bluuebunny/crossref_metadata_2025 huggingface dataset:
Walking for transport and all-cause mortality: a prospective cohort study of Australian community-dwelling older adults
Authors: Shah Shivangi , Chen Yang , Owen Alice , Woods Robyn L , Ryan Joanne , Owen Neville , Wolfe Rory , Dunstan David W , Beck Ben , Britt Carlene , Gasevic Danijela
Published: April 2024

Background

Walking for transport may prolong survival in younger and middle-aged adults; however, evidence for older adults is scarce. We examined a prospective relationship between transport-related walking and all-cause mortality among adults aged 70 years and over.

Methods

Community-dwelling, apparently healthy older adults (n=11 539; mean age 75.1 years, 53.1% females), participants of the ASPirin in Reducing Events in the Elderly Longitudinal Study of Older Persons, reported their frequency of transport-related walking (never, rarely/once a week, more than once a week or every day). All-cause mortality was verified by two independent sources. Cox proportional-hazards models (HR and 95% CI) assessed the association between transport-related walking and all-cause mortality.

Results

Of participants, 44.1% reported walking every day, 31.5% more than once a week, 21.7% rarely or once a week and 2.7% never engaged in transport-related walking. During the median follow-up of 8.6 years (IQR: 7.4–10.1), 1599 participants (13.9%) died. Compared with those who reported never walking for transport, the risk of all-cause mortality was lower for those walking rarely or once a week (HR 0.73, 95% CI 0.56 to 0.96); more than once a week (HR 0.76, 95% CI 0.59 to 0.99) and every day (HR 0.74, 95% CI 0.57 to 0.96). Analyses were adjusted for age, sex, education, smoking, alcohol consumption, living status, rurality, household income, socioeconomic status, chronic conditions, body mass index and overall physical activity levels.

Conclusions

Engaging in any weekly transport-related walking helps older adults prolong survival. Public health campaigns and urban planning should promote and support transport-related walking to boost physical activity levels of older adults and support healthier ageing.
Shared decision-making with athletes: a survey study of healthcare professionals’ perspectives
Authors: Nelis Sofie , Dijkstra Hendrik Paul , Damman Olga Catherina , Farooq Abdulaziz , Verhagen Evert
Published: April 2024

Objectives

Shared decision-making (SDM) is a trending topic in athlete health care; however, little is known about its use in a sports context. This study aimed to measure knowledge and self-perceived practice of SDM among healthcare professionals working with athletes. This study evaluates SDM attitudes and preferences and explores how healthcare professionals perceive the factors influencing SDM.

Methods

A web-based cross-sectional survey with open-ended and closed-ended questions.

Results

Our survey was completed by 131 healthcare professionals. The majority (63.6%) reported to prefer SDM and to be confident in their SDM skills (81.1%). Despite this inclination and confidence, only one in four clinicians reported consistent practice of SDM when feasible. Additionally, most clinicians lacked SDM knowledge. The barriers perceived by healthcare professionals included time constraints (17.6%), limited patient knowledge (17.6%), limited patient motivation (13.5%) and language barriers (16.2%). Importantly, two-thirds of the participants believed that SDM in athlete health care differs from SDM in non-athletes due to the high-pressure environment, the tension between performance and health, and the involvement of multiple stakeholders with potentially conflicting interests.

Conclusions

Although healthcare professionals preferred SDM, they did not fully understand nor routinely practice it. Most healthcare professionals perceive SDM in athlete health care to differ from SDM in the general population. Therefore, to inform the implementation of SDM in athlete health care, future research is crucial to understand better what makes practising SDM unique in this setting.
Incidence and risk factors for development of left ventricular hypertrophy in Fabry disease
Authors: Monda Emanuele , Bakalakos Athanasios , Lachmann Robin , Syrris Petros , Limongelli Giuseppe , Murphy Elaine , Hughes Derralynn , Elliott Perry Mark
Published: April 2024

Background

Left ventricular hypertrophy (LVH) is the principal cardiac manifestation of Fabry disease (FD). This study aimed to determine the incidence and predictors of LVH development in a contemporary cohort of patients with FD and no LVH at baseline evaluation.

Methods

Consecutively referred adult (aged ≥16 years) patients with FD were enrolled into an observational cohort study. Patients were prospectively followed in a specialist cardiomyopathy centre and the primary endpoint was the first detection of LVH (left ventricular mass index (LVMi) ≥115 g/m2in men and ≥95 g/m2in women).

Results

From a cohort of 393 patients, 214 (aged 35.8±13.8 years; 61 (29%) males) had no LVH at first evaluation. During a median follow-up of 9.4 years (IQR 4.7–12.7), 55 patients (24.6%) developed LVH. The estimated incidence of LVH was 11.3% (95% CI 6.5% to 16.1%) at 5 years, 29.1% (95% CI 21.5% to 36.7%) at 10 years and 45.0% (95% CI 33.8% to 62.4%) at 15 years of follow-up. On multivariable analysis, independent predictors for LVH development were age (HR 1.04 (95% CI 1.02 to 1.06) per 1-year increase, p<0.001), male sex (HR 2.90 (95% CI 1.66 to 5.09), p<0.001) and an abnormal ECG (HR 3.10 (95% CI 1.72 to 5.57), p<0.001). The annual rate of change in LVMi was +2.77 (IQR 1.45–4.62) g/m2/year in males and +1.38 (IQR 0.09–2.85) g/m2/year in females (p<0.001).

