bluuebunny/crossref_metadata_2025 huggingface dataset:
Spesolimab, the first‐in‐class anti‐IL‐36R antibody: From bench to clinic
Authors: Morita Akimichi , Okubo Yukari , Imafuku Shinichi , Terui Tadashi
Published: October 2024

Inflammatory diseases that are driven by several pro‐inflammatory cytokines has resulted in in the development of targeted therapies across different disease settings. Interleukin (IL)‐36 cytokines have been implicated in several inflammatory diseases. In this review we describe the scientific evidence surrounding the use of the IL‐36 receptor (IL‐36R)‐targeting antibody, spesolimab, in IL‐36‐mediated skin diseases: generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP), hidradenitis suppurativa, and Netherton syndrome (NS). Spesolimab, a high affinity, specific, humanized, antagonistic immunoglobulin G1 antibody, targets the IL‐36R at a binding site distinct from its agonists, IL‐36α/β/γ, and at least one endogenous antagonist, IL‐36R antagonist. In vitro and in vivo data for spesolimab show effective inhibition of IL‐36R‐mediated signaling pathways, and six Phase I studies in healthy volunteers presented a favorable safety and pharmacokinetic (PK) profile, leading to the development of a clinical trial program to evaluate spesolimab in the treatment of IL‐36R‐mediated diseases. Six studies (including an expanded access program) have evaluated the efficacy, safety, PKs, and pharmacogenomics of spesolimab in patients with GPP flares. Spesolimab treatment of GPP flares resulted in rapid and sustained improvements in pustular and skin clearance, and clinically significant improvements in patient‐reported symptoms and quality of life. Spesolimab also significantly reduces the risk of GPP flares and flare occurrence, preventing disease worsening and has a favorable safety profile. There have been three trials of spesolimab in PPP; further evaluation is needed to better define those patients who might benefit from the treatment. A trial of spesolimab in NS is ongoing, while other spesolimab trials suggest that IL‐36 may only play a secondary role in the pathogenesis of atopic dermatitis. In conclusion, research into spesolimab has provided much needed insight into the role of IL‐36 in the human immune system and the mechanism behind IL‐36‐mediated inflammatory diseases. Spesolimab provides an efficacious targeted treatment for GPP, a disease with a high unmet medical need.
The Contribution of Hypertensive Disorders of Pregnancy to Neonatal Unit Admissions and Iatrogenic Preterm Delivery at < 34+0 Weeks' Gestation in the UK: A Population‐Based Study Using the National Neonatal Research Database
Authors: Conti‐Ramsden Frances , Fleminger Jessica , Lanoue Julia , Chappell Lucy C. , Battersby Cheryl ,   the UK Neonatal Collaborative
Published: October 2024

Objectives

The objectives of this study were to (i) quantify the contribution of maternal hypertensive disorders of pregnancy (HDP) to iatrogenic preterm birth (PTB) and neonatal unit (NNU) admissions < 34+0 weeks and (ii) describe short‐term population‐level outcomes for HDP infants, exploring ethnic disparities and comparing outcomes by HDP exposure.

Design

Retrospective population‐based study using the National Neonatal Research Database.

Setting

England and Wales.

Population

Infants born < 34+0 weeks and admitted to NNU 2012–2020.

Methods

Descriptive statistics, linear and logistic regression models to compare outcomes between groups.

Main Outcome Measures

Survival to discharge with/without comorbidity.

Results

122 228 infants met inclusion criteria. Where collected, 49 839/114 164 (43.7%, 95% CI 43.4%–43.9%) of infants had an iatrogenic PTB. HDP was recorded in 16 510/122 228 (13.5%) of all infants and 13 560/49 839 (27.2%) of iatrogenic PTBs. HDP and/or foetal growth restriction (FGR) were recorded in 24 124/49 839 (48.4%) of iatrogenic PTBs. Singleton HDP infants < 10th BWC had ≥ 90% survival to discharge from 28 weeks' gestation, versus from 26 weeks' gestation for those born ≥ 10th BWC. In extreme preterm HDP infants (< 27 weeks), 27.3% of infants < 10th BWC died compared to 15.2% of those ≥ 10th BWC. Survival without comorbidity was ≥ 90% from 32 weeks' gestation in HDP infants across BWC.

