingwei , Jiang Han , Lun Yu , Zhang Jian
Published: November 2024

Rupture of advanced carotid atherosclerotic plaques increases the risk of ischaemic stroke, which has significant global morbidity and mortality rates. However, the specific characteristics of immune cells with dysregulated function and proven biomarkers for the diagnosis of atherosclerotic plaque progression remain poorly characterised. Our study elucidated the role of immune cells and explored diagnostic biomarkers in advanced plaque progression using single‐cell RNA sequencing and high‐dimensional weighted gene co‐expression network analysis. We identified a subcluster of monocytes with significantly increased infiltration in the advanced plaques. Based on the monocyte signature and machine‐learning approaches, we accurately distinguished advanced plaques from early plaques, with an area under the curve (AUC) of 0.899 in independent external testing. Using microenvironment cell populations (MCP) counter and non‐negative matrix factorisation, we determined the association between monocyte signatures and immune cell infiltration as well as the heterogeneity of the patient. Finally, we constructed a convolutional neural network deep learning model based on gene‐immune correlation, which achieved an AUC of 0.933, a sensitivity of 92.3%, and a specificity of 87.5% in independent external testing for diagnosing advanced plaques. Our findings on unique subpopulations of monocytes that contribute to carotid plaque progression are crucial for the development of diagnostic tools for clinical diseases.
LINC01929 Is a Prognostic Biomarker for Multiple Tumours and Promotes Cell Proliferation in Breast Cancer Through the TNF/STAT3 Axis
Authors: Gu Yanlin , Feng Zhengyang , Xu Xiaoyan , Jin Liyan , Jiang Guoqin
Published: November 2024

The aim of this study was to investigate whether long intergenic non‐coding RNA 1929 (LINC01929), a novel long non‐coding RNA, could serve as a prognostic biomarker for various tumours and explore its function. The expression and prognosis of LINC01929 across 33 different tumour types in patients in the Cancer Genome Atlas (TCGA) database were analysed. Also, the correlation between LINC01929 expression, tumour mutational burden (TMB), microsatellite instability (MSI), immune checkpoint status and immune cell infiltration was examined. Moreover, the function of LINC01929 in the breast cancer cell lines was explored via CCK‐8, colony formation and cell cycle assays. In addition, the downstream mechanisms of LINC01929 were analysed via transcriptome sequencing, RT–qPCR, and western blotting. Our analysis revealed that LINC01929 was weakly expressed in 3 tumour types and highly expressed in 14 tumour types, and low expression of LINC01929 was correlated with better clinical outcomes in 15 tumour types. Furthermore, LINC01929 expression was correlated significantly with the TMB, MSI, immune checkpoint and immune cell infiltration across multiple tumour types. The knockdown of LINC01929 inhibited cell cycle progression, cell proliferation, and tumorigenesis and downregulated the TNF pathway and STAT3 expression. The treatment with exogenous TNF‐α partially reversed the cell cycle progression and proliferation inhibition caused by LINC01929 knockdown, and these effects were accompanied by changes in STAT3 expression. LINC01929 may serve as an effective biomarker affecting the TMB, MSI, immune cell infiltration and immune checkpoint status. Mechanistically, LINC01929 affects cell cycle progression and cell proliferation through the TNF/STAT3 axis. These findings offer valuable insights into the potential applications of LINC01929 in tumour therapy, which may yield novel targets and strategies for the diagnosis and treatment of patients.
Editorial Perspective: A systems approach to addressing young people's mental health
Authors: Hobbs Tim , Berry Vashti , Fonagy Peter
Published: November 2024

This editorial explores how adopting a social determinants and systemic perspective can enhance preventative measures to boost the mental health of young people. It argues that to effectively elevate the mental health of young people, it is essential to tackle both the overarching influences and their specific local impacts. We maintain that a strategy combining systems thinking with evidence tailored to the local environment and participatory design is essential.
Fish‐Finder: A robust small target detection method for aquaculture fish in low‐quality underwater images
Authors: Liu Liang , Wu Junfeng , Zhao Haiyan , Kong Han , Zheng Tao , Qu Boyu , Yu Hong
Published: November 2024

