bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive diagnostic and therapeutic approach to male factor infertility aimed at natural fertility: A multicentric retrospective cohort study
Authors: Grande Giuseppe , Garolla Andrea , Graziani Andrea , Astorri Anna Laura , Cammarota Maria Vittoria , Merola Annamaria , Polidori Maria Pia , Lulli Emanuela , Busato Enrico , Pesce Francesco , Pompa Giuseppina , Pontecorvi Alfredo , Milardi Domenico , Ferlin Alberto
Published: February 2025

Background

In infertile couples whose male partner has alterations in semen parameters frequently, a comprehensive andrological approach is lacking and approximately 30–50% are classified as idiopathic infertility. These couples are often directly addressed to assisted reproduction techniques (ARTs). However, several clinical conditions may benefit from medical treatment. By acting on etiology and/or risk factors, this aims at improving seminal parameters and restoring natural fertility.

Objectives

To verify the impact of a comprehensive andrological assessment on the management of infertility (in particular, in couples with isolated male factor infertility) using as the primary outcome the natural pregnancy rate.

Materials and Methods

A multicenter retrospective study was conducted between 2015 and 2022 in 1014 couples with primary infertility seeking natural conception (including 266 couples with previous ART failure). Each couple underwent a multidisciplinary evaluation. This involved: a gynecologist and an andrologist both with expertise in infertility, a psychologist when requested, and a fertility awareness practitioner according to a unique diagnostic and therapeutic multidisciplinary protocol.

Results

An isolated male factor was found in 23% of couples. In 45%, it was associated with female factors also. The comprehensive diagnostic approach reduced the proportion of idiopathic infertility to 8% of the couples. Targeted treatment, based on diagnostic categories, was associated with spontaneous pregnancy in 40.9% of the couples. In the 233 cases without female factors, normal semen parameters were observed only in 13% of patients. Male genital tract inflammation was observed in 48.8% of the patients, genital tract infection in 43.1%, and hypospermatogenesis in 16.7%. Patients with infections were treated with antibiotics and probiotics. If further inflammation was documented, this was followed by low‐dose corticosteroids and antioxidants. Follicle stimulating hormone (FSH) treatment was used in patients with hypospermatogenesis, and varicocele repair surgery was performed in four patients.

Discussion and Conclusions

Our data underline the efficacy of a comprehensive approach to the diagnostic process of male factor infertility, both in reducing the percentage of idiopathic infertility and in restoring natural fertility based on a targeted treatment.
“Who Islamises us?”: Does political ideology moderate the effects of exposure to different Great Replacement Conspiracy explanations on radical collective action against different targets?
Authors: Çakmak Hakan , Mang Valentin , Long Feiteng
Published: February 2025

Conspiracy theories against outgroups (e.g., the Great Replacement Conspiracy [GRC]) are believed to fuel radicalisation. Two experimental studies with British and American samples (Ntotal = 1690) examined how different GRC narratives and political ideologies influence radical collective action against Muslims and ideologically opposed political elites. We predicted that the Muslim conspirator and left‐wing conspirator (vs. control) narratives would increase radical action intentions against Muslims among right‐wingers (Hypothesis 1). We also predicted that the left‐wing conspirator narrative (vs. other conditions) would increase radical action intentions against left‐wing elites among right‐wingers (Hypothesis 2a), and the Muslim conspirator narrative (vs. control) would do the same (Hypothesis 2b). Furthermore, we predicted stronger radical intentions towards right‐wing elites among left‐wingers when exposed to the left‐wing conspirator condition (Hypothesis 3). Despite limited support for these hypotheses, both studies showed that exposure to any GRC narrative increased radical intentions against Muslims, suggesting that the conspirator group does not play a strong role in anti‐Muslim radicalisation. The lack of statistically significant effects on other targets may be due to conservative hypothesis testing. Theoretical and societal implications are discussed, providing critical conceptual and methodological avenues for future research on conspiracy theories and radicalisation.
Targeting FDX1 by trilobatin to inhibit cuproptosis in doxorubicin‐induced cardiotoxicity
Authors: Wei Jiajia , Lan Guozhen , Zhang Wenfang , Ran Wang , Wei Yu , Liu Xin , Zhang Yuandong , Gong Qihai , Li Haibo , Gao Jianmei
Published: February 2025

Background and Purpose

Doxorubicin (DOX), an anthracycline chemotherapeutic agent, whose use is limited owing to its dose‐dependent cardiotoxicity. Mitochondrial oxidative stress plays a crucial role in the pathogenesis of DOX‐induced cardiotoxicity (DIC). Trilobatin (TLB), a naturally occurring food additive, exhibits strong antioxidant properties, but its cardioprotective effects in DIC is unclear. This study investigates the cardioprotective effect of TLB on DIC.

Experimental Approach

DOX was used to generate an in vivo and in vitro model of cardiotoxicity. Echocardiography, enzyme‐linked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining were used to evaluate the cardiac function in these models. To identify the targets of TLB, RNA‐sequence analysis, molecular dynamics simulations, surface plasmon resonance binding assays and protein immunoblotting techniques were used. Transmission electron microscopy, along with dihydroethidium and Mito‐SOX staining, was conducted to examine the impact of trilobatin on mitochondrial oxidative stress. SiRNA transfection was performed to confirm the role of ferredoxin 1 (FDX1) in DIC development.

