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BackgroundPAI-1 gain-of-function variants promote airway fibrosis and are associated with asthma and with worse lung function in subjects with asthma.ObjectiveWe sought to determine whether the association of a gain-of-function polymorphism in plasminogen activator inhibitor-1 (PAI-1) with airway obstruction is modified by asthma status, and whether any genotype effect persists after accounting for common exposures that increase PAI-1 level.MethodsWe studied 2070 Latino children (8-21y) with genotypic and pulmonary function data from the GALA II cohort. We estimated the relationship of the PAI-1 risk allele with FEV1/FVC by multivariate linear regression, stratified by asthma status. We examined the association of the polymorphism with asthma and airway obstruction within asthmatics via multivariate logistic regression. We replicated associations in the SAPPHIRE cohort of African Americans (n=1056). Secondary analysis included the effect of the at-risk polymorphism on postbronchodilator lung function.ResultsThere was an interaction between asthma status and the PAI-1 polymorphism on FEV1 /FVC (P=.03). The gain-of-function variants, genotypes (AA/AG), were associated with lower FEV1 /FVC in subjects with asthma (β=-1.25, CI: -2.14,-0.35, P=.006), but not in controls. Subjects with asthma and the AA/AG genotypes had a 5% decrease in FEV1 /FVC (P

BackgroundYounger maternal age at birth is associated with increased risk of asthma in offspring in European descent populations, but has not been studied in Latino populations.ObjectivesWe sought to examine the relationship between maternal age at birth and prevalence of asthma in a nationwide study of Latino children.MethodsWe included 3473 Latino children aged 8-21 years (1696 subjects with physician-diagnosed asthma and 1777 healthy controls) from five US centres and Puerto Rico recruited from July 2008 through November 2011. We used multiple logistic regression models to examine the effect of maternal age at birth on asthma in offspring overall and in analyses stratified by ethnic subgroup (Mexican American, Puerto Rican and other Latino). Secondary analyses evaluated the effects of siblings, acculturation and income on this relationship.ResultsMaternal age < 20 years was significantly associated with decreased odds of asthma in offspring, independent of other risk factors (OR = 0.73, 95% CI: 0.57-0.93). In subgroup analyses, the protective effect of younger maternal age was observed only in Mexican Americans (OR = 0.53, 95% CI: 0.36, 0.79). In Puerto Ricans, older maternal age was associated with decreased odds of asthma (OR = 0.65, 95% CI: 0.44-0.97). In further stratified models, the protective effect of younger maternal age in Mexican Americans was seen only in children without older siblings (OR = 0.44, 95% CI: 0.23-0.81).Conclusion and clinical relevanceIn contrast to European descent populations, younger maternal age was associated with decreased odds of asthma in offspring in Mexican American women. Asthma is common in urban minority populations but the factors underlying the varying prevalence among different Latino ethnicities in the United States is not well understood. Maternal age represents one factor that may help to explain this variability.

Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children. Our study population consisted of 1227 (812 asthma cases, 415 controls) African American children with genome-wide single nucleotide polymorphism (SNP) data. Logistic regression was used to identify associations between SNP genotype and asthma status. We identified a novel variant in the PTCHD3 gene that is significantly associated with asthma (rs660498, p = 2.2 × 10(-7)) independent of obesity status. Approximately 5 % of previously reported asthma genetic associations identified in European populations replicated in African Americans. Our identification of novel variants associated with asthma in African American children, coupled with our inability to replicate the majority of findings reported in European Americans, underscores the necessity for including diverse populations in biomedical studies of asthma.

Objective: A better understanding of the molecular mechanisms underlying the development and progression of diabetic neuropathy (DN) is essential for the design of mechanism-based therapies. We examined changes in global gene expression to define pathways regulated by diabetes in peripheral nerve.Research Design and Methods: Microarray data for 24-week-old BKS db/db and db/+ mouse sciatic nerve were analyzed to define significantly differentially expressed genes (DEGs); DEGs were further analyzed to identify regulated biological processes and pathways. Expression profile clustering was performed to identify coexpressed DEGs. A set of coexpressed lipid metabolism genes was used for promoter sequence analysis.Results: Gene expression changes are consistent with structural changes of axonal degeneration. Pathways regulated in the db/db nerve include lipid metabolism, carbohydrate metabolism, energy metabolism, peroxisome proliferator-activated receptor signaling, apoptosis, and axon guidance. Promoter sequences of lipid metabolism-related genes exhibit evidence of coregulation of lipid metabolism and nervous system development genes.Conclusions: Our data support existing hypotheses regarding hyperglycemia-mediated nerve damage in DN. Moreover, our analyses revealed a possible coregulation mechanism connecting hyperlipidemia and axonal degeneration. [ABSTRACT FROM AUTHOR]