Conclusions

These contemporaneous population‐level data show that almost one in two PTB < 34+0 weeks' gestation are iatrogenic, with HDP and/or FGR being the major contributors to iatrogenic prematurity. This has substantial implications for strategies to reduce preterm birth in the UK and internationally. The data further inform antenatal and at‐birth counselling of HDP‐exposed infants.
Interaction Between Age Pension Means Testing and Innovative Income Streams in Australia*
Authors: Ai Wenqi , Butt Adam , Khemka Gaurav
Published: October 2024

We investigate the interaction between Age Pension means testing and innovative income streams in Australia, considering the use of an investment‐linked annuity that allows a choice of drawdown level. We find that current means testing arrangements incentivise a very specific usage of investment‐linked annuities that is not materially impacted by individual characteristics or fees, due to incoherencies across the income test and assets test. We investigate alternative means test structures, including a structure that includes only an income test and incorporates capital consumption by adjusting taper rates with age according to an annuitisation schedule. This structure removes the distortions impacting annuity usage, generates the most stable Age Pension over lifetime, encourages drawdown of assets over retirement and more accurately reflects the means of retirees to generate an income at each age.
Job competition in civil service public exams and sick leave behaviour
Authors: Armijos Bravo Grace , Vall Castelló Judit
Published: October 2024

In several countries, a traditional public exam system is the way to secure a job in the civil service. In this setting, candidates have to take and pass exams that involve studying large quantities of material, and this takes up a large amount of time. Candidates who are working while preparing for public exams may find it difficult to find time for both tasks. Thus, they might experience increased stress/anxiety related to the high stakes nature of the civil service recruitment process. In this paper, we investigate the impact of new openings for civil service positions on sickness absences. Using a unique administrative data set on the universe of sickness absences and civil service positions offered in Spain from 2009 to 2015, we find a significant increase in health‐related absences several months before the exam date. In particular, this effect is stronger for individuals working in the educational sector as well as for calls offering a large number of positions. An important element is that our results are mostly driven by stress‐related absences. To corroborate the health‐related origins of our results, we use data on visits to general practitioners and specialists and show a significant deterioration in the health of public‐sector workers. Our results are important from a policy perspective as they highlight the existence of important negative consequences of the civil service recruitment process that have been previously overlooked.
Trade‐offs and synergies: Examining the impact of natural resource rents and energy efficiency on financial development in the RCEP context
Authors: Tang Yuhong , Imran Muhammad
Published: October 2024

This study investigates the complex interplay between financial and economic development within the Regional Comprehensive Economic Partnership (RCEP) countries—Australia, China, Indonesia, Japan, and South Korea—from 2000 to 2022, with a focus on the impacts of natural resource rents and energy efficiency. Employing moment quantile regression to address non‐normal data distribution identified by the Jarque–Bera (JB) test, we unveil diverse slopes and cross‐sectional interdependencies, necessitating a nuanced examination. Panel unit root tests confirm non‐stationarity, enabling a thorough investigation. Our findings reveal a long‐term cointegration relationship between natural resource rents, energy efficiency, economic development, and foreign direct investment (FDI), providing a holistic understanding of their dynamics. Notably, our analysis exposes the trade‐off between natural resource abundance and financial growth, as evidenced by negative coefficients for natural resource rents, while positive coefficients for economic growth, energy efficiency, and FDI counterbalance this effect, fostering a conducive financial environment. Additionally, our examination of location and scale characteristics unveils vulnerabilities associated with natural resources alongside stability indicators linked to economic growth, energy efficiency, and FDI. By employing quantile regression, our study sheds light on the nuanced impacts of natural resources, offering valuable insights for policymakers and researchers in navigating sustainable financial development within the RCEP framework.
Prediction models incorporating second metacarpal cortical index for osteoporosis in rheumatoid arthritis: Externally validated machine learning models developed using data from the KURAMA cohort
Authors: Saito Ryohei , Fujii Takayuki , Murata Koichi , Onishi Akira , Murakami Kosaku , Tanaka Masao , Ohmura Koichiro , Yasuda Tadashi , Morinobu Akio , Matsuda Shuichi
Published: October 2024