Underwater fish object detection serves as a pivotal research direction in marine biology, aquaculture management, and computer vision, yet it poses substantial challenges due to the complexity of underwater environments, occultations, and the small‐sized and frequently moving fish in aquaculture. Addressing these challenges, we propose a novel underwater fish object detection algorithm named Fish‐Finder. First, we engendered a structure titled “C2fBF,” utilizing the dual‐path routing attention protocol of BiFormer. The primary objective of this structure is to alleviate the perturbations induced by underwater intricacies during the phase of downsampling in the backbone network, thereby discerning and conserving finer contextual features. Subsequently, we co‐opted the RepGFPN method within our neck network—a distinctive approach that adeptly merges high‐level semantic constructs with low‐level spatial specifics, thus fortifying its multi‐scale detection prowess. Then, in an endeavor to diminish the sensitivity toward positional aberrations during the detection of diminutive aquatic creatures, we incorporated a novel bounding box regression loss function, the Wasserstein loss, to the existing CIoU. This innovative function gauges the congruity between the predicted bounding box Gaussian distribution and the reference bounding box Gaussian distribution. Finally, in regard to the dataset, we independently assembled a specific dataset termed “SmallFish.” This unique dataset, meticulously designed for the detection of small‐scale fish within intricate underwater settings, includes 5000 annotated images of small fish. Experimental results demonstrate that, compared to the state‐of‐the‐art detection methods, our proposed method improves the accuracy by and , and mean average precision (mAP) increases and in public dataset Kaggle‐Fish and our SmallFish dataset, respectively.
Transient receptor potential a1b regulates primordial germ cell numbers and sex differentiation in developing zebrafish
Authors: Gong Xiaoting , Yan Qianqian , Chen Liangbiao
Published: November 2024

Temperature is a leading environmental factor determining the sex ratio of some animal populations, such as fish, amphibians, and reptiles. However, the underlying mechanism by which temperature affects gender is still poorly understood. Transient receptor potential a1b (Trpa1b) belongs to the ion channel family of transient receptor potentials and exhibits dual thermosensitivity to heat and cold. In this study, we have unveiled a novel function of the trpa1b gene. Zebrafish generated through clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 with Trpa1b‐null manifest a male‐biased sex ratio. The quantity of primordial germ cells (PGCs) in zebrafish is closely linked to gender determination and gonadal development. Yet the role of the trpa1b gene in zebrafish reproductive development remains unexplored in the literature. Our investigation revealed a significant reduction in PGCs in Trpa1b mutant zebrafish compared to their wild‐type counterparts 24‐h postfertilization (hpf). Transcriptome sequencing of tissues near the reproductive crest of embryos at 1.25 days postfertilization (dpf) revealed differential changes in PGC‐related marker genes and genes related to sperm cell development and differentiation. The relative expression of ddx4 and sycp3 genes was significantly downregulated, whereas amh was significantly upregulated at 20 dpf in trpa1b−/− zebrafish. The results of this study provide valuable insights and references for studying the molecular mechanism of sex determination in zebrafish. Undoubtedly, these results will further enhance our understanding of gender differentiation and gonadal development in fish and other vertebrates.
Dietitians' perspectives on key components relevant for successful dietetic treatment of adults with obesity in primary health care: a qualitative study in the Netherlands
Authors: van de Riet Annemieke , Otte Rebecca S. , Jager‐Wittenaar Harriët , de van der Schueren Marian A. E. , Naumann Elke ,   the Dietetics Building the Future consortium
Published: November 2024

Background

Dietetic treatment of adults with obesity can result in effective weight loss with health improvements. However, it remains unclear which components of dietetic consultation are key for successful treatment of individual patients. Therefore, the aim of this study is to explore dietitians' perceptions of key components relevant for successful dietetic treatment of adults with obesity in primary health care in the Netherlands.