Key Results

In DIC mice, TLB improved cardiac function in a dose‐dependent manner and inhibited myocardial fibrosis in DIC mice. TLB also attenuated DOX‐induced mitochondrial dysfunction and reduced cardiac mitochondrial oxidative stress. TLB was found to directly bind to FDX1 and suppresses cuproptosis after DOX treatment, causing significant inhibition of cuproptosis‐related proteins.

Conclusions and Implications

This is the first study to show that TLB strongly inhibits DIC by reducing mitochondrial oxidative stress and controlling DOX‐mediated cuproptosis by targeting FDX1. Therefore, TLB is as a potential phytochemical cardioprotective candidate for ameliorating DIC.
Fathers' Experiences in Parenting Autistic Children: A Qualitative Study
Authors: André Tatiane Geralda , Prizantelli Laura Marques , de Lucca Milena , Esper Marcos Venicio , Machado‐Kayzuka Giovanna Cristina , Pinto Manoela Henriques , Silva‐Rodrigues Fernanda Machado , Nascimento Lucila Castanheira
Published: February 2025

Autism can disrupt family dynamics and affect childcare. However, fathers' roles in childcare are rarely explored in the literature. The study aims to analyse paternal experiences in caring for autistic children. This is a secondary analysis conducted from qualitative data, focusing on interpreting the meanings of fathers' experiences in caring for autistic children. Participant recruitment was twofold: in‐person via a non‐governmental Brazilian organization to assist children with disabilities and remotely through social networks. The principles of inductive content analysis guided this analysis. The study analysed 11 interviews with fathers of autistic children, revealing two main themes, each comprising subthemes: (1) between traits and embraces: understanding autism and building support networks and (2) paternal experiences in caring for autistic children and their confrontations in building a future. The fathers' active participation in his autistic child's daily life was crucial in promoting communication, mitigating challenging behaviours and encouraging social interaction, laying a foundation for future studies in this area.
Localized Foot Amyloidosis From Monoclonal B Cell Lymphoma
Authors: McIntyre Emma R. , Sharma Jasdeep K.
Published: February 2025

Localized cutaneous amyloidosis is a rare dermatologic finding necessitating extensive diagnostic workup to include serum protein electrophoresis, fat pad biopsy, and imaging to rule out underlying hematologic disease or systemic involvement. Herein we detail a case of AL amyloidoma in a 73‐year‐old male that presented as chronic violaceous patches of the bilateral feet. Punch biopsy of these lesions revealed congo red‐positive amyloid deposits, and further testing revealed an underlying monoclonal B cell lymphocytosis that remained stable at 6 months follow up. This case highlights the importance of distinguishing localized amyloidoma from systemic disease and other hematological malignancies.
The Bridge: Supernatant Derived From Cytological Sample Preparations
Authors: Roy‐Chowdhuri Sinchita
Published: February 2025

The scope and extent of molecular cytopathology in the era of precision medicine has been expanding in recent years. The versatility of cytology specimen preparations has provided ample opportunity for the cytopathology community to evolve, innovate and ‘do more with less’ using limited amounts of tissue. More recently, cytology‐derived supernatant liquid biopsy samples have been identified as a substantial source of high‐quality genomic material that can be interrogated for genotyping for therapeutic decision‐making, as well as other roles in cancer screening for early‐stage disease, longitudinal monitoring for therapeutic response and disease prognostication. These novel substrates, including supernatants from body fluids such as urine, pleural effusion, ascitic fluid, cerebrospinal fluid, as well as fine‐needle aspiration (FNA) specimens, serve as a bridge between tissue‐based testing and conventional liquid biopsy testing from the patient's plasma. Cytologically derived liquid biopsy samples can only be used in situations where the tissue sample is inadequate for genotyping, or when plasma‐based liquid biopsy fails to identify an oncogenic driver alteration, but they can be used as a stand‐alone complementary specimen source that can provide reliable genomic information for therapeutic decisions. This review aims to highlight some of the advances in the field and the clinical applications of the cytology‐derived supernatant specimen.
Chromosomal localization of PHOX2B during M‐phase is disrupted in disease‐associated mutants
Authors: Sato Yuki , Hayashi Shinichi , Oe Souichi , Koike Taro , Nakano Yousuke , Seki‐Omura Ryohei , Iwashita Hikaru , Hirahara Yukie , Kitada Masaaki
Published: February 2025

In the M‐phase, the nuclear membrane is broken down, nucleosomes are condensed as mitotic chromosomes, and transcription factors are generally known to be dislocated from their recognition sequences and dispersed to the cytoplasm. However, some transcription factors have recently been reported to remain on mitotic chromosomes and facilitate the rapid re‐activation of the target genes in early G1‐phase. Paired‐like homeobox 2B (PHOX2B) is a transcription factor exhibiting chromosomal localization during M‐phase. PHOX2B mutations are associated with congenital central hypoventilation syndrome, Hirschsprung disease, and neuroblastoma. In this study, we investigated PHOX2B chromosomal localization during M‐phase through immunostaining and fluorescence recovery after photobleaching analysis to determine whether the chromosomal localization of disease‐associated PHOX2B mutants is altered during M‐phase. Missense mutations in the homeodomain and the frameshift mutation in the C‐terminal domain disrupted the chromosomal localization of PHOX2B in M‐phase, leading to its dispersion in the cell. Furthermore, a PHOX2B mutant with polyalanine expansion showed a line‐shaped localization to the restricted region of mitotic chromosomes. Our findings suggest an association between the disease‐associated mutations and defective chromosomal localization of transcription factors during M‐phase. Further investigations of PHOX2B chromosomal localization during M‐phase could reveal pathogenic mechanisms of such diseases.
Guidelines for the management of diabetes‐related ketoacidosis (DKA) have been poorly adopted and implemented, resulting in a lack of improvement in outcomes
Authors: Sharma Angelica , Rengarajan Lakshmi , Narendran Parth , Dhatariya Ketan , Kempegowda Punith ,   DEKODE Working Group
Published: February 2025

Aims

The Joint British Diabetes Society‐Inpatient (JBDS‐IP) group recommends reducing fixed rate intravenous insulin infusion (FRIII) from 0.1 to 0.05 units/kg/h when blood glucose falls <14 mmol/L to reduce the risk of complications associated with acute management of diabetes‐related ketoacidosis. However, whether this change results in real‐world improvements is not known.