Common buckwheat ( Fagopyrum esculentum Moench.) is one of the most important orphan crops worldwide. Various research efforts have been done to improve cultivation methods to enhance important agronomic traits such as productivity and biotic/abiotic resistance. One important aspect is the seed trait, which has not been extensively studied due to the time-consuming and tedious nature of its examination. Despite this, understanding seed traits is crucial for meeting consumer needs and optimizing crop yields. Therefore, the aim of the study is to investigate the inheritance of common buckwheat seed traits-such as shape, size, and coat color-using an image-based approach. This method allows for the analysis of a large number of seeds with a level of accuracy and precision that was previously unattainable. The results indicate that seed coat color is inherited maternally. Notably, the parameters in size had substantial increases acting like overdominance. The number of seeds that were harvested from F 1 s of each cross differed a lot depending on the cross combinations and pin/thrum type. In addition, seed size had large reduction in F 1 s from the different seed-sized parents, especially in thrum type. These may show that there could be cross barriers. The results revealed trends of maternal inheritance for seed shape and coat color in buckwheat, an area that has not been extensively studied. These findings could support buckwheat breeding efforts, helping to address market needs and food demands in the face of significant climate change., Competing Interests: Author YC was employed by the company Phytomix Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RM declared a past co-authorship with the author SM, YSC to the handling editor., (Copyright © 2024 Oh, Park, Kim, Kang, Min Oh, Mansoor and Chung.)

This study aimed to determine whether punitive state alcohol policies targeting pregnant women who drink alcohol are associated with decreased alcohol consumption among pregnant women over time. This study used data from the Pregnancy Risk Assessment Monitoring System (15 states) between 1990 and 2015. A difference-in-difference (DiD) approach was employed to determine whether passage of state laws changed alcohol consumption rates among pregnant women, while controlling for state and time fixed effects. The study specifically examined punitive state alcohol policies that clarify the admissibility of evidence in child welfare proceedings related to prenatal alcohol exposure, focusing on allegations of child abuse, child neglect, child deprivation, or child dependence, as well as proceedings seeking termination of parental rights. Punitive state alcohol policies were not significantly associated with decreased rates of alcohol consumption among pregnant women (+ 1.54%, 95% CI, -1.47-4.55), within 3 years of implementation. State alcohol policies that adopted a punitive stance toward pregnant women who drink alcohol did not result in the reduction of drinking during pregnancy. Given that punitive policies may not effectively reduce alcohol consumption during pregnancy, our findings highlight the need for reevaluation and potential reform to better address maternal/child health outcomes., (© 2024. The Author(s).)