Conclusions

Approximately one-quarter of patients with FD developed LVH during follow-up. Age, male sex and ECG abnormalities were associated with a higher risk of developing LVH in patients with FD.
‘The book’s a conversation starter’: a realist exploration of the salutogenic potential of reading for pleasure
Authors: Sirisena Mihirini , Lhussier Monique , Kaner Eileen , Wearn Angela , Gray Joanne , James Rebecca , Redgate Sam
Published: April 2024

Reading for Wellbeing (RfW) is a pilot initiative, aimed at improving mental health and well-being through supporting access and increasing opportunities to read for pleasure. RfW was implemented across six North-East local authorities in England and employed Community Reading Workers to support access to books and reading for targeted populations. The current study used realist methodology to understand context, potential mechanisms of action, acceptability and reported outcomes. Data generation and analysis were conducted iteratively, using focus groups, interviews and observations.

The analysis of the collated data highlighted that a positive attitude towards reading and a desire for social connections were significant motivators for engagement with RfW. This paper postulates eight programme theories relating to that context, which describe key mechanisms within RfW linked to engagement with reading, well-being, connections and practice. The paper concludes that previous notions of positivity associated with reading for pleasure enable participants to experience RfW as a positive social encounter. This positive social encounter enhances participants’ multiple resistance resources such as increased sense of self-efficacy and connectedness that could impact on their sense of well-being.
Changes in haemoglobin and ferritin levels during basic combat training: relevance for attrition and injury frequency
Authors: Taube Fabian , Larsson I , Navren M , Ekblom Ö
Published: April 2024

Introduction

The primary aim of the present study was to assess interindividual and intraindividual variations in haemoglobin and ferritin concentrations in Swedish recruits over 5 months of basic combat training (BCT). The secondary aim was to find predictors for missing training (a precursor for attrition) and overuse injuries during BCT.

Methods

In a cohort design, a total of 58 female and 104 male recruits provided complete data. We assessed the ferritin concentrations and haemoglobin concentrations at baseline and after 5 months of BCT and physical work capacity at baseline.

Results

During BCT, haemoglobin concentrations increased significantly in both females and males. Ferritin concentrations decreased significantly in both sexes and the prevalence of iron deficiency (ID) (ie, ferritin levels <30 µg/L) increased significantly in females. The physical work capacity at baseline was related to the risk of missing training in fully adjusted models. In gender-adjusted analyses, baseline ferritin was related to the risk of overuse injury, but neither baseline nor change in iron status was related to injuries or risk of missing training when controlling for confounders. Body mass increased significantly in both genders, but we found no correlation between individual change in body mass and change in haemoglobin or ferritin nor was change in body mass related to the risk of overuse injury or missing training.

Conclusion

In the present study, the prevalence of ID increased over the course of 5 months, while haemoglobin concentrations increased. As baseline physical work capacity was related to missing training, there are reasons to support preparatory physical training before BCT. These findings may inform future preventive interventions aimed at preventing detrimental effects of ID.
Thyroid disease in ANCA-associated vasculitis: a clinical and epidemiological study
Authors: Wilding Anna , Smith Rona , Jayne David , Segelmark Mårten , Mohammad Aladdin J
Published: April 2024

Objectives

To describe clinical and laboratory characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and thyroid disease (TD). We also aimed to calculate incidence and identify predictors of TD in two large cohorts of patients with AAV.

Methods

The study comprised 644 patients with AAV in a population-based cohort from southern Sweden (n=325) and a cohort from a specialised vasculitis centre in Cambridge, UK (n=319). Diagnosis and classification of AAV and TD were confirmed by medical record review. Person-years (PY) of follow-up were calculated from AAV diagnosis to the earliest of TD, death or the end of study. Cox-regression analysis was employed to study predictors of TD.

Results

At AAV diagnosis, 100 individuals (15.5%, 77 females) had TD, 59 had myeloperoxidase (MPO)-ANCA+ and 34 had proteinase-3 (PR3)-ANCA+. Patients with TD tended to have lower C reactive protein, lower haemoglobin and fewer constitutional symptoms. Survival and renal survival was greater in those patients with AAV with pre-existing TD. During 4522 PY of follow-up, a further 29 subjects developed TD, yielding an incidence rate of 641/100 000 PY. No analysed factor predicted de novo TD in AAV. The prevalence of TD among patients with AAV in southern Sweden was 18%.

Conclusion

TD is a common comorbidity in AAV, affecting nearly one in five. While TD diagnosis is more common in females and MPO-ANCA+, these factors do not predict de novo TD after initiation of AAV treatment, necessitating monitoring of all patients with AAV with respect to this comorbidity.
Biomarkers of metal exposure in adolescent e-cigarette users: correlations with vaping frequency and flavouring
Authors: Kochvar Andrew , Hao Gary , Dai Hongying Daisy
Published: April 2024

Background

Youth vaping poses a significant public health concern as metals have been detected in e-cigarette aerosols and liquids. This study investigated factors associated with biomarkers of metal exposure.

Methods

Data were drawn from Wave 5 of the Population Assessment of Tobacco and Health (PATH) Study Youth Panel, a nationally representative sample of US adolescents aged 13–17 years. Urinary biomarkers of exposure to cadmium, lead, and uranium were assessed by vaping frequency (occasional (1–5 days), intermittent (6–19 days), and frequent (20+ days)) in the past 30 days and flavour type (menthol/mint, fruit, and sweet).

