bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of Faecal Immunochemical Testing for Colorectal Cancer Screening at Varying Positivity Thresholds
Authors: Randel Kristin Ranheim , Botteri Edoardo , de Lange Thomas , Schult Anna Lisa , Eskeland Sigrun Losada , El‐Safadi Badboni , Norvard Espen R. , Bolstad Nils , Bretthauer Michael , Hoff Geir , Holme Øyvind 
Published: October 2024

ABSTRACTBackgroundThe positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries.AimsTo explore the trade‐off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial.MethodsWe included first participation in biennial FIT screening for 47,265 individuals aged 50–74 years. Individuals with FIT > 15 μg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen‐detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 μg/g.ResultsAt the 15 μg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 μg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 μg/g threshold. At 150 μg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 μg/g and 0.11% at 150 μg/g. Post‐colonoscopy bleeding rates were 0.8% and 1.7%, respectively.ConclusionsIncreasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country‐specific information on adverse events.Trial RegistrationClinicaltrials.gov identifier: NCT01538550
Editorial: Effectiveness and Safety of Ustekinumab in Ulcerative Colitis—Where We Are Now in Real Life. Authors' Reply
Authors: Chaparro María , Gisbert Javier P. 
Published: October 2024

LINKED CONTENTThis article is linked to Chaparro et al papers. To view these articles, visit https://doi.org/10.1111/apt.18230 and https://doi.org/10.1111/apt.18272.
Inactivation induced by pathogenic Cav1.3 L‐type Ca2+‐channel variants enhances sensitivity for dihydropyridine Ca2+ channel blockers
Authors: Török Ferenc , Salamon Sarah , Ortner Nadine J. , Fernández‐Quintero Monica L. , Matthes Jan , Striessnig Jörg 
Published: October 2024

AbstractBackground and PurposePathogenic gain‐of‐function mutations in Cav1.3 L‐type voltage‐gated Ca2+‐channels (CACNA1D) cause neurodevelopmental disorders with or without endocrine symptoms. We aimed to confirm a pathogenic gain‐of function phenotype of CACNA1D de novo missense mutations A749T and L271H, and investigated the molecular mechanism causing their enhanced sensitivity for the Ca2+‐channel blocker isradipine, a potential therapeutic for affected patients.Experimental ApproachWildtype and mutant channels were expressed in tsA‐201 cells and their gating analysed using whole‐cell and single‐channel patch‐clamp recordings. The voltage‐dependence of isradipine action was quantified using protocols inducing variable fractions of inactivated channels. The molecular basis for altered channel gating in the mutants was investigated using in silico modelling and molecular dynamics simulations.Key ResultsBoth mutations were confirmed pathogenic due to characteristic shifts of voltage‐dependent activation and inactivation towards negative potentials (~20 mV). At negative holding potentials both mutations showed significantly higher isradipine sensitivity compared to wildtype. The affinity for wildtype and mutant channels increased with channel inactivation as predicted by the modulated receptor hypothesis (30‐ to 40‐fold). The IC50 was indistinguishable for wildtype and mutants when >50% of channels were inactivated.Conclusions and ImplicationsMutations A749T and L271H induce pathogenic gating changes. Like wildtype, isradipine inhibition is strongly voltage‐dependent. Our data explains their apparent higher drug sensitivity at a given negative voltage by the availability of more inactivated channels due to their more negative inactivation voltage range. Low nanomolar isradipine concentrations will only inhibit Cav1.3 channels in neurons during prolonged depolarized states without selectivity for mutant channels.
Supporting inclusive scientific communities: Insights from the ATBC society survey
Authors: Maas Bea , Cardelus Catherine , Carrasco‐Rueda Farah , Chirango Yolanda , Gowda Vinita , Montaño‐Centellas Flavia , Ostertag Rebecca , Roopsind Anand , Vargas German , Yadok Biplang Godwill , Santiago Louis 
Published: October 2024

AbstractAcademic societies have a special responsibility in supporting the inclusivity of scientific communities. A survey of 224 Association for Tropical Biology and Conservation society members indicates that, while the society provides stronger support for equity and inclusion compared to workplaces, there is a need for continued promotion of diversity within the broader scientific community.Abstract in Spanish is available with online material.
Recent Advances in Medicinal Chemistry of Memantine Against Alzheimer's Disease
Authors: Singh Yash Pal , Kumar Harish 
Published: October 2024