Objective

Osteoporosis and osteopenia are significant concerns in rheumatoid arthritis (RA), predisposing patients to fragility fractures. While dual‐energy X‐ray absorptiometry (DXA) is the gold standard for bone mineral density (BMD) assessment, simpler screening tools are needed. This study aims to assess the correlation between the second metacarpal cortical index (2MCI) and BMD in RA patients, and to evaluate machine learning (ML) models utilizing 2MCI and clinical parameters for predicting osteoporosis/osteopenia presence and BMD.

Methods

Data from the KURAMA cohort (n = 302) and an external validation cohort (n = 32) were analyzed. BMD in the hip and forearm was obtained using DXA and 2MCI was calculated from plain hand X‐ray. ML models were trained to predict osteoporosis/osteopenia presence and BMD using 2MCI and clinical variables and validated using external cohort.

Results

2MCI correlated significantly with hip and forearm BMD. ML models incorporating 2MCI and other clinical parameters showed good performance in predicting osteoporosis/osteopenia presence and BMD. External validation demonstrated the generalizability of the models.

Conclusion

ML models utilizing 2MCI and clinical parameters show promise for osteoporosis screening in RA patients.
SimpleMetaPipeline: Breaking the bioinformatics bottleneck in metabarcoding
Authors: Williams Jake , Pettorelli Nathalie , Dowell Rosalie , Macdonald Kenneth , Meyer Christopher , Steyaert Margaux , Tweedt Sarah , Ransome Emma
Published: October 2024

The democratisation of next‐generation sequencing has vastly increased the availability of sequencing data from metabarcoding. However, to effectively prepare these metabarcoding data for subsequent analysis, researchers must consistently apply several different bioinformatic tools—including those which denoise reads, cluster sequences and assign taxonomic identities. This often creates a bioinformatics bottleneck in workflows for non‐specialists due to obstacles around: (a) integrating different tools, (b) the inability to easily modify and rerun bioinformatic pipelines involving non‐scripted (‘point‐and‐click’) elements and (c) the multiple outputs that may be required of a single dataset (e.g. amplicon sequence variants [ASVs] and operational taxonomic units [OTUs]), which often results in users running pipelines multiple times.

Here, we introduce SimpleMetaPipeline, an open‐source bioinformatics pipeline implemented in R, which addresses these obstacles. SimpleMetaPipeline integrates the most robust and commonly used existing bioinformatic tools in a single reproducible pipeline, with a streamlined choice of parameters, to generate a sequence data table containing alternative clustering and assignment options. SimpleMetaPipeline accepts demultiplexed paired‐end and single reads from multiple sequencing runs.

We describe the pipeline and demonstrate how alternative annotations enable the easy implementation of multi‐algorithm agreement tests to strengthen inferences.

SimpleMetaPipeline represents a valuable addition to the existing library of pipelines, providing easy and reproducible bioinformatics, including a range of commonly desired clustering and assignment options, such as OTUs and ASVs.
Two Anthropomorphic Stelae Connected With a Platform‐Like Structure in the Area of Ḥimā (Saudi Arabia): New Data From Southwestern Arabia
Authors: Lischi Silvia , Haquet Jérôme‐François , Schiettecatte Jérémie , Prioletta Alessia
Published: October 2024