Methods

In this phenomenological study, semistructured interviews were conducted with 18 dietitians who have experience in treating adults with obesity in primary care. Validation of interview data was performed through two focus group discussions with 14 dietitians. Thematic analysis was used to analyse the data.

Results

Four main themes were identified: (i) building a good relationship; (ii) identifying patient needs; (iii) supporting behaviour change and (iv) providing advice. Dietitians highlighted the relevance of building a good relationship with their patients and emphasised adopting a counselling role alongside their role of educator. They also recommended the use of educational materials, counselling techniques and behaviour change strategies (e.g. goal setting, self‐monitoring, addressing barriers) to address specific patient needs, such as health literacy, self‐efficacy and motivation.

Conclusions

This study demonstrates that dietitians perceive the ability to build a trusted relationship, in which patient needs are properly explored and addressed, as the key to successful dietetic treatment of adults with obesity. Our findings emphasise the importance of the dietitian's approach in this process and show that patient factors influence the choice of appropriate treatment approaches.
Annual report of the committee on gynecologic oncology, the Japan Society of Obstetrics and Gynecology: Annual patient report for 2021 and annual treatment report for 2016
Authors: Kajiyama Hiroaki , Tamauchi Satoshi , Takahashi Fumiaki , Kawana Kei ,   Board members of the 2023 Committee on Gynecologic Oncology of the Japan Society of Obstetrics and Gynecology
Published: November 2024

Aim

To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2021 and the Annual Treatment Report for 2016, on the outcomes of patients who started treatment in 2016.

Methods

The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry, where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment with gynecologic malignancies was initiated in 2021 were analyzed retrospectively. Survival of the patients who started treatment with cervical, endometrial, and ovarian cancer in 2016 was analyzed by using the Kaplan–Meier, log‐rank, and Wilcoxson tests.

Results

Treatment was initiated in 2021 for 8006 patients with cervical cancer, 13 912 with endometrial cancer, 8337 with ovarian, tubal, and peritoneal cancer, 2375 with ovarian borderline tumors, and with the others (226 vulvar cancer, 161 vaginal cancer, 437 uterine sarcoma, 47 uterine adenosarcoma, 160 trophoblastic diseases). This clinicopathological information was summarized as the Patient Annual Report. The 5‐year survival rates of the patients with cervical cancer were 92.3%, 77.0%, 56.1%, and 30.3% for stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with endometrial cancer were 94.1%, 88.8%, 71.2%, and 24.5% for stages I, II, III, and IV, respectively. The 5‐year survival rates for the patients with ovarian cancer (surface epithelial‐stromal tumors) were 91.3%, 78.8%, 54.3%, and 36.8% for stages I, II, III, and IV, respectively.

Conclusion

The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.
Real‐world glycaemic outcomes in children and young people on advanced hybrid closed‐loop therapy: A population‐based study in Western Australia
Authors: Gehrmann Frances E , Smith Grant J , Irwine Kathleen , Ellis Katrina L , Davis Elizabeth A , Jones Timothy W , Taplin Craig E , Abraham Mary B
Published: November 2024

Aims

To evaluate real‐world glycaemic outcomes in children with type 1 diabetes (T1D) commencing advanced hybrid closed loop therapy (AHCL) and to explore these outcomes based on the cohort's clinical and socioeconomic characteristics.

Methods

A single‐centre, population‐based retrospective study in children commencing AHCL (Smart Guard, Control IQ, CamAPS) with minimum 70% data from two‐weeks CGM pre‐AHCL was conducted between December 2021 and June 2023 in Western Australia. CGM metrics (time in range (TIR) 3.9–10 mmol/L, time below range (TBR) < 3.9 mmol/L, glucose management indicator (GMI)) were analysed at baseline, monthly and 6 months. HbA1c at baseline and 6 months were also collected. The proportion meeting glycaemic targets of TIR > 70%, TBR < 4% and GMI < 7.0% were determined. Change in TIR from baseline to 6 months was examined by the following characteristics: %TIR, age group and Index of Relative Socioeconomic Disadvantage (IRSD) of residential postcode.