It is self-evident that our chests expand and contract during breathing but, surprisingly, exactly how individual alveoli change shape over the respiratory cycle is still a matter of debate. Some argue that all the alveoli expand and contract rhythmically. Others claim that the lung volume change is due to groups of alveoli collapsing and reopening during ventilation. Although this question might seem to be an insignificant detail for healthy individuals, it might be a matter of life and death for patients with compromised lungs. Past analyses were based on static post-mortem preparations primarily due to technological limitations, and therefore, by definition, incapable of providing dynamic information. In contrast, this study provides the first comprehensive dynamic data on how the shape of the alveoli changes, and, further, provides valuable insights into the optimal lung volume for efficient gas exchange. It is concluded that alveolar micro-dynamics is nonlinear; and at medium lung volume, alveoli expand more than the ducts., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: This study describes a research protocol for a behavioral marker-based predictive model that examines the functional status of older adults with subjective cognitive decline and mild cognitive impairment., Methods: A total of 130 older adults aged ≥65 years with subjective cognitive decline or mild cognitive impairment will be recruited from the Dementia Relief Centers or the Community Service Centers. Data on behavioral and psychosocial markers (e.g. physical activity, mobility, sleep/wake patterns, social interaction, and mild behavioral impairment) will be collected using passive wearable actigraphy, in-person questionnaires, and smartphone-based ecological momentary assessments. Two follow-up assessments will be performed at 12 and 24 months after baseline. Mixed-effect machine learning models: MErf, MEgbm, MEmod, and MEctree, and standard machine learning models without random effects [random forest, gradient boosting machine] will be employed in our analyses to predict functional status over time., Results: The results of this study will be fundamental for developing tailored digital interventions that apply deep learning techniques to behavioral data to predict, identify, and aid in the management of functional decline in older adults with subjective cognitive decline and mild cognitive impairment. These older adults are considered the optimal target population for preventive interventions and will benefit from such tailored strategies., Conclusions: Our study will contribute to the development of self-care interventions that utilize behavioral data and machine learning techniques to provide automated analyses of the functional decline of older adults who are at risk for dementia., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Introduction: Migraine is a debilitating neurological disorder, with a wide range of symptoms and disease burden, underscoring the heterogeneity of patients' disease characteristics and treatment needs. To characterize the profile of migraine patients in the US who may be eligible for preventive treatment with an anti-CGRP pathway mAb and to better understand treatment patterns and real-world use of acute and preventive medications for migraine, we conducted a retrospective cohort study of adult patients., Methods: These patients were identified as having migraine using diagnosis codes or migraine-specific medication use (first = index) in the IQVIA PharMetrics® Plus database. Patients were required to have ≥ 12 months of continuous enrollment in medical and pharmacy benefits prior to index (baseline) and after index (follow-up). Patients were stratified into chronic migraine (CM) and non-chronic migraine (non-CM) by diagnosis codes. Based on acute migraine-specific medication dispensing data in the follow-up period, non-CM patients were divided into 3 cohorts: highest, middle, and lowest tertile of total units of dispensed acute migraine-specific medication (gepants, ditans, ergot derivatives, and triptans). Migraine medication use was captured in the baseline and follow-up periods., Results: A total of 22,584 CM and 216,807 non-CM patients (72,269 patients in each tertile) were identified and included in the study. Over the follow-up, CM patients had a mean of 70 units of acute migraine-specific medications dispensed, while the highest, middle, and lowest tertile of non-CM patients had a mean of 92, 29, and 10 units, respectively. Anti-calcitonin gene-related peptide pathway mAbs were dispensed for 28.9% of CM patients, and for 6.9%, 4.1%, and 2.9% of non-CM patients in the highest, middle, and lowest tertiles, respectively., Conclusion: A lower proportion of non-CM patients had use of anti-calcitonin gene-related peptide pathway mAbs compared to CM patients, confirming the unmet need with appropriate preventive medication. There appears to be a persistent gap in management of patients without a diagnosis of CM who are dispensed high quantities of acute migraine-specific medications., Competing Interests: JM and KH are employees of IQVIA. IQVIA was hired by Amgen to conduct this study. SO, FV, and AK are employees and stockholders of Amgen. MB is an employee of Benofit Consulting. Benofit Consulting was contracted by Amgen to support study design and reporting. C-CC participates in Advisory Board for Satsuma Pharmaceuticals. KS was affiliated with IQVIA at the time of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khodavirdi, Multani, Oh, Vuvu, Bensink, Stockl, Hawkins, Chiang, Green and Tepper.)

