bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a novel malignant colorectal polyp prognostic nomogram
Authors: Zammit Andrew P , Aksoy Yagiz Alp , Brown Ian , Hooper John D , Clark David A , Fuchs Talia L , Riddell Andrew D , Gill Anthony J
Published: January 2025

Background

There is uncertainty when determining the optimal treatment for malignant polyps. Clinicians must balance the oncological risk of a malignant polyp with the risk of morbidity and mortality from surgery. This study developed an online risk‐calculator using machine‐learning techniques to predict the risk of an adverse outcome from a malignant colorectal polyp following polypectomy.

Methods

Retrospective data collection of a population‐wide database of all malignant polyps from 2011 to 2020 was performed. Utilizing an artificial intelligence‐based machine learning approach a generalized linear mixed (GLM) model was developed to predict the risk of an adverse outcome after polypectomy. The presence of an adverse outcome was determined by assessing for the presence of residual disease or lymphatic disease if colorectal resection was undertaken. Delayed disease recurrence was also assessed as an additional adverse outcome. Patient and pathological details from the Queensland Cancer Registry were collected and included in the calculator development.

Results

The following variables were included in the final model: age, gender, polyp location (right colon, left colon, rectum), depth of tumour invasion, lymphovascular space invasion, tumour grade, associated polyp type, mismatch repair immunohistochemistry status and margin status. Based on ROC analysis, the AUC for the final GLM model was 0.76. The mean accuracy of the GLM model was 0.76 (95% CI: 0.72–0.80).

Conclusion

This web‐based nomogram will facilitate the discussion of whether individual patients with malignant colorectal polyps can be safely managed with polypectomy or whether the patient should undergo colorectal resection. This nomogram is now available at https://malignantpolyp.com/risk-calculator.
Blocking the mineralocorticoid receptor prevents cardiac and mitochondrial dysfunction through the activation of NOX‐4 in female hormone deprivation rats
Authors: Rodrigues Samya Mere L. , Ximenes Carolina F. , Rodrigues Nathália , Ronconi Karoline , Costa Anna Karolina Nascimento , Vieira Livia Barroca , da Silva Maria Luiza Yago , Ferreira Katyana K. S. , Eliezeck Marcos , Scalzo Sergio , Monteiro André , Sanches Bruno , Spalenza Thiago , Fernandes Aurélia Araújo , Guatimosim Silvia , Varner Kurt J. , Ribeiro Eduardo Hertel , Stefanon Ivanita
Published: January 2025

Aim

Young women exhibit lower rates of cardiovascular disease (CVD) than age‐matched men, a protective effect often attributed to estrogen's influence on cardiac and mitochondrial function. The risk of CVD increases in post‐menopausal women, likely due to estrogen deficiency and aldosterone's negative effects, including those on mitochondria and other cellular targets. This study aimed to explore the link between estrogen deficiency and mitochondrial dysfunction in cardiac health. We hypothesized that in estrogen‐deprived conditions, aldosterone could stimulate NADPH oxidase, leading to mitochondrial dysfunction, and reduced cardiac contractility.

Methods

Wistar rats were divided into four groups: Sham, Ovariectomy‐induced hormone deprivation (Ovx), Ovx with apocynin treatment, and Ovx with spironolactone treatment for 60 days.

Results

Both apocynin and spironolactone countered the adverse effects of hormone deprivation by preserving myocardial contractility, improving cellular responses to calcium and isoproterenol, and normalizing the expression of key mitochondrial proteins. These compounds also attenuated the increase in reactive oxygen species (ROS) and maintained mitochondrial respiration rates.

Conclusion

We concluded that estrogen deficiency contributes to cardiac oxidative stress via the NADPH oxidase and mitochondrial pathways. Apocynin and spironolactone offer significant protective effects, opening new avenues for treating cardiac issues related to estrogen deficiency.
The 5‐year results of the Stratified Cancer Active Surveillance programme for men with prostate cancer
Authors: Gnanapragasam Vincent J. , Keates Alexandra , Lophatananon Artitaya , Thankapannair Vineetha
Published: January 2025

Objectives

To report 5‐year outcomes from the STRATified CANcer Surveillance (STRATCANS) programme based on progression risks using National Institute for Health and Clinical Excellence (NICE) Cambridge Prognostic Group (CPG) at diagnosis, prostate specific antigen density and magnetic resonance imaging (MRI) visibility.

Patients and Methods

Men with CPG1 and CPG2 disease selecting active surveillance (AS) were included into STRATCANS and allocated to one of three increasing follow‐up intensities. Outcome measures were: (i) treatment for CPG≥3 progression (main outcome), (ii) any treatment, (iii) conversion to watchful waiting (WW), (iv) patient self‐attrition, and (v) mortality.

Results

A total of 297 men (median age 66.0 years) were reviewed. The median (interquartile range, mean) follow‐up for men still on AS was 4.9 (2.7–7.6, 5.3) years. In the cohort, 38.0% were CPG2 and 25.0% Grade Group (GG) 2 at AS entry. Overall, 214/297 (72.1%) remained treatment free: 158 (53.1%) were still on AS, 17 (5.7%) died of other causes, and 39 (13.1%) progressed to WW/discharge. Only 10 (3.4%) left AS from anxiety. There were no cancer deaths or metastatic events. In all, 80 men (26.9%) converted to treatment due to biopsy/MRI progression but only 35 (11.7%) of these reached CPG≥3 disease. Treatment for CPG≥3 occurred in 7.6% of CPG1 and 18.5% of CPG2 disease and 9.9% of GG1 and 17.5% of GG2 disease. By STRATCANS tier, treatment for CPG≥3 disease was 4.7% in STRATCANS 1, 12.9% in STRATCANS 2, and 27.4% in STRATCANS 3 (P < 0.001). STRATCANS had an area under the curve (AUC) of 0.74 for predicting CPG≥3 progression out‐performing stratification by GG (AUC 0.64), CPG (0.69) and Likert score (0.51) alone or a combination of MRI visibility and GG (0.64). Longitudinal data have allowed further refinement of the STRATCANS schedule.

