bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment trajectories for Danish individuals with type 2 diabetes in the era of emerging glucose‐lowering therapies
Authors: Pottegård Anton , Andersen Jacob H. , Søndergaard Jens , Rasmussen Lotte , Kildegaard Helene , Vilsbøll Tina , Thomsen Reimar W.
Published: September 2024

Aim

To analyse patterns of glucose‐lowering therapies among people with type 2 diabetes (T2D) in Denmark from 2016 to 2023.

Materials and Methods

We examined time trends in the clinical profiles of people with T2D who initiated different glucose‐lowering therapy classes for the first time. We furthermore investigated individual‐level treatment trajectories following first‐ever glucose‐lowering therapy in people with or without cardiorenal disease. The study utilized data from the nationwide Danish health registries and included all individuals who filled a first‐ever prescription for metformin, dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is) or insulin, excluding those without HbA1c‐confirmed T2D or probable type 1 diabetes.

Results

We included 260 393 individuals initiating a new glucose‐lowering therapy class from 2016 to 2023, during which there were 6‐ and 3‐fold increases in initiators of GLP‐1RAs and SGLT‐2is, respectively. The median HbA1c level at treatment initiation with GLP‐1RAs or SGLT‐2is decreased, from 67‐68 mmol/mol in 2016‐2017 to 57‐58 mmol/mol in 2022‐2023. Among individuals who initiated metformin as first‐line therapy, the proportion who started additional glucose‐lowering therapy within 2 years increased from 25% in 2016 to 40% in 2021. Among the 38% of individuals who had established cardiorenal disease when they initiated first‐ever glucose‐lowering therapy in 2020, 22% used SGLT‐2is and 18% GLP‐1RAs after 2.5 years, compared with 17% and 21% among initiators without cardiorenal disease, respectively.

Conclusions

Our study documents a trend towards earlier T2D treatment intensification and an increase in the use of GLP‐1RAs and SGLT‐2is in Denmark. However, optimal T2D treatment is still not received by most individuals with early T2D and established cardiorenal disease.
Associations between cuprotosis‐related genes and the spectrum of metabolic dysfunction‐associated fatty liver disease: An exploratory study
Authors: Yuan Hai‐Yang , Liu Wen‐Yue , Feng Gong , Chen Sui‐Dan , Jin Xin‐Zhe , Chen Li‐Li , Song Zi‐Jun , Li Ke , Byrne Christopher D. , Targher Giovanni , Tian Na , Li Gang , Zhang Xin‐Lei , George Jacob , Zhou Meng , Wang Fudi , Zheng Ming‐Hua
Published: September 2024

Aims

To explore the associations between cuprotosis‐related genes (CRGs) across different stages of liver disease in metabolic dysfunction‐associated fatty liver disease (MAFLD), including hepatocellular carcinoma (HCC).

Materials and Methods

We analysed several bulk RNA sequencing datasets from patients with MAFLD (n = 331) and MAFLD‐related HCC (n = 271) and two MAFLD single‐cell RNA sequencing datasets. To investigate the associations between CRGs and MAFLD, we performed differential correlation, logistic regression and functional enrichment analyses. We also validated the findings in an independent Wenzhou PERSONS cohort of MAFLD patients (n = 656) used for a genome‐wide association study (GWAS).

Results

GLS, GCSH and ATP7B genes showed significant differences across the MAFLD spectrum and were significantly associated with liver fibrosis stages. GLS was closely associated with fibrosis stages in patients with MAFLD and those with MAFLD‐related HCC. GLS is predominantly expressed in monocytes and T cells in MAFLD. During the progression of metabolic dysfunction‐associated fatty liver to metabolic‐associated steatohepatitis, GLS expression in T cells decreased. GWAS revealed that multiple single nucleotide polymorphisms in GLS were associated with clinical indicators of MAFLD.

Conclusions

GLS may contribute to liver inflammation and fibrosis in MAFLD mainly through cuprotosis and T‐cell activation, promoting the progression of MAFLD to HCC. These findings suggest that cuprotosis may play a role in MAFLD progression, potentially providing new insights into MAFLD pathogenesis.
Debating the Yemen conflict: Toward a synthesis of debates and diverse perspectives on causes and actors
Authors: Tsalikis Antonios , Pedi Revecca
Published: September 2024

During the last decade, a significant amount of academic research focusing on the causes of, and the actors involved in the Yemen conflict has been published in peer‐reviewed journals, edited volumes, and books. Yet this research has emerged in a fragmented way that renders a comprehensive understanding of the conflict a challenging enterprise. Through our systematic review of peer‐reviewed academic articles and meta‐analysis of their findings, we identified and analyzed three main debates about the Yemen conflict. We conclude that each of these discussions contributes valuable insights but alone cannot fully explain the complex reasons behind the Yemen conflict. Instead, they offer individual pieces of the puzzle. We argue that a comprehensive understanding of the conflict necessitates considering and synthesizing all three debates.
Cross‐validation matters in species distribution models: a case study with goatfish species
Authors: Huang Hongwei , Zhang Zhixin , Bede-Fazekas Ákos , Mammola Stefano , Gu Jiqi , Zhou Jinxin , Qu Junmei , Lin Qiang
Published: September 2024