Since 2020, the Saudi‐French Archaeological and Epigraphic Mission to Najrān (MAFSN) has been conducting additional archaeological surveys and small‐scale excavations in the Ḥimā area, providing a wealth of data from different historical periods. Preliminary analysis of the structures and artefacts discovered revealed a complex landscape characterised by patterns of continuous human activity from the Palaeolithic to modern times, underlining the historical importance of this area as a transit hub along the caravan routes. The identification of various structures has made it possible to establish a basic typology and enabled a distribution study of the human presence, allowing comparisons with neighbouring regions. This paper presents the discovery of two anthropomorphic stelae associated with a platform‐like structure excavated in November 2021 on the eastern side of Jabal al‐Kawkab, al‑Gharaziyyāt area. The documentation of these stelae lays the groundwork for a re‐evaluation of the Bronze Age occupation of the area.
Cockayne syndrome B protein is implicated in transcription and associated chromatin dynamics in homeostatic and genotoxic conditions
Authors: Liakos Anastasios , Ntakou‐Zamplara Katerina Z. , Angelova Nelina , Konstantopoulos Dimitris , Synacheri Anna‐Chloe , Spyropoulou Zoi , Tsarmaklis Iason A. , Korrou‐Karava Despoina , Nikolopoulos Georgios , Lavigne Matthieu D. , Fousteri Maria
Published: October 2024

The integrity of the actively transcribed genome against helix‐distorting DNA lesions relies on a multilayered cellular response that enhances Transcription‐Coupled Nucleotide Excision Repair (TC‐NER). When defective, TC‐NER is causatively associated with Cockayne‐Syndrome (CS), a rare severe human progeroid disorder. Although the presence of unresolved transcription‐blocking lesions is considered a driver of the aging process, the molecular features of the transcription‐driven response to genotoxic stress in CS‐B cells remain largely unknown. Here, an in‐depth view of the transcriptional and associated chromatin dynamics that occur in CS‐B cells illuminates the role of CSB therein. By employing high‐throughput genome‐wide approaches, we observed that absence of a functional CSB protein results in a delay in transcription progression, more positioned +1 nucleosomes, and less dynamic chromatin structure, compared to normal cells. We found that early after exposure to UV, CS‐B cells released RNA polymerase II (RNAPII) from promoter‐proximal pause sites into elongation. However, the magnitude of this response and the progression of RNAPII were reduced compared to normal counterparts. Notably, we detected increased post‐UV retainment of unprocessed nascent RNA transcripts and chromatin‐associated elongating RNAPII molecules. Contrary to the prevailing models, we found that transcription initiation is operational in CS‐B fibroblasts early after UV and that chromatin accessibility showed a marginal increase. Our study provides robust evidence for the role of CSB in shaping the transcription and chromatin landscape both in homeostasis and in response to genotoxic insults, which is independent of its known role in TC‐NER, and which may underlie major aspects of the CS phenotype.
A retrospective evaluation of SwePEWS use in paediatric patients with COVID‐19 and RSV infection
Authors: Bodlund Julia , Wimmerdahl Albin , Honoré Antoine , Härenstam Karin Pukk , Forsberg David
Published: October 2024

Aim

As early detection of deterioration is a challenge in children, the Swedish Paediatric Early Warning Score (SwePEWS) is used to systematically assess paediatric patients' clinical state. Here, we aimed to evaluate the use and predictive ability of SwePEWS.

Methods

Electronic health records of paediatric patients admitted due to respiratory syncytial virus infection or COVID‐19 were reviewed retrospectively. Registered vital signs were compared to the assigned SwePEWS score and monitored vital sign values to identify discrepancies. Additionally, SwePEWS's ability to predict transfer to the paediatric intensive care unit (PICU) was assessed.

Results

Among 1374 SwePEWS assessments, one‐third were either incomplete or contained errors. Incomplete SwePEWS assessments were more frequent during night‐time. Single measurements of oxygen saturation presented lower values compared to average saturation from continuous monitoring. SwePEWS's ability to predict PICU transfer was low.