Methods

We performed a retrospective review of DKA admissions between October 2021 and March 2023 across five hospitals in the United Kingdom. We collated data on demographics, biochemical profiles, management interventions, complications, and outcomes.

Results

We identified 753 DKA admissions. There was a slow uptake of reduced‐rate FRIII, reaching 49.7% over 18 months. In DKA episodes where FRIII rate reduction guidelines were adopted, there was a significant lag (median [IQR] hours) between starting 10% Dextrose and FRIII rate reduction when blood glucose became <14 mmol/L (0.5 (0.1–1.8) vs. 3.2 (0.7–6.5), p = 0.00001). There was no significant reduction in hypoglycaemia (16.5% vs. 13.8%, p = 0.344) in episodes that adopted FRIII reduction. There were no significant differences in the frequency of hypokalaemia, hyperkalaemia, DKA duration, and length of stay between episodes with FRIII rate reduction versus those without FRIII.

Conclusions

Our study demonstrates suboptimal adoption of guidelines. Therefore, it was perhaps unsurprising that no favourable effect on the rate of complications or outcomes in DKA episodes with reduced‐rate FRIII was demonstrated. In DKA episodes where FRIII rate reduction was adopted, there was a significant delay in adjusting the FRIII when glucose levels were <14 mmol/L. Understanding the barriers and facilitators is vital in creating resources to safely implement guidelines.
Norwegian lemmings, Lemmus lemmus: a case for a strong herbivore–plant interaction
Authors: Oksanen Lauri , Vuorinen Katariina E. M. , Kyrö Kukka , Mäkynen Aurelia , Olofsson Johan , Ruffino Lise , Tuomi Maria , Oksanen Tarja
Published: February 2025

In his classical contributions, Olavi Kalela proposed that, due to the low primary productivity of the tundra, Norwegian lemmings are locked in a strong interaction with their winter forage plants. Proposedly, Norwegian lemmings respond to the threat of critical resource depletion by conducting long‐range migrations at their population peaks. A tacit premise of this conjecture is that predation pressure on the Fennoscandian tundra is too weak to prevent runaway increases of lemming populations, creating violent boom–crash dynamics. Our results on the dynamics of Norwegian lemmings on the Finnmarksvidda tundra during 1977–2017 are in line with the predictions of Kalela's hypothesis. In contrast to the Siberian and North American tundra, densities of avian predators in our study area have been low even during lemming years, and efficient ones have been lacking from lemming habitats. Lemmings have thus increased unhinged in peak summers and crashed to densities below the trappability threshold during post‐peak winters. Each lemming crash has been accompanied by massive habitat destruction. Indications of predator activity have been concentrated to productive shrublands, where lemmings have never reached high densities. Young lemmings have responded to high densities by becoming extremely mobile: they have been trapped in large numbers on islands, including a small island in the middle of Iešjávri, a 10 × 8 km tundra lake. Many lemmings have been seen swimming across the lake, and many drowned lemmings have been observed. The dynamics and behavior of Norwegian lemmings recorded by us differ radically from those of other Lemmus spp., indicating that cycles generated by lemming–vegetation interactions have two alternative states – one with and the other without intense summer predation. We propose that the cycles of Norwegian lemmings shifted to the latter state during their unique evolutionary history, when they survived the Last Glacial Maximum in a tiny refugium archipelago.
‘Euclimatch': an R package for climate matching with Euclidean distance metrics
Authors: Hubbard Justin A. G. , Andrew R. Drake D. , Mandrak Nicholas E.
Published: February 2025

Climate matching, a tool for predicting non‐native species survival in target (recipient) regions, is commonly used in invasive species frameworks such as horizon scanning and screening‐level risk assessment protocols. Screening‐level risk assessments often require the analysis of many species with limited resources, and climate matching can be advantageous to identify a reduced number of species for more detailed analyses. Additionally, risk screening may require examination of non‐native species' source pools where species occurrence records are not used in model training data. In these instances, climate matching is an effective method for assessing the survival of non‐native species or their source pools in a target region and has practical advantages over species distribution models. We introduce the R package ‘Euclimatch' for quantitative climate matching with the Euclidean distance algorithm Climatch. The package provides tools for creating a streamlined data‐agnostic climate‐matching workflow. First, climate data are extracted for species occurrence records or regions. Second, climate match is modelled between two regions as a similarity score per grid cell or summarized across a target region. Third, visualizations of the climate match model outputs are created. We demonstrate the use of the ‘Euclimatch' package with the climate match of two popular aquarium trade species and a region‐to‐region analysis. We also demonstrate differences in results between Euclidean distance metric standardization methods when incorporating climate‐change projections. The scale of each example is global, under historical and projected climates. ‘Euclimatch' provides a scripting interface for Euclidean climate matching for the screening assessment of non‐native species or regions under any climatic conditions. ‘Euclimatch' can be downloaded from the comprehensive R archive network (CRAN).
An Unintended Consequence? The Impact of Higher Education Expansion on the Retake Rate of the College Entrance Examination
Authors: Guo Yanbin
Published: February 2025