Conclusions

The STRATCANS 5‐year outcomes demonstrate that a simple risk stratified surveillance using a prognostically meaningful endpoint is safe, durable, has low treatment rates, high patient compliance and appropriately tailors monitoring based on risks of progression. A website and implementation toolkit are now available.
Does Financial Development Affect the Emission of CO2 Uniformly Across Economies? Global Evidence From Heterogeneous Analysis
Authors: Sikhawal Shobhana
Published: January 2025

The study investigates financial development's heterogeneous impact on emission of CO2, especially in the pre‐ and post‐global financial crisis phases and analyzes the mediators through which financial development affects the emission of CO2. Using panel quantile estimation with non‐additive fixed effects method, on a comprehensive sample of 125 countries over the period 1991–2015, we find that the overall financial development activities increase the emission of CO2. However, financial development has a much greater effect on increasing CO2 emissions in countries with fewer emissions than in those with higher emissions.
Genomic profiles of patients with skin melanoma in the era of immune checkpoint inhibitors
Authors: Liang Yao , Maeda Osamu , Nishida Kazuki , Chretien Basile , Ando Yuichi
Published: January 2025

The use of immune checkpoint inhibitors (ICIs) for treating melanoma has dramatically improved patient prognosis. The genomic profiles of patients receiving ICI therapy would provide valuable information for disease management and treatment. We investigated the genomic profiles of patients with melanoma who had received ICI therapy and explored associations with clinical features and outcomes via a large‐scale nationwide database in Japan (the C‐CAT database). We identified 339 patients eligible for this study. The most frequent genetic mutations were found in the BRAF (27%), TERT (24%), and NRAS (19%) genes, and the most common copy number variations (CNVs) were in the CDKN2A (36%), CDKN2B (26%), and MTAP (19%) genes. Associations with high tumor mutational burden (TMB‐high) status were significant for TERT (p < 0.001), NF1 (p < 0.001), ROS1 (p = 0.015), POLE (p = 0.045), and POLD1 (p = 0.008) mutations, along with older age (≥65 years, p = 0.036). Patients with multiple metastases (two or more) were more likely to have NOTCH3 mutations (p = 0.017) and be younger than 65 years (p = 0.024). In particular, as well as younger age, patients with brain metastases were more likely to harbor BRAF mutations (p < 0.001), while those with liver metastases were more likely to harbor NOTCH3 mutations (p < 0.001) but not CDKN2B CNVs (p = 0.041). Patients with NRAS mutations were less likely to respond to ICI therapy (p = 0.014) and exhibited shorter overall survival (p = 0.006). In this population, the frequency of BRAF mutations was lower than that in fair‐skinned populations, but the associations between genomic profiles, clinical features, and outcomes were similar to those previously reported in fair‐skinned populations.
Cladistic estimates of evolutionary rates focused on palaeontological datasets using TNT
Authors: Pol Diego , Ezcurra Martín D.
Published: January 2025

We describe a protocol for estimating evolutionary rates from phylogenetic trees based on parsimony character optimization. The rate estimation is conducted through a TNT script and the results are analysed in a script for the software environment R. The TNT script allows analysing multiple optimal topologies, considering optimization ambiguity, and alternative time‐calibrations or pre‐calibrated trees. The R script summarizes estimated rates on a consensus tree and plots the variation of evolutionary rates through time, jointly with the phylogenetic diversity and a new metric (clade completeness index) that measures the distribution of missing data along the tree. We present results for simulated and empirical analyses, and evaluate the impact of missing data and alternative calibration methods in rate estimates. We found that while missing data can lower the nominal values of evolutionary rates, the overall pattern of rate variation through time remained robust. Empirical cases highlight different scenarios, such as datasets in which peaks of evolutionary rates can be coupled or decoupled from diversification dynamics (phylogenetic diversity) and cases in which missing data may influence the variation of estimated evolutionary rates. We conclude with recommendations for using this protocol and interpreting the results of parsimony‐based rate estimates.
Change in glucose, insulin and serum lipids due to ultra‐processed food consumption in children with obesity
Authors: Cortes Caroline , Brandão Joana Maia , Cunha Diana Barbosa , Paravidino Vitor Barreto , Sichieri Rosely
Published: January 2025