Arginine-rich cell-penetrating peptides (CPPs) have emerged as valuable tools for the intracellular delivery of bioactive molecules, but their membrane perturbation during cell penetration is not fully understood. Here, nona-arginine (R 9 )-mediated membrane reorganization that facilitates the translocation of peptides across laterally heterogeneous membranes is directly visualized. The electrostatic binding of cationic R 9 to anionic phosphatidylserine (PS)-enriched domains on a freestanding lipid bilayer induces lateral lipid rearrangements; in particular, in real-time it is observed that R 9 fluidizes PS-rich liquid-ordered (L o ) domains into liquid-disordered (L d ) domains, resulting in the membrane permeabilization. The experiments with giant unilamellar vesicles (GUVs) confirm the preferential translocation of R 9 through L d domains without pore formation, even when L o domains are more negatively charged. Indeed, whenever R 9 comes into contact with negatively charged L o domains, it dissolves the L o domains first, promoting translocation across phase-separated membranes. Collectively, the findings imply that arginine-rich CPPs modulate lateral membrane heterogeneity, including membrane fluidization, as one of the fundamental processes for their effective cell penetration across densely packed lipid bilayers., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Decreased medial cheek fat volume during aging leads to loss of a youthful facial shape. Increasing facial volume by methods such as adipose-derived stem cell (ASC) injection can produce facial rejuvenation. High-intensity focused ultrasound (HIFU) can increase adipogenesis in subcutaneous fat by modulating cilia on ASCs, which is accompanied by increased HSP70 and decreased NF-κB expression. Thus, we evaluated the effect of HIFU on increasing facial adipogenesis in swine ( n = 2) via modulation of ASC cilia. Expression of CD166 , an ASC marker, differed by subcutaneous adipose tissue location. CD166 expression in the zygomatic arch (ZA) was significantly higher than that in the subcutaneous adipose tissue in the mandible or lateral temporal areas. HIFU was applied only on the right side of the face, which was compared with the left side, where HIFU was not applied, as a control. HIFU produced a significant increase in HSP70 expression, decreased expression of NF-κB and a cilia disassembly factor ( AURKA ), and increased expression of a cilia increasing factor ( ARL13B ) and PPARG and CEBPA , which are the main regulators of adipogenesis. All of these changes were most prominent at the ZA. Facial adipose tissue thickness was also increased by HIFU. Adipose tissue volume, evaluated by magnetic resonance imaging, was increased by HIFU, most prominently in the ZA. In conclusion, HIFU increased ASC marker expression, accompanied by increased HSP70 and decreased NF-κB expression. Additionally, changes in cilia disassembly and length and expression of adipogenesis were observed. These results suggest that HIFU could be used to increase facial volume by modulating adipogenesis.

Astrocytes play a crucial role in maintaining brain homeostasis by regulating synaptic activity, providing metabolic support to neurons, and modulating immune responses in the central nervous system (CNS). During aging, astrocytes undergo senescence with various changes that affect their function and frequently lead to neurodegeneration. This study presents the first evidence of senescent astrocytes derived from human pluripotent stem cells (hPSCs). These senescent hPSC-derived astrocytes exhibited altered cellular and nuclear morphologies, along with increased expression of senescence-associated markers. Additionally, nuclear localization of NFκB, telomere shortening, and frequent signs of DNA damage were observed in these cells. Furthermore, senescent astrocytes showed defects in various critical functions necessary for maintaining a healthy CNS environment, including a reduced ability to support neuronal survival and clear neurotransmitters, synaptic debris, and toxic protein aggregates. Altered structural dynamics and reduced mitochondrial function were also observed in senescent astrocytes. Notably, treating hPSC-derived senescent astrocytes with chemicals targeting reactive oxygen species or an enzyme that regulates mitochondrial function can reverse senescence phenotypes. Thus, this study offers a valuable cellular model that can be utilized to investigate the mechanisms of brain aging and may present new avenues for discovering innovative therapeutic approaches for neurodegenerative diseases.

Objective: Subjective cognitive decline (SCD) refers to self-reported memory loss despite normal cognitive function and is considered a preclinical stage of Alzheimer's disease. This study aimed to examine the mediating effects of depression and Instrumental Activities of Daily Living (IADL) on the association between the scoring of Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) and Subjective Cognitive Decline Questionnaire (SCD-Q)., Methods: A sample of 139 community-dwelling older adults aged 65-79 with normal cognitive function completed the SCD-Q, a comprehensive neuropsychological battery, and functional/psychiatric scales. We conducted 1) a correlation analysis between SCD-Q scores and other variables and 2) a path analysis to examine the mediating effects of depression and IADL on the relationship between CDR-SB and SCD-Q., Results: CDR-SB was found to be indirectly associated with SCD-Q, with depressive symptoms mediating this relationship. However, no direct association was observed between SCD-Q and CDR-SB. Additionally, IADL was not associated with SCD-Q and did not mediate the relationship between CDR-SB and SCD-Q. The model fit was acceptable (minimum discrepancy function by degrees of freedom divided [CMIN/DF]=1.585, root mean square error of approximation [RMSEA]=0.065, comparative fit index [CFI]=0.955, Tucker-Lewis index [TLI]=0.939)., Conclusion: Our results suggest that SCD-Q is influenced by depressive symptoms, but not by IADL. The role of depressive symptoms as a mediator between CDR-SB and SCD-Q indicates that psychological factors may contribute to the perception of SCD. Therefore, interventions targeting depression may mitigate the concerns associated with SCD and reduce feelings of worse performance compared to others of the same age group.