High participation systems (HPS) of higher education (HE) are common throughout the world. The consequences of HE expansion has attracted enough academic attention; however, much less discussed is the impact of the HE expansion on retaking the college entrance examination. Drawing upon China's provincial panel data, a battery of econometric methods, and the effectively maintained inequality theory, this paper explores whether and how HE expansion influences the retake rate of college entrance examinations. Estimation results suggest that HE expansion leads to an increase in retake rates. For every unit increase in HE expansion intensity, the retake rate increases by 0.014 percentage points. This is an unintended impact of HE expansion on retake rates in the context of increased access to HE worldwide and an overall decline in retake rates worldwide. Above findings still hold after an array of robustness checks. This positive relationship is more prominent in provinces with more key higher education institutions (HEIs) than in provinces without key HEIs. This implies the diploma devaluation of ordinary HEIs might be one of the reasons for the increase in retake rates due to HE expansion. The findings of this paper will be informative for economies that have experienced HE expansion.
Regional Disparities in Literacy and Numeracy Skills Among Romanian Adults: Evidence From e‐PASS 2023
Authors: Stancea Andreea , Corbu Nicoleta , Buzoianu Corina
Published: February 2025

This article investigates regional disparities in Romanian adults' numeracy and literacy skills. We analyse a novel data set that combines the assessment of numeracy and literacy competencies of the adult population in Romania with information about regional economic conditions and educational administrative data. Using a background questionnaire and a cognitive test following e‐PASS methodology and tools (everyday‐life Practices and Skills Survey), the study is one of the first to assess the key skills of the Romanian adult population. The e‐PASS survey is based on the Literacy Assessment and Monitoring Programme (LAMP), developed by the UNESCO Institute for Statistics (UIS), and corresponds to PIAAC levels 1 and below 1. The findings indicate that individuals performing better at literacy and numeracy assessments have higher levels of education, are part of younger generations, and live in urban areas and economically developed Romania's regions. The results of this study provide a detailed picture of the current situation and can serve as a benchmark against which to compare current results in the region or future longitudinal findings.
Fake reviews in the ‘here and now’: Psychological distance and falsified online reviews
Authors: Harris Lloyd C. , Istanbulluoglu Doga
Published: February 2025

There is a growing popularity of consumer reviews on online platforms that is attached to an increase in the pervasiveness of falsified online reviews. The key aim of this study is to provide insights into how falsified online reviews are created by exploring the perceptions of the psychological distance of the creators of falsified reviews. We conducted 48 in‐depth interviews with online reviewers who were actively engaged in reviewing food and beverage serving outlets. We investigated four dimensions of psychological distance (spatial, temporal, social, and hypothetical) and how they are linked to the valence of the review. Our findings illustrate that the way online reviewers cognitively process the psychological distance between themselves and the target of their review shapes how falsified online reviews are created. We also provide an inventory of propositions regarding how individuals' psychological distance from their subject relates to the valance of falsified online reviews. We conclude with a discussion of contributions and implications.
Diffusion‐Weighted Magnetic Resonance Imaging: A Diagnostic Tool for Auditory (Axonal) Neuropathy
Authors: Zanin Julien , Rance Gary
Published: February 2025

Background

Axonal neuropathies are disorders that impair neural transmission, leading to substantial sensory deficits. In the auditory system, axonal degeneration can disrupt auditory processing, causing significant hearing difficulties. Understanding the extent of axonal degeneration and its impact on auditory function is crucial for improving diagnosis and management. This study aims to quantify axonal degeneration in the VIIIth nerve using diffusion‐weighted MRI and to correlate these findings with auditory function.

Methods

Fifty‐two children and adults participated. A total of, 27 with normal hearing, 7 with cochlear hearing loss and 18 with auditory neuropathy (AN). Hearing thresholds and dMRI data was collected for all participants and the VIIIth nerve was evaluated using the fixel‐based analysis metric of Apparent Fibre Density (AFD).

Results

AFD was significantly lower in participants with AN compared to participants with normal hearing and cochlear hearing loss (p < 0.05). 9/18 participants with AN exhibited AFD values ≥ 2 standard deviations below the normal range. Additionally, AFD was strongly correlated with hearing thresholds in participants with no evidence of cochlear dysfunction (r = −0.776, p < 0.001), suggesting reduced auditory nerve fibre density is associated with impaired sound detection.

Conclusions

dMRI‐derived AFD is a sensitive marker for axonal degeneration in the VIIIth nerve. This study provides the first in vivo evidence linking VIIIth nerve microstructure with hearing thresholds, highlighting the potential of dMRI in diagnosing and monitoring AN. The findings suggest that dMRI could be a valuable tool in clinical settings for assessing auditory nerve health and guiding treatment strategies for individuals with AN.
SCN1A pathogenic variants do not have a distinctive blood‐derived DNA methylation signature
Authors: LaFlamme Christy W. , Karimi Karim , Rastin Cassandra , Almanza Fuerte Edith P. , Allan Talia , Russ‐Hall Sophie J. , Schneider Amy L. , Stobo Daniel , Lesca Gaetan , Symonds Joseph D. , Brunklaus Andreas , Sadleir Lynette G. , Scheffer Ingrid E. , Sadikovic Bekim , Mefford Heather C.
Published: February 2025