While the association between ultra‐processed food (UPF) consumption and chronic non‐communicable diseases in adults is well‐established, its relationship with serum markers of chronic diseases in children remains underexplored. This research investigates changes in serum markers in children with obesity during a trial aimed at reducing UPF consumption. The study is a prospective cohort, based on a parallel randomized controlled trial conducted between August 2018 and February 2020, with children aged 7–12 years. Over 6 months, children and their guardians attended monthly consultations and educational activities aimed at reducing UPF consumption. Body weight, height, and 24‐h dietary recall were measured at all visits. Serum markers were collected at baseline and at the 2‐ and 5‐month visit (during the intervention). Data from 95 children were analysed. Body mass index (BMI), UPF consumption in grams and energy, and percentage of UPF in grams showed a quadratic trend, initially decreasing, followed by an increase in the following months. Glucose, insulin, and HOMA‐IR decreased throughout the study, but after adjustment for BMI, the associations no longer persisted, except for glucose levels, which decreased linearly by 2.25 mg/dL. Reducing UPF consumption may lower blood glucose levels in children with obesity, independent of BMI changes.
Oral antibiotic prophylaxis induces changes in the microbiology of surgical site infection after colorectal surgery. A matched comparative study
Authors: Flores‐Yelamos Miriam , Juvany Montserrat , Badia Josep M. , Vázquez Ana , Pascual Marta , Parés David , Almendral Alexander , Limón Enric , Pujol Miquel , Gomila‐Grange Aina ,   Members of the VINCat Colorectal Surveillance Team
Published: January 2025

Aim

Oral antibiotic prophylaxis (OAP) lowers rates of surgical site infection (SSI) and may aid anastomotic healing in colorectal surgery. The aim of this study was to analyse the understudied impact of OAP on SSI microbiology after colorectal surgery.

Method

A post hoc analysis was performed on a previous prospective, multicentre study of elective colorectal surgery. For 1000 patients with SSI, this study compared the microbiology of SSIs in procedures without OAP (SSI/OAP–) and with OAP (SSI/OAP+).

Results

There were 340 patients in the SSI/OAP– group and 660 in the SSI/OAP+ group. The use of OAP increased the presence of Gram‐positive cocci (GPC) (OR 1.542, 95% CI 1.153–2.062) and fungi (OR 2.037, 95% CI 1.206–3.440), but reduced rates of Gram‐negative bacteria (GNB) (OR 1.461, 95% CI 1.022–2.088) and anaerobe isolation (OR 0.331, 95% CI 0.158–0.696). Specifically, it led to increases in the isolation of Enterococcus faecium (OR 1.450, 95% CI 0.812–2.591), methicillin‐resistant Staphylococcus aureus (OR 2.000, 95% CI 1.043–3.834) and Candida spp. (OR 2.037, 95% CI 1.206–3.440). In colon surgery with OAP, GPC infections were more likely (OR 1.461, 95% CI 1.022–2.088). In rectal surgery, organ/space SSIs had a higher risk of harbouring GPC (OR 1.860, 95% CI 1.153–2.999) and a lower risk of GNB (OR 0.321, 95% CI 0.200–0.515).

Conclusion

OAP reduced the presence of anaerobes and GNB in SSIs, but increased the isolation of GPCs and fungi, with E. faecium and Candida being of particular concern. This information should guide empirical antibiotic therapy for postoperative colorectal SSIs in patients who have received preoperative OAP.
Public pathways to influencing pro‐nature decision‐making in government: A case study in southeastern Australia
Authors: van Eeden Lily M. , Smith Liam , Bekessy Sarah , Dovers Stephen , Lowe Kim W. , Hames Fern M.
Published: January 2025

The biodiversity crisis calls for more collective effort, and a close examination of the tools available to effect change. We documented insider knowledge into how pro‐nature decision‐making can be influenced in the Australian state of Victoria, focusing on the role of public advocacy targeting government. We interviewed 12 experts who currently or previously held influential roles in government or advocacy‐focused environmental non‐government organizations (ENGOs) and used thematic analysis to explore their responses. Experts described influence from individuals, grassroots groups, or ENGOs, and factors shaping success. These included attributes of the decision‐making context, having resources and commitment to see out long‐term change, having relevant networks, and being able to act when opportunities arise. Barriers described included lack of environmental literacy among the public and some decision‐makers, biodiversity concern being crowded out by climate change concern, and the difficulty of shifting from incremental to systemic change. Understanding these factors can better equip advocates to have impact. Democratic governments recognize that societies make progress where there is two‐way exchange between public and state, so should foster public pathways toward political engagement in conservation.
Comparative effectiveness of insulin glargine, glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter‐2 inhibitors in veterans with type 2 diabetes
Authors: Shen Jincheng , Sarwal Amara , Singh Ravinder , Hartsell Sydney E. , Wei Guo , Nevers McKenna , Christensen Jesse C. , Takyi Augustine , Katkam Niharika , Derington Catherine G. , Deshmukh Vikrant G. , Boucher Robert E. , Drakos Stavros G. , Greene Tom , Beddhu Srinivasan
Published: January 2025

Aims

To compare the risk of all‐cause death and cardiovascular events in new users of insulin glargine, glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2i), particularly in subgroups defined by baseline haemoglobin A1C (HbA1C), body mass index (BMI) and estimated glomerular filtration rate (eGFR).

Materials and Methods

We conducted an active comparator, new user design study in a national cohort of 161 405 veterans with type 2 diabetes (T2D) on metformin and initiated insulin glargine (n = 54 375), GLP‐1RA (n = 22 145) or SGLT2i (n = 84 885) between 1 January 2018 and 31 December 2021. Patients were followed until 31 March 2023. Inverse probability weighted Cox regression models were used for treatment comparisons on all‐cause deaths and cardiovascular events in the entire cohort and above subgroups.