In an era of ongoing biodiversity, it is critical to map biodiversity patterns in space and time for better‐informing conservation and management. Species distribution models (SDMs) are widely applied in various types of such biodiversity assessments. Cross‐validation represents a prevalent approach to assess the discrimination capacity of a target SDM algorithm and determine its optimal parameters. Several alternative cross‐validation methods exist; however, the influence of choosing a specific cross‐validation method on SDM performance and predictions remains unresolved. Here, we tested the performance of random versus spatial cross‐validation methods for SDM using goatfishes (Actinopteri: Syngnathiformes: Mullidae) as a case study, which are recognized as indicator species for coastal waters. Our results showed that the random versus spatial cross‐validation methods resulted in different optimal model parameterizations in 57 out of 60 modeled species. Significant difference existed in predictive performance between the random and spatial cross‐validation methods, and the two cross‐validation methods yielded different projected present‐day spatial distribution and future projection patterns of goatfishes under climate change exposure. Despite the disparity in species distributions, both approaches consistently suggested the Indo‐Australian Archipelago as the hotspot of goatfish species richness and also as the most vulnerable area to climate change. Our findings highlight that the choice of cross‐validation method is an overlooked source of uncertainty in SDM studies. Meanwhile, the consistency in richness predictions highlights the usefulness of SDMs in marine conservation. These findings emphasize that we should pay special attention to the selection of cross‐validation methods in SDM studies.
‘Good Rain Nurtures Things Silently’: A Longitudinal Study of EFL Teacher Emotion and Identity Learning in Curriculum Reform
Authors: Yang Shanshan , Yin Hongbiao
Published: September 2024

Identity serves as a valuable lens through which to investigate, understand and facilitate teacher learning during curriculum reform. Identity learning is the core process of educational change, with teacher emotion at the heart of professional learning processes. In this study, we traced the 1‐year journeys of four Chinese EFL teachers during a tertiary EFL curriculum reform that focused on ideological and political education. The Dynamic Systems Model of Role Identity was utilised to understand identity learning. By drawing on interviews, documents and observations, we collected rich data and analysed four types of identity learning along a continuum from fake learning to transformation, mediated by teacher emotion. A multiplicity of emotions acted as indicators and potential catalysts for identity learning. However, an overly demanding context might lead to a retrogressive identity learning trajectory. The integration of ideological and political education in foreign language education was also discussed.
Exploring the Relationships Among Display Rules, Emotional Job Demands, Emotional Labour and Kindergarten Teachers' Occupational Well‐Being
Authors: Zheng Xin , Fu Jiameng , Peng Jingyi
Published: September 2024

This study investigates the intricate relationships among display rules, emotional job demands (EJD), emotional labour and the occupational well‐being (OWB) of kindergarten teachers in China. Utilising the job demands–resources (JD‐R) model, this study specifically assesses the influence of EJD and displays rules on two dimensions of teachers' OWB (job satisfaction and emotional exhaustion), while exploring the mediating role of emotional labour strategies. Data were collected from a sample of 1220 Chinese kindergarten teachers. By employing structural equation modelling and mediation analysis, the findings reveal that positive display rules can enhance job satisfaction and alleviate emotional exhaustion. Conversely, negative display rules are linked to heightened emotional exhaustion and diminished job satisfaction. The analysis further discerns that two emotional labour strategies significantly mediate these associations. Surface acting exacerbates adverse outcomes, whereas the natural expression of emotions acts as a salient buffer, augmenting job satisfaction and reducing emotional exhaustion. In addition, EJD can positively predict job satisfaction through deep acting. These insights underscore the necessity of cultivating educational environments that advocate for natural emotional expression and reinforce positive display rules, thereby enhancing teachers' OWB. This research offers valuable implications for educational policymakers and practitioners, emphasising the need to address the emotional aspects of teaching in early childhood education.
Health‐Promoting Learning Environments in Higher Education: A Scoping Review of Structural Interventions to Protect Student Mental Health
Authors: Olsson Tina M. , Broberg Malin , Frisk Sylva , Wackenhut Arne F. , Kjellin David , Gullstrand Sofia , Rost Stephanie , Skoog Therése
Published: September 2024

A rapidly growing body of research spanning several scientific disciplines and countries converges to show that mental health problems among students are an increasing challenge for higher education institutions. Mental health problems among students threaten academic performance, degree completion and student well‐being. Structural efforts aimed at building health‐promoting, learning environments for all students are lacking in the literature. This study aims to identify and describe what is currently known about structural approaches to promote mental health or prevent mental health problems among students in higher educational settings. We conducted a scoping review of studies published in peer‐reviewed journals between 2001 and 2021, which studied structural interventions to promote mental health or prevent mental health problems among students in higher educational settings. The search identified 8372 articles, and 27 were included in the final sample. Four broad categories of approach were identified: (1) inclusion and diversity approaches, (2) adaptations to the physical environment, (3) teaching health‐related skills and behaviours and (4) adaptations to pedagogical practices and teaching approaches. The general finding from the studies reporting student perceptions was that students were favourable to the interventions to which they were exposed. Studies investigating pre‐ to post‐test changes in well‐being had mixed findings. Institutions aiming to support student mental health at the structural level should rigorously study and describe these approaches and their outcomes to advance our combined understanding of how we might design and deliver structural interventions to support students' mental health.
Workload and Need for Recovery in the Academy: The Moderating Role of Student Demands and Meaningful Work Perceptions
Authors: Sciotto Giulia , Pace Francesco , Moavero Cristina
Published: September 2024