ABSTRACTAlzheimer's disease (AD) is a chronic progressive, age‐related neurodegenerative brain disorder characterized by the irreversible decline of memory and other cognitive functions. It is one of the major health threat of the 21st century, which affects around 60% of the population over the age of 60 years. The problem of this disease is even more major because the existing pharmacotherapies only provide symptomatic relief without addressing the basic factors of the disease. It is characterized by the extracellular deposition of amyloid β (Aβ) to form senile plaques, and the intracellular hyperphosphorylation of tau to form neurofibrillary tangles (NFTs). Due to the complex pathophysiology of this disease, various hypotheses have been proposed, including the cholinergic, Aβ, tau, oxidative stress, and the metal–ion hypothesis. Among these, the cholinergic and Aβ hypotheses are the primary targets for addressing AD. Therefore, continuous advances have been made in developing potential cholinesterase inhibitors and N‐methyl‐D‐aspartate (NMDA) receptor antagonists to delay disease progression and restore cholinergic neurotransmission. In this review article, we tried to comprehensively summarize the recent advancement in NMDA receptor antagonist (memantine) and their hybrid analogs as potential disease‐modifying agents for the treatment of AD. Furthermore, we also depicted the design, rationale, and SAR analysis of the memantine‐based hybrids used in the last decade for the treatment of AD.
Remission of Acromegaly: The Sooner the Better
Authors: Cuny Thomas , Maione Luigi , Störmann Sylvère 
Published: October 2024

ABSTRACTRemission of acromegaly is defined by normalization of GH/IGF‐1 values according to age and gender. While treatment strategies, biochemical cut‐off to reach, and morbidities related to the persistence of the disease are well described in the literature, there is little data focusing on the delay to reach remission and its consequences. In this commentary, the authors discussed the results obtained from the UK acromegaly registry showing that the time to biochemical remission predicts the overall survival of patients in acromegaly.
Are Sleeves Necessary in Static Computer‐Assisted Implant Surgery? A Comparative In Vitro Analysis
Authors: Hang Jenna , Guentsch Arndt 
Published: October 2024

ABSTRACTObjectivesThis study aims to examine differences in trueness and precision between surgical guides with (S) and without sleeves (SL). A secondary aim was to assess the impact of the sleeve‐to‐bone distance.Materials and MethodsMandible replicas (n = 120) were printed from an STL file obtained from a clinical CBCT. The mandibles were divided into sleeved (S, n = 60) and sleeveless (SL, n = 60) groups, each further divided into three categories (n = 20 each) with different heights from the guide to the implant platform: 2 mm (H2), 4 mm (H4), or 6 mm (H6). Digital planning and surgical guide design were done for a 4.1 × 10 mm implant for site #30. Post‐op positions were captured using a scan body and lab scanner. Angular deviation was the primary outcome, with 3D and 2D deviations as secondary parameters. Statistical analysis included two‐sample t‐tests, and one‐way and two‐way ANOVA.ResultsGroup S (2.41 ± 1.41°) had significantly greater angular deviation than Group SL (1.65 ± 0.93°; p = 0.0001). Angular deviation increased with sleeve‐to‐bone distance. H2 deviations were 1.48 ± 0.80° (S) vs. 1.02 ± 0.45° (SL; p < 0.05), H4: 2.36 ± 1.04° (S) vs. 1.48 ± 0.79° (SL; p < 0.05), H6: 3.37 ± 0.67° (S) vs. 2.46 ± 0.89° (SL; p < 0.05). 3D deviation at the implant platform was 0.36 ± 0.17 mm (S) vs. 0.30 ± 0.15 mm (SL; p < 0.05) and at the apex 0.74 ± 0.34 mm (S) vs. 0.53 ± 0.31 mm (SL; p < 0.01). Group SL at H2 had the smallest inter‐implant distance (0.53 ± 0.37°), while Group S at H4 had the largest (1.20 ± 0.84°; p < 0.05).ConclusionsSleeveless guides are more accurate than sleeved guides, and angular deviation is influenced by the distance from the guide to the implant platform.
Neuroprotective effects of punicalagin and/or micronized zeolite clinoptilolite on manganese‐induced Parkinson's disease in a rat model: Involvement of multiple pathways
Authors: Abu‐Elfotuh Karema , Abbas Ashwaq N. , Najm Mazin A. A. , Qasim Qutaiba A. , Hamdan Ahmed M. E. , Abdelrehim Amany B. , Gowifel Ayah M. H. , Al‐Najjar Aya H. , Atwa Ahmed M. , Kozman Magy R. , Khalil Azza S. , Negm Amira M. , Mousa Sara Nagdy Mahmoud , Hamdan Amira M. , Abd El‐Rhman Rana H. , Abdelmohsen Shaimaa R. , Tolba Amina M. A. , Aboelsoud Heba Abdelnaser , Salahuddin Ahmad , Darwish Alshaymaa 
Published: October 2024