Results

There were 20 788 cardiovascular events/414 414 person‐years and 15 268 all‐cause deaths/446 458 person‐years. Insulin glargine had a higher hazard of all‐cause death compared to GLP‐1RA (hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.48–1.67) or SGLT2i (HR 1.55, 95% CI 1.48–1.61) in the entire cohort and across subgroups, especially in those with HbA1C levels <9.0%. Results were similar for secondary outcomes. Compared to GLP‐1RA, SGLT2i had similar risk of all‐cause death (HR 1.03, 95% CI 0.97–1.10) but higher hazard of cardiovascular events (HR 1.13, 95% CI 1.08–1.19). Across subgroups, GLP‐1RA and SGLT2i had generally similar effects, with SGLT2i showing a slightly higher risk in some cases.

Conclusions

Insulin glargine might be deleterious particularly in those with HbA1C <9.0%. There was no clear evidence for prioritization of SGLT2i versus GLP‐1RA across subgroups.
Clinical effectiveness and cost‐effectiveness of first‐line early combination of dipeptidyl peptidase 4 inhibitors and metformin in patients with type 2 diabetes in Taiwan: A modelling study
Authors: Nguyen Thi Thuy Dung , Chen Hsuan‐Ming , Lin Hung‐Wei , Ou Huang‐Tz , Wang Chih‐Yuan
Published: January 2025

Aims

Early dipeptidyl peptidase‐4 inhibitors and metformin (DPP4i‐Met) combination has been shown to extend the time to treatment failure and provide better glycaemic control for newly diagnosed type 2 diabetes (T2D) patients; however, the long‐term clinical and economic outcomes of early DPP4i‐Met combination remain unknown. We seek to assess the comparative long‐term clinical and cost‐effectiveness of DPP4i‐Met versus Met for treatment‐naïve T2D patients with inadequately controlled HbA1c (i.e., ≥8.5%).

Methods

The IQVIA CORE Diabetes Model was used to simulate the quality‐adjusted life years (QALYs) and healthcare costs over a lifetime from Taiwan's National Health Insurance Administration's perspective, with both QALYs and costs discounted at 3% annually. Model inputs were taken from the analyses of Taiwanese or Asian populations. Primary outcomes included the number needed to treat (NNT) to prevent one case of a clinical event and the incremental cost‐effectiveness ratios (ICERs). Costs are presented in 2023 US dollars.

Results

Over 40 years of projection, Met‐DPP4i‐treated patients had fewer complications than those using Met alone (e.g., lowering the incidence of stroke by 2.21% [2.68, 1.74]). The NNT using DPP4i‐Met versus Met alone to prevent one case of stroke, microalbuminuria, neuropathy and background retinopathy was 45, 135, 65 and 182, respectively. Such long‐term benefits in reducing costly complications offset the higher treatment cost of DDP4i‐Met versus Met ($5796 vs. $5484/person). As a result, using DPP4i‐Met versus Met yielded 0.086 QALYs gained and savings of $489 for overall treatment‐naïve T2D patients and 0.064 QALYs gained and savings of $714 for young‐onset T2D patients.

Conclusions

Early DPP4i‐Met provides long‐term clinical and economic benefits compared to Met alone for newly diagnosed T2D patients, including those with young‐onset T2D.
Factors and Considerations in No‐Treatment Decisions in Patients With Key Hematological Malignancies: A Nationwide, Population‐Based Study in the Netherlands
Authors: Zijlstra Myrte , Snijders Rolf A. H. , de Boer Fransien , Chamuleau Martine E. D. , Fransen Heidi P. , Oerlemans Simone , van der Padt‐Pruijsten Annemieke , Posthuma Eduardus F. M. , Visser Otto , Zweegman Sonja , Raijmakers Natasja J. H. , Dinmohamed Avinash G.
Published: January 2025

Comprehensive insights are lacking into why patients with hematological malignancies (HMs) receive no cancer‐directed treatment. We evaluated socio‐demographic and cancer‐related characteristics, decision‐making rationales, and overall survival in patients with three common HMs―diffuse large B‐cell lymphoma (DLBCL), symptomatic multiple myeloma (MM), and acute myeloid leukemia (AML)―who do not receive cancer‐directed treatment, using the nationwide Netherlands Cancer Registry. A total of 26 945 patients diagnosed with DLBCL (47%), symptomatic MM (29%), or AML (25%) between 2014 and 2021 were included. About 16% of the patients did not receive cancer‐directed treatment, ranging from 26% in AML to 15% in DLBCL and 10% in MM. The primary reason for not receiving cancer‐directed treatment in all three HMs was related to physical condition. The second main reason was patient/family choice in DLBCL and MM, whereas in AML it was rapid disease progression. In female patients, patient/family choice was a more prevalent reason for not receiving cancer‐directed treatment than in male patients. Patients with a lower socio‐economic position more often did not receive cancer‐directed treatment. Median OS varied by reason for not receiving cancer‐directed treatment, with the shortest OS in patients experiencing rapid disease progression or death before treatment initiation (0·4 to 0·6 months).
Value Creation for Multiple Stakeholders in Higher Education Institutions
Authors: Sarturi Greici , Aragão Paula Balardin Ribeiro
Published: January 2025

A comprehensive understanding of value creation in higher education institutions (HEIs) and the organisational practices that drive this value is essential for strategic management. Grounded in stakeholder theory, this study adopts Harrison and Wicks' model to examine the perceptions of five stakeholder groups regarding key drivers of value. The findings extend the original model—focused on goods and services, organisational justice, affiliation and opportunity costs—by introducing reputation and inter‐stakeholder relationships as complementary dimensions shaping stakeholder perceptions of value. Additionally, the study identifies stakeholder engagement as a critical outcome of the value creation process. This research advances stakeholder theory by applying and expanding it within the context of public HEIs, providing a robust framework for measuring and managing value across diverse stakeholder groups. It also offers practical insights for HEI managers to align institutional strategies with stakeholder expectations, fostering synergy, engagement and improved institutional performance.
15‐Month‐Olds’ Understanding of Imitation in Social and Instrumental Contexts
Authors: Yasuda Shannon , Li Wenjie , Martinez Deisy , Lake Brenden M. , Dillon Moira R.
Published: January 2025