Research has often focused on which teaching‐related stressors might undermine teachers' effectiveness, with spillover effects on students' performance. This connection makes studies on teacher well‐being crucial, as well as the search for variables that can act as a buffer for unavoidable job stressors. The present study investigates whether the relationship between academic workload and the need for recovery varies based on student demands and meaningful work perceptions. Hence, a moderated moderation model was tested on 236 Italian university teachers. The results show that the effect of academic workload on the need for recovery is higher in conditions of high student demands. Meaningful work plays a protective role, mitigating the effect of academic workload in both high and low student demands conditions. These findings suggest the promotion of protective elements that can trigger a virtuous process such that teachers' well‐being improves effectiveness, which, in turn, improves students' learning experience.
Association of anti‐calcitonin gene‐related peptide with other monoclonal antibodies for different diseases: A multicenter, prospective, cohort study
Authors: Iannone Luigi Francesco , Romozzi Marina , Russo Antonio , Saporito Gennaro , De Santis Federico , Ornello Raffaele , Sances Grazia , Vaghi Gloria , Tassorelli Cristina , Albanese Maria , Guerzoni Simona , Casalena Alfonsina , Vollono Catello , Calabresi Paolo , Prudenzano Maria Pia , Mampreso Edoardo , Volta Giorgio Dalla , Valente Maria Rosaria , Avino Gianluca , Chiarugi Alberto , Sacco Simona , Pistoia Francesca ,   the Italian Headache Registry (RICe) study group
Published: September 2024

Background and purpose

Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene‐related peptide (anti‐CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6‐month effectiveness and tolerability of anti‐CGRP mAbs in combination with other mAbs for different diseases.

Methods

Patients included in the Italian Headache Registry and treated concomitantly with an anti‐CGRP mAb and another mAb were included. Effectiveness outcomes for migraine included reduction from baseline of monthly headache days (MHDs), Migraine Disability Assessment (MIDAS) score, Headache Impact Test‐6 (HIT‐6) scores, and Patients' Global Impression of Change (PGIC) scale. Adverse events (AEs) were recorded.

Results

Thirty‐eight patients were included. In 27 patients (71.1%), the anti‐CGRP mAb was added to a previously ongoing mAb. Nine patients (23.7%) discontinued one of the two mAbs before the end of treatment (seven discontinued the anti‐CGRP mAb and two the other mAb). One patient discontinued for AEs. Anti‐CGRP mAbs were discontinued due to ineffectiveness (n = 5, 55.5%) and one each (11.1%) for clinical remission and lost to follow‐up. MHDs significantly decreased from baseline to 3 months (p < 0.0001) and 6 months (p < 0.001), as did the MIDAS and the HIT‐6 scores at 3 and 6 months (p < 0.001). For anti‐CGRP mAbs, 27.4% of patients reported PGIC ≥ 5 at 3 months and 48.3% at 6 months. Mild AEs associated with introduction of a second mAb were detected in six patients (15.8%).

Conclusions

In this real‐world study, anti‐CGRP mAbs showed safety and effectiveness when administered concomitantly with other mAbs.
“Code Headache”: Development of a protocol for optimizing headache management in the emergency room
Authors: Membrilla Javier A. , Alpuente Alicia , Gómez‐Dabo Laura , Raúl García‐Yu , Mariño Eduardo , Díaz‐de‐Terán Javier , Pozo‐Rosich Patricia
Published: September 2024

Background and Purpose

Patients presenting at the emergency room (ER) with headache often encounter a hostile atmosphere and experience delays in diagnosis and treatment. The aim of this study was to design a protocol for the ER with the goal of optimizing the care of patients with urgent headache to facilitate diagnosis and expedite treatment.

Methods

A narrative literature review was conducted via a MEDLINE search in October 2021. The “Code Headache” protocol was then developed considering the available characteristics and resources of the ER at a tertiary care center within the Spanish National Public Health system.

Results

The Code Headache protocol comprises three assessments: two scales and one checklist. The assessments identify known red flags and stratify patients based on suspected primary/secondary headaches and the need for pain treatment. Initial assessments, performed by the triage nurse, aim to first exclude potentially high morbidity and mortality etiologies (HEAD1 scale) and then expedite appropriate pain management (HEAD2 scale) based on scoring criteria. HEAD1 evaluates vital signs and symptoms of secondary serious headache disorders that can most benefit from earlier identification and treatment, while HEAD2 assesses symptoms indicative of status migrainosus, pain intensity, and vital signs. Subsequently, ER physicians employ a third assessment that reviews red flags for secondary headaches (grouped under the acronym ‘PEACE’) to guide the selection of complementary tests and aid diagnosis.

Conclusions

The Code Headache protocol is a much needed tool to facilitate quick clinical assessment and improve patient care in the ER. Further validation through comparison with standard clinical practice is warranted.
ITPR3‐associated neuropathy: Report of a further family with adult onset intermediate Charcot–Marie–Tooth disease
Authors: Cabello‐Murgui Javier , Jiménez‐Jiménez Jesús , Vílchez Juan J , Azorín Inmaculada , Martí‐Martínez Pilar , Millet Elvira , Lupo Vincenzo , Sevilla Teresa , Sivera Rafael
Published: September 2024

Background and Purpose

ITPR3 encodes type 3 inositol‐tri‐phosphate receptor (IP3R3), a protein expressed in Schwann cells, predominantly in the paranodal region, and involved in the regulation of Ca2+ release from the endoplasmic reticulum. Dominant variants in ITPR3 have recently been recognized as a rare cause of intermediate Charcot–Marie–Tooth disease (CMT).