AbstractBackgroundManganism, a central nervous system dysfunction correlated with neurological deficits such as Parkinsonism, is caused by the substantial collection of manganese chloride (MnCl2) in the brain.ObjectivesTo explore the neuroprotective effects of natural compounds, namely, micronized zeolite clinoptilolite (ZC) and punicalagin (PUN), either individually or in combination, against MnCl2‐induced Parkinson's disease (PD).MethodsFifty male albino rats were divided into 5 groups (Gps). Gp I was used as the control group, and the remaining animals received MnCl2 (Gp II–Gp V). Rats in Gps III and IV were treated with ZC and PUN, respectively. Gp V received both ZC and PUN as previously reported for the solo‐treated plants.ResultsZC and/or PUN reversed the depletion of monoamines in the brain and decreased acetyl choline esterase activity, which primarily adjusted the animals' behavior and motor coordination. ZC and PUN restored the balance between glutamate/γ‐amino butyric acid content and markedly improved the brain levels of brain‐derived neurotrophic factor and nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 and decreased glycogen synthase kinase‐3 beta activity. ZC and PUN also inhibited inflammatory and oxidative markers, including nuclear factor kappa‐light‐chain‐enhancer of activated B cells, Toll‐like receptor 4, nucleotide‐binding domain, leucine‐rich‐containing family, pyrin domain‐containing‐3 and caspase‐1. Bcl‐2‐associated X‐protein and B‐cell leukemia/lymphoma 2 protein (Bcl‐2) can significantly modify caspase‐3 expression. ZC and/or PUN ameliorated PD in rats by decreasing the levels of endoplasmic reticulum (ER) stress markers (p‐protein kinase‐like ER kinase (PERK), glucose‐regulated protein 78, and C/EBP homologous protein (CHOP)) and enhancing the levels of an autophagy marker (Beclin‐1).Discussion and ConclusionZC and/or PUN mitigated the progression of PD through their potential neurotrophic, neurogenic, anti‐inflammatory, antioxidant, and anti‐apoptotic activities and by controlling ER stress through modulation of the PERK/CHOP/Bcl‐2 pathway.
Lack variation of low slow‐wave activity over time in the frontal region in NREM sleep may be associated with dyskinesia in Parkinson's disease
Authors: Wang Yi‐Ming , Liu Jun‐Yi , Gao Fan , Xie Wei‐ye , Chen Jing , Gu Han‐Ying , Wang Fen , Zhong Chong‐Ke , Li Kai , Zhuang Sheng , Cheng Xiao‐Yu , Jin Hong , Zhang Jin‐Ru , Mao Cheng‐Jie , Liu Chun‐Feng 
Published: October 2024