Results

Among 200 exclusive e-cigarette users (median age 15.9 years, 62.9% female), 65 reported occasional use, 45 reported intermittent use, and 81 reported frequent use. The average number of recent puffs per day increased exponentially by vaping frequency (occasional: 0.9 puffs, intermittent: 7.9 puffs, frequent: 27.0 puffs; p=0.001). Both intermittent (0.21 ng/mg creatinine) and frequent users (0.20 ng/mg creatinine) had higher urine lead levels than occasional users (0.16 ng/mg creatinine). Frequent users also had higher urine uranium levels compared with occasional users (0.009 vs 0.005 ng/mg creatinine, p=0.0004). Overall, 33.0% of users preferred using menthol/mint flavours, 49.8% fruit flavours, and 15.3% sweet flavours. Sweet flavour users had higher uranium levels compared with menthol/mint users (0.009 vs 0.005 ng/mg creatinine, p=0.02).

Conclusions

Vaping in early life could increase the risk of exposure to metals, potentially harming brain and organ development. Regulations on vaping should safeguard the youth population against addiction and exposure to metals.
Postselected communication over quantum channels
Authors: Ji Kaiyuan , Regula Bartosz , Wilde Mark M.
Published: April 2024

The single-letter characterization of the entanglement-assisted capacity of a quantum channel is one of the seminal results of quantum information theory. In this paper, we consider a modified communication scenario in which the receiver is allowed an additional, “inconclusive” measurement outcome, and we employ an error metric given by the error probability in decoding the transmitted message conditioned on a conclusive measurement result. We call this setting postselected communication and the ensuing highest achievable rates the postselected capacities. Here, we provide a precise single-letter characterization of postselected capacities in the setting of entanglement assistance as well as the more general nonsignaling assistance, establishing that they are both equal to the channel’s projective mutual information — a variant of mutual information based on the Hilbert projective metric. We do so by establishing bounds on the one-shot postselected capacities, with a lower bound that makes use of a postselected teleportation-based protocol and an upper bound in terms of the postselected hypothesis testing relative entropy. As such, we obtain fundamental limits on a channel’s ability to communicate even when this strong resource of postselection is allowed, implying limitations on communication even when the receiver has access to postselected closed timelike curves.
Global Path Planning Algorithm in a Two-Dimensional Environment with Polygonal Obstacles on the Class of Piecewise Polygonal Trajectories
Authors: Kostyukov Vladimir , Medvedev Mikhail , Pshikhopov Viacheslav
Published: April 2024

The paper discusses a motion planner with increased performance in relation to a number of common planning algorithms for maps with obstacles of complex shapes. An algorithm is substantiated for searching for the optimal path in terms of length in the class of piecewise broken curves on a special graph that combines some characteristic points of each obstacle. An estimate of the improved upper bound on the complexity of the algorithm as a function of the number of obstacles is given. Theoretical calculations are confirmed by the results of numerical simulation.
Molecular Dynamics Simulations on Epoxy Resin Composite via Grafting Acryloyl-chloride to Inhibit Electron Transport and Improve Thermal-mechanical Properties
Authors: Li Shuang Cui , Liu Guan Yu , Wang Juan , Liu Zhi Hai , Wang Lei
Published: April 2024

Electrical, thermal, and mechanical properties of cross-linked epoxy resin (EP) modified by the chemical grafting of acryloyl chloride (AC) were studied to explore the trapping mechanism of charge transport inhibition. The bound state traps deriving from grafted molecules were analyzed by first-principles calculations combined with electron transmission spectra to study the underlying mechanism of the electrical properties. In contrast to pure EP, the EP-graft-AC (EP-g-AC) represents significantly depressed conductivity due to the electron scattering from polar-groups of the grafted AC molecule. The substantial deep traps are generated in EP-g-AC molecules by the polar group of grafted AC and accordingly decrease charge mobility and raise the charge injection barrier, consequently suppressing space charge accumulation and charge carrier transport. EP-g-AC polymer acquires a significant amelioration in thermal and mechanical properties, as indicated by the higher cohesive energy density, glass transition temperature, and decomposition temperature in consistence with the lower thermal vibrations compared with pure EP polymer, except that the resulting higher fractional free volume is not preferable, which is attributed to the mixing incompatibility of the grafted AC molecules with EP molecular-chains.
Influence of Chromium Carbide-Derived Carbon Support and Ceria Nanocrystals on Pt–CeO2/C Catalysts for Fuel Cell Applications
Authors: Quí Vinh Nguyen Huy , Nerut Jaak , Kasuk Heili , Thomberg Thomas , Romann Tavo , Aruväli Jaan , Külaviir Marian , Paaver Peeter , Kochovski Zdravko , Härk Eneli , Lust Enn
Published: April 2024

The influence of different synthesis parameters on CeO2 and Pt nanoparticle (NP) deposition on Ketjenblack carbon (C(KB)) was examined. The Pt NP diameter (3.1–4.1 nm) was not influenced by CeO2 synthesis parameters. The CeO2 NPs synthesized using ultrasound sonication contribute to a better durability of the Pt–CeO2/C against CO poisoning. In contrast, CeO2 synthesized using the microwave heating method contributes to better methanol oxidation reaction (MOR) activity at low electrode potential. Synthesis parameters of CeO2 and Pt NPs developed for the C(KB)-based catalysts were applied for C(Cr3C2)-based catalysts. The Pt NP diameter of C(Cr3C2)-based catalysts was slightly higher (7.2 nm) as some Pt NPs were agglomerated. The C(Cr3C2) support facilitates the MOR and CO stripping, especially in the case of the Pt/C on C(Cr3C2) support. The MOR activity at 0.85 V of Pt NPs on the C(Cr3C2) support is as good as the MOR activity for the best Pt–CeO2 on the C(KB) support. The C(Cr3C2) support also improves the CO removal from the Pt surface. All the synthesized catalysts had better MOR activity than the commercial Pt/C(Vulcan) catalyst. The oxygen reduction reaction activity of Pt–CeO2/C catalysts with higher CeO2 content synthesized with the microwave heating method was very good.
Novel SLC18A2 Variant in Infantile Dystonia‐Parkinsonism Type 2
Authors: Kaasalainen Sakari , Arikka Harri , Martikainen Mika H. , Kaasinen Valtteri
Published: April 2024