Methods

We collected the clinical data of a family with autosomal dominant neuropathy whose proband was diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) for many years. The genetic diagnosis was achieved by whole exome sequencing.

Results

The proband developed symmetrical sensory–motor neuropathy with demyelinating features at 32 years old. He was diagnosed with CIDP and received numerous immunomodulatory treatments. However, his condition progressed, leading to severe proximal leg and hand atrophy that confined him to a wheelchair at 60 years. The patient's two sons began to exhibit symptoms suggestive of neuropathy shortly after age 30 years, and the condition was reoriented as inherited. Exome sequencing identified a heterozygous c.4271C > T variant in the ITPR3 gene segregating with the disease. Nerve conduction studies showed a combination of demyelinating and axonal features that vary by nerve, disease duration, and patient. A uniform thickening of the nerves was identified on nerve echography, as was distal symmetric fatty infiltration in lower limb muscle imaging.

Conclusions

The c.4271C > T ITPR3 variant causes a late onset CMT that can be considered an intermediate CMT. Considering the electrophysiological findings and the distribution of IP3R3, we hypothesize that this variant could start as nodal dysfunction that progresses to widespread nerve degeneration.
Statistical characteristics of large‐scale objective tonic–clonic seizure records from medical smartwatches used in daily life
Authors: Zhang Boyu , Chen Weixuan V. , Regalia Giulia , Goldenholz Daniel M. , Picard Rosalind W.
Published: September 2024

Objective

This study aimed to assess whether population‐level patterns in seizure occurrence previously observed in self‐reported diaries, medical records, and electroencephalographic recordings were also present in tonic–clonic seizure (TCS) diaries produced via the combined input of a US Food and Drug Administration‐cleared wristband with an artificial intelligence detection algorithm and patient self‐reports. We also investigated the characteristics of patient interactions with wearable seizure alerts.

Methods

We analyzed wristband data from patients with TCSs who had at least three reported TCSs over a minimum of 90 days. We quantified TCS frequency and cycles, and the relationship between the mean and variability of monthly TCS counts. We also assessed interaction metrics such as false alarm dismissal and seizure confirmation rates.

Results

Applying strict criteria for usable data, we reviewed 137 490 TCSs from 3012 patients, with a median length of TCS alert records of 445 days (range = 90–1806). Analyses showed consistency between prior diary studies and the present data concerning (1) the distribution of monthly TCS frequency (median = 3.1, range = .08–26); (2) the linear relationship (slope = .79, R2 = .83) between the logarithm of the mean and the logarithm of the SD of monthly TCS frequency (L‐relationship); and (iii) the prevalence of multiple coexisting seizure cycles, including circadian (84.0%), weekly (24.6%), and long‐term cycles (31.1%).

Significance

Key population‐level patterns in seizure occurrence are recapitulated in wrist‐worn device recordings, supporting their validity for tracking TCS burden. Compared to other approaches, wearables can provide noninvasive, objective, long‐term data, revealing cycles in seizure risk. However, improved patient engagement with wristband alerts and further validation of detection accuracy in ambulatory settings are needed. Together, these findings suggest that data from smart wristbands may be used to derive features of TCS records and, ultimately, facilitate remote monitoring and the development of personalized forecasting tools for TCS management. Our findings may not generalize to other types of seizures.
Unveiling the disease progression in developmental and epileptic encephalopathies: Insights from EEG and neuropsychology
Authors: Surdi Paolo , Trivisano Marina , De Dominicis Angela , Mercier Mattia , Piscitello Ludovica Maria , Pavia Giusy Carfì , Calabrese Costanza , Cappelletti Simona , Correale Cinzia , Mazzone Luigi , Vigevano Federico , Specchio Nicola
Published: September 2024

Objective

Developmental and epileptic encephalopathies (DEEs) are neurological disorders characterized by developmental impairment and epilepsy. Our study aims to assess disease progression by comparing clinical findings, electroencephalography (EEG), and neuropsychological data from seizure onset to the last follow‐up evaluation.

Methods

We retrospectively reviewed patients with genetic DEEs who were followed‐up at the epilepsy unit of Bambino Gesù Children's Hospital, Rome. We collected information regarding gender, family history, genetic variant, age at onset and at last follow‐up, neurological examination, type of seizure, drug resistance, occurrence of status epilepticus, and movement and cognitive and behavioral disorders. We compared EEG background activity, epileptiform abnormalities, and cognitive functions between seizure onset and the last follow‐up evaluation using the McNemar‐Bowker test (α = 5%).

Results

A total of 160 patients (94 female) were included. Genetic analysis revealed a spectrum of pathogenic variants, with SCN1A being the most prevalent (25%). The median age at seizure onset and at the last follow‐up was 0.37 (interquartile range [IQR]: 0.09–0.75) and 8.54 years (IQR: 4.32–14.55), respectively. We documented a statistically significant difference in EEG background activity (p = .017) and cognitive impairment (p = .01) from seizure onset to the last follow‐up evaluation. No significant differences were detected for epileptiform abnormalities (p = .2). In addition, high prevalence rates were observed for drug resistance (81.9%), movement disorders (60.6%), behavioral and autism spectrum disorders (45%), neurological deficits (31.3%), and occurrence of status epilepticus (23.1%).