DNA methylation signatures (“episignatures”) can be used as biomarkers of genetic aberrations, clinical phenotypes, and environmental exposures in rare diseases. Episignatures are utilized in molecular diagnostics and can clarify variants of uncertain significance. A growing number of disease genes, including epilepsy genes, exhibit robust and reproducible episignatures. However, whether SCN1A, the most prominent epilepsy gene, has one or more episignatures has not yet been determined. We generated genome‐wide DNA methylation data and performed episignature analysis on 64 individuals with Dravet syndrome due to pathogenic loss‐of‐function (LOF) variants in SCN1A and seven individuals with early infantile SCN1A developmental and epileptic encephalopathy due to pathogenic gain‐of‐function (GOF) variants in SCN1A, relative to a large reference database of controls and rare disease episignature‐positive cohorts. We analyzed all samples with LOF variants together and performed separate analyses for missense, nonsense, and GOF variant cohorts. A reproducible blood‐derived episignature was not evident in any of the cohorts using current analytical approaches and reference data.
α‐Ketoglutarate inhibits the pluripotent‐to‐totipotent state transition in stem cells
Authors: Yin Mengran , Li Yan , Sun Zhenzhu , Wu Xinyu , Ding Liang , Zhang Qiang , Zhou Hai , Zhang Man , Qin Dajiang , Qin Baoming , Wang Lulu
Published: February 2025

In early mouse embryogenesis, the distinct enrichment of α‐ketoglutarate (αKG) in blastocysts and L‐2‐hydroxyglutarate (L‐2HG) in 2‐cell (2C) embryos serves as a key metabolic signature. While elevated L‐2HG levels inhibit the resolution of totipotency during the transition from the 2C stage to the blastocyst, the role of αKG remains elusive. Mouse embryonic stem cells (mESCs) cultured in vitro naturally harbor a subpopulation that transitions dynamically into a 2C‐like totipotent state, providing a convenient model to investigate the role of αKG in totipotency reprogramming. This study demonstrates that αKG significantly inhibits the pluripotency to totipotency transition through upregulating ten‐eleven translocation (TET) DNA hydroxylases. We further show that reducing endogenous αKG levels via glutamine withdrawal or inhibiting αKG‐dependent dioxygenases by blocking succinate dehydrogenase (SDH) markedly enhances the induction of 2C‐like cells (2CLCs). Finally, leveraging the potent SDH inhibitor dimethyl malonate (DMM), we have developed a highly efficient protocol for 2CLC induction, producing cells that transcriptionally resemble mid‐to‐late 2C embryos. Our findings deepen the understanding of the metabolic regulation of totipotency and provide a previously undescribed approach for capturing totipotent‐like stem cells in vitro.
Redox imbalance and hypoxia‐inducible factors: a multifaceted crosstalk
Authors: Ravi  , Singh Jogender
Published: February 2025

Redox homeostasis, the delicate balance between oxidative and reductive processes, is crucial for cellular function and overall organismal health. At the molecular level, cells need to maintain a fine balance between the levels of reactive oxygen species (ROS) and reducing equivalents such as glutathione and nicotinamide adenine dinucleotide phosphate. The perturbation of redox homeostasis due to excessive ROS production leads to oxidative stress that can damage lipids, proteins, and nucleic acids. Conversely, an overly reduced cellular environment due to overabundant reducing equivalents results in reductive stress, which also interferes with important cellular signaling and physiological processes. Disrupted redox homeostasis is linked to various pathological conditions, including neurodegenerative diseases, inflammatory diseases, cancer, and cardiovascular diseases. Cells employ diverse mechanisms to manage redox imbalance. The hypoxia response pathway, mediated by hypoxia‐inducible factors and responsible for sensing and defending against low oxygen levels, plays a vital role in maintaining redox homeostasis. In this review, we highlight the complex and multifaceted crosstalk between hypoxia‐inducible factors and redox homeostasis and discuss avenues for future research. Understanding the molecular mechanisms that link hypoxia‐inducible factors to oxidative and reductive stresses is essential for comprehending several pathological conditions associated with hypoxia and redox imbalance.
Post‐colonoscopy colorectal cancer in the Western Australian population: analysis of patient, histopathological and molecular characteristics
Authors: Harma Claire L. , Jayawardena Thisuri , Ismail Ali G. M. , Lall Vidit , Kumarasinghe Priyanthi , De Boer Bastiaan , Hemmings Christine , Amanuel Benhur , Kelty Erin , Mirzai Bob , Guo Belinda B. , Allcock Richard , Salama Muna , Raftopoulos Spiro , Yusoff Ian , Segarajasingam Dev , Erber Wendy N. , Ee Hooi
Published: February 2025

Background

Post‐colonoscopy colorectal cancer (PCCRC), defined as colorectal cancer (CRC) detected after a cancer‐negative colonoscopy, represents a key quality indicator for CRC detection and prevention. While most PCCRC is attributed to missed lesions, few studies examine pathologic and molecular characteristics of PCCRC to assess for possible de novo cancer formation causing PCCRC.

Aim

The aim of this study was to identify cases of PCCRC where prior colonoscopy was adequate (A‐PCCRC) versus inadequate (I‐PCCRC) and compare both subtypes with spontaneous CRC (sCRC) in terms of patient factors, histopathology and molecular characteristics.