Infantile dystonia‐parkinsonism type 2 (PKDYS2) is a rare inherited autosomal recessive movement disorder with onset in infancy. The disease is associated with a mutation in the solute carrier family 18 member A2 gene (SLC18A2). There are reports of trials with dopaminergic drugs and the condition of patients given levodopa almost always worsens and dopamine agonists give varying degrees of benefit to some. Here, we report a PKDYS2 patient with a new variant in the SLC18A2 gene who underwent multiple trials of pharmacotherapy. The abnormalities in development and neurological examination of the case were first noted at the age of 2 months, and after a series of treatment attempts (e.g., with antiepileptics) and diagnostic procedures, the diagnosis of PKDYS2 was determined when whole exome sequencing (WES) at age 6, revealed a homozygous pathologic variant NM_003054.4:c.1107dup, p.(Val370Serfs ∗91) in the SLC18A2 gene. The patient then received treatment with multiple dopaminergic drugs (e.g., levodopa, pramipexole, and methylphenidate). The patient with PKDYS2 harbored a new variant in SLC18A2. The phenotype of the patient resembles that of some previously reported patients with PKDYS2. The patient received minor benefits from certain dopaminergic drugs, such as pramipexole, but side effects led to the discontinuation of tested medications.
Water Absorption, Thermal, and Mechanical Properties of Bamboo Fiber with Chopped Glass Fiber Filler-Reinforced Polyester Composites
Authors: Alfeki Mohammed Abdulkedir , Feyissa Ephrem Assefa
Published: April 2024

This study explores the investigations of bamboo fiber-reinforced polyester composites with chopped glass fiber (CGF) filler, focusing on addressing the challenges of low mechanical properties, limited thermal stability, and high moisture absorption. The two types of composites were fabricated using the hand layup method, that is, long unidirectional 0° bamboo fiber (BF) and randomly oriented short bamboo fiber (BP) reinforced a polyester matrix with chopped glass fiber (CGF) filler. By incorporating CGF filler, significant improvements in mechanical properties were achieved across both types of bamboo fiber, surpassing the limitations of unfilled composites. Notably, the composite formulation consisting of 40% wt. of unidirectional 0° BF and 5% wt. of CGF filler exhibited superior ultimate tensile strength, flexural strength, impact strength, water absorption, and thermal stability. This composite demonstrated remarkable enhancements, with increases of up to 131.22 MPa, 128.76 MPa, 113.3 kJ/m2, 1.94% water absorption, and up to 255°C (representing a 10% improvement) in thermal stability compared to the unfilled composite. Statistical analysis revealed quadratic models for the mechanical properties of long unidirectional 0° bamboo fiber composites, while water absorption exhibited a linear two-factor interaction model. For randomly oriented short bamboo fiber, the models for tensile, flexural, and water absorption properties were linear, while the impact energy model showed a quadratic relationship. These statistical models provide valuable insights into predicting the properties of bamboo fiber-reinforced polyester composites. This research underscores the significance of bamboo fiber-reinforced polyester composites in wall partition systems. This study paves the way for improved performance in these areas. The findings highlight the potential of incorporating CGF filler, enabling enhanced mechanical strength, increased thermal stability, and improved resistance to moisture-related issues. The derived statistical models offer valuable guidance for predicting the properties of these composites, facilitating their application and adoption in the construction industry.
Hsa_circ_0051908 Promotes Hepatocellular Carcinoma Progression by Regulating the Epithelial–Mesenchymal Transition Process
Authors: Wu Yinbing , Tang Huafei , Cui Shuzhong , Liao Quanxing , Zeng Lisi , Tu Yinuo
Published: April 2024

Background/Aims. Circular RNAs (circRNAs) are often used for tumor diagnosis and treatment owing to their high stability, high expression abundance, and strong tissue specificity. The role of hsa_circ_0051908, a newly reported circRNA, in the development of hepatocellular carcinoma (HCC) is unknown. Materials and Methods. Hsa_circ_0051908 expression was determined using RT‐qPCR. HCC cell proliferation, apoptosis, invasion, and migration were assessed using CCK‐8 assay, EdU staining, TUNEL staining, flow cytometry, and transwell assay. The molecular mechanism was analyzed using western blotting. In addition, the role of hsa_circ_0051908 in tumor growth was evaluated in vivo. Results. Hsa_circ_0051908 expression was increased in both HCC tissues and cell lines. The proliferation, migration, and invasion of HCC cells were significantly decreased after hsa_circ_0051908 knockdown, while cell apoptosis was notably increased. Furthermore, we found that hsa_circ_0051908 silencing downregulated vimentin and Snail and upregulated E‐cadherin. In vivo, hsa_circ_0051908 silencing significantly inhibited the growth of the tumor. Conclusions. Our data provide evidence that hsa_circ_0051908 promotes HCC progression partially by mediating the epithelial–mesenchymal transition process, and it may be used for HCC treatment.
Enhancing CsSn0.5Ge0.5I3 Perovskite Solar Cell Performance via Cu2O Hole Transport Layer Integration
Authors: Rayhan Abu , Khan M. A. , Islam Md. Rabiul
Published: April 2024