From early in development, humans use imitation to express social engagement, to understand social affiliations, and to learn from others. Nevertheless, the social and instrumental goals that drive imitation in everyday and pedagogical contexts are highly intertwined. What cues might infants use to infer that a social goal is driving imitation? Here we use minimal and tightly controlled visual displays to evaluate 15‐month‐olds’ attribution of social goals to imitation. In particular, we ask whether they see the very same simple, imitative actions shared between two agents as social or nonsocial when those actions occur in the absence or presence of intentional cues such as obstacles, object goals, and efficient, causally effective action. Our results suggest that infants' attributing social value to imitation only in the absence of such intentional cues may be a signature of humans' early understanding of imitation. We propose, moreover, that a systematic evaluation of a set of simple scenarios that probe candidate principles of early knowledge about social and instrumental actions and goals is possible and promises to inform our understanding of the foundational knowledge on which human social learning is built, as well as to aid the building of human‐like artificial intelligence.
Exploring the Acceptability of a Peer‐Delivered Mental Health Intervention to Support Young Adults With Intellectual and/or Developmental Disabilities
Authors: Schwartz Ariel , Davern Nikola , Herer Alix , Peace‐Urquilla Micah , Corey Jesse , Muthuramalingam Dheva , Vallabhaneni Neha
Published: January 2025

Background

Young adults with intellectual and/or developmental disabilities lack access to mental health supports. Peer‐delivered services may fill this gap. We adapted a theory‐driven and evidence‐based peer mentoring intervention for virtual‐delivery and investigated its acceptability and participants' preliminary response.

Methods

Twelve young adults with intellectual and/or developmental disabilities participated in the 16‐week intervention and completed outcome measures at pre‐mentoring, post‐mentoring and 1‐month follow‐up. To evaluate acceptability, participants completed interviews and a survey. Preliminary response was measured with the Alexithymia Questionnaire for Children and PROMIS short forms (Self‐efficacy for Managing Emotions, Anxiety, and Physical Stress).

Results

Participants felt emotionally supported, increased self‐understanding, and learned to use coping strategies. Participants reported improvements in alexithymia, self‐efficacy for managing emotions and anxiety; no changes were observed for physical stress symptoms.

Conclusions

Participants were satisfied with peer mentoring and data suggest it may have promise to support development of skills that support mental health outcomes.
Reverse Torque and Wear of Internal Connections of Metal‐Based Abutments Under Cyclic Loading
Authors: Queiroz Daher Antonio , Freitas Mariana Itaborai Moreira , Ockey Kaden Thomas , Lee Damian Jaewhan , Zheng Fengyuan
Published: January 2025

Objective

Evaluate the reverse torque values and wear of internal connections caused by metal‐based zirconia abutments under cyclic loading.

Material and Methods

Thirty implants were divided into three groups (n = 10), based on connection systems: Interference‐fit cone‐screw (Cortical Master Flash MI Fit—MTA and Cortical Master Flash MI RP—MTB), and Internal hexagon (Cortical Titanium Master Connect AR—IH). Metal‐based zirconia abutments were tightened into the implant, and zirconia crowns were bonded using resin cement. All specimens underwent cyclic loading at 300 N and 9 Hz for 1,000,000 cycles. Reverse torques were assessed postloading, and wear was analyzed using scanning electron microscopy (SEM). Statistical analysis employed one‐way ANOVA for reverse torque and wear values, with significant differences assessed via the Tukey test (α = 0.05).

Results

Significant differences in reverse torque values were found among groups: MTA (24.9 N), MTB (24.1 N), and IH (14.4 N). The IH group showed higher mean wear values on the tension side (121.0) and compression side (112.6), with a wear difference of 8.4.

Conclusion

The interference‐fit cone‐screw abutments demonstrated significantly reduced torque loss and morphology after cyclic loading, reflecting enhanced performance.

Clinical Significance

Although the stability of the metal base zirconia abutments to the implants was accurate, clinicians should be cautious about torque loss and more wear when using internal hexagon connections.
A Risk Prediction Model for Hepatocellular Carcinoma in the General Population Without Traditional Risk Factors for Liver Disease
Authors: Song Byeong Geun , Park GoEun , Goh Myung Ji , Kang Wonseok , Gwak Geum‐Youn , Paik Yong‐Han , Choi Moon Seok , Lee Joon Hyeok , Sinn Dong Hyun
Published: January 2025

Background and Aim

Existing hepatocellular carcinoma (HCC) prediction models for the general population without traditional risk factors for chronic liver disease are limited. This study aimed to develop an HCC prediction model for individuals lacking these traditional risk factors.

Methods

The total of 138 452 adult participants without chronic viral hepatitis or significant alcohol intake who underwent regular health checkup at a tertiary hospital in South Korea were followed up for the development of HCC. Risk factors for HCC development were analyzed using Cox regression analysis, and prediction model was developed using the risk factors.