Methods

This was a 12‐year retrospective population‐based study using a data set from the Western Australian Cancer Registry between 2000 and 2011. A‐PCCRCs were identified by excluding lesions likely missed due to procedural factors or incomplete prior resection at index colonoscopy performed within 3–36 months of cancer diagnosis. Histopathological review and next‐generation sequencing were conducted on subsets of patients with A‐PCCRC and sCRC. Statistical analysis included univariable and multivariable regression models and chi‐squared and Wilcoxon rank sum tests.

Results

A total of 524 (3.81%) cases of PCCRC were identified out of 13 757 cases of CRC; 272 were A‐PCCRC (1.98%) and 252 I‐PCCRC (1.83%). Female sex, older age and proximal location were associated with A‐PCCRC. Mutations in the PIK3CA gene were less common in A‐PCCRC compared to sCRC.

Conclusion

A significant percentage of PCCRC occurred despite adequate prior colonoscopy. Missed sessile serrated lesions may contribute to many of these cases; however, further studies are required to examine possible de novo cancer as a cause of PCCRC that may involve unique biological pathways.
Quality of Vertical Bitewings Radiographs and Common Errors of Positioning in Children
Authors: Olegário Isabel C. , Leith Rona , O'Connell Anne C.
Published: February 2025

Background

Vertical bitewing radiographs (VBWs) are often used in paediatric dentistry but no clinical studies have been conducted to evaluate the feasibility or effectiveness of their use.

Hypothesis/Aim

To evaluate the quality of VBWs taken in children by undergraduate dental students.

Design

VBWs were taken for high‐caries‐risk children using two types of vertical holders: Snap‐A‐Ray and Red Rinn XCP. Trained and calibrated examiners assessed VBW quality including positioning errors, visibility of crown and furcation area of primary molars and presence of permanent successor. Association between VBW quality scores and independent variables was investigated using ordinal logistic regression (α = 5%).

Results

A total of 150 VBWs were evaluated. Radiographs were rated as excellent (10.67%), diagnostically acceptable (72%) and diagnostically compromised (17.33%). VBWs allowed the visualisation of the entire primary molar crown (80.55%), furcation (90.54%) and permanent successors (86.37%).

Common positioning errors included horizontal errors (48.67%) and coning off (38.67%). Use of the Red Rinn XCP holder was significantly associated with improved VBW quality compared to Snap‐A‐Ray (p = 0.045).

Conclusions

The use of vertical bitewings allowed visualisation of the primary molars crown, furcation area and presence of permanent successors. The use of a Red Rinn vertical holder can improve the quality of the bitewing radiographs by avoiding positioning errors.
Single or dual rollover? The product rollover strategy of an electric vehicle manufacturer with strategic consumers
Authors: Tong Yang , Xiao Tiaojun , Ning Yu , Xu Songhe
Published: February 2025

Although it has been widely acknowledged that the positive effect of consumer subsidy on the development of the electric vehicle industry, its effect on product rollover strategy remains unknown. To address this issue, a two‐period model is conducted to determine the manufacturer's product rollover strategy choice between a single rollover (in which companies cease the production of the old version when launching a new upgraded version of a product) and a dual rollover (in which companies continue offering it at a discounted price), considering the consumer subsidy scheme and consumers’ strategic behavior. Our results show that in the low‐level innovation case, the manufacturer will benefit more from the single rollover strategy if the subsidy level of the old version is large but the subsidy level of the new version is small; when the old version's subsidy is small or the subsidy levels of the two versions are large, the manufacturer benefits more from the dual rollover strategy. In the high‐level innovation case, the manufacturer prefers the single rollover strategy if and only if the subsidy levels of the two versions are relatively large. Although the manufacturer can benefit from the single rollover strategy through consumer subsidy, it may increase the negative environmental impact and further, decrease social welfare. In addition, compared with the monopolistic setting, we find that the manufacturer becomes more willing to implement a single rollover in the competitive setting. Finally, the manufacturer is more likely to implement the single rollover strategy when more consumers are strategic.
Understanding interfacial bonding properties and mechanical properties of in situ synthesis of Cf/ZrB2–ZrC–SiC composite
Authors: Liu Yingjun , Fu Yuanzhe , Zu Yufei , Zhang Yang , Dong Hongfeng , Li Wenhu , Ai Taotao , Sha Jianjun
Published: February 2025

The relationship between the interfacial bonding properties and the mechanical properties of carbon fiber reinforced ZrB2–ZrC–SiC composites (Cf/ZrB2–ZrC–SiC) is currently under investigation. In this study, Cf/ZrB2–ZrC–SiC composites with varying fiber–matrix interfacial bonding properties were prepared using slurry infiltration and in‐situ reactive hot pressing. Polydopamine‐derived carbon with different thicknesses was employed as the interphase to create various interfacial bonding properties, where interfacial bonding properties were evaluated using the single‐fiber push‐out method. Results indicated that a uniform and dense ZrB2–ZrC–SiC matrix was constructed, and low‐porosity composites without fiber degradation were obtained. For composites with a higher interfacial shear strength (ISS) of 342 MPa, flexural strength and fracture toughness were 209 MPa and 7.5 MPa·m1/2, respectively. For composites with a lower ISS of 64 MPa, flexural strength and fracture toughness increased by 41% and 13%, with showing non‐brittle behavior and work of fracture up to 10 kJ·m2. By combining analyses of thermal expansion behavior, residual thermal stresses, and thermal shock properties at ultrahigh temperatures, thermal mismatch and thermal damage can be minimized through the modulation of ISS. This approach is beneficial for optimizing the mechanical properties of fiber‐reinforced ceramic composites.
Co‐Designing a Toolkit of Approaches and Resources for End‐of‐Life Care Planning With People With Intellectual Disabilities Within Adult Social Care Settings: A Multi‐Phase Study
Authors: Tuffrey‐Wijne Irene , Bruun Andrea , Tilley Elizabeth , Giles Jo , Gibson Sarah , Cresswell Amanda , Keagan‐Bull Richard , Jordan Leon , Allen Gemma , Swindells Sarah , Payne Nicola , Hughes Rhidian , Anderson‐Kittow Rebecca
Published: February 2025

Background

People with intellectual disabilities are rarely involved in end‐of‐life decisions. This study investigated and further developed approaches and resources to enable inclusive end‐of‐life care planning.