Perovskite solar cells (PSCs) have emerged as a promising alternative to traditional silicon solar cells due to their low cost of fabrication and high power conversion efficiency (PCE). The utilization of lead halide perovskites as absorber layers in perovskite solar cells has been impeded by two major issues: lead poisoning and stability concerns. These hindrances have greatly impeded the industrialization of this cutting-edge technology. In light of the harmful effects of lead in perovskite solar cells, researchers have shifted their attention to exploring lead-free metal halide perovskites. However, the present alternatives to lead-based perovskite exhibit poor performance, thus prompting further inquiry into this matter. The primary objective of this research is to investigate the use of Cu2O as a hole transport layer in combination with lead-free metal halide perovskite (CsSn0.5Ge0.5I3) to achieve superior performance. Through meticulous experimentation, the suggested model has achieved outstanding results by optimizing several key variables. These variables include the thickness of the absorber layer (CsSn0.5Ge0.5I3), defect density, and doping densities, as well as the back contact work function and the operating temperature associated with each layer. The proposed FTO/PC60BM/CsSn0.5Ge0.5I3/Cu2O/Au solar cell structure surpassed prior configurations by comprehensively examining key aspects such as absorber layer thickness and defect density, doping densities, and back contact work. The structure has been also compared with multiple electron transport elements and concluded that the proposed model functions superior due to the use of PC60BM as an electron transport layer and it has an improved electron extraction procedure. Finally, the proposed model has achieved the optimized values as Jsc of 31.56 mA/cm-2, Voc of 1.12 V, FF of 81.47%, and PCE of 27.72%. As a consequence of this research, the investigated structure may be an excellent contender for the eventual creation of lead-free solar power cells made from perovskite.
Supplementary Table 3 from A Phase I Study of KIN-3248, an Irreversible Small-molecule Pan-FGFR Inhibitor, in Patients with Advanced FGFR2/3-driven Solid Tumors
Authors: Garmezy Benjamin , Borad Mitesh J. , Bahleda Rastilav , Perez Cesar A. , Chen Li-Tzong , Kato Shumei , Oh Do-Youn , Severson Paul , Tam Betty Y. , Quah Cheng S. , Harding James J.
Published: April 2024

Supplemental Table 3 - Summary of Pharmacokinetic Parameters of KIN-3248 (Cycle 1 Day 1)
Supplementary Figure 3 from A Phase I Study of KIN-3248, an Irreversible Small-molecule Pan-FGFR Inhibitor, in Patients with Advanced FGFR2/3-driven Solid Tumors
Authors: Garmezy Benjamin , Borad Mitesh J. , Bahleda Rastilav , Perez Cesar A. , Chen Li-Tzong , Kato Shumei , Oh Do-Youn , Severson Paul , Tam Betty Y. , Quah Cheng S. , Harding James J.
Published: April 2024

Supplemental Figure 3 - Serum Phosphate Over Time by KIN-3248 Dose Level
Biallelic Deletion of PEX26 Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease
Authors: Yalçınkaya Burhanettin , Sağlam Kübra Adanur , Terali Kerem , Tekin Emine , Taslak Hava , Türkyılmaz Ayberk
Published: April 2024

Introduction: Peroxisome biogenesis disorders (PBDs) encompass a group of diseases marked by clinical and genetic heterogeneity. Phenotypes linked to PBDs include Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease (IRD), rhizomelic chondrodysplasia punctata type 1, and Heimler syndrome. PBD phenotypes manifest through hypotonia, developmental delay, facial dysmorphism, seizures, liver dysfunction, sensorineural hearing loss, and retinal dystrophy. Methods: The proband underwent comprehensive clinical evaluation, followed by whole-exome sequencing (WES) coupled with copy number analysis (CNV), aimed at identifying potential disease-causing variants aligning with the observed phenotype. Results: Our findings detail an individual exhibiting developmental delay, hearing loss, visual impairment, hepatomegaly, and splenomegaly, attributed to a biallelic deletion of exon 4 in the PEX26 gene. The WES analysis of the index case did not uncover any pathogenic/likely pathogenic single-nucleotide variations that could account for the observed clinical findings. However, the CNV data derived from WES revealed a homozygous deletion in exon 4 of the PEX26 gene (NM_001127649.3), providing a plausible explanation for the patient’s clinical features. The exon 4 region of PEX26 encodes the transmembrane domain of the protein. The transmembrane domain plays a crucial role in anchoring the protein within lipid bilayers, and its absence can disrupt proper localization and functioning. As a result, this structural alteration may impact the protein’s ability to facilitate essential cellular processes related to peroxisome biogenesis and function. Conclusion: The index patient, which presented with hearing loss, retinal involvement and hepatic dysfunction in adolescence age, has atypical clinical course that can be considered unusual for Zellweger syndrome (ZS) and IRD phenotypes, and its rare genotypic data (in-frame single exon deletion) expands the PBD disease spectrum. This study revealed for the first time that PEX26 protein transmembrane domain loss exhibits an unusual course with clinical findings of IRD and ZS phenotypes. WES studies, incorporating CNV analyses, empower the identification of novel genetic alterations in genes seldom associated with gross deletion/duplication variations, such as those in the PEX26 gene. This not only enhances diagnostic rates in rare diseases but also contributes to broadening the spectrum of causal mutations.
Eine pathogene De-novo-BRCA1-Variante bei einer 29-jährigen Frau mit tripel-negativem Brustkrebs
Authors: Gebhart Paulina , Tan Yen , Muhr Daniela , Stein Christina , Singer Christian
Published: April 2024