Results

Significant predictors of HCC development included older age, male sex, higher body mass index, presence of diabetes mellitus, and levels of aspartate aminotransferase, total cholesterol, and platelet count. A new HCC prediction model using these variables was developed. Harrell's concordance index and Heagerty's integrated area under the receiver operating characteristics (AUROC) curve of the model were 0.88 (95% confidence interval [CI] 0.85–0.91) and 0.89 (95% CI 0.86–0.91), respectively. The 5‐ and 10‐year AUROC were 0.89 (95% CI 0.88–0.89) and 0.87 (95% CI 0.87–0.88), respectively. This model significantly outperformed the FIB‐4 scoring model in predicting HCC and effectively stratified individuals into low‐, intermediate‐, and high‐risk groups with significantly different cumulative incidences of HCC.

Conclusions

The new model, based on clinical parameters, provides a valuable tool for clinicians to stratify HCC risk in the general population without risk factors for chronic liver disease.
Prevalence and Determinants of Sarcopenia Among Older Adults in India: Insights From the Longitudinal Aging Study in India
Authors: Rao Abhijith R. , Bhagwasia Manjusha , Singh Vishwajeet , Bajpai Swati , Singhal Sunny , Chatterjee Prasun , Chakrawarty Avinash , Dey Sharmishtha , Dey Aparajit Ballav
Published: January 2025

Background

Sarcopenia, characterized by declining muscle mass and function, is a growing concern among India's aging population. This study investigates sarcopenia's prevalence and determinants using the nationally representative LASI dataset.

Methods

This analysis included 26,780 community‐dwelling adults aged 60 and above, with informed consent obtained from all participants. Sarcopenia was defined using the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Demographic, socioeconomic, health, and geriatric factors, including age, sex, living arrangements, economic status, comorbidities, and geriatric syndromes, were examined. Multinomial logistic regression was used to analyze associations with sarcopenia and severe sarcopenia, and results were expressed as relative risk ratios (RRR) with 95% confidence intervals (CI).

Results

The prevalence of sarcopenia was 43.6% (n = 11,665), and 19.4% (n = 5202) had severe sarcopenia. Sociodemographic factors significantly associated with sarcopenia and severe sarcopenia included being widowed (RRR: 1.24, 95% CI: 1.12–1.37 for sarcopenia; RRR: 1.82, 95% CI: 1.64–2.03 for severe sarcopenia) or divorced (RRR: 1.68, 95% CI: 1.12–2.54 for severe sarcopenia). Additionally, a higher BMI and higher education level were associated with a lower risk of sarcopenia. Among comorbidities, joint and bone diseases were linked to both sarcopenia (RRR: 1.21, 95% CI: 1.07–1.35) and severe sarcopenia (RRR: 1.4, 95% CI: 1.23–1.58), while hypertension (RRR: 1.22, 95% CI: 1.1–1.36), chronic lung disease (RRR: 1.22, 95% CI: 1.02–1.44), and cerebrovascular accident (RRR: 1.5, 95% CI: 1.09–2.08) were specifically associated with severe sarcopenia. Geriatric syndromes such as tooth loss, impaired vision and hearing, history of falls, and depression were significantly associated with increased risk of sarcopenia.

Conclusion

This study reveals significant associations between sarcopenia and various sociodemographic factors, comorbidities, and geriatric syndromes in older adults in India, suggesting potential areas for targeted intervention. However, further longitudinal studies are needed to validate these findings and clarify the causal relationships of the observed associations.
Inter‐Laboratory Validation of Nodal/Paranodal Antibody Testing
Authors: Lleixà Cinta , Titulaer Maarten , Rohrbacher Sophia , Mgbachi Victor , Halstead Susan , Fehmi Janev , Pascual‐Goñi Elba , Zhu Louisa , Appeltshauser Luise , Franken Suzanne , Paunovic Manuela , Waters Patrick , Willison Hugh , Sommer Claudia , Querol Luis , Huizinga Ruth , Doppler Kathrin , Rinaldi Simon
Published: January 2025

Background and Aims

Reliable detection of antibodies against nodal targets is vital for the diagnosis of autoimmune nodopathies. The performance characteristics of recently developed in‐house assays are unknown. We compared testing at four centres.

Methods

Each submitted 29–40 serum samples to a coordinating centre from one of three groups: (1) autoimmune nodopathy patients, with positive nodal/paranodal antibodies; (2) seronegative patients with other inflammatory neuropathies, and (3) healthy individuals or those with other neurological diseases. The coordinating centre recoded all samples and returned 160 identical aliquots to each testing centre for blinded testing. Once data from all centres had been received by the coordinating centre, unblinded results were returned for analysis. Sensitivity was defined by the proportion of group 1 samples returned as positive. Accuracy was defined as 0.075(sensitivity) + 0.925(specificity).

Results

Centres performed various combinations of ELISA, cell‐based (CBAs) and teased‐nerve fibre assays. All labs produced highly accurate results (96%–100%) and concordance for the overall result across at least 3 or all 4 test centres was observed for 98% and 89% of the samples respectively. However, 10/30 individual assays (6/14 CBAs and 4/16 ELISAs) were less than 90% sensitive. Only 3 assays had more than 1 false positive result (2 ELISAs and 1 CBA). Combining different assay modalities to produce an overall result did not improve accuracy. Inter‐laboratory consistency in the determination of antibody subclasses was poor.