AbstractObjectiveLevodopa‐induced dyskinesia (DYS) adversely affects the quality of life of Parkinson's disease (PD) patients. However, few studies have focused on the relationship between DYS and sleep and electroencephalography (EEG). Our study aimed to establish the objective physiological indicators assessed by polysomnography (PSG) that are associated with DYS in PD patients.MethodsWe enrolled 122 patients with PD, divided into two groups: PD with DYS (n = 27) and PD without DYS group (non‐DYS, n = 95). The demographics and clinical characteristics and sleep assessment in the two groups were collected. More importantly, overnight six‐channel PSG parameters were compared in the two groups. We also compared different bands and brain regions of average power spectral density within each group.ResultsCompared with the non‐DYS group, the DYS group tended to have a significantly higher percentage of nonrapid eye movement sleep (NREM). Gender, levodopa equivalent daily dose (LEDD), rapid eye movement (REM) sleep (min), and the NREM percentage were positively correlated with the occurrence of DYS. After adjusting for gender, disease duration, LEDD, taking amantadine or not, and Montreal Cognitive Assessment (MoCA), NREM%, N3%, and REM (min), the percentage of NREM sleep (p = 0.035), female (p = 0.002), and LEDD (p = 0.005), and REM sleep time (min) (p = 0.012) were still associated with DYS. There was no significant difference in whole‐night different bands of average power spectral density between two groups. There was no significant difference in normalized average power spectral density of slow wave activity (SWA) (0.5–2 Hz, 0.5–4 Hz, and 2–4 Hz) of early and late NREM sleep in the DYS group. Dynamic normalized average power spectral density of SWA of low‐frequency (0.5–2 Hz) reduction in the frontal region (p = 0.013) was associated with DYS in logistic regression after adjusting for confounding factors.ConclusionPD patients with DYS have substantial sleep structure variations. Higher NREM percentage and less REM percentage were observed in PD patients with DYS. Dynamic normalized average power spectral density of low‐frequency (0.5–2 Hz) SWA reduction in the frontal area could be a new electrophysiological marker of DYS in PD.
Export policy cooperation in a pandemic: the good, the bad and the hopeful
Authors: Dewit Gerda , Leahy Dermot 
Published: October 2024

AbstractWe develop a model in which vaccine‐producing firms from different developed countries supply vaccines to the developing world during a pandemic. Exporting countries experience a negative externality from incomplete global vaccination, which they try to mitigate by exporting vaccines to developing countries. A cooperative export policy is compared to the alternative regimes of non‐cooperation and non‐intervention. When the negative externality is low, cooperation among exporting countries is worse for global welfare than non‐intervention. However, at high externality levels, export policy cooperation is globally superior to non‐cooperative export subsidization. It then even has the potential to maximize global welfare.
Hypercholesterolemia and inflammation—Cooperative cardiovascular risk factors
Authors: Gallo Antonio , Le Goff Wilfried , Santos Raul D. , Fichtner Isabella , Carugo Stefano , Corsini Alberto , Sirtori Cesare , Ruscica Massimiliano 
Published: October 2024

AbstractBackgroundMaintaining low concentrations of plasma low‐density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events. In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation.ResultsChanges in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti‐inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid‐lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C‐reactive protein appears to be independent of the magnitude of LDLc lowering.ConclusionIdentifying clinical biomarkers of inflammation (e.g. interleukin‐6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.
Proteomic Analysis Reveals Oxidative Phosphorylation and JAK‐STAT Pathways Mediated Pathogenesis of Pemphigus Vulgaris
Authors: Cheng Yuqi , Zhao Mingming , Zhu CaiHong , Tang Xianfa , Wang Wenjun , Tang Huayang , Zheng Xiaodong , Zhu Zhengwei , Sheng Yujun , Wang Zaixing , Zhou Fusheng , Gao Jinping 
Published: October 2024