Einleitung: Pathogene Keimbahnvarianten der Gene BRCA1 und BRCA2 führen zu einem stark erhöhten Lebenszeitrisiko für Brust- und Eierstockkrebs. Diese Varianten werden in der Regel vererbt, und Berichte über ein De-novo-Auftreten sind sehr selten. Falldarstellung: Wir berichten über eine Brustkrebspatientin mit der De-novo-BRCA1-Variante c.121C>T (p.His41Tyr). Die pathogene Variante wurde in der Leukozyten-DNA einer Patientin mit negativer Familienanamnese entdeckt, bei der sich ein früh einsetzender tripel-negativer Brustkrebs entwickelt hatte. Die Variante wurde in keinem der untersuchten mütterlichen und väterlichen Gewebe gefunden, aber sie wurde in mehreren Proben aus allen drei Keimblättern der betroffenen Trägerin nachgewiesen, was einen somatischen Mosaizismus unwahrscheinlich macht. Schlussfolgerung: Dieser Fall unterstreicht, wie wichtig es ist, auch bei Patienten ohne Familienanamnese einen frühen Krankheitsbeginn und eine Tripel-Negativität des Tumors als Kriterien für einen Gentest zu berücksichtigen. In Anbetracht der Verfügbarkeit wirksamer Brustkrebstherapien bei Patientinnen mit pathogenen Varianten in den BRCA-Genen unterstreicht dieser Befund die Bedeutung von Gentests bei Brustkrebspatientinnen.
Moving from Insulin Substitution to the Treatment of the Underlying Autoimmune Disease in Type 1 Diabetes
Authors: Weiskorn Jantje , Danne Thomas
Published: April 2024

Currently, a paradigm change occurs in type 1 diabetes from insulin substitution to the treatment of the underlying autoimmune disease. Teplizumab, a humanized monoclonal anti-CD3 antibody, is the first FDA-approved disease-modifying treatment of preclinical stage 2 diabetes. Research of drugs like golimumab, a monoclonal antibody specific for TNF alpha, baricitinib, a tyrosine kinase inhibitor, or frexalimab, a monoclonal antibody against the CD40 ligand, is still ongoing. Repurposing drugs that have been used in other indications like the calcium channel blocker verapamil, antithymocyte globulin (ATG), an antibody preparation used in solid organ transplantation, glucagon-like peptide-1 agonists utilized in type 2 diabetes and obesity, or the antiviral drugs pleconaril and ribavirin have shown positive effects in preserving beta-cell function. While new therapies to halt autoimmunity and restore beta cells in stages one to three are being developed, replacing beta-cell function via inducible pluripotent stem cells have shown glucose control and insulin independence in long-standing type 1 diabetes, albeit with concomitant immunosuppression. Multicenter multinational initiatives developing a clinical trial network like INNODIA or a research platform with the goal of stopping type 1 diabetes in its early stages like EDENT1FI will be instrumental to study these new strategies.
Ciclo progresista e inclusión en la educación superior en Ecuador
Authors: Unda-Lara René , Llanos-Erazo Daniel , Bustillos-Caranqui Joselyn , Guananga Dennis , Rivadeneira-Peñafiel Jessica
Published: April 2024

(analytical)This analysis examines the tendencies on the academic production regarding inclusion at Higher Education at Ecuador as from de irruption of the progressive cicle (2007-2017). The results show that the points of research interest focus on the institutional reforms, the economic policies, the free access, the disabilities, and the interculturality. It has been done a systematic revision of 26 academic papers published between 2017 and 2022, and complementary literature of normative and contextual nature. It's concluded that the implemented policies during the progressive cicle establish a significant twist, not exempt of tensions, regarding the extension of rights, as well as signals of significant differences about college inclusion among the progressive and the post progressive cicle, in reference to the sense, character and management of Higher Education policies.
Immunomodulatory Activity of Cytokines in Hypertension: A Vascular Perspective
Authors: dos Passos Rinaldo R. , Santos Cintia V. , Priviero Fernanda , Briones Ana M. , Tostes Rita C. , Webb R. Clinton , Bomfim Gisele F.
Published: April 2024

Cytokines play a crucial role in the structure and function of blood vessels in hypertension. Hypertension damages blood vessels by mechanisms linked to shear forces, activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, oxidative stress, and a proinflammatory milieu that lead to the generation of neoantigens and damage-associated molecular patterns, ultimately triggering the release of numerous cytokines. Damage-associated molecular patterns are recognized by PRRs (pattern recognition receptors) and activate inflammatory mechanisms in endothelial cells, smooth muscle cells, perivascular nerves, and perivascular adipose tissue. Activated vascular cells also release cytokines and express factors that attract macrophages, dendritic cells, and lymphocytes to the blood vessels. Activated and differentiated T cells into Th1, Th17, and Th22 in secondary lymphoid organs migrate to the vessels, releasing specific cytokines that further contribute to vascular dysfunction and remodeling. This chronic inflammation alters the profile of endothelial and smooth muscle cells, making them dysfunctional. Here, we provide an overview of how cytokines contribute to hypertension by impacting the vasculature. Furthermore, we explore clinical perspectives about the modulation of cytokines as a potential therapeutic intervention to specifically target hypertension-linked vascular dysfunction.
International Migration and Cardiovascular Health: Unraveling the Disease Burden Among Migrants to North America and Europe
Authors: Agyemang Charles , van der Linden Eva L. , Chilunga Felix , van den Born Bert‐Jan H.
Published: April 2024