Results

CGM data of 309 children, mean (SD) age 12.4 (3.2) years were analysed. Glycaemia improved from baseline to 6 months with (mean) TIR +8% (95% CI 7, 9; P ≤ 0.001), GMI −0.3% (95% CI −0.3, −0.2; P < 0.001) and (median) TBR −0.3% (95% CI −0.4, −0.1; P < 0.001). Proportion meeting glycaemic targets increased from 13.3% at baseline to 30.6% at 6 months. Improvement in TIR did not differ based on age group or IRSD Quintile. Greater increase in TIR was seen in those with lowest TIR at baseline (+20.9%, −0.2%; P < 0.001 for baseline TIR < 40%, >70%). There was a 0.27% reduction in HbA1c in 6 months (n = 116) (P < 0.001).

Conclusions

AHCL improves glycaemia, irrespective of age and socioeconomic characteristics, with greatest changes seen in those with lowest baseline TIR.
Rheological and Tribological Properties of Konjac Gum‐Lecithin Composite System: Effect of Incorporation of Saliva and Friction Surface Properties
Authors: Pang Zhihua , Bourouis Imane , Li Mengfei , Chen Cunshe , Liu Xinqi
Published: November 2024

This research explored the development of composite systems using konjac gum (KGM) and soy lecithin at concentrations of 1% KGM–0.01% lecithin and 1% KGM–0.2% lecithin. The study investigated the influence of both oral and artificial saliva on the rheological and tribological properties of these systems, as well as the lubrication on different friction surfaces with varying characteristics. It has been found that different friction surfaces exhibited distinct morphological features and roughness values, significantly impacting surface wettability when treated with saliva. The viscosity of KGM–lecithin composite systems increased slightly compared to KGM hydrogel. However, adding oral or artificial saliva led to a noticeable decrease in viscosity. Lecithin did not significantly alter the viscoelastic properties of KGM gel, but the incorporation of artificial and oral saliva introduced some changes. CLSM images showed that the stability and distribution of lecithin within the composite system varied with lecithin concentration and saliva type, with artificial saliva ensuring a stable and even distribution, while oral saliva caused aggregation and irregular distribution. Furthermore, the study found that the lubrication performance of the KGM‐lecithin system was influenced by the properties of the friction surface, with hydrophilic rough surfaces providing superior lubrication compared to rough surfaces. The addition of lecithin enhanced lubrication across all tested surfaces, and artificial saliva surpassed oral saliva in reducing friction coefficients. These findings offer valuable insights into the potential use of KGM‐lecithin composite systems as fat mimetics, particularly in enhancing lubrication for various applications.
Role of Air Pollution in Development of Hepatocellular Carcinoma Among Chronic Hepatitis B Patients Treated With Nucleotide/Nucleoside Analogues
Authors: Jang Tyng‐Yuan , Zeng Yu‐ting , Liang Po‐Cheng , Wu Chih‐Da , Wei Yu‐Ju , Tsai Pei‐Chien , Hsu Po‐Yao , Hsieh Ming‐Yen , Lin Yi‐Hung , Hsieh Meng‐Hsuan , Wang Chih‐Wen , Yang Jeng‐Fu , Yeh Ming‐Lun , Huang Chung‐Feng , Chuang Wan‐Long , Huang Jee‐Fu , Cheng Ya‐Yun , Dai Chia‐Yen , Chen Pau‐Chung , Yu Ming‐Lung
Published: November 2024

Background and Aims

To investigate the association between air pollution and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues.

Methods

We enrolled 1298 CHB patients treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for HCC. Daily estimates of air pollutants were estimated since the previous year from the enrolment date.