Interpretation

Although most samples were correctly categorised in all 4 centres, the use of a specific test modality or multiple tests did not guarantee accuracy. Early and repeated interlaboratory testing with sharing of samples is important to understand test performance and reproducibility, identify areas for improvement and maintain consistency. To aid this, we provide detailed methods for the best performing tests. Further standardisation of antibody subclass determination is required.
Catastrophe risk sharing among individuals, private insurance, and government
Authors: Jia Ruo , Lin Jieyu , Powers Michael R. , Wang Hanyang
Published: January 2025

Limited research has been conducted on the optimal public–private risk‐sharing for catastrophe risks. This paper develops a theoretical framework to study the risk‐sharing decisions and interactions of three types of catastrophe‐market participants: a large number of individuals, a large number of private insurers in a competitive market, and a government that can choose between alternatives of re/insurance or ex post relief. Our analysis shows that the optimal government intervention varies depending on the correlation levels among individual losses. For moderately positive levels of loss correlation, it is optimal for the government to offer an ex post relief program to supplement private insurance. However, for higher levels of loss correlation, government reinsurance becomes optimal, although not to the extent of replacing private insurance if the government is less efficient than private firms. In sum, as catastrophe‐loss correlations increase, that is, as the risk becomes more catastrophic, more risk‐sharing tools and funding are needed to maximize social welfare.
Dental Care Use Among Children and Adolescents in Medicaid: Associations With State‐Level Medicaid Policy Factors and Provider Availability
Authors: Reynolds Julie C. , Comnick Cari , Heeren Tessa , Damiano Peter C. , Xie Xianjin
Published: January 2025

Objectives

The aim of this study was to assess the relative strength of association of four state‐level factors—Medicaid reimbursement, Medicaid adult dental benefit (MADB) generosity, dentist Medicaid participation, and dentist supply—on individual‐level dental care use among children and adolescents in Medicaid.

Methods

This national cross‐sectional study used 2018–2019 National Survey of Children's Health data to estimate dental care utilization among children aged 1–17 enrolled in Medicaid. Subgroup analyses were conducted by child age group. A hierarchical regression approach was used; a series of logistic regression models assessed relative effect sizes among the four state‐level variables.

Results

Among children aged 1–17, and the age 1–3 subgroup, dentist Medicaid participation was positively associated with dental care use. Among children aged 4–11, children in states with Emergency/No dental coverage for adults had greater odds of having a dental visit compared to children in states with Extensive dental coverage. Among adolescents aged 12–17, no state‐level factors were associated with dental utilization.

Conclusions

There was considerable variation by age group in the associations of state‐level factors on dental care use among children and adolescents in Medicaid. Dentist participation in Medicaid was associated with dental care use among very young children. State‐level policy levers have the potential to improve access to dental care for children enrolled in Medicaid, and are critical to achieve improvement toward oral health equity for children.
Epiberberine Improves Hyperglycemia and Ameliorates Insulin Sensitivity in Type 2 Diabetic Mice
Authors: Ma Xiaohong , Shi Yufeng , Shang Zhitao
Published: January 2025

Aim

Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterised by absolute or relative insufficiency of insulin secretion. The alkaloids from Rhizoma coptidis have potential hypoglycemic effects. Epiberberine (EPI), a protoberberine alkaloid extracted from Rhizome coptidis, has been found to regulate lipid metabolism. Our study aimed to investigate the antidiabetic effects of EPI on mice with T2DM, as well as its underlying mechanism.

Methods

The T2DM model in mice was established using a combination of high‐fat diet and streptozotocin. Animals were divided into the control, T2DM, EPI‐low dose (50 mg/kg EPI), EPI‐medium dose (100 mg/kg EPI), EPI‐high dose (200 mg/kg EPI) and metformin (MTF) (200 mg/kg MTF) groups. Body weight, water/food intake, serum lipids, blood glucose tolerance, insulin sensitivity, histopathological alterations, insulin signalling pathway and inflammation‐related pathways in each group were detected.

Results

EPI significantly reduced blood glucose levels and water/food intake in T2DM mice. EPI reduced the levels of total cholesterol, total triglyceride, low‐density lipoprotein cholesterol, aspartate aminotransferase and alanine aminotransferase, and elevated the levels of high‐density lipoprotein cholesterol in serum. EPI effectively improved oral glucose tolerance, alleviated hepatic insulin resistance, decreased glycosylated haemoglobin levels and increased liver glycogen content. EPI ameliorated the histopathological alterations of skeletal muscle and liver in T2DM mice. EPI stimulated the insulin signalling pathway by increasing glucose transporter type 4 levels and activating insulin receptor substrate‐1, phosphatidylinositol 3‐kinase and protein kinase B in skeletal muscle and liver. EPI reduced the levels of proinflammatory cytokine in serum and inhibited the activation of mitogen‐activated protein kinase signalling in skeletal muscle and liver of diabetic mice.

Conclusion

Overall, these data demonstrate that EPI alleviates the symptoms of T2DM, providing new insights into EPI as a therapeutic compound for the alleviation of T2DM.
Evolution and diversification of the momilactone biosynthetic gene cluster in the genus Oryza
Authors: Priego‐Cubero Santiago , Liu Youming , Toyomasu Tomonobu , Gigl Michael , Hasegawa Yuto , Nojiri Hideaki , Dawid Corinna , Okada Kazunori , Becker Claude
Published: January 2025

Plants are master chemists and collectively are able to produce hundreds of thousands of different organic compounds. The genes underlying the biosynthesis of many specialized metabolites are organized in biosynthetic gene clusters (BGCs), which is hypothesized to ensure their faithful coinheritance and to facilitate their coordinated expression. In rice (Oryza sativa), momilactones are diterpenoids that act in plant defence and various organismic interactions. Many of the genes essential for momilactone biosynthesis are grouped in a BGC.