Europe and North America are the 2 largest recipients of international migrants from low‐resource regions in the world. Here, large differences in cardiovascular disease (CVD) morbidity and death exist between migrants and the host populations. This review discusses the CVD burden and its most important contributors among the largest migrant groups in Europe and North America as well as the consequences of migration to high‐income countries on CVD diagnosis and therapy. The available evidence indicates that migrants in Europe and North America generally have a higher CVD risk compared with the host populations. Cardiometabolic, behavioral, and psychosocial factors are important contributors to their increased CVD risk. However, despite these common denominators, there are important ethnic differences in the propensity to develop CVD that relate to pre‐ and postmigration factors, such as socioeconomic status, cultural factors, lifestyle, psychosocial stress, access to health care and health care usage. Some of these pre‐ and postmigration environmental factors may interact with genetic (epigenetics) and microbial factors, which further influence their CVD risk. The limited number of prospective cohorts and clinical trials in migrant populations remains an important culprit for better understanding pathophysiological mechanism driving health differences and for developing ethnic‐specific CVD risk prediction and care. Only by improved understanding of the complex interaction among human biology, migration‐related factors, and sociocultural determinants of health influencing CVD risk will we be able to mitigate these differences and truly make inclusive personalized treatment possible.
Comprehensive Review of Tenecteplase for Thrombolysis in Acute Ischemic Stroke
Authors: Wang Liyuan , Hao Manjun , Wu Na , Wu Shuangzhe , Fisher Marc , Xiong Yunyun
Published: April 2024

Although intravenous thrombolysis with alteplase remains the primary treatment for acute ischemic stroke, tenecteplase has shown potential advantages over alteplase. Animal studies have demonstrated the favorable pharmacokinetics and pharmacodynamics of tenecteplase. Moreover, it is easier to administer. Clinical trials have demonstrated that tenecteplase is not inferior to alteplase and may even be superior in cases of acute ischemic stroke with large vessel occlusion. Current evidence supports the time and cost benefits of tenecteplase, suggesting that it could potentially replace alteplase as the main option for thrombolytic therapy, especially in patients with large vessel occlusion.
Rate of Change in Cardiac Magnetic Resonance Imaging Measures Is Associated With Death in Duchenne Muscular Dystrophy
Authors: Starnes Joseph R. , Xu Meng , George‐Durrett Kristen , Crum Kimberly , Raucci Frank J. , Spurney Christopher F. , Hor Kan N. , Cripe Linda H. , Husain Nazia , Buddhe Sujatha , Gambetta Katheryn , Tamaroff Jaclyn , Slaughter James C. , Markham Larry W. , Soslow Jonathan H.
Published: April 2024

Background

Cardiovascular disease is the leading cause of death among patients with Duchenne muscular dystrophy (DMD). Identifying patients at risk of early death could allow for increased monitoring and more intensive therapy. Measures that associate with death could serve as surrogate outcomes in clinical trials.

Methods and Results

Duchenne muscular dystrophy subjects prospectively enrolled in observational studies were included. Models using generalized least squares were used to assess the difference of cardiac magnetic resonance measurements between deceased and alive subjects. A total of 63 participants underwent multiple cardiac magnetic resonance imaging and were included in the analyses. Twelve subjects (19.1%) died over a median follow‐up of 5 years (interquartile range, 3.1–7.0). Rate of decline in left ventricular ejection fraction was faster in deceased than alive subjects (
P
<0.0001). Rate of increase in indexed left ventricular end‐diastolic (
P
=0.0132) and systolic (
P
<0.0001) volumes were higher in deceased subjects. Faster worsening in midcircumferential strain was seen in deceased subjects (
P
=0.049) while no difference in global circumferential strain was seen. The rate of increase in late gadolinium enhancement, base T1, and mid T1 did not differ between groups.

Conclusions

Duchenne muscular dystrophy death is associated with the rate of change in left ventricular ejection fraction, midcircumferential strain, and ventricular volumes. Aggressive medical therapy to decrease the rate of progression may improve the mortality rate in this population. A decrease in the rate of progression may serve as a valid surrogate outcome for therapeutic trials.
Prevalence of Cardiovascular Conditions After Traumatic Brain Injury: A Comparison Between the Traumatic Brain Injury Model Systems and the National Health and Nutrition Examination Survey
Authors: Pinto Shanti M. , Thakur Bhaskar , Kumar Raj G. , Rabinowitz Amanda , Zafonte Ross , Walker William C. , Ding Kan , Driver Simon , Venkatesan Umesh M. , Moralez Gilbert , Bell Kathleen R.
Published: April 2024

Background

The purpose of this study is to compare the prevalence of self‐reported cardiovascular conditions among individuals with moderate to severe traumatic brain injury (TBI) to a propensity‐matched control cohort.

Methods and Results

A cross‐sectional study described self‐reported cardiovascular conditions (hypertension, congestive heart failure [CHF], myocardial infarction [MI], and stroke) from participants who completed interviews between January 2015 and March 2020 in 2 harmonized large cohort studies, the TBI Model Systems and the National Health and Nutrition Examination Survey. Mixed‐effect logistic regression models were used to compare the prevalence of cardiovascular conditions after 1:1 propensity‐score matching based on age, sex, race, ethnicity, body mass index, education level, and smoking status. The final sample was 4690 matched pairs. Individuals with TBI were more likely to report hypertension (odds ratio [OR], 1.18 [95% CI, 1.08–1.28]) and stroke (OR, 1.70 [95% CI, 1.56–1.98]) but less likely to report CHF (OR, 0.81 [95% CI, 0.67–0.99]) or MI (OR, 0.66 [95% CI, 0.55–0.79]). There was no difference in rate of CHF or MI for those ≤50 years old; however, rates of CHF and MI were lower in the TBI group for individuals >50 years old. Over 65% of individuals who died before the first follow‐up interview at 1 year post‐TBI were >50 years old, and those >50 years old were more likely to die of heart disease than those ≤50 years old (17.6% versus 8.6%).