Significance

Our study provides evidence that a clinical progression may appear in genetic DEEs, manifesting as development or worsening of cognitive impairment and disruption of EEG background activity. These results highlight the challenging clinical course and the importance of early intervention and personalized care in the management of patients with DEEs.
Mycobacterial peptidyl prolyl isomerase A activates STING‐TBK1‐IRF3 signaling to promote IFNβ release in macrophages
Authors: Sharma Arun Kumar , Mal Soumya , Sahu Sanjaya Kumar , Bagchi Shreya , Majumder Debayan , Chakravorty Debangana , Saha Sudipto , Kundu Manikuntala , Basu Joyoti
Published: September 2024

Peptidyl prolyl isomerases (PPIases) are well‐conserved protein‐folding enzymes that moonlight as regulators of bacterial virulence. Peptidyl prolyl isomerase A, PPiA (Rv0009) is a secretory protein of Mycobacterium tuberculosis that possesses sequence and structural similarity to eukaryotic cyclophilins. In this study, we validated the interaction of PPiA with stimulator of interferon genes (STING) using both, Escherichia coli‐based and mammalian in vitro expression systems. In vitro pull‐down assays confirmed that the cytosolic domain of STING interacts with PPiA, and moreover, we found that PPiA could induce dimerization of STING in macrophages. In silico docking analyses suggested that the PXXP (PDP) motif of PPiA is crucial for interaction with STING, and concordantly, mutations in the PDP domain (PPiA MUT‐II) abrogated this interaction, as well as the ability of PPiA to facilitate STING dimerization. In agreement with these observations, fluorescence microscopy demonstrated that STING and wild‐type PPiA, but not PPiA MUT‐II, could colocalize when expressed in HEK293 cells. Highlighting the importance of the PDP domain further, PPiA, but not PPiA MUT‐II could activate Tank binding kinase 1 (TBK1)‐interferon regulatory factor 3 (IRF3) signaling to promote the release of interferon‐beta (IFNβ). PPiA, but not PPiA MUT‐II expressed in Mycobacterium smegmatis induced IFNβ release and facilitated bacterial survival in macrophages in a STING‐dependent manner. The PPiA‐induced release of IFNβ was c‐GAS independent. We conclude that PPiA is a previously undescribed mycobacterial regulator of STING‐dependent type I interferon production from macrophages.
Estrogen receptors and extracellular matrix: the critical interplay in cancer development and progression
Authors: Mangani Sylvia , Piperigkou Zoi , Koletsis Nikolaos E. , Ioannou Paraskevi , Karamanos Nikos K.
Published: September 2024

Cancer remains a significant global health concern. Breast cancer is a multifaceted and prevalent disease influenced by several factors, among which estrogen receptors (ERs) and the extracellular matrix (ECM) play pivotal roles. ERs, encompassing ERα and ERβ, exert significant diversity on tumor behavior, cell signaling, invasion, and metastatic potential, thus guiding breast cancer prognosis. Understanding the multifunctional connections between ERs and ECM that mediate the dynamics of tumor microenvironment is vital for unraveling the complexity of breast cancer pathobiology and identifying novel therapeutic targets. This critical review delves into the intricate nature of ERs, emphasizing their structural isoforms and the consequential impact on breast cancer outcomes. A detailed examination of ER‐mediated cell signaling pathways reveals how differential expression of ERα and ERβ isoforms influence breast cancer cell behavior. The functional ERs‐matrix interactions emerge as a pivotal factor in modulating epigenetic mechanisms of breast cancer cells, orchestrating changes in cellular phenotype and expression patterns of matrix modulators. Specifically, ERα isoforms are shown to regulate ECM signaling cascades, while the effects of ECM components on ERα activity highlight a bidirectional regulatory axis. The diversity of ERβ isoforms is also highlighted, illustrating their distinct contribution to ECM‐mediated cellular responses. This review underscores the complex interplay between ERα/β isoforms and the ECM, shedding light onto the potential therapeutic strategies targeting these interactions to improve breast cancer management.
The Z isomer of pyridoxilidenerhodanine 5′‐phosphate is an efficient inhibitor of human pyridoxine 5′‐phosphate oxidase, a crucial enzyme in vitamin B6 salvage pathway and a potential chemotherapeutic target
Authors: Graziani Claudio , Barile Anna , Antonelli Lorenzo , Fiorillo Annarita , Ilari Andrea , Vetica Fabrizio , di Salvo Martino Luigi , Paiardini Alessandro , Tramonti Angela , Contestabile Roberto
Published: September 2024

Pyridoxal 5′‐phosphate (PLP), the catalytically active form of vitamin B6, acts as a cofactor in many metabolic processes. In humans, PLP is produced in the reactions catalysed by pyridox(am)ine 5′‐phosphate oxidase (PNPO) and pyridoxal kinase (PDXK). Both PNPO and PDXK are involved in cancer progression of many tumours. The silencing of PNPO and PDXK encoding genes determines a strong reduction in tumour size and neoplastic cell invasiveness in models of acute myeloid leukaemia (in the case of PDXK) and ovarian and breast cancer (in the case of PNPO). In the present work, we demonstrate that pyridoxilidenerhodanine 5′‐phosphate (PLP‐R), a PLP analogue that has been tested by other authors on malignant cell lines reporting a reduction in proliferation, inhibits PNPO in vitro following a mixed competitive and allosteric mechanism. We also show that the unphosphorylated precursor of this inhibitor (PL‐R), which has more favourable pharmacokinetic properties according to our predictions, is phosphorylated by PDXK and therefore transformed into PLP‐R. On this ground, we propose the prototype of a novel prodrug‐drug system as a useful starting point for the development of new, potential, antineoplastic agents.
QTL Mapping of Melampsora Leaf Rust Resistance and Yield Component Traits in the SalixF1 Hybrid Common Parent Population
Authors: Wilkerson Dustin G. , Crowell Chase R. , Smart Christine D. , Smart Lawrence B.
Published: September 2024