Methods

A multi‐centre, multi‐method four‐phase study, involving 195 researchers, participants, advisors and co‐design members, including 36 people with intellectual disabilities: (i) evidence review; (ii) stakeholder focus groups; (iii) Experience‐Based Co‐Design and (iv) testing of co‐designed resources.

Results

There was little empirical evidence regarding the efficacy of existing resources. Focus group participants signalled overwhelming support for inclusive end‐of‐life care planning but notable variance around where/what/when/who/how. The co‐design group developed a toolkit of existing and new resources. Feedback from toolkit testers was positive but barriers to staff engagement through the testing period were noted.

Conclusions

Flexible, creative and interactive approaches that open up conversations are the building blocks for inclusive end‐of‐life care planning. Barriers include lack of staff confidence, time and resources and a death avoidance culture.
Catheter Ablation for Atrial Fibrillation in Octogenarians—Outcome and Impact for Future Same Day Discharge Strategies
Authors: Wahedi Rahin , Willems Stephan , Jularic Mario , Hartmann Jens , Anwar Omar , Dickow Jannis , Harloff Tim , Bengel Philipp , Wohlmuth Peter , Metzner Andreas , Gessler Nele , Gunawardene Melanie A.
Published: February 2025

Background

Catheter ablation (CA) for atrial fibrillation (AF) in the elderly poses a growing challenge. Outcome data regarding CA in these patients are scarce.

Methods

Octogenarians with AF or consecutive atrial tachycardia undergoing index or re‐ablation (pulmonary vein isolation [PVI] and ablation beyond PVI with different energy sources) in a single center, were analyzed. Study endpoints were efficacy as well as procedural safety. Secondary endpoints included periprocedural complications and predictors for prolonged hospital stay.

Results

In total, 301 patients (82.1 ± 1.9 years, paroxysmal AF n = 94 [31.2%], CHA2DS2‐VASc‐Score 4.2 ± 1.2) undergoing index ablation (n = 172/301, 57.1% [PVI only n = 156/172, radiofrequency n = 92, cryoballoon n = 59, pulsed‐field ablation n = 5]) and re‐ablation (n = 129/301 [42.9%]) were included. Arrhythmia‐free survival at 1 year was 72.6%. Complication rates were low (groin site n = 2/301 [0.7%], tamponade n = 2/301 [0.7%] and stroke n = 1/301 [0.3%]). However concomitant infections (pneumonia n = 5/301 [1.7%], urinary‐tract‐infections n = 4/301, [1.3%]) and pacemaker‐implantation n = 6/301 (2%) occurred more commonly. Hospital stay after CA was 2.3 ± 2 nights. Predictors for prolonged hospitalization were complications (odds ratio: 3.1), infections (odds ratio: 2.1), female sex (odds ratio: 1.15) and frailty assessed by Barthel index (odds ratio: 1.02).

Conclusions

CA for AF in octogenarians shows low procedural complications and reasonable efficacy. However, concomitant infections and pacemaker implantations occur in this cohort. Due to prolonged hospitalization after CA, especially in female and frail octogenarians, same‐day discharge may not be suitable for this specific patient cohort.
Rehabilitation Strategies and Occlusal Vertical Dimension Considerations in the Management of Worn Dentitions: Consensus Statement From SSRD, SEPES, and PROSEC Conference on Minimally Invasive Restorations
Authors: Ioannidis Alexis , Pitta João , Panadero Rubén Agustín , Chantler Jennifer G. M. , Villar Sandra Fernández , Fonseca Manrique , Lozano Jaime Gil , Hämmerle Christoph H. F. , Hey Jeremias , Karasan Duygu , Kraljevic Iris , Mainjot Amélie , Pachiou Aspasia , Rutten Patrick , von Stein‐Lausnitz Manja , Strasding Malin , Zaugg Lucia K.
Published: February 2025

Objective

The Joint SSRD, SEPES, and PROSEC Consensus Conference aimed to provide clinical statements and recommendations for the rehabilitation of worn dentition and to evaluate the necessity of an evaluation phase when increasing the occlusal vertical dimension (OVD) during full‐mouth rehabilitation.

Materials and Methods

Two systematic reviews were conducted before the conference. The findings of the reviews were analyzed, discussed in working group 2, and debated in plenary sessions until a consensus was reached. Consensus statements were formulated based on available evidence and expert opinion.

Results

Both direct and indirect minimally invasive approaches, utilizing materials such as composite resins and lithium disilicate ceramics, were deemed viable for managing worn dentitions. The choice of approach and material should depend on the extent of tooth substance loss and the treatment goals. Evidence on the necessity of an evaluation phase was inconclusive. However, an evaluation phase can aid in managing patient expectations, refining treatment sequencing, and supporting less experienced clinicians. Emphasis was placed on non‐invasive and minimally invasive techniques, adequate diagnostics, and the potential benefits of fixed interim restorations when evaluating increased OVD.