Conclusions

Individuals with moderate to severe TBI had an increased rate of self‐reported hypertension and stroke but lower rate of MI and CHF than uninjured adults, which may be due to survival bias.
Glycated Hemoglobin Variability Is Associated With Adverse Outcomes in Patients With Heart Failure Irrespective of Diabetic Status
Authors: Xu Xin , Ren Qing‐Wen , Chandramouli Chanchal , Ng Ming‐Yen , Tsang Christopher Tze‐Wei , Tse Yi‐Kei , Li Xin‐Li , Liu Ming‐Ya , Wu Mei‐Zhen , Huang Jia‐Yi , Cheang Iok‐Fai , Yang Jie‐Fu , Wang Fang , Lam Carolyn S.P. , Yiu Kai‐Hang
Published: April 2024

Background

The effect of glycated hemoglobin (HbA
1c
) variability on adverse outcomes in patients with heart failure (HF) is unclear. We aim to investigate the predictive value of HbA
1c
variability on the risks of all‐cause death and HF rehospitalization in patients with HF irrespective of their diabetic status.

Methods and Results

Using a previously validated territory‐wide clinical data registry, HbA
1c
variability was assessed by average successive variability (ASV) or SD of all HbA
1c
measurements after HF diagnosis. Multivariable Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and its corresponding 95% CI. A total of 65 950 patients with HF were included in the study. Over a median follow‐up of 6.7 (interquartile range, 4.0–10.6) years, 34 508 patients died and 52 446 required HF rehospitalization. Every unit increment of variability in HbA
1c
was significantly associated with higher HF rehospitalization (HR ASV, 1.20 [95% CI, 1.18–1.23]) and all‐cause death (HR ASV, 1.50 [95% CI, 1.47–1.53]). Diabetes significantly modified the association between HbA
1c
variability and outcomes (
P
interaction
<0.001). HbA
1c
variability in patients with HF without diabetes conferred a higher risk of rehospitalization (HR ASV, 1.92 [95% CI, 1.70–2.17] versus HR ASV, 1.19 [95% CI, 1.17–1.21]), and all‐cause death (HR ASV, 3.90 [95% CI, 3.31–4.61] versus HR ASV, 1.47 [95% CI, 1.43–1.50] compared with patients with diabetes).

Conclusions

HbA
1c
variability is significantly associated with greater risk of rehospitalization and all‐cause death in patients with HF, irrespective of their diabetic status. These observations were more pronounced in patients with HF without diabetes.
Nanonematicides: production, mechanisms, efficacy, opportunities and challenges
Authors: Abd-Elgawad Mahfouz M.M.
Published: April 2024

Classical methods of using many toxic chemical pesticides for managing plant-parasitic nematodes (PPN) on key crops are inappropriate and have unfavourable consequences on human health and the environment. By contrast, nanotechnology can provide a wide range of alternative applications with additional merits based on nanoparticle (NP) pesticides. Three major categories, i.e., physical, chemical and biological methods, have been generally used for synthesis of nanonematicides. The merits and demerits of these methods are highlighted. The biological method generally involves easy, fast, scalable, cheap and environmentally safe techniques. As nanonematicides can reduce the non-selective use of classical nematicides with their high pollution and unhealthy levels, mechanisms underlying PPN population suppression by these nanonematicides are presented to help in their further optimisation. Nanonematicides are guiding a radical change in their efficacy against PPN, but more attention should be given to secure their clean production and application with cost-effective methods.
Repeated bout effect and muscle damage at variable eccentric exercise intensities in active young men: a longitudinal repeated measures investigation
Authors: Rai A. , Bhati P. , Pal S. , Anand P.
Published: April 2024

Exercise-induced muscle damage (EIMD) and repeated bout effect (RBE) are widely researched across various populations and at various intensities. Despite the existence of vast literature, there is lack of comparison of low versus submaximal versus maximal intensity required for preconditioning. The aim of the study was to compare the muscle damage and RBE at various intensities of eccentric exercise in active young men. Thirty-six healthy, physically active men were recruited and randomly assigned to three different groups low-high (L-H, n = 12), submaximal-high (M-H, n = 12) and maximal-high (H-H, n = 12). All participants performed 2 exercise bouts separated by 14 days. L-H, M-H and H-H groups performed low (10% of 1RM), moderate (50% of 1RM) and high (90% of 1RM) intensity eccentric exercise for knee extensors, respectively, in the 1st bout followed by high (100% of 1RM) intensity in the second bout. Muscle soreness (SOR), thigh circumference (CIR), maximal voluntary isometric contraction (MVIC), range of motion (ROM) and blood lactate (Bl Lac) were measured before, immediately, at 24 h, at 48 h and at 72 h after exercise. A significant effect of time appeared for MVIC (), CIR (), ROM () and Bl Lac (). The bout × time interaction, as well as bout × time × group interaction was also found significant indicating changes in muscle strength and ROM. Circumference changed significantly with a significant bout × group interaction effect . SOR () was significant between the bouts. Therefore, exhibiting attenuation of muscle damage markers after the second bout. Findings of the present study showed that muscle damage was evident at all three intensities. Moreover, it was greater after moderate and high intensity as compared to low intensity eccentric exercise. RBE was elicited after three intensities indicating their role in preconditioning the muscles of active men.