Detecting biomarkers in biofluids directly without sample treatments makes molecular diagnostics faster and more efficient. Aptasensors, the nucleic acid-based molecular biosensors, can detect a wide range of target molecules, but their susceptibility to degradation and aggregation by nucleases and charged proteins, respectively, limits their direct use in clinical samples. In this work, we demonstrate that when aptasensors are encapsulated in proteinosomes, the protein-based liposome mimics, clinically important small molecules can be sensitively and selectively detected in non-treated specimens, such as 100 % unpurified serum. As serum albumin is used to form the membrane, the nanomeshed proteinosomes become semi-permeable and antifouling, which enables exclusive admission of small molecules while blocking unwanted large proteins. Consequently, the enclosed aptasensors can maintain close-to-optimal performance for target binding, and nucleolytic degradation and electrostatic aggregation are effectively suppressed. Three different structure-switching aptamers specific for estradiol, dopamine, and cocaine, respectively, are demonstrated to fully conserve their high affinities and specificities inside the microcapsules. The shielding effect of proteinosomes is indeed exceptional; the enclosed DNA aptasensors remain completely intact over 18 h in serum and even in an extremely concentrated DNase solution (1 mg/ml, ∼300,000× the serum level). Moreover, the proteinosome-mediated compartmentalization enables independent operation of multiple aptasensors in the same mixture. Hence, simultaneous real-time sensing of two different targets is demonstrated with different operation modes, 'recording' target appearance and 'reporting' target concentration changes. This work is the first demonstration of small-molecule-specific aptasensors operating with optimal performance in serum environments and will find promising applications in molecular diagnostics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this paper, a volumetric Rotman lens antenna operating at 28 GHz is proposed. The design formula and procedure were derived for the 3-D Rotman lens antenna. The number of tilted beams is 3 × 3. The six rectangular blocks are assembled using a metallic bolt. The input port consists of a waveguide, and the output port is made of an open-ended waveguide. The input and output waveguides are drilled in a flat conducting plate. The input and output port positions are optimized. Simulated and measured results show that the radiating beam is controlled almost exactly as calculated. Compared with the previous two-stage stacked Rotman lens antenna, the proposed Rotman lens antenna can dramatically decrease the antenna volume by approximately 75%.

Knowledge of input blood to the brain, which is represented as total cerebral blood flow (tCBF), is important in evaluating brain health. Phase-contrast (PC) magnetic resonance imaging (MRI) enables blood velocity mapping, allowing for noninvasive measurements of tCBF. In the procedure, manual selection of brain-feeding arteries is an essential step, but is time-consuming and often subjective. Thus, the purpose of this work was to develop and validate a deep learning (DL)-based technique for automated tCBF quantifications. To enhance the DL segmentation performance on arterial blood vessels, in the preprocessing step magnitude and phase images of PC MRI were multiplied several times. Thereafter, a U-Net was trained on 218 images for three-class segmentation. Network performance was evaluated in terms of the Dice coefficient and the intersection-over-union (IoU) on 40 test images, and additionally, on externally acquired 20 datasets. Finally, tCBF was calculated from the DL-predicted vessel segmentation maps, and its accuracy was statistically assessed with the correlation of determination (R 2 ), the intraclass correlation coefficient (ICC), paired t-tests, and Bland-Altman analysis, in comparison to manually derived values. Overall, the DL segmentation network provided accurate labeling of arterial blood vessels for both internal (Dice=0.92, IoU=0.86) and external (Dice=0.90, IoU=0.82) tests. Furthermore, statistical analyses for tCBF estimates revealed good agreement between automated versus manual quantifications in both internal (R 2 =0.85, ICC=0.91, p=0.52) and external (R 2 =0.88, ICC=0.93, p=0.88) test groups. The results suggest feasibility of a simple and automated protocol for quantifying tCBF from neck PC MRI and deep learning., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Surface potential in a topological matter could unprecedentedly localize the waves. However, this surface potential is yet to be exploited in topological photonic systems. Here, we demonstrate that photonic surface states can be induced and controlled by the surface potential in a dielectric double gyroid (DG) photonic crystal. The basis translation in a unit cell enables tuning of the surface potential, which in turn regulates the degree of wave localization. The gradual modulation of DG photonic crystals enables the generation of a pseudomagnetic field. Overall, this study shows the interplay between surface potential and pseudomagnetic field regarding the surface states. The physical consequences outlined herein not only widen the scope of surface states in 3D photonic crystals but also highlight the importance of surface treatments in a photonic system., (© 2024. The Author(s).)