Conclusion

There was a surprisingly high occurrence of underestimated SwePEWS scores. This study provides new insights into pitfalls when developing and implementing paediatric early warning scores for systematic re‐evaluations in paediatric patients.
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

Background

The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries.

Aims

To explore the trade‐off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial.

Methods

We 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.

Results

At 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.

Conclusions

Increasing 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 Registration

Clinicaltrials.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 CONTENT

This 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

Background and Purpose

Pathogenic 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 Approach

Wildtype 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 Results

Both 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 Implications

Mutations 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

Academic 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

Alzheimer'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

Remission 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

Objectives

This 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 Methods

Mandible 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.

Results

Group 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).

Conclusions

Sleeveless 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

Background

Manganism, 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.

Objectives

To 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).

Methods

Fifty 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.

Results

ZC 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 Conclusion

ZC 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

Objective

Levodopa‐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.

Methods

We 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.

Results

Compared 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.

Conclusion

PD 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

We 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

Background

Maintaining 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.

Results

Changes 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.

Conclusion

Identifying 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

Pemphigus 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

The 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

Based 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.
Herpes zoster development in living kidney transplant recipients receiving low‐dose rituximab
Authors: Nishida Hayato , Fukuhara Hiroki , Takai Satoshi , Nawano Takaaki , Takehara Tomohiro , Narisawa Takafumi , Kanno Hidenori , Yagi Mayu , Yamagishi Atsushi , Naito Sei , Tsuchiya Norihiko
Published: October 2024

Objectives

We evaluated whether a history of low‐dose rituximab treatment affected herpes zoster development after living kidney transplantation.

Methods

We enrolled 103 living kidney transplant recipients. Patients were divided into two groups according to their history of rituximab treatment; rituximab was administered to 50 living kidney transplant recipients. We assessed the difference in herpes zoster events between the two groups and determined the risk factors for herpes zoster using multivariate regression analysis.

Results

The total dose of rituximab in each kidney transplant recipient who received rituximab therapy was 200–400 mg. The rate of herpes zoster events after transplantation in recipients who received rituximab therapy (4 of 50, 8%) was not higher than that in recipients who did not receive rituximab (9 of 53, 17%) (p = 0.238). Herpes zoster‐free survival did not significantly differ between the two groups (p = 0.409). In the multivariate regression analysis, the association between varicella zoster vaccination before transplantation and herpes zoster events after transplantation was confirmed, whereas rituximab therapy was not associated with herpes zoster events.

Conclusions

Low‐dose rituximab therapy in kidney transplant recipients did not influence herpes zoster development after transplantation. Varicella zoster vaccination before transplantation may play an important role in preventing herpes zoster after transplantation.
Peer‐to‐Peer Human Milk Sharing Through Social Media Groups: The Experiences of Women Donors and Recipients in Hong Kong
Authors: Li Junyan , Ip Hoi Lam , Liao Qiuyan , Lee Jung Jae , Lok Kris Yuet Wan
Published: October 2024

Aim

To explore the lived experience of donors and recipients involved in peer‐to‐peer human milk donation.

Design

An exploratory descriptive qualitative study.

Method

Semi‐structured interviews were conducted between November 2022 and April 2023. A total of 50 women consisting of 34 donors and 16 recipients were recruited using purposive sampling from specific social media groups in Hong Kong that focus on breast milk donation and sharing. Data were analysed based on thematic analysis.

Results

Five key themes were identified in this study: Motivation; Milk sharing as a social act; Not a Norm; Recommendation to formal milk banks; and Formal donation as the preferred route.

Conclusion

The findings indicate informal milk sharing is seen as an inferior alternative to formal milk donation systems. The establishment of formal milk banks is viewed as a way to address the shortcomings of informal sharing.

Implications for the Profession

The findings have implications for the healthcare field, particularly in improving the experiences of those involved in informal milk sharing. The insights gained from the experiences of informal milk sharers can directly inform and enhance the services provided by formal milk banks.