ABSTRACTPemphigus vulgaris (PV) stands as a rare autoimmune bullous disease, while the precise underlying mechanism remains incompletely elucidated. High‐throughput proteomic methodologies, such as LC‐MS/MS, have facilitated the quantification and characterisation of proteomes from clinical skin samples, enhancing our comprehension of PV pathogenesis. The objective of this study is to elucidate the signalling mechanisms underlying PV through proteomic analysis. Proteins and cell suspension were extracted from skin biopsies obtained from both PV patients and healthy volunteers and subsequently analysed using LC‐MS/MS and scRNA‐seq. Cultured keratinocytes were treated with PV serum, followed by an assessment of protein expression levels using immunofluorescence and western blotting. A total of 880, 605, and 586 differentially expressed proteins (DEPs) were identified between the lesion vs. control, non‐lesion vs. control, and lesion vs. non‐lesion groups, respectively. The oxidative phosphorylation (OXPHOS) pathway showed activation in PV. Keratinocytes are the major cell population in the epidermis and highly expressed ATP5PF, ATP6V1G1, COX6B1, COX6A1, and NDUFA9. In the cellular model, there was a notable increase in the expression levels of OXPHOS‐related proteins (V‐ATP5A, III‐UQCRC2, II‐SDHB, I‐NDUFB8), along with STAT1, p‐STAT1, and p‐JAK1. Furthermore, both the OXPHOS inhibitor metformin and the JAK1 inhibitor tofacitinib demonstrated therapeutic effects on PV serum‐induced cell separation, attenuating cell detachment. Metformin notably reduced the expression of V‐ATP5A, III‐UQCRC2, II‐SDHB, I‐NDUFB8, p‐STAT1, p‐JAK1, whereas tofacitinib decreased the expression of p‐STAT1 and p‐JAK1, with minimal impact on the expression of V‐ATP5A, III‐UQCRC2, II‐SDHB, and I‐NDUFB8. Our results indicate a potential involvement of the OXPHOS and JAK‐STAT1 pathways in the pathogenesis of PV.
Valence state and redox property of Fe‐CNTs added CeO2/TiO2 catalyst
Authors: Lee Minseo , Park Gwanhee , Kim Myungju , Lee Jaekwang , Jo Ilguk , Lee Heesoo 
Published: October 2024

AbstractThe investigation focused on examining the impact of incorporating Fe‐carbon nanotubes (CNTs) on the valence state and oxygen vacancies, and the physicochemical parameters of the catalytic system. For the CeO2/TiO2 catalyst with Fe‐CNTs, no distinct X‐ray diffraction (XRD) peaks corresponding to Fe‐CNTs were observed. This indicated their uniform dispersion, supported by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) imaging. X‐ray photoelectron spectroscopy (XPS) analysis was conducted to observe the changes in the valence state due to the addition of Fe‐CNTs. The concentration of Ce3+ on catalyst surface increased from 19.90% to 29.48% with an increased concentration of the chemisorbed oxygen species (Oα). This suggests that the addition of Fe‐CNTs into CeO2/TiO2 catalyst reduced Ce4+ on the catalyst surface, resulting in the formation of oxygen vacancies. Oxygen temperature‐programmed desorption (O2‐TPD) and hydrogen temperature‐programmed reduction (H2‐TPR) analyses showed both the adsorbed oxygen species and H2 consumption increased with adding Fe‐CNTs. Furthermore, the onset temperatures for O2 desorption and H2 consumption became lower, confirming the enhancement of catalytic redox properties.
Scoring the Big Five for longitudinally assessed academic achievement predictiveness: Manifest, correlated‐factors model, and bifactor modeling across multiple contexts
Authors: Krammer Georg , Schermer Julie Aitken , Koschmieder Corinna , Goffin Richard , Hendy Nhung T. , Biderman Michael 
Published: October 2024

AbstractBased on a large (N = 612) longitudinal sample in a teacher education program, we compared how three methods of personality scoring—manifest mean scores, correlated‐factors model scores, and bifactor model scores—predict academic achievement assessed by grade point averages. Furthermore, we compared predictiveness across honest responses, applicants' responses and responses collected under laboratory faking‐good instructions. To this end, a real‐life selection setting was part of our study (i.e., applicants to initial teacher education selected, among other things on their personality). We found the expected pattern of manifest mean scores (honest responses were the lowest, applicants' responses higher and faking‐good responses highest) and could demonstrate that applicant faking does not reduce personality assessment's predictiveness. Overall, correlated‐factors model scoring increased the predictiveness of honest and applicants' responses, and scoring via bifactor model even more so. No method of scoring could retrieve the predictiveness in the faking‐good response condition. Regarding the practical application within selection processes, bifactor model scores only slightly outperformed mean scores, and this only occurred in the case of small selection ratios. Nevertheless, we showed that there is criterion‐related and systematic variance within applicants' personality scores above and beyond their personality traits that can be extracted when modeled with bifactor models.