The first step in trait introgression is to identify and assess novel sources of variation. For shrub willow (Salix) breeders, there is an abundance of understudied species within a genus that readily hybridizes. Breeding targets in shrub willow center on traits contributing to biomass yield for bioenergy. These include stem biomass, insect and pathogen resistance, and leaf architecture traits. More specifically, breeding for durable resistance to willow leaf rust (Melampsora spp.) is of particular importance as the pathogen can significantly reduce biomass yields in commercial production. The Salix F1 hybrid common parent population (Salix F1 HCP) was created to characterize the variation among eight species‐hybrid families and map QTL for targeted traits. A female and male S. purpurea were used as common parents in crosses made to male S. suchowensis, S. viminalis, S. koriyanagi, and S. udensis and female S. viminalis, S. integra, S. suchowensis to produce eight families that were planted in field trials at Cornell AgriTech in Geneva, NY and phenotyped. Using 16 previously described parental backcross linkage maps and two newly generated S. purpurea consensus maps, we identified 215 QTL across all eight families and in every parent. These included 15 leaf rust severity, 61 herbivory, 65 leaf architecture, and 74 yield component QTL, resulting in 50 unique overlapping regions within the population. These genetic loci serve as an important foundation for future shrub willow breeding, and each interspecific family was identified as a novel source of useful alleles for trait introgression into high yielding cultivars.
Cretaceous Fore‐Arc Basin and Its Provenance in Sakhalin, Far East Russia: U‐Pb Ages of Detrital Zircons From the Yezo Group
Authors: Sato Tomohiko , Isozaki Yukio , Tsutsumi Yukiyasu , Shigeta Yasunari , Kodama Kazuto , Hasegawa Takashi
Published: September 2024

In order to reconstruct the pre‐Japan Sea configuration of the Cretaceous arc‐trench system, we measured U‐Pb ages of detrital zircons in the five sandstone samples from the Yezo Group in Sakhalin using LA‐ICP‐MS. A sandstone sample from the lowermost horizon (Ai Formation) contains abundant Early Cretaceous (110–100 Ma) zircons with minor amounts of pre‐Jurassic ones. Four sandstones from the uppermost (Krasnoyarka Formation) are enriched dominantly in Late Cretaceous (100–66 Ma) grains. The YC1σ ages of these samples are generally consistent with the previous fossil ages; nonetheless, a possible age extension of the Ai Fm up possibly into the Cenomanian was newly suggested. The stepwise younging in peak age of zircons according to the stratigraphy suggests the continuous replacement of arc granitoid exposures in the Cretaceous magmatic arc in the provenance likely developed on the continent side. This secular trend in zircon age spectra of the Yezo Group in Sakhalin is properly correlated with that in Hokkaido and also with that of coeval sandstones in southwest Japan, suggesting a monotonous sedimentation in the fore‐arc basin of the Late Cretaceous arc‐trench system developed along the Pacific margin, from Sakhalin to southwest Japan for ca. 2500 km in length. Its spatial dimension corresponds to that of the modern representative fore‐arc basin in the Java‐Sumatra region.
IgE versus IgG and IgA: Differential roles of allergen‐specific antibodies in sensitization, tolerization, and treatment of allergies
Authors: Knol E. F. , van Neerven R. J. J.
Published: September 2024

The prevalence of asthma, rhinitis, and food allergies has increased dramatically over the last few decades. This increase originally started in western countries, but is now also evident in many other regions of the world. Given the fact that the increase is so quick, the noted increase cannot be linked to a genetic effect, and many environmental factors have been identified that are associated with increased or reduced prevalence of allergies, like changing dietary habits, increased urbanization, pollution, exposure to microorganisms and LPS, and the farming environment and raw milk consumption. Although the key role of allergen‐specific IgE in allergies is well known, the role of allergen‐specific IgG and IgA antibodies is less well defined. This review will provide an overview of the functions of allergen‐specific IgE in allergy, the role of allergen‐specific antibodies (IgG (4) and IgA) in allergen immunotherapy (AIT), the possibility to use allergen‐specific antibodies for treatment of ongoing allergies, and the potential role of allergen‐specific antibodies in tolerance induction to allergens in a preventive setting. In the last, more speculative, section we will present novel hypotheses on the potential role of allergen‐specific non‐IgE antibodies in allergies by directing antigen presentation, Th2 development, and innate immune training.
Exploring the Effects of Irrigation Schedules on Evapotranspiration Partitioning and Crop Water Productivity of Winter Wheat (Triticum aestivum L.) in North China Plain Using RZWQM2
Authors: Gao Mingliang , Liu Fuying , Zhang Haoze , Yuan Huabin , Zong Rui , Zhang Mingming , Li Quanqi
Published: September 2024