To date, there are no efficacious translational solutions for end-stage urinary bladder dysfunction. Current surgical strategies, including urinary diversion and bladder augmentation enterocystoplasty (BAE), utilize autologous intestinal segments (e.g. ileum) to increase bladder capacity to protect renal function. Considered the standard of care, BAE is fraught with numerous short- and long-term clinical complications. Previous clinical trials employing tissue engineering approaches for bladder tissue regeneration have also been unable to translate bench-top findings into clinical practice. Major obstacles still persist that need to be overcome in order to advance tissue-engineered products into the clinical arena. These include scaffold/bladder incongruencies, the acquisition and utility of appropriate cells for anatomic and physiologic tissue recapitulation, and the choice of an appropriate animal model for testing. In this study, we demonstrate that the elastomeric, bladder biomechanocompatible poly(1,8-octamethylene-citrate-co-octanol) (PRS; synthetic) scaffold coseeded with autologous bone marrow-derived mesenchymal stem cells and CD34 + hematopoietic stem/progenitor cells support robust long-term, functional bladder tissue regeneration within the context of a clinically relevant baboon bladder augmentation model simulating bladder trauma. Partially cystectomized baboons were independently augmented with either autologous ileum or stem-cell-seeded small-intestinal submucosa (SIS; a commercially available biological scaffold) or PRS grafts. Stem-cell synergism promoted functional trilayer bladder tissue regeneration, including whole-graft neurovascularization, in both cell-seeded grafts. However, PRS-augmented animals demonstrated fewer clinical complications and more advantageous tissue characterization metrics compared to ileum and SIS-augmented animals. Two-year study data demonstrate that PRS/stem-cell-seeded grafts drive bladder tissue regeneration and are a suitable alternative to BAE., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Beyond storage and transmission of genetic information in cellular life, nucleic acids can perform diverse interesting functions, including specific target recognition and biochemical reaction acceleration; the versatile biopolymers, however, are acutely vulnerable to hydrolysis-driven degradation. Here, we demonstrate that the cage effect of choline dihydrogen phosphate permits active folding of nucleic acids like water, but prevents their phosphodiester hydrolysis unlike water. The choline-based ionic liquid not only serves as a universal inhibitor of nucleases, exceptionally extending half-lives of nucleic acids up to 6 500 000 times, but highly useful tasks of nucleic acids (e.g. mRNA detection of molecular beacons, ligand recognition of aptamers, and transesterification reaction of ribozymes) can be also conducted with well-conserved affinities and specificities. As liberated from the function loss and degradation risk, the presence of undesired and unknown nucleases does not undermine desired molecular functions of nucleic acids without hydrolysis artifacts even in nuclease cocktails and human saliva., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Firefighters are exposed to shift work, as well as unpredictable emergency calls and traumatic events, which can lead to sleep problems. This study aimed to investigate the risk of insomnia by work schedule instability in Korean firefighters., Methods: This study used the Insomnia Severity Index to assess the insomnia in firefighters. The work schedule stability was classified with the frequency of the substitute work and the timing of notification for work schedule changes. Logistic regression analysis was used to assess the adjusted odds ratio of insomnia by work schedule stability with covariates including sex, age, education, smoking, alcohol, caffeine intake, shift type, job, and underlying conditions., Results: Of the 8,587 individuals, 751 (8.75%) had moderate to severe insomnia (Insomnia Severity Index ≥ 15). The prevalence of insomnia was statistically significantly higher as the frequency of substitute work increased: <1 time per month (6.8%), 1-2 times (9.5%), 3-5 times (13.4%), and more than 5 times (15.7%) (p < 0.001). Additionally, the prevalence of insomnia was statistically significantly higher when the timing of the schedule change notification was urgent or irregular: no change or several weeks before (5.4%), several days before (7.9%), one day before or on the day (11.2%), irregularly notification (11.6%) (p < 0.001). In comparison to the group with good frequency of the substitute work/good timing of schedule change notification group, the adjusted odds ratios of insomnia were 1.480 (95% confidence interval [CI]: 1.237-1.771) for Good/Bad group, 1.862 (95% CI: 1.340-2.588) for Bad/Good group, and 1.885 (95% CI: 1.366-2.602) for Bad/Bad group., Conclusions: Work schedule instability was important risk factor of insomnia in firefighters. It suggests that improving the stability of work schedules could be a key strategy for reducing sleep problems in this occupational group.