Results

The annual incidence of HCC was 2.1/100 person‐years after a follow‐up period of over 4840.5 person‐years. Factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.00/1.55–5.81; p = 0.001), male sex (2.98/1.51–5.90; p = 0.02), body mass index (1.11/1.04–1.18; p = 0.002) and age (1.06/1.04–1.09; p < 0.001). Among patients with cirrhosis, the factors associated with HCC development were male sex (HR/95% CI: 2.10/1.00–4.25; p = 0.04) and NO2 (per one‐unit increment, parts per billion; 1.07/1.01–1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO2 exposure had more than a three‐fold risk of HCC than those with the lowest quartile of annual exposure (HR/95% CI: 3.26/1.34–7.93; p = 0.01). Among patients without cirrhosis, the strongest factors associated with HCC development were male sex (HR/95% CI: 5.86/1.79–19.23; p = 0.004), age (1.12/1.07–1.17; p < 0.001) and platelet count (0.99/0.98–1.00; p = 0.04).

Conclusions

Air pollution influences HCC development in CHB patients who receive nucleotide/nucleoside analogue therapy. Long‐term NO2 exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment.
Comparison of Tegoprazan and Lansoprazole in Patients With Erosive Esophagitis up to 4 Weeks: A Multi‐Center, Randomized, Double‐Blind, Active‐Comparator Phase 4 Trial
Authors: Shin Cheol Min , Choi Suck Chei , Cho Jin Woong , Kim Seung Young , Lee Ok Jae , Kim Do Hoon , Cho Yu Kyung , Lee Ju Yup , Lee Sang Kil , Shin Jeong Eun , Kim Gwang Ha , Park Seon‐Young , Hong Su Jin , Jung Hye‐Kyung , Lee Sang Jin , Youn Young Hoon , Jeon Seong Woo , Sung In Kyung , Park Moo In , Lee Oh Young
Published: November 2024

Background

The aims of this study were to confirm the non‐inferiority of tegoprazan to lansoprazole up to week 4 in patients with erosive esophagitis (EE) and to evaluate its effectiveness in rapid mucosal healing and symptom relief at week 2.

Methods

In this multi‐center, randomized, double‐blind, active‐comparator non‐inferiority trial, 218 patients with endoscopically confirmed EE (Los Angeles Classification Grades A–D) were randomly allocated to either the tegoprazan (50 mg) or lansoprazole (30 mg) group. The primary endpoint was the cumulative proportion of patients with healed EE up to week 4, as confirmed through endoscopy. The proportion of patients with healed EE at week 2 was also evaluated. Furthermore, CYP2C19 genotypes, symptoms, safety, and tolerability were assessed.

Key Results

In the full‐analysis set, 103 and 109 participants in the tegoprazan and lansoprazole groups, respectively, were analyzed. The cumulative healing rates up to week 4 were 95.2% (98/103) and 86.2% (94/109) (difference [95% confidence interval], 8.91 [1.22–16.59]; p < 0.0001 for non‐inferiority and 0.0266 for superiority), while those at week 2 were 88.4% (91/103) and 82.6% (90/109) (5.78 [−3.66–15.22], p = 0.0005 for non‐inferiority) for tegoprazan and lansoprazole, respectively. Tegoprazan showed consistent healing rates regardless of CYP2C19 genotypes.

Conclusions and Inferences

Tegoprazan was superior to lansoprazole in the treatment of EE up to 4 weeks. Further studies are necessary to confirm these findings and clarify the superiority of tegoprazan, especially in the treatment of severe EE.

Trial Registration

ClinicalTrials.gov identifier: NCT05267743
New IPCL Classification Using NBI for Early Detection of OPMDs Malignant Transformation
Authors: Xu Yiming , Zhang Tianyu , Liu Dan , Qiu Xuemei , Hou Feifei , Wang Jiongke , Luo Xiaobo , Dan Hongxia , Zhou Yu , Zeng Xing , Jiang Lu , Chen Qianming
Published: November 2024

Objectives

Introduce a new intrapapillary capillary loop (IPCL) classification using narrow‐band imaging (NBI) to diagnose early malignant transformation in oral potentially malignant disorders (OPMDs).

Methods

In the exploratory phase, NBI images from 241 patients with OPMDs and oral squamous cell carcinoma (OSCC) were assessed for three basic IPCL features—dilation, unevenness, and tortuosity—to identify patterns associated with OPMDs malignant transformation. Chi‐square analysis and logistic regression differentiated these patterns between low‐risk (no/mild dysplasia) and high‐risk (moderate/severe dysplasia, invasive carcinoma) lesions, establishing a new classification system. In the validation phase, the system was applied to 90 patients with histopathological results confirming diagnostic accuracy.