A significant basis for winter wheat production in China is the North China Plain (NCP). However, winter wheat production is severely hampered by water shortages in this area. Transpiration co‐occurs with photosynthesis, affecting crop water productivity (CWP). The purpose of this experiment is to use Root Zone Water Quality Model (RZWQM2) to study actual transpiration (AT) and evaporation (AE) under different irrigation schedules and then determine its impact on grain yield and CWP. In the 2019–2022 winter wheat growing seasons, four experimental treatments were set up: no irrigation during growth period (I0), irrigation at jointing stage (I1), irrigation at jointing and anthesis stage (I2) and irrigation at jointing, anthesis and filling stage (I3), and the RZWQM2 model was calibrated and verified in this experiment. A higher yield (7840.90 kg/ha for an average of 3 years) and the highest CWP can be obtained in I2 treatment (increased by 12.72%, 5.98% and 4.28% for an average of 3 years, respectively, compared to the other three treatments). The model has a good simulation effect on soil water dynamic change and plant physiological performance of the four treatments; the model showed that irrigation increased the simulated AE and AT; however, reduced AE/actual evapotranspiration. For the whole growth period, AT in I3, I2, I1 and I0 was 351.70, 317.30, 271.50 and 223.70 mm, respectively. Especially in the late growth stage of winter wheat, the AT in I3 was 65.20 mm for an average of 3 years, which was significantly higher than I2, I1 and I0 by 31.60, 13.50 and 10.00 mm, respectively. Thus, I3 increased AT at the late growth stage of winter wheat and resulted in an increase in grain yield; however, it did not significantly increase CWP. This study demonstrated that irrigation at winter wheat jointing and anthesis stages can improve the CWP to achieve the goal of stable grain yield and water saving.
Synthesis of near‐spherical BN powders by templated carbothermal reduction and nitridation
Authors: Zhao Dengke , Tian Zhaobo , Du Songmo , Zhao Shuo , Fan Binbin , Zhang Shijia , Wang Bohan , Li Fei , Cao Wenbin , Chen Kexin , Liu Guanghua
Published: September 2024

Boron nitride (BN) powders with near‐spherical particles of more than 10 µm were synthesized by templated carbothermal reduction and nitridation. The effects of processing factors, such as raw material mixing methods, C/B2O3 molar ratios, and carbon templates, were systematically studied, and the reaction mechanism was discussed. The experimental results showed that the integrity and morphology of the carbon templates was usually destroyed during ball milling or grinding, but preserved during magnetic stirring. The morphology of synthesized BN particles depended on the C/B2O3 molar ratio in starting reactant mixtures and gradually changed from sheet‐like to near‐spherical shape with decreasing C/B2O3 molar ratio. The morphology and size of synthesized BN particles agreed with that of the carbon templates, which means that the morphology and size of synthesized BN particles can be tailored by controlling that of the carbon template. The BN near‐spherical particles synthesized in this work may be used as thermally conductive fillers for electronic packaging.
Influence of germanium concentration on the microstructure and optical transparency of terbium gallium garnet ceramics
Authors: Li Xiao , Zhang Lixuan , Zhu Danyang , Wu Junlin , Hu Chen , Li Tingsong , Wu Lexiang , Hreniak Dariusz , Li Jiang
Published: September 2024

In recent years, transparent terbium gallium garnet (TGG) ceramics have garnered significant interest for their application in high‐power Faraday isolators. However, challenges in achieving high transparency have led researchers to explore the addition of various sintering aids as a key strategy to enhance the optical quality of TGG ceramics. Through this work, the effect of germanium (Ge) addition on the microstructure and optical transparency of TGG magneto‐optical ceramics was investigated. TGG powders were synthesized by the co‐precipitation method, and the source Ge was Ge ethoxide added through a ball‐milling step. Transparent TGG ceramics were prepared by air pre‐sintering combined with hot isostatic pressing post‐treatment and subsequent annealing. The ceramics containing 200 ppm Ge exhibit optimal transmittance of 81.3% at 1064 nm (a value of theoretical transmittance), the Verdet constant was −133.0 rad·T−1·m−1 at 633 nm. When the addition of Ge reaches 600 ppm, a secondary phase can be observed on the surface of ceramic. Subsequently, TGG ceramics prepared from 1425°C to 1500°C with 200 ppm of Ge were analyzed, which revealed that the optimal pre‐sintering temperature is 1450°C.
Electrospun CaZrO3‐BaZrO3 fibrous membrane with enhanced high‐temperature stability and flexibility
Authors: Yuan Kangkang , Shu Chen , Meng Kexin , Zhao Wenjun , Sun Guosheng , Zhu Jien , Chen Jin , Huang Yunlong , Li Chengshun , Jin Xiaotong
Published: September 2024

Calcium zirconate (CaZrO3)‐based fibrous membrane is a promising candidate in high‐temperature areas for its high melting point, good phase stability up to 1900°C, low thermal conductivity, and low cost. To further enhance the high temperature flexibility of CaZrO3‐based fibrous membrane without sacrificing stability, modification methods should be conducted. In the present work, a CaZrO3‐BaZrO3 dual‐phasic structure was proposed to modify the high‐temperature properties from the standpoint of phase competition. CaZrO3‐BaZrO3 fibrous membranes were prepared with the combination of the electrospinning method and pyrolysis process. The decomposition process, phase transformation, crystallize size, and microstructure evolution of CaZrO3‐BaZrO3 precursor fibrous membrane were characterized. The grain size, particle size, NIR reflectivity, high‐temperature stability, fire retardancy, and high‐temperature flexibility were also characterized and compared with other CaZrO3‐based fibrous membranes. The higher thermal stability and flexibility of the CaZrO3‐BaZrO3 fibrous membrane at 1200°C would make it a good candidate for high‐temperature insulating, high‐temperature supporting, and high‐temperature filtration.
Selenium alleviates dextran sulfate sodium‐induced colitis and inhibits ferroptosis of intestinal epithelial cells via upregulating glutathione peroxidase 4
Authors: Zhao Mengxue , Wang Hongqian , Zhang Yumeng , Lv Chuang , Guan Jing , Chen Xi
Published: September 2024

Background and Aim

Selenium, an essential micronutrient for humans, has been shown to be protective against ulcerative colitis (UC), but the exact mechanism remains unclear. The role of selenium, protecting against ferroptosis of intestinal epithelial cells (IECs) in colitis, was investigated in this current study.