Conclusions

The consensus statements provide a framework for managing worn dentitions and decisions regarding OVD increases, emphasizing minimally invasive approaches and individualized treatment planning. However, gaps in evidence remain, particularly regarding the long‐term effectiveness of materials and the evaluation phase. Future research is required to address these uncertainties, focusing on long‐term outcomes, material comparisons, and patient‐reported outcomes.
Proprioceptive Training Induced Adaptations of Static Balance Control: An RCT Study in Adults With Intellectual Disability
Authors: Rallis Konstantinos , Konstantinidou Elisavet , Hatzitaki Vassilia , Mavrommatis Georgios , Fotiadou Eleni
Published: February 2025

Background

Adults with intellectual disability (ID) experience injurious falls that may affect their quality of life. The present randomised control trial (RCT) study examined the efficacy of a 10‐week proprioceptive training programme, on static balance performance, in adults with mild to moderate ID.

Methods

Participants were voluntarily recruited from a day care centre and randomly assigned into the intervention (IG; n = 14; 36.4 ± 3.8 years; males/females = 8/6) and the control group (CG; n = 13; 37.6 ± 4.8 years; males/females = 7/6). The IG trained three times per week with the proprioceptive training programme, whereas both groups followed the regular adapted physical activity programme of the day care centre. Static balance was assessed before and after the intervention with three static balance tests [bipedal stance (60″), Tandem Romberg stance (30″) and single leg stance (15″)] performed on a force platform, whereas the Mini‐BESTest was also used to assess aspects of static and dynamic balance in the field.

Results

The IG significantly improved (p < 0.05) test scores of the Mini‐BESTest and decreased the range and the root mean square of the centre of pressure displacement during the bipedal, Tandem Romberg and single leg stance, in contrast to the CG who showed no improvement.

Conclusion

The specific proprioceptive training programme improved the static balance of adults with ID and this could have a positive, significant impact in their daily life, as it may reduce the incidence of falls and relative injuries.
Examining the Relation Between Sleep Problems and Behavioural Challenges in Youth With Down Syndrome
Authors: Soltani Amanallah , Wiley Susan , Williams‐Arya Pamela , Hoffman Emily K. , Esbensen Anna J.
Published: February 2025

Background

The connection between sleep problems and behavioural challenges in individuals with Down syndrome (DS) has been a central focus of research across different age groups. However, uncertainty remains regarding this association, particularly when relying solely on daily‐based assessments. This study aimed to examine the relationship between sleep problems and behavioural challenges at both overall (macro) and daily (micro) levels among youth with DS.

Methods

Sleep disturbances were measured in a sample of 65 youth with DS aged 6–17 years using the Children's Sleep Habits Questionnaire (CSHQ) and actigraph watches assessing sleep efficiency, sleep duration and wake after sleep onset. Behavioural challenges were evaluated through externalising and internalising subscales of the Child Behavior Checklist (CBCL) and of the Scales of Independent Behavior, Revised (SIB‐R).

Results

The findings demonstrated that over a period of time, sleep problems are significantly associated with both externalising and internalising behaviours as measured by CSHQ and CBCL, even after accounting for the effects of IQ and SIB‐R Broad Independence. No significant correlations were observed on a daily basis over seven consecutive days, as measured by actigraphy and both externalising and internalising indices of SIB‐R.

Conclusions

The results highlight the complexity of the sleep–behaviour relationship in DS, indicating that while chronic sleep issues impact long‐term behaviours, nightly variations do not predict immediate behavioural changes.
Eye Tracking as a Tool for Detecting Alzheimer's Disease in People With Down Syndrome
Authors: Piro‐Gambetti Brianna , Krinsky‐McHale Sharon , Kovacs Cynthia , Handen Benjamin , Christian Bradley , Laymon Charles M. , Minhas Davneet , Luo Weiquan , Yoon Dasoo Milton , Fleming Victoria L. , Schworer Emily , Kirkorian Heather , Hartley Sigan L. ,   Alzheimer Biomarkers Consortium‐Down Syndrome
Published: February 2025

Background

Adults with Down syndrome (DS) experience an increased risk of Alzheimer's disease (AD). Valid cognitive assessments for adults with DS with severe/profound intellectual disability (ID) are needed. It is unclear whether eye tracking is feasible for detecting AD in DS.

Method

Fifty‐three adults with DS completed a visual paired comparison (VPC) task, a battery of cognitive measures, and underwent PET scanning. Study partners reported on the participant's dementia symptoms. Bivariate correlations assessed associations between eye‐tracking metrics and AD‐related pathology and symptomatology. Analyses included the full sample (n = 53) and a subgroup with an IQ ≤ 45 (n = 33).

Results

Greater fixation duration during the habituation phase was associated with better cognitive performance on the Modified Cued Recall Test (mCRT) (intrusions: r = −0.39, p = 0.011) and less PET tau (r = −0.47, p = 0.014). Larger saccadic amplitudes during the test phase were associated with younger age (r = −0.45, p < 0.001), better cognitive performance on the mCRT (total: r = 0.31, p = 0.041; intrusions: r = −0.33, p = 0.032) and less PET Aβ (r = −0.40, p = 0.025). Greater preference to fixate on the novel image was associated with fewer dementia symptoms (count: r = −0.44, p = 0.002; duration: r = −0.38, p = 0.009). This pattern of significance remained for the subgroup with lower IQ scores.

Conclusion

The VPC task is a potentially useful method for assessing AD‐related cognitive impairments in adults with DS across varying ID levels.