We applied comparative genomics of diploid and allotetraploid Oryza species to reconstruct the species‐specific architecture, evolutionary trajectory, and sub‐functionalisation of the momilactone biosynthetic gene cluster (MBGC) in the Oryza genus.

Our data show that the evolution of the MBGC is marked by lineage‐specific rearrangements and gene copy number variation, as well as by occasional cluster loss. We identified a distinct cluster architecture in Oryza coarctata, which represents the first instance of an alternative architecture of the MBGC in Oryza and strengthens the idea of a common origin of the cluster in Oryza and the distantly related genus Echinochloa.

Our research illustrates the evolutionary and functional dynamics of a biosynthetic gene cluster within a plant genus.
Intermittent theta burst stimulation for negative symptoms in schizophrenia patients with moderate to severe cognitive impairment: A randomized controlled trial
Authors: Li Jing , Jiang Dan , Huang Xingyu , Wang Xiao , Xia Tingting , Zhang Wei
Published: January 2025

Aims

This study aims to assess the therapeutic effects of intermittent theta burst stimulation (iTBS) targeting the bilateral dorsomedial prefrontal cortex (DMPFC) on negative symptoms in patients with schizophrenia, utilizing functional near‐infrared spectroscopy for evaluation.

Methods

Thirty‐five schizophrenia patients with negative symptoms and moderate to severe cognitive impairment were randomly assigned to a treatment group (n = 18) or a control group (n = 17). The treatment group received iTBS via bilateral DMPFC. Negative symptoms, cognitive function, emotional state, and social function were assessed using Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Montreal Cognitive Assessment (MoCA), Calgary Depression Scale for Schizophrenia (CDSS), and Social Dysfunction Screening Questionnaire (SDSS) scales at pretreatment, posttreatment, and follow‐up at 4, 8, and 12 weeks. Brain activation in regions of interest (ROIs) was evaluated through verbal fluency tasks.

Results

Prior to treatment there was no significant difference in the two groups. After 20 iTBS sessions, a significant difference was observed in SANS total score, its related subscales, PANSS total score, and PANSS‐negative symptoms (all P < 0.05). The group‐by‐time interaction showed statistical significance, indicating improvements in negative symptoms and related dimensions over time, with therapeutic effects persisting for at least 8 weeks posttreatment. Prior to treatment, there were no significant differences in activation across all ROIs between the two groups. Posttreatment, the activation of right inferior frontal gyrus (t = 2.19, P = 0.036) and right frontal eye field (t = 2.14, P = 0.04) in the treatment group was significantly higher than in the control group.

Conclusions

iTBS stimulation of bilateral DMPFC demonstrates therapeutic effects in improving negative symptoms in schizophrenia patients, and this treatment approach has the potential to enhance activation within the prefrontal cortex.
Associations Between Mental Disorders, Personality Disorders, and Filicide‐Suicide and Parental Suicide: A Nationwide Cohort Study
Authors: Yen Cheng‐Fang , Chen Yi‐Lung
Published: January 2025

Aim

Filicide‐suicide represents a critical intersection of psychiatric and familial crises, yet the literature remains scant on differentiated risk profiles among family members. This study addresses a gap in understanding the specific mental health correlates of filicide‐suicide, especially within a comprehensive family context, distinct from traditional parental or child‐focused perspectives.

Method

This study used the Taiwan National Health Insurance Research Database to identify a nationally representative sample of families from 2004 to 2020, with continuous monitoring extending into 2021. Families were classified into those affected by filicide‐suicide, parental suicide, and those without such incidents. Multinomial logistic regression was conducted to explore the association between family status and mental health. Analyses of effect modification were conducted to evaluate whether low‐income status modified these relationships.

Results

The study encompassed 1,898,299 families, revealing that filicide‐suicide is notably rare, with an incidence of 1.64 deaths per 100,000 newborn children from 2004 to 2020, with an increasing trend observed after 2014. Fathers and children in filicide‐suicide families had the highest prevalence of mental disorders, followed by those in parental‐suicide families and then other families (those where no child has been recorded as a homicide victim and no parent has committed suicide). There was a tendency for stronger associations between filicide‐suicide families and paternal schizophrenia as well as autistic spectrum disorder in children among low‐income families.

Conclusion

The findings underscore the profound impact of severe mental disorders within the familial framework, emphasizing the need for an integrated approach to mental health care that considers the familial context in order to better predict and prevent such devastating events.
Goodness‐of‐fit testing based on graph functionals for homogeneous Erdös–Rényi graphs
Authors: Brune Barbara , Flossdorf Jonathan , Jentsch Carsten
Published: January 2025

The Erdös–Rényi graph is a popular choice to model network data as it is parsimoniously parameterized, straightforward to interpret and easy to estimate. However, it has limited suitability in practice, since it often fails to capture crucial characteristics of real‐world networks. To check its adequacy, we propose a novel class of goodness‐of‐fit tests for homogeneous Erdös–Rényi models against heterogeneous alternatives that permit nonconstant edge probabilities. We allow for both asymptotically dense and sparse networks. The tests are based on graph functionals that cover a broad class of network statistics for which we derive limiting distributions in a unified manner. The resulting class of asymptotic tests includes several existing tests as special cases. Further, we propose a parametric bootstrap and prove its consistency, which avoids the often tedious variance estimation for asymptotic tests and enables performance improvements for small network sizes. Moreover, under certain fixed and local alternatives, we provide a power analysis for some popular choices of subgraph counts as goodness‐of‐fit test statistics. We evaluate the proposed class of tests and illustrate our theoretical findings by simulations.