Results

Four distinct IPCL types were identified: normal, dilated, irregular, and chaotic, with increasing odds ratios for high‐risk lesions. The ROC curve had an AUC of 0.913, with irregular and chaotic types providing the best diagnostic performance, achieving sensitivities and specificities of 84.2% and 88.4%, respectively. In the validation phase, the new classification achieved an overall diagnostic accuracy of 84.4% and substantial inter‐observer consistency (κ = 0.694).

Conclusion

The new IPCL classification effectively identifies high‐risk oral lesions, enhancing the diagnostic utility of NBI for early detection of OPMDs malignant transformations.
Antinuclear Positivity and Malignant Transformation Potential of Oral Potentially Malignant Disorder
Authors: Hong Seok Woo , Kang Jeong‐Hyun
Published: November 2024

Objective

This multicenter cohort study aimed to investigate the impact of antinuclear antibody (ANA) positivity on the malignant transformation potential of oral potentially malignant disorders (OPMDs) using the Observational Health Sciences and Informatics network tools for the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM).

Materials and Methods

Retrospective cohort data from five medical centers were analyzed. Cox regression and 1:4 propensity score matching followed by aggregated meta‐analysis were used to evaluate association between ANA positivity and the risk of oral squamous cell carcinoma (OSCC). The index date was defined as the first day of diagnosis of OPMD. The target and comparator cohorts comprised patients who tested positive and negative for ANA within 180 days before or after the index date, respectively.

Results

Among 27,984 OPMD patients, 1302 patients (4.65%) confirmed malignant transformation. Among these, 3035 patients had ANA laboratory data. After 1:4 PS matching, 523 and 1598 patients with positive and negative for ANA were analyzed. Meta‐analysis of the hazard ratios demonstrated that ANA positivity significantly increased the risk of malignant transformation compared to ANA negativity.

Conclusions

ANA positivity is a significant prognostic marker for predicting malignant transformation in patients with OPMD.
ZNF331 Represses the Proliferation of Head and Neck Squamous Cell Carcinoma via Co‐Repressor TRIM28
Authors: Li Ju , Cheng Hao , Zhao Yong , Wang Yunkang , Gong Chen , Gong Renguo , Li Yan
Published: November 2024

Objective

This study aims to explore the regulatory effect of Zinc Finger Protein 331 (ZNF331), a KRAB domain‐containing transcriptional repressor, in Head and Neck Squamous Cell Carcinoma (HNSCC).

Materials and Methods

Data from The Cancer Genome Atlas (TCGA)‐HNSC were analyzed. The roles of ZNF331 in HNSCC cell proliferation, cell cycle progression, and its interacting proteins were explored through in vitro manipulation of ZNF331 expression and in vivo xenograft experiments. The epigenetic mechanisms underlying ZNF331 dysregulation were investigated by assessing its promoter methylation and the effects of DNA methyltransferase (DNMT) knockdown.

Results

Patients with higher ZNF331 expression had a significantly improved progression‐free interval (PFI). ZNF331 overexpression inhibits HNSCC cell proliferation and induces G2/M arrest, while its knockdown enhances oncogenic features. ZNF331 can downregulate the expression of oncogenes such as DDX5, EIF5A, and SET. ZNF331's tumor‐suppressive activity requires TRIM28, a universal co‐repressor of KRAB‐ZNF proteins. ZNF331 expression is suppressed by DNMT3B‐mediated promoter hypermethylation. Selective knockdown of DNMT3B, but not DNMT3A, restored ZNF331 expression.

Conclusions

ZNF331 acts as a potential tumor suppressor in HNSCC, whose inactivation through DNMT3B‐mediated hypermethylation may contribute to HNSCC tumorigenesis. Restoring ZNF331 expression through targeted epigenetic therapies may offer a novel strategy for the treatment of HNSCC.