Methods

Serum selenium level and ferroptosis‐related gene expression in the colonic mucosa were measured in UC patients and healthy controls. The effects of sodium selenite supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)‐treated mice. The influence of sodium selenite on IEC ferroptosis was evaluated through assessing cell death rate, intracellular ferrous iron content, lipid reactive oxygen species level, and mitochondrial membrane damage of DSS‐treated Caco‐2 cells. Moreover, glutathione peroxidase 4 (GPX4) and acyl‐CoA synthetase long‐chain family member 4, ferroptosis‐related genes, were detected in Caco‐2 cells and mouse intestines.

Results

Serum selenium was decreased in UC patients in comparison with healthy individuals. Additionally, serum selenium level was negatively correlated with disease activity and was associated with clinical inflammation and nutrition indicators. The expression of GPX4 in the mucosa of UC was positively correlated with serum selenium level. The in vivo experiments showed that selenium treatment ameliorated DSS‐induced colitis and inhibited ferroptosis in IECs. The in vitro results suggested that selenium supplementation inhibited DSS‐induced ferroptosis in Caco‐2 cells. GPX4 was upregulated after selenium supplementation both in vivo and in vitro.

Conclusions

Serum selenium level was associated with IEC ferroptosis in UC patients. Selenium supplementation alleviates DSS‐induced colitis and inhibits ferroptosis in IECs by upregulating the expression of GPX4.
Home alone and high risk: Supporting medication management in older adults living alone with cognitive impairment
Authors: Hoang Peter M. , Stall Nathan M. , Rochon Paula A.
Published: September 2024

See related article by Growdon et al.
The Mediation Impact of Compassion Competence on the Link Between Mindfulness and Job Burnout in Nurses: A Cross‐Sectional Study
Authors: Li Jiaoyue , Wang Fengling , Zhang Xiao , Zhang Hongqiang , Lan Mengfei , Chen Shuya , Su Jiacheng , Yang Li
Published: September 2024

Aims

This study explores the link between mindfulness, compassion competence and job burnout among nurses, and analyses the mediating role that compassion competence plays in this relationship.

Background

Understanding nurses' mindfulness, compassion competence and job burnout is important, which could help devise interventions to relieve burnout in clinical nurses.

Methods

This study adopts convenience sampling method and descriptive design quantitative research. A cross‐sectional study of 513 nurses was conducted from June to October 2023 in mainland China. The Socio‐demographic Questionnaire, Mindful Attention Awareness Scale, Maslach Burnout Inventory‐Human Service Survey and Compassion Competence Scale for the Nurses were utilised to gather basic demographic information on nurses and to evaluate their level of mindfulness, compassion competence and job burnout. Descriptive statistics, Spearman's correlation analyses and structural equation model were used to analyse the data.

Results

Five hundred and thirteen valid questionnaires were gathered. Spearman's correlation analysis revealed a strong negative link between mindfulness and job burnout, and between compassion competence and burnout, and a significant positive correlation between mindfulness and compassion competence. The results of the mediation analysis revealed that the relationship between mindfulness and job burnout was partially mediated by compassion competence, and the mediating effect accounted for 18.6% of the total effect.

Conclusion

Compassion competence performed as a partial mediator between mindfulness and job burnout among nurses. Nursing managers could enhance nurses' mindfulness level and compassion competence through Mindfulness interventions and Compassion training to reduce their burnout.

Relevance to Clinical Practice

This study offers a fresh viewpoint on enhancing clinical nurses' compassion competence and reducing job burnout. Healthcare organisations and medical institutions can mitigate nurses' job burnout by improving their mindfulness levels and compassion competence.

Reporting Method

The study used the STROBE checklist for reporting.

Patient or Public Contribution

All participants were nurses who completed an electronic questionnaire related to this study.
Specialized medical equipment for people with intellectual and developmental disabilities allocated in Home and Community Based Services
Authors: Friedman Carli
Published: September 2024

Specialized medical equipment, includes both durable medical equipment—nondisposable, reusable medical equipment—and nondurable medical equipment—disposable, often one time use medical supplies. The aim of this study was to examine if, and how, states allocated specialized medical equipment for people with IDD in their Medicaid HCBS programs. To do so, we examined Medicaid HCBS 1915(c) waivers for people with IDD from across the United States. We found 55 waivers (51.40%) from 27 states (60.00%) provided 71 specialized medical equipment services to people with IDD. HCBS waivers projected spending $61 million on specialized medical equipment for 33 305 people with IDD. The average annual spending per person was $2433. In addition to helping promote community living and integration, for some people with IDD, specialized medical equipment can be life sustaining; as such, it is critical that unmet needs for specialized medical equipment not go unaddressed.