Impact

Given the growing prevalence of online informal milk sharing, healthcare professionals should enhance their understanding of this practice. However, the practice has remained understudied, particularly in Asian region. This study brings together the experiences of both milk donors and recipients, providing a comprehensive view on the phenomenon.

Reporting Method

The Standards for Reporting Qualitative Research (SRQR).

Patient or Public Contribution

No patient or public contribution.
Perceived Impact of COVID‐19 in an Underserved Community: A Natural Language Processing Approach
Authors: Holmes Ashleigh , Sachar Amanjot Singh , Chang Yu‐Ping
Published: October 2024

Aim

To utilise natural language processing (NLP) to analyse interviews about the impact of COVID‐19 in underserved communities and to compare it to traditional thematic analysis in a small subset of interviews.

Design

NLP and thematic analysis were used together to comprehensively examine the interview data.

Methods

Fifty transcribed interviews with purposively sampled adults living in underserved communities in the United States, conducted from June 2021 to May 2022, were analysed to explore the impact of the COVID‐19 pandemic on social activities, mental and emotional stress and physical and spiritual well‐being. NLP includes several stages: data extraction, preprocessing, processing using word embeddings and topic modelling and visualisation. This was compared to thematic analysis in a random sample of 10 interviews.

Results

Six themes emerged from thematic analysis: The New Normal, Juxtaposition of Emotions, Ripple Effects on Health, Brutal yet Elusive Reality, Evolving Connections and Journey of Spirituality and Self‐Realisation. With NLP, four clusters of similar context words for each approach were analysed visually and numerically. The frequency‐based word embedding approach was most interpretable and well aligned with the thematic analysis.

Conclusion

The NLP results complemented the thematic analysis and offered new insights regarding the passage of time, the interconnectedness of impacts and the semantic connections among words. This research highlights the interdependence of pandemic impacts, simultaneously positive and negative effects and deeply individual COVID‐19 experiences in underserved communities.

Implications

The iterative integration of NLP and thematic analysis was efficient and effective, facilitating the analysis of many transcripts and expanding nursing research methodology.

Impact

While thematic analysis provided richer, more detailed themes, NLP captured new elements and combinations of words, making it a promising tool in qualitative analysis.

Reporting Method

Not applicable.

Patient or Public Contribution

No patient or public contribution.
Blood Pressure Reduction and Changes in Antihypertensive Medication Use Among Patients With Hypertension Who Initiated Sodium‐Glucose Cotransporter‐2 Inhibitors
Authors: An Jaejin , Sim John J. , Zhou Matt M. , Zhou Hui , Choi Soon Kyu , Brettler Jeffrey W. , Ong‐Su Angeline L. , Reynolds Kristi
Published: October 2024

Sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) have demonstrated a blood pressure (BP) reduction benefit despite other indications for use. We evaluated BP changes and antihypertensive medication use pre‐ and post‐SGLT2i initiation among 12 960 patients with treated hypertension and among subgroups with apparent treatment‐resistant hypertension (aTRH) and/or proteinuria. Post‐SGLT2i initiation, the mean (SD) systolic blood pressure (SBP) was reduced from 133.9 (16.4) to 128.6 (15.5) mmHg and the mean diastolic blood pressure (DBP) was reduced from 70.8 (11.8) to 68.3 (11.3) mmHg among all patients. The mean SBP/DBP reduction was 5.3/2.5, 6.2/2.8, and 6.1/2.9 mmHg among all patients, patients with aTRH, and patients with proteinuria, respectively. Achieved BP < 130/80 mmHg increased by 12.5%, 16.9%, and 11.1% for all patients, patients with aTRH, and patients with proteinuria, respectively. Discontinuation of ≥ 1 antihypertensive medication within 12 months of SGLT2i initiation occurred in 33.4% overall, 47.6% of patients with aTRH, and 38.7% of patients